Lupeol targets liver tumor‐initiating cells through phosphatase and tensin homolog modulation

Terence Kin Wah Lee, Antonia Castilho, Vincent Chi Ho Cheung, Kwan Ho Tang, Stephanie Ma, Irene Oi Lin Ng – 20 September 2010 – Liver tumor‐initiating cells (T‐ICs) are capable of self‐renewal and tumor initiation and are more chemoresistant to chemotherapeutic drugs. The current therapeutic strategies for targeting stem cell self‐renewal pathways therefore represent rational approaches for cancer prevention and treatment.

Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis

Wing‐Kin Syn, Steve S. Choi, Evaggelia Liaskou, Gamze F. Karaca, Kolade M. Agboola, Ye Htun Oo, Zhiyong Mi, Thiago A. Pereira, Marzena Zdanowicz, Padmini Malladi, Yuping Chen, Cynthia Moylan, Youngmi Jung, Syamal D. Bhattacharya, Vanessa Teaberry, Alessia Omenetti, Manal F. Abdelmalek, Cynthia D. Guy, David H. Adams, Paul C. Kuo, Gregory A. Michelotti, Peter F. Whitington, Anna Mae Diehl – 20 September 2010 – Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. Recently, we showed that NASH‐related cirrhosis is associated with Hedgehog (Hh) pathway activation.

Human T cell microparticles circulate in blood of hepatitis patients and induce fibrolytic activation of hepatic stellate cells

Miroslaw Kornek, Yury Popov, Towia A. Libermann, Nezam H. Afdhal, Detlef Schuppan – 20 September 2010 – Microparticles (MPs) are small cell membrane vesicles that are released from cells during apoptosis or activation. Although circulating platelet MPs have been studied in some detail, the existence and functional role of T cell MPs remain elusive. We show that blood from patients with active hepatitis C (alanine aminotransferase [ALT] level >100 IU/mL) contains elevated numbers of T cell MPs compared with patients with mild hepatitis C (ALT <40 IU/mL) and healthy controls.

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Marco Antonio Montes‐Cano, José Raúl García‐Lozano, Cristina Abad‐Molina, Manuel Romero‐Gómez, Natalia Barroso, José Aguilar‐Reina, Antonio Núñez‐Roldán, María Francisca González‐Escribano – 17 September 2010

Accelerated liver fibrosis in hepatitis B virus transgenic mice: Involvement of natural killer T cells

Zixue Jin, Rui Sun, Haiming Wei, Xiang Gao, Yongyan Chen, Zhigang Tian – 14 September 2010 – The immunopathogenic process from hepatitis B virus (HBV) infection to liver fibrosis is incompletely understood because it lacks an animal model. In this study we observed the development of liver fibrosis in HBV transgenic (HBV‐tg) mice and found the roles of natural killer T (NKT) cells in HBV‐related liver fibrosis.

Improved dendritic cell‐based immunization against hepatitis C virus using peptide inhibitors of interleukin 10

Nancy Díaz‐Valdés, Lorea Manterola, Virginia Belsúe, José I. Riezu‐Boj, Esther Larrea, Itziar Echeverria, Diana Llópiz, Jacinto López‐Sagaseta, Hervé Lerat, Jean‐Michel Pawlotsky, Jesús Prieto, Juan J. Lasarte, Francisco Borrás‐Cuesta, Pablo Sarobe – 14 September 2010 – The high levels of interleukin 10 (IL‐10) present in chronic hepatitis C virus (HCV) infection have been suggested as responsible for the poor antiviral cellular immune responses found in these patients.

Organic anion–transporting polypeptide 1b2 (Oatp1b2) is important for the hepatic uptake of unconjugated bile acids: Studies in Oatp1b2‐null mice

Iván L. Csanaky, Hong Lu, Youcai Zhang, Kenichiro Ogura, Supratim Choudhuri, Curtis D. Klaassen – 14 September 2010 – The organic anion–transporting polypeptide 1b family (Oatp1b2 in rodents and OATP1B1/1B3 in humans) is liver‐specific and transports various chemicals into the liver. However, the role of the Oatp1b family in the hepatic uptake of bile acids (BAs) into the liver is unknown. Therefore, in Oatp1b2‐null mice, the concentrations of BAs in plasma, liver, and bile were compared with wild‐type (WT) mice.

Ribavirin potentiates interferon action by augmenting interferon‐stimulated gene induction in hepatitis C virus cell culture models

Emmanuel Thomas, Jordan J. Feld, Qisheng Li, Zongyi Hu, Michael W. Fried, T. Jake Liang – 14 September 2010 – The combination of pegylated interferon (PEG‐IFN) and ribavirin is the standard treatment for chronic hepatitis C. Our recent clinical study suggests that ribavirin augments the induction of interferon‐stimulated genes (ISGs) in patients treated for hepatitis C virus (HCV) infection. In order to further characterize the mechanisms of action of ribavirin, we examined the effect of ribavirin treatment on ISG induction in cell culture.

Ablation of the tumor suppressor histidine triad nucleotide binding protein 1 is protective against hepatic ischemia/reperfusion injury

Juliette Martin, Pamela Romanque, Olivier Maurhofer, Karin Schmitter, Caroline Hora, Gisèle Ferrand, Jean‐François Dufour – 10 September 2010 – The identification of cellular pathways capable of limiting ischemia/reperfusion (I/R) injury remains a frontier in medicine, and its clinical relevance is urgent. Histidine triad nucleotide binding protein 1 (HINT1) is a tumor suppressor that influences apoptosis. Because apoptotic pathways are a feature of I/R injury, we asked whether Hint1 influences hepatic I/R injury.

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