Blocking Sodium‐Taurocholate Cotransporting Polypeptide Stimulates Biliary Cholesterol and Phospholipid Secretion in Mice

Reinout L.P. Roscam Abbing, Davor Slijepcevic, Joanne M. Donkers, Rick Havinga, Suzanne Duijst, Coen C. Paulusma, Johan Kuiper, Folkert Kuipers, Albert K. Groen, Ronald P.J. Oude Elferink, Stan F.J. Graaf – 28 May 2019 – Active secretion of bile salts into the canalicular lumen drives bile formation and promotes biliary cholesterol and phospholipid output. Disrupting hepatic bile salt uptake, by inhibition of sodium‐taurocholate cotransporting polypetide (NTCP; Slc10a1) with Myrcludex B, is expected to limit bile salt flux through the liver and thereby to decrease biliary lipid excretion.

Ablation of Hepatocyte Smad1, Smad5, and Smad8 Causes Severe Tissue Iron Loading and Liver Fibrosis in Mice

Chia‐Yu Wang, Xia Xiao, Abraham Bayer, Yang Xu, Som Dev, Susanna Canali, Anil V. Nair, Ricard Masia, Jodie L. Babitt – 24 May 2019 – A failure of iron to appropriately regulate liver hepcidin production is central to the pathogenesis of hereditary hemochromatosis. SMAD1/5 transcription factors, activated by bone morphogenetic protein (BMP) signaling, are major regulators of hepcidin production in response to iron; however, the role of SMAD8 and the contribution of SMADs to hepcidin production by other systemic cues remain uncertain.

Acetyl‐3‐Aminoethyl Salicylate Ameliorates Hepatic Ischemia/Reperfusion Injury and Liver Graft Survival Through a High‐Mobility Group Box 1/Toll‐Like Receptor 4–Dependent Mechanism

Xing Lai, Junhua Gong, Weiming Wang, Ding Cao, Menghao Wang, Yiming Liu, Hao Wu, Yakun Wu, Yong Chen, Zhong Zeng, Jinzheng Li, Jianping Gong – 24 May 2019 – In liver transplant cases, severe hepatic ischemia/reperfusion injury (HIRI) is a strong predictor of adverse liver graft and overall outcomes. During HIRI, high‐mobility group box 1 (HMGB1) promotes hepatocellular death and proinflammatory cytokine secretion by toll‐like receptor 4 (TLR4).

The Novel N,N‐bis‐2‐Hydroxyethyl‐2‐Aminoethanesulfonic Acid–Gluconate–Polyethylene Glycol–Hypothermic Machine Perfusion Solution Improves Static Cold Storage and Reduces Ischemia/Reperfusion Injury in Rat Liver Transplant

Matías E. Carnevale, Natalia Lausada, Leonardo Juan de Paz, Pablo Stringa, Mariana Machuca, Martin Rumbo, Edgardo E. Guibert, Claudio Tiribelli, Gabriel E. Gondolesi, Joaquin V. Rodriguez – 23 May 2019 – Organ transplantation is the treatment of choice against terminal and irreversible organ failure. Optimal preservation of the graft is crucial to counteract cold ischemia effects.

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Benedikt Schaefer, Armin Finkenstedt, Maria Effenberger, André Viveiros, Herbert Tilg, Heinz Zoller – 23 May 2019

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