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Hepatology: Official Journal of the American Association for the Study of Liver Diseases

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https://www.readbyqxmd.com/read/29790592/hepatitis-b-virus-upregulated-lnc-hur1-promotes-cell-proliferation-and-tumorigenesis-by-blocking-p53-activity
#1
Ningning Liu, Qi Liu, Xiaohai Yang, Fang Zhang, Xinda Li, Yuanwu Ma, Feifei Guan, Xin Zhao, Zhiwei Li, Lianfeng Zhang, Xin Ye
Recent studies have indicated that a number of lncRNAs are dysregulated in hepatocellular carcinoma, while their aberrant expressions are associated with tumorigenesis and poor prognosis. To identify HBV-related lncRNAs, we used RNA deep sequencing to quantify the abundances of lncRNAs in HepG2 cells and HBV transgenic HepG2-4D14 cells. Here, we demonstrate that lnc-HUR1 is significantly upregulated in HepG2-4D14 cells. We found that HBV-encoded HBx can enhance the transcription of lnc-HUR1. Overexpression of lnc-HUR1 promotes cell proliferation, while knockdown of lnc-HUR1 inhibits cell growth...
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29790588/the-lncrna-casc9-and-rna-binding-protein-hnrnpl-form-a-complex-and-co-regulate-genes-linked-to-akt-signaling
#2
Marcel Klingenberg, Matthias Groß, Ashish Goyal, Maria Polycarpou-Schwarz, Thilo Miersch, Anne-Sophie Ernst, Jörg Leupold, Nitin Patil, Uwe Warnken, Heike Allgayer, Thomas Longerich, Peter Schirmacher, Michael Boutros, Sven Diederichs
The identification of viability-associated long non-coding RNAs (lncRNA) might be a promising rationale for new therapeutic approaches in liver cancer. Here, we applied the first RNAi screening approach in hepatocellular carcinoma (HCC) cell lines to find viability-associated lncRNAs. Among the multiple identified lncRNAs with a significant impact on HCC cell viability, we selected CASC9 (Cancer Susceptibility 9) due to the strength of its phenotype, expression, and upregulation in HCC versus normal liver. CASC9 regulated viability across multiple HCC cell lines as shown by CRISPR interference, single siRNA- and siPOOL-mediated depletion of CASC9...
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29790582/acetyl-coa-carboxylase-inhibition-reverses-nafld-and-hepatic-insulin-resistance-but-promotes-hypertriglyceridemia-in-rodents
#3
Leigh Goedeke, Jamie Bates, Daniel F Vatner, Rachel J Perry, Ting Wang, Ricardo Ramirez, Li Li, Matthew W Ellis, Dongyan Zhang, Kari E Wong, Carine Beysen, Gary W Cline, Adrian S Ray, Gerald I Shulman
Pharmacologic inhibition of acetyl-CoA carboxylase (ACC) enzymes, ACC1 and ACC2, offers an attractive therapeutic strategy for non-alcoholic fatty liver disease (NAFLD) via simultaneous inhibition of fatty acid synthesis and stimulation of fatty acid oxidation. However, the effects of ACC inhibition on hepatic mitochondrial oxidation, anaplerosis, and ketogenesis in vivo are unknown. Here, we evaluated the impact of a novel liver-directed allosteric inhibitor of ACC1 and ACC2 (Compound 1) on these parameters, as well as glucose and lipid metabolism, in control and diet-induced rodent models of NAFLD...
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29790196/rituximab-is-ineffective-for-treatment-of-fatigue-in-primary-biliary-cholangitis-a-phase-2-randomised-controlled-trial
#4
Amardeep Khanna, Laura Jopson, Denise Howel, Andrew Bryant, Andrew Blamire, Julia L Newton, David E Jones
Primary Biliary Cholangitis (PBC) is a chronic cholestatic liver disease. Half of patients experience debilitating fatigue which is currently untreatable. Previous studies have shown muscle bioenergetic abnormalities in PBC, including increased muscle acidosis with exercise linked to the anti-mitochondrial antibody (AMA) diagnostic of the disease, and reduced anaerobic threshold. In this study we addressed the hypothesis that fatigue in PBC is driven by muscle bioenergetic abnormality related to AMA, and that AMA reduction with B-cell depletion therapy will improve fatigue...
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29790191/pay-it-forward-building-capacity-to-treat-hepatitis-c-by-training-our-own-residents
#5
Thomas Couri, Tanmayi Gupta, George Weyer, Andrew Aronsohn
No abstract text is available yet for this article.
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29790188/coagulation-failure-in-patients-with-acute-on-chronic-liver-failure-aclf-and-decompensated-cirrhosis-beyond-inr
#6
Annabel Blasi, Andrea Calvo, Verónica Prado, Enric Reverter, Juan Carlos Reverter, María Hernández-Tejero, Fátima Aziz, Alex Amoros, Andres Cardenas, Javier Fernández
Balanced hemostasis with hypo and hypercoagulable features may occur in acute-on-chronic liver failure. Characteristics and prognostic impact of the coagulation profile in acute-on-chronic liver failure are unknown. METHODS: Consecutive patients with acute-on-chronic liver failure (n=36) and acute decompensation (n=24) were included. Blood samples for thromboelastometry (ROTEM®) were obtained at admission and 72h thereafter. Coagulation profile was evaluated in patients with and without acute-on-chronic liver failure and in those with and without systemic inflammatory response syndrome...
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29790184/fat10-overexpression-disturbs-wisp1-protein-and-mrna-expression-to-promote-hepatocellular-carcinoma-progression
#7
Jinlong Yan, Jun Lei, Leifeng Chen, Huan Deng, Dingxiang Dong, Tao Jin, Xiuxia Liu, Rongfa Yuan, Yumin Qiu, Jin Ge, Xiaogang Peng, Jianghua Shao
Recently, studies on transcriptome-proteome relationships have revealed mRNA/protein expression discordance for certain genes and speculated that protein post-translational modification (PTM) may be involved. However, there is currently no evidence to support this hypothesis. Wnt-induced secreted protein-1 (WISP1) is the downstream target gene of β-catenin and plays an important role in tumorigenesis and progression, but the expression and role of WISP1 in different tumor types are controversial. Here, we first confirmed WISP1 protein expression was significantly downregulated in hepatocellular carcinoma (HCC) tissue, and could be an independent predictor of poor prognosis for patients with HCC...
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29790183/fasting-inhibits-the-recruitment-of-kinesin-1-to-lipid-droplets-and-stalls-hepatic-triglyceride-secretion
#8
Ryan J Schulze, Mark A McNiven
No abstract text is available yet for this article.
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29774589/healthcare-cost-and-utilization-in-nonalcoholic-fatty-liver-disease-real-world-data-from-a-large-us-claims-database
#9
Alina M Allen, Holly K Van Houten, Lindsey R Sangaralingham, Jayant A Talwalkar, Rozalina G McCoy
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. The health care burden resulting from the multidisciplinary management of this complex disease is unknown. We assessed the total health care cost and resource utilization associated with a new NAFLD diagnosis, compared to controls with similar comorbidities. We used OptumLabs Data Warehouse, a large national administrative claims database with longitudinal health data of over 100 million individuals enrolled in private and Medicare Advantage health plans...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29774579/integrative-epigenetic-analysis-reveals-therapeutic-targets-to-the-dna-methyltransferase-inhibitor-sgi-110-in-hepatocellular-carcinoma
#10
Minmin Liu, Lian Zhang, Hongtao Li, Toshinori Hinoue, Wanding Zhou, Hitoshi Ohtani, Anthony El-Khoueiry, John Daniels, Casey O'Connell, Tanya B Dorff, Qianjin Lu, Daniel J Weisenberger, Gangning Liang
There is an urgent need for developing more effective therapies for hepatocellular carcinoma (HCC) because of its aggressiveness. Guadecitabine (SGI-110) is a second-generation DNA methyltransferase inhibitor (DNMTi) currently in clinical trials for HCC and shows greater stability and performance over first generation DNMTis. In order to identify potential therapeutic targets of SGI-110 for clinical trials, HCC cell lines (SNU398, HepG2 and SNU475) were used to evaluate effects of transient SGI-110 treatment by an integrative analysis of DNA methylation, nucleosome accessibility, gene expression profiles and its clinical relevance by comparisons to TCGA HCC clinical data...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29774578/the-immunobiology-of-rankl-and-myeloid-derived-suppressor-cell-activation-in-igg4-related-sclerosing-cholangitis
#11
Min Lian, Qixia Wang, Xiang Jiang, Jun Zhang, Yiran Wei, Yanmei Li, Bo Li, Weihua Chen, Haiyan Zhang, Qi Miao, Yanshen Peng, Xiao Xiao, Li Sheng, Weici Zhang, Jingyuan Fang, Ruqi Tang, M Eric Gershwin, Xiong Ma
The primary function of myeloid derived suppressor cells (MDSCs) is reflected in their immune modulatory role in several immune-mediated diseases. In IgG4-related disease (IgG4-RD), it has been hypothesized that there are selective regulatory defects that lead to a Th2 bias immune response. Herein we have taken advantage of a large cohort of patients with IgG4-related sclerosing cholangitis (IgG4-SC), the most common extra-pancreatic involvement of IgG4-RD, as well as controls consisting of primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH) and healthy volunteers, to study MDSC...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29774575/fecal-microbial-transplant-for-antibiotic-associated-disruption-in-cirrhosis
#12
LETTER
Jasmohan S Bajaj, Tor Savidge, Zain A Kassam, Phillip B Hylemon, Patrick M Gillevet
No abstract text is available yet for this article.
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29774570/high-mobility-group-box-1-drives-fibrosis-progression-signaling-via-the-receptor-for-advanced-glycation-end-products-in-mice
#13
Xiaodong Ge, Elena Arriazu, Fernando Magdaleno, Daniel J Antoine, Rouchelle Dela Cruz, Neil Theise, Natalia Nieto
BACKGROUND & RATIONALE: High-mobility group box-1 (HMGB1) is a damage-associated molecular pattern (DAMP) increased in response to liver injury. Since HMGB1 is a ligand for the receptor for advanced glycation end-products (RAGE), we hypothesized that induction of HMGB1 could participate in the pathogenesis of liver fibrosis via RAGE cell-specific signaling mechanisms. RESULTS: liver HMGB1 protein expression correlated with fibrosis stage in patients with chronic Hepatitis C virus (HCV) infection, primary biliary cirrhosis (PBC) and alcoholic steatohepatitis (ASH)...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29774567/antibiotic-associated-disruption-of-microbiota-composition-and-function-in-cirrhosis-is-restored-by-fecal-transplant
#14
LETTER
Benjamin H Mullish, Julie A K McDonald, Mark R Thursz, Julian R Marchesi
No abstract text is available yet for this article.
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29752806/thomas-d-boyer-md-a-visionary-hepatologist-investigator-mentor-and-colleague
#15
Teresa L Wright, K Rajender Reddy
No abstract text is available yet for this article.
May 12, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29742812/binding-of-free-and-immune-complex-associated-hepatitis-c-virus-to-erythrocytes-is-mediated-by-the-complement-system
#16
Kazi Abdus Salam, Richard Y Wang, Teresa Grandinetti, Valeria De Giorgi, Harvey J Alter, Robert D Allison
Erythrocytes bind circulating immune complexes (IC) and facilitate IC clearance from the circulation. Chronic hepatitis C virus (HCV) infection is associated with IC-related disorders. In this study we investigated the kinetics and mechanism of HCV and HCV-IC binding to and dissociation from erythrocytes. Cell culture-produced HCV was mixed with erythrocytes from healthy blood donors and erythrocyte-associated virus particles were quantified. Purified complement proteins, complement-depleted serum, and complement receptor antibodies were used to investigate complement-mediated HCV-erythrocyte binding...
May 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29742811/primary-sclerosing-cholangitis-risk-estimate-tool-presto-predicts-outcomes-in-psc-a-derivation-validation-study-using-machine-learning
#17
John E Eaton, Mette Vesterhus, Bryan M McCauley, Elizabeth J Atkinson, Erik M Schlicht, Brian D Juran, Andrea A Gossard, Nicholas F LaRusso, Gregory J Gores, Tom H Karlsen, Konstantinos N Lazaridis
BACKGROUND & AIMS: Improved methods are needed to risk stratify and predict outcomes in patients with primary sclerosing cholangitis (PSC). Therefore, we sought to derive and validate a new prediction model and compare its performance to existing surrogate markers. METHODS: The model was derived using 509 subjects from a multicenter North American cohort and validated in an international multicenter cohort (n=278). Gradient boosting, a machine based learning technique, was used to create the model...
May 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29742809/b-cell-mediated-maintenance-of-cd169-cells-is-critical-for-liver-regeneration
#18
Kristina Behnke, Yuan Zhuang, Haifeng C Xu, Balamurugan Sundaram, Maria Reich, Prashant V Shinde, Jun Huang, Nastaran Fazel Modares, Alexei V Tumanov, Robin Polz, Jürgen Scheller, Carl F Ware, Klaus Pfeffer, Verena Keitel, Dieter Häussinger, Aleksandra A Pandyra, Karl S Lang, Philipp A Lang
The liver has an extraordinary capacity to regenerate via activation of key molecular pathways. However, central regulators controlling liver regeneration remain insufficiently studied. Here we show that B cell-deficient animals failed to induce sufficient liver regeneration after partial hepatectomy (PHx). Consistently, adoptive transfer of B cells could rescue defective liver regeneration. B cell mediated lymphotoxin beta production promoted recovery from PHx. Absence of B cells coincided with loss of splenic CD169+ macrophages...
May 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29742805/novel-genetic-activation-screening-in-liver-repopulation-and-cancer-now-crispr-than-ever
#19
EDITORIAL
Morgan Preziosi, Satdarshan P Monga
No abstract text is available yet for this article.
May 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29742804/monocyte-chemoattractant-protein-induced-protein-1-targets-hypoxia-inducible-factor-1%C3%AE-to-protect-against-hepatic-ischemia-reperfusion-injury
#20
Peng Sun, Yue-Xin Lu, Daqing Cheng, Kuo Zhang, Jilin Zheng, Yupeng Liu, Xiaozhan Wang, Yu-Feng Yuan, Yi-Da Tang
Sterile inflammation is an essential factor causing hepatic ischemia/reperfusion (I/R) injury. As a critical regulator of inflammation, the role of monocyte chemoattractant protein-induced protein 1 (MCPIP1) in hepatic I/R injury remains undetermined. In this study, we discovered that MCPIP1 downregulation was associated with hepatic I/R injury in liver transplant patients and a mouse model. Hepatocyte-specific Mcpip1 gene knockout (HKO) and transgenic (HTG) mice demonstrated that MCPIP1 functions to ameliorate liver damage, reduce inflammation, prevent cell death, and promote regeneration...
May 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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