NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice

Alexander Wree, Akiko Eguchi, Matthew D. McGeough, Carla A. Pena, Casey D. Johnson, Ali Canbay, Hal M. Hoffman, Ariel E. Feldstein – 28 June 2013 – Inflammasome activation plays a central role in the development of drug‐induced and obesity‐associated liver disease. However, the sources and mechanisms of inflammasome‐mediated liver damage remain poorly understood. Our aim was to investigate the effect of NLRP3 inflammasome activation on the liver using novel mouse models.

A novel role of nucleostemin in maintaining the genome integrity of dividing hepatocytes during mouse liver development and regeneration

Tao Lin, Wessam Ibrahim, Cheng‐Yuan Peng, Milton J. Finegold, Robert Y.L. Tsai – 28 June 2013 – During liver development and regeneration, hepatocytes undergo rapid cell division and face an increased risk of DNA damage associated with active DNA replication. The mechanism that protects proliferating hepatocytes from replication‐induced DNA damage remains unclear. Nucleostemin (NS) is known to be up‐regulated during liver regeneration, and loss of NS is associated with increased DNA damage in cancer cells.

Overactivation of the TGF‐β pathway confers a mesenchymal‐like phenotype and CXCR4‐dependent migratory properties to liver tumor cells

Esther Bertran, Eva Crosas‐Molist, Patricia Sancho, Laia Caja, Judit Lopez‐Luque, Estanislao Navarro, Gustavo Egea, Raquel Lastra, Teresa Serrano, Emilio Ramos, Isabel Fabregat – 28 June 2013 – Transforming growth factor‐beta (TGF‐β) is an important regulatory suppressor factor in hepatocytes. However, liver tumor cells develop mechanisms to overcome its suppressor effects and respond to this cytokine by inducing other processes, such as the epithelial‐mesenchymal transition (EMT), which contributes to tumor progression and dissemination.

First experience of high‐intensity focused ultrasound combined with transcatheter arterial embolization as local control for hepatoblastoma

Shan Wang, Chao Yang, Jun Zhang, Xiang‐ru Kong, Hui Zhu, Feng Wu, Zhibiao Wang – 28 June 2013 – The purpose of this study was to assess the effectiveness of high‐intensity focused ultrasound (HIFU) combined with transarterial chemoembolization (TACE) in treating pediatric hepatoblastoma. Twelve patients with initially unresectable hepatoblastoma were enrolled in the study. All patients received chemotherapy, TACE, and HIFU ablation. Follow‐up materials were obtained in all patients. The tumor response, survival rate, and complications were analyzed.

Cannabinoid receptor 2 counteracts interleukin‐17‐induced immune and fibrogenic responses in mouse liver

Adrien Guillot, Nabila Hamdaoui, Alexandra Bizy, Keve Zoltani, Rachid Souktani, Elie‐Serge Zafrani, Ariane Mallat, Sophie Lotersztajn, Fouad Lafdil – 28 June 2013 – Interleukin (IL)‐17 is a proinflammatory and fibrogenic cytokine mainly produced by T‐helper (Th)17 lymphocytes, together with the hepatoprotective and antifibrogenic cytokine, IL‐22. Cannabinoid receptor 2 (CB2) is predominantly expressed in immune cells and displays anti‐inflammatory and antifibrogenic effects.

CD39 expression by hepatic myeloid dendritic cells attenuates inflammation in liver transplant ischemia‐reperfusion injury in mice

Osamu Yoshida, Shoko Kimura, Edwin K. Jackson, Simon C. Robson, David A. Geller, Noriko Murase, Angus W. Thomson – 28 June 2013 – Hepatic innate immune cells, in particular, interstitial dendritic cells (DCs), regulate inflammatory responses and may promote inherent liver tolerogenicity. After tissue injury, adenosine triphosphate (ATP) is released and acts as a damage‐associated molecular pattern that activates innate immune cells by pattern recognition receptors. CD39 (ectonucleoside triphosphate diphosphohydrolase‐1) rapidly hydrolyzes extracellular ATP to maintain physiological levels.

High‐fat and high‐sucrose (western) diet induces steatohepatitis that is dependent on fructokinase

Takuji Ishimoto, Miguel A. Lanaspa, Christopher J. Rivard, Carlos A. Roncal‐Jimenez, David J. Orlicky, Christina Cicerchi, Rachel H. McMahan, Manal F. Abdelmalek, Hugo R. Rosen, Matthew R. Jackman, Paul S. MacLean, Christine P. Diggle, Aruna Asipu, Shinichiro Inaba, Tomoki Kosugi, Waichi Sato, Shoichi Maruyama, Laura G. Sánchez‐Lozada, Yuri Y. Sautin, James O. Hill, David T. Bonthron, Richard J. Johnson – 28 June 2013 – Fructose intake from added sugars has been implicated as a cause of nonalcoholic fatty liver disease.

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