Chromosome 8p tumor suppressor genes SH2D4A and SORBS3 cooperate to inhibit interleukin‐6 signaling in hepatocellular carcinoma

Carolin Ploeger, Nina Waldburger, Angelika Fraas, Benjamin Goeppert, Stefan Pusch, Kai Breuhahn, Xin Wei Wang, Peter Schirmacher, Stephanie Roessler – 16 June 2016 – Several chronic inflammatory liver diseases, e.g., chronic hepatitis B or C viral infection and steatohepatitis, have been shown to predispose to the development of hepatocellular carcinoma (HCC). In patients with chronic liver disease, interleukin‐6 (IL‐6) serum levels are elevated and increase even more when HCC develops.

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.

Lack of immunological DNA sensing in hepatocytes facilitates hepatitis B virus infection

Martin K. Thomsen, Ramya Nandakumar, Daniela Stadler, Antje Malo, Roser Marin Valls, Fan Wang, Line S. Reinert, Frederik Dagnæs‐Hansen, Anne Kruse Hollensen, Jacob Giehm Mikkelsen, Ulrike Protzer, Søren R. Paludan – 16 June 2016 – Hepatitis B virus (HBV) is a major human pathogen, and about one third of the global population will be exposed to the virus in their lifetime. HBV infects hepatocytes, where it replicates its DNA and infection can lead to acute and chronic hepatitis with a high risk of liver cirrhosis and hepatocellular carcinoma.

SIRT1‐mediated transcriptional regulation of SOX2 is important for self‐renewal of liver cancer stem cells

Limei Liu, Chungang Liu, Qianzhen Zhang, Junjie Shen, Heng Zhang, Juanjuan Shan, Guangjie Duan, Deyu Guo, Xuejiao Chen, Jiamin Cheng, Yanmin Xu, Zhi Yang, Chao Yao, Maode Lai, Cheng Qian – 16 June 2016 – Hepatocellular carcinoma (HCC) is a highly aggressive liver tumor containing cancer stem cells (CSCs), which participate in tumor invasion, therapeutic resistance, and tumor relapse leading to poor outcome and limited therapeutic options. Histone deacetylatase sirtuin 1 (SIRT1) has been shown to be up‐regulated in human cancers; however, its role in liver CSCs is unknown.

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).

Prevalence of chronic liver disease and cirrhosis by underlying cause in understudied ethnic groups: The multiethnic cohort

Veronica Wendy Setiawan, Daniel O. Stram, Jacqueline Porcel, Shelly C. Lu, Loïc Le Marchand, Mazen Noureddin – 15 June 2016 – Chronic liver disease (CLD) and cirrhosis are major sources of morbidity and mortality in the United States. Little is known about the epidemiology of these two diseases in ethnic minority populations in the United States. We examined the prevalence of CLD and cirrhosis by underlying etiologies among African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the Multiethnic Cohort.

The P2X4 purinergic receptor impacts liver regeneration after partial hepatectomy in mice through the regulation of biliary homeostasis

Aurore Besnard, Julien Gautherot, Boris Julien, Ali Tebbi, Isabelle Garcin, Isabelle Doignon, Noémie Péan, Emmanuel Gonzales, Doris Cassio, Brigitte Grosse, Bingkaï Liu, Hanaa Safya, Florent Cauchois, Lydie Humbert, Dominique Rainteau, Thierry Tordjmann – 15 June 2016 – Many regulatory pathways are involved in liver regeneration after partial hepatectomy (PH), to initiate growth, protect liver cells, and sustain remnant liver functions.

Chemokine (C‐C motif) receptor 2–positive monocytes aggravate the early phase of acetaminophen‐induced acute liver injury

Jana C. Mossanen, Oliver Krenkel, Can Ergen, Olivier Govaere, Anke Liepelt, Tobias Puengel, Felix Heymann, Sandra Kalthoff, Eric Lefebvre, Dirk Eulberg, Tom Luedde, Gernot Marx, Christian P. Strassburg, Tania Roskams, Christian Trautwein, Frank Tacke – 15 June 2016 – Acetaminophen (APAP, paracetamol) poisoning is a leading cause of acute liver failure (ALF) in humans and induces hepatocyte necrosis, followed by activation of the innate immune system, further aggravating liver injury. The role of infiltrating monocytes during the early phase of ALF is still ambiguous.

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