=== Generating (published_papers) ===
=== Generating (teaching_experience) ===
=== Generating (education) ===
=== Generating (research_experience) ===
=== Generating (misc) ===
=== Generating (research_projects) ===
=== Generating (books_etc) ===
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==== begin registerFile(/WWW/pub2/data/ERD/person/60638/researchmap/published_papers.jsonl) ====
line:1, {"insert":{"user_id":"1000193501","type":"published_papers","id":"45594100"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=405088","label":"url"}],"paper_title":{"en":"Weak electric current increases ceramide levels by inducing ceramide synthase expression","ja":"Weak electric current increases ceramide levels by inducing ceramide synthase expression"},"authors":{"en":[{"name":"Yamazaki Naoshi"},{"name":"Chiho Ohtsuka"},{"name":"Kogure Kentaro"}],"ja":[{"name":"山﨑 尚志"},{"name":"大塚 ちほ"},{"name":"小暮 健太朗"}]},"publication_date":"2024-01-26","publication_name":{"en":"Journal of Asian Association of Schools of Pharmacy","ja":"Journal of Asian Association of Schools of Pharmacy"},"volume":"Vol.13","starting_page":"1","ending_page":"5","languages":["eng"],"referee":true,"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:2, {"insert":{"user_id":"1000193501","type":"published_papers","id":"44187691"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/118787","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/38246645","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=404188","label":"url"}],"paper_title":{"en":"Development of an effective psoriasis treatment by combining tacrolimus-encapsulated liposomes and iontophoresis","ja":"Development of an effective psoriasis treatment by combining tacrolimus-encapsulated liposomes and iontophoresis"},"authors":{"en":[{"name":"Nakamura Seiko"},{"name":"Ohzono Mizune"},{"name":"Yanagi Karen"},{"name":"Kogure Kentaro"}],"ja":[{"name":"中村 聖子"},{"name":"大園 瑞音"},{"name":"柳 香蓮"},{"name":"小暮 健太朗"}]},"description":{"en":"Psoriasis is a chronic T-cell-mediated autoimmune skin disease. Tacrolimus (FK506) is commonly used treatment for psoriasis. However, since the molecular weight of FK506 is more than 500 Da, its skin penetration is limited, so that there is a need to improve the penetrability of FK506 to allow for more effective treatment. To this end, we employed iontophoresis (ItP), which is a physical, intradermal drug delivery technology that relies on the use of weak electric current. Previous findings suggest that activation of cell signaling by the weak electric current applied during ItP may affect the expression of inflammatory cytokines, leading to aggravation of psoriasis. In this study, we analyzed the effect of ItP on the expression of various inflammatory cytokines in the skin, and subsequently examined the therapeutic effect of ItP using negatively-charged liposomes encapsulating FK506 (FK-Lipo) in a rat psoriasis model induced by imiquimod. We found that ItP (0.34 mA/cm, 1 h) did not affect mRNA levels of inflammatory cytokines or epidermis thickness, indicating that ItP is a safe technology for psoriasis treatment. ItP of FK-Lipo suppressed the expression of inflammatory cytokines induced by imiquimod treatment to a greater extent than skin treated with FK506 ointment for 1 h. Furthermore, epidermis thickening was significantly suppressed only by ItP of FK-Lipo. Taken together, results of this study demonstrate the successful development of an efficient treatment for psoriasis by combining FK-Lipo and ItP, without disease aggravation associated with the weak electric current.","ja":"Psoriasis is a chronic T-cell-mediated autoimmune skin disease. Tacrolimus (FK506) is commonly used treatment for psoriasis. However, since the molecular weight of FK506 is more than 500 Da, its skin penetration is limited, so that there is a need to improve the penetrability of FK506 to allow for more effective treatment. To this end, we employed iontophoresis (ItP), which is a physical, intradermal drug delivery technology that relies on the use of weak electric current. Previous findings suggest that activation of cell signaling by the weak electric current applied during ItP may affect the expression of inflammatory cytokines, leading to aggravation of psoriasis. In this study, we analyzed the effect of ItP on the expression of various inflammatory cytokines in the skin, and subsequently examined the therapeutic effect of ItP using negatively-charged liposomes encapsulating FK506 (FK-Lipo) in a rat psoriasis model induced by imiquimod. We found that ItP (0.34 mA/cm, 1 h) did not affect mRNA levels of inflammatory cytokines or epidermis thickness, indicating that ItP is a safe technology for psoriasis treatment. ItP of FK-Lipo suppressed the expression of inflammatory cytokines induced by imiquimod treatment to a greater extent than skin treated with FK506 ointment for 1 h. Furthermore, epidermis thickening was significantly suppressed only by ItP of FK-Lipo. Taken together, results of this study demonstrate the successful development of an efficient treatment for psoriasis by combining FK-Lipo and ItP, without disease aggravation associated with the weak electric current."},"publication_date":"2023-12-04","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"Vol.47","number":"No.1","starting_page":"196","ending_page":"203","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b23-00667"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:3, {"insert":{"user_id":"1000193501","type":"published_papers","id":"43690031"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/118618","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37838355","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=403376","label":"url"}],"paper_title":{"en":"Vitamin E succinate mediated apoptosis by juxtaposing endoplasmic reticulum and mitochondria","ja":"Vitamin E succinate mediated apoptosis by juxtaposing endoplasmic reticulum and mitochondria"},"authors":{"en":[{"name":"Ray Nath Manobendro"},{"name":"Kiyofuji Michiko"},{"name":"Ohzono Mizune"},{"name":"Kogure Kentaro"}],"ja":[{"name":"MANOBENDRO NATH RAY"},{"name":"清藤 迪子"},{"name":"大園 瑞音"},{"name":"小暮 健太朗"}]},"description":{"en":"Vitamin E succinate (VES) is an esterified form of natural α-tocopherol, has turned out to be novel anticancer agent. However, its anticancer mechanisms have not been illustrated. Previously, we reported VES mediated Ca release from the endoplasmic reticulum (ER) causes mitochondrial Ca overload, leading to mitochondrial depolarization and apoptosis. Here, we elucidated the mechanism of VES-induced Ca transfer from ER to mitochondria by investigating the role of VES in ER-mitochondria contact formation. Transmission electron microscopic observation confirms VES mediated ER-mitochondria contact while fluorescence microscopic analysis revealed that VES increased mitochondria-associated ER membrane (MAM) formation. Pre-treatment with the inositol 1,4,5-triphosphate receptor (IPR) antagonist 2-aminoethyl diphenylborinate (2-APB) decreased VES-induced MAM formation, suggesting the involvement of VES-induced Ca efflux from ER in MAM formation. The ER IPR receptor is known to interact with voltage-dependent anion channels (VDAC) via the chaperone glucose-regulated protein 75 kDa (GRP75) to bring ER and mitochondria nearby. Although we revealed that VES treatment does not affect GRP75 protein level, it increases GRP75 localization in the MAM. In addition, the inhibition of Ca release from ER by 2-APB decreases GRP75 localization in the MAM, suggesting the possibility of Ca-induced conformational change of GRP75 that promotes formation of the IPR-GRP75-VDAC complex and thereby encourages MAM formation. This study identifies the mechanism of VES-induced enhanced Ca transfer from ER to mitochondria, which causes mitochondrial Ca overload leading to apoptosis.","ja":"Vitamin E succinate (VES) is an esterified form of natural α-tocopherol, has turned out to be novel anticancer agent. However, its anticancer mechanisms have not been illustrated. Previously, we reported VES mediated Ca release from the endoplasmic reticulum (ER) causes mitochondrial Ca overload, leading to mitochondrial depolarization and apoptosis. Here, we elucidated the mechanism of VES-induced Ca transfer from ER to mitochondria by investigating the role of VES in ER-mitochondria contact formation. Transmission electron microscopic observation confirms VES mediated ER-mitochondria contact while fluorescence microscopic analysis revealed that VES increased mitochondria-associated ER membrane (MAM) formation. Pre-treatment with the inositol 1,4,5-triphosphate receptor (IPR) antagonist 2-aminoethyl diphenylborinate (2-APB) decreased VES-induced MAM formation, suggesting the involvement of VES-induced Ca efflux from ER in MAM formation. The ER IPR receptor is known to interact with voltage-dependent anion channels (VDAC) via the chaperone glucose-regulated protein 75 kDa (GRP75) to bring ER and mitochondria nearby. Although we revealed that VES treatment does not affect GRP75 protein level, it increases GRP75 localization in the MAM. In addition, the inhibition of Ca release from ER by 2-APB decreases GRP75 localization in the MAM, suggesting the possibility of Ca-induced conformational change of GRP75 that promotes formation of the IPR-GRP75-VDAC complex and thereby encourages MAM formation. This study identifies the mechanism of VES-induced enhanced Ca transfer from ER to mitochondria, which causes mitochondrial Ca overload leading to apoptosis."},"publication_date":"2023-10-05","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - General Subjects","ja":"Biochimica et Biophysica Acta (BBA) - General Subjects"},"volume":"Vol.1867","number":"No.12","starting_page":"130485","ending_page":"130485","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbagen.2023.130485"],"issn":["1872-8006"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:4, {"insert":{"user_id":"1000193501","type":"published_papers","id":"43381638"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/118568","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37914367","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=402917","label":"url"}],"paper_title":{"en":"Non-invasive intradermal delivery of hyaluronic acid via iontophoresis","ja":"Non-invasive intradermal delivery of hyaluronic acid via iontophoresis"},"authors":{"en":[{"name":"Inoue Shinya"},{"name":"Ohshima Yasufumi"},{"name":"Kogure Kentaro"}],"ja":[{"name":"井上 慎也"},{"name":"大島 康史"},{"name":"小暮 健太朗"}]},"description":{"en":"Hyaluronic acid (HA) is a hydrophilic supra-macromolecule, with a molecular weight (MW) 1000000<. HA is recognized as a biomaterial for skin moisturization. HA solution is typically injected into the skin using a needle. However, needle injection is invasive and does not result in homogeneous distribution of HA over a large area of skin. Therefore, non-invasive and effective technologies for homogenous intradermal delivery of HA are needed. Recently, we demonstrated the use of iontophoresis (ItP) for non-invasive intradermal delivery of various macromolecules, such as small interfering RNA (siRNA) (MW: 12000) and antibodies (MW: 150000). Based on our previous studies, we hypothesized that HA can also be delivered non-invasively into the skin by ItP. In this study, we applied ItP to fluorescence-labeled HA (MW: 600000-1120000 and 1200000-1600000) on rat dorsal skin. Following treatment, fluorescence was observed to be widely distributed in the skin, demonstrating successful intradermal delivery of HA via ItP. In addition, the relative moisture content and elasticity of skin treated with ItP/HA was temporarily higher than that of control skin. This is the first report demonstrating successful non-invasive intradermal delivery of HA and improvement of skin conditions by high-molecular weight HA delivered by ItP. In conclusion, ItP would be a useful technology for non-invasive intradermal delivery of high-molecular weight HA for treatment of skin diseases and cosmetology applications.","ja":"Hyaluronic acid (HA) is a hydrophilic supra-macromolecule, with a molecular weight (MW) 1000000<. HA is recognized as a biomaterial for skin moisturization. HA solution is typically injected into the skin using a needle. However, needle injection is invasive and does not result in homogeneous distribution of HA over a large area of skin. Therefore, non-invasive and effective technologies for homogenous intradermal delivery of HA are needed. Recently, we demonstrated the use of iontophoresis (ItP) for non-invasive intradermal delivery of various macromolecules, such as small interfering RNA (siRNA) (MW: 12000) and antibodies (MW: 150000). Based on our previous studies, we hypothesized that HA can also be delivered non-invasively into the skin by ItP. In this study, we applied ItP to fluorescence-labeled HA (MW: 600000-1120000 and 1200000-1600000) on rat dorsal skin. Following treatment, fluorescence was observed to be widely distributed in the skin, demonstrating successful intradermal delivery of HA via ItP. In addition, the relative moisture content and elasticity of skin treated with ItP/HA was temporarily higher than that of control skin. This is the first report demonstrating successful non-invasive intradermal delivery of HA and improvement of skin conditions by high-molecular weight HA delivered by ItP. In conclusion, ItP would be a useful technology for non-invasive intradermal delivery of high-molecular weight HA for treatment of skin diseases and cosmetology applications."},"publication_date":"2023-09-07","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"Vol.46","number":"No.11","starting_page":"1635","ending_page":"1638","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b23-00408"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:5, {"insert":{"user_id":"1000193501","type":"published_papers","id":"43063038"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/118472","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37779041","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=400092","label":"url"}],"paper_title":{"en":"Nanoparticles Encapsulated γ-Oryzanol as a Natural Prodrug of Ferulic Acid for the Treatment of Oxidative Liver Damage","ja":"Nanoparticles Encapsulated γ-Oryzanol as a Natural Prodrug of Ferulic Acid for the Treatment of Oxidative Liver Damage"},"authors":{"en":[{"name":"Ara Tabassum"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Tabassum Ara"},{"name":"小暮 健太朗"}]},"description":{"en":"Antioxidants are promising therapeutics for treating oxidative stress-mediated liver diseases. Previously, we studied a potent natural antioxidant, ferulic acid, and developed a liposomal formulation of ferulic acid (ferulic-lipo) to improve its solubility. Ferulic-lipo significantly attenuated oxidative damage in the liver by inhibiting reactive oxygenase species (ROS). However, antioxidative liposomes must be less reactive with ROS prior to reaching the target sites to effectively neutralize existing ROS. But ferulic-lipo tends to be oxidized before reaching the liver. Besides, γ-oryzanol has been reported to decompose into ferulic acid in vivo; accordingly, we hypothesized that γ-oryzanol could be employed as a natural prodrug of ferulic acid to improve stability and antioxidative effectiveness. Therefore, in this study, we prepared a liposomal formulation of γ-oryzanol (γ-ory-lipo) and investigated its therapeutic effects in a CCl-induced rat model of liver injury. We found that γ-ory-lipo has a higher chemical stability than does free γ-oryzanol. Although the antioxidative effect of γ-ory-lipo was lower than that of ferulic-lipo, pretreatment of the HepG2 cells with γ-ory-lipo improved the viability of CCl-treated cells to a similar level as treatment with ferulic-lipo. γ-Oryzanol was shown to be converted into ferulic acid in vitro and in vivo. Furthermore, intravenous administration of γ-ory-lipo exhibited a similar effectiveness as ferulic-lipo against CCl-induced hepatotoxicity, which should be the due to the conversion of γ-oryzanol into ferulic acid. These findings demonstrated that γ-ory-lipo could be a good natural prodrug of ferulic acid for eradicating its stability problem.","ja":"Antioxidants are promising therapeutics for treating oxidative stress-mediated liver diseases. Previously, we studied a potent natural antioxidant, ferulic acid, and developed a liposomal formulation of ferulic acid (ferulic-lipo) to improve its solubility. Ferulic-lipo significantly attenuated oxidative damage in the liver by inhibiting reactive oxygenase species (ROS). However, antioxidative liposomes must be less reactive with ROS prior to reaching the target sites to effectively neutralize existing ROS. But ferulic-lipo tends to be oxidized before reaching the liver. Besides, γ-oryzanol has been reported to decompose into ferulic acid in vivo; accordingly, we hypothesized that γ-oryzanol could be employed as a natural prodrug of ferulic acid to improve stability and antioxidative effectiveness. Therefore, in this study, we prepared a liposomal formulation of γ-oryzanol (γ-ory-lipo) and investigated its therapeutic effects in a CCl-induced rat model of liver injury. We found that γ-ory-lipo has a higher chemical stability than does free γ-oryzanol. Although the antioxidative effect of γ-ory-lipo was lower than that of ferulic-lipo, pretreatment of the HepG2 cells with γ-ory-lipo improved the viability of CCl-treated cells to a similar level as treatment with ferulic-lipo. γ-Oryzanol was shown to be converted into ferulic acid in vitro and in vivo. Furthermore, intravenous administration of γ-ory-lipo exhibited a similar effectiveness as ferulic-lipo against CCl-induced hepatotoxicity, which should be the due to the conversion of γ-oryzanol into ferulic acid. These findings demonstrated that γ-ory-lipo could be a good natural prodrug of ferulic acid for eradicating its stability problem."},"publication_date":"2023-08-09","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"Vol.46","number":"No.10","starting_page":"1403","ending_page":"1411","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b23-00181"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:6, {"insert":{"user_id":"1000193501","type":"published_papers","id":"42487731"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/118301","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37532560","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=397825","label":"url"}],"paper_title":{"en":"Development of functional chimeric nanoparticles by membrane fusion of small extracellular vesicles and drug-encapsulated liposomes","ja":"Development of functional chimeric nanoparticles by membrane fusion of small extracellular vesicles and drug-encapsulated liposomes"},"authors":{"en":[{"name":"Fukuta Tatsuya"},{"name":"Nishikawa Akina"},{"name":"Hiramachi Ami"},{"name":"Yamashita Sachika"},{"name":"Kogure Kentaro"}],"ja":[{"name":"福田 達也"},{"name":"西川 明菜"},{"name":"平町 愛美"},{"name":"山下 祥花"},{"name":"小暮 健太朗"}]},"description":{"en":"Since small extracellular vesicle (sEVs) are involved in cell-to-cell communication via transfer of certain bioactive molecules and have the capability to overcome biological barriers against drug transport, their use as a drug delivery system (DDS) has been demonstrated in treatment of a diverse range of diseases. However, some issues in drug encapsulation have been pointed out, including low encapsulation efficiency and poor reproducibility. It was previously reported that liposomes containing phosphatidylserine (PS) can fuse together in the presence of calcium ion, which allows for drug encapsulation into the resultant liposomes (i.e., calcium fusion method). On the other hand, PS is reportedly present in lipid membrane of sEVs as a distinct lipid composition. We therefore hypothesized that PS-mediated membrane fusion of sEVs with PS-liposomes encapsulating therapeutic agents via the calcium fusion method can be applied to convenient drug encapsulation into sEVs. Membrane fusion of PS-liposomes and sEVs derived from murine melanoma B16F1 cells (B16-sEVs) was firstly confirmed. The obtained nanoparticles, termed chimeric nanoparticles (CM-NP), showed comparable cellular uptake to B16-sEVs into B16F1 cells. Moreover, CM-NP encapsulating an anticancer drug doxorubicin (DOX) (CM-NP-DOX) could be prepared by membrane fusion of PS-liposomes encapsulating DOX (PS-Lipo-DOX) and B16-sEVs. CM-NP-DOX exhibited a superior anticancer effect on B16F1 cells in vitro compared with PS-Lipo-DOX. These findings suggest that the calcium fusion method could be applied for membrane fusion of sEVs and PS-liposomes, and that this approach would likely be useful for efficient drug encapsulation into sEVs, as well as increasing liposome functionality.","ja":"Since small extracellular vesicle (sEVs) are involved in cell-to-cell communication via transfer of certain bioactive molecules and have the capability to overcome biological barriers against drug transport, their use as a drug delivery system (DDS) has been demonstrated in treatment of a diverse range of diseases. However, some issues in drug encapsulation have been pointed out, including low encapsulation efficiency and poor reproducibility. It was previously reported that liposomes containing phosphatidylserine (PS) can fuse together in the presence of calcium ion, which allows for drug encapsulation into the resultant liposomes (i.e., calcium fusion method). On the other hand, PS is reportedly present in lipid membrane of sEVs as a distinct lipid composition. We therefore hypothesized that PS-mediated membrane fusion of sEVs with PS-liposomes encapsulating therapeutic agents via the calcium fusion method can be applied to convenient drug encapsulation into sEVs. Membrane fusion of PS-liposomes and sEVs derived from murine melanoma B16F1 cells (B16-sEVs) was firstly confirmed. The obtained nanoparticles, termed chimeric nanoparticles (CM-NP), showed comparable cellular uptake to B16-sEVs into B16F1 cells. Moreover, CM-NP encapsulating an anticancer drug doxorubicin (DOX) (CM-NP-DOX) could be prepared by membrane fusion of PS-liposomes encapsulating DOX (PS-Lipo-DOX) and B16-sEVs. CM-NP-DOX exhibited a superior anticancer effect on B16F1 cells in vitro compared with PS-Lipo-DOX. These findings suggest that the calcium fusion method could be applied for membrane fusion of sEVs and PS-liposomes, and that this approach would likely be useful for efficient drug encapsulation into sEVs, as well as increasing liposome functionality."},"publication_date":"2023-06","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"Vol.46","number":"No.8","starting_page":"1098","ending_page":"1104","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b23-00135"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:7, {"insert":{"user_id":"1000193501","type":"published_papers","id":"41633906"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/118028","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36986496","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=394326","label":"url"}],"paper_title":{"en":"Increasing Skeletal Muscle Mass in Mice by Non-Invasive Intramuscular Delivery of Myostatin Inhibitory Peptide by Iontophoresis","ja":"Increasing Skeletal Muscle Mass in Mice by Non-Invasive Intramuscular Delivery of Myostatin Inhibitory Peptide by Iontophoresis"},"authors":{"en":[{"name":"Michiue Kohki"},{"name":"Takayama Kentaro"},{"name":"Taniguchi Atsuhiko"},{"name":"Hayashi Yoshio"},{"name":"Kogure Kentaro"}],"ja":[{"name":"道上 巧基"},{"name":"Takayama Kentaro"},{"name":"Taniguchi Atsuhiko"},{"name":"Hayashi Yoshio"},{"name":"小暮 健太朗"}]},"description":{"en":"Sarcopenia is a major public health issue that affects older adults. Myostatin inhibitory-D-peptide-35 (MID-35) can increase skeletal muscle and is a candidate therapeutic agent, but a non-invasive and accessible technology for the intramuscular delivery of MID-35 is required. Recently, we succeeded in the intradermal delivery of various macromolecules, such as siRNA and antibodies, by iontophoresis (ItP), a non-invasive transdermal drug delivery technology that uses weak electricity. Thus, we expected that ItP could deliver MID-35 non-invasively from the skin surface to skeletal muscle. In the present study, ItP was performed with a fluorescently labeled peptide on mouse hind leg skin. Fluorescent signal was observed in both skin and skeletal muscle. This result suggested that the peptide was effectively delivered to skeletal muscle from skin surface by ItP. Then, the effect of MID-35/ItP on skeletal muscle mass was evaluated. The skeletal muscle mass increased 1.25 times with ItP of MID-35. In addition, the percentage of new and mature muscle fibers tended to increase, and ItP delivery of MID-35 showed a tendency to induce alterations in the levels of mRNA of genes downstream of myostatin. In conclusion, ItP of myostatin inhibitory peptide is a potentially useful strategy for treating sarcopenia.","ja":"Sarcopenia is a major public health issue that affects older adults. Myostatin inhibitory-D-peptide-35 (MID-35) can increase skeletal muscle and is a candidate therapeutic agent, but a non-invasive and accessible technology for the intramuscular delivery of MID-35 is required. Recently, we succeeded in the intradermal delivery of various macromolecules, such as siRNA and antibodies, by iontophoresis (ItP), a non-invasive transdermal drug delivery technology that uses weak electricity. Thus, we expected that ItP could deliver MID-35 non-invasively from the skin surface to skeletal muscle. In the present study, ItP was performed with a fluorescently labeled peptide on mouse hind leg skin. Fluorescent signal was observed in both skin and skeletal muscle. This result suggested that the peptide was effectively delivered to skeletal muscle from skin surface by ItP. Then, the effect of MID-35/ItP on skeletal muscle mass was evaluated. The skeletal muscle mass increased 1.25 times with ItP of MID-35. In addition, the percentage of new and mature muscle fibers tended to increase, and ItP delivery of MID-35 showed a tendency to induce alterations in the levels of mRNA of genes downstream of myostatin. In conclusion, ItP of myostatin inhibitory peptide is a potentially useful strategy for treating sarcopenia."},"publication_date":"2023-03-03","publication_name":{"en":"Pharmaceuticals","ja":"Pharmaceuticals"},"volume":"Vol.16","starting_page":"397","ending_page":"397","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/ph16030397"],"issn":["1424-8247"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:8, {"insert":{"user_id":"1000193501","type":"published_papers","id":"41135896"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117908","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36858579","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=393581","label":"url"}],"paper_title":{"en":"The effect of iontophoretic-delivered polyplex vaccine on melanoma regression","ja":"The effect of iontophoretic-delivered polyplex vaccine on melanoma regression"},"authors":{"en":[{"name":"Husseini A. Rabab"},{"name":"Fukuta Tatsuya"},{"name":"Ohzono Mizune"},{"name":"Hasan A. Azza"},{"name":"Megrab, El A. Nagia"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Husseini A. Rabab"},{"name":"福田 達也"},{"name":"大園 瑞音"},{"name":"Hasan A. Azza"},{"name":"Megrab, El A. Nagia"},{"name":"小暮 健太朗"}]},"description":{"en":"Although the strategy in cancer vaccination is to provide a therapeutic effect against an established tumor, there is an urgent need to develop prophylactic vaccines for non-viral cancers. In this study, we prepared polyplex nanoparticles through electrostatic interactions between a positively-charged modified tumor associated antigen, namely human derived melanoma gp100 peptide (KVPRNQDWL-RRRR), and a negatively charged cytosine-phosphate-guanosine motif (CpG-ODN) adjuvant. We previously demonstrated successful transdermal delivery of various hydrophilic macromolecules by iontophoresis (IP) using weak electricity. Herein, we investigated the effectiveness of IP in the transdermal delivery of a prophylactic polyplex vaccine. IP was successful in establishing a homogenous distribution of the vaccine throughout skin. Efficacy of the vaccine was demonstrated against melanoma growth. A significant tumor regression effect was observed, which was confirmed by elevated mRNA expression levels of various cytokines, mainly interferon (IFN)-γ, as well as infiltration of cytotoxic CD8 T cells. Additionally, we evaluated the therapeutic effect of the vaccine and we found a significant reduction in tumor burden. Stimulation of systemic immunity was confirmed by upregulation of IFN-γ. This is the first report to demonstrate the use of IP in the transdermal delivery of a prophylactic melanoma vaccine.","ja":"Although the strategy in cancer vaccination is to provide a therapeutic effect against an established tumor, there is an urgent need to develop prophylactic vaccines for non-viral cancers. In this study, we prepared polyplex nanoparticles through electrostatic interactions between a positively-charged modified tumor associated antigen, namely human derived melanoma gp100 peptide (KVPRNQDWL-RRRR), and a negatively charged cytosine-phosphate-guanosine motif (CpG-ODN) adjuvant. We previously demonstrated successful transdermal delivery of various hydrophilic macromolecules by iontophoresis (IP) using weak electricity. Herein, we investigated the effectiveness of IP in the transdermal delivery of a prophylactic polyplex vaccine. IP was successful in establishing a homogenous distribution of the vaccine throughout skin. Efficacy of the vaccine was demonstrated against melanoma growth. A significant tumor regression effect was observed, which was confirmed by elevated mRNA expression levels of various cytokines, mainly interferon (IFN)-γ, as well as infiltration of cytotoxic CD8 T cells. Additionally, we evaluated the therapeutic effect of the vaccine and we found a significant reduction in tumor burden. Stimulation of systemic immunity was confirmed by upregulation of IFN-γ. This is the first report to demonstrate the use of IP in the transdermal delivery of a prophylactic melanoma vaccine."},"publication_date":"2023-03","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"Vol.46","number":"No.3","starting_page":"494","ending_page":"504","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b22-00873"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:9, {"insert":{"user_id":"1000193501","type":"published_papers","id":"40597288"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117788","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36083714","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85138289941&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=393054","label":"url"}],"paper_title":{"en":"Only one carbon difference determines the pro-apoptotic activity of α-tocopheryl esters","ja":"Only one carbon difference determines the pro-apoptotic activity of α-tocopheryl esters"},"authors":{"en":[{"name":"Manobendro Nath Ray"},{"name":"Ohzono Mizune"},{"name":"Nakao Michiyasu"},{"name":"Sano Shigeki"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Ray Manobendro Nath"},{"name":"大園 瑞音"},{"name":"中尾 允泰"},{"name":"佐野 茂樹"},{"name":"小暮 健太朗"}]},"description":{"en":"α-Tocopheryl succinate (TS), a redox-silent succinyl ester of natural α-Tocopherol, has emerged as a novel anti-cancer agent. However, the underlying mechanism is unclear. We found that the terminal dicarboxylic moiety of tocopheryl esters contributes to apoptosis induction and thus cytotoxicity. To further examine this relationship, we compared the pro-apoptotic activity of TS, which has four carbon atoms in the terminal dicarboxylic moiety, to that of a newly synthesized, tocopheryl glutarate (Tglu), which has five. Cytotoxicity assays in vitro confirmed that TS stimulated apoptosis, while Tglu was non-cytotoxic. In investigating biological mechanisms leading to these opposing effects, we found that TS caused an elevation of intracellular superoxide, but Tglu did not. TS increased intracellular Ca in cultured cells, suggesting induction of endoplasmic reticulum (ER) stress; however, Tglu did not affect Ca homeostasis. 1,4,5-trisphosphate (IP ) receptor antagonist 2-Aminoethyl diphenylborinate (2-APB) decreased TS-induced intracellular Ca , restored mitochondrial activity and cell viability in TS-treated cells, establishing the ER-mitochondria relationship in apoptosis induction. Moreover, real-time PCR, immunostaining and Western blotting assays revealed that TS downregulated glucose-regulated protein 78 (GRP78), which maintains ER homeostasis and promotes cell survival. Conversely, Tglu upregulates GRP78. Taken together, our results suggest a model in which TS-mediated superoxide production and GRP78 inhibition induce ER stress, which elevates intracellular Ca and depolarizes mitochondria, leading to apoptosis. Because Tglu does not affect superoxide generation and increases GRP78 expression, it inhibits ER stress and is thereby non-cytotoxic. Our research provides insight into the structure-activity relationship of tocopheryl esters regarding the induction of apoptosis.","ja":"α-Tocopheryl succinate (TS), a redox-silent succinyl ester of natural α-Tocopherol, has emerged as a novel anti-cancer agent. However, the underlying mechanism is unclear. We found that the terminal dicarboxylic moiety of tocopheryl esters contributes to apoptosis induction and thus cytotoxicity. To further examine this relationship, we compared the pro-apoptotic activity of TS, which has four carbon atoms in the terminal dicarboxylic moiety, to that of a newly synthesized, tocopheryl glutarate (Tglu), which has five. Cytotoxicity assays in vitro confirmed that TS stimulated apoptosis, while Tglu was non-cytotoxic. In investigating biological mechanisms leading to these opposing effects, we found that TS caused an elevation of intracellular superoxide, but Tglu did not. TS increased intracellular Ca in cultured cells, suggesting induction of endoplasmic reticulum (ER) stress; however, Tglu did not affect Ca homeostasis. 1,4,5-trisphosphate (IP ) receptor antagonist 2-Aminoethyl diphenylborinate (2-APB) decreased TS-induced intracellular Ca , restored mitochondrial activity and cell viability in TS-treated cells, establishing the ER-mitochondria relationship in apoptosis induction. Moreover, real-time PCR, immunostaining and Western blotting assays revealed that TS downregulated glucose-regulated protein 78 (GRP78), which maintains ER homeostasis and promotes cell survival. Conversely, Tglu upregulates GRP78. Taken together, our results suggest a model in which TS-mediated superoxide production and GRP78 inhibition induce ER stress, which elevates intracellular Ca and depolarizes mitochondria, leading to apoptosis. Because Tglu does not affect superoxide generation and increases GRP78 expression, it inhibits ER stress and is thereby non-cytotoxic. Our research provides insight into the structure-activity relationship of tocopheryl esters regarding the induction of apoptosis."},"publication_date":"2023-02","publication_name":{"en":"The FEBS Journal","ja":"The FEBS Journal"},"volume":"Vol.290","starting_page":"1027","ending_page":"1048","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1111/febs.16623"],"issn":["1742-4658"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:10, {"insert":{"user_id":"1000193501","type":"published_papers","id":"40597287"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117787","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36724958","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=393051","label":"url"}],"paper_title":{"en":"Use of iontophoresis technology for transdermal delivery of a minimal mRNA vaccine as a potential melanoma therapeutic","ja":"Use of iontophoresis technology for transdermal delivery of a minimal mRNA vaccine as a potential melanoma therapeutic"},"authors":{"en":[{"name":"Husseini R A"},{"name":"Abe Naoko"},{"name":"Hara Tomoaki"},{"name":"Abe Hiroshi"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Rabab Ahmed ZeinElAbdin Husseini"},{"name":"Abe Naoko"},{"name":"Hara Tomoaki"},{"name":"Abe Hiroshi"},{"name":"小暮 健太朗"}]},"description":{"en":"mRNA vaccines have attracted considerable attention as a result of the 2019 coronavirus pandemic; however, challenges remain regarding use of mRNA vaccines, including insufficient delivery owing to the high molecular weights and high negative charges associated with mRNA. These characteristics of mRNA vaccines impair intracellular uptake and subsequent protein translation. In the current study, we prepared a minimal mRNA vaccine encoding a tumor associated antigen human gp100 peptide (KVPRNQDWL), as a potential treatment for melanoma. Minimal mRNA vaccines have recently shown promise at improving the translational process, and can be prepared via a simple production method. Moreover, we previously reported the successful use of iontophoresis (IP) technology in the delivery of hydrophilic macromolecules into skin layers, as well as intracellular delivery of small interfering RNA (siRNA). We hypothesized that combining IP technology with a newly synthesized minimal mRNA vaccine can improve both transdermal and intracellular delivery of mRNA. Following IP-induced delivery of a mRNA vaccine, an immune response is elicited resulting in activation of skin resident immune cells. As expected, combining both technologies led to potent stimulation of the immune system, which was observed via potent tumor inhibition in mice bearing melanoma. Additionally, there was an elevation in mRNA expression levels of various cytokines, mainly interferon (IFN)-γ, as well as infiltration of cytotoxic CD8 T cells in the tumor tissue, which are responsible for tumor clearance. This is the first report demonstrating the application of IP for delivery of a minimal mRNA vaccine as a potential melanoma therapeutic.","ja":"mRNA vaccines have attracted considerable attention as a result of the 2019 coronavirus pandemic; however, challenges remain regarding use of mRNA vaccines, including insufficient delivery owing to the high molecular weights and high negative charges associated with mRNA. These characteristics of mRNA vaccines impair intracellular uptake and subsequent protein translation. In the current study, we prepared a minimal mRNA vaccine encoding a tumor associated antigen human gp100 peptide (KVPRNQDWL), as a potential treatment for melanoma. Minimal mRNA vaccines have recently shown promise at improving the translational process, and can be prepared via a simple production method. Moreover, we previously reported the successful use of iontophoresis (IP) technology in the delivery of hydrophilic macromolecules into skin layers, as well as intracellular delivery of small interfering RNA (siRNA). We hypothesized that combining IP technology with a newly synthesized minimal mRNA vaccine can improve both transdermal and intracellular delivery of mRNA. Following IP-induced delivery of a mRNA vaccine, an immune response is elicited resulting in activation of skin resident immune cells. As expected, combining both technologies led to potent stimulation of the immune system, which was observed via potent tumor inhibition in mice bearing melanoma. Additionally, there was an elevation in mRNA expression levels of various cytokines, mainly interferon (IFN)-γ, as well as infiltration of cytotoxic CD8 T cells in the tumor tissue, which are responsible for tumor clearance. This is the first report demonstrating the application of IP for delivery of a minimal mRNA vaccine as a potential melanoma therapeutic."},"publication_date":"2023-02","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"Vol.46","number":"No.2","starting_page":"301","ending_page":"308","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b22-00746"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:11, {"insert":{"user_id":"1000193501","type":"published_papers","id":"41135895"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117909","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36796910","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=393582","label":"url"}],"paper_title":{"en":"Heat stress disrupts spermatogenesis via modulation of sperm-specific calcium channels in rats","ja":"Heat stress disrupts spermatogenesis via modulation of sperm-specific calcium channels in rats"},"authors":{"en":[{"name":"Mahran Mohamed Abd El-Emam"},{"name":"Manobendro Nath Ray"},{"name":"Ohzono Mizune"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Mahran Mohamed Abd El-Emam"},{"name":"Ray Manobendro Nath"},{"name":"大園 瑞音"},{"name":"小暮 健太朗"}]},"description":{"en":"Heat is a detrimental environmental stressor that disrupts spermatogenesis and results in male infertility. Previous investigations have shown that heat stress reduces the motility, number, and fertilization ability of living spermatozoa. Sperm hyperactivation, capacitation, acrosomal reaction, and chemotaxis towards the ova are regulated by the cation channel of sperm (CatSper). This sperm-specific ion channel triggers the influx of calcium ions into sperm cells. The aim of this study in rats was to investigate whether heat treatment affected the expression levels of CatSper-1 and -2, together with the sperm parameters, testicular histology and weight. The rats were exposed to heat stress for 6 days and the cauda epididymis and testis were collected 1, 14, and 35 days after heat treatment to measure sperm parameters, gene and protein expression, testicular weight, and histology. Interestingly, we found that heat treatment caused a notable downregulation of CatSper-1 and -2 expression at all three time points. In addition, there were significant reductions in sperm motility and number and an increase in the percentage of abnormal sperm at 1 and 14 days, with cessation of sperm production at 35 days. Furthermore, expression of the steroidogenesis regulator, 3 beta-hydroxysteroid dehydrogenase (3β-HSD) was upregulated in the 1-, 14- and 35-day samples. Heat treatment also upregulated the expression of the apoptosis regulator, BCL2-associated X protein (BAX), decreased testicular weight, and altered testicular histology. Therefore, our data showed for the first time that heat stress downregulated CatSper-1 and -2 in the rat testis, and that this may be a mechanism involved in heat stress-induced impairment of spermatogenesis.","ja":"Heat is a detrimental environmental stressor that disrupts spermatogenesis and results in male infertility. Previous investigations have shown that heat stress reduces the motility, number, and fertilization ability of living spermatozoa. Sperm hyperactivation, capacitation, acrosomal reaction, and chemotaxis towards the ova are regulated by the cation channel of sperm (CatSper). This sperm-specific ion channel triggers the influx of calcium ions into sperm cells. The aim of this study in rats was to investigate whether heat treatment affected the expression levels of CatSper-1 and -2, together with the sperm parameters, testicular histology and weight. The rats were exposed to heat stress for 6 days and the cauda epididymis and testis were collected 1, 14, and 35 days after heat treatment to measure sperm parameters, gene and protein expression, testicular weight, and histology. Interestingly, we found that heat treatment caused a notable downregulation of CatSper-1 and -2 expression at all three time points. In addition, there were significant reductions in sperm motility and number and an increase in the percentage of abnormal sperm at 1 and 14 days, with cessation of sperm production at 35 days. Furthermore, expression of the steroidogenesis regulator, 3 beta-hydroxysteroid dehydrogenase (3β-HSD) was upregulated in the 1-, 14- and 35-day samples. Heat treatment also upregulated the expression of the apoptosis regulator, BCL2-associated X protein (BAX), decreased testicular weight, and altered testicular histology. Therefore, our data showed for the first time that heat stress downregulated CatSper-1 and -2 in the rat testis, and that this may be a mechanism involved in heat stress-induced impairment of spermatogenesis."},"publication_date":"2023-01-09","publication_name":{"en":"Journal of Thermal Biology","ja":"Journal of Thermal Biology"},"volume":"Vol.112","starting_page":"103465","ending_page":"103465","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jtherbio.2023.103465"],"issn":["0306-4565"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:12, {"insert":{"user_id":"1000193501","type":"published_papers","id":"39048735"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117266","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36777075","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=386965","label":"url"}],"paper_title":{"en":"Protective effects of liposomes encapsulating ferulic acid against CCl4-induced oxidative liver damage in vivo rat model","ja":"Protective effects of liposomes encapsulating ferulic acid against CCl4-induced oxidative liver damage in vivo rat model"},"authors":{"en":[{"name":"Tabassum Ara"},{"name":"Ono Satoko"},{"name":"Hasan M"},{"name":"Ohzono Mizune"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Tabassum Ara"},{"name":"小野 智子"},{"name":"Hasan M"},{"name":"大園 瑞音"},{"name":"小暮 健太朗"}]},"description":{"en":"Antioxidants are useful for the treatment of oxidative stress mediated liver damage. A naturally occurring antioxidant γ-oryzanol is rapidly hydrolyzed to its active hydrophobic metabolite, ferulic acid, inside the body. Limitations associated with the hydrophobicity of ferulic acid can be overcome by encapsulating in a liposomal formulation. As intravenously administered nanoparticles (including liposomes) can effectively reach the liver, such systems may be suitable drug delivery carriers to treat liver injury. In this study, we prepared a liposomal formulation of ferulic acid (ferulic-lipo) and examined its effects on liver damage induced by CCl. Ferulic-lipo were ~100 nm in size and drug encapsulation efficiency was about 92%. Ferulic-lipo showed potent scavenging efficacy against hydroxyl radical compared to α-tocopherol liposomes. Ferulic-lipo significantly prevented CCl-mediated cytotoxicity in human hepatocarcinoma cells. Furthermore, intravenous administration of ferulic-lipo significantly reduced alanine aminotransferase and aspartate amino transferase levels in a rat model of liver injury. CCl-mediated reactive oxygen species generation in liver was also reduced by intravenous administration of ferulic-lipo. Hepatoprotective effects of ferulic-lipo were demonstrated by histological observation of CCl-induced liver tissue damage. Therefore, ferulic-lipo exhibit potent antioxidative capacity and were suggested to be an effective formulation for prevention of oxidative damage of liver tissue.","ja":"Antioxidants are useful for the treatment of oxidative stress mediated liver damage. A naturally occurring antioxidant γ-oryzanol is rapidly hydrolyzed to its active hydrophobic metabolite, ferulic acid, inside the body. Limitations associated with the hydrophobicity of ferulic acid can be overcome by encapsulating in a liposomal formulation. As intravenously administered nanoparticles (including liposomes) can effectively reach the liver, such systems may be suitable drug delivery carriers to treat liver injury. In this study, we prepared a liposomal formulation of ferulic acid (ferulic-lipo) and examined its effects on liver damage induced by CCl. Ferulic-lipo were ~100 nm in size and drug encapsulation efficiency was about 92%. Ferulic-lipo showed potent scavenging efficacy against hydroxyl radical compared to α-tocopherol liposomes. Ferulic-lipo significantly prevented CCl-mediated cytotoxicity in human hepatocarcinoma cells. Furthermore, intravenous administration of ferulic-lipo significantly reduced alanine aminotransferase and aspartate amino transferase levels in a rat model of liver injury. CCl-mediated reactive oxygen species generation in liver was also reduced by intravenous administration of ferulic-lipo. Hepatoprotective effects of ferulic-lipo were demonstrated by histological observation of CCl-induced liver tissue damage. Therefore, ferulic-lipo exhibit potent antioxidative capacity and were suggested to be an effective formulation for prevention of oxidative damage of liver tissue."},"publication_date":"2023-01","publication_name":{"en":"Journal of Clinical Biochemistry and Nutrition","ja":"Journal of Clinical Biochemistry and Nutrition"},"volume":"Vol.72","number":"No.1","starting_page":"46","ending_page":"53","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3164/jcbn.22-37"],"issn":["0912-0009"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:13, {"insert":{"user_id":"1000193501","type":"published_papers","id":"42512687"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/118324","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37940524","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=397874","label":"url"}],"paper_title":{"en":"Molecular species profiles of plasma ceramides in different clinical types of X-linked adrenoleukodystrophy","ja":"Molecular species profiles of plasma ceramides in different clinical types of X-linked adrenoleukodystrophy"},"authors":{"en":[{"name":"Katsuya Morito"},{"name":"Ryota Shimizu"},{"name":"Hanif Ali"},{"name":"Akina Shimada"},{"name":"Tohru Miyazaki"},{"name":"Naoko Takahashi"},{"name":"M. Motiur Rahman"},{"name":"Kazuki Tsuji"},{"name":"Nobuyuki Shimozawa"},{"name":"Nakao Michiyasu"},{"name":"Sano Shigeki"},{"name":"Azuma Momoyo"},{"name":"Meera Nanjundan"},{"name":"Kogure Kentaro"},{"name":"Tanaka Tamotsu"}],"ja":[{"name":"Katsuya Morito"},{"name":"Ryota Shimizu"},{"name":"Hanif Ali"},{"name":"Akina Shimada"},{"name":"Tohru Miyazaki"},{"name":"Naoko Takahashi"},{"name":"M. Motiur Rahman"},{"name":"Kazuki Tsuji"},{"name":"Nobuyuki Shimozawa"},{"name":"中尾 允泰"},{"name":"佐野 茂樹"},{"name":"東 桃代"},{"name":"Meera Nanjundan"},{"name":"小暮 健太朗"},{"name":"田中 保"}]},"description":{"en":"X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder associated with peroxisomal dysfunction. Patients with this rare disease accumulate very long-chain fatty acids (VLCFAs) in their bodies because of impairment of peroxisomal VLCFA ?-oxidation. Several clinical types of X-ALD, ranging from mild (axonopathy in the spinal cord) to severe (cerebral demyelination), are known. However, the molecular basis for this phenotypic variability remains largely unknown. In this study, we determined plasma ceramide (CER) profile using liquid chromatography-tandem mass spectrometry. We characterized the molecular species profile of CER in the plasma of patients with mild (adrenomyeloneuropathy;AMN) and severe (cerebral) X-ALD. Eleven X-ALD patients (five cerebral, five AMN, and one carrier) and 10 healthy volunteers participated in this study. Elevation of C26:0 CER was found to be a common feature regardless of the clinical types. The level of C26:1 CER was significantly higher in AMN but not in cerebral type, than that in healthy controls. The C26:1 CER level in the cerebral type was significantly lower than that in the AMN type. These results suggest that a high level of C26:0 CER, along with a control level of C26:1 CER, is a characteristic feature of the cerebral type X-ALD. J. Med. Invest. 70 : 403-410, August, 2023.","ja":"X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder associated with peroxisomal dysfunction. Patients with this rare disease accumulate very long-chain fatty acids (VLCFAs) in their bodies because of impairment of peroxisomal VLCFA ?-oxidation. Several clinical types of X-ALD, ranging from mild (axonopathy in the spinal cord) to severe (cerebral demyelination), are known. However, the molecular basis for this phenotypic variability remains largely unknown. In this study, we determined plasma ceramide (CER) profile using liquid chromatography-tandem mass spectrometry. We characterized the molecular species profile of CER in the plasma of patients with mild (adrenomyeloneuropathy;AMN) and severe (cerebral) X-ALD. Eleven X-ALD patients (five cerebral, five AMN, and one carrier) and 10 healthy volunteers participated in this study. Elevation of C26:0 CER was found to be a common feature regardless of the clinical types. The level of C26:1 CER was significantly higher in AMN but not in cerebral type, than that in healthy controls. The C26:1 CER level in the cerebral type was significantly lower than that in the AMN type. These results suggest that a high level of C26:0 CER, along with a control level of C26:1 CER, is a characteristic feature of the cerebral type X-ALD. J. Med. Invest. 70 : 403-410, August, 2023."},"publication_date":"2023","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.70","number":"No.3.4","starting_page":"403","ending_page":"410","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.70.403"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:14, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117361","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390033","label":"url"}],"paper_title":{"en":"Development of a novel tocopheryl ester for suppression of lipid accumulation without cytotoxicity by optimization of dicarboxylic ester moiety","ja":"Development of a novel tocopheryl ester for suppression of lipid accumulation without cytotoxicity by optimization of dicarboxylic ester moiety"},"authors":{"en":[{"name":"Yamasaki Misaki"},{"name":"Seto Yuika"},{"name":"Ohzono Mizune"},{"name":"Nakao Michiyasu"},{"name":"Shigenaga Akira"},{"name":"Otaka Akira"},{"name":"Sano Shigeki"},{"name":"Kogure Kentaro"}],"ja":[{"name":"山﨑 美沙季"},{"name":"瀬戸 唯加"},{"name":"大園 瑞音"},{"name":"中尾 允泰"},{"name":"重永 章"},{"name":"大髙 章"},{"name":"佐野 茂樹"},{"name":"小暮 健太朗"}]},"publication_date":"2022-08-16","publication_name":{"en":"Biochemistry and Biophysics Reports","ja":"Biochemistry and Biophysics Reports"},"volume":"Vol.31","starting_page":"101329","ending_page":"101329","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbrep.2022.101329"],"issn":["2405-5808"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:15, {"insert":{"user_id":"1000193501","type":"published_papers","id":"39048736"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117238","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35477093","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=386964","label":"url"}],"paper_title":{"en":"Enhancement of cerebroprotective effects of lipid nanoparticles encapsulating FK506 on cerebral ischemia/reperfusion injury by particle size regulation","ja":"Enhancement of cerebroprotective effects of lipid nanoparticles encapsulating FK506 on cerebral ischemia/reperfusion injury by particle size regulation"},"authors":{"en":[{"name":"Yoneda Shintaroh"},{"name":"Fukuta Tatsuya"},{"name":"Ohzono Mizune"},{"name":"Kogure Kentaro"}],"ja":[{"name":"米田 晋太朗"},{"name":"福田 達也"},{"name":"大園 瑞音"},{"name":"小暮 健太朗"}]},"description":{"en":"Delivery of cerebroprotective agents using liposomes has been demonstrated to be useful for treating cerebral ischemia/reperfusion (I/R) injury. We previously reported that intravenous administration of liposomes with diameters of 100 nm showed higher accumulation in the I/R region compared with larger liposomes (>200 nm) by passage through the disintegrated blood-brain barrier, suggesting a size-dependence for liposome-mediated drug delivery. Based on these findings, we hypothesized that regulation of liposomal particle size (<100 nm) may enhance the therapeutic efficacy of encapsulated drugs on cerebral I/R injury. Herein, we prepared lipid nanoparticles (LNP) with particle sizes <100 nm by the microfluidics method and compared their therapeutic potential with LNP exhibiting sizes >100 nm in cerebral I/R model rats. Intravenously administered smaller LNP (ca. 60 nm) exhibited wider accumulation and diffusivity in the brain parenchyma of the I/R region compared with larger LNP (>100 nm). Importantly, treatment with LNP encapsulating the cerebroprotective agent FK506 (FK-LNP) with particle sizes <100 nm showed greater cerebroprotective effects than FK-LNP with sizes >100 nm, and also significantly ameliorated brain injury. These results suggest that particle size regulation of LNP to sizes <100 nm can enhance the therapeutic effect of encapsulated drugs for treatment of cerebral I/R injury, and that FK-LNP could be a promising cerebroprotective agent.","ja":"Delivery of cerebroprotective agents using liposomes has been demonstrated to be useful for treating cerebral ischemia/reperfusion (I/R) injury. We previously reported that intravenous administration of liposomes with diameters of 100 nm showed higher accumulation in the I/R region compared with larger liposomes (>200 nm) by passage through the disintegrated blood-brain barrier, suggesting a size-dependence for liposome-mediated drug delivery. Based on these findings, we hypothesized that regulation of liposomal particle size (<100 nm) may enhance the therapeutic efficacy of encapsulated drugs on cerebral I/R injury. Herein, we prepared lipid nanoparticles (LNP) with particle sizes <100 nm by the microfluidics method and compared their therapeutic potential with LNP exhibiting sizes >100 nm in cerebral I/R model rats. Intravenously administered smaller LNP (ca. 60 nm) exhibited wider accumulation and diffusivity in the brain parenchyma of the I/R region compared with larger LNP (>100 nm). Importantly, treatment with LNP encapsulating the cerebroprotective agent FK506 (FK-LNP) with particle sizes <100 nm showed greater cerebroprotective effects than FK-LNP with sizes >100 nm, and also significantly ameliorated brain injury. These results suggest that particle size regulation of LNP to sizes <100 nm can enhance the therapeutic effect of encapsulated drugs for treatment of cerebral I/R injury, and that FK-LNP could be a promising cerebroprotective agent."},"publication_date":"2022-06-30","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"Vol.611","starting_page":"53","ending_page":"59","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbrc.2022.04.080"],"issn":["1090-2104"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:16, {"insert":{"user_id":"1000193501","type":"published_papers","id":"39048737"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117424","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35253340","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=386963","label":"url"}],"paper_title":{"en":"Intraperitoneal administration of nanoparticles containing tocopheryl succinate prevents peritoneal dissemination","ja":"Intraperitoneal administration of nanoparticles containing tocopheryl succinate prevents peritoneal dissemination"},"authors":{"en":[{"name":"Hama S"},{"name":"Nishi T"},{"name":"Isono E"},{"name":"Itakura S"},{"name":"Yoshikawa Y"},{"name":"Nishimoto A"},{"name":"Suzuki S"},{"name":"Kirimura N"},{"name":"Todo H"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Hama S"},{"name":"Nishi T"},{"name":"Isono E"},{"name":"Itakura S"},{"name":"Yoshikawa Y"},{"name":"Nishimoto A"},{"name":"Suzuki S"},{"name":"Kirimura N"},{"name":"Todo H"},{"name":"小暮 健太朗"}]},"description":{"en":"Intraperitoneal administration of anticancer nanoparticles is a rational strategy for preventing peritoneal dissemination of colon cancer due to the prolonged retention of nanoparticles in the abdominal cavity. However, instability of nanoparticles in body fluids causes inefficient retention, reducing its anticancer effects. We have previously developed anticancer nanoparticles containing tocopheryl succinate, which showed high in vivo stability and multifunctional anticancer effects. In the present study, we have demonstrated that peritoneal dissemination derived from colon cancer was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. The biodistribution of tocopheryl succinate nanoparticles was evaluated using inductively coupled plasma mass spectroscopy and imaging analysis in mice administered quantum dot encapsulated tocopheryl succinate nanoparticles. Intraperitoneal administration of tocopheryl succinate nanoparticles showed longer retention in the abdominal cavity than by its intravenous (i.v.) administration. Moreover, due to effective biodistribution, tumor growth was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. Furthermore, the anticancer effect was attributed to the inhibition of cancer cell proliferation and improvement of the intraperitoneal microenvironment, such as decrease in the levels of vascular endothelial growth factor A, interleukin 10, and M2-like phenotype of tumor-associated macrophages. Collectively, intraperitoneal administration of tocopheryl succinate nanoparticles is expected to have multifaceted antitumor effects against colon cancer with peritoneal dissemination.","ja":"Intraperitoneal administration of anticancer nanoparticles is a rational strategy for preventing peritoneal dissemination of colon cancer due to the prolonged retention of nanoparticles in the abdominal cavity. However, instability of nanoparticles in body fluids causes inefficient retention, reducing its anticancer effects. We have previously developed anticancer nanoparticles containing tocopheryl succinate, which showed high in vivo stability and multifunctional anticancer effects. In the present study, we have demonstrated that peritoneal dissemination derived from colon cancer was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. The biodistribution of tocopheryl succinate nanoparticles was evaluated using inductively coupled plasma mass spectroscopy and imaging analysis in mice administered quantum dot encapsulated tocopheryl succinate nanoparticles. Intraperitoneal administration of tocopheryl succinate nanoparticles showed longer retention in the abdominal cavity than by its intravenous (i.v.) administration. Moreover, due to effective biodistribution, tumor growth was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. Furthermore, the anticancer effect was attributed to the inhibition of cancer cell proliferation and improvement of the intraperitoneal microenvironment, such as decrease in the levels of vascular endothelial growth factor A, interleukin 10, and M2-like phenotype of tumor-associated macrophages. Collectively, intraperitoneal administration of tocopheryl succinate nanoparticles is expected to have multifaceted antitumor effects against colon cancer with peritoneal dissemination."},"publication_date":"2022-03","publication_name":{"en":"Cancer Science","ja":"Cancer Science"},"volume":"Vol.113","number":"No.5","starting_page":"1779","ending_page":"1788","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1111/cas.15321"],"issn":["1349-7006"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:17, {"insert":{"user_id":"1000193501","type":"published_papers","id":"39048738"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117569","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35209214","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=386962","label":"url"}],"paper_title":{"en":"Tocopheryl phosphate inhibits rheumatoid arthritis-related gene expression in vitro and ameliorates arthritic symptoms in mice","ja":"Tocopheryl phosphate inhibits rheumatoid arthritis-related gene expression in vitro and ameliorates arthritic symptoms in mice"},"authors":{"en":[{"name":"Hama S"},{"name":"Kirimura N"},{"name":"Obara A"},{"name":"Takatsu H"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Hama S"},{"name":"Kirimura N"},{"name":"Obara A"},{"name":"Takatsu H"},{"name":"小暮 健太朗"}]},"description":{"en":"Anti-rheumatoid arthritis (RA) effects of α-tocopherol (α-T) have been shown in human patients in a double-blind trial. However, the effects of α-T and its derivatives on fibroblast-like synoviocytes (FLS) during the pathogenesis of RA remain unclear. In the present study, we compared the expression levels of genes related to RA progression in FLS treated with α-T, succinic ester of α-T (TS), and phosphate ester of α-T (TP), as determined via RT-PCR. The mRNA levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), matrix metalloproteinase (MMP)-3, and MMP-13 were reduced by treatment with TP without cytotoxicity, while α-T and TS did not show such effects. Furthermore, intraperitoneal injection of TP ameliorated the edema of the foot and joint and improved the arthritis score in laminarin-induced RA model mice. Therefore, TP exerted anti-RA effects through by inhibiting RA-related gene expression.","ja":"Anti-rheumatoid arthritis (RA) effects of α-tocopherol (α-T) have been shown in human patients in a double-blind trial. However, the effects of α-T and its derivatives on fibroblast-like synoviocytes (FLS) during the pathogenesis of RA remain unclear. In the present study, we compared the expression levels of genes related to RA progression in FLS treated with α-T, succinic ester of α-T (TS), and phosphate ester of α-T (TP), as determined via RT-PCR. The mRNA levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), matrix metalloproteinase (MMP)-3, and MMP-13 were reduced by treatment with TP without cytotoxicity, while α-T and TS did not show such effects. Furthermore, intraperitoneal injection of TP ameliorated the edema of the foot and joint and improved the arthritis score in laminarin-induced RA model mice. Therefore, TP exerted anti-RA effects through by inhibiting RA-related gene expression."},"publication_date":"2022-02-20","publication_name":{"en":"Molecules","ja":"Molecules"},"volume":"Vol.27","number":"No.4","starting_page":"1425","ending_page":"1425","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/molecules27041425"],"issn":["1420-3049"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:18, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117237","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35131371","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=386961","label":"url"}],"paper_title":{"en":"Iontophoresis-mediated direct delivery of nucleic acid therapeutics, without use of carriers, to internal organs via non-blood circulatory pathways","ja":"Iontophoresis-mediated direct delivery of nucleic acid therapeutics, without use of carriers, to internal organs via non-blood circulatory pathways"},"authors":{"en":[{"name":"Hasan M"},{"name":"Fukuta Tatsuya"},{"name":"Inoue Shinya"},{"name":"Mori Hinako"},{"name":"Kagawa Mayuko"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Hasan M"},{"name":"福田 達也"},{"name":"井上 慎也"},{"name":"森 日向子"},{"name":"賀川 真夕子"},{"name":"小暮 健太朗"}]},"description":{"en":"Nanoparticle drug carriers have been employed to achieve systemic delivery of nucleic acid therapeutics, including small interfering RNA (siRNA); however, non-specific distribution and immune-related events often cause undesired adverse effects. Thus, there is a need for a new technology capable of specifically delivering nucleic acid therapeutics to desired sites. We demonstrated the utility of iontophoresis (IP) using weak electric current (0.3-0.5 mA/cm) as a local drug delivery technology. Our previous studies revealed that IP allows for transdermal permeation of nucleic acid therapeutics via induction of intercellular junction cleavage initiated by Ca influx-mediated cellular signaling activation, and subsequent cytoplasmic delivery through a unique endocytosis process in both skin and other cells. Based on these findings, we hypothesized that IP may enable direct delivery of nucleic acid therapeutics to internal organs through non-blood circulatory pathways without the use of delivery carriers. Permeation of fluorescent-labeled nucleic acids administered via IP applied to the surface of the liver and pancreas was observed in both organs, but not with topical application. IP-mediated local delivery of siRNA into the liver and pancreas significantly suppressed target mRNA expression in each organ. Moreover, IP administration of therapeutic siRNA against the molecules responsible for liver steatosis and fibrosis significantly inhibited lipid accumulation and fibrotic hepatic damage in individual model mice. These findings suggest that IP may be a useful technology to directly deliver nucleic acid therapeutics to internal organs without use of drug delivery carriers via non-blood circulatory pathways.","ja":"Nanoparticle drug carriers have been employed to achieve systemic delivery of nucleic acid therapeutics, including small interfering RNA (siRNA); however, non-specific distribution and immune-related events often cause undesired adverse effects. Thus, there is a need for a new technology capable of specifically delivering nucleic acid therapeutics to desired sites. We demonstrated the utility of iontophoresis (IP) using weak electric current (0.3-0.5 mA/cm) as a local drug delivery technology. Our previous studies revealed that IP allows for transdermal permeation of nucleic acid therapeutics via induction of intercellular junction cleavage initiated by Ca influx-mediated cellular signaling activation, and subsequent cytoplasmic delivery through a unique endocytosis process in both skin and other cells. Based on these findings, we hypothesized that IP may enable direct delivery of nucleic acid therapeutics to internal organs through non-blood circulatory pathways without the use of delivery carriers. Permeation of fluorescent-labeled nucleic acids administered via IP applied to the surface of the liver and pancreas was observed in both organs, but not with topical application. IP-mediated local delivery of siRNA into the liver and pancreas significantly suppressed target mRNA expression in each organ. Moreover, IP administration of therapeutic siRNA against the molecules responsible for liver steatosis and fibrosis significantly inhibited lipid accumulation and fibrotic hepatic damage in individual model mice. These findings suggest that IP may be a useful technology to directly deliver nucleic acid therapeutics to internal organs without use of drug delivery carriers via non-blood circulatory pathways."},"publication_date":"2022-02-04","publication_name":{"en":"Journal of Controlled Release","ja":"Journal of Controlled Release"},"volume":"Vol.343","starting_page":"392","ending_page":"399","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jconrel.2022.01.052"],"issn":["1873-4995"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:19, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117236","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35110506","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=386960","label":"url"}],"paper_title":{"en":"Effective Anticancer Therapy by Combination of Nanoparticles Encapsulating Chemotherapeutic Agents and Weak Electric Current","ja":"Effective Anticancer Therapy by Combination of Nanoparticles Encapsulating Chemotherapeutic Agents and Weak Electric Current"},"authors":{"en":[{"name":"Khatun A"},{"name":"Hasan M"},{"name":"Mahran M A E"},{"name":"Fukuta Tatsuya"},{"name":"Mimura Miyuki"},{"name":"Tashima Riho"},{"name":"Yoneda S"},{"name":"Yoshimi Shintaroh"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Khatun A"},{"name":"Hasan M"},{"name":"MAHRAN MONAMED ABDELEMAM MAHRAN"},{"name":"福田 達也"},{"name":"三村 美夕紀"},{"name":"田嶋 里帆"},{"name":"米田 晋太朗"},{"name":"吉見 真太朗"},{"name":"小暮 健太朗"}]},"description":{"en":"Delivery of medicines using nanoparticles via the enhanced permeability and retention (EPR) effect is a common strategy for anticancer chemotherapy. However, the extensive heterogeneity of tumors affects the applicability of the EPR effect, which needs to overcome for effective anticancer therapy. Previously, we succeeded in the noninvasive transdermal delivery of nanoparticles by weak electric current (WEC) and confirmed that WEC regulates the intercellular junctions in the skin by activating cell signaling pathways (J. Biol. Chem., 289, 2014, Hama et al.). In this study, we applied WEC to tumors and investigated the EPR effect with polyethylene glycol (PEG)-modified doxorubicin (DOX) encapsulated nanoparticles (DOX-NP) administered via intravenous injection into melanoma-bearing mice. The application of WEC resulted in a 2.3-fold higher intratumor accumulation of nanoparticles. WEC decreased the amount of connexin 43 in tumors while increasing its phosphorylation; therefore, the enhancing of intratumor delivery of DOX-NP is likely due to the opening of gap junctions. Furthermore, WEC combined with DOX-NP induced a significant suppression of tumor growth, which was stronger than with DOX-NP alone. In addition, WEC alone showed tumor growth inhibition, although it was not significant compared with non-treated group. These results are the first to demonstrate that effective anticancer therapy by combination of nanoparticles encapsulating chemotherapeutic agents and WEC.","ja":"Delivery of medicines using nanoparticles via the enhanced permeability and retention (EPR) effect is a common strategy for anticancer chemotherapy. However, the extensive heterogeneity of tumors affects the applicability of the EPR effect, which needs to overcome for effective anticancer therapy. Previously, we succeeded in the noninvasive transdermal delivery of nanoparticles by weak electric current (WEC) and confirmed that WEC regulates the intercellular junctions in the skin by activating cell signaling pathways (J. Biol. Chem., 289, 2014, Hama et al.). In this study, we applied WEC to tumors and investigated the EPR effect with polyethylene glycol (PEG)-modified doxorubicin (DOX) encapsulated nanoparticles (DOX-NP) administered via intravenous injection into melanoma-bearing mice. The application of WEC resulted in a 2.3-fold higher intratumor accumulation of nanoparticles. WEC decreased the amount of connexin 43 in tumors while increasing its phosphorylation; therefore, the enhancing of intratumor delivery of DOX-NP is likely due to the opening of gap junctions. Furthermore, WEC combined with DOX-NP induced a significant suppression of tumor growth, which was stronger than with DOX-NP alone. In addition, WEC alone showed tumor growth inhibition, although it was not significant compared with non-treated group. These results are the first to demonstrate that effective anticancer therapy by combination of nanoparticles encapsulating chemotherapeutic agents and WEC."},"publication_date":"2022-01","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"Vol.45","number":"No.2","starting_page":"194","ending_page":"199","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b21-00714"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:20, {"insert":{"user_id":"1000193501","type":"published_papers","id":"33236682"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/116134","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/34352337","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=377807","label":"url"}],"paper_title":{"en":"A simple, fast, and orientation-controllable technology for preparing antibody-modified liposomes","ja":"A simple, fast, and orientation-controllable technology for preparing antibody-modified liposomes"},"authors":{"en":[{"name":"Hirata Yuma"},{"name":"Tashima Riho"},{"name":"Mitsuhashi N"},{"name":"Yoneda S"},{"name":"Ozono M"},{"name":"Fukuta Tatsuya"},{"name":"Majima E"},{"name":"Kogure Kentaro"}],"ja":[{"name":"平田 悠真"},{"name":"田嶋 里帆"},{"name":"Mitsuhashi N"},{"name":"米田 晋太朗"},{"name":"Ozono M"},{"name":"福田 達也"},{"name":"Majima E"},{"name":"小暮 健太朗"}]},"description":{"en":"Modification with antibodies is a useful strategy for the delivery of nanoparticles to target cells. However, the complexity of the required chemical modifications makes them time-consuming and low efficiency, and the orientation of the antibody is challenging to control. To develop a simple, fast, effective, and orientation-controllable technology, we employed staphylococcal protein A, which can bind to the Fc region of antibodies, as a tool for conjugating antibodies to nanoparticles. Specifically, we modified the C-domain dimer of protein A to contain a lysine cluster to create a molecule, DPACK, that would electrostatically bind to anionic liposomes. Using this protein, antibody-modified liposomes can be prepared in 35 min with two steps: (1) interaction of DPACK with liposomes and (2) interaction of an antibody with DPACK-modified liposomes. Binding efficiencies of DPACK with liposomes and IgG with DPACK-modified liposomes were 75% and 72-84%, respectively. Uptake of liposomes modified with anti-epidermal growth factor receptor (EGFR) antibodies via DPACK by EGFR-expressing cancer cells was significantly higher than that of unmodified liposomes, and the liposomes accumulated in tumors and colocalized with EGFR. This simple, fast, effective and orientation-controllable technology for preparing antibody-modified liposomes will be useful for active targeting drug delivery.","ja":"Modification with antibodies is a useful strategy for the delivery of nanoparticles to target cells. However, the complexity of the required chemical modifications makes them time-consuming and low efficiency, and the orientation of the antibody is challenging to control. To develop a simple, fast, effective, and orientation-controllable technology, we employed staphylococcal protein A, which can bind to the Fc region of antibodies, as a tool for conjugating antibodies to nanoparticles. Specifically, we modified the C-domain dimer of protein A to contain a lysine cluster to create a molecule, DPACK, that would electrostatically bind to anionic liposomes. Using this protein, antibody-modified liposomes can be prepared in 35 min with two steps: (1) interaction of DPACK with liposomes and (2) interaction of an antibody with DPACK-modified liposomes. Binding efficiencies of DPACK with liposomes and IgG with DPACK-modified liposomes were 75% and 72-84%, respectively. Uptake of liposomes modified with anti-epidermal growth factor receptor (EGFR) antibodies via DPACK by EGFR-expressing cancer cells was significantly higher than that of unmodified liposomes, and the liposomes accumulated in tumors and colocalized with EGFR. This simple, fast, effective and orientation-controllable technology for preparing antibody-modified liposomes will be useful for active targeting drug delivery."},"publication_date":"2021-07","publication_name":{"en":"International Journal of Pharmaceutics","ja":"International Journal of Pharmaceutics"},"volume":"Vol.607","starting_page":"120966","ending_page":"120966","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.ijpharm.2021.120966"],"issn":["1873-3476"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:21, {"insert":{"user_id":"1000193501","type":"published_papers","id":"33172811"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/116179","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85107022552&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=377108","label":"url"}],"paper_title":{"en":"Development of a novel antioxidant based on a dimeric dihydroisocoumarin derivative","ja":"Development of a novel antioxidant based on a dimeric dihydroisocoumarin derivative"},"authors":{"en":[{"name":"Nakayama Atsushi"},{"name":"Nakamura Tenta"},{"name":"Ara Tabassum"},{"name":"fukuta tatsuya"},{"name":"Karanjit Sangita"},{"name":"Harada Takeshi"},{"name":"Oda Asuka"},{"name":"Sato Hideo"},{"name":"Abe Masahiro"},{"name":"Kogure Kentaro"},{"name":"Namba Kosuke"}],"ja":[{"name":"中山 淳"},{"name":"中村 天太"},{"name":"Tabassum Ara"},{"name":"fukuta tatsuya"},{"name":"カランジット サンギータ"},{"name":"原田 武志"},{"name":"小田 明日香"},{"name":"佐藤 次朗"},{"name":"安倍 正博"},{"name":"小暮 健太朗"},{"name":"難波 康祐"}]},"publication_date":"2021-06-22","publication_name":{"en":"Tetrahedron Letters","ja":"Tetrahedron Letters"},"volume":"Vol.74","starting_page":"153176","ending_page":"153176","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.tetlet.2021.153176"],"issn":["0040-4039"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:22, {"insert":{"user_id":"1000193501","type":"published_papers","id":"33236683"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/116683","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/34258398","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=377806","label":"url"}],"paper_title":{"en":"Rapid modification of antibodies on the surface of liposomes composed of high-affinity protein A-conjugated phospholipid for selective drug delivery","ja":"Rapid modification of antibodies on the surface of liposomes composed of high-affinity protein A-conjugated phospholipid for selective drug delivery"},"authors":{"en":[{"name":"Hama S"},{"name":"Sakai M"},{"name":"Itakura S"},{"name":"Majima E"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Hama S"},{"name":"Sakai M"},{"name":"Itakura S"},{"name":"Majima E"},{"name":"小暮 健太朗"}]},"description":{"en":"Antibody-modified liposomes, immuno-liposomes, can selectively deliver encapsulated drug 'cargos' to cells via the interaction of cell surface proteins with antibodies. However, chemical modification of both the antibodies and phospholipids is required for the preparation of immuno-liposomes for each target protein using conventional methods, which is time-consuming. In the present study, we demonstrated that high-affinity protein A- (Protein A-R28: PAR28) displaying liposomes prepared by the post-insertion of PAR28-conjugated phospholipid through polyethylene glycol (PEG)-linkers (PAR28-PEG-lipo) can undergo rapid modification of antibodies on their surface, and the liposomes can be delivered to cells based on their modified antibodies. Anti-CD147 and anti-CD31 antibodies could be modified with PAR28-PEG-lipo within 1 h, and each liposome was specifically taken up by CD147- and CD31-positive cells, respectively. The cellular amounts of doxorubicin delivered by anti-CD147 antibody-modified PAR28-PEG-lipo were significantly higher than those of isotype control antibody-modified liposomes. PAR28-PEG-lipo can easily and rapidly undergo modification of various antibodies on their surface, which then makes them capable of selective drug delivery dependent on the antibodies.","ja":"Antibody-modified liposomes, immuno-liposomes, can selectively deliver encapsulated drug 'cargos' to cells via the interaction of cell surface proteins with antibodies. However, chemical modification of both the antibodies and phospholipids is required for the preparation of immuno-liposomes for each target protein using conventional methods, which is time-consuming. In the present study, we demonstrated that high-affinity protein A- (Protein A-R28: PAR28) displaying liposomes prepared by the post-insertion of PAR28-conjugated phospholipid through polyethylene glycol (PEG)-linkers (PAR28-PEG-lipo) can undergo rapid modification of antibodies on their surface, and the liposomes can be delivered to cells based on their modified antibodies. Anti-CD147 and anti-CD31 antibodies could be modified with PAR28-PEG-lipo within 1 h, and each liposome was specifically taken up by CD147- and CD31-positive cells, respectively. The cellular amounts of doxorubicin delivered by anti-CD147 antibody-modified PAR28-PEG-lipo were significantly higher than those of isotype control antibody-modified liposomes. PAR28-PEG-lipo can easily and rapidly undergo modification of various antibodies on their surface, which then makes them capable of selective drug delivery dependent on the antibodies."},"publication_date":"2021-06","publication_name":{"en":"Biochemistry and Biophysics Reports","ja":"Biochemistry and Biophysics Reports"},"volume":"Vol.27","starting_page":"101067","ending_page":"101067","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbrep.2021.101067"],"issn":["2405-5808"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:23, {"insert":{"user_id":"1000193501","type":"published_papers","id":"33236686"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/116139","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33905867","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=377805","label":"url"}],"paper_title":{"en":"Overcoming thickened pathological skin in psoriasis via iontophoresis combined with tight junction-opening peptide AT1002 for intradermal delivery of NF-κB decoy oligodeoxynucleotide","ja":"Overcoming thickened pathological skin in psoriasis via iontophoresis combined with tight junction-opening peptide AT1002 for intradermal delivery of NF-κB decoy oligodeoxynucleotide"},"authors":{"en":[{"name":"Fukuta Tatsuya"},{"name":"Tanaka Daichi"},{"name":"Inoue Shinya"},{"name":"Michiue Kohki"},{"name":"Kogure Kentaro"}],"ja":[{"name":"福田 達也"},{"name":"田中 太智"},{"name":"井上 慎也"},{"name":"道上 巧基"},{"name":"小暮 健太朗"}]},"description":{"en":"Transdermal delivery of nucleic acid therapeutics has been demonstrated to be effective for psoriasis treatment. We previously reported the utility of iontophoresis (IP) using weak electric current (0.3-0.5 mA/cm) for intradermal delivery of nucleic acid therapeutics via weak electricity-mediated intercellular junction cleavage, and subsequent exertion of nucleic acid function. However, the thickened pathological skin in psoriasis hampers permeation of IP-administered macromolecules. Thus, approaches are needed to more strongly cleave intercellular spaces and overcome the psoriatic skin barrier. Herein, we applied a combination of tight junction-opening peptide AT1002 with IP, as synergistic effects of weak electricity-mediated intercellular junction cleavage and the tight junction-opening ability of AT1002 may help overcome thickened psoriatic skin and facilitate macromolecule delivery. Pretreatment with IP of an AT1002 analog exhibiting positively-charged moieties before fluorescence-labeled oligodeoxynucleotide IP resulted in the oligodeoxynucleotide permeation into psoriatic skin, whereas IP of the oligodeoxynucleotide alone did not. Moreover, psoriasis-induced upregulation of inflammatory cytokine mRNA levels was significantly suppressed by NF-κB decoy oligodeoxynucleotide IP combined with the AT1002 analog, resulting in amelioration of epidermis hyperplasia. These results suggest that synergistic effects of IP and an AT1002 analog can overcome thickened psoriatic skin and enable intradermal delivery of NF-κB decoy oligodeoxynucleotide for psoriasis treatment.","ja":"Transdermal delivery of nucleic acid therapeutics has been demonstrated to be effective for psoriasis treatment. We previously reported the utility of iontophoresis (IP) using weak electric current (0.3-0.5 mA/cm) for intradermal delivery of nucleic acid therapeutics via weak electricity-mediated intercellular junction cleavage, and subsequent exertion of nucleic acid function. However, the thickened pathological skin in psoriasis hampers permeation of IP-administered macromolecules. Thus, approaches are needed to more strongly cleave intercellular spaces and overcome the psoriatic skin barrier. Herein, we applied a combination of tight junction-opening peptide AT1002 with IP, as synergistic effects of weak electricity-mediated intercellular junction cleavage and the tight junction-opening ability of AT1002 may help overcome thickened psoriatic skin and facilitate macromolecule delivery. Pretreatment with IP of an AT1002 analog exhibiting positively-charged moieties before fluorescence-labeled oligodeoxynucleotide IP resulted in the oligodeoxynucleotide permeation into psoriatic skin, whereas IP of the oligodeoxynucleotide alone did not. Moreover, psoriasis-induced upregulation of inflammatory cytokine mRNA levels was significantly suppressed by NF-κB decoy oligodeoxynucleotide IP combined with the AT1002 analog, resulting in amelioration of epidermis hyperplasia. These results suggest that synergistic effects of IP and an AT1002 analog can overcome thickened psoriatic skin and enable intradermal delivery of NF-κB decoy oligodeoxynucleotide for psoriasis treatment."},"publication_date":"2021-04-24","publication_name":{"en":"International Journal of Pharmaceutics","ja":"International Journal of Pharmaceutics"},"volume":"Vol.602","starting_page":"120601","ending_page":"120601","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.ijpharm.2021.120601"],"issn":["1873-3476"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:24, {"insert":{"user_id":"1000193501","type":"published_papers","id":"30504746"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115369","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33390549","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85098660216&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=371853","label":"url"}],"paper_title":{"en":"Suppression of lipid accumulation in 3T3-L1 adipocytes by α-tocopheryl succinate","ja":"Suppression of lipid accumulation in 3T3-L1 adipocytes by α-tocopheryl succinate"},"authors":{"en":[{"name":"Majima Dai"},{"name":"Mitsuhashi Ryosuke"},{"name":"Yamasaki M"},{"name":"Kajimoto K"},{"name":"Fukuta Tatsuya"},{"name":"Kogure Kentaro"}],"ja":[{"name":"真島 大"},{"name":"三橋 亮介"},{"name":"山﨑 美沙季"},{"name":"Kajimoto K"},{"name":"福田 達也"},{"name":"小暮 健太朗"}]},"description":{"en":"Obesity is a pathological state related to various lifestyle-related diseases, such as diabetes and dyslipidemia, that may be prevented through the development of anti-obesity treatments. Lipid accumulation in cells could be affected by vitamin E ester α-tocopheryl succinate (TS), which has various biological activities, such as anti-cancer effect, via activation of cell signaling pathways, although the antioxidative activity of TS is lost due to esterification of the phenolic OH group. In this study, we found for the first time that TS significantly suppressed lipid accumulation in mouse 3T3-L1 adipocytes. TS treatment reduced the amount of triglycerides in the culture medium, and inhibited activity of glycerol-3-phosphate dehydrogenase, a marker of lipid synthesis. Furthermore, TS accelerated lipolysis. Treatment of adipocytes with TS for 24 h induced no significant cytotoxicity. In TS-treated cells, phosphorylation of Akt, which is involved in fatty acid synthesis via sterol regulatory element-binding proteins (SREBP), was prevented, while levels of phosphorylated protein kinase A (PKA) did not change. Taken together, these results suggest that vitamin E ester TS can suppress lipid accumulation in adipocytes by regulating lipid metabolic cell signaling.","ja":"Obesity is a pathological state related to various lifestyle-related diseases, such as diabetes and dyslipidemia, that may be prevented through the development of anti-obesity treatments. Lipid accumulation in cells could be affected by vitamin E ester α-tocopheryl succinate (TS), which has various biological activities, such as anti-cancer effect, via activation of cell signaling pathways, although the antioxidative activity of TS is lost due to esterification of the phenolic OH group. In this study, we found for the first time that TS significantly suppressed lipid accumulation in mouse 3T3-L1 adipocytes. TS treatment reduced the amount of triglycerides in the culture medium, and inhibited activity of glycerol-3-phosphate dehydrogenase, a marker of lipid synthesis. Furthermore, TS accelerated lipolysis. Treatment of adipocytes with TS for 24 h induced no significant cytotoxicity. In TS-treated cells, phosphorylation of Akt, which is involved in fatty acid synthesis via sterol regulatory element-binding proteins (SREBP), was prevented, while levels of phosphorylated protein kinase A (PKA) did not change. Taken together, these results suggest that vitamin E ester TS can suppress lipid accumulation in adipocytes by regulating lipid metabolic cell signaling."},"publication_date":"2021-01","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"Vol.44","number":"No.1","starting_page":"46","ending_page":"50","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b20-00573"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:25, {"insert":{"user_id":"1000193501","type":"published_papers","id":"31339834"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115754","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33129835","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85096382956&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=373040","label":"url"}],"paper_title":{"en":"Leukocyte-mimetic liposomes penetrate into tumor spheroids and suppress spheroid growth by encapsulated doxorubicin","ja":"Leukocyte-mimetic liposomes penetrate into tumor spheroids and suppress spheroid growth by encapsulated doxorubicin"},"authors":{"en":[{"name":"Fukuta Tatsuya"},{"name":"Yoshimi Shintaroh"},{"name":"Kogure Kentaro"}],"ja":[{"name":"福田 達也"},{"name":"吉見 真太朗"},{"name":"小暮 健太朗"}]},"description":{"en":"As leukocytes can penetrate into deep regions of a tumor mass, leukocyte-mimetic liposomes (LM-Lipo) containing leukocyte membrane proteins are also expected to penetrate into tumors by exerting properties of those membrane proteins. The aim of the present study was to examine whether LM-Lipo, which were recently demonstrated to actively pass through inflamed endothelial layers, can penetrate into tumor spheroids, and to investigate the potential of LM-Lipo for use as an anticancer drug carrier. We prepared LM-Lipo via intermembrane protein transfer from human leukemia cells; transfer of leukocyte membrane proteins onto the liposomes was determined by Western blotting. LM-Lipo demonstrated a significantly high association with human lung cancer A549 cells compared with plain liposomes, which contributed to effective anti-proliferative action by encapsulated doxorubicin hydrochloride (DOX). Confocal microscopic images showed that LM-Lipo, but not plain liposomes, could efficiently penetrate into A549 tumor spheroids. Moreover, DOX-encapsulated LM-Lipo significantly suppressed tumor spheroid growth. Thus, leukocyte membrane proteins transferred onto LM-Lipo retained their unique function, which allowed for efficient penetration of the liposomes into tumor spheroids, similar to leukocytes. In conclusion, these results suggest that LM-Lipo could be a useful tumor-penetrating drug delivery system for cancer treatment.","ja":"As leukocytes can penetrate into deep regions of a tumor mass, leukocyte-mimetic liposomes (LM-Lipo) containing leukocyte membrane proteins are also expected to penetrate into tumors by exerting properties of those membrane proteins. The aim of the present study was to examine whether LM-Lipo, which were recently demonstrated to actively pass through inflamed endothelial layers, can penetrate into tumor spheroids, and to investigate the potential of LM-Lipo for use as an anticancer drug carrier. We prepared LM-Lipo via intermembrane protein transfer from human leukemia cells; transfer of leukocyte membrane proteins onto the liposomes was determined by Western blotting. LM-Lipo demonstrated a significantly high association with human lung cancer A549 cells compared with plain liposomes, which contributed to effective anti-proliferative action by encapsulated doxorubicin hydrochloride (DOX). Confocal microscopic images showed that LM-Lipo, but not plain liposomes, could efficiently penetrate into A549 tumor spheroids. Moreover, DOX-encapsulated LM-Lipo significantly suppressed tumor spheroid growth. Thus, leukocyte membrane proteins transferred onto LM-Lipo retained their unique function, which allowed for efficient penetration of the liposomes into tumor spheroids, similar to leukocytes. In conclusion, these results suggest that LM-Lipo could be a useful tumor-penetrating drug delivery system for cancer treatment."},"publication_date":"2020-12","publication_name":{"en":"Journal of Pharmaceutical Sciences","ja":"Journal of Pharmaceutical Sciences"},"volume":"Vol.110","number":"No.4","starting_page":"1701","ending_page":"1709","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.xphs.2020.10.049"],"issn":["1520-6017"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:26, {"insert":{"user_id":"1000193501","type":"published_papers","id":"30458778"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115159","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33132318","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=370517","label":"url"}],"paper_title":{"en":"Weak electric current treatment to artificially enhance vascular permeability in embryonated chicken eggs","ja":"Weak electric current treatment to artificially enhance vascular permeability in embryonated chicken eggs"},"authors":{"en":[{"name":"Fukuta Tatsuya"},{"name":"Nakatani Natsu"},{"name":"YONEDA Shintaroh"},{"name":"Kogure Kentaro"}],"ja":[{"name":"福田 達也"},{"name":"中谷 奈津"},{"name":"米田 晋太朗"},{"name":"小暮 健太朗"}]},"description":{"en":"Technologies that overcome the barrier presented by vascular endothelial cells are needed to facilitate targeted delivery of drugs into tissue parenchyma by intravenous administration. We previously reported that weak electric current treatment (ET: 0.3-0.5 mA/cm) applied onto skin tissue in a transdermal drug delivery technique termed iontophoresis induces cleavage of intercellular junctions that results in permeation of macromolecules such as small interfering RNA and cytosine-phosphate-guanine (CpG) oligonucleotide through the intercellular space. Based on these findings, we hypothesized that application of ET to blood vessels could promote cleavage of intercellular junctions that artificially induces increase in vascular permeability to enhance extravasation of drugs from the vessels into target tissue parenchyma. Here we investigated the effect of ET (0.34 mA/cm) on vascular permeability using embryonated chicken eggs, which have blood vessels in the chorioallantoic membrane (CAM), as an animal model. ET onto the CAM of the eggs significantly increased extravasation of intravenously injected calcein (M.W. 622.6), a low molecular weight compound model, and the macromolecule fluorescein isothiocyanate (FITC)-dextran (M.W. 10000). ET-mediated promotion of penetration of FITC-dextran through vascular endothelial cells was also observed in transwell permeability assay using monolayer of human umbilical vein endothelial cells without induction of obvious cellular damage. Confocal microscopy detected remarkable fluorescence derived from injected FITC-dextran in blood vessel walls. These results in embryonated chicken eggs suggest that ET onto blood vessels could artificially enhance vascular permeability to facilitate extravasation of macromolecules from blood vessels.","ja":"Technologies that overcome the barrier presented by vascular endothelial cells are needed to facilitate targeted delivery of drugs into tissue parenchyma by intravenous administration. We previously reported that weak electric current treatment (ET: 0.3-0.5 mA/cm) applied onto skin tissue in a transdermal drug delivery technique termed iontophoresis induces cleavage of intercellular junctions that results in permeation of macromolecules such as small interfering RNA and cytosine-phosphate-guanine (CpG) oligonucleotide through the intercellular space. Based on these findings, we hypothesized that application of ET to blood vessels could promote cleavage of intercellular junctions that artificially induces increase in vascular permeability to enhance extravasation of drugs from the vessels into target tissue parenchyma. Here we investigated the effect of ET (0.34 mA/cm) on vascular permeability using embryonated chicken eggs, which have blood vessels in the chorioallantoic membrane (CAM), as an animal model. ET onto the CAM of the eggs significantly increased extravasation of intravenously injected calcein (M.W. 622.6), a low molecular weight compound model, and the macromolecule fluorescein isothiocyanate (FITC)-dextran (M.W. 10000). ET-mediated promotion of penetration of FITC-dextran through vascular endothelial cells was also observed in transwell permeability assay using monolayer of human umbilical vein endothelial cells without induction of obvious cellular damage. Confocal microscopy detected remarkable fluorescence derived from injected FITC-dextran in blood vessel walls. These results in embryonated chicken eggs suggest that ET onto blood vessels could artificially enhance vascular permeability to facilitate extravasation of macromolecules from blood vessels."},"publication_date":"2020-11","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"Vol.43","number":"No.11","starting_page":"1729","ending_page":"1734","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b20-00423"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:27, {"insert":{"user_id":"1000193501","type":"published_papers","id":"30458779"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32741858","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=367408","label":"url"}],"paper_title":{"en":"Development of DDS to actively overcome the blood-brain barrier in the region of ischemic stroke","ja":"脳梗塞部位の血液脳関門の能動的突破を目指したDDS 開発"},"authors":{"en":[{"name":"Fukuta Tatsuya"},{"name":"Kogure Kentaro"}],"ja":[{"name":"福田 達也"},{"name":"小暮 健太朗"}]},"description":{"en":"We previously showed that increased permeability of the blood-brain barrier (BBB) after ischemic stroke enables extravasation of nano-sized liposomes and accumulation in the ischemic region, and that delivery of neuroprotective agents using liposomal drug delivery systems (DDS) is applicable for treating cerebral ischemia/reperfusion (I/R) injury. However, entry of liposomes into the brain parenchyma was limited in the early stages after I/R possibly due to microvascular dysfunction induced by pathological progression. As such, new approaches to overcome the BBB are needed. Leukocytes can pass through inflamed BBB in I/R region due to membrane proteins displayed on their surface. We thus hypothesized that incorporation of leukocyte membrane proteins onto liposomal membranes would impart leukocyte-mimicking functions to liposomes and that leukocyte-mimetic liposomes (LM-Lipo) may pass through inflamed endothelial cells and BBB, similar to leukocytes. LM-Lipo prepared using intermembrane protein transfer from human leukemia cells showed significantly increased association to inflamed human umbilical vein endothelial cells relative to plain liposomes. Moreover, LM-Lipo passed through inflamed endothelial cell layer by regulating intercellular junctions. These results suggest that imparting leukocyte-like properties to liposomes via intermembrane protein transfer would be an effective strategy to overcome inflamed endothelial barriers. In this review, we describe our findings on ischemic stroke treatment using liposomal DDS and the potential of LM-Lipo to overcome inflamed endothelial barriers.","ja":"We previously showed that increased permeability of the blood-brain barrier (BBB) after ischemic stroke enables extravasation of nano-sized liposomes and accumulation in the ischemic region, and that delivery of neuroprotective agents using liposomal drug delivery systems (DDS) is applicable for treating cerebral ischemia/reperfusion (I/R) injury. However, entry of liposomes into the brain parenchyma was limited in the early stages after I/R possibly due to microvascular dysfunction induced by pathological progression. As such, new approaches to overcome the BBB are needed. Leukocytes can pass through inflamed BBB in I/R region due to membrane proteins displayed on their surface. We thus hypothesized that incorporation of leukocyte membrane proteins onto liposomal membranes would impart leukocyte-mimicking functions to liposomes and that leukocyte-mimetic liposomes (LM-Lipo) may pass through inflamed endothelial cells and BBB, similar to leukocytes. LM-Lipo prepared using intermembrane protein transfer from human leukemia cells showed significantly increased association to inflamed human umbilical vein endothelial cells relative to plain liposomes. Moreover, LM-Lipo passed through inflamed endothelial cell layer by regulating intercellular junctions. These results suggest that imparting leukocyte-like properties to liposomes via intermembrane protein transfer would be an effective strategy to overcome inflamed endothelial barriers. In this review, we describe our findings on ischemic stroke treatment using liposomal DDS and the potential of LM-Lipo to overcome inflamed endothelial barriers."},"publication_date":"2020-08","publication_name":{"en":"Journal of the Pharmaceutical Society of Japan","ja":"薬学雑誌"},"volume":"Vol.140","number":"No.8","starting_page":"1007","ending_page":"1012","languages":["jpn"],"referee":true,"invited":true,"identifiers":{"doi":["10.1248/yakushi.20-00012-7"],"issn":["1347-5231"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:28, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115195","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32615533","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=370497","label":"url"}],"paper_title":{"en":"Isolation of glycosylinositol phosphoceramide and phytoceramide 1-phosphate in plants and their chemical stabilities.","ja":"Isolation of glycosylinositol phosphoceramide and phytoceramide 1-phosphate in plants and their chemical stabilities."},"authors":{"en":[{"name":"Hasi Yesmin Rumana"},{"name":"Majima Dai"},{"name":"Morito Katsuya"},{"name":"Ali Hanif"},{"name":"Kogure Kentaro"},{"name":"Nanjundan Meera"},{"name":"Hayashi Junji"},{"name":"Kawakami Ryushi"},{"name":"Kanemaru Kaori"},{"name":"Tanaka Tamotsu"}],"ja":[{"name":"Rumana Hasi Yesmin"},{"name":"真島 大"},{"name":"森戸 克弥"},{"name":"MD HANIF ALI"},{"name":"小暮 健太朗"},{"name":"ミエラ ナンジュンダン"},{"name":"林 順司"},{"name":"川上 竜巳"},{"name":"金丸 芳"},{"name":"田中 保"}]},"description":{"en":"Glycosylinositol phosphoceramide (GIPC) is a sphingophospholipid in plants. Recently, we identified that GIPC is hydrolyzed to phytoceramide 1-phosphate (PC1P) by an uncharacterized phospholipase D activity following homogenization of certain plant tissues. We now developed methods for isolation of GIPC and PC1P from plant tissues and characterized their chemical stabilities. Hydrophilic solvents, namely a lower layer of a mixed solvent system consisting of isopropanol/hexane/water (55:20:25, v/v/v) was efficient solvent for extraction and eluent in column chromatography. GIPC was isolated by Sephadex column chromatography followed by TLC. A conventional method, such as the Bligh and Dyer method, was applicable for PC1P extraction. Specifically, PC1P was isolated by TLC following mild alkali treatment of lipid extracts of plants. The yields of GIPC and PC1P in our methods were both around 50-70%. We found that PC1P is tolerant against heat (up to 125 °C), strong acid (up to 10 M HCl), and mild alkali (0.1 M KOH). In contrast, significant degradation of GIPC occurred at 100 °C and 1.0 M HCl treatment, suggesting the instability of the inositol glycan moiety in these conditions. These data will be useful for further biochemical and nutritional studies on these sphingolipids.","ja":"Glycosylinositol phosphoceramide (GIPC) is a sphingophospholipid in plants. Recently, we identified that GIPC is hydrolyzed to phytoceramide 1-phosphate (PC1P) by an uncharacterized phospholipase D activity following homogenization of certain plant tissues. We now developed methods for isolation of GIPC and PC1P from plant tissues and characterized their chemical stabilities. Hydrophilic solvents, namely a lower layer of a mixed solvent system consisting of isopropanol/hexane/water (55:20:25, v/v/v) was efficient solvent for extraction and eluent in column chromatography. GIPC was isolated by Sephadex column chromatography followed by TLC. A conventional method, such as the Bligh and Dyer method, was applicable for PC1P extraction. Specifically, PC1P was isolated by TLC following mild alkali treatment of lipid extracts of plants. The yields of GIPC and PC1P in our methods were both around 50-70%. We found that PC1P is tolerant against heat (up to 125 °C), strong acid (up to 10 M HCl), and mild alkali (0.1 M KOH). In contrast, significant degradation of GIPC occurred at 100 °C and 1.0 M HCl treatment, suggesting the instability of the inositol glycan moiety in these conditions. These data will be useful for further biochemical and nutritional studies on these sphingolipids."},"publication_date":"2020-06-12","publication_name":{"en":"Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences","ja":"Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences"},"volume":"Vol.1152","starting_page":"122213","ending_page":"122213","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jchromb.2020.122213"],"issn":["1873-376X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:29, {"insert":{"user_id":"1000193501","type":"published_papers","id":"30458780"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/114731","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=365848","label":"url"}],"paper_title":{"en":"Protective effect of high-affinity liposomes encapsulating astaxanthin against corneal disorder in the in vivo rat dry eye disease model","ja":"Protective effect of high-affinity liposomes encapsulating astaxanthin against corneal disorder in the in vivo rat dry eye disease model"},"authors":{"en":[{"name":"Shimokawa Tatsuharu"},{"name":"Fukuta Tatsuya"},{"name":"Inagi Toshio"},{"name":"Kogure Kentaro"}],"ja":[{"name":"下川 達張"},{"name":"福田 達也"},{"name":"Inagi Toshio"},{"name":"小暮 健太朗"}]},"publication_date":"2020-05","publication_name":{"en":"Journal of Clinical Biochemistry and Nutrition","ja":"Journal of Clinical Biochemistry and Nutrition"},"volume":"Vol.66","number":"No.3","starting_page":"224","ending_page":"232","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3164/jcbn.19-102"],"issn":["1880-5086"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:30, {"insert":{"user_id":"1000193501","type":"published_papers","id":"30458781"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/114732","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32741949","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=365842","label":"url"}],"paper_title":{"en":"Protective effect of antioxidative liposomes co-encapsulating astaxanthin and capsaicin on CCl4-induced liver injury","ja":"Protective effect of antioxidative liposomes co-encapsulating astaxanthin and capsaicin on CCl4-induced liver injury"},"authors":{"en":[{"name":"Fukuta Tatsuya"},{"name":"Hirai Shota"},{"name":"Yoshida Tatsusada"},{"name":"Maoka T"},{"name":"Kogure Kentaro"}],"ja":[{"name":"福田 達也"},{"name":"平井 将太"},{"name":"吉田 達貞"},{"name":"Maoka T"},{"name":"小暮 健太朗"}]},"description":{"en":"Our previous study reported that co-encapsulation of potent antioxidants astaxanthin (Asx) and capsaisin (Cap) into liposomes brought about synergistically higher antioxidative activity than the calculated additive activity of each single antioxidant encapsulating liposome. Based on the previous computational chemistry analysis, the synergistic effect was revealed to be resulted from intermolecular interactions between Asx, especially 3R,3'R-form of Asx stereoisomer (Asx-R), and Cap, by which changes of electronic states of the polyene moiety of Asx-R were induced. Although liposomes co-encapsulating Asx-R and Cap (Asx-R/Cap-Lipo) at an optimal ratio clearly showed synergistic antioxidative activity in vitro, it is unclear whether the effective antioxidative activity derived from intermolecular interaction between Asx-R and Cap is also exerted in vivo. Therefore, in this study, we investigated therapeutic potential of Asx-R/Cap-Lipo as an antioxidant formulation in vivo. For this purpose, we employed carbon tetrachloride (CCl)-induced acute liver injury rat model, since CCl is known to cause oxidative damage in liver. CCl administration significantly increased the levels of aspartate transaminase (AST) and alanine aminotransferase (ALT). Intravenous combined administration of liposomes encapsulating Asx-R (Asx-R-Lipo) and liposomes encapsulating Cap (Cap-Lipo) significantly decreased CCl-induced increase of AST and ALT levels. Importantly, the treatment with Asx-R/Cap-Lipo tended to show higher protective effect on acute liver injury than combined treatment with Asx-R-Lipo plus Cap-Lipo. These results suggest that co-encapsulated Asx-R and Cap in liposomal membranes could exert more effective antioxidative activities in vivo, and that Asx-R/Cap-Lipo would be a hopeful antioxidant formulation for treating reactive oxygen species-related diseases.","ja":"Our previous study reported that co-encapsulation of potent antioxidants astaxanthin (Asx) and capsaisin (Cap) into liposomes brought about synergistically higher antioxidative activity than the calculated additive activity of each single antioxidant encapsulating liposome. Based on the previous computational chemistry analysis, the synergistic effect was revealed to be resulted from intermolecular interactions between Asx, especially 3R,3'R-form of Asx stereoisomer (Asx-R), and Cap, by which changes of electronic states of the polyene moiety of Asx-R were induced. Although liposomes co-encapsulating Asx-R and Cap (Asx-R/Cap-Lipo) at an optimal ratio clearly showed synergistic antioxidative activity in vitro, it is unclear whether the effective antioxidative activity derived from intermolecular interaction between Asx-R and Cap is also exerted in vivo. Therefore, in this study, we investigated therapeutic potential of Asx-R/Cap-Lipo as an antioxidant formulation in vivo. For this purpose, we employed carbon tetrachloride (CCl)-induced acute liver injury rat model, since CCl is known to cause oxidative damage in liver. CCl administration significantly increased the levels of aspartate transaminase (AST) and alanine aminotransferase (ALT). Intravenous combined administration of liposomes encapsulating Asx-R (Asx-R-Lipo) and liposomes encapsulating Cap (Cap-Lipo) significantly decreased CCl-induced increase of AST and ALT levels. Importantly, the treatment with Asx-R/Cap-Lipo tended to show higher protective effect on acute liver injury than combined treatment with Asx-R-Lipo plus Cap-Lipo. These results suggest that co-encapsulated Asx-R and Cap in liposomal membranes could exert more effective antioxidative activities in vivo, and that Asx-R/Cap-Lipo would be a hopeful antioxidant formulation for treating reactive oxygen species-related diseases."},"publication_date":"2020-05","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"Vol.43","number":"No.8","starting_page":"1272","ending_page":"1274","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b20-00116"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:31, {"insert":{"user_id":"1000193501","type":"published_papers","id":"30458782"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/114727","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32360305","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85084069379&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=365844","label":"url"}],"paper_title":{"en":"Non-invasive delivery of biological macromolecular drugs into the skin by iontophoresis and its application to psoriasis treatment","ja":"Non-invasive delivery of biological macromolecular drugs into the skin by iontophoresis and its application to psoriasis treatment"},"authors":{"en":[{"name":"Fukuta Tatsuya"},{"name":"Oshima Yasufumi"},{"name":"Michiue Kohki"},{"name":"Tanaka Daichi"},{"name":"Kogure Kentaro"}],"ja":[{"name":"福田 達也"},{"name":"大島 康史"},{"name":"道上 巧基"},{"name":"田中 太智"},{"name":"小暮 健太朗"}]},"description":{"en":"Biological macromolecular drugs, such as antibodies and fusion protein drugs, have been widely employed for the treatment of various diseases. Administration routes are typically via invasive intravenous or subcutaneous injection with needles; the latter is challenging for applications involving inflamed skin (e.g., psoriasis) due to concerns of expansion of inflammation. As a method of non-invasive transdermal drug delivery, we previously demonstrated that iontophoresis (IP) using weak electric current (0.3-0.5 mA/cm) enables transdermal permeation of hydrophilic macromolecules, such as small interfering RNA and nanoparticles into the skin, and subsequent exertion of their functions. The underlying mechanism was revealed to be via intercellular junction cleavage by cellular signaling activation initiated by Ca influx. Based on these findings, in the present study, we hypothesized that non-invasive intradermal delivery of biological macromolecular drugs could be efficiently achieved via IP. Fluorescence of FITC-labeled IgG antibody was broadly observed in the skin after IP administration (0.4 mA/cm for 1 h) and extended from the epidermis to the dermis layer of hairless rats; passive antibody diffusion was not observed. In imiquimod-induced psoriasis model rats, antibodies were also delivered via IP into inflamed skin tissue. Additionally, upregulation of interleukin-6 mRNA levels, which is related to pathological progression of psoriasis, was significantly inhibited by IP of the anti-tumor necrosis factor-α drug etanercept, but not by its subcutaneous injection. Importantly, IP administration of etanercept significantly ameliorated epidermis hyperplasia, a symptom of psoriasis. Taken together, the present study is the first to demonstrate that IP can be applied as a non-invasive and efficient intradermal drug delivery technology for biological macromolecular drugs.","ja":"Biological macromolecular drugs, such as antibodies and fusion protein drugs, have been widely employed for the treatment of various diseases. Administration routes are typically via invasive intravenous or subcutaneous injection with needles; the latter is challenging for applications involving inflamed skin (e.g., psoriasis) due to concerns of expansion of inflammation. As a method of non-invasive transdermal drug delivery, we previously demonstrated that iontophoresis (IP) using weak electric current (0.3-0.5 mA/cm) enables transdermal permeation of hydrophilic macromolecules, such as small interfering RNA and nanoparticles into the skin, and subsequent exertion of their functions. The underlying mechanism was revealed to be via intercellular junction cleavage by cellular signaling activation initiated by Ca influx. Based on these findings, in the present study, we hypothesized that non-invasive intradermal delivery of biological macromolecular drugs could be efficiently achieved via IP. Fluorescence of FITC-labeled IgG antibody was broadly observed in the skin after IP administration (0.4 mA/cm for 1 h) and extended from the epidermis to the dermis layer of hairless rats; passive antibody diffusion was not observed. In imiquimod-induced psoriasis model rats, antibodies were also delivered via IP into inflamed skin tissue. Additionally, upregulation of interleukin-6 mRNA levels, which is related to pathological progression of psoriasis, was significantly inhibited by IP of the anti-tumor necrosis factor-α drug etanercept, but not by its subcutaneous injection. Importantly, IP administration of etanercept significantly ameliorated epidermis hyperplasia, a symptom of psoriasis. Taken together, the present study is the first to demonstrate that IP can be applied as a non-invasive and efficient intradermal drug delivery technology for biological macromolecular drugs."},"publication_date":"2020-04-28","publication_name":{"en":"Journal of Controlled Release","ja":"Journal of Controlled Release"},"volume":"Vol.323","starting_page":"323","ending_page":"332","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jconrel.2020.04.044"],"issn":["1873-4995"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:32, {"insert":{"user_id":"1000193501","type":"published_papers","id":"30458783"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/114072","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31718328","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85081234098&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=361354","label":"url"}],"paper_title":{"en":"Enhancement of antioxidative activity of astaxanthin by combination with an antioxidant capable of forming intermolecular interactions","ja":"Enhancement of antioxidative activity of astaxanthin by combination with an antioxidant capable of forming intermolecular interactions"},"authors":{"en":[{"name":"Fukuta Tatsuya"},{"name":"Hirai Shota"},{"name":"Yoshida Tatsusada"},{"name":"Maoka T"},{"name":"Kogure Kentaro"}],"ja":[{"name":"福田 達也"},{"name":"平井 将太"},{"name":"吉田 達貞"},{"name":"Maoka T"},{"name":"小暮 健太朗"}]},"description":{"en":"We previously demonstrated that coencapsulation of the potent antioxidant astaxanthin (Asx) and tocotrienols into liposomes results in synergistically higher antioxidative activity than the calculated additive activity of each individual antioxidant-containing liposome, due to intermolecular interactions between terminal ring moieties of the two antioxidants and the polyene chain and the triene moiety. We reported that intermolecular interactions depend on the stereochemistry of Asx, and change the electronic state of the Asx polyene moiety. Based on these findings, we hypothesised that antioxidants that interact with Asx at the terminal ring and polyene moieties may enhance the antioxidative activity. Herein, we selected two candidate antioxidants, capsaicin (Cap) and resveratrol, based on their structures, in which the compounds exhibit similar characteristics to tocotrienols. We evaluated the antioxidative capacities of liposomes coencapsulating Asx and the selected candidates. Based on hydroxyl radical scavenging activity, Cap was found to synergistically enhance the antioxidative activity of Asx at an optimal Asx/Cap ratio. Intermolecular interactions between Asx and Cap are necessary for the synergistic effect, and the Asx stereoisomer 3,3'-form (Asx-) was predicted to most potently interact. Liposomes coencapsulating Asx- and Cap exhibited clear synergistic antioxidative activity at an optimal ratio, whereas liposomes coencapsulating the other Asx stereoisomer and Cap did not demonstrate such activity. Computational chemistry analysis showed that changes in the electronic state of the polyene moiety of Asx- are crucial for the synergistic activity. These results suggest that antioxidants that can change the electronic state of Asx via intermolecular interactions may enhance the function of Asx.","ja":"We previously demonstrated that coencapsulation of the potent antioxidant astaxanthin (Asx) and tocotrienols into liposomes results in synergistically higher antioxidative activity than the calculated additive activity of each individual antioxidant-containing liposome, due to intermolecular interactions between terminal ring moieties of the two antioxidants and the polyene chain and the triene moiety. We reported that intermolecular interactions depend on the stereochemistry of Asx, and change the electronic state of the Asx polyene moiety. Based on these findings, we hypothesised that antioxidants that interact with Asx at the terminal ring and polyene moieties may enhance the antioxidative activity. Herein, we selected two candidate antioxidants, capsaicin (Cap) and resveratrol, based on their structures, in which the compounds exhibit similar characteristics to tocotrienols. We evaluated the antioxidative capacities of liposomes coencapsulating Asx and the selected candidates. Based on hydroxyl radical scavenging activity, Cap was found to synergistically enhance the antioxidative activity of Asx at an optimal Asx/Cap ratio. Intermolecular interactions between Asx and Cap are necessary for the synergistic effect, and the Asx stereoisomer 3,3'-form (Asx-) was predicted to most potently interact. Liposomes coencapsulating Asx- and Cap exhibited clear synergistic antioxidative activity at an optimal ratio, whereas liposomes coencapsulating the other Asx stereoisomer and Cap did not demonstrate such activity. Computational chemistry analysis showed that changes in the electronic state of the polyene moiety of Asx- are crucial for the synergistic activity. These results suggest that antioxidants that can change the electronic state of Asx via intermolecular interactions may enhance the function of Asx."},"publication_date":"2020-03-05","publication_name":{"en":"Free Radical Research","ja":"Free Radical Research"},"languages":["eng"],"referee":true,"identifiers":{"doi":["10.1080/10715762.2019.1693042"],"issn":["1029-2470"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:33, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/114729","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31828227","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=361357","label":"url"}],"paper_title":{"en":"Low level electricity increases the secretion of extracellular vesicles from cultured cells","ja":"Low level electricity increases the secretion of extracellular vesicles from cultured cells"},"authors":{"en":[{"name":"Fukuta Tatsuya"},{"name":"Nishikawa Akina"},{"name":"Kogure Kentaro"}],"ja":[{"name":"福田 達也"},{"name":"西川 明菜"},{"name":"小暮 健太朗"}]},"description":{"en":"Exosomes, a type of extracellular vesicles, can be collected from the conditioned medium of cultured cells, and are expected to be used in disease therapy and drug delivery systems. However, since the yield of exosomes from conditioned medium is generally low, investigations to develop new methods to increase exosome secretion and to elucidate the secretion mechanism have been performed. Our previous studies demonstrated that activation of intracellular signaling including Rho GTPase and subsequent endocytosis of extraneous molecules in cells could be induced by low level electricity (0.3-0.5 mA/cm). Since exosomes are produced in the process of endocytosis and secreted by exocytosis via certain signaling pathways, we hypothesized that low level electric treatment (ET) would increase exosome secretion from cultured cells via intracellular signaling activation. In the present study, the influence of ET (0.34 mA/cm) on extracellular vesicle (EV) secretion from cultured cells was examined by using murine melanoma and murine fibroblast cells. The results showed that the number of EV particles collected by ultracentrifugation was remarkably increased by ET in both cell lines without cellular toxicity or changes in the particle distribution. Also, protein amounts of the collected EVs were significantly increased in both cells by ET without alteration of expression of representative exosome marker proteins. Moreover, in both cells, the ratio of particle numbers to protein amount was not significantly changed by ET. Rho GTPase inhibition significantly suppressed ET-mediated increase of EV secretion in murine melanoma, indicating that Rho GTPase activation could be involved in ET-mediated EV secretion in the cell. Additionally, there were almost no differences in uptake of each EV into each donor cell regardless of whether the cells had been exposed to ET for EV collection. Taken together, these results suggest that ET could increase EV secretion from both cancer and normal cells without apparent changes in EV quality.","ja":"Exosomes, a type of extracellular vesicles, can be collected from the conditioned medium of cultured cells, and are expected to be used in disease therapy and drug delivery systems. However, since the yield of exosomes from conditioned medium is generally low, investigations to develop new methods to increase exosome secretion and to elucidate the secretion mechanism have been performed. Our previous studies demonstrated that activation of intracellular signaling including Rho GTPase and subsequent endocytosis of extraneous molecules in cells could be induced by low level electricity (0.3-0.5 mA/cm). Since exosomes are produced in the process of endocytosis and secreted by exocytosis via certain signaling pathways, we hypothesized that low level electric treatment (ET) would increase exosome secretion from cultured cells via intracellular signaling activation. In the present study, the influence of ET (0.34 mA/cm) on extracellular vesicle (EV) secretion from cultured cells was examined by using murine melanoma and murine fibroblast cells. The results showed that the number of EV particles collected by ultracentrifugation was remarkably increased by ET in both cell lines without cellular toxicity or changes in the particle distribution. Also, protein amounts of the collected EVs were significantly increased in both cells by ET without alteration of expression of representative exosome marker proteins. Moreover, in both cells, the ratio of particle numbers to protein amount was not significantly changed by ET. Rho GTPase inhibition significantly suppressed ET-mediated increase of EV secretion in murine melanoma, indicating that Rho GTPase activation could be involved in ET-mediated EV secretion in the cell. Additionally, there were almost no differences in uptake of each EV into each donor cell regardless of whether the cells had been exposed to ET for EV collection. Taken together, these results suggest that ET could increase EV secretion from both cancer and normal cells without apparent changes in EV quality."},"publication_date":"2020-03","publication_name":{"en":"Biochemistry and Biophysics Reports","ja":"Biochemistry and Biophysics Reports"},"volume":"Vol.21","starting_page":"100713","ending_page":"100713","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbrep.2019.100713"],"issn":["2405-5808"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:34, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/114728","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=362596","label":"url"}],"paper_title":{"en":"Characteristics of unique endocytosis induced by weak current for cytoplasmic drug delivery","ja":"Characteristics of unique endocytosis induced by weak current for cytoplasmic drug delivery"},"authors":{"en":[{"name":"Torao Tasuku"},{"name":"Mimura Miyuki"},{"name":"Ohshima Yasufumi"},{"name":"Fujikawa Kohki"},{"name":"Hasan Mahadi"},{"name":"Shimokawa Tatsuharu"},{"name":"Yamazaki Naoshi"},{"name":"ANDO Hidenori"},{"name":"Ishida Tatsuhiro"},{"name":"Fukuta Tatsuya"},{"name":"Tanaka Tamotsu"},{"name":"Kogure Kentaro"}],"ja":[{"name":"虎尾 祐"},{"name":"三村 美夕紀"},{"name":"大島 康史"},{"name":"藤川 昂樹"},{"name":"Hasan Mahadi"},{"name":"下川 達張"},{"name":"山﨑 尚志"},{"name":"安藤 英紀"},{"name":"石田 竜弘"},{"name":"福田 達也"},{"name":"田中 保"},{"name":"小暮 健太朗"}]},"publication_date":"2020-02","publication_name":{"en":"International Journal of Pharmaceutics","ja":"International Journal of Pharmaceutics"},"volume":"Vol.576","starting_page":"119010","ending_page":"119010","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.ijpharm.2019.119010"],"issn":["0378-5173"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:35, {"insert":{"user_id":"1000193501","type":"published_papers","id":"30458784"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/114071","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31718795","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85075357860&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=361352","label":"url"}],"paper_title":{"en":"α-Tocopheryl succinate stabilizes the structure of tumor vessels by inhibiting angiopoietin-2 expression","ja":"α-Tocopheryl succinate stabilizes the structure of tumor vessels by inhibiting angiopoietin-2 expression"},"authors":{"en":[{"name":"Hama Susumu"},{"name":"Okamura Yuriko"},{"name":"Kamei Kazuho"},{"name":"Nagao Saki"},{"name":"Hayashi Mari"},{"name":"Shizuka Maeda"},{"name":"Fukuzawa Kenji"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Hama Susumu"},{"name":"Okamura Yuriko"},{"name":"Kamei Kazuho"},{"name":"Nagao Saki"},{"name":"Hayashi Mari"},{"name":"Shizuka Maeda"},{"name":"福澤 健治"},{"name":"小暮 健太朗"}]},"description":{"en":"α-Tocopheryl succinate (TS) is a tocopherol derivative and has multifaceted anti-cancer effects; TS not only causes cancer cell-specific apoptosis but also inhibits tumor angiogenesis. Although TS has the potential to be used as a well-tolerated anti-angiogenic drug, it is still unclear which step of the angiogenic process is inhibited by TS. Here, we show that TS inhibits the expression of angiopoietin (Ang)-2, which induces destabilization of vascular structure in the initial steps of the angiogenic process. In mouse melanoma cells, TS treatment decreased mRNA and extracellular protein levels of Ang-2; however, the mRNA level of Ang-1, which stabilizes the vascular structure, remained unchanged. Furthermore, aorta ring and Matrigel plug angiogenesis assays indicated that the conditioned medium from TS-treated cells (CM-TS) inhibited neovascularization and blood leakage from the existing blood vessels, respectively. Following immunohistochemical staining of the vessels treated with CM-TS, imaging studies showed that the vascular endothelial cells were highly packed with pericytes. In conclusion, we found that TS inhibits Ang-2 expression and, consequently, stabilizes the vascular structure during the initial step of tumor angiogenesis.","ja":"α-Tocopheryl succinate (TS) is a tocopherol derivative and has multifaceted anti-cancer effects; TS not only causes cancer cell-specific apoptosis but also inhibits tumor angiogenesis. Although TS has the potential to be used as a well-tolerated anti-angiogenic drug, it is still unclear which step of the angiogenic process is inhibited by TS. Here, we show that TS inhibits the expression of angiopoietin (Ang)-2, which induces destabilization of vascular structure in the initial steps of the angiogenic process. In mouse melanoma cells, TS treatment decreased mRNA and extracellular protein levels of Ang-2; however, the mRNA level of Ang-1, which stabilizes the vascular structure, remained unchanged. Furthermore, aorta ring and Matrigel plug angiogenesis assays indicated that the conditioned medium from TS-treated cells (CM-TS) inhibited neovascularization and blood leakage from the existing blood vessels, respectively. Following immunohistochemical staining of the vessels treated with CM-TS, imaging studies showed that the vascular endothelial cells were highly packed with pericytes. In conclusion, we found that TS inhibits Ang-2 expression and, consequently, stabilizes the vascular structure during the initial step of tumor angiogenesis."},"publication_date":"2020-01-22","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbrc.2019.11.017"],"issn":["1090-2104"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:36, {"insert":{"user_id":"1000193501","type":"published_papers","id":"30458785"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/113682","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31351225","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=359915","label":"url"}],"paper_title":{"en":"Gut microbial metabolites of linoleic acid are metabolized by accelerated peroxisomal β-oxidation in mammalian cells","ja":"Gut microbial metabolites of linoleic acid are metabolized by accelerated peroxisomal β-oxidation in mammalian cells"},"authors":{"en":[{"name":"Morito Katsuya"},{"name":"Shimizu Ryota"},{"name":"Kitamura Nahoko"},{"name":"Park Si-Bum"},{"name":"Kishino Shigenobu"},{"name":"Ogawa Jun"},{"name":"Fukuta Tatsuya"},{"name":"Kogure Kentaro"},{"name":"Tanaka Tamotsu"}],"ja":[{"name":"森戸 克弥"},{"name":"清水 良多"},{"name":"Kitamura Nahoko"},{"name":"Park Si-Bum"},{"name":"Kishino Shigenobu"},{"name":"Ogawa Jun"},{"name":"福田 達也"},{"name":"小暮 健太朗"},{"name":"田中 保"}]},"description":{"en":"Microorganisms in animal gut produce unusual fatty acids from the ingested diet. Two types of hydroxy fatty acids (HFAs), 10-hydroxy-cis-12-octadecenoic acid (HYA) and 10-hydroxy-octadecanoic acid (HYB), are linoleic acid (LA) metabolites produced by Lactobacillus plantarum. In this study, we investigated the metabolism of these HFAs in mammalian cells. When Chinese hamster ovary (CHO) cells were cultured with HYA, approximately 50% of the supplemented HYA disappeared from the dish within 24 h. On the other hand, the amount of HYA that disappeared from the dish of peroxisome (PEX)-deficient CHO cells was lower than 20%. Significant amounts of C2- and C4-chain-shortened metabolites of HYA were detected in culture medium of HYA-supplemented CHO cells, but not in medium of PEX-deficient cells. These results suggested that peroxisomal β-oxidation is involved in the disappearance of HYA. The PEX-dependent disappearance was observed in the experiment with HYB, but not with LA. We also found that HYA treatment up-regulates peroxisomal β-oxidation activity of human gastric MKN74 cells and intestinal Caco-2 cells. These results indicate a possibility that HFAs produced from gut bacteria affect lipid metabolism of host via modulation of peroxisomal β-oxidation activity.","ja":"Microorganisms in animal gut produce unusual fatty acids from the ingested diet. Two types of hydroxy fatty acids (HFAs), 10-hydroxy-cis-12-octadecenoic acid (HYA) and 10-hydroxy-octadecanoic acid (HYB), are linoleic acid (LA) metabolites produced by Lactobacillus plantarum. In this study, we investigated the metabolism of these HFAs in mammalian cells. When Chinese hamster ovary (CHO) cells were cultured with HYA, approximately 50% of the supplemented HYA disappeared from the dish within 24 h. On the other hand, the amount of HYA that disappeared from the dish of peroxisome (PEX)-deficient CHO cells was lower than 20%. Significant amounts of C2- and C4-chain-shortened metabolites of HYA were detected in culture medium of HYA-supplemented CHO cells, but not in medium of PEX-deficient cells. These results suggested that peroxisomal β-oxidation is involved in the disappearance of HYA. The PEX-dependent disappearance was observed in the experiment with HYB, but not with LA. We also found that HYA treatment up-regulates peroxisomal β-oxidation activity of human gastric MKN74 cells and intestinal Caco-2 cells. These results indicate a possibility that HFAs produced from gut bacteria affect lipid metabolism of host via modulation of peroxisomal β-oxidation activity."},"publication_date":"2019-11","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids","ja":"Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids"},"volume":"Vol.1864","number":"No.11","starting_page":"1619","ending_page":"1628","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbalip.2019.07.010"],"issn":["1879-2618"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:37, {"insert":{"user_id":"1000193501","type":"published_papers","id":"30458786"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115197","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31619623","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85073476996&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=363543","label":"url"}],"paper_title":{"en":"Quantitative Analysis of Glycosylinositol Phosphoceramide and Phytoceramide 1-Phosphate in Vegetables","ja":"Quantitative Analysis of Glycosylinositol Phosphoceramide and Phytoceramide 1-Phosphate in Vegetables"},"authors":{"en":[{"name":"Hasi Yesmin Rumana"},{"name":"Miyagi Makoto"},{"name":"Kida Takashi"},{"name":"Fukuta Tatsuya"},{"name":"Kogure Kentaro"},{"name":"Hayashi Junji"},{"name":"Kawakami Ryushi"},{"name":"Kanemaru Kaori"},{"name":"Tanaka Tamotsu"}],"ja":[{"name":"Rumana Hasi Yesmin"},{"name":"宮城 諒"},{"name":"喜田 孝史"},{"name":"福田 達也"},{"name":"小暮 健太朗"},{"name":"林 順司"},{"name":"川上 竜巳"},{"name":"金丸 芳"},{"name":"田中 保"}]},"description":{"en":"Previously, we found an unidentified sphingolipid in cabbage, and determined it as phytoceramide 1-phosphate (PC1P). PC1P is found to be produced from glycosylinositol phosphoceramide (GIPC) by the action of phospholipase D (PLD) activity. Although GIPC is abundant sphingolipid, especially in cruciferous vegetables, amount of daily intake, digestibility and nutritional activity of GIPC are not well understood. Here, we investigated amounts of GIPC and PC1P in vegetables. GIPC was found in all vegetables examined (13 kinds) at levels 3-20 mg/100 g (wet weight). On the other hand, PC1P was present in limited vegetables which show higher GIPC-PLD activity, such as inner cabbage leaves (5.2 mg/100 g). Because PC1P is formed during homogenization by activated GIPC-PLD, level of PC1P in boiled cabbage leaves was very low. Although digestibility of GIPC is unknown at present, a portion of dietary GIPC is considered to be converted to PC1P during mastication by plant-derived GIPC-PLD activity in some vegetables.","ja":"Previously, we found an unidentified sphingolipid in cabbage, and determined it as phytoceramide 1-phosphate (PC1P). PC1P is found to be produced from glycosylinositol phosphoceramide (GIPC) by the action of phospholipase D (PLD) activity. Although GIPC is abundant sphingolipid, especially in cruciferous vegetables, amount of daily intake, digestibility and nutritional activity of GIPC are not well understood. Here, we investigated amounts of GIPC and PC1P in vegetables. GIPC was found in all vegetables examined (13 kinds) at levels 3-20 mg/100 g (wet weight). On the other hand, PC1P was present in limited vegetables which show higher GIPC-PLD activity, such as inner cabbage leaves (5.2 mg/100 g). Because PC1P is formed during homogenization by activated GIPC-PLD, level of PC1P in boiled cabbage leaves was very low. Although digestibility of GIPC is unknown at present, a portion of dietary GIPC is considered to be converted to PC1P during mastication by plant-derived GIPC-PLD activity in some vegetables."},"publication_date":"2019-10-11","publication_name":{"en":"Journal of Nutritional Science and Vitaminology","ja":"Journal of Nutritional Science and Vitaminology"},"volume":"Vol.65","number":"No.Supplement","starting_page":"S175","ending_page":"S179","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3177/jnsv.65.S175"],"issn":["1881-7742"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:38, {"insert":{"user_id":"1000193501","type":"published_papers","id":"30458787"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/113685","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31504617","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85073764089&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=363542","label":"url"}],"paper_title":{"en":"Glycosylinositol phosphoceramide-specific phospholipase D activity catalyzes transphosphatidylation","ja":"Glycosylinositol phosphoceramide-specific phospholipase D activity catalyzes transphosphatidylation"},"authors":{"en":[{"name":"Rumana Yesmin Hasi"},{"name":"Miyagi Makoto"},{"name":"Morito Katsuya"},{"name":"Ishikawa Toshiki"},{"name":"Kawai-Yamada Maki"},{"name":"Imai Hiroyuki"},{"name":"Fukuta Tatsuya"},{"name":"Kogure Kentaro"},{"name":"Kanemaru Kaori"},{"name":"Hayashi Junji"},{"name":"Kawakami Ryushi"},{"name":"Tanaka Tamotsu"}],"ja":[{"name":"Rumana Hasi Yesmin"},{"name":"宮城 諒"},{"name":"森戸 克弥"},{"name":"Ishikawa Toshiki"},{"name":"Kawai-Yamada Maki"},{"name":"Imai Hiroyuki"},{"name":"福田 達也"},{"name":"小暮 健太朗"},{"name":"金丸 芳"},{"name":"林 順司"},{"name":"川上 竜巳"},{"name":"田中 保"}]},"description":{"en":"Glycosylinositol phosphoceramide (GIPC) is the most abundant sphingolipid in plants and fungi. Recently, we detected GIPC-specific phospholipase D (GIPC-PLD) activity in plants. Here, we found that GIPC-PLD activity in young cabbage leaves catalyzes transphosphatidylation. The available alcohol for this reaction is a primary alcohol with a chain length below C4. Neither secondary alcohol, tertiary alcohol, choline, serine nor glycerol serves as an acceptor for transphosphatidylation of GIPC-PLD. We also found that cabbage GIPC-PLD prefers GIPC containing two sugars. Neither inositol phosphoceramide, mannosylinositol phosphoceramide nor GIPC with three sugar chains served as substrate. GIPC-PLD will become a useful catalyst for modification of polar head group of sphingophospholipid.","ja":"Glycosylinositol phosphoceramide (GIPC) is the most abundant sphingolipid in plants and fungi. Recently, we detected GIPC-specific phospholipase D (GIPC-PLD) activity in plants. Here, we found that GIPC-PLD activity in young cabbage leaves catalyzes transphosphatidylation. The available alcohol for this reaction is a primary alcohol with a chain length below C4. Neither secondary alcohol, tertiary alcohol, choline, serine nor glycerol serves as an acceptor for transphosphatidylation of GIPC-PLD. We also found that cabbage GIPC-PLD prefers GIPC containing two sugars. Neither inositol phosphoceramide, mannosylinositol phosphoceramide nor GIPC with three sugar chains served as substrate. GIPC-PLD will become a useful catalyst for modification of polar head group of sphingophospholipid."},"publication_date":"2019-08-26","publication_name":{"en":"The Journal of Biochemistry","ja":"The Journal of Biochemistry"},"volume":"Vol.166","number":"No.5","starting_page":"441","ending_page":"448","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1093/jb/mvz056"],"issn":["1756-2651"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:39, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31299884","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85068907161&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=359917","label":"url"}],"paper_title":{"en":"No enhancing effects of plasmid-specific histone acetyltransferase recruitment system on transgene expression in vivo","ja":"No enhancing effects of plasmid-specific histone acetyltransferase recruitment system on transgene expression in vivo"},"authors":{"en":[{"name":"Suzuki Tetsuya"},{"name":"Wakao Yusuke"},{"name":"Watanabe Tadashi"},{"name":"Hori Mika"},{"name":"Ikeda Yoshito"},{"name":"Tsuchiya Hiroyuki"},{"name":"Kogure Kentaro"},{"name":"Harada-Shiba Mariko"},{"name":"Fujimuro Masahiro"},{"name":"Kamiya Hiroyuki"}],"ja":[{"name":"Suzuki Tetsuya"},{"name":"Wakao Yusuke"},{"name":"Watanabe Tadashi"},{"name":"Hori Mika"},{"name":"Ikeda Yoshito"},{"name":"Tsuchiya Hiroyuki"},{"name":"小暮 健太朗"},{"name":"Harada-Shiba Mariko"},{"name":"Fujimuro Masahiro"},{"name":"Kamiya Hiroyuki"}]},"description":{"en":"Altered levels of histone acetylation are associated with changes in chromosomal gene expression. Thus, the specific acetylation of histones bound to plasmid DNA might increase transgene expression. Previously, the expression of the histone acetyltransferase domain of CREB-binding protein fused to the sequence-dependent DNA binding domain of GAL4 (GAL4-HAT) successfully improved reporter gene expression in cultured cells [ 123, 277-280 (2017)]. In this study, the same approach was applied for transgene expression in mice. The activator and reporter plasmid DNAs bearing the genes for GAL4-HAT and luciferase, respectively, were co-administered into the mouse liver by hydrodynamics-based tail vein injection, and the luciferase activity in serum was measured for two weeks. Unexpectedly, the co-injection of the GAL4-HAT and luciferase plasmid DNAs seemed to decrease, rather than increase, luciferase expression. Moreover, the co-injection apparently reduced the amount of luciferase DNA in the liver. These results indicated that this system is ineffective in vivo and suggested the exclusion of hepatic cells expressing GAL4-HAT.","ja":"Altered levels of histone acetylation are associated with changes in chromosomal gene expression. Thus, the specific acetylation of histones bound to plasmid DNA might increase transgene expression. Previously, the expression of the histone acetyltransferase domain of CREB-binding protein fused to the sequence-dependent DNA binding domain of GAL4 (GAL4-HAT) successfully improved reporter gene expression in cultured cells [ 123, 277-280 (2017)]. In this study, the same approach was applied for transgene expression in mice. The activator and reporter plasmid DNAs bearing the genes for GAL4-HAT and luciferase, respectively, were co-administered into the mouse liver by hydrodynamics-based tail vein injection, and the luciferase activity in serum was measured for two weeks. Unexpectedly, the co-injection of the GAL4-HAT and luciferase plasmid DNAs seemed to decrease, rather than increase, luciferase expression. Moreover, the co-injection apparently reduced the amount of luciferase DNA in the liver. These results indicated that this system is ineffective in vivo and suggested the exclusion of hepatic cells expressing GAL4-HAT."},"publication_date":"2019-07-12","publication_name":{"en":"Nucleosides, Nucleotides & Nucleic Acids","ja":"Nucleosides, Nucleotides & Nucleic Acids"},"starting_page":"1","ending_page":"8","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1080/15257770.2019.1638514"],"issn":["1532-2335"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:40, {"insert":{"user_id":"1000193501","type":"published_papers","id":"30458788"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/114730","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30978483","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=359918","label":"url"}],"paper_title":{"en":"Leukocyte-mimetic liposomes possessing leukocyte membrane proteins pass through inflamed endothelial cell layer by regulating intercellular junctions","ja":"Leukocyte-mimetic liposomes possessing leukocyte membrane proteins pass through inflamed endothelial cell layer by regulating intercellular junctions"},"authors":{"en":[{"name":"Fukuta Tatsuya"},{"name":"Yoshimi Shintaroh"},{"name":"Tanaka Tamotsu"},{"name":"Kogure Kentaro"}],"ja":[{"name":"福田 達也"},{"name":"吉見 真太朗"},{"name":"田中 保"},{"name":"小暮 健太朗"}]},"description":{"en":"Nanoparticles such as liposomes have been applied for the treatment of various diseases such as cancer and inflammatory diseases by utilizing the enhanced permeability and retention effect. However, their entry into inflammation sites is still limited since passive delivery of nanoparticles is often hampered by the presence of endothelial barriers. As leukocytes can pass through the inflamed endothelium via utilizing membrane protein functions, we hypothesized that incorporating leukocyte membrane proteins onto liposomal membranes may impart leukocyte-mimicking functions to liposomes, allowing for their adherence to and active passage through the inflamed endothelium. Herein, we developed leukocyte-mimetic liposomes (LM-Lipo) by leukocyte membrane protein transfer and evaluated their function in vitro. Transfer of membrane proteins from human leukemia cells onto liposomal membranes allowed for significant association of the liposomes with inflamed human endothelial cells, and subsequent passage through inflamed endothelial cell layer. The confocal images showed that LM-Lipo significantly induced vascular endothelial-cadherin displacement. These results indicate that LM-Lipo adhered to and regulated intercellular junctions of inflamed endothelial cell layer, resulting in passage through the layer, by mimicking the function of leukocytes. Furthermore, it is suggested that liposomes possessing leukocyte-like functions could be useful for drug delivery to inflammation sites by overcoming endothelial barriers.","ja":"Nanoparticles such as liposomes have been applied for the treatment of various diseases such as cancer and inflammatory diseases by utilizing the enhanced permeability and retention effect. However, their entry into inflammation sites is still limited since passive delivery of nanoparticles is often hampered by the presence of endothelial barriers. As leukocytes can pass through the inflamed endothelium via utilizing membrane protein functions, we hypothesized that incorporating leukocyte membrane proteins onto liposomal membranes may impart leukocyte-mimicking functions to liposomes, allowing for their adherence to and active passage through the inflamed endothelium. Herein, we developed leukocyte-mimetic liposomes (LM-Lipo) by leukocyte membrane protein transfer and evaluated their function in vitro. Transfer of membrane proteins from human leukemia cells onto liposomal membranes allowed for significant association of the liposomes with inflamed human endothelial cells, and subsequent passage through inflamed endothelial cell layer. The confocal images showed that LM-Lipo significantly induced vascular endothelial-cadherin displacement. These results indicate that LM-Lipo adhered to and regulated intercellular junctions of inflamed endothelial cell layer, resulting in passage through the layer, by mimicking the function of leukocytes. Furthermore, it is suggested that liposomes possessing leukocyte-like functions could be useful for drug delivery to inflammation sites by overcoming endothelial barriers."},"publication_date":"2019-05","publication_name":{"en":"International Journal of Pharmaceutics","ja":"International Journal of Pharmaceutics"},"volume":"Vol.563","starting_page":"314","ending_page":"323","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.ijpharm.2019.04.027"],"issn":["1873-3476"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:41, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/114945","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30858501","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85062766468&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=359919","label":"url"}],"paper_title":{"en":"Low electric treatment activates Rho GTPase via heat shock protein 90 and protein kinase c for intracellular delivery of siRNA","ja":"Low electric treatment activates Rho GTPase via heat shock protein 90 and protein kinase c for intracellular delivery of siRNA"},"authors":{"en":[{"name":"Hasan Mahadi"},{"name":"Hama Susumu"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Hasan Mahadi"},{"name":"Hama Susumu"},{"name":"小暮 健太朗"}]},"description":{"en":"Low electric treatment (LET) promotes intracellular delivery of naked siRNA by altering cellular physiology. However, which signaling molecules and cellular events contribute to LET-mediated siRNA uptake are unclear. Here, we used isobaric tags in relative and absolute quantification (iTRAQ) proteomic analysis to identify changes in the levels of phosphorylated proteins that occur during cellular uptake of siRNA promoted by LET. iTRAQ analysis revealed that heat shock protein 90 (Hsp90)α and myristoylated alanine-rich C-kinase substrate (Marcks) were highly phosphorylated following LET of NIH 3T3 cells, but not untreated cells. Furthermore, the levels of phosphorylated Hsp90α and protein kinase C (PKC)γ were increased by LET both with siRNA and liposomes having various physicochemical properties used as model macromolecules, suggesting that PKCγ activated partly by Ca influx as well as Hsp90 chaperone function were involved in LET-mediated cellular siRNA uptake. Furthermore, LET with siRNA induced activation of Rho GTPase via Hsp90 and PKC, which could contribute to cellular siRNA uptake accompanied by actin cytoskeleton remodeling. Collectively, our results suggested that LET-induced Rho GTPase activation via Hsp90 and PKC would participate in actin-dependent cellular uptake of siRNA.","ja":"Low electric treatment (LET) promotes intracellular delivery of naked siRNA by altering cellular physiology. However, which signaling molecules and cellular events contribute to LET-mediated siRNA uptake are unclear. Here, we used isobaric tags in relative and absolute quantification (iTRAQ) proteomic analysis to identify changes in the levels of phosphorylated proteins that occur during cellular uptake of siRNA promoted by LET. iTRAQ analysis revealed that heat shock protein 90 (Hsp90)α and myristoylated alanine-rich C-kinase substrate (Marcks) were highly phosphorylated following LET of NIH 3T3 cells, but not untreated cells. Furthermore, the levels of phosphorylated Hsp90α and protein kinase C (PKC)γ were increased by LET both with siRNA and liposomes having various physicochemical properties used as model macromolecules, suggesting that PKCγ activated partly by Ca influx as well as Hsp90 chaperone function were involved in LET-mediated cellular siRNA uptake. Furthermore, LET with siRNA induced activation of Rho GTPase via Hsp90 and PKC, which could contribute to cellular siRNA uptake accompanied by actin cytoskeleton remodeling. Collectively, our results suggested that LET-induced Rho GTPase activation via Hsp90 and PKC would participate in actin-dependent cellular uptake of siRNA."},"publication_date":"2019-03-11","publication_name":{"en":"Scientific Reports","ja":"Scientific Reports"},"volume":"Vol.9","number":"No.1","starting_page":"4114","ending_page":"4114","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s41598-019-40904-z"],"issn":["2045-2322"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:42, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30705509","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85059761043&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=359920","label":"url"}],"paper_title":{"en":"Efficacy of high-affinity liposomal astaxanthin on up-regulation of age-related markers induced by oxidative stress in human corneal epithelial cells","ja":"Efficacy of high-affinity liposomal astaxanthin on up-regulation of age-related markers induced by oxidative stress in human corneal epithelial cells"},"authors":{"en":[{"name":"Shimokawa Tatsuharu"},{"name":"Yoshida Mai"},{"name":"Fukuta Tatsuya"},{"name":"Tanaka Tamotsu"},{"name":"Inagi Toshio"},{"name":"Kogure Kentaro"}],"ja":[{"name":"下川 達張"},{"name":"Yoshida Mai"},{"name":"福田 達也"},{"name":"田中 保"},{"name":"Inagi Toshio"},{"name":"小暮 健太朗"}]},"description":{"en":"Decreases in tear volume, unstable tear films and excessive tear evaporation are known to cause desiccation and hyperosmolar stress. These, in turn, induce oxidative stress that is thought to cause dry eye, which is also considered to be age-related disease. We hypothesized that oxidative stress induces up-regulation of age-related markers, and that the antioxidant astaxanthin prepared as a liposomal formulation may be a candidate for the treatment of dry eye. Herein, we examined age-related markers in an dry eye model, and evaluated the efficacy of high-affinity liposomes containing astaxanthin. The dry eye model showed desiccation time-dependent increases in reactive oxygen species. We confirmed the up-regulation of p53, p21 and p16 as a function of desiccation time. Pretreatment with both neutral and slightly-positively-charged astaxanthin liposomal formulations showed significant suppression of up-regulation of all markers, with the positively-charged liposomes exhibiting the greatest efficacy. Furthermore, positively-charged liposomes labeled with fluorescent dyes demonstrated much higher affinity to normal human corneal epithelial cells (HCECs) than neutral liposomes. Taken together, we confirmed the up-regulation of age-related markers, especially p16, in an dry eye model, and demonstrated the potential of high-affinity liposomal astaxanthin for the treatment of dry eye.","ja":"Decreases in tear volume, unstable tear films and excessive tear evaporation are known to cause desiccation and hyperosmolar stress. These, in turn, induce oxidative stress that is thought to cause dry eye, which is also considered to be age-related disease. We hypothesized that oxidative stress induces up-regulation of age-related markers, and that the antioxidant astaxanthin prepared as a liposomal formulation may be a candidate for the treatment of dry eye. Herein, we examined age-related markers in an dry eye model, and evaluated the efficacy of high-affinity liposomes containing astaxanthin. The dry eye model showed desiccation time-dependent increases in reactive oxygen species. We confirmed the up-regulation of p53, p21 and p16 as a function of desiccation time. Pretreatment with both neutral and slightly-positively-charged astaxanthin liposomal formulations showed significant suppression of up-regulation of all markers, with the positively-charged liposomes exhibiting the greatest efficacy. Furthermore, positively-charged liposomes labeled with fluorescent dyes demonstrated much higher affinity to normal human corneal epithelial cells (HCECs) than neutral liposomes. Taken together, we confirmed the up-regulation of age-related markers, especially p16, in an dry eye model, and demonstrated the potential of high-affinity liposomal astaxanthin for the treatment of dry eye."},"publication_date":"2019-01","publication_name":{"en":"Journal of Clinical Biochemistry and Nutrition","ja":"Journal of Clinical Biochemistry and Nutrition"},"volume":"Vol.64","number":"No.1","starting_page":"27","ending_page":"35","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3164/jcbn.18-27"],"issn":["0912-0009"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:43, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/113562","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29962454","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85049232130&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=339050","label":"url"}],"paper_title":{"en":"Carotenoid Stereochemistry Affects Antioxidative Activity of Liposomes Co-encapsulating Astaxanthin and Tocotrienol","ja":"Carotenoid Stereochemistry Affects Antioxidative Activity of Liposomes Co-encapsulating Astaxanthin and Tocotrienol"},"authors":{"en":[{"name":"Ishikawa Misuzu"},{"name":"Hirai Shota"},{"name":"Yoshida Tatsusada"},{"name":"Shibuya Natsumi"},{"name":"Hama, Susumu"},{"name":"Takahashi Yu"},{"name":"Fukuta Tatsuya"},{"name":"Tanaka Tamotsu"},{"name":"Hosoi Shinzo"},{"name":"Kogure Kentaro"}],"ja":[{"name":"石川 みすず"},{"name":"平井 将太"},{"name":"吉田 達貞"},{"name":"渋谷 菜摘"},{"name":"濵 進"},{"name":"高橋 侑"},{"name":"福田 達也"},{"name":"田中 保"},{"name":"細井 信造"},{"name":"小暮 健太朗"}]},"description":{"en":"We previously found that antioxidative activity of liposomes co-encapsulating astaxanthin (Asx) and tocotrienols (T3s) was higher than the calculated additive activity, which results from intermolecular interactions between both antioxidants (J. Clin. Biochem. Nutr., 59, 2016, Kamezaki et al.). Herein, we conducted experiments to optimize Asx/α-T3 ratio for high antioxidative activity, and tried to elucidate details of intermolecular interaction of Asx with α-T3. Higher activity than calculated additive value was clearly observed at an Asx/α-T3 ratio of 2 : 1, despite two α-T3 would potentially interact with two terminal rings of one Asx. The synthetic Asx used in this study was a mixture of three stereoisomers, 3R,3'R-form (Asx-R), 3S,3'S-form (Asx-S) and 3R,3'S-meso form (Asx-meso). The calculated binding energy of the Asx-S/α-T3 complex was higher than those of Asx-R/α-T3 and Asx-meso/α-T3, suggesting that Asx-S and α-T3 is the most preferable combination for the intermolecular interaction. The optimal Asx-S/α-T3 ratio for antioxidation was shown to be 1 : 2. These results suggest that the Asx stereochemistry affects the intermolecular interaction of Asx/α-T3. Moreover, the absorption spectrum changes of Asx-S upon co-encapsulation with α-T3 in liposomes indicate that the electronic state of Asx-S is affected by intermolecular interactions with α-T3. Further, intermolecular interactions with α-T3 affected the electronic charges on the C9, C10 and C15 atoms in the polyene moiety of Asx-S. In conclusion, the intermolecular interaction of Asx/T3 depends on the Asx stereochemistry, and caused a change in the electronic state of the Asx polyene moiety by the presence of double bond in the T3 triene moiety.","ja":"We previously found that antioxidative activity of liposomes co-encapsulating astaxanthin (Asx) and tocotrienols (T3s) was higher than the calculated additive activity, which results from intermolecular interactions between both antioxidants (J. Clin. Biochem. Nutr., 59, 2016, Kamezaki et al.). Herein, we conducted experiments to optimize Asx/α-T3 ratio for high antioxidative activity, and tried to elucidate details of intermolecular interaction of Asx with α-T3. Higher activity than calculated additive value was clearly observed at an Asx/α-T3 ratio of 2 : 1, despite two α-T3 would potentially interact with two terminal rings of one Asx. The synthetic Asx used in this study was a mixture of three stereoisomers, 3R,3'R-form (Asx-R), 3S,3'S-form (Asx-S) and 3R,3'S-meso form (Asx-meso). The calculated binding energy of the Asx-S/α-T3 complex was higher than those of Asx-R/α-T3 and Asx-meso/α-T3, suggesting that Asx-S and α-T3 is the most preferable combination for the intermolecular interaction. The optimal Asx-S/α-T3 ratio for antioxidation was shown to be 1 : 2. These results suggest that the Asx stereochemistry affects the intermolecular interaction of Asx/α-T3. Moreover, the absorption spectrum changes of Asx-S upon co-encapsulation with α-T3 in liposomes indicate that the electronic state of Asx-S is affected by intermolecular interactions with α-T3. Further, intermolecular interactions with α-T3 affected the electronic charges on the C9, C10 and C15 atoms in the polyene moiety of Asx-S. In conclusion, the intermolecular interaction of Asx/T3 depends on the Asx stereochemistry, and caused a change in the electronic state of the Asx polyene moiety by the presence of double bond in the T3 triene moiety."},"publication_date":"2018-05","publication_name":{"en":"Chemical & Pharmaceutical Bulletin","ja":"Chemical & Pharmaceutical Bulletin"},"volume":"Vol.66","number":"No.7","starting_page":"714","ending_page":"720","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/cpb.c18-00035"],"issn":["1347-5223"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:44, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/112025","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29462674","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85042401633&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=339054","label":"url"}],"paper_title":{"en":"Lysophosphatidic acid in medicinal herbs enhances prostaglandin E2 and protects against indomethacin-induced gastric cell damage in vivo and in vitro","ja":"Lysophosphatidic acid in medicinal herbs enhances prostaglandin E2 and protects against indomethacin-induced gastric cell damage in vivo and in vitro"},"authors":{"en":[{"name":"Afroz Sheuli"},{"name":"Yagi Ayano"},{"name":"Fujikawa Kouki"},{"name":"Rahman Motiur M."},{"name":"Morito Katsuya"},{"name":"Fukuta Tatsuya"},{"name":"Watanabe Shiro"},{"name":"Toida Kazunori"},{"name":"Kiyokage Emi"},{"name":"Shimizu Taro"},{"name":"Ishida Tatsuhiro"},{"name":"Kogure Kentaro"},{"name":"Tokumura Akira"},{"name":"Tanaka Tamotsu"}],"ja":[{"name":"SHEULI AFROZ"},{"name":"屋宜 亜耶乃"},{"name":"藤川 昂樹"},{"name":"Md. Motiur Rahman"},{"name":"森戸 克弥"},{"name":"福田 達也"},{"name":"Watanabe Shiro"},{"name":"Toida Kazunori"},{"name":"Kiyokage Emi"},{"name":"清水 太郎"},{"name":"石田 竜弘"},{"name":"小暮 健太朗"},{"name":"德村 彰"},{"name":"田中 保"}]},"description":{"en":"Lysophosphatidic acid (LPA) is a bioactive phospholipid that induces diverse biological responses. Recently, we found that LPA ameliorates NSAIDs-induced gastric ulcer in mice. Here, we quantified LPA in 21 medicinal herbs used for treatment of gastrointestinal (GI) disorders. We found that half of them contained LPA at relatively high levels (40-240 μg/g) compared to soybean seed powder (4.6 μg/g), which we previously identified as an LPA-rich food. The LPA in peony (Paeonia lactiflora) root powder is highly concentrated in the lipid fraction that ameliorates indomethacin-induced gastric ulcer in mice. Synthetic 18:1 LPA, peony root LPA and peony root lipid enhanced prostaglandin E production in a gastric cancer cell line, MKN74 cells that express LPA abundantly. These materials also prevented indomethacin-induced cell death and stimulated the proliferation of MKN74 cells. We found that LPA was present in stomach fluids at 2.4 μM, which is an effective LPA concentration for inducing a cellular response in vitro. These results indicated that LPA is one of the active components of medicinal herbs for the treatment of GI disorder and that orally administered LPA-rich herbs may augment the protective actions of endogenous LPA on gastric mucosa.","ja":"Lysophosphatidic acid (LPA) is a bioactive phospholipid that induces diverse biological responses. Recently, we found that LPA ameliorates NSAIDs-induced gastric ulcer in mice. Here, we quantified LPA in 21 medicinal herbs used for treatment of gastrointestinal (GI) disorders. We found that half of them contained LPA at relatively high levels (40-240 μg/g) compared to soybean seed powder (4.6 μg/g), which we previously identified as an LPA-rich food. The LPA in peony (Paeonia lactiflora) root powder is highly concentrated in the lipid fraction that ameliorates indomethacin-induced gastric ulcer in mice. Synthetic 18:1 LPA, peony root LPA and peony root lipid enhanced prostaglandin E production in a gastric cancer cell line, MKN74 cells that express LPA abundantly. These materials also prevented indomethacin-induced cell death and stimulated the proliferation of MKN74 cells. We found that LPA was present in stomach fluids at 2.4 μM, which is an effective LPA concentration for inducing a cellular response in vitro. These results indicated that LPA is one of the active components of medicinal herbs for the treatment of GI disorder and that orally administered LPA-rich herbs may augment the protective actions of endogenous LPA on gastric mucosa."},"publication_date":"2018-01-25","publication_name":{"en":"Prostaglandins & Other Lipid Mediators","ja":"Prostaglandins & Other Lipid Mediators"},"volume":"Vol.135","starting_page":"36","ending_page":"44","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.prostaglandins.2018.01.003"],"issn":["1098-8823"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:45, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28566638","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85020052387&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=323515","label":"url"}],"paper_title":{"en":"Prevention of UV-induced Melanin Production by Accumulation of Redox Nanoparticles in the Epidermal Layer via Iontophoresis","ja":"Prevention of UV-induced Melanin Production by Accumulation of Redox Nanoparticles in the Epidermal Layer via Iontophoresis"},"authors":{"en":[{"name":"Shiota Kanako"},{"name":"Hama Susumu"},{"name":"Yoshitomi Toru"},{"name":"Nagasaki Yukio"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Shiota Kanako"},{"name":"Hama Susumu"},{"name":"Yoshitomi Toru"},{"name":"Nagasaki Yukio"},{"name":"小暮 健太朗"}]},"description":{"en":"UV rays induce melanin production in the skin, which, from a cosmetic point of view, is problematic. Reactive oxygen species (ROS) generated in the skin upon UV irradiation are thought to be responsible for melanin production. Thus, effective antioxidants are recognized as useful tools for prevention of UV-induced melanin production. Redox nanoparticles (RNPs) containing nitroxide radicals as free radical scavengers were previously developed, and shown to be effective ROS scavengers in the body. RNPs are therefore expected to be useful for effective protection against UV-induced melanin production. However, as the sizes of RNPs are typically larger than the intercellular spaces of the skin, transdermal penetration is difficult. We recently demonstrated effective transdermal delivery and accumulation of nanoparticles in the epidermal layer via faint electric treatment, i.e., iontophoresis, suggesting that iontophoresis of RNPs may be a useful strategy for prevention of UV-induced melanin production in the skin. Herein, we performed iontophoresis of RNPs on the dorsal skin of hairless mice that produce melanin in response to light exposure. RNPs accumulated in the epidermal layer upon application of iontophoresis. Further, the combination of RNPs with iontophoresis decreased UV-induced melanin spots and melanin content in the skin. Taken together, we successfully demonstrated that iontophoresis-mediated accumulation of RNPs in the epidermis prevented melanin production.","ja":"UV rays induce melanin production in the skin, which, from a cosmetic point of view, is problematic. Reactive oxygen species (ROS) generated in the skin upon UV irradiation are thought to be responsible for melanin production. Thus, effective antioxidants are recognized as useful tools for prevention of UV-induced melanin production. Redox nanoparticles (RNPs) containing nitroxide radicals as free radical scavengers were previously developed, and shown to be effective ROS scavengers in the body. RNPs are therefore expected to be useful for effective protection against UV-induced melanin production. However, as the sizes of RNPs are typically larger than the intercellular spaces of the skin, transdermal penetration is difficult. We recently demonstrated effective transdermal delivery and accumulation of nanoparticles in the epidermal layer via faint electric treatment, i.e., iontophoresis, suggesting that iontophoresis of RNPs may be a useful strategy for prevention of UV-induced melanin production in the skin. Herein, we performed iontophoresis of RNPs on the dorsal skin of hairless mice that produce melanin in response to light exposure. RNPs accumulated in the epidermal layer upon application of iontophoresis. Further, the combination of RNPs with iontophoresis decreased UV-induced melanin spots and melanin content in the skin. Taken together, we successfully demonstrated that iontophoresis-mediated accumulation of RNPs in the epidermis prevented melanin production."},"publication_date":"2017-03-18","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"Vol.40","number":"No.6","starting_page":"941","ending_page":"944","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b17-00155"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:46, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28055201","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85012306090&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=322832","label":"url"}],"paper_title":{"en":"Tumor microenvironment-sensitive liposomes penetrate tumor tissue via attenuated interaction of the extracellular matrix and tumor cells, and accompanying actin depolymerization","ja":"Tumor microenvironment-sensitive liposomes penetrate tumor tissue via attenuated interaction of the extracellular matrix and tumor cells, and accompanying actin depolymerization"},"authors":{"en":[{"name":"Suzuki Satoko"},{"name":"Itakura Shoko"},{"name":"Matsui Ryo"},{"name":"Nakayama Kayoko"},{"name":"Nishi Takayuki"},{"name":"Nishimoto Akinori"},{"name":"Hama Susumu"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Suzuki Satoko"},{"name":"Itakura Shoko"},{"name":"Matsui Ryo"},{"name":"Nakayama Kayoko"},{"name":"Nishi Takayuki"},{"name":"Nishimoto Akinori"},{"name":"Hama Susumu"},{"name":"小暮 健太朗"}]},"description":{"en":"Delivery of anticancer drugs into tumor cores comprised of malignant cancer cells can result in potent therapeutic effects. However, conventional nanoparticle-based drug delivery systems used for cancer therapy often exhibit inefficient tumor-penetrating properties, thus, suggesting the need to improve the functional design of such systems. Herein, we focus on the interactions between cancer cells and the extracellular matrix (ECM) and demonstrate that liposomes modified with slightly acidic pH-sensitive peptide (SAPSp-lipo) can penetrate in vivo tumor tissue and in vitro spheroids comprised of cancer cells and ECM. We previously reported SAPSp-lipo, tumor microenvironment-sensitive liposomes, are effectively delivered to tumor tissue (Hama et al. J Control Release 2015, 206, 67-74). Compared with conventional liposomes, SAPSp-lipo could be delivered to deeper regions within both spheroids and tumor tissues. Furthermore, tumor penetration was found to be promoted at regions where actin depolymerization was induced by SAPSp-lipo and inhibited by the polymerization of actin. In addition, SAPSp-lipo attenuated the interaction between cancer cells and ECM, contributing to the penetration of SAPSp-lipo. These results suggest that SAPSp-lipo penetrates tumors via the interspace route and is accompanied by actin depolymerization. Taken together, SAPSp-lipo demonstrates potential as a novel tumor-penetrable drug carrier for induction of therapeutic effects against malignant cells that comprise tumor cores.","ja":"Delivery of anticancer drugs into tumor cores comprised of malignant cancer cells can result in potent therapeutic effects. However, conventional nanoparticle-based drug delivery systems used for cancer therapy often exhibit inefficient tumor-penetrating properties, thus, suggesting the need to improve the functional design of such systems. Herein, we focus on the interactions between cancer cells and the extracellular matrix (ECM) and demonstrate that liposomes modified with slightly acidic pH-sensitive peptide (SAPSp-lipo) can penetrate in vivo tumor tissue and in vitro spheroids comprised of cancer cells and ECM. We previously reported SAPSp-lipo, tumor microenvironment-sensitive liposomes, are effectively delivered to tumor tissue (Hama et al. J Control Release 2015, 206, 67-74). Compared with conventional liposomes, SAPSp-lipo could be delivered to deeper regions within both spheroids and tumor tissues. Furthermore, tumor penetration was found to be promoted at regions where actin depolymerization was induced by SAPSp-lipo and inhibited by the polymerization of actin. In addition, SAPSp-lipo attenuated the interaction between cancer cells and ECM, contributing to the penetration of SAPSp-lipo. These results suggest that SAPSp-lipo penetrates tumors via the interspace route and is accompanied by actin depolymerization. Taken together, SAPSp-lipo demonstrates potential as a novel tumor-penetrable drug carrier for induction of therapeutic effects against malignant cells that comprise tumor cores."},"publication_date":"2017-02-13","publication_name":{"en":"Biomacromolecules","ja":"Biomacromolecules"},"volume":"Vol.18","number":"No.2","starting_page":"535","ending_page":"543","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1021/acs.biomac.6b01688"],"issn":["1526-4602"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:47, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117827","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28175321","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1522262180608136704/","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85015919191&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=338861","label":"url"}],"paper_title":{"en":"Distribution of glycosylinositol phosphoceramide-specific phospholipase D activity in plants","ja":"Distribution of glycosylinositol phosphoceramide-specific phospholipase D activity in plants"},"authors":{"en":[{"name":"Takashi Kida"},{"name":"Aoi Itoh"},{"name":"Akari Kimura"},{"name":"Hisatsugu Matsuoka"},{"name":"Hiroyuki Imai"},{"name":"Kogure Kentaro"},{"name":"Tokumura Akira"},{"name":"Tanaka Tamotsu"}],"ja":[{"name":"喜田 孝史"},{"name":"Aoi Itoh"},{"name":"Akari Kimura"},{"name":"Hisatsugu Matsuoka"},{"name":"Hiroyuki Imai"},{"name":"小暮 健太朗"},{"name":"德村 彰"},{"name":"田中 保"}]},"description":{"en":"Previously, we detected an unknown sphingophospholipid in cabbage leaves and identified it as phytoceramide-1-phosphate (PC1P). We also found an enzyme activity that produces PC1P by glycosylinositol phosphoceramide (GIPC)-specific hydrolysis in cabbage leaves. To characterize the GIPC-specific phospholipase D (GIPC-PLD) activity, we investigated distributions of GIPC-PLD activity in 25 tissues of 10 plants. In most plants, the GIPC-PLD activity was the highest in roots. Young leaves of cabbage and Welsh onion had higher activities than corresponding aged outer leaves. The GIPC-PLD activities in leaves, stems and roots of mung bean were higher in the sprouting stage than in more mature stages. We also examined the distribution of substrate GIPC and product PC1P and found that GIPC was ubiquitously distributed at 50-280 nmol/g (wet wt) in tissues of plants, whereas PC1P was detectable (3-60 nmol/g wet wt.) only in tissues showing considerable GIPC-PLD activity. These results suggest a possibility that GIPC-PLD activity is involved in plant growth.","ja":"Previously, we detected an unknown sphingophospholipid in cabbage leaves and identified it as phytoceramide-1-phosphate (PC1P). We also found an enzyme activity that produces PC1P by glycosylinositol phosphoceramide (GIPC)-specific hydrolysis in cabbage leaves. To characterize the GIPC-specific phospholipase D (GIPC-PLD) activity, we investigated distributions of GIPC-PLD activity in 25 tissues of 10 plants. In most plants, the GIPC-PLD activity was the highest in roots. Young leaves of cabbage and Welsh onion had higher activities than corresponding aged outer leaves. The GIPC-PLD activities in leaves, stems and roots of mung bean were higher in the sprouting stage than in more mature stages. We also examined the distribution of substrate GIPC and product PC1P and found that GIPC was ubiquitously distributed at 50-280 nmol/g (wet wt) in tissues of plants, whereas PC1P was detectable (3-60 nmol/g wet wt.) only in tissues showing considerable GIPC-PLD activity. These results suggest a possibility that GIPC-PLD activity is involved in plant growth."},"publication_date":"2017-02-01","publication_name":{"en":"The Journal of Biochemistry","ja":"The Journal of Biochemistry"},"volume":"Vol.161","number":"No.2","starting_page":"187","ending_page":"195","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1093/jb/mvw060"],"issn":["1756-2651"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:48, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/110902","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/27871835","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84997108932&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=321618","label":"url"}],"paper_title":{"en":"Development of flexible nanocarriers for siRNA delivery into tumor tissue","ja":"Development of flexible nanocarriers for siRNA delivery into tumor tissue"},"authors":{"en":[{"name":"Jung Hyunkyung"},{"name":"Shimatani Yuri"},{"name":"Hasan Mahadi"},{"name":"Uno Kohei"},{"name":"Hama Susumu"},{"name":"Kogure Kentaro"}],"ja":[{"name":"鄭 賢卿"},{"name":"島谷 悠里"},{"name":"Hasan Mahadi"},{"name":"宇野 晃平"},{"name":"濱 進"},{"name":"小暮 健太朗"}]},"description":{"en":"Various non-viral delivery systems for small interfering RNAs (siRNA) have been developed. Such delivery systems generally exhibit tightly formed spherical structures. While such carriers have demonstrated good transfection activity in mono-layered cell systems, effects against solid tumors are often less apparent and difficult to demonstrate, likely due to the rigid structures of the carriers, which may prevent penetration to deeper regions within tumor tissue. Herein, we developed a flexible nanocarrier (FNC) system that is able to penetrate to deeper regions within tumor tissue. Specifically, we employed previously found flexible polyplexes comprised of siRNA and poly-l-lysine as wick structures for the preparation of FNCs. FNCs were constructed by coating the wick structures with lipids using a liposomal membrane fusion method. The diameters of the resulting FNCs were ca. 170nm, and the shapes were non-spherical. Lipid coating was confirmed using a nuclease resistance assay. Furthermore, FNCs showed significant RNA interference effects, comparable to Lipofectamine 2000, in a mono-layered cell system. To accelerate tumor penetration, the FNC surface was modified with polyethylene glycol (PEG) and the tight junction opener peptide AT1002. Surface-modified FNCs demonstrated effective penetrability into a cancer spheroid. Thus, we developed a novel and unique tumor-penetrable siRNA FNC system.","ja":"Various non-viral delivery systems for small interfering RNAs (siRNA) have been developed. Such delivery systems generally exhibit tightly formed spherical structures. While such carriers have demonstrated good transfection activity in mono-layered cell systems, effects against solid tumors are often less apparent and difficult to demonstrate, likely due to the rigid structures of the carriers, which may prevent penetration to deeper regions within tumor tissue. Herein, we developed a flexible nanocarrier (FNC) system that is able to penetrate to deeper regions within tumor tissue. Specifically, we employed previously found flexible polyplexes comprised of siRNA and poly-l-lysine as wick structures for the preparation of FNCs. FNCs were constructed by coating the wick structures with lipids using a liposomal membrane fusion method. The diameters of the resulting FNCs were ca. 170nm, and the shapes were non-spherical. Lipid coating was confirmed using a nuclease resistance assay. Furthermore, FNCs showed significant RNA interference effects, comparable to Lipofectamine 2000, in a mono-layered cell system. To accelerate tumor penetration, the FNC surface was modified with polyethylene glycol (PEG) and the tight junction opener peptide AT1002. Surface-modified FNCs demonstrated effective penetrability into a cancer spheroid. Thus, we developed a novel and unique tumor-penetrable siRNA FNC system."},"publication_date":"2017","publication_name":{"en":"International Journal of Pharmaceutics","ja":"International Journal of Pharmaceutics"},"volume":"Vol.516","number":"No.1-2","starting_page":"258","ending_page":"265","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.ijpharm.2016.11.042"],"issn":["1873-3476"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:49, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/27561232","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=327660","label":"url"}],"paper_title":{"en":"Concentrated phosphatidic acid in cereal brans as potential protective agents against indomethacin-induced stomach ulcer.","ja":"Concentrated phosphatidic acid in cereal brans as potential protective agents against indomethacin-induced stomach ulcer."},"authors":{"en":[{"name":"Afroz S"},{"name":"Ikoma Teru"},{"name":"Yagi Ayano"},{"name":"Kogure Kentaro"},{"name":"Tokumura Akira"},{"name":"Tanaka Tamotsu"}],"ja":[{"name":"Afroz S"},{"name":"生駒 照"},{"name":"屋宜 亜耶乃"},{"name":"小暮 健太朗"},{"name":"德村 彰"},{"name":"田中 保"}]},"description":{"en":"One of complications associated with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is peptic ulcer. Recently, we found that orally administered phosphatidic acid (PA) ameliorated aspirin-induced stomach lesions in mice. In this study, we identified PA-rich food sources and examined the effects of the food materials on indomethacin-induced stomach ulcer. Among examined, buckwheat (Fagopyrum esculentum) bran contained the highest level of PA (188 mg/100 g). PA was the richest phospholipid (25%) in the lipid fraction of the buckwheat bran. Administration of the lipid extracts of buckwheat bran significantly ameliorated indomethacin-induced stomach lesions in mice. In contrast, wheat (Triticum durum) bran lipids (PA, 4%) and soybean (Glycine max) lipids (PA, 3%) were not associated with ameliorative effects. These results indicated that PA-rich lipids can be used as an effective supplement for prevention of NSAID-induced stomach ulcer.","ja":"One of complications associated with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is peptic ulcer. Recently, we found that orally administered phosphatidic acid (PA) ameliorated aspirin-induced stomach lesions in mice. In this study, we identified PA-rich food sources and examined the effects of the food materials on indomethacin-induced stomach ulcer. Among examined, buckwheat (Fagopyrum esculentum) bran contained the highest level of PA (188 mg/100 g). PA was the richest phospholipid (25%) in the lipid fraction of the buckwheat bran. Administration of the lipid extracts of buckwheat bran significantly ameliorated indomethacin-induced stomach lesions in mice. In contrast, wheat (Triticum durum) bran lipids (PA, 4%) and soybean (Glycine max) lipids (PA, 3%) were not associated with ameliorative effects. These results indicated that PA-rich lipids can be used as an effective supplement for prevention of NSAID-induced stomach ulcer."},"publication_date":"2016-12","publication_name":{"en":"Journal of Agricultural and Food Chemistry","ja":"Journal of Agricultural and Food Chemistry"},"volume":"Vol.64","number":"No.37","starting_page":"6950","ending_page":"6957","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1021/acs.jafc.6b02884"],"issn":["1520-5118"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:50, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115720","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/27877903","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85019070861&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=317627","label":"url"}],"paper_title":{"en":"The novel functional nucleic acid iRed effectively regulates target genes following cytoplasmic delivery by faint electric treatment","ja":"The novel functional nucleic acid iRed effectively regulates target genes following cytoplasmic delivery by faint electric treatment"},"authors":{"en":[{"name":"Hasan Mahadi"},{"name":"Saito-Tarashima Noriko"},{"name":"Fujikawa Koki"},{"name":"Ohgita Takashi"},{"name":"Hama Susumu"},{"name":"Tanaka Tamotsu"},{"name":"Saito Hiroyuki"},{"name":"Minakawa Noriaki"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Hasan Mahadi"},{"name":"田良島 典子"},{"name":"Fujikawa Koki"},{"name":"Ohgita Takashi"},{"name":"Hama Susumu"},{"name":"田中 保"},{"name":"斎藤 博幸"},{"name":"南川 典昭"},{"name":"小暮 健太朗"}]},"description":{"en":"An intelligent shRNA expression device (iRed) contains the minimum essential components needed for shRNA production in cells, and could be a novel tool to regulate target genes. However, general delivery carriers consisting of cationic polymers/lipids could impede function of a newly generated shRNA via electrostatic interaction in the cytoplasm. Recently, we found that faint electric treatment (fET) of cells enhanced delivery of siRNA and functional nucleic acids into the cytoplasm in the absence of delivery carriers. Here, we examined fET of cells stably expressing luciferase in the presence of iRed encoding anti-luciferase shRNA. Transfection of lipofectamine 2000 (LFN)/iRed lipoplexes showed an RNAi effect, but fET-mediated iRed transfection did not, likely because of the endosomal localization of iRed after delivery. However, fET in the presence of lysosomotropic agent chloroquine significantly improved the RNAi effect of iRed/fET to levels that were higher than those for the LFN/iRed lipoplexes. Furthermore, the amount of lipid droplets in adipocytes significantly decreased following fET with iRed against resistin in the presence of chloroquine. Thus, iRed could be a useful tool to regulate target genes following fET-mediated cytoplasmic delivery with endosomal escape devices.","ja":"An intelligent shRNA expression device (iRed) contains the minimum essential components needed for shRNA production in cells, and could be a novel tool to regulate target genes. However, general delivery carriers consisting of cationic polymers/lipids could impede function of a newly generated shRNA via electrostatic interaction in the cytoplasm. Recently, we found that faint electric treatment (fET) of cells enhanced delivery of siRNA and functional nucleic acids into the cytoplasm in the absence of delivery carriers. Here, we examined fET of cells stably expressing luciferase in the presence of iRed encoding anti-luciferase shRNA. Transfection of lipofectamine 2000 (LFN)/iRed lipoplexes showed an RNAi effect, but fET-mediated iRed transfection did not, likely because of the endosomal localization of iRed after delivery. However, fET in the presence of lysosomotropic agent chloroquine significantly improved the RNAi effect of iRed/fET to levels that were higher than those for the LFN/iRed lipoplexes. Furthermore, the amount of lipid droplets in adipocytes significantly decreased following fET with iRed against resistin in the presence of chloroquine. Thus, iRed could be a useful tool to regulate target genes following fET-mediated cytoplasmic delivery with endosomal escape devices."},"publication_date":"2016-08-04","publication_name":{"en":"Science and Technology of Advanced Materials","ja":"Science and Technology of Advanced Materials"},"volume":"Vol.17","number":"No.17","starting_page":"554","ending_page":"562","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1080/14686996.2016.1221726"],"issn":["1468-6996"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:51, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/27145993","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84971232259&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=317620","label":"url"}],"paper_title":{"en":"Effective cytoplasmic release of siRNA from liposomal carriers by controlling the electrostatic interaction of siRNA with a charge-invertible peptide, in response to cytoplasmic pH","ja":"Effective cytoplasmic release of siRNA from liposomal carriers by controlling the electrostatic interaction of siRNA with a charge-invertible peptide, in response to cytoplasmic pH"},"authors":{"en":[{"name":"Itakura Shoko"},{"name":"Hama Susumu"},{"name":"Matsui Ryo"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Itakura Shoko"},{"name":"Hama Susumu"},{"name":"Matsui Ryo"},{"name":"小暮 健太朗"}]},"description":{"en":"Condensing siRNA with cationic polymers is a major strategy used in the development of siRNA carriers that can avoid degradation by nucleases and achieve effective delivery of siRNA into the cytoplasm. However, ineffective release of siRNA from such condensed forms into the cytoplasm is a limiting step for induction of RNAi effects, and can be attributed to tight condensation of siRNA with the cationic polymers, due to potent electrostatic interactions. Here, we report that siRNA condensed with a slightly acidic pH-sensitive peptide (SAPSP), whose total charge is inverted from positive to negative in response to cytoplasmic pH, is effectively released via electrostatic repulsion of siRNA with negatively charged SAPSP at cytoplasmic pH (7.4). The condensed complex of siRNA and positively-charged SAPSP at acidic pH (siRNA/SAPSP) was found to result in almost complete release of siRNA upon charge inversion of SAPSP at pH 7.4, with the resultant negatively-charged SAPSP having no undesirable interactions with endogenous mRNA. Moreover, liposomes encapsulating siRNA/SAPSP demonstrated knockdown efficiencies comparable to those of commercially available siRNA carriers. Taken together, SAPSP may be very useful as a siRNA condenser, as it facilitates effective cytoplasmic release of siRNA, and subsequent induction of specific RNAi effects.","ja":"Condensing siRNA with cationic polymers is a major strategy used in the development of siRNA carriers that can avoid degradation by nucleases and achieve effective delivery of siRNA into the cytoplasm. However, ineffective release of siRNA from such condensed forms into the cytoplasm is a limiting step for induction of RNAi effects, and can be attributed to tight condensation of siRNA with the cationic polymers, due to potent electrostatic interactions. Here, we report that siRNA condensed with a slightly acidic pH-sensitive peptide (SAPSP), whose total charge is inverted from positive to negative in response to cytoplasmic pH, is effectively released via electrostatic repulsion of siRNA with negatively charged SAPSP at cytoplasmic pH (7.4). The condensed complex of siRNA and positively-charged SAPSP at acidic pH (siRNA/SAPSP) was found to result in almost complete release of siRNA upon charge inversion of SAPSP at pH 7.4, with the resultant negatively-charged SAPSP having no undesirable interactions with endogenous mRNA. Moreover, liposomes encapsulating siRNA/SAPSP demonstrated knockdown efficiencies comparable to those of commercially available siRNA carriers. Taken together, SAPSP may be very useful as a siRNA condenser, as it facilitates effective cytoplasmic release of siRNA, and subsequent induction of specific RNAi effects."},"publication_date":"2016-05-19","publication_name":{"en":"Nanoscale","ja":"Nanoscale"},"volume":"Vol.8","number":"No.20","starting_page":"10649","ending_page":"10658","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1039/c5nr08365f"],"issn":["2040-3372"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:52, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/110843","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/27698536","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84988934724&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=317555","label":"url"}],"paper_title":{"en":"Synergistic antioxidative effect of astaxanthin and tocotrienol by co-encapsulated in liposomes","ja":"Synergistic antioxidative effect of astaxanthin and tocotrienol by co-encapsulated in liposomes"},"authors":{"en":[{"name":"Kamezaki Chihiro"},{"name":"Nakashima Ami"},{"name":"Yamada Asako"},{"name":"Uenishi Sachiko"},{"name":"Ishibashi Hiroshi"},{"name":"Shibuya Natsumi"},{"name":"Hama Susumu"},{"name":"Hosoi Shinzo"},{"name":"Yamashita Eiji"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Kamezaki Chihiro"},{"name":"Nakashima Ami"},{"name":"Yamada Asako"},{"name":"Uenishi Sachiko"},{"name":"Ishibashi Hiroshi"},{"name":"Shibuya Natsumi"},{"name":"Hama Susumu"},{"name":"Hosoi Shinzo"},{"name":"Yamashita Eiji"},{"name":"小暮 健太朗"}]},"description":{"en":"Astaxanthin and vitamin E are both effective antioxidants that are frequently used in cosmetics, as food additives, and in to prevent oxidative damage. A combination of astaxanthin and vitamin E would be expected to show an additive anntioxidative effect. In this study, liposomes co-encapsulating astaxanthin and the vitamin E derivatives α-tocopherol (α-T) or tocotrienols (T3) were prepared, and the antioxidative activity of these liposomes toward singlet oxygen and hydroxyl radical was evaluated in vitro. Liposomes co-encapsulating astaxanthin and α-T showed no additive anntioxidative effect, while the actual scavenging activity of liposomes co-encapsulating astaxanthin and T3 was higher than the calculated additive activity. To clarify why this synergistic effect occurs, the most stable structure of astaxanthin in the presence of α-T or α-T3 was calculated. Only α-T3 was predicted to form hydrogen bonding with astaxanthin, and the astaxanthin polyene chain would partially interact with the α-T3 triene chain, which could explain why there was a synergistic effect between astaxanthin and T3 but not α-T. In conclusion, co-encapsulation of astaxanthin and T3 induces synergistic scavenging activity by intermolecular interactions between the two antioxidants.","ja":"Astaxanthin and vitamin E are both effective antioxidants that are frequently used in cosmetics, as food additives, and in to prevent oxidative damage. A combination of astaxanthin and vitamin E would be expected to show an additive anntioxidative effect. In this study, liposomes co-encapsulating astaxanthin and the vitamin E derivatives α-tocopherol (α-T) or tocotrienols (T3) were prepared, and the antioxidative activity of these liposomes toward singlet oxygen and hydroxyl radical was evaluated in vitro. Liposomes co-encapsulating astaxanthin and α-T showed no additive anntioxidative effect, while the actual scavenging activity of liposomes co-encapsulating astaxanthin and T3 was higher than the calculated additive activity. To clarify why this synergistic effect occurs, the most stable structure of astaxanthin in the presence of α-T or α-T3 was calculated. Only α-T3 was predicted to form hydrogen bonding with astaxanthin, and the astaxanthin polyene chain would partially interact with the α-T3 triene chain, which could explain why there was a synergistic effect between astaxanthin and T3 but not α-T. In conclusion, co-encapsulation of astaxanthin and T3 induces synergistic scavenging activity by intermolecular interactions between the two antioxidants."},"publication_date":"2016-04-15","publication_name":{"en":"Journal of Clinical Biochemistry and Nutrition","ja":"Journal of Clinical Biochemistry and Nutrition"},"volume":"Vol.59","number":"No.2","starting_page":"100","ending_page":"106","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3164/jcbn.15-153"],"issn":["0912-0009"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:53, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/110029","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26944781","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84961631654&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=310729","label":"url"}],"paper_title":{"en":"Faint electric treatment-induced rapid and efficient delivery of extraneous hydrophilic molecules into the cytoplasm","ja":"Faint electric treatment-induced rapid and efficient delivery of extraneous hydrophilic molecules into the cytoplasm"},"authors":{"en":[{"name":"Hasan Mahadi"},{"name":"Nishimoto Akinori"},{"name":"Ohgita Takashi"},{"name":"Hama Susumu"},{"name":"Kashida Hiromu"},{"name":"Asanuma Hiroyuki"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Hasan Mahadi"},{"name":"Nishimoto Akinori"},{"name":"Ohgita Takashi"},{"name":"Hama Susumu"},{"name":"Kashida Hiromu"},{"name":"Asanuma Hiroyuki"},{"name":"小暮 健太朗"}]},"description":{"en":"Effective delivery of extraneous molecules into the cytoplasm of the target cells is important for several drug therapies. Previously, we showed effective in vivo transdermal delivery of naked siRNA into skin cells induced by faint electric treatment (ET) iontophoresis, and significant suppression of target mRNA levels (Kigasawa et al., Int. J. Pharm., 2010). This result indicates that electricity promoted the delivery of siRNA into cytoplasm. In the present study, we analyzed the intracellular delivery of naked anti-luciferase siRNA by faint ET, and found that the luciferase activity of cells expressing luciferase was reduced by in vitro ET like in vivo iontophoresis. Cellular uptake of fluorescent-label siRNA was increased by ET, while low temperature exposure, macropinocytosis inhibitor amiloride and caveolae-mediated endocytosis inhibitor filipin significantly prevented siRNA uptake. These results indicate that the cellular uptake mechanism involved endocytosis. In addition, voltage sensitive fluorescent dye DiBAC4 (3) penetration was increased by ET, and the transient receptor potential channel inhibitor SKF96365 reduced siRNA uptake, suggesting that faint ET reduced membrane potentials by changing intracellular ion levels. Moreover, to analyze cytoplasmic delivery, we used in-stem molecular beacon (ISMB), which fluoresces upon binding to target mRNA in the cytoplasm. Surprisingly, cytoplasmic ISMB fluorescence appeared rapidly and homogeneously after ET, indicating that cytoplasmic delivery is markedly enhanced by ET. In conclusion, we demonstrated for the first time that faint ET can enhance cellular uptake and cytoplasmic delivery of extraneous molecules.","ja":"Effective delivery of extraneous molecules into the cytoplasm of the target cells is important for several drug therapies. Previously, we showed effective in vivo transdermal delivery of naked siRNA into skin cells induced by faint electric treatment (ET) iontophoresis, and significant suppression of target mRNA levels (Kigasawa et al., Int. J. Pharm., 2010). This result indicates that electricity promoted the delivery of siRNA into cytoplasm. In the present study, we analyzed the intracellular delivery of naked anti-luciferase siRNA by faint ET, and found that the luciferase activity of cells expressing luciferase was reduced by in vitro ET like in vivo iontophoresis. Cellular uptake of fluorescent-label siRNA was increased by ET, while low temperature exposure, macropinocytosis inhibitor amiloride and caveolae-mediated endocytosis inhibitor filipin significantly prevented siRNA uptake. These results indicate that the cellular uptake mechanism involved endocytosis. In addition, voltage sensitive fluorescent dye DiBAC4 (3) penetration was increased by ET, and the transient receptor potential channel inhibitor SKF96365 reduced siRNA uptake, suggesting that faint ET reduced membrane potentials by changing intracellular ion levels. Moreover, to analyze cytoplasmic delivery, we used in-stem molecular beacon (ISMB), which fluoresces upon binding to target mRNA in the cytoplasm. Surprisingly, cytoplasmic ISMB fluorescence appeared rapidly and homogeneously after ET, indicating that cytoplasmic delivery is markedly enhanced by ET. In conclusion, we demonstrated for the first time that faint ET can enhance cellular uptake and cytoplasmic delivery of extraneous molecules."},"publication_date":"2016-03-02","publication_name":{"en":"Journal of Controlled Release","ja":"Journal of Controlled Release"},"volume":"Vol.228","starting_page":"20","ending_page":"25","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jconrel.2016.02.048"],"issn":["1873-4995"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:54, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26667208","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=310732","label":"url"}],"paper_title":{"en":"Tri-membrane nanoparticles produced by combining liposome fusion and a novel patchwork of bicelles to overcome endosomal and nuclear membrane barriers to cargo delivery","ja":"Tri-membrane nanoparticles produced by combining liposome fusion and a novel patchwork of bicelles to overcome endosomal and nuclear membrane barriers to cargo delivery"},"authors":{"en":[{"name":"Yamada Asako"},{"name":"Mitsueda Asako"},{"name":"Hasan Mahadi"},{"name":"Ueda Miho"},{"name":"Hama Susumu"},{"name":"Warashina Shota"},{"name":"Nakamura Takashi"},{"name":"Harashima Hideyoshi"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Yamada Asako"},{"name":"Mitsueda Asako"},{"name":"Hasan Mahadi"},{"name":"Ueda Miho"},{"name":"Hama Susumu"},{"name":"Warashina Shota"},{"name":"Nakamura Takashi"},{"name":"Harashima Hideyoshi"},{"name":"小暮 健太朗"}]},"description":{"en":"Membrane fusion is a rational strategy for crossing intracellular membranes that present barriers to liposomal nanocarrier-mediated delivery of plasmid DNA into the nucleus of non-dividing cells, such as dendritic cells. Based on this strategy, we previously developed nanocarriers consisting of a nucleic acid core particle coated with four lipid membranes [Akita, et al., Biomaterials, 2009, 30, 2940-2949]. However, including the endosomal membrane and two nuclear membranes, cells possess three intracellular membranous barriers. Thus, after entering the nucleus, nanoparticles coated with four membranes would still have one lipid membrane remaining, and could impede cargo delivery. Until now, coating a core particle with an odd number of lipid membranes was challenging. To produce nanocarriers with an odd number of lipid membranes, we developed a novel coating method involving lipid nano-discs, also known as bicelles, as a material for packaging DNA in a carrier with an odd number of lipid membranes. In this procedure, bicelles fuse to form an outer coating that resembles a patchwork quilt, which allows the preparation of nanoparticles coated with only three lipid membranes. Moreover, the transfection activity of dendritic cells with these three-membrane nanoparticles was higher than that for nanoparticles coated with four lipid membranes. In summary, we developed novel nanoparticles coated with an odd number of lipid membranes using the novel \"patchwork-packaging method\" to deliver plasmid DNA into the nucleus via membrane fusion.","ja":"Membrane fusion is a rational strategy for crossing intracellular membranes that present barriers to liposomal nanocarrier-mediated delivery of plasmid DNA into the nucleus of non-dividing cells, such as dendritic cells. Based on this strategy, we previously developed nanocarriers consisting of a nucleic acid core particle coated with four lipid membranes [Akita, et al., Biomaterials, 2009, 30, 2940-2949]. However, including the endosomal membrane and two nuclear membranes, cells possess three intracellular membranous barriers. Thus, after entering the nucleus, nanoparticles coated with four membranes would still have one lipid membrane remaining, and could impede cargo delivery. Until now, coating a core particle with an odd number of lipid membranes was challenging. To produce nanocarriers with an odd number of lipid membranes, we developed a novel coating method involving lipid nano-discs, also known as bicelles, as a material for packaging DNA in a carrier with an odd number of lipid membranes. In this procedure, bicelles fuse to form an outer coating that resembles a patchwork quilt, which allows the preparation of nanoparticles coated with only three lipid membranes. Moreover, the transfection activity of dendritic cells with these three-membrane nanoparticles was higher than that for nanoparticles coated with four lipid membranes. In summary, we developed novel nanoparticles coated with an odd number of lipid membranes using the novel \"patchwork-packaging method\" to deliver plasmid DNA into the nucleus via membrane fusion."},"publication_date":"2016-02-23","publication_name":{"en":"Biomaterials Science","ja":"Biomaterials Science"},"volume":"Vol.4","number":"No.3","starting_page":"439","ending_page":"447","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1039/c5bm00327j"],"issn":["2047-4849"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:55, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/27150475","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84969579933&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=310731","label":"url"}],"paper_title":{"en":"Transmission of external environmental pH information to the inside of liposomes via pore-forming proteins embedded within the liposomal membrane","ja":"Transmission of external environmental pH information to the inside of liposomes via pore-forming proteins embedded within the liposomal membrane"},"authors":{"en":[{"name":"Takagi Keita"},{"name":"Ohgita Takashi"},{"name":"Yamamoto Takenori"},{"name":"Shinohara Yasuo"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Takagi Keita"},{"name":"Ohgita Takashi"},{"name":"山本 武範"},{"name":"篠原 康雄"},{"name":"小暮 健太朗"}]},"description":{"en":"Liposomes are closed-membrane vesicles comprised of lipid bilayers, in which the inside of the vesicles is isolated from the external environment. Liposomes are therefore often used as models for biomembranes and as drug delivery carriers. However, materials encapsulated within liposomes often cannot respond to changes in the external environment. The ability of enclosed materials to maintain their responsiveness to changes in the external environment following encapsulation into liposomes would greatly expand the applicability of such systems. We hypothesize that embedding pore-like \"access points\" into the liposomal membrane could allow for the transmission of information between the internal and external liposomal environments and thus overcome this inherent limitation of conventional liposomes. To investigate this, we evaluated whether a change in the pH of an external solution could be transmitted to the inside of liposomes through the pore-forming protein, yeast voltage-dependent anion channel (VDAC). Transmission of a pH change via VDAC was evaluated using a polyglutamic acid/doxorubicin complex (PGA/Dox) as an internal pH sensor. Upon encapsulation into conventional liposomes, PGA/Dox exhibits no pH sensitivity due to isolation from the external environment. On the other hand, PGA/Dox was found to retain its pH sensitivity upon encapsulation into VDAC-reconstituted liposomes, suggesting that VDAC facilitated the transmission of information on the pH of the external environment to the inside of the liposomes. In conclusion, we successfully demonstrated the transmission of information between the external and internal liposomal environments by a stable pore-like structure embedded into the liposomal membranes, which serve as access points.","ja":"Liposomes are closed-membrane vesicles comprised of lipid bilayers, in which the inside of the vesicles is isolated from the external environment. Liposomes are therefore often used as models for biomembranes and as drug delivery carriers. However, materials encapsulated within liposomes often cannot respond to changes in the external environment. The ability of enclosed materials to maintain their responsiveness to changes in the external environment following encapsulation into liposomes would greatly expand the applicability of such systems. We hypothesize that embedding pore-like \"access points\" into the liposomal membrane could allow for the transmission of information between the internal and external liposomal environments and thus overcome this inherent limitation of conventional liposomes. To investigate this, we evaluated whether a change in the pH of an external solution could be transmitted to the inside of liposomes through the pore-forming protein, yeast voltage-dependent anion channel (VDAC). Transmission of a pH change via VDAC was evaluated using a polyglutamic acid/doxorubicin complex (PGA/Dox) as an internal pH sensor. Upon encapsulation into conventional liposomes, PGA/Dox exhibits no pH sensitivity due to isolation from the external environment. On the other hand, PGA/Dox was found to retain its pH sensitivity upon encapsulation into VDAC-reconstituted liposomes, suggesting that VDAC facilitated the transmission of information on the pH of the external environment to the inside of the liposomes. In conclusion, we successfully demonstrated the transmission of information between the external and internal liposomal environments by a stable pore-like structure embedded into the liposomal membranes, which serve as access points."},"publication_date":"2016","publication_name":{"en":"Chemical & Pharmaceutical Bulletin","ja":"Chemical & Pharmaceutical Bulletin"},"volume":"Vol.64","number":"No.5","starting_page":"432","ending_page":"438","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/cpb.c15-00985"],"issn":["1347-5223"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:56, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://cir.nii.ac.jp/crid/1390001205191889280/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=310728","label":"url"}],"paper_title":{"en":"食品に含まれるグリコシルイノシトールホスホセラミドおよびフィトセラミド-1-リン酸","ja":"食品に含まれるグリコシルイノシトールホスホセラミドおよびフィトセラミド-1-リン酸"},"authors":{"en":[{"name":"喜田 孝史"},{"name":"木村 朱里"},{"name":"伊藤 葵"},{"name":"山下 量平"},{"name":"Kogure Kentaro"},{"name":"Tokumura Akira"},{"name":"Tanaka Tamotsu"}],"ja":[{"name":"喜田 孝史"},{"name":"木村 朱里"},{"name":"伊藤 葵"},{"name":"山下 量平"},{"name":"小暮 健太朗"},{"name":"德村 彰"},{"name":"田中 保"}]},"publication_date":"2016","publication_name":{"en":"Journal of Lipid Nutrition","ja":"脂質栄養学"},"volume":"Vol.25","starting_page":"75","ending_page":"85","languages":["jpn"],"referee":true,"identifiers":{"doi":["10.4010/jln.25.75"],"issn":["1343-4594"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:57, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26694604","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84957439211&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=310727","label":"url"}],"paper_title":{"en":"Analysis of molecular species profiles of ceramide-1-phosphate and sphingomyelin using MALDI-TOF mass spectrometry","ja":"Analysis of molecular species profiles of ceramide-1-phosphate and sphingomyelin using MALDI-TOF mass spectrometry"},"authors":{"en":[{"name":"Yamashita Ryouhei"},{"name":"Tabata Yumika"},{"name":"Iga Erina"},{"name":"Nakao Michiyasu"},{"name":"Sano Shigeki"},{"name":"Kogure Kentaro"},{"name":"Tokumura Akira"},{"name":"Tanaka Tamotsu"}],"ja":[{"name":"Yamashita Ryouhei"},{"name":"Tabata Yumika"},{"name":"Iga Erina"},{"name":"中尾 允泰"},{"name":"佐野 茂樹"},{"name":"小暮 健太朗"},{"name":"德村 彰"},{"name":"田中 保"}]},"description":{"en":"Ceramide-1-phosphate (C1P) is a potential signaling molecule that modulates various cellular functions in animals. It has been known that C1P with different N-acyl lengths induce biological responses differently. However, molecular species profiles of the C1P in animal tissues have not been extensively examined yet. Here, we developed a method for determination of the molecular species of a C1P using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with Phos-tag, a phosphate capture molecule. The amounts of total C1P in skin, brain, liver, kidney and small intestine of mice were determined to be 344, 151, 198, 96 and 90 pmol/g wet weight, respectively. We found a C1P species having an α-hydroxypalmitoyl residue (h-C1P, 44 pmol/g wet weight) in mouse skin. The h-C1P was detected only in the skin, and not other tissues of mice. The same analysis was applied to sphingomyelin after conversion of sphingomyelin to C1P by Streptomyces chromofuscus phospholipase D. We found that molecular species profiles of sphingomyelin in skin, kidney and small intestine of mice were similar to those of C1P in corresponding tissues. In contrast, molecular species profiles of sphingomyelin in liver and brain were quite different from those of C1P in these tissues, indicating selective synthesis or degradation of C1P in these tissues. The method described here will be useful for detection of changes in molecular species profiles of C1P and sphingomyelin.","ja":"Ceramide-1-phosphate (C1P) is a potential signaling molecule that modulates various cellular functions in animals. It has been known that C1P with different N-acyl lengths induce biological responses differently. However, molecular species profiles of the C1P in animal tissues have not been extensively examined yet. Here, we developed a method for determination of the molecular species of a C1P using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with Phos-tag, a phosphate capture molecule. The amounts of total C1P in skin, brain, liver, kidney and small intestine of mice were determined to be 344, 151, 198, 96 and 90 pmol/g wet weight, respectively. We found a C1P species having an α-hydroxypalmitoyl residue (h-C1P, 44 pmol/g wet weight) in mouse skin. The h-C1P was detected only in the skin, and not other tissues of mice. The same analysis was applied to sphingomyelin after conversion of sphingomyelin to C1P by Streptomyces chromofuscus phospholipase D. We found that molecular species profiles of sphingomyelin in skin, kidney and small intestine of mice were similar to those of C1P in corresponding tissues. In contrast, molecular species profiles of sphingomyelin in liver and brain were quite different from those of C1P in these tissues, indicating selective synthesis or degradation of C1P in these tissues. The method described here will be useful for detection of changes in molecular species profiles of C1P and sphingomyelin."},"publication_date":"2016","publication_name":{"en":"Lipids","ja":"Lipids"},"volume":"Vol.51","number":"No.2","starting_page":"263","ending_page":"270","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s11745-015-4082-0"],"issn":["1558-9307"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:58, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/18054323","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=192166","label":"url"}],"paper_title":{"en":"MITO-Porter: A liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion.","ja":"MITO-Porter: A liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion."},"authors":{"en":[{"name":"Yamada Yuma"},{"name":"Akita Hidetaka"},{"name":"Kamiya Hiroyuki"},{"name":"Kogure Kentaro"},{"name":"Yamamoto Takenori"},{"name":"Shinohara Yasuo"},{"name":"Yamashita Kikuji"},{"name":"Kobayashi Hideo"},{"name":"Kikuchi Hiroshi"},{"name":"Harashima Hideyoshi"}],"ja":[{"name":"Yamada Yuma"},{"name":"Akita Hidetaka"},{"name":"Kamiya Hiroyuki"},{"name":"小暮 健太朗"},{"name":"山本 武範"},{"name":"篠原 康雄"},{"name":"山下 菊治"},{"name":"Kobayashi Hideo"},{"name":"Kikuchi Hiroshi"},{"name":"Harashima Hideyoshi"}]},"description":{"en":"Mitochondria are the principal producers of energy in higher cells. Mitochondrial dysfunction is implicated in a variety of human diseases, including cancer and neurodegenerative disorders. Effective medical therapies for such diseases will ultimately require targeted delivery of therapeutic proteins or nucleic acids to the mitochondria, which will be achieved through innovations in the nanotechnology of intracellular trafficking. Here we describe a liposome-based carrier that delivers its macromolecular cargo to the mitochondrial interior via membrane fusion. These liposome particles, which we call MITO-Porters, carry octaarginine surface modifications to stimulate their entry into cells as intact vesicles (via macropinocytosis). We identified lipid compositions for the MITO-Porter which promote both its fusion with the mitochondrial membrane and the release of its cargo to the intra-mitochondrial compartment in living cells. Thus, the MITO-Porter holds promise as an efficacious system for the delivery of both large and small therapeutic molecules into mitochondria.","ja":"Mitochondria are the principal producers of energy in higher cells. Mitochondrial dysfunction is implicated in a variety of human diseases, including cancer and neurodegenerative disorders. Effective medical therapies for such diseases will ultimately require targeted delivery of therapeutic proteins or nucleic acids to the mitochondria, which will be achieved through innovations in the nanotechnology of intracellular trafficking. Here we describe a liposome-based carrier that delivers its macromolecular cargo to the mitochondrial interior via membrane fusion. These liposome particles, which we call MITO-Porters, carry octaarginine surface modifications to stimulate their entry into cells as intact vesicles (via macropinocytosis). We identified lipid compositions for the MITO-Porter which promote both its fusion with the mitochondrial membrane and the release of its cargo to the intra-mitochondrial compartment in living cells. Thus, the MITO-Porter holds promise as an efficacious system for the delivery of both large and small therapeutic molecules into mitochondria."},"publication_date":"2007-11-12","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - Biomembranes","ja":"Biochimica et Biophysica Acta (BBA) - Biomembranes"},"volume":"Vol.1778","number":"No.2","starting_page":"423","ending_page":"432","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbamem.2007.11.002"],"issn":["0005-2736"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:59, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16521697","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-31444446546&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=145002","label":"url"}],"paper_title":{"en":"Cytotoxicity of α-tocopheryl succinate, malonate and oxalate in normal and cancer cells in vitro and their anti-cancer effects on mouse melanoma in vivo","ja":"Cytotoxicity of α-tocopheryl succinate, malonate and oxalate in normal and cancer cells in vitro and their anti-cancer effects on mouse melanoma in vivo"},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"Manabe Sachie"},{"name":"Suzuki Ichiro"},{"name":"Tokumura Akira"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"小暮 健太朗"},{"name":"Manabe Sachie"},{"name":"鈴木 一郎"},{"name":"德村 彰"},{"name":"福澤 健治"}]},"description":{"en":"alpha-Tocopheryl succinate (TS), which is known to induce apoptosis selectively in cancer cells, has attracted attention as a chemotherapeutic agent. Recently, we found that alpha-tocopheryl malonate (TM) and alpha-tocopheryl oxalate (TO), among the alpha-tocopheryl esters tested, have high apoptogenic activity as well as TS. In this study, we investigated the characteristics of their cytotoxicity on normal cells and cancer cells in vitro, and their anti-cancer effects on mice inoculated with melanoma B16-F1 cells in vivo. The order of in vitro cytotoxicity was TO > or = TM > TS in all cell lines examined. Addition of exogenous superoxide dismutase (SOD) and the antioxidant N-acetyl cysteine (NAC) inhibited TS- and TM- but not TO-induced cell deaths. A selective cytotoxic effect on cancer cells was observed with TS but not with TM or TO. c-Jun N-terminal kinase (JNK) inhibitor II prevented cell death induced by TS but did not prevent cell deaths induced either by TM or TO. Intravenous administration of vesiculated TS and TM to mice inoculated with melanoma B16-F1 cells prevented tumor growth and enhanced the mean survival time, but TO administration killed the mice due to its acute high toxicity. From these results, we discussed the characteristics of their selective cytotoxicity toward tumor cells in vitro and anti-cancer effects in vivo.","ja":"alpha-Tocopheryl succinate (TS), which is known to induce apoptosis selectively in cancer cells, has attracted attention as a chemotherapeutic agent. Recently, we found that alpha-tocopheryl malonate (TM) and alpha-tocopheryl oxalate (TO), among the alpha-tocopheryl esters tested, have high apoptogenic activity as well as TS. In this study, we investigated the characteristics of their cytotoxicity on normal cells and cancer cells in vitro, and their anti-cancer effects on mice inoculated with melanoma B16-F1 cells in vivo. The order of in vitro cytotoxicity was TO > or = TM > TS in all cell lines examined. Addition of exogenous superoxide dismutase (SOD) and the antioxidant N-acetyl cysteine (NAC) inhibited TS- and TM- but not TO-induced cell deaths. A selective cytotoxic effect on cancer cells was observed with TS but not with TM or TO. c-Jun N-terminal kinase (JNK) inhibitor II prevented cell death induced by TS but did not prevent cell deaths induced either by TM or TO. Intravenous administration of vesiculated TS and TM to mice inoculated with melanoma B16-F1 cells prevented tumor growth and enhanced the mean survival time, but TO administration killed the mice due to its acute high toxicity. From these results, we discussed the characteristics of their selective cytotoxicity toward tumor cells in vitro and anti-cancer effects in vivo."},"publication_date":"2005-12","publication_name":{"en":"Journal of Nutritional Science and Vitaminology","ja":"Journal of Nutritional Science and Vitaminology"},"volume":"Vol.51","number":"No.6","starting_page":"392","ending_page":"397","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3177/jnsv.51.392"],"issn":["0301-4800"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:60, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15670740","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=144836","label":"url"}],"paper_title":{"en":"Antioxidant effect of bovine serum albumin on membrane lipid peroxidation induced by iron chelate and superoxide","ja":"Antioxidant effect of bovine serum albumin on membrane lipid peroxidation induced by iron chelate and superoxide"},"authors":{"en":[{"name":"Fukuzawa Kenji"},{"name":"Saitoh Yasuaki"},{"name":"Akai Kaori"},{"name":"Kogure Kentaro"},{"name":"Ueno Satoru"},{"name":"Tokumura Akira"},{"name":"Otagiri Masaki"},{"name":"Shibata Akira"}],"ja":[{"name":"福澤 健治"},{"name":"Saitoh Yasuaki"},{"name":"Akai Kaori"},{"name":"小暮 健太朗"},{"name":"植野 哲"},{"name":"德村 彰"},{"name":"Otagiri Masaki"},{"name":"Shibata Akira"}]},"description":{"en":"Albumin is supposed to be the major antioxidant circulating in blood. This study examined the prevention of membrane lipid peroxidation by bovine serum albumin (BSA). Lipid peroxidation was induced by the exposing of enzymatically generated superoxide radicals to egg yolk phosphatidylcholine liposomes incorporating lipids with different charges in the presence of chelated iron catalysts. We used three kinds of Fe3+-chelates, which initiated reactions that were dependent on membrane charge: Fe3+-EDTA and Fe3+-EGTA catalyzed peroxidation in positively and negatively charged liposomes, respectively, and Fe3+-NTA, a renal carcinogen, catalyzed the reaction in liposomes of either charge. Fe3+-chelates initiated more lipid peroxidation in liposomes with increased zeta potentials, followed by an increase of their availability for the initiation of the reaction at the membrane surface. BSA inhibits lipid peroxidation by preventing the interaction of iron chelate with membranes, followed by a decrease of its availability in a charge-dependent manner depending on the iron-chelate concentration: one is accompanied and the other is unaccompanied by a change in the membrane charge. The inhibitory effect of BSA in the former at high concentrations of iron chelate would be attributed to its electrostatic binding with oppositely charged membranes. The inhibitory effect in the latter at low concentrations of iron chelate would be caused by BSA binding with iron chelates and keeping them away from membrane surface where lipid peroxidation is initiated. Although these results warrant further in vivo investigation, it was concluded that BSA inhibits membrane lipid peroxidation by decreasing the availability of iron for the initiation of membrane lipid peroxidation, in addition to trapping active oxygens and free radicals.","ja":"Albumin is supposed to be the major antioxidant circulating in blood. This study examined the prevention of membrane lipid peroxidation by bovine serum albumin (BSA). Lipid peroxidation was induced by the exposing of enzymatically generated superoxide radicals to egg yolk phosphatidylcholine liposomes incorporating lipids with different charges in the presence of chelated iron catalysts. We used three kinds of Fe3+-chelates, which initiated reactions that were dependent on membrane charge: Fe3+-EDTA and Fe3+-EGTA catalyzed peroxidation in positively and negatively charged liposomes, respectively, and Fe3+-NTA, a renal carcinogen, catalyzed the reaction in liposomes of either charge. Fe3+-chelates initiated more lipid peroxidation in liposomes with increased zeta potentials, followed by an increase of their availability for the initiation of the reaction at the membrane surface. BSA inhibits lipid peroxidation by preventing the interaction of iron chelate with membranes, followed by a decrease of its availability in a charge-dependent manner depending on the iron-chelate concentration: one is accompanied and the other is unaccompanied by a change in the membrane charge. The inhibitory effect of BSA in the former at high concentrations of iron chelate would be attributed to its electrostatic binding with oppositely charged membranes. The inhibitory effect in the latter at low concentrations of iron chelate would be caused by BSA binding with iron chelates and keeping them away from membrane surface where lipid peroxidation is initiated. Although these results warrant further in vivo investigation, it was concluded that BSA inhibits membrane lipid peroxidation by decreasing the availability of iron for the initiation of membrane lipid peroxidation, in addition to trapping active oxygens and free radicals."},"publication_date":"2005-02-01","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - Biomembranes","ja":"Biochimica et Biophysica Acta (BBA) - Biomembranes"},"volume":"Vol.1668","number":"No.1","starting_page":"145","ending_page":"155","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbamem.2004.12.006"],"issn":["0005-2736"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:61, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://dx.doi.org/10.1016/j.phymed.2003.09.004","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15636179","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=127100","label":"url"}],"paper_title":{"en":"Novel antioxidants isolated from plants of the genera Ferula, Inula, Prangos and Rheum collected in Uzbekistan","ja":"Novel antioxidants isolated from plants of the genera Ferula, Inula, Prangos and Rheum collected in Uzbekistan"},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"Yamauchi Aiko"},{"name":"Tokumura Akira"},{"name":"Kondou Kyoko"},{"name":"Tanaka Naonobu"},{"name":"Takaishi Yoshihisa"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"小暮 健太朗"},{"name":"山内 あい子"},{"name":"德村 彰"},{"name":"Kondou Kyoko"},{"name":"田中 直伸"},{"name":"高石 喜久"},{"name":"福澤 健治"}]},"description":{"en":"We examined the effects of 48 compounds isolated from Ferula pallida, F. penninervis, Inula macrophylla, Prangos pabularia, P. tschimganica and Rheum maximowiczii collected in Uzbekistan on ADP/Fe2+-induced lipid peroxidation of egg yolk phosphatidylcholine liposomes. Of those compounds, 23 inhibited ADP/Fe2+-induced lipid peroxidation and nine showed especially strong inhibition of lipid peroxidation. Most compounds that inhibited peroxidation scavenged the 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical, indicating that the inhibition was due to radical scavenging. However, some compounds did not scavenge DPPH but inhibited lipid peroxidation significantly, suggesting that their inhibitory effect was not due to radical scavenging but to some other mechanism, such as prevention of Fe2+ function. Thus, we found various new antioxidants, some of which had a unique mechanism of action, in Ferula, Inula, Prangos and Rheum plants collected in Uzbekistan as seeds used in medicine.","ja":"We examined the effects of 48 compounds isolated from Ferula pallida, F. penninervis, Inula macrophylla, Prangos pabularia, P. tschimganica and Rheum maximowiczii collected in Uzbekistan on ADP/Fe2+-induced lipid peroxidation of egg yolk phosphatidylcholine liposomes. Of those compounds, 23 inhibited ADP/Fe2+-induced lipid peroxidation and nine showed especially strong inhibition of lipid peroxidation. Most compounds that inhibited peroxidation scavenged the 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical, indicating that the inhibition was due to radical scavenging. However, some compounds did not scavenge DPPH but inhibited lipid peroxidation significantly, suggesting that their inhibitory effect was not due to radical scavenging but to some other mechanism, such as prevention of Fe2+ function. Thus, we found various new antioxidants, some of which had a unique mechanism of action, in Ferula, Inula, Prangos and Rheum plants collected in Uzbekistan as seeds used in medicine."},"publication_date":"2004-11-25","publication_name":{"en":"Phytomedicine","ja":"Phytomedicine"},"volume":"Vol.11","number":"No.7-8","starting_page":"645","ending_page":"651","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.phymed.2003.09.004"],"issn":["0944-7113"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:62, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15621713","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=113758","label":"url"}],"paper_title":{"en":"Ability of ferric nitrilotriacetate complex with three pH-dependent conformations to induce lipid peroxidation.","ja":"Ability of ferric nitrilotriacetate complex with three pH-dependent conformations to induce lipid peroxidation."},"authors":{"en":[{"name":"Akai Kaori"},{"name":"Tsuchiya Koichiro"},{"name":"Tokumura Akira"},{"name":"Kogure Kentaro"},{"name":"Ueno Satoru"},{"name":"Shibata Akira"},{"name":"Tamaki Toshiaki"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"Akai Kaori"},{"name":"土屋 浩一郎"},{"name":"德村 彰"},{"name":"小暮 健太朗"},{"name":"植野 哲"},{"name":"柴田 瑩"},{"name":"玉置 俊晃"},{"name":"福澤 健治"}]},"publication_date":"2004-09","publication_name":{"en":"Free Radical Research","ja":"Free Radical Research"},"volume":"Vol.38","number":"No.9","starting_page":"951","ending_page":"962","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1080/1071576042000261945"],"issn":["1071-5762"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:63, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://dx.doi.org/10.1021/np0304823","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15217293","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=127102","label":"url"}],"paper_title":{"en":"New Stilbene Derivatives from Calligonum leucocladum","ja":"New Stilbene Derivatives from Calligonum leucocladum"},"authors":{"en":[{"name":"Okasaka Mamoru"},{"name":"Takaishi Yoshihisa"},{"name":"Kogure Kentaro"},{"name":"Fukuzawa Kenji"},{"name":"Shibata Hirofumi"},{"name":"Higuti Tomihiko"},{"name":"Honda Gisho"},{"name":"Ito Michiho"},{"name":"Kodzhimatov K. Olimjon"},{"name":"Ashurmetov Ozodbek"}],"ja":[{"name":"Okasaka Mamoru"},{"name":"高石 喜久"},{"name":"小暮 健太朗"},{"name":"福澤 健治"},{"name":"柴田 洋文"},{"name":"樋口 富彦"},{"name":"Honda Gisho"},{"name":"Ito Michiho"},{"name":"Kodzhimatov K. Olimjon"},{"name":"Ashurmetov Ozodbek"}]},"description":{"en":"Two new stilbene derivatives, (E)-resveratrol 3-(6' '-galloyl)-O-beta-D-glucopyranoside (1) and (E)-resveratrol 3-(4' '-acetyl)-O-beta-D-xylopyranoside (2), and five known stilbene derivatives (3-7) were isolated from the dried aerial parts of Calligonum leucocladum. Their structures were established on the basis of spectroscopic evidence. Compound 1 showed antioxidant activity and a restorative effect of the inhibition of oxacillin to oxacillin/methicillin-resistant Staphylococcus aureus.","ja":"Two new stilbene derivatives, (E)-resveratrol 3-(6' '-galloyl)-O-beta-D-glucopyranoside (1) and (E)-resveratrol 3-(4' '-acetyl)-O-beta-D-xylopyranoside (2), and five known stilbene derivatives (3-7) were isolated from the dried aerial parts of Calligonum leucocladum. Their structures were established on the basis of spectroscopic evidence. Compound 1 showed antioxidant activity and a restorative effect of the inhibition of oxacillin to oxacillin/methicillin-resistant Staphylococcus aureus."},"publication_date":"2004-06","publication_name":{"en":"Journal of Natural Products","ja":"Journal of Natural Products"},"volume":"Vol.67","number":"No.6","starting_page":"1044","ending_page":"1046","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1021/np0304823"],"issn":["0163-3864"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:64, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15110091","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-1942510597&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=98310","label":"url"}],"paper_title":{"en":"Structural characteristic of terminal dicarboxyric moiety required for apoptogenic activity of α-Tocopheryl esters.","ja":"Structural characteristic of terminal dicarboxyric moiety required for apoptogenic activity of α-Tocopheryl esters."},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"Hama Susumu"},{"name":"Kisaki Mayumi"},{"name":"Takemasa Hideaki"},{"name":"Tokumura Akira"},{"name":"Suzuki Ichiro"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"小暮 健太朗"},{"name":"Hama Susumu"},{"name":"Kisaki Mayumi"},{"name":"Takemasa Hideaki"},{"name":"德村 彰"},{"name":"鈴木 一郎"},{"name":"福澤 健治"}]},"description":{"en":"alpha-Tocopheryl succinate (TS) is known to induce apoptosis in various cells and has attracted attention as a chemotherapeutic agent. Recently, we reported the structural significance of the terminal dicarboxylic moiety for the action of TS [J. Nutr. Sci. Vitaminol. 49 (2003) 310-314]. In this study, to determine details of the relationship between the structure and the function of the terminal ester moiety of alpha-tocopherol (alpha-T), we synthesized four novel esters, alpha-tocopheryl oxalate (TO), alpha-tocopheryl malonate (TM), alpha-tocopheryl pimelate (TP) and alpha-tocopheryl succinate ethyl ester (TSE), and compared their apoptogenic activities with those of TS, alpha-T, gamma-tocopherol (gamma-T) and two commercially available alpha-T derivatives, alpha-tocopheryl nicotinate (TN) and alpha-tocopheryl acetate (TA), in vascular smooth muscle cells and a mouse breast cancer cell line C127I. TO and TM in addition to TS, but not the others, induced apoptosis in both cells. Particularly, TO was the most potent of all alpha-T derivatives used. The addition of exogenous superoxide dismutase (SOD) significantly prevented the apoptosis induced by TM as well as that by TS as reported previously, but did not affect TO-induced apoptosis. These results suggest that O(2)(-) generated exogenously participates in TM-induced apoptosis but not in TO-induced apoptosis. The difference in their apoptotic effects is attributed to structural properties of the terminal dicarboxylic moiety, which has an inflexible plane conformation in TO, while it is highly flexible in TM and TS.","ja":"alpha-Tocopheryl succinate (TS) is known to induce apoptosis in various cells and has attracted attention as a chemotherapeutic agent. Recently, we reported the structural significance of the terminal dicarboxylic moiety for the action of TS [J. Nutr. Sci. Vitaminol. 49 (2003) 310-314]. In this study, to determine details of the relationship between the structure and the function of the terminal ester moiety of alpha-tocopherol (alpha-T), we synthesized four novel esters, alpha-tocopheryl oxalate (TO), alpha-tocopheryl malonate (TM), alpha-tocopheryl pimelate (TP) and alpha-tocopheryl succinate ethyl ester (TSE), and compared their apoptogenic activities with those of TS, alpha-T, gamma-tocopherol (gamma-T) and two commercially available alpha-T derivatives, alpha-tocopheryl nicotinate (TN) and alpha-tocopheryl acetate (TA), in vascular smooth muscle cells and a mouse breast cancer cell line C127I. TO and TM in addition to TS, but not the others, induced apoptosis in both cells. Particularly, TO was the most potent of all alpha-T derivatives used. The addition of exogenous superoxide dismutase (SOD) significantly prevented the apoptosis induced by TM as well as that by TS as reported previously, but did not affect TO-induced apoptosis. These results suggest that O(2)(-) generated exogenously participates in TM-induced apoptosis but not in TO-induced apoptosis. The difference in their apoptotic effects is attributed to structural properties of the terminal dicarboxylic moiety, which has an inflexible plane conformation in TO, while it is highly flexible in TM and TS."},"publication_date":"2004-05-03","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - General Subjects","ja":"Biochimica et Biophysica Acta (BBA) - General Subjects"},"volume":"Vol.1672","number":"No.2","starting_page":"93","ending_page":"99","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbagen.2004.03.001"],"issn":["0304-4165"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:65, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://dx.doi.org/10.1016/S0031-9422(03)00422-9","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/14561516","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=116148","label":"url"}],"paper_title":{"en":"Two lignan dimers from bamboo stems (Phyllostachys edulis)","ja":"Two lignan dimers from bamboo stems (Phyllostachys edulis)"},"authors":{"en":[{"name":"Suga Ai"},{"name":"Takaishi Yoshihisa"},{"name":"GOTO Satoru"},{"name":"Munakata Tatsuo"},{"name":"Yamauchi Izumi"},{"name":"Kogure Kentaro"}],"ja":[{"name":"菅 愛"},{"name":"高石 喜久"},{"name":"後藤 了"},{"name":"宗像 達夫"},{"name":"山内 いずみ"},{"name":"小暮 健太朗"}]},"description":{"en":"Phyllostadimers A and B, two bis-lignans in which the two lignan units are directly connected by a C-C bond, were isolated from stems of bamboo, Phyllostachys edulis. Their structures were determined on the basis of spectral evidence. In addition, 14 known compounds were also obtained throughout the investigation. Phyllostadimer A significantly inhibited liposomal lipid peroxidation.","ja":"Phyllostadimers A and B, two bis-lignans in which the two lignan units are directly connected by a C-C bond, were isolated from stems of bamboo, Phyllostachys edulis. Their structures were determined on the basis of spectral evidence. In addition, 14 known compounds were also obtained throughout the investigation. Phyllostadimer A significantly inhibited liposomal lipid peroxidation."},"publication_date":"2003-11","publication_name":{"en":"Phytochemistry","ja":"Phytochemistry"},"volume":"Vol.64","number":"No.5","starting_page":"991","ending_page":"996","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0031-9422(03)00422-9"],"issn":["0031-9422"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:66, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/14580708","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0142090711&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=98313","label":"url"}],"paper_title":{"en":"Temporary membrane distortion of vascular smooth muscle cells is responsible for their apoptosis induced by platelet-activating factor-like oxidized phospholipids and thair degradation product lysophosphatidylcholine.","ja":"Temporary membrane distortion of vascular smooth muscle cells is responsible for their apoptosis induced by platelet-activating factor-like oxidized phospholipids and thair degradation product lysophosphatidylcholine."},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"Nakashima Sawa"},{"name":"Tsuchie Akiko"},{"name":"Tokumura Akira"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"小暮 健太朗"},{"name":"Nakashima Sawa"},{"name":"Tsuchie Akiko"},{"name":"德村 彰"},{"name":"福澤 健治"}]},"description":{"en":"To obtain information about the mechanism of apoptosis induced by oxidized low density lipoproteins (oxLDL) in atherosclerotic plaques, we examined the effects of lysophosphatidylcholine (LPC) and platelet-activating factor (PAF)-like lipids (PAF-LL), which can be derived from oxLDL, on rat vascular smooth muscle cells (VSMC). All the lipids with different structures examined induced apoptosis of VSMC, so we studied the mechanism of induction of apoptosis by LPC. LPC-induced apoptosis was inhibited by alpha-tocopherol (alpha-T) and cholesterol (Chol), but not by other antioxidants such as palmitoyl ascorbic acid and PAF receptor antagonist. The cells temporarily became spherical and highly permeable before induction of apoptosis, and their change in shape was prevented by alpha-T and Chol. From these results, we suggest that the apoptosis induced by oxLDL-derived phospholipids in VSMC is caused by temporary membrane distortion, not through specific receptors.","ja":"To obtain information about the mechanism of apoptosis induced by oxidized low density lipoproteins (oxLDL) in atherosclerotic plaques, we examined the effects of lysophosphatidylcholine (LPC) and platelet-activating factor (PAF)-like lipids (PAF-LL), which can be derived from oxLDL, on rat vascular smooth muscle cells (VSMC). All the lipids with different structures examined induced apoptosis of VSMC, so we studied the mechanism of induction of apoptosis by LPC. LPC-induced apoptosis was inhibited by alpha-tocopherol (alpha-T) and cholesterol (Chol), but not by other antioxidants such as palmitoyl ascorbic acid and PAF receptor antagonist. The cells temporarily became spherical and highly permeable before induction of apoptosis, and their change in shape was prevented by alpha-T and Chol. From these results, we suggest that the apoptosis induced by oxLDL-derived phospholipids in VSMC is caused by temporary membrane distortion, not through specific receptors."},"publication_date":"2003-11","publication_name":{"en":"Chemistry and Physics of Lipids","ja":"Chemistry and Physics of Lipids"},"volume":"Vol.126","number":"No.1","starting_page":"29","ending_page":"38","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0009-3084(03)00091-4"],"issn":["0009-3084"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:67, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/10012074064/","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/14703304","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390001206326223360/","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0242492228&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=116151","label":"url"}],"paper_title":{"en":"alpha-Tocopheryl succinate activates protein kinase C in cellular and cell-free systems","ja":"alpha-Tocopheryl succinate activates protein kinase C in cellular and cell-free systems"},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"Hama Susumu"},{"name":"GOTO Satoru"},{"name":"Munakata Tatsuo"},{"name":"Tokumura Akira"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"小暮 健太朗"},{"name":"濱 進"},{"name":"後藤 了"},{"name":"宗像 達夫"},{"name":"德村 彰"},{"name":"福澤 健治"}]},"description":{"en":"The effect of alpha-tocopheryl succinate (TS) on protein kinase C (PKC) activity was examined. TS increased the auto-phosphorylation of PKC in vascular smooth muscle cells. Furthermore TS activated isolated PKC-like phorbol 12-myristate 13-acetate (PMA), although it was required at a significantly higher concentration than PMA for PKC activation. Molecular superimposition of the TS on PMA by computation suggested that TS took an active binding conformation to the PKC-like PMA, but that the conformational population was about 1/1.000. Consequently, we conclude that TS interacts directly with PKC, and activates it by taking an active conformation like PMA.","ja":"The effect of alpha-tocopheryl succinate (TS) on protein kinase C (PKC) activity was examined. TS increased the auto-phosphorylation of PKC in vascular smooth muscle cells. Furthermore TS activated isolated PKC-like phorbol 12-myristate 13-acetate (PMA), although it was required at a significantly higher concentration than PMA for PKC activation. Molecular superimposition of the TS on PMA by computation suggested that TS took an active binding conformation to the PKC-like PMA, but that the conformational population was about 1/1.000. Consequently, we conclude that TS interacts directly with PKC, and activates it by taking an active conformation like PMA."},"publication_date":"2003-10-01","publication_name":{"en":"Journal of Nutritional Science and Vitaminology","ja":"Journal of Nutritional Science and Vitaminology"},"volume":"Vol.49","number":"No.5","starting_page":"310","ending_page":"314","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3177/jnsv.49.310"],"issn":["0301-4800"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:68, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12829254","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=113748","label":"url"}],"paper_title":{"en":"Direct radical scavenging by the bisbenzylisoquinoline alkaloid cepharanthine.","ja":"Direct radical scavenging by the bisbenzylisoquinoline alkaloid cepharanthine."},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"Tsuchiya Koichiro"},{"name":"Abe Kazutoyo"},{"name":"Akasu Michinori"},{"name":"Tamaki Toshiaki"},{"name":"Fukuzawa Kenji"},{"name":"Terada Hiroshi"}],"ja":[{"name":"小暮 健太朗"},{"name":"土屋 浩一郎"},{"name":"Abe Kazutoyo"},{"name":"Akasu Michinori"},{"name":"玉置 俊晃"},{"name":"福澤 健治"},{"name":"Terada Hiroshi"}]},"description":{"en":"Cepharanthine (Ceph) is known as a potent antiperoxidative agent. Recently, we characterized the antiperoxidative effects of Ceph [Biochim. Biophys. Acta 1426 (1999) 133]. However, it was not clear whether the antiperoxidative effect is really due to its direct radical scavenging activity. Therefore, we studied the interaction of Ceph with the hydroxyl radical (*OH) by the electron paramagnetic resonance (EPR) technique. Results showed that Ceph actually scavenged *OH derived by the Fenton reaction. We also found that Ceph radicals were generated on interaction of Ceph with *OH in neutral aqueous solution, but not in acidic solution, consistent with the pH-dependent anti-lipid peroxidation activity of Ceph. Hence, we concluded that anti-lipid peroxidation by Ceph is due to its direct radical scavenging activity.","ja":"Cepharanthine (Ceph) is known as a potent antiperoxidative agent. Recently, we characterized the antiperoxidative effects of Ceph [Biochim. Biophys. Acta 1426 (1999) 133]. However, it was not clear whether the antiperoxidative effect is really due to its direct radical scavenging activity. Therefore, we studied the interaction of Ceph with the hydroxyl radical (*OH) by the electron paramagnetic resonance (EPR) technique. Results showed that Ceph actually scavenged *OH derived by the Fenton reaction. We also found that Ceph radicals were generated on interaction of Ceph with *OH in neutral aqueous solution, but not in acidic solution, consistent with the pH-dependent anti-lipid peroxidation activity of Ceph. Hence, we concluded that anti-lipid peroxidation by Ceph is due to its direct radical scavenging activity."},"publication_date":"2003-06-20","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - General Subjects","ja":"Biochimica et Biophysica Acta (BBA) - General Subjects"},"volume":"Vol.1622","number":"No.1","starting_page":"1","ending_page":"5","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0304-4165(03)00095-3"],"issn":["0304-4165"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:69, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12637149","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0037456691&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=98316","label":"url"}],"paper_title":{"en":"Potentiation of anti-cancer effect by intravenous administration of vesiculated α-tocopheryl hemisuccinate on mouse melanoma in vivo.","ja":"Potentiation of anti-cancer effect by intravenous administration of vesiculated α-tocopheryl hemisuccinate on mouse melanoma in vivo."},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"Manabe Sachie"},{"name":"Hama Susumu"},{"name":"Tokumura Akira"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"小暮 健太朗"},{"name":"Manabe Sachie"},{"name":"Hama Susumu"},{"name":"德村 彰"},{"name":"福澤 健治"}]},"description":{"en":"We examined the effect of alpha-tocopheryl hemisuccinate (TS) on the growth of mouse melanoma cells B16-F1 inoculated on the back of hairless mice by two administration procedures of TS, i.p. administration of TS dissolved with dimethyl sulfoxide (TS i.p.) and i.v. administration of TS vesicles (TS-vesicle i.v.). TS i.p. significantly prevented the tumor growth of only half the mice in the group. However, TS-vesicle i.v. almost completely inhibited the tumor growth of all mice. Furthermore, the mean survival of the TS-vesicle i.v. group was 1.4-fold those of the control and TS i.p. groups.","ja":"We examined the effect of alpha-tocopheryl hemisuccinate (TS) on the growth of mouse melanoma cells B16-F1 inoculated on the back of hairless mice by two administration procedures of TS, i.p. administration of TS dissolved with dimethyl sulfoxide (TS i.p.) and i.v. administration of TS vesicles (TS-vesicle i.v.). TS i.p. significantly prevented the tumor growth of only half the mice in the group. However, TS-vesicle i.v. almost completely inhibited the tumor growth of all mice. Furthermore, the mean survival of the TS-vesicle i.v. group was 1.4-fold those of the control and TS i.p. groups."},"publication_date":"2003-03-20","publication_name":{"en":"Cancer Letters","ja":"Cancer Letters"},"volume":"Vol.192","number":"No.1","starting_page":"19","ending_page":"24","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0304-3835(02)00683-3"],"issn":["0304-3835"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:70, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12213284","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0037027755&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=98349","label":"url"}],"paper_title":{"en":"High cytotoxicity of α-tocopheryl hemisuccinate to cancer cells is due to failure of their antioxidative defense systems.","ja":"High cytotoxicity of α-tocopheryl hemisuccinate to cancer cells is due to failure of their antioxidative defense systems."},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"Hama Susumu"},{"name":"Manabe Sachie"},{"name":"Tokumura Akira"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"小暮 健太朗"},{"name":"Hama Susumu"},{"name":"Manabe Sachie"},{"name":"德村 彰"},{"name":"福澤 健治"}]},"description":{"en":"Alpha-tocopheryl hemisuccinate (TS) has been reported to induce apoptosis in various cells, and to show higher toxicity to cancer cells than to normal cells. In this study, although TS induced apoptosis in both a mouse breast normal cell line NMuMG and a mouse breast cancer cell line C127I, the latter were more susceptible to TS. TS-induced apoptosis in C127I was inhibited by superoxide dismutase, alpha-tocopherol and butylated hydroxyanisol. From these results, superoxide (O(2)(-)) itself and reactive oxygen species derived from O(2)(-) and/or free radicals are assumed to be associated with TS toxicity, and the high toxicity of TS to cancer cells is suggested to be due to failure of their antioxidative defense systems.","ja":"Alpha-tocopheryl hemisuccinate (TS) has been reported to induce apoptosis in various cells, and to show higher toxicity to cancer cells than to normal cells. In this study, although TS induced apoptosis in both a mouse breast normal cell line NMuMG and a mouse breast cancer cell line C127I, the latter were more susceptible to TS. TS-induced apoptosis in C127I was inhibited by superoxide dismutase, alpha-tocopherol and butylated hydroxyanisol. From these results, superoxide (O(2)(-)) itself and reactive oxygen species derived from O(2)(-) and/or free radicals are assumed to be associated with TS toxicity, and the high toxicity of TS to cancer cells is suggested to be due to failure of their antioxidative defense systems."},"publication_date":"2002-12-05","publication_name":{"en":"Cancer Letters","ja":"Cancer Letters"},"volume":"Vol.186","number":"No.2","starting_page":"151","ending_page":"156","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0304-3835(02)00344-0"],"issn":["0304-3835"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:71, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12383946","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=73473","label":"url"}],"paper_title":{"en":"Mechanism of potent antiperoxidative effect of capsaicin","ja":"Mechanism of potent antiperoxidative effect of capsaicin"},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"GOTO Satoru"},{"name":"Nishimura Miki"},{"name":"Yasumoto Mina"},{"name":"Abe Kazutoyo"},{"name":"Ohiwa Chie"},{"name":"Sassa Hironori"},{"name":"Kusumi Takenori"},{"name":"Terada Hiroshi"}],"ja":[{"name":"小暮 健太朗"},{"name":"後藤 了"},{"name":"Nishimura Miki"},{"name":"Yasumoto Mina"},{"name":"Abe Kazutoyo"},{"name":"Ohiwa Chie"},{"name":"Sassa Hironori"},{"name":"楠見 武徳"},{"name":"寺田 弘"}]},"description":{"en":"The effect of a pungent ingredient of red pepper, capsaicin, on lipid peroxidation of rat liver mitochondria (RLM) induced by ADP/Fe(2+) was studied. Capsaicin inhibited the lipid peroxidation significantly, being more effective than the well-known antioxidant alpha-tocopherol. Capsaicin was also found to scavenge 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radicals both in solution and in membranes, especially the latter. Capsaicin was found to scavenge radicals both at/near the membrane surface and in the interior of the membrane. The phenolic OH-group of capsaicin remained intact after reaction with DPPH radicals, indicating that the hydroxyl group is not associated with the radical scavenging reaction. From the results of quantum chemical calculations of various radical intermediates derived from the model compound N-vanillylacetamide, and the findings that vanillin and 8-methyl-6-noneamide were major reaction products of capsaicin with DPPH radicals, it was concluded that the radical scavenging site of capsaicin is the C7-benzyl carbon.","ja":"The effect of a pungent ingredient of red pepper, capsaicin, on lipid peroxidation of rat liver mitochondria (RLM) induced by ADP/Fe(2+) was studied. Capsaicin inhibited the lipid peroxidation significantly, being more effective than the well-known antioxidant alpha-tocopherol. Capsaicin was also found to scavenge 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radicals both in solution and in membranes, especially the latter. Capsaicin was found to scavenge radicals both at/near the membrane surface and in the interior of the membrane. The phenolic OH-group of capsaicin remained intact after reaction with DPPH radicals, indicating that the hydroxyl group is not associated with the radical scavenging reaction. From the results of quantum chemical calculations of various radical intermediates derived from the model compound N-vanillylacetamide, and the findings that vanillin and 8-methyl-6-noneamide were major reaction products of capsaicin with DPPH radicals, it was concluded that the radical scavenging site of capsaicin is the C7-benzyl carbon."},"publication_date":"2002-10-10","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - General Subjects","ja":"Biochimica et Biophysica Acta (BBA) - General Subjects"},"volume":"Vol.1573","number":"No.1","starting_page":"84","ending_page":"92","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0304-4165(02)00335-5"],"issn":["0304-4165"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:72, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11982483","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1570854176748304256/","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0036683314&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=177236","label":"url"}],"paper_title":{"en":"Human platelets respond differentially to lysophosphatidic acids having a highly unsaturated fatty acyl group and alkyl ether-linked lysophosphatidic acids","ja":"Human platelets respond differentially to lysophosphatidic acids having a highly unsaturated fatty acyl group and alkyl ether-linked lysophosphatidic acids"},"authors":{"en":[{"name":"Tokumura Akira"},{"name":"Shinomiya Junya"},{"name":"Kishimoto Seishi"},{"name":"Tanaka Tamotsu"},{"name":"Kogure Kentaro"},{"name":"Sugiura Takayuki"},{"name":"Satouchi Kiyoshi"},{"name":"Waku Keizo"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"德村 彰"},{"name":"Shinomiya Junya"},{"name":"Kishimoto Seishi"},{"name":"田中 保"},{"name":"小暮 健太朗"},{"name":"Sugiura Takayuki"},{"name":"Satouchi Kiyoshi"},{"name":"Waku Keizo"},{"name":"福澤 健治"}]},"description":{"en":"Lysophosphatidic acid (LPA) is a physiological agonist that is produced by lysophospholipase D, phospholipase A(1) and phospholipase A(2) in the blood of animals. It exerts diverse biological actions on a broad range of animal cells. Specific receptors for this important agonist have been characterized. In this investigation, for the first time we prepared LPAs having a highly unsaturated fatty acyl group, such as the eicosapentaenoyl or docosahexaenoyl residue, and their acetylated derivatives. Human platelets aggregated more potently in response to the highly unsaturated acyl-LPAs than to LPAs with a C(18) fatty acyl group, such as an oleoyl group, while alkyl ether-linked LPAs (alkyl-LPA) had much stronger aggregating activity. Two positional isomers of LPAs with an arachidonoyl, eicosapentaenoyl or docosahexaenoyl group had equipotent aggregatory activity as well as the positional isomers of their acetylated analogues, indicating that putative LPA receptors could not distinguish the difference between the positional isomers. We found that platelet preparations from two individuals showed no aggregatory response to alkyl-LPAs, although they contained mRNAs for known LPA receptors in the following order of expression level: endothelial differentiation gene (Edg)-4>Edg-7>Edg-2. We also obtained evidence that 2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid (ONO-RS-082), a phospholipase A(2) inhibitor, potentiated alkyl-LPA-induced platelet aggregation, but inhibited highly unsaturated acyl-LPA-induced platelet aggregation. These results indicated that human platelets express acyl-LPA-selective and alkyl-LPA-selective receptors on their plasma membrane.","ja":"Lysophosphatidic acid (LPA) is a physiological agonist that is produced by lysophospholipase D, phospholipase A(1) and phospholipase A(2) in the blood of animals. It exerts diverse biological actions on a broad range of animal cells. Specific receptors for this important agonist have been characterized. In this investigation, for the first time we prepared LPAs having a highly unsaturated fatty acyl group, such as the eicosapentaenoyl or docosahexaenoyl residue, and their acetylated derivatives. Human platelets aggregated more potently in response to the highly unsaturated acyl-LPAs than to LPAs with a C(18) fatty acyl group, such as an oleoyl group, while alkyl ether-linked LPAs (alkyl-LPA) had much stronger aggregating activity. Two positional isomers of LPAs with an arachidonoyl, eicosapentaenoyl or docosahexaenoyl group had equipotent aggregatory activity as well as the positional isomers of their acetylated analogues, indicating that putative LPA receptors could not distinguish the difference between the positional isomers. We found that platelet preparations from two individuals showed no aggregatory response to alkyl-LPAs, although they contained mRNAs for known LPA receptors in the following order of expression level: endothelial differentiation gene (Edg)-4>Edg-7>Edg-2. We also obtained evidence that 2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid (ONO-RS-082), a phospholipase A(2) inhibitor, potentiated alkyl-LPA-induced platelet aggregation, but inhibited highly unsaturated acyl-LPA-induced platelet aggregation. These results indicated that human platelets express acyl-LPA-selective and alkyl-LPA-selective receptors on their plasma membrane."},"publication_date":"2002-08-01","publication_name":{"en":"The Biochemical Journal","ja":"The Biochemical Journal"},"volume":"Vol.365","number":"No.Pt 3","starting_page":"617","ending_page":"628","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1042/BJ20020348"],"issn":["0264-6021"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:73, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/80015568784/","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11985620","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1571698601676950784/","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0036091121&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=98362","label":"url"}],"paper_title":{"en":"Enhancement by α-tocopheryl hemisuccinate of nitric oxide production induced by lypopolysaccharide and interferon-γ through up-regulation of protein kinase C in rat vascular smooth muscle cells.","ja":"Enhancement by α-tocopheryl hemisuccinate of nitric oxide production induced by lypopolysaccharide and interferon-γ through up-regulation of protein kinase C in rat vascular smooth muscle cells."},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"Morita Motoki"},{"name":"Hama Susumu"},{"name":"Nakashima Sawa"},{"name":"Tokumura Akira"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"小暮 健太朗"},{"name":"Morita Motoki"},{"name":"Hama Susumu"},{"name":"Nakashima Sawa"},{"name":"德村 彰"},{"name":"福澤 健治"}]},"description":{"en":"The effect of alpha-tocopheryl hemisuccinate (TS) on lipopolysaccharide (LPS)/interferon-gamma (IFN)-induced nitric oxide production in rat vascular smooth muscle cells (VSMC) was examined. The LPS/IFN-induced NO production was enhanced by TS but not by the other alpha-tocopherol (alpha-T) derivatives alpha-tocopheryl acetate (TA) and alpha-tocopheryl nicotinate (TN), or alpha-T itself. alpha-T, TA and TN inhibited the enhancement by TS of LPS/IFN-induced NO production. The enhancing effect of TS was observed in the presence of LPS, but not IFN, suggesting that TS participates in the LPS-stimulated signal pathway leading to NO production. Protein kinase C (PKC) inhibitors, but not protein kinase A inhibitors, inhibited the enhancing effect of TS on LPS/IFN-induced NO production. Furthermore, TS enhanced the amount of PKCalpha in VSMC. From these results, we concluded that the enhancing effect of LPS/IFN-induced NO production was caused by upregulation of PKC in VSMC.","ja":"The effect of alpha-tocopheryl hemisuccinate (TS) on lipopolysaccharide (LPS)/interferon-gamma (IFN)-induced nitric oxide production in rat vascular smooth muscle cells (VSMC) was examined. The LPS/IFN-induced NO production was enhanced by TS but not by the other alpha-tocopherol (alpha-T) derivatives alpha-tocopheryl acetate (TA) and alpha-tocopheryl nicotinate (TN), or alpha-T itself. alpha-T, TA and TN inhibited the enhancement by TS of LPS/IFN-induced NO production. The enhancing effect of TS was observed in the presence of LPS, but not IFN, suggesting that TS participates in the LPS-stimulated signal pathway leading to NO production. Protein kinase C (PKC) inhibitors, but not protein kinase A inhibitors, inhibited the enhancing effect of TS on LPS/IFN-induced NO production. Furthermore, TS enhanced the amount of PKCalpha in VSMC. From these results, we concluded that the enhancing effect of LPS/IFN-induced NO production was caused by upregulation of PKC in VSMC."},"publication_date":"2002-05","publication_name":{"en":"European Journal of Biochemistry","ja":"European Journal of Biochemistry"},"volume":"Vol.269","number":"No.9","starting_page":"2367","ending_page":"2372","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1046/j.1432-1033.2002.02894.x"],"issn":["0014-2956"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:74, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11815970","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0036140653&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=145201","label":"url"}],"paper_title":{"en":"Lack of significant differences in the corrected activity of lysophospholipase D, producer of phospholipid mediator lysophosphatidic acid, in incubated serum from women with and without ovarian tumors","ja":"Lack of significant differences in the corrected activity of lysophospholipase D, producer of phospholipid mediator lysophosphatidic acid, in incubated serum from women with and without ovarian tumors"},"authors":{"en":[{"name":"Tokumura Akira"},{"name":"Tominaga Kyoko"},{"name":"Katsuhiko Yasuda"},{"name":"Kanzaki Hideharu"},{"name":"Kogure Kentaro"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"德村 彰"},{"name":"Tominaga Kyoko"},{"name":"Katsuhiko Yasuda"},{"name":"Kanzaki Hideharu"},{"name":"小暮 健太朗"},{"name":"福澤 健治"}]},"description":{"en":"Several studies have shown that lysophosphatidic acid (LPA), a phospholipidic chemical mediator, is relevant to the pathogenesis of ovarian carcinoma. Higher plasma levels of LPA have been reported in patients with ovarian carcinoma than in healthy patients, and LPA is known to activate ovarian carcinoma cells. To determine the reason for the increased plasma LPA levels in ovarian carcinoma patients, we compared the activities of serum lysophospholipase D, a novel LPA-producing metallo-enzyme, in healthy volunteers, patients with benign ovarian tumor, and patients with ovarian carcinoma. Lysophospholipase D activity was assessed by measuring the percentage conversion of [14C]palmitoyl-lysophosphatidylcholine (LPC) added to human serum. The apparent enzyme activities were corrected based on the serum levels of palmitoyl-LPC determined by gas-liquid chromatography after its purification and conversion to fatty acid methyl esters. The apparent activity of lysophospholipase D in serum preparations from four patients with ovarian carcinoma at Stage IV was significantly higher than those from five healthy subjects, five patients with benign ovarian tumors, and fourteen patients with ovarian carcinoma at Stages I (n = 5), II (n = 4), and III (n = 5). The serum levels of LPC, an endogenous substrate of lysophospholipase D, in ovarian carcinoma patients were less than those in patients with benign ovarian tumors. There were no significant differences in the corrected lysophospholipase D activity for the LPC levels in healthy women, patients with benign ovarian tumors, and patients with ovarian carcinoma at various stages. The current results suggest that lysophospholipase D is not associated with the elevated plasma levels of LPA in ovarian carcinoma patients previously reported, although only a limited number of patients were analyzed.","ja":"Several studies have shown that lysophosphatidic acid (LPA), a phospholipidic chemical mediator, is relevant to the pathogenesis of ovarian carcinoma. Higher plasma levels of LPA have been reported in patients with ovarian carcinoma than in healthy patients, and LPA is known to activate ovarian carcinoma cells. To determine the reason for the increased plasma LPA levels in ovarian carcinoma patients, we compared the activities of serum lysophospholipase D, a novel LPA-producing metallo-enzyme, in healthy volunteers, patients with benign ovarian tumor, and patients with ovarian carcinoma. Lysophospholipase D activity was assessed by measuring the percentage conversion of [14C]palmitoyl-lysophosphatidylcholine (LPC) added to human serum. The apparent enzyme activities were corrected based on the serum levels of palmitoyl-LPC determined by gas-liquid chromatography after its purification and conversion to fatty acid methyl esters. The apparent activity of lysophospholipase D in serum preparations from four patients with ovarian carcinoma at Stage IV was significantly higher than those from five healthy subjects, five patients with benign ovarian tumors, and fourteen patients with ovarian carcinoma at Stages I (n = 5), II (n = 4), and III (n = 5). The serum levels of LPC, an endogenous substrate of lysophospholipase D, in ovarian carcinoma patients were less than those in patients with benign ovarian tumors. There were no significant differences in the corrected lysophospholipase D activity for the LPC levels in healthy women, patients with benign ovarian tumors, and patients with ovarian carcinoma at various stages. The current results suggest that lysophospholipase D is not associated with the elevated plasma levels of LPA in ovarian carcinoma patients previously reported, although only a limited number of patients were analyzed."},"publication_date":"2002-01-01","publication_name":{"en":"Cancer","ja":"Cancer"},"volume":"Vol.94","number":"No.1","starting_page":"141","ending_page":"151","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/cncr.10146"],"issn":["0008-543X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:75, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11514094","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=98368","label":"url"}],"paper_title":{"en":"Superoxide is responsible for apoptosis in rat vascular smooth muscle cells induced by α-tocopheryl hemisuccinate.","ja":"Superoxide is responsible for apoptosis in rat vascular smooth muscle cells induced by α-tocopheryl hemisuccinate."},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"Morita Motoki"},{"name":"Nakashima Sawa"},{"name":"Hama Susumu"},{"name":"Tokumura Akira"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"小暮 健太朗"},{"name":"Morita Motoki"},{"name":"Nakashima Sawa"},{"name":"Hama Susumu"},{"name":"德村 彰"},{"name":"福澤 健治"}]},"description":{"en":"We investigated the mechanism of cell toxicity of alpha-tocopheryl hemisuccinate (TS). TS concentration- and time-dependently induced the lactate dehydrogenase release and DNA fragmentation of rat vascular smooth muscle cells (VSMC). Exogenous addition of superoxide dismutase, but not catalase, significantly inhibited the cell toxicity of TS. The NADPH-dependent oxidase activity of VSMC was stimulated by TS treatment. The cell toxicity of TS was inhibited by NADPH oxidase inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride. Consequently, TS-induced apoptosis of VSMC was suggested to be caused by exogenous O(2)(-) generated via the oxidase system activated with TS.","ja":"We investigated the mechanism of cell toxicity of alpha-tocopheryl hemisuccinate (TS). TS concentration- and time-dependently induced the lactate dehydrogenase release and DNA fragmentation of rat vascular smooth muscle cells (VSMC). Exogenous addition of superoxide dismutase, but not catalase, significantly inhibited the cell toxicity of TS. The NADPH-dependent oxidase activity of VSMC was stimulated by TS treatment. The cell toxicity of TS was inhibited by NADPH oxidase inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride. Consequently, TS-induced apoptosis of VSMC was suggested to be caused by exogenous O(2)(-) generated via the oxidase system activated with TS."},"publication_date":"2001-09-03","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - General Subjects","ja":"Biochimica et Biophysica Acta (BBA) - General Subjects"},"volume":"Vol.1528","number":"No.1","starting_page":"25","ending_page":"30","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0304-4165(01)00168-4"],"issn":["0304-4165"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:76, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11406102","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=73475","label":"url"}],"paper_title":{"en":"Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin","ja":"Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin"},"authors":{"en":[{"name":"GOTO Satoru"},{"name":"Kogure Kentaro"},{"name":"Abe Kazutoyo"},{"name":"Kimata Yukari"},{"name":"Kitahama Katsuhiro"},{"name":"Yamashita Eiji"},{"name":"Terada Hiroshi"}],"ja":[{"name":"後藤 了"},{"name":"小暮 健太朗"},{"name":"Abe Kazutoyo"},{"name":"Kimata Yukari"},{"name":"Kitahama Katsuhiro"},{"name":"Yamashita Eiji"},{"name":"寺田 弘"}]},"description":{"en":"The effects of the carotenoids beta-carotene and astaxanthin on the peroxidation of liposomes induced by ADP and Fe(2+) were examined. Both compounds inhibited production of lipid peroxides, astaxanthin being about 2-fold more effective than beta-carotene. The difference in the modes of destruction of the conjugated polyene chain between beta-carotene and astaxanthin suggested that the conjugated polyene moiety and terminal ring moieties of the more potent astaxanthin trapped radicals in the membrane and both at the membrane surface and in the membrane, respectively, whereas only the conjugated polyene chain of beta-carotene was responsible for radical trapping near the membrane surface and in the interior of the membrane. The efficient antioxidant activity of astaxanthin is suggested to be due to the unique structure of the terminal ring moiety.","ja":"The effects of the carotenoids beta-carotene and astaxanthin on the peroxidation of liposomes induced by ADP and Fe(2+) were examined. Both compounds inhibited production of lipid peroxides, astaxanthin being about 2-fold more effective than beta-carotene. The difference in the modes of destruction of the conjugated polyene chain between beta-carotene and astaxanthin suggested that the conjugated polyene moiety and terminal ring moieties of the more potent astaxanthin trapped radicals in the membrane and both at the membrane surface and in the membrane, respectively, whereas only the conjugated polyene chain of beta-carotene was responsible for radical trapping near the membrane surface and in the interior of the membrane. The efficient antioxidant activity of astaxanthin is suggested to be due to the unique structure of the terminal ring moiety."},"publication_date":"2001-06-06","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - Biomembranes","ja":"Biochimica et Biophysica Acta (BBA) - Biomembranes"},"volume":"Vol.1512","number":"No.2","starting_page":"251","ending_page":"258","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0005-2736(01)00326-1"],"issn":["0005-2736"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:77, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11245836","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=132367","label":"url"}],"paper_title":{"en":"A comparative study of the ability of ferric nitrilotriacetate and other iron chelators to assist membrane lipid peroxidation by superoxide radicals","ja":"A comparative study of the ability of ferric nitrilotriacetate and other iron chelators to assist membrane lipid peroxidation by superoxide radicals"},"authors":{"en":[{"name":"Fukuzawa Kenji"},{"name":"Tokumura Akira"},{"name":"Kogure Kentaro"},{"name":"Iemura Masahito"},{"name":"Gondoh Naoto"},{"name":"Fujii Masanobu"},{"name":"Ueno Satoru"},{"name":"Shibata Akira"}],"ja":[{"name":"福澤 健治"},{"name":"德村 彰"},{"name":"小暮 健太朗"},{"name":"Iemura Masahito"},{"name":"Gondoh Naoto"},{"name":"藤井 正信"},{"name":"植野 哲"},{"name":"柴田 瑩"}]},"description":{"en":"This study examined some of the variables determining the efficiency of lipid peroxidation in egg yolk phosphatidylcholine liposomes and in microsomes exposed to enzymatically-generated superoxide radicals. The initiation of peroxidation required the presence of preformed lipid peroxides and a chelated metal catalyst. Comparison of the relative effectiveness of four iron chelating agents showed that the chelate must bind to the membrane by coulombic attraction between the charged membrane and a chelate carrying an opposite net charge. Of the chelates tested, only the carcinogenic ferric nitrilotriacetate [corrected] (Fe(3+)-NTA) was an effective catalyst of oxidation of all membranes, whether carrying a net charge, or not. We postulate that the unique catalytic capacity of the ferric nitrilotriacetate [corrected] (Fe(3+)-NTA) can be explained by its existence in two forms at neutral pH, each binding to oppositely charged membranes and initiating their peroxidation. This gives the complex the unique ability to bind to any membrane, which may be a factor in its carcinogenicity.","ja":"This study examined some of the variables determining the efficiency of lipid peroxidation in egg yolk phosphatidylcholine liposomes and in microsomes exposed to enzymatically-generated superoxide radicals. The initiation of peroxidation required the presence of preformed lipid peroxides and a chelated metal catalyst. Comparison of the relative effectiveness of four iron chelating agents showed that the chelate must bind to the membrane by coulombic attraction between the charged membrane and a chelate carrying an opposite net charge. Of the chelates tested, only the carcinogenic ferric nitrilotriacetate [corrected] (Fe(3+)-NTA) was an effective catalyst of oxidation of all membranes, whether carrying a net charge, or not. We postulate that the unique catalytic capacity of the ferric nitrilotriacetate [corrected] (Fe(3+)-NTA) can be explained by its existence in two forms at neutral pH, each binding to oppositely charged membranes and initiating their peroxidation. This gives the complex the unique ability to bind to any membrane, which may be a factor in its carcinogenicity."},"publication_date":"2001-03","publication_name":{"en":"Chemistry and Physics of Lipids","ja":"Chemistry and Physics of Lipids"},"volume":"Vol.110","number":"No.1","starting_page":"69","ending_page":"84","languages":["eng"],"referee":true,"identifiers":{"issn":["0009-3084"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:78, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11200253","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=70771","label":"url"}],"paper_title":{"en":"Preventive effects of lecithinized superoxide dismutase and methylprednisolone on spinal cord injury in rats --- Transcriptional regulation of inflammatory and neurotrophic genes","ja":"Preventive effects of lecithinized superoxide dismutase and methylprednisolone on spinal cord injury in rats --- Transcriptional regulation of inflammatory and neurotrophic genes"},"authors":{"en":[{"name":"Chikawa Takashi"},{"name":"Ikata Takaaki"},{"name":"Katoh Shinsuke"},{"name":"Hamada Yoshitaka"},{"name":"Kogure Kentaro"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"Chikawa Takashi"},{"name":"Ikata Takaaki"},{"name":"加藤 真介"},{"name":"Hamada Yoshitaka"},{"name":"小暮 健太朗"},{"name":"福澤 健治"}]},"description":{"en":"The effects of lecithinized superoxide dismutase (PC-SOD) and/or methylpredisolone (MP) in preventing secondary pathological changes after spinal cord injury (SCI) were investigated in rats with reference to recovery of hindlimb motor function and expression of mRNA of pro-inflammatory and neurotrophic genes. Hindlimb motor function was assessed as the BBB open field locomotor scores. The BBB scores of three groups treated with either PC-SOD (40,000 units/kg), MP (30 mg/kg), or a combination of PC-SOD and MP (PC-SOD+MP) increased with time until 3 days after SCI, and were significantly higher than that of the control group (p < 0.05). Thereafter, the score of the PC-SOD group increased, whereas that of the MP group showed a temporary decrease from day 3 to 5 and then it gradually recovered. The scores in all groups reached a plateau about 18 days after SCI. The PC-SOD+MP group did not show a synergism but a tendency similar to that of the MP group. PC-SOD and MP had down-regulatory effects on mRNA expression of pro-inflammatory substances such as interleukin-1beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1), and inducible-nitric oxide synthetase (i-NOS) after spinal cord compression at 3, 6, and 24 h, respectively, as judged by a semiquantitative reverse transcription-polymerase chain reaction and on the lipid peroxide (LPO) level 1 h after injury as determined by thiobarbituric acid-reactive substances. The suppression of pro-inflammatory genes expression, especially IL-1beta were greater in the MP group than in the PC-SOD group, while suppression of LPO level was similar in these two groups. PC-SOD+MP treatment augmented the suppression of all three pro-inflammatory genes expression and the decrease of the LPO level. The level of neurotrophin-3 (NT-3) mRNA increased from 6 h after SCI and reached a maximum after 48 h. NT-3 mRNA level was enhanced by PC-SOD treatment, but not by MP treatment. Thus, the effect of MP in suppressing these pro-inflammatory genes expression was more than that of PC-SOD. The difference in motor function in the early and later stage may be partially due to differences in expression of IL-1beta and NT-3 after either treatment, through an IL-1beta-dependent or NT-3-mediated repair response.","ja":"The effects of lecithinized superoxide dismutase (PC-SOD) and/or methylpredisolone (MP) in preventing secondary pathological changes after spinal cord injury (SCI) were investigated in rats with reference to recovery of hindlimb motor function and expression of mRNA of pro-inflammatory and neurotrophic genes. Hindlimb motor function was assessed as the BBB open field locomotor scores. The BBB scores of three groups treated with either PC-SOD (40,000 units/kg), MP (30 mg/kg), or a combination of PC-SOD and MP (PC-SOD+MP) increased with time until 3 days after SCI, and were significantly higher than that of the control group (p < 0.05). Thereafter, the score of the PC-SOD group increased, whereas that of the MP group showed a temporary decrease from day 3 to 5 and then it gradually recovered. The scores in all groups reached a plateau about 18 days after SCI. The PC-SOD+MP group did not show a synergism but a tendency similar to that of the MP group. PC-SOD and MP had down-regulatory effects on mRNA expression of pro-inflammatory substances such as interleukin-1beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1), and inducible-nitric oxide synthetase (i-NOS) after spinal cord compression at 3, 6, and 24 h, respectively, as judged by a semiquantitative reverse transcription-polymerase chain reaction and on the lipid peroxide (LPO) level 1 h after injury as determined by thiobarbituric acid-reactive substances. The suppression of pro-inflammatory genes expression, especially IL-1beta were greater in the MP group than in the PC-SOD group, while suppression of LPO level was similar in these two groups. PC-SOD+MP treatment augmented the suppression of all three pro-inflammatory genes expression and the decrease of the LPO level. The level of neurotrophin-3 (NT-3) mRNA increased from 6 h after SCI and reached a maximum after 48 h. NT-3 mRNA level was enhanced by PC-SOD treatment, but not by MP treatment. Thus, the effect of MP in suppressing these pro-inflammatory genes expression was more than that of PC-SOD. The difference in motor function in the early and later stage may be partially due to differences in expression of IL-1beta and NT-3 after either treatment, through an IL-1beta-dependent or NT-3-mediated repair response."},"publication_date":"2001-01","publication_name":{"en":"Journal of Neurotrauma","ja":"Journal of Neurotrauma"},"volume":"Vol.18","number":"No.1","starting_page":"93","ending_page":"103","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1089/089771501750055802"],"issn":["0897-7151"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:79, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/10828088","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0033934565&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=98377","label":"url"}],"paper_title":{"en":"Structural identification of phosphatidylcholines having an oxidatively shortened linoleate residue generated through its oxygenation with soybean or rabbit reticulocyte lipoxygenase.","ja":"Structural identification of phosphatidylcholines having an oxidatively shortened linoleate residue generated through its oxygenation with soybean or rabbit reticulocyte lipoxygenase."},"authors":{"en":[{"name":"Tokumura Akira"},{"name":"Sumida T."},{"name":"Toujima M."},{"name":"Kogure Kentaro"},{"name":"Fukuzawa Kenji"},{"name":"Takahashi Y."},{"name":"Yamamoto S."}],"ja":[{"name":"德村 彰"},{"name":"Sumida T."},{"name":"Toujima M."},{"name":"小暮 健太朗"},{"name":"福澤 健治"},{"name":"Takahashi Y."},{"name":"Yamamoto S."}]},"description":{"en":"Phosphatidylcholines (PCs) with platelet-activating factor (PAF)-like biological activities are known to be generated by fragmentation of the sn-2-esterified polyunsaturated fatty acyl group. The reaction is free radical-mediated and triggered by oxidants such as metal ions, oxyhemoglobin, and organic hydroperoxides. In this study, we characterized the PAF-like phospholipids produced on reaction of PC having a linoleate group with lipoxygenase enzymes at low oxygen concentrations. When the oxidized PCs were analyzed by gas chromatography-mass spectrometry, two types of oxidatively fragmented PC were detected. One PC had an sn-2-short chain saturated or unsaturated acyl group (C(8)-C(13)) with an aldehydic terminal; the abundant species were PCs with C(9) and C(13). The other PC had a short chain saturated acyl group (C(6)-C(9)) with a methyl terminal, and the most predominant species was PC with C(8). When the extracts of oxidation products were subjected to catalytic hydrogenation, PCs having saturated acyl groups (C(6)-C(14)) were detected; the most abundant was C(12) species. The less regiospecific formation of PAF-like lipids suggests that they were generated by oxidative fragmentation of PC hydroperoxides formed by non-stereoselective oxygenation of the alkyl radical of esterified linoleate that escaped from the active centers of lipoxygenases. One of the PAF-like PC with an aldehydic terminal was found to be bioactive; it inhibited the production of nitric oxide induced by lipopolysaccharide and interferon-gamma in vascular smooth muscle cells from rat aorta.","ja":"Phosphatidylcholines (PCs) with platelet-activating factor (PAF)-like biological activities are known to be generated by fragmentation of the sn-2-esterified polyunsaturated fatty acyl group. The reaction is free radical-mediated and triggered by oxidants such as metal ions, oxyhemoglobin, and organic hydroperoxides. In this study, we characterized the PAF-like phospholipids produced on reaction of PC having a linoleate group with lipoxygenase enzymes at low oxygen concentrations. When the oxidized PCs were analyzed by gas chromatography-mass spectrometry, two types of oxidatively fragmented PC were detected. One PC had an sn-2-short chain saturated or unsaturated acyl group (C(8)-C(13)) with an aldehydic terminal; the abundant species were PCs with C(9) and C(13). The other PC had a short chain saturated acyl group (C(6)-C(9)) with a methyl terminal, and the most predominant species was PC with C(8). When the extracts of oxidation products were subjected to catalytic hydrogenation, PCs having saturated acyl groups (C(6)-C(14)) were detected; the most abundant was C(12) species. The less regiospecific formation of PAF-like lipids suggests that they were generated by oxidative fragmentation of PC hydroperoxides formed by non-stereoselective oxygenation of the alkyl radical of esterified linoleate that escaped from the active centers of lipoxygenases. One of the PAF-like PC with an aldehydic terminal was found to be bioactive; it inhibited the production of nitric oxide induced by lipopolysaccharide and interferon-gamma in vascular smooth muscle cells from rat aorta."},"publication_date":"2000-06","publication_name":{"en":"Journal of Lipid Research","ja":"Journal of Lipid Research"},"volume":"Vol.41","number":"No.6","starting_page":"953","ending_page":"962","languages":["eng"],"referee":true,"identifiers":{"issn":["0022-2275"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:80, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/9878710","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=73479","label":"url"}],"paper_title":{"en":"Potent anti-peroxidation activity of the bisbenzylisoquinoline alkaloid cepharanthine: The amine moiety is responsible for its pH-dependent radical scavenge activity","ja":"Potent anti-peroxidation activity of the bisbenzylisoquinoline alkaloid cepharanthine: The amine moiety is responsible for its pH-dependent radical scavenge activity"},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"GOTO Satoru"},{"name":"Abe Kazutoyo"},{"name":"Ohiwa Chie"},{"name":"Akasu Michinori"},{"name":"Terada Hiroshi"}],"ja":[{"name":"小暮 健太朗"},{"name":"後藤 了"},{"name":"Abe Kazutoyo"},{"name":"Ohiwa Chie"},{"name":"Akasu Michinori"},{"name":"寺田 弘"}]},"description":{"en":"The bisbenzylisoquinoline alkaloid cepharanthine, which has been considered to exhibit antiperoxidation activity due to its membrane stabilizing effect, was found to scavenge radicals such as .OH and DPPH (1,1-diphenyl-2-picrylhydrazyl) in solution, and to inhibit lipid peroxidation in mitochondria and liposomes by Fe2+/ADP. The antiperoxidation activity of cepharanthine in rat liver mitochondria initiated by Fe2+/ADP at pH 7.4 was much greater than that of alpha-tocopherol, its half-inhibitory concentration being about 23 microM. However, cepharanthine was effective only at neutral pH values such as pH 7.4, not in a moderately acidic pH region below pH 6.5. Accordingly, the neutral form of the deprotonated amine moiety in the tetrahydroisoquinoline ring is concluded to be responsible for the radical scavenging activity of cepharanthine. There are two amine moieties in the cepharanthine molecule, but we specified the effective amine moiety from the antiperoxidation activities of the imine analogs of cepharanthine.","ja":"The bisbenzylisoquinoline alkaloid cepharanthine, which has been considered to exhibit antiperoxidation activity due to its membrane stabilizing effect, was found to scavenge radicals such as .OH and DPPH (1,1-diphenyl-2-picrylhydrazyl) in solution, and to inhibit lipid peroxidation in mitochondria and liposomes by Fe2+/ADP. The antiperoxidation activity of cepharanthine in rat liver mitochondria initiated by Fe2+/ADP at pH 7.4 was much greater than that of alpha-tocopherol, its half-inhibitory concentration being about 23 microM. However, cepharanthine was effective only at neutral pH values such as pH 7.4, not in a moderately acidic pH region below pH 6.5. Accordingly, the neutral form of the deprotonated amine moiety in the tetrahydroisoquinoline ring is concluded to be responsible for the radical scavenging activity of cepharanthine. There are two amine moieties in the cepharanthine molecule, but we specified the effective amine moiety from the antiperoxidation activities of the imine analogs of cepharanthine."},"publication_date":"1999-01-04","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - General Subjects","ja":"Biochimica et Biophysica Acta (BBA) - General Subjects"},"volume":"Vol.1426","number":"No.1","starting_page":"133","ending_page":"142","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0304-4165(98)00146-9"],"issn":["0304-4165"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:81, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/7873617","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=104075","label":"url"}],"paper_title":{"en":"Nucleotide sequence of the 5'-flanking region of the rat type II hexokinase gene","ja":"Nucleotide sequence of the 5'-flanking region of the rat type II hexokinase gene"},"authors":{"en":[{"name":"Ichihara Junji"},{"name":"Shinohara Yasuo"},{"name":"Kogure Kentaro"},{"name":"Terada Hiroshi"}],"ja":[{"name":"Ichihara Junji"},{"name":"篠原 康雄"},{"name":"小暮 健太朗"},{"name":"Terada Hiroshi"}]},"description":{"en":"In a previous study, we found that the steady state transcript level of type II hexokinase was specifically and remarkably elevated in rat hepatoma AH130 cells. To determine the molecular mechanism of transcriptional control of the type II hexokinase gene, we examined the nucleotide sequence of its 5'-flanking region and analyzed putative transcription factor binding sites. We also examined the type II hexokinase promoter activity by the chloramphenicol acetyltransferase (CAT) assay.","ja":"In a previous study, we found that the steady state transcript level of type II hexokinase was specifically and remarkably elevated in rat hepatoma AH130 cells. To determine the molecular mechanism of transcriptional control of the type II hexokinase gene, we examined the nucleotide sequence of its 5'-flanking region and analyzed putative transcription factor binding sites. We also examined the type II hexokinase promoter activity by the chloramphenicol acetyltransferase (CAT) assay."},"publication_date":"1995-02-21","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression","ja":"Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression"},"volume":"Vol.1260","number":"No.3","starting_page":"365","ending_page":"368","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/0167-4781(94)00226-S"],"issn":["0167-4781"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:82, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=104070","label":"url"}],"paper_title":{"en":"Steady state transcript levels of the type II hexokinase and type 1 glucose transporter in human tumor cell line","ja":"Steady state transcript levels of the type II hexokinase and type 1 glucose transporter in human tumor cell line"},"authors":{"en":[{"name":"Shinohara Yasuo"},{"name":"Yamamoto Kenji"},{"name":"Kogure Kentaro"},{"name":"Ichihara Junji"},{"name":"Terada Hiroshi"}],"ja":[{"name":"篠原 康雄"},{"name":"Yamamoto Kenji"},{"name":"小暮 健太朗"},{"name":"Ichihara Junji"},{"name":"Terada Hiroshi"}]},"publication_date":"1994-07-15","publication_name":{"en":"Cancer Letters","ja":"Cancer Letters"},"volume":"Vol.82","number":"No.1","starting_page":"27","ending_page":"32","languages":["eng"],"referee":true,"identifiers":{"issn":["0304-3835"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:83, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=146260","label":"url"}],"paper_title":{"en":"リン脂質酸化二次作物による血管平滑筋細胞のアポトーシス誘導とビタミンEによる抑制作用","ja":"リン脂質酸化二次作物による血管平滑筋細胞のアポトーシス誘導とビタミンEによる抑制作用"},"authors":{"en":[{"name":"Fukuzawa Kenji"},{"name":"Kogure Kentaro"},{"name":"中島 佐和"},{"name":"土江 明子"},{"name":"Tokumura Akira"}],"ja":[{"name":"福澤 健治"},{"name":"小暮 健太朗"},{"name":"中島 佐和"},{"name":"土江 明子"},{"name":"德村 彰"}]},"publication_date":"2004","publication_name":{"en":"ビタミンE研究の進歩Ⅺ","ja":"ビタミンE研究の進歩Ⅺ"},"starting_page":"115","ending_page":"127","languages":["jpn"],"published_paper_type":"research_institution"},"priority":"input_data"}
line:84, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=146259","label":"url"}],"paper_title":{"en":"抗ガン作用の増強を志向したビタミンEコハク酸ベシクル","ja":"抗ガン作用の増強を志向したビタミンEコハク酸ベシクル"},"authors":{"en":[{"name":"真鍋 幸恵"},{"name":"Kogure Kentaro"},{"name":"森田 健之"},{"name":"Tokumura Akira"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"真鍋 幸恵"},{"name":"小暮 健太朗"},{"name":"森田 健之"},{"name":"德村 彰"},{"name":"福澤 健治"}]},"publication_date":"2004","publication_name":{"en":"ビタミンE研究の進歩Ⅺ","ja":"ビタミンE研究の進歩Ⅺ"},"starting_page":"45","ending_page":"49","languages":["jpn"],"published_paper_type":"research_institution"},"priority":"input_data"}
line:85, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/10024570625/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1570572700727485440/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=146256","label":"url"}],"paper_title":{"en":"正常および異常妊娠時のヒト血清リゾホスホリパーゼD活性","ja":"正常および異常妊娠時のヒト血清リゾホスホリパーゼD活性"},"authors":{"en":[{"name":"Tokumura Akira"},{"name":"平尾 恵理"},{"name":"丸山 祐史"},{"name":"Kogure Kentaro"},{"name":"Fukuzawa Kenji"},{"name":"安田 勝彦"},{"name":"神崎 秀暢"}],"ja":[{"name":"德村 彰"},{"name":"平尾 恵理"},{"name":"丸山 祐史"},{"name":"小暮 健太朗"},{"name":"福澤 健治"},{"name":"安田 勝彦"},{"name":"神崎 秀暢"}]},"publication_date":"2003-06-20","publication_name":{"en":"Proceedings of the Japanese Conference on the Biochemistry of Lipids","ja":"脂質生化学研究"},"volume":"Vol.45","number":"No.0","starting_page":"95","ending_page":"97","languages":["jpn"],"identifiers":{"issn":["0285-1520"]},"published_paper_type":"research_institution"},"priority":"input_data"}
line:86, {"insert":{"user_id":"1000193501","type":"published_papers","id":"13929706"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=146255","label":"url"}],"paper_title":{"en":"生理活性リン脂質LPAを産生するヒト血漿リゾホスホリパーゼDは多機能性ヌクレオチドホスジエステラーゼautotaxinである","ja":"生理活性リン脂質LPAを産生するヒト血漿リゾホスホリパーゼDは多機能性ヌクレオチドホスジエステラーゼautotaxinである"},"authors":{"en":[{"name":"Tokumura Akira"},{"name":"富永 恭子"},{"name":"Kogure Kentaro"},{"name":"Fukuzawa Kenji"},{"name":"安田 勝彦"},{"name":"刈谷 優子"},{"name":"真島 英司"}],"ja":[{"name":"德村 彰"},{"name":"富永 恭子"},{"name":"小暮 健太朗"},{"name":"福澤 健治"},{"name":"安田 勝彦"},{"name":"刈谷 優子"},{"name":"真島 英司"}]},"publication_date":"2002","publication_name":{"en":"Proceedings of the Japanese Conference on the Biochemistry of Lipids","ja":"脂質生化学研究"},"volume":"Vol.44","starting_page":"78","ending_page":"881","languages":["jpn"],"identifiers":{"issn":["0285-1520"]},"published_paper_type":"research_institution"},"priority":"input_data"}
line:87, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/10013379143/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1570009750154718208/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=146245","label":"url"}],"paper_title":{"en":"モルモット腹腔洗浄液のリゾホスホリパーゼD活性","ja":"モルモット腹腔洗浄液のリゾホスホリパーゼD活性"},"authors":{"en":[{"name":"Tokumura Akira"},{"name":"富永 恭子"},{"name":"金谷 由美"},{"name":"Kogure Kentaro"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"德村 彰"},{"name":"富永 恭子"},{"name":"金谷 由美"},{"name":"小暮 健太朗"},{"name":"福澤 健治"}]},"publication_date":"2001-05-10","publication_name":{"en":"Proceedings of the Japanese Conference on the Biochemistry of Lipids","ja":"脂質生化学研究"},"volume":"Vol.43","starting_page":"82","ending_page":"85","languages":["jpn"],"identifiers":{"issn":["0285-1520"]},"published_paper_type":"research_institution"},"priority":"input_data"}
line:88, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=146246","label":"url"}],"paper_title":{"en":"Enhancement by α-tocopherol hemisuccinate of nitric oxide production induced by lipopolysaccharide and interferon-γ through up-regulation of protein kinase C in rat vascular smooth muscle cells","ja":"Enhancement by α-tocopherol hemisuccinate of nitric oxide production induced by lipopolysaccharide and interferon-γ through up-regulation of protein kinase C in rat vascular smooth muscle cells"},"authors":{"en":[{"name":"Fukuzawa Kenji"},{"name":"Kogure Kentaro"},{"name":"Morita M"},{"name":"Hama S"},{"name":"Nakashima S"},{"name":"Tokumura Akira"}],"ja":[{"name":"福澤 健治"},{"name":"小暮 健太朗"},{"name":"Morita M"},{"name":"Hama S"},{"name":"Nakashima S"},{"name":"德村 彰"}]},"publication_date":"2001","publication_name":{"en":"Proc.Of the second China-Japan international Conference on Vitamins","ja":"Proc.Of the second China-Japan international Conference on Vitamins"},"starting_page":"262","ending_page":"267","languages":["eng"],"published_paper_type":"research_institution"},"priority":"input_data"}
line:89, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=146241","label":"url"}],"paper_title":{"en":"血清リゾホスホリパーゼDによるリゾホスファチジン酸産生の病態下での変動","ja":"血清リゾホスホリパーゼDによるリゾホスファチジン酸産生の病態下での変動"},"authors":{"en":[{"name":"Tokumura Akira"},{"name":"金谷 由美"},{"name":"富永 恭子"},{"name":"Kogure Kentaro"},{"name":"Fukuzawa Kenji"},{"name":"北原 真樹"},{"name":"安田 勝彦"}],"ja":[{"name":"德村 彰"},{"name":"金谷 由美"},{"name":"富永 恭子"},{"name":"小暮 健太朗"},{"name":"福澤 健治"},{"name":"北原 真樹"},{"name":"安田 勝彦"}]},"publication_date":"2000","publication_name":{"en":"Proceedings of the Japanese Conference on the Biochemistry of Lipids","ja":"脂質生化学研究"},"volume":"Vol.42","starting_page":"41","ending_page":"44","languages":["jpn"],"identifiers":{"issn":["0285-1520"]},"published_paper_type":"research_institution"},"priority":"input_data"}
line:90, {"insert":{"user_id":"1000193501","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=146240","label":"url"}],"paper_title":{"en":"高度不飽和脂肪酸を有するリゾホスファチジン酸:血漿中での生成と血小板凝集活性","ja":"高度不飽和脂肪酸を有するリゾホスファチジン酸:血漿中での生成と血小板凝集活性"},"authors":{"en":[{"name":"Tokumura Akira"},{"name":"四宮 淳也"},{"name":"Kogure Kentaro"},{"name":"Fukuzawa Kenji"},{"name":"田中 保"},{"name":"里内 清"}],"ja":[{"name":"德村 彰"},{"name":"四宮 淳也"},{"name":"小暮 健太朗"},{"name":"福澤 健治"},{"name":"田中 保"},{"name":"里内 清"}]},"publication_date":"1999","publication_name":{"en":"Proceedings of the Japanese Conference on the Biochemistry of Lipids","ja":"脂質生化学研究"},"volume":"Vol.41","starting_page":"193","ending_page":"195","languages":["jpn"],"identifiers":{"issn":["0285-1520"]},"published_paper_type":"research_institution"},"priority":"input_data"}
==== end registerFile(/WWW/pub2/data/ERD/person/60638/researchmap/published_papers.jsonl, 1wE7HI8B7kacV6CWX1RU) ====
==== begin registerFile(/WWW/pub2/data/ERD/person/60638/researchmap/misc.jsonl) ====
line:1, {"insert":{"user_id":"1000193501","type":"misc","id":"43140924"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=402244","label":"url"}],"paper_title":{"en":"ビタミンEエステル体の抗肥満薬としての可能性","ja":"ビタミンEエステル体の抗肥満薬としての可能性"},"authors":{"en":[{"name":"Kogure Kentaro"}],"ja":[{"name":"小暮 健太朗"}]},"publication_date":"2023-08-12","publication_name":{"en":"バイオインダストリー","ja":"バイオインダストリー"},"volume":"Vol.40","number":"No.8","starting_page":"49","ending_page":"54","languages":["jpn"],"invited":true,"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:2, {"insert":{"user_id":"1000193501","type":"misc","id":"39048733"},"force":{"see_also":[{"@id":"http://repo.lib.tokushima-u.ac.jp/117239","label":"url"},{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117239","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1050574411836978048/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=386975","label":"url"}],"paper_title":{"en":"Intradermal delivery of drugs by weak electric current","ja":"微弱電流による薬剤の皮内送達"},"authors":{"en":[{"name":"Kogure Kentaro"}],"ja":[{"name":"小暮 健太朗"}]},"publication_date":"2022-05-05","publication_name":{"en":"Chemical engineering","ja":"化学工学"},"volume":"Vol.36","number":"No.5","starting_page":"219","ending_page":"222","languages":["jpn"],"identifiers":{"issn":["0375-9253"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:3, {"insert":{"user_id":"1000193501","type":"misc","id":"39666218"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35491189","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390035","label":"url"}],"paper_title":{"en":"Biomimetic nanoparticle drug delivery systems to overcome biological barriers for therapeutic applications.","ja":"Biomimetic nanoparticle drug delivery systems to overcome biological barriers for therapeutic applications."},"authors":{"en":[{"name":"Fukuta Tatsuya"},{"name":"Kogure Kentaro"}],"ja":[{"name":"福田 達也"},{"name":"小暮 健太朗"}]},"description":{"en":"Targeted drug delivery using nanoparticles has been applied for the treatment of diverse diseases, including cancer and inflammatory diseases. Nanoparticle-mediated delivery of therapeutic agents via the enhanced permeability and retention effect generally augments their therapeutic efficiency; however, limitations with passive entry of nanoparticles into diseased sites, due to the presence of biological barriers represented by the endothelial layer, remain to be addressed. To this end, development of nanoparticles with intrinsic characteristics similar to circulatory cells (e.g., leukocytes, platelets) for use as biomimetic drug delivery systems (DDS) has been focused as a means to overcome the issues of conventional DDS. In particular, synthetic biomimetic nanoparticles coated with cellular membranes were recently prepared and shown to actively overcome the inflamed vessels and tumor microenvironment as a result of the functionality of membrane proteins, which allowed secure drug delivery into diseased sites. We recently developed liposomes modified with leukocyte membrane proteins via intermembrane protein transfer, a simple method to reconstitute cellular membrane proteins onto lipid bilayers. The resultant liposomes demonstrated the ability to cross the inflamed endothelial layer and permeate into tumor tissue by mimicking the properties of leukocytes. Thus, biomimetic DDS offer promise as new therapeutic approaches for various diseases by overcoming biological barriers that typically inhibit drug delivery. Herein, we review recent approaches to develop biomimetic DDS using the cell membrane coating method, and highlight our recent findings on leukocyte-mimetic liposomes prepared via intermembrane protein transfer.","ja":"Targeted drug delivery using nanoparticles has been applied for the treatment of diverse diseases, including cancer and inflammatory diseases. Nanoparticle-mediated delivery of therapeutic agents via the enhanced permeability and retention effect generally augments their therapeutic efficiency; however, limitations with passive entry of nanoparticles into diseased sites, due to the presence of biological barriers represented by the endothelial layer, remain to be addressed. To this end, development of nanoparticles with intrinsic characteristics similar to circulatory cells (e.g., leukocytes, platelets) for use as biomimetic drug delivery systems (DDS) has been focused as a means to overcome the issues of conventional DDS. In particular, synthetic biomimetic nanoparticles coated with cellular membranes were recently prepared and shown to actively overcome the inflamed vessels and tumor microenvironment as a result of the functionality of membrane proteins, which allowed secure drug delivery into diseased sites. We recently developed liposomes modified with leukocyte membrane proteins via intermembrane protein transfer, a simple method to reconstitute cellular membrane proteins onto lipid bilayers. The resultant liposomes demonstrated the ability to cross the inflamed endothelial layer and permeate into tumor tissue by mimicking the properties of leukocytes. Thus, biomimetic DDS offer promise as new therapeutic approaches for various diseases by overcoming biological barriers that typically inhibit drug delivery. Herein, we review recent approaches to develop biomimetic DDS using the cell membrane coating method, and highlight our recent findings on leukocyte-mimetic liposomes prepared via intermembrane protein transfer."},"publication_date":"2022-05","publication_name":{"en":"Chemical & Pharmaceutical Bulletin","ja":"Chemical & Pharmaceutical Bulletin"},"volume":"Vol.70","number":"No.5","starting_page":"334","ending_page":"340","languages":["eng"],"identifiers":{"doi":["10.1248/cpb.c21-00961"],"issn":["1347-5223"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:4, {"insert":{"user_id":"1000193501","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117589","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35335900","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390037","label":"url"}],"paper_title":{"en":"Iontophoresis of Biological Macromolecular Drugs.","ja":"Iontophoresis of Biological Macromolecular Drugs."},"authors":{"en":[{"name":"Hasan Mahadi"},{"name":"Khatun Anowara"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Hasan Mahadi"},{"name":"Khatun Anowara"},{"name":"小暮 健太朗"}]},"description":{"en":"Over the last few decades, biological macromolecular drugs (e.g., peptides, proteins, and nucleic acids) have become a significant therapeutic modality for the treatment of various diseases. These drugs are considered superior to small-molecule drugs because of their high specificity and favorable safety profiles. However, such drugs are limited by their low oral bioavailability and short half-lives. Biological macromolecular drugs are typically administrated via invasive methods, e.g., intravenous or subcutaneous injections, which can be painful and induce needle phobia. Noninvasive transdermal delivery is an alternative administration route for the local and systemic delivery of biological macromolecular drugs. However, a challenge with the noninvasive transdermal delivery of biological macromolecular drugs is the outermost layer of the skin, known as the stratum corneum, which is a physical barrier that restricts the entry of extraneous macromolecules. Iontophoresis (IP) relies on the application of a low level of electricity for transdermal drug delivery, in order to facilitate the skin permeation of hydrophilic and charged molecules. The IP of several biological macromolecular drugs has recently been investigated. Herein, we review the IP-mediated noninvasive transdermal delivery of biological macromolecular drugs, their routes of skin permeation, their underlying mechanisms, and their advance applications.","ja":"Over the last few decades, biological macromolecular drugs (e.g., peptides, proteins, and nucleic acids) have become a significant therapeutic modality for the treatment of various diseases. These drugs are considered superior to small-molecule drugs because of their high specificity and favorable safety profiles. However, such drugs are limited by their low oral bioavailability and short half-lives. Biological macromolecular drugs are typically administrated via invasive methods, e.g., intravenous or subcutaneous injections, which can be painful and induce needle phobia. Noninvasive transdermal delivery is an alternative administration route for the local and systemic delivery of biological macromolecular drugs. However, a challenge with the noninvasive transdermal delivery of biological macromolecular drugs is the outermost layer of the skin, known as the stratum corneum, which is a physical barrier that restricts the entry of extraneous macromolecules. Iontophoresis (IP) relies on the application of a low level of electricity for transdermal drug delivery, in order to facilitate the skin permeation of hydrophilic and charged molecules. The IP of several biological macromolecular drugs has recently been investigated. Herein, we review the IP-mediated noninvasive transdermal delivery of biological macromolecular drugs, their routes of skin permeation, their underlying mechanisms, and their advance applications."},"publication_date":"2022-02-26","publication_name":{"en":"Pharmaceutics","ja":"Pharmaceutics"},"volume":"Vol.14","number":"No.3","starting_page":"525","ending_page":"525","languages":["eng"],"identifiers":{"doi":["10.3390/pharmaceutics14030525"],"issn":["1999-4923"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:5, {"insert":{"user_id":"1000193501","type":"misc","id":"39666219"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117590","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35214092","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390036","label":"url"}],"paper_title":{"en":"Application and utility of liposomal neuroprotective agents and biomimetic nanoparticles for the treatment of ischemic stroke","ja":"Application and utility of liposomal neuroprotective agents and biomimetic nanoparticles for the treatment of ischemic stroke"},"authors":{"en":[{"name":"Fukuta Tatsuya"},{"name":"Oku Naoto"},{"name":"Kogure Kentaro"}],"ja":[{"name":"福田 達也"},{"name":"Oku Naoto"},{"name":"小暮 健太朗"}]},"description":{"en":"Ischemic stroke is still one of the leading causes of high mortality and severe disability worldwide. Therapeutic options for ischemic stroke and subsequent cerebral ischemia/reperfusion injury remain limited due to challenges associated with drug permeability through the blood-brain barrier (BBB). Neuroprotectant delivery with nanoparticles, including liposomes, offers a promising solution to address this problem, as BBB disruption following ischemic stroke allows nanoparticles to pass through the intercellular gaps between endothelial cells. To ameliorate ischemic brain damage, a number of nanotherapeutics encapsulating neuroprotective agents, as well as surface-modified nanoparticles with specific ligands targeting the injured brain regions, have been developed. Combination therapy with nanoparticles encapsulating neuroprotectants and tissue plasminogen activator (t-PA), a globally approved thrombolytic agent, has been demonstrated to extend the narrow therapeutic time window of t-PA. In addition, the design of biomimetic drug delivery systems (DDS) employing circulating cells (e.g., leukocytes, platelets) with unique properties has recently been investigated to overcome the injured BBB, utilizing these cells' inherent capability to penetrate the ischemic brain. Herein, we review recent findings on the application and utility of nanoparticle DDS, particularly liposomes, and various approaches to developing biomimetic DDS functionalized with cellular membranes/membrane proteins for the treatment of ischemic stroke.","ja":"Ischemic stroke is still one of the leading causes of high mortality and severe disability worldwide. Therapeutic options for ischemic stroke and subsequent cerebral ischemia/reperfusion injury remain limited due to challenges associated with drug permeability through the blood-brain barrier (BBB). Neuroprotectant delivery with nanoparticles, including liposomes, offers a promising solution to address this problem, as BBB disruption following ischemic stroke allows nanoparticles to pass through the intercellular gaps between endothelial cells. To ameliorate ischemic brain damage, a number of nanotherapeutics encapsulating neuroprotective agents, as well as surface-modified nanoparticles with specific ligands targeting the injured brain regions, have been developed. Combination therapy with nanoparticles encapsulating neuroprotectants and tissue plasminogen activator (t-PA), a globally approved thrombolytic agent, has been demonstrated to extend the narrow therapeutic time window of t-PA. In addition, the design of biomimetic drug delivery systems (DDS) employing circulating cells (e.g., leukocytes, platelets) with unique properties has recently been investigated to overcome the injured BBB, utilizing these cells' inherent capability to penetrate the ischemic brain. Herein, we review recent findings on the application and utility of nanoparticle DDS, particularly liposomes, and various approaches to developing biomimetic DDS functionalized with cellular membranes/membrane proteins for the treatment of ischemic stroke."},"publication_date":"2022-02-04","publication_name":{"en":"Pharmaceutics","ja":"Pharmaceutics"},"volume":"Vol.14","number":"No.2","starting_page":"361","ending_page":"361","languages":["eng"],"identifiers":{"doi":["10.3390/pharmaceutics14020361"],"issn":["1999-4923"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:6, {"insert":{"user_id":"1000193501","type":"misc","id":"39048734"},"force":{"see_also":[{"@id":"https://www.jstage.jst.go.jp/article/dds/36/3/36_198/_pdf","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390289920608691840/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=387035","label":"url"}],"paper_title":{"en":"Transdermal drug delivery by iontophoresis","ja":"イオントフォレシスによる経皮デリバリー"},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"Fukuta Tatsuya"}],"ja":[{"name":"小暮 健太朗"},{"name":"福田 達也"}]},"description":{"en":"Functional macromolecules, such as siRNA, are expected as the ideal drugs to induce immune response and suppress specific genes for therapy of skin disorders and cancer. However, delivery of the macromolecules into skin is difficult due to large molecular weight and high hydrophilicity. Since iontophoresis is known to accelerate transdermal permeation of charged molecules by applying a weak electric current to the skin, we paid attention to iontophoresis as an ideal technology for transdermal delivery, and attempted transdermal delivery of macromolecules. siRNA is expected as novel nucleic acid medicines. Thus, we examined iontophoresis of naked siRNA on rat skin <i>in vivo</i>. Naked siRNA was effectively accumulated in the skin after iontophoresis. In addition, iontophoretic delivery of siRNA significantly reduced the target mRNA. From this result, it was suggested that siRNA was delivered into not only the skin tissue, but also cytoplasm of target cells. Then, we analyzed the <i>in vitro</i> intracellular delivery of fluorescent-labeled siRNA by weak electric current(WEC), and found that cellular uptake of fluorescent-labeled siRNA was increased by WEC, while endocytosis inhibitors significantly prevented siRNA uptake. These results indicate that the cellular uptake mechanism by WEC is endocytosis. Moreover, we compared the intracellular trafficking of macromolecule FITC-dextran, which has different molecular weight, 10,000 and 70,000, taken up by weak electric current. The 10,000 dextran spread to cytoplasm, but 70,000 dextran remained in endosome/lysosomes. This result suggested that WEC treatment induced very unique endosome that leaked macromolecules with a molecular weight of less than 70,000. Transmission electron microscopy of cells treated by WEC showed that the WEC-induced endosomes exhibited an elliptical shape. In the WEC-induced endosomes, ceramide, which makes pore structures in the membrane, was localized. Interestingly, we found that WEC accelerates the production of exosomes as a result of stimulation of the endocytosis. In this review, we also introduce recent findings regarding IP-mediated transdermal drug delivery of bio-macromolecules such as antibody and WEC-mediated increases in vascular permeability.","ja":"イオントフォレシス(IP)は，微弱電流を用いる経皮デリバリー技術であるが，従来その適用は荷電を有する疎水性化合物に限定され，親水性高分子はIPに適用できないと考えられてきた．しかし筆者らは，核酸医薬siRNAなどのIPによる経皮デリバリーに成功した．メカニズム解析の結果，微弱電流処理により，細胞シグナル系が活性化されて皮膚組織細胞間隙が開裂することで，高分子が皮内に浸透可能になること，さらに，エンドサイトーシスが誘起され細胞質まで送達されることが明らかになってきた．また，微弱電流によってエクソソーム分泌が促進されることも見出している．本稿では，最近の知見も交えてIPによる経皮デリバリーについて紹介する．"},"publication_date":"2021-10","publication_name":{"en":"Drug Delivery System","ja":"Drug Delivery System"},"volume":"Vol.36","number":"No.3","starting_page":"90","ending_page":"100","languages":["jpn"],"identifiers":{"doi":["10.2745/dds.36.198"],"issn":["0913-5006"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:7, {"insert":{"user_id":"1000193501","type":"misc","id":"33233758"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32589904","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=367404","label":"url"}],"paper_title":{"en":"Noninvasive transdermal delivery of liposomes by weak electric current.","ja":"Noninvasive transdermal delivery of liposomes by weak electric current."},"authors":{"en":[{"name":"Hasan Mahadi"},{"name":"Khatun Anowara"},{"name":"Fukuta Tatsuya"},{"name":"Kogure Kentaro"}],"ja":[{"name":"Hasan Mahadi"},{"name":"Khatun Anowara"},{"name":"福田 達也"},{"name":"小暮 健太朗"}]},"description":{"en":"Noninvasive transdermal drug delivery (NTDD) offers an exciting new method of administration relative to conventional routes, but is associated with some challenges. Liposomes are capable of encapsulating transdermally-unfavorable drugs. However, the horny layer of skin is a significant barrier that limits efficient transdermal delivery of liposomes. Iontophoresis using weak electric current (WEC) represents a NTDD technology. WEC treatment of liposomes applied to the skin surface improves transdermal penetration of encapsulated drugs by cooperative effects. In this review, we provide an overview of the application of WEC/liposomes for transdermal delivery of macromolecules and low molecular weight drugs. We compare the transdermal delivery and therapeutic efficiency of the combined system with conventional routes of administration and their individual use. We discuss a novel perspective on the mechanism of WEC-mediated transdermal delivery of liposomes, which suggests that WEC activates the intracellular signaling pathway for transdermal permeation and induces unique endocytosis in skin cells.","ja":"Noninvasive transdermal drug delivery (NTDD) offers an exciting new method of administration relative to conventional routes, but is associated with some challenges. Liposomes are capable of encapsulating transdermally-unfavorable drugs. However, the horny layer of skin is a significant barrier that limits efficient transdermal delivery of liposomes. Iontophoresis using weak electric current (WEC) represents a NTDD technology. WEC treatment of liposomes applied to the skin surface improves transdermal penetration of encapsulated drugs by cooperative effects. In this review, we provide an overview of the application of WEC/liposomes for transdermal delivery of macromolecules and low molecular weight drugs. We compare the transdermal delivery and therapeutic efficiency of the combined system with conventional routes of administration and their individual use. We discuss a novel perspective on the mechanism of WEC-mediated transdermal delivery of liposomes, which suggests that WEC activates the intracellular signaling pathway for transdermal permeation and induces unique endocytosis in skin cells."},"publication_date":"2020-06-24","publication_name":{"en":"Advanced Drug Delivery Reviews","ja":"Advanced Drug Delivery Reviews"},"volume":"Vol.154-155","starting_page":"227","ending_page":"235","languages":["eng"],"identifiers":{"doi":["10.1016/j.addr.2020.06.016"],"issn":["1872-8294"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:8, {"insert":{"user_id":"1000193501","type":"misc","id":"33233759"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32378660","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=367405","label":"url"}],"paper_title":{"en":"[Drug Delivery to Various Body Organs via Non-blood Circulatory Pathway].","ja":"[Drug Delivery to Various Body Organs via Non-blood Circulatory Pathway]."},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"Fukuta Tatsuya"}],"ja":[{"name":"小暮 健太朗"},{"name":"福田 達也"}]},"description":{"en":"Delivery of nucleic acid therapeutics to target body organs requires injection of nanocarriers into the bloodstream. However, as such nanocarriers would also be delivered to non-target organs, low delivery efficiency to target organs and risk of unexpected effects are clear limitations of this technology. We recently applied iontophoresis (IP) for direct delivery of nucleic acid therapeutics to various organs. IP relies on a weak electric current for noninvasive transdermal drug delivery. We found that IP can deliver hydrophilic macromolecules and nanoparticles into the skin. We previously succeeded in transdermal delivery of siRNA, and subsequent knockdown (70%) of target mRNA levels in the skin via IP of siRNA (Int. J. Pharm., 383, 2010, Kigasawa et al.). Moreover, we found that cell signal activation and cleavage of intercellular junctions are induced by IP (J. Biol. Chem., 289, 2014, Hama et al.). We hypothesized that this phenomenon should be observed in not only skin but also other organs, and subsequently carried out IP of nucleic acid therapeutics to various body organs including liver, pancreas and kidney. This technique resulted in delivery of nucleic acid therapeutics into the various target body organs, and subsequent knockdown of target genes. These results suggest that direct delivery to target body organs via non-blood circulatory pathway is possible. This technology may offer a solution to the various limitations associated with current drug delivery systems (DDS).","ja":"Delivery of nucleic acid therapeutics to target body organs requires injection of nanocarriers into the bloodstream. However, as such nanocarriers would also be delivered to non-target organs, low delivery efficiency to target organs and risk of unexpected effects are clear limitations of this technology. We recently applied iontophoresis (IP) for direct delivery of nucleic acid therapeutics to various organs. IP relies on a weak electric current for noninvasive transdermal drug delivery. We found that IP can deliver hydrophilic macromolecules and nanoparticles into the skin. We previously succeeded in transdermal delivery of siRNA, and subsequent knockdown (70%) of target mRNA levels in the skin via IP of siRNA (Int. J. Pharm., 383, 2010, Kigasawa et al.). Moreover, we found that cell signal activation and cleavage of intercellular junctions are induced by IP (J. Biol. Chem., 289, 2014, Hama et al.). We hypothesized that this phenomenon should be observed in not only skin but also other organs, and subsequently carried out IP of nucleic acid therapeutics to various body organs including liver, pancreas and kidney. This technique resulted in delivery of nucleic acid therapeutics into the various target body organs, and subsequent knockdown of target genes. These results suggest that direct delivery to target body organs via non-blood circulatory pathway is possible. This technology may offer a solution to the various limitations associated with current drug delivery systems (DDS)."},"publication_date":"2020","publication_name":{"en":"Journal of the Pharmaceutical Society of Japan","ja":"薬学雑誌"},"volume":"Vol.140","number":"No.5","starting_page":"611","ending_page":"615","languages":["jpn"],"identifiers":{"doi":["10.1248/yakushi.19-00218-1"],"issn":["1347-5231"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
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line:10, {"insert":{"user_id":"1000193501","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=338993","label":"url"}],"paper_title":{"en":"アスタキサンチンのヘマトコッカス培養による生産と機能性研究","ja":"アスタキサンチンのヘマトコッカス培養による生産と機能性研究"},"authors":{"en":[{"name":"Kogure Kentaro"}],"ja":[{"name":"小暮 健太朗"}]},"publication_date":"2017-04","publication_name":{"en":"アグリバイオ","ja":"アグリバイオ"},"volume":"Vol.1","starting_page":"9","ending_page":"13","languages":["jpn"],"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
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line:12, {"insert":{"user_id":"1000193501","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://ci.nii.ac.jp/naid/40020987954/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1523951030575326592/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=327661","label":"url"}],"paper_title":{"en":"Control of Tissue and Cellular Physiology by Faint Electricity for Delivery of Nanomedicine","ja":"ナノメディシン送達のための微弱電流による組織細胞生理の制御"},"authors":{"en":[{"name":"Kogure Kentaro"}],"ja":[{"name":"小暮 健太朗"}]},"publication_date":"2016-11","publication_name":{"en":"Chemical Industry","ja":"化学工業"},"volume":"Vol.67","number":"No.11","starting_page":"14","ending_page":"20","languages":["jpn"],"identifiers":{"issn":["0451-2014"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:13, {"insert":{"user_id":"1000193501","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/14972018","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-3543145018&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=145252","label":"url"}],"paper_title":{"en":"Enhancement of Nitric Oxide and Superoxide Generations by α-Tocopheryl Succinate and Its Apoptotic and Anticancer Effects","ja":"Enhancement of Nitric Oxide and Superoxide Generations by α-Tocopheryl Succinate and Its Apoptotic and Anticancer Effects"},"authors":{"en":[{"name":"Fukuzawa Kenji"},{"name":"Kogure Kentaro"},{"name":"Morita Motoki"},{"name":"Hama Susumu"},{"name":"Tokumura Akira"}],"ja":[{"name":"福澤 健治"},{"name":"小暮 健太朗"},{"name":"Morita Motoki"},{"name":"Hama Susumu"},{"name":"德村 彰"}]},"description":{"en":"Tocopheryl succinate (TS), a succinyl ester of alpha-tocopherol (alpha-T), has been reported to have various biological activities. In this communication, we review the current findings about TS including our recent studies of its effects on nitric oxide (NO) and superoxide (O2-) generations implicated in cancer and atherosclerosis. First, we investigated the effect of TS on NO production in vascular smooth muscle cells (VSMC) under atherosclerosis-like conditions using lipopolysaccharide (LPS) and interferon-gamma (IFN). TS enhanced LPS/IFN-dependent NO production, but alpha-T itself did not. The enhancement by TS of NO production was inhibited by alpha-T but not by antioxidants such as ascorbic acid and 2[3]-t-butyl-4-hydroxyanisole (BHA). TS enhanced the amount of protein kinase Calpha (PKCalpha) in VSMC, and PKC inhibitors inhibited TS-enhanced NO production, suggesting that the enhancing effect of TS on NO production is caused by up-regulation of PKC. Second, we found that TS induced apoptosis in VSMC associated with increase in O2- generation via NADPH-dependent oxidase. We further observed that a mouse breast cancer cell line C127I was more susceptible for TS-induced apoptosis than a mouse breast normal cell line NmuMG, and that superoxide dismutase, alpha-T, and BHA inhibited TS-caused morphological cell damage in C127I. From these results, O2- itself and/or other reactive oxygen species are assumed to associate with TS-induced cell toxicity, and antioxidative defense systems are supposed to be lowered in cancer cells. Finally, we found that intravenous injection of TS vesicles completely inhibited the growth of melanoma cells B16-F1 inoculated on the back of hairless mice and enhanced their survival time.","ja":"Tocopheryl succinate (TS), a succinyl ester of alpha-tocopherol (alpha-T), has been reported to have various biological activities. In this communication, we review the current findings about TS including our recent studies of its effects on nitric oxide (NO) and superoxide (O2-) generations implicated in cancer and atherosclerosis. First, we investigated the effect of TS on NO production in vascular smooth muscle cells (VSMC) under atherosclerosis-like conditions using lipopolysaccharide (LPS) and interferon-gamma (IFN). TS enhanced LPS/IFN-dependent NO production, but alpha-T itself did not. The enhancement by TS of NO production was inhibited by alpha-T but not by antioxidants such as ascorbic acid and 2[3]-t-butyl-4-hydroxyanisole (BHA). TS enhanced the amount of protein kinase Calpha (PKCalpha) in VSMC, and PKC inhibitors inhibited TS-enhanced NO production, suggesting that the enhancing effect of TS on NO production is caused by up-regulation of PKC. Second, we found that TS induced apoptosis in VSMC associated with increase in O2- generation via NADPH-dependent oxidase. We further observed that a mouse breast cancer cell line C127I was more susceptible for TS-induced apoptosis than a mouse breast normal cell line NmuMG, and that superoxide dismutase, alpha-T, and BHA inhibited TS-caused morphological cell damage in C127I. From these results, O2- itself and/or other reactive oxygen species are assumed to associate with TS-induced cell toxicity, and antioxidative defense systems are supposed to be lowered in cancer cells. Finally, we found that intravenous injection of TS vesicles completely inhibited the growth of melanoma cells B16-F1 inoculated on the back of hairless mice and enhanced their survival time."},"publication_date":"2004-01","publication_name":{"en":"Biochemistry (Moscow)","ja":"Biochemistry (Moscow)"},"volume":"Vol.69","number":"No.1","starting_page":"50","ending_page":"57","languages":["eng"],"identifiers":{"doi":["10.1023/B:BIRY.0000016351.77553.74"],"issn":["0006-2979"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:14, {"insert":{"user_id":"1000193501","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=145256","label":"url"}],"paper_title":{"en":"Tocopheryl succinate-versatile function due to its unique physicochemical properties","ja":"Tocopheryl succinate-versatile function due to its unique physicochemical properties"},"authors":{"en":[{"name":"Kogure Kentaro"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"小暮 健太朗"},{"name":"福澤 健治"}]},"publication_date":"2004","publication_name":{"en":"Journal of Clinical Biochemistry and Nutrition","ja":"Journal of Clinical Biochemistry and Nutrition"},"volume":"Vol.35","number":"No.1","starting_page":"29","ending_page":"34","identifiers":{"doi":["10.3164/jcbn.35.29"],"issn":["1880-5086"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
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line:16, {"insert":{"user_id":"1000193501","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=146198","label":"url"}],"paper_title":{"en":"喫煙が血液中で悪玉リン脂質をつくるー動脈硬化との関連ー","ja":"喫煙が血液中で悪玉リン脂質をつくるー動脈硬化との関連ー"},"authors":{"en":[{"name":"土江 明子"},{"name":"Tokumura Akira"},{"name":"Kogure Kentaro"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"土江 明子"},{"name":"德村 彰"},{"name":"小暮 健太朗"},{"name":"福澤 健治"}]},"publication_date":"2002","publication_name":{"en":"日本薬学会 第122年会講演ハイライト","ja":"日本薬学会 第122年会講演ハイライト"},"starting_page":"22","ending_page":"22","languages":["jpn"],"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
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