Conditional disruption of mouse HFE2 gene: Maintenance of systemic iron homeostasis requires hepatic but not skeletal muscle hemojuvelin

Konstantinos Gkouvatsos, John Wagner, George Papanikolaou, Giada Sebastiani, Kostas Pantopoulos – 11 July 2011 – Mutations of the HFE2 gene are linked to juvenile hemochromatosis, a severe hereditary iron overload disease caused by chronic hyperabsorption of dietary iron. HFE2 encodes hemojuvelin (Hjv), a membrane‐associated bone morphogenetic protein (BMP) coreceptor that enhances expression of the liver‐derived iron regulatory hormone hepcidin. Hjv is primarily expressed in skeletal muscles and at lower levels in the heart and the liver.

Endothelial nitric oxide synthase is a key mediator of hepatocyte proliferation in response to partial hepatectomy in mice

Yu Mei, Sundararajah Thevananther – 11 July 2011 – Endothelial nitric oxide synthase (eNOS) is a critical modulator of vascular tone and blood flow and plays major roles in liver physiology and pathophysiology. Nitric oxide (NO) is widely recognized as one of the key humoral factors important for the initiation of liver regeneration in response to partial hepatectomy. Liver regeneration in response to partial hepatectomy is dependent on the efficiency of growth factor‐mediated cell‐cycle progression.

Human hepatocellular carcinomas with “Stemness”‐related marker expression: keratin 19 expression and a poor prognosis

Haeryoung Kim, Gi Hong Choi, Deuk Chae Na, Ei Young Ahn, Gwang Il Kim, Jae Eun Lee, Jai Young Cho, Jeong Eun Yoo, Jin Sub Choi, Young Nyun Park – 11 July 2011 – There is a recently proposed subtype of hepatocellular carcinoma (HCC) that is histologically similar to usual HCC, but characterized by the expression of “stemness”‐related markers. A large‐scale study on two different cohorts of HCCs was performed to investigate the clinicopathologic features and epithelial‐mesenchymal transition (EMT)‐related protein expression status of this subtype of HCCs.

Role of cyclophilin B in tumorigenesis and cisplatin resistance in hepatocellular carcinoma in humans

Yeonghwan Kim, Miran Jang, Sangbin Lim, Hyeran Won, Kyung‐Sik Yoon, Jae‐Hoon Park, Hyo Jong Kim, Byung‐Ho Kim, Won‐Sang Park, Joohun Ha, Sung‐Soo Kim – 11 July 2011 – Cyclophilin B (CypB) performs diverse roles in living cells, but its role in hepatocellular carcinoma (HCC) is largely unclear. To reveal its role in HCC, we investigated the induction of CypB under hypoxia and its functions in tumor cells in vitro and in vivo. Here, we demonstrated that hypoxia‐inducible factor 1α (HIF‐1α) induces CypB under hypoxia.

Hepatotoxicity mediated by pyrazole (cytochrome P450 2E1) plus tumor necrosis factor alpha treatment occurs in c‐Jun N‐terminal kinase 2−/− but not in c‐Jun N‐terminal kinase 1−/− mice

Xiaodong Wang, Defeng Wu, Lili Yang, Arthur I. Cederbaum – 11 July 2011 – Cytochrome P450 2E1 (CYP2E1) induction and tumor necrosis factor alpha (TNF‐α) production are key risk factors in alcoholic liver injury. Increased oxidative stress from CYP2E1 induction by pyrazole in vivo sensitizes the liver to TNF‐α‐induced hepatotoxicity by a mechanism involving the activation of c‐jun N‐terminal kinase (JNK) and mitochondrial damage. The aim of this study was to evaluate whether JNK1 or JNK2 plays a role in this potentiated hepatotoxicity.

Pentoxifylline improves nonalcoholic steatohepatitis: A randomized placebo‐controlled trial

Claudia O. Zein, Lisa M. Yerian, Prema Gogate, Rocio Lopez, John P. Kirwan, Ariel E. Feldstein, Arthur J. McCullough – 11 July 2011 – The primary aim of this study was to compare the effects of pentoxifylline (PTX) versus placebo on the histological features of nonalcoholic steatohepatitis (NASH). In all, 55 adults with biopsy‐confirmed NASH were randomized to receive PTX at a dose of 400 mg three times a day (n = 26) or placebo (n = 29) over 1 year.

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