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https://www.readbyqxmd.com/read/27902328/hepatitis-c-virus-core-activates-proteasomal-activator-28-gamma-expression-via-upregulation-of-p53-levels-to-control-virus-propagation
#1
Juri Kwak, Indira Tiwari, Kyung Lib Jang
The proteasomal activator PA28γ, frequently overexpressed in hepatocellular carcinoma (HCC), is believed to play several important roles in hepatitis C virus (HCV) replication and viral pathogenesis. However, the underlying mechanism for PA28γ overexpression in HCC and its role during HCV replication are still unclear. In the present study, we found that HCV Core derived from either ectopic expression or HCV infection upregulates PA28γ levels in p53-positive human hepatocytes. For this effect, HCV Core sequentially activated ataxia telangiectasia mutated and checkpoint kinase 2 via phosphorylation at Ser-1981 and Thr-68 residues, respectively, resulting in stabilization of p53 via phosphorylation at Ser-15 and Ser-20 residues and subsequent transcriptional activation of PA28γ expression...
November 11, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27853236/regulation-of-sirt1-nrf2-tnf-%C3%AE-signaling-pathway-by-luteolin-is-critical-to-attenuate-acute-mercuric-chloride-exposure-induced-hepatotoxicity
#2
Daqian Yang, Xiao Tan, Zhanjun Lv, Biying Liu, Ruiqi Baiyun, Jingjing Lu, Zhigang Zhang
Inorganic mercury, though a key component of pediatric vaccines, is an environmental toxicant threatening human health via accumulating oxidative stress in part. Luteolin has been of great interest because of its antiinflammatory, anticarcinogenic and antioxidative effects. Here we hypothesized that luteolin would attenuate hepatotoxicity induced by acute inorganic mercury exposure. Kunming mice were treated with luteolin (100 mg/kg) 24 h after administration of 4 mg/kg mercuric chloride (HgCl2). The results showed that luteolin ameliorated HgCl2 induced anemia and hepatotoxicity, regulating radical oxygen species (ROS) production and hepatocyte viability in vitro and oxidative stress and apoptosis in vivo...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27832471/expression-pattern-of-bccip-in-hepatocellular-carcinoma-is-correlated-with-poor-prognosis-and-enhanced-cell-proliferation
#3
Zhipeng Lin, Baoying Hu, Wenkai Ni, Xiaofei Mao, Huiling Zhou, Jiale Lv, Bihui Yin, Zhongyi Shen, Miaomiao Wu, Wensen Ding, Mingbing Xiao, Runzhou Ni
BCCIP was originally identified as a BRCA2- and CDKN1A- (Cip1/waf1/p21) interacting protein, also known as BCCIP. It has been reported to express in various types of cancers, including colorectal cancer (CRC), astrocytic brain tumors, and glioblastomas. However, the relationship between BCCIP expression and clinicopathological features of hepatocellular carcinoma (HCC) remains to be determined. Herein, we demonstrated that BCCIP was downregulated in clinical HCC tissues; its level was inversely correlated with multiple clinicopathological factors, such as tumor grade, tumor size, and Ki67 expression...
November 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27824900/sirt6-depletion-suppresses-tumor-growth-by-promoting-cellular-senescence-induced-by-dna-damage-in-hcc
#4
Namgyu Lee, Hye Guk Ryu, Jung-Hee Kwon, Dae-Kyum Kim, Sae Rom Kim, Hee Jung Wang, Kyong-Tai Kim, Kwan Yong Choi
The role of Sirtuin 6 (SIRT6) as a tumor suppressor or oncogene in liver cancer remains controversial. Thus, we identified the specific role of SIRT6 in the progression of hepatocellular carcinoma (HCC). SIRT6 expression was significantly higher in HCC cell lines and HCC tissues from 138 patients than in an immortalized hepatocyte cell line, THLE-2 and non-tumor tissues, respectively. SIRT6 knockdown by shRNA suppressed the growth of HCC cells and inhibited HCC tumor growth in vivo. In addition, SIRT6 silencing significantly prevented the growth of HCC cell lines by inducing cellular senescence in the p16/Rb- and p53/p21-pathway independent manners...
2016: PloS One
https://www.readbyqxmd.com/read/27811061/liver-p53-is-stabilized-upon-starvation-and-required-for-amino-acid-catabolism-and-gluconeogenesis
#5
Andreas Prokesch, Franziska A Graef, Tobias Madl, Jennifer Kahlhofer, Steffi Heidenreich, Anne Schumann, Elisabeth Moyschewitz, Petra Pristoynik, Astrid Blaschitz, Miriam Knauer, Matthias Muenzner, Juliane G Bogner-Strauss, Gottfried Dohr, Tim J Schulz, Michael Schupp
The ability to adapt cellular metabolism to nutrient availability is critical for survival. The liver plays a central role in the adaptation to starvation by switching from glucose-consuming processes and lipid synthesis to providing energy substrates like glucose to the organism. Here we report a previously unrecognized role of the tumor suppressor p53 in the physiologic adaptation to food withdrawal. We found that starvation robustly increases p53 protein in mouse liver. This induction was posttranscriptional and mediated by a hepatocyte-autonomous and AMP-activated protein kinase-dependent mechanism...
November 3, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27791012/notch3-drives-development-and-progression-of-cholangiocarcinoma
#6
Rachel V Guest, Luke Boulter, Benjamin J Dwyer, Timothy J Kendall, Tak-Yung Man, Sarah E Minnis-Lyons, Wei-Yu Lu, Andrew J Robson, Sofia Ferreira Gonzalez, Alexander Raven, Davina Wojtacha, Jennifer P Morton, Mina Komuta, Tania Roskams, Stephen J Wigmore, Owen J Sansom, Stuart J Forbes
The prognosis of cholangiocarcinoma (CC) is dismal. Notch has been identified as a potential driver; forced exogenous overexpression of Notch1 in hepatocytes results in the formation of biliary tumors. In human disease, however, it is unknown which components of the endogenously signaling pathway are required for tumorigenesis, how these orchestrate cancer, and how they can be targeted for therapy. Here we characterize Notch in human-resected CC, a toxin-driven model in rats, and a transgenic mouse model in which p53 deletion is targeted to biliary epithelia and CC induced using the hepatocarcinogen thioacetamide...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27770462/il-6-trans-signaling-is-essential-for-the-development-of-hepatocellular-carcinoma
#7
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
https://www.readbyqxmd.com/read/27764939/nrf2-knockdown-disrupts-the-protective-effect-of-curcumin-on-alcohol-induced-hepatocyte-necroptosis
#8
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
https://www.readbyqxmd.com/read/27756472/%C3%AE-hydroxybutyrate-induces-bovine-hepatocyte-apoptosis-via-an-ros-p38-signaling-pathway
#9
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
https://www.readbyqxmd.com/read/27730025/cytotoxicity-of-methanol-extracts-of-annona-muricata-passiflora-edulis-and-nine-other-cameroonian-medicinal-plants-towards-multi-factorial-drug-resistant-cancer-cell-lines
#10
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
https://www.readbyqxmd.com/read/27723467/pomegranate-protects-against-arsenic-induced-p53-dependent-ros-mediated-inflammation-and-apoptosis-in-liver-cells
#11
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
https://www.readbyqxmd.com/read/27698449/cr-vi-induces-premature-senescence-through-ros-mediated-p53-pathway-in-l-02-hepatocytes
#12
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
https://www.readbyqxmd.com/read/27697592/suppressing-pitx2-inhibits-proliferation-and-promotes-differentiation-of-ihepscs
#13
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
https://www.readbyqxmd.com/read/27686696/development-of-a-methodology-for-in-vivo-follow-up-of-hepatocellular-carcinoma-in-hepatocyte-specific-trim24-null-mice-treated-with-myo-inositol-trispyrophosphate
#14
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
https://www.readbyqxmd.com/read/27664064/multiple-cyclin-kinase-inhibitors-promote-bile-acid-induced-apoptosis-and-autophagy-in-primary-hepatocytes-via-p53-cd95-dependent-signaling
#15
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
https://www.readbyqxmd.com/read/27639250/sirtuin-1-activation-alleviates-cholestatic-liver-injury-in-a-cholic-acid-fed-mouse-model-of-cholestasis
#16
Supriya R Kulkarni, Carol J Soroka, Lee R Hagey, James L Boyer
: Sirtuin1 (Sirt1; mammalian homolog of Saccharomyces cerevisiae enzyme Sir2) is a transcriptional and transactivational regulator of murine farnesoid X receptor (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...
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27591765/distinct-pathways-of-pathogenesis-of-intraductal-oncocytic-papillary-neoplasms-and-intraductal-papillary-mucinous-neoplasms-of-the-pancreas
#17
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...
November 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27570113/ceramide-and-polyunsaturated-phospholipids-are-strongly-reduced-in-human-hepatocellular-carcinoma
#18
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...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27556439/curcumin-ameliorates-furazolidone-induced-dna-damage-and-apoptosis-in-human-hepatocyte-l02-cells-by-inhibiting-ros-production-and-mitochondrial-pathway
#19
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
https://www.readbyqxmd.com/read/27541702/immunoprofile-of-the-adenomatoid-odontogenic-tumour
#20
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
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