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Sarcopenia in Chronic Liver Disease:A metabolic Perspective

Journal of Clinical and Translational Hepatology 2022年第6期10卷 1213-1222页

作者： Ramesh Kumar Sabbu Surya Prakash Rajeev Nayan Priyadarshi Utpal Anand Department of Gastroenterology All India Institute of Medical SciencesPatnaIndia Department of Radiodiagnosis All India Institute of Medical SciencesPatnaIndia Department of surgical Gastroenterology All India Institute of Medical SciencesPatnaIndia

Sarcopenia,a condition of low muscle mass,quality,and strength,is commonly found in patients with chronic liver disease(CLD)and is associated with adverse clinical out-comes including reduction in quality of life,increased mor-tality,and complications.A major contributor to sarcopenia in CLD is the imbalance in muscle protein turnover wherein changes in various metabolic factors such as hyperammone-mia,amino acid deprivation,hormonal imbalance,gut dys-biosis,insulin resistance,chronic inflammation,*** important *** particular,hyperammonemia is a key mediator of the liver-gut axis and is known to contribute to sarcopenia by various mechanisms including increased ex-pression of myostatin,increased phosphorylation of eukary-otic initiation factor 2a,cataplerosis ofα-ketoglutarate,mi-tochondrial dysfunction,increased reactive oxygen species that decrease protein synthesis and increased autophagy-mediated *** muscle is a major organ of insulin-induced glucose metabolism,and sarcopenia is closely linked to insulin resistance and metabolic *** with liver cirrhosis are in a hypermetabolic state that is associated with catabolism and depletion of amino acids,particularly branched-chain amino *** can have significant implications for nonalcoholic fatty liver disease,the most common form of CLD worldwide,because of the close link between metabolic syndrome and *** review discusses the potential metabolic derange-ment as a cause or effect of sarcopenia in CLD,as well as interorgan crosstalk,which that might help identifying a novel therapeutic strategies.

关键词： Sarcopenia Liver cirrhosis Chronic liver disease Metabolism Hy-perammonemia

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Non-alcoholic Fatty Liver Disease:Growing Burden, Adverse Outcomes and Associations

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Journal of Clinical and Translational Hepatology 2020年第1期8卷 76-86页

作者： Ramesh Kumar Rajeev Nayan Priyadarshi Utpal Anand Department of Gastroenterology All India Institute of Medical SciencesPatnaIndia Department of Radiodiagnosis All India Institute of Medical SciencesPatnaIndia Department of surgical Gastroenterology All India Institute of Medical SciencesPatnaIndia

Nonalcoholic fatty liver disease(NAFLD)is a systemic disor-der with a complex multifactorial pathogenesis and hetero-genous clinical ***,once believed to be an innocuous condition,has now become the most common cause of chronic liver disease in many countries *** is already highly prevalent in the general population,and owing to a rising incidence of obesity and diabetes mellitus,the incidence of NAFLD and its impact on global healthcare are expected to increase in the future.A subset of patients with NAFLD develops progressive liver disease lead-ing to cirrhosis,hepatocellular carcinoma,and liver *** has emerged as one of the leading causes of cirrhosis and hepatocellular carcinoma in recent ***,HCC can occur in NAFLD even in absence of *** with the general population,NAFLD increases the risk of liver-related,cardiovascular and all-cause *** is bidirectionally associated with metabolic *** increases the risk and contributes to aggravation of the pathophysiology of atherosclerosis,cardiovascular diseases,diabetes mellitus,and chronic kidney *** addition,NAFLD is linked to colorectal polyps,polycystic ovarian syndrome,osteoporosis,obstructive sleep apnea,stroke,and various extrahepatic *** resection of steatotic liver is associated with increased risk of liver failure and *** is an increasing trend of NAFLD-related cirrhosis requiring liver transplantation,and the recurrence of NAFLD in such patients is almost *** review discusses the growing burden of NAFLD,its outcomes,and adverse associations with various diseases.

关键词： NAFLD NASH metabolic Outcome Association

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Coronavirus disease 2019 and non-alcoholic fatty liver disease

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World Journal of Hepatology 2021年第9期13卷 969-978页

作者： Francesco Bellanti Gianluigi Vendemiale Department of medical and surgical sciences University of FoggiaFoggia 71122Italy

The coronavirus disease 2019(COVID-19)pandemic may present with a broad range of clinical manifestations,from no or mild symptoms to severe *** with specific pre-existing comorbidities,such as obesity and type 2 diabetes,are at high risk of coming out with a critical form of *** fatty liver disease(NAFLD)is the most common chronic liver disease,and,because of its frequent association with metabolic alterations including obesity and type 2 diabetes,it has recently been re-named as metabolic-associated fatty liver disease(MAFLD).Several studies and systematic reviews pointed out the increased risk of severe COVID-19 in NAFLD/MAFLD *** though dedicated mechanistic studies are missing,this higher probability may be justified by systemic low-grade chronic inflammation associated with immune dysregulation in NAFLD/MAFLD,which could trigger cytokine storm and hypercoagulable state after severe acute respiratory syndrome coronavirus 2 *** review focuses on the predisposing role of NAFLD/MAFLD in favoring severe COVID-19,discussing the available information on specific risk factors,clinical features,outcomes,and pathogenetic mechanisms.

关键词： Non-alcoholic fatty liver disease metabolic-associated fatty liver disease COVID-19 SARS-CoV-2 Liver injury Immune dysregulation

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Chronic hepatitis C virus infection and atherosclerosis: Clinical impact and mechanisms

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World Journal of Gastroenterology 2014年第13期20卷 3410-3417页

作者： Luigi E Adinolfi Rosa Zampino Luciano Restivo Amedeo Lonardo Barbara Guerrera Aldo Marrone Fabio Nascimbeni Anna Florio Paola Loria Department of medical SurgicalNeurologicalMetabolicand Geriatric SciencesSecond University of Naples80100 NaplesItaly Department of Internal Medicine EndocrinologyMetabolism and GeriatricsUniversity of Modena and Reggio Emilia41126 Modena Italy Vascular Surgery Second University of Naples80100 NaplesItaly

Hepatitis C virus(HCV)infection represents a major health issue worldwide due to its burden of chronic liver disease and extrahepatic manifestations including cardiovascular diseases,which are associated with excess *** of published studies supports the view that HCV infection should be considered a risk factor for the development of carotid atherosclerosis,heart failure and *** contrast,findings from studies addressing coronary artery disease and HCV have yielded conflicting ***,meta-analytic reviews and prospective studies are *** pathogenic mechanisms connecting HCV infection,chronic liver disease,and atherogenesis are not completely ***,it has been hypothesized that HCV may promote atherogenesis and its complications through several direct and indirect biological mechanisms involving HCV colonization and replication within arterial walls,liver steatosis and fibrosis,enhanced and imbalanced secretion of inflammatory cytokines,oxidative stress,endotoxemia,mixed cryoglobulinemia,perturbed cellular and humoral immunity,hyperhomocysteinemia,hypo-adiponectinaemia,insulin resistance,type 2 diabetes and other components of the metabolic *** these complex mechanisms is of fundamental importance for the development of novel therapeutic approaches to prevent and to treat vascular complications in patients with chronic HCV ***,it seems that HCV clearance by interferon and ribavirin treatment significantly reduces non-liver-related mortality;moreover,interferon-based treatment appears to decrease the risk of ischemic stroke.

关键词： Hepatitis C virus Atherosclerosis Coronary artery disease Stroke Inflammation

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Sorafenib and metformin: to be, or not to be, that is the question

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Hepatobiliary Surgery and Nutrition 2019年第4期8卷 411-413页

作者： Giulia Orsi Andrea Casadei-Gardini Division of medical Oncology Department of Medical and Surgical Sciences for Children and Adults University Hospital of Modena Modena Italy

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and ranks second among global causes of cancer-related death (1). The epidemiological and etiological landscape of the disease is facing remarkable changes, due to an increasing incidence of non-alcoholic fatty liver disease (NAFLD)-associated HCC and a concomitant decrease of virus-related cases over the last two decades in Western countries (1). High prevalence of metabolic syndrome in particular in Caucasian patients is contributing to this trend. Moreover, the growing spread of these metabolic conditions in Asian countries is likely to translate into a significant increase in NAFLD-related HCC in the future even in this geographic area (1). In this scenario, exploring the impact of diabetes and anti-diabetic medications on HCC tumorigenesis and prognosis has become of paramount importance.

关键词： NAFLD translate likely

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Clinical features and natural history of cryptogenic cirrhosis compared to hepatitis C virus-related cirrhosis

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World Journal of Gastroenterology 2017年第8期23卷 1458-1468页

作者： Luca Rinaldi Fabio Nascimbeni Mauro Giordano Chiara Masetti Barbara Guerrera Annalisa Amelia Maria Chiara Fascione Stefano Ballestri Dante Romagnoli Rosa Zampino Riccardo Nevola Enrica Baldelli Natalina Iuliano Valerio Rosato Amedeo Lonardo Luigi Elio Adinolfi Internal Medicine Clinical Hospital of MarcianiseSecond University of Naples Department of medical SurgicalNeurologicalMetabolicand Geriatric SciencesSecond University of Naples Outpatient Liver Clinic and Internal Medicine NOCSAEBaggiovaraAzienda USLModena Internal Medicine Pavullo HospitalAzienda Sanitaria Locale

To characterize natural history of cryptogenic cirrhosis (CC) and compare its clinical features and outcomes to those of hepatitis C virus (HCV)-related *** prospective cohort of 102 consecutive patients at their first diagnosis of CC were enrolled in this study. The clinical data and outcomes were compared to an age- and Child-Pugh class-matched cohort of 110 patients with HCV-related cirrhosis. Diagnosis of cirrhosis was based on compatible clinical and laboratory parameters, ultrasound/endoscopic parameters and, whenever possible, on histological grounds and transient elastography. All cases of cirrhosis without a definite etiology were enrolled in the CC group. The parameters assessed were: (1) severity of liver disease at the time of first diagnosis; (2) liver decompensation during follow-up; (3) hepatocellular carcinoma (HCC); (4) orthotopic liver transplantation; and (5) death. The independent associated factors were evaluated by multiple logistic regression analysis, and survival and its determinants by the Kaplan-Meier model, log-rank test and Cox *** the first observation, median age was 66 and 65 years and male gender was 36% and 58% for CC and HCV cirrhosis, respectively. CC showed Child-Pugh class A/B/C of 47%/31%/22%, respectively. Compared to HCV cirrhosis, CC exhibited a significantly higher prevalence of metabolic syndrome (12% vs 54%, respectively), overweight/obesity, high BMI, impaired glucose tolerance, high blood pressure, dyslipidemia, hyperuricemia, cardiovascular diseases, extrahepatic cancer, and gallstones. Over a median period of 42 mo of follow-up, liver decompensation, HCC development and death for CC and HCV-related cirrhosis were 60.8%, and 54.4%, 16.7% and 17.2%, 39.2% and 30%, respectively. The median survival was 60 mo for CC. Independent predictors of death were age and Child-Pugh class at diagnosis. CC showed an approximately twofold higher incidence of HCC in Child-Pugh class ***

关键词： Liver cirrhosis Hepatocellular carcinoma metabolic syndrome Nonalcoholic fatty liver disease Cardiovascular diseases

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Association of Bisphenol A Exposure with Circulating Sex Hormone Concentrations in Men and Postmenopausal Women

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Biomedical and Environmental sciences 2014年第8期27卷 633-636页

作者： LI Mian WANG Tian Ge XU Yu ZHANG Jie XU Bai Hui XU Min CHEN Yu Hong LU Jie Li Bi Yu Fang WANG Wei Qing GU Yan Yun NING Guang Key Laboratory for endocrine and metabolic Diseases of Ministry of Health Ruijin HospitalShanghai Jiaotong University Medical School E-Institute of Shanghai Universities Shanghai Clinical Center for endocrine and metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Department of Endocrinology and Metabolism Ruijin Hospital Shanghai Jiaotong University Medical School

A total of 1 116 middle-aged and elderly men and 1 442 postmenopausal women were recruited in this study. Whether bisphenol A exposure was associated with circulating sex hormone concentrations was studied. Univariate analysis revealed that the urinary bisphenol A concentration was negatively correlated with the serum levels of luteinizing hormone （B=-0.061, P〈0.0001） and follicle-stimulating hormone （B=-0.086, P〈0.0001） in men, and with the serum levels of follicle-stimulating hormone （B=-0.037, P=0.018） and sex hormone-binding globulin （B=-0.043, P=0.006） in women. However, no significant association was observed between the serum levels of urinary bisphenol A and circulating sex hormone after adjustment for the potential confounders.

关键词： SHBG Association of Bisphenol A Exposure with Circulating Sex Hormone Concentrations in Men and Postmenopausal Women FSH

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Autophagy induced by glibenclamide serves as a defense against apoptosis in INS-1 rat insulinoma cells

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Journal of Diabetes Mellitus 2013年第3期3卷 122-128页

作者： Hua Su Xingyan Liu Ling Su Li Zhang Xiangguo Liu Hong Ji Haiqin Rong Institute of endocrine and metabolic Diseases Shandong Academy of Medical Sciences. Jinan China School of Life sciences Shandong University. Jinan China

Glibenclamide, a blocker of ATP-sensitive potassium channels, has been found to induce apoptosis in some cell types, including pancreatic beta-cells. Since autophagy plays doubleedged roles in pancreatic beta-cell survival, frequently through cross-talking with apoptosis, we investigated if glibenclamide induced autophagy in INS-1 rat insulinoma cells and the influence of autophagy on apoptosis. Mammalian target of rapamycin (mTOR) is a negative regulator of autophagy. As one of the substrates of mTOR, p70 S6 kinase (p70 S6K) is phosphorylated upon mTOR activation. Our results showed that glibenclamide induced an elevated protein level of the autophagy marker LC3-II, while decreasing phosphorylated p70 S6K, indicative of inhibition on mTOR signaling in INS-1 cells. Furthermore, inhibiting glibenclamide-induced autophagy via knocking down the autophagy essential gene Atg7 decreased cell viability and increased apoptosis in INS-1 cells. Our results indicate that glibenclamide induces autophagy in INS-1 cells, and that autophagy activation is exerting a protective activity against apoptosis.

关键词： Glibenclamide Pancreatic Beta-Cell Autophagy Apoptosis p70 S6K

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Current status of PI3K-mTOR inhibition in hormone-receptor positive, HER2-negative breast cancer

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World Journal of Clinical Oncology 2018年第8期9卷 172-179页

作者： Navid Sobhani Daniele Generali Fabrizio Zanconati Marina Bortul Bruna Scaggiante Department of medical Surgical and Health Sciences University of Trieste Cattinara Academic Hospital Department of Life sciences University of Trieste

Breast cancer (BC) is the most common cancer in women and second only to lung cancer in terms of mortality. Among the three different BC subtypes, the oestrogen receptor positive represents nearly 70% of all cases and it is usually treated with anti-oestrogen drugs. However, the majority of hormone receptor positive metastatic BC patients develop resistance to anti-oestrogen *** need for more down-stream therapies brought to the development of therapeutic strategies inhibiting the phosphatidylinositol 3-kinase-mammalian target of rapamycin (mTOR) pathway. Inhibitors of the mTOR have been tested in different clinical trials; everolimus has been Food and Drug Administration approved for the treatment of oestrogen receptor positive/human epidermal growth factor receptor 2 negative BC patients in combination with exemestane in patients who have progressed to anastrozole or letrozole after the encouraging results coming from BOLERO-2 trial. Similar results were obtained by the TAMRAD investigatory study testing tamoxifen in combination with everolimus in advanced BC. This editorial focuses on the results from BOLERO-2, BOLERO 4 and BOLERO-6, which tested the clinical importance of mTOR inhibition. We comment also on the role of phosphatidylinositol 3-kinase-mTOR inhibition as reported in the BELLE-2 and BELLE-3 trials and the future directions for the inhibition of this tumour metabolic axis.

关键词： Hormone receptor positive/Her2-negative breast cancer PI3K mTOR TORC1/2 Akt Everolimus

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Microbiota in health and diseases

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1491-1518页

作者： Kaijian Hou Zhuo-Xun Wu Xuan-Yu Chen Jing-Quan Wang Dongya Zhang Chuanxing Xiao Dan Zhu Jagadish B.Koya Liuya Wei Jilin Li Zhe-Sheng Chen Department of endocrine and metabolic Diseases Longhu HospitalThe First Affiliated Hospital of Medical College of Shantou UniversityShantouGuangdong 515000China Department of Pharmaceutical sciences Institute for BiotechnologyCollege of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA Microbiome Research Center Moon(Guangzhou)Biotech LtdGuangzhou 510535China School of Pharmacy Weifang Medical UniversityWeifangShandong 261053China Department of Cardiovascular The Second Affiliated Hospital of Medical College of Shantou UniversityShantouGuangdong 515000China

The role of microbiota in health and diseases is being highlighted by numerous studies since its *** on the localized regions,microbiota can be classified into gut,oral,respiratory,and skin *** microbial communities are in symbiosis with the host,contributing to homeostasis and regulating immune ***,microbiota dysbiosis can lead to dysregulation of bodily functions and diseases including cardiovascular diseases(CVDs),cancers,respiratory diseases.

关键词： diseases respiratory homeostasis

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