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

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

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

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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

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Role of inflammatory response in liver diseases: Therapeutic strategies

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World Journal of Hepatology 2018年第1期10卷 1-7页

作者： josé A del campo Paloma Gallego Lourdes Grande Department of Digestive Diseases Valme University Hospital and CIBERehd

Inflammation and tumorigenesis are tightly linked pathways impacting cancer development. Inflammasomes are key signalling platforms that detect pathogenic microorganisms, including hepatitis C virus(HCV) infection, and sterile stressors(oxidative stress, insulin resistance, lipotoxicity) able to activate pro-inflammatory cytokines interleukin-1β and IL-18. Most of the inflammasome complexes that have been described to date contain a NOD-like receptor sensor molecule. Redox state and autophagy can regulate inflammasome complex and, depending on the conditions, can be either pro-or antiapoptotic. Acute and chronic liver diseases are cytokinedriven diseases as several proinflammatory cytokines(IL-1α, IL-1β, tumor necrosis factor-alpha, and IL-6) are critically involved in inflammation, steatosis, fibrosis, and cancer development. NLRP3 inflammasome gain of function aggravates liver disease, resulting in severe liver fibrosis and highlighting this pathway in the pathogenesis of non-alcoholic fatty liver disease. On the other hand, HCV infection is the primary catalyst for progressive liver disease and development of liver cancer. It is well established that HCV-induced IL-1β production by hepatic macrophages plays a critical and central process that promotes liver inflammation and disease. In this review, we aim to clarify the role of the inflammasome in the aggravation of liver disease, and how selective blockade of this main pathway may be a useful strategy to delay fibrosis progression in liver diseases.

关键词： Caspase-1 Fibrosis Hepatitis C virus Inflammasome Interleukin-1α Interleukin-1β Liver disease Non-alcoholic fatty liver disease NLRP3 Tumor necrosis factor-alpha

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

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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

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Analysis of the relation between organic products consumption and box schemes use in Alicante (Spain)

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Agricultural Sciences 2011年第4期2卷 505-510页

作者： Fernando Vidal David Bernardo López Francisco josé del campo 不详

Box-schemes or organic food subscription plans consist on a regular delivery of a box of seasonal fruits and/or vegetables, preferably organic, cultivated in the vicinity at a specified point using subscription, The object of the present work is trying to examine whether there is a relationship between consumer knowledge about these short distribution channels and the consumption of organic products in the province of Alicante. A survey has been conducted among 400 usual food buyers in this Spanish province. It has been found that the consumption of organic products and the knowledge of such initiatives are linked. We recommend to companies that use this type of distribution channel to publicize its benefits.

关键词： Box-Scheme Environmental Consumer Knowledge Distribution

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地基与海洋建筑物相互作用——以最近西班牙海岸线建筑物内部损坏为例(英文)

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工程地质学报 2011年第3期19卷 297-303页

作者： CARLOS delgado jos M.del campo VICENTE Negro 马德里理工大学土木工程系

海洋工程通常是一个细长的线。我们通常看到的仅仅是建筑物狭长的表面,而不分析支撑他们的大量水下材料。毋庸置疑,海底地基将承受来自于海洋的周期性和交替的静力以及变化的动力。外部和内部的海上工程均在复杂的环境中运行。固态颗粒... 详细信息

海洋工程通常是一个细长的线。我们通常看到的仅仅是建筑物狭长的表面,而不分析支撑他们的大量水下材料。毋庸置疑,海底地基将承受来自于海洋的周期性和交替的静力以及变化的动力。外部和内部的海上工程均在复杂的环境中运行。固态颗粒(防波堤)可以吸入入射水流,并且通过颗粒之间的间距吸收海浪的能量。回流试图从固态颗粒中抽离物质,这样一个遵从太沙基原理的基于有效拉力和中性拉力之间的平衡建立起来。在某些情况下,防护层的液化已经造成了防波堤崩溃(Sines,葡萄牙,1978年2月)。在其他情况下,虹吸作用或液化导致巨石(垂直的防波堤)毁坏或崩溃(新巴塞罗那港口,西班牙,2001年11月)。结合复合设计工具的地基-作用力——结构相互作用的过程是一个复杂的分析,关于其研究刚刚开始。本文介绍了最近发生在西班牙的、由于地基失效导致的海上工程内部损坏的两个例子(马拉加,2004年7月,巴塞罗那,2007年1月),分析了其成因。

关键词：地基海洋建筑物破坏海岸线西班牙

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Modulation of faecal metagenome in Crohn's disease:Role of microRNAs as biomarkers

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World Journal of Gastroenterology 2018年第46期24卷 5223-5233页

作者： María Rojas-Feria Teresa Romero-García jose Angel Fernández Caballero-Rico Helena Pastor Ramírez Marta Avilés-Recio Manuel Castro-Fernandez Natalia Chueca Porcuna Manuel Romero-Gomez Federico García Lourdes Grande joséa del campo Department of Digestive Diseases Valme University HospitalUGC Digestive Disease and CIBERehdServicio Andaluz de SaludSeville E-41014Spain Complejo Hospitalario Universitario de Granada MicrobiologyGranada E-18016Spain Institute of Biomedicine of Seville Digestive DiseasesHospital Universitario Virgen del Rocío and CIBERehdSeville E-41013Spain Facultad de ciencias de la salud.Universidad Europea Miguel de Cervantes Madrid E-28280Spain

BACKGROUND The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16 S rRNA gene sequencing has shown that the microbiota in inflammatory bowel disease(IBD) is abnormal and characterized by reduced diversity. Micro RNAs(miRNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn's disease(CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with miRNA profile from gut *** To investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with miRNA profile from gut *** Patients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of newonset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCR using primers directed to the 16 S bacterial rRNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MGRAST server with the database Ribosomal Project was used. MiRNA profile and their relative abundance were analyzed by quantitative *** Microbial community was characterized using 16 S rRNA gene sequencing in 29 samples(n = 13 CD patients, and n = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group(5.5 vs 3.7). A reduction in Firmicutes and an increase in Bacteroidetes were found. Clostridia class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showe

关键词： Crohn’s disease Dysbiosis microRNAs Firmicutes Bacteroidetes

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Association between vitamin D and hepatitis C virus infection: A meta-analysis

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World Journal of Gastroenterology 2013年第35期19卷 5917-5924页

作者： Livia Melo Villar josé Antonio del campo Isidora Ranchal Elisabeth Lampe Manuel Romero-Gomez Laboratory of Viral Hepatitis Oswaldo Cruz Institute Fiocruz Rio de Janeiro RJ 210360-040 Brazil Unit for the Clinical Management of Digestive Diseases and CIBERehd Hospital Universitario de Valme41014 SevillaSpain

AIM:To evaluate the association between 25-hydroxyvitamin D[25(OH)D]and sustained virological response(SVR)in hepatitis C virus(HCV)infected ***:Relevant studies were identified by systematically searching MEDLINE databases up to March2012 and abstracts of the European and American Congress of Hepatology conducted in *** must provide information on SVR and the levels of 25(OH)D3and/or 25(OH)D2[henceforth referred to as 25(OH)D]in sera samples from HCV infected *** inclusion criteria were:clinical studies that included HCV infected patients aged older than 18 years regardless of HCV genotype or ethnic group;provided information on SVR rates;and were reported in the English languageas full *** to the heterogeneity of studies in categorizing serum vitamin D levels,a cut-off value of30 ng/mL of serum 25(OH)D was *** was assessed using *** summary odds ratios with their corresponding 95%CI were calculated based on a random-effects ***:Overall,11 studies(8 observational and 3interventional)involving 1575 individuals were included and 1117 HCV infected individuals(71%)showed low vitamin D *** of the studies included monoinfected HCV individuals with the mean age ranging from 38 to 56 *** studies were conducted in human immunodeficiency virus/HCV infected *** vitamin D measurement,most of the studies employed radioimmunoassays(n=5)followed by chemiluminescence(n=4)and just one study employed high performance/pressure liquid chromatography(HPLC).Basal vitamin D levels varied from 17 to43 ng/mL in the studies selected,and most of the HCV infected individuals had genotype 1(1068/1575)with mean viral load varying from log 4.5-5.9 UI/*** regard to HCV treatment,most of the studies(n=8)included HCV individuals without previous treatment,where the pooled SVR rate was 46.4%.High rates of SVR were observed in HCV individuals with vitamin D levels above 30 ng/mL(OR=1

关键词： Vitamin D Hepatitis C Therapy Metaanalysis Sustained virological response

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Hyperammonemia induced oxidative stress in cirrhotic rats without promoting differential protein expression in the brain cortex: A 2D-DIGE analysis

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Advances in Bioscience and Biotechnology 2012年第8期3卷 1116-1123页

作者： Pilar Carbonero-Aguilar Ma del Mar Diaz-Herrero josé A. del campo Olga Cremades Manuel Romero-Gómez Juan Bautista Departamento de Bioquímica y Biología Molecular Facultad de Farmacia Universidad de Sevilla Sevilla Spain UCM Digestive Diseases and CIBERehd Hospital Universitario de Valme Sevilla Spain

Oxidative stress induced by a high ammonia concentration could modify protein expression in the brain. This study was undertaken in order to investigate the impact of hyperammonemia, caused by thioacetmide (TAA) in rats, on brain cortex protein expression using 2D-DIGE, and analyzing its role in the pathogenesis of HE. Hyperammonemia was induced with TAA. Ammonia and active oxidants were measured by L-glutamate dehydrogenase and dichlorodihydrofluorescein diacetate methods, respectively. Lipid peroxidation and protein oxidation biomarkers were also studied. Differential protein expression in the cortex of TAA- and control-rats was studied by 2D-DIGE. Image analysis was performed using the DeCyder? Software. Ammonia concentration in plasma and brain tissue was higher in TAA-rats compared to control-rats, 3.12 and 2.43 fold higher, respectively. Active oxidants production in TAA-rats was increased by 2.7 fold compared to control-rats. Measurements of MDA, HNE and carbonyl groups, biomarkers of lipid peroxidation and protein oxidation respectively, were found to be statistically significantly increased in TAA-rats compared to control-rats (3.16-, 2.44- and 1.95-fold, respectively), reflecting the presence of oxidative stress in the brain of TAA-rats. 2D-DIGE analysis of brain cortex protein allowed the detection of 2896 spots, however, image analysis showed no statistically significant differential protein expression between the proteins expressed in TAA- and control-rats. No statistical significant differential protein expression in the cortex of TAA-rats was observed, although oxidative stress biomarkers for lipid and proteins were higher in the brain of TAA-rats than in control-rats. These results support the idea that oxidative post-translational modifications are implicated in HE physiopathology.

关键词： Oxidative Stress Hyperammonemia Cirrhosis Hepatic Encephalopathy Protein Expression

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什么是模型

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模型世界 2019年第2期 3-3页

作者： josé Isidro del campo

我们所要做的就是放眼看看世界各地的模型秀、比赛和展览。显而易见,模型依然极具生命力,很受欢迎。看到人们对模型的兴趣横跨了几代人,实在让人感到欣慰。这要归功于各种形式的社交网络,从孩童到老人,每个年龄段都有许多人乐此不疲。... 详细信息

我们所要做的就是放眼看看世界各地的模型秀、比赛和展览。显而易见,模型依然极具生命力,很受欢迎。看到人们对模型的兴趣横跨了几代人,实在让人感到欣慰。这要归功于各种形式的社交网络,从孩童到老人,每个年龄段都有许多人乐此不疲。无需担心这项爱好成为明日夕阳,年轻的一代人正前

关键词：爱好者

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