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p53 hepatocyte

Juri Bergmann, Miryam Müller, Niklas Baumann, Manuel Reichert, Carola Heneweer, Julia Bolik, Karsten Lücke, Sabine Gruber, Antonella Carambia, Susanne Boretius, Ivo Leuschner, Thomas Becker, Björn Rabe, Johannes Herkel, F Thomas Wunderlich, Hans-Willi Mitrücker, Stefan Rose-John, Dirk Schmidt-Arras
: Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide with rising incidence. The inflammatory cytokine interleukin 6 (IL-6) is a critical mediator of HCC development. It can signal through two distinct pathways, the IL-6 classic and the IL-6 trans-signaling pathway. While IL-6 classic signaling is important for innate and acquired immunity, IL-6 trans-signaling has been linked to accelerated liver regeneration and several chronic inflammatory pathologies. However, its implication in liver tumorigenesis has not been addressed yet...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Chunfeng Lu, Wenxuan Xu, Feng Zhang, Jiangjuan Shao, Shizhong Zheng
It has emerged that hepatocyte necroptosis plays a critical role in chronic alcoholic liver disease (ALD). Our previous study has identified that the beneficial therapeutic effect of curcumin on alcohol-caused liver injury might be attributed to activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), whereas the role of curcumin in regulating necroptosis and the underlying mechanism remain to be determined. We firstly found that chronic alcohol consumption triggered obvious hepatocyte necroptosis, leading to increased expression of receptor-interacting protein 1, receptor-interacting protein 3, high-mobility group box 1, and phosphorylated mixed lineage kinase domain-like in murine livers...
October 20, 2016: Molecular Pharmaceutics
Yuxiang Song, Na Li, Jingmin Gu, Shoupeng Fu, Zhicheng Peng, Chenxu Zhao, Yuming Zhang, Xiaobing Li, Zhe Wang, Xinwei Li, Guowen Liu
β-Hydroxybutyrate (BHB) is an important indicator for metabolic disorders in dairy cows, such as ketosis and fatty liver. Dairy cows with ketosis display oxidative stress that may be associated with high levels of BHB. The purpose of this study was to demonstrate a correlation between the high levels of BHB and oxidative stress in dairy cows with ketosis, and to investigate the molecular mechanisms underlying oxidative damage in bovine hepatocytes. The results showed that dairy cows with ketosis exhibited oxidative stress and liver damage, which was significantly correlated with plasma BHB...
November 2016: Journal of Dairy Science
Victor Kuete, Joachim K Dzotam, Igor K Voukeng, Aimé G Fankam, Thomas Efferth
BACKGROUND: Cancer cells rapidly acquire resistance leading to treatment failures. In the present study, we have evaluated the cytotoxicity of 17 methanol extracts from 11 Cameroonian medicinal plants against the sensitive leukemia CCRF-CEM cells and the best ones were further tested on a panel of 8 other human cancer cell lines, including various MDR phenotypes as well as against the normal AML12 hepatocytes. METHODS: The cytotoxicity of the extracts was determined using a resazurin reduction assay meanwhile flow cytometry was used to measure cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species...
2016: SpringerPlus
Sreetama Choudhury, Sayan Ghosh, Sudeshna Mukherjee, Payal Gupta, Saurav Bhattacharya, Arghya Adhikary, Sreya Chattopadhyay
Molecular mechanisms involved in arsenic-induced toxicity are complex and elusive. Liver is one of the most favored organs for arsenic toxicity as methylation of arsenic occurs mostly in the liver. In this study, we have selected a range of environmentally relevant doses of arsenic to examine the basis of arsenic toxicity and the role of pomegranate fruit extract (PFE) in combating it. Male Swiss albino mice exposed to different doses of arsenic presented marked hepatic injury as evident from histological and electron microscopic studies...
September 6, 2016: Journal of Nutritional Biochemistry
Yujing Zhang, Yiyuan Zhang, Caigao Zhong, Fang Xiao
Hexavalent Chromium [Cr(VI)], which can be found of various uses in industries such as metallurgy and textile dying, can cause a number of human disease including inflammation and cancer. Unlike previous research that focused on Cr(VI)-induced oxidative damage and apoptosis, this study placed emphasis on premature senescence that can be induced by low-dose and long-term Cr(VI) exposure. We found Cr(VI) induced premature senescence in L-02 hepatocytes, as confirmed by increase in senescence associated-β-galactosidase (SA-β-Gal) activity...
October 4, 2016: Scientific Reports
Fei Chen, Hao Yao, Minjun Wang, Bing Yu, Qinggui Liu, Jianxiu Li, Zhiying He, Yi-Ping Hu
Induced hepatic stem cells (iHepSCs) have great potential as donors for liver cell therapy due to their abilities for self-renewal and bi-potential differentiation. However, the molecular mechanism regulating proliferation and differentiation of iHepSCs is poorly understood. In this study, we provide evidence that the homeodomain transcription factor, Pitx2, is essential to maintain iHepSCs stem cell characteristics. Suppressing Pitx2 expression in iHepSCs by lentivirus mediated specific shRNA markedly reduced the expression of the hepatic stem cell-associated genes (Lgr5, EpCAM, and Sox9) with concomitant inhibition of proliferation by blocking the G1/S phase transition, and these phenotypic changes were reversed upon re-expression of Pitx2...
September 30, 2016: International Journal of Biochemistry & Cell Biology
Mihaela Ignat, Cherif Youssef Akladios, Véronique Lindner, Konstantin Khetchoumian, Marius Teletin, Didier Muttter, Pierre Marc Aprahamian, Jacques Marescaux
BACKGROUND: Genetically induced hepatocellular carcinoma (HCC) models are generally used to investigate carcinogenesis pathways, but very few attempts were made to valorize them for pharmacological testing. This study describes a micro-computed tomography (micro-CT) - based methodology for the diagnostic and lifelong follow-up of HCC in the hepatocyte-specific Trim24-null mouse line. Myo-inositol trispyrophosphate (ITPP) was tested as anti-cancer drug. METHODS: Partial hepatectomy was performed in 2 months-old Trim24-null mice, in order to accelerate the carcinogenesis process...
September 29, 2016: Journal of Experimental & Clinical Cancer Research: CR
Guo Zhang, Margaret A Park, Clint Mitchell, Teneille Walker, Hossein Hamed, Elaine Studer, Martin Graf, Mohamed Rahmani, Seema Gupta, Philip B Hylemon, Paul B Fisher, Steven Grant, Paul Dent
No abstract text is available yet for this article.
September 23, 2016: Journal of Biological Chemistry
Supriya R Kulkarni, Carol J Soroka, Lee R Hagey, James L Boyer
Sirtuin1 (Sirt1, mammalian homolog of S. Cerevisiae enzyme Sir2) is a transcriptional and transactivational regulator of murine Fxr, which is the primary bile acid (BA) sensor, and critical regulator of BA metabolism in physiological and pathophysiological conditions. Previous studies have suggested compromised Sirt1 expression in rodent models of cholestatic liver injury. We hypothesized that Sirt1 could be potentially targeted to alleviate cholestatic liver injury. In cultured primary human hepatocytes, SIRT1 mRNA was downregulated after GCA treatment, potentially via induction of miR-34a, whereas TUDCA induced SIRT1 expression without affecting miR-34a expression...
September 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Olca Basturk, Sun M Chung, Ralph H Hruban, N Volkan Adsay, Gokce Askan, Christine Iacobuzio-Donahue, Serdar Balci, Sui Y Zee, Bahar Memis, Jinru Shia, David S Klimstra
Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is classified as a variant of intraductal papillary mucinous neoplasm (IPMN) in the WHO guidelines. However, the neoplastic cells of IOPNs are unique, with distinctive architecture/oncocytic cytoplasm. Although molecular/immunohistochemical features of other IPMN variants have been extensively studied, those of IOPNs have not been well characterized. Expression profile of antibodies associated with genetic alterations previously described for ductal adenocarcinomas (DAs) and IPMNs (SMAD4/β-catenin/p53/mesothelin/claudin-4) as well as antibodies to mucins and differentiation markers [MUC1/MUC2/MUC5AC/MUC6/CDX2/hepatocyte paraffin-1 (HepPar-1)] was investigated in 24 IOPNs and 22 IPMNs to assess the similarities/differences between these tumors...
September 3, 2016: Virchows Archiv: An International Journal of Pathology
Sabrina Krautbauer, Elisabeth M Meier, Lisa Rein-Fischboeck, Rebekka Pohl, Thomas S Weiss, Alexander Sigruener, Charalampos Aslanidis, Gerhard Liebisch, Christa Buechler
Lipid composition affects membrane function, cell proliferation and cell death and is changed in cancer tissues. Hepatocellular carcinoma (HCC) is an aggressive cancer and this study aimed at a comprehensive characterization of hepatic and serum lipids in human HCC. Cholesteryl ester were higher in tumorous tissues (TT) compared to adjacent non-tumorous tissues (NT). Free cholesterol exerting cytotoxic effects was not changed. Phosphatidylethanolamine, -serine (PS) and -inositol but not phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) were reduced in HCC tissues...
August 25, 2016: Biochimica et Biophysica Acta
Chongshan Dai, Daowen Li, Lijing Gong, Xilong Xiao, Shusheng Tang
Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells. The results showed that curcumin pre-treatment significantly ameliorated FZD-induced oxidative stress, characterized by decreased reactive oxygen species (ROS) and malondialdehyde formation, and increased superoxide dismutase, catalase activities and glutathione contents...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Peter A Reichart, Hans Peter Philipsen, Pathawee Khongkhunthian, James J Sciubba
The present study was focused on the immunohistochemical profile of the adenomatoid odontogenic tumor. A Pub/Medline search revealed a number of immunohistochemical studies including cytokeratin profiles, extracellular matrix proteins, Integrins, ameloblast-associated proteins resorption regulators (RANK, RANKL), p53, PCNA, MDM2 protein, cyclin D1, Ki-67, Bcl-2 metallothionein, metalloproteinases, D56 hepatocyte growth factor, c-met, DNA methyltransferase, podoplanin, TGF-βI, Smad-2/3, Smad-I-5/-8, Smad 4, beta- catenin, calretinin and clonality...
August 19, 2016: Oral Diseases
Sheng-Tsai Lin, Shih-Hsin Tu, Po-Sheng Yang, Sung-Po Hsu, Wei-Hwa Lee, Chi-Tang Ho, Chih-Hsiung Wu, Yu-Hsin Lai, Ming-Yao Chen, Li-Ching Chen
Glucose transporters (GLUTs) are required for glucose uptake in malignant cells, and they can be used as molecular targets for cancer therapy. An RT-PCR analysis was performed to investigate the mRNA levels of 14 subtypes of GLUTs in human colorectal cancer (COLO 205 and HT-29) and normal (FHC) cells. RT-PCR (n = 27) was used to assess the differences in paired tissue samples (tumor vs normal) isolated from colorectal cancer patients. GLUT2 was detected in all tested cells. The average GLUT2 mRNA level in 12 of 27 (44...
September 14, 2016: Journal of Agricultural and Food Chemistry
Manikankana Bandopadhyay, Neelakshi Sarkar, Sibnarayan Datta, Dipanwita Das, Ananya Pal, Rajesh Panigrahi, Arup Banerjee, Chinmay K Panda, Chandrima Das, Shekhar Chakrabarti, Runu Chakravarty
BACKGROUND: Hepatitis B virus (HBV) X protein (HBx) reported to be associated with pathogenesis of hepatocellular carcinoma (HCC) and miR-122 expression is down regulated in HCC. Previous studies reported miR-122 targets cyclin G1 (CCNG1) expression and this in turn abolishes p53-mediated inhibition of HBV replication. Here we investigated the involvement of HBx protein in the modulation of miR-122 expression in hepatoblastoma cells. METHODS: Expression of miR-122 was measured in HepG2 cells transfected with HBx plasmid (HBx-HepG2), full length HBV genome (HBV-HepG2) and in constitutively HBV synthesizing HepG2...
2016: Infectious Agents and Cancer
Victor Kuete, Cedric F Tchinda, Flora T Mambe, Veronique P Beng, Thomas Efferth
BACKGROUND: Cancer chemotherapy is still hampered by clinical failures due to multi-drug resistance (MDR) of tumor cells. In the present study, we have investigated the cytotoxicity of 20 methanol extracts from 10 medicinal plants against the sensitive leukemia CCRF-CEM cells. The most cytotoxic extracts were then further tested on a panel of 8 human cancer cell lines, including various MDR phenotypes. METHODS: The cytotoxicity of the 20 methanol extracts from 10 Cameroonian medicinal plants was determined using a resazurin reduction assay...
2016: BMC Complementary and Alternative Medicine
Chen Huang, Xiaobing Zheng, Haijun Mei, Min Zhou
BACKGROUND: Current commercially available drug eluting stents (DESs) are criticized for the problem of stent thrombosis by induced impaired re-endothelialization (RE). The solving of this challenge could be boosted by endothelial progenitor cells (EPCs). The purpose of this study was to examine the effects of hepatocyte growth factor (HGF) on this process. METHODS: The abundance and functional capacity of circulating EPC were analyzed by a fluorescence-activated cell sorter (FACS) and western blot...
July 13, 2016: Annals of Vascular Surgery
Luis E Gomez-Quiroz, Daekwan Seo, Yun-Han Lee, Mitsuteru Kitade, Timo Gaiser, Matthew Gillen, Seung-Bum Lee, Ma Concepcion Gutierrez-Ruiz, Elizabeth A Conner, Valentina M Factor, Snorri S Thorgeirsson, Jens U Marquardt
Recent studies confirmed a critical importance of c-Met signaling for liver regeneration by modulating redox balance. Here we used liver-specific conditional knockout mice (MetKO) and a nutritional model of hepatic steatosis to address the role of c-Met in cholesterol-mediated liver toxicity. Liver injury was assessed by histopathology and plasma enzymes levels. Global transcriptomic changes were examined by gene expression microarray, and key molecules involved in liver damage and lipid homeostasis were evaluated by Western blotting...
June 15, 2016: Toxicology
Xiao-Feng Tian, Fu-Jian Ji, Hong-Liang Zang, Hong Cao
Liver fibrosis results from a sustained wound healing response to chronic liver injury, and the activation of nonparenchymal hepatic stellate cells (HSCs) is the pivotal process. MicroRNA-34a (miR-34a) is the direct target gene of p53 and activates p53 through sirtuin 1 (SIRT1) simultaneously. The miR-34a/SIRT1/p53 signaling pathway thus forms a positive feedback loop wherein p53 induces miR-34a and miR-34a activates p53 by inhibiting SIRT1, playing an important role in cell proliferation and apoptosis. miR-34a expression has been found to be increased in animal models or in human patients with different liver diseases, including liver fibrosis...
2016: PloS One
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