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Immunopathogenesis of inflammatory bowel disease

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World Journal of Gastroenterology 2008年第3期14卷 390-400页

作者： david Q shih Stephan R Targan Cedars-Sinai Inflammatory Bowel Disease Center Los Angeles CA United States Department of Medicine Division of Digestive Diseases University of California Los Angeles CA United States Cedars-Sinai Inflammatory Bowel Disease Center Los Angeles CA United States

Crohn＇s disease and ulcerative colitis are chronic relapsing immune mediated disorders that results from an aberrant response to gut luminal antigen in genetically susceptible host. The adaptive immune response that is then triggered was widely considered to be a T-helper-1 mediated condition in Crohn＇s disease and T-helpero2 mediated condition in ulcerative colitis. Recent studies in animal models, genome wide association, and basic science has provided important insights in in the immunopathogenesis of inflammatory bowel disease, one of which was the characterization of the interleukin-23/Th-17 axis.

关键词： Crohn's disease Ulcerative colitis Innate andadaptive immune system

A case of steroid-dependent myeloid granulocytic sarcoma masquerading as Crohn's disease

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World Journal of Gastroenterology 2011年第19期17卷 2446-2449页

作者： Lola Y Kwan Stephan R Targan david Q shih Division of Gastroenterology and Hepatology University of Rochester Medical CenterRochesterNY 14642United States Inflammatory Bowel Disease Center and Immunobiology Research Institute Cedars-Sinai Medical CenterLos AngelesCA 90048United States Cedars-Sinai Inflammatory Bowel and Immunobiology Research Institute 8700 Beverly Blvd.Suite 4066Los AngelesCA 90048United States

Small bowel tumors and Crohn's disease are common causes of small bowel *** stage neoplasms can easily be mistaken for Crohn's ***,thorough work-ups including imaging studies and endoscopic evaluation with biopsies are critical for accurate *** we report a case of an otherwise healthy female with progressive onset of multiple,recurrent obstructive symptoms secondary to terminal ileal narrowing who was referred for management of steroid-dependent Crohn's *** thorough evaluation,the diagnosis was revised to myeloid granulocytic sarcoma involving the terminal *** this case,a delay in diagnosis can be detrimental for prognosis,as myeloid granulocytic sarcoma is highly predictive of underlying acute myeloid leukemia and needs urgent referral for chemotherapy and/or resection.

关键词： Crohn's disease Myeloid sarcoma Ileum Steroids

Insights on the use of biosimilars in the treatment of inflammatory bowel disease

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World Journal of Gastroenterology 2017年第11期23卷 1932-1943页

作者： Michael K Zheng david Q shih Gary C Chen F.Widjaja Foundation Inflammatory Bowel and Immunobiology Research InstituteCedars-Sinai Medical Center Comprehensive Digestive Institute of Nevada

Biologic therapy, such as those that target tumor necrosis factor(TNF) signaling, has proven to be an efficacious method of treatment for patients with inflammatory bowel disease(IBD) with regards to symptom management and mucosal healing. However, the rising prevalence of IBD worldwide and the everincreasing burden of biologic pharmaceuticals in the health care industry is alarming for insurance companies, clinicians, and patients. The impending patent expiry and the relatively high costs of biologics, particularly anti-TNF agents, have paved the way for biosimilar development for IBD. The United States Food and Drug Administration defines a biosimilar as a biological product that is highly similar to its reference medicinal product, with no clinically meaningful differences in terms of safety, purity, and potency. The hope with biosimilars is that their entry into the market will be able to drive competition between pharmaceutical companies to reduce prices like that of the generic market, and that access to appropriate biologic treatments for IBD patients is increased in the long-term. Yet, there are challenging issues such as indication extrapolation and interchangeability that are still being debated in the field of IBD and must be addressed in future issued guidance. This review will discuss the issues and implications concerning the use of biosimilar therapy for IBD.

关键词： Biosimilar Biologic Inflammatory bowel disease Ulcerative colitis Crohn’s disease Indication extrapolation Interchangeability

Immunopathology of inflammatory bowel disease

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World Journal of Gastroenterology 2014年第1期20卷 6-21页

作者： Kori L Wallace Li-Bo Zheng Yoshitake Kanazawa david Q shih F Widjaja Foundation Inflammatory Bowel and Immunobiology Research InstituteCedars-Sinai Medical CenterLos Angeles CA 90048United States Department of Gastroenterology The Second Hospital of Hebei Medical University

Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed.

关键词： Inflammatory bowel disease, Crohn’ s disease, Ulcerative colitis, Microbiome, Autophagy, T helper 17, Innate immune system, Adaptive immune system, Innate lymphoid cells, TL1A

Effects and mechanism of adenovirus-mediated phosphatase and tension homologue deleted on chromosome ten gene on collagen deposition in rat liver fibrosis

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World Journal of Gastroenterology 2017年第32期23卷 5904-5912页

作者： Shu-rui Xie Jun-yan An Li-bo Zheng Xiao-Xia Huo Jian Guo david shih Xiao-Lan Zhang Department of Gastroenterology The Second Hospital of Hebei Medical University Hebei Key Laboratory of Gastroenterology Hebei Institute of Gastro- enterology Department of Gastroenterology Xingtai People's Hospital Inflammatory Bowel and Immunobiology Research Institute F. Widjaja Foundation Cedars-Sinai Medical Center

AIM To evaluate the effects of phosphatase and tension homologue deleted on chromosome ten(PTEN) gene on collagen metabolism in hepatic fibrosis and the underlying *** rat primary hepatic stellate cells(HSCs) and human LX-2 cells were transfected with adenovirus containing c DNA constructs encoding wild-type PTEN(Ad-PTEN), PTEN mutant G129 E gene(Ad-G129E), and r NA interference constructs targeting the PTEN sequence PTEN short hairpin r NA to up-regulate and downregulate the expression of PTEN. HSCs were assayed using fluorescent microscopy, real-time polymerase chain reaction, and western blotting. Moreover, a CCl_4-induced rat hepatic fibrosis model was established to investigate the in vivo effects. Hematoxylin and eosin, and Masson's trichrome were used to assess the histological changes. The expression of collagen Ⅰ and Ⅲ was assessed using immunohistochemistry and western blot *** Elevated expression of PTEN gene reduced serum levels of alanine transaminase and aspartate transaminase, decreased collagen deposition in the liver, and reduced hepatocyte necrosis. In contrast, knockdown of PTEN expression had an opposite effect, such as increased collagen deposition in the liver, and was molecularly characterized by the increased expression of matrix metalloproteinase(MMP)-13(P < 0.01) and MMP-2(P < 0.01), as well as decreased expression of the tissue inhibitor of metalloproteinase(TIMP)-1(P < 0.01) and TIMP-2(P < 0.01).CONCLUSION These data indicated that gene therapy using recombinant adenovirus encoding PTEN might be a novel way of treating hepatic fibrosis.

关键词： Collagen metabolism Hepatic stellate cells Phosphatase and tension homologue deleted on chromosome ten PTEN Gene therapy Hepatic fibrosis

肿瘤坏死因子样配体1A在慢性实验性结肠炎相关肠纤维化中的作用与机制

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中华消化杂志 2019年第7期39卷 452-457页

作者：战蓉蓉王冬贾文秀宋佳吴梦瑶李辉尹凤荣王娜彭晨星张红宋梅陈爽 david Quan shih 张晓岚河北医科大学第二医院消化内科河北省消化病重点实验室河北省消化病研究所石家庄050035 雪松西奈山医学中心生物医学科学系免疫学科和儿科免疫与传染病中心洛杉矶加利福尼亚州90001 雪松西奈山医学中心洛杉矶席徳炎症性肠病和免疫生物研究所洛杉矶加利福尼亚州90001

目的探讨肿瘤坏死因子样配体1A(TL1A)在慢性实验性结肠炎相关肠纤维化中的作用与机制.方法通过右旋葡聚糖硫酸钠(DSS)诱导建立慢性实验性结肠炎相关肠纤维化模型,将淋系细胞高表达TL1A(L-Tg)小鼠和具有相同遗传背景的野生型小鼠分成... 详细信息

目的探讨肿瘤坏死因子样配体1A(TL1A)在慢性实验性结肠炎相关肠纤维化中的作用与机制.方法通过右旋葡聚糖硫酸钠(DSS)诱导建立慢性实验性结肠炎相关肠纤维化模型,将淋系细胞高表达TL1A(L-Tg)小鼠和具有相同遗传背景的野生型小鼠分成野生型对照组、野生型DSS组、转基因对照组和转基因DSS组.比较各组小鼠体质量、结肠长度、疾病活动指数(DAI)评分和结肠病理评分的变化,采用H-E染色评估结肠炎症程度,Masson染色与天狼星红染色评估肠纤维化程度,免疫组织化学法检测结肠组织中波形蛋白、α平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原、Ⅲ型胶原及TGF-β1/丝-苏氨酸激酶3(Smad3)表达.采用t检验进行统计学分析.结果转基因DSS组体质量下降(9.6±1.8)%,高于野生型DSS组下降的(6.2±1.3)%,差异有统计学意义(t=3.751,P<0.01),转基因DSS组DAI评分和结肠病理评分均高于野生型DSS组[分别为(7.33±0.58)分比(6.00±1.00)分,(14.00±1.05)分比(11.75±0.50)分],差异均有统计学意义(t=2.818、4.739,P均<0.05),且Masson染色与天狼星红染色均提示肠纤维化程度加重.免疫组织化学染色结果显示,野生型DSS组小鼠波形蛋白、α-SMA、TGF-β1和Smad3的累积阳性吸光度值均低于转基因DSS组(分别为0.650±0.050比0.800±0.020,0.390±0.040比0.600±0.040,0.550±0.040比0.730±0.040,0.590±0.020比0.830±0.040),差异均有统计学意义(t=6.823、9.093、7.794、10.390,P均<0.01).结论 TL1A可能通过激活TGF-β1/Smad3通路促进肠成纤维细胞的活化与增殖,导致实验性结肠炎相关肠纤维化的发生、发展.

关键词：炎性肠疾病肠纤维化肿瘤坏死因子样配体1A

Advancements in Liver Tumor Detection:A Comprehensive Review of Various Deep Learning Models

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 91-122页

作者： Shanmugasundaram Hariharan D.Anandan Murugaperumal Krishnamoorthy Vinay Kukreja Nitin Goyal shih-Yu Chen Deptartment of Artificial Intelligence and Data Science Vardhaman College of EngineeringHyderabad501218India Deptartment of CSE V.S.B College of EngineeringKarur639111India Deptartment of Electrical and Electronics Engineering Vardhaman College of EngineeringHyderabad501218India Centre for Research Impact&Outcome Chitkara UniversityRajpura140401PunjabIndia Department of Computer Science and Engineering School of Engineering and TechnologyCentral University of HaryanaMahendergarh123031HaryanaIndia Department of Computer Science and Information Engineering National Yunlin University of Science and TechnologyYunlin64002Taiwan Intelligence Recognition Industry Service Research Center National Yunlin University of Science and TechnologyYunlin64002Taiwan

Liver cancer remains a leading cause of mortality worldwide,and precise diagnostic tools are essential for effective treatment *** Tumors(LTs)vary significantly in size,shape,and location,and can present with tissues of similar intensities,making automatically segmenting and classifying LTs from abdominal tomography images crucial and *** review examines recent advancements in Liver Segmentation(LS)and Tumor Segmentation(TS)algorithms,highlighting their strengths and limitations regarding precision,automation,and *** metrics are utilized to assess key detection algorithms and analytical methods,emphasizing their effectiveness and relevance in clinical *** review also addresses ongoing challenges in liver tumor segmentation and identification,such as managing high variability in patient data and ensuring robustness across different imaging *** suggests directions for future research,with insights into technological advancements that can enhance surgical planning and diagnostic accuracy by comparing popular *** paper contributes to a comprehensive understanding of current liver tumor detection techniques,provides a roadmap for future innovations,and improves diagnostic and therapeutic outcomes for liver cancer by integrating recent progress with remaining challenges.

关键词： Liver tumor detection liver tumor segmentation image processing liver tumor diagnosis feature extraction tumor classification deep learning machine learning

Making bridges between preclinical and clinical insights into age-related cognitive decline

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Neural Regeneration Research 2025年第8期20卷 2321-2322页

作者： david VC Brito Clévio Nóbrega Algarve Biomedical Center-Research Institute(ABC-RI) Campus GambelasFaroPortugal Algarve Biomedical Center-(ABC) Campus GambelasFaroPortugal Faculty of Medicine and Biomedical Sciences(FMCB) University of AlgarveGambelas CampusFaroPortugal

With people living longer,the societal impact of age-related cognitive decline is becoming more pronounced(Crimmins,2015).Thus,it is increasingly important to comprehend the cognitive shifts linked to aging-whether th... 详细信息

关键词： bridges becoming insight

Women in visual neural regeneration research

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Neural Regeneration Research 2025年第2期20卷 489-490页

作者： Tonia S.Rex david J.Calkins Vanderbilt Eye Institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of *** take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this *** National Eye Institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in ***,we focus on this *** sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue Ridge Institute for Medical Research and data from the major professional organization for eye and vision research,the Association for Research in Vision and Ophthalmology(ARVO).

关键词： neural visual Times