Maternal high‐fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression

Kimberley D. Bruce, Felino R. Cagampang, Marco Argenton, Junlong Zhang, Priya L. Ethirajan, Graham C. Burdge, Adrian C. Bateman, Geraldine F. Clough, Lucilla Poston, Mark A. Hanson, Josie M. McConnell, Christopher D. Byrne – 20 November 2009 – Nonalcoholic fatty liver disease (NAFLD) describes an increasingly prevalent spectrum of liver disorders associated with obesity and metabolic syndrome. It is uncertain why steatosis occurs in some individuals, whereas nonalcoholic steatohepatitis (NASH) occurs in others.

Sorafenib inhibits signal transducer and activator of transcription‐3 signaling in cholangiocarcinoma cells by activating the phosphatase shatterproof 2

Boris R. A. Blechacz, Rory L. Smoot, Steven F. Bronk, Nathan W. Werneburg, Alphonse E. Sirica, Gregory J. Gores – 20 November 2009 – The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is one of the key signaling cascades in cholangiocarcinoma (CCA) cells, mediating their resistance to apoptosis. Our aim was to ascertain if sorafenib, a multikinase inhibitor, may also inhibit JAK/STAT signaling and, therefore, be efficacious for CCA. Sorafenib treatment of three human CCA cell lines resulted in Tyr705 phospho‐STAT3 dephosphorylation.

Not interferon, but interleukin‐6 controls early gene expression in hepatitis B virus infection

Marianna Hösel, Maria Quasdorff, Katja Wiegmann, Dennis Webb, Uta Zedler, Mathias Broxtermann, Raindy Tedjokusumo, Knud Esser, Silke Arzberger, Carsten J. Kirschning, Anja Langenkamp, Christine Falk, Hildegard Büning, Stefan Rose‐John, Ulrike Protzer – 20 November 2009 – With about 350 million virus carriers, hepatitis B virus (HBV) infection remains a major health problem. HBV is a noncytopathic virus causing persistent infection, but it is still unknown whether host recognition of HBV may activate an innate immune response.

B‐cell depletion with anti‐CD20 ameliorates autoimmune cholangitis but exacerbates colitis in transforming growth factor‐β receptor II dominant negative mice

Yuki Moritoki, Zhe‐Xiong Lian, Keith Lindor, Joseph Tuscano, Koichi Tsuneyama, Weici Zhang, Yoshiyuki Ueno, Robert Dunn, Marilyn Kehry, Ross L. Coppel, Ian R. Mackay, M. Eric Gershwin – 20 November 2009 – The treatment of primary biliary cirrhosis (PBC) with conventional immunosuppressive drugs has been relatively disappointing and there have been few efforts in defining a role for the newer biological agents useful in rheumatoid arthritis and other systemic autoimmune diseases.

Severe lactic acidosis during treatment of chronic hepatitis B with entecavir in patients with impaired liver function

Christian M. Lange, Jörg Bojunga, Wolf Peter Hofmann, Katrin Wunder, Ulrike Mihm, Stefan Zeuzem, Christoph Sarrazin – 20 November 2009 – Entecavir is a potent nucleoside inhibitor of the hepatitis B virus (HBV) polymerase with a high antiviral efficacy and a high genetic barrier to viral resistance. After approval in 2006, knowledge on the side effect profile in patients with advanced liver disease and impaired liver function is still limited. Here, we report on 16 patients with liver cirrhosis and chronic hepatitis B who were treated with entecavir.

Combined deletion of Hfe and transferrin receptor 2 in mice leads to marked dysregulation of hepcidin and iron overload

Daniel F. Wallace, Lesa Summerville, Emily M. Crampton, David M. Frazer, Gregory J. Anderson, V. Nathan Subramaniam – 20 November 2009 – Hepcidin is a central regulator of iron homeostasis. HFE and transferrin receptor 2 (TFR2) are mutated in adult‐onset forms of hereditary hemochromatosis and regulate the expression of hepcidin in response to iron. Whether they act through the same or parallel pathways is unclear. To investigate this, we generated a mouse model with deletion of both Hfe and Tfr2 genes by crossing Hfe and Tfr2 null mice on a genetically identical background.

Ikappa B kinaseβ/nuclear factor‐κB activation controls the development of liver metastasis by way of interleukin‐6 expression

Shin Maeda, Yohko Hikiba, Kei Sakamoto, Hayato Nakagawa, Yoshihiro Hirata, Yoku Hayakawa, Ayako Yanai, Keiji Ogura, Michael Karin, Masao Omata – 20 November 2009 – Nuclear factor kappaB (NF‐κB) plays an important role in the regulation of innate immune responses, apoptosis, inflammation, and oncogenesis. NF‐κB activation in the liver was observed after intrasplenic administration of a lung carcinoma cell line, LLC, which induces liver metastasis.

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