A novel GSK‐3 beta–C/EBP alpha–miR‐122–insulin‐like growth factor 1 receptor regulatory circuitry in human hepatocellular carcinoma

Chunxian Zeng, Ruizhi Wang, Daochuan Li, Xue‐Jia Lin, Qing‐Kun Wei, Yunfei Yuan, Qing Wang, Wen Chen, Shi‐Mei Zhuang – 29 October 2010 – miR‐122 is a highly abundant, hepatocyte‐specific microRNA. The biomedical significance and regulatory mechanisms of miR‐122 remain obscure. We explored the role of miR‐122 in tumorigenesis in the context of gene regulatory network. The miR‐122 promoter and its transactivator were identified by way of luciferase reporter system, electrophoretic mobility shift, and chromatin immunoprecipitation assays.

Activation of LKB1‐Akt pathway independent of phosphoinositide 3‐kinase plays a critical role in the proliferation of hepatocellular carcinoma from nonalcoholic steatohepatitis

Nuria Martínez‐López, Marta Varela‐Rey, David Fernández‐Ramos, Ashwin Woodhoo, Mercedes Vázquez‐Chantada, Nieves Embade, Luis Espinosa‐Hevia, Francisco Javier Bustamante, Luis A. Parada, Manuel S. Rodriguez, Shelly C. Lu, José M. Mato, Maria L. Martínez‐Chantar – 29 October 2010 – LKB1, originally considered a tumor suppressor, plays an important role in hepatocyte proliferation and liver regeneration.

Interferon regulatory factor 3 and type I interferons are protective in alcoholic liver injury in mice by way of crosstalk of parenchymal and myeloid cells

Jan Petrasek, Angela Dolganiuc, Timea Csak, Bharath Nath, Istvan Hritz, Karen Kodys, Donna Catalano, Evelyn Kurt‐Jones, Pranoti Mandrekar, Gyongyi Szabo – 29 October 2010 – Alcoholic liver disease (ALD) features increased hepatic exposure to bacterial lipopolysaccharide (LPS). Toll‐like receptor‐4 (TLR4) recognizes LPS and activates signaling pathways depending on MyD88 or TRIF adaptors. We previously showed that MyD88 is dispensable in ALD. TLR4 induces Type I interferons (IFNs) in an MyD88‐independent manner that involves interferon regulatory factor‐3 (IRF3).

Hyponatremia in patients treated with terlipressin for severe gastrointestinal bleeding due to portal hypertension

Elsa Solà, Sabela Lens, Mónica Guevara, Marta Martín‐Llahí, Claudia Fagundes, Gustavo Pereira, Marco Pavesi, Javier Fernández, Juan González‐Abraldes, Angels Escorsell, Antoni Mas, Jaume Bosch, Vicente Arroyo, Pere Ginès – 29 October 2010 – Terlipressin is frequently used in acute variceal bleeding due to its powerful effect on vasopressin V1 receptors. Although terlipressin is also a partial agonist of renal vasopressin V2 receptors, its effects on serum sodium concentration have not been specifically investigated.

A phase 1/2, dose‐escalation trial of deferasirox for the treatment of iron overload in HFE‐related hereditary hemochromatosis

Pradyumna Phatak, Pierre Brissot, Mark Wurster, Paul C Adams, Herbert L. Bonkovsky, John Gross, Peter Malfertheiner, Gordon D. McLaren, Claus Niederau, Alberto Piperno, Lawrie W. Powell, Mark W. Russo, Ulrich Stoelzel, Wolfgang Stremmel, Louis Griffel, Nicola Lynch, Yiyun Zhang, Antonello Pietrangelo – 29 October 2010 – Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in iron overload.

Anti–tumor necrosis factor α treatment promotes apoptosis and prevents liver regeneration in a transgenic mouse model of chronic hepatitis C

Erwin Daniel Brenndörfer, Malin Weiland, Lars Frelin, Emma Derk, Gustaf Ahlén, Jian Jiao, Johannes Georg Bode, Matti Sällberg – 29 October 2010 – Tumor necrosis factor α (TNFα) has been implicated in a variety of inflammatory diseases, and anti‐TNFα has been shown to improve therapy when added to standard of care in chronic hepatitis C virus (HCV) infection. In addition, patients with chronic HCV have increased serum levels of TNFα and the macrophage‐attracting chemokine (C‐C motif) ligand 2 (CCL2).

Association of anti‐E1E2 antibodies with spontaneous recovery or sustained viral response to therapy in patients infected with hepatitis C virus

Ndiémé Ndongo, Pascale Berthillon, Pierre Pradat, Claude Vieux, Isabelle Bordes, Françoise Berby, Marianne Maynard, Fabien Zoulim, Christian Trépo, Marie‐Anne Petit – 29 October 2010 – The monoclonal antibody (mAb) D32.10 recognizes a discontinuous epitope encompassing three regions E1 (amino acids 297‐306), E2A (amino acids 480‐494), and E2B (amino acids 613‐621) juxtaposed on the surface of serum‐derived hepatitis C virus (HCV) particles (HCVsp). The mAb D32.10 inhibits efficiently and specifically the binding of HCVsp to human hepatocytes.

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