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Probiotics VSL#3 are effective in reversing non-alcoholic steatohepatitis in a mouse model

Hepatobiliary Surgery and Nutrition 2020年第2期9卷 170-182页

作者： Prasant Kumar Jena Lili Sheng Yongchun Li yui-jui yvonne wan Department of Pathology and Laboratory Medicine University of CaliforniaDavisSacramentoCAUSA Department of Gastroenterology Zhujiang HospitalSouthern Medical UniversityGuangzhou 510282China Department of Infectious Diseases Nanhai HospitalSouthern Medical UniversityFoshan 528200China

Background:Probiotic VSL#3 is used to treat ulcerative *** study examines the effect of VSL#3 in non-alcoholic steatohepatitis(NASH)that has liver carcinogenic ***:Western diet(WD)-fed wild-type(WT)mice that do not have hepatic inflammation with lymphocyte infiltration and carcinogenic potential were used for baseline ***-,sex-,and diet-matched bile acid(BA)receptor farnesoid X receptor(FXR)knockout(KO)mice,which developed severe NASH and had the potential for liver cancer development,were supplemented with and without VSL#3 for 7 *** the mice were euthanized when they were 10 months ***:Supplementation with VSL#3 completely abolished hepatic lymphocyte infiltration,reduced hepatic fat content,and improved insulin sensitivity in WD-fed FXR KO *** addition,VSL#3 normalized dysregulated BA homoeostasis by inhibiting the classical BA synthesis pathway,inducing the alternative BA pathway,and activating ileal G-protein coupled BA receptor 1(GPBAR1)-regulated ***,VSL#3 reconstructed the gut microbiota by reducing Bacteroidaceae,Porphyromonadaceae,and Helicobacteraceae as well as increasing ***,VSL#3 enriched the abundance of Ruminococcus and Faecalibacterium,which generate butyrate,at the genus *** also increased the copy number of the butyrate-producing genes bcoA and buk,suggesting their anti-inflammatory and metabolic ***:VSL#3 is useful in reversing NASH that occurred due to dysregulated BA synthesis and dysbiosis,suggesting its potential in liver cancer prevention.

关键词： Bile acid(BA) farnesoid X receptor(FXR) G-protein coupled bile acid receptor-1(GPBAR1) microbiota inflammation.

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Targeting stroma and tumor,silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma

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Acta Pharmaceutica Sinica B 2024年第1期14卷 292-303页

作者： Tahereh Setayesh Ying Hu Farzam Vaziri Xin Chen Jinping Lai Dongguang Wei Yu-jui yvonne wan Department of Medical Pathology and Laboratory Medicine University of CaliforniaDavisSacramentoCA 95817USA Cancer Biology Program the University of Hawaii Cancer CenterHonoluluHI 96813USA Department of Pathology and Laboratory Medicine Kaiser Permanente Sacramento Medical CenterSacramentoCA 95825USA

This study examines inhibiting galectin 1(Gal1)as a treatment option for hepatocellular carcinoma(HCC).Gal1 has immunosuppressive and cancer-promoting *** data showed that Gal1 was highly expressed in human and mouse *** levels of Gal1 positively correlated with the stages of human HCC and negatively with *** roles of Gal1 in HCC were studied using overexpression(OE)or silencing using Igals1 siRNA delivered by *** to HCC initiation induced by RAS and AKT mutations,lgals1-OE and silencing had opposite impacts on tumor *** treatment effect of lgals1 siRNAwas further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9%or even 42%of the body *** spatial transcriptomic profiles of Gal1 silenced and OE HCC,inhibiting matrix formation and recognition of foreign antigen in CD45t cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 *** the tumors,silencing Gal1 inhibited translational initiation,elongation,and ***,Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor,and the anti-HCC effect of lgals1 siRNAwas ***,Gal1 silencing has a promising potential for HCC treatment.

关键词： Liver Hepatocellular carcinoma Carbohydrate-binding lectin Galectin 1 Extracellular matrix Translation Spatial transcriptomics Tumor-margin

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Regulation of bile acid receptor activity

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Liver Research 2018年第4期2卷 180-185页

作者： Yu-jui yvonne wan Lili Sheng Department of Medical Pathology and Laboratory Medicine University of CaliforniaDavisSacramentoCAUSA

Many receptors can be activated by bile acids(BAs)and their *** include nuclear receptors farnesoid X receptor(FXR),pregnane X receptor(PXR),and vitamin D receptor(VDR),as well as membrane receptors Takeda G protein receptor 5(TGR5),sphingosine-1-phosphate receptor 2(S1PR2),and cholinergic receptor muscarinic 2(CHRM2).All of them are implicated in the development of metabolic and immunological diseases in response to endobiotic and xenobiotic *** epigenetic regulation is critical for organisms to adapt to constant environmental changes,this review article summarizes epigenetic regulation as well as post-transcriptional modification of bile acid *** addition,the focus of this review is on the liver and digestive tract although these receptors may have effects on other *** regulatory mechanisms are implicated in the disease process and critically important in uncovering innovative strategy for prevention and treatment of metabolic and immunological diseases.

关键词： Bile acid receptor Farnesoid X receptor(FXR) G protein-coupled bile acid receptor Takeda G protein receptor 5(TGR5) Sphingosine-1-phosphate receptor 2 (S1PR2) Acetylation Methylation Glycosylation

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Golgi protein 73, hepatocellular carcinoma and other types of cancers

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Liver Research 2020年第4期4卷 161-167页

作者： Yanan wang Yu-jui yvonne wan Department of Pathology and Laboratory Medicine University of California DavisSacramentoCAUSA State Key Laboratory of Medical Molecular Biology Department of Physiolog

Hepatocellular carcinoma(HCC)is one of the most common malignant tumors with a low survival *** identification of mechanisms underlying the development of HCC helps uncover cellular and mo-lecular targets for the diagnosis,prevention,and treatment of *** protein 73(GP73)level is up-regulated in HCC patients and potentially can be a therapeutic *** many studies devoted to GP73 as a marker for HCC early diagnosis,there is little discussion about the function of GP73 in HCC *** the poor response to currently available HCC therapies,a better understanding of the role of GP73 in HCC may provide a new therapeutic target for *** current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver *** roles in other types of cancer are also discussed.

关键词： Liver cancer Hepatocellular carcinoma(HCC) Diagnostic markers Golgi protein 73(GP73) Alpha-fetoprotein(AFP) Gamma-glutamyl transferase(GGT) Hepatitis C virus(HCV) Hepatitis B virus(HBV)

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The role of gut microbiota in liver disease development and treatment

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Liver Research 2019年第1期3卷 3-18页

作者： Lijun wang Yu-jui yvonne wan Department of Medical Pathology and Laboratory Medicine University of CaliforniaDavisSacramentoCAUSA The College of Life Science Yangtze UniversityJingzhouHubeiChina

Liver cancer is the sixth most common cancer worldwide,and the third most common cause of cancer-related *** carcinoma(HCC),which accounts for more than 90%of primary liver cancers,is an important public health *** addition to cirrhosis caused by hepatitis B viral(HBV)or hepatitis C viral(HCV)infection,non-alcoholic fatty liver disease(NAFLD)is becoming a major risk factor for liver cancer because of the prevalence of ***-alcoholic steatohepatitis(NASH)will likely become the leading indication for liver transplantation in the *** is well recognized that gut microbiota is a key environmental factor in the pathogenesis of liver disease and *** interplay between gut microbiota and liver disease has been investigated in animal and clinical *** this article,we summarize the roles of gut microbiota in the development of liver disease as well as gut microbiota-targeted therapies.

关键词： Microorganism Hepatocellular carcinoma(HCC) Non-alcoholic fatty liver disease(NAFLD) Non-alcoholic steatohepatitis(NASH) Cirrhosis Probiotics Prebiotics Synbiotics

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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 ***,metabolic diseases increase the risk of having infectious *** treatment of metabolic disease may require a long-term strategy of taking multiple medications,which can be costly and have side *** 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 *** non-specific effects of BCG occur likely due to the induction of trained *** this regard,understanding how BCG influences the development of chronic metabolic health including liver diseases would be *** 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

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Effectiveness of post-COVID-19 primary care attendance in improving survival in very old patients with multimorbidity:a territory-wide target trial emulation

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Family Medicine and Community Health 2024年第3期12卷 25-35页

作者： Cuiling Wei Vincent Ka Chun Yan Camille Maringe Wenxin Tian Rachel yui Ki Chu Wenlong Liu Boyan Liu Yuqi Hu Lingyue Zhou Celine Sze Ling Chui Xue Li Eric Yuk Fai wan Ching Lung Cheung Esther Wai Yin Chan William Chi Wai Wong Ian Chi Kei Wong Francisco Tsz Tsun Lai Centre for Safe Medication Practice and Research Department of Pharmacology and PharmacyLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongHong Kong Department of Health Services Research and Policy Faculty of Public Health and PolicyLondon School of Hygiene and Tropical MedicineLondonUK School of Nursing Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongHong Kong School of Public Health Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongHong Kong Laboratory of Data Discovery for Health(D24H) Hong KongHong Kong Advanced Data Analytics for Medical Science(ADAMS)Limited Hong KongHong Kong Department of Medicine School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongHong Kong Department of Family Medicine and Primary Care School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongHong Kong Department of Pharmacy The University of Hong Kong-Shenzhen HospitalShenzhenPeople's Republic of China Aston Pharmacy School Aston UniversityBirminghamUK School of Pharmacy Macao University of Science and TechnologyTaipaMacao

Objectives Older individuals with multimorbidity are at an elevated risk of infection and complications from *** of post-COVID-19 interventions or care models in reducing subsequent adverse outcomes in these individuals have rarely been *** study aims to examine the effectiveness of attending general outpatient within 30 days after discharge from COVID-19 on 1-year survival among older adults aged 85 years or above with *** Retrospective cohort study emulating a randomised target trial using electronic health *** We used data from the Hospital Authority and the Department of Health in Hong Kong,which provided comprehensive electronic health records,COVID-19 confirmed case data,population-based vaccination records and other individual characteristics for the *** Adults aged 85 years or above with multimorbidity who were discharged after hospitalisation for COVID-19 between January 2020 and August *** Attending a general outpatient within 30 days of last COVID-19 discharge defined the exposure,compared to no outpatient *** outcome measures Primary outcome was all-cause mortality within one *** outcomes included mortality from respiratory,cardiovascular and cancer *** A total of 6183 eligible COVID-19 survivors were included in the *** all-cause mortality rate following COVID-19 hospitalisation was lower in the general outpatient visit group(17.1 deaths per 100 person-year)compared with non-visit group(42.8 deaths per 100 person-year).After adjustment,primary care consultations within 30 days after discharge were associated with a significantly greater 1-year survival(difference in 1-year survival:11.2%,95%CI 8.1%to 14.4%).We also observed significantly better survival from respiratory diseases in the general outpatient visit group(difference in 1-year survival:6.3%,95%CI 3.5%to 8.9%).In a sensitivity analysis for different grace period lengths

关键词： morbidity visit records

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The contributions of bacteria metabolites to the development of hepatic encephalopathy

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Liver Research 2023年第4期7卷 296-303页

作者： Miranda Claire Gilbert Tahereh Setayesh Yu-jui yvonne wan Department of Pathology and Laboratory Medicine University of CaliforniaDavisSacramentoCAUSA

Over 20%of mortality during acute liver failure is associated with the development of hepatic encephalopathy(HE).Thus,HE is a complication of acute liver failure with a broad spectrum of neuropsychiatric abnormalities ranging from subclinical alterations to *** is caused by the diversion of portal blood into systemic circulation through portosystemic collateral ***,the brain is exposed to intestinal-derived toxic ***,the strategies to prevent advancement and improve the prognosis of such a liver-brain disease rely on intestinal microbial *** is supported by the findings that antibiotics such as rifaximin and laxative lactulose can alleviate hepatic cirrhosis and/or prevent ***,the significance of the gut-liver-brain axis in human health warrants *** review paper focuses on the roles of bacteria metabolites,mainly ammonia and bile acids(BAs)as well as BA receptors in *** literature search conducted for this review included searches for phrases such as BA receptors,BAs,ammonia,farnesoid X receptor(FXR),G protein-coupled bile acid receptor 1(GPBAR1 or TGR5),sphingosine-1-phosphate receptor 2(S1PR2),and cirrhosis in conjunction with the phrase hepatic encephalopathy and portosystemic ***,as well as Google Scholar,was the search engines used to find relevant publications.

关键词： Liver Gut-liver-brain axis Bile acids(BAs) Bile acid(BA)receptors Farnesoid X receptor(FXR) Takeda G protein-coupled receptor 5(TGR5) Sphingosine-1-phosphate receptor 2 (S1PR2) Brain

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泛Clifford分析中具有双LR正则核的奇异积分算子的性质

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数学的实践与认识 2024年第3期54卷 213-223页

作者：李万营郭欣杨贺菊河北科技大学理学院河北石家庄050018

泛Clifford分析是Clifford分析更为一般化的推广.首先研究泛Clifford代数上双LR正则函数的Cauchy积分表示,以及其Cauchy型主值积分的性质.通过定义L正则函数,R正则函数,LR正则函数,双LR正则函数给出泛Clifford分析中双LR正则的核函数,... 详细信息

泛Clifford分析是Clifford分析更为一般化的推广.首先研究泛Clifford代数上双LR正则函数的Cauchy积分表示,以及其Cauchy型主值积分的性质.通过定义L正则函数,R正则函数,LR正则函数,双LR正则函数给出泛Clifford分析中双LR正则的核函数,并给出其Cauchy积分表示.最后通过插项的方法研究了一类泛Clifford分析中具有双正则核的Cauchy型奇异积分算子的收敛性.

关键词：泛Clifford代数双LR正则函数奇异积分算子 Cauchy主值积分

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Age-specific microbiota in altering host inflammatory and metabolic signaling as well as metabolome based on the sex

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Hepatobiliary Surgery and Nutrition 2021年第1期10卷 31-48,I0003-I0005页

作者： Lili Sheng Prasant Kumar Jena Ying Hu Yu-jui yvonne wan Department of Pathology and Laboratory Medicine Davis HealthUniversity of CaliforniaSacramentoCAUSA Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese MedicineShanghaiChina Department of Pediatrics Cedars Sinai Medical CenterLos AngelesCAUSA

Background:Metabolism is sex-different,and the direct link between gut microbiota and aging-associated metabolic changes needs to be established in both ***:Gene expression,metabolic and inflammatory signaling,gut microbiota profile,and metabolome were studied during aging and after fecal microbiota transplantation(FMT)in mice of both ***:Our data revealed young female mice and aged male mice were the most insulin sensitive and resistant group,*** addition,aging reduced sex difference in insulin *** age-and sex-dependent metabolic phenotypes were accompanied by shifted gut microbiota profile and altered abundance of bacterial genes that produce butyrate,propionate,and bile *** receiving feces from the aged males(AFMT),the most insulin-resistant group,recipients of both sexes had increased hepatic inflammation and serum ***,AFMT only increased insulin resistance in female mice and abolished sex difference in insulin ***,such changes were accompanied by narrowed sex difference in *** data revealed that age-associated insulin resistance in males was accompanied by increased sugar alcohols and dicarboxylic acids as well as reduced aromatic and branched-chain amino ***,receiving feces from the young females(YFMT),the most insulin-sensitive group,reduced body weight and fasting blood glucose in male recipients and improved insulin sensitivity in females,leading to enhanced sex differences in insulin sensitivity and ***:Aging systemically affected inflammatory and metabolic signaling based on the *** microbiome is age and sex-specific,which affects inflammation and metabolism in a sex-dependent manner.

关键词： Aging microbiome metabolome insulin sensitivity fecal transplantation

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