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Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease

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World Journal of Gastroenterology 2007年第42期13卷 5581-5593页

作者： Mayumi Kawada Atsuko Arihiro emiko mizoguchi Gastrointestinal Unit Department of Medicine Massachusetts General Hospital Harvard Medical School Boston MA 02114 United States

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 *** the pathogenesis of IBD remains unclear,it is widely accepted that genetic,environmental,and immunological factors are *** studies suggest that intestinal epithelial defenses are important to prevent inflammation by protecting against microbial pathogens and oxidative *** investigate the etiology of IBD,animal models of experimental colitis have been developed and are frequently used to evaluate new anti-inflammatory treatments for *** models of experimental colitis that demonstrate various pathophysiological aspects of the human disease have been *** this manuscript,we review the characteristic features of IBD through a discussion of the various chemically induced experimental models of colitis(*** 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.

关键词： Inflammatory bowel disease Experimental colitis Dextran sodium sulfate Trinitrobenzene sulfonicacid Oxazolone Pathogenesis

Potential role of chitinase 3-like-1 in inflammation-associated carcinogenic changes of epithelial cells

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World Journal of Gastroenterology 2009年第42期15卷 5249-5259页

作者： Katrin Eurich Mayuko Segawa Satoko Toei-Shimizu emiko mizoguchi Gastrointestinal Unit Department of MedicineMassachusetts General HospitalHarvard Medical SchoolBostonMA 02114United States Center for the Study of Inflammatory Bowel Disease Massachusetts General HospitalHarvard Medical SchoolBostonMA 02114United States

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 CHI3Ll-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells.

关键词： Mammals Chitinase 3-1ike 1 Colon Epithelial cells Inflammation Colitis Colon neoplasms Inflammatory bowel disease

Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease

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World Journal of Gastroenterology 2014年第5期20卷 1127-1138页

作者： In-Ah Lee Alan Kamba Daren Low emiko mizoguchi Gastrointestinal Unit Department of Medicine Harvard Medical School Center for the Study of Inflammatory Bowel Disease Massachusetts General Hospital Harvard Medical School

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.

关键词： Adherent-invasive Escherichia coli Chitinase 3-like 1 Chitinase inhibitors Intestinal epithelial cells Host-microbial interactions Inflammatory bowel disease

DNA methylation in inflammatory bowel disease and beyond

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World Journal of Gastroenterology 2013年第32期19卷 5238-5249页

作者： Daren Low Atsushi mizoguchi emiko mizoguchi Gastrointestinal Unit Department of MedicineMassachusetts General HospitalHarvard Medical School Molecular Pathology Unit Department of PathologyMassachusetts General HospitalHarvard Medical School Center for the Study of Inflammatory Bowel Disease Massachusetts General HospitalHarvard Medical School

Inflammatory bowel disease(IBD)is a consequence of the complex,dysregulated interplay between genetic predisposition,environmental factors,and microbial composition in the *** a great advancement in identifying host-susceptibility genes using genome-wide association studies(GWAS),the majority of IBD cases are still *** immediate challenge in post-GWAS era is to identify other causative genetic factors of *** methylation has received increasing attention for its mechanistical role in IBD *** stable,yet dynamic DNA modification,can directly affect gene expression that have important implications in IBD *** alterations in DNA methylation associated with IBD are likely to outset as early as embryogenesis all the way until *** this review,we will discuss the recent advancement in understanding how DNA methylation alterations can contribute to the development of IBD.

关键词： Intestinal inflammation Crohn’s disease Colitis DNA methyltransferase Epi-therapy

Learning excited states from ground states by using an artificial neural network

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npj Computational Materials 2020年第1期6卷 1056-1061页

作者： Shin Kiyohara Masashi Tsubaki Teruyasu mizoguchi Institute of Industrial Science University of Tokyo153-8505 TokyoJapan National Institute of Advanced Industrial Science and Technology(AIST) 135-0064 TokyoJapan

Excited states are different quantum states from their ground states,and spectroscopy methods that can assess excited states are widely used in materials *** the spectra reflecting excited states is thus of great importance for materials ***,understanding such spectra remains difficult because excited states have usually different atomic or electronic configurations from their corresponding ground *** excited states could be predicted from ground states,the knowledge of the excited states would be ***,we used an artificial neural network to predict the excited states of the core-electron absorption spectra from their ground ***,our model correctly learned and predicted the excited states from their ground states,providing several thousand times computational ***,it showed excellent transferability to other ***,we found two physical insights about excited states:core-hole effects of amorphous silicon oxides are stronger than those of crystalline silicon oxides,and the excited-ground states relationships of some metal oxides are similar to those of the silicon oxides,which could not be obtained by conventional spectral simulation nor found until using machine leaning.

关键词： ground artificial oxides

On scalability of the Semantic Web

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Journal of Zhejiang University-Science C(Computers and Electronics) 2012年第4期13卷 245-246页

作者： Riichiro mizoguchi Institute of Scientific and Industrial Research Osaka University

Although people believe that both the Semantic Web (SW) and SW applications scale up,we have to make sure we know what they mean by ‘scale up’ in order to

关键词：语义Web 可扩展性关联数据 WWW 万维网

Simulation of Reductive Dechlorination Processes in a Lab-Scale Anaerobic Biobarrier with Enriched TCP Dechlorinating Consortium

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Transactions of Tianjin University 2012年第6期18卷 441-449页

作者： LI Zhiling INOUE Yasushi mizoguchi Takuya SIMIZU Yohei YOSHIDA Naoko KATAYAMA Arata EcoTopia Science Institute Nagoya University Nagoya 464-8603 Japan Department of Civil Engineering Graduate School of Engineering Nagoya University Nagoya 464-8603 Japan Electronics-Inspired Interdisciplinary Research Institute Toyohashi University of Technology Toyohashi 441-8580 Japan

In order to design and predict the dechlorination processes for remediating the halogenated aromatic com- pounds in the biobarrier system applied in situ, an anaerobic continuous-flow column was set up with the introduction of an enriched 2, 4, 6-trichlorophenol （TCP） reductive dechlorinating consortium. The fates of TCP and its metabo- lites were simulated according to the first-order sequential dechlorination kinetic model. The enriched TCP anaerobic dechlorinating consortium dechlorinated 100 ***/L TCP to 4-chlorophenol （4-CP） via 2,4-dichlorophenol （DCP） in 10 d. The consortium was predominated with the phylum of Firmicutes and Bacteroidetes, based on the PCR- denaturing gradient gel electrophoresis （DGGE） analysis. After the consortium was applied to the colunm, the ex- perimental data in the steady state were fitted by the least square method, and the first-order dechlorination kinetic constants from TCP to 2,4-DCP, from 2,4-DCP to 4-CP and from 4-CP to phenol, were 1.58 d-1, 2.23 d 1 and 0.206 d-1, respectively. According to the fitting results, the required biobarrier width for the complete remediation of TCP, 2,4- DCP and 4-CP were 126 cm, 130 cm and 689 cm, respectively. The dechlorination/degradation of 4-CP must be in- creased when the technology is applied to the real site.

关键词： biobarrier 2,4,6-TCP anaerobic dechlorination first-order kinetic model simulation

Global social archaeologies

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Global social archaeologies

Stick–slip behavior of Indian gabbro as studied using a NIED large-scale biaxial friction apparatus

作者： Koji mizoguchi and Claire Smith.

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Earthquake Science 2015年第2期28卷 97-118页

作者： Tetsuhiro Togo Toshihiko Shimamoto Futoshi Yamashita Eiichi Fukuyama Kazuo mizoguchi Yumi Urata State Key Laboratory of Earthquake Dynamics Institute of Geology China Earthquake Administration Geological Survey of Japan AIST Tsukuba Central 7 National Research Institute for Earth Science and Disaster Prevention (NIED) Central Research Institute of Electric Power Industry

This paper reports stick-slip behaviors of Indian gabbro as studied using a new large-scale biaxial friction apparatus, built in the National Research Institute for Earth Science and Disaster Prevention （NIED）, Tsukuba, Japan. The apparatus consists of the existing shaking table as the shear-loading device up to 3,600 kN, the main frame for holding two large rectangular prismatic specimens with a sliding area of 0.75 m^2 and for applying normal stresses an up to 1.33 MPa, and a reaction force unit holding the stationary specimen to the ground. The shaking table can produce loading rates v up to 1.0 m/s, accelerations up to 9.4 m/s^2, and displacements d up to 0.44 m, using four servocontrolled actuators. We report results from eight preliminary experiments conducted with room humidity on the same gabbro specimens at v = 0.1-100 mm/s and an = 0.66-1.33 MPa, and with d of about 0.39 m. The peak and steady-state friction coefficients were about 0.8 and 0.6, respectively, consistent with the Byerlee friction. The axial force drop or shear stress drop during an abrupt slip is linearly proportional to the amount of displacement, and the slope of this rela- tionship determines the stiffness of the apparatus as 1.15 × 10^8 N/m or 153 MPa/m for the specimens we used. This low stiffness makes fault motion very unstable and the overshooting of shear stress to a negative value was recognized in some violent stick-slip events. An abrupt slip occurred in a constant rise time of 16-18 ms despite wide variation of the stress drop, and an average velocity during an abrupt slip is linearly proportional to the stress drop. The use of a large-scale shaking table has a great potential in increasing the slip rate and total displacement in biaxial friction experiments with large specimens.

关键词： Stick-slip in gabbro - Biaxial frictionapparatus - Shaking table Friction experiment Faultmechanics