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Expression and functions of transient receptor potential channels in Liver diseases

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Acta Pharmaceutica Sinica B 2023年第2期13卷 445-459页

作者： Wenhui Wang Pengyu Liu Yalin Zhang Li Yan Michael X.Zhu Jin Wang Ye Yu Department of Pharmacology School of PharmacyChina Pharmaceutical UniversityNanjing 210009China Department of Medical Genetics and Developmental Biology School of Medicinethe Key Laboratory of Developmental Genes and Human DiseasesMinistry of EducationSoutheast UniversityNanjing 210009China School of Basic Medicine and Clinical Pharmacy and State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Department of Integrative Biology and Pharmacology McGovern Medical Schoolthe University of Texas Health Science Center at HoustonHoustonTX 77030USA

Liver diseases constitute a major healthcare burden globally,including acute hepatic injury resulted from acetaminophen overdose,ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis,alcoholic Liver disease(ALD),non-alcoholic fatty Liver disease(NAFLD)and hepatocellular carcinoma(HCC).Attainable treatment strategies for most Liver diseases remain inadequate,highlighting the importance of substantial pathogenesis.The transient receptor potential(TRP)channels represent a versatile signalling mechanism regulating fundamental physiological processes in the liver.It is not surprising that Liver diseases become a newly explored field to enrich our knowledge of TRP channels.Here,we discuss recent findings revealing TRP functions across the fundamental pathological course from early hepatocellular injury caused by various insults,to inflammation,subsequent fibrosis and hepatoma.We also explore expression levels of TRPs in liver tissues of ALD,NAFLD and HCC patients from Gene Expression Omnibus(GEO)or The Cancer Genome Atlas(TCGA)database and survival analysis estimated by Kaplan-Meier Plotter.At last,we address the therapeutical potential and challenges by pharmacologically targeting TRPs to treat Liver diseases.The aim is to provide a better understanding of the implications of TRP channels in Liver diseases,contributing to the discovery of novel therapeutic targets and efficient drugs.

关键词： TRP Liver disease liver injury ALD NAFLD Fibrosis Inflammation HCC

Effects of Bacillus Calmette-Guerin on immunometabolism,microbiome and Liver diseases

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liver Research 2023年第2期7卷 116-123页

作者： Muhammad Umair Ijaz Farzam Vaziri Yu-Jui Yvonne Wan Department of Medical Pathology and Laboratory Medicine University of California Davis School of MedicineSacramentoCAUSA

Metabolic diseases have overtaken infectious diseases as the most serious public health issue and economic burden in most countries.Moreover,metabolic diseases increase the risk of having infectious diseases.The treatment of metabolic disease may require a long-term strategy of taking multiple medications,which can be costly and have side effects.Attempts to expand the therapeutic use of vaccination to prevent or treat metabolic diseases have attracted significant interest.A growing body of evidence indicates that Bacillus Calmette-Guerin(BCG)offers protection against non-infectious diseases.The non-specific effects of BCG occur likely due to the induction of trained immunity.In this regard,understanding how BCG influences the development of chronic metabolic health including Liver diseases would be important.This review focuses on research on BCG,the constellation of disorders associated with metabolic health issues including Liver diseases and diabetes as well as how BCG affects the gut microbiome,immunity,and metabolism.

关键词： Bacillus Calmette-Guerin(BCG) Liver disease Vaccination Gut microbiota Metabolic diseases Trained immunity Diabetes

Telehealth interventions for alcohol use disorder:A systematic review

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liver Research 2022年第3期6卷 146-154页

作者： Arpad Kelemen Elizabeth Minarcik Christopher Steets Yulan Liang Department of Organizational Systems and Adult Health University of MarylandBaltimoreMDUSA Department of Family and Community Health University of MarylandBaltimoreMDUSA

Alcohol use disorder(AUD)is a worldwide problem for individuals of varying ages and backgrounds and is associated with the underlying cause of alcoholic Liver disease,liver cirrhosis,liver cancer,or many other common diseases and health conditions.Existing treatments such as cognitive behavioral therapy(CBT)have been demonstrated as an evidence-based treatment to aid individuals struggling with AUD.However,these treatments have excessive costs and time demand with trained experts.In this paper,we examine the efficacy and long-term impacts of digitally delivered CBT and other online telehealth tools and apps for AUD patients.Results show the effectiveness in the ability of digitally delivered CBT to decrease alcohol use in AUD patients.The additional use of online technologies and smartphone apps for post-CBT care demonstrates that such computer-aided apps could have long-term effects when it is continually employed,which opens the door for AUD patients who were not seeking treatment elsewhere.Further longitudinal examination research is needed to evaluate the lasting effects in liver health and other chronic diseases associated with digitally delivered alcohol reduction for AUD patients.

关键词： Alcohol use disorder(AUD) Liver disease Cognitive behavioral therapy(CBT) Telehealth Digitally delivered Systematic review

Non-alcoholic steatohepatitis and risk of hepatocellular carcinoma

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Chinese Medical Journal 2021年第24期134卷 2911-2921页

作者： Rafael S.Rios Kenneth I.Zheng Ming-Hua Zheng NAFLD Research Center Department of Hepatologythe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325000China

The emergence of non-alcoholic fatty Liver disease(NAFLD)as the leading chronic Liver disease worldwide raises some concerns.In particular,NAFLD is closely tied to sedentary lifestyle habits and associated with other metabolic diseases,such as obesity and diabetes.At the end of the disease spectrum,non-alcoholic steatohepatitis(NASH)may progress to cirrhosis and hepatocellular carcinoma(HCC),representing a serious health problem to modern society.Recently,an increasing number of HCC cases originating from this progressive disease spectrum have been identified,with different levels of severity and complications.Updating the current guidelines by placing a bigger focus on this emerging cause and highlighting some of its unique features is necessary.Since,the drivers of the disease are complex and multifactorial,in order to improve future outcomes,having a better understanding of NASH progression into HCC may be helpful.The risks that can promote disease progression and currently available management strategies employed to monitor and treat NASH-related HCC make up the bulk of this review.

关键词： Non-alcoholic fatty Liver disease Non-alcoholic steatohepatitis Liver disease Hepatocellular carcinoma Insulin resistance Oxidative stress Metabolic associated fatty Liver disease

Neutrophils in Liver diseases:pathogenesis and therapeutic targets

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Cellular & Molecular Immunology 2021年第1期18卷 38-44页

作者： Kai Liu Fu-Sheng Wang Ruonan Xu Peking University 302 Clinical Medical School BeijingChina Treatment and Research Center for Infectious diseases The Fifth Medical Center of PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijingChina

Previously,it was assumed that peripheral neutrophils are a homogeneous population that displays antimicrobial functions.However,recent data have revealed that neutrophils are heterogeneous and are additionally involved in tissue damage and immune regulation.The phenotypic and functional plasticity of neutrophils has been identified in patients with cancer,inflammatory disorders,infections,and other diseases.Currently,neutrophils,with their autocrine,paracrine,and immune modulation functions,have been shown to be involved in Liver diseases,including viral hepatitis,nonalcoholic steatohepatitis,alcoholic Liver disease,liver fibrosis,cirrhosis,liver failure,and liver cancer.Accordingly,this review summarizes the role of neutrophils in Liver diseases.

关键词： Liver disease liver injury Neutrophil Innate immunity Immunotherapy

Environmental exposure as a risk-modifying factor in Liver diseases:Knowns and unknowns

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3768-3778页

作者： Juliane I.Beier Gavin E.Arteel Department of Medicine Division of GastroenterologyHepatology and NutritionUniversity of PittsburghPittsburghPA 15213USA Pittsburgh liver Research Center and University of Pittsburgh PittsburghPA 15213USA Department of Environmental and Occupational Health University of PittsburghPA 15213USA

Liver diseases are considered to predominantly possess an inherited or xenobiotic etiology.However,inheritance drives the ability to appropriately adapt to environmental stressors,and disease is the culmination of a maladaptive response.Thus "pure" genetic and "pure" xenobiotic Liver diseases are modified by each other and other factors,identified or unknown.The purpose of this review is to highlight the knowledgebase of environmental exposure as a potential risk modifying agent for the development of Liver disease by other causes.This exercise is not to argue that all Liver diseases have an environmental component,but to challenge the assumption that the current state of our knowledge is sufficient in all cases to conclusively dismiss this as a possibility.This review also discusses key new tools and approaches that will likely be critical to address this question in the future.Taken together,identifying the key gaps in our understanding is critical for the field to move forward,or at the very least to "know what we don't know."

关键词： Hepatic injury Exposomics Liver disease Drug-induced liver injury Alcoholic Liver disease Non-alcoholic Liver disease Inherited Liver disease Autoimmune Liver disease

Innate lymphocytes:pathogenesis and therapeutic targets of Liver diseases and cancer

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Cellular & Molecular Immunology 2021年第1期18卷 57-72页

作者： Yongyan Chen Zhigang Tian Hefei National Laboratory for Physical Sciences at Microscale the CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina Institute of Immunology University of Science and Technology of ChinaHefeiChina

The liver is a lymphoid organ with unique immunological properties,particularly,its predominant innate immune system.The balance between immune tolerance and immune activity is critical to liver physiological functions and is responsible for the sensitivity of this organ to numerous diseases,including hepatotropic virus infection,alcoholic Liver disease,nonalcoholic fatty Liver disease,autoimmune Liver disease,and liver cancer,which are major health problems globally.In the past decade,with the discovery of liver-resident natural killer cells,the importance of innate lymphocytes with tissue residency has gradually become the focus of research.In this review,we address the current knowledge regarding hepatic innate lymphocytes with unique characteristics,including NK cells,ILC1/2/3s,NKT cells,γδ T cells,and MAIT cells,and their potential roles in liver homeostasis maintenance and the progression of Liver diseases and cancer.A better understanding of the immunopathogenesis of hepatic innate lymphocytes will be helpful for proposing effective treatments for Liver diseases and cancer.

关键词： Innate lymphocyte Liver disease liver cancer Innate lymphoid cell Innate-like T lymphocyte

The natural history of patients with compensated cirrhosis and elevated hepatic venous pressure gradient

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Portal Hypertension & Cirrhosis 2022年第2期1卷 101-106页

作者： Andrew Wortham Ali Khalifa Don C.Rockey Digestive disease Research Center Medical University of South CarolinaCharlestonSouth CarolinaUSA

Aims:Portal hypertension is a major complication of liver cirrhosis.Hepatic venous pressure gradient(HVPG)appears to be one of the best surrogates of clinical outcomes.However,the utility of elevated HVPG in predicting subsequent clinical decompensation is unclear.Methods:We analyzed 410 patients who underwent HVPG assessment between 2014 and 2018.Of these,we identified and analyzed 20 patients with HVPG>12 mmHg without evidence of clinical decompensation(defined as ascites,nonbleeding esophageal varices or bleeding esophageal varices,hepatic encephalopathy,hepatopulmonary syndrome,or hepatic hydrothorax).Additionally,we compared this group to 40 randomly selected cirrhotic patients with HVPG>12 mmHg with signs of clinical decompensation.Clinical events were subsequently assessed(mean=33 months)after HVPG measurement.Results:Patients with high HVPG without evidence of clinical decompensation had a significantly lower model for end‐stage Liver disease(MELD)scores(8±4)compared to decompensated patients(13±8,p=0.05).HVPG measurements were similar in compensated(17±6 mmHg)and decompensated(18±4 mmHg)patients.Over follow‐up for 33 months,8/20 compensated patients had a decompensating event and neither MELD(8 and 8,respectively)nor HVPG(17 and 18 mmHg,respectively)differentiated patients who remained compensated versus those that decompensated.Serum albumin at the time of HVPG measurement was significantly higher in patients who remained compensated than those with a decompensating event(3.5 vs.2.6 g/dl,respectively,p=0.05).Conclusions:A small,unique,population of cirrhotic patients with substantially elevated HVPG appear to remain free of complications over long‐term follow‐up.

关键词： Child‐Pugh score fibrosis Liver disease mortality portal hypertension

Diagnostic and Therapeutic Strategies for Peritoneal Tuberculosis: A Review

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Journal of Clinical and Translational Hepatology 2019年第2期7卷 140-148页

作者： David C.Wu Leon D.Averbukh George Y.Wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Peritoneal tuberculosis(PTB),although rarer than its pulmonary counterpart,is a serious health concern in regions of the world with high tuberculosis prevalence.Individuals with baseline immunocompromise condition,whether acquired or medically induced,are at greatest risk for experiencing PTB.While medical treatment of the condition is similar to that of the pulmonary disease,the generally immunocompromised state of those infected with PTB,along with a lack of highly sensitive and specific testing methods make early diagnosis difficult.This review discusses the risks factors,clinical features,diagnostic methods,and treatment options for PTB.

关键词： Peritoneal tuberculosis Tuberculosis Liver disease Human immunodeficiency virus