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https://www.readbyqxmd.com/read/28534962/galectin%C3%A2-9-ameliorates-fulminant-liver-injury
#1
Tomoko Tadokoro, Asahiro Morishita, Teppei Sakamoto, Shintaro Fujihara, Koji Fujita, Shima Mimura, Kyoko Oura, Takako Nomura, Joji Tani, Hirohito Yoneyama, Hisakazu Iwama, Takashi Himoto, Toshiro Niki, Mitsuomi Hirashima, Tsutomu Masaki
Fulminant hepatitis is a severe liver disease resulting in hepatocyte necrosis. Galectin‑9 (Gal‑9) is a tandem‑repeat‑type galectin that has been evaluated as a potential therapeutic agent for various diseases that regulate the host immune system. Concanavalin A (ConA) injection into mice results in serious, immune‑mediated liver injury similar to human viral, autoimmune and fulminant hepatitis. The present study investigated the effects of Gal‑9 treatment on fulminant hepatitis in vivo and the effect on the expression of microRNAs (miRNAs), in order to identify specific miRNAs associated with the immune effects of Gal‑9...
May 18, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28529483/identification-of-a-novel-allosteric-inhibitory-site-on-tryptophan-hydroxylase-1-enabling-unprecedented-selectivity-over-all-related-hydroxylases
#2
Mike Petrassi, Rob Barber, Celine Be, Sarah Beach, Brian Cox, Anne-Marie D'Souza, Nick Duggan, Martin Hussey, Roy Fox, Peter Hunt, Gabor Jarai, Takatoshi Kosaka, Paul Oakley, Viral Patel, Neil Press, David Rowlands, Clemens Scheufler, Oliver Schmidt, Honnappa Srinivas, Mary Turner, Rob Turner, John Westwick, Alison Wolfreys, Nuzhat Pathan, Simon Watson, Matthew Thomas
Pulmonary arterial hypertension (PAH) has demonstrated multi-serotonin receptor dependent pathologies, characterized by increased tone (5-HT1B receptor) and complex lesions (SERT, 5-HT1B, 5-HT2B receptors) of the pulmonary vasculature together with right ventricular hypertrophy, ischemia and fibrosis (5-HT2B receptor). Selective inhibitors of individual signaling elements - SERT, 5-HT2A, 5HT2B, and combined 5-HT2A/B receptors, have all been tested clinically and failed. Thus, inhibition of tryptophan hydroxylase 1 (TPH1), the rate limiting step in 5-HT synthesis, has been suggested as a more broad, and thereby more effective, mode of 5-HT inhibition...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28526812/soluble-axl-is-an-accurate-biomarker-of-cirrhosis-and-hepatocellular-carcinoma-development-results-from-a-large-scale-multicenter-analysis
#3
Mirko Dengler, Katharina Staufer, Heidemarie Huber, Rudolf Stauber, Heike Bantel, Karl Heinz Weiss, Patrick Starlinger, Hannelore Pock, Petra Klöters-Plachky, Daniel N Gotthardt, Peter Rauch, Carolin Lackner, Judith Stift, Christine Brostjan, Thomas Gruenberger, Takashi Kumada, Hidenori Toyoda, Toshifumi Tada, Thomas S Weiss, Michael Trauner, Wolfgang Mikulits
Patients with chronic liver disease (CLD) and cirrhosis are at high risk for hepatocellular carcinoma (HCC). Current diagnostic tools for HCC detection include imaging techniques and serum biomarkers such as α-fetoprotein (AFP). Yet, these methods are limited in sensitivity and specificity to accurately detect early HCC. Here we focused on the potential of soluble Axl (sAxl) as a biomarker in CLD patients by analyzing serum samples of 1067 patients and healthy controls from centers in Europe and Asia. We show that serum concentrations of sAxl were significantly increased at early (82...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523578/prevalence-and-predictors-of-significant-fibrosis-among-subjects-with-transient-elastography-defined-nonalcoholic-fatty-liver-disease
#4
Hye Won Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang Joon Kim, Kwang-Hyub Han
BACKGROUND/AIMS: Transient elastography (TE) can be used to assess the degree of liver fibrosis and steatosis. We investigated the prevalence and predictors of nonalcoholic fatty liver disease (NAFLD) with or without significant liver fibrosis in the general population. METHODS: A total of 3033 subjects without alcoholic or chronic viral liver diseases who underwent a medical health check-up including TE were recruited from April 2013 to August 2014. TE-defined NAFLD was defined as a controlled attenuation parameter of ≥250 dB/m, and significant liver fibrosis was defined as a liver stiffness (LS) value of ≥8 kPa...
May 18, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28523305/the-impact-of-liver-steatosis-on-early-and-sustained-treatment-response-in-chronic-hepatitis-c-patients
#5
Alice Elena Găman, Anca Marilena Ungureanu, Adriana Turculeanu, Dan IonuŢ Gheonea, Andrei Ioan Drocaş, George Mitroi, Maria DobriŢoiu, Maria Victoria Comănescu, Andreea Doriana Stănculescu, Ramona Cioboată, Claudiu Florin Jieanu, Paul Ioan Tomescu
Steatosis is a frequent feature of hepatitis C virus (HCV) infection. Steatosis may be an important cofactor in both accelerating fibrosis and increasing liver necroinflammatory activity in chronic hepatitis C. The main objective of this study was the evaluation of biological response rates, early viral response, sustained viral response in patients with chronic hepatitis C treated with Interferon-alpha (IFN-α), Pegylated (PEG)-IFN-α2a or -α2b plus Ribavirin and to relate it to the presence of hepatic steatosis...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28521797/multiple-cause-of-death-data-among-people-with-aids-in-italy-a-nationwide-cross-sectional-study
#6
Enrico Grande, Antonella Zucchetto, Barbara Suligoi, Francesco Grippo, Marilena Pappagallo, Saverio Virdone, Laura Camoni, Martina Taborelli, Vincenza Regine, Diego Serraino, Luisa Frova
BACKGROUND: Multiple cause-of-death (MCOD) data allow analyzing the contribution to mortality of conditions reported on the death certificate that are not selected as the underlying cause of death. Using MCOD data, this study aimed to fully describe the cause-specific mortality of people with AIDS (PWA) compared to people without AIDS. METHODS: We conducted a nationwide investigation based on death certificates of 2,515 Italian PWA and 123,224 people without AIDS who had died between 2006 and 2010...
May 18, 2017: Population Health Metrics
https://www.readbyqxmd.com/read/28513591/zinc-is-a-potent-and-specific-inhibitor-of-ifn-%C3%AE-3-signalling
#7
Scott A Read, Kate S O'Connor, Vijay Suppiah, Chantelle L E Ahlenstiel, Stephanie Obeid, Kristina M Cook, Anthony Cunningham, Mark W Douglas, Philip J Hogg, David Booth, Jacob George, Golo Ahlenstiel
Lambda interferons (IFNL, IFN-λ) are pro-inflammatory cytokines important in acute and chronic viral infection. Single-nucleotide polymorphisms rs12979860 and rs8099917 within the IFNL gene locus predict hepatitis C virus (HCV) clearance, as well as inflammation and fibrosis progression in viral and non-viral liver disease. The underlying mechanism, however, is not defined. Here we show that the rs12979860 CC genotype correlates with increased hepatic metallothionein expression through increased systemic zinc levels...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28506744/hepatic-stellate-cells-as-key-target-in-liver-fibrosis
#8
Takaaki Higashi, Scott L Friedman, Yujin Hoshida
Progressive liver fibrosis, induced by chronic viral and metabolic disorders, leads to more than one million deaths annually via development of cirrhosis, although no antifibrotic therapy has been approved to date. Transdifferentiation (or "activation") of hepatic stellate cells is the major cellular source of matrix protein-secreting myofibroblasts, the major driver of liver fibrogenesis. Paracrine signals from injured epithelial cells, fibrotic tissue microenvironment, immune and systemic metabolic dysregulation, enteric dysbiosis, and hepatitis viral products can directly or indirectly induce stellate cell activation...
May 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28498407/respiratory-syncytial-virus-infection-accelerates-lung-fibrosis-through-the-unfolded-protein-response-in-a-bleomycin-induced-pulmonary-fibrosis-animal-model
#9
Lina Wang, Wei Cheng, Zhimin Zhang
Emerging evidence has demonstrated that endoplasmic reticulum stress (ER) is involved in the pathogenesis of idiopathic pulmonary fibrosis, however, the underlying mechanism remains unclear. Viral infection often triggers a hyperinflammatory response by an expansion of the ER. The present study was designed to observe the role of respiratory syncytial virus infection (RSV)‑induced ER stress on lung fibrosis. In order to determine the role of ER stress on the onset and progression of pulmonary fibrosis, mice received an intratracheal combined injection of RSV and bleomycin on day 0...
May 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28492391/hepatitis-c-virus-drives-increased-type-i-interferon-associated-impairments-associated-with-fibrosis-severity-in-antiretroviral-treatment-treated-hiv-1-hepatitis-c-virus-coinfected-individuals
#10
Morgane Griesbeck, Marc-Antoine Valantin, Karine Lacombe, Assia Samri-Hassimi, Julie Bottero, Catherine Blanc, Zineb Sbihi, Rima Zoorob, Christine Katlama, Marguerite Guiguet, Marcus Altfeld, Brigitte Autran
BACKGROUND: Viral coinfections might contribute to the increased immune activation and inflammation that persist in antiretroviral treatment (ART)-treated HIV-1 patients. We investigated whether the hepatitis C virus (HCV) coinfection contributes to such alterations by impairing the plasmacytoid dendritic cell (pDC) IFNα/TLR7 pathway in a highly homogeneous group of ART-treated HIV-1-HCV-coinfected patients. METHODS: Twenty-nine HIV-1-infected patients with fully suppressive ART were included, 15 of whom being HCV-coinfected with mild-to-moderate fibrosis and matched for their HIV-1 disease, and 13 control healthy donors...
June 1, 2017: AIDS
https://www.readbyqxmd.com/read/28491877/nodular-regenerative-hyperplasia-a-case-of-rare-prognosis
#11
Mindy Lee, Manhal Izzy, Ashwin Akki, Kathryn Tanaka, Harmit Kalia
Introduction: Nodular regenerative hyperplasia (NRH) is a known etiology of noncirrhotic portal hypertension. Cases of biopsy-proven NRH in human immunodeficiency virus (HIV)-positive patients have been described. While these patients often have normal synthetic liver function, several reports described disease progression to liver failure. Case: We here present a 26-year-old woman with history of congenital HIV on antiretroviral therapy complicated by Pneumocystis carinii pneumonia at age 14. CD4 counts have been >300 with undetectable viral load...
January 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28487545/mechanisms-of-hepatic-stellate-cell-activation
#12
REVIEW
Takuma Tsuchida, Scott L Friedman
Hepatic fibrosis is a dynamic process characterized by the net accumulation of extracellular matrix resulting from chronic liver injury of any aetiology, including viral infection, alcoholic liver disease and NASH. Activation of hepatic stellate cells (HSCs) - transdifferentiation of quiescent, vitamin-A-storing cells into proliferative, fibrogenic myofibroblasts - is now well established as a central driver of fibrosis in experimental and human liver injury. Yet, the continued discovery of novel pathways and mediators, including autophagy, endoplasmic reticulum stress, oxidative stress, retinol and cholesterol metabolism, epigenetics and receptor-mediated signals, reveals the complexity of HSC activation...
May 10, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28487469/phosphoinositide-3-kinase-p110%C3%AE-gene-delivery-limits-diabetes-induced-cardiac-nadph-oxidase-and-cardiomyopathy-in-a-mouse-model-with-established-diastolic-dysfunction
#13
Darnel Prakoso, Miles J DeBlasio, Chengxue Qin, Sarah Rosli, Helen Kiriazis, Hongwei Qian, Xiao-Jun Du, Kate L Weeks, Paul Gregorevic, Julie R McMullen, Rebecca H Ritchie
Phosphoinositide 3-kinase [PI3K (p110α)] is able to negatively regulate the diabetes-induced increase in NADPH oxidase in the heart. Patients affected by diabetes exhibit significant cardiovascular morbidity and mortality, at least in part due to a cardiomyopathy characterised by oxidative stress and left ventricular (LV) dysfunction. Thus, PI3K (p110α) may represent a novel approach to protect the heart from diabetes-induced cardiac oxidative stress and dysfunction. In the current study, we investigated the therapeutic potential of a delayed intervention with cardiac-targeted PI3K gene therapy, administered to mice with established diabetes-induced LV diastolic dysfunction...
May 9, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28481637/hydrogen-sulfide-a-novel-player-in-airway-development-pathophysiology-of-respiratory-diseases-and-antiviral-defenses
#14
Nikolay Bazhanov, Maria Ansar, Teodora Ivanciuc, Roberto P Garofalo, Antonella Casola
Hydrogen sulfide (H2S) is a biologically relevant signaling molecule in mammals. Together with the volatile substances nitric oxide (NO) and carbon monoxide (CO), H2S is defined as a gasotransmitter, playing a physiological role in a variety of functions such as synaptic transmission, vascular tone, angiogenesis, inflammation and cellular signaling. The generation of H2S is catalyzed by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3 mercaptopyruvate sulfurtransferase (3-MST). The expression of CBS and CSE is tissue-specific with CBS being expressed predominantly in the brain and CSE in peripheral tissues, including lungs...
May 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28480063/viral-hepatitis-and-hepatocellular-carcinoma-etiology-and-management
#15
REVIEW
Philippe J Zamor, Andrew S deLemos, Mark W Russo
Chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) are associated with hepatic fibrosis and development of hepatocellular carcinoma (HCC). There are differences and variation with the incidence of HCC worldwide. Additionally, HCC develops via different pathways with these viral hepatitides. This review outlines the various mechanisms and pathophysiology that contributes to this process. There will also be a review on the recommended screening for HCC. Treatment considerations, which are different for these viruses, will be outlined in this review...
April 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28479504/magnitude-and-kinetics-of-decrease-in-liver-stiffness-after-anti-viral-therapy-in-patients-with-chronic-hepatitis-c-a-systematic-review-and-meta-analysis
#16
REVIEW
Siddharth Singh, Antonio Facciorusso, Rohit Loomba, Yngve T Falck-Ytter
BACKGROUND & AIMS: We performed a systematic review and meta-analysis to estimate the decrease in liver stiffness, measured by vibration-controlled transient elastrography (VCTE), in patients with hepatitis C virus (HCV) infection who achieved a sustained virologic response (SVR). METHODS: We searched the literature through October 2016 for observational studies or randomized controlled trials of adults with HCV infection who received antiviral therapy (either direct acting antiviral agents or interferon-based therapies), underwent liver stiffness measurement using VCTE before starting therapy, and had at least 1 follow-up VCTE after completion of therapy; studies also provided data on mean or median liver stiffness measurements for patients who did and did not achieve an SVR...
May 4, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28475652/serum-microrna-122-and-wisteria-floribunda-agglutinin-positive-mac-2-binding-protein-are-useful-tools-for-liquid-biopsy-of-the-patients-with-hepatitis-b-virus-and-advanced-liver-fibrosis
#17
Masato Nakamura, Tatsuo Kanda, Xia Jiang, Yuki Haga, Koji Takahashi, Shuang Wu, Shin Yasui, Shingo Nakamoto, Osamu Yokosuka
BACKGROUND: Noninvasive methods to accurately and conveniently evaluate liver fibrosis are desirable. MicroRNA (miR) is one of the candidates. MiRs are small RNAs consisting of 19-25 nucleotides that negatively regulate many target genes at transcriptional levels. Recently, many researchers have focused on circulating miRs in the blood stream as biomarkers. Hepatic miR-122 has been reported to have an association with viral replication and hepatic fibrosis in chronic hepatitis B virus (HBV) and hepatic C virus (HCV) infection...
2017: PloS One
https://www.readbyqxmd.com/read/28468011/overcoming-cd8-t-cell-exhaustion-in-viral-hepatitis-lessons-from-the-mouse-model-and-clinical-perspectives
#18
Dominik Wieland, Maike Hofmann, Robert Thimme
About 500 million people all over the world are chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) and are thus at high risk of developing liver fibrosis, cirrhosis or hepatocellular carcinoma. While in adults about 90% of acutely HBV-infected patients clear the virus, only 30% of acute HCV infections clear spontaneously. Several mechanisms contribute to the failure in viral clearance. The main factors responsible for the chronification of HBV and HCV infection are, on the one hand, viral escape mutations leading to lack of recognition by antiviral immune cells and, on the other hand, loss of antiviral effector functions of virus-specific CD8+ T cells, called T-cell exhaustion...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28464883/late-presentation-of-chronic-viral-hepatitis-for-medical-care-a-consensus-definition
#19
Stefan Mauss, Stanislas Pol, Maria Buti, Erika Duffell, Charles Gore, Jeffrey V Lazarus, Hilje Logtenberg-van der Grient, Jens Lundgren, Antons Mozalevskis, Dorthe Raben, Eberhard Schatz, Stefan Wiktor, Jürgen K Rockstroh
INTRODUCTION: We present two consensus definitions of advanced and late stage liver disease being used as epidemiological tools. These definitions can be applied to assess the morbidity caused by liver diseases in different health care systems. We focus is on hepatitis B and C virus infections, because effective and well tolerated treatments for both of these infections have greatly improved our ability to successfully treat and prevent advanced and late stage disease, especially if diagnosed early...
May 3, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28458673/inflammatory-responses-regulating-alveolar-ion-transport-during-pulmonary-infections
#20
REVIEW
Christin Peteranderl, Jacob I Sznajder, Susanne Herold, Emilia Lecuona
The respiratory epithelium is lined by a tightly balanced fluid layer that allows normal O2 and CO2 exchange and maintains surface tension and host defense. To maintain alveolar fluid homeostasis, both the integrity of the alveolar-capillary barrier and the expression of epithelial ion channels and pumps are necessary to establish a vectorial ion gradient. However, during pulmonary infection, auto- and/or paracrine-acting mediators induce pathophysiological changes of the alveolar-capillary barrier, altered expression of epithelial Na,K-ATPase and of epithelial ion channels including epithelial sodium channel and cystic fibrosis membrane conductance regulator, leading to the accumulation of edema and impaired alveolar fluid clearance...
2017: Frontiers in Immunology
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