{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/118311","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37164748","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=399093","label":"url"}],"paper_title":{"en":"The impact of nutritional status and changes of body composition on the prognosis of metastatic renal cell carcinoma patients.","ja":"The impact of nutritional status and changes of body composition on the prognosis of metastatic renal cell carcinoma patients."},"authors":{"en":[{"name":"Ozaki Keisuke"},{"name":"Fukawa Tomoya"},{"name":"Daizumoto Kei"},{"name":"Sasaki Yutaro"},{"name":"Ueno Yoshiteru"},{"name":"Tsuda Megumi"},{"name":"Uchida Takayuki"},{"name":"Kusuhara Yoshito"},{"name":"Yamamoto Yasuyo"},{"name":"Yamaguchi Kunihisa"},{"name":"Takahashi Masayuki"},{"name":"Kanayama Hiro-omi"}],"ja":[{"name":"Ozaki Keisuke"},{"name":"布川 朋也"},{"name":"大豆本 圭"},{"name":"佐々木 雄太郎"},{"name":"Ueno Yoshiteru"},{"name":"津田 恵"},{"name":"内田 貴之"},{"name":"楠原 義人"},{"name":"山本 恭代"},{"name":"山口 邦久"},{"name":"高橋 正幸"},{"name":"金山 博臣"}]},"description":{"en":"Nutritional status of mRCC patients may predict changes in body composition and be associated with their prognosis. J. Med. Invest. 70 : 80-87, February, 2023.","ja":"Nutritional status of mRCC patients may predict changes in body composition and be associated with their prognosis. J. Med. Invest. 70 : 80-87, February, 2023."},"publication_date":"2023","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.70","number":"No.1.2","starting_page":"80","ending_page":"87","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.70.80"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35977398","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=396622","label":"url"}],"paper_title":{"en":"Morin improves dexamethasone-induced muscle atrophy by modulating atrophy-related genes and oxidative stress in female mice.","ja":"Morin improves dexamethasone-induced muscle atrophy by modulating atrophy-related genes and oxidative stress in female mice."},"authors":{"en":[{"name":"ULLA ANAYT"},{"name":"Osaki Kanae"},{"name":"Rahman Md Mizanur"},{"name":"Nakao Reiko"},{"name":"Uchida Takayuki"},{"name":"Maru Isafumi"},{"name":"Mawatari Kazuaki"},{"name":"Fukawa Tomoya"},{"name":"Kanayama Hiro-omi"},{"name":"Sakakibara Iori"},{"name":"Hirasaka Katsuya"},{"name":"Nikawa Takeshi"}],"ja":[{"name":"ウラ アナイツト"},{"name":"Osaki Kanae"},{"name":"Rahman Md Mizanur"},{"name":"中尾 玲子"},{"name":"内田 貴之"},{"name":"Maru Isafumi"},{"name":"馬渡 一諭"},{"name":"布川 朋也"},{"name":"金山 博臣"},{"name":"榊原 伊織"},{"name":"平坂 勝也"},{"name":"二川 健"}]},"description":{"en":"This study investigated the effect of morin, a flavonoid, on dexamethasone-induced muscle atrophy in C57BL/6J female mice. Dexamethasone (10 mg/kg body weight) for 10 days significantly reduced body weight, gastrocnemius and tibialis anterior muscle mass, and muscle protein in mice. Dexamethasone significantly upregulated muscle atrophy-associated ubiquitin ligases, including atrogin-1 and MuRF-1, and the upstream transcription factors FoxO3a and Klf15. Additionally, dexamethasone significantly induced the expression of oxidative stress-sensitive ubiquitin ligase Cbl-b and the accumulation of the oxidative stress markers malondialdehyde and advanced protein oxidation products in both the plasma and skeletal muscle samples. Intriguingly, morin treatment (20 mg/kg body weight) for 17 days effectively attenuated the loss of muscle mass and muscle protein and suppressed the expression of ubiquitin ligases while reducing the expression of upstream transcriptional factors. Therefore, morin might act as a potential therapeutic agent to attenuate muscle atrophy by modulating atrophy-inducing genes and preventing oxidative stress.","ja":"This study investigated the effect of morin, a flavonoid, on dexamethasone-induced muscle atrophy in C57BL/6J female mice. Dexamethasone (10 mg/kg body weight) for 10 days significantly reduced body weight, gastrocnemius and tibialis anterior muscle mass, and muscle protein in mice. Dexamethasone significantly upregulated muscle atrophy-associated ubiquitin ligases, including atrogin-1 and MuRF-1, and the upstream transcription factors FoxO3a and Klf15. Additionally, dexamethasone significantly induced the expression of oxidative stress-sensitive ubiquitin ligase Cbl-b and the accumulation of the oxidative stress markers malondialdehyde and advanced protein oxidation products in both the plasma and skeletal muscle samples. Intriguingly, morin treatment (20 mg/kg body weight) for 17 days effectively attenuated the loss of muscle mass and muscle protein and suppressed the expression of ubiquitin ligases while reducing the expression of upstream transcriptional factors. Therefore, morin might act as a potential therapeutic agent to attenuate muscle atrophy by modulating atrophy-inducing genes and preventing oxidative stress."},"publication_date":"2022-09-23","publication_name":{"en":"Bioscience, Biotechnology, and Biochemistry","ja":"Bioscience, Biotechnology, and Biochemistry"},"volume":"Vol.86","number":"No.10","starting_page":"1448","ending_page":"1458","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1093/bbb/zbac140"],"issn":["1347-6947"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117429","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35318262","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=391703","label":"url"}],"paper_title":{"en":"All-trans retinoic acid changes muscle fiber type via increasing GADD34 dependent on MAPK signal.","ja":"All-trans retinoic acid changes muscle fiber type via increasing GADD34 dependent on MAPK signal."},"authors":{"en":[{"name":"Adachi Yuichiro"},{"name":"Masuda Masashi"},{"name":"Sakakibara Iori"},{"name":"Uchida Takayuki"},{"name":"Niida Yuki"},{"name":"Mori Yuki"},{"name":"Kamei Yuki"},{"name":"Okumura Yosuke"},{"name":"Ohminami Hirokazu"},{"name":"Ohnishi Kohta"},{"name":"Okumura Hisami"},{"name":"Nikawa Takeshi"},{"name":"Taketani Yutaka"}],"ja":[{"name":"足立 雄一郎"},{"name":"増田 真志"},{"name":"榊原 伊織"},{"name":"内田 貴之"},{"name":"Niida Yuki"},{"name":"森 優樹"},{"name":"亀井 優輝"},{"name":"奥村 陽介"},{"name":"大南 博和"},{"name":"大西 康太"},{"name":"奥村 仙示"},{"name":"二川 健"},{"name":"竹谷 豊"}]},"description":{"en":"All-trans retinoic acid (ATRA) increases the sensitivity to unfolded protein response in differentiating leukemic blasts. The downstream transcriptional factor of PERK, a major arm of unfolded protein response, regulates muscle differentiation. However, the role of growth arrest and DNA damage-inducible protein 34 (GADD34), one of the downstream factors of PERK, and the effects of ATRA on GADD34 expression in muscle remain unclear. In this study, we identified ATRA increased the GADD34 expression independent of the PERK signal in the gastrocnemius muscle of mice. ATRA up-regulated GADD34 expression through the transcriptional activation of gene via inhibiting the interaction of homeobox Six1 and transcription co-repressor TLE3 with the MEF3-binding site on the gene promoter in skeletal muscle. ATRA also inhibited the interaction of TTP, which induces mRNA degradation, with AU-rich element on mRNA via p-38 MAPK, resulting in the instability of mRNA. Overexpressed GADD34 in C2C12 cells changes the type of myosin heavy chain in myotubes. These results suggest ATRA increases GADD34 expression via transcriptional and post-transcriptional regulation, which changes muscle fiber type.","ja":"All-trans retinoic acid (ATRA) increases the sensitivity to unfolded protein response in differentiating leukemic blasts. The downstream transcriptional factor of PERK, a major arm of unfolded protein response, regulates muscle differentiation. However, the role of growth arrest and DNA damage-inducible protein 34 (GADD34), one of the downstream factors of PERK, and the effects of ATRA on GADD34 expression in muscle remain unclear. In this study, we identified ATRA increased the GADD34 expression independent of the PERK signal in the gastrocnemius muscle of mice. ATRA up-regulated GADD34 expression through the transcriptional activation of gene via inhibiting the interaction of homeobox Six1 and transcription co-repressor TLE3 with the MEF3-binding site on the gene promoter in skeletal muscle. ATRA also inhibited the interaction of TTP, which induces mRNA degradation, with AU-rich element on mRNA via p-38 MAPK, resulting in the instability of mRNA. Overexpressed GADD34 in C2C12 cells changes the type of myosin heavy chain in myotubes. These results suggest ATRA increases GADD34 expression via transcriptional and post-transcriptional regulation, which changes muscle fiber type."},"publication_date":"2022-03-22","publication_name":{"en":"Life Science Alliance","ja":"Life Science Alliance"},"volume":"Vol.5","number":"No.7","languages":["eng"],"referee":true,"identifiers":{"doi":["10.26508/lsa.202101345"],"issn":["2575-1077"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/116937","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35466134","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=387076","label":"url"}],"paper_title":{"en":"Additional effects of simultaneous treatment with C14-Cblin and celastrol on the clinorotation-induced rat L6 myotube atrophy","ja":"Additional effects of simultaneous treatment with C14-Cblin and celastrol on the clinorotation-induced rat L6 myotube atrophy"},"authors":{"en":[{"name":"Kanako Kitahata"},{"name":"Uchida Takayuki"},{"name":"Runa Taniguchi"},{"name":"Ayano Kato"},{"name":"Sugiura Kosuke"},{"name":"Sakakibara Iori"},{"name":"Motoko Oarada"},{"name":"Fukawa Tomoya"},{"name":"Park Junsoo"},{"name":"Choi Inho"},{"name":"Nikawa Takeshi"}],"ja":[{"name":"北畑 香菜子"},{"name":"内田 貴之"},{"name":"谷口 瑠菜"},{"name":"加藤 彩乃"},{"name":"杉浦 宏祐"},{"name":"榊原 伊織"},{"name":"Motoko Oarada"},{"name":"布川 朋也"},{"name":"Park Junsoo"},{"name":"Choi Inho"},{"name":"二川 健"}]},"description":{"en":"Two novel reagents, N-myristoylated Cbl-b inhibitory peptide (C14-Cblin) and celastrol, a quinone methide triterpene, are reported to be effective in preventing myotube atrophy. The combined effects of C14-Cblin and celastrol on rat L6 myotubes atrophy induced by 3D-clinorotation, a simulated microgravity model, was investigated in the present study. We first examined their effects on expression in atrogenes. Increase in MAFbx1/atrogin-1 and MuRF-1 by 3D-clinorotation was significantly suppressed by treatment with C14-Cblin or celastrol, but there was no additive effect of simultaneous treatment. However, celastrol significantly suppressed the upregulation of Cbl-b and HSP70 by 3D-clinorotation. Whereas 3D-clinorotation decreased the protein level of IRS-1 in L6 myotubes, C14-Cblin and celastrol inhibited the degradation of IRS-1. C14-Cblin and celastrol promoted the phosphorylation of FOXO3a even in microgravity condition. Simultaneous administration of C14-Cblin and celastrol had shown little additive effect in reversing the impairment of IGF-1 signaling by 3D-clinorotation. While 3D-clinorotation-induced marked oxidative stress in L6 myotubes, celastrol suppressed 3D-clinorotation-induced ROS production. Finally, the C14-Cblin and celastrol-treated groups were inhibited decrease in L6 myotube diameter and increased the protein content of slow-twitch MyHC cultured under 3D-clinorotation. The simultaneous treatment of C14-Cblin and celastrol additively prevented 3D-clinorotation-induced myotube atrophy than single treatment. J. Med. Invest. 69 : 127-134, February, 2022.","ja":"Two novel reagents, N-myristoylated Cbl-b inhibitory peptide (C14-Cblin) and celastrol, a quinone methide triterpene, are reported to be effective in preventing myotube atrophy. The combined effects of C14-Cblin and celastrol on rat L6 myotubes atrophy induced by 3D-clinorotation, a simulated microgravity model, was investigated in the present study. We first examined their effects on expression in atrogenes. Increase in MAFbx1/atrogin-1 and MuRF-1 by 3D-clinorotation was significantly suppressed by treatment with C14-Cblin or celastrol, but there was no additive effect of simultaneous treatment. However, celastrol significantly suppressed the upregulation of Cbl-b and HSP70 by 3D-clinorotation. Whereas 3D-clinorotation decreased the protein level of IRS-1 in L6 myotubes, C14-Cblin and celastrol inhibited the degradation of IRS-1. C14-Cblin and celastrol promoted the phosphorylation of FOXO3a even in microgravity condition. Simultaneous administration of C14-Cblin and celastrol had shown little additive effect in reversing the impairment of IGF-1 signaling by 3D-clinorotation. While 3D-clinorotation-induced marked oxidative stress in L6 myotubes, celastrol suppressed 3D-clinorotation-induced ROS production. Finally, the C14-Cblin and celastrol-treated groups were inhibited decrease in L6 myotube diameter and increased the protein content of slow-twitch MyHC cultured under 3D-clinorotation. The simultaneous treatment of C14-Cblin and celastrol additively prevented 3D-clinorotation-induced myotube atrophy than single treatment. J. Med. Invest. 69 : 127-134, February, 2022."},"publication_date":"2022-03","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.69","number":"No.1,2","starting_page":"127","ending_page":"134","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.69.127"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36596550","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=396751","label":"url"}],"paper_title":{"en":"Daily Dietary Supplementation with Steamed Soybean Improves Muscle Volume and Strength in Healthy People Lacking Exercise.","ja":"Daily Dietary Supplementation with Steamed Soybean Improves Muscle Volume and Strength in Healthy People Lacking Exercise."},"authors":{"en":[{"name":"Kohno Madoka"},{"name":"ULLA ANAYT"},{"name":"Taniguchi Rina"},{"name":"Ohishi Akane"},{"name":"Hirayama Kako"},{"name":"Takemura Yuma"},{"name":"Takao Shoichiro"},{"name":"Kanazawa Yuki"},{"name":"Matsumoto Yuki"},{"name":"Harada Masafumi"},{"name":"Fukawa Tomoya"},{"name":"Kanayama Hiro-omi"},{"name":"Uchida Takayuki"},{"name":"Suzuki Toshio"},{"name":"Nikawa Takeshi"}],"ja":[{"name":"鴻野 まどか"},{"name":"ウラ アナイツト"},{"name":"谷口 瑠菜"},{"name":"大石 あかね"},{"name":"平山 楓子"},{"name":"竹村 祐馬"},{"name":"髙尾 正一郎"},{"name":"金澤 裕樹"},{"name":"松元 友暉"},{"name":"原田 雅史"},{"name":"布川 朋也"},{"name":"金山 博臣"},{"name":"内田 貴之"},{"name":"Suzuki Toshio"},{"name":"二川 健"}]},"description":{"en":"Various dietary protein supplements are used by the elderly and bedridden to maintain their skeletal muscle mass and functions. High-quality proteins act as an anabolic driver and help to improve muscle strength and performance. Previously, we reported that soy protein significantly attenuates denervation-induced loss of muscle mass and myofiber cross sectional area in mice with inhibition of ubiquitination and degradation of IRS-1 in tibialis anterior muscle. It also increased muscle volume and strength in bedridden patients. In the present study, we investigated the effects of dietary soybean supplementation on muscle functions in taxi drivers lacking vigorous physical exercise. We conducted a case-control study on 25 healthy, male taxi drivers between the ages of 36 and 71 y performing minimal physical exercise. They were divided into two dietary groups: the soybean diet group (n=13) who ate daily meals (dinner) supplemented with 50 g of steamed soybean for 30 d and the control diet group (n=12) who received no soybean supplement. Next, we measured the muscle cross-sectional area (CSA) and muscle strength and function in both the groups before and after 30 d of soybean intake. The body weights of both diet groups did not differ significantly over time. However, after 30 d of soybean supplementation, the soybean-fed group developed significantly higher muscle CSA and grip strength compared to the control groups. In conclusion, dietary soybean supplementation improved muscle function in taxi drivers who lacked exercise.","ja":"Various dietary protein supplements are used by the elderly and bedridden to maintain their skeletal muscle mass and functions. High-quality proteins act as an anabolic driver and help to improve muscle strength and performance. Previously, we reported that soy protein significantly attenuates denervation-induced loss of muscle mass and myofiber cross sectional area in mice with inhibition of ubiquitination and degradation of IRS-1 in tibialis anterior muscle. It also increased muscle volume and strength in bedridden patients. In the present study, we investigated the effects of dietary soybean supplementation on muscle functions in taxi drivers lacking vigorous physical exercise. We conducted a case-control study on 25 healthy, male taxi drivers between the ages of 36 and 71 y performing minimal physical exercise. They were divided into two dietary groups: the soybean diet group (n=13) who ate daily meals (dinner) supplemented with 50 g of steamed soybean for 30 d and the control diet group (n=12) who received no soybean supplement. Next, we measured the muscle cross-sectional area (CSA) and muscle strength and function in both the groups before and after 30 d of soybean intake. The body weights of both diet groups did not differ significantly over time. However, after 30 d of soybean supplementation, the soybean-fed group developed significantly higher muscle CSA and grip strength compared to the control groups. In conclusion, dietary soybean supplementation improved muscle function in taxi drivers who lacked exercise."},"publication_date":"2022","publication_name":{"en":"Journal of Nutritional Science and Vitaminology","ja":"Journal of Nutritional Science and Vitaminology"},"volume":"Vol.68","number":"No.6","starting_page":"521","ending_page":"526","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3177/jnsv.68.521"],"issn":["1881-7742"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.mdpi.com/2076-3417/11/21/10436/pdf","label":"url"},{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117280","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=387078","label":"url"}],"paper_title":{"en":"Transcriptome Analyses of In Vitro Exercise Models by Clenbuterol Supplementation or Electrical Pulse Stimulation","ja":"Transcriptome Analyses of In Vitro Exercise Models by Clenbuterol Supplementation or Electrical Pulse Stimulation"},"authors":{"en":[{"name":"Fukushima Taku"},{"name":"Takata Miho"},{"name":"Kato Ayano"},{"name":"Uchida Takayuki"},{"name":"Nikawa Takeshi"},{"name":"Sakakibara Iori"}],"ja":[{"name":"福島 拓"},{"name":"高田 実穂"},{"name":"加藤 彩乃"},{"name":"内田 貴之"},{"name":"二川 健"},{"name":"榊原 伊織"}]},"publication_date":"2021-11","publication_name":{"en":"Applied Sciences","ja":"Applied Sciences"},"volume":"Vol.11","number":"No.21","starting_page":"10436","ending_page":"10436","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/app112110436"],"issn":["2076-3417"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.nature.com/articles/s41538-021-00108-0.pdf","label":"url"},{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117588","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/34504092","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=387064","label":"url"}],"paper_title":{"en":"Oral intake of rice overexpressing ubiquitin ligase inhibitory pentapeptide prevents atrophy in denervated skeletal muscle","ja":"Oral intake of rice overexpressing ubiquitin ligase inhibitory pentapeptide prevents atrophy in denervated skeletal muscle"},"authors":{"en":[{"name":"Nakao Reiko"},{"name":"Weilin Shen"},{"name":"Yasuka Shimajiri"},{"name":"Kumiko Kainou"},{"name":"Yuki Sato"},{"name":"Anayt Ulla"},{"name":"Ohnishi Kohta"},{"name":"Miyuki Ninomiya"},{"name":"Ayako Ohno"},{"name":"Uchida Takayuki"},{"name":"Mitsuru Tanaka"},{"name":"Kazuhito Akama"},{"name":"Toshiro Matsui"},{"name":"Nikawa Takeshi"}],"ja":[{"name":"中尾 玲子"},{"name":"Weilin Shen"},{"name":"Yasuka Shimajiri"},{"name":"Kumiko Kainou"},{"name":"佐藤 友紀"},{"name":"ANAYTULLA"},{"name":"大西 康太"},{"name":"二宮 みゆき"},{"name":"Ayako Ohno"},{"name":"内田 貴之"},{"name":"Mitsuru Tanaka"},{"name":"Kazuhito Akama"},{"name":"Toshiro Matsui"},{"name":"二川 健"}]},"description":{"en":"We previously reported that intramuscular injections of ubiquitin ligase CBLB inhibitory pentapeptide (Cblin; Asp-Gly-pTyr-Met-Pro) restored lost muscle mass caused by sciatic denervation. Here, we detected Cblin on the basolateral side of Caco-2 cells after being placed on the apical side, and found that cytochalasin D, a tight junction opener, enhanced Cblin transport. Orally administered Cblin was found in rat plasma, indicating that intact Cblin was absorbed in vitro and in vivo. Furthermore, transgenic Cblin peptide-enriched rice (CbR) prevented the denervation-induced loss of muscle mass and the upregulation of muscle atrophy-related ubiquitin ligases in mice. These findings indicated that CbR could serve as an alternative treatment for muscle atrophy.","ja":"We previously reported that intramuscular injections of ubiquitin ligase CBLB inhibitory pentapeptide (Cblin; Asp-Gly-pTyr-Met-Pro) restored lost muscle mass caused by sciatic denervation. Here, we detected Cblin on the basolateral side of Caco-2 cells after being placed on the apical side, and found that cytochalasin D, a tight junction opener, enhanced Cblin transport. Orally administered Cblin was found in rat plasma, indicating that intact Cblin was absorbed in vitro and in vivo. Furthermore, transgenic Cblin peptide-enriched rice (CbR) prevented the denervation-induced loss of muscle mass and the upregulation of muscle atrophy-related ubiquitin ligases in mice. These findings indicated that CbR could serve as an alternative treatment for muscle atrophy."},"publication_date":"2021-09-09","publication_name":{"en":"NPJ Science of Food","ja":"NPJ Science of Food"},"volume":"Vol.5","number":"No.1","starting_page":"25","ending_page":"25","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s41538-021-00108-0"],"issn":["2396-8370"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/116581","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/34185335","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85109422486&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=382763","label":"url"}],"paper_title":{"en":"MuRF1 deficiency prevents age-related fat weight gain, possibly through accumulation of PDK4 in skeletal muscle mitochondria in older mice","ja":"MuRF1 deficiency prevents age-related fat weight gain, possibly through accumulation of PDK4 in skeletal muscle mitochondria in older mice"},"authors":{"en":[{"name":"Sugiura Kosuke"},{"name":"Hirasaka Katsuya"},{"name":"Maeda Tasuku"},{"name":"Uchida Takayuki"},{"name":"Kishimoto Koji"},{"name":"Oarada Motoko"},{"name":"Labeit Siegfried"},{"name":"Ulla Anayt"},{"name":"Sakakibara Iori"},{"name":"Nakao Reiko"},{"name":"Sairyo Koichi"},{"name":"Nikawa Takeshi"}],"ja":[{"name":"杉浦 宏祐"},{"name":"平坂 勝也"},{"name":"Maeda Tasuku"},{"name":"内田 貴之"},{"name":"岸本 幸治"},{"name":"Oarada Motoko"},{"name":"Labeit Siegfried"},{"name":"Ulla Anayt"},{"name":"榊原 伊織"},{"name":"中尾 玲子"},{"name":"西良 浩一"},{"name":"二川 健"}]},"publication_date":"2021-06","publication_name":{"en":"Journal of Orthopaedic Research","ja":"Journal of Orthopaedic Research"},"volume":"Vol.40","number":"No.5","starting_page":"1026","ending_page":"1038","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/jor.25131"],"issn":["1554-527X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/116344","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33848514","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=387067","label":"url"}],"paper_title":{"en":"Morin attenuates dexamethasone-mediated oxidative stress and atrophy in mouse C2C12 skeletal myotubes","ja":"Morin attenuates dexamethasone-mediated oxidative stress and atrophy in mouse C2C12 skeletal myotubes"},"authors":{"en":[{"name":"Anayt Ulla"},{"name":"Uchida Takayuki"},{"name":"Yukari Miki"},{"name":"Sugiura Kosuke"},{"name":"Atsushi Higashitani"},{"name":"Takeshi Kobayashi"},{"name":"Ayako Ohno"},{"name":"Nakao Reiko"},{"name":"Hirasaka Katsuya"},{"name":"Sakakibara Iori"},{"name":"Nikawa Takeshi"}],"ja":[{"name":"ANAYTULLA"},{"name":"内田 貴之"},{"name":"三木 裕加里"},{"name":"杉浦 宏祐"},{"name":"Atsushi Higashitani"},{"name":"Takeshi Kobayashi"},{"name":"Ayako Ohno"},{"name":"中尾 玲子"},{"name":"平坂 勝也"},{"name":"榊原 伊織"},{"name":"二川 健"}]},"description":{"en":"Glucocorticoids are the drugs most commonly used to manage inflammatory diseases. However, they are prone to inducing muscle atrophy by increasing muscle proteolysis and decreasing protein synthesis. Various studies have demonstrated that antioxidants can mitigate glucocorticoid-induced skeletal muscle atrophy. Here, we investigated the effect of a potent antioxidative natural flavonoid, morin, on the muscle atrophy and oxidative stress induced by dexamethasone (Dex) using mouse C2C12 skeletal myotubes. Dex (10 μM) enhanced the production of reactive oxygen species (ROS) in C2C12 myotubes via glucocorticoid receptor. Moreover, Dex administration reduced the diameter and expression levels of the myosin heavy chain protein in C2C12 myotubes, together with the upregulation of muscle atrophy-associated ubiquitin ligases, such as muscle atrophy F-box protein 1/atrogin-1, muscle ring finger protein-1, and casitas B-lineage lymphoma proto-oncogene-b. Dex also significantly decreased phosphorylated Foxo3a and increased total Foxo3a expression. Interestingly, Dex-induced ROS accumulation and Foxo3a expression were inhibited by morin (10 μM) pretreatment. Morin also prevented the Dex-induced reduction of myotube thickness, together with muscle protein degradation and suppression of the upregulation of atrophy-associated ubiquitin ligases. In conclusion, our results suggest that morin effectively prevents glucocorticoid-induced muscle atrophy by reducing oxidative stress.","ja":"Glucocorticoids are the drugs most commonly used to manage inflammatory diseases. However, they are prone to inducing muscle atrophy by increasing muscle proteolysis and decreasing protein synthesis. Various studies have demonstrated that antioxidants can mitigate glucocorticoid-induced skeletal muscle atrophy. Here, we investigated the effect of a potent antioxidative natural flavonoid, morin, on the muscle atrophy and oxidative stress induced by dexamethasone (Dex) using mouse C2C12 skeletal myotubes. Dex (10 μM) enhanced the production of reactive oxygen species (ROS) in C2C12 myotubes via glucocorticoid receptor. Moreover, Dex administration reduced the diameter and expression levels of the myosin heavy chain protein in C2C12 myotubes, together with the upregulation of muscle atrophy-associated ubiquitin ligases, such as muscle atrophy F-box protein 1/atrogin-1, muscle ring finger protein-1, and casitas B-lineage lymphoma proto-oncogene-b. Dex also significantly decreased phosphorylated Foxo3a and increased total Foxo3a expression. Interestingly, Dex-induced ROS accumulation and Foxo3a expression were inhibited by morin (10 μM) pretreatment. Morin also prevented the Dex-induced reduction of myotube thickness, together with muscle protein degradation and suppression of the upregulation of atrophy-associated ubiquitin ligases. In conclusion, our results suggest that morin effectively prevents glucocorticoid-induced muscle atrophy by reducing oxidative stress."},"publication_date":"2021-04-10","publication_name":{"en":"Archives of Biochemistry and Biophysics","ja":"Archives of Biochemistry and Biophysics"},"volume":"Vol.704","starting_page":"108873","ending_page":"108873","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.abb.2021.108873"],"issn":["1096-0384"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/116285","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33530505","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85099928726&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=381804","label":"url"}],"paper_title":{"en":"Astaxanthin Prevents Atrophy in Slow Muscle Fibers by Inhibiting Mitochondrial Reactive Oxygen Species via a Mitochondria-Mediated Apoptosis Pathway","ja":"Astaxanthin Prevents Atrophy in Slow Muscle Fibers by Inhibiting Mitochondrial Reactive Oxygen Species via a Mitochondria-Mediated Apoptosis Pathway"},"authors":{"en":[{"name":"Luchuanyang Sun"},{"name":"Nobuyuki Miyaji"},{"name":"Min Yang"},{"name":"Edward M Mills"},{"name":"Shigeto Taniyama"},{"name":"Uchida Takayuki"},{"name":"Nikawa Takeshi"},{"name":"Jifeng Li"},{"name":"Jie Shi"},{"name":"Katsuyasu Tachibana"},{"name":"Hirasaka Katsuya"}],"ja":[{"name":"Luchuanyang Sun"},{"name":"Nobuyuki Miyaji"},{"name":"Min Yang"},{"name":"Edward M Mills"},{"name":"Shigeto Taniyama"},{"name":"内田 貴之"},{"name":"二川 健"},{"name":"Jifeng Li"},{"name":"Jie Shi"},{"name":"Katsuyasu Tachibana"},{"name":"平坂 勝也"}]},"description":{"en":"Astaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in the lipid bilayer. This study aimed to investigate the effects of AX on muscle-atrophy-mediated disturbance of mitochondria, which have a lipid bilayer. Tail suspension was used to establish a muscle-atrophied mouse model. AX diet fed to tail-suspension mice prevented loss of muscle weight, inhibited the decrease of myofiber size, and restrained the increase of hydrogen peroxide (HO) production in the soleus muscle. Additionally, AX improved downregulation of mitochondrial respiratory chain complexes I and III in the soleus muscle after tail suspension. Meanwhile, AX promoted mitochondrial biogenesis by upregulating the expressions of , , in the soleus muscle of tail-suspension mice. To confirm the AX phenotype in the soleus muscle, we examined its effects on mitochondria using Sol8 myotubes derived from the soleus muscle. We found that AX was preferentially detected in the mitochondrial fraction; it significantly suppressed mitochondrial reactive oxygen species (ROS) production in Sol8 myotubes. Moreover, AX inhibited the activation of caspase 3 via inhibiting the release of cytochrome c into the cytosol in antimycin A-treated Sol8 myotubes. These results suggested that AX protected the functional stability of mitochondria, alleviated mitochondrial oxidative stress and mitochondria-mediated apoptosis, and thus, prevented muscle atrophy.","ja":"Astaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in the lipid bilayer. This study aimed to investigate the effects of AX on muscle-atrophy-mediated disturbance of mitochondria, which have a lipid bilayer. Tail suspension was used to establish a muscle-atrophied mouse model. AX diet fed to tail-suspension mice prevented loss of muscle weight, inhibited the decrease of myofiber size, and restrained the increase of hydrogen peroxide (HO) production in the soleus muscle. Additionally, AX improved downregulation of mitochondrial respiratory chain complexes I and III in the soleus muscle after tail suspension. Meanwhile, AX promoted mitochondrial biogenesis by upregulating the expressions of , , in the soleus muscle of tail-suspension mice. To confirm the AX phenotype in the soleus muscle, we examined its effects on mitochondria using Sol8 myotubes derived from the soleus muscle. We found that AX was preferentially detected in the mitochondrial fraction; it significantly suppressed mitochondrial reactive oxygen species (ROS) production in Sol8 myotubes. Moreover, AX inhibited the activation of caspase 3 via inhibiting the release of cytochrome c into the cytosol in antimycin A-treated Sol8 myotubes. These results suggested that AX protected the functional stability of mitochondria, alleviated mitochondrial oxidative stress and mitochondria-mediated apoptosis, and thus, prevented muscle atrophy."},"publication_date":"2021-01-26","publication_name":{"en":"Nutrients","ja":"Nutrients"},"volume":"Vol.13","number":"No.379","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/nu13020379"],"issn":["2072-6643"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/116821","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33820827","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85103997820&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=382709","label":"url"}],"paper_title":{"en":"Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza.","ja":"Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza."},"authors":{"en":[{"name":"Ayako Ohno"},{"name":"Maita Nobuo"},{"name":"Takanori Tabata"},{"name":"Hikaru Nagano"},{"name":"Kyohei Arita"},{"name":"Mariko Ariyoshi"},{"name":"Uchida Takayuki"},{"name":"Nakao Reiko"},{"name":"Anayt Ulla"},{"name":"Sugiura Kosuke"},{"name":"Kishimoto Koji"},{"name":"Shigetada Teshima-Kondo"},{"name":"Yuushi Okumura"},{"name":"Nikawa Takeshi"}],"ja":[{"name":"大野 綾子"},{"name":"真板 宣夫"},{"name":"Takanori Tabata"},{"name":"Hikaru Nagano"},{"name":"Kyohei Arita"},{"name":"Mariko Ariyoshi"},{"name":"内田 貴之"},{"name":"中尾 玲子"},{"name":"ANAYTULLA"},{"name":"杉浦 宏祐"},{"name":"岸本 幸治"},{"name":"Shigetada Teshima-Kondo"},{"name":"Yuushi Okumura"},{"name":"二川 健"}]},"description":{"en":"Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19.","ja":"Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19."},"publication_date":"2021-01","publication_name":{"en":"Life Science Alliance","ja":"Life Science Alliance"},"volume":"Vol.4","number":"No.6","starting_page":"e202000849","ending_page":"e202000849","languages":["eng"],"referee":true,"identifiers":{"doi":["10.26508/LSA.202000849"],"issn":["2575-1077"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://ci.nii.ac.jp/naid/130007894915/","label":"url"},{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/114720","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33041516","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390566775163696384/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=369577","label":"url"}],"paper_title":{"en":"Reduction of stearoyl-CoA desaturase (SCD) contributes muscle atrophy through the excess endoplasmic reticulum stress in chronic kidney disease","ja":"Reduction of stearoyl-CoA desaturase (SCD) contributes muscle atrophy through the excess endoplasmic reticulum stress in chronic kidney disease"},"authors":{"en":[{"name":"Niida Yuki"},{"name":"Masuda Masashi"},{"name":"Adachi Yuichiro"},{"name":"Yoshizawa Aika"},{"name":"Ohminami Hirokazu"},{"name":"Mori Yuki"},{"name":"Ohnishi Kohta"},{"name":"Okumura Hisami"},{"name":"Uchida Takayuki"},{"name":"Nikawa Takeshi"},{"name":"Yamamoto Hironori"},{"name":"Miyazaki Makoto"},{"name":"Taketani Yutaka"}],"ja":[{"name":"Niida Yuki"},{"name":"増田 真志"},{"name":"Adachi Yuichiro"},{"name":"Yoshizawa Aika"},{"name":"大南 博和"},{"name":"Mori Yuki"},{"name":"大西 康太"},{"name":"奥村 仙示"},{"name":"内田 貴之"},{"name":"二川 健"},{"name":"山本 浩範"},{"name":"Miyazaki Makoto"},{"name":"竹谷 豊"}]},"description":{"en":"
Skeletal muscle atrophy is associated with mortality and poor prognosis in patients with chronic kidney disease (CKD). However, underlying mechanism by which CKD causes muscle atrophy has not been completely understood. The quality of lipids (lipoquality), which is defined as the functional features of diverse lipid species, has recently been recognized as the pathology of various diseases. In this study, we investigated the roles of the stearoyl-CoA desaturase (SCD), which catalyzes the conversion of saturated fatty acids into monounsaturated fatty acids, in skeletal muscle on muscle atrophy in CKD model animals. In comparison to control rats, CKD rats decreased the SCD activity and its gene expression in atrophic gastrocnemius muscle. Next, oleic acid blocked the reduction of the thickness of C2C12 myotubes and the increase of the endoplasmic reticulum stress induced by SCD inhibitor. Furthermore, endoplasmic reticulum stress inhibitor ameliorated CKD-induced muscle atrophy (the weakness of grip strength and the decrease of muscle fiber size of gastrocnemius muscle) in mice and the reduction of the thickness of C2C12 myotubes by SCD inhibitor. These results suggest that the repression of SCD activity causes muscle atrophy through excessive endoplasmic reticulum stress in CKD.
","ja":"Skeletal muscle atrophy is associated with mortality and poor prognosis in patients with chronic kidney disease (CKD). However, underlying mechanism by which CKD causes muscle atrophy has not been completely understood. The quality of lipids (lipoquality), which is defined as the functional features of diverse lipid species, has recently been recognized as the pathology of various diseases. In this study, we investigated the roles of the stearoyl-CoA desaturase (SCD), which catalyzes the conversion of saturated fatty acids into monounsaturated fatty acids, in skeletal muscle on muscle atrophy in CKD model animals. In comparison to control rats, CKD rats decreased the SCD activity and its gene expression in atrophic gastrocnemius muscle. Next, oleic acid blocked the reduction of the thickness of C2C12 myotubes and the increase of the endoplasmic reticulum stress induced by SCD inhibitor. Furthermore, endoplasmic reticulum stress inhibitor ameliorated CKD-induced muscle atrophy (the weakness of grip strength and the decrease of muscle fiber size of gastrocnemius muscle) in mice and the reduction of the thickness of C2C12 myotubes by SCD inhibitor. These results suggest that the repression of SCD activity causes muscle atrophy through excessive endoplasmic reticulum stress in CKD.
"},"publication_date":"2020","publication_name":{"en":"Journal of Clinical Biochemistry and Nutrition","ja":"Journal of Clinical Biochemistry and Nutrition"},"volume":"Vol.67","number":"No.2","starting_page":"179","ending_page":"187","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3164/jcbn.20-24"],"issn":["1880-5086"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30389140","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85056802520&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=347594","label":"url"}],"paper_title":{"en":"Morin suppresses cachexia-induced muscle wasting by binding to ribosomal protein S10 in carcinoma cells.","ja":"Morin suppresses cachexia-induced muscle wasting by binding to ribosomal protein S10 in carcinoma cells."},"authors":{"en":[{"name":"Yoshimura Tomohiro"},{"name":"Saitoh Kanae"},{"name":"Sun Luchuanyang"},{"name":"Wang Yao"},{"name":"Taniyama Shigeto"},{"name":"Yamaguchi Kenichi"},{"name":"Uchida Takayuki"},{"name":"Ohkubo Tsutomu"},{"name":"Higashitani Atsushi"},{"name":"Nikawa Takeshi"},{"name":"Tachibana Katsuyasu"},{"name":"Hirasaka Katsuya"}],"ja":[{"name":"Yoshimura Tomohiro"},{"name":"Saitoh Kanae"},{"name":"Sun Luchuanyang"},{"name":"Wang Yao"},{"name":"Taniyama Shigeto"},{"name":"Yamaguchi Kenichi"},{"name":"内田 貴之"},{"name":"Ohkubo Tsutomu"},{"name":"Higashitani Atsushi"},{"name":"二川 健"},{"name":"Tachibana Katsuyasu"},{"name":"Hirasaka Katsuya"}]},"description":{"en":"Cachexia, observed in most cancer patients, is a syndrome that includes wasting of bodily energy reserves and is characterized by muscle atrophy and fat loss. We have previously demonstrated that isoflavones, such as genistein and daidzein, prevent muscle wasting in tumor-bearing mice. In this study, we examined the effect of morin, a flavonoid, on cachexia. The wet weight and myofiber size of muscles in Lewis lung carcinoma (LLC) cell-bearing mice fed a normal diet were decreased, compared with those in control mice fed a normal diet. In contrast, intake of morin prevented the reduction of muscle wet weight and myofiber size. Moreover, the tumor weight in mice fed the morin diet was lower than that in mice fed the normal diet. Both cell viability and protein synthetic ability of LLC cells were reduced by treatment with morin, but C2C12 myotubes were not affected. Binding assay using morin-conjugated magnetic beads identified ribosomal protein S10 (RPS10) as a target protein of morin. Consistent with the result of morin treatment, knockdown of RPS10 suppressed LLC cell viability. These results suggest that morin indirectly prevents muscle wasting induced by cancer cachexia by suppressing cancer growth via binding to RPS10.","ja":"Cachexia, observed in most cancer patients, is a syndrome that includes wasting of bodily energy reserves and is characterized by muscle atrophy and fat loss. We have previously demonstrated that isoflavones, such as genistein and daidzein, prevent muscle wasting in tumor-bearing mice. In this study, we examined the effect of morin, a flavonoid, on cachexia. The wet weight and myofiber size of muscles in Lewis lung carcinoma (LLC) cell-bearing mice fed a normal diet were decreased, compared with those in control mice fed a normal diet. In contrast, intake of morin prevented the reduction of muscle wet weight and myofiber size. Moreover, the tumor weight in mice fed the morin diet was lower than that in mice fed the normal diet. Both cell viability and protein synthetic ability of LLC cells were reduced by treatment with morin, but C2C12 myotubes were not affected. Binding assay using morin-conjugated magnetic beads identified ribosomal protein S10 (RPS10) as a target protein of morin. Consistent with the result of morin treatment, knockdown of RPS10 suppressed LLC cell viability. These results suggest that morin indirectly prevents muscle wasting induced by cancer cachexia by suppressing cancer growth via binding to RPS10."},"publication_date":"2018-10-30","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"Vol.506","number":"No.4","starting_page":"773","ending_page":"779","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbrc.2018.10.184"],"issn":["1090-2104"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/111606","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29532881","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85042801496&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=338763","label":"url"}],"paper_title":{"en":"VEGF pathway-targeting drugs induce evasive adaptation by activation of neuropilin-1/cMet in colon cancer cells.","ja":"VEGF pathway-targeting drugs induce evasive adaptation by activation of neuropilin-1/cMet in colon cancer cells."},"authors":{"en":[{"name":"Tomida Chisato"},{"name":"Yakagishi Naoko"},{"name":"Nagano Hikaru"},{"name":"Uchida Takayuki"},{"name":"Maita Ayako"},{"name":"Hirasaka Katsuya"},{"name":"Nikawa Takeshi"},{"name":"Kondo Shigetada"}],"ja":[{"name":"冨田 知里"},{"name":"Yakagishi Naoko"},{"name":"Nagano Hikaru"},{"name":"内田 貴之"},{"name":"真板 綾子"},{"name":"Hirasaka Katsuya"},{"name":"二川 健"},{"name":"近藤 茂忠"}]},"description":{"en":"Anti-angiogenic therapies targeting vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) are important treatments for a number of human malignancies, including colorectal cancers. However, there is increasing evidence that VEGF/VEGF-R inhibitors promote the adaptive and evasive resistance of tumor cells to the therapies. The mechanism by which the cancer cells become resistant remains unclear. One potential mechanism is that VEGF/VEGF-R blockers directly act on tumor cells independently of anti-angiogenic effects. In this study, the direct effects of an anti-VEGF antibody (bevacizumab) and a VEGF-R tyrosine kinase inhibitor (sunitinib) on the evasive adaptation of colon cancer cells were compared. HCT116 and RKO human colon cancer cell lines were chronically exposed (3 months) to bevacizumab or sunitinib in vitro to establish bevacizumab- and sunitinib-adapted cells, respectively. Transwell migration and invasion assays, western blotting, reverse transcription-quantitative polymerase chain reaction, co-immunoprecipitation analysis, cell survival assays and ELISAs were conducted to analyze the adapted cells. Compared with the control vehicle-treated cells, the two cell models exhibited increased migration and invasion activities to different degrees and through different mechanisms. The bevacizumab-adapted cells, but not in the sunitinib-adapted cells, exhibited redundantly increased expression levels of VEGF/VEGF-R family members, including VEGF-A, placental growth factor, VEGF-C, VEGF-R1 and VEGF-R3. In addition, the phosphorylation levels of VEGF-R1 and VEGF-R3 were increased in the bevacizumab-adapted cells compared with the control cells. Thus, the inhibition of VEGF-R1 and VEGF-R3 decreased the evasive activities of the cells, suggesting that they remained dependent on redundant VEGF/VEGF-R signaling. By contrast, the sunitinib-adapted cells exhibited increased neuropilin-1 (NRP1) expression levels compared with the control cells. In the sunitinib-adapted cells, NRP1 interacted with phosphorylated cMet, and the cMet activation was dependent on NRP1. Thus, NRP1 or cMet blockade suppressed the evasive activation of the sunitinib-adapted cells. These results suggest that the sunitinib-adapted cells switched from a VEGF-R-dependent pathway to an alternative NRP1/cMet-dependent one. The findings of the present study indicate that VEGF/VEGF-R inhibitors directly act on colon cancer cells and activate their evasive adaptation via different mechanisms.","ja":"Anti-angiogenic therapies targeting vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) are important treatments for a number of human malignancies, including colorectal cancers. However, there is increasing evidence that VEGF/VEGF-R inhibitors promote the adaptive and evasive resistance of tumor cells to the therapies. The mechanism by which the cancer cells become resistant remains unclear. One potential mechanism is that VEGF/VEGF-R blockers directly act on tumor cells independently of anti-angiogenic effects. In this study, the direct effects of an anti-VEGF antibody (bevacizumab) and a VEGF-R tyrosine kinase inhibitor (sunitinib) on the evasive adaptation of colon cancer cells were compared. HCT116 and RKO human colon cancer cell lines were chronically exposed (3 months) to bevacizumab or sunitinib in vitro to establish bevacizumab- and sunitinib-adapted cells, respectively. Transwell migration and invasion assays, western blotting, reverse transcription-quantitative polymerase chain reaction, co-immunoprecipitation analysis, cell survival assays and ELISAs were conducted to analyze the adapted cells. Compared with the control vehicle-treated cells, the two cell models exhibited increased migration and invasion activities to different degrees and through different mechanisms. The bevacizumab-adapted cells, but not in the sunitinib-adapted cells, exhibited redundantly increased expression levels of VEGF/VEGF-R family members, including VEGF-A, placental growth factor, VEGF-C, VEGF-R1 and VEGF-R3. In addition, the phosphorylation levels of VEGF-R1 and VEGF-R3 were increased in the bevacizumab-adapted cells compared with the control cells. Thus, the inhibition of VEGF-R1 and VEGF-R3 decreased the evasive activities of the cells, suggesting that they remained dependent on redundant VEGF/VEGF-R signaling. By contrast, the sunitinib-adapted cells exhibited increased neuropilin-1 (NRP1) expression levels compared with the control cells. In the sunitinib-adapted cells, NRP1 interacted with phosphorylated cMet, and the cMet activation was dependent on NRP1. Thus, NRP1 or cMet blockade suppressed the evasive activation of the sunitinib-adapted cells. These results suggest that the sunitinib-adapted cells switched from a VEGF-R-dependent pathway to an alternative NRP1/cMet-dependent one. The findings of the present study indicate that VEGF/VEGF-R inhibitors directly act on colon cancer cells and activate their evasive adaptation via different mechanisms."},"publication_date":"2018-04","publication_name":{"en":"International Journal of Oncology","ja":"International Journal of Oncology"},"volume":"Vol.52","number":"No.4","starting_page":"1350","ending_page":"1362","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3892/ijo.2018.4291"],"issn":["1791-2423"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/111610","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29513566","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=337953","label":"url"}],"paper_title":{"en":"Reactive oxygen species up-regulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells.","ja":"Reactive oxygen species up-regulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells."},"authors":{"en":[{"name":"Uchida Takayuki"},{"name":"Sakashita Yoshihiro"},{"name":"Kitahata Kanako"},{"name":"Yamashita Yui"},{"name":"Tomida Chisato"},{"name":"Kimori Yuki"},{"name":"Komatsu Akio"},{"name":"Hirasaka Katsuya"},{"name":"Maita Ayako"},{"name":"Nakao Reiko"},{"name":"Higashitani Atsushi"},{"name":"Higashibata Akira"},{"name":"Ishioka Noriaki"},{"name":"Shimazu Toru"},{"name":"Kobayashi Takeshi"},{"name":"Okumura Yuushi"},{"name":"Choi Inho"},{"name":"Oarada Motoko"},{"name":"Mills Edward M"},{"name":"Kondo Shigetada"},{"name":"Takeda Shin'ichi"},{"name":"Tanaka Eiji"},{"name":"Tanaka Keiji"},{"name":"Sokabe Masahiro"},{"name":"Nikawa Takeshi"}],"ja":[{"name":"内田 貴之"},{"name":"坂下 宏"},{"name":"北畑 香菜子"},{"name":"Yamashita Yui"},{"name":"冨田 知里"},{"name":"木森 有希"},{"name":"小松 明生"},{"name":"平坂 勝也"},{"name":"真板 綾子"},{"name":"中尾 玲子"},{"name":"Higashitani Atsushi"},{"name":"東端 晃"},{"name":"石岡 憲昭"},{"name":"Shimazu Toru"},{"name":"Kobayashi Takeshi"},{"name":"奥村 裕司"},{"name":"Choi Inho"},{"name":"Oarada Motoko"},{"name":"Mills Edward M"},{"name":"近藤 茂忠"},{"name":"Takeda Shin'ichi"},{"name":"田中 栄二"},{"name":"Tanaka Keiji"},{"name":"Sokabe Masahiro"},{"name":"二川 健"}]},"description":{"en":"Unloading-mediated muscle atrophy is associated with increased reactive oxygen species (ROS) production. We previously demonstrated that elevated ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) resulted in the loss of muscle volume [Nakao R. et al. Mol Cell Biol, 29: 4798-4811, 2009]. However, the pathological role of ROS production associated with unloading-mediated muscle atrophy still remains unknown. Here, we showed the ROS-mediated signal transduction caused by microgravity or its simulation contributes to Cbl-b expression. In L6 myotubes, the assessment of redox status revealed that oxidized glutathione was increased under microgravity conditions, and simulated microgravity caused a burst of ROS, implicating ROS as a critical upstream mediator linking to downstream atrophic signaling. ROS generation activated the ERK1/2-early growth response protein (Egr) 1/2-Cbl-b signaling pathway, an established contributing pathway to muscle volume loss. Interestingly, antioxidant treatment, such as N-acetylcysteine and TEMPOL, but not catalase, blocked the clinorotation-mediated activation of ERK1/2. The increased ROS induced transcriptional activity of Egr 1 and/or Egr 2 to stimulate Cbl-b expression through the ERK 1/2 pathway in L6 myoblasts, since treatment with Egr 1/2 siRNA and an ERK 1/2 inhibitor significantly suppressed clinorotation-induced Cbl-b and Egr expression, respectively. Promoter and gel mobility shift assays revealed that Cbl-b was upregulated via an Egr consensus oxidative responsive element at -110 to -60 bp of the Cbl-b promoter. Together this indicates that under microgravity conditions, elevated ROS may be a crucial mechanotransducer in skeletal muscle cells, regulating muscle mass, through Cbl-b expression activated by the ERK-Egr signaling pathway.","ja":"Unloading-mediated muscle atrophy is associated with increased reactive oxygen species (ROS) production. We previously demonstrated that elevated ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) resulted in the loss of muscle volume [Nakao R. et al. Mol Cell Biol, 29: 4798-4811, 2009]. However, the pathological role of ROS production associated with unloading-mediated muscle atrophy still remains unknown. Here, we showed the ROS-mediated signal transduction caused by microgravity or its simulation contributes to Cbl-b expression. In L6 myotubes, the assessment of redox status revealed that oxidized glutathione was increased under microgravity conditions, and simulated microgravity caused a burst of ROS, implicating ROS as a critical upstream mediator linking to downstream atrophic signaling. ROS generation activated the ERK1/2-early growth response protein (Egr) 1/2-Cbl-b signaling pathway, an established contributing pathway to muscle volume loss. Interestingly, antioxidant treatment, such as N-acetylcysteine and TEMPOL, but not catalase, blocked the clinorotation-mediated activation of ERK1/2. The increased ROS induced transcriptional activity of Egr 1 and/or Egr 2 to stimulate Cbl-b expression through the ERK 1/2 pathway in L6 myoblasts, since treatment with Egr 1/2 siRNA and an ERK 1/2 inhibitor significantly suppressed clinorotation-induced Cbl-b and Egr expression, respectively. Promoter and gel mobility shift assays revealed that Cbl-b was upregulated via an Egr consensus oxidative responsive element at -110 to -60 bp of the Cbl-b promoter. Together this indicates that under microgravity conditions, elevated ROS may be a crucial mechanotransducer in skeletal muscle cells, regulating muscle mass, through Cbl-b expression activated by the ERK-Egr signaling pathway."},"publication_date":"2018-03-07","publication_name":{"en":"American Journal of Physiology, Cell Physiology","ja":"American Journal of Physiology, Cell Physiology"},"volume":"Vol.314","number":"No.6","starting_page":"C721","ending_page":"C731","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajpcell.00184.2017"],"issn":["1522-1563"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/111609","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=337952","label":"url"}],"paper_title":{"en":"Distinct Gene Expression Profile Distinguishes Increased Metabolic Activity in Spontaneously Hyperactive Rats While Sedentary from That Induced by Exercise","ja":"Distinct Gene Expression Profile Distinguishes Increased Metabolic Activity in Spontaneously Hyperactive Rats While Sedentary from That Induced by Exercise"},"authors":{"en":[{"name":"Abe Manami"},{"name":"Matsuo Yuki"},{"name":"Harada Akiko"},{"name":"Uchida Takayuki"},{"name":"Kitahata Kanako"},{"name":"Tomida Chisato"},{"name":"Hirasaka Katsuya"},{"name":"Kondo Shigetada"},{"name":"Harada Nagakatsu"},{"name":"Nakaya Yutaka"},{"name":"Sakaue Hiroshi"},{"name":"Nakao Reiko"},{"name":"Nikawa Takeshi"}],"ja":[{"name":"阿部 愛波"},{"name":"松尾 侑季"},{"name":"原田 晃子"},{"name":"内田 貴之"},{"name":"北畑 香菜子"},{"name":"冨田 知里"},{"name":"平坂 勝也"},{"name":"近藤 茂忠"},{"name":"原田 永勝"},{"name":"中屋 豊"},{"name":"阪上 浩"},{"name":"中尾 玲子"},{"name":"二川 健"}]},"publication_date":"2018-02-02","publication_name":{"en":"Advances in Biological Chemistry","ja":"Advances in Biological Chemistry"},"volume":"Vol.8","number":"No.01","starting_page":"1","ending_page":"14","languages":["eng"],"referee":true,"identifiers":{"doi":["10.4236/abc.2018.81001"],"issn":["2162-2183"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://repo.lib.tokushima-u.ac.jp/111128","label":"url"},{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/111128","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28954993","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390282679224220288/","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85030250811&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=338761","label":"url"}],"paper_title":{"en":"Regorafenib induces adaptive resistance of colorectal cancer cells via inhibition of vascular endothelial growth factor receptor.","ja":"Regorafenib induces adaptive resistance of colorectal cancer cells via inhibition of vascular endothelial growth factor receptor."},"authors":{"en":[{"name":"Tomida Chisato"},{"name":"Nagano Hikaru"},{"name":"Yamagishi Naoko"},{"name":"Uchida Takayuki"},{"name":"Maita Ayako"},{"name":"Hirasaka Katsuya"},{"name":"Nikawa Takeshi"},{"name":"Kondo Shigetada"}],"ja":[{"name":"冨田 知里"},{"name":"Nagano Hikaru"},{"name":"Yamagishi Naoko"},{"name":"内田 貴之"},{"name":"真板 綾子"},{"name":"Hirasaka Katsuya"},{"name":"二川 健"},{"name":"近藤 茂忠"}]},"description":{"en":"Recently, inhibition of tumor angiogenesis has become an important anti-cancer therapy. Tumor angiogenesis is regulated by multiple signaling pathways, including VEGF and VEGF receptor (VEGF-R), FGF and FGF receptor (FGF-R), and PDGF and PDGF receptor (PDGF-R) pathways. Thus, the antiangiogenic agents, such as regorafenib, simultaneously target those receptors on vascular endothelial cells. In addition to endothelial cells, cancer cells express the three receptors, suggesting that the antiangiogenic inhibitors affect tumor cells. In fact, we previously demonstrated that regorafenib directly acted on human colorectal cancer cells and accelerated their apoptosis resistance and migration capability. Thus, we here elucidated how regorafenib induced the malignant phenotypes in colorectal cancer cells. To identify the responsible receptor among the regorafenib-targeting proangiogenic receptors, we examined the effects of a potent selective inhibitor for VEGF-R, FGF-R or PDGF-R on apoptosis resistance and migration capability. We clarified that blockade of VEGF-R, but not FGF-R and PDGF-R, induced the malignant phenotypes. We confirmed that blocking of VEGF ligands derived from colorectal cancer cells also induced the phenotypes. These results suggest that regorafenib progressed the malignancy via prevention of autocrine and paracrine VEGF signaling in colorectal cancer cells. J. Med. Invest. 64: 262-265, August, 2017.","ja":"Recently, inhibition of tumor angiogenesis has become an important anti-cancer therapy. Tumor angiogenesis is regulated by multiple signaling pathways, including VEGF and VEGF receptor (VEGF-R), FGF and FGF receptor (FGF-R), and PDGF and PDGF receptor (PDGF-R) pathways. Thus, the antiangiogenic agents, such as regorafenib, simultaneously target those receptors on vascular endothelial cells. In addition to endothelial cells, cancer cells express the three receptors, suggesting that the antiangiogenic inhibitors affect tumor cells. In fact, we previously demonstrated that regorafenib directly acted on human colorectal cancer cells and accelerated their apoptosis resistance and migration capability. Thus, we here elucidated how regorafenib induced the malignant phenotypes in colorectal cancer cells. To identify the responsible receptor among the regorafenib-targeting proangiogenic receptors, we examined the effects of a potent selective inhibitor for VEGF-R, FGF-R or PDGF-R on apoptosis resistance and migration capability. We clarified that blockade of VEGF-R, but not FGF-R and PDGF-R, induced the malignant phenotypes. We confirmed that blocking of VEGF ligands derived from colorectal cancer cells also induced the phenotypes. These results suggest that regorafenib progressed the malignancy via prevention of autocrine and paracrine VEGF signaling in colorectal cancer cells. J. Med. Invest. 64: 262-265, August, 2017."},"publication_date":"2017","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.64","number":"No.3-4","starting_page":"262","ending_page":"265","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.64.262"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"} {"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://repo.lib.tokushima-u.ac.jp/111126","label":"url"},{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/111126","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28954991","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390001204247522048/","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85030217718&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=338759","label":"url"}],"paper_title":{"en":"Antiangiogenic agent sunitinib induces epithelial to mesenchymal transition and accelerates motility of colorectal cancer cells.","ja":"Antiangiogenic agent sunitinib induces epithelial to mesenchymal transition and accelerates motility of colorectal cancer cells."},"authors":{"en":[{"name":"Tomida Chisato"},{"name":"Yamagishi Naoko"},{"name":"Nagano Hikaru"},{"name":"Uchida Takayuki"},{"name":"Maita Ayako"},{"name":"Hirasaka Katsuya"},{"name":"Nikawa Takeshi"},{"name":"Kondo Shigetada"}],"ja":[{"name":"冨田 知里"},{"name":"Yamagishi Naoko"},{"name":"永野 ひかる"},{"name":"内田 貴之"},{"name":"真板 綾子"},{"name":"Hirasaka Katsuya"},{"name":"二川 健"},{"name":"近藤 茂忠"}]},"description":{"en":"Although vascular endothelial growth factor receptor (VEGF-R)-targeted antiangiogenic agents are important treatment for a number of human malignancies, there is accumulating evidence that the therapies may promote disease progression, such as invasion and metastasis. How tumors become to promote their evasiveness remains fully uncertain. One of possible mechanisms for the adaptation may be a direct effect of VEGF-R inhibitors on tumor cells expressing VEGF-R. To elucidate a direct effect of VEGF-R-targeting drug (sunitinib), we established a human colorectal cancer cell model adapted to sunitinib. The sunitinib-conditioned cells showed a significant increase in cellular motility and migration activities, compared to the vehicle-treated control cells. Consistent with the phenotype, the sunitinib-conditioned cells decreased the expression levels of E-cadherin (an epithelial marker), while significantly increased the levels of Slug and Zeb1 (mesenchymal markers). Expression profiles of VEGF-R in the sunitinib-conditioned cells showed that only neuropilin-1 (NRP1) expression was significantly increased among all VEGF-R tested. Blockade of NRP1 using its antagonist clearly repressed the migration activation in sunitinib-conditioned cells, but not in the control cells. These results suggest that inhibition of VEGF-R on colorectal cancer cells can drive the epithelial-mesenchymal transition, leading to activation of cell motility in an NRP1-dependent manner. J. Med. Invest. 64: 250-254, August, 2017.","ja":"Although vascular endothelial growth factor receptor (VEGF-R)-targeted antiangiogenic agents are important treatment for a number of human malignancies, there is accumulating evidence that the therapies may promote disease progression, such as invasion and metastasis. How tumors become to promote their evasiveness remains fully uncertain. One of possible mechanisms for the adaptation may be a direct effect of VEGF-R inhibitors on tumor cells expressing VEGF-R. To elucidate a direct effect of VEGF-R-targeting drug (sunitinib), we established a human colorectal cancer cell model adapted to sunitinib. The sunitinib-conditioned cells showed a significant increase in cellular motility and migration activities, compared to the vehicle-treated control cells. Consistent with the phenotype, the sunitinib-conditioned cells decreased the expression levels of E-cadherin (an epithelial marker), while significantly increased the levels of Slug and Zeb1 (mesenchymal markers). Expression profiles of VEGF-R in the sunitinib-conditioned cells showed that only neuropilin-1 (NRP1) expression was significantly increased among all VEGF-R tested. Blockade of NRP1 using its antagonist clearly repressed the migration activation in sunitinib-conditioned cells, but not in the control cells. These results suggest that inhibition of VEGF-R on colorectal cancer cells can drive the epithelial-mesenchymal transition, leading to activation of cell motility in an NRP1-dependent manner. J. Med. Invest. 64: 250-254, August, 2017."},"publication_date":"2017","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.64","number":"No.3-4","starting_page":"250","ending_page":"254","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.64.250"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}