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Potential effects of mesenchymal stem cell derived extracellular vesicles and exosomal miRNAs in neurological disorders

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Neural Regeneration Research 2021年第12期16卷 2359-2366页

作者： Masako Nakano mineko fujimiya Department of Anatomy Sapporo Medical University School of MedicineSapporoHokkaidoJapan

Mesenchymal stem cells are multipotent cells that possess anti-inflammatory,antiapoptotic and immunomodulatory properties.The effects of existing drugs for neurodegenerative disorders such as Alzheimer’s disease are limited,thus mesenchymal stem cell therapy has been anticipated as a means of ameliorating neuronal dysfunction.Since mesenchymal stem cells are known to scarcely differentiate into neuronal cells in damaged brain after transplantation,paracrine factors secreted from mesenchymal stem cells have been suggested to exert therapeutic effects.Extracellular vesicles and exosomes are small vesicles released from mesenchymal stem cells that contain various molecules,including proteins,mRNAs and microRNAs.In recent years,administration of exosomes/extracellular vesicles in models of neurological disorders has been shown to improve neuronal dysfunctions,via exosomal transfer into damaged cells.In addition,various microRNAs derived from mesenchymal stem cells that regulate various genes and reduce neuropathological changes in various neurological disorders have been identified.This review summarizes the effects of exosomes/extracellular vesicles and exosomal microRNAs derived from mesenchymal stem cells on models of stroke,subarachnoid and intracerebral hemorrhage,traumatic brain injury,and cognitive impairments,including Alzheimer’s disease.

关键词： exosomes extracellular vesicles mesenchymal stem cells microRNA neurological disorders

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Different effects of ghrelin, des-acyl ghrelin and obestatin on gastroduodenal motility in conscious rats

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World Journal of Gastroenterology 2008年第41期14卷 6318-6326页

作者： mineko fujimiya Akihiro Asakawa Koji Ataka Ikuo Kato Akio Inui Department of Anatomy Sapporo Medical University School of Medicine Department of Behavioral Medicine Kagoshima University Graduate School of Medical and Dental Sciences Research Institute Taiko Pharmaceutical Co. Ltd Department of Bioorganic Chemistry Faculty of Pharmaceutical Sciences Hokuriku University

Three peptides, ghrelin, des-acyl ghrelin and obestatin are derived from a common prohormone, preproghrelin by posttranslational processing, originating from endocrine cells in the stomach. To examine the effects of these peptides, we applied the manometric measurement of gastrointestinal motility in freely moving conscious rat models. Ghrelin exerts stimulatory effects on the motility of antrum and duodenum in both fed and fasted state of animals. Des-acyl ghrelin exerts inhibitory effects on the motility of antrum, but not on the motility of duodenum in the fasted state of animals. Obestatin exerts inhibitory effects on the motility of antrum and duodenum in the fed state, but not in the fasted state of animals. NPY Y2 or Y4 receptors in the brain may mediate the action of ghrelin, CRF type 2 receptors in the brain mediate the action of des-acy ghrelin, whereas CRF type 1 and type 2 receptors in the brain mediate the action of obestatin. Vagal afferent pathways might be involved in the action of ghrelin, but not involved in the action of des-acyl ghrelin, whereas vagal afferent pathways might be partially involved in the action of obestatin.

关键词：胃肠动力消化功能下丘脑症状

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Anal cushion lifting method is a novel radical management strategy for hemorrhoids that does not involve excision or cause postoperative anal complications

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World Journal of Gastrointestinal Surgery 2015年第10期7卷 273-278页

作者： Gentaro Ishiyama Toshihiko Nishidate Yuji Ishiyama Akihiko Nishio Ken Tarumi Maiko Kawamura Kenji Okita Toru Mizuguchi mineko fujimiya Koichi Hirata Department of Anorectal Surgery Sapporo Ishiyama Hospital Department of Anatomy II Graduate School of Medicine Sapporo Medical University Department of Surgery Surgical Oncology and ScienceGraduate School of Medicine Sapporo Medical University

AIM: To describe the anal cushion lifting(ACL) method with preliminary clinical results. METHODS: Between January to September 2007, 127 patients who received ACL method for hemorrhoid was investigated with informed consent. In this study, three surgeons who specialized in anorectal surgery performed the procedures. Patients with grade two or more severe hemorrhoids according to Goligher's classification were considered to be indicated for surgery. The patients were given the choice to undergo either the ACL method or theligation and excision method. ACL method is an original technique for managing hemorrhoids without excision. After dissecting the anal cushion from the internal sphincter muscle, the anal cushion was lifted to oral side and ligated at the proper position. Clinical characteristics and outcomes of patients were recorded including complications after surgery. RESULTS: A total of 127 patients were enrolled. Their median age was 42(19-84) years, and 74.8% were female. In addition, more than 99% of the patients had grade 3 or worse hemorrhoids. The median followup period was 26(0-88) mo, and the median operative time was 15(4-30) min. After surgery, analgesics were used for a median period of three days(0-21). Pain control was achieved using extra-oral analgesic drugs, although some patients required intravenous injections of analgesic drugs. The median duration of the patients' postoperative hospital stay was 7(2-13) d. A total of 10 complications(7.9%) occurred. Bleeding was observed in one patient and was successfully controlled with manual compression. Urinary retention occurred in 6 patients, but it disappeared spontaneously in all cases. Recurrent hemorrhoids developed in 3 patients after 36, 47, and 61 mo, respectively. No anal stenosis or persistent anal pain occurred. CONCLUSION: We consider that the ACL method might be better than all other current methods for managing hemorrhoids.

关键词： Hemorrhoidectomy Anal stenosis Anal cushion liftin

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Delayed ethanol elimination and enhanced susceptibility to ethanol-induced hepatosteatosis after liver resection

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World Journal of Gastroenterology 2014年第48期20卷 18249-18259页

作者： Xu Liu Ayako Hakucho Jinyao Liu Tatsuya fujimiya Department of Legal Medicine Yamaguchi University Graduate School of Medicine

AIM:To investigate ethanol-induced hepatic steatosis after liver resection and the mechanisms behind it.METHODS:First,the preliminary examination was performed on 6 sham-operated(Sham)and 30 partial hepatectomy(PH)male Wistar rats(8-wk-old)to evaluate the recovery of the liver weight and liver function after liver resection.PH rats were sacrificed at the indicated time points(4,8,and 12 h;1,3,and 7d)after PH.Second,the time point for the beginning of the chronic ethanol exposure(1 wk after sham-or PH-operation)was determined based on the results of the preliminary examination.Finally,pair-feeding was performed with a controlled diet or with a 5-g/d L ethanol liquid diet for 28 d in another 35 age-matched male Wistar rats with a one-week recovery after undergoing a sham-(n=15)or PH-operation(n=20)to evaluate the ethanol-induced liver injury after liver resection.Hepatic steatosis,liver function,fatty acid synthase(Fas)gene expression level,the expression of lipid metabolism-associated enzyme regulator genes[sterol regulatory element binding protein(Srebp)-1and pe roxis ome prol i fe rat or-ac t ivat e d re c e pt or(Ppar)-α],the mediators that alter lipid metabolism[plasminogen activator(Pai)-1 gene expression level and tumor necrosis factor(Tnf)-αproduction],and hepatic class-1 alcohol dehydrogenase(Adh1)-associated ethanol elimination were investigated in the4 groups based on histological,immunohistochemical,biochemical,Western blotting,reverse transcriptase chain reaction,and blood ethanol concentration analyses.The relevant gene expression levels,liver weight,and liver function were assessed before and 1wk after surgery to determine the subject’s recovery from the liver resection using the rats that had been subjected to the preliminary examination.RESULTS:In the PH rats,ethanol induced marked hepatic steatosis with impaired liver functioning,as evidenced by the accumulation of fatty droplets within the hepatocytes,the higher increases in their hepatic triglyceride and blood alanine aminotransferase and blood

关键词： Ethanol Hepatic class-1 alcohol dehydrogenase Etha

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