Simultaneous knockdown of multiple ligands of innate receptor NKG2D prevents natural killer cell–mediated fulminant hepatitis in mice

Mei Huang, Rui Sun, Haiming Wei, Zhigang Tian – 13 July 2012 – NKG2D activation plays an important role in initiating and maintaining liver inflammation, and blockade of NKG2D recognition becomes a promising approach to alleviate liver inflammation. Treatment by silencing NKG2D ligands on hepatocytes, but not NKG2D on circulating immune cells, is more liver‐specific, and simultaneous knockdown of multiple NKG2D ligands on hepatocytes will be more efficient in liver disease intervention.

Second infections independently increase mortality in hospitalized patients With cirrhosis: the north american consortium for the study of end‐stage liver disease (NACSELD) experience

Jasmohan S. Bajaj, Jacqueline G. O'Leary, K. Rajender Reddy, Florence Wong, Jody C. Olson, Ram M. Subramanian, Geri Brown, Nicole A. Noble, Leroy R. Thacker, Patrick S. Kamath,, on behalf of NACSELD – 13 July 2012 – Bacterial infections are an important cause of mortality in cirrhosis, but there is a paucity of multicenter studies. The aim was to define factors predisposing to infection‐related mortality in hospitalized patients with cirrhosis. A prospective, cohort study of patients with cirrhosis with infections was performed at eight North American tertiary‐care hepatology centers.

PTEN‐mediated akt/β‐Catenin/foxo1 signaling regulates innate immune responses in mouse liver ischemia/reperfusion injury

Naoko Kamo, Bibo Ke, Ronald W. Busuttil, Jerzy W. Kupiec‐Weglinski – 13 July 2012 – The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) regulates innate immune responses inversely with phosphoinositide 3‐kinase (PI3K) and its direct downstream target gene, Akt. The Forkhead box O (Foxo) transcription factors are essential in the regulation of tissue development, immune homeostasis, and cell survival.

Identification of an intrahepatic transcriptional signature associated with self‐limiting infection in the woodchuck model of hepatitis B

Simon P. Fletcher, Daniel J. Chin, Donavan T. Cheng, Palanikumar Ravindran, Hans Bitter, Lore Gruenbaum, Paul J. Cote, Han Ma, Klaus Klumpp, Stephan Menne – 13 July 2012 – The woodchuck model of hepatitis B virus (HBV) infection displays many characteristics of human infection and has particular value for characterizing the host immune responses during the development of chronic infection.

Short‐term feedback regulation of bile salt uptake by bile salts in rodent liver

Stefanie Mühlfeld, Olga Domanova, Thomas Berlage, Claudia Stross, Angelika Helmer, Verena Keitel, Dieter Häussinger, Ralf Kubitz – 13 July 2012 – The sodium taurocholate cotransporting polypeptide (Ntcp) is the major bile salt uptake transporter at the sinusoidal membrane of hepatocytes. Short‐term feedback regulation of Ntcp by primary bile salts has not yet been investigated in vivo. Subcellular localization of Ntcp was analyzed in Ntcp‐transfected HepG2‐cells by flow cytometry and in immunofluorescence images from tissue sections by a new automated image analysis method.

Interleukin‐33 Is hepatoprotective during liver ischemia/reperfusion in mice

Nozomu Sakai, Heather L. Van Sweringen, R. Cutler Quillin, Rebecca Schuster, John Blanchard, Justin M. Burns, Amit D. Tevar, Michael J. Edwards, Alex B. Lentsch – 10 July 2012 – Interleukin (IL)‐33 is a recently identified member of the IL‐1 family that binds to the receptor, ST2L. In the current study, we sought to determine whether IL‐33 is an important regulator in the hepatic response to ischemia/reperfusion (I/R). Male C57BL/6 mice were subjected to 90 minutes of partial hepatic ischemia, followed by up to 8 hours of reperfusion.

MicroRNA‐27b is a regulatory hub in lipid metabolism and is altered in dyslipidemia

Kasey C. Vickers, Bassem M. Shoucri, Michael G. Levin, Han Wu, Daniel S. Pearson, David Osei‐Hwedieh, Francis S. Collins, Alan T. Remaley, Praveen Sethupathy – 6 July 2012 – Cellular and plasma lipid levels are tightly controlled by complex gene regulatory mechanisms. Elevated plasma lipid content, or hyperlipidemia, is a significant risk factor for cardiovascular morbidity and mortality.

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