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Can control of gut microbiota be a future therapeutic option for inflammatory bowel disease?

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World Journal of Gastroenterology 2021年第23期27卷 3317-3326页

作者： atsushi nishida Kyohei Nishino Keitaro Sakai Yuji Owaki Yoshika Noda Hirotsugu Imaeda Department of Gastroenterology and Hepatology Nagahama City HospitalNagahama 5268580ShigaJapan

Inflammatory bowel disease(IBD)is a chronic inflammatory condition of the gastrointestinal tract encompassing two main clinical entities,Crohn’s disease and ulcerative colitis.Accumulated evidence indicates that an aberrant immune activation caused by the interplay of genetic susceptibility and environmental impact on the gut microbiota may be involved in the pathogenesis of IBD.Rapid advances in next-generation sequencing technology have enabled a number of studies to identify the alteration of the gut microbiota,termed dysbiosis,in IBD.Moreover,the alteration in the metabolites derived from the gut microbiota in IBD has also been described in many studies.Therefore,microbiota-based interventions such as fecal microbiota transplantation(FMT)have attracted attention as a novel therapeutic option in IBD.However,in clinical trials,the efficacy of FMT for IBD remains controversial.Additional basic and clinical studies are required to validate whether FMT can assume a complementary role in the treatment of IBD.The present review provides a synopsis on dysbiosis in IBD and on the association between the gut microbiota and the pathogenesis of IBD.In addition,we summarize the use of probiotics in IBD and the results of current clinical trials of FMT for IBD.

关键词： Inflammatory bowel disease Dysbiosis Fecal microbiota transplantation Short chain fatty acid Probiotics

Application of novel magnified single balloon enteroscopy for a patient with Cronkhite-Canada syndrome

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World Journal of Gastroenterology 2017年第22期23卷 4121-4126页

作者： Masaki Murata Shigeki Bamba Kenichiro Takahashi Hirotsugu Imaeda atsushi nishida Osamu Inatomi Tomoyuki Tsujikawa Ryoji Kushima Mitsushige Sugimoto Akira Andoh Department of Medicine Shiga University of Medical Science Comprehensive Internal Medicine Shiga University of Medical ScienceSeta-Tsukinowa Department of Clinical Laboratory Medicine Shiga University of Medical Science Division of Digestive endoscopy Shiga University of Medical Science

We present a case of Cronkhite-Canada syndrome(CCS) in which the entire intestine was observed using a prototype of magnifying single-balloon enteroscope(SIF Y-0007, Olympus). CCS is a rare, non-familial gastrointestinal polyposis with ectodermal abnormalities. To our knowledge, this is the first report showing magnified intestinal lesions of CCS. A 73-year-old female visited our hospital with complaints of diarrhea and dysgeusia. The blood test showed mild anemia and hypoalbuminemia. The esophagogastroduodenoscopy and colonoscopy revealed diffuse and reddened sessile to semi-pedunculated polyps, resulting in the diagnosis of CCS. In addition to the findings of conventional balloon-assisted enteroscopy or capsule endoscopy, magnifying observation revealed tiny granular structures, non-uniformity of the villus, irregular caliber of the loop-like capillaries, scattered white spots in the villous tip, and patchy redness of the villus. Histologically, the scattered white spots and patchy redness of the villus reflect lymphangiectasia and bleeding to interstitium, respectively.

关键词：帮助汽球的 enteroscopy 放大内视镜检查法缩小乐队成像小肠

Expression of Interleukin-26 is upregulated in inflammatory bowel disease

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World Journal of Gastroenterology 2017年第30期23卷 5519-5529页

作者： Makoto Fujii atsushi nishida Hirotsugu Imaeda Masashi Ohno Kyohei Nishino Shigeki Sakai Osamu Inatomi Shigeki Bamba Masahiro Kawahara Tomoharu Shimizu Akira Andoh Department of Medicine Shiga University of Medical Science Department of Surgery Shiga University of Medical Science

AIM To investigate interleukin(IL)-26 expression in the inflamed mucosa of patients with inflammatory bowel disease(IBD) and the function of IL-26. METHODS Human colonic subepithelial myofibroblasts(SEMFs) were isolated from colon tissue surgically resected. The expression of IL-26 protein and its receptor complex was analyzed by immunohistochemistry. The gene expression induced by IL-26 was evaluated by realtime polymerase chain reaction. Intracellular signaling pathways were evaluated by immunoblotting and specific small interfering(si) RNA transfection. RESULTS The m RNA and protein expression of IL-26 were significantly enhanced in the inflamed mucosa of patients with IBD. IL-26 receptor complex was expressed in colonic SEMFs in vivo and in vitro. IL-26 stimulated the m RNA expression of IL-6 and IL-8 in colonic SEMFs. The inhibitors of mitogen-activated protein kinases and phosphoinositide 3-kinase, and si RNAs for signal transducers and activator of transcription 1/3, nuclear factor-kappa B and activator protein-1 significantly reduced the m RNA expression of IL-6 and IL-8 induced by IL-26.CONCLUSION These results suggest that IL-26 plays a role in the pathophysiology of IBD through induction of inflammatory mediators.

关键词：煽动性的肠疾病 Interleukin-26 Myofibroblasts

Mucosal cytokine network in inflammatory bowel disease

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World Journal of Gastroenterology 2008年第33期14卷 5154-5161页

作者： Akira Andoh Yuhki Yagi Makoto Shioya atsushi nishida Tomoyuki Tsujikawa Yoshihide Fujiyama Department of Medicine Shiga University of Medical ScienceSeta-Tukinowa Otsu 520-2192 Japan

Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) are characterized by ongoing mucosal inflammation in which dysfunction of the host immunologic response against dietary factors and commensal bacteria is involved. The chronic in-flammatory process leads to disruption of the epithelial barrier, and the formation of epithelial ulceration. This permits easy access for the luminal microbiota and dietary antigens to cells resident in the lamina pro-pria, and stimulates further pathological immune cell responses. Cytokines are essential mediators of the interactions between activated immune cells and non-immune cells, including epithelial and mesenchymal cells. The clinical efficacy of targeting TNF-α clearly indicates that cytokines are the therapeutic targets in IBD patients. In this manuscript, we focus on the bio-logical activities of recently-reported cytokines [Inter-leukin (IL)-17 cytokine family, IL-31 and IL-32], which might play a role through interaction with TNF-α in the pathophysiology of IBD.

关键词：肠疾病消化系统疾病发病机理肠炎肠黏膜

FR167653,a p38 mitogen-activated protein kinase inhibitor,aggravates experimental colitis in mice

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World Journal of Gastroenterology 2008年第38期14卷 5851-5856页

作者： Takashi Nishimura Akira Andoh atsushi nishida Makoto Shioya Yuhsuke Koizumi Tomoyuki Tsujikawa Yoshihide Fujiyama Department of Medicine Shiga University of Medical Science Seta TsukinowaOtsu 520-2192 Japan

AIM: To investigate the effects of FR167653 on the development of dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: BALB/c mice were fed rodent chow containing 3.5% (wt/wt) DSS. The recipient mice underwent intra-peritoneal injection of vehicles or FR167653 (30 mg/kg per day). The mice were sacrificed on day 14, and the degree of colitis was assessed. Immunohistochemical analyses for CD4+ T cell and F4/80+ macrophage infiltration were also performed. Mucosal cytokine expression was analyzed by RT-PCR. RESULTS: The body weight loss was more apparent in the FR167653-treated DSS mice than in the vehicle- treated DSS mice. The colon length was shorter in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. Disease activity index and histological colitis score were significantly higher in FR167653- than in vehicle-treated DSS animals. Microscopically, mucosal edema, cellular infiltration (CD4 T cells and F4/80 macrophages), and the disruption of the epithelium were much more severe in FR167653-treated mice than in controls. Mucosal mRNA expression for interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were found to be markedly reduced in FR167653-treated DSS mice. CONCLUSION: Treatment with FR167653 aggravated DSS colitis in mice. This effect was accompanied by a reduction of mucosal IL-1β and TNF-α expression, suggesting a role of p38 mitogen-activated protein kinase (MAPK)-mediated proinflammatory cytokine induction in host defense mechanisms.

关键词：结肠炎肿瘤坏死因子α 肠炎活性蛋白激酶抑制剂

Severity of gastric mucosal atrophy affects the healing speed of post-endoscopic submucosal dissection ulcers

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World Journal of Gastrointestinal Endoscopy 2018年第5期10卷 83-92页

作者： Taketo Otsuka Mitsushige Sugimoto Hiromitsu Ban Toshiro Nakata Masaki Murata atsushi nishida Osamu Inatomi Shigeki Bamba Akira Andoh Division of Digestive Endoscopy Shiga University of Medical Science Hospital Department of Gastroenterology Shiga University of Medical Science Hospital

AIM To investigate factors associated with the healing of endoscopic submucosal dissection(ESD)-induced ulcers.METHODS We enrolled 132 patients with gastric tumors scheduled for ESD. Following ESD, patients were treated with daily lansoprazole 30 mg or vonoprazan 20 mg. Ulcer size was endoscopically measured on the day after ESD and at 4 and 8 wk. The gastric mucosa was endoscopically graded according to the Kyoto gastritis scoring system. We assessed the number of patients with and without a 90% reduction in ulcer area at 4 wk post-ESD and scar formation at 8 wk, and looked for risk factors for slower healing.RESULTS The mean size of gastric tumors and post-ESD ulcers was 17.4 ± 12.1 mm and 32.9 ± 13.0 mm. The meanreduction rates in ulcer area were 90.4% ± 0.8% at 4 wk and 99.8% ± 0.1% at 8 wk. The reduction rate was associated with the Kyoto grade of gastric atrophy at 4 wk(A0: 97.9% ± 0.6%, A1: 93.4% ± 4.1%, and A2: 89.7% ± 1.0%, respectively). In multivariate analysis, the factor predicting 90% reduction at 4 wk was gastric atrophy(Odds ratio: 5.678, 95%CI: 1.190-27.085, P = 0.029).CONCLUSION The healing speed of post-ESD ulcers was associated with the degree of gastric mucosal atrophy, and Helicobacter pylori eradication therapy is required to perform at younger age.

关键词： Helicobacter pylori Gastric mucosal/AB Endoscopic submucosal dissection Gastric ulcer

Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

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Cancer Communications 2024年第2期44卷 287-293页

作者： Kouya Shiraishi atsushi Takahashi Yukihide Momozawa Yataro Daigo Syuzo Kaneko Takahisa Kawaguchi Hideo Kunitoh Shingo Matsumoto Hidehito Horinouchi Akiteru Goto Takayuki Honda Kimihiro Shimizu Masahiro Torasawa Daisuke Takayanagi Motonobu Saito Akira Saito Yuichiro Ohe Shun-ichi Watanabe Koichi Goto Masahiro Tsuboi Katsuya Tsuchihara Sadaaki Takata Tomomi Aoi atsushi Takano Masashi Kobayashi Yohei Miyagi Kazumi Tanaka Hiroyuki Suzuki Daichi Maeda Takumi Yamaura Maiko Matsuda Yoko Shimada Takaaki Mizuno Hiromi Sakamoto Teruhiko Yoshida Yasushi Goto Tatsuya Yoshida Taiki Yamaji Makoto Sonobe Shinichi Toyooka Kazue Yoneda Katsuhiro Masago Fumihiro Tanaka Megumi Hara Nobuo Fuse Satoshi S.Nishizuka Noriko Motoi Norie Sawada Yuichiro nishida Kazuki Kumada Kenji Takeuchi Kozo Tanno Yasushi Yatabe Kuniko Sunami Tomoyuki Hishida Yasunari Miyazaki Hidemi Ito Mitsuhiro Amemiya Hirohiko Totsuka Haruhiko Nakayama Tomoyuki Yokose Kazuyoshi Ishigaki Toshiteru Nagashima Yoichi Ohtaki Kazuhiro Imai Ken Takasawa Yoshihiro Minamiya Kazuma Kobayashi Kenichi Okubo Kenji Wakai atsushi Shimizu Masayuki Yamamoto Motoki Iwasaki Koichi Matsuda Johji Inazawa Yuichi Shiraishi Hiroyoshi Nishikawa Yoshinori Murakami Michiaki Kubo Fumihiko Matsuda Yoichiro Kamatani Ryuji Hamamoto Keitaro Matsuo Takashi Kohno Division of Genome Biology National Cancer Center Research InstituteTokyoJapan Department of Clinical Genomics National Cancer Center Research InstituteTokyoJapan Laboratory for Statistical Analysis Center for Integrative Medical SciencesRIKENYokohamaJapan Department of Genomic Medicine Research InstituteNational Cerebral and Cardiovascular CenterOsakaJapan Laboratory for Genotyping Development Center for Integrative Medical SciencesRIKENYokohamaJapan Center for Antibody and Vaccine Therapy Research HospitalInstitute of Medical ScienceThe University of TokyoTokyoJapan Department of Medical Oncology and Cancer Center and Center for Advanced Medicine against CancerShiga University of Medical ScienceOtsuJapan Division of Medical AI Research and Development National Cancer Center Research InstituteTokyoJapan Center for Genomic Medicine Graduate School of MedicineKyoto UniversityKyotoJapan Department of Medical Oncology Japanese Red Cross Medical CenterTokyoJapan Department of Thoracic Oncology National Cancer Center Hospital EastJapan Department of Thoracic Oncology National Cancer Center HospitalTokyoJapan Department of Cellular and Organ Pathology Graduate School of MedicineAkita UniversityAkitaJapan Department of Respiratory Medicine Tokyo Medical and Dental UniversityBunkyo-kuTokyoJapan Division of General Thoracic Surgery Department of SurgeryShinshu University School of MedicineMatsumotoNaganoJapan Department of General Surgical Science Division of General Thoracic SurgeryGunma University Graduate School of MedicineIntegrative Center of General SurgeryGunma University HospitalGunmaJapan Department of Gastrointestinal Tract Surgery Fukushima Medical University School of MedicineFukushimaJapan StaGen Co. LtdTokyoJapan Division of Thoracic Surgery National Cancer Center HospitalTokyoJapan Department of Thoracic Surgery National Cancer Center Hospital EastChibaJapan Division of Translational Informatics Exploratory Oncology Research and Clinical Trial Center(EPOC

Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.

关键词： adenocarcinoma lung Lung

Body composition changes following chemotherapy for testicular germ cell tumor:obesity is the long-term problem

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Asian Journal of Andrology 2022年第5期24卷 458-462页

作者： Yuki Takai Sei Naito Hidenori Kanno atsushi Yamagishi Mayu Yagi Toshihiko Sakurai Hayato nishida Takuya Yamanobe Tomoyuki Kato Norihiko Tsuchiya Department of Urology Yamagata University Faculty of MedicineYamagata 990-9585Japan

Metabolic syndrome is a long-term complication of systemic chemotherapy for testicular germ cell tumor(TGCT).It is believed to be caused by secondary hypogonadism or toxic medicines because of orchidectomy followed by systemic chemotherapy.In this study,changes in the body composition of patients over time were quantitatively analyzed up to 24 months after chemotherapy.This study retrospectively analyzed 44 patients with TGCT who underwent chemotherapy at our institution from January 2008 to December 2016.Subcutaneous and visceral fat areas and psoas and skeletal muscle areas were measured by computed tomography before and immediately after chemotherapy as well as 3 months,6 months,12 months,and 24 months after chemotherapy.The subcutaneous and visceral fat indices and psoas and skeletal muscle indices were calculated as each area divided by body height squared.The total fat area had already significantly increased 3 months after the initiation of chemotherapy(P=0.004).However,it did not return to prechemotherapeutic levels even at 24 months after chemotherapy.The skeletal muscle area was significantly decreased at the end of chemotherapy(P<0.001);however,the value returned to baseline within 12 months.In multivariable analysis,the prechemotherapeutic skeletal muscle index and number of chemotherapy cycles were independently associated with the reduction of skeletal muscle at the end of chemotherapy(P=0.001 and P=0.027,respectively).In patients with TGCT,skeletal muscle mass decreased during chemotherapy and recovered within 12 months,whereas fat mass progressively increased from the initiation of chemotherapy until 24 months after chemotherapy.

关键词： body composition chemotherapy obesity sarcopenia secondary hypogonadism testicular cancer

Complete response to an anti-programmed cell death 1 antibody following a combination therapy of an anti-programmed cell death ligand 1 antibody and a tyrosine kinase inhibitor for metastatic renal cell carcinoma

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Asian Journal of Urology 2023年第1期10卷 103-105页

作者： Masayuki Kurokawa Sei Naito Tomoyuki Kato Masaki Ushijima atsushi Yamagishi Toshihiko Sakurai Hayato nishida Norihiko Tsuchiya Department of Urology Yamagata University Faculty of MedicineYamagataJapan

Dear Editor,Several Phase 3 trials have demonstrated the efficacy of immune checkpoint inhibitor(ICI)-based combination therapies in the treatment of advanced clear cell renal cell carcinoma(RCC)[1-5].However,there is still no well-defined adequate treatment for patients who experience disease progression after initial ICI-based combination therapy.

关键词： death carcinoma treatment