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Proteomics and metabolic phenotyping define principal roles for the aryl hydrocarbon receptor in mouse liver

Acta Pharmaceutica Sinica B 2021年第12期11卷 3806-3819页

作者： Jian Jin Banrida Wahlang Monika Thapa Kimberly Z.Head Josiah E.Hardesty Sudhir Srivastava michael L.merchant Shesh N.Rai Russell A.Prough Matthew C.Cave Department of Pharmacology&Toxicology theUniversity of Louisville School ofMedicineLouisvilleKY 40202USA Department of Endocrinology the Second Affiliated Hospital&Yuying Children’s HospitalWenzhou Medical UniversityWenzhou 325027China Division of Gastroenterology Hepatology&NutritionDepartment of Medicinethe University of Louisville School of MedicineLouisvilleKY 40202USA Superfund Research Center the University of LouisvilleLouisvilleKY 40202USA eDepartment of Biochemistry and Molecular Geneticsthe University of Louisville School of MedicineLouisvilleKY 40202USA Department of Bioinformatics and Biostatistics the School of Public Health and Information Sciencesthe University of LouisvilleLouisvilleKY 40202USA Centre for Agricultural Bioinformatics ICAR-Indian Agricultural Statistics Research InstituteNew Delhi 110012India The Center for Integrative Environmental Health Sciences University of LouisvilleLouisvilleKY 40202USA Division of Nephrology&Hypertension Department of Medicinethe University of Louisville School of MedicineLouisvilleKY 40202USA The Hepatobiology and Toxicology Center University of LouisvilleLouisvilleKY 40202USA Alcohol Research Center University of LouisvilleLouisvilleKY 40202USA Biostatistics and Bioinformatics Facility James Graham Brown Cancer CenterLouisvilleKY 40202USA

Dioxin-like molecules have been associated with endocrine disruption and liver *** better understand aryl hydrocarbon receptor(AHR)biology,metabolic phenotyping and liver proteomics were performed in mice following ligand-activation or whole-body genetic ablation of this *** wild type(WT)and Ahr^(-/-) mice(Taconic)were fed a control diet and exposed to 3,3',4,4',5-pentachlorobiphenyl(PCB126)(61 nmol/kg by gavage)or vehicle for two ***126 increased expression of canonical AHR targets(Cyp1 a1 and Cyp1 a2)in WT but not Ahr^(-/-).Knockouts had increased adiposity with decreased glucose tolerance;smaller livers with increased steatosis and perilipin-2;and paradoxically decreased blood ***126 was associated with increased hepatic triglycerides in Ahr^(-/-).The liver proteome was impacted more so by Ahr^(-/-) genotype than ligandactivation,but top gene ontology(GO)processes were *** PCB126-associated liver proteome was *** principally regulated liver metabolism(e.g.,lipids,xenobiotics,organic acids)and bioenergetics,but it also impacted liver endocrine response(e.g.,the insulin receptor)and function,including the production of steroids,hepatokines,and pheromone binding *** effects could have been indirectly mediated by interacting transcription factors or *** biologic roles of the AHR and its ligands warrant more research in liver metabolic health and disease.

关键词： AHR Endocrine disruption Environmental liver disease Nonalcoholic fatty liver disease Perilipin-2 Pheromones PCB126

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Microbiome data analysis with applications to pre-clinical studies using QIIME2: Statistical considerations

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Genes & Diseases 2021年第2期8卷 215-223页

作者： Shesh N.Rai Chen Qian Jianmin Pan Jayesh P.Rai Ming Song Juhi Bagaitkar michael merchant Matthew Cave Nejat K.Egilmez Craig J.McClain Biostatistics and Bioinformatics Facility James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleKY40202USA Department of Biostatistics and Bioinformatics University of LouisvilleLouisvilleKY40202USA University of Louisville Alcohol Research Center University of LouisvilleLouisvilleKY40202USA University of Louisville Hepatobiology&Toxicology Center University of LouisvilleLouisvilleKY40202USA Department of Oral Immunology&Infectious Diseases University of LouisvilleLouisvilleKY40202USA Department of Medicine University of LouisvilleLouisvilleKY40202USA Robley Rex Louisville VAMC LouisvilleKY40206USA Department of Microbiology&Immunology University of LouisvilleLouisvilleKY40202USA

Diversity analysis and taxonomic profiles can be generated from marker-gene sequence data with the help of many available computational *** Quantitative Insights into Microbial Ecology Version 2(QIIME2)has been widely used for 16S rRNA data *** many articles have demonstrated the use of QIIME2 with suitable datasets,the application to preclinical data has rarely been talked *** issues involved in the pre-clinical data include the low-quality score and small sample size that should be addressed properly during *** addition,there are few articles that discuss the detailed statistical methods behind those alpha and beta diversity significance tests that researchers are eager to *** the program without knowing the logic behind it is extremely *** this article,we first provide a guideline for analyzing 16S rRNA data using *** we will talk about issues in pre-clinical data,and how they could impact the ***,we provide brief explanations of statistical methods such as group significance tests and sample size calculation.

关键词： 16S rRNA gene Alpha diversity ANOVA Beta diversity Bioinformatics Microbiome data QIIME Sample size calculation

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Racial and ethnic disparities in gastric cancer outcomes: More important than surgical technique?

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World Journal of Gastroenterology 2014年第33期20卷 11546-11551页

作者： Shaila J merchant Lily Li Joseph Kim Division of Surgical Oncology Department of Surgery City of Hope National Medical Center Duarte CA 91010 United States

Racial and ethnic disparities in cancer care are major public health concerns and their identification is necessary to develop interventions to eliminate these disparities. We and others have previously observed marked disparities in gastric cancer outcomes between Eastern and Western patients. These disparities have long been attributed to surgical technique and extent of lymphadenectomy. However, more recent evidence suggests that other factors such as tumor biology, environmental factors such as Helicobacter pylori infection and stage migration may also significantly contribute to these observed disparities. We review the literature surrounding disparities in gastric cancer and provide data pertaining to potential contributing factors.

关键词： Race Ethnicity Disparities Gastric cancer Gastric adenocarcinoma

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Myeloid-derived suppressor cells in gastrointestinal cancers:A systemic review

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World Journal of Gastrointestinal Oncology 2021年第1期13卷 1-11页

作者： Maham Farshidpour Monjur Ahmed Shilpa Junna Juanita L merchant Inpatient Medicine Banner University of Medical CenterTucsonAZ 85724United States Division of Gastroenterology and Hepatology Department of Internal MedicineThomas Jefferson UniversityPhiladelphiaPA 19107United States Division of Gastroenterology and Hepatology Banner University of Medical CenterTucsonAZ 85724United States

Gastrointestinal(GI)cancers are one of the most common malignancies worldwide,with high rates of morbidity and ***-derived suppressor cells(MDSCs)are major components of the tumor microenvironment(TME).MDSCs facilitate the transformation of premalignant cells and play roles in tumor growth and ***,in patients with GI malignancies,MDSCs can lead to the suppression of T cells and natural killer ***,a better understanding of the role and mechanism of action of MDSCs in the TME will aid in the development of novel immune-targeted therapies.

关键词： Myeloid-derived suppressor cells Gastrointestinal cancers Immune checkpoint inhibitors Tumor progression

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H pylori infection causes chronic pancreatitis in Mongolian gerbils

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World Journal of Gastroenterology 2007年第29期13卷 3939-3947页

作者： Gabriele Rieder Arno Karnholz Mechthild Stoeckelhuber Juanita L merchant Rainer Haas Max von Pettenkofer-Institute for Hygiene and Medical Microbiology Ludwig-Maximilians-University 80336 Munich Germany Institute of Anatomy Ludwig- Maximilians-University 80336 Munich Germany University of Michigan Departments of Internal Medicine and Molecular and Integrative Physiology Ann Arbor Michigan United States

AIM： To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system. METHODS： Mongolian gerbils were infected with wild type （WT） H pylori type Ⅰ strain B128 or its isogenic mutant B128 △cag γ （defective type Ⅳ secretion）. After seven months of infection, H pylori was reisolated from antrum and corpus and Hpylori DNA was analyzed by seminested polymerase chain reaction （PCR）. Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry. Cytokine mRNA, gastric pH, plasma gastrin, amylase, lipase, and glucose levels were determined. RESULTS： The H pylori infection rate was 95%. Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immuno-histochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals andthose developing transmural inflammation and pancreatitis were significantly increased. Levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue,but not in the pancreas CONCLUSION： H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type Ⅳ secretion system, probably by an indirect mechanism associated with a penetrating ulcer.

关键词： H pylori Mongolian gerbil Pancreatitis Gastritis Penetrating ulcer

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Introduction of new techniques and technologies in surgery: Where is transanal total mesorectal excision today?

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World Journal of Gastrointestinal Surgery 2020年第5期12卷 203-207页

作者： Antonio Caycedo-Marulanda Sunil Patel Shaila merchant Carl Brown Department of surgery Queen’s University and Kingston General HospitalKingston K7L 2V7OntarioCanada Department of Surgery University of British Columbia and St.Paul HospitalVancouver V6Z 1Y6British ColumbiaCanada

The introduction of new surgical techniques and technologies has traditionally been *** many settings surgeons frequently adopt novel procedures without following a structured program of implementation or *** appearance of innovative technology played a pivotal role in the advancement of new surgical techniques during the industrial *** has been an essential component of surgical development,which led to contemporary surgical techniques such as minimally invasive *** initiatives have been developed to guide the safe introduction of new surgical techniques and other *** include comprehensive concepts such as the Idea,Development,Exploration,Assessment,Long-term study framework,which could be particularly relevant when reflecting on the novel transanal total mesorectal excision(taTME),introduced a decade *** relatively novel and complex procedure promised to overcome some of the major limitations of traditional surgical approaches for rectal *** to the Idea,Development,Exploration,Assessment,Long-term study framework,taTME is in the phase of exploration,where there is an existing and increasing number of reports being published as the experience *** current management of rectal cancer is in a state of radical evolution,with multiple options that were not previously *** TME is only one technique amongst many which could be part of a rectal cancer surgeon’s armamentarium;however,it requires further rigorous study and evaluation.

关键词： Rectal cancer New technology Safety Innovation Transanal surgery

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Prospective evaluation of health status, quality of life and clinical outcomes following implantable defibrillator generator exchange

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Journal of Geriatric Cardiology 2021年第9期18卷 720-727页

作者： Faisal M merchant John Larson Leon Darghosian Paige Smith Soroosh Kiani Stacy Westerman Anand D.Shah David S.Hirsh michael S.Lloyd Angel R.Leon Mikhael F.El-Chami Section of Cardiac Electrophysiology Emory University School of MedicineAtlantaGAUSA Department of Medicine University of Michigan School of MedicineAnn ArborMIUSA Grady Health System AtlantaGAUSA

BACKGROUND Little is known about health status and quality of life(QoL)after implantable cardioverter-defibrillator(ICD)generator exchange(GE).METHODS We prospectively followed patients undergoing first-time ICD *** assessments of health status were performed by administering the 36-Item Short Form Survey(SF-36).RESULTS Mean age was 67.5±14.3 years,left ventricle ejection fraction(LVEF)was 36.5%±15.0%and over 40%of the cohort had improved LVEF to>35%at the time of ***-36 scores were significantly worse in physical/general health domains compared to domains of emotional/social well-being(P<0.001 for each comparison).Physical health scores were significantly worse among those with medical comorbidities including diabetes,chronic obstructive pulmonary disease and atrial *** follow-up was 1.6±0.5 years after *** SF-36 scores remained stable across all domains during *** at 3 years post-GE was estimated at 80%.Five patients died during follow-up and most deaths were adjudicated as non-arrhythmic in *** patients experienced appropriate ICD shocks after GE,three of whom had LVEF which remains impaired LVEF(i.e.,<35%)at the time of *** Patients undergoing ICD GE have significantly worse physical health compared to emotional/social well-being,which is associated with the presence of medical *** terms of clinical outcomes,the incidence of appropriate shocks after GE among those with improvement in LVEF is very low,and most deaths post-procedure appear to be non-arrhythmic in *** data represent an attempt to more fully characterize the spectrum of QoL and clinical outcomes after GE.

关键词： ICD quality of life and clinical outcomes following implantable defibrillator generator exchange Prospective evaluation of health status

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Low skeletal muscle mass is associated with non-alcoholic fatty liver disease in Korean adults： the Fifth Korea National Health and Nutrition Examination Survey

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Hepatobiliary & Pancreatic Diseases International 2016年第1期15卷 39-47页

作者： hee yeon kim chang wook kim chung-hwa park jong young choi kyungdo han anwar t merchant yong-moon park division of hepatology department of internal medicinecollege of medicinethe catholic university of korea222Banpo-daeroSeocho-guSeou1 06591Republic of Korea department of biostatistics college of medicinethe catholic university of korea222Banpo-daeroSeocho-guSeou1 06591Republic of Korea department of epidemiology and biostatistics arnold school of public healthuniversity of south carolinaColumbiaSC 29208USA epidemiology branch national institute of environmental health sciencesnational institutes of healthdepartment of health and human servicesResearch Triangle ParkNC 27709USA

BACKGROUND： Sarcopenia and non-alcoholic fatty liver dis- ease （NAFLD） share similar pathophysiological mechanisms, and the relationship between sarcopenia and NAFLD has been recently investigated. The study investigated whether low skel- etal muscle mass is differentially associated with NAFLD by gender in Korean adults. METHODS： We conducted a cross-sectional analysis of the data from the Fifth Korea National Health and Nutrition Examination Survey. The skeletal muscle index （SMI） was obtained by the appendicular skeletal muscle mass divided by the weight. NAFLD was defined as a fatty liver index （FLI）〉60 in the absence of other chronic liver disease. RESULTS： Among the included subjects, 18.3% （SE： 1.4%） in men and 7.0% （SE： 0.7%） in women were classified as having FLI-defined NAFLD. Most of the risk factors for FLI-defined NAFLD showed a significant negative correlation with the SMI in both genders. Multiple logistic regression analysis showed that low SMI was associated with FLI-defined NAFLD, inde- pendent of other metabolic and lifestyle parameters in both genders [males： odds ratio （OR）=1.35; 95% confidence inter- val （CI）： 1.17-1.54; females： OR=1.36; 95% CI： 1.18-1.55]. The magnitude of the association between FLI-defined NAFLD and low SMI was higher in middle aged to elderly males （OR-1.50; 95% CI： 1.22-1.84） than in males less than 45 years of age （OR=1.25; 95% CI： 1.02-1.52） and in premenopausal females （OR=l.50; 95% CI： 1.12-2.03） than in postmenopausal females （OR-1.36; 95% CI： 1.20-1.54）.CONCLUSIONS： Low SMI is associated with the risk of FLI- defined NAFLD independent of other well-known metabolic risk factors in both genders. This association may differ ac- cording to age group or menopausal status. Further studies are warranted to confirm this relationship.

关键词： Korea National Health and Nutrition Examination Survey non-alcoholic fatty liver disease sarcopenia skeletal muscle

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Immunohistochemical analysis of the Wnt/β-catenin signaling pathway in pancreatic neuroendocrine neoplasms

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World Journal of Gastrointestinal Oncology 2016年第8期8卷 615-622页

作者： Vivian Weiss Julie Dueber Jesse P Wright Justin Cates Frank Revetta Alexander A Parikh Nipun B merchant Chanjuan Shi Department of Pathology Microbiology and Immunology Vanderbilt University Medical Center Department of Surgery Surgical Oncology Vanderbilt University Medical Center Department of Surgery Surgical Oncology University of Miami Hospital

AIM: To investigate the role of the Wnt/β-catenin pathway in pancreatic neuroendocrine neoplasms(PanN ENs). METHODS: Tissue microarrays containing 88 PanN ENs were immunohistochemically labeled with antibodies to β-catenin, E-cadherin, adenomatous polyposis coli(APC), chromogranin and synaptophysin. One case had only metastatic tumors resected, whereas others(n = 87) received pancreatectomy with or without partial hepatectomy. Pathology slides, demographic, clinicopathologic, and follow up data were reviewed. Patients' demographics, clinicopathologic features, and immunohistochemical results from 87 primary tumors were compared between patients with low stage(stage Ⅰ/Ⅱ) and high stage(stage Ⅲ/Ⅳ) tumors. In addition, correlation of immunohistochemical results from primary tumors with disease-specific survival(DSS) was evaluated. RESULTS: Strong membranous β-catenin staining in the primary tumor was observed in all 13 stage Ⅲ/Ⅳ Pan NENs as compared to 47%(35/74) of stage Ⅰ/Ⅱtumors(P < 0.01). However, the strong membranous β-catenin staining was unassociated with tumor grade or DSS. Decreased membranous β-catenin staining was associated with decreased membranous E-cadherin labeling. Nuclear β-catenin staining was seen in 15%(2/13) of stage Ⅲ/Ⅳ Pan NENs as compared to 0%(0/74) of stage Ⅰ/Ⅱ tumors(P = 0.02). The case with metastasectomy only also showed nuclear β-catenin staining. Two of the three cases with nuclear β-catenin staining were familial adenomatous polyposis(FAP) patients. Lack of APC expression was seen in 70%(57/81) of the cases, including the 3 cases with nuclear β-catenin staining. Expression of E-cadherin and APC in primary tumor was not correlated with tumor grade, tumor stage, or disease specific survival. CONCLUSION: The Wnt/β-catenin pathway was altered in some PanN ENs, but did not Impact DSS. PanN ENs in FAP patients demonstrated nuclear β-catenin accumulation and loss of APC.

关键词： β-catenin Familial adenomatous polyposis Pancreatic neuroendocrine neoplasm Adenomatous polyposis coli E-cadherin

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Phenoloxidase and Melanization Innate Immune Activities in Green Darner Dragonfly Nymphs (Anax junius)

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Advances in Biological Chemistry 2022年第4期12卷 130-141页

作者： Mark merchant Matthew R. McClure Department of Chemistry McNeese State University Lake Charles USA Department of Biology Lamar State College Orange Orange USA

Insects in the Order Odonata are highly subject to infection by gregarine parasites. However, despite the important ecological roles that insects play in every ecosystem in which they exist, little research has been devoted to the description of insect immunity. Insects rely heavily on the rapid actions of innate immune mechanisms to prevent infection. We characterized the melanization response in the hemolymph of green darner dragonfly (Anax junius) nymphs. Incubation of chymotrypsin-activated hemolymph with L-DOPA resulted in volume- and time-dependent production of dopaquinone via the phenoloxidase (PO) enzyme, with biphasic accumulation of product. The PO activity was temperature-dependent, with a stepwise increase from 20℃ - 35℃ and maximum activity measured at 35℃ - 40℃. The formation of product was also inhibited in a concentration-dependent manner by diethylcarbonate, a specific inhibitor of PO activity, which indicated that the observed activity was due to the presence of PO enzyme. The rate of formation and quantity of melanin was dependent on exposure to different titers of bacteria. This is the first characterization of both PO activity and melanization response in green darner dragonflies.

关键词： Aquatic Insects Arthropod Dragonfly Hemolymph Innate Immunity Insect

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