Hepatocyte TNF Receptor–Associated Factor 6 Aggravates Hepatic Inflammation and Fibrosis by Promoting Lysine 6–Linked Polyubiquitination of Apoptosis Signal‐Regulating Kinase 1

Yutao Wang, Huan Wen, Jiajun Fu, Lin Cai, Peng‐Long Li, Chang‐Ling Zhao, Zhu‐feng Dong, Jun‐peng Ma, Xi Wang, Han Tian, Yan Zhang, Ye Liu, Jingjing Cai, Zhi‐Gang She, Zan Huang, Wenhua Li, Hongliang Li – 20 June 2019 – Activation of apoptosis signal‐regulating kinase 1 (ASK1) is a key driving force of the progression of nonalcoholic steatohepatitis (NASH) and represents an attractive therapeutic target for NASH treatment. However, the molecular and cellular mechanisms underlying ASK1 activation in the pathogenesis of NASH remain incompletely understood.

Liver Injury and Failure in Critical Illness

Thomas Horvatits, Andreas Drolz, Michael Trauner, Valentin Fuhrmann – 19 June 2019 – The frequency of acquired liver injury and failure in critical illness has been significantly increasing over recent decades. Currently, liver injury and failure are observed in up to 20% of patients in intensive care units and are associated with significantly increased morbidity and mortality. Secondary forms of liver injury in critical illness are divided primarily into cholestatic, hypoxic, or mixed forms.

NAD(P)H Quinone Dehydrogenase 1 Ablation Inhibits Activation of the Phosphoinositide 3‐Kinase/Akt Serine/Threonine Kinase and Mitogen‐Activated Protein Kinase/Extracellular Signal‐Regulated Kinase Pathways and Blocks Metabolic Adaptation in Hepatocellular

Manali Dimri, Ashley Humphries, Archana Laknaur, Sawsan Elattar, Tae Jin Lee, Ashok Sharma, Ravindra Kolhe, Ande Satyanarayana – 19 June 2019 – Cancer cells undergo metabolic adaptation to sustain uncontrolled proliferation. Aerobic glycolysis and glutaminolysis are two of the most essential characteristics of cancer metabolic reprogramming.

Sestrin 3 Protects Against Diet‐Induced Nonalcoholic Steatohepatitis in Mice Through Suppression of Transforming Growth Factor β Signal Transduction

Menghao Huang, Hyeong Geug Kim, Xiaolin Zhong, Chuanpeng Dong, Brian Zhang, Zhigang Fang, Yang Zhang, Xiaoyu Lu, Romil Saxena, Yunlong Liu, Chi Zhang, Suthat Liangpunsakul, X. Charlie Dong – 19 June 2019 – Sestrin 3 (Sesn3) belongs to the three‐member sestrin protein family. Sestrins have been implicated in antioxidative stress, adenosine monophosphate–activated protein kinase and mammalian target of rapamycin signal transduction, and metabolic homeostasis. However, the role of Sesn3 in the development of nonalcoholic steatohepatitis (NASH) has not been previously studied.

Body Composition and Genetic Lipodystrophy Risk Score Associate With Nonalcoholic Fatty Liver Disease and Liver Fibrosis

Vincent L. Chen, Andrew P. Wright, Brian Halligan, Yanhua Chen, Xiaomeng Du, Samuel K. Handelman, Michelle T. Long, Douglas P. Kiel, Elizabeth K. Speliotes – 18 June 2019 – Up to 25% of patients with nonalcoholic fatty liver disease (NAFLD) are not obese but may have a fat or muscle composition that predisposes them to NAFLD. Our aim was to determine whether body composition parameters associate with NAFLD and to identify genetic contributors to this association. This study included two cohorts.

Identification of a Pan‐Gamma‐Secretase Inhibitor Response Signature for Notch‐Driven Cholangiocarcinoma

Colm J. O’Rourke, Matthias S. Matter, Chirag Nepal, Rui Caetano‐Oliveira, Phuongnga T. Ton, Valentina M. Factor, Jesper B. Andersen – 18 June 2019 – Cholangiocarcinoma (CCA) mortality rates are increasing as a result of rising incidence and limited curative treatment(s) for patients with advanced disease. NOTCH pathway reactivation has been reported in biliary malignancies to conflicting degrees, hindering prioritization of key therapeutic targets within the network and identification of candidate responder patients for NOTCH‐directed therapies.

Analysis of Host Responses to Hepatitis B and Delta Viral Infections in a Micro‐scalable Hepatic Co‐culture System

Benjamin Y. Winer, Jenna M. Gaska, Gabriel Lipkowitz, Yaron Bram, Amit Parekh, Lance Parsons, Robert Leach, Rohit Jindal, Cheul H. Cho, Anil Shrirao, Eric Novik, Robert E. Schwartz, Alexander Ploss – 17 June 2019 – Hepatitis B virus (HBV) remains a major global health problem with 257 million chronically infected individuals worldwide, of whom approximately 20 million are co‐infected with hepatitis delta virus (HDV).

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