Vertical sleeve gastrectomy activates GPBAR‐1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice

Lili Ding, Kyle M. Sousa, Lihua Jin, Bingning Dong, Byung‐Wook Kim, Ricardo Ramirez, Zhenzhou Xiao, Ying Gu, Qiaoling Yang, Jie Wang, Donna Yu, Alessio Pigazzi, Dustin Schones, Li Yang, David Moore, Zhengtao Wang, Wendong Huang – 16 June 2016 – Vertical sleeve gastrectomy (VSG) is one of the most commonly performed clinical bariatric surgeries used for the remission of obesity and diabetes. However, the precise molecular mechanism by which VSG exerts its beneficial effects remains elusive.

Inhibition of epoxyeicosatrienoic acid production in rats with cirrhosis has beneficial effects on portal hypertension by reducing splanchnic vasodilation

Marco Di Pascoli, Francesca Zampieri, Alberto Verardo, Paola Pesce, Cristian Turato, Paolo Angeli, David Sacerdoti, Massimo Bolognesi – 16 June 2016 – In cirrhosis, 11,12‐epoxyeicosatrienoic acid (EET) induces mesenteric arterial vasodilation, which contributes to the onset of portal hypertension. We evaluated the hemodynamic effects of in vivo inhibition of EET production in experimental cirrhosis. Sixteen control rats and 16 rats with carbon tetrachloride‐induced cirrhosis were studied.

Receptor interacting protein 3 protects mice from high‐fat diet‐induced liver injury

Sanjoy Roychowdhury, Rebecca L. McCullough, Carlos Sanz‐Garcia, Paramananda Saikia, Naim Alkhouri, Ammar Matloob, Katherine A. Pollard, Megan R. McMullen, Colleen M. Croniger, Laura E. Nagy – 15 June 2016 – Multiple pathways of programmed cell death are important in liver homeostasis. Hepatocyte death is associated with progression of nonalcoholic fatty liver disease, and inhibition of apoptosis partially protects against liver injury in response to a high‐fat diet (HFD).

Five‐year histological and serological follow‐up of operationally tolerant pediatric liver transplant recipients enrolled in WISP‐R

Sandy Feng, Anthony J. Demetris, Katharine M. Spain, Sai Kanaparthi, Bryna E. Burrell, Udeme D. Ekong, Estella M. Alonso, Philip Rosenthal, Laurence A. Turka, David Ikle, Nadia K. Tchao – 15 June 2016 – Pediatric liver transplant recipients arguably have the most to gain and the most to lose from discontinuing immunosuppression (IS). Whereas IS undoubtedly exerts a cumulative toll, there is concern that insufficient or no IS may contribute to allograft deterioration.

Inhibition of spleen tyrosine kinase activation ameliorates inflammation, cell death, and steatosis in alcoholic liver disease

Terence N. Bukong, Arvin Iracheta‐Vellve, Banishree Saha, Aditya Ambade, Abhishek Satishchandran, Benedek Gyongyosi, Patrick Lowe, Donna Catalano, Karen Kodys, Gyongyi Szabo – 15 June 2016 – The spectrum of alcoholic liver disease (ALD) is a major cause of mortality with limited therapies available. Because alcohol targets numerous signaling pathways in hepatocytes and in immune cells, the identification of a master regulatory target that modulates multiple signaling processes is attractive.

Predicting renal recovery after liver transplant with severe pretransplant subacute kidney injury: The impact of warm ischemia time

Heather L. Laskey, Nathan Schomaker, Kenneth W. Hung, Sumeet K. Asrani, Linda Jennings, Trevor L. Nydam, Jane Gralla, Alex Wiseman, Hugo R. Rosen, Scott W. Biggins – 15 June 2016 – Identifying which liver transplantation (LT) candidates with severe kidney injury will have a full recovery of renal function after liver transplantation alone (LTA) is difficult. Avoiding unnecessary simultaneous liver‐kidney transplantation (SLKT) can optimize the use of scarce kidney grafts. Incorrect predictions of spontaneous renal recovery after LTA can lead to increased morbidity and mortality.

A Model to predict severity of drug‐induced liver injury in humans

Minjun Chen, Jürgen Borlak, Weida Tong – 15 June 2016 – Drug‐induced liver injury (DILI) is a major public health concern, and improving its prediction remains an unmet challenge. Recently, we reported the Rule‐of‐2 (RO2) and found lipophilicity (logP ≥3) and daily dose ≥100 mg of oral medications to be associated with significant risk for DILI; however, the RO2 failed to estimate grades of DILI severity.

The liver‐specific microRNA‐122*, the complementary strand of microRNA‐122, acts as a tumor suppressor by modulating the p53/mouse double minute 2 homolog circuitry

Alina Simerzin, Elina Zorde‐Khvalevsky, Mila Rivkin, Revital Adar, Jessica Zucman‐Rossi, Gabrielle Couchy, Tania Roskams, Olivier Govaere, Moshe Oren, Hilla Giladi, Eithan Galun – 15 June 2016 – The tumor suppressor p53 is a central regulator of signaling pathways that controls the cell cycle and maintains the integrity of the human genome. p53 level is regulated by mouse double minute 2 homolog (Mdm2), which marks p53 for proteasomal degradation. The p53‐Mdm2 circuitry is subjected to complex regulation by a variety of mechanisms, including microRNAs (miRNAs).

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