检索结果-南通市图书馆

glutaminolysis-ammonia-urea Cycle Axis,Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies

引用

Journal of Clinical and Translational Hepatology 2022年第2期10卷 356-362页

作者： Ángela Rojas María Rosario garcía-Lozano Antonio gil-gómez manuel romero-gómez Javier Ampuero Department of Unit of Digestive Diseases Virgen del Rocío University HospitalSevilleSpain SeLiver group at the Insti-tute of Biomedicine of Seville(IBIS) Virgen del Rocío University Hospital/CSIC/University of SevilleSevilleSpain Center for the Study of Liver and gastrointestinal Diseases(CIBERehd) Carlos III National Institute of HealthMadridSpain De-partment of Organic and Medicinal Chemistry Faculty of PharmacyUniversity of SevilleE-41071SevilleSpain

The prevalence of non-alcoholic fatty liver disease(NAFLD)is increasing worldwide,reflecting the current epidemics of obesity,insulin resistance,type 2 diabetes mellitus,and metabolic syndrome.NAFLD is characterized by the accumulation of fat in the liver,and is known to be a cause of cirrhosis.Although many pathways have been proposed,the cause of NAFLD-linked fibrosis progression is still unclear,which posed challenges for the development of new therapies to prevent NASH-related cirrhosis and hepatocellular carcinoma.Cirrhosis is associated with activation of hepatic stellate cells(HSC)and accumulation of excess extracellular matrix proteins,and inhibiting the activation of HSCs would be expected to slow the progression of NAFLD-cirrhosis.Multiple molecular signals and pathways such as oxidative stress and glutaminolysis have been reported to promote HSC activation.Both mechanisms are plausible antifibrotic targets in NASH,as the activation of HSCs the proliferation of myofibroblasts depend on those processes.This review summarizes the role of the glutaminolysis-ammonia-urea cycle axis in the context of NAFLD progression,and shows how the axis could be a novel therapeutic target.

关键词： Non-alcoholic fatty liver disease Cirrhosis Fibrosis glutaminoly-sis Ammonia Urea

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Steatosis and insulin resistance in hepatitis C: A way out for the virus?

引用

World Journal of gastroenterology 2009年第40期15卷 5014-5019页

作者： José A Del Campo manuel romero-gómez Unit for The Clinical Management of Digestive Diseases and CIBERehd Hospital Universitario de Valme

The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, whereas meta-bolic steatosis is often associated with genotype 1 and metabolic syndrome. Several molecular mechanisms responsible for steatosis have been associated with the HCV core protein, which is able to induce gene expres-sion and activity of sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activat-ed receptor γ (PPARγ), increasing the transcription of genes involved in hepatic fatty acid synthesis. Steatosis has been also implicated in viral replication. In infected cells, HCV core protein is targeted to lipid droplets which serve as intracellular storage organelles. These studies have shown that lipid droplets are essential for virus assembly. Thus, HCV promotes steatosis as an eff icient mechanism for stable viral replication. Chronic HCV in-fection can also induce insulin resistance. In patients with HCV, insulin resistance is more strongly associated with viral load than visceral obesity. HCV seems to lead to insulin resistance through interference of intracellular insulin signalling by HCV proteins, mainly, the serine phosphorylation of insulin receptor-1 (IRS-1) and im-pairment of the downstream Akt signalling pathway. The HCV core protein interferes with in vitro insulin signal-ling by genotype-specif ic mechanisms, where the role of suppressor of cytokine signal 7 (SOCS-7) in genotype 3aand mammalian target of rapamycin (mTOR) in geno-type 1 in IRS-1 downregulation play key roles. Steatosis and insulin resistance have been associated with f ibrosis progression and a reduced rate of sustained response to peginterferon plus ribavirin.

关键词：胰岛素抵抗丙型肝炎病毒脂肪

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Entry of hepatitis C virus into the cell: A therapeutic target

引用

World Journal of gastroenterology 2012年第33期18卷 4481-4485页

作者： José Antonio Del Campo ngela Rojas manuel romero-gómez Unit for Medical and Surgical Management of Digestive Diseases Center for Biomedical Research in Digestive and Liver Diseases Network (CIBERehd) Valme University Hospital University of Seville E-41014 Sevilla Spain

Several receptors have been identified as implicated on viral entry into the hepatocyte; and, this interaction between the virus and potential receptors could modulate infection, spontaneous viral clearance, persistence of the infection and the widespread of the virus as outbreak. Nevertheless, the playing role of each of them remains controversial. The NiemannPick type C1 like 1 gene (NPC1L1) receptor has been recently implicated on hepatitis C virus (HCV) entry into the cell and ezetimibe, an anti-cholesterol drug seems to block that, emerging the idea to control hepatitis C outbreak modulating lipid-related receptors. Hepatitis C infection seems to modulate lipid metabolism according to host genetic background. Indeed, it circulates like a lipoviroparticle. The main aim of this field of vision would be to discuss the role of hepatocyte receptors implicated on virus entry, especially NPC1L1 and the therapeutic options derived from the better knowledge about HCV-lipidsreceptors interaction.

关键词：丙型肝炎病毒治疗方案肝细胞细胞受体入口病毒感染相互作用病毒清除

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Insulin resistance and hepatitis C

引用

World Journal of gastroenterology 2006年第44期12卷 7075-7080页

作者： manuel romero-gómez Unit for the Clinical Management of Digestive Diseases. Hospital Universitario de Valme. Ctra de Cádiz s/n 41014 Sevilla Spain

Insulin resistance is the major feature of the meta- bolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resist- ance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients. Hepatitis C virus (HCV) infection promotes insulin resist- ance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients: “viral” and “metabolic” insulin resistance. In- sulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARγ recep- tors. Lastly, insulin resistance has been found as a com- mon denominator in patients difficult-to-treat like cir- rhotics, overweight, HIV coinfected and Afro-American. Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin. Indeed, in genotype 1, the sustained response rate was twice (60%) in patients with HOMA ≤ 2 than patients with HOMA > 2. In experiments carried out on Huh-7 cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin (at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state) was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abol- ished. In summary, hepatitis C promotes insulin resist- ance and insulin resistance induces interferon resistance, steatosis and fibrosis progression.

关键词：丙型肝炎纤维化胰岛素乃药性持续反应抗病毒药物

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Combination of squamous cell carcinoma antigen immunocomplex and alpha-fetoprotein in mid-and long-term prediction of hepatocellular carcinoma among cirrhotic patients

引用

World Journal of gastroenterology 2021年第48期27卷 8343-8356页

作者： Antonio gil-gómez Ángela Rojas Chang-Hai Liu Rocio gallego-Duran Rocio Muñoz-Hernandez giorgio Fassina Patrizia Pontisso Javier Ampuero manuel romero-gómez SeLiver group Institute of Biomedicine of SevilleSeville 41013Spain CIBERehd Instituto de Salud Carlos IIIMadrid 28029Spain Mucosal Immunity Lab IRCCS Humanitas Research HospitalMilan 20089Italy Center of Infectious Diseases West China Hospital of Sichuan UniversityChengdu 610017Sichuan ProvinceChina State Key Laboratory of Biotherapy and Center of Infectious Diseases West China HospitalChengdu 610017Sichuan ProvinceChina Life Biotechnology Padua UniversityVenice 30175Italy Department of Clinical and Experimental Medicine University of PadovaPadova 35123Italy UCM Digestive Diseases Virgen del Rocío University HospitalSeville 41014Spain

BACKgROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.AIM To determine the role of the combination of SCCA-IgM and AFP in predicting mid-and long-term appearance of HCC.METHODS Two-hundred and three cirrhotic patients(Child A 74.9%,B 21.2%,C 3.9%)were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines.The estimation cohort was recruited in Italy(30.5%;62/203)and validation cohort from Spain(69.5%;141/203).Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay(Hepa-IC,Xeptagen,Italy)and AFP levels at baseline.Patients were followed-up for 60 mo,being censored at the time of the appearance of HCC.RESULTS There were 10.8%and 23.1%of HCC development at two-and five-years followup.Patients with HCC showed higher levels of SCCA-IgM than those without it(425.72±568.33 AU/mL vs 195.93±188.40 AU/mL,P=0.009)during the fiveyear follow-up.In multivariate analysis,after adjusting by age,sex,aspartate transaminase and Child-Pugh,the following factors were independently associated with HCC:SCCA-IgM[Hazard ratio(HR)=1.001,95%CI:1.000-1.002;P=0.003],AFP(HR=1.028,95%CI:1.009-1.046;P=0.003)and creatinine(HR=1.56495%CI:1.151-2.124;P=0.004).The log-rank test of the combination resulted in 7.488(P=0.024)in estimation cohort and 11.061(P=0.004)in the validation cohort,and a 100%of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.CONCLUSION We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method,which could be followed by tailored HCC surveillance for individual patients,especially for those cirrhotic patients belonging t

关键词： Squamous cell carcinoma antigen Hepatocellular carcinoma prediction Precision medicine Stratification of cirrhotic patient

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Wilson's disease:Revisiting an old friend

引用

World Journal of Hepatology 2021年第6期13卷 634-649页

作者： Ana Lucena-Valera Domingo Perez-Palacios Rocio Muñoz-Hernandez manuel romero-gómez Javier Ampuero Department of gastroenterology Hospital Universitario Virgen del RocioSevilla 41013Spain SeLiver group Instituto de Biomedicina de Sevilla(IBiS)Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaEspaña Department of Unit of Digestive Diseases Hospital Universitario Virgen del RocioSevilla 41014Spain

Wilson's disease(WD)is a rare condition caused by copper accumulation primarily in the liver and secondly in other organs,such as the central nervous system.It is a hereditary autosomal recessive disease caused by a deficiency in the ATP7B transporter.This protein facilitates the incorporation of copper into ceruloplasmin.More than 800 mutations associated with WD have been described.The onset of the disease frequently includes manifestations related to the liver(as chronic liver disease or acute liver failure)and neurological symptoms,although it can sometimes be asymptomatic.Despite it being more frequent in young people,WD has been described in all life stages.Due to its fatal prognosis,WD should be suspected in all patients with unexplained biochemical liver abnormalities or neurological or psychiatric symptoms.The diagnosis is established with a combination of clinical signs and tests,including the measurement of ceruloplasmin,urinary copper excretion,copper quantification in liver biopsy,or genetic assessment.The pharmacological therapies include chelating drugs,such as D-penicillamine or trientine,and zinc salts,which are able to change the natural history of the disease,increasing the survival of these patients.In some cases of end-stage liver disease or acute liver failure,liver transplantation must be an option to increase survival.In this narrative review,we offer an overview of WD,focusing on the importance of clinical suspicion,the correct diagnosis,and treatment.

关键词： Wilson´s disease Copper ATP7B Ceruloplasmin Chelator Liver disease

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cardiovascular assessment in liver transplant for nonalcoholic steatohepatitis patients:What we do,what we should do

引用

World Journal of Hepatology 2017年第15期9卷 697-703页

作者： Yolanda Sanchez-Torrijos Javier Ampuero manuel romero-gómez Unidad Intercentros de Aparato Digestivo Hospitales Universitarios Virgen del Rocio-Virgen Macarena Instituto de Biomedicina de Sevilla Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd)

Non-alcoholic fatty liver disease(NAFLD) is increasing considerably due to the current lifestyle,which means that it is becoming one of the main indications for liver transplantation.On the other hand,there is a strong association between NAFLD and cardiovascular disease.This has been evidenced in many studies revealing a higher presence of carotid plaques or carotid intima-media thickness,leading to cardiovascular events and,ultimately,mortality.According to the liver transplant guidelines,screening for heart disease in transplant candidates should be performed by electrocardiogram and transthoracic echocardiography while a stress echocardiogram should be reserved for those with more than two cardiovascular risk factors or greater than 50 years old.However,there are no specific recommendations in NAFLD patients requiring a liver transplantation,despite its well-known cardiovascular risk association.Many studies have shown that these patients probably require a more exhaustive assessment and a global approach including other specialists such as cardiologists or nutritionists.Also,the incidence of cardiovascular disease is also increased in NAFLD patients in the post-transplantation period in comparison with other etiologies,because of the pre-existent risk factors together with the immunosuppressive therapy.Therefore,an early intervention on the lifestyle and the individualized selection of the immunosuppressive regimen could lead to a modification of the cardiovascular risk factors in NAFLD patients requiring a liver transplantation.

关键词：心血管的风险非酒精的脂肪肝疾病非酒精的 steatohepatitis 预先移植评价肝移植

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Modulation of host lipid metabolism by hepatitis C virus: role of new therapies

引用

World Journal of gastroenterology 2015年第38期21卷 10776-10782页

作者： José A Del Campo manuel romero-gómez Digestive Diseases and CIBERehd Valme University Hospital

It is well established that hepatitis C virus(HCV) infection and replication relies on host lipid metabolism. HCV proteins interact and associate with lipid droplets to facilitate virion assembly and production. Besides,circulating infective particles are associated with verylow-density lipoprotein. On the other hand,higher serum lipid levels have been associated with sustained viral response to pegylated interferon and ribavirin therapy in chronic HCV infection,suggesting a relevant role in viral clearance for host proteins. Host and viral genetic factors play an essential role in chronic infection. Lipid metabolism is hijacked by viral infection and could determine the success of viral replication. Recently development of direct acting antiviral agents has shown a very high efficacy(> 90%) in sustained viral response rates even for cirrhotic patients and most of the viral genotypes. HCV RNA clearance induced by Sofosbuvir has been associated with an increased concentration and size of the low-density lipoprotein particles. In this review,host genetic factors,viral factors and the interaction between them will be depicted to clarify the major issues involved in viral infection and lipid metabolism.

关键词： Hepatitis C virus Lipid metabolism Direct acting a

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Hepatobiliary manifestations in inflammatory bowel disease: The gut,the drugs and the liver

引用

World Journal of gastroenterology 2013年第42期19卷 7327-7340页

作者： María Rojas-Feria manuel Castro Emilio Suárez Javier Ampuero manuel romero-gómez Unit for Medical and Surgical Management of Digestive Diseases and CIBERehd Valme University HospitalUniversity of SevilleE-41014 SevillaSpain

Abnormal liver biochemical tests are present in up to30%of patients with inflammatory bowel disease(IBD),and therefore become a diagnostic challenge.Liver and biliary tract diseases are common extraintestinal manifestations for both Crohn’s disease and ulcerative colitis(UC),and typically do not correlate with intestinal activity.Primary sclerosing cholangitis(PSC)is the most common hepatobiliary manifestation of IBD,and is more prevalent in UC.Approximately 5%of patients with UC develop PSC,with the prevalence reaching up to 90%.Cholangiocarcinoma and colon cancer risks are increased in these patients.Less common disorders include autoimmune hepatitis/PSC overlap syndrome,Igg4-associated cholangiopathy,primary biliary cirrhosis,hepatic amyloidosis,granulomatous hepatitis,cholelithiasis,portal vein thrombosis,liver abscess,and non-alcoholic fatty liver disease.Hepatitis B reactivation during immunosuppressive therapy is a major concern,with screening and vaccination being recommended in serologically negative cases for patients with IBD.Reactivation prophylaxis with entecavir or tenofovir for 6to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen(HBsAg)positive,independently from viral load.HBsAg negative and anti-HBc positive patients,with or without anti-HBs,should be closely monitored,measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy,and should be treated if the viral load increases.On the other hand,immunosuppressive therapy does not seem to promote reactivation of hepatitis C,and hepatitis C antiviral treatment does not influence IBD natural history either.Most of the drugs used for IBD treatment may induce hepatotoxicity,although the incidence of serious adverse events is low.Abnormalities in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically relevant.Methotrexaterelated hepatotoxicity has been described in 14%of patients with IBD,in a dose-dependen

关键词： Inflammatory bowel disease Hepatobiliary disorders Extraintestinal manifestations Primary sclerosing cholangitis Drug-induced liver injury Hepatotoxicity Hepatitis B Hepatitis C

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Epigenetic mechanisms in non-alcoholic fatty liver disease:An emerging field

引用

World Journal of Hepatology 2015年第24期7卷 2497-2502页

作者： Rocío gallego-Durán manuel romero-gómez Inter-Centre Unit of Digestive Diseases and CIBERehd Virgen Macarena-Virgen del Rocío University Hospitals Instituto de Biomedicina de Sevilla University of Sevilla

Non-alcoholic fatty liver disease(NAFLD) is an emerging health concern in both developed and non-developed world, encompassing from simple steatosis to nonalcoholic steatohepatitis(NASH), cirrhosis and liver cancer. Incidence and prevalence of this disease are increasing due to the socioeconomic transition and change to harmful diet. Currently, gold standard method in NAFLD diagnosis is liver biopsy, despite complications and lack of accuracy due to sampling error. Further, pathogenesis of NAFLD is not fully understood, but is well-known that obesity, diabetes and metabolic derangements played a major role in disease development and progression. Besides, gut microbioma and host genetic and epigenetic background could explain considerable interindividual variability. Knowledge that epigenetics, heritable events not caused by changes in DNA sequence, contribute to development of diseases has been a revolution in the last few years. Recently, evidences are accumulating revealing the important role of epigenetics in NAFLD pathogenesis and in NASH genesis. Histone modifications, changes in DNA methylation and aberrant profiles or micro RNAs could boost development of NAFLD and transition into clinical relevant status. PNPLA3 genotype gg has been associated with a more progressive disease and epigenetics could modulate this effect. The impact of epigenetic on NAFLD progression could deserve further applications on therapeutic targets together with future non-invasive methods useful for the diagnosis and staging of NAFLD.

关键词： Non-alcoholic steatohepatitis Epigenetics Diagnosi

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：