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Identification and Analysis of Gut Microbiota and Functional Metabolism in Decompensated Cirrhosis with Infection

Journal of Clinical and Translational Hepatology 2023年第1期11卷 15-25页

作者： Cyriac Abby Philips Rizwan Ahamed Jinsha K.P.Abduljaleel Sasidharan Rajesh Philip Augustine Clinical and Translational Hepatology Monarch Liver LaboratoryThe Liver InstituteCenter of Excellence in GI SciencesRajagiri HospitalAluvaKeralaIndia Gastroenterology and Advanced GI Endoscopy Center for Excellence in Gastrointestinal SciencesRajagiri HospitalAluvaKeralaIndia Diagnostic and Interventional Gastroenterology and Hepatology Center for Excellence in Gastrointestinal SciencesRajagiri HospitalAluvaKeralaIndia

Background and Aims:Intestinal dysbiosis play a role in the adverse outcomes of sepsis and septic ***,variations in bacterial diversity and microbiota-related functional metabolic alterations within the gut microbiome in decompensated cirrhosis(DC)patients with infection remain ***:We conducted 16-srRNA sequencing on stool samples(n=51:sepsis,27/no sepsis,24)collected from consecutive DC patients upon *** diversity,significant taxa,and respective metabolic profiling were performed based on subgroup ***/Cytoscape was utilized to identify significant non-random patterns of bacterial copresence and mutual exclusion for clinical ***:Genera associated with pathogenicity in conditions of immune exhaustion(Corynebacterium,Lautropia)were predominant in patients with *** pathways associated with oxidative stress and endotoxemia[lipopolysaccharide(LPS)synthesis and sulfur relay]were significantly upregulated in *** taxa were associated with sites of infection in DC *** oxidant pathways that increase glutathione were upregulated in those without *** family of sulfur-metabolizing bacteria,exaggeration of orally predominant pathogens(Prevotella),and pathways of severe LPS-related hyperinflammatory stress were notable in those with interleukin-6 levels>1,000 pg/*** genera related to an immune deficient state was significant in DC with≥2 infection *** was associated with survival during the same ***:Specific gut microbiota and their metabolites were associated with sepsis and related events in patients with *** beneficial strains that reduce immune exhaustion and supplementation of favorable metabolites could improve therapeutics for DC and sepsis,for which larger prospective,well controlled population-based studies remain an unmet need.

关键词： Microbiome Portal hypertension Sepsis Acute-on-chronic liver failure Multidrug resistance

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gastrointestinal stromal tumor causing small bowel intussusception in a patient with Crohn’s disease

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World Journal of Gastroenterology 2009年第41期15卷 5224-5227页

作者： George E Theodoropoulos Dimitrios Linardoutsos Dimitrios Tsamis Paraskevas Stamopoulos Dimitrios Giannopoulos Flora Zagouri Nikolaos V Michalopoulos First Department of Propaedeutic Surgery Hippocration University Hospital Department of Pathology Hippocration University Hospital Department of Clinical therapeutics Alexandra Hospital

We report a case of jejunoileal intussusception in a 42-year-old patient with Crohn's disease caused by a gastrointestinal stromal tumor. The patient complained of vague diffuse abdominal pain for a period of 4 mo. Intussusception was suspected at computer tomography and magnetic resonance imaging scans. Segmental resection of the small intestine was performed. Pathological examination of the surgical specimen revealed a gastrointestinal stromal tumor as well as aphthous ulcerations and areas of inflammation, which were characteristic of Crohn's disease. This is the f irst report of small bowel intussusception due to a gastrointestinal stromal tumor coexisting with Crohn's disease.

关键词： gastrointestinal stromal tumor Crohn's disease Intussusception

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Personalizing therapies for gastric cancer: Molecular mechanisms and novel targeted therapies

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World Journal of Gastroenterology 2013年第38期19卷 6383-6397页

作者： Michael Luis Ana Tavares Liliana S Carvalho Lúcio Lara-Santos António Araújo Ramon Andrade de Mello gastrointestinal Unit Service of Medical OncologyPortuguese Oncology Institute4200-072 PortoPortugal gastrointestinal Unit Experimental Pathology and Therapeutics GroupResearch Center-Portuguese Oncology Institute4200-072 PortoPortugal Department of Pharmacology and therapeutics Faculty of MedicineUniversity of Porto4200-319 PortoPortugal Institute of Cellular and Molecular Biology 4150-180 PortoPortugal gastrointestinal Unit Section of Surgical OncologyPortuguese Oncology Institute4200-072 PortoPortugal Department of Medicine Faculty of MedicineUniversity of Porto4200-319 PortoPortugal

Globally,gastric cancer is the 4thmost frequently diagnosed cancer and the 2ndleading cause of death from cancer,with an estimated 990000 new cases and738000 deaths registered in *** the advanced setting,standard chemotherapies protocols acquired an important role since last decades in prolong ***,recent advances in molecular therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2(HER2)***,an anti-HER2 monoclonal antibody,was the first target drug in the metastatic setting that showed benefit in overall survival when in association with platinum-5-fluorouracil based ***,HER2 overexpression analysis acquired a main role in predict response for trastuzumab in this ***,we conducted a review that will discuss the main points concerning trastuzumab and HER2 in gastric cancer,providing a comprehensive overview of molecular mechanisms and novel trials involved.

关键词： Gastric cancer Human epidermal growth factor receptor 2 Biomarkers Target therapies Trastuzumab Lapatinib Pertuzumab Trastuzumab-DM1 Afatinib

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Antibody Therapies Targeting Complex Membrane Proteins

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Engineering 2021年第11期7卷 1541-1551页

作者： Georgina To’a Salazar Ziyi Huang Ningyan Zhang Xue-Guang Zhang Zhiqiang An Texas therapeutics Institute Brown Foundation Institute of Molecular MedicineThe University of Texas Health Science Center at HoustonHoustonTX 77030USA Jiangsu Institute of Clinical Immunology The First Affiliated Hospital of Soochow UniversitySuzhou 215123China Jiangsu Key Laboratory of Clinical Immunology Soochow UniversitySuzhou 215123China Jiangsu Key Laboratory of gastrointestinal Tumor Immunology The First Affiliation Hospital of Soochow UniversitySuzhou 215123China State Key Laboratory of Radiation Medicine and Protection Soochow UniversitySuzhou 215123China

In analyses of protein families that may serve as drug targets,membrane-associated G-protein-coupled receptors(GPCRs)dominate,followed by ion channels,transporters,and—to a lesser extent—membrane-bound ***,various challenges put such membrane proteins among key groups of underutilized opportunities for the application of therapeutic *** hold the promise of exquisite specificity,as they are able to target even specific conformations of a particular membrane protein,as well as adaptability through engineering into various antibody ***,the ease of raising and isolating specific,effective antibodies targeting membrane proteins depends on many *** particular,the generation of specific antibodies is easier when targeting larger,simpler,extracellular domains with greater uniqueness of amino acid *** rareness of such ideal conditions is illustrated by the limited number of approved biologics for targeting GPCRs and other complex membrane *** in developing antibodies to complex membrane proteins such as GPCRs,ion channels,transporters,and membrane-bound enzymes can be addressed by the design of the antigen,antibody-generation strategies,lead optimization technologies,and antibody modalities.A better understanding of the membrane proteins being targeted would facilitate mechanism-based drug *** review describes the advantages and challenges of targeting complex membrane proteins with antibodies and discusses the preparation of membrane protein antigens and antibody generation,illustrated by select examples of success.

关键词： Antibody therapy Complex membrane protein Ion channels Transporters Membrane-bound enzymes GPCRs Drug discovery

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Roles of galectins in inflammatory bowel disease

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World Journal of Gastroenterology 2008年第33期14卷 5133-5137页

作者： Akira Hokama Emiko Mizoguchi Atsushi Mizoguchi Department of Medicine and therapeutics (First Department of Internal Medicine) Control and Prevention of Infectious Disease Faculty of Medicine University of the RyukyusOkinawa 903-0215 Japan gastrointestinal Unit Department of Medicine Massachusetts General Hospital Harvard Medical SchoolBoston MA 02114 United States Center for the Study of Inflammatory Bowel Disease Massachusetts General Hospital Harvard Medical School Boston MA 02114 United States Experimental Pathology Unit Department of Pathology Massachusetts General Hospital Harvard Medical SchoolBoston MA 02114 United States

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.

关键词： Galectin Inflammatory bowel disease Crohn's disease Ulcerative colitis Pathogenesis Apoptosis Glycosylation

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Peptidomic Analysis Reveals that Novel Peptide LDP2 Protects Against Hepatic Ischemia/Reperfusion Injury

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Journal of Clinical and Translational Hepatology 2023年第2期11卷 405-415页

作者： Qun Bao Zhengxin Wang Sheng Cheng Jin Zhang Qiuli Liu Yunpeng Zhang Daqing Cheng Xirong Guo Xingyun Wang Bo Han Peng Sun Department of General Surgery Tongren HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Key Laboratory for Translational Research and Innovative therapeutics of gastrointestinal Oncology Hongqiao International Institute of MedicineTongren HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of General Surgery Huashan HospitalFudan UniversityShanghaiChina Institute of Organ Transplantation Fudan UniversityShanghaiChina Department of Anesthesiology and SICU Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Background and Aims:Hepatic ischemia/reperfusion(I/R)injury has become an inevitable issue during liver transplantation,with no effective treatments ***,peptide drugs provide promising regimens for the treatment of this injury and peptidomics has gradually attracted increasing *** study was designed to analyze the spectrum of peptides in injured livers and explore the potential beneficial peptides involved in I/R ***:C57BL/6 mice were used to establish a liver I/R injury animal *** in peptide profiles in I/R-injured livers were analyzed by mass spectrometry,and the functions of the identified peptides were predicted by ***12 cells were used to simulate hepatic I/R injury in *** treatment with candidate liver-derived peptides(LDPs)1–10,the cells were collected at various reperfusion times for further ***:Our preliminary study demonstrated that 6 h of reperfusion caused the most liver I/R *** results suggested that 10 down-regulated peptides were most likely to alleviate I/R injury by supporting mitochondrial *** importantly,a novel peptide,LDP2,was identified that alleviated I/R injury of AML12 *** increased cell viability and reduced the expression of inflammation-and apoptosis-related *** addition,LDP2 inhibited the expression of proteins related to ***:Investigation of changes in the profiles of peptides in I/R-injured livers led to identification of a novel peptide,LDP2 with potential function in liver protection by inhibiting inflammation,apoptosis,and autophagy.

关键词： Hepatic ischemia/reperfusion(I/R)injury Peptidomics Peptide LDP2 Apoptosis Autophagy

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Non-responsive celiac disease in children on a gluten free diet

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World Journal of Gastroenterology 2021年第13期27卷 1311-1320页

作者： Gopal Veeraraghavan Amelie Therrien Maya Degroote Allison McKeown Paul D Mitchell Jocelyn A Silvester Daniel A Leffler Alan M Leichtner Ciaran P Kelly Dascha C Weir Division of Gastroenterology Hepatology and NutritionBoston Children's HospitalBostonMA 02115United States The Celiac Center Department of Medicine and Division of GastroenterologyBeth Israel Deaconess Medical CenterBostonMA 02215United States Celiac Research Program Harvard Medical SchoolBostonMA 02115United States Institutional Centers for Clinical and Translational Research Boston Children's HospitalBostonMA 02115United States gastrointestinal therapeutics Takeda Pharmaceutical International CoCambridgeMA 02139United States

BACKGROUND Non-responsive celiac disease(NRCD) is defined as the persistence of symptoms in individuals with celiac disease(CeD) despite being on a gluten-free diet(GFD). There is scant literature about NRCD in the pediatric *** To determine the incidence, clinical characteristics and underlying causes of NRCD in *** Retrospective cohort study performed at Boston Children’s Hospital(BCH). Children < 18 years diagnosed with CeD by positive serology and duodenal biopsies compatible with Marsh Ⅲ histology between 2008 and 2012 were identified in the BCH’s Celiac Disease Program database. Medical records were longitudinally reviewed from the time of diagnosis through September 2015. NRCD was defined as persistent symptoms at 6 mo after the initiation of a GFD and causes of NRCD as well as symptom evolution were detailed. The children without symptoms at 6 mo(responders) were compared with the NRCD group. Additionally, presenting signs and symptoms at the time of diagnosis of CeD among the responders and NRCD patients were collected and compared to identify any potential predictors for NRCD at 6 mo of GFD *** Six hundred and sixteen children were included. Ninety-one(15%) met criteria for NRCD. Most were female(77%). Abdominal pain [odds ratio(OR) 1.8 95% confidence interval(CI) 1.1-2.9], constipation(OR 3.1 95%CI 1.9-4.9) and absence of abdominal distension(OR for abdominal distension 0.4 95%CI 0.1-0.98) at diagnosis were associated with NRCD. NRCD was attributed to a wide variety of diagnoses with gluten exposure(30%) and constipation(20%) being the most common causes. Other causes for NRCD included lactose intolerance(9%), gastroesophageal reflux(8%), functional abdominal pain(7%), irritable bowel syndrome(3%), depression/anxiety(3%), eosinophilic esophagitis(2%), food allergy(1%), eating disorder(1%), gastric ulcer with Helicobacter pylori(1%), lymphocytic colitis(1%), aerophagia(1%) and undetermined(13%). 64% of children with NRCD

关键词： Celiac disease Non-responsive celiac disease Children Gluten-free diet Constipation Abdominal pain

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Immune checkpoint B7-H1 monoclonal antibodies for immunohistochemistry test in the diagnosis of colorectal cancer

Immune checkpoint B7-H1 monoclonal antibodies for immunohist...

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第十二届全国免疫学学术大会

作者： Huang Ziyi Cao Lei Gu Yanzheng Zhang Ningyan An Zhiqiang Zhang Xueguang The First Affiliated Hospital of Soochow University Jiangsu Key Laboratory of Clinical Immunology Soochow University Jiangsu Key Laboratory of gastrointestinal tumor Immunology Texas therapeutics Institute University of Texas Health Science Center at Houston

The finding that tumors could actively suppress immunity has led to the development of ’checkpoint blockades’ that prevent this *** of the recently discovered mechanisms was co-inhibitory molecules expressed by tumor cells,immune cells and stromal cells in the tumor microenvironment attenuated T cell responses against cancer *** group of co-inhibitory molecules is called immune checkpoint molecules including CTLA-4,PD-1,B7-H1(PD-L1),B7-H3 and *** therapies targeting the inhibitory checkpoint PD-1 have demonstrated promising activity in several cancers,among which some PD-L1 positive tumors demonstrated higher response rates to anti PD-1 therapies,suggesting that identifying PD-L1 expression could be a predictive biomarker to select patients likely to respond to anti PD-1 ***,we found that B7-H1 was highly expressed in colorectal cancer tissues and showed differential expression levels during disease progression.B7-H1 expression in colorectal cancer tissues can be heterogeneous in staining intensity and have variable distribution throughout an individual *** succeeded in developing anti-human B7-H1 and CD8 mAbs suitable for immunohistochemical staining in formalin-fixed tissue sections with reliable clarity and *** was applied to identify B7-H1 that correlated with colorectal cancer status,T cell infiltrate,and patient survival.B7-H1 expressed in the early stages of colorectal evolution was one of the earliest inhibitory molecules of the B7 family to be engaged in the development of colorectal cancer,which could be significant to determine the immune classification(immunoscore) in cancer *** mAbs are potentially useful as companion diagnostic agents to analyze B7-H1 expression in the clinical setting while the expression pattern in the corresponding stage will be important to clarify tumor immune escape mechanism at different stages of colorectal cancer.

关键词： immune checkpoint monoclonal antibodies colorectal cancer immunohistochemistry

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Early-onset colorectal cancer:Current insights and future directions

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World Journal of gastrointestinal Oncology 2022年第1期14卷 230-241页

作者： Claudia Wing-Kwan Wu Rashid N Lui Division of Gastroenterology and Hepatology Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina Department of Clinical Oncology The Chinese University of Hong KongHong KongChina

Early-onset colorectal cancer(EOCRC)has seen an alarming rise worldwide over the past two *** reason for this global trend is poorly *** appears to have its own unique clinical and molecular features when compared with late-onset colorectal *** patients appear to have more distal or rectal disease,a more advanced stage of disease at presentation,and more unfavorable histological *** risk factors for EOCRC is the first step in mitigating the rising burden of this *** we summarize several noteworthy biological factors and environmental exposures that are postulated to be responsible *** can hopefully translate in clinical practice to the development of better risk stratification tool for identifying highrisk individuals for early colorectal cancer screening,and identifying areas needed for further research to curb this rising trend.

关键词： Early-onset colorectal cancer Young-onset colorectal cancer Risk factors Environmental exposures Microbiome Genetics

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Salvage Photodynamic Therapy Is an Effective and Safe Treatment for Patients with Local Failure after Definitive Chemoradiotherapy for Esophageal Squamous Cell Carcinoma

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Journal of Cancer Therapy 2014年第7期5卷 647-656页

作者： Yoko Mashimo Yasumasa Ezoe Kosuke Ueda Yoshinao Ozaki Yusuke Amanuma Ikuo Aoyama Takahiro Horimatsu Shuko Morita Shin’ichi Miyamoto Tomonori Yano Koji Higashino Tsutomu Chiba Manabu Muto Department of Experimental therapeutics Institute for Advancement of Clinical and Translational Science (iACT) Kyoto University Hospital Kyoto Japan Department of Gastroenterology and Hepatology Graduate School of Medicine Kyoto University Kyoto Japan Department of gastrointestinal Oncology Osaka Medical Centre for Cancer and Cardiovascular Diseases Osaka Japan Department of Therapeutic Oncology Graduate School of Medicine Kyoto University Kyoto Japan Division of Digestive Endoscopy and gastrointestinal Oncology National Cancer Center Hospital East Kashiwa Japan

Although chemoradiotherapy (CRT) is one curative treatment option for patients with esophageal squamous cell carcinoma (ESCC), local failure after CRT remains a major problem for patients’ curability. The aim of this study was to evaluate the efficacy and safety of photodynamic therapy (PDT) as a salvage treatment for local failure. From August 2007 to March 2012, 193 consecutive ESCC patients were treated with definitive CRT in Kyoto University Hospital. Eighteen of the patients with T2 or earlier T-stage local failure after CRT underwent salvage PDT. After the salvage PDT, 11 patients (61.1%) achieved a complete response at the primary site. Over a median follow-up period of 28.3 months, the 1-year survival and progression-free survival rates were 77.8% and 38.9%, respectively;and the 2-year survival and progression-free survival rates were 60.6% and 33.3%, respectively. Adverse events were mild esophageal stricture in seven (38.9%), esophageal obstruction because of necrotic tissue in nine (50.0%), and photosensitivity in three (16.7%) patients. There were no severe complications or treatment-related deaths. Salvage PDT may be a promising treatment option for the patients with a local residual or recurrent tumor after CRT for ESCC when the lesion is suspected to be in T2 or earlier.

关键词： Esophageal Cancer Salvage Treatment Photodynamic Therapy Chemoradiotherapy Local Failure

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