Chemicals and Drugs Commons^™

Proton Pump Inhibitors Increase The Severity Of Hepatic Encephalopathy In Cirrhotic Patients, Matthew J. Fasullo, Prashanth Rau, Dong-Qi Liu, Erik Holzwanger, Jomol Mathew, Yurima Guilarte-Walker, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites, esophageal/gastric varices or encephalopathy. The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy (HE). Well established triggers for HE include infection, gastrointestinal bleeding, constipation, and medications. Alterations to the gut microbiome is one of the leading ammonia producers in the body, and therefore may make patients more susceptible to HE.

AIM: To investigate the relationship between the use of proton pump inhibitors (PPIs) and HE …

Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage- and pathogen-associated molecular patterns contribute to a self-perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a surface receptor that amplifies inflammation induced by toll-like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM-1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand-independent TREM-1 inhibitory peptides that were formulated into human high-density lipoprotein (HDL)-mimicking complexes GF9-HDL and GA/E31-HDL. As revealed …

Increased Number Of Circulating Exosomes And Their Microrna Cargos Are Potential Novel Biomarkers In Alcoholic Hepatitis, Fatemeh Momen-Heravi, Banishree Saha, Karen Kodys, Donna Catalano, Abhishek Satishchandran, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: It has been well documented that alcohol and its metabolites induce injury and inflammation in the liver. However, there is no potential biomarker to monitor the extent of liver injury in alcoholic hepatitis patients. MicroRNAs (miRNAs) are a class of non-coding RNAs that are involved in various physiologic and pathologic processes. In the circulation, a great proportion of miRNAs is associated with extracellular vesicles (EVs)/exosomes. Here, we hypothesized that the exosome-associated miRNAs can be used as potential biomarkers in alcoholic hepatitis (AH).

METHODS: Exosomes were isolated from sera of alcohol-fed mice or pair-fed mice, and plasma of alcoholic hepatitis …

A Novel Human Radixin Peptide Inhibits Hepatitis C Virus Infection At The Level Of Cell Entry, Terence Bukong, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Hepatitis C virus infection of hepatocytes is a multistep process involving the interaction between viral and host cell molecules. Recently, we identified ezrin-moesin-radixin proteins and spleen tyrosine kinase (SYK) as important host therapeutic targets for HCV treatment development. Previously, an ezrin hinge region peptide (Hep1) has been shown to exert anti-HCV properties in vivo, though its mechanism of action remains limited. In search of potential novel inhibitors of HCV infection and their functional mechanism we analyzed the anti-HCV properties of different human derived radixin peptides. Sixteen different radixin peptides were derived, synthesized and tested. Real-time quantitative PCR, cell toxicity assay, …

Micrornas In Alcoholic Liver Disease, Gyongyi Szabo, Abhishek Satishchandran

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by hepatocyte damage, inflammatory cell activation and increased intestinal permeability leading to the clinical manifestations of alcoholic hepatitis. Selected members of the family of microRNAs are affected by alcohol, resulting in an abnormal miRNA profile in the liver and circulation in ALD. Increasing evidence suggests that mRNAs that regulate inflammation, lipid metabolism and promote cancer are affected by excessive alcohol administration in mouse models of ALD. This communication highlights recent findings in miRNA expression and functions as they relate to the pathogenesis of ALD. The cell-specific distribution of miRNAs, as well as the significance …

Alcohol Facilitates Hcv Rna Replication Via Up-Regulation Of Mir-122 Expression And Inhibition Of Cyclin G1 In Human Hepatoma Cells, Wei Hou, Terence Bukong, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Clinical studies demonstrate synergistic liver damage by alcohol and hepatitis C virus (HCV); however, the mechanisms by which alcohol promotes HCV infection remain obscure. The liver-specific microRNA-122 (miR-122) regulates HCV replication and expression of host genes, including Cyclin G1. Here, we hypothesized that alcohol regulates miR-122 expression and thereby modulates HCV RNA replication. METHODS: The J6/JFH/Huh-7.5 model of HCV infection was used in this study. Real-time quantitative polymerase chain reaction, Western blotting, electrophoretic mobility shift assay, and confocal microscopy were used for experimental analysis. RESULTS: We found that acute alcohol exposure (25 mM) significantly increased intracellular HCV RNA as …