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| 1 | Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease显示文摘Inflammatory bowel disease(IBD),the most important being Crohn's disease and ulcerative colitis,results from chronic dysregulation of the mucosal immune system in the gastrointestinal tract.Although the pathogenesis of IBD remains unclear,it is widely accepted that genetic,environmental,and immunological factors are involved.Recent studies suggest that intestinal epithelial defenses are important to prevent inflammation by protecting against microbial pathogens and oxidative stresses.To investigate the etiology of IBD,animal models of experimental colitis have been developed and are frequently used to evaluate new anti-inflammatory treatments for IBD.Several models of experimental colitis that demonstrate various pathophysiological aspects of the human disease have been described.In this manuscript,we review the characteristic features of IBD through a discussion of the various chemically induced experimental models of colitis(e.g.dextran sodium sulfate-,2,4,6-trinitrobenzene sulfonic acid-,oxazolone-,acetic acid-,and indomethacin-induced models).We also summarize some regulatory and pathogenic factors demonstrated by these models that can,hopefully,be exploited to develop future therapeutic strategies against IBD. | Mayumi Kawada Atsuko Arihiro Emiko Mizoguchi | 2007 | World Journal of Gastroenterology2007，13，42： | 12 |
| 2 | Inhibition of neprilysin by infusion of thiorphan into the hippocampus causes an accumulation of amyloid Beta and impairment of learning and memory.显示文摘 | Zou LB Mouri A Iwata N Saido TC Wang D Wang MW Mizoguchi H Noda Y Nabeshima T | 2006 | 中国生物学文摘2006，20，9： | 10 |
| 3 | Potential role of chitinase 3-like-1 in inflammation-associated carcinogenic changes of epithelial cells显示文摘The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin,a polymer of N-acetylglucosamine.Chitin is the structural component of fungi,crustaceans,insects and parasitic nematodes,but is completely absent in mammals.Exposure to antigens containing chitin-or chitin-like structures sometimes induces strong T helper type-I responses in mammals,which may be associated with the induction of mammalian chitinases.Chitinase 3-like-1(CHI3L1) ,a member of the mammalian chitinase family,is induced specifically during the course of inflammation in such disorders as inflammatory bowel disease,hepatitis and asthma.In addition,CHI3L1 is expressed and secreted by several types of solid tumors including glioblastoma,colon cancer,breast cancer and malignant melanoma.Although the exact function of CHI3L1 in inflammation and cancer is still largely unknown,CHI3L1 plays a pivotal role in exacerbating the inflammatory processes and in promoting angiogenesis and remodeling of the extracellular matrix.CHI3L1 may be highly involved in the chronic engagement of inflammation which potentiates development of epithelial tumorigenesis presumably by activating the mitogen-activated protein kinase and the protein kinase B signaling pathways.Anti-CHI3L1 antibodies or pan-chitinase inhibitors may have the potential to suppress CHI3L1-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells. | Katrin Eurich Mayuko Segawa Satoko Toei-Shimizu Emiko Mizoguchi | 2009 | World Journal of Gastroenterology2009，15，42： | 9 |
| 4 | 大鼠急性内囊出血后血液流变特性经时变化的研究显示文摘目的观察大鼠急性内囊出血后血液流变特性的经时变化,总结变化规律,分析其对微循环的影响。方法将大鼠随机分为假手术组及出血组,后者又分为出血后3、6、12、24h四个亚组,每组6只。尾尖剪断取自体血0.1ml定位注射至大鼠右侧内囊,假手术组除不注血外,其余操作同出血组。假手术组即刻取血,出血组分别于各时间点取血做血液流变学检测。结果各出血组与假手术组比较,血液流变学各指标总体水平呈上升趋势(P<0.05);出血各组间比较,全血低切黏度在出血后3~12h明显升高,全血高切黏度、血浆黏度在24h升高最明显,红细胞压积(HCT)、红细胞聚集指数(EAI)及纤维蛋白原(Fib)含量随时间推移逐渐升高,前者在24h达高峰,后两者高峰时间为出血后12~24h。结论大鼠急性内囊出血后不同时段的血液流变学参数发生了有统计学意义的改变,将影响中枢神经系统的微循环功能。 | 张丽敏 金学隆 王世忠 李之烨 Mizoguchi Kazushige | 2009 | 中国微循环2009，13，3： | 5 |
| 5 | TTYH2,a human homologue of the Drosophila melanogaster gene tweety,is up-regulated in colon carcinoma and involved in cell proliferation and cell aggregation显示文摘AIM: To investigate the expression patterns of TTYH2 in the human colon cancer and colon cancer cell lines and to evaluate the inhibitory effect of small interfering RNA (siRNA) on the expression of TTYH2 in colon cancer cell lines.METHODS: We investigated the expression patterns of TTYH2 in colon cancer, adjacent non-tumorous colon mucosa, and cancer cell lines (DLD-1, caco-2, and Lovo) by RT-PCR. Furthermore, a siRNA plasmid expression vector against TTYH2 was constructed and transfected into DLD-1 and Caco-2 with LipofectamineTM 2000. The down regulation of TTYH2 expression was detected by RT-PCR and the role of siRNA in inducing cell proliferation and cell aggregation was evaluated by MTT and aggregation assay.RESULTS: TTYH2 gene expression in colon cancer tissue was significantly up-regulated compared with normal colonic mucosa (1.23 ± 0.404 vs 0.655 ± 0.373, P = 0.0103). Colon cancer derived cell lines including DLD-1, Caco-2, and Lovo also expressed high levels of TTYH2. In contrast, transfection with siRNA-TTYH2 signifi cantly inhibited both proliferation and scattering of these cancer cell lines.CONCLUSION: The present work demonstrates, for the fi rst time, that the TTYH2 gene expression is signifi cantly up-regulated in colon cancer. The TTYH2 gene may play an important role in regulating both proliferating andmetastatic potentials of colorectal cancer. | Yuji Toiyama Akira Mizoguchi Kazushi Kimura Junichirou Hiro Yasuhiro Inoue Tomonari Tutumi Chikao Miki Masato Kusunoki | 2007 | World Journal of Gastroenterology2007，13，19： | 4 |
| 6 | Animal Models of Inflammatory Bowel Disease显示文摘 | Atsushi Mizoguchi | 2012 | Progress in Molecular Biology and Translational Science2012，，： | 3 |
| 7 | Chitinase 3-Like-1 Expression in Colonic Epithelial Cells as a Potentially Novel Marker for Colitis-Associated Neoplasia显示文摘 | Chun-Chuan Chen Joel Pekow Victoria Llado Manasa Kanneganti Cindy W. Lau Atsushi Mizoguchi Mari Mino-Kenudson Marc Bissonnette Emiko Mizoguchi | 2011 | The American Journal of Pathology2011，，3： | 3 |
| 8 | Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease显示文摘Family 18 chitinases have a binding capacity with chitin, a polymer of N-acetylglucosamine. Recent studies strongly suggested that chitinase 3-like 1(CHI3L1, also known as YKL-40) and acidic mammalian chitinase, the two major members of family 18 chitinases, play a pivotal role in the pathogenesis of inflammatory bowel disease(IBD), bronchial asthma and several other inflammatory disorders. Based on the data from highthroughput screening, it has been found that three methylxanthine derivatives, caffeine, theophylline, and pentoxifylline, have competitive inhibitory effects against a fungal family 18 chitinase by specifically interacting with conserved tryptophans in the active site of this protein. Methylxanthine derivatives are also known as adenosine receptor antagonists, phosphodiesterase inhibitors and histone deacetylase inducers. Anti-in-flammatory effects of methylxanthine derivatives have been well-documented in the literature. For example, a beneficial link between coffee or caffeine consumption and type 2 diabetes as well as liver cirrhosis has been reported. Furthermore, theophylline has a long history of being used as a bronchodilator in asthma therapy, and pentoxifylline has an immuno-modulating effect for peripheral vascular disease. However, it is still largely unknown whether these methylxanthine derivativemediated anti-inflammatory effects are associated with the inhibition of CHI3L1-induced cytoplasmic signaling cascades in epithelial cells. In this review article we will examine the above possibility and summarize the biological significance of methylxanthine derivatives in intestinal epithelial cells. We hope that this study will provide a rationale for the development of methylxanthine derivatives, in particular caffeine,-based antiinflammatory therapeutics in the field of IBD and IBDassociated carcinogenesis. | In-Ah Lee Alan Kamba Daren Low Emiko Mizoguchi | 2014 | World Journal of Gastroenterology2014，20，5： | 3 |
| 9 | Persistence of gene expression changes in noninflamed and inflamed colonic mucosa in ulcerative colitis and their presence in colonic carcinoma显示文摘AIM: A few studies have applied genomic-wide gene expression analysis in inflamed colon tissue sample in ulcerative colitis (UC). We reported the first study of non-inflamed mucosal gene expression in UC and explored its clinical implication.METHODS: Non-inflamed mucosa was obtained from 6 UC patients who received total colectomy. The gene expression of UC in noninfliamed mucosa was monitored with a microarray. For a selected gene, RT-PCR was performed to verify array results and to further examine expression pattern in inflamed mucosa of UC, colorectal cancer tissue and normal mucosa using additional matched pairs.RESULTS: Two genes showing 2.5-fold decreased expression with significance set at in UC samples were bomeo box a4 (HOXa4) and mads box transcription enhancer factor 2, polypeptide B (MEF2b). RT-PCR showed that MEF2b expression in non-inflamed mucosa was significantly downregulated, whereas the expression of MEF2b increased in accordance with the severity of mucosal inflammation. HOXa4 expression both in inflamed and non-inflamed mucosa in UC was consistently downregulated, and the downregulation of HOXa4 was also found in colorectal carcinoma.CONCLUSION: It is suggested that the MEF2b expression in UC which increase in accordance with inflammation may be induced by the inflammatory mediator. In contrast the downregulation of HOXa4 may be partly involved in the pathogenesis of disease including UC and UC-related carcinogenesis. | Yuji Toiyama Akira Mizoguchi Kazushi Kimura Toshimitsu Araki Shigeyuki Yoshiyama Kouhei Sakaguchi Chikao Miki Masato Kusunoki | 2005 | World Journal of Gastroenterology2005，11，33： | 2 |
| 10 | Animal Models of Colitis-Associated Carcinogenesis显示文摘 | Manasa Kanneganti Mari Mino-Kenudson Emiko Mizoguchi Andrea Vecchione | 2011 | Journal of Biomedicine and Biotechnology2011，，： | 2 |
| 11 | Roles of galectins in inflammatory bowel disease显示文摘Protein/carbohydrate interactions through specific protein families termed lectin control essential biological processes. Galectins, a family of animal lectins defined by shared amino acid sequence with affinity for β-galactosides, appear to be functionally polyvalent in a wide range of biological activity. Recent studies have identified immunoregulatory roles of galectins in intestinal inflammatory disorders. Galectin-1 and galectin -2 contribute to the suppression of intestinal inflammation by the induction of apoptosis of activated T cells, whereas galectin-4 is involved in the exacerbation of this inflammation by specifically stimulating intestinal CD4+ T cells to produce IL-6. We review how different members of the galectins provide inhibitory or stimulatory signals to control intestinal immune response under intestinal inflammation. | Akira Hokama Emiko Mizoguchi Atsushi Mizoguchi | 2008 | World Journal of Gastroenterology2008，14，33： | 2 |
| 12 | Serum levels of vascular endothelial growth factor dependent on the stage progression of lung cancer显示文摘 | Matsuyama W Hashiguchi T Mizoguchi A | | 0，，04： | 2 |
| 13 | Oncoplastic Surgery for Japanese Patients with Centrally Located Breast Cancer: Partial Resection and Reconstruction Using a Local Skin-Glandular Flap显示文摘 | Yuko Kijima Heiji Yoshinaka Munetsugu Hirata Tadao Mizoguchi Sumiya Ishigami Akihiro Nakajo Hideo Arima Youta Kawasaki Shinichi Ueno Shoji Natsugoe | 2011 | Journal of US-China Medical Science2011，8，3： | 2 |
| 14 | Protective effect of Irsogladine on monochloramineinduced gastric mucosallesions in rats:a comparative study with rebamipide显示文摘AIM To examine the effect of irsogladine, a novel antiulcer drug, on the mucosal ulcerogenic response to monochloramine (NH 2Cl) in rat stomach, in comparison with rebamipide, another antiulcer drug with cytoprotective activity. METHODS AND RESULTS Oral administration of NH 2Cl (120*!mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs. Both irsogladine ( 1*!mg/*!kg - 10*!mg/*!kg , po ) and rebamipide ( 30*!mg/*!kg - 100*!mg/*!kg , po ) dose dependently prevented the development of these lesions in response to NH 2Cl, the effect of irsogladine was significant at 3*!mg/*!kg or greater, and that of rebamipide only at 100*!mg/*!kg . The protective effect of irsogladine on NH 2Cl induced gastric lesions was significantly reduced by N G nitro L arginine methyl ester (L NAME) but not by indomethacin, while that of rebamipide was significantly mitigated by indomethacin but not by L NAME. Topical application of NH 2Cl (20*!mM) caused a marked reduction of potential difference (PD) in ex vivo stomachs. This PD reduction was not affected by mucosal application of irsogladine, but significantly prevented by rebamipide. The mucosal exposure to NH 4OH (120*!mM) also caused a marked PD reduction in the ischemic stomach (bleeding from the carotid artery), resulting in gastric lesions. These ulcerogenic and PD responses caused by NH 4OH plus ischemia were also significantly mitigated by rebamipide, in an indomethacin sensitive manner, while irsogladine potently prevented such lesions without affecting the PD response, in a L NAME sensitive manner. CONCLUSION These results suggest that ① NH 2Cl generated either exogenously or endogenously damages the gastric mucosa, ② both irsogladine and rebamipide protect the stomach against injury caused by NH 2Cl, and ③ the mechanism underlying the protective action of irsogladine is partly mediated by endogenous nitric oxide, while that of rebamipide is in part mediated by endogenous prostaglandins. | H Yamamoto, M Umeda, H Mizoguchi, S Kato and K Takeuchi | 1999 | World Journal of Gastroenterology1999，5，6： | 2 |
| 15 | Amount of unfrozen water in frozen porous media saturated with solution 显示文摘 | Watanabe K Mizoguchi M | 2002 | Cold Regions Science and Technology2002，34，： | 2 |
| 16 | Effect of MnS on the heterogeneous nucleation of Cu precipitates in Fe-10 and -5mass% Cu alloys 显示文摘 | Hasegawa H Nakajima K Mizoguchi S | 2003 | ISIJ International2003，43，7： | 1 |
| 17 | Reduction of methamphetamine-induced sensitization and reward in matrix metalloproteinase-2 and -9-deficient mice显示文摘 | Mizoguchi H Yamada K Niwa M | 2007 | J Neurochem2007，100，6： | 1 |
| 18 | Analysis of solute distribution in dendrites of carbon steel with 8/7 transformation during solidifieation显示文摘 | Yoshiyuki Ueshima Shozo Mizoguchi Tooru Matsumiya | 1986 | Metallurgical Transactions1986，17，： | 1 |
| 19 | A case for regulatory B cells显示文摘 | Mizoguchi A Bhan AK | 2006 | J Immunol2006，176，2： | 1 |
| 20 | The Protective effects of prostaglandin E1 in an experimental rassive hepatic cell necrosis model 显示文摘 | Mizoguchi Y Tsutsui H Miyajima K | 1987 | Hepatology1987，7，： | 1 |
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