Phosphodiesterase 4 Inhibition as a Therapeutic Target for Alcoholic Liver Disease: From Bedside to Bench

Walter E. Rodriguez, Banrida Wahlang, Yali Wang, Jingwen Zhang, Manicka V. Vadhanam, Swati Joshi‐Barve, Philip Bauer, Robert Cannon, Ali Reza Ahmadi, Zhaoli Sun, Andrew Cameron, Shirish Barve, Claudio Maldonado, Craig McClain, Leila Gobejishvili – 13 May 2019 – Alcoholic liver disease (ALD) is a major cause of liver‐related mortality. There is still no US Food and Drug Administration–approved therapy for ALD, and therefore, identifying therapeutic targets is needed.

Hepatocyte Deletion of Triglyceride‐Synthesis Enzyme Acyl CoA: Diacylglycerol Acyltransferase 2 Reduces Steatosis Without Increasing Inflammation or Fibrosis in Mice

Nina L. Gluchowski, Katlyn R. Gabriel, Chandramohan Chitraju, Roderick T. Bronson, Niklas Mejhert, Sebastian Boland, Kun Wang, Zon Weng Lai, Robert V. Farese, Tobias C. Walther – 13 May 2019 – Nonalcoholic fatty liver disease (NAFLD) is characterized by excess lipid accumulation in hepatocytes and represents a huge public health problem owing to its propensity to progress to nonalcoholic steatohepatitis, fibrosis, and liver failure. The lipids stored in hepatic steatosis (HS) are primarily triglycerides (TGs) synthesized by two acyl‐CoA:diacylglycerol acyltransferase (DGAT) enzymes.

CD8+ T Cells Promote Maturation of Liver‐Resident NK Cells Through the CD70‐CD27 axis

Lu Bai, Hui Peng, Xiaolei Hao, Ling Tang, Cheng Sun, Meijuan Zheng, Fubao Liu, Zhexiong Lian, Li Bai, Haiming Wei, Rui Sun, Zhigang Tian – 11 May 2019 – Liver‐resident natural killer (LrNK) cells are a unique subset of NK cells that are distinct from conventional NK cells. However, little is known about the mechanisms by which LrNK cells mature. In this study, we discovered that LrNK cells exhibit a relatively immature phenotype and impaired cytotoxic capacity in the absence of CD8+ T cells.

Necroptotic Cell Death in Liver Transplantation and Underlying Diseases: Mechanisms and Clinical Perspective

Shaojun Shi, Monique M. A. Verstegen, Laura Mezzanotte, Jeroen Jonge, Clemens W. G. M. Löwik, Luc J. W. Laan – 11 May 2019 – Cell death is a natural process for the turnover of aged cells, but it can also arise as a result of pathological conditions. Cell death is recognized as a key feature in both acute and chronic hepatobiliary diseases caused by drug, alcohol, and fat uptake; by viral infection; or after surgical intervention. In the case of chronic disease, cell death can lead to (chronic) secondary inflammation, cirrhosis, and the progression to liver cancer.

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