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New aspects of a small GTPase RAB35 in brain development and function

Neural Regeneration Research 2025年第7期20卷 1971-1980页

作者： Ikuko Maejima ken sato Laboratory of Molecular Traffic Institute for Molecular and Cellular RegulationGunma UniversityMaebashiJapan

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or *** processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS *** of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative ***,it is important to understand the physiological and pathological roles of RAB proteins in brain ***35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell ***35 is also involved in neurite outgrowth and turnover of synaptic *** generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and *** mice exhibited defects in anxiety-related behaviors and spatial ***,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal *** contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex *** studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's *** this review,we provide an overview of the current understanding of subcellular functions of *** also provide insights into the phys

关键词： endocytosis endosomes hippocampal development neurodegenerative diseases RAB35

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Challenge to overcome: Nonstructural protein 5A-P32 deletion in direct-acting antiviral-based therapy for hepatitis C virus

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World Journal of Gastroenterology 2018年第38期24卷 4304-4310页

作者： ken sato Toshio Uraoka Department of Gastroenterology and Hepatology Gunma University Graduate School of Medicine

Interferon(IFN)-based therapy for hepatitis C virus(HCV) infection has recently been replaced by IFNfree direct-acting antiviral(DAA)-based therapy, which has been established as a 1^(st) line therapy with high efficacy and tolerability due to its reasonable safety profile. Resistance-associated substitutions(RASs) have been a weakness of DAA-based therapy. For example, combination therapy with daclatasvir and asunaprevir(DCV/ASV) is less effective for HCV genotype 1-infected patients with Y93H as a nonstructural protein 5A RAS. However, the problem regarding RASs has been gradually overcome with the advent of recently developed DAAs, such as sofosbuvir-based regimens or combination therapy with glecaprevir and pibrentasvir. Despite the high efficiency of DAA-based therapy, some cases fail to achieve viral eradication. P32 deletion, an NS5A RAS, has been gradually noticed in patients with DCV/ASV failure. P32 deletion has been sporadically reported and the prevalence of this RAS has been considered to be low in patients with DCV/ASV failure. Thus, the picture of P32 deletion has not been fully evaluated. Importantly, currently-commercialized DAA-based combination therapy was not likely to be effective for patients with P32 deletion. Exploring and overcoming this RAS is essential for antiviral therapy for chronic hepatitis C.

关键词： Chronic hepatitis C Direct-acting antivirals Resistant-associated substitution P32 deletion Nonstructural protein 5A

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Strategy for the control of drug-induced liver injury due to investigational treatments/drugs for COVID-19

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World Journal of Gastroenterology 2021年第48期27卷 8370-8373页

作者： ken sato Yuichi Yamazaki Toshio Uraoka Department of Gastroenterology and Hepatology Gunma University Graduate School of MedicineMaebashi 371-8511GunmaJapan

Investigational treatments/drugs for coronavirus disease 2019(COVID-19)have been applied,with repurposed or newly developed drugs,and their effectiveness has been *** of these drugs may be hepatotoxic,and each monotherapy or combination therapy may increase the risk of drug-induced liver injury(DILI).We should aim to control dysregulation of liver function,as well as the progression of COVID-19,as much as *** discussed the potential risks of investigational treatments/drugs and promising drugs for both COVID-19 and DILI due to investigational treatments/drugs.

关键词： Coronavirus disease 2019 Drug-induced liver injury Cytochrome P450 Drug-drug interaction Drug-disease interaction Cytokine

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Triple therapy of interferon and ribavirin with zinc supplementation for patients with chronic hepatitis C:A randomized controlled clinical trial

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World Journal of Gastroenterology 2006年第8期12卷 1265-1269页

作者： Hideyuki Suzuki Hitoshi Takagi Naondo Sohara Daisuke Kanda satoru Kakizaki ken sato Masatomo Mori Department of Medicine and Molecular Science Gunma University Graduate School of MedicineShowa-machi 3-39MaebashiGunma 371-8511Japan

AIM： To study the therapeutic effect of interferon （IFN） and ribavirin with zinc supplement on patients with chronic hepatitis C viral （HCV） infection. METHODS： A total of 102 patients confirmed histologically to have chronic HCV infection with genotype lb and more than 100 KIU/mL of HCV were randomly assigned to each arm of the study and each received 10 million units of pegylated interferon （IFN- alpha-2b） daily for 4 wk followed by the same dose every other day for 20 wk plus ribavirin （600 or 800 mg/d depending on body weight）, with or without polaprezinc （150 mg/d） orally for 24 wk. The primary endpoint was sustained virological response （SVR） defined as negative HCV-RNA in the serum 6 mo after treatment. RESULTS： There were no differences in the clinical background between the two groups except for more females in the dual therapy group than in the other group （P〈 0.05）. SVR was observed in 33.3% of the triple therapy group and 33.3% of the dual therapy group. The side effects were almost the same in both groups except for gastrointestinal symptoms, which were less in the triple therapy group （P= 0.019）. CONCLUSION： Considered together, triple therapy of zinc plus IFN and ribavirin for HCV infection patients with genotype lb and high viral load is not better than dual therapy except for lower incidence of gastrointestinal side effects.

关键词： HCV Zinc Interferon Ribavirin

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Different outcomes of nosocomial infection with hepatitis C virus from the same origin

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World Journal of Gastroenterology 2006年第4期12卷 659-661页

作者： satoru Kakizaki Hitoshi Takagi Yuichi Yamazaki Naondo Sohara ken sato Takeaki Nagamine Masatomo Mori Department of Medicine and Molecular Science Gunma University Graduate School of MedicineMaebashiGunma 371-8511Japan Department of Clinical Nursing Gunma University School of Health SciencesMaebashiGunma 371-8511Japan

The outcome of infection with hepatitis C virus （HCV） varies substantially from self-limiting infection to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma among the individuals. The mechanisms that determine the clearance or the persistence of HCV have not yet been clarified. Here, we experienced two cases of hospital-related infection with HCV from the same origin but with quite different outcomes. One case resolved after an episode of acute hepatitis, while the other case developed a chronic hepatitis although they were infected with HCV of the same origin. Although infected with the virus of the same origin, the clinical and virological courses were completely different. This suggests that host factors play a major role in conditioning the outcome of acute HCV infection.

关键词： Nosocomial infection Hepatitis C virus HLA

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World Journal of Gastroenterology 2006年第11期12卷 1805-1809页

作者： Yoshimi Nakajima Hitoshi Takagi Naondo Sohara ken sato satoru Kakizaki kenichi Nomoto Hideki Suzuki Taketoshi Suehiro Tatsuo Shimura Takayuki Asao Hiroyuki Kuwano Masatomo Mori ken Nishikura Department of Medicine and Molecular Science Gunma University Graduate School of Medicine MaebashiGunma 371-8511Japan Department of Surgery Gunma University Graduate School of Medicine MaebashiGunma 371-8511Japan Division of Molecular and Functional Pathology Department of Cellular Function Niigata University Graduate School of Medicine and Dental SciencesNiigataNiigata 951-8510Japan

A 42-year-old woman was admitted to our hospital because of multiple liver tumors detected by ultrasonography. Colonoscopy revealed submucosal tumor in the rectum, which was considered the primary lesion. Endoscopic mucosal resection followed by histopathological examination revealed that the tumor was carcinoid. The resected margin of the tumor was positive for malignant cells. Two courses to transcatheter arterial chemotherapy for liver metastasis were ineffective. Accordingly, the rectal tumor and metastatic lymph nodes were surgically resected. One month after the operation, she received liver transplantation （left lateral segment and caudate lobe） from her son. No recurrent lesion has been observed at two years after the liver transplantation. Liver transplantation should be considered as a treatment option even in advanced case of carcinoid metastasis to the liver. We also discuss the literature on liver transplantation for metastatic carcinoid tumor.

关键词： Carcinoid Liver metastasis Living related liver transplantation

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Acute esophageal necrosis caused by alcohol abuse

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World Journal of Gastroenterology 2005年第35期11卷 5568-5570页

作者： Tetsu Endo Juichi Sakamoto ken sato Miyako Takimoto Koji Shimaya Tatsuya Mikami Akihiro Munakata Tadashi Shimoyama Shinsaku Fukuda First Department of Internal Medicine Hirosaki University School of Medicine 5 Zaifucho Hirosaki Aomori 036-8562 Japan

Acute esophageal necrosis (AEN) is extremely rare and the pathogenesis of this is still unknown. We report a case of AEN caused by alcohol abuse. In our case, the main pathogenesis could be accounted for low systemic perfusion caused by severe alcoholic lactic acidosis. After the healing of AEN, balloon dilatation was effective to manage the stricture.

关键词： Esophagus Lactic acidosis Alcohol drinking Balloon dilatation

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MK-0626,a selective DPP-4 inhibitor,attenuates hepatic steatosis in ob/ob mice

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World Journal of Gastroenterology 2014年第43期20卷 16227-16235页

作者： Tatsuya Ohyama ken sato Yuichi Yamazaki Hiroaki Hashizume Norio Horiguchi satoru Kakizaki Masatomo Mori Motoyasu Kusano Masanobu Yamada Department of Medicine and Molecular Science Gunma University Graduate School of MedicineGunma 371-8511Japan Department of Endoscopy and Endoscopic Surgery Gunma University HospitalGunma 371-8511Japan

AIM: To investigate the mechanism and in vivo effects of MK-0626, a dipeptidyl peptidase-4 inhibitor, on hepatic steatosis using ob/ob mice.

关键词： Dipeptidyl peptidase-4 inhibitor Hepatic steatosis ob/ob mice AMP-activated protein kinase Microsomal triglyceride transfer protein Adiponectin

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Kummer’s 24 Solutions of the Hypergeometric Differential Equation with the Aid of Fractional Calculus

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Advances in Pure Mathematics 2016年第3期6卷 180-191页

作者： Tohru Morita ken-ichi sato Tohoku University Sendai Japan College of Engineering Nihon University Koriyama Japan

We know that the hypergeometric function, which is a solution of the hypergeometric differential equation, is expressed in terms of the Riemann-Liouville fractional derivative (fD). The solution of the differential equation obtained by the Euler method takes the form of an integral, which is confirmed to be expressed in terms of the Riemann-Liouville fD of a function. We can rewrite this derivation such that we obtain the solution in the form of the Riemann-Liouville fD of a function. We present a derivation of Kummer’s 24 solutions of the hypergeometric differential equation by this method.

关键词： Fractional Derivative Hypergeometric Differential Equation Hypergeometric Function

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Combination therapy with daclatasvir and asunaprevir for dialysis patients infected with hepatitis C virus

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World Journal of Clinical Cases 2016年第3期4卷 88-93页

作者： ken sato Yuichi Yamazaki Tatsuya Ohyama Takeshi Kobayashi Norio Horiguchi satoru Kakizaki Motoyasu Kusano Masanobu Yamada Department of Medicine and Molecular Science Gunma University Graduate School of Medicine Department of Gastroenterology Heisei Hidaka Clinic Department of Endoscopy and Endoscopic Surgery Gunma University Hospital

The standard antiviral therapy for dialysis patients infected with hepatitis C virus(HCV) is(pegylated) interferon monotherapy, but its efficacy is insufficient. Oral direct-acting antiviral agents(DAAs) have recently been developed for chronic hepatitis C patients. However, some DAAs have contraindications for chronic renal failure(CRF). Daclatasvir and asunaprevir are metabolized largely in the liver and are not contraindicated in CRF. Combination therapy with daclatasvir and asunaprevir was used for 4 dialysis patients infected with genotype 1b HCV. One patient had viral breakthrough, and the 3 others had sustained virological response 12. One patient was admitted for heart failure and percutaneous coronary intervention due to concomitant ischemic disease. Heart failure was unlikely to be caused by the combination therapy, as it was probably due to water overload. The patient continued to receive the combination therapy after the remission of the heart failure. The combination therapy was well tolerated in the other patients.

关键词： Hepatitis C Oral drug Daclatasvir Asunaprevir Dialysis

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