Mitochondrial respiratory chain activity is associated with severity, corticosteroid response and prognosis of alcoholic hepatitis.

Background And Aims: Little is known about the extent of mitochondrial respiratory chain (MRC) activity dysfunction in patients with alcoholic hepatitis (AH). We aimed to assess the hepatic MRC activity in AH patients and its potential impact on the severity and prognosis of this life-threatening liver disease.

Methods: MRC complexes were measured in liver biopsies of 98 AH patients (non-severe, 17; severe, 81) and in 12 histologically normal livers (NL).

Protein tyrosine phosphatase 1b deficiency protects against hepatic fibrosis by modulating nadph oxidases.

Inflammation is typically associated with the development of fibrosis, cirrhosis and hepatocellular carcinoma. The key role of protein tyrosine phosphatase 1B (PTP1B) in inflammatory responses has focused this study in understanding its implication in liver fibrosis. Here we show that hepatic PTP1B mRNA expression increased after bile duct ligation (BDL), while BDL-induced liver fibrosis was markedly reduced in mice lacking Ptpn1 (PTP1B) as assessed by decreased collagen deposition and α-smooth muscle actin (α-SMA) expression.

Omentectomy Prevents Metabolic Syndrome By Reducing Appetite and Body Weight In A Diet-Induced Obesity Rat Model.

Visceral fat deposition is associated with impairment of glucose and lipid metabolism while leptin levels are frequently related to subcutaneous fat area. At present, there is considerable controversy regarding the role of visceral adipose tissue accumulation in the development of metabolic syndrome (MS). Here we show the effects of omentectomy on the liver and MS in a diet induced obesity rat model.

Interlobar Artery Resistive Index predicts Acute-on-Chronic Liver Failure Syndrome in Cirrhotic Patients with Acute Decompensation.

Introduction: Patients with acutely decompensated (AD) cirrhosis are at risk for developing acute-on-chronic liver failure (ACLF) syndrome. This syndrome is associated with a high short-term mortality rate. The aim of our study was to identify reliable early predictors of developing ACLF in cirrhotic patients with AD.

NADPH oxidase is implicated in the pathogenesis of oxidative phosphorylation dysfunction in mice fed a high-fat diet.

The aim of this study was to evaluate the role of NADPH oxidase (NADPHox) in the pathogenesis of oxidative phosphorylation (OXPHOS) dysfunction as found in mice fed a high-fat diet (HFD). C57BL/6J mice were distributed in four groups: WT/SCD: six wild-type (WT) mice fed a standard chow diet (SCD); WT/HFD, six WT mice fed a HFD; NOX2(-/-)/SCD, six NADPHox-deficient mice on a SCD; (4) NOX2(-/-)/HFD, six NADPHox-deficient mice on a HFD. After 32 weeks, we studied the liver for: histology; OXPHOS complex activity; fully assembled OXPHOS complexes and their subunits; gene expression of OXPHOS subunits; oxidative and nitrosative stress; and oxidative DNA damage.

C/EBPβ-Thr217 Phosphorylation Stimulates Macrophage Inflammasome Activation and Liver Injury.

Amplification of liver injury is mediated by macrophages but the signaling by which the macrophage inflammasome enhances liver injury is not completely understood. The CCAAT/Enhancer Binding Protein-β (C/EBPβ) is a critical signaling molecule for macrophages because expression of a dominant inhibitor of C/EBPβ DNA-binding sites or a targeted deletion of C/EBPβ results in impaired macrophage differentiation. We reported that expression of the phosphorylation-mutant C/EBPβ-Glu217, which mimics phosphorylated C/EBPβ-Thr217, was sufficient to confer macrophage survival to Anthrax lethal toxin.

In vitro treatment of HepG2 cells with saturated fatty acids reproduces mitochondrial dysfunction found in nonalcoholic steatohepatitis.

Activity of the oxidative phosphorylation system (OXPHOS) is decreased in humans and mice with nonalcoholic steatohepatitis. Nitro-oxidative stress seems to be involved in its pathogenesis. The aim of this study was to determine whether fatty acids are implicated in the pathogenesis of this mitochondrial defect.

High-fat diet decreases activity of the oxidative phosphorylation complexes and causes nonalcoholic steatohepatitis in mice.

Nonalcoholic fatty liver disease (NAFLD) is the most frequent histological finding in individuals with abnormal liver-function tests in the Western countries. In previous studies, we have shown that oxidative phosphorylation (OXPHOS) is decreased in individuals with NAFLD, but the cause of this mitochondrial dysfunction remains uncertain. The aims of this study were to determine whether feeding mice a high-fat diet (HFD) induces any change in the activity of OXPHOS, and to investigate the mechanisms involved in the pathogenesis of this defect.

Fecal incontinence in men: causes and clinical and manometric features.

Aim: To determine the causes and characteristics of fecal incontinence in men and to compare these features with those presented by a group of women with the same problem.

Methods: We analyzed the medical history, clinical and manometric data from 119 men with fecal incontinence studied in our unit and compared these data with those obtained from 645 women studied for the same problem. Response to treatment was evaluated after 6 mo of follow-up.

Experience of the endoscopist increases detection rates of smaller size and higher histological grade polyps.

Background: Adenoma and polyp detection rates (ADR and PDR, respectively) are important indicators of endoscopy quality, particularly in colorectal carcinoma screening.

Objective: To assess the influence of the endoscopist's experience on the ADR and PDR.

Patients And Methods: In this study, 9635 colonoscopies were screened during a 5-year period.

Pioglitazone leads to an inactivation and disassembly of complex I of the mitochondrial respiratory chain.

Background: Thiazolidinediones are antidiabetic agents that increase insulin sensitivity but reduce glucose oxidation, state 3 respiration, and activity of complex I of the mitochondrial respiratory chain (MRC). The mechanisms of the latter effects are unclear. The aim of this study was to determine the mechanisms by which pioglitazone (PGZ), a member of the thiazolidinedione class of antidiabetic agents, decreases the activity of the MRC.

Sp1 and Sp3 transcription factors mediate leptin-induced collagen α1(I) gene expression in primary culture of male rat hepatic stellate cells.

Mechanisms by which leptin stimulates collagen α(1)(I) [Col1a(I)] gene expression are unclear. The purposes of this study were to identify the trans-acting factors and cis-acting elements in Col1a(I) promoter involved in this effect as well as the pathways that are implicated. In primary cultures of rat hepatic stellate cells (HSCs), we measured the effects of leptin on Col1a(I) gene and protein expression and on the binding of nuclear proteins to the Col1a(I) promoter.

Protein-tyrosine phosphatases are involved in interferon resistance associated with insulin resistance in HepG2 cells and obese mice.

Insulin resistance is a risk factor for non-response to interferon/ribavirin therapy in patients with chronic hepatitis C. The aim of this study was to determine the role played by protein-tyrosine phosphatases (PTPs) in the absence of interferon-α (IFNα) response associated with insulin resistance. We induced insulin resistance by silencing IRS-2 or by treating HepG2 cells with tumor necrosis factor-α (TNFα) and analyzed insulin response by evaluating Akt phosphorylation and IFNα response by measuring Stat-1 tyrosine phosphorylation and 2',5'-oligoadenylate synthase and myxovirus resistance gene expression.

Melatonin improves mitochondrial respiratory chain activity and liver morphology in ob/ob mice.

In previous studies, we have shown that mitochondrial respiratory chain (MRC) activity is decreased in patients with nonalcoholic steatohepatitis and in ob/ob mice and that peroxynitrite plays a pathogenic role. The present study examined whether melatonin, a peroxynitrite scavenger, prevents: (i) the in vitro effects of peroxynitrite on normal mitochondrial proteins and (ii) the development of nonalcoholic liver disease, MRC dysfunction and proteomic changes found in the mitochondrial complexes from ob/ob mice. We studied MRC activity, assembly of mitochondrial complexes and its subunits in normal mitochondrial proteins exposed to peroxynitrite in the absence and presence of melatonin.

Mitochondrial complex I subunits are decreased in murine nonalcoholic fatty liver disease: implication of peroxynitrite.

We investigate the cause of the low activity of mitochondrial complex I found in ob/ob mice with nonalcoholic fatty liver disease. In mitochondrial proteins from ob/ob mice, we assessed complex I activity, fully assembled complex I, and its subunits, oxygen consumption, gene expression of complex I subunits, and oxidative damage to DNA. In mitochondrial proteins from the liver of ob/ob mice, complex I activity, fully assembly of this complex and complex I subunits were markedly reduced.

Fibronectin increases survival of rat hepatic stellate cells--a novel profibrogenic mechanism of fibronectin.

Unlabelled: The aims of this study were to determine whether fibronectin increases survival of hepatic stellate cells (HSCs) in starving conditions, and to identify the signal transduction pathways involved in this effect.

Methods: Primary culture of rat HSCs were plated on fibronectin-uncoated or coated culture wells, and grown in the presence of 0.2% or 20% fetal calf serum.

Incidence, risk factors, and outcome of chronic rejection during antiviral therapy for posttransplant recurrent hepatitis C.

Antiviral therapy for recurrent hepatitis C in liver transplantation has been associated with the development of chronic rejection. The aim of this study was to assess the incidence, evolution, and risk factors associated with the development of chronic rejection during posttransplant hepatitis C virus antiviral therapy. Seventy-nine patients with posttransplant recurrent hepatitis C who were treated with pegylated interferon and ribavirin were prospectively followed.

Interferon alpha increases metalloproteinase-13 gene expression through a polyomavirus enhancer activator 3-dependent pathway in hepatic stellate cells.

Background/aims: To determine the effects of IFNalpha on MMP-13 gene expression in primary culture of hepatic stellate cells.

Methods: We measured MMP-13 mRNA, MMP-13 protein, MMP-13 luciferase activity, binding of AP1 and PEA3 to DNA, and binding of PEA3 to Jak1 and Stat1.

Results: IFNalpha increased MMP-13 mRNA, MMP-13 protein, and luciferase activity in cells transfected either with a luciferase plasmid driven by the MMP-13 promoter or with the same plasmid in which the AP1 binding site has been mutated.

Effects of rosiglitazone on the liver histology and mitochondrial function in ob/ob mice.

Unlabelled: Insulin resistance is present in almost all patients with nonalcoholic steatohepatitis (NAFLD), and mitochondrial dysfunction likely plays a critical role in the progression of fatty liver into nonalcoholic steatohepatitis. Rosiglitazone, a selective ligand of peroxisome proliferator-activated receptor gamma (PPARgamma), is an insulin sensitizer drug that has been used in a number of insulin-resistant conditions, including NAFLD. The aim of this study was to analyze the effects of rosiglitazone on the liver histology and mitochondrial function in a model of NAFLD.

Clinical and histological efficacy of pegylated interferon and ribavirin therapy of recurrent hepatitis C after liver transplantation.

Treatment of recurrent hepatitis C in liver transplant is controversial. The aim of our study was to evaluate the clinical and histological efficacy of pegylated interferon alpha 2b (PEG-IFN) and ribavirin therapy of recurrent hepatitis C after liver transplantation (LT). We prospectively included 47 liver transplant patients with: 1) a positive test for hepatitis C virus (HCV)-ribonucleic acid (RNA) in serum; 2) alanine aminotransferase (ALT) >45 UI/mL; and 3) a liver biopsy showing chronic hepatitis without rejection in the previous 2 months.