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{"insert":{"user_id":"1000193501","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2010392","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":"14","number":"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"}
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{"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/pages/publications/3543145018","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":"69","number":"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"}
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{"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"}
{"insert":{"user_id":"1000193501","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11237195","label":"url"},{"@id":"https://www.scopus.com/pages/publications/0034490867","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=146173","label":"url"}],"paper_title":{"en":"Platelet-activating factor (PAF)- like oxidized phospholipids: relevance to atherosclerosis","ja":"Platelet-activating factor (PAF)- like oxidized phospholipids: relevance to atherosclerosis"},"authors":{"en":[{"name":"Tokumura Akira"},{"name":"Sumida Tuneki"},{"name":"Toujima Masaoki"},{"name":"Kogure Kentaro"},{"name":"Fukuzawa Kenji"}],"ja":[{"name":"德村 彰"},{"name":"Sumida Tuneki"},{"name":"Toujima Masaoki"},{"name":"小暮 健太朗"},{"name":"福澤 健治"}]},"description":{"en":"Lipid peroxidation is involved in the pathogenesis of chronic diseases including atherosclerosis. Oxidized lipoprotein has diverse biological activities and is believed to initiate atheroma formation and maturate fatty plaque. The active components of oxidized lipoproteins still remain to be clarified, but a likely candidate is the phosphatidylcholine (PC) having an sn-2-short-chain acyl group with a methyl, hydroxyl, aldehydic or carboxylic terminal. These unique PCs, formed by oxidative fragmentation of the polyunsaturated acyl group of the parent PC in liposomes, low density lipoproteins and blood plasma, induce platelet aggregation through the activation of the receptor for platelet-activating factor (PAF), due to their resemblance in structure with PAF. We have found that PAF-like lipids regulate DNA synthesis and production of nitric oxide independently of the activation of the PAF receptor in vascular smooth muscle cells. Regulation of vascular cell function through two distinct signaling pathways mediated by PAF-like lipids provides new insight into the mechanism of induction of atherosclerosis.","ja":"Lipid peroxidation is involved in the pathogenesis of chronic diseases including atherosclerosis. Oxidized lipoprotein has diverse biological activities and is believed to initiate atheroma formation and maturate fatty plaque. The active components of oxidized lipoproteins still remain to be clarified, but a likely candidate is the phosphatidylcholine (PC) having an sn-2-short-chain acyl group with a methyl, hydroxyl, aldehydic or carboxylic terminal. These unique PCs, formed by oxidative fragmentation of the polyunsaturated acyl group of the parent PC in liposomes, low density lipoproteins and blood plasma, induce platelet aggregation through the activation of the receptor for platelet-activating factor (PAF), due to their resemblance in structure with PAF. We have found that PAF-like lipids regulate DNA synthesis and production of nitric oxide independently of the activation of the PAF receptor in vascular smooth muscle cells. Regulation of vascular cell function through two distinct signaling pathways mediated by PAF-like lipids provides new insight into the mechanism of induction of atherosclerosis."},"publication_date":"2000","publication_name":{"en":"BioFactors","ja":"BioFactors"},"volume":"13","number":"1-4","starting_page":"29","ending_page":"33","languages":["eng"],"identifiers":{"issn":["0951-6433"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
