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Articles 1 - 13 of 13
Full-Text Articles in Gastroenterology
Microrna Signature In Alcoholic Liver Disease, Shashi Bala, Gyongyi Szabo
Microrna Signature In Alcoholic Liver Disease, Shashi Bala, Gyongyi Szabo
Gyongyi Szabo
Alcoholic liver disease (ALD) is a major global health problem. Chronic alcohol use results in inflammation and fatty liver, and in some cases, it leads to fibrosis and cirrhosis or hepatocellular carcinoma. Increased proinflammatory cytokines, particularly TNF alpha, play a central role in the pathogenesis of ALD. TNF alpha is tightly regulated at transcriptional and posttranscriptional levels. Recently, microRNAs (miRNAs) have been shown to modulate gene functions. The role of miRNAs in ALD is getting attention, and recent studies suggest that alcohol modulates miRNAs. Recently, we showed that alcohol induces miR-155 expression both in vitro (RAW 264.7 macrophage) and in …
Human Monoclonal Antibody Hcv1 Effectively Prevents And Treats Hcv Infection In Chimpanzees, Trevor J. Morin, Teresa J. Broering, Brett A. Leav, Barbara M. Blair, Kirk J. Rowley, Elisabeth N. Boucher, Yang Wang, Peter S. Cheslock, Michael Knauber, David B. Olsen, Steve W. Ludmerer, Gyongyi Szabo, Robert W. Finberg, Robert H. Purcell, Robert E. Lanford, Donna M. Ambrosino, Deborah C. Molrine, Gregory J. Babcock
Human Monoclonal Antibody Hcv1 Effectively Prevents And Treats Hcv Infection In Chimpanzees, Trevor J. Morin, Teresa J. Broering, Brett A. Leav, Barbara M. Blair, Kirk J. Rowley, Elisabeth N. Boucher, Yang Wang, Peter S. Cheslock, Michael Knauber, David B. Olsen, Steve W. Ludmerer, Gyongyi Szabo, Robert W. Finberg, Robert H. Purcell, Robert E. Lanford, Donna M. Ambrosino, Deborah C. Molrine, Gregory J. Babcock
Gyongyi Szabo
Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers. Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population. Human monoclonal antibody HCV1 recognizes a highly-conserved linear epitope of the HCV E2 envelope glycoprotein (amino acids 412-423) and neutralizes a broad range of HCV genotypes. In a chimpanzee model, a single dose of 250 mg/kg HCV1 delivered 30 minutes prior to infusion with genotype 1a H77 HCV provided complete protection from HCV infection, …
Il-1 Receptor Antagonist Ameliorates Inflammasome-Dependent Alcoholic Steatohepatitis In Mice, Jan Petrasek, Shashi Bala, Timea Csak, Dora Lippai, Karen Kodys, Victoria Menashy, Matthew Barrieau, So-Yun Min, Evelyn A. Kurt-Jones, Gyongyi Szabo
Il-1 Receptor Antagonist Ameliorates Inflammasome-Dependent Alcoholic Steatohepatitis In Mice, Jan Petrasek, Shashi Bala, Timea Csak, Dora Lippai, Karen Kodys, Victoria Menashy, Matthew Barrieau, So-Yun Min, Evelyn A. Kurt-Jones, Gyongyi Szabo
Gyongyi Szabo
Alcoholic liver disease (ALD) is characterized by steatosis and upregulation of proinflammatory cytokines, including IL-1beta. IL-1beta, type I IL-1 receptor (IL-1R1), and IL-1 receptor antagonist (IL-1Ra) are all important regulators of the IL-1 signaling complex, which plays a role in inflammation. Furthermore, IL-1beta maturation is dependent on caspase-1 (Casp-1). Using IL-1Ra-treated mice as well as 3 mouse models deficient in regulators of IL-1beta activation (Casp-1 and ASC) or signaling (IL-1R1), we found that IL-1beta signaling is required for the development of alcohol-induced liver steatosis, inflammation, and injury. Increased IL-1beta was due to upregulation of Casp-1 activity and inflammasome activation. The …
Plasma Microrna Profiles Distinguish Lethal Injury In Acetaminophen Toxicity: A Research Study, Jeanine Ward, Shashi Bala, Jan Petrasek, Gyongyi Szabo
Plasma Microrna Profiles Distinguish Lethal Injury In Acetaminophen Toxicity: A Research Study, Jeanine Ward, Shashi Bala, Jan Petrasek, Gyongyi Szabo
Gyongyi Szabo
AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5 p, 466 g, 466 f-3p, 375, 29 c, and 148 a, have …
Lipopolysaccharide Induces And Activates The Nalp3 Inflammasome In The Liver, Michal Ganz, Timea Csak, Bharath D. Nath, Gyongyi Szabo
Lipopolysaccharide Induces And Activates The Nalp3 Inflammasome In The Liver, Michal Ganz, Timea Csak, Bharath D. Nath, Gyongyi Szabo
Gyongyi Szabo
AIM: To examine the activation of the Nalp3 inflammasome and its downstream targets following lipopolysaccharide (LPS)-induced stimulation in the liver. METHODS: Six-to-eight-week-old C57BL/6 chow fed mice were injected intraperitoneally with 0.5 mug/g bodyweight LPS and sacrificed 2, 4, 6, 18 or 24 h later. LPS-induced liver damage was confirmed by a biochemical assay to detect alanine aminotransferase (ALT) levels. To determine if LPS stimulation in the liver led to activation of the inflammasome, real-time quantitative polymerase chain reaction was used to evaluate the mRNA expression of components of the Nalp3 inflammasome. Enzyme-linked immunosorbent assays were used to determine the protein …
Helicobacter Pylori Infection Rate Decreases In Symptomatic Children: A Retrospective Analysis Of 13 Years (1993-2005) From A Gastroenterology Clinic In West Virginia, Yoram Elitsur, Yulia Dementieva, Mary Rewalt, Zanda Lawrence
Helicobacter Pylori Infection Rate Decreases In Symptomatic Children: A Retrospective Analysis Of 13 Years (1993-2005) From A Gastroenterology Clinic In West Virginia, Yoram Elitsur, Yulia Dementieva, Mary Rewalt, Zanda Lawrence
Mary Rewalt
Background: The rate of Helicobacter pylori is decreasing in the developed countries, but few long-term studies are available from the United States. We retrospectively assessed the annual H. pylori infection rate in symptomatic children seen in our clinic over a 13-year study period. Study: A retrospective analysis of all children who had histologic diagnosis of H. pylori infection between January 1993 and December 2005 in our pediatric gastroenterology clinic was performed. The annual infection rate and the overall infection rate were calculated. Results: A total of 1743 upper endoscopy reports were reviewed, of which 212 (12.1%) were diagnosed with H. …
Increased Microrna-155 Expression In The Serum And Peripheral Monocytes In Chronic Hcv Infection, Shashi Bala, Yaphet Tilahun, Odette Taha, Hawau Alao, Karen Kodys, Donna Catalano, Gyongyi Szabo
Increased Microrna-155 Expression In The Serum And Peripheral Monocytes In Chronic Hcv Infection, Shashi Bala, Yaphet Tilahun, Odette Taha, Hawau Alao, Karen Kodys, Donna Catalano, Gyongyi Szabo
Gyongyi Szabo
BACKGROUND: Hepatitis C Virus (HCV), a single stranded RNA virus, affects millions of people worldwide and leads to chronic infection characterized by chronic inflammation in the liver and in peripheral immune cells. Chronic liver inflammation leads to progressive liver damage. MicroRNAs (miRNA) regulate inflammation (miR-155, -146a and -125b) as well as hepatocyte function (miR-122). METHODS: Here we hypothesized that microRNAs are dysregulated in chronic HCV infection. We examined miRNAs in the circulation and in peripheral monocytes of patients with chronic HCV infection to evaluate if specific miRNA expression correlated with HCV infection. RESULTS: We found that monocytes from chronic HCV …
Helicobacter Pylori Infection Rate Decreases In Symptomatic Children: A Retrospective Analysis Of 13 Years (1993-2005) From A Gastroenterology Clinic In West Virginia, Yoram Elitsur, Yulia Dementieva, Mary Rewalt, Zanda Lawrence
Helicobacter Pylori Infection Rate Decreases In Symptomatic Children: A Retrospective Analysis Of 13 Years (1993-2005) From A Gastroenterology Clinic In West Virginia, Yoram Elitsur, Yulia Dementieva, Mary Rewalt, Zanda Lawrence
Yoram Elitsur
Background: The rate of Helicobacter pylori is decreasing in the developed countries, but few long-term studies are available from the United States. We retrospectively assessed the annual H. pylori infection rate in symptomatic children seen in our clinic over a 13-year study period. Study: A retrospective analysis of all children who had histologic diagnosis of H. pylori infection between January 1993 and December 2005 in our pediatric gastroenterology clinic was performed. The annual infection rate and the overall infection rate were calculated. Results: A total of 1743 upper endoscopy reports were reviewed, of which 212 (12.1%) were diagnosed with H. …
Serum Microrna-122 And Mir-155 As Biomarkers Of Liver Injury And Inflammation In Models Of Acute And Chronic Liver Disease, Shashi Bala, Jan Petrasek, Shiv Mundkur, Donna Catalano, Jeanine Ward, Ivan Levin, Hawau Alao, Karen Kodys, Gyongyi Szabo
Serum Microrna-122 And Mir-155 As Biomarkers Of Liver Injury And Inflammation In Models Of Acute And Chronic Liver Disease, Shashi Bala, Jan Petrasek, Shiv Mundkur, Donna Catalano, Jeanine Ward, Ivan Levin, Hawau Alao, Karen Kodys, Gyongyi Szabo
Gyongyi Szabo
Background: MicroRNAs (miRs) are small non-coding molecules that regulate gene expression. MiRs expression levels change not only in diseased tissues but also in circulation. Further, miRs are stable in frozen samples that make them attractive for biomarker discovery. Recent reports suggest altered expression of circulating miRNAs in various diseases. MiR-122 is highly abundant in hepatocytes where it regulates different metabolic pathways while miR-155 is a central regulator of inflammation. The aim of this study was to evaluate circulating miRNAs as potential markers of hepatocyte damage and inflammation in liver diseases. Methods: Serum/plasma and liver samples were collected from C57/BL6 mice …
Increased Oxidative Capacity Of Circulating Polymorphonuclear Neutrophils (Pmns) In Non-Diabetic Nash Patients, Timea Csak, Karen Kodys, Angela Dolganiuc, Dora Lippai, Michal Ganz, Christopher Marshall, Gyongyi Szabo
Increased Oxidative Capacity Of Circulating Polymorphonuclear Neutrophils (Pmns) In Non-Diabetic Nash Patients, Timea Csak, Karen Kodys, Angela Dolganiuc, Dora Lippai, Michal Ganz, Christopher Marshall, Gyongyi Szabo
Gyongyi Szabo
Background: Inflammation and oxidative stress are key factors in the pathogenesis of non-alcoholic steatohepatitis (NASH). Polymorphonuclear neutrophils are capable to produce significant amounts of reactive oxygen species (ROS) via the NADPH oxidase complex. Increased hepatic neutrophil infiltration has been described in steatohepatitis. We aimed to investigate the in vitro ROS generation by neutrophils of NASH patients and the hepatic NADPH oxidase activity in murine steatohepatitis. Material and methods: PMNs were isolated from peripheral blood of NASH patients (n=16) and healthy controls (n=16). In vitro ROS production was measured by luminol chemiluminescence after phorbol myristate acetate (PMA) or opsonized zymosan stimulation. …
Caspase-1-Dependent, Il-1ss-Mediated Alcoholic Steatohepatitis Is Ameliorated By Il-1 Receptor Antagonist Treatment In Mice, Jan Petrasek, Shashi Bala, Dora Lippai, Karen Kodys, Victoria Menashy, Matthew Barrieau, Evelyn A. Kurt-Jones, Gyongyi Szabo
Caspase-1-Dependent, Il-1ss-Mediated Alcoholic Steatohepatitis Is Ameliorated By Il-1 Receptor Antagonist Treatment In Mice, Jan Petrasek, Shashi Bala, Dora Lippai, Karen Kodys, Victoria Menashy, Matthew Barrieau, Evelyn A. Kurt-Jones, Gyongyi Szabo
Gyongyi Szabo
Alcoholic liver disease (ALD) is characterized by steatosis and upregulation of pro-inflammatory cytokines, including interleukin (IL)-1β. IL-1β, Type-I IL-1 receptor (IL1R1) and IL-1 receptor antagonist (IL-1Ra) are all part of the IL-1 superfamily that play a role in inflammation. IL-1β maturation is dependent on Caspase-1. Using wild-type (WT), Caspase-1-, IL-1R1- and IL-1Ra deficient mice fed with Lieber-DeCarli alcohol or control diet, we have identified that signaling mediated by the active IL-1β was required for development of alcohol-induced steatosis, inflammation and injury. Increased IL-1β was due to upregulation of Caspase-1 activity and inflammatory activation. The pathogenic role of IL-1 signaling in …
Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnα, Shuye Zhang, Karen Kodys, Gyongyi Szabo
Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnα, Shuye Zhang, Karen Kodys, Gyongyi Szabo
Gyongyi Szabo
Recognition of hepatitis C virus (HCV)-infected hepatocyes and interferon (IFN) induction are critical in antiviral immune response. We hypothesized that cell-cell contact between pDCs and HCV-infected cells was required for IFNα induction via involvement of cell surface molecules. Co-culture of human peripheral blood mononuclear cells (PBMCs) with genotype 1a full length HCV genomic replicon cells (FL) or genotype 2a JFH-1 virus infected hepatoma cells (JFH-1), not with uninfected hepatoma cells (Huh7.5), induced IFNα production. Depletion of pDCs from PBMCs attenuated IFNα release and purified pDCs produced high levels of IFNα after co-culture with FL replicons or JFH-1 infected cells. IFNα …
Inhibition Of Tlr8- And Tlr4-Induced Type I Ifn Induction By Alcohol Is Different From Its Effects On Inflammatory Cytokine Production In Monocytes, Maoyin Pang, Shashi Bala, Karen Kodys, Donna Catalano, Gyongyi Szabo
Inhibition Of Tlr8- And Tlr4-Induced Type I Ifn Induction By Alcohol Is Different From Its Effects On Inflammatory Cytokine Production In Monocytes, Maoyin Pang, Shashi Bala, Karen Kodys, Donna Catalano, Gyongyi Szabo
Gyongyi Szabo
BACKGROUND: Prolonged alcohol consumption is a significant co-factor in the progression of chronic viral infections including hepatitis C and HIV, which are both single-stranded RNA viruses. Toll like receptor 8 (TLR8), a pattern recognition receptor expressed in monocytes, senses viral single stranded RNA as a danger signal and leads to the induction of Type I interferon (IFN) as well as the pro-inflammatory cytokine, tumor necrosis factor alpha (TNF alpha). Lipopolysaccharide (LPS), a Toll like receptor 4 (TLR4) ligand, was shown to affect inflammatory cell activation after alcohol consumption and in HIV and HCV infections. Here we hypothesized that alcohol exposure …