=== Generating (published_papers) ===
=== Generating (research_interests) ===
=== Generating (education) ===
=== Generating (research_experience) ===
=== Generating (misc) ===
=== Generating (research_projects) ===
=== Generating (books_etc) ===
=== Generating (industrial_property_rights) ===
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=== Generating (presentations) ===
==== begin registerFile(/WWW/pub2/data/ERD/person/219499/researchmap/published_papers-propagate.jsonl) ====
line:1, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2012831","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/39179333","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=414311","label":"url"}],"paper_title":{"en":"Effects of D-Allose on experimental cardiac hypertrophy.","ja":"Effects of D-Allose on experimental cardiac hypertrophy."},"authors":{"en":[{"name":"Akumwami Steeve"},{"name":"Rahman Asadur"},{"name":"Funamoto Masafumi"},{"name":"Hossain Akram"},{"name":"Morishita Asahiro"},{"name":"Ikeda Yasumasa"},{"name":"Kitamura Hiroaki"},{"name":"Kitada Kento"},{"name":"Noma Takahisa"},{"name":"Ogino Yuichi"},{"name":"Nishiyama Akira"}],"ja":[{"name":"Akumwami Steeve"},{"name":"Rahman Asadur"},{"name":"船本 雅文"},{"name":"Hossain Akram"},{"name":"Morishita Asahiro"},{"name":"池田 康将"},{"name":"Kitamura Hiroaki"},{"name":"Kitada Kento"},{"name":"Noma Takahisa"},{"name":"Ogino Yuichi"},{"name":"Nishiyama Akira"}]},"description":{"en":"The hallmark of pathological cardiac hypertrophy is the decline in myocardial contractility caused by an energy deficit resulting from metabolic abnormalities, particularly those related to glucose metabolism. Here, we aim to explore whether D-Allose, a rare sugar that utilizes the same transporters as glucose, may restore metabolic equilibrium and reverse cardiac hypertrophy. Isolated neonatal rat cardiomyocytes were stimulated with phenylephrine and treated with D-Allose simultaneously for 48 h. D-Allose treatment resulted in a pronounced reduction in cardiomyocyte size and cardiac remodelling markers accompanied with a dramatic reduction in the level of intracellular glucose in phenylephrine-stimulated cells. The metabolic flux analysis provided further insights revealing that D-Allose exerted a remarkable inhibition of glycolysis as well as glycolytic capacity. Furthermore, in mice subjected to a 14-day continuous infusion of isoproterenol (ISO) to induce cardiac hypertrophy, D-Allose treatment via drinking water notably reduced ISO-induced cardiac hypertrophy and remodelling markers, with minimal effects on ventricular wall thickness observed in echocardiographic analyses. These findings indicate that D-Allose has the ability to attenuate the progression of cardiomyocyte hypertrophy by decreasing intracellular glucose flux and inhibiting glycolysis.","ja":"The hallmark of pathological cardiac hypertrophy is the decline in myocardial contractility caused by an energy deficit resulting from metabolic abnormalities, particularly those related to glucose metabolism. Here, we aim to explore whether D-Allose, a rare sugar that utilizes the same transporters as glucose, may restore metabolic equilibrium and reverse cardiac hypertrophy. Isolated neonatal rat cardiomyocytes were stimulated with phenylephrine and treated with D-Allose simultaneously for 48 h. D-Allose treatment resulted in a pronounced reduction in cardiomyocyte size and cardiac remodelling markers accompanied with a dramatic reduction in the level of intracellular glucose in phenylephrine-stimulated cells. The metabolic flux analysis provided further insights revealing that D-Allose exerted a remarkable inhibition of glycolysis as well as glycolytic capacity. Furthermore, in mice subjected to a 14-day continuous infusion of isoproterenol (ISO) to induce cardiac hypertrophy, D-Allose treatment via drinking water notably reduced ISO-induced cardiac hypertrophy and remodelling markers, with minimal effects on ventricular wall thickness observed in echocardiographic analyses. These findings indicate that D-Allose has the ability to attenuate the progression of cardiomyocyte hypertrophy by decreasing intracellular glucose flux and inhibiting glycolysis."},"publication_date":"2024-08-08","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"156","number":"2","starting_page":"142","ending_page":"148","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jphs.2024.08.002"],"issn":["1347-8648"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:2, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36940907","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1360017282221457024/","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85151399970","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=397020","label":"url"}],"paper_title":{"en":"Pemafibrate inhibited renal dysfunction and fibrosis in a mouse model of adenine-induced chronic kidney disease.","ja":"Pemafibrate inhibited renal dysfunction and fibrosis in a mouse model of adenine-induced chronic kidney disease."},"authors":{"en":[{"name":"Horinouchi Yuya"},{"name":"Murashima Yuka"},{"name":"Yamada Yuto"},{"name":"Yoshioka Shun"},{"name":"Fukushima Keijo"},{"name":"Kure Takumi"},{"name":"Sasaki Naofumi"},{"name":"Imanishi Masaki"},{"name":"Fujino Hiromichi"},{"name":"Tsuchiya Koichiro"},{"name":"Shinomiya Kazuaki"},{"name":"Ikeda Yasumasa"}],"ja":[{"name":"堀ノ内 裕也"},{"name":"Murashima Yuka"},{"name":"Yamada Yuto"},{"name":"Yoshioka Shun"},{"name":"福島 圭穣"},{"name":"Kure Takumi"},{"name":"Sasaki Naofumi"},{"name":"今西 正樹"},{"name":"藤野 裕道"},{"name":"土屋 浩一郎"},{"name":"Shinomiya Kazuaki"},{"name":"池田 康将"}]},"description":{"en":"These results demonstrated the renoprotective effects of pemafibrate in CKD mice, confirming its potential as a therapeutic agent for renal disorders.","ja":"The risks associated with conventional fibrates (fenofibrate, bezafibrate) to the kidneys were evaluated using the Food and Drug Administration Adverse Event Reporting System. Pemafibrate (1 or 0.3 mg/kg/day) was administered daily using an oral sonde. Its renoprotective effects were examined in unilateral ureteral obstruction (UUO)-induced renal fibrosis model mice (UUO mice) and adenine-induced CKD model mice (CKD mice)."},"publication_date":"2023-03-18","publication_name":{"en":"Life Sciences","ja":"Life Sciences"},"volume":"321","starting_page":"121590","ending_page":"121590","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.lfs.2023.121590"],"issn":["1879-0631"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:3, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2011020","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36244745","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=393955","label":"url"}],"paper_title":{"en":"Plasma Heparin Cofactor II Activity Is Inversely Associated with Hepatic Fibrosis of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus.","ja":"Plasma Heparin Cofactor II Activity Is Inversely Associated with Hepatic Fibrosis of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus."},"authors":{"en":[{"name":"Hara Tomoyo"},{"name":"Uemoto Ryoko"},{"name":"Sekine Akiko"},{"name":"Mitsui Yukari"},{"name":"Masuda Shiho"},{"name":"Yamagami Hiroki"},{"name":"Kurahashi Kiyoe"},{"name":"Yoshida Sumiko"},{"name":"Otoda Toshiki"},{"name":"Yuasa Tomoyuki"},{"name":"Kuroda Akio"},{"name":"Ikeda Yasumasa"},{"name":"Endo Itsuro"},{"name":"Honda Soichi"},{"name":"Yoshimoto Katsuhiko"},{"name":"Kondo Akira"},{"name":"Tamaki Toshiaki"},{"name":"Matsumoto Toshio"},{"name":"Matsuhisa Munehide"},{"name":"Abe Masahiro"},{"name":"Aihara Ken-ichi"}],"ja":[{"name":"原 倫世"},{"name":"Uemoto Ryoko"},{"name":"Sekine Akiko"},{"name":"Mitsui Yukari"},{"name":"桝田 志保"},{"name":"山上 紘規"},{"name":"倉橋 清衛"},{"name":"吉田 守美子"},{"name":"乙田 敏城"},{"name":"湯浅 智之"},{"name":"黒田 暁生"},{"name":"池田 康将"},{"name":"遠藤 逸朗"},{"name":"Honda Soichi"},{"name":"吉本 勝彦"},{"name":"Kondo Akira"},{"name":"玉置 俊晃"},{"name":"松本 俊夫"},{"name":"松久 宗英"},{"name":"安倍 正博"},{"name":"粟飯原 賢一"}]},"description":{"en":"Plasma HCII activity was inversely associated with clinical hepatic fibrosis indices including FIB-4 index, NFS and APRI and with the prevalence of advanced hepatic fibrosis in patients with T2DM. The results suggest that HCII can serve as a novel biomarker for assessment of hepatic fibrosis of NAFLD in patients with T2DM.","ja":"Multiple regression analysis including confounding factors showed that plasma HCII activity independently contributed to decreases in FIB-4 index (p<0.001), NFS (p<0.001) and APRI (p=0.004). In addition, logistic regression analysis for the prevalence of advanced hepatic fibrosis defined by the cutoff points of the clinical scores showed that plasma HCII activity was the sole and common negative factor for prevalence of advanced hepatic fibrosis (FIB-4 index: p=0.002, NFS: p=0.026 and APRI: p=0.012)."},"publication_date":"2022-10-14","publication_name":{"en":"Journal of Atherosclerosis and Thrombosis","ja":"Journal of Atherosclerosis and Thrombosis"},"languages":["eng"],"referee":true,"identifiers":{"doi":["10.5551/jat.63752"],"issn":["1880-3873"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:4, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2011191","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36172003","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=392443","label":"url"}],"paper_title":{"en":"Effects of high-absorption curcumin for the prevention of hypertensive heart disease: a double-blind, placebo-controlled, randomized clinical study.","ja":"Effects of high-absorption curcumin for the prevention of hypertensive heart disease: a double-blind, placebo-controlled, randomized clinical study."},"authors":{"en":[{"name":"Funamoto Masafumi"},{"name":"Sunagawa Yoichi"},{"name":"Katanasaka Yasufumi"},{"name":"Kato Toru"},{"name":"Funada Junichi"},{"name":"Ajiro Yoichi"},{"name":"Komiyama Maki"},{"name":"Akao Masaharu"},{"name":"Yasoda Akihiro"},{"name":"Yamakage Hajime"},{"name":"Satoh-Asahara Noriko"},{"name":"Wada Hiromichi"},{"name":"Ikeda Yasumasa"},{"name":"Morimoto Tatsuya"},{"name":"Hasegawa Koji"}],"ja":[{"name":"船本 雅文"},{"name":"Sunagawa Yoichi"},{"name":"Katanasaka Yasufumi"},{"name":"Kato Toru"},{"name":"Funada Junichi"},{"name":"Ajiro Yoichi"},{"name":"Komiyama Maki"},{"name":"Akao Masaharu"},{"name":"Yasoda Akihiro"},{"name":"Yamakage Hajime"},{"name":"Satoh-Asahara Noriko"},{"name":"Wada Hiromichi"},{"name":"池田 康将"},{"name":"Morimoto Tatsuya"},{"name":"Hasegawa Koji"}]},"description":{"en":"' ratio, rather it significantly inhibited the increase in plasma BNP levels in patients with initial signs of hypertensive heart disease.","ja":"for interaction = 0.011)."},"publication_date":"2022-09-10","publication_name":{"en":"European Heart Journal Open","ja":"European Heart Journal Open"},"volume":"107","starting_page":"154457","ending_page":"154457","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1093/ehjopen/oeac057"],"issn":["2752-4191"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:5, {"insert":{"user_id":"B000241782","type":"published_papers","id":"33322220"},"force":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2009447","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/34043882","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=376531","label":"url"}],"paper_title":{"en":"Plasma Heparin Cofactor II Activity Is Inversely Associated with Albuminuria and Its Annual Deterioration in Patients with Diabetes.","ja":"Plasma Heparin Cofactor II Activity Is Inversely Associated with Albuminuria and Its Annual Deterioration in Patients with Diabetes."},"authors":{"en":[{"name":"Hara Tomoyo"},{"name":"Uemoto Ryoko"},{"name":"Sekine Akiko"},{"name":"Mitsui Yukari"},{"name":"Masuda Shiho"},{"name":"Kurahashi Kiyoe"},{"name":"Yoshida Sumiko"},{"name":"Otoda Toshiki"},{"name":"Yuasa Tomoyuki"},{"name":"Kuroda Akio"},{"name":"Ikeda Yasumasa"},{"name":"Endo Itsuro"},{"name":"Honda Soichi"},{"name":"Yoshimoto Katsuhiko"},{"name":"Kondo Akira"},{"name":"Tamaki Toshiaki"},{"name":"Matsumoto Toshio"},{"name":"Matsuhisa Munehide"},{"name":"Abe Masahiro"},{"name":"Aihara Ken-ichi"}],"ja":[{"name":"原 倫世"},{"name":"Uemoto Ryoko"},{"name":"Sekine Akiko"},{"name":"Mitsui Yukari"},{"name":"桝田 志保"},{"name":"倉橋 清衛"},{"name":"吉田 守美子"},{"name":"乙田 敏城"},{"name":"湯浅 智之"},{"name":"黒田 暁生"},{"name":"池田 康将"},{"name":"遠藤 逸朗"},{"name":"Honda Soichi"},{"name":"吉本 勝彦"},{"name":"Kondo Akira"},{"name":"玉置 俊晃"},{"name":"松本 俊夫"},{"name":"松久 宗英"},{"name":"安倍 正博"},{"name":"粟飯原 賢一"}]},"description":{"en":"The plasma HCII activity was inversely and specifically associated with glomerular injury in patients with diabetes. The results suggest that HCII can serve as a novel predictive factor for early-stage DKD development, as represented by albuminuria.","ja":"The plasma HCII activity was inversely and specifically associated with glomerular injury in patients with diabetes. The results suggest that HCII can serve as a novel predictive factor for early-stage DKD development, as represented by albuminuria."},"publication_date":"2021-05-27","publication_name":{"en":"Journal of Diabetes Investigation","ja":"Journal of Diabetes Investigation"},"languages":["eng"],"referee":true,"identifiers":{"doi":["10.1111/jdi.13602"],"issn":["2040-1124"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:6, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://repo.lib.tokushima-u.ac.jp/116038","label":"url"},{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2008973","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1050585658873174784/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390121","label":"url"}],"paper_title":{"en":"薬剤誘発性大動脈解離易発症モデルマウスを用いた薬効評価","ja":"薬剤誘発性大動脈解離易発症モデルマウスを用いた薬効評価"},"authors":{"en":[{"name":"Izawa-Ishizawa Yuki"},{"name":"Goda Mitsuhiro"},{"name":"Aizawa Fuka"},{"name":"Zamami Yoshito"},{"name":"Hamano Hirofumi"},{"name":"Yagi Kenta"},{"name":"Ikeda Yasumasa"},{"name":"Ishizawa Keisuke"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 有紀"},{"name":"合田 光寛"},{"name":"相澤 風花"},{"name":"座間味 義人"},{"name":"濱野 裕章"},{"name":"八木 健太"},{"name":"池田 康将"},{"name":"石澤 啓介"},{"name":"玉置 俊晃"}]},"description":{"en":"Aortic dissection (or dissecting aortic aneurysm) is a condition in which the aortic wall is separated into two layers at the medial level to form a pseudocavity. The intima crack, called the ``entry'', allows blood to tear through the medial layer and flow in. The location of the ``entry'' and the extent of the dissection can cause a variety of serious complications, including rupture, cardiac tamponade, and obstruction of branched vessels. According to the Guideline on Diagnosis and Treatment of Aortic Aneurysm and Aortic Dissection 2020, it is estimated that 61.4% of the onset of dissection die before arrival at the hospital, and 93% will die within 24 hours after the onset. It has been suggested that the morbidity rate has been increasing in recent years. Since many of them have a fatal prognosis, it is an important issue to prevent the onset itself. However, no effective therapeutic agent or preventive strategy has been established so far. The first reason is that it is extremely difficult to design clinical studies because aortic dissection traced the rapid onset and progression. The second is that the pathophysiology and preventive drug search are not sufficiently conducted even at the basic research level. Epidemiologically, the results of the International Registry of Aortic Dissection (IRAD) revealed that aging, hypertension, atherosclerosis, and hereditary connective tissue diseases are risk factors. The aortic aneurysm also shows similar pathological conditions caused by these risk factors. However, one of the major differences between aneurysm and dissection is the presence of aortic intima rupture. Therefore, we attempted to establish a mouse model developing dissection at a high rate by adding the endothelial dysfunction to a pharmacologically induced aortic aneurysm model mouse. Furthermore, we evaluated the efficacy of pitavastatin and several nutrients using our novel model mice and verified its usefulness as a model animal.","ja":"Aortic dissection (or dissecting aortic aneurysm) is a condition in which the aortic wall is separated into two layers at the medial level to form a pseudocavity. The intima crack, called the ``entry'', allows blood to tear through the medial layer and flow in. The location of the ``entry'' and the extent of the dissection can cause a variety of serious complications, including rupture, cardiac tamponade, and obstruction of branched vessels. According to the Guideline on Diagnosis and Treatment of Aortic Aneurysm and Aortic Dissection 2020, it is estimated that 61.4% of the onset of dissection die before arrival at the hospital, and 93% will die within 24 hours after the onset. It has been suggested that the morbidity rate has been increasing in recent years. Since many of them have a fatal prognosis, it is an important issue to prevent the onset itself. However, no effective therapeutic agent or preventive strategy has been established so far. The first reason is that it is extremely difficult to design clinical studies because aortic dissection traced the rapid onset and progression. The second is that the pathophysiology and preventive drug search are not sufficiently conducted even at the basic research level. Epidemiologically, the results of the International Registry of Aortic Dissection (IRAD) revealed that aging, hypertension, atherosclerosis, and hereditary connective tissue diseases are risk factors. The aortic aneurysm also shows similar pathological conditions caused by these risk factors. However, one of the major differences between aneurysm and dissection is the presence of aortic intima rupture. Therefore, we attempted to establish a mouse model developing dissection at a high rate by adding the endothelial dysfunction to a pharmacologically induced aortic aneurysm model mouse. Furthermore, we evaluated the efficacy of pitavastatin and several nutrients using our novel model mice and verified its usefulness as a model animal."},"publication_date":"2021-04-25","publication_name":{"en":"Shikoku Acta Medica","ja":"四国医学雑誌"},"volume":"77","number":"1,2","starting_page":"57","ending_page":"62","languages":["jpn"],"referee":true,"identifiers":{"issn":["0037-3699"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:7, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33845306","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=374831","label":"url"}],"paper_title":{"en":"Dual disruption of eNOS and ApoE gene accelerates kidney fibrosis and senescence after injury.","ja":"Dual disruption of eNOS and ApoE gene accelerates kidney fibrosis and senescence after injury."},"authors":{"en":[{"name":"Nishimura Kenji"},{"name":"Taguchi Kensei"},{"name":"Kishi Seiji"},{"name":"Brooks Craig R"},{"name":"Ochi Arisa"},{"name":"Kadoya Hiroyuki"},{"name":"Ikeda Yasumasa"},{"name":"Miyoshi Masashi"},{"name":"Tamaki Masanori"},{"name":"Abe Hideharu"},{"name":"Aihara Ken-Ichi"},{"name":"Kashihara Naoki"},{"name":"Nagai Kojiro"}],"ja":[{"name":"西村 賢二"},{"name":"Taguchi Kensei"},{"name":"岸 誠司"},{"name":"Brooks Craig R"},{"name":"Ochi Arisa"},{"name":"Kadoya Hiroyuki"},{"name":"池田 康将"},{"name":"Miyoshi Masashi"},{"name":"田蒔 昌憲"},{"name":"Abe Hideharu"},{"name":"Aihara Ken-Ichi"},{"name":"Kashihara Naoki"},{"name":"Nagai Kojiro"}]},"description":{"en":"mice (DKO) were obtained by breeding. Unilateral ureteral obstruction (UUO) was performed on 8-10 week old male mice and the degree of renal tubular injury, fibrosis and kidney senescence were evaluated. DKO manifested elevated blood pressure, higher total cholesterol and lower HDL than WT. DKO showed sustained kidney injury molecule-1 protein expression. Kidney fibrosis was significantly higher in ApoEKO and DKO. mRNA expression of genes related to kidney fibrosis was the highest in DKO. The mRNA expression of Zinc-α2-Glycoprotein and heme oxygenase-1 were significantly decreased in DKO. Furthermore, mRNA expression of p53, p21 and p16 were increased both in ApoEKO and DKO, with DKO being the highest. Senescence associated β-gal positive tubule area was significantly increased in DKO. Increased DNA damage and target of rapamycin-autophagy spatial coupling compartments (TASCCs) formation was found in DKO. Mice with endothelial dysfunction and dyslipidemia developed kidney fibrosis and accelerated senescence even in young mice after injury. These data highlight the fact managing lifestyle-related diseases from a young age is important for CKD prevention.","ja":"mice (DKO) were obtained by breeding. Unilateral ureteral obstruction (UUO) was performed on 8-10 week old male mice and the degree of renal tubular injury, fibrosis and kidney senescence were evaluated. DKO manifested elevated blood pressure, higher total cholesterol and lower HDL than WT. DKO showed sustained kidney injury molecule-1 protein expression. Kidney fibrosis was significantly higher in ApoEKO and DKO. mRNA expression of genes related to kidney fibrosis was the highest in DKO. The mRNA expression of Zinc-α2-Glycoprotein and heme oxygenase-1 were significantly decreased in DKO. Furthermore, mRNA expression of p53, p21 and p16 were increased both in ApoEKO and DKO, with DKO being the highest. Senescence associated β-gal positive tubule area was significantly increased in DKO. Increased DNA damage and target of rapamycin-autophagy spatial coupling compartments (TASCCs) formation was found in DKO. Mice with endothelial dysfunction and dyslipidemia developed kidney fibrosis and accelerated senescence even in young mice after injury. These data highlight the fact managing lifestyle-related diseases from a young age is important for CKD prevention."},"publication_date":"2021-04-09","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"556","starting_page":"142","ending_page":"148","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbrc.2021.03.111"],"issn":["1090-2104"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:8, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2007366","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32430665","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85085484596","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=363775","label":"url"}],"paper_title":{"en":"Deletion of H-ferritin in macrophages alleviates obesity and diabetes induced by high-fat diet in mice","ja":"Deletion of H-ferritin in macrophages alleviates obesity and diabetes induced by high-fat diet in mice"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Watanabe Hiroaki"},{"name":"Shiuchi Tetsuya"},{"name":"Hamano Hirofumi"},{"name":"Horinouchi Yuya"},{"name":"Imanishi Masaki"},{"name":"Goda Mitsuhiro"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Miyamoto Licht"},{"name":"Ishizawa Keisuke"},{"name":"Aihara Ken-ichi"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"渡邊 大晃"},{"name":"志内 哲也"},{"name":"濱野 裕章"},{"name":"堀ノ内 裕也"},{"name":"今西 正樹"},{"name":"合田 光寛"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"石澤 有紀"},{"name":"宮本 理人"},{"name":"石澤 啓介"},{"name":"粟飯原 賢一"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Iron accumulation affects obesity and diabetes, both of which are ameliorated by iron reduction. Ferritin, an iron-storage protein, plays a crucial role in iron metabolism. H-ferritin exerts its cytoprotective action by reducing toxicity via its ferroxidase activity. We investigated the role of macrophage H-ferritin in obesity and diabetes. Conditional macrophage-specific H-ferritin (Fth, also known as Fth1) knockout (LysM-Cre Fth KO) mice were used and divided into four groups: wild-type (WT) and LysM-Cre Fth KO mice with normal diet (ND), and WT and LysM-Cre Fth KO mice with high-fat diet (HFD). These mice were analysed for characteristics of obesity and diabetes, tissue iron content, inflammation, oxidative stress, insulin sensitivity and metabolic measurements. RAW264.7 macrophage cells were used for in vitro experiments. Iron concentration reduced, and mRNA expression of ferroportin increased, in macrophages from LysM-Cre Fth KO mice. HFD-induced obesity was lower in LysM-Cre Fth KO mice than in WT mice at 12 weeks (body weight: KO 34.6 ± 5.6 g vs WT 40.1 ± 5.2 g). mRNA expression of inflammatory cytokines and infiltrated macrophages and oxidative stress increased in the adipose tissue of HFD-fed WT mice, but was not elevated in HFD-fed LysM-Cre Fth KO mice. However, WT mice fed an HFD had elevated iron concentration in adipose tissue and spleen, which was not observed in LysM-Cre Fth KO mice fed an HFD (adipose tissue [μmol Fe/g protein]: KO 1496 ± 479 vs WT 2316 ± 866; spleen [μmol Fe/g protein]: KO 218 ± 54 vs WT 334 ± 83). Moreover, HFD administration impaired both glucose tolerance and insulin sensitivity in WT mice, which was ameliorated in LysM-Cre Fth KO mice. In addition, energy expenditure, mRNA expression of thermogenic genes, and body temperature were higher in KO mice with HFD than WT mice with HFD. In vitro experiments showed that iron content was reduced, and lipopolysaccharide-induced Tnf-α (also known as Tnf) mRNA upregulation was inhibited in a macrophage cell line transfected with Fth siRNA. Deletion of macrophage H-ferritin suppresses the inflammatory response by reducing intracellular iron levels, resulting in the prevention of HFD-induced obesity and diabetes. The findings from this study highlight macrophage iron levels as a potential therapeutic target for obesity and diabetes.","ja":"Iron accumulation affects obesity and diabetes, both of which are ameliorated by iron reduction. Ferritin, an iron-storage protein, plays a crucial role in iron metabolism. H-ferritin exerts its cytoprotective action by reducing toxicity via its ferroxidase activity. We investigated the role of macrophage H-ferritin in obesity and diabetes. Conditional macrophage-specific H-ferritin (Fth, also known as Fth1) knockout (LysM-Cre Fth KO) mice were used and divided into four groups: wild-type (WT) and LysM-Cre Fth KO mice with normal diet (ND), and WT and LysM-Cre Fth KO mice with high-fat diet (HFD). These mice were analysed for characteristics of obesity and diabetes, tissue iron content, inflammation, oxidative stress, insulin sensitivity and metabolic measurements. RAW264.7 macrophage cells were used for in vitro experiments. Iron concentration reduced, and mRNA expression of ferroportin increased, in macrophages from LysM-Cre Fth KO mice. HFD-induced obesity was lower in LysM-Cre Fth KO mice than in WT mice at 12 weeks (body weight: KO 34.6 ± 5.6 g vs WT 40.1 ± 5.2 g). mRNA expression of inflammatory cytokines and infiltrated macrophages and oxidative stress increased in the adipose tissue of HFD-fed WT mice, but was not elevated in HFD-fed LysM-Cre Fth KO mice. However, WT mice fed an HFD had elevated iron concentration in adipose tissue and spleen, which was not observed in LysM-Cre Fth KO mice fed an HFD (adipose tissue [μmol Fe/g protein]: KO 1496 ± 479 vs WT 2316 ± 866; spleen [μmol Fe/g protein]: KO 218 ± 54 vs WT 334 ± 83). Moreover, HFD administration impaired both glucose tolerance and insulin sensitivity in WT mice, which was ameliorated in LysM-Cre Fth KO mice. In addition, energy expenditure, mRNA expression of thermogenic genes, and body temperature were higher in KO mice with HFD than WT mice with HFD. In vitro experiments showed that iron content was reduced, and lipopolysaccharide-induced Tnf-α (also known as Tnf) mRNA upregulation was inhibited in a macrophage cell line transfected with Fth siRNA. Deletion of macrophage H-ferritin suppresses the inflammatory response by reducing intracellular iron levels, resulting in the prevention of HFD-induced obesity and diabetes. The findings from this study highlight macrophage iron levels as a potential therapeutic target for obesity and diabetes."},"publication_date":"2020-07-11","publication_name":{"en":"Diabetologia","ja":"Diabetologia"},"volume":"63","number":"8","starting_page":"1588","ending_page":"1602","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00125-020-05153-0"],"issn":["1432-0428"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:9, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32307577","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=366414","label":"url"}],"paper_title":{"en":"Fibroblast-specific ERK5 deficiency changes tumor vasculature and exacerbates tumor progression in a mouse model.","ja":"Fibroblast-specific ERK5 deficiency changes tumor vasculature and exacerbates tumor progression in a mouse model."},"authors":{"en":[{"name":"Imanishi Masaki"},{"name":"Yamakawa Yusuke"},{"name":"Fukushima Keijo"},{"name":"Ikuto Raiki"},{"name":"Maegawa Akiko"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Horinouchi Yuya"},{"name":"Kondo Masateru"},{"name":"Kishuku Masatoshi"},{"name":"Goda Mitsuhiro"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Chuma Masayuki"},{"name":"Ikeda Yasumasa"},{"name":"Tsuchiya Koichiro"},{"name":"Fujino Hiromichi"},{"name":"Tsuneyama Koichi"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"今西 正樹"},{"name":"Yamakawa Yusuke"},{"name":"福島 圭穣"},{"name":"生藤 来希"},{"name":"前川 晃子"},{"name":"石澤 有紀"},{"name":"堀ノ内 裕也"},{"name":"近藤 正輝"},{"name":"木宿 昌俊"},{"name":"合田 光寛"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"中馬 真幸"},{"name":"池田 康将"},{"name":"土屋 浩一郎"},{"name":"藤野 裕道"},{"name":"常山 幸一"},{"name":"石澤 啓介"}]},"description":{"en":"The roles of cancer-associated fibroblasts (CAFs) have been studied in the tumor progression, and CAFs are expected to become the new targets for cancer pharmacotherapies. CAFs contribute to tumor cell survival and proliferation, tumor angiogenesis, immune suppression, tumor inflammation, tumor cell invasion and metastasis, and extracellular matrix remodeling. However, detailed mechanisms of how CAFs function in the living system remain unclear. CAFs include α-smooth muscle actin, expressing activated fibroblasts similar to myofibroblasts, and are highly capable of producing collagen. Several reports have demonstrated the contributions of extracellular-signal-regulated kinase 5 (ERK5) in fibroblasts to the fibrotic processes; however, the roles of CAF-derived ERK5 remain unclear. To investigate the roles of CAF-derived ERK5 in the tumor progression, we created mice lacking the ERK5 gene specifically in fibroblasts. Colon-26 mouse colon cancer cells were implanted into the mice subcutaneously, and the histological analyses of the tumor tissue were performed after 2 weeks. Immunofluorescence analyses showed that recipient-derived fibroblasts existed within the tumor tissue. The present study demonstrated that fibroblast-specific ERK5 deficiency exacerbated tumor progression and it was accompanied with thicker tumor vessel formation and the increase in the number of activated fibroblasts. We combined the results of The Cancer Genome Atlas (TCGA) database analysis with our animal studies, and indicated that regulating ERK5 activity in CAFs or CAF invasion into the tumor tissue can be important strategies for the development of new targets in cancer pharmacotherapies.","ja":"The roles of cancer-associated fibroblasts (CAFs) have been studied in the tumor progression, and CAFs are expected to become the new targets for cancer pharmacotherapies. CAFs contribute to tumor cell survival and proliferation, tumor angiogenesis, immune suppression, tumor inflammation, tumor cell invasion and metastasis, and extracellular matrix remodeling. However, detailed mechanisms of how CAFs function in the living system remain unclear. CAFs include α-smooth muscle actin, expressing activated fibroblasts similar to myofibroblasts, and are highly capable of producing collagen. Several reports have demonstrated the contributions of extracellular-signal-regulated kinase 5 (ERK5) in fibroblasts to the fibrotic processes; however, the roles of CAF-derived ERK5 remain unclear. To investigate the roles of CAF-derived ERK5 in the tumor progression, we created mice lacking the ERK5 gene specifically in fibroblasts. Colon-26 mouse colon cancer cells were implanted into the mice subcutaneously, and the histological analyses of the tumor tissue were performed after 2 weeks. Immunofluorescence analyses showed that recipient-derived fibroblasts existed within the tumor tissue. The present study demonstrated that fibroblast-specific ERK5 deficiency exacerbated tumor progression and it was accompanied with thicker tumor vessel formation and the increase in the number of activated fibroblasts. We combined the results of The Cancer Genome Atlas (TCGA) database analysis with our animal studies, and indicated that regulating ERK5 activity in CAFs or CAF invasion into the tumor tissue can be important strategies for the development of new targets in cancer pharmacotherapies."},"publication_date":"2020-04-19","publication_name":{"en":"Naunyn-Schmiedeberg's Archives of Pharmacology","ja":"Naunyn-Schmiedeberg's Archives of Pharmacology"},"volume":"393","number":"7","starting_page":"1239","ending_page":"1250","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00210-020-01859-5"],"issn":["1432-1912"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:10, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2008457","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31882204","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=366415","label":"url"}],"paper_title":{"en":"Rho-associated protein kinase and cyclophilin a are involved in inorganic phosphate-induced calcification signaling in vascular smooth muscle cells.","ja":"Rho-associated protein kinase and cyclophilin a are involved in inorganic phosphate-induced calcification signaling in vascular smooth muscle cells."},"authors":{"en":[{"name":"Tsuda Tatsuya"},{"name":"Imanishi Masaki"},{"name":"Oogoshi Mizuho"},{"name":"Goda Mitsuhiro"},{"name":"Kihira Yoshitaka"},{"name":"Horinouchi Yuya"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"},{"name":"Ikeda Yasumasa"},{"name":"Hashimoto Ichiro"},{"name":"Tamaki Toshiaki"},{"name":"Izawa-Ishizawa Yuki"}],"ja":[{"name":"津田 達也"},{"name":"今西 正樹"},{"name":"Oogoshi Mizuho"},{"name":"合田 光寛"},{"name":"木平 孝高"},{"name":"堀ノ内 裕也"},{"name":"座間味 義人"},{"name":"石澤 啓介"},{"name":"池田 康将"},{"name":"橋本 一郎"},{"name":"玉置 俊晃"},{"name":"石澤 有紀"}]},"description":{"en":"Arterial calcification, a risk factor of cardiovascular events, develops with differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Cyclophilin A (CypA) is a peptidyl-prolyl isomerase involved in cardiovascular diseases such as atherosclerosis and aortic aneurysms, and rho-associated protein kinase (ROCK) is involved in the pathogenesis of vascular calcification. CypA is secreted in a ROCK activity-dependent manner and works as a mitogen via autocrine or paracrine mechanisms in VSMCs. We examined the involvement of the ROCK-CypA axis in VSMC calcification induced by inorganic phosphate (Pi), a potent cell mineralization initiator. We found that Pi stimulated ROCK activity, CypA secretion, extracellular signal-regulated protein kinase (ERK) 1/2 phosphorylation, and runt-related transcription factor 2 expression, resulting in calcium accumulation in rat aortic smooth muscle cells (RASMCs). The ROCK inhibitor Y-27632 significantly suppressed Pi-induced CypA secretion, ERK1/2 phosphorylation, and calcium accumulation. Recombinant CypA was found to be associated with increased calcium accumulation in RASMCs. Based on these results, we suggest that autocrine CypA is mediated by ROCK activity and is involved in Pi-induced ERK1/2 phosphorylation following calcification signaling in RASMCs.","ja":"Arterial calcification, a risk factor of cardiovascular events, develops with differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Cyclophilin A (CypA) is a peptidyl-prolyl isomerase involved in cardiovascular diseases such as atherosclerosis and aortic aneurysms, and rho-associated protein kinase (ROCK) is involved in the pathogenesis of vascular calcification. CypA is secreted in a ROCK activity-dependent manner and works as a mitogen via autocrine or paracrine mechanisms in VSMCs. We examined the involvement of the ROCK-CypA axis in VSMC calcification induced by inorganic phosphate (Pi), a potent cell mineralization initiator. We found that Pi stimulated ROCK activity, CypA secretion, extracellular signal-regulated protein kinase (ERK) 1/2 phosphorylation, and runt-related transcription factor 2 expression, resulting in calcium accumulation in rat aortic smooth muscle cells (RASMCs). The ROCK inhibitor Y-27632 significantly suppressed Pi-induced CypA secretion, ERK1/2 phosphorylation, and calcium accumulation. Recombinant CypA was found to be associated with increased calcium accumulation in RASMCs. Based on these results, we suggest that autocrine CypA is mediated by ROCK activity and is involved in Pi-induced ERK1/2 phosphorylation following calcification signaling in RASMCs."},"publication_date":"2020-03","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"142","number":"3","starting_page":"109","ending_page":"115","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jphs.2019.12.005"],"issn":["1347-8648"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:11, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2006818","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31669099","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=360423","label":"url"}],"paper_title":{"en":"Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway","ja":"Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway"},"authors":{"en":[{"name":"Hamano Hirofumi"},{"name":"Niimura Takahiro"},{"name":"Horinouchi Yuya"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Goda Mitsuhiro"},{"name":"Imanishi Masaki"},{"name":"Chuma Masayuki"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Miyamoto Licht"},{"name":"Fukushima Keijo"},{"name":"Fujino Hiromichi"},{"name":"Tsuchiya Koichiro"},{"name":"Ishizawa Keisuke"},{"name":"Tamaki Toshiaki"},{"name":"Ikeda Yasumasa"}],"ja":[{"name":"濱野 裕章"},{"name":"新村 貴博"},{"name":"堀ノ内 裕也"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"合田 光寛"},{"name":"今西 正樹"},{"name":"中馬 真幸"},{"name":"石澤 有紀"},{"name":"宮本 理人"},{"name":"福島 圭穣"},{"name":"藤野 裕道"},{"name":"土屋 浩一郎"},{"name":"石澤 啓介"},{"name":"玉置 俊晃"},{"name":"池田 康将"}]},"description":{"en":"Proton pump inhibitors (PPIs) have been used worldwide to treat gastrointestinal disorders. A recent study showed that long-term use of PPIs caused iron deficiency; however, it is unclear whether PPIs affect iron metabolism directly. We investigated the effect of PPIs on the peptide hepcidin, an important iron regulatory hormone. First, we used the FDA Adverse Event Reporting System database and analyzed the influence of PPIs. We found that PPIs, as well as H2 blockers, increased the odds ratio of iron-deficient anemia. Next, HepG2 cells were used to examine the action of PPIs and H2 blockers on hepcidin. PPIs augmented hepcidin expression, while H2 blockers did not. In fact, the PPI omeprazole increased hepcidin secretion, and omeprazole-induced hepcidin upregulation was inhibited by gene silencing or the pharmacological inhibition of the aryl hydrocarbon receptor. In mouse experiments, omeprazole also increased hepatic hepcidin mRNA expression and blood hepcidin levels. In mice treated with omeprazole, protein levels of duodenal and splenic ferroportin decreased. Taken together, PPIs directly affect iron metabolism by suppressing iron absorption through the inhibition of duodenal ferroportin via hepcidin upregulation. These findings provide a new insight into the molecular mechanism of PPI-induced iron deficiency.","ja":"Proton pump inhibitors (PPIs) have been used worldwide to treat gastrointestinal disorders. A recent study showed that long-term use of PPIs caused iron deficiency; however, it is unclear whether PPIs affect iron metabolism directly. We investigated the effect of PPIs on the peptide hepcidin, an important iron regulatory hormone. First, we used the FDA Adverse Event Reporting System database and analyzed the influence of PPIs. We found that PPIs, as well as H2 blockers, increased the odds ratio of iron-deficient anemia. Next, HepG2 cells were used to examine the action of PPIs and H2 blockers on hepcidin. PPIs augmented hepcidin expression, while H2 blockers did not. In fact, the PPI omeprazole increased hepcidin secretion, and omeprazole-induced hepcidin upregulation was inhibited by gene silencing or the pharmacological inhibition of the aryl hydrocarbon receptor. In mouse experiments, omeprazole also increased hepatic hepcidin mRNA expression and blood hepcidin levels. In mice treated with omeprazole, protein levels of duodenal and splenic ferroportin decreased. Taken together, PPIs directly affect iron metabolism by suppressing iron absorption through the inhibition of duodenal ferroportin via hepcidin upregulation. These findings provide a new insight into the molecular mechanism of PPI-induced iron deficiency."},"publication_date":"2020-01","publication_name":{"en":"Toxicology Letters","ja":"Toxicology Letters"},"volume":"318","starting_page":"86","ending_page":"91","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.toxlet.2019.10.016"],"issn":["1879-3169"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:12, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2006761","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31145863","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=351099","label":"url"}],"paper_title":{"en":"Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress","ja":"Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Satoh Akiho"},{"name":"Horinouchi Yuya"},{"name":"Hamano Hirofumi"},{"name":"Watanabe Hiroaki"},{"name":"Imao Mizuki"},{"name":"Imanishi Masaki"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Miyamoto Licht"},{"name":"Tasuku Hirayama"},{"name":"Nagasawa Hideko"},{"name":"Ishizawa Keisuke"},{"name":"Aihara Ken-ichi"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"佐藤 明穂"},{"name":"堀ノ内 裕也"},{"name":"濱野 裕章"},{"name":"渡邉 大晃"},{"name":"今尾 瑞季"},{"name":"今西 正樹"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"石澤 有紀"},{"name":"宮本 理人"},{"name":"Tasuku Hirayama"},{"name":"永澤 秀子"},{"name":"石澤 啓介"},{"name":"粟飯原 賢一"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Skeletal muscle atrophy is caused by disruption in the homeostatic balance of muscle degeneration and regeneration under various pathophysiological conditions. We have previously reported that iron accumulation induces skeletal muscle atrophy a ubiquitin ligase-dependent pathway. However, the potential effect of iron accumulation on muscle regeneration remains unclear. To examine the effect of iron accumulation on myogenesis, we used a mouse model with cardiotoxin (CTX)-induced muscle regeneration and C2C12 mouse myoblast cells . In mice with iron overload, the skeletal muscles exhibited increased oxidative stress and decreased expression of satellite cell markers. Following CTX-induced muscle injury, these mice also displayed delayed muscle regeneration with a decrease in the size of regenerating myofibers, reduced expression of myoblast differentiation markers, and decreased phosphorylation of MAPK signaling pathways. , iron overload also suppressed the differentiation of C2C12 myoblast cells but the suppression could be reversed by superoxide scavenging using tempol. Excess iron inhibits myogenesis oxidative stress, leading to an imbalance in skeletal muscle homeostasis.-Ikeda, Y., Satoh, A., Horinouchi, Y., Hamano, H., Watanabe, H., Imao, M., Imanishi, M., Zamami, Y., Takechi, K., Izawa-Ishizawa, Y., Miyamoto, L., Hirayama, T., Nagasawa, H., Ishizawa, K., Aihara, K.-I., Tsuchiya, K., Tamaki, T. Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress.","ja":"Skeletal muscle atrophy is caused by disruption in the homeostatic balance of muscle degeneration and regeneration under various pathophysiological conditions. We have previously reported that iron accumulation induces skeletal muscle atrophy a ubiquitin ligase-dependent pathway. However, the potential effect of iron accumulation on muscle regeneration remains unclear. To examine the effect of iron accumulation on myogenesis, we used a mouse model with cardiotoxin (CTX)-induced muscle regeneration and C2C12 mouse myoblast cells . In mice with iron overload, the skeletal muscles exhibited increased oxidative stress and decreased expression of satellite cell markers. Following CTX-induced muscle injury, these mice also displayed delayed muscle regeneration with a decrease in the size of regenerating myofibers, reduced expression of myoblast differentiation markers, and decreased phosphorylation of MAPK signaling pathways. , iron overload also suppressed the differentiation of C2C12 myoblast cells but the suppression could be reversed by superoxide scavenging using tempol. Excess iron inhibits myogenesis oxidative stress, leading to an imbalance in skeletal muscle homeostasis.-Ikeda, Y., Satoh, A., Horinouchi, Y., Hamano, H., Watanabe, H., Imao, M., Imanishi, M., Zamami, Y., Takechi, K., Izawa-Ishizawa, Y., Miyamoto, L., Hirayama, T., Nagasawa, H., Ishizawa, K., Aihara, K.-I., Tsuchiya, K., Tamaki, T. Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress."},"publication_date":"2019-08-01","publication_name":{"en":"The FASEB journal","ja":"The FASEB journal"},"volume":"33","number":"8","starting_page":"9551","ending_page":"9564","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1096/fj.201802724RR"],"issn":["1530-6860"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:13, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30351343","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=347373","label":"url"}],"paper_title":{"en":"Xanthine Oxidase Inhibition by Febuxostat in Macrophages Suppresses Angiotensin II-induced Aortic Fibrosis.","ja":"Xanthine Oxidase Inhibition by Febuxostat in Macrophages Suppresses Angiotensin II-induced Aortic Fibrosis."},"authors":{"en":[{"name":"Kondo Masateru"},{"name":"Imanishi Masaki"},{"name":"Fukushima Keijo"},{"name":"Ikuto Raiki"},{"name":"Murai Yoichi"},{"name":"Horinouchi Yuya"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Goda Mitsuhiro"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Chuma Masayuki"},{"name":"Ikeda Yasumasa"},{"name":"Fujino Hiromichi"},{"name":"Tsuchiya Koichiro"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"近藤 正輝"},{"name":"今西 正樹"},{"name":"福島 圭穣"},{"name":"生藤 来希"},{"name":"村井 陽一"},{"name":"堀ノ内 裕也"},{"name":"石澤 有紀"},{"name":"合田 光寛"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"中馬 真幸"},{"name":"池田 康将"},{"name":"藤野 裕道"},{"name":"土屋 浩一郎"},{"name":"石澤 啓介"}]},"description":{"en":"Our results suggested that FEB ameliorates Ang II-induced aortic fibrosis via suppressing macrophage-derived TGF-1 expression.","ja":"Our results suggested that FEB ameliorates Ang II-induced aortic fibrosis via suppressing macrophage-derived TGF-1 expression."},"publication_date":"2019-02-12","publication_name":{"en":"American Journal of Hypertension","ja":"American Journal of Hypertension"},"volume":"32","number":"3","starting_page":"249","ending_page":"256","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1093/ajh/hpy157"],"issn":["1941-7225"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:14, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2006373","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30303488","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=347382","label":"url"}],"paper_title":{"en":"Development of a novel aortic dissection mouse model and evaluation of drug efficacy using in-vivo assays and database analyses.","ja":"Development of a novel aortic dissection mouse model and evaluation of drug efficacy using in-vivo assays and database analyses."},"authors":{"en":[{"name":"Izawa-Ishizawa Yuki"},{"name":"Imanishi Masaki"},{"name":"Zamami Yoshito"},{"name":"Hiroki Toya"},{"name":"Tomoko Nagao"},{"name":"Morishita Marin"},{"name":"Tsuneyama Koichi"},{"name":"Horinouchi Yuya"},{"name":"Kihira Yoshitaka"},{"name":"Takechi Kenshi"},{"name":"Ikeda Yasumasa"},{"name":"Tsuchiya Koichiro"},{"name":"Yoshizumi Masanori"},{"name":"Tamaki Toshiaki"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"石澤 有紀"},{"name":"今西 正樹"},{"name":"座間味 義人"},{"name":"戸谷 紘基"},{"name":"長尾 朋子"},{"name":"Morishita Marin"},{"name":"常山 幸一"},{"name":"堀ノ内 裕也"},{"name":"木平 孝高"},{"name":"武智 研志"},{"name":"池田 康将"},{"name":"土屋 浩一郎"},{"name":"吉栖 正典"},{"name":"玉置 俊晃"},{"name":"石澤 啓介"}]},"description":{"en":"Aortic dissection is a life-threatening disease. At present, the only therapeutic strategies available are surgery and antihypertensive drugs. Moreover, the molecular mechanisms underlying the onset of aortic dissection are still unclear. We established a novel aortic dissection model in mice using pharmacologically induced endothelial dysfunction. We then used the Japanese Adverse Drug Event Report database to investigate the role of pitavastatin in preventing the onset of aortic dissection. To induce endothelial dysfunction, Nω-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, was administered to C57BL/6 mice. Three weeks later, angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, were administered with osmotic mini-pumps. False lumen formation was used as the pathological determinant of aortic dissection. The incidences of aortic dissection and death from aneurysmal rupture were significantly higher in the Nω-nitro-L-arginine methyl ester, Ang II, and BAPN (LAB) group than they were in the Ang II and BAPN (AB) group.Pitavastatin was administered orally to LAB mice. It significantly lowered the incidences of dissection and rupture. It also decreased inflammation and medial degradation, both of which were exacerbated in the LAB group. The Japanese Adverse Drug Event Report database analysis indicated that there were 113 cases of aortic dissection out of 95 090 patients (0.12%) not receiving statins but only six cases out of 16 668 patients receiving statins (0.04%) (odds ratio: 0.30; P = 0.0043). Our results suggest that endothelial dysfunction is associated with the onset of aortic dissection and pitavastatin can help prevent this condition.","ja":"Aortic dissection is a life-threatening disease. At present, the only therapeutic strategies available are surgery and antihypertensive drugs. Moreover, the molecular mechanisms underlying the onset of aortic dissection are still unclear. We established a novel aortic dissection model in mice using pharmacologically induced endothelial dysfunction. We then used the Japanese Adverse Drug Event Report database to investigate the role of pitavastatin in preventing the onset of aortic dissection. To induce endothelial dysfunction, Nω-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, was administered to C57BL/6 mice. Three weeks later, angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, were administered with osmotic mini-pumps. False lumen formation was used as the pathological determinant of aortic dissection. The incidences of aortic dissection and death from aneurysmal rupture were significantly higher in the Nω-nitro-L-arginine methyl ester, Ang II, and BAPN (LAB) group than they were in the Ang II and BAPN (AB) group.Pitavastatin was administered orally to LAB mice. It significantly lowered the incidences of dissection and rupture. It also decreased inflammation and medial degradation, both of which were exacerbated in the LAB group. The Japanese Adverse Drug Event Report database analysis indicated that there were 113 cases of aortic dissection out of 95 090 patients (0.12%) not receiving statins but only six cases out of 16 668 patients receiving statins (0.04%) (odds ratio: 0.30; P = 0.0043). Our results suggest that endothelial dysfunction is associated with the onset of aortic dissection and pitavastatin can help prevent this condition."},"publication_date":"2019-01","publication_name":{"en":"Journal of Hypertension","ja":"Journal of Hypertension"},"volume":"37","number":"1","starting_page":"73","ending_page":"83","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1097/HJH.0000000000001898"],"issn":["1473-5598"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:15, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2005594","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30022146","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=342025","label":"url"}],"paper_title":{"en":"Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis.","ja":"Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis."},"authors":{"en":[{"name":"Horinouchi Yuya"},{"name":"Ikeda Yasumasa"},{"name":"Fukushima Keijo"},{"name":"Imanishi Masaki"},{"name":"Hamano Hirofumi"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Miyamoto Licht"},{"name":"Fujino Hiromichi"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"堀ノ内 裕也"},{"name":"池田 康将"},{"name":"福島 圭穣"},{"name":"今西 正樹"},{"name":"Hamano Hirofumi"},{"name":"石澤 有紀"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"宮本 理人"},{"name":"藤野 裕道"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Renal tubulointerstitial injury, an inflammation-associated condition, is a major cause of chronic kidney disease (CKD). Levels of activated factor X (FXa), a blood coagulation factor, are increased in various inflammatory diseases. Therefore, we investigated the protective effects of an FXa inhibitor against renal tubulointerstitial injury using unilateral ureteral obstruction (UUO) mice (a renal tubulointerstitial fibrosis model) and the Food and Drug Administration Adverse Events Reporting System (FAERS) database. The renal expression levels of FX and the FXa receptors protease-activated receptor (PAR)-1 and PAR-2 were significantly higher in UUO mice than in sham-operated mice. UUO-induced tubulointerstitial fibrosis and extracellular matrix expression were suppressed in UUO mice treated with the FXa inhibitor edoxaban. Additionally, edoxaban attenuated UUO-induced macrophage infiltration and inflammatory molecule upregulation. In an analysis of the FAERS database, there were significantly fewer reports of tubulointerstitial nephritis for patients treated with FXa inhibitors than for patients not treated with inhibitors. These results suggest that FXa inhibitors exert protective effects against CKD by inhibiting tubulointerstitial fibrosis.","ja":"Renal tubulointerstitial injury, an inflammation-associated condition, is a major cause of chronic kidney disease (CKD). Levels of activated factor X (FXa), a blood coagulation factor, are increased in various inflammatory diseases. Therefore, we investigated the protective effects of an FXa inhibitor against renal tubulointerstitial injury using unilateral ureteral obstruction (UUO) mice (a renal tubulointerstitial fibrosis model) and the Food and Drug Administration Adverse Events Reporting System (FAERS) database. The renal expression levels of FX and the FXa receptors protease-activated receptor (PAR)-1 and PAR-2 were significantly higher in UUO mice than in sham-operated mice. UUO-induced tubulointerstitial fibrosis and extracellular matrix expression were suppressed in UUO mice treated with the FXa inhibitor edoxaban. Additionally, edoxaban attenuated UUO-induced macrophage infiltration and inflammatory molecule upregulation. In an analysis of the FAERS database, there were significantly fewer reports of tubulointerstitial nephritis for patients treated with FXa inhibitors than for patients not treated with inhibitors. These results suggest that FXa inhibitors exert protective effects against CKD by inhibiting tubulointerstitial fibrosis."},"publication_date":"2018-07-18","publication_name":{"en":"Scientific Reports","ja":"Scientific Reports"},"volume":"8","number":"1","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s41598-018-29008-2"],"issn":["2045-2322"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:16, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2005397","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30282865","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=356163","label":"url"}],"paper_title":{"en":"Methanol extraction fraction from Citrus Sudachi peel exerts lipid reducing effects in cultured cells.","ja":"Methanol extraction fraction from Citrus Sudachi peel exerts lipid reducing effects in cultured cells."},"authors":{"en":[{"name":"Xu Wenting"},{"name":"Miyamoto Licht"},{"name":"Aihara Haruna"},{"name":"Yamaoka Tomomi"},{"name":"Tanaka Naonobu"},{"name":"Tsuchihashi Yuki"},{"name":"Ikeda Yasumasa"},{"name":"Tamaki Toshiaki"},{"name":"Kashiwada Yoshiki"},{"name":"Tsuchiya Koichiro"}],"ja":[{"name":"許 文婷"},{"name":"宮本 理人"},{"name":"粟飯原 遥奈"},{"name":"山岡 朋美"},{"name":"田中 直伸"},{"name":"土橋 有希"},{"name":"池田 康将"},{"name":"玉置 俊晃"},{"name":"柏田 良樹"},{"name":"土屋 浩一郎"}]},"description":{"en":"Ectopic fat accumulation is associated with insulin resistance and type 2 diabetes mellitus. Citrus sudachi is an evergreen tree that is found mainly in Tokushima Prefecture in Japan. Previously, it was demonstrated that Citrus sudachi could inhibit the rising trend of blood glucose and fatty acid in human subjects. In the current study, we illustrated the function of methanol extracts from sudachi peel and investigated the mechanism of this effect. We got the five kinds of methanol extracts by using diaion HP-20, and those were named by hydrophobicity from M-F1 to M-F5. Among the 5 kinds of sudachi methanol extracts, only M-F4 significantly decreased the intracellular triglyceride of C2C12 cells. It augmented the AMPK activity and increased the transcription of PPARα and its downstream targets CPT-1b and UCP2. In conclusion, M-F4 improved the lipid metabolism possibly through AMPK, PPARα and their downstream targets like CPT-1b and UCP2. Furthermore, this extract may be useful for preventing obesity and diabetes related diseases. J. Med. Invest. 65:225-230, August, 2018.","ja":"Ectopic fat accumulation is associated with insulin resistance and type 2 diabetes mellitus. Citrus sudachi is an evergreen tree that is found mainly in Tokushima Prefecture in Japan. Previously, it was demonstrated that Citrus sudachi could inhibit the rising trend of blood glucose and fatty acid in human subjects. In the current study, we illustrated the function of methanol extracts from sudachi peel and investigated the mechanism of this effect. We got the five kinds of methanol extracts by using diaion HP-20, and those were named by hydrophobicity from M-F1 to M-F5. Among the 5 kinds of sudachi methanol extracts, only M-F4 significantly decreased the intracellular triglyceride of C2C12 cells. It augmented the AMPK activity and increased the transcription of PPARα and its downstream targets CPT-1b and UCP2. In conclusion, M-F4 improved the lipid metabolism possibly through AMPK, PPARα and their downstream targets like CPT-1b and UCP2. Furthermore, this extract may be useful for preventing obesity and diabetes related diseases. J. Med. Invest. 65:225-230, August, 2018."},"publication_date":"2018","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"65","number":"3.4","starting_page":"225","ending_page":"230","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.65.225"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:17, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2005547","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29263333","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=335442","label":"url"}],"paper_title":{"en":"Hydrocortisone administration was associated with improved survival in Japanese patients with cardiac arrest.","ja":"Hydrocortisone administration was associated with improved survival in Japanese patients with cardiac arrest."},"authors":{"en":[{"name":"Niimura Takahiro"},{"name":"Zamami Yoshito"},{"name":"Koyama Toshihiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Miyake Masashi"},{"name":"Koga Tadashi"},{"name":"Harada Keisaku"},{"name":"Ohshima Ayako"},{"name":"Imai Toru"},{"name":"Kondo Yutaka"},{"name":"Imanishi Masaki"},{"name":"Takechi Kenshi"},{"name":"Fukushima Keijo"},{"name":"Horinouchi Yuya"},{"name":"Ikeda Yasumasa"},{"name":"Fujino Hiromichi"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"},{"name":"Hinotsu Shiro"},{"name":"Kano Mitsunobu R"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"新村 貴博"},{"name":"座間味 義人"},{"name":"Koyama Toshihiro"},{"name":"石澤 有紀"},{"name":"Miyake Masashi"},{"name":"Koga Tadashi"},{"name":"Harada Keisaku"},{"name":"Ohshima Ayako"},{"name":"Imai Toru"},{"name":"Kondo Yutaka"},{"name":"今西 正樹"},{"name":"武智 研志"},{"name":"福島 圭穣"},{"name":"堀ノ内 裕也"},{"name":"池田 康将"},{"name":"藤野 裕道"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"},{"name":"Hinotsu Shiro"},{"name":"Kano Mitsunobu R"},{"name":"石澤 啓介"}]},"description":{"en":"There are few reports on hydrocortisone administration after cardiac arrest, and those that have been published included few subjects. This study aimed to evaluate the effect of hydrocortisone administration on the outcomes of patients who experienced cardiac arrest. We investigated the survival discharge rates and the length of hospital stay from cardiac arrest to discharge, stratified by use of hydrocortisone, using a Japanese health-insurance claims dataset that covers approximately 2% of the Japanese population. The study included the data of 2233 subjects who experienced either in-hospital or out-of-hospital cardiac arrest between January 2005 and May 2014. These patients were divided into two groups, based on the administration of hydrocortisone. We adjusted the baseline characteristics, medical treatment, and drug administration data of the two groups using propensity scores obtained via the inverse probability of treatment weighted method. The hydrocortisone group had a significantly higher survival discharge rate (13/61 [21.1%] vs. 240/2172 [11.0%], adjusted odds ratio: 4.2, 95% CI: 1.60-10.98, p = 0.004). In addition, the administration of hydrocortisone was independent predictor of survival to discharge (hazard ratio: 4.6, p < 0.001). The results demonstrate a correlation between hydrocortisone administration and the high rates of survival to discharge.","ja":"There are few reports on hydrocortisone administration after cardiac arrest, and those that have been published included few subjects. This study aimed to evaluate the effect of hydrocortisone administration on the outcomes of patients who experienced cardiac arrest. We investigated the survival discharge rates and the length of hospital stay from cardiac arrest to discharge, stratified by use of hydrocortisone, using a Japanese health-insurance claims dataset that covers approximately 2% of the Japanese population. The study included the data of 2233 subjects who experienced either in-hospital or out-of-hospital cardiac arrest between January 2005 and May 2014. These patients were divided into two groups, based on the administration of hydrocortisone. We adjusted the baseline characteristics, medical treatment, and drug administration data of the two groups using propensity scores obtained via the inverse probability of treatment weighted method. The hydrocortisone group had a significantly higher survival discharge rate (13/61 [21.1%] vs. 240/2172 [11.0%], adjusted odds ratio: 4.2, 95% CI: 1.60-10.98, p = 0.004). In addition, the administration of hydrocortisone was independent predictor of survival to discharge (hazard ratio: 4.6, p < 0.001). The results demonstrate a correlation between hydrocortisone administration and the high rates of survival to discharge."},"publication_date":"2017-12-20","publication_name":{"en":"Scientific Reports","ja":"Scientific Reports"},"volume":"7","number":"1","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s41598-017-17686-3"],"issn":["2045-2322"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:18, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2005519","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28878231","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=329173","label":"url"}],"paper_title":{"en":"Dietary iron restriction alleviates renal tubulointerstitial injury induced by protein overload in mice","ja":"Dietary iron restriction alleviates renal tubulointerstitial injury induced by protein overload in mice"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Horinouchi Yuya"},{"name":"Hirofumi Hamano"},{"name":"Tasuku Hirayama"},{"name":"Kishi Seiji"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Imanishi Masaki"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Miyamoto Licht"},{"name":"Ishizawa Keisuke"},{"name":"Aihara Ken-ichi"},{"name":"Nagasawa Hideko"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"堀ノ内 裕也"},{"name":"濱野 裕章"},{"name":"Tasuku Hirayama"},{"name":"岸 誠司"},{"name":"石澤 有紀"},{"name":"今西 正樹"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"宮本 理人"},{"name":"石澤 啓介"},{"name":"粟飯原 賢一"},{"name":"永澤 秀子"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Increased proteinuria causes tubulointerstitial injury due to inflammation in chronic kidney disease (CKD). Iron restriction exhibits protective effects against renal dysfunction; however, its effects against protein overload-induced tubulointerstitial damage remain unclear. Here, we investigated dietary iron restriction effect on tubulointerstitial damage in mice with protein-overload tubulointerstitial injury. Renal tubulointerstitial injury in animal model was induced by intraperitoneal injection of an overdose of bovine serum albumin (BSA). We divided mice into three groups: normal saline + normal diet (ND), BSA + ND, and BSA + iron-restricted diet (IRD). BSA overload induced renal tubulointerstitial injury in the ND mice, which was ameliorated in the IRD mice. Inflammatory cytokines and extracellular matrix mRNA expression was upregulated in BSA + ND mice kidneys and was inhibited by IRD. BSA-induced increase in renal superoxide production, NADPH oxidase activity, and p22(phox) expression was diminished in the IRD mice. IRD suppression increased BSA-induced renal macrophage infiltration. Moreover, BSA mice exhibited nucleotide-binding oligomerisation domain-like receptor pyrin domain-containing protein (NLRP) inflammasome activation, which was inhibited by IRD. Ferrous iron increased in kidneys with BSA overload and was inhibited by IRD. Thus, iron restriction inhibited oxidative stress and inflammatory changes, contributing to the protective effect against BSA overload-induced tubulointerstitial injury.","ja":"Increased proteinuria causes tubulointerstitial injury due to inflammation in chronic kidney disease (CKD). Iron restriction exhibits protective effects against renal dysfunction; however, its effects against protein overload-induced tubulointerstitial damage remain unclear. Here, we investigated dietary iron restriction effect on tubulointerstitial damage in mice with protein-overload tubulointerstitial injury. Renal tubulointerstitial injury in animal model was induced by intraperitoneal injection of an overdose of bovine serum albumin (BSA). We divided mice into three groups: normal saline + normal diet (ND), BSA + ND, and BSA + iron-restricted diet (IRD). BSA overload induced renal tubulointerstitial injury in the ND mice, which was ameliorated in the IRD mice. Inflammatory cytokines and extracellular matrix mRNA expression was upregulated in BSA + ND mice kidneys and was inhibited by IRD. BSA-induced increase in renal superoxide production, NADPH oxidase activity, and p22(phox) expression was diminished in the IRD mice. IRD suppression increased BSA-induced renal macrophage infiltration. Moreover, BSA mice exhibited nucleotide-binding oligomerisation domain-like receptor pyrin domain-containing protein (NLRP) inflammasome activation, which was inhibited by IRD. Ferrous iron increased in kidneys with BSA overload and was inhibited by IRD. Thus, iron restriction inhibited oxidative stress and inflammatory changes, contributing to the protective effect against BSA overload-induced tubulointerstitial injury."},"publication_date":"2017-09-06","publication_name":{"en":"Scientific Reports","ja":"Scientific Reports"},"volume":"7","number":"1","starting_page":"10621","ending_page":"10621","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s41598-017-11089-0"],"issn":["2045-2322"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:19, {"insert":{"user_id":"B000241782","type":"published_papers","id":"30376217"},"force":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2003323","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28090711","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=323552","label":"url"}],"paper_title":{"en":"Topical Application of Nitrosonifedipine, a Novel Radical Scavenger, Ameliorates Ischemic Skin Flap Necrosis in a Mouse Model.","ja":"Topical Application of Nitrosonifedipine, a Novel Radical Scavenger, Ameliorates Ischemic Skin Flap Necrosis in a Mouse Model."},"authors":{"en":[{"name":"Fukunaga Yutaka"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Horinouchi Yuya"},{"name":"Sairyo Eriko"},{"name":"Ikeda Yasumasa"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Abe Yoshiro"},{"name":"Hashimoto Ichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"福永 豊"},{"name":"石澤 有紀"},{"name":"堀ノ内 裕也"},{"name":"Sairyo Eriko"},{"name":"池田 康将"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"安倍 吉郎"},{"name":"橋本 一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Ischemic skin flap necrosis can occur in random pattern flaps. An excess amount of reactive oxygen species is generated and causes necrosis in the ischemic tissue. Nitrosonifedipine (NO-NIF) has been demonstrated to possess potent radical scavenging ability. However, there has been no study on the effects of NO-NIF on ischemic skin flap necrosis. Therefore, they evaluated the potential of NO-NIF in ameliorating ischemic skin flap necrosis in a mouse model. A random pattern skin flap (1.0 × 3.0 cm) was elevated on the dorsum of C57BL/6 mice. NO-NIF was administered by topical injection immediately after surgery and every 24 hours thereafter. Flap survival was evaluated on postoperative day 7. Tissue samples from the skin flaps were harvested on postoperative days 1 and 3 to analyze oxidative stress, apoptosis and endothelial dysfunction. The viable area of the flap in the NO-NIF group was significantly increased (78.30 ± 7.041%) compared with that of the control group (47.77 ± 6.549%, p < 0.01). NO-NIF reduced oxidative stress, apoptosis and endothelial dysfunction, which were evidenced by the decrease of malondialdehyde, p22phox protein expression, number of apoptotic cells, phosphorylated p38 MAPK protein expression, and vascular cell adhesion molecule-1 protein expression while endothelial nitric oxide synthase protein expression was increased. In conclusion, they demonstrated that NO-NIF ameliorated ischemic skin flap necrosis by reducing oxidative stress, apoptosis, and endothelial dysfunction. NO-NIF is considered to be a candidate for the treatment of ischemic flap necrosis.","ja":"Ischemic skin flap necrosis can occur in random pattern flaps. An excess amount of reactive oxygen species is generated and causes necrosis in the ischemic tissue. Nitrosonifedipine (NO-NIF) has been demonstrated to possess potent radical scavenging ability. However, there has been no study on the effects of NO-NIF on ischemic skin flap necrosis. Therefore, they evaluated the potential of NO-NIF in ameliorating ischemic skin flap necrosis in a mouse model. A random pattern skin flap (1.0 × 3.0 cm) was elevated on the dorsum of C57BL/6 mice. NO-NIF was administered by topical injection immediately after surgery and every 24 hours thereafter. Flap survival was evaluated on postoperative day 7. Tissue samples from the skin flaps were harvested on postoperative days 1 and 3 to analyze oxidative stress, apoptosis and endothelial dysfunction. The viable area of the flap in the NO-NIF group was significantly increased (78.30 ± 7.041%) compared with that of the control group (47.77 ± 6.549%, p < 0.01). NO-NIF reduced oxidative stress, apoptosis and endothelial dysfunction, which were evidenced by the decrease of malondialdehyde, p22phox protein expression, number of apoptotic cells, phosphorylated p38 MAPK protein expression, and vascular cell adhesion molecule-1 protein expression while endothelial nitric oxide synthase protein expression was increased. In conclusion, they demonstrated that NO-NIF ameliorated ischemic skin flap necrosis by reducing oxidative stress, apoptosis, and endothelial dysfunction. NO-NIF is considered to be a candidate for the treatment of ischemic flap necrosis."},"publication_date":"2017-02-17","publication_name":{"en":"Wound Repair and Regeneration","ja":"Wound Repair and Regeneration"},"volume":"25","number":"2","starting_page":"217","ending_page":"223","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1111/wrr.12510"],"issn":["1524-475X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:20, {"insert":{"user_id":"B000241782","type":"published_papers","id":"30376218"},"force":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2006764","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/27049128","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=306466","label":"url"}],"paper_title":{"en":"Iron-induced skeletal muscle atrophy involves an Akt-forkhead box O3-E3 ubiquitin ligase-dependent pathway","ja":"Iron-induced skeletal muscle atrophy involves an Akt-forkhead box O3-E3 ubiquitin ligase-dependent pathway"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Imao Mizuki"},{"name":"Satoh Akiho"},{"name":"Watanabe Hiroaki"},{"name":"Hamano Hirofumi"},{"name":"Horinouchi Yuya"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Miyamoto Licht"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"今尾 瑞季"},{"name":"佐藤 明穂"},{"name":"渡邉 大晃"},{"name":"濱野 裕章"},{"name":"堀ノ内 裕也"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"宮本 理人"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Skeletal muscle wasting or sarcopenia is a critical health problem. Skeletal muscle atrophy is induced by an excess of iron, which is an essential trace metal for all living organisms. Excessive amounts of iron catalyze the formation of highly toxic hydroxyl radicals via the Fenton reaction. However, the molecular mechanism of iron-induced skeletal muscle atrophy has remained unclear. In this study, 8-weeks-old C57BL6/J mice were divided into 2 groups: vehicle-treated group and the iron-injected group (10 mg iron·day-1·mouse-1) during 2 weeks. Mice in the iron-injected group showed an increase in the iron content of the skeletal muscle and serum and ferritin levels in the muscle, along with reduced skeletal muscle mass. The skeletal muscle showed elevated mRNA expression of the muscle atrophy-related E3 ubiquitin ligases, atrogin-1 and muscle ring finger-1(MuRF1), on days 7 and 14 of iron treatment. Moreover, iron-treated mice showed reduced phosphorylation of Akt and forkhead box O3 (FOXO3a) in skeletal muscles. Inhibition of FOXO3a using siRNA in vitro in C2C12 myotube cells inhibited iron-induced upregulation of atrogin-1 and MuRF1 and reversed the reduction in myotube diameters. Iron-load caused oxidative stress, and an oxidative stress inhibitor abrogated iron-induced muscle atrophy by reactivating the Akt-FOXO3 pathway. Iron-induced skeletal muscle atrophy is suggested to involve the E3 ubiquitin ligase mediated by the reduction of Akt-FOXO3a signaling by oxidative stress.","ja":"Skeletal muscle wasting or sarcopenia is a critical health problem. Skeletal muscle atrophy is induced by an excess of iron, which is an essential trace metal for all living organisms. Excessive amounts of iron catalyze the formation of highly toxic hydroxyl radicals via the Fenton reaction. However, the molecular mechanism of iron-induced skeletal muscle atrophy has remained unclear. In this study, 8-weeks-old C57BL6/J mice were divided into 2 groups: vehicle-treated group and the iron-injected group (10 mg iron·day-1·mouse-1) during 2 weeks. Mice in the iron-injected group showed an increase in the iron content of the skeletal muscle and serum and ferritin levels in the muscle, along with reduced skeletal muscle mass. The skeletal muscle showed elevated mRNA expression of the muscle atrophy-related E3 ubiquitin ligases, atrogin-1 and muscle ring finger-1(MuRF1), on days 7 and 14 of iron treatment. Moreover, iron-treated mice showed reduced phosphorylation of Akt and forkhead box O3 (FOXO3a) in skeletal muscles. Inhibition of FOXO3a using siRNA in vitro in C2C12 myotube cells inhibited iron-induced upregulation of atrogin-1 and MuRF1 and reversed the reduction in myotube diameters. Iron-load caused oxidative stress, and an oxidative stress inhibitor abrogated iron-induced muscle atrophy by reactivating the Akt-FOXO3 pathway. Iron-induced skeletal muscle atrophy is suggested to involve the E3 ubiquitin ligase mediated by the reduction of Akt-FOXO3a signaling by oxidative stress."},"publication_date":"2016-05","publication_name":{"en":"Journal of Trace Elements in Medicine and Biology","ja":"Journal of Trace Elements in Medicine and Biology"},"volume":"35","number":"5","starting_page":"66","ending_page":"76","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jtemb.2016.01.011"],"issn":["1878-3252"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:21, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2006765","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26134126","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84946558014","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=294522","label":"url"}],"paper_title":{"en":"Bilirubin exerts pro-angiogenic effects through an Akt-eNOS-dependent pathway","ja":"Bilirubin exerts pro-angiogenic effects through an Akt-eNOS-dependent pathway"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Hamano Hirofumi"},{"name":"Satoh Akiho"},{"name":"Horinouchi Yuya"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Aihara Ken-ichi"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"濱野 裕章"},{"name":"佐藤 明穂"},{"name":"堀ノ内 裕也"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"粟飯原 賢一"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as antioxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin-treated group). The analysis of laser speckle blood flow demonstrated the enhancement of blood flow recovery in response to ischemia of mice with bilirubin treatment. The density of capillaries was significantly higher in ischemic-adductor muscles of bilirubin-treated mice. The phosphorylated levels of endothelial nitric oxide synthase (eNOS) and Akt were increased in ischemic skeletal muscles of mice with bilirubin treatment compared with vehicle treatment. In in vitro experiments by using human aortic endothelial cells, bilirubin augmented eNOS and Akt phosphorylation, cell proliferation, cell migration and tube formation. These bilirubin actions on endothelial cell activation were inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. In conclusion, bilirubin promotes angiogenesis through endothelial cells activation via Akt-eNOS-dependent manner.","ja":"Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as antioxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin-treated group). The analysis of laser speckle blood flow demonstrated the enhancement of blood flow recovery in response to ischemia of mice with bilirubin treatment. The density of capillaries was significantly higher in ischemic-adductor muscles of bilirubin-treated mice. The phosphorylated levels of endothelial nitric oxide synthase (eNOS) and Akt were increased in ischemic skeletal muscles of mice with bilirubin treatment compared with vehicle treatment. In in vitro experiments by using human aortic endothelial cells, bilirubin augmented eNOS and Akt phosphorylation, cell proliferation, cell migration and tube formation. These bilirubin actions on endothelial cell activation were inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. In conclusion, bilirubin promotes angiogenesis through endothelial cells activation via Akt-eNOS-dependent manner."},"publication_date":"2015-07-02","publication_name":{"en":"Hypertension Research","ja":"Hypertension Research"},"volume":"38","number":"11","starting_page":"733","ending_page":"740","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/hr.2015.74"],"issn":["1348-4214"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:22, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2006767","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/25096756","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84937513465","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=280180","label":"url"}],"paper_title":{"en":"Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice","ja":"Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice"},"authors":{"en":[{"name":"Tajima Soichiro"},{"name":"Ikeda Yasumasa"},{"name":"Enomoto Hideaki"},{"name":"Imao Mizuki"},{"name":"Horinouchi Yuya"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Miyamoto Licht"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"Tajima Soichiro"},{"name":"池田 康将"},{"name":"榎本 英明"},{"name":"今尾 瑞季"},{"name":"堀ノ内 裕也"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"宮本 理人"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Angiotensin II (ANG II) has been shown to affect iron metabolism through alteration of iron transporters, leading to increased cellular and tissue iron contents. Serum ferritin, a marker of body iron storage, is elevated in various cardiovascular diseases, including hypertension. However, the associated changes in iron absorption and the mechanism underlying increased iron content in a hypertensive state remain unclear. The C57BL6/J mice were treated with ANG II to generate a model of hypertension. Mice were divided into three groups: (1) control, (2) ANG II-treated, and (3) ANG II-treated and ANG II receptor blocker (ARB)-administered (ANG II-ARB) groups. Mice treated with ANG II showed increased serum ferritin levels compared to vehicle-treated control mice. In ANG II-treated mice, duodenal divalent metal transporter-1 and ferroportin (FPN) expression levels were increased and hepatic hepcidin mRNA expression and serum hepcidin concentration were reduced. The mRNA expression of bone morphogenetic protein 6 and CCAAT/enhancer-binding protein alpha, which are regulators of hepcidin, was also down-regulated in the livers of ANG II-treated mice. In terms of tissue iron content, macrophage iron content and renal iron content were increased by ANG II treatment, and these increases were associated with reduced expression of transferrin receptor 1 and FPN and increased expression of ferritin. These changes induced by ANG II treatment were ameliorated by the administration of an ARB. Angiotensin II (ANG II) altered the expression of duodenal iron transporters and reduced hepcidin levels, contributing to the alteration of body iron distribution.","ja":"Angiotensin II (ANG II) has been shown to affect iron metabolism through alteration of iron transporters, leading to increased cellular and tissue iron contents. Serum ferritin, a marker of body iron storage, is elevated in various cardiovascular diseases, including hypertension. However, the associated changes in iron absorption and the mechanism underlying increased iron content in a hypertensive state remain unclear. The C57BL6/J mice were treated with ANG II to generate a model of hypertension. Mice were divided into three groups: (1) control, (2) ANG II-treated, and (3) ANG II-treated and ANG II receptor blocker (ARB)-administered (ANG II-ARB) groups. Mice treated with ANG II showed increased serum ferritin levels compared to vehicle-treated control mice. In ANG II-treated mice, duodenal divalent metal transporter-1 and ferroportin (FPN) expression levels were increased and hepatic hepcidin mRNA expression and serum hepcidin concentration were reduced. The mRNA expression of bone morphogenetic protein 6 and CCAAT/enhancer-binding protein alpha, which are regulators of hepcidin, was also down-regulated in the livers of ANG II-treated mice. In terms of tissue iron content, macrophage iron content and renal iron content were increased by ANG II treatment, and these increases were associated with reduced expression of transferrin receptor 1 and FPN and increased expression of ferritin. These changes induced by ANG II treatment were ameliorated by the administration of an ARB. Angiotensin II (ANG II) altered the expression of duodenal iron transporters and reduced hepcidin levels, contributing to the alteration of body iron distribution."},"publication_date":"2015-07","publication_name":{"en":"European Journal of Nutrition","ja":"European Journal of Nutrition"},"volume":"54","number":"5","starting_page":"709","ending_page":"719","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00394-014-0749-1"],"issn":["1436-6215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:23, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2003177","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/25832631","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390001204631777920/","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84928951796","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=289231","label":"url"}],"paper_title":{"en":"Hypoxia decreases glucagon-like peptide-1 secretion from GLUTag cell line","ja":"Hypoxia decreases glucagon-like peptide-1 secretion from GLUTag cell line"},"authors":{"en":[{"name":"Kihira Yoshitaka"},{"name":"Burentogtokh Ariunzaya"},{"name":"Itoh Mari"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ishizawa Keisuke"},{"name":"Ikeda Yasumasa"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"木平 孝高"},{"name":"Burentogtokh Ariunzaya"},{"name":"Itoh Mari"},{"name":"石澤 有紀"},{"name":"石澤 啓介"},{"name":"池田 康将"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Glucagon-like peptide-1 (GLP-1), an incretin hormone, is secreted from L cells located in the intestinal epithelium. It is known that intestinal oxygen tension is decreased postprandially. In addition, we found that the expression of hypoxia-inducible factor-1α (HIF-1α), which accumulates in cells under hypoxic conditions, was significantly increased in the colons of mice with food intake, indicating that the oxygen concentration is likely reduced in the colon after eating. Therefore, we hypothesized that GLP-1 secretion is affected by oxygen tension. We found that forskolin-stimulated GLP-1 secretion from GLUTag cells, a model of intestinal L cells, is suppressed in hypoxia (1% O2). Forskolin-stimulated elevations of preproglucagon (ppGCG) and proprotein convertase 1/3 (PC1/3) mRNA expression were decreased under hypoxic conditions. The finding that H89, a protein kinase A (PKA) inhibitor, inhibited the forskolin-stimulated increase of ppGCG and PC1/3 indicated that the cAMP-PKA pathway is involved in the hypoxia-induced suppression of the genes. Hypoxia decreased hexokinase 2 mRNA and protein expression and increased lactate dehydrogenase A mRNA and protein expression. Concomitantly, lactate production was increased and ATP production was decreased. Together, the results indicate that hypoxia decreases glucose utilization for ATP production, which probably causes a decrease in cAMP production and in subsequent GLP-1 production. Our findings suggest that the postprandial decrease in oxygen tension in the intestine attenuates GLP-1 secretion.","ja":"Glucagon-like peptide-1 (GLP-1), an incretin hormone, is secreted from L cells located in the intestinal epithelium. It is known that intestinal oxygen tension is decreased postprandially. In addition, we found that the expression of hypoxia-inducible factor-1α (HIF-1α), which accumulates in cells under hypoxic conditions, was significantly increased in the colons of mice with food intake, indicating that the oxygen concentration is likely reduced in the colon after eating. Therefore, we hypothesized that GLP-1 secretion is affected by oxygen tension. We found that forskolin-stimulated GLP-1 secretion from GLUTag cells, a model of intestinal L cells, is suppressed in hypoxia (1% O2). Forskolin-stimulated elevations of preproglucagon (ppGCG) and proprotein convertase 1/3 (PC1/3) mRNA expression were decreased under hypoxic conditions. The finding that H89, a protein kinase A (PKA) inhibitor, inhibited the forskolin-stimulated increase of ppGCG and PC1/3 indicated that the cAMP-PKA pathway is involved in the hypoxia-induced suppression of the genes. Hypoxia decreased hexokinase 2 mRNA and protein expression and increased lactate dehydrogenase A mRNA and protein expression. Concomitantly, lactate production was increased and ATP production was decreased. Together, the results indicate that hypoxia decreases glucose utilization for ATP production, which probably causes a decrease in cAMP production and in subsequent GLP-1 production. Our findings suggest that the postprandial decrease in oxygen tension in the intestine attenuates GLP-1 secretion."},"publication_date":"2015-04","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"38","number":"4","starting_page":"514","ending_page":"521","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b14-00612"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:24, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/40020377946/","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/25994136","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390282681302013696/","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84929747372","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=288751","label":"url"}],"paper_title":{"en":"A Long-Term High-Fat Diet Changes Iron Distribution in Body, Increasing Iron Accumulation Specifically in the Mouse Spleen","ja":"A Long-Term High-Fat Diet Changes Iron Distribution in Body, Increasing Iron Accumulation Specifically in the Mouse Spleen"},"authors":{"en":[{"name":"Yamano Noriko"},{"name":"Ikeda Yasumasa"},{"name":"Sakama Minoru"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Miyamoto Licht"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"山野 範子"},{"name":"池田 康将"},{"name":"阪間 稔"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"宮本 理人"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Although iron is an essential trace metal, its presence in excess causes oxidative stress in the human body. Recent studies have indicated that iron storage is a risk factor for type 2 diabetes mellitus. Dietary iron restriction or iron chelation ameliorates symptoms of type 2 diabetes in mouse models. However, whether iron content in the body changes with the development of diabetes is unknown. Here, we investigated the dynamics of iron accumulation and changes in iron absorption-related genes in mice that developed obesity and diabetes by consuming a high-fat diet (HFD-fed mice). HFD-fed mice (18-20 wk) were compared with control mice for hematologic features, serum ferritin levels, and iron contents in the gastrocnemius muscle, heart, epididymal fat, testis, liver, duodenum, and spleen. In addition, the spleen was examined histologically. Iron absorption-related gene expression in the liver and duodenum was also examined. Hemoglobin and serum ferritin levels were increased in HFD-fed mice. The HFD-fed mice showed iron accumulation in the spleen, but not in the heart or liver. Increased percentages of the splenic red pulp and macrophages were observed in HFD-fed mice and iron accumulation in the spleen was found mainly in the splenic red pulp. The HFD-fed mice also showed decreased iron content in the duodenum. The mRNA expression of divalent metal transporter-1 (DMT-1), an iron absorption-related gene, was elevated in the duodenum of HFD-fed mice. These results indicate that iron accumulation (specifically accumulation in the spleen) is enhanced by the development of type 2 diabetes induced by HFD.","ja":"Although iron is an essential trace metal, its presence in excess causes oxidative stress in the human body. Recent studies have indicated that iron storage is a risk factor for type 2 diabetes mellitus. Dietary iron restriction or iron chelation ameliorates symptoms of type 2 diabetes in mouse models. However, whether iron content in the body changes with the development of diabetes is unknown. Here, we investigated the dynamics of iron accumulation and changes in iron absorption-related genes in mice that developed obesity and diabetes by consuming a high-fat diet (HFD-fed mice). HFD-fed mice (18-20 wk) were compared with control mice for hematologic features, serum ferritin levels, and iron contents in the gastrocnemius muscle, heart, epididymal fat, testis, liver, duodenum, and spleen. In addition, the spleen was examined histologically. Iron absorption-related gene expression in the liver and duodenum was also examined. Hemoglobin and serum ferritin levels were increased in HFD-fed mice. The HFD-fed mice showed iron accumulation in the spleen, but not in the heart or liver. Increased percentages of the splenic red pulp and macrophages were observed in HFD-fed mice and iron accumulation in the spleen was found mainly in the splenic red pulp. The HFD-fed mice also showed decreased iron content in the duodenum. The mRNA expression of divalent metal transporter-1 (DMT-1), an iron absorption-related gene, was elevated in the duodenum of HFD-fed mice. These results indicate that iron accumulation (specifically accumulation in the spleen) is enhanced by the development of type 2 diabetes induced by HFD."},"publication_date":"2015-03","publication_name":{"en":"Journal of Nutritional Science and Vitaminology","ja":"Journal of Nutritional Science and Vitaminology"},"volume":"61","number":"1","starting_page":"20","ending_page":"27","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3177/jnsv.61.20"],"issn":["0301-4800"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:25, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2002346","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24623277","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84901457818","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=275488","label":"url"}],"paper_title":{"en":"Smooth muscle cell specific Hif-1 deficiency suppresses angiotensin II-induced vascular remodeling in mice","ja":"Smooth muscle cell specific Hif-1 deficiency suppresses angiotensin II-induced vascular remodeling in mice"},"authors":{"en":[{"name":"Imanishi Masaki"},{"name":"Tomita Shuhei"},{"name":"Ishizawa Keisuke"},{"name":"Kihira Yoshitaka"},{"name":"Ueno Masaki"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ikeda Yasumasa"},{"name":"Yamano Noriko"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"今西 正樹"},{"name":"冨田 修平"},{"name":"石澤 啓介"},{"name":"木平 孝高"},{"name":"Ueno Masaki"},{"name":"石澤 有紀"},{"name":"池田 康将"},{"name":"山野 範子"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Vascular remodelling is mediated by vascular smooth muscle cell (VSMC) proliferation and hypertrophy, both processes of which are linked to medial thickening and fibrosis. Here, we show that hypoxia-inducible factor-1α (Hif-1α) expressed in smooth muscle cells (SMCs) is involved in angiotensin II (Ang II)-induced vascular remodelling in an in vivo model. To clarify the role of Hif-1α in vascular remodelling, we created mice lacking the Hif-1α gene in SMCs (SMKO mice). Ang II infusion induced medial thickening and vascular fibrosis, accompanied by Hif-1α up-regulation, in the aortae of control mice, but not in those of SMKO mice. In accordance with those results, our in vitro studies showed that the deletion of SMC-derived Hif-1α suppressed the Ang II-induced hypertrophy of VSMCs, and our in vivo studies showed that the Ang II-induced expression of fibrosis-related genes in aortae was suppressed by SMC-specific Hif-1α deficiency. In addition, the SMC-specific Hif-1α deficiency suppressed Ang II-induced macrophage infiltration and Ang II-induced expression of inflammation-related genes in aortae. The superoxide production observed in the aortae of control mice with Ang II was suppressed in those of SMKO mice with Ang II, and this finding was consistent with the results of little Ang II-induced c-Src phosphorylation in SMKO mouse aortae. Loss- and gain-of-function analysis in in vitro experiments confirmed that VSMC-derived Hif-1α functions as an intrinsic modulator of vascular remodelling-related gene expression. Our results revealed that SMC-derived Hif-1α is a crucial mediator of Ang II-induced vascular remodelling.","ja":"Vascular remodelling is mediated by vascular smooth muscle cell (VSMC) proliferation and hypertrophy, both processes of which are linked to medial thickening and fibrosis. Here, we show that hypoxia-inducible factor-1α (Hif-1α) expressed in smooth muscle cells (SMCs) is involved in angiotensin II (Ang II)-induced vascular remodelling in an in vivo model. To clarify the role of Hif-1α in vascular remodelling, we created mice lacking the Hif-1α gene in SMCs (SMKO mice). Ang II infusion induced medial thickening and vascular fibrosis, accompanied by Hif-1α up-regulation, in the aortae of control mice, but not in those of SMKO mice. In accordance with those results, our in vitro studies showed that the deletion of SMC-derived Hif-1α suppressed the Ang II-induced hypertrophy of VSMCs, and our in vivo studies showed that the Ang II-induced expression of fibrosis-related genes in aortae was suppressed by SMC-specific Hif-1α deficiency. In addition, the SMC-specific Hif-1α deficiency suppressed Ang II-induced macrophage infiltration and Ang II-induced expression of inflammation-related genes in aortae. The superoxide production observed in the aortae of control mice with Ang II was suppressed in those of SMKO mice with Ang II, and this finding was consistent with the results of little Ang II-induced c-Src phosphorylation in SMKO mouse aortae. Loss- and gain-of-function analysis in in vitro experiments confirmed that VSMC-derived Hif-1α functions as an intrinsic modulator of vascular remodelling-related gene expression. Our results revealed that SMC-derived Hif-1α is a crucial mediator of Ang II-induced vascular remodelling."},"publication_date":"2014-06","publication_name":{"en":"Cardiovascular Research","ja":"Cardiovascular Research"},"volume":"102","number":"3","starting_page":"460","ending_page":"468","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1093/cvr/cvu061"],"issn":["0008-6363"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:26, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24599965","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84901845393","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=273735","label":"url"}],"paper_title":{"en":"HIF-2α/ARNT complex regulates hair development via induction of p21Waf1/Cip1 and p27Kip1","ja":"HIF-2α/ARNT complex regulates hair development via induction of p21Waf1/Cip1 and p27Kip1"},"authors":{"en":[{"name":"Imamura Yuko"},{"name":"Tomita Shuhei"},{"name":"Imanishi Masaki"},{"name":"Kihira Yoshitaka"},{"name":"Ikeda Yasumasa"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"Imamura Yuko"},{"name":"冨田 修平"},{"name":"今西 正樹"},{"name":"木平 孝高"},{"name":"池田 康将"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"The hypoxia-inducible factors HIF-1α or HIF-2α form heterodimeric complexes with the aryl hydrocarbon receptor nuclear translocator (ARNT). HIF-1α/ARNT and HIF-2α/ARNT complexes activate hypoxia-inducible genes that play critical roles in angiogenesis, anaerobic metabolism, and other processes in response to O2 deprivation. HIF-2α is known to regulate the function and/or differentiation of stem cells by activating the POU domain transcription factor Oct4; however, the precise underlying mechanism is unknown. This study examined the role of HIF-2α/ARNT in hair development using conditional-knockout mice, in which Arnt was specifically deleted in keratinocytes. In wild-type mice, HIF-2α and ARNT were highly expressed in the precortex above the hair matrix, an area containing differentiating stem cells. An analysis of hair size and type in these mice showed that loss of ARNT decreased the production of zigzag hairs, corresponding to reduced expression of HIF-2α and induction of the mammalian cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27 (Kip1). The results suggest that the HIF-2α/ARNT complex regulates hair follicle differentiation via induction of p21(Waf1/Cip1) and possibly p27(Kip1), as p27(Kip1) expression was not altered in ARNT knockout mice. The findings provide insight into a possible mechanism underlying hair growth disorders and can be useful for future studies on hair follicle response to insults, such as chemotherapy and ionizing radiation.-Imamura, Y., Tomita, S., Imanishi, M., Kihira, Y., Ikeda, Y., Ishizawa, K., Tsuchiya, K., Tamaki, T. HIF-2α/ARNT complex regulates hair development via induction of p21(Waf1/Cip1) and p27(Kip1).","ja":"The hypoxia-inducible factors HIF-1α or HIF-2α form heterodimeric complexes with the aryl hydrocarbon receptor nuclear translocator (ARNT). HIF-1α/ARNT and HIF-2α/ARNT complexes activate hypoxia-inducible genes that play critical roles in angiogenesis, anaerobic metabolism, and other processes in response to O2 deprivation. HIF-2α is known to regulate the function and/or differentiation of stem cells by activating the POU domain transcription factor Oct4; however, the precise underlying mechanism is unknown. This study examined the role of HIF-2α/ARNT in hair development using conditional-knockout mice, in which Arnt was specifically deleted in keratinocytes. In wild-type mice, HIF-2α and ARNT were highly expressed in the precortex above the hair matrix, an area containing differentiating stem cells. An analysis of hair size and type in these mice showed that loss of ARNT decreased the production of zigzag hairs, corresponding to reduced expression of HIF-2α and induction of the mammalian cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27 (Kip1). The results suggest that the HIF-2α/ARNT complex regulates hair follicle differentiation via induction of p21(Waf1/Cip1) and possibly p27(Kip1), as p27(Kip1) expression was not altered in ARNT knockout mice. The findings provide insight into a possible mechanism underlying hair growth disorders and can be useful for future studies on hair follicle response to insults, such as chemotherapy and ionizing radiation.-Imamura, Y., Tomita, S., Imanishi, M., Kihira, Y., Ikeda, Y., Ishizawa, K., Tsuchiya, K., Tamaki, T. HIF-2α/ARNT complex regulates hair development via induction of p21(Waf1/Cip1) and p27(Kip1)."},"publication_date":"2014-06","publication_name":{"en":"The FASEB journal","ja":"The FASEB journal"},"volume":"28","number":"6","starting_page":"2517","ending_page":"2524","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1096/fj.13-244079"],"issn":["0892-6638"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:27, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2000082","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24705496","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84899440448","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=276331","label":"url"}],"paper_title":{"en":"Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation.","ja":"Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation."},"authors":{"en":[{"name":"Kihira Yoshitaka"},{"name":"Miyake Mariko"},{"name":"Hirata Manami"},{"name":"Hoshina Yoji"},{"name":"Kato Kana"},{"name":"Shirakawa Hitoshi"},{"name":"Sakaue Hiroshi"},{"name":"Yamano Noriko"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ishizawa Keisuke"},{"name":"Ikeda Yasumasa"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"},{"name":"Tomita Shuhei"}],"ja":[{"name":"木平 孝高"},{"name":"Miyake Mariko"},{"name":"Hirata Manami"},{"name":"Hoshina Yoji"},{"name":"Kato Kana"},{"name":"Shirakawa Hitoshi"},{"name":"阪上 浩"},{"name":"山野 範子"},{"name":"石澤 有紀"},{"name":"石澤 啓介"},{"name":"池田 康将"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"},{"name":"冨田 修平"}]},"description":{"en":"It is known that obese adipose tissues are hypoxic and express hypoxia-inducible factor (HIF)-1α. Although some studies have shown that the expression of HIF-1α in adipocytes induces glucose intolerance, the mechanisms are still not clear. In this study, we examined its effects on the development of type 2 diabetes by using adipocyte-specific HIF-1α knockout (ahKO) mice. ahKO mice showed improved glucose tolerance compared with wild type (WT) mice. Macrophage infiltration and mRNA levels of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor α (TNFα) were decreased in the epididymal adipose tissues of high fat diet induced obese ahKO mice. The results indicated that the obesity-induced adipose tissue inflammation was suppressed in ahKO mice. In addition, in the ahKO mice, serum insulin levels were increased under the free-feeding but not the fasting condition, indicating that postprandial insulin secretion was enhanced. Serum glucagon-like peptide-1 (GLP-1) levels were also increased in the ahKO mice. Interestingly, adiponectin, whose serum levels were increased in the obese ahKO mice compared with the obese WT mice, stimulated GLP-1 secretion from cultured intestinal L cells. Therefore, insulin secretion may have been enhanced through the adiponectin-GLP-1 pathway in the ahKO mice. Our results suggest that the deletion of HIF-1α in adipocytes improves glucose tolerance by enhancing insulin secretion through the GLP-1 pathway and by reducing macrophage infiltration and inflammation in adipose tissue.","ja":"It is known that obese adipose tissues are hypoxic and express hypoxia-inducible factor (HIF)-1α. Although some studies have shown that the expression of HIF-1α in adipocytes induces glucose intolerance, the mechanisms are still not clear. In this study, we examined its effects on the development of type 2 diabetes by using adipocyte-specific HIF-1α knockout (ahKO) mice. ahKO mice showed improved glucose tolerance compared with wild type (WT) mice. Macrophage infiltration and mRNA levels of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor α (TNFα) were decreased in the epididymal adipose tissues of high fat diet induced obese ahKO mice. The results indicated that the obesity-induced adipose tissue inflammation was suppressed in ahKO mice. In addition, in the ahKO mice, serum insulin levels were increased under the free-feeding but not the fasting condition, indicating that postprandial insulin secretion was enhanced. Serum glucagon-like peptide-1 (GLP-1) levels were also increased in the ahKO mice. Interestingly, adiponectin, whose serum levels were increased in the obese ahKO mice compared with the obese WT mice, stimulated GLP-1 secretion from cultured intestinal L cells. Therefore, insulin secretion may have been enhanced through the adiponectin-GLP-1 pathway in the ahKO mice. Our results suggest that the deletion of HIF-1α in adipocytes improves glucose tolerance by enhancing insulin secretion through the GLP-1 pathway and by reducing macrophage infiltration and inflammation in adipose tissue."},"publication_date":"2014-04-04","publication_name":{"en":"PLoS ONE","ja":"PLoS ONE"},"volume":"9","number":"4","starting_page":"e93856","ending_page":"e93856","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.pone.0093856"],"issn":["1932-6203"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:28, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2006766","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24586712","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84897786390","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=274493","label":"url"}],"paper_title":{"en":"Iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction","ja":"Iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Ozono Iori"},{"name":"Tajima Soichro"},{"name":"Imao Mizuki"},{"name":"Horinouchi Yuya"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Miyamoto Licht"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"大園 伊織"},{"name":"Tajima Soichro"},{"name":"今尾 瑞季"},{"name":"堀ノ内 裕也"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"宮本 理人"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases (CKD). Although several mechanisms underlying renal fibrosis and candidate drugs for its treatment have been identified, the effect of iron chelator on renal fibrosis remains unclear. In the present study, we examined the effect of an iron chelator, deferoxamine (DFO), on renal fibrosis in mice with surgically induced unilateral ureter obstruction (UUO). Mice were divided into 4 groups: UUO with vehicle, UUO with DFO, sham with vehicle, and sham with DFO. One week after surgery, augmented renal tubulointerstitial fibrosis and the expression of collagen I, III, and IV increased in mice with UUO; these changes were suppressed by DFO treatment. Similarly, UUO-induced macrophage infiltration of renal interstitial tubules was reduced in UUO mice treated with DFO. UUO-induced expression of inflammatory cytokines and extracellular matrix proteins was abrogated by DFO treatment. DFO inhibited the activation of the transforming growth factor-β1 (TGF-β1)-Smad3 pathway in UUO mice. UUO-induced NADPH oxidase activity and p22(phox) expression were attenuated by DFO. In the kidneys of UUO mice, divalent metal transporter 1, ferroportin, and ferritin expression was higher and transferrin receptor expression was lower than in sham-operated mice. Increased renal iron content was observed in UUO mice, which was reduced by DFO treatment. These results suggest that iron reduction by DFO prevents renal tubulointerstitial fibrosis by regulating TGF-β-Smad signaling, oxidative stress, and inflammatory responses.","ja":"Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases (CKD). Although several mechanisms underlying renal fibrosis and candidate drugs for its treatment have been identified, the effect of iron chelator on renal fibrosis remains unclear. In the present study, we examined the effect of an iron chelator, deferoxamine (DFO), on renal fibrosis in mice with surgically induced unilateral ureter obstruction (UUO). Mice were divided into 4 groups: UUO with vehicle, UUO with DFO, sham with vehicle, and sham with DFO. One week after surgery, augmented renal tubulointerstitial fibrosis and the expression of collagen I, III, and IV increased in mice with UUO; these changes were suppressed by DFO treatment. Similarly, UUO-induced macrophage infiltration of renal interstitial tubules was reduced in UUO mice treated with DFO. UUO-induced expression of inflammatory cytokines and extracellular matrix proteins was abrogated by DFO treatment. DFO inhibited the activation of the transforming growth factor-β1 (TGF-β1)-Smad3 pathway in UUO mice. UUO-induced NADPH oxidase activity and p22(phox) expression were attenuated by DFO. In the kidneys of UUO mice, divalent metal transporter 1, ferroportin, and ferritin expression was higher and transferrin receptor expression was lower than in sham-operated mice. Increased renal iron content was observed in UUO mice, which was reduced by DFO treatment. These results suggest that iron reduction by DFO prevents renal tubulointerstitial fibrosis by regulating TGF-β-Smad signaling, oxidative stress, and inflammatory responses."},"publication_date":"2014-02-19","publication_name":{"en":"PLoS ONE","ja":"PLoS ONE"},"volume":"9","number":"2","starting_page":"e89355","ending_page":"e89355","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.pone.0089355"],"issn":["1932-6203"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:29, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2000100","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24489716","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84900332178","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=275165","label":"url"}],"paper_title":{"en":"Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects","ja":"Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects"},"authors":{"en":[{"name":"Ishizawa Keisuke"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Yamano Noriko"},{"name":"Urushihara Maki"},{"name":"Sakurada Takumi"},{"name":"Imanishi Masaki"},{"name":"Fujii Shoko"},{"name":"Nuno Asami"},{"name":"Miyamoto Licht"},{"name":"Kihira Yoshitaka"},{"name":"Ikeda Yasumasa"},{"name":"Kagami Shoji"},{"name":"Kobori Hiroyuki"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 啓介"},{"name":"石澤 有紀"},{"name":"山野 範子"},{"name":"漆原 真樹"},{"name":"Sakurada Takumi"},{"name":"今西 正樹"},{"name":"Fujii Shoko"},{"name":"Nuno Asami"},{"name":"宮本 理人"},{"name":"木平 孝高"},{"name":"池田 康将"},{"name":"香美 祥二"},{"name":"Kobori Hiroyuki"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Diabetic nephropathy (DN) is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF) is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice), NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM)-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS) knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT) excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects.","ja":"Diabetic nephropathy (DN) is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF) is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice), NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM)-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS) knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT) excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects."},"publication_date":"2014-01-28","publication_name":{"en":"PLoS ONE","ja":"PLoS ONE"},"volume":"9","number":"1","starting_page":"e86335","ending_page":"e86335","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.pone.0086335"],"issn":["1932-6203"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:30, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23723256","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=265044","label":"url"}],"paper_title":{"en":"Androgen receptor promotes sex-independent angiogenesis in response to ischemia and is required for activation of vascular endothelial growth factor receptor signaling.","ja":"Androgen receptor promotes sex-independent angiogenesis in response to ischemia and is required for activation of vascular endothelial growth factor receptor signaling."},"authors":{"en":[{"name":"Yoshida Sumiko"},{"name":"Aihara Ken-ichi"},{"name":"Ikeda Yasumasa"},{"name":"Sumitomo-Ueda Yuka"},{"name":"Uemoto Ryoko"},{"name":"Ishikawa Kazue"},{"name":"Ise Takayuki"},{"name":"Yagi Shusuke"},{"name":"Iwase Takashi"},{"name":"Mouri Yasuhiro"},{"name":"Sakari Matomo"},{"name":"Matsumoto Takahiro"},{"name":"Takeyama Ken-ichi"},{"name":"Akaike Masashi"},{"name":"Matsumoto Mitsuru"},{"name":"Sata Masataka"},{"name":"Walsh Kenneth"},{"name":"Kato Shigeaki"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"吉田 守美子"},{"name":"粟飯原 賢一"},{"name":"池田 康将"},{"name":"Sumitomo-Ueda Yuka"},{"name":"Uemoto Ryoko"},{"name":"Ishikawa Kazue"},{"name":"伊勢 孝之"},{"name":"八木 秀介"},{"name":"岩瀬 俊"},{"name":"毛利 安宏"},{"name":"盛 真友"},{"name":"松本 高広"},{"name":"Takeyama Ken-ichi"},{"name":"赤池 雅史"},{"name":"松本 満"},{"name":"佐田 政隆"},{"name":"Walsh Kenneth"},{"name":"Kato Shigeaki"},{"name":"松本 俊夫"}]},"description":{"en":"These results document a physiological role of AR in sex-independent angiogenic potency and provide evidence of novel cross-talk between the androgen/AR signaling and VEGF/kinase insert domain protein receptor signaling pathways.","ja":"These results document a physiological role of AR in sex-independent angiogenic potency and provide evidence of novel cross-talk between the androgen/AR signaling and VEGF/kinase insert domain protein receptor signaling pathways."},"publication_date":"2013-05-30","publication_name":{"en":"Circulation","ja":"Circulation"},"volume":"128","number":"1","starting_page":"60","ending_page":"71","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1161/CIRCULATIONAHA.113.001533"],"issn":["1524-4539"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:31, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23389454","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=261038","label":"url"}],"paper_title":{"en":"Dietary iron restriction inhibits progression of diabetic nephropathy in db/db mice.","ja":"Dietary iron restriction inhibits progression of diabetic nephropathy in db/db mice."},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Enomoto Hideaki"},{"name":"Tajima Soichiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"榎本 英明"},{"name":"Tajima Soichiro"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Excess iron causes oxidative stress through hydroxyl-radical production via Fenton/Haber-Weiss reactions. Recently, body iron reduction has been found to ameliorate diabetes. In the present study, we examined the protective effect of dietary iron restriction against diabetic nephropathy in the db/db mouse model of diabetic nephropathy using db/m mice as controls. The db/db mice were divided into 2 groups and fed a normal diet (ND) or a low iron diet (LID). Increasing urinary albumin excretion was observed in the ND db/db mice, but this was suppressed in db/db mice with LID. Histologically, the db/db mice in the ND group had increased glomerular volume and mesangial area compared to the LID group. Augmented deposition of extracellular matrices was decreased in db/db mice with LID. In terms of oxidative stress, increased superoxide production observed in the kidneys of the ND db/db mice was diminished in the LID group. NADPH oxidase activity and renal expression of NADPH oxidase components p22(phox) and NOX4 were augmented in the ND group, and this was abolished by LID. There were no differences in expression of renal iron importers, transferrin receptor, or divalent metal transporter-1 between db/m mice and db/db mice. The level of ferroportin, an iron exporter, increased in the kidneys of the db/db mice. Urinary iron excretion was significantly higher in ND db/db mice and was reduced in the LID group. These findings suggest that dietary iron restriction exerts a preventive effect on the progression of diabetic nephropathy partly due to the reduction of oxidative stress.","ja":"Excess iron causes oxidative stress through hydroxyl-radical production via Fenton/Haber-Weiss reactions. Recently, body iron reduction has been found to ameliorate diabetes. In the present study, we examined the protective effect of dietary iron restriction against diabetic nephropathy in the db/db mouse model of diabetic nephropathy using db/m mice as controls. The db/db mice were divided into 2 groups and fed a normal diet (ND) or a low iron diet (LID). Increasing urinary albumin excretion was observed in the ND db/db mice, but this was suppressed in db/db mice with LID. Histologically, the db/db mice in the ND group had increased glomerular volume and mesangial area compared to the LID group. Augmented deposition of extracellular matrices was decreased in db/db mice with LID. In terms of oxidative stress, increased superoxide production observed in the kidneys of the ND db/db mice was diminished in the LID group. NADPH oxidase activity and renal expression of NADPH oxidase components p22(phox) and NOX4 were augmented in the ND group, and this was abolished by LID. There were no differences in expression of renal iron importers, transferrin receptor, or divalent metal transporter-1 between db/m mice and db/db mice. The level of ferroportin, an iron exporter, increased in the kidneys of the db/db mice. Urinary iron excretion was significantly higher in ND db/db mice and was reduced in the LID group. These findings suggest that dietary iron restriction exerts a preventive effect on the progression of diabetic nephropathy partly due to the reduction of oxidative stress."},"publication_date":"2013-02-06","publication_name":{"en":"American Journal of Physiology, Renal Physiology","ja":"American Journal of Physiology, Renal Physiology"},"volume":"304","number":"7","starting_page":"F1028","ending_page":"F1036","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajprenal.00473.2012"],"issn":["1522-1466"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:32, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2006768","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23364610","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=259318","label":"url"}],"paper_title":{"en":"Bovine milk-derived lactoferrin exerts proangiogenic effects in an Src-Akt-eNOS-dependent manner in response to ischemia","ja":"Bovine milk-derived lactoferrin exerts proangiogenic effects in an Src-Akt-eNOS-dependent manner in response to ischemia"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Tajima Soichiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Yoshida Sumiko"},{"name":"Aihara Ken-ichi"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"Tajima Soichiro"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"吉田 守美子"},{"name":"粟飯原 賢一"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Lactoferrin (LF) exerts a variety of biological effects, including the promotion of angiogenesis by increasing the expression of angiogenesis-related genes and reducing blood pressure via a nitric oxide-dependent mechanism. In this study, we investigated the effects of LF on angiogenesis using C57BL/6J mice that received daily unilateral treatment with or without bovine milk-derived LF (bLF) after unilateral hindlimb surgery. The analysis of laser speckle blood flow showed that bLF treatment promoted blood flow recovery in response to ischemic hindlimb. The capillary density of ischemic adductor muscles and the phosphorylation of Src, Akt, and endothelial nitric oxide synthase (eNOS) were also significantly higher in bLF-treated mice than in vehicle-treated mice. Furthermore, bLF increased the phosphorylation levels of Src, Akt, and eNOS in in vitro experiments using human aortic endothelial cells. The action of bLF on eNOS phosphorylation was abolished by both LY294002, a phosphatidylinositol 3-kinase inhibitor, and 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo [3,4-d]pyrimidine (PP2), an Src inhibitor. Similarly, bLF-induced acceleration of tube formation, cell proliferation, and cell migration in human aortic endothelial cells were inhibited by LY294002 or PP2. Thus, bLF promotes vascular endothelial cell function via an Src Akt eNOS-dependent pathway, thereby contributing to revascularization in response to ischemia.","ja":"Lactoferrin (LF) exerts a variety of biological effects, including the promotion of angiogenesis by increasing the expression of angiogenesis-related genes and reducing blood pressure via a nitric oxide-dependent mechanism. In this study, we investigated the effects of LF on angiogenesis using C57BL/6J mice that received daily unilateral treatment with or without bovine milk-derived LF (bLF) after unilateral hindlimb surgery. The analysis of laser speckle blood flow showed that bLF treatment promoted blood flow recovery in response to ischemic hindlimb. The capillary density of ischemic adductor muscles and the phosphorylation of Src, Akt, and endothelial nitric oxide synthase (eNOS) were also significantly higher in bLF-treated mice than in vehicle-treated mice. Furthermore, bLF increased the phosphorylation levels of Src, Akt, and eNOS in in vitro experiments using human aortic endothelial cells. The action of bLF on eNOS phosphorylation was abolished by both LY294002, a phosphatidylinositol 3-kinase inhibitor, and 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo [3,4-d]pyrimidine (PP2), an Src inhibitor. Similarly, bLF-induced acceleration of tube formation, cell proliferation, and cell migration in human aortic endothelial cells were inhibited by LY294002 or PP2. Thus, bLF promotes vascular endothelial cell function via an Src Akt eNOS-dependent pathway, thereby contributing to revascularization in response to ischemia."},"publication_date":"2013-01","publication_name":{"en":"Journal of Cardiovascular Pharmacology","ja":"Journal of Cardiovascular Pharmacology"},"volume":"61","number":"5","starting_page":"423","ending_page":"429","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1097/FJC.0b013e318287d526"],"issn":["1533-4023"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:33, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23149861","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84872316103","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=257964","label":"url"}],"paper_title":{"en":"Nitrosonifedipine ameliorates angiotensin II-induced vascular remodeling via antioxidative effects","ja":"Nitrosonifedipine ameliorates angiotensin II-induced vascular remodeling via antioxidative effects"},"authors":{"en":[{"name":"Sakurada Takumi"},{"name":"Ishizawa Keisuke"},{"name":"Imanishi Masaki"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Fujii Shoko"},{"name":"Tominaga Erika"},{"name":"Tsuneishi Teppei"},{"name":"Horinouchi Yuya"},{"name":"Kihira Yoshitaka"},{"name":"Ikeda Yasumasa"},{"name":"Tomita Shuhei"},{"name":"Aihara Ken-ichi"},{"name":"Minakuchi Kazuo"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"Sakurada Takumi"},{"name":"石澤 啓介"},{"name":"今西 正樹"},{"name":"石澤 有紀"},{"name":"Fujii Shoko"},{"name":"Tominaga Erika"},{"name":"Tsuneishi Teppei"},{"name":"堀ノ内 裕也"},{"name":"木平 孝高"},{"name":"池田 康将"},{"name":"冨田 修平"},{"name":"粟飯原 賢一"},{"name":"水口 和生"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Nifedipine is unstable under light and decomposes to a stable nitroso analog, nitrosonifedipine (NO-NIF). The ability of NO-NIF to block calcium channels is quite weak compared with that of nifedipine. Recently, we have demonstrated that NO-NIF reacts with unsaturated fatty acid leading to generate NO-NIF radical, which acquires radical scavenging activity. However, the effects of NO-NIF on the pathogenesis related with oxidative stress, such as atherosclerosis and hypertension, are unclear. In this study, we investigated the effects of NO-NIF on angiotensin II (Ang II)-induced vascular remodeling. Ang II-induced thickening and fibrosis of aorta were inhibited by NO-NIF in mice. NO-NIF decreased reactive oxygen species (ROS) in the aorta and urinary 8-hydroxy-20-deoxyguanosine. Ang II-stimulated mRNA expressions of p22(phox), CD68, F4/80, monocyte chemoattractant protein-1, and collagen I in the aorta were inhibited by NO-NIF. Moreover, NO-NIF inhibited Ang II-induced cell migration and proliferation of vascular smooth muscle cells (VSMCs). NO-NIF reduced Ang II-induced ROS to the control level detected by dihydroethidium staining and lucigenin chemiluminescence assay in VSMCs. NO-NIF suppressed phosphorylations of Akt and epidermal growth factor receptor induced by Ang II. However, NO-NIF had no effects on intracellular Ca(2+) increase and protein kinase C-δ phosphorylation induced by Ang II in VSMCs. The electron paramagnetic resonance spectra indicated the continuous generation of NO-NIF radical of reaction with cultured VSMCs. These findings suggest that NO-NIF improves Ang II-induced vascular remodeling via the attenuation of oxidative stress.","ja":"Nifedipine is unstable under light and decomposes to a stable nitroso analog, nitrosonifedipine (NO-NIF). The ability of NO-NIF to block calcium channels is quite weak compared with that of nifedipine. Recently, we have demonstrated that NO-NIF reacts with unsaturated fatty acid leading to generate NO-NIF radical, which acquires radical scavenging activity. However, the effects of NO-NIF on the pathogenesis related with oxidative stress, such as atherosclerosis and hypertension, are unclear. In this study, we investigated the effects of NO-NIF on angiotensin II (Ang II)-induced vascular remodeling. Ang II-induced thickening and fibrosis of aorta were inhibited by NO-NIF in mice. NO-NIF decreased reactive oxygen species (ROS) in the aorta and urinary 8-hydroxy-20-deoxyguanosine. Ang II-stimulated mRNA expressions of p22(phox), CD68, F4/80, monocyte chemoattractant protein-1, and collagen I in the aorta were inhibited by NO-NIF. Moreover, NO-NIF inhibited Ang II-induced cell migration and proliferation of vascular smooth muscle cells (VSMCs). NO-NIF reduced Ang II-induced ROS to the control level detected by dihydroethidium staining and lucigenin chemiluminescence assay in VSMCs. NO-NIF suppressed phosphorylations of Akt and epidermal growth factor receptor induced by Ang II. However, NO-NIF had no effects on intracellular Ca(2+) increase and protein kinase C-δ phosphorylation induced by Ang II in VSMCs. The electron paramagnetic resonance spectra indicated the continuous generation of NO-NIF radical of reaction with cultured VSMCs. These findings suggest that NO-NIF improves Ang II-induced vascular remodeling via the attenuation of oxidative stress."},"publication_date":"2013-01","publication_name":{"en":"Naunyn-Schmiedeberg's Archives of Pharmacology","ja":"Naunyn-Schmiedeberg's Archives of Pharmacology"},"volume":"386","number":"1","starting_page":"29","ending_page":"39","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00210-012-0810-7"],"issn":["1432-1912"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:34, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23052181","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84867214872","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=256474","label":"url"}],"paper_title":{"en":"Angiotensin II receptor blocker improves tumor necrosis factor-α-induced cytotoxicity via antioxidative effect in human glomerular endothelial cells","ja":"Angiotensin II receptor blocker improves tumor necrosis factor-α-induced cytotoxicity via antioxidative effect in human glomerular endothelial cells"},"authors":{"en":[{"name":"Izawa-Ishizawa Yuki"},{"name":"Ishizawa Keisuke"},{"name":"Sakurada Takumi"},{"name":"Imanishi Masaki"},{"name":"Miyamoto Licht"},{"name":"Fujii Shoko"},{"name":"Taira Hironori"},{"name":"Kihira Yoshitaka"},{"name":"Ikeda Yasumasa"},{"name":"Hamano Shuichi"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 有紀"},{"name":"石澤 啓介"},{"name":"Sakurada Takumi"},{"name":"今西 正樹"},{"name":"宮本 理人"},{"name":"Fujii Shoko"},{"name":"Taira Hironori"},{"name":"木平 孝高"},{"name":"池田 康将"},{"name":"濱野 修一"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Tumor necrosis factor-α (TNF-α) is known to involve the progression of renal dysfunction through its cytotoxicity and proinflammatory effects such as the induction of intercellular adhesion molecule (ICAM)-1 expression in vascular endothelial cells (ECs). Olmesartan, one of the angiotensin II type 1 receptor blockers (ARBs), has been reported to show protective effects on injured ECs by some causal factors of renal disorder other than angiotensin II. However, the effects of olmesartan on TNF-α-induced glomerular EC damage have not been investigated. In the present study, we investigated the effects of RNH-6270, an active metabolite of olmesartan, on TNF-α-induced human glomerular EC (HGEC) damage to clarify the renoprotective mechanisms of ARBs. Cultured HGECs were stimulated by TNF-α, and then cell viability and cytotoxicity were measured by MTT assay and lactate dehydrogenase release assay, respectively. TNF-α-induced oxidative stress was estimated by dihydroethidium assay and lucigenin chemiluminescence assay. ICAM-1 expression and the phosphorylations of mitogen-activated protein kinases were measured using Western blotting assay. RNH-6270 suppressed cell death and the increase in ICAM-1 expression induced by TNF-α via the inhibition of reactive oxygen species in HGECs. Our findings suggested that olmesartan might have protective effects against TNF-α-induced glomerular EC dysfunction.","ja":"Tumor necrosis factor-α (TNF-α) is known to involve the progression of renal dysfunction through its cytotoxicity and proinflammatory effects such as the induction of intercellular adhesion molecule (ICAM)-1 expression in vascular endothelial cells (ECs). Olmesartan, one of the angiotensin II type 1 receptor blockers (ARBs), has been reported to show protective effects on injured ECs by some causal factors of renal disorder other than angiotensin II. However, the effects of olmesartan on TNF-α-induced glomerular EC damage have not been investigated. In the present study, we investigated the effects of RNH-6270, an active metabolite of olmesartan, on TNF-α-induced human glomerular EC (HGEC) damage to clarify the renoprotective mechanisms of ARBs. Cultured HGECs were stimulated by TNF-α, and then cell viability and cytotoxicity were measured by MTT assay and lactate dehydrogenase release assay, respectively. TNF-α-induced oxidative stress was estimated by dihydroethidium assay and lucigenin chemiluminescence assay. ICAM-1 expression and the phosphorylations of mitogen-activated protein kinases were measured using Western blotting assay. RNH-6270 suppressed cell death and the increase in ICAM-1 expression induced by TNF-α via the inhibition of reactive oxygen species in HGECs. Our findings suggested that olmesartan might have protective effects against TNF-α-induced glomerular EC dysfunction."},"publication_date":"2012-12","publication_name":{"en":"Pharmacology","ja":"Pharmacology"},"volume":"90","number":"5-6","starting_page":"324","ending_page":"331","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1159/000343244"],"issn":["1423-0313"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:35, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2012615","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22904320","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=253941","label":"url"}],"paper_title":{"en":"Heparin cofactor II, a serine protease inhibitor, promotes angiogenesis via activation of the AMP-activated protein kinase-endothelial nitric-oxide synthase signaling pathway","ja":"Heparin cofactor II, a serine protease inhibitor, promotes angiogenesis via activation of the AMP-activated protein kinase-endothelial nitric-oxide synthase signaling pathway"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Aihara Ken-ichi"},{"name":"Yoshida Sumiko"},{"name":"Iwase Takashi"},{"name":"Tajima Soichiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Sata Masataka"},{"name":"Akaike Masashi"},{"name":"Kato Shigeaki"},{"name":"Matsumoto Toshio"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"粟飯原 賢一"},{"name":"吉田 守美子"},{"name":"岩瀬 俊"},{"name":"Tajima Soichiro"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"佐田 政隆"},{"name":"赤池 雅史"},{"name":"Kato Shigeaki"},{"name":"松本 俊夫"},{"name":"玉置 俊晃"}]},"description":{"en":"We previously clarified that heparin cofactor II (HCII), a serine proteinase inhibitor, exerts various protective actions on cardiovascular diseases in both experimental and clinical studies. In the present study, we aimed to clarify whether HCII participates in the regulation of angiogenesis. Male heterozygous HCII-deficient (HCII(+/-)) mice and male littermate wild-type (HCII(+/+)) mice at the age of 12-16 weeks were subjected to unilateral hindlimb ligation surgery. Laser speckle blood flow analysis showed that blood flow recovery in response to hindlimb ischemia was delayed in HCII(+/-) mice compared with that in HCII(+/+) mice. Capillary number, arteriole number, and endothelial nitric-oxide synthase (eNOS), AMP-activated protein kinase (AMPK), and liver kinase B1 (LKB1) phosphorylation in ischemic muscles were decreased in HCII(+/-) mice. Human purified HCII (h-HCII) administration almost restored blood flow recovery, capillary density, and arteriole number as well as phosphorylation levels of eNOS, AMPK, and LKB1 in ischemic muscles of HCII(+/-) mice. Although treatment with h-HCII increased phosphorylation levels of eNOS, AMPK, and LKB1 in human aortic endothelial cells (HAECs), the h-HCII-induced eNOS phosphorylation was abolished by compound C, an AMPK inhibitor, and by AMPK siRNA. In a similar fashion, tube formation, proliferation, and migration of HAECs were also promoted by h-HCII treatment and were abrogated by pretreatment with compound C. HCII potentiates the activation of vascular endothelial cells and the promotion of angiogenesis in response to hindlimb ischemia via an AMPK-eNOS signaling pathway. These findings suggest that HCII is a novel therapeutic target for treatment of patients with peripheral circulation insufficiency.","ja":"We previously clarified that heparin cofactor II (HCII), a serine proteinase inhibitor, exerts various protective actions on cardiovascular diseases in both experimental and clinical studies. In the present study, we aimed to clarify whether HCII participates in the regulation of angiogenesis. Male heterozygous HCII-deficient (HCII(+/-)) mice and male littermate wild-type (HCII(+/+)) mice at the age of 12-16 weeks were subjected to unilateral hindlimb ligation surgery. Laser speckle blood flow analysis showed that blood flow recovery in response to hindlimb ischemia was delayed in HCII(+/-) mice compared with that in HCII(+/+) mice. Capillary number, arteriole number, and endothelial nitric-oxide synthase (eNOS), AMP-activated protein kinase (AMPK), and liver kinase B1 (LKB1) phosphorylation in ischemic muscles were decreased in HCII(+/-) mice. Human purified HCII (h-HCII) administration almost restored blood flow recovery, capillary density, and arteriole number as well as phosphorylation levels of eNOS, AMPK, and LKB1 in ischemic muscles of HCII(+/-) mice. Although treatment with h-HCII increased phosphorylation levels of eNOS, AMPK, and LKB1 in human aortic endothelial cells (HAECs), the h-HCII-induced eNOS phosphorylation was abolished by compound C, an AMPK inhibitor, and by AMPK siRNA. In a similar fashion, tube formation, proliferation, and migration of HAECs were also promoted by h-HCII treatment and were abrogated by pretreatment with compound C. HCII potentiates the activation of vascular endothelial cells and the promotion of angiogenesis in response to hindlimb ischemia via an AMPK-eNOS signaling pathway. These findings suggest that HCII is a novel therapeutic target for treatment of patients with peripheral circulation insufficiency."},"publication_date":"2012-10","publication_name":{"en":"The Journal of Biological Chemistry","ja":"The Journal of Biological Chemistry"},"volume":"287","number":"41","starting_page":"34256","ending_page":"34263","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1074/jbc.M112.353532"],"issn":["1083-351X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:36, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2002170","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22880134","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=253920","label":"url"}],"paper_title":{"en":"Systemic Preconditioning by a Prolyl Hydroxylase Inhibitor Promotes Prevention of Skin Flap Necrosis via HIF-1-Induced Bone Marrow-Derived Cells.","ja":"Systemic Preconditioning by a Prolyl Hydroxylase Inhibitor Promotes Prevention of Skin Flap Necrosis via HIF-1-Induced Bone Marrow-Derived Cells."},"authors":{"en":[{"name":"Takaku Mitsuru"},{"name":"Tomita Shuhei"},{"name":"Kurobe Hirotsugu"},{"name":"Kihira Yoshitaka"},{"name":"Morimoto Atsushi"},{"name":"Higashida Mayuko"},{"name":"Ikeda Yasumasa"},{"name":"Ushiyama Akira"},{"name":"Hashimoto Ichiro"},{"name":"Nakanishi Hideki"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"Takaku Mitsuru"},{"name":"冨田 修平"},{"name":"黒部 裕嗣"},{"name":"木平 孝高"},{"name":"森本 篤志"},{"name":"Higashida Mayuko"},{"name":"池田 康将"},{"name":"Ushiyama Akira"},{"name":"橋本 一郎"},{"name":"中西 秀樹"},{"name":"玉置 俊晃"}]},"description":{"en":"We demonstrated that transient activation of the HIF signaling pathway by a single systemic DMOG treatment upregulates not only anti-apoptotic pathways but also enhances neovascularization with concomitant increase in the numbers of bone marrow-derived progenitor cells.","ja":"We demonstrated that transient activation of the HIF signaling pathway by a single systemic DMOG treatment upregulates not only anti-apoptotic pathways but also enhances neovascularization with concomitant increase in the numbers of bone marrow-derived progenitor cells."},"publication_date":"2012-08-07","publication_name":{"en":"PLoS ONE","ja":"PLoS ONE"},"volume":"7","number":"8","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.pone.0042964"],"issn":["1932-6203"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:37, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/40019353020/","label":"url"},{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2000214","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22792339","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84863827034","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=248250","label":"url"}],"paper_title":{"en":"Estrogen regulates hepcidin expression via GPR30-BMP6-dependent signaling in hepatocytes","ja":"Estrogen regulates hepcidin expression via GPR30-BMP6-dependent signaling in hepatocytes"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Tajima Soichiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"Tajima Soichiro"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Hepcidin, a liver-derived iron regulatory protein, plays a crucial role in iron metabolism. It is known that gender differences exist with respect to iron storage in the body; however, the effects of sex steroid hormones on iron metabolism are not completely understood. We focused on the effects of the female sex hormone estrogen on hepcidin expression. First, ovariectomized (OVX) and sham-operated mice were employed to investigate the effects of estrogen on hepcidin expression in an in vivo study. Hepcidin expression was decreased in the livers of OVX mice compared to the sham-operated mice. In OVX mice, bone morphologic protein-6 (BMP6), a regulator of hepcidin, was also found to be downregulated in the liver, whereas ferroportin (FPN), an iron export protein, was upregulated in the duodenum. Both serum and liver iron concentrations were elevated in OVX mice relative to their concentrations in sham-operated mice. In in vitro studies, 17β-estradiol (E(2)) increased the mRNA expression of hepcidin in HepG2 cells in a concentration-dependent manner. E(2)-induced hepatic hepcidin upregulation was not inhibited by ICI 182720, an inhibitor of the estrogen receptor; instead, hepcidin expression was increased by ICI 182720. E(2) and ICI 182720 exhibit agonist actions with G-protein coupled receptor 30 (GPR30), the 7-transmembrane estrogen receptor. G1, a GPR30 agonist, upregulated hepcidin expression, and GPR30 siRNA treatment abolished E(2)-induced hepcidin expression. BMP6 expression induced by E(2) was abolished by GPR30 silencing. Finally, both E(2) and G1 supplementation restored reduced hepatic hepcidin and BMP6 expression and reversed the augmentation of duodenal FPN expression in the OVX mice. In contrast, serum hepcidin was elevated in OVX mice, which was reversed in these mice with E(2) and G1. Thus, estrogen is involved in hepcidin expression via a GPR30-BMP6-dependent mechanism, providing new insight into the role of estrogen in iron metabolism.","ja":"Hepcidin, a liver-derived iron regulatory protein, plays a crucial role in iron metabolism. It is known that gender differences exist with respect to iron storage in the body; however, the effects of sex steroid hormones on iron metabolism are not completely understood. We focused on the effects of the female sex hormone estrogen on hepcidin expression. First, ovariectomized (OVX) and sham-operated mice were employed to investigate the effects of estrogen on hepcidin expression in an in vivo study. Hepcidin expression was decreased in the livers of OVX mice compared to the sham-operated mice. In OVX mice, bone morphologic protein-6 (BMP6), a regulator of hepcidin, was also found to be downregulated in the liver, whereas ferroportin (FPN), an iron export protein, was upregulated in the duodenum. Both serum and liver iron concentrations were elevated in OVX mice relative to their concentrations in sham-operated mice. In in vitro studies, 17β-estradiol (E(2)) increased the mRNA expression of hepcidin in HepG2 cells in a concentration-dependent manner. E(2)-induced hepatic hepcidin upregulation was not inhibited by ICI 182720, an inhibitor of the estrogen receptor; instead, hepcidin expression was increased by ICI 182720. E(2) and ICI 182720 exhibit agonist actions with G-protein coupled receptor 30 (GPR30), the 7-transmembrane estrogen receptor. G1, a GPR30 agonist, upregulated hepcidin expression, and GPR30 siRNA treatment abolished E(2)-induced hepcidin expression. BMP6 expression induced by E(2) was abolished by GPR30 silencing. Finally, both E(2) and G1 supplementation restored reduced hepatic hepcidin and BMP6 expression and reversed the augmentation of duodenal FPN expression in the OVX mice. In contrast, serum hepcidin was elevated in OVX mice, which was reversed in these mice with E(2) and G1. Thus, estrogen is involved in hepcidin expression via a GPR30-BMP6-dependent mechanism, providing new insight into the role of estrogen in iron metabolism."},"publication_date":"2012-07-11","publication_name":{"en":"PLoS ONE","ja":"PLoS ONE"},"volume":"7","number":"7","starting_page":"e40465","ending_page":"e40465","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.pone.0040465"],"issn":["1932-6203"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:38, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=250567","label":"url"}],"paper_title":{"en":"ロスバスタチンによる脂質低下作用非依存的な形態的および機能的頸動脈硬化改善作用","ja":"ロスバスタチンによる脂質低下作用非依存的な形態的および機能的頸動脈硬化改善作用"},"authors":{"en":[{"name":"Yoshida Sumiko"},{"name":"Aihara Ken-ichi"},{"name":"Ueda Yuka"},{"name":"Ise Takayuki"},{"name":"Ikeda Yasumasa"},{"name":"倉橋 清衛"},{"name":"Kinouchi Mizuho"},{"name":"Endo Itsuro"},{"name":"Fujinaka Yuichi"},{"name":"Iwase Takashi"},{"name":"Akaike Masashi"},{"name":"Sata Masataka"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"吉田 守美子"},{"name":"粟飯原 賢一"},{"name":"上田 由佳"},{"name":"伊勢 孝之"},{"name":"池田 康将"},{"name":"倉橋 清衛"},{"name":"木内 美瑞穂"},{"name":"遠藤 逸朗"},{"name":"藤中 雄一"},{"name":"岩瀬 俊"},{"name":"赤池 雅史"},{"name":"佐田 政隆"},{"name":"松本 俊夫"}]},"publication_date":"2012-02-01","publication_name":{"en":"Progress in Medicine","ja":"Progress in Medicine"},"volume":"32","number":"2","starting_page":"315","ending_page":"320","languages":["jpn"],"referee":true,"identifiers":{"issn":["0287-3648"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:39, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21917632","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=243340","label":"url"}],"paper_title":{"en":"Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice.","ja":"Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice."},"authors":{"en":[{"name":"Tajima Soichiro"},{"name":"Ikeda Yasumasa"},{"name":"Sawada Kaori"},{"name":"Yamano Noriko"},{"name":"Horinouchi Yuya"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kawazoe Kazuyoshi"},{"name":"Tomita Shuhei"},{"name":"Minakuchi Kazuo"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"Tajima Soichiro"},{"name":"池田 康将"},{"name":"澤田 香織"},{"name":"山野 範子"},{"name":"堀ノ内 裕也"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"石澤 有紀"},{"name":"川添 和義"},{"name":"冨田 修平"},{"name":"水口 和生"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Iron is an essential trace metal for most organisms. However, excess iron causes oxidative stress through production of highly toxic hydroxyl radicals via the Fenton/Haber-Weiss reaction. Iron storage in the body is reported to be associated with fat accumulation and type 2 diabetes mellitus. We investigated the role of iron in adiposity by using KKAy mice and obese and diabetic model mice. Eight-week-old KKAy mice were divided into two groups and treated with deferoxamine (DFO), an iron chelator agent, or a vehicle for 2 wk. DFO treatment diminished fat iron concentration and serum ferritin levels in KKAy mice. Fat weight and adipocyte size were reduced significantly in DFO-treated mice compared with vehicle-treated mice. Macrophage infiltration into fat was also decreased in DFO-treated mice compared with vehicle-treated mice. Superoxide production and NADPH oxidase activity in fat, as well as urinary 8-hydroxy-2'-deoxyguanosine excretion, were decreased in KKAy mice after DFO treatment while p22(phox) expression in adipose tissue was diminished in such mice. Ferritin expression in the fat of DFO-treated KKAy mice was decreased. In addition, F4/80-positive cells also presented through both p22(phox) and ferritin expression. The mRNA expression levels of inflammatory cytokines were also reduced in fat tissue of DFO-treated mice. These findings suggest that reduction of iron levels ameliorates adipocyte hypertrophy via suppression of oxidative stress, inflammatory cytokines, and macrophage infiltration, thereby breaking a vicious cycle in obesity.","ja":"Iron is an essential trace metal for most organisms. However, excess iron causes oxidative stress through production of highly toxic hydroxyl radicals via the Fenton/Haber-Weiss reaction. Iron storage in the body is reported to be associated with fat accumulation and type 2 diabetes mellitus. We investigated the role of iron in adiposity by using KKAy mice and obese and diabetic model mice. Eight-week-old KKAy mice were divided into two groups and treated with deferoxamine (DFO), an iron chelator agent, or a vehicle for 2 wk. DFO treatment diminished fat iron concentration and serum ferritin levels in KKAy mice. Fat weight and adipocyte size were reduced significantly in DFO-treated mice compared with vehicle-treated mice. Macrophage infiltration into fat was also decreased in DFO-treated mice compared with vehicle-treated mice. Superoxide production and NADPH oxidase activity in fat, as well as urinary 8-hydroxy-2'-deoxyguanosine excretion, were decreased in KKAy mice after DFO treatment while p22(phox) expression in adipose tissue was diminished in such mice. Ferritin expression in the fat of DFO-treated KKAy mice was decreased. In addition, F4/80-positive cells also presented through both p22(phox) and ferritin expression. The mRNA expression levels of inflammatory cytokines were also reduced in fat tissue of DFO-treated mice. These findings suggest that reduction of iron levels ameliorates adipocyte hypertrophy via suppression of oxidative stress, inflammatory cytokines, and macrophage infiltration, thereby breaking a vicious cycle in obesity."},"publication_date":"2012-01","publication_name":{"en":"American Journal of Physiology, Endocrinology and Metabolism","ja":"American Journal of Physiology, Endocrinology and Metabolism"},"volume":"302","number":"1","starting_page":"E77","ending_page":"86","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajpendo.00033.2011"],"issn":["1522-1555"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:40, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21810481","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=241773","label":"url"}],"paper_title":{"en":"Basic fibroblast growth factor regulates glucose metabolism through glucose transporter 1 induced by hypoxia-inducible factor-1α in adipocytes","ja":"Basic fibroblast growth factor regulates glucose metabolism through glucose transporter 1 induced by hypoxia-inducible factor-1α in adipocytes"},"authors":{"en":[{"name":"Kihira Yoshitaka"},{"name":"Yamano Noriko"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ishizawa Keisuke"},{"name":"Ikeda Yasumasa"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"},{"name":"Tomita Shuhei"}],"ja":[{"name":"木平 孝高"},{"name":"山野 範子"},{"name":"石澤 有紀"},{"name":"石澤 啓介"},{"name":"池田 康将"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"},{"name":"冨田 修平"}]},"description":{"en":"Hypoxia-inducible factor-1 (HIF-1), which is a transcription factor that enhances glycolysis in cells in response to hypoxia, is induced in hypertrophied adipocytes in obesity. Recent studies have shown that growth factors are able to induce HIF-1 by mechanisms independent of hypoxia. Since basic fibroblast growth factor (bFGF), an angiogenic factor, is concentrated in expanding adipose tissue, the possible effects of bFGF on regulation of HIF-1 in adipocytes were investigated. Treatment of differentiated 3T3-L1 adipocytes with bFGF induced HIF-1. Concomitantly, glucose transporter 1 (GLUT1), which is a target gene of HIF-1, was induced at both mRNA and protein levels and was translocated to the plasma membrane. A chromatin immunoprecipitation assay and an RNA interference study indicated that bFGF-induced HIF-1 directly upregulates GLUT1. In addition, it was observed that bFGF increases lactate production of adipocytes. This result indicates that bFGF reprograms the metabolism toward glycolysis. Intraperitoneal injection of bFGF into mice upregulated HIF-1 and GLUT1 in adipose tissues, suggesting that bFGF regulates the metabolism of adipocytes via HIF-1-GLUT1 regulation in vivo. We also found that bFGF inhibits insulin-induced phosphorylation of insulin receptor substrate-1 and Akt, suggesting that bFGF attenuates the insulin signal in adipocytes. Taken together, the findings suggest that bFGF has a harmful effect on the development of type 2 diabetes through metabolism reprogramming and attenuation of the insulin signal.","ja":"Hypoxia-inducible factor-1 (HIF-1), which is a transcription factor that enhances glycolysis in cells in response to hypoxia, is induced in hypertrophied adipocytes in obesity. Recent studies have shown that growth factors are able to induce HIF-1 by mechanisms independent of hypoxia. Since basic fibroblast growth factor (bFGF), an angiogenic factor, is concentrated in expanding adipose tissue, the possible effects of bFGF on regulation of HIF-1 in adipocytes were investigated. Treatment of differentiated 3T3-L1 adipocytes with bFGF induced HIF-1. Concomitantly, glucose transporter 1 (GLUT1), which is a target gene of HIF-1, was induced at both mRNA and protein levels and was translocated to the plasma membrane. A chromatin immunoprecipitation assay and an RNA interference study indicated that bFGF-induced HIF-1 directly upregulates GLUT1. In addition, it was observed that bFGF increases lactate production of adipocytes. This result indicates that bFGF reprograms the metabolism toward glycolysis. Intraperitoneal injection of bFGF into mice upregulated HIF-1 and GLUT1 in adipose tissues, suggesting that bFGF regulates the metabolism of adipocytes via HIF-1-GLUT1 regulation in vivo. We also found that bFGF inhibits insulin-induced phosphorylation of insulin receptor substrate-1 and Akt, suggesting that bFGF attenuates the insulin signal in adipocytes. Taken together, the findings suggest that bFGF has a harmful effect on the development of type 2 diabetes through metabolism reprogramming and attenuation of the insulin signal."},"publication_date":"2011-11","publication_name":{"en":"The International Journal of Biochemistry & Cell Biology","ja":"The International Journal of Biochemistry & Cell Biology"},"volume":"43","number":"11","starting_page":"1602","ending_page":"1611","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.biocel.2011.07.009"],"issn":["1878-5875"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:41, {"insert":{"user_id":"B000241782","type":"published_papers","id":"30376222"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21297301","label":"url"},{"@id":"https://www.scopus.com/pages/publications/79551489998","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=314653","label":"url"}],"paper_title":{"en":"Antioxidant effects of photodegradation product of nifedipine","ja":"Antioxidant effects of photodegradation product of nifedipine"},"authors":{"en":[{"name":"Horinouchi Yuya"},{"name":"Tsuchiya Koichiro"},{"name":"Taoka Chiaki"},{"name":"Tajima Soichiro"},{"name":"Kihira Yoshitaka"},{"name":"Matsuda Yuko"},{"name":"Shishido Kozo"},{"name":"Yoshida Masahiro"},{"name":"Hamano Shuichi"},{"name":"Kawazoe Kazuyoshi"},{"name":"Ikeda Yasumasa"},{"name":"Ishizawa Keisuke"},{"name":"Tomita Shuhei"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"堀ノ内 裕也"},{"name":"土屋 浩一郎"},{"name":"Taoka Chiaki"},{"name":"Tajima Soichiro"},{"name":"木平 孝高"},{"name":"Matsuda Yuko"},{"name":"宍戸 宏造"},{"name":"吉田 昌裕"},{"name":"濱野 修一"},{"name":"川添 和義"},{"name":"池田 康将"},{"name":"石澤 啓介"},{"name":"冨田 修平"},{"name":"玉置 俊晃"}]},"description":{"en":"Recently, increasing evidence suggests that the antihypertensive drug nifedipine acts as a protective agent for endothelial cells, and that the activity is unrelated to its calcium channel blocking. Nifedipine is unstable under light and reportedly decomposes to a stable nitrosonifedipine (NO-NIF). NO-NIF has no antihypertensive effect, and it has been recognized as a contaminant of nifedipine. The present study for the first time demonstrated that NO-NIF changed to a NO-NIF radical in a time-dependent manner when it interacted with human umbilical vein endothelial cells (HUVECs). The electron paramagnetic resonance (EPR) signal of NO-NIF radicals in HUVECs showed an asymmetric pattern suggesting that the radicals were located in the membrane. The NO-NIF radicals had radical scavenging activity for 1,1-diphenyl-2-picrylhydrazyl, whereas neither NO-NIF nor nifedipine did. In addition, the NO-NIF radical more effectively quenched lipid peroxides than NO-NIF or nifedipine. Furthermore, NO-NIF attenuated the superoxide-derived free radicals in HUVECs stimulated with LY83583, and suppressed iron-nitrilotriacetic acid (Fe-NTA)-induced cytotoxicity in rat pheochromocytoma (PC12) cells. Our findings suggest that NO-NIF is a candidate for a new class of antioxidative drugs that protect cells against oxidative stress.","ja":"Recently, increasing evidence suggests that the antihypertensive drug nifedipine acts as a protective agent for endothelial cells, and that the activity is unrelated to its calcium channel blocking. Nifedipine is unstable under light and reportedly decomposes to a stable nitrosonifedipine (NO-NIF). NO-NIF has no antihypertensive effect, and it has been recognized as a contaminant of nifedipine. The present study for the first time demonstrated that NO-NIF changed to a NO-NIF radical in a time-dependent manner when it interacted with human umbilical vein endothelial cells (HUVECs). The electron paramagnetic resonance (EPR) signal of NO-NIF radicals in HUVECs showed an asymmetric pattern suggesting that the radicals were located in the membrane. The NO-NIF radicals had radical scavenging activity for 1,1-diphenyl-2-picrylhydrazyl, whereas neither NO-NIF nor nifedipine did. In addition, the NO-NIF radical more effectively quenched lipid peroxides than NO-NIF or nifedipine. Furthermore, NO-NIF attenuated the superoxide-derived free radicals in HUVECs stimulated with LY83583, and suppressed iron-nitrilotriacetic acid (Fe-NTA)-induced cytotoxicity in rat pheochromocytoma (PC12) cells. Our findings suggest that NO-NIF is a candidate for a new class of antioxidative drugs that protect cells against oxidative stress."},"publication_date":"2011-02","publication_name":{"en":"Chemical & Pharmaceutical Bulletin","ja":"Chemical & Pharmaceutical Bulletin"},"volume":"59","number":"2","starting_page":"208","ending_page":"214","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/cpb.59.208"],"issn":["1347-5223"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:42, {"insert":{"user_id":"B000241782","type":"published_papers","id":"30376223"},"force":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/130004465233/","label":"url"},{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2001197","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21372496","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390001204242892288/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=223410","label":"url"}],"paper_title":{"en":"Protective effect of photodegradation product of nifedipine against tumor necrosis factor alpha-induced oxidative stress in human glomerular endothelial cells","ja":"Protective effect of photodegradation product of nifedipine against tumor necrosis factor alpha-induced oxidative stress in human glomerular endothelial cells"},"authors":{"en":[{"name":"Fukuhara Yayoi"},{"name":"Tsuchiya Koichiro"},{"name":"Horinouchi Yuya"},{"name":"Tajima Soichiro"},{"name":"Kihira Yoshitaka"},{"name":"Hamano Shuichi"},{"name":"Kawazoe Kazuyoshi"},{"name":"Ikeda Yasumasa"},{"name":"Ishizawa Keisuke"},{"name":"Tomita Shuhei"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"福原 弥生"},{"name":"土屋 浩一郎"},{"name":"堀ノ内 裕也"},{"name":"Tajima Soichiro"},{"name":"木平 孝高"},{"name":"濱野 修一"},{"name":"川添 和義"},{"name":"池田 康将"},{"name":"石澤 啓介"},{"name":"冨田 修平"},{"name":"玉置 俊晃"}]},"description":{"en":"Recently, increasing evidence suggests that the antihypertensive drug nifedipine acts as a protective agent for endothelial cells, and that the activity is unrelated to its calcium channel blocking. Nitrosonifedipine (NO-NIF) is metabolically and photochemically produced from nifedipine, and NO-NIF has been recognized as a contaminant of nifedipine because it has no antihypertensive effect. Treatment of tumor necrosis factor-α (TNF-α) suppressed the cell viability and facilitated the expression of Inter-Cellular Adhesion Molecule 1(ICAM-1) in human glomerular endothelial cells (HGECs) though, pretreatment of NO-NIF significantly recovered the TNF-α-induced cell damage to the same extent as Trolox-C did, and suppressed the ICAM-1 expression in a concentration dependent manner. In addition, NO-NIF inhibited the cell toxicity induced by cumene hydroperoxide, which hampers the integrity of cell membrane through oxidative stress, as effective as Trolox-c. These data suggest that NO-NIF is a candidate for a new class of antioxidative drug that protect cells against oxidative stress in glomerular endothelial cells.","ja":"Recently, increasing evidence suggests that the antihypertensive drug nifedipine acts as a protective agent for endothelial cells, and that the activity is unrelated to its calcium channel blocking. Nitrosonifedipine (NO-NIF) is metabolically and photochemically produced from nifedipine, and NO-NIF has been recognized as a contaminant of nifedipine because it has no antihypertensive effect. Treatment of tumor necrosis factor-α (TNF-α) suppressed the cell viability and facilitated the expression of Inter-Cellular Adhesion Molecule 1(ICAM-1) in human glomerular endothelial cells (HGECs) though, pretreatment of NO-NIF significantly recovered the TNF-α-induced cell damage to the same extent as Trolox-C did, and suppressed the ICAM-1 expression in a concentration dependent manner. In addition, NO-NIF inhibited the cell toxicity induced by cumene hydroperoxide, which hampers the integrity of cell membrane through oxidative stress, as effective as Trolox-c. These data suggest that NO-NIF is a candidate for a new class of antioxidative drug that protect cells against oxidative stress in glomerular endothelial cells."},"publication_date":"2011-02","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"58","number":"1, 2","starting_page":"118","ending_page":"126","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.58.118"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:43, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21315355","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=222278","label":"url"}],"paper_title":{"en":"Deferoxamine promotes angiogenesis via the activation of vascular endothelial cell function.","ja":"Deferoxamine promotes angiogenesis via the activation of vascular endothelial cell function."},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Tajima Soichiro"},{"name":"Yoshida Sumiko"},{"name":"Yamano Noriko"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Aihara Ken-ichi"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"Tajima Soichiro"},{"name":"吉田 守美子"},{"name":"山野 範子"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"粟飯原 賢一"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"BACKGROUND: Deferoxamine (DFO), an iron chelator for disorders of excess iron, upregulates the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2), indicating that it affects angiogenesis. Herein, we clarify the effect and mechanism of action of DFO on angiogenesis. METHODS AND RESULTS: In an in vitro study, DFO increased endothelial nitric oxide synthesis (eNOS) phosphorylation in human aortic endothelial cells (HAECs), which were inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002. Tube formation, cell proliferation, and cell migration in HAECs were promoted by DFO, which were significantly reduced by LY294002. In an in vivo study, DFO promoted blood flow recovery in response to the hindlimb ischemia in mice with unilateral hindlimb surgery. The density of capillaries and arterioles in ischemic muscle was higher in DFO-treated mice compared to vehicle-treated mice. Endothelial cell proliferation increased and oxidative stress and apoptosis decreased in ischemic muscles of DFO-treated mice. The phosphorylation of Akt and eNOS on the ischemic side was elevated and urinary nitric oxide/nitric dioxide (NOx) excretion was higher in DFO-treated mice compared to vehicle-treated mice. The effect of DFO on angiogenesis was abolished in eNOS-deficient mice with hindlimb ischemia. CONCLUSION: These findings indicate that DFO promotes revascularization via the activation of vascular endothelial cell function by an Akt-eNOS-dependent mechanism.","ja":"BACKGROUND: Deferoxamine (DFO), an iron chelator for disorders of excess iron, upregulates the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2), indicating that it affects angiogenesis. Herein, we clarify the effect and mechanism of action of DFO on angiogenesis. METHODS AND RESULTS: In an in vitro study, DFO increased endothelial nitric oxide synthesis (eNOS) phosphorylation in human aortic endothelial cells (HAECs), which were inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002. Tube formation, cell proliferation, and cell migration in HAECs were promoted by DFO, which were significantly reduced by LY294002. In an in vivo study, DFO promoted blood flow recovery in response to the hindlimb ischemia in mice with unilateral hindlimb surgery. The density of capillaries and arterioles in ischemic muscle was higher in DFO-treated mice compared to vehicle-treated mice. Endothelial cell proliferation increased and oxidative stress and apoptosis decreased in ischemic muscles of DFO-treated mice. The phosphorylation of Akt and eNOS on the ischemic side was elevated and urinary nitric oxide/nitric dioxide (NOx) excretion was higher in DFO-treated mice compared to vehicle-treated mice. The effect of DFO on angiogenesis was abolished in eNOS-deficient mice with hindlimb ischemia. CONCLUSION: These findings indicate that DFO promotes revascularization via the activation of vascular endothelial cell function by an Akt-eNOS-dependent mechanism."},"publication_date":"2011-01-21","publication_name":{"en":"Atherosclerosis","ja":"Atherosclerosis"},"volume":"215","number":"2","starting_page":"339","ending_page":"347","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.atherosclerosis.2011.01.009"],"issn":["1879-1484"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:44, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21060209","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=226738","label":"url"}],"paper_title":{"en":"Activation of peroxisome proliferator-activated receptor α in megakaryocytes reduces platelet-derived growth factor-BB in platelets.","ja":"Activation of peroxisome proliferator-activated receptor α in megakaryocytes reduces platelet-derived growth factor-BB in platelets."},"authors":{"en":[{"name":"Hashizume Shunji"},{"name":"Akaike Masashi"},{"name":"Azuma Hiroyuki"},{"name":"Ishikawa Kazue"},{"name":"Yoshida Sumiko"},{"name":"Ueda Yuka"},{"name":"Yagi Shusuke"},{"name":"Ikeda Yasumasa"},{"name":"Iwase Takashi"},{"name":"Aihara Ken-ichi"},{"name":"Abe Masahiro"},{"name":"Sata Masataka"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"Hashizume Shunji"},{"name":"赤池 雅史"},{"name":"東 博之"},{"name":"Ishikawa Kazue"},{"name":"吉田 守美子"},{"name":"上田 由佳"},{"name":"八木 秀介"},{"name":"池田 康将"},{"name":"岩瀬 俊"},{"name":"粟飯原 賢一"},{"name":"安倍 正博"},{"name":"佐田 政隆"},{"name":"松本 俊夫"}]},"description":{"en":"Platelet-derived growth factor (PDGF)-BB plays a crucial role in atherosclerosis and vascular remodeling by promoting the migration and proliferation of vascular smooth muscle cells. The objective of this study was to clarify the pleiotropic effect of peroxisome proliferator-activated receptor α (PPARα) activators on PDGF-BB expression in megakaryocytes and platelets. The expression of PPARα in a human erythroleukemia (HEL) cells was clearly detected by reverse transcriptase-PCR and immunofluorescence microscopy. The expression level of PPARα in HEL cells was unchanged regardless of differentiation into megakaryocytic cells by treatment with phorbol 12-myristate 13 acetate (TPA). The TPA-induced expression of PDGF-B mRNA and PDGF-BB protein levels in culture media was significantly decreased by treatment with PPARα activators, Wy14643 and fenofibric acid, in a dose-dependent manner. PDGF-BB expression induced by inflammatory cytokines, including interleukin-1β or interleukin-6, was also significantly suppressed by treatment with PPARα activators. Immunohistochemistry of human bone marrow showed the expression of PPARα in both the nucleus and cytoplasm of megakaryocytes. In addition, PDGF-BB levels in platelets were significantly decreased from 1,800±870 to 1,470±840 pg/10(5) platelets (mean±SD, p<0.05) by treatment with 300 mg fenofibrate once daily for 4 weeks in 13 patients with dyslipidemia. Activation of PPARα in megakaryocytes reduces PDGF-BB expression in platelets. PPARα activators may exert vasculo-protective action through suppression of PDGF-BB production in a megakaryocyte/platelet pathway.","ja":"Platelet-derived growth factor (PDGF)-BB plays a crucial role in atherosclerosis and vascular remodeling by promoting the migration and proliferation of vascular smooth muscle cells. The objective of this study was to clarify the pleiotropic effect of peroxisome proliferator-activated receptor α (PPARα) activators on PDGF-BB expression in megakaryocytes and platelets. The expression of PPARα in a human erythroleukemia (HEL) cells was clearly detected by reverse transcriptase-PCR and immunofluorescence microscopy. The expression level of PPARα in HEL cells was unchanged regardless of differentiation into megakaryocytic cells by treatment with phorbol 12-myristate 13 acetate (TPA). The TPA-induced expression of PDGF-B mRNA and PDGF-BB protein levels in culture media was significantly decreased by treatment with PPARα activators, Wy14643 and fenofibric acid, in a dose-dependent manner. PDGF-BB expression induced by inflammatory cytokines, including interleukin-1β or interleukin-6, was also significantly suppressed by treatment with PPARα activators. Immunohistochemistry of human bone marrow showed the expression of PPARα in both the nucleus and cytoplasm of megakaryocytes. In addition, PDGF-BB levels in platelets were significantly decreased from 1,800±870 to 1,470±840 pg/10(5) platelets (mean±SD, p<0.05) by treatment with 300 mg fenofibrate once daily for 4 weeks in 13 patients with dyslipidemia. Activation of PPARα in megakaryocytes reduces PDGF-BB expression in platelets. PPARα activators may exert vasculo-protective action through suppression of PDGF-BB production in a megakaryocyte/platelet pathway."},"publication_date":"2011","publication_name":{"en":"Journal of Atherosclerosis and Thrombosis","ja":"Journal of Atherosclerosis and Thrombosis"},"volume":"18","number":"2","starting_page":"138","ending_page":"147","languages":["eng"],"referee":true,"identifiers":{"doi":["10.5551/jat.5868"],"issn":["1880-3873"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:45, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21107326","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=250559","label":"url"}],"paper_title":{"en":"Plasma heparin cofactor II activity is inversely associated with left atrial volume and diastolic dysfunction in humans with cardiovascular risk factors.","ja":"Plasma heparin cofactor II activity is inversely associated with left atrial volume and diastolic dysfunction in humans with cardiovascular risk factors."},"authors":{"en":[{"name":"Ise Takayuki"},{"name":"Aihara Ken-ichi"},{"name":"Ueda Yuka"},{"name":"Yoshida Sumiko"},{"name":"Ikeda Yasumasa"},{"name":"Yagi Shusuke"},{"name":"Iwase Takashi"},{"name":"Yamada Hirotsugu"},{"name":"Akaike Masashi"},{"name":"Sata Masataka"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"伊勢 孝之"},{"name":"粟飯原 賢一"},{"name":"上田 由佳"},{"name":"吉田 守美子"},{"name":"池田 康将"},{"name":"八木 秀介"},{"name":"岩瀬 俊"},{"name":"山田 博胤"},{"name":"赤池 雅史"},{"name":"佐田 政隆"},{"name":"松本 俊夫"}]},"description":{"en":"Thrombin has a crucial role in cardiac remodeling through protease-activated receptor-1 activation in cardiac fibroblasts and cardiomyocytes. As heparin cofactor II (HCII) inhibits the action of tissue thrombin in the cardiovascular system, it is possible that HCII counteracts the development of cardiac remodeling. We investigated the relationships between plasma HCII activity and surrogate markers of cardiac geometry, including left atrial volume index (LAVI), relative wall thickness (RWT) and left ventricular mass index, and deceleration time (DcT) and the ratio of peak E velocity to early diastolic mitral annulus velocity (E/e' ratio) as surrogate markers of left ventricular diastolic dysfunction measured using echocardiography in 304 Japanese elderly individuals without systolic heart failure (169 men and 135 women; mean age: 65.4 ± 11.8 years). Mean plasma HCII activity in all participants was 95.8 ± 17.0% and there was no difference between the mean plasma HCII activities in males and females. Multiple regression analysis revealed that there were significant inverse relationships between plasma HCII activity and LAVI (coefficient: -0.2302, P<0.001), between HCII activity and RWT (coefficient: -0.0007, P<0.05), between HCII activity and DcT (coefficient: -0.5189, P<0.05) and between HCII activity and E/e' ratio (coefficient: -0.0558, P<0.01). Plasma HCII activity was independently and inversely associated with the development of cardiac remodeling, including cardiac concentric change, left atrial enlargement and left ventricular diastolic dysfunction. These findings suggest that cardiac tissue thrombin inactivation by HCII is a novel therapeutic target for cardiac remodeling and atherosclerosis.","ja":"Thrombin has a crucial role in cardiac remodeling through protease-activated receptor-1 activation in cardiac fibroblasts and cardiomyocytes. As heparin cofactor II (HCII) inhibits the action of tissue thrombin in the cardiovascular system, it is possible that HCII counteracts the development of cardiac remodeling. We investigated the relationships between plasma HCII activity and surrogate markers of cardiac geometry, including left atrial volume index (LAVI), relative wall thickness (RWT) and left ventricular mass index, and deceleration time (DcT) and the ratio of peak E velocity to early diastolic mitral annulus velocity (E/e' ratio) as surrogate markers of left ventricular diastolic dysfunction measured using echocardiography in 304 Japanese elderly individuals without systolic heart failure (169 men and 135 women; mean age: 65.4 ± 11.8 years). Mean plasma HCII activity in all participants was 95.8 ± 17.0% and there was no difference between the mean plasma HCII activities in males and females. Multiple regression analysis revealed that there were significant inverse relationships between plasma HCII activity and LAVI (coefficient: -0.2302, P<0.001), between HCII activity and RWT (coefficient: -0.0007, P<0.05), between HCII activity and DcT (coefficient: -0.5189, P<0.05) and between HCII activity and E/e' ratio (coefficient: -0.0558, P<0.01). Plasma HCII activity was independently and inversely associated with the development of cardiac remodeling, including cardiac concentric change, left atrial enlargement and left ventricular diastolic dysfunction. These findings suggest that cardiac tissue thrombin inactivation by HCII is a novel therapeutic target for cardiac remodeling and atherosclerosis."},"publication_date":"2010-11-25","publication_name":{"en":"Hypertension Research","ja":"Hypertension Research"},"volume":"34","number":"2","starting_page":"225","ending_page":"231","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/hr.2010.211"],"issn":["1348-4214"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:46, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20861841","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219670","label":"url"}],"paper_title":{"en":"High plasma aldosterone concentration is a novel risk factor of cognitive impairment in patients with hypertension.","ja":"High plasma aldosterone concentration is a novel risk factor of cognitive impairment in patients with hypertension."},"authors":{"en":[{"name":"Yagi Shusuke"},{"name":"Akaike Masashi"},{"name":"Aihara Ken-ichi"},{"name":"Iwase Takashi"},{"name":"Yoshida Sumiko"},{"name":"Ueda Yuka"},{"name":"Ikeda Yasumasa"},{"name":"Ishikawa Kazue"},{"name":"Matsumoto Toshio"},{"name":"Sata Masataka"}],"ja":[{"name":"八木 秀介"},{"name":"赤池 雅史"},{"name":"粟飯原 賢一"},{"name":"岩瀬 俊"},{"name":"吉田 守美子"},{"name":"上田 由佳"},{"name":"池田 康将"},{"name":"Ishikawa Kazue"},{"name":"松本 俊夫"},{"name":"佐田 政隆"}]},"description":{"en":"Cognitive impairment leading to dementia is associated with high prevalence of hypertension, decreased quality of life and poor prognosis. Aldosterone is known as a risk factor for cardiovascular and cerebrovascular diseases. In addition, mineral corticoid receptors are abundantly expressed in the hippocampus, which plays a pivotal role in cognitive function; however, it has not been determined whether plasma aldosterone level is associated with cognitive impairment in patients with hypertension. We enrolled 68 patients with essential hypertension and assessed their cardiovascular risk factors, including blood pressure, hyperlipidemia, diabetes mellitus, obesity, smoking, history of cerebral infarction, renal function, parameters of inflammation, oxidative stress and nitric oxide bioavailability, a parameter of cerebral blood flow and carotid plaque by ultrasound examination, plasma renin activity and plasma aldosterone concentration (PAC). The mini-mental state examination (MMSE) was used to evaluate cognitive function. The relevance of cardiovascular risk factors and MMSE score was statistically evaluated. Multiple regression analysis showed that age (P<0.01), PAC (P<0.01) and history of cerebral infarction (P<0.05) were inversely and independently associated with MMSE score. Mineral corticoid receptor antagonists, including spironolactone and eplerenone, increased MMSE score in seven patients with hypertension, but not in the controls. In conclusion, increased PAC is associated with impaired cognitive function and mineral corticoid receptor blockade may protect against not only cardiovascular mortality, but also cognitive impairment in patients with hypertension.Hypertension Research advance online publication, 23 September 2010; doi:10.1038/hr.2010.179.","ja":"Cognitive impairment leading to dementia is associated with high prevalence of hypertension, decreased quality of life and poor prognosis. Aldosterone is known as a risk factor for cardiovascular and cerebrovascular diseases. In addition, mineral corticoid receptors are abundantly expressed in the hippocampus, which plays a pivotal role in cognitive function; however, it has not been determined whether plasma aldosterone level is associated with cognitive impairment in patients with hypertension. We enrolled 68 patients with essential hypertension and assessed their cardiovascular risk factors, including blood pressure, hyperlipidemia, diabetes mellitus, obesity, smoking, history of cerebral infarction, renal function, parameters of inflammation, oxidative stress and nitric oxide bioavailability, a parameter of cerebral blood flow and carotid plaque by ultrasound examination, plasma renin activity and plasma aldosterone concentration (PAC). The mini-mental state examination (MMSE) was used to evaluate cognitive function. The relevance of cardiovascular risk factors and MMSE score was statistically evaluated. Multiple regression analysis showed that age (P<0.01), PAC (P<0.01) and history of cerebral infarction (P<0.05) were inversely and independently associated with MMSE score. Mineral corticoid receptor antagonists, including spironolactone and eplerenone, increased MMSE score in seven patients with hypertension, but not in the controls. In conclusion, increased PAC is associated with impaired cognitive function and mineral corticoid receptor blockade may protect against not only cardiovascular mortality, but also cognitive impairment in patients with hypertension.Hypertension Research advance online publication, 23 September 2010; doi:10.1038/hr.2010.179."},"publication_date":"2010-09-23","publication_name":{"en":"Hypertension Research","ja":"Hypertension Research"},"volume":"34","number":"1","starting_page":"74","ending_page":"78","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/hr.2010.179"],"issn":["1348-4214"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:47, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20660821","label":"url"},{"@id":"https://www.scopus.com/pages/publications/77955984037","label":"url"},{"@id":"https://www.scopus.com/pages/publications/78149260566","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219671","label":"url"}],"paper_title":{"en":"Heparin cofactor II protects against angiotensin II-induced cardiac remodeling via attenuation of oxidative stress in mice.","ja":"Heparin cofactor II protects against angiotensin II-induced cardiac remodeling via attenuation of oxidative stress in mice."},"authors":{"en":[{"name":"Sumitomo-Ueda Yuka"},{"name":"Aihara Ken-ichi"},{"name":"Ise Takayuki"},{"name":"Yoshida Sumiko"},{"name":"Ikeda Yasumasa"},{"name":"Uemoto Ryoko"},{"name":"Yagi Shusuke"},{"name":"Iwase Takashi"},{"name":"Ishikawa Kazue"},{"name":"Hirata Yoichiro"},{"name":"Akaike Masashi"},{"name":"Sata Masataka"},{"name":"Kato Shigeaki"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"Sumitomo-Ueda Yuka"},{"name":"粟飯原 賢一"},{"name":"Ise Takayuki"},{"name":"吉田 守美子"},{"name":"池田 康将"},{"name":"Uemoto Ryoko"},{"name":"八木 秀介"},{"name":"岩瀬 俊"},{"name":"Ishikawa Kazue"},{"name":"Hirata Yoichiro"},{"name":"赤池 雅史"},{"name":"佐田 政隆"},{"name":"Kato Shigeaki"},{"name":"松本 俊夫"}]},"description":{"en":"Heparin cofactor II (HCII), a serine protease inhibitor, inhibits tissue thrombin action after binding with dermatan sulfate proteoglycans in the extracellular matrix of the vascular system. We previously reported that heterozygous HCII-deficient (HCII(+/-)) humans and mice demonstrate acceleration of vascular remodeling, including atherosclerosis. However, the action of HCII on cardiac remodeling never has been determined. HCII(+/+) and HCII(+/-) mice at age 25 weeks were infused with angiotensin II (Ang II; 2.0 mg/kg/d) for 2 weeks by an osmotic mini-pump. Echocardiography revealed acceleration of cardiac concentric remodeling in HCII(+/-) mice and larger left atrial volume in HCII(+/-) mice than in HCII(+/+) mice. Histopathologic studies showed more prominent interstitial fibrosis in both the left atrium and left ventricle in HCII(+/-) mice than in HCII(+/+) mice. Daily urinary excretion of 8-hydroxy-2'-deoxyguanosine, a parameter of oxidative stress, and dihydroethidium-positive spots, indicating superoxide production in the myocardium, were markedly increased in Ang II-treated HCII(+/-) mice compared to those in HCII(+/+) mice. Cardiac gene expression levels of atrial natriuretic peptides and brain natriuretic peptides, members of the natriuretic peptide family, Nox 4, Rac-1, and p67(phox) as components of NAD(P)H oxidase, and transforming growth factor-beta1 and procollagen III were more augmented in HCII(+/-) mice than in HCII(+/+) mice. However, administration of human HCII protein attenuated all of those abnormalities in Ang II-treated HCII(+/-) mice. Moreover, human HCII protein supplementation almost abolished cardiac fibrosis in Ang II-treated HCII(+/+) mice. The results indicate that HCII has a protective role against Ang II-induced cardiac remodeling through suppression of the NAD(P)H oxidase-transforming growth factor-beta1 pathway.","ja":"Heparin cofactor II (HCII), a serine protease inhibitor, inhibits tissue thrombin action after binding with dermatan sulfate proteoglycans in the extracellular matrix of the vascular system. We previously reported that heterozygous HCII-deficient (HCII(+/-)) humans and mice demonstrate acceleration of vascular remodeling, including atherosclerosis. However, the action of HCII on cardiac remodeling never has been determined. HCII(+/+) and HCII(+/-) mice at age 25 weeks were infused with angiotensin II (Ang II; 2.0 mg/kg/d) for 2 weeks by an osmotic mini-pump. Echocardiography revealed acceleration of cardiac concentric remodeling in HCII(+/-) mice and larger left atrial volume in HCII(+/-) mice than in HCII(+/+) mice. Histopathologic studies showed more prominent interstitial fibrosis in both the left atrium and left ventricle in HCII(+/-) mice than in HCII(+/+) mice. Daily urinary excretion of 8-hydroxy-2'-deoxyguanosine, a parameter of oxidative stress, and dihydroethidium-positive spots, indicating superoxide production in the myocardium, were markedly increased in Ang II-treated HCII(+/-) mice compared to those in HCII(+/+) mice. Cardiac gene expression levels of atrial natriuretic peptides and brain natriuretic peptides, members of the natriuretic peptide family, Nox 4, Rac-1, and p67(phox) as components of NAD(P)H oxidase, and transforming growth factor-beta1 and procollagen III were more augmented in HCII(+/-) mice than in HCII(+/+) mice. However, administration of human HCII protein attenuated all of those abnormalities in Ang II-treated HCII(+/-) mice. Moreover, human HCII protein supplementation almost abolished cardiac fibrosis in Ang II-treated HCII(+/+) mice. The results indicate that HCII has a protective role against Ang II-induced cardiac remodeling through suppression of the NAD(P)H oxidase-transforming growth factor-beta1 pathway."},"publication_date":"2010-07-26","publication_name":{"en":"Hypertension","ja":"Hypertension"},"volume":"56","number":"3","starting_page":"430","ending_page":"436","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1161/HYPERTENSIONAHA.110.152207"],"issn":["1524-4563"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:48, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20627295","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219706","label":"url"}],"paper_title":{"en":"Dehydroepiandrosterone sulfate is inversely associated with sex-dependent diverse carotid atherosclerosis regardless of endothelial function.","ja":"Dehydroepiandrosterone sulfate is inversely associated with sex-dependent diverse carotid atherosclerosis regardless of endothelial function."},"authors":{"en":[{"name":"Yoshida Sumiko"},{"name":"Aihara Ken-ichi"},{"name":"Azuma Hiroyuki"},{"name":"Uemoto Ryoko"},{"name":"Sumitomo-Ueda Yuka"},{"name":"Yagi Shusuke"},{"name":"Ikeda Yasumasa"},{"name":"Iwase Takashi"},{"name":"Nishio Susumu"},{"name":"Kawano Hiromi"},{"name":"Miki Junko"},{"name":"Yamada Hirotsugu"},{"name":"Hirata Yoichiro"},{"name":"Akaike Masashi"},{"name":"Sata Masataka"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"吉田 守美子"},{"name":"粟飯原 賢一"},{"name":"東 博之"},{"name":"Uemoto Ryoko"},{"name":"住友(上田) 由香"},{"name":"八木 秀介"},{"name":"池田 康将"},{"name":"岩瀬 俊"},{"name":"西尾 進"},{"name":"河野 裕美"},{"name":"三木 淳子"},{"name":"山田 博胤"},{"name":"平田 陽一郎"},{"name":"赤池 雅史"},{"name":"佐田 政隆"},{"name":"松本 俊夫"}]},"description":{"en":"BACKGROUND: Dehydroepiandrosterone sulfate (DHEAS) is thought to be associated with life expectancy and anti-aging. However, its biological significance in atherosclerosis remains controversial. Therefore, the aim of this study was to determine whether DHEAS is associated with development of carotid atherosclerosis in subjects with cardiovascular risk factors. SUBJECTS AND METHODS: A total of 419 Japanese individuals (208 males and 211 females) were recruited from Tokushima University Hospital, Japan. In all subjects, maximum intima-media thickness (max-IMT) in all carotid arteries, and mean-IMT and mean blood flow volume (BFV) in the common carotid arteries (CCA) were measured by ultrasonography; endothelial function was assessed by flow-mediated vasodilation of the brachial artery (%FMD). Serum DHEAS and classical cardiovascular risk factors were also evaluated. Statistical significance was determined by multiple regression analysis to elucidate independent determinants of max-IMT, mean-IMT, mean CCA-BFV, and %FMD. RESULTS: Serum DHEAS levels were higher in males than in females. Multiple regression analysis revealed that DHEAS was an independent negative factor for both max-IMT and mean-IMT in males but not in females. In contrast, DHEAS was the sole positive factor for mean CCA-BFV in females but not in males. In addition, there was no significant relationship between %FMD and DHEAS regardless of sex and other confounding factors. CONCLUSION: Although DHEAS is not involved in endothelial function, DHEAS is inversely associated with sex-dependent diverse carotid atherosclerosis such as increased max-IMT and mean-IMT in males and decreased CCA-BFV in females.","ja":"BACKGROUND: Dehydroepiandrosterone sulfate (DHEAS) is thought to be associated with life expectancy and anti-aging. However, its biological significance in atherosclerosis remains controversial. Therefore, the aim of this study was to determine whether DHEAS is associated with development of carotid atherosclerosis in subjects with cardiovascular risk factors. SUBJECTS AND METHODS: A total of 419 Japanese individuals (208 males and 211 females) were recruited from Tokushima University Hospital, Japan. In all subjects, maximum intima-media thickness (max-IMT) in all carotid arteries, and mean-IMT and mean blood flow volume (BFV) in the common carotid arteries (CCA) were measured by ultrasonography; endothelial function was assessed by flow-mediated vasodilation of the brachial artery (%FMD). Serum DHEAS and classical cardiovascular risk factors were also evaluated. Statistical significance was determined by multiple regression analysis to elucidate independent determinants of max-IMT, mean-IMT, mean CCA-BFV, and %FMD. RESULTS: Serum DHEAS levels were higher in males than in females. Multiple regression analysis revealed that DHEAS was an independent negative factor for both max-IMT and mean-IMT in males but not in females. In contrast, DHEAS was the sole positive factor for mean CCA-BFV in females but not in males. In addition, there was no significant relationship between %FMD and DHEAS regardless of sex and other confounding factors. CONCLUSION: Although DHEAS is not involved in endothelial function, DHEAS is inversely associated with sex-dependent diverse carotid atherosclerosis such as increased max-IMT and mean-IMT in males and decreased CCA-BFV in females."},"publication_date":"2010-06-01","publication_name":{"en":"Atherosclerosis","ja":"Atherosclerosis"},"volume":"212","number":"1","starting_page":"310","ending_page":"315","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.atherosclerosis.2010.05.011"],"issn":["1879-1484"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:49, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20501642","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219675","label":"url"}],"paper_title":{"en":"Androgen receptor counteracts Doxorubicin-induced cardiotoxicity in male mice.","ja":"Androgen receptor counteracts Doxorubicin-induced cardiotoxicity in male mice."},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Aihara Ken-ichi"},{"name":"Akaike Masashi"},{"name":"Sato Takashi"},{"name":"Ishikawa Kazue"},{"name":"Ise Takayuki"},{"name":"Yagi Shusuke"},{"name":"Iwase Takashi"},{"name":"Ueda Yuka"},{"name":"Yoshida Sumiko"},{"name":"Azuma Hiroyuki"},{"name":"Walsh Kenneth"},{"name":"Tamaki Toshiaki"},{"name":"Kato Shigeaki"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"池田 康将"},{"name":"粟飯原 賢一"},{"name":"赤池 雅史"},{"name":"Sato Takashi"},{"name":"Ishikawa Kazue"},{"name":"Ise Takayuki"},{"name":"八木 秀介"},{"name":"岩瀬 俊"},{"name":"Ueda Yuka"},{"name":"吉田 守美子"},{"name":"東 博之"},{"name":"Walsh Kenneth"},{"name":"玉置 俊晃"},{"name":"Kato Shigeaki"},{"name":"松本 俊夫"}]},"description":{"en":"Doxorubicin (Dox) has been used as a potent anticancer agent, but serious cardiotoxicity precludes its use in a wide range of patients. We have reported that the androgen-androgen receptor (AR) system plays important roles in cardiac growth and protection from angiotensin II-induced cardiac remodeling. The present study was undertaken to clarify whether the androgen-AR system exerts a cardioprotective effect against Dox-induced cardiotoxicity. Male AR knockout (ARKO) and age-matched littermate male wild-type (WT) mice at 25 wk of age were given ip injections of Dox (20 mg/kg) or a vehicle. The survival rate and left ventricular function in Dox-treated male ARKO mice were reduced compared with those in Dox-treated male WT mice. Electron microscopic study showed prominent vacuole formation of myocardial mitochondria in Dox-treated male ARKO mice. Cardiac oxidative stress and apoptosis of cardiomyocytes were increased more prominently by Dox treatment in male ARKO mice than in male WT mice. In addition, Dox-induced reduction in the expression of cardiac mitochondria transcription factor A (Tfam) and phosphorylation of serine-threonine kinase (Akt) was more pronounced in male ARKO mice than in male WT mice. In cardiac myoblast cells, testosterone up-regulated Akt phosphorylation and Tfam expression and exerted an antiapoptotic effect against Dox-induced cardiotoxicity. Collectively, the results demonstrate that Dox-induced cardiotoxicity is aggravated in male ARKO mice via exacerbation of mitochondrial damage and superoxide generation, leading to enhanced apoptosis of cardiomyocytes. Thus, the androgen-AR system is thought to counteract Dox-induced cardiotoxicity partly through activation of the Akt pathway and up-regulation of Tfam to protect cardiomyocytes from mitochondrial damage and apoptosis.","ja":"Doxorubicin (Dox) has been used as a potent anticancer agent, but serious cardiotoxicity precludes its use in a wide range of patients. We have reported that the androgen-androgen receptor (AR) system plays important roles in cardiac growth and protection from angiotensin II-induced cardiac remodeling. The present study was undertaken to clarify whether the androgen-AR system exerts a cardioprotective effect against Dox-induced cardiotoxicity. Male AR knockout (ARKO) and age-matched littermate male wild-type (WT) mice at 25 wk of age were given ip injections of Dox (20 mg/kg) or a vehicle. The survival rate and left ventricular function in Dox-treated male ARKO mice were reduced compared with those in Dox-treated male WT mice. Electron microscopic study showed prominent vacuole formation of myocardial mitochondria in Dox-treated male ARKO mice. Cardiac oxidative stress and apoptosis of cardiomyocytes were increased more prominently by Dox treatment in male ARKO mice than in male WT mice. In addition, Dox-induced reduction in the expression of cardiac mitochondria transcription factor A (Tfam) and phosphorylation of serine-threonine kinase (Akt) was more pronounced in male ARKO mice than in male WT mice. In cardiac myoblast cells, testosterone up-regulated Akt phosphorylation and Tfam expression and exerted an antiapoptotic effect against Dox-induced cardiotoxicity. Collectively, the results demonstrate that Dox-induced cardiotoxicity is aggravated in male ARKO mice via exacerbation of mitochondrial damage and superoxide generation, leading to enhanced apoptosis of cardiomyocytes. Thus, the androgen-AR system is thought to counteract Dox-induced cardiotoxicity partly through activation of the Akt pathway and up-regulation of Tfam to protect cardiomyocytes from mitochondrial damage and apoptosis."},"publication_date":"2010-05-25","publication_name":{"en":"Molecular Endocrinology","ja":"Molecular Endocrinology"},"volume":"24","number":"7","starting_page":"1338","ending_page":"1348","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1210/me.2009-0402"],"issn":["1944-9917"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:50, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20194307","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219677","label":"url"}],"paper_title":{"en":"Endothelial nitric oxide synthase-independent protective action of statin against angiotensin II-induced atrial remodeling via reduced oxidant injury.","ja":"Endothelial nitric oxide synthase-independent protective action of statin against angiotensin II-induced atrial remodeling via reduced oxidant injury."},"authors":{"en":[{"name":"Yagi Shusuke"},{"name":"Akaike Masashi"},{"name":"Aihara Ken-ichi"},{"name":"Ishikawa Kazue"},{"name":"Iwase Takashi"},{"name":"Ikeda Yasumasa"},{"name":"Soeki Takeshi"},{"name":"Yoshida Sumiko"},{"name":"Sumitomo-Ueda Yuka"},{"name":"Matsumoto Toshio"},{"name":"Sata Masataka"}],"ja":[{"name":"八木 秀介"},{"name":"赤池 雅史"},{"name":"粟飯原 賢一"},{"name":"Ishikawa Kazue"},{"name":"岩瀬 俊"},{"name":"池田 康将"},{"name":"添木 武"},{"name":"吉田 守美子"},{"name":"Sumitomo-Ueda Yuka"},{"name":"松本 俊夫"},{"name":"佐田 政隆"}]},"description":{"en":"Activation of the renin-angiotensin system exacerbates atrial remodeling, leading to atrial fibrillation and thrombosis, especially in a condition with decreased NO bioavailability. Recently, it has been reported that statins reduce the incidence of atrial fibrillation through attenuation of atrial remodeling; however, the mechanisms have not been completely elucidated. Therefore, we aimed to clarify the beneficial effect of statin on atrial remodeling in condition with reduced NO bioavailability. Endothelial NO synthase(-/-) mice were sham operated or infused with angiotensin II (Ang II) via an osmotic minipump for 2 weeks, and Ang II-infused mice were divided into 3 treatment groups: pitavastatin, Tempol (a free radical scavenger), or vehicle. Echocardiography and electrocardiography showed that Ang II infusion caused left atrial enlargement and a high incidence of atrial fibrillation, whereas pitavastatin and Tempol prevented these abnormalities. In histological analysis, Ang II-induced atrial interstitial fibrosis, perivascular fibrosis, and cardiomyocyte hypertrophy were all attenuated by pitavastatin and Tempol. Immunohistochemical staining showed that Ang II downregulated thrombomodulin and tissue factor pathway inhibitor and upregulated tissue factor and plasminogen activator inhibitor 1 in the left atrium and that pitavastatin and Tempol corrected the thrombogenic condition. Moreover, pitavastatin and Tempol reduced Ang II-induced atrial superoxide production and atrial transforming growth factor-beta1 expression and Smad 2/3 phosphorylation. Atrial rac1-GTPase activity, known to activate NADPH oxidase, was attenuated by pitavastatin but not by Tempol. In conclusion, pitavastatin exerts endothelial NO synthase-independent protective actions against Ang II-induced atrial remodeling and atrial fibrillation with enhanced thrombogenicity through suppression of oxidant injury.","ja":"Activation of the renin-angiotensin system exacerbates atrial remodeling, leading to atrial fibrillation and thrombosis, especially in a condition with decreased NO bioavailability. Recently, it has been reported that statins reduce the incidence of atrial fibrillation through attenuation of atrial remodeling; however, the mechanisms have not been completely elucidated. Therefore, we aimed to clarify the beneficial effect of statin on atrial remodeling in condition with reduced NO bioavailability. Endothelial NO synthase(-/-) mice were sham operated or infused with angiotensin II (Ang II) via an osmotic minipump for 2 weeks, and Ang II-infused mice were divided into 3 treatment groups: pitavastatin, Tempol (a free radical scavenger), or vehicle. Echocardiography and electrocardiography showed that Ang II infusion caused left atrial enlargement and a high incidence of atrial fibrillation, whereas pitavastatin and Tempol prevented these abnormalities. In histological analysis, Ang II-induced atrial interstitial fibrosis, perivascular fibrosis, and cardiomyocyte hypertrophy were all attenuated by pitavastatin and Tempol. Immunohistochemical staining showed that Ang II downregulated thrombomodulin and tissue factor pathway inhibitor and upregulated tissue factor and plasminogen activator inhibitor 1 in the left atrium and that pitavastatin and Tempol corrected the thrombogenic condition. Moreover, pitavastatin and Tempol reduced Ang II-induced atrial superoxide production and atrial transforming growth factor-beta1 expression and Smad 2/3 phosphorylation. Atrial rac1-GTPase activity, known to activate NADPH oxidase, was attenuated by pitavastatin but not by Tempol. In conclusion, pitavastatin exerts endothelial NO synthase-independent protective actions against Ang II-induced atrial remodeling and atrial fibrillation with enhanced thrombogenicity through suppression of oxidant injury."},"publication_date":"2010-03-01","publication_name":{"en":"Hypertension","ja":"Hypertension"},"volume":"55","number":"4","starting_page":"918","ending_page":"923","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1161/HYPERTENSIONAHA.109.146076"],"issn":["1524-4563"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:51, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19812233","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=194522","label":"url"}],"paper_title":{"en":"Angiotensin II receptor blocker attenuates PDGF-induced mesangial cell migration in a receptor-independent manner","ja":"Angiotensin II receptor blocker attenuates PDGF-induced mesangial cell migration in a receptor-independent manner"},"authors":{"en":[{"name":"Ishizawa Keisuke"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Dorjsuren Narantungalag"},{"name":"Miki Erika"},{"name":"Kihira Yoshitaka"},{"name":"Ikeda Yasumasa"},{"name":"Hamano Shuichi"},{"name":"Kawazoe Kazuyoshi"},{"name":"Minakuchi Kazuo"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 啓介"},{"name":"石澤 有紀"},{"name":"Dorjsuren Narantungalag"},{"name":"Miki Erika"},{"name":"木平 孝高"},{"name":"池田 康将"},{"name":"濱野 修一"},{"name":"川添 和義"},{"name":"水口 和生"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Clinical studies have shown that angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) are able to provide renoprotection independent of their blood pressure lowering effects. ARBs also are reported to suppress oxidative stress, inflammation and certain other cellular responses in a receptor-independent manner. We investigated the effects of an ARB, olmesartan, on the cell migration induced by platelet-derived growth factor (PDGF), a major mitogen involved in the pathogenesis of glomerulonephritis in rat mesangial cells (RMCs). Cell migration was determined by a modified Boyden chamber assay. The intracellular signalling pathway was examined by western blotting. AT1 receptor expression was knocked down by small interfering RNAs. The intracellular reactive oxygen species (ROS) was measured by using a fluorescent probe. The O(2)(.-) scavenging activities were studied by the electron paramagnetic resonance-spin trapping method. PDGF-induced cell migration was inhibited by olmesartan in AT1 receptor knockdown RMCs. Olmesartan attenuated big mitogen-activated protein (MAP) kinase 1 (BMK1) and Src activation by PDGF in AT1 receptor knockdown RMCs. PDGF-induced BMK1 activation was suppressed by the Src family tyrosine kinase inhibitors, indicating that Src exists upstream of BMK1. The NADPH oxidase inhibitors inhibited not only PDGF-induced BMK1 and Src activation but also RMC migration. The elevation in ROS generation induced by PDGF was decreased by olmesartan. Olmesartan displayed neither directly ROS scavenging activity nor the inhibition of ROS-mediated intracellular signalling in RMCs. Olmesartan attenuates ROS generation by PDGF, leading to the subsequent inhibition of Src/ BMK1/migration in an AT1 receptor-independent manner in RMCs.","ja":"Clinical studies have shown that angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) are able to provide renoprotection independent of their blood pressure lowering effects. ARBs also are reported to suppress oxidative stress, inflammation and certain other cellular responses in a receptor-independent manner. We investigated the effects of an ARB, olmesartan, on the cell migration induced by platelet-derived growth factor (PDGF), a major mitogen involved in the pathogenesis of glomerulonephritis in rat mesangial cells (RMCs). Cell migration was determined by a modified Boyden chamber assay. The intracellular signalling pathway was examined by western blotting. AT1 receptor expression was knocked down by small interfering RNAs. The intracellular reactive oxygen species (ROS) was measured by using a fluorescent probe. The O(2)(.-) scavenging activities were studied by the electron paramagnetic resonance-spin trapping method. PDGF-induced cell migration was inhibited by olmesartan in AT1 receptor knockdown RMCs. Olmesartan attenuated big mitogen-activated protein (MAP) kinase 1 (BMK1) and Src activation by PDGF in AT1 receptor knockdown RMCs. PDGF-induced BMK1 activation was suppressed by the Src family tyrosine kinase inhibitors, indicating that Src exists upstream of BMK1. The NADPH oxidase inhibitors inhibited not only PDGF-induced BMK1 and Src activation but also RMC migration. The elevation in ROS generation induced by PDGF was decreased by olmesartan. Olmesartan displayed neither directly ROS scavenging activity nor the inhibition of ROS-mediated intracellular signalling in RMCs. Olmesartan attenuates ROS generation by PDGF, leading to the subsequent inhibition of Src/ BMK1/migration in an AT1 receptor-independent manner in RMCs."},"publication_date":"2010-02","publication_name":{"en":"Nephrology, Dialysis, Transplantation","ja":"Nephrology, Dialysis, Transplantation"},"volume":"25","number":"2","starting_page":"364","ending_page":"372","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1093/ndt/gfp520"],"issn":["1460-2385"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:52, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19966184","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219678","label":"url"}],"paper_title":{"en":"Inhibition of thrombin action ameliorates insulin resistance in type 2 diabetic db/db mice.","ja":"Inhibition of thrombin action ameliorates insulin resistance in type 2 diabetic db/db mice."},"authors":{"en":[{"name":"Mihara Masatomo"},{"name":"Aihara Ken-ichi"},{"name":"Ikeda Yasumasa"},{"name":"Yoshida Sumiko"},{"name":"Kinouchi Mizuho"},{"name":"Kurahashi Kiyoe"},{"name":"Fujinaka Yuichi"},{"name":"Akaike Masashi"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"Mihara Masatomo"},{"name":"粟飯原 賢一"},{"name":"池田 康将"},{"name":"吉田 守美子"},{"name":"木内 美瑞穂"},{"name":"Kurahashi Kiyoe"},{"name":"藤中 雄一"},{"name":"赤池 雅史"},{"name":"松本 俊夫"}]},"description":{"en":"The binding of thrombin to its receptor stimulates inflammatory cytokines including IL-6 and monocyte chemoattractant protein-1 (MCP-1); both are associated with the development of insulin resistance. Because increased adiposity enhanced the expression of coagulation factor VII that stimulates the coagulation pathway in adipose tissue, we tested whether the inhibition of thrombin action ameliorates insulin resistance in obese diabetic (Lpr(-/-):db/db) mice. The 4-wk administration of argatroban, a selective thrombin inhibitor, reduced fasting plasma glucose and ameliorated insulin resistance in these mice. It also reduced adipocyte size and macrophage infiltration into adipose tissue. The aberrant gene expression of MCP-1, IL-6, adiponectin, and factor VII and suppressed insulin receptor substrate-1-Akt signaling in adipose tissue of db/db mice were reversed by argatroban treatment. These results demonstrate that increased adiposity enhances the production of thrombin in adipose tissue by stimulating factor VII expression and suggest that increased thrombin activity in adipose tissue plays an important role in the development of insulin resistance via enhancing MCP-1 production, leading to macrophage infiltration and insulin receptor substrate-1-Akt pathway inactivation.","ja":"The binding of thrombin to its receptor stimulates inflammatory cytokines including IL-6 and monocyte chemoattractant protein-1 (MCP-1); both are associated with the development of insulin resistance. Because increased adiposity enhanced the expression of coagulation factor VII that stimulates the coagulation pathway in adipose tissue, we tested whether the inhibition of thrombin action ameliorates insulin resistance in obese diabetic (Lpr(-/-):db/db) mice. The 4-wk administration of argatroban, a selective thrombin inhibitor, reduced fasting plasma glucose and ameliorated insulin resistance in these mice. It also reduced adipocyte size and macrophage infiltration into adipose tissue. The aberrant gene expression of MCP-1, IL-6, adiponectin, and factor VII and suppressed insulin receptor substrate-1-Akt signaling in adipose tissue of db/db mice were reversed by argatroban treatment. These results demonstrate that increased adiposity enhances the production of thrombin in adipose tissue by stimulating factor VII expression and suggest that increased thrombin activity in adipose tissue plays an important role in the development of insulin resistance via enhancing MCP-1 production, leading to macrophage infiltration and insulin receptor substrate-1-Akt pathway inactivation."},"publication_date":"2009-12-04","publication_name":{"en":"Endocrinology","ja":"Endocrinology"},"volume":"151","number":"2","starting_page":"513","ending_page":"519","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1210/en.2009-0661"],"issn":["1945-7170"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:53, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20058503","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219707","label":"url"}],"paper_title":{"en":"Decrease in plasma brain natriuretic peptide level in the early phase after the start of carvedilol therapy is a novel predictor of long-term outcome in patients with chronic heart failure.","ja":"Decrease in plasma brain natriuretic peptide level in the early phase after the start of carvedilol therapy is a novel predictor of long-term outcome in patients with chronic heart failure."},"authors":{"en":[{"name":"Fujimura Mitsunori"},{"name":"Akaike Masashi"},{"name":"Iwase Takashi"},{"name":"Yoshida Sumiko"},{"name":"Sumitomo Yuka"},{"name":"Yagi Shusuke"},{"name":"Ikeda Yasumasa"},{"name":"Hashizume Shunji"},{"name":"Aihara Ken-ichi"},{"name":"Nishiuchi Takeshi"},{"name":"Yasumura Yoshio"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"Fujimura Mitsunori"},{"name":"Akaike Masashi"},{"name":"Iwase Takashi"},{"name":"吉田 守美子"},{"name":"Sumitomo Yuka"},{"name":"Yagi Shusuke"},{"name":"池田 康将"},{"name":"Hashizume Shunji"},{"name":"粟飯原 賢一"},{"name":"Nishiuchi Takeshi"},{"name":"Yasumura Yoshio"},{"name":"松本 俊夫"}]},"description":{"en":"OBJECTIVE: The purpose of the present study was to determine whether change in plasma brain natriuretic peptide (BNP) level at an early phase of carvedilol therapy is a predictor of improvement in cardiac function and long-term prognosis in patients with systolic chronic heart failure (CHF). METHODS AND RESULTS: Neurohumoral factors and haemodynamics were examined in 64 patients with systolic CHF (left ventricular ejection fraction (LVEF) below 45%) before and one month (early phase) and 3 to 6 months (late phase) after the start of carvedilol therapy. These patients were followed up for a mean period of 57 months. Plasma BNP levels were already decreased in the early phase before improvement of LVEF in response to carvedilol therapy. Univariate and multivariate linear regression analyses showed that Delta log brain natriuretic peptide (BNP)E (= log BNP at baseline--log BNP at early phase) (P < 0.0001) was a significant independent predictor of improvement in LVEF in the late phase. Cardiac events occurred in I I patients during the follow-up period. In addition, multivariate Cox proportional hazards regression analysis showed that Delta log BNPE (P = 0.0045) and systolic blood pressure at baseline (P = -0.048) were significant independent predictors of the development of cardiac events. CONCLUSIONS: Decrease in plasma BNP level in the early phase of carvedilol therapy is a novel predictor of not only improvement of LVEF in the late phase but also prognosis in patients with systolic CHF.","ja":"OBJECTIVE: The purpose of the present study was to determine whether change in plasma brain natriuretic peptide (BNP) level at an early phase of carvedilol therapy is a predictor of improvement in cardiac function and long-term prognosis in patients with systolic chronic heart failure (CHF). METHODS AND RESULTS: Neurohumoral factors and haemodynamics were examined in 64 patients with systolic CHF (left ventricular ejection fraction (LVEF) below 45%) before and one month (early phase) and 3 to 6 months (late phase) after the start of carvedilol therapy. These patients were followed up for a mean period of 57 months. Plasma BNP levels were already decreased in the early phase before improvement of LVEF in response to carvedilol therapy. Univariate and multivariate linear regression analyses showed that Delta log brain natriuretic peptide (BNP)E (= log BNP at baseline--log BNP at early phase) (P < 0.0001) was a significant independent predictor of improvement in LVEF in the late phase. Cardiac events occurred in I I patients during the follow-up period. In addition, multivariate Cox proportional hazards regression analysis showed that Delta log BNPE (P = 0.0045) and systolic blood pressure at baseline (P = -0.048) were significant independent predictors of the development of cardiac events. CONCLUSIONS: Decrease in plasma BNP level in the early phase of carvedilol therapy is a novel predictor of not only improvement of LVEF in the late phase but also prognosis in patients with systolic CHF."},"publication_date":"2009-10","publication_name":{"en":"Acta Cardiologica","ja":"Acta Cardiologica"},"volume":"64","number":"5","starting_page":"589","ending_page":"595","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2143/AC.64.5.2042687"],"issn":["0001-5385"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:54, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19460854","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=193058","label":"url"}],"paper_title":{"en":"Inhibitory effects of adiponectin on platelet-derived growth factor-induced mesangial cell migration","ja":"Inhibitory effects of adiponectin on platelet-derived growth factor-induced mesangial cell migration"},"authors":{"en":[{"name":"Ishizawa Keisuke"},{"name":"Dorjsuren Narantungalag"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Sugimoto Rika"},{"name":"Ikeda Yasumasa"},{"name":"Kihira Yoshitaka"},{"name":"Kawazoe Kazuyoshi"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Minakuchi Kazuo"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 啓介"},{"name":"Dorjsuren Narantungalag"},{"name":"石澤 有紀"},{"name":"Sugimoto Rika"},{"name":"池田 康将"},{"name":"木平 孝高"},{"name":"川添 和義"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"水口 和生"},{"name":"玉置 俊晃"}]},"description":{"en":"Adiponectin, an adipocyte-derived hormone, has been involved in metabolic syndrome, a known risk factor for the development of chronic kidney disease (CKD). Recent studies have demonstrated that plasma adiponectin levels are elevated when kidney function declines in patients with CKD. Excessive mesangial cell (MC) turnover is one of the important features of CKD. The aim of the present study is to elucidate the effects of adiponectin on platelet-derived growth factor (PDGF)-induced cell migration and intracellular signaling pathways, in cultured rat MCs (RMCs). PDGF-induced RMC migration was significantly inhibited by the pretreatment of adiponectin. Adiponectin alone had no effect on RMC migration. Big mitogen-activated protein (MAP) kinase 1 (BMK1), p38 MAP kinase, and Akt were activated by PDGF stimulation in a time- and concentration-dependent manner in RMC. Adiponectin alone did not affect BMK1, p38 MAP kinase, and Akt phosphorylations in RMC. PDGF-induced BMK1 and p38 MAP kinase phosphorylations were significantly attenuated by the pretreatment of adiponectin in RMCs. On the other hand, the phosphorylation of Akt by PDGF was not diminished by the pretreatment of adiponectin. Adiponectin had no effects on PDGF-receptor autophosphorylation by PDGF. We also confirmed that PDGF-induced RMC migration was significantly suppressed by siBMK1 transfection or SB203580, a p38 MAP kinase inhibitor. From these findings, it is implied that the elevated plasma adiponectin levels in patients with CKD might play a compensatory role aimed at counteracting renal dysfunction related to MC disorders.","ja":"Adiponectin, an adipocyte-derived hormone, has been involved in metabolic syndrome, a known risk factor for the development of chronic kidney disease (CKD). Recent studies have demonstrated that plasma adiponectin levels are elevated when kidney function declines in patients with CKD. Excessive mesangial cell (MC) turnover is one of the important features of CKD. The aim of the present study is to elucidate the effects of adiponectin on platelet-derived growth factor (PDGF)-induced cell migration and intracellular signaling pathways, in cultured rat MCs (RMCs). PDGF-induced RMC migration was significantly inhibited by the pretreatment of adiponectin. Adiponectin alone had no effect on RMC migration. Big mitogen-activated protein (MAP) kinase 1 (BMK1), p38 MAP kinase, and Akt were activated by PDGF stimulation in a time- and concentration-dependent manner in RMC. Adiponectin alone did not affect BMK1, p38 MAP kinase, and Akt phosphorylations in RMC. PDGF-induced BMK1 and p38 MAP kinase phosphorylations were significantly attenuated by the pretreatment of adiponectin in RMCs. On the other hand, the phosphorylation of Akt by PDGF was not diminished by the pretreatment of adiponectin. Adiponectin had no effects on PDGF-receptor autophosphorylation by PDGF. We also confirmed that PDGF-induced RMC migration was significantly suppressed by siBMK1 transfection or SB203580, a p38 MAP kinase inhibitor. From these findings, it is implied that the elevated plasma adiponectin levels in patients with CKD might play a compensatory role aimed at counteracting renal dysfunction related to MC disorders."},"publication_date":"2009-08","publication_name":{"en":"The Journal of Endocrinology","ja":"The Journal of Endocrinology"},"volume":"202","number":"2","starting_page":"309","ending_page":"316","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1677/JOE-08-0469"],"issn":["1479-6805"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:55, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19403987","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219712","label":"url"}],"paper_title":{"en":"Heparin cofactor II is an independent protective factor against peripheral arterial disease in elderly subjects with cardiovascular risk factors.","ja":"Heparin cofactor II is an independent protective factor against peripheral arterial disease in elderly subjects with cardiovascular risk factors."},"authors":{"en":[{"name":"Aihara Ken-ichi"},{"name":"Azuma Hiroyuki"},{"name":"Akaike Masashi"},{"name":"Kurobe Hirotsugu"},{"name":"Takamori Nobuyuki"},{"name":"Ikeda Yasumasa"},{"name":"Sumitomo Yuka"},{"name":"Yoshida Sumiko"},{"name":"Yagi Shusuke"},{"name":"Iwase Takashi"},{"name":"Ishikawa Kazue"},{"name":"Sata Masataka"},{"name":"Kitagawa Tetsuya"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"粟飯原 賢一"},{"name":"東 博之"},{"name":"赤池 雅史"},{"name":"黒部 裕嗣"},{"name":"Takamori Nobuyuki"},{"name":"池田 康将"},{"name":"Sumitomo Yuka"},{"name":"吉田 守美子"},{"name":"八木 秀介"},{"name":"岩瀬 俊"},{"name":"Ishikawa Kazue"},{"name":"佐田 政隆"},{"name":"北川 哲也"},{"name":"松本 俊夫"}]},"description":{"en":"AIM: Heparin cofactor II (HCII) specifically inactivates thrombin action at the injured vascular wall. We have reported that HCII is a protective factor against coronary in-stent restenosis and carotid atherosclerosis; however, it is unclear whether there is any correlation between plasma HCII levels and the development of peripheral arterial disease (PAD). METHODS: Plasma HCII activity and the ankle brachial pressure index (ABI) were determined in 494 elderly subjects with cardiovascular risk factors. PAD was diagnosed by ABI below 0.9, and 62 subjects were diagnosed with PAD. The relationship between factors that affect cardiovascular events and the prevalence of PAD was statistically evaluated. RESULTS: Mean HCII activity in PAD subjects was significantly lower than in non-PAD subjects (87.5+/-19.7% v.s. 94.6+/-17.8%, p=0.009). Multivariate logistic regression analysis showed that age (odds ratio [OR]: 1.062, p=0.0016), current smoking (OR 3.028, p=0.002) and diabetes mellitus (OR 2.656, p=0.008) were independent and progressive determinants of PAD. In contrast, HCII was an independent inhibitory factor of PAD (OR: 0.982, p=0.048). CONCLUSIONS: Plasma HCII activity is inversely related to the prevalence of PAD. HCII may function as the sole protective factor against PAD in elderly people with cardiovascular risk factors.","ja":"AIM: Heparin cofactor II (HCII) specifically inactivates thrombin action at the injured vascular wall. We have reported that HCII is a protective factor against coronary in-stent restenosis and carotid atherosclerosis; however, it is unclear whether there is any correlation between plasma HCII levels and the development of peripheral arterial disease (PAD). METHODS: Plasma HCII activity and the ankle brachial pressure index (ABI) were determined in 494 elderly subjects with cardiovascular risk factors. PAD was diagnosed by ABI below 0.9, and 62 subjects were diagnosed with PAD. The relationship between factors that affect cardiovascular events and the prevalence of PAD was statistically evaluated. RESULTS: Mean HCII activity in PAD subjects was significantly lower than in non-PAD subjects (87.5+/-19.7% v.s. 94.6+/-17.8%, p=0.009). Multivariate logistic regression analysis showed that age (odds ratio [OR]: 1.062, p=0.0016), current smoking (OR 3.028, p=0.002) and diabetes mellitus (OR 2.656, p=0.008) were independent and progressive determinants of PAD. In contrast, HCII was an independent inhibitory factor of PAD (OR: 0.982, p=0.048). CONCLUSIONS: Plasma HCII activity is inversely related to the prevalence of PAD. HCII may function as the sole protective factor against PAD in elderly people with cardiovascular risk factors."},"publication_date":"2009-04-30","publication_name":{"en":"Journal of Atherosclerosis and Thrombosis","ja":"Journal of Atherosclerosis and Thrombosis"},"volume":"16","number":"2","starting_page":"127","ending_page":"134","languages":["eng"],"referee":true,"identifiers":{"doi":["10.5551/jat.E695"],"issn":["1880-3873"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:56, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19196803","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219697","label":"url"}],"paper_title":{"en":"Androgen-androgen receptor system protects against angiotensin II-induced vascular remodeling.","ja":"Androgen-androgen receptor system protects against angiotensin II-induced vascular remodeling."},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Aihara Ken-ichi"},{"name":"Yoshida Sumiko"},{"name":"Sato Takashi"},{"name":"Yagi Shusuke"},{"name":"Iwase Takashi"},{"name":"Sumitomo Yuka"},{"name":"Ise Takayuki"},{"name":"Ishikawa Kazue"},{"name":"Azuma Hiroyuki"},{"name":"Akaike Masashi"},{"name":"Kato Shigeaki"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"池田 康将"},{"name":"粟飯原 賢一"},{"name":"吉田 守美子"},{"name":"Sato Takashi"},{"name":"Yagi Shusuke"},{"name":"Iwase Takashi"},{"name":"Sumitomo Yuka"},{"name":"Ise Takayuki"},{"name":"Ishikawa Kazue"},{"name":"Azuma Hiroyuki"},{"name":"Akaike Masashi"},{"name":"Kato Shigeaki"},{"name":"Matsumoto Toshio"}]},"description":{"en":"Age-related andropause promotes cardiovascular disease in males. Although we had previously reported that the androgen-androgen receptor (AR) system plays important roles in cardiac growth and remodeling, the system's involvement in vascular remodeling remains unclear. To clarify this role, 25-wk-old male AR knockout (ARKO) mice and littermate male wild-type (WT) mice were divided into two groups with and without angiotensin II (Ang II) administration (2.0 mg/kg . d) for 14 d, respectively. No morphological differences in the coronary artery and thoracic aorta were observed between the groups without Ang II. Ang II stimulation markedly increased medial thickness and perivascular fibrosis in ARKO mice, with enhanced TGF-beta1, collagen type I, and collagen type III gene expression in the aorta. Ang II stimulation also prominently increased superoxide production, lipid peroxidation, and gene expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase components in ARKO mice compared with WT mice. In addition, phosphorylation of c-Jun N-terminal kinase (JNK) and phosphorylated (Smad2/3) was remarkably enhanced in Ang II-treated ARKO mice compared with Ang II-treated WT mice. Notably, daily urinary nitric oxide (NO) metabolites excretion as a marker of NO bioavailability, aortic endothelial NO synthase expression and phosphorylation, and Akt phosphorylation were significantly reduced in ARKO mice compared with WT mice, regardless of Ang II stimulation. In conclusion, the androgen-AR system is required for the preservation of NO bioavailability through Akt-endothelial NO synthase system activation and exerts protective effects against Ang II-induced vascular remodeling by regulating oxidative stress, c-Jun N-terminal kinase (JNK) signaling, and the TGF-beta-phosphorylated Smad pathway.","ja":"Age-related andropause promotes cardiovascular disease in males. Although we had previously reported that the androgen-androgen receptor (AR) system plays important roles in cardiac growth and remodeling, the system's involvement in vascular remodeling remains unclear. To clarify this role, 25-wk-old male AR knockout (ARKO) mice and littermate male wild-type (WT) mice were divided into two groups with and without angiotensin II (Ang II) administration (2.0 mg/kg . d) for 14 d, respectively. No morphological differences in the coronary artery and thoracic aorta were observed between the groups without Ang II. Ang II stimulation markedly increased medial thickness and perivascular fibrosis in ARKO mice, with enhanced TGF-beta1, collagen type I, and collagen type III gene expression in the aorta. Ang II stimulation also prominently increased superoxide production, lipid peroxidation, and gene expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase components in ARKO mice compared with WT mice. In addition, phosphorylation of c-Jun N-terminal kinase (JNK) and phosphorylated (Smad2/3) was remarkably enhanced in Ang II-treated ARKO mice compared with Ang II-treated WT mice. Notably, daily urinary nitric oxide (NO) metabolites excretion as a marker of NO bioavailability, aortic endothelial NO synthase expression and phosphorylation, and Akt phosphorylation were significantly reduced in ARKO mice compared with WT mice, regardless of Ang II stimulation. In conclusion, the androgen-AR system is required for the preservation of NO bioavailability through Akt-endothelial NO synthase system activation and exerts protective effects against Ang II-induced vascular remodeling by regulating oxidative stress, c-Jun N-terminal kinase (JNK) signaling, and the TGF-beta-phosphorylated Smad pathway."},"publication_date":"2009-02-05","publication_name":{"en":"Endocrinology","ja":"Endocrinology"},"volume":"150","number":"6","starting_page":"2857","ending_page":"2864","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1210/en.2008-1254"],"issn":["1945-7170"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:57, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=266433","label":"url"}],"paper_title":{"en":"アンジオテンシンII受容体拮抗薬バルサルタンのNO bioavailability改善効果に関する臨床的検討","ja":"アンジオテンシンII受容体拮抗薬バルサルタンのNO bioavailability改善効果に関する臨床的検討"},"authors":{"en":[{"name":"Aihara Ken-ichi"},{"name":"Akaike Masashi"},{"name":"Ikeda Yasumasa"},{"name":"Ueda Yuka"},{"name":"Yoshida Sumiko"},{"name":"Ise Takayuki"},{"name":"Yagi Shusuke"},{"name":"Iwase Takashi"},{"name":"近藤 彰"},{"name":"田村 克也"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"粟飯原 賢一"},{"name":"赤池 雅史"},{"name":"池田 康将"},{"name":"上田 由佳"},{"name":"吉田 守美子"},{"name":"伊勢 孝之"},{"name":"八木 秀介"},{"name":"岩瀬 俊"},{"name":"近藤 彰"},{"name":"田村 克也"},{"name":"松本 俊夫"}]},"description":{"en":"バルサルタンの降圧作用，動脈硬化抑制作用および糖代謝改善作用に一酸化窒素(NO)のバイオアベイラビリティの改善効果が関与しているか検討した．高血圧治療目的で通院加療中の42例を対象とした．バルサルタン投与にて，BMIやリポプロテイン(a)を含む脂質プロファイルに有意な変化は認めなかったが，収縮期血圧，脈圧，baPWVおよびHbA1cは有意に低下した．投与3ヵ月後には投与前と比較して，NOのバイオアベイラビリティのマーカーである血清硝酸/亜硝酸イオン(NOx)は約1.5倍に増加した．血清NOxの増加が，他の測定因子にどのように影響を与えているか，単変量および多変量解析を用いて解析し，血清NOxの増加量は収縮期血圧の低下と脈圧の減少との間においてそれぞれ有意な相関がみられた．また，HbA1cはバルサルタン投与3ヵ月後に有意に低下していたが，その変化はNOxの増加量と有意な相関がみられた．","ja":"バルサルタンの降圧作用，動脈硬化抑制作用および糖代謝改善作用に一酸化窒素(NO)のバイオアベイラビリティの改善効果が関与しているか検討した．高血圧治療目的で通院加療中の42例を対象とした．バルサルタン投与にて，BMIやリポプロテイン(a)を含む脂質プロファイルに有意な変化は認めなかったが，収縮期血圧，脈圧，baPWVおよびHbA1cは有意に低下した．投与3ヵ月後には投与前と比較して，NOのバイオアベイラビリティのマーカーである血清硝酸/亜硝酸イオン(NOx)は約1.5倍に増加した．血清NOxの増加が，他の測定因子にどのように影響を与えているか，単変量および多変量解析を用いて解析し，血清NOxの増加量は収縮期血圧の低下と脈圧の減少との間においてそれぞれ有意な相関がみられた．また，HbA1cはバルサルタン投与3ヵ月後に有意に低下していたが，その変化はNOxの増加量と有意な相関がみられた．"},"publication_date":"2009","publication_name":{"en":"Progress in Medicine","ja":"Progress in Medicine"},"volume":"29","number":"7","starting_page":"1777","ending_page":"1782","languages":["jpn"],"referee":true,"identifiers":{"issn":["0287-3648"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:58, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/18552468","label":"url"},{"@id":"https://www.scopus.com/pages/publications/48049096600","label":"url"},{"@id":"https://www.scopus.com/pages/publications/56349127735","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219679","label":"url"}],"paper_title":{"en":"Infective endocarditis caused by lactobacillus.","ja":"Infective endocarditis caused by lactobacillus."},"authors":{"en":[{"name":"Yagi Shusuke"},{"name":"Akaike Masahi"},{"name":"Fujimura Mitsunori"},{"name":"Ise Takayuki"},{"name":"Yoshida Sumiko"},{"name":"Sumitomo Yuka"},{"name":"Ikeda Yasumasa"},{"name":"Iwase Takashi"},{"name":"Aihara Ken-ichi"},{"name":"Azuma Hiroyuki"},{"name":"Kurushima Atsushi"},{"name":"Ichikawa Youichi"},{"name":"Kitagawa Tetsuya"},{"name":"Kimura Takehiko"},{"name":"Nishiuchi Takeshi"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"八木 秀介"},{"name":"Akaike Masahi"},{"name":"Fujimura Mitsunori"},{"name":"Ise Takayuki"},{"name":"吉田 守美子"},{"name":"Sumitomo Yuka"},{"name":"池田 康将"},{"name":"岩瀬 俊"},{"name":"粟飯原 賢一"},{"name":"東 博之"},{"name":"Kurushima Atsushi"},{"name":"Ichikawa Youichi"},{"name":"北川 哲也"},{"name":"Kimura Takehiko"},{"name":"Nishiuchi Takeshi"},{"name":"松本 俊夫"}]},"description":{"en":"Lactobacillus (LB) is a gram-positive rod-shaped bacterium that inhabits the oral cavity, gastrointestinal tract, vagina and nasal cavity. Although LB plays a role in the prevention of infections caused by pathogenic bacteria, it causes some critical infectious diseases such as infective endocarditis (IE). IE due to LB is rare; however, early diagnosis and early treatment are important because of its high mortality rate. We report the onset of IE after otologic treatment in a heavy drinker of alcohol, the second case of IE due to LB in Japan.","ja":"Lactobacillus (LB) is a gram-positive rod-shaped bacterium that inhabits the oral cavity, gastrointestinal tract, vagina and nasal cavity. Although LB plays a role in the prevention of infections caused by pathogenic bacteria, it causes some critical infectious diseases such as infective endocarditis (IE). IE due to LB is rare; however, early diagnosis and early treatment are important because of its high mortality rate. We report the onset of IE after otologic treatment in a heavy drinker of alcohol, the second case of IE due to LB in Japan."},"publication_date":"2008-06-16","publication_name":{"en":"Internal Medicine","ja":"Internal Medicine"},"volume":"47","number":"12","starting_page":"1113","ending_page":"1116","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2169/internalmedicine.47.0744"],"issn":["1349-7235"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:59, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/18339320","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219699","label":"url"}],"paper_title":{"en":"Cyclooxygenase-2 induction by adiponectin is regulated by a sphingosine kinase-1 dependent mechanism in cardiac myocytes.","ja":"Cyclooxygenase-2 induction by adiponectin is regulated by a sphingosine kinase-1 dependent mechanism in cardiac myocytes."},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Ohashi Koji"},{"name":"Shibata Rei"},{"name":"Pimentel David R"},{"name":"Kihara Shinji"},{"name":"Ouchi Noriyuki"},{"name":"Walsh Kenneth"}],"ja":[{"name":"池田 康将"},{"name":"Ohashi Koji"},{"name":"Shibata Rei"},{"name":"Pimentel David R"},{"name":"Kihara Shinji"},{"name":"Ouchi Noriyuki"},{"name":"Walsh Kenneth"}]},"description":{"en":"The adipose-derived plasma protein, adiponectin (APN), has various protective effects on cardiovascular diseases. In this study, we show that endogenous APN is required for full cyclooxygenase-2 (COX-2) induction by ischemia-reperfusion injury in the heart in vivo. In rat neonatal cardiac myocytes, APN-induced COX-2 expression was reduced by treatment with a sphingosine kinase-1 (SphK-1) inhibitor or siRNA targeting SphK-1. Treatment with a sphingosine-1-phosphate (S1P) receptor antagonist also diminished COX-2 expression in response to APN stimulation. These findings suggest that APN is a physiological regulator of COX-2 signaling in the heart and that this regulation occurs in part via a SphK-1-S1P receptor dependent mechanism in cardiac myocytes.","ja":"The adipose-derived plasma protein, adiponectin (APN), has various protective effects on cardiovascular diseases. In this study, we show that endogenous APN is required for full cyclooxygenase-2 (COX-2) induction by ischemia-reperfusion injury in the heart in vivo. In rat neonatal cardiac myocytes, APN-induced COX-2 expression was reduced by treatment with a sphingosine kinase-1 (SphK-1) inhibitor or siRNA targeting SphK-1. Treatment with a sphingosine-1-phosphate (S1P) receptor antagonist also diminished COX-2 expression in response to APN stimulation. These findings suggest that APN is a physiological regulator of COX-2 signaling in the heart and that this regulation occurs in part via a SphK-1-S1P receptor dependent mechanism in cardiac myocytes."},"publication_date":"2008-03-11","publication_name":{"en":"FEBS Letters","ja":"FEBS Letters"},"volume":"582","number":"7","starting_page":"1147","ending_page":"1150","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.febslet.2008.03.002"],"issn":["0014-5793"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:60, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17967781","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219713","label":"url"}],"paper_title":{"en":"Pitavastatin, an HMG-CoA reductase inhibitor, exerts eNOS-independent protective actions against angiotensin II induced cardiovascular remodeling and renal insufficiency.","ja":"Pitavastatin, an HMG-CoA reductase inhibitor, exerts eNOS-independent protective actions against angiotensin II induced cardiovascular remodeling and renal insufficiency."},"authors":{"en":[{"name":"Yagi Shusuke"},{"name":"Aihara Ken-ichi"},{"name":"Ikeda Yasumasa"},{"name":"Sumitomo Yuka"},{"name":"Yoshida Sumiko"},{"name":"Ise Takayuki"},{"name":"Iwase Takashi"},{"name":"Ishikawa Kazue"},{"name":"Azuma Hiroyuki"},{"name":"Akaike Masashi"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"八木 秀介"},{"name":"粟飯原 賢一"},{"name":"池田 康将"},{"name":"Sumitomo Yuka"},{"name":"吉田 守美子"},{"name":"Ise Takayuki"},{"name":"岩瀬 俊"},{"name":"Ishikawa Kazue"},{"name":"Azuma Hiroyuki"},{"name":"Akaike Masashi"},{"name":"Matsumoto Toshio"}]},"description":{"en":"Angiotensin II (Ang II) plays a pivotal role in cardiovascular remodeling leading to hypertension, myocardial infarction, and stroke. Pitavastatin, an HMG-CoA reductase inihibitor, is known to have pleiotropic actions against the development of cardiovascular remodeling. The objectives of this study were to clarify the beneficial effects as well as the mechanism of action of pitavastatin against Ang II-induced organ damage. C57BL6/J mice at 10 weeks of age were infused with Ang II for 2 weeks and were simultaneously administered pitavastatin or a vehicle. Pitavastatin treatment improved Ang II-induced left ventricular hypertrophy and diastolic dysfunction and attenuated enhancement of cardiac fibrosis, cardiomyocyte hypertrophy, coronary perivascular fibrosis, and medial thickening. Ang II-induced oxidative stress, cardiac TGFbeta-1 expression, and Smad 2/3 phosphorylation were all attenuated by pitavastatin treatment. Pitavastatin also reduced Ang II-induced cardiac remodeling and diastolic dysfunction in eNOS-/- mice as in wild-type mice. In eNOS-/- mice, the Ang II-induced cardiac oxidative stress and TGF-beta-Smad 2/3 signaling pathway were enhanced, and pitavastatin treatment attenuated the enhanced oxidative stress and the signaling pathway. Moreover, pitavastatin treatment reduced the high mortality rate and improved renal insufficiency in Ang II-treated eNOS-/- mice, with suppression of glomerular oxidative stress and TGF-beta-Smad 2/3 signaling pathway. In conclusion, pitavastatin exerts eNOS-independent protective actions against Ang II-induced cardiovascular remodeling and renal insufficiency through inhibition of the TGF-beta-Smad 2/3 signaling pathway by suppression of oxidative stress.","ja":"Angiotensin II (Ang II) plays a pivotal role in cardiovascular remodeling leading to hypertension, myocardial infarction, and stroke. Pitavastatin, an HMG-CoA reductase inihibitor, is known to have pleiotropic actions against the development of cardiovascular remodeling. The objectives of this study were to clarify the beneficial effects as well as the mechanism of action of pitavastatin against Ang II-induced organ damage. C57BL6/J mice at 10 weeks of age were infused with Ang II for 2 weeks and were simultaneously administered pitavastatin or a vehicle. Pitavastatin treatment improved Ang II-induced left ventricular hypertrophy and diastolic dysfunction and attenuated enhancement of cardiac fibrosis, cardiomyocyte hypertrophy, coronary perivascular fibrosis, and medial thickening. Ang II-induced oxidative stress, cardiac TGFbeta-1 expression, and Smad 2/3 phosphorylation were all attenuated by pitavastatin treatment. Pitavastatin also reduced Ang II-induced cardiac remodeling and diastolic dysfunction in eNOS-/- mice as in wild-type mice. In eNOS-/- mice, the Ang II-induced cardiac oxidative stress and TGF-beta-Smad 2/3 signaling pathway were enhanced, and pitavastatin treatment attenuated the enhanced oxidative stress and the signaling pathway. Moreover, pitavastatin treatment reduced the high mortality rate and improved renal insufficiency in Ang II-treated eNOS-/- mice, with suppression of glomerular oxidative stress and TGF-beta-Smad 2/3 signaling pathway. In conclusion, pitavastatin exerts eNOS-independent protective actions against Ang II-induced cardiovascular remodeling and renal insufficiency through inhibition of the TGF-beta-Smad 2/3 signaling pathway by suppression of oxidative stress."},"publication_date":"2007-10-25","publication_name":{"en":"Circulation Research","ja":"Circulation Research"},"volume":"102","number":"1","starting_page":"68","ending_page":"76","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1161/CIRCRESAHA.107.163493"],"issn":["1524-4571"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:61, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://www.jci.org/cgi/content/abstract/117/6/1514","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17549254","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=159074","label":"url"}],"paper_title":{"en":"Strain-dependent embryonic lethality and exaggerated vascular remodeling in heparin cofactor II-deficient mice","ja":"Strain-dependent embryonic lethality and exaggerated vascular remodeling in heparin cofactor II-deficient mice"},"authors":{"en":[{"name":"Aihara Ken-ichi"},{"name":"Azuma Hiroyuki"},{"name":"Akaike Masashi"},{"name":"Ikeda Yasumasa"},{"name":"Sata Masataka"},{"name":"Takamori Nobuyuki"},{"name":"Yagi Shusuke"},{"name":"Iwase Takashi"},{"name":"Sumitomo Yuka"},{"name":"Kawano Hirotaka"},{"name":"Yamada Takashi"},{"name":"Fukuda Toru"},{"name":"Matsumoto Takahiro"},{"name":"Sekine Keisuke"},{"name":"Sato Takashi"},{"name":"Nakamichi Yuko"},{"name":"Yamamoto Yoko"},{"name":"Yoshimura Kimihiro"},{"name":"Watanabe Tomoyuki"},{"name":"Nakamura Takashi"},{"name":"Oomizu Akimasa"},{"name":"Tsukada Minoru"},{"name":"Hayashi Hideki"},{"name":"Sudo Toshiki"},{"name":"Kato Shigeaki"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"粟飯原 賢一"},{"name":"東 博之"},{"name":"赤池 雅史"},{"name":"池田 康将"},{"name":"佐田 政隆"},{"name":"Takamori Nobuyuki"},{"name":"Yagi Shusuke"},{"name":"岩瀬 俊"},{"name":"Sumitomo Yuka"},{"name":"Kawano Hirotaka"},{"name":"Yamada Takashi"},{"name":"Fukuda Toru"},{"name":"松本 高広"},{"name":"Sekine Keisuke"},{"name":"Sato Takashi"},{"name":"Nakamichi Yuko"},{"name":"Yamamoto Yoko"},{"name":"Yoshimura Kimihiro"},{"name":"Watanabe Tomoyuki"},{"name":"Nakamura Takashi"},{"name":"Oomizu Akimasa"},{"name":"Tsukada Minoru"},{"name":"Hayashi Hideki"},{"name":"Sudo Toshiki"},{"name":"Kato Shigeaki"},{"name":"松本 俊夫"}]},"description":{"en":"Heparin cofactor II (HCII) specifically inhibits thrombin action at sites of injured arterial wall, and patients with HCII deficiency exhibit advanced atherosclerosis. However, the in vivo effects and the molecular mechanism underlying the action of HCII during vascular remodeling remain elusive. To clarify the role of HCII in vascular remodeling, we generated HCII-deficient mice by gene targeting. In contrast to a previous report, HCII(-/-) mice were embryonically lethal. In HCII(+/-) mice, prominent intimal hyperplasia with increased cellular proliferation was observed after tube cuff and wire vascular injury. The number of protease-activated receptor-1-positive (PAR-1-positive) cells was increased in the thickened vascular wall of HCII(+/-) mice, suggesting enhanced thrombin action in this region. Cuff injury also increased the expression levels of inflammatory cytokines and chemokines in the vascular wall of HCII(+/-) mice. The intimal hyperplasia in HCII(+/-) mice with vascular injury was abrogated by human HCII supplementation. Furthermore, HCII deficiency caused acceleration of aortic plaque formation with increased PAR-1 expression and oxidative stress in apoE-KO mice. These results demonstrate that HCII protects against thrombin-induced remodeling of an injured vascular wall by inhibiting thrombin action and suggest that HCII is potentially therapeutic against atherosclerosis without causing coagulatory disturbance.","ja":"Heparin cofactor II (HCII) specifically inhibits thrombin action at sites of injured arterial wall, and patients with HCII deficiency exhibit advanced atherosclerosis. However, the in vivo effects and the molecular mechanism underlying the action of HCII during vascular remodeling remain elusive. To clarify the role of HCII in vascular remodeling, we generated HCII-deficient mice by gene targeting. In contrast to a previous report, HCII(-/-) mice were embryonically lethal. In HCII(+/-) mice, prominent intimal hyperplasia with increased cellular proliferation was observed after tube cuff and wire vascular injury. The number of protease-activated receptor-1-positive (PAR-1-positive) cells was increased in the thickened vascular wall of HCII(+/-) mice, suggesting enhanced thrombin action in this region. Cuff injury also increased the expression levels of inflammatory cytokines and chemokines in the vascular wall of HCII(+/-) mice. The intimal hyperplasia in HCII(+/-) mice with vascular injury was abrogated by human HCII supplementation. Furthermore, HCII deficiency caused acceleration of aortic plaque formation with increased PAR-1 expression and oxidative stress in apoE-KO mice. These results demonstrate that HCII protects against thrombin-induced remodeling of an injured vascular wall by inhibiting thrombin action and suggest that HCII is potentially therapeutic against atherosclerosis without causing coagulatory disturbance."},"publication_date":"2007-06-01","publication_name":{"en":"The Journal of Clinical Investigation","ja":"The Journal of Clinical Investigation"},"volume":"117","number":"6","starting_page":"1514","ending_page":"1526","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1172/JCI27095"],"issn":["0021-9738"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:62, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16864946","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=164577","label":"url"}],"paper_title":{"en":"Intra-vascular ultrasound findings of diffuse coronary atherosclerotic change in systemic lupus erythematosus with secondary antiphospholipid syndrome","ja":"Intra-vascular ultrasound findings of diffuse coronary atherosclerotic change in systemic lupus erythematosus with secondary antiphospholipid syndrome"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Yagi, Shusuke"},{"name":"Yamaguchi, Hiroshi"},{"name":"Fujimura, Mitsunori"},{"name":"Hashizume, Shunji"},{"name":"Aihara, Ken-ichi"},{"name":"Akaike Masashi"},{"name":"Azuma, Hiroyuki"},{"name":"Matsumoto, Toshio"}],"ja":[{"name":"池田 康将"},{"name":"Yagi, Shusuke"},{"name":"Yamaguchi, Hiroshi"},{"name":"Fujimura, Mitsunori"},{"name":"Hashizume, Shunji"},{"name":"Aihara, Ken-ichi"},{"name":"赤池 雅史"},{"name":"Azuma, Hiroyuki"},{"name":"Matsumoto, Toshio"}]},"description":{"en":"Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are autoimmune inflammatory diseases associated with juvenile atherosclerosis and thrombosis, respectively. A 44-year-old woman who had SLE with secondary APS had been treated with corticosteroid therapy, however, her inflammatory marker had never been within a normal range in her clinical course, and finally acute myocardial infarction was developed. Intra-vascular ultrasound also revealed diffuse coronary atherosclerosis progression for her age, which might result from SLE and APS, including vascular inflammation.","ja":"Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are autoimmune inflammatory diseases associated with juvenile atherosclerosis and thrombosis, respectively. A 44-year-old woman who had SLE with secondary APS had been treated with corticosteroid therapy, however, her inflammatory marker had never been within a normal range in her clinical course, and finally acute myocardial infarction was developed. Intra-vascular ultrasound also revealed diffuse coronary atherosclerosis progression for her age, which might result from SLE and APS, including vascular inflammation."},"publication_date":"2006-08","publication_name":{"en":"Circulation Journal","ja":"Circulation Journal"},"volume":"70","number":"8","starting_page":"1082","ending_page":"1085","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1253/circj.70.1082"],"issn":["1346-9843"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:63, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16327955","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219717","label":"url"}],"paper_title":{"en":"Acute myocardial infarction in a patient with essential thrombocythemia who underwent successful stenting. A case report","ja":"Acute myocardial infarction in a patient with essential thrombocythemia who underwent successful stenting. A case report"},"authors":{"en":[{"name":"Watanabe Tomonori"},{"name":"Fujinaga Hiroyuki"},{"name":"Ikeda Yasumasa"},{"name":"HIgashi Teruo"},{"name":"Murakami Masaru"},{"name":"Kawahara Keiji"},{"name":"Hayashi Ikuo"},{"name":"Niki Toshiharu"},{"name":"Shigekiyo Toshio"},{"name":"Wakatsuki Tetsuzo"}],"ja":[{"name":"Watanabe Tomonori"},{"name":"Fujinaga Hiroyuki"},{"name":"池田 康将"},{"name":"HIgashi Teruo"},{"name":"Murakami Masaru"},{"name":"Kawahara Keiji"},{"name":"Hayashi Ikuo"},{"name":"Niki Toshiharu"},{"name":"Shigekiyo Toshio"},{"name":"若槻 哲三"}]},"description":{"en":"Essential thrombocythemia (ET) can cause systemic vascular thrombosis, but involvement of coronary arteries in the setting of ET is rare. This report describes a case of acute myocardial infarction (MI) in a patient with ET. A 67-year-old man with ET complained of severe acute chest pain. Emergent coronary angiography revealed subtotal thrombotic occlusion of the left main trunk (LMT) coronary artery. Coronary angioplasty and stenting were performed successfully. Coronary angiography 4 weeks later revealed no significant restenosis. The patient has done well after primary coronary stenting with the use of only an antiplatelet agent to treat the thrombocythemia.","ja":"Essential thrombocythemia (ET) can cause systemic vascular thrombosis, but involvement of coronary arteries in the setting of ET is rare. This report describes a case of acute myocardial infarction (MI) in a patient with ET. A 67-year-old man with ET complained of severe acute chest pain. Emergent coronary angiography revealed subtotal thrombotic occlusion of the left main trunk (LMT) coronary artery. Coronary angioplasty and stenting were performed successfully. Coronary angiography 4 weeks later revealed no significant restenosis. The patient has done well after primary coronary stenting with the use of only an antiplatelet agent to treat the thrombocythemia."},"publication_date":"2005-11","publication_name":{"en":"Angiology","ja":"Angiology"},"volume":"56","number":"6","starting_page":"771","ending_page":"774","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1177/000331970505600616"],"issn":["0003-3197"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:64, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15961403","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=241203","label":"url"}],"paper_title":{"en":"Androgen receptor gene knockout male mice exhibit impaired cardiac growth and exacerbation of angiotensin II-induced cardiac fibrosis.","ja":"Androgen receptor gene knockout male mice exhibit impaired cardiac growth and exacerbation of angiotensin II-induced cardiac fibrosis."},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Aihara Ken-ichi"},{"name":"Sato Takashi"},{"name":"Akaike Masashi"},{"name":"Yoshizumi Masanori"},{"name":"Suzaki Yuki"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Fujimura Mitsunori"},{"name":"Hashizume Shunji"},{"name":"Kato Midori"},{"name":"Yagi Shusuke"},{"name":"Tamaki Toshiaki"},{"name":"Kawano Hirotaka"},{"name":"Matsumoto Takahiro"},{"name":"Azuma Hiroyuki"},{"name":"Kato Shigeaki"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"池田 康将"},{"name":"粟飯原 賢一"},{"name":"Sato Takashi"},{"name":"赤池 雅史"},{"name":"吉栖 正典"},{"name":"Suzaki Yuki"},{"name":"石澤 有紀"},{"name":"Fujimura Mitsunori"},{"name":"Hashizume Shunji"},{"name":"Kato Midori"},{"name":"八木 秀介"},{"name":"玉置 俊晃"},{"name":"Kawano Hirotaka"},{"name":"松本 高広"},{"name":"東 博之"},{"name":"Kato Shigeaki"},{"name":"松本 俊夫"}]},"description":{"en":"Androgen has anabolic effects on cardiac myocytes and has been shown to enhance left ventricular enlargement and function. However, the physiological and patho-physiological roles of androgen in cardiac growth and cardiac stress-induced remodeling remains unclear. We aimed to clarify whether the androgen-nuclear androgen receptor (AR) system contributes to the cardiac growth and angiotensin II (Ang II)-stimulated cardiac remodeling by using systemic AR-null male mice. AR knock-out (ARKO) male mice, at 25 weeks of age, and age-matched wild-type (WT) male mice were treated with or without Ang II stimulation (2.0 mg/kg/day) for 2 weeks. ARKO mice with or without Ang II stimulation showed a significant reduction in the heart-to-body weight ratio compared with those of WT mice. In addition, echocardiographic analysis demonstrated impairments of both the concentric hypertrophic response and left ventricular function in Ang II-stimulated ARKO mice. Western blot analysis of the myocardium revealed that activation of extracellular signal-regulated kinases (ERK) 1/2 and ERK5 by Ang II stimulation were lower in ARKO mice than those of WT mice. Ang II stimulation caused more prominent cardiac fibrosis in ARKO mice than in WT mice with enhanced expression of types I and III collagen and transforming growth factor-beta1 genes and with increased Smad2 activation. These results suggest that, in male mice, the androgen-AR system participates in normal cardiac growth and modulates cardiac adaptive hypertrophy and fibrosis during the process of cardiac remodeling under hypertrophic stress.","ja":"Androgen has anabolic effects on cardiac myocytes and has been shown to enhance left ventricular enlargement and function. However, the physiological and patho-physiological roles of androgen in cardiac growth and cardiac stress-induced remodeling remains unclear. We aimed to clarify whether the androgen-nuclear androgen receptor (AR) system contributes to the cardiac growth and angiotensin II (Ang II)-stimulated cardiac remodeling by using systemic AR-null male mice. AR knock-out (ARKO) male mice, at 25 weeks of age, and age-matched wild-type (WT) male mice were treated with or without Ang II stimulation (2.0 mg/kg/day) for 2 weeks. ARKO mice with or without Ang II stimulation showed a significant reduction in the heart-to-body weight ratio compared with those of WT mice. In addition, echocardiographic analysis demonstrated impairments of both the concentric hypertrophic response and left ventricular function in Ang II-stimulated ARKO mice. Western blot analysis of the myocardium revealed that activation of extracellular signal-regulated kinases (ERK) 1/2 and ERK5 by Ang II stimulation were lower in ARKO mice than those of WT mice. Ang II stimulation caused more prominent cardiac fibrosis in ARKO mice than in WT mice with enhanced expression of types I and III collagen and transforming growth factor-beta1 genes and with increased Smad2 activation. These results suggest that, in male mice, the androgen-AR system participates in normal cardiac growth and modulates cardiac adaptive hypertrophy and fibrosis during the process of cardiac remodeling under hypertrophic stress."},"publication_date":"2005-06-16","publication_name":{"en":"The Journal of Biological Chemistry","ja":"The Journal of Biological Chemistry"},"volume":"280","number":"33","starting_page":"29661","ending_page":"29666","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1074/jbc.M411694200"],"issn":["0021-9258"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:65, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16216591","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219716","label":"url"}],"paper_title":{"en":"Aspirin inhibits thrombin action on endothelial cells via up-regulation of aminopeptidase N/CD13 expression.","ja":"Aspirin inhibits thrombin action on endothelial cells via up-regulation of aminopeptidase N/CD13 expression."},"authors":{"en":[{"name":"Kato Midori"},{"name":"Azuma Hiroyuki"},{"name":"Akaike Masashi"},{"name":"Iuchi Takahiko"},{"name":"Aihara Ken-ichi"},{"name":"Ikeda Yasumasa"},{"name":"Fujimura Mitsunori"},{"name":"Yoshida Tomonori"},{"name":"Yamaguchi Hiroshi"},{"name":"Hashizume Shunji"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"Kato Midori"},{"name":"東 博之"},{"name":"赤池 雅史"},{"name":"Iuchi Takahiko"},{"name":"粟飯原 賢一"},{"name":"池田 康将"},{"name":"Fujimura Mitsunori"},{"name":"Yoshida Tomonori"},{"name":"Yamaguchi Hiroshi"},{"name":"Hashizume Shunji"},{"name":"松本 俊夫"}]},"description":{"en":"OBJECTIVE: We hypothesized that aspirin may exhibit its anti-atherosclerotic effects via mechanisms other than cyclooxygenase inhibition in platelets. METHODS AND RESULTS: Using enhanced subtraction hybridization analysis, we found in human umbilical vein endothelial cells (HUVECs) that aspirin up-regulates the expression of aminopeptidase N (APN/CD13) mRNA and its surface protein levels in a dose-dependent manner. Enzymatic activity of APN/CD13 on HUVECs was increased approximately 1.5-fold by 1 mmol L(-1) of aspirin, and treatment with bestatin, an inhibitor for APN/CD13 metalloprotease activity, attenuated the enhanced activities of APN/CD13. Since activated thrombin receptor is reported to be inactivated by APN/CD13 in vitro, protective actions of aspirin on HUVECs by thrombin stimulation were examined, resulting in the suppression of endothelin-1 and reactive oxygen species productions in HUVECs. These inhibitory actions of aspirin were partially abrogated by bestatin. CONCLUSIONS: Aspirin may exert its anti-atherothrombotic effects in part via the inhibition of thrombin action by up-regulating APN/CD13 on endothelial cells.","ja":"OBJECTIVE: We hypothesized that aspirin may exhibit its anti-atherosclerotic effects via mechanisms other than cyclooxygenase inhibition in platelets. METHODS AND RESULTS: Using enhanced subtraction hybridization analysis, we found in human umbilical vein endothelial cells (HUVECs) that aspirin up-regulates the expression of aminopeptidase N (APN/CD13) mRNA and its surface protein levels in a dose-dependent manner. Enzymatic activity of APN/CD13 on HUVECs was increased approximately 1.5-fold by 1 mmol L(-1) of aspirin, and treatment with bestatin, an inhibitor for APN/CD13 metalloprotease activity, attenuated the enhanced activities of APN/CD13. Since activated thrombin receptor is reported to be inactivated by APN/CD13 in vitro, protective actions of aspirin on HUVECs by thrombin stimulation were examined, resulting in the suppression of endothelin-1 and reactive oxygen species productions in HUVECs. These inhibitory actions of aspirin were partially abrogated by bestatin. CONCLUSIONS: Aspirin may exert its anti-atherothrombotic effects in part via the inhibition of thrombin action by up-regulating APN/CD13 on endothelial cells."},"publication_date":"2005-04-15","publication_name":{"en":"Atherosclerosis","ja":"Atherosclerosis"},"volume":"183","number":"1","starting_page":"49","ending_page":"55","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.atherosclerosis.2005.03.003"],"issn":["0021-9150"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:66, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15887482","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219701","label":"url"}],"paper_title":{"en":"Successful percutaneous coronary intervention for acute myocardial infarction caused by simultaneous occlusion of two major coronary arteries in patients with diabetes mellitus. A report of two cases.","ja":"Successful percutaneous coronary intervention for acute myocardial infarction caused by simultaneous occlusion of two major coronary arteries in patients with diabetes mellitus. A report of two cases."},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Fujinaga Hiroyuki"},{"name":"Niki Toshiharu"}],"ja":[{"name":"池田 康将"},{"name":"Fujinaga Hiroyuki"},{"name":"Niki Toshiharu"}]},"description":{"en":"Percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) is a common therapeutic method. Although two or more culprit lesions are rarely observed simultaneously in AMI patients, we present two cases of AMI caused by simultaneous occlusion of two major coronary arteries, the left anterior descending and right coronary arteries. In both cases, emergency PCI for the two major vessels was successful. Both patients had type 2 diabetes mellitus, which might have contributed to simultaneous occlusion of the two coronary arteries.","ja":"Percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) is a common therapeutic method. Although two or more culprit lesions are rarely observed simultaneously in AMI patients, we present two cases of AMI caused by simultaneous occlusion of two major coronary arteries, the left anterior descending and right coronary arteries. In both cases, emergency PCI for the two major vessels was successful. Both patients had type 2 diabetes mellitus, which might have contributed to simultaneous occlusion of the two coronary arteries."},"publication_date":"2005-04","publication_name":{"en":"Acta Cardiologica","ja":"Acta Cardiologica"},"volume":"60","number":"2","starting_page":"225","ending_page":"228","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2143/AC.60.2.2005037"],"issn":["0001-5385"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:67, {"insert":{"user_id":"B000241782","type":"published_papers","id":"30376230"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=267166","label":"url"}],"paper_title":{"en":"アミオダロン肺合併症との鑑別を要したマイコプラズマ肺炎合併拡張型心筋症の1例","ja":"アミオダロン肺合併症との鑑別を要したマイコプラズマ肺炎合併拡張型心筋症の1例"},"authors":{"en":[{"name":"山口 普史"},{"name":"Ikeda Yasumasa"},{"name":"藤村 光則"},{"name":"森岡 将臣"},{"name":"橋詰 俊二"},{"name":"加藤 みどり"},{"name":"Aihara Ken-ichi"},{"name":"Akaike Masashi"},{"name":"Azuma Hiroyuki"},{"name":"Matsumoto Toshio"},{"name":"稲山 真美"},{"name":"Hanibuchi Masaki"}],"ja":[{"name":"山口 普史"},{"name":"池田 康将"},{"name":"藤村 光則"},{"name":"森岡 将臣"},{"name":"橋詰 俊二"},{"name":"加藤 みどり"},{"name":"粟飯原 賢一"},{"name":"赤池 雅史"},{"name":"東 博之"},{"name":"松本 俊夫"},{"name":"稲山 真美"},{"name":"埴淵 昌毅"}]},"description":{"en":"52歳男.47歳時に拡張型心筋症と診断され,持続性心室頻拍でアミオダロン150mg/日を開始した.その後,心室頻拍が頻回となり,心臓電気生理学的検査で心室細動が誘発されたため除細動器植込み術を受け,アミオダロンは増量して継続していた.今回,乾性咳が出現し,胸部X線で左右下肺野にスリガラス状陰影を指摘された.検査所見では高度の炎症所見を認めたが,KL-6は正常範囲で,C型肝炎ウイルスとヒトT細胞性白血病ウイルスI型のキャリアであった.胸部CTでは両側下肺野を中心として壁の肥厚を伴う気管支拡張や小葉中心性の粒状・樹枝状の陰影が多発しており,周囲の肺野に淡い濃度上昇を認めた.アミオダロンの副作用か感染症かは判断できなかったが,アミオダロンは中止し,アンピシリンナトリウム・スルバクタムナトリウム合剤を開始すると共にサイトメガロウイルス高力価免疫グロブリン投与を行った.入院10日目にマイコプラズマ抗体異常高値が判明し,マイコプラズマ肺炎と診断しミノサイクリン100mg/日を開始した.その結果,炎症所見,画像所見は徐々に軽快し,アミオダロンも再開して退院となった","ja":"52歳男.47歳時に拡張型心筋症と診断され,持続性心室頻拍でアミオダロン150mg/日を開始した.その後,心室頻拍が頻回となり,心臓電気生理学的検査で心室細動が誘発されたため除細動器植込み術を受け,アミオダロンは増量して継続していた.今回,乾性咳が出現し,胸部X線で左右下肺野にスリガラス状陰影を指摘された.検査所見では高度の炎症所見を認めたが,KL-6は正常範囲で,C型肝炎ウイルスとヒトT細胞性白血病ウイルスI型のキャリアであった.胸部CTでは両側下肺野を中心として壁の肥厚を伴う気管支拡張や小葉中心性の粒状・樹枝状の陰影が多発しており,周囲の肺野に淡い濃度上昇を認めた.アミオダロンの副作用か感染症かは判断できなかったが,アミオダロンは中止し,アンピシリンナトリウム・スルバクタムナトリウム合剤を開始すると共にサイトメガロウイルス高力価免疫グロブリン投与を行った.入院10日目にマイコプラズマ抗体異常高値が判明し,マイコプラズマ肺炎と診断しミノサイクリン100mg/日を開始した.その結果,炎症所見,画像所見は徐々に軽快し,アミオダロンも再開して退院となった"},"publication_date":"2005","publication_name":{"en":"Progress in Medicine","ja":"Progress in Medicine"},"volume":"25","number":"Suppl.1","starting_page":"1552","ending_page":"1556","languages":["jpn"],"referee":true,"identifiers":{"issn":["0287-3648"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:68, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/80016878495/","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15205460","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1362262945661168512/","label":"url"},{"@id":"https://www.scopus.com/pages/publications/4143096123","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219674","label":"url"}],"paper_title":{"en":"Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice","ja":"Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice"},"authors":{"en":[{"name":"Aihara Ken-ichi"},{"name":"Azuma Hiroyuki"},{"name":"Akaike Masashi"},{"name":"Ikeda Yasumasa"},{"name":"Yamashita Michiko"},{"name":"Sudo Toshiki"},{"name":"Hayashi Hideki"},{"name":"Yamada Yoshihisa"},{"name":"Endoh Fuminari"},{"name":"Fujimura Mitsunori"},{"name":"Yoshida Tomonori"},{"name":"Yamaguchi Hiroshi"},{"name":"Hashizume Shunji"},{"name":"Kato Midori"},{"name":"Yoshimura Kimihiro"},{"name":"Yamamoto Yoko"},{"name":"Kato Shigeaki"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"粟飯原 賢一"},{"name":"東 博之"},{"name":"赤池 雅史"},{"name":"池田 康将"},{"name":"山下 理子"},{"name":"Sudo Toshiki"},{"name":"Hayashi Hideki"},{"name":"Yamada Yoshihisa"},{"name":"Endoh Fuminari"},{"name":"Fujimura Mitsunori"},{"name":"Yoshida Tomonori"},{"name":"Yamaguchi Hiroshi"},{"name":"Hashizume Shunji"},{"name":"加藤 みどり"},{"name":"Yoshimura Kimihiro"},{"name":"Yamamoto Yoko"},{"name":"Kato Shigeaki"},{"name":"松本 俊夫"}]},"description":{"en":"Vitamin D metabolites influence the expression of various genes involved in calcium homeostasis, cell differentiation, and regulation of the immune system. Expression of these genes is mediated by the activation of the nuclear vitamin D receptor (VDR). Previous studies have shown that a hormonally active form of vitamin D, 1alpha,25-dihydroxyvitamin D3, exerts anticoagulant effects in cultured monocytic cells. To clarify whether activation of VDR plays any antithrombotic actions in vivo, hemostatic/thrombogenic systems were examined in normocalcemic VDR knock-out (KO) mice on a high calcium diet and compared with wild type and hypocalcemic VDRKO mice that were fed a regular diet. Platelet aggregation was enhanced significantly in normocalcemic VDRKO mice compared with wild type and hypocalcemic VDRKO mice. Aortic endothelial nitric-oxide (NO) synthase expression and urinary NOx excretions were reduced in hypocalcemic VDRKO mice, but not in normocalcemic VDRKO mice. Northern blot and RT-PCR analyses revealed that the gene expression of antithrombin in the liver as well as that of thrombomodulin in the aorta, liver and kidney was down-regulated in hypo- and normocalcemic VDRKO mice. Whereas tissue factor mRNA expression in the liver and kidney was up-regulated in VDRKO mice regardless of plasma calcium level. Furthermore, VDRKO mice manifested an exacerbated multi-organ thrombus formation after exogenous lipopolysaccharide injection regardless of the calcemic conditions. These results demonstrate that activation of nuclear VDR elicits antithrombotic effects in vivo, and suggest that the VDR system may play a physiological role in the maintenance of antithrombotic homeostasis.","ja":"Vitamin D metabolites influence the expression of various genes involved in calcium homeostasis, cell differentiation, and regulation of the immune system. Expression of these genes is mediated by the activation of the nuclear vitamin D receptor (VDR). Previous studies have shown that a hormonally active form of vitamin D, 1alpha,25-dihydroxyvitamin D3, exerts anticoagulant effects in cultured monocytic cells. To clarify whether activation of VDR plays any antithrombotic actions in vivo, hemostatic/thrombogenic systems were examined in normocalcemic VDR knock-out (KO) mice on a high calcium diet and compared with wild type and hypocalcemic VDRKO mice that were fed a regular diet. Platelet aggregation was enhanced significantly in normocalcemic VDRKO mice compared with wild type and hypocalcemic VDRKO mice. Aortic endothelial nitric-oxide (NO) synthase expression and urinary NOx excretions were reduced in hypocalcemic VDRKO mice, but not in normocalcemic VDRKO mice. Northern blot and RT-PCR analyses revealed that the gene expression of antithrombin in the liver as well as that of thrombomodulin in the aorta, liver and kidney was down-regulated in hypo- and normocalcemic VDRKO mice. Whereas tissue factor mRNA expression in the liver and kidney was up-regulated in VDRKO mice regardless of plasma calcium level. Furthermore, VDRKO mice manifested an exacerbated multi-organ thrombus formation after exogenous lipopolysaccharide injection regardless of the calcemic conditions. These results demonstrate that activation of nuclear VDR elicits antithrombotic effects in vivo, and suggest that the VDR system may play a physiological role in the maintenance of antithrombotic homeostasis."},"publication_date":"2004-08-20","publication_name":{"en":"The Journal of Biological Chemistry","ja":"The Journal of Biological Chemistry"},"volume":"279","number":"34","starting_page":"35798","ending_page":"35802","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1074/jbc.M404865200"],"issn":["0021-9258"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:69, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11345202","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=219673","label":"url"}],"paper_title":{"en":"Successful combination therapy--flunarizine,pentoxifylline, and cholestyramine--for spur cell anemia","ja":"Successful combination therapy--flunarizine,pentoxifylline, and cholestyramine--for spur cell anemia"},"authors":{"en":[{"name":"Aihara Ken-ichi"},{"name":"Azuma Hiroyuki"},{"name":"Ikeda Yasumasa"},{"name":"Akaike Masashi"},{"name":"Abe Masahiro"},{"name":"Sugihara Takashi"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"粟飯原 賢一"},{"name":"東 博之"},{"name":"池田 康将"},{"name":"赤池 雅史"},{"name":"安倍 正博"},{"name":"Sugihara Takashi"},{"name":"松本 俊夫"}]},"description":{"en":"Spur cell anemia, a hemolytic anemia observed in patients with alcoholic cirrhosis, is characterized by unusual erythrocyte morphology and an increased ratio of free cholesterol to phospholipid in the erythrocyte membrane. The prognosis of spur cell anemia is usually extremely poor, however, we describe here a patient with spur cell anemia who was successfully treated with combination therapy consisting of flunarizine, pentoxifylline, and cholestyramine. Initial therapy with flunarizine alone for 6 weeks did not significantly decrease the number of spur cells on peripheral blood smears. So pentoxifylline was added to the regimen. The patient recovered from the anemia, showed remarkable improvement with regard to the hyperbilirubinemia, and the changes were accompanied by a significant decrease in the number of spur cells in peripheral blood smears. To correct the hypercholesterolemia, cholestyramine was added to the regimen, which resulted in a reduction in the serum level of free cholesterol and an increase in the molar ratio of free cholesterol to phospholipid in erythrocyte membrane. However, 6 months later a skin eruption developed that was considered an adverse reaction to the drugs, so the flunarizine and pentoxifylline were discontinued. With cholestyramine therapy alone, the remission of spur cell anemia was maintained for more than 11 months. These observations suggest that non-invasive combination therapy with flunarizine, pentoxifylline, and cholestyramine is effective and valuable in the treatment of patients with spur cell anemia.","ja":"Spur cell anemia, a hemolytic anemia observed in patients with alcoholic cirrhosis, is characterized by unusual erythrocyte morphology and an increased ratio of free cholesterol to phospholipid in the erythrocyte membrane. The prognosis of spur cell anemia is usually extremely poor, however, we describe here a patient with spur cell anemia who was successfully treated with combination therapy consisting of flunarizine, pentoxifylline, and cholestyramine. Initial therapy with flunarizine alone for 6 weeks did not significantly decrease the number of spur cells on peripheral blood smears. So pentoxifylline was added to the regimen. The patient recovered from the anemia, showed remarkable improvement with regard to the hyperbilirubinemia, and the changes were accompanied by a significant decrease in the number of spur cells in peripheral blood smears. To correct the hypercholesterolemia, cholestyramine was added to the regimen, which resulted in a reduction in the serum level of free cholesterol and an increase in the molar ratio of free cholesterol to phospholipid in erythrocyte membrane. However, 6 months later a skin eruption developed that was considered an adverse reaction to the drugs, so the flunarizine and pentoxifylline were discontinued. With cholestyramine therapy alone, the remission of spur cell anemia was maintained for more than 11 months. These observations suggest that non-invasive combination therapy with flunarizine, pentoxifylline, and cholestyramine is effective and valuable in the treatment of patients with spur cell anemia."},"publication_date":"2001-04","publication_name":{"en":"International Journal of Hematology","ja":"International Journal of Hematology"},"volume":"73","number":"3","starting_page":"351","ending_page":"355","languages":["eng"],"referee":true,"identifiers":{"issn":["0925-5710"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:70, {"insert":{"user_id":"B000241782","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/9852729","label":"url"},{"@id":"https://www.scopus.com/pages/publications/0031742881","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=451745","label":"url"}],"paper_title":{"en":"A case of Cowden's disease associated with rectal carcinoid","ja":"A case of Cowden's disease associated with rectal carcinoid"},"authors":{"en":[{"name":"Kitazoe Ken Ichi"},{"name":"Hosijima Yasuo"},{"name":"Aoki Hidetosi"},{"name":"Kurinaga Atsunobu"},{"name":"Ikeda Yasumasa"},{"name":"Shibata Youko"},{"name":"Yosida Tomonori"}],"ja":[{"name":"Kitazoe Ken Ichi"},{"name":"Hosijima Yasuo"},{"name":"Aoki Hidetosi"},{"name":"Kurinaga Atsunobu"},{"name":"池田 康将"},{"name":"Shibata Youko"},{"name":"Yosida Tomonori"}]},"publication_date":"1998-11","publication_name":{"en":"The Japanese Journal of Gastro-enterology","ja":"日本消化器病学会雑誌"},"volume":"95","number":"11","starting_page":"1244","ending_page":"1248","languages":["jpn"],"referee":true,"identifiers":{"issn":["0446-6586"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
==== end registerFile(/WWW/pub2/data/ERD/person/219499/researchmap/published_papers-propagate.jsonl, V4gymaEBn_HdSsNV1q8d) ====
==== begin registerFile(/WWW/pub2/data/ERD/person/219499/researchmap/misc-propagate.jsonl) ====
line:1, {"insert":{"user_id":"B000241782","type":"misc","id":"41903674"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37008337","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=395079","label":"url"}],"paper_title":{"en":"Roles of histone acetylation sites in cardiac hypertrophy and heart failure.","ja":"Roles of histone acetylation sites in cardiac hypertrophy and heart failure."},"authors":{"en":[{"name":"Funamoto Masafumi"},{"name":"Imanishi Masaki"},{"name":"Tsuchiya Koichiro"},{"name":"Ikeda Yasumasa"}],"ja":[{"name":"船本 雅文"},{"name":"今西 正樹"},{"name":"土屋 浩一郎"},{"name":"池田 康将"}]},"description":{"en":"Heart failure results from various physiological and pathological stimuli that lead to cardiac hypertrophy. This pathological process is common in several cardiovascular diseases and ultimately leads to heart failure. The development of cardiac hypertrophy and heart failure involves reprogramming of gene expression, a process that is highly dependent on epigenetic regulation. Histone acetylation is dynamically regulated by cardiac stress. Histone acetyltransferases play an important role in epigenetic remodeling in cardiac hypertrophy and heart failure. The regulation of histone acetyltransferases serves as a bridge between signal transduction and downstream gene reprogramming. Investigating the changes in histone acetyltransferases and histone modification sites in cardiac hypertrophy and heart failure will provide new therapeutic strategies to treat these diseases. This review summarizes the association of histone acetylation sites and histone acetylases with cardiac hypertrophy and heart failure, with emphasis on histone acetylation sites.","ja":"Heart failure results from various physiological and pathological stimuli that lead to cardiac hypertrophy. This pathological process is common in several cardiovascular diseases and ultimately leads to heart failure. The development of cardiac hypertrophy and heart failure involves reprogramming of gene expression, a process that is highly dependent on epigenetic regulation. Histone acetylation is dynamically regulated by cardiac stress. Histone acetyltransferases play an important role in epigenetic remodeling in cardiac hypertrophy and heart failure. The regulation of histone acetyltransferases serves as a bridge between signal transduction and downstream gene reprogramming. Investigating the changes in histone acetyltransferases and histone modification sites in cardiac hypertrophy and heart failure will provide new therapeutic strategies to treat these diseases. This review summarizes the association of histone acetylation sites and histone acetylases with cardiac hypertrophy and heart failure, with emphasis on histone acetylation sites."},"publication_date":"2023-03-15","publication_name":{"en":"Frontiers in Cardiovascular Medicine","ja":"Frontiers in Cardiovascular Medicine"},"volume":"10","languages":["eng"],"identifiers":{"doi":["10.3389/fcvm.2023.1133611"],"issn":["2297-055X"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:2, {"insert":{"user_id":"B000241782","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://ci.nii.ac.jp/naid/130007754372/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390001277399772544/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=361601","label":"url"}],"paper_title":{"en":"Body iron accumulation in obesity, diabetes and complications, and thepossibility of therapeutic application by iron regulation","ja":"肥満・糖尿病とその合併症における生体内鉄蓄積と鉄制限による治療応用への可能性"},"authors":{"en":[{"name":"Horinouchi Yuya"},{"name":"Ikeda Yasumasa"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"堀ノ内 裕也"},{"name":"池田 康将"},{"name":"玉置 俊晃"}]},"description":{"en":"<p>Iron is an essential trace metal element for maintaining vital functions, and it is involved in hemoglobin synthesis, redox reaction, enzyme activity, cell proliferation and apoptosis in various cells. Iron deficient-related diseases represented anemia are well-known, on the other hand, iron overload disease has attracted little attention. Excessive iron produces hydroxyl radicals via Fenton/Haber-Weiss reaction, causing organ damage in hereditary iron overload diseases. Additionally, it has been clarified that iron accumulation is involved in the pathological conditions even in metabolic diseases thought to be unrelated to iron so far. Therefore, the role of iron in the living body has been raised attention again. Recent studies have reported that body iron content is associated with both obesity and diabetes, and iron might be an aggravating factor of obesity and diabetes. We have revealed that iron chelating agent reduced oxidative stress and inflammation, suppressing the development of adipose hypertrophy in KKAy mice. Dietary iron restriction also diminishes oxidative stress, leading to the inhibition of increased albuminuria excretion and glomerular lesions in <i>db/db</i> mice. In this review, we give an outline of the role of iron on obese and diabetes, and diabetic kidney disease, and present the possibility of application to treatment with iron regulation in those disorders.</p>","ja":"<p>鉄は生体内に最も多く存在する生命機能維持に必須の微量金属元素であり，赤血球のヘモグロビン合成，各種細胞における酸化還元反応，酵素活性，細胞増殖ならびにアポトーシスなどに関与する．そのため，貧血に代表される鉄欠乏疾患はよく知られているものの，鉄過剰疾患はあまり注目されてこなかった．過剰な鉄はフェントン/ハーバー・ワイス反応を介して酸化力が強力なヒドロキシルラジカルを生成し，遺伝性鉄過剰疾患における臓器障害の原因となるが，C型肝炎やアルツハイマー病などの従来は鉄と無関係と考えられていた疾患においても鉄が病態に関与していることが明らかとなり，生体内での鉄の役割が改めて注目されている．近年，生体内鉄量の増加が肥満ならびに糖尿病と関連することが示唆されており，鉄は肥満・糖尿病の増悪因子の可能性がある．しかし，肥満・糖尿病における鉄除去の効果については不明であった．我々は，肥満・糖尿病モデルKKAyマウスを用いて，鉄キレート剤投与が酸化ストレスや炎症を低減して，脂肪細胞肥大の進展が抑制されること，糖尿病性腎臓病モデル<i>db/db</i>マウスでは，食餌性鉄制限が酸化ストレスを減少して，アルブミン尿排泄増加や糸球体病変を抑制することで糖尿病性腎臓病の進行抑制につながることを報告した．本稿では，肥満・糖尿病とその合併症における鉄の役割と鉄制限による治療応用への可能性について，我々が明らかにした研究成果を含めて概説する．</p>"},"publication_date":"2019-12","publication_name":{"en":"Folia Pharmacologica Japonica","ja":"日本薬理学雑誌"},"volume":"154","number":"6","starting_page":"316","ending_page":"321","languages":["jpn"],"identifiers":{"doi":["10.1254/fpj.154.316"],"issn":["0015-5691"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:3, {"insert":{"user_id":"B000241782","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://ci.nii.ac.jp/naid/120006464485/","label":"url"},{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2004750","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1050304183898996992/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=347857","label":"url"}],"paper_title":{"en":"The role of iron, a trace nutrient, on diabetes","ja":"糖尿病における微量栄養素「鉄」の役割"},"authors":{"en":[{"name":"Ikeda Yasumasa"}],"ja":[{"name":"池田 康将"}]},"description":{"en":"The nutrient balance is an important factor to keep healthy state in the body. In various nutrients, iron is a most abundant trace metal element. Iron-deficient anemia is often seen in the iron-related disorders, therefore, lots of functional food, drink, and nutritional supplement are widely provided and used to prevent iron deficiency. On the other hand, over iron intake induces excess iron status, causing increased oxidative stress production via catalyzing Fenton reaction. Recent evidences suggest that iron involves the pathological conditions of non-iron accumulating diseases, and the role of iron is noticed again.Diabetes is associated with poor prognosis to develop a variety of complications such as cardiovascular disease and diabetic kidney disease(DKD)in addition to diabetic retinopathy and neuropathy. Moreover, patients with diabetes often present reduced skeletal muscle mass, and it causes more impaired insulin resistance by diminishing glucose uptake. Recent studies have shown that iron content is associated with diabetic and obese condition, and high iron intake increases diabetes risk. We have clarified the favorable effect of iron reduction on obesity and DKD through diminishing oxidative stress. In addition, excess iron caused skeletal muscle atrophy and it was ameliorated by an anti-oxidant drug.Thus, iron plays an important role in diabetes and its complication through oxidative stress production. Further studies are clarifying an important role of trace nutrient including iron and so on, contributing to the development of new therapeutic strategy.","ja":"The nutrient balance is an important factor to keep healthy state in the body. In various nutrients, iron is a most abundant trace metal element. Iron-deficient anemia is often seen in the iron-related disorders, therefore, lots of functional food, drink, and nutritional supplement are widely provided and used to prevent iron deficiency. On the other hand, over iron intake induces excess iron status, causing increased oxidative stress production via catalyzing Fenton reaction. Recent evidences suggest that iron involves the pathological conditions of non-iron accumulating diseases, and the role of iron is noticed again.Diabetes is associated with poor prognosis to develop a variety of complications such as cardiovascular disease and diabetic kidney disease(DKD)in addition to diabetic retinopathy and neuropathy. Moreover, patients with diabetes often present reduced skeletal muscle mass, and it causes more impaired insulin resistance by diminishing glucose uptake. Recent studies have shown that iron content is associated with diabetic and obese condition, and high iron intake increases diabetes risk. We have clarified the favorable effect of iron reduction on obesity and DKD through diminishing oxidative stress. In addition, excess iron caused skeletal muscle atrophy and it was ameliorated by an anti-oxidant drug.Thus, iron plays an important role in diabetes and its complication through oxidative stress production. Further studies are clarifying an important role of trace nutrient including iron and so on, contributing to the development of new therapeutic strategy."},"publication_date":"2018-04-25","publication_name":{"en":"Shikoku Acta Medica","ja":"四国医学雑誌"},"volume":"74","number":"1,2","starting_page":"13","ending_page":"20","languages":["jpn"],"identifiers":{"issn":["0037-3699"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:4, {"insert":{"user_id":"B000241782","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26522430","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84959258899","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=306912","label":"url"}],"paper_title":{"en":"Roles of the Androgen - Androgen Receptor System in Vascular Angiogenesis.","ja":"Roles of the Androgen - Androgen Receptor System in Vascular Angiogenesis."},"authors":{"en":[{"name":"Yoshida Sumiko"},{"name":"Ikeda Yasumasa"},{"name":"Aihara Ken-ichi"}],"ja":[{"name":"吉田 守美子"},{"name":"池田 康将"},{"name":"粟飯原 賢一"}]},"publication_date":"2016-03","publication_name":{"en":"Journal of Atherosclerosis and Thrombosis","ja":"Journal of Atherosclerosis and Thrombosis"},"volume":"23","number":"3","starting_page":"257","ending_page":"265","languages":["eng"],"identifiers":{"doi":["10.5551/jat.31047"],"issn":["1880-3873"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:5, {"insert":{"user_id":"B000241782","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=277203","label":"url"}],"paper_title":{"en":"抗酸化薬","ja":"抗酸化薬"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"publication_date":"2014-04-10","publication_name":{"en":"腎・高血圧の最新治療","ja":"腎・高血圧の最新治療"},"volume":"3","number":"2","starting_page":"93","ending_page":"99","languages":["jpn"],"invited":true,"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:6, {"insert":{"user_id":"B000241782","type":"misc"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/40019952227/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1520290882774966784/","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84892762387","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=274418","label":"url"}],"paper_title":{"en":"Role of Dietary Essential Trace Metals in the Pathogenesis of Diabetes Mellitus","ja":"糖尿病と食事由来金属元素"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"publication_date":"2013-12","publication_name":{"en":"Journal of the The Japan Diabetes Society","ja":"糖尿病"},"volume":"56","number":"12","starting_page":"919","ending_page":"921","languages":["jpn"],"invited":true,"identifiers":{"issn":["0021-437X"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:7, {"insert":{"user_id":"B000241782","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2012649","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22792467","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=253919","label":"url"}],"paper_title":{"en":"Effects of Statins on Cardiorenal Syndrome.","ja":"Effects of Statins on Cardiorenal Syndrome."},"authors":{"en":[{"name":"Yagi Shusuke"},{"name":"Aihara Ken-ichi"},{"name":"Ikeda Yasumasa"},{"name":"Akaike Masashi"},{"name":"Sata Masataka"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"八木 秀介"},{"name":"粟飯原 賢一"},{"name":"池田 康将"},{"name":"赤池 雅史"},{"name":"佐田 政隆"},{"name":"松本 俊夫"}]},"description":{"en":"Cardiovascular disease and renal disease have a close relationship that forms a vicious cycle as a cardiorenal syndrome (CRS). Oxidative stress, endothelial dysfunction, and vascular inflammation could be therapeutic targets when the renin-angiotensin-aldosterone system is activated by accumulation of conventional cardiovascular risk factors; however, a strategy for management of CRS has not been established yet. Statins, HMG-CoA reductase inhibitors, have not only cholesterol-lowering effects but also pleiotropic effects on cardiovascular systems, including anti-inflammatory and antioxidant effects and improvement of nitric oxide bioavailability. Since recent studies have indicated that statins have beneficial effects on chronic kidney disease and heart failure as well as coronary artery disease in cholesterol-lowering-dependent/independent manners, treatment with statins might be a successful strategy for preventing deterioration of CRS.","ja":"Cardiovascular disease and renal disease have a close relationship that forms a vicious cycle as a cardiorenal syndrome (CRS). Oxidative stress, endothelial dysfunction, and vascular inflammation could be therapeutic targets when the renin-angiotensin-aldosterone system is activated by accumulation of conventional cardiovascular risk factors; however, a strategy for management of CRS has not been established yet. Statins, HMG-CoA reductase inhibitors, have not only cholesterol-lowering effects but also pleiotropic effects on cardiovascular systems, including anti-inflammatory and antioxidant effects and improvement of nitric oxide bioavailability. Since recent studies have indicated that statins have beneficial effects on chronic kidney disease and heart failure as well as coronary artery disease in cholesterol-lowering-dependent/independent manners, treatment with statins might be a successful strategy for preventing deterioration of CRS."},"publication_date":"2012-06-26","publication_name":{"en":"International Journal of Vascular Medicine","ja":"International Journal of Vascular Medicine"},"volume":"2012","starting_page":"162545","ending_page":"162545","languages":["eng"],"identifiers":{"doi":["10.1155/2012/162545"],"issn":["2090-2832"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:8, {"insert":{"user_id":"B000241782","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=247531","label":"url"}],"paper_title":{"en":"Iron metabolism in the progression of adipocyte hypertrophy","ja":"Iron metabolism in the progression of adipocyte hypertrophy"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Tajima Soichiro"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"田島 壮一郎"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"publication_date":"2012-06","publication_name":{"en":"The Cell","ja":"細胞"},"volume":"44","number":"6","starting_page":"282","ending_page":"286","languages":["jpn"],"invited":true,"identifiers":{"issn":["1346-7557"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:9, {"insert":{"user_id":"B000241782","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22493003","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=246743","label":"url"}],"paper_title":{"en":"Effects of androgens on cardiovascular remodeling.","ja":"Effects of androgens on cardiovascular remodeling."},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Aihara Ken-ichi"},{"name":"Yoshida Sumiko"},{"name":"Akaike Masashi"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"池田 康将"},{"name":"粟飯原 賢一"},{"name":"吉田 守美子"},{"name":"赤池 雅史"},{"name":"松本 俊夫"}]},"description":{"en":"Androgens, the male sex hormones, exert various biological effects on many target organs through the transcriptional effects of the nuclear androgen receptor (AR). ARs are expressed not only in classical target organs, such as the brain, genital organs, bone, and skeletal muscles, but also in the cardiovascular system. Because the female sex hormones estrogens are well known to protect against cardiovascular disease, sex has been considered to have a significant clinical impact on cardiovascular mortality. However, the influence of androgens on the cardiovascular system has not been fully elucidated. To clarify this issue, we analyzed the effects of administration of angiotensin II and doxorubicin, an anticancer agent, in a loading model in male wild-type and AR-deficient mice. In this review, we focus on the actions of androgens as potential targets for the prevention of cardiovascular diseases in males.","ja":"Androgens, the male sex hormones, exert various biological effects on many target organs through the transcriptional effects of the nuclear androgen receptor (AR). ARs are expressed not only in classical target organs, such as the brain, genital organs, bone, and skeletal muscles, but also in the cardiovascular system. Because the female sex hormones estrogens are well known to protect against cardiovascular disease, sex has been considered to have a significant clinical impact on cardiovascular mortality. However, the influence of androgens on the cardiovascular system has not been fully elucidated. To clarify this issue, we analyzed the effects of administration of angiotensin II and doxorubicin, an anticancer agent, in a loading model in male wild-type and AR-deficient mice. In this review, we focus on the actions of androgens as potential targets for the prevention of cardiovascular diseases in males."},"publication_date":"2012-04-05","publication_name":{"en":"The Journal of Endocrinology","ja":"The Journal of Endocrinology"},"languages":["eng"],"identifiers":{"doi":["10.1530/JOE-12-0126"],"issn":["1479-6805"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:10, {"insert":{"user_id":"B000241782","type":"misc"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/10029400903/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1572543024868677632/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=231192","label":"url"}],"paper_title":{"en":"The role of iron on cardiovascular disease and diabetes mellitus","ja":"循環器疾患と糖尿病における生体内鉄の意義"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"田島 壮一郎"},{"name":"Yamano Noriko"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"田島 壮一郎"},{"name":"山野 範子"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"publication_date":"2011-07-06","publication_name":{"en":"Japanese Journal of Circulation Research","ja":"血管"},"volume":"34","number":"2","starting_page":"75","ending_page":"85","languages":["jpn"],"identifiers":{"issn":["0911-4637"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:11, {"insert":{"user_id":"B000241782","type":"misc"},"similar_merge":{"see_also":[{"@id":"http://repo.lib.tokushima-u.ac.jp/110344","label":"url"},{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2003542","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1050022708923023232/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=230705","label":"url"}],"paper_title":{"en":"Role of Hypoxia-Inducible Factor1a (HIF-1a) in T cells in development of vascular remodeling","ja":"生体の低酸素応答と病態 -血管リモデリングにおける転写因子HIFの関与-"},"authors":{"en":[{"name":"Tomita Shuhei"},{"name":"Imanishi Masaki"},{"name":"Sakurada Takumi"},{"name":"Yamano Noriko"},{"name":"Kihira Yoshitaka"},{"name":"Ikeda Yasumasa"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"冨田 修平"},{"name":"今西 正樹"},{"name":"櫻田 巧"},{"name":"山野 範子"},{"name":"木平 孝高"},{"name":"池田 康将"},{"name":"玉置 俊晃"}]},"description":{"en":"Recent studies have shown that the cellular immune response to the hypoxic microenvironment constructed by vascular remodeling development modulates the resulting pathologic alterations. A major mechanism mediating adaptive responses to reduced oxygen availability is the regulation of transcription by hypoxia-inducible factor1(HIF‐1). Impairment of HIF‐1‐ dependent inflammatory responses in T cells causes an augmented vascular remodeling induced by arterial injury, which is shown as prominent neointimal hyperplasia and increase in infiltration of inflammatory cells at the adventitia in mice lacking Hif‐1α specifically in T cells. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice have shown enhanced production of cytokines in activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. This minireview shows that HIF‐1α in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of the T cell-mediated immune response and suggests potential new therapeutic strategies that target HIF‐1α.","ja":"Recent studies have shown that the cellular immune response to the hypoxic microenvironment constructed by vascular remodeling development modulates the resulting pathologic alterations. A major mechanism mediating adaptive responses to reduced oxygen availability is the regulation of transcription by hypoxia-inducible factor1(HIF‐1). Impairment of HIF‐1‐ dependent inflammatory responses in T cells causes an augmented vascular remodeling induced by arterial injury, which is shown as prominent neointimal hyperplasia and increase in infiltration of inflammatory cells at the adventitia in mice lacking Hif‐1α specifically in T cells. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice have shown enhanced production of cytokines in activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. This minireview shows that HIF‐1α in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of the T cell-mediated immune response and suggests potential new therapeutic strategies that target HIF‐1α."},"publication_date":"2011-04-25","publication_name":{"en":"Shikoku Acta Medica","ja":"四国医学雑誌"},"volume":"67","number":"1, 2","starting_page":"3","ending_page":"6","languages":["jpn"],"identifiers":{"issn":["0037-3699"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:12, {"insert":{"user_id":"B000241782","type":"misc"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21234356","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=237315","label":"url"}],"paper_title":{"en":"Transforming Growth Factor-1 as a Common Target Molecule for Development of Cardiovascular Diseases, Renal Insufficiency and Metabolic Syndrome.","ja":"Transforming Growth Factor-1 as a Common Target Molecule for Development of Cardiovascular Diseases, Renal Insufficiency and Metabolic Syndrome."},"authors":{"en":[{"name":"Aihara Ken-ichi"},{"name":"Ikeda Yasumasa"},{"name":"Yagi Shusuke"},{"name":"Akaike Masashi"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"粟飯原 賢一"},{"name":"池田 康将"},{"name":"八木 秀介"},{"name":"赤池 雅史"},{"name":"松本 俊夫"}]},"description":{"en":"Transforming growth factor-1 (TGF-1) is a polypeptide member of the transforming growth factor superfamily of cytokines. It is a secreted protein that performs many cellular functions including control of cell growth, cell proliferation, cell differentiation and apoptosis. In the cardiovascular system, TGF-1 plays pivotal roles in the pathogenesis of hypertension, restenosis after percutaneous coronary intervention, atherosclerosis, cardiac hypertrophy and heart failure. In addition, TGF-1 has been shown to be increased in adipose tissue of obese subjects with insulin resistance. Furthermore, TGF-1 is a potent initiator of proliferation of renal mesangial cells leading to chronic kidney disease. Some currently available agents can manipulate TGF-1 expression leading to amelioration of cardiovascular diseases. Thus, an understanding of interactions between chronic kidney disease and metabolic syndrome and the development of cardiovascular diseases is an important issue, and attention should be given to TGF-1 as a crucial factor for regulation and modulation of those pathological conditions.","ja":"Transforming growth factor-1 (TGF-1) is a polypeptide member of the transforming growth factor superfamily of cytokines. It is a secreted protein that performs many cellular functions including control of cell growth, cell proliferation, cell differentiation and apoptosis. In the cardiovascular system, TGF-1 plays pivotal roles in the pathogenesis of hypertension, restenosis after percutaneous coronary intervention, atherosclerosis, cardiac hypertrophy and heart failure. In addition, TGF-1 has been shown to be increased in adipose tissue of obese subjects with insulin resistance. Furthermore, TGF-1 is a potent initiator of proliferation of renal mesangial cells leading to chronic kidney disease. Some currently available agents can manipulate TGF-1 expression leading to amelioration of cardiovascular diseases. Thus, an understanding of interactions between chronic kidney disease and metabolic syndrome and the development of cardiovascular diseases is an important issue, and attention should be given to TGF-1 as a crucial factor for regulation and modulation of those pathological conditions."},"publication_date":"2010-12-28","publication_name":{"en":"Cardiology Research and Practice","ja":"Cardiology Research and Practice"},"volume":"2011","starting_page":"175381","ending_page":"175381","languages":["eng"],"identifiers":{"doi":["10.4061/2011/175381"],"issn":["2090-0597"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
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java.net.UnknownHostException: api.researchmap.jp
	at java.base/sun.nio.ch.NioSocketImpl.connect(NioSocketImpl.java:569)
	at java.base/java.net.SocksSocketImpl.connect(SocksSocketImpl.java:307)
	at java.base/java.net.Socket.connect(Socket.java:659)
	at java.base/sun.security.ssl.SSLSocketImpl.connect(SSLSocketImpl.java:304)
	at java.base/sun.net.NetworkClient.doConnect(NetworkClient.java:161)
	at java.base/sun.net.www.http.HttpClient.openServer(HttpClient.java:524)
	at java.base/sun.net.www.http.HttpClient.openServer(HttpClient.java:612)
	at java.base/sun.net.www.protocol.https.HttpsClient.<init>(HttpsClient.java:207)
	at java.base/sun.net.www.protocol.https.HttpsClient.New(HttpsClient.java:289)
	at java.base/sun.net.www.protocol.https.AbstractDelegateHttpsURLConnection.getNewHttpClient(AbstractDelegateHttpsURLConnection.java:196)
	at java.base/sun.net.www.protocol.http.HttpURLConnection.plainConnect0(HttpURLConnection.java:967)
	at java.base/sun.net.www.protocol.http.HttpURLConnection.plainConnect(HttpURLConnection.java:903)
	at java.base/sun.net.www.protocol.http.HttpURLConnection.connect(HttpURLConnection.java:876)
	at java.base/sun.net.www.protocol.https.AbstractDelegateHttpsURLConnection.connect(AbstractDelegateHttpsURLConnection.java:181)
	at java.base/sun.net.www.protocol.https.HttpsURLConnectionImpl.connect(HttpsURLConnectionImpl.java:141)
	at jp.researchmap.RMapAPI.registerFile(RMapAPI.java:781)
	at jp.researchmap.Researchmap$DataSet.writeToFiles(Researchmap.java:372)
	at jp.ac.tokushima_u.edb.erd.ErdPerson.createResearchmapExports(ErdPerson.java:9505)
	at jp.ac.tokushima_u.edb.erd.ErdPerson.createResearchmapExportsAndDownloads(ErdPerson.java:9590)
	at jp.ac.tokushima_u.db.common.TaskWorkers$Task0._executeTask(TaskWorkers.java:163)
	at jp.ac.tokushima_u.db.common.TaskWorkers.execute_a_task(TaskWorkers.java:278)
	at jp.ac.tokushima_u.db.common.TaskWorkers.access$500(TaskWorkers.java:26)
	at jp.ac.tokushima_u.db.common.TaskWorkers$Executor.run(TaskWorkers.java:265)
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