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G protein-coupled receptors as potential targets for nonalcoholic fatty liver disease treatment

World Journal of Gastroenterology 2021年第8期27卷 677-691页

作者： Ming Yang chun-ye zhang Department of Surgery University of MissouriColumbiaMO 65212United States Department of Veterinary Pathobiology University of MissouriColumbiaMO 65212United States

Nonalcoholic fatty liver disease(NAFLD)is a broad-spectrum disease,ranging from simple hepatic steatosis to nonalcoholic steatohepatitis,which can progress to cirrhosis and liver *** hepatic lipid accumulation is the major manifestation of this disease,and lipotoxicity promotes NAFLD *** addition,intermediate metabolites such as succinate can stimulate the activation of hepatic stellate cells to produce extracellular matrix proteins,resulting in progression of NAFLD to fibrosis and even cirrhosis.G protein-coupled receptors(GPCRs)have been shown to play essential roles in metabolic disorders,such as NAFLD and obesity,through their function as receptors for bile acids and free fatty *** addition,GPCRs link gut microbiota-mediated connections in a variety of diseases,such as intestinal diseases,hepatic steatosis,diabetes,and cardiovascular *** latest findings show that gut microbiota-derived acetate contributes to liver lipogenesis by converting dietary fructose into hepatic acetyl-CoA and fatty *** agonists,including peptides and natural products like docosahexaenoic acid,have been applied to investigate their role in liver *** such as probiotics and GPCR agonists may be applied to modulate GPCR function to ameliorate liver metabolism *** review summarizes the current findings regarding the role of GPCRs in the development and progression of NAFLD and describes some preclinical and clinical studies of GPCR-mediated ***,understanding GPCR-mediated signaling in liver disease may provide new therapeutic options for NAFLD.

关键词： Nonalcoholic fatty liver disease G protein-coupled receptors Metabolism Bile acids Short-chain fatty acids Gut microbiota

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Diagnostic biomarkers for pancreatic cancer:An update

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World Journal of Gastroenterology 2021年第45期27卷 7862-7865页

作者： Ming Yang chun-ye zhang Department of Surgery University of MissouriColumbiaMO 65212United States Department of Veterinary Pathobiology University of MissouriColumbiaMO 65212United States

Pancreatic ductal adenocarcinoma accounts for the primary type of pancreatic cancer(PC)with a 5-year survival rate of only about 10%in the United *** diagnosis will improve chances for curative *** date,a broadly used serum marker for PC diagnosis is carbohydrate antigen 19-9,which is the only approved biomarker currently by the United States Food and Drug ***,it has low specificity;therefore,development of novel biomarkers is urgently *** trials are ongoing to evaluate candidate biomarkers for PC diagnosis,and the use of a multi-biomarker panel with current PC diagnostic biomarkers appears promising.

关键词： Pancreatic ductal adenocarcinoma Diagnosis Biomarkers Panel Clinical trials

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Roles of fibroblast growth factors in the treatment of diabetes

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World Journal of Diabetes 2024年第3期15卷 392-402页

作者： chun-ye zhang Ming Yang Bond Life Sciences Center University of MissouriColumbiaMO 65211United States Department of Surgery University of MissouriColumbiaMO 65212United States NextGen Precision Health Institution University of MissouriColumbiaMO 65212United States

Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each ***,the incidence of diabetes is increasing,including several types of *** 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the *** evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 *** consists of 23 family members(FGF-1-23)in ***,we review current findings of FGFs in the treatment of diabetes and management of diabetic *** FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical ***,the roles of FGFs in diabetes and diabetic complications are involved in numerous ***,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose ***,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and ***,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.

关键词： Fibroblast growth factors Type 1 diabetes Type 2 diabetes Metabolic disorders Treatment Clinical trials

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Crosstalk between gut microbiota and COVID-19 impacts pancreatic cancer progression

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World Journal of Gastrointestinal Oncology 2022年第8期14卷 1456-1468页

作者： chun-ye zhang Shuai Liu Ming Yang Department of Veterinary Pathobiology University of MissouriColumbiaMO 65211United States The First Affiliated Hospital Zhejiang UniversityHangzhou 310006Zhejiang ProvinceChina Department of Surgery University of MissouriColumbiaMO 65211United States

Pancreatic cancer(PC)is one of the most common causes of cancer-associated death worldwide,with a low rate of 5-year ***,the pathogenesis of PC is complicated,with no efficient *** disease 2019(COVID-19)disease caused by severe acute respiratory syndrome coronavirus 2 further exacerbates the challenge of patients with *** alteration of gut microbiota caused by COVID-19 infection may impact PC progression in patients via immune *** expression of inflammatory immune mediators such as interleukin(IL)-6,IL-8,and IL-10 has been found to increase in both PC and COVID-19 patients,which is associated with the disease severity and prognostic *** microbiome serves as a critical connector between viral infection and *** can regulate host systemic immune response and impact the efficacy of ***,we first demonstrated the features of inflammatory cytokines in both diseases and their impact on disease ***,we demonstrated the importance of immunotherapeutic *** includes the immune modulation that targets a single or dual receptors using a single agent or their combinations for the treatment of PC in patients who get infected with ***,we explored the possibility of managing the disease by regulating gut ***,modulation of the lung-gut-pancreases axis can boost anti-cancer immunotherapy and reduce adverse prognostic outcomes.

关键词： COVID-19 SARS-CoV-2 Gut microbiota Pancreatic cancer Interleukin-6 Interleukin-8 Interleukin-10 Monoclonal antibodies Modulatory treatment

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Clinical diagnosis and management of pancreatic cancer: Markers, molecular mechanisms, and treatment options

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World Journal of Gastroenterology 2022年第48期28卷 6827-6845页

作者： chun-ye zhang Shuai Liu Ming Yang Christopher S.Bond Life Sciences Center University of MissouriColumbiaMO 65211United States The First Affiliated Hospital Zhejiang UniversityHangzhou 310006Zhejiang ProvinceChina Department of Surgery University of MissouriColumbiaMO 65211United States

Pancreatic cancer(PC)is the third-leading cause of cancer *** overall 5-year survival rate of PC is 9%,and this rate for metastatic PC is below 3%.However,the PC-induced death cases will increase about 2-fold by *** factors such as genetic and environmental factors and metabolic diseases can drive PC development and *** most common type of PC in the clinic is pancreatic ductal adenocarcinoma,comprising approximately 90%of PC *** pathogenic processes including but not limited to inflammation,fibrosis,angiogenesis,epithelial-mesenchymal transition,and proliferation of cancer stem cells are involved in the initiation and progression of *** diagnosis is essential for curable therapy,for which a combined panel of serum markers is very *** some mono or combined therapies have been approved by the United States Food and Drug Administration for PC treatment,current therapies have not shown promising ***,the development of novel immunotherapies,such as oncolytic viruses-mediated treatments and chimeric antigen receptor-T cells,combined with therapies such as neoadjuvant therapy plus surgery,and advanced delivery systems of immunotherapy will improve therapeutic outcomes and combat drug resistance in PC ***,the pathogenesis,molecular signaling pathways,diagnostic markers,prognosis,and potential treatments in completed,ongoing,and recruiting clinical trials for PC were reviewed.

关键词： Pancreatic cancer Pancreatic ductal adenocarcinoma Molecular mechanisms Diagnostic and prognostic markers Treatment Clinical trials

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Regulatory T cells and their associated factors in hepatocellular carcinoma development and therapy

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World Journal of Gastroenterology 2022年第27期28卷 3346-3358页

Liver cancer is the third leading cause of cancer-related death worldwide with primary type hepatocellular carcinoma(HCC).Factors,including carcinogens,infection of hepatitis viruses,alcohol abuse,and non-alcoholic fatty liver disease(NAFLD),can induce HCC initiation and promote HCC *** prevalence of NAFLD accompanying the increased incidence of obesity and type 2 diabetes becomes the most increasing factor causing HCC ***,the benefit of current therapeutic options is still *** immunity plays critically important roles in HCC initiation,development,and *** T cells(Tregs)and their associated factors such as metabolites and secreting cytokines mediate the immune tolerance of the tumor microenvironment in ***,targeting Tregs and blocking their mediated factors may prevent HCC *** review summarizes the functions of Tregs in HCC-inducing factors including alcoholic and NAFLD,liver fibrosis,cirrhosis,and viral ***,a better understanding of the role of Tregs in the development and progression of HCC provides treatment strategies for liver cancer treatment.

关键词： Hepatocellular carcinoma Regulatory T cells Alcoholic fatty liver disease Non-alcoholic fatty liver disease Treatment Clinical trials

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Important role of acute care surgery during pandemic time

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World Journal of Gastrointestinal Surgery 2022年第6期14卷 626-628页

作者： Ming Yang chun-ye zhang Department of Surgery University of MissouriColumbiaMO 65211United States Department of Veterinary Pathobiology University of MissouriColumbiaMO 65201United States

Pandemic impacts acute care surgery for diseases,such as gallbladder disease and acute *** the early stage of coronavirus disease 2019(COVID-19)pandemic,the case number of patients needing surgery decreased in hospitals from different *** decline was associated with the stay-home order and fear of getting COVID-19 ***,recent reports show that the case number for acute surgery returns to the normal level,which is comparable to that before the beginning of the *** addition,a variety of diseases show more severe than the cases before the pandemic,which might be caused by factors such as lack of regular follow-up and screening diagnosis and infection of viruses.

关键词： Pandemic impact Acute care surgery Outcome Disease pattern and severity

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Nutrition deprivation affects the cytotoxic effect of CD8 T cells in hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2022年第9期14卷 1887-1891页

Hepatocellular carcinoma(HCC) is the most common type of liver cancer and the third leading cause of cancer-related death worldwide. Factors including carcinogens, infection of hepatitis viruses, alcohol abuse, and metabolic disorders such as non-alcoholic fatty liver disease mainly contribute to HCC initiation and progression. Immunotherapy is one of the most powerful tools for unresectable HCC treatment in patients. CD8T cells are a major immune component in the tumor microenvironment with cytotoxic effects against cancer cells. However, these CD8T cells commonly display an exhaustion phenotype with high expression of programmed cell death protein 1, T-cell immunoglobulin and mucindomain containing-3, and/or lymphocyte-activation gene 3, producing low levels of perforin(PRF1) and granzyme B(GZMB), as well as anti-tumor cytokines, such as interferon gamma and tumor necrosis factor alpha. In the referenced study, the authors also showed that deprivation of glutamine decreased the antitumor function of CD8T cells, as well as the production of PRF1 and GZMB. However, the role of each amino acid in T cell function and exhaustion may depend on tumor type and tumor microenvironment, including the source of other nutrients. Overall, amino acids or other nutrient metabolites in the tumor microenvironment play a pivotal role in both tumor growth and immune response.

关键词： Hepatocellular carcinoma Metabolism Amino acids Tumor microenvironment T cell function

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Functions of three ubiquitin-conjugating enzyme 2 genes in hepatocellular carcinoma diagnosis and prognosis

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World Journal of Hepatology 2022年第5期14卷 956-971页

作者： chun-ye zhang Ming Yang Department of Veterinary Pathobiology University of MissouriColumbiaMO 65211United States Department of Surgery University of MissouriColumbiaMO 65211United States

BACKGROUND Liver cancer ranks the third cause of cancer-related death *** most common type of liver cancer is hepatocellular carcinoma(HCC).The survival time for HCC patients is very limited by years due to the lack of efficient treatment,failure of early diagnosis,and poor *** plays an essential role in the biochemical processes of a variety of cellular *** To investigate three ubiquitination-associated genes in *** Herein,the expression levels of ubiquitin-conjugating enzymes 2(UBE2)including UBE2C,UBE2T,and UBE2S in tumor samples of HCC patients and nontumor controls at the Cancer Genome Atlas(TCGA)database,was comprehensively *** relationship of UBE2 gene expression level with cancer stage,prognostic outcome,and TP53 mutant status was *** Our results showed that UBE2C,UBE2T,and UBE2S genes were overexpressed in HCC samples compared to non-tumor *** on the cancer progression stage,three UBE2 genes showed higher expression in tumor tissues at all four stages compared to non-tumor control ***,a significantly higher expression of these genes was found in stage 2 and stage 3 cancers compared to stage 1 ***,overexpression of those genes was negatively associated with prognostic outcome and overall survival *** with TP53 mutation showed a higher expression level of three UBE2 genes,indicating an association between UBE2 expression with p53 *** In summary,this study shed light on the potential roles of UBE2C,UBE2T,UBE2S on diagnostic and prognostic biomarkers for ***,based on our findings,it is appealing to further explore the correlation of those genes with TP53 mutation in HCC and the related mechanisms.

关键词： Hepatocellular carcinoma Ubiquitin-conjugating enzyme 2 UBE2C UBE2T UBE2S TP53 mutant Biomarker Diagnostic Prognostics

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Anti-oxidative stress treatment and current clinical trials

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World Journal of Hepatology 2024年第2期16卷 294-299页

作者： chun-ye zhang Ming Yang Bond Life Sciences Center University of MissouriColumbiaMO 65211United States Department of Surgery University of MissouriColumbiaMO 65212United States

Oxidative stress disturbs the balance between the production of reactive oxygen species(ROS)and the detoxification biological *** plays an important role in the development and progression of many chronic *** exposure to oxidative stress or the inducers of ROS,the cellular nucleus undergoes some biological processes via different signaling pathways,such as stress adaption through the forkhead box O signaling pathway,inflammatory response through the IκB kinase/nuclear factor-κB signaling pathway,hypoxic response via the hypoxia-inducible factor/prolyl hydroxylase domain proteins pathway,DNA repair or apoptosis through the p53 signaling pathway,and antioxidant response through the Kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 signaling *** processes are involved in many ***,oxidative stress has gained more attraction as a targeting process for disease ***,anti-oxidative stress agents have been widely explored in pre-clinical ***,only limited clinical trials are performed to evaluate the efficacy of anti-oxidative stress agents or antioxidants in *** this letter,we further discuss the current clinical trials related to anti-oxidative stress treatment in different *** pre-clinical studies and clinical trials are expected to use anti-oxidative stress strategies as disease treatment or dietary supplementation to improve disease treatment outcomes.

关键词： Anti-oxidative stress treatment Clinical trials Drugs Dietary invention Reactive oxygen species

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