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Chemogenetic activation of G12 signaling enhances adipose tissue browning

Signal Transduction and Targeted Therapy 2023年第9期8卷 3923-3926页

作者： Yuki Ono Ryo Ito kaito Arai Gurdeep Singh Tsuyoshi Saitoh Robert BRussell Francesco Raimondi Junken Aoki Juro Sakai Asuka Inoue Molecular and Cellular Biochemistry Graduate School of Pharmaceutical SciencesTohoku UniversitySendaiMiyagi 980-8578Japan Division of Molecular Physiology and Metabolism Graduate School of MedicineTohoku UniversitySendaiMiyagi 980-8574Japan Bioquant Heidelberg UniversityIm Neuenheimer Feld 26769120 HeidelbergGermany Biochemie Zentrum Heidelberg(BZH) Heidelberg UniversityIm Neuenheimer Feld 32869120 HeidelbergGermany International Institute for Integrative Sleep Medicine(WPI-IIIS) University of Tsukuba1-1-1 TennodaiTsukubaIbaraki 305-8575Japan Graduate School of Comprehensive Human Sciences University of Tsukuba1-1-1 TennodaiTsukubaIbaraki 305-8575Japan Laboratorio di Biologia Bio@SNS Scuola Normale SuperiorePiazza dei Cavalieri 7Pisa 56126Italy Department of Health Chemistry Graduate School of Pharmaceutical SciencesThe University of TokyoBunkyo-kuTokyo 113-0033Japan Division of Metabolic Medicine Research Center for Advanced Science and TechnologyThe University of TokyoMeguro-kuTokyo 153-8904Japan

Dear Editor,Beige adipocytes,which increase energy expenditure by dissipating energy as heat,have gained attention as a therapeutic target for combating obesity.1 Adipocytes express many types of G-protein-coupled receptors(GPCRs),each of which has a unique preference for the Gs,Gi,Gq,and G12 *** the function of Gs-coupledβ-adrenergic receptors in beige adipocyte induction is well established,2 little is known about the function of G12-coupled GPCRs beyond its suppressive roles in white adipocyte maturation.3 In this study,we generated transgenic mice conditionally expressing a G12-coupled designer GPCR using a Cre-loxP system and investigated the potential effects of G12 signaling on adipocyte biology.

关键词： activation gained expressing

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Automatic Identification for Laparoscopic Surgical Procedure for Ligation and Online Distinction of Abnormal Manipulation for Thread Knotting

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International Journal of Clinical Medicine 2015年第12期6卷 887-898页

作者： Chiharu Ishii Takanori Sato kaito Murano Hideki Kawamura Department of Mechanical Engineering Faculty of Science and Engineering Hosei Universitty Tokyo Japan Nihon Kohden Corporation Tokyo Japan Gastroenterological Surgery Graduate School of Medicine Hokkaido University Sapporo Japan

Laparoscopic surgery is a difficult surgical procedure compared with laparotomy. In particular, considerable skills and care are required for thread knotting in laparoscopic surgery. In this paper, a method for automatic identification of a laparoscopic surgical procedure for ligation and online distinction of an abnormality, defined as any unusual manipulation, in the identified surgical procedure is proposed. Ligation is divided into several individual surgical procedures, and on the basis of the threshold criteria, each surgical procedure is identified. Next, the identified surgical procedure, thread knotting, is classified as either normal or abnormal using a self-organizing map. Finally, to reduce surgical error, an abnormality warning system which warns detection of an unusual manipulation in the surgical procedure to the operator is constructed.

关键词： Automatic Identification of Surgical Procedure Distinction of Abnormal Manipulation in Surgical Procedure Abnormality Warning System Surface Electromyogram (SEMG) Self-Organizing Map (SOM)

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A novel negative regulatory mechanism of Smurf2 in BMP/Smad signaling in bone

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Bone Research 2020年第4期8卷 429-438页

作者： Junichi Kushioka Takashi kaito Rintaro Okada Hiroyuki Ishiguro Zeynep Bal Joe Kodama Ryota Chijimatsu Melanie Pye Masahiro Narimatsu Jeffrey LWrana Yasumichi Inoue Hiroko Ninomiya Shin Yamamoto Takashi Saitou Hideki Yoshikawa Takeshi Imamura Department of Orthopaedic Surgery Osaka University Graduate School of Medicine2-2 YamadaokaSuitaOsaka 565-0871Japan Bone and Cartilage Regenerative Medicine The University of Tokyo7-3-1HongoBunkyo-kuTokyo 113-8655Japan Centre for Systems Biology Lunenfeld-Tanenbaum Research InstituteMount Sinai Hospital600 University AveTorontoON M5G 1X5Canada Department of Cell Signaling Graduate School of Pharmaceutical SciencesNagoya City University3-1 Tanabe-doriMizuho-kuNagoyaAichi 467-8603Japan Department of Molecular Medicine for Pathogenesis Ehime University Graduate School of Medicine454 ShitsukawaToonEhime 791-0295Japan Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine454 ShitsukawaToonEhime 791-0295Japan Translational Research Center Ehime University Hospital454 ShitsukawaToonEhime 791-0295Japan

Transforming growth factor-β(TGF-β)and bone morphogenetic protein(BMP)play important roles in bone *** ubiquitination regulatory factors(Smurfs)regulate TGF-β/BMP signaling via ubiquitination,resulting in degradation of signaling molecules to prevent excessive activation of TGF-β/BMP *** Smurf2 has been shown to negatively regulate TGF-β/Smad signaling,its involvement in BMP/Smad signaling in bone metabolism has not been thoroughly *** the present study,we sought to evaluate the role of Smurf2 in BMP/Smad signaling in bone *** collagen sponges containing 3μg of recombinant human BMP2(rhBMP2)were implanted in the dorsal muscle pouches of wild type(WT)and Smurf2−/−*** rhBMP2-induced ectopic bone in Smurf2−/−mice showed greater bone mass,higher mineral apposition and bone formation rates,and greater osteoblast numbers than the ectopic bone in WT *** WT mice,the ectopic bone consisted of a thin discontinuous outer cortical shell and scant inner trabecular *** contrast,in Smurf2−/−mice,the induced bone consisted of a thick,continuous outer cortical shell and abundant inner trabecular ***,rhBMP2-stimulated bone marrow stromal cells(BMSCs)from Smurf2−/−mice showed increased osteogenic ***2 induced the ubiquitination of Smad1/***/Smad signaling was enhanced in Smurf2−/−BMSCs stimulated with rhBMP2,and the inhibition of BMP/Smad signaling suppressed osteogenic differentiation of these *** findings demonstrate that Smurf2 negatively regulates BMP/Smad signaling,thereby identifying a new regulatory mechanism in bone metabolism.

关键词： Smurf2 metabolism involvement

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Robotic gastrectomy for gastric cancer

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Journal of Cancer Metastasis and Treatment 2018年第1期4卷 459-467页

作者： Masanori Tokunaga Masahiro Watanabe Shizuki Sugita Akiko Tonouchi Akio kaito Takahiro Kinoshita Gastric Cancer Division National Cancer Center Hospital EastKashiwa 277-8577Japan

Robotic gastrectomy(RG)is increasingly performed,particularly in East *** articulated devices,surgeons are able to perform every procedure more comfortably and meticulously,which makes RG ideal from the surgeon’s ***,it is still unclear whether it is a suitable treatment strategy from the patient’s viewpoint,due to the lack of solid evidence obtained from randomized controlled *** feasibility of RG has been demonstrated in many retrospective comparative studies,which showed similar trends,including relatively less estimated blood loss and longer operation time with RG than laparoscopic gastrectomy(LG),equivalent number of harvested lymph nodes and similar length of postoperative hospital stay between RG and ***,considering the higher medical expenses associated with RG,its superiority in terms of long-term survival outcomes will need to be confirmed for it to be accepted more widely.

关键词： da Vinci robot gastric cancer robot assisted gastrectomy laparoscopic gastrectomy

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Crystallization of Cellobiohydrolase in the Presence of Cellulose-Degraded Cellobiose: Analysis of Intermolecular Interactions and Association Dynamics

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Journal of Crystallization Process and Technology 2014年第1期4卷 1-13页

作者： Kazuo Onuma Naoki Furubayashi Fujiko Shibata Yoshiko Kobayashi Sachiko kaito Yuki Ohnishi Koji Inaka Maruwa Foods and Biosciences Inc. Tsutsui-cho Yamatokoriyama Nara Japan National Institute of Advanced Industrial Science and Technology (AIST) Tsukuba Ibaraki Japan

Crystallization of enzymes in presence of impurities is important for clarifying the role of enzymes in natural world. Although it is proposed that impurities inhibit nucleation of enzyme crystallization, details are unclear. In this study, crystallization of cellobiohydrolase from Aspergillus niger was investigated by dynamic and time-resolved static light scattering using cellobiose as an impurity. We aimed to clarify how cellobiose inhibits cellobiohydrolase crystallization and to crystallize cellobiohydrolase in concentrated cellobiose without using seeds. The contribution of attractive forces to total intermolecular interactions of cellobiohydrolase monomers increased with the molar ratio of cellobiose/cellobiohydrolase (R(cb/ce)). Association dynamics of cellobiohydrolase using lithium sulfate, however, showed that the initial aggregation rate decreased with an increase in R(cb/ce). Because binding sites of cellobioses to cellobiohydrolase molecules differed from those for the growth of protein crystals, the binding of cellobioses would increase the chemical potential of the cellobiohydrolase monomers, which gradually reduced supersaturation for growth as the aggregate size increased. This result was in contrast with the conventional idea that cellobiose inhibits the nucleation of cellobiohydrolase crystals. Gentle agitation of cellobiose-containing cellobiohydrolase solutions during sitting-drop vapor-diffusion growth resulted in the growth of cellobiohydrolase single crystals for all R(cb/ce) conditions without using seeds.

关键词： Enzyme Crystallization Inhibitor Hamaker Constant Light Scattering

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Granulocyte Colony-Stimulating Factor Enhances the Anticancer Effects of Cisplatin against Lung Cancer by Promoting Angiogenesis

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Advances in Lung Cancer 2017年第1期6卷 1-11页

作者： Yun-Mo Li Yasushi Ohno Norihiko Funaguchi Takenobu Gomyo Yuka Sasaki Sayaka Toyoshi Daizo kaito Komei Yanase Junki Endo Fumitaka Ito Masanori Kawasaki Shinya Minatoguchi Department of Cardiology and Respirology Graduate School of Medicine Gifu University Gifu Japan Department of Respiratory Medicine Murakami Memorial Hospital Asahi University Mizuho Japan

The G-CSF is used as a therapeutic drug of the febrile neutropenia in lung cancer chemotherapy, however, there were few reports that showed the effects of combination effects of G-CSF and anticancer drugs against lung cancer. In the present study, we investigated the effects of G-CSF and the combination effects of G-CSF and cisplatin on lung cancer growth. We investigated the effect of G-CSF against the LL-2 and KLN-205 cells by MTT assay and tried to detect the G-CSF receptor by RT-PCR. Next, to analyze the G-CSF effects in vivo, we transplanted the LL-2 into C57BL/6 mice, intraperitoneally administered G-CSF (30 micro/kg/day) with or without cisplatin (5 mg/kg), measured the tumor size and analyzed pathologically by HE and immunostaining. In vitro analyses, G-CSF showed no effects in LL-2 and KLN-205 cells, and RT-PCR revealed no G-CSF receptor mRNA. In vivo analyses, G-CSF alone did not significantly suppress tumor growth. However, concurrent G-CSF administration with cisplatin significantly enhanced the tumor suppressing effect of cisplatin in early stage of tumor growth. The analysis data of vWF immunostaining indicated that the neovascularization in the peripheral region of the tumors was more enhanced in G-CSF treatment mice. ELISA assay revealed that G-CSF did not influence the serum concentration of TNF-alpha and IL-12 in tumor-bearing mice. This study suggests that concurrent (combination) administration of cisplatin with G-CSF is a safe and effective method for enhancing anticancer effects and reducing chemotherapeutic agent-induced myelosuppression.

关键词： Granulocyte Colony-Stimulating Factor Lung Cancer G-CSF Receptor Angiogenesis Anticancer Agent Cisplatin TNF-Alpha IL-12

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慢性丙型肝炎患者肝脏中8-硝基鸟嘌呤的蓄积

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世界核心医学期刊文摘（胃肠病学分册） 2005年第12期1卷 46-47页

作者： Horiike S. Kawanishi S. kaito M. 李宏宇 Division of Gastroenterology and Hepatology Third De-partment of Internal Medicine Mie University School of Medicine 2- 174 Edobashi Tsu Mie 514- 8507 Japan

Background/Aims: Nucleic acid damage by reactive nitrogen and oxygen species may contribute to inflammation- related carcinogenesis. To investigate the extent of nucleic acid damage in hepatitis C virus infection and its change after interferon treatment, we measured 8- nitrogua- nine and 8- hydroxy- 2’ - deoxyguanosine (8- OHdG) in the liver of patients with chronic hepatitis C (CHC) before and after interferon therapy. Methods: Hepatic accumulation of 8- nitroguanine and 8- OHdG was immunohistochemically evaluated in 20 CHC patients and 7 control patients with non- alcoholic fatty liver. Results: Immunoreactivities of 8- nitroguanine and 8- OHdG were strongly detected in the liver from patients with CHC, but not in control livers. 8- Nitroguanine accumulation was found not only in infiltrating inflammatory cells, but also hepatocytes particularly in the periportal area. The accumulation of 8- nitroguanine and 8- OHdG increased with inflammatory grade (8- nitroguanine; P=0.0019, 8- OHdG; P=0.0009). In the sustained virological responder group after interferon therapy, 8- nitroguanine and 8- OHdG accumulationweremarkedly decreased in the liver (8- nitroguanine; P=0.018, 8- OHdG; P=0.018). Conclusions: In this study,we demonstrated for the first time that 8- nitroguanine accumulated in the liver of patients with CHC. 8- Nitroguanine is a useful biomarker to evaluate the severity of HCV- induced chronic inflammation in relation to hepatocellular carcinoma.

关键词：丙型肝炎患者鸟嘌呤慢性丙型肝炎干扰素治疗丙肝病毒脱氧鸟苷肝细胞癌酒精性脂肪肝免疫反应性持续病毒应答

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前胡咳痰汤药理作用黏膜免疫机制研究

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中国中医基础医学杂志 2005年第7期11卷 506-507页

作者：水野海腾吴皓周超凡吕爱平中国中医研究院基础理论研究所北京100700

目的:探讨前胡咳痰汤药理作用的黏膜免疫机制。方法:以流感病毒滴鼻法造成模型,观察了本方的抗病毒作用,并运用免疫组化的方法,研究了本药对黏膜免疫的影响。结果:前胡咳痰汤大剂量组肺重比病毒组减轻。前胡咳痰汤组小鼠的肠道IgA与空... 详细信息

目的:探讨前胡咳痰汤药理作用的黏膜免疫机制。方法:以流感病毒滴鼻法造成模型,观察了本方的抗病毒作用,并运用免疫组化的方法,研究了本药对黏膜免疫的影响。结果:前胡咳痰汤大剂量组肺重比病毒组减轻。前胡咳痰汤组小鼠的肠道IgA与空白对照组及病毒组比较显著增高。病毒组小鼠肠道的ICAM1表达明显高于未感染组,而服用前胡咳痰汤的小鼠ICAM1表达得到明显抑制,其表达水平基本与空白组相似。结论:前胡咳痰汤有明显的抗病毒作用,能增加肠道IgA并抑制肠道ICAM1表达可能是其药理作用的黏膜免疫机制。

关键词：前胡咳痰汤 IgA ICAM-1 黏膜免疫

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模式生物家蚕在药物研发中的应用(全译)

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广西蚕业 2015年第3期52卷 69-72页

作者： Don Daniel Nwib Hiroshi Hamamoto Yasuhiko Matsumoto Chikara kaito Kazuhisa Sekimizul 蒋璇张桂征何骥日本东京大学药物科学研究院微生物研究室日本基因药物研究所广西壮族自治区蚕业科学研究院南宁市530007

家蚕幼虫已经被提倡作为模式生物用于新药的开发研制,并建立了几种疾病模型,为药物开发和宿主—病原体互作作用机理研究提供了技术支持。简述非哺乳动物蚕幼虫在新药研发中的最近趋势,展望模式生物家蚕在生物医药研究中的广泛前景。

关键词：动物模型家蚕药物研发

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Erratum: Author’s Affiliation Correction. Type Ⅱ human epidermal growth factor receptor heterogeneity is a poor prognosticator for type Ⅱ human epidermal growth factor receptor positive gastric cancer (World J Clin Cases 2019;Aug 6;7 (15): 1964-1977)

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World Journal of Clinical Cases 2020年第21期8卷 5494-5495页

作者： Akio kaito Takeshi Kuwata Masanori Tokunaga Kohei Shitara Reo Sato Tetsuo Akimoto Takahiro Kinoshita Gastric Surgery Division National Cancer Center Hospital EastKashiwa 277-8577Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastKashiwa 277-8577Japan Department of Gastrointestinal Oncology National Cancer Center Hospital EastKashiwa 277-8577Japan Course of Advanced Clinical Research of Cancer Juntendo University Graduate School of MedicineTokyo 163-8001Japan Exploratory Oncology Research and Clinical Trial Center(EPOC) National Cancer Center Hospital EastKashiwa 277-8577Japan Department of Radiation Oncology National Cancer Center Hospital EastKashiwa 277-8577Japan

Correction to"Type II human epidermal growth factor receptor heterogeneity is a poor prognosticator for type II human epidermal growth factor receptor-positive gastric cancer"World J Clin Cases 2019;7(15):*** this article,one of the affiliation of the first author was *** kaito,the first author,belonged to Course of Advanced Clinical Research of Cancer,Juntendo University Graduate School of Medicine,Tokyo 163-8001,Japan.

关键词： Correction

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