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https://www.readbyqxmd.com/read/28421122/potential-antitumor-activity-and-apoptosis-induction-of-glossostemon-bruguieri-root-extract-against-hepatocellular-carcinoma-cells
#1
Mona S Alwhibi, Mahmoud I M Khalil, Mohamed M Ibrahim, Gehan A El-Gaaly, Ahmed S Sultan
Glossostemon bruguieri (moghat) is used as a nutritive and demulcent drink. This study was performed to investigate the antiproliferative effects of moghat root extract (MRE) and its apoptotic mechanism in hepatocellular carcinoma (HCC) cells, HepG2 and Hep3B. MTT assay, morphological changes, apoptosis enzyme linked immunosorbent assay, caspase and apoptotic activation, flow cytometry, and immunoblot analysis were employed. The IC50 of MRE for HepG2 (910 ± 6 μg/ml) and for Hep3B (1510 ± 5 μg/ml) induced significant growth-inhibitory effects against HCC cells, with no cytotoxic effect on normal hepatocytes...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28408319/deriving-and-testing-of-dysplastic-murine-hepatocytes-a-new-platform-in-liver-cancer-research
#2
Sharon Pok, Harpreet Vohra, Charbel Wehbe, Vanessa A Barn, Evi Arfianti, Yock-Young Dan, Geoffrey C Farrell, Narci C Teoh
Dysplastic hepatocytes(DH) represent altered hepatocytes with potential for malignant transformation. To date, most research on pathways to hepatocarcinogenesis has focused on use of "hepatoma" cell-lines derived from hepatocellular carcinoma(HCC). We describe a novel technique for deriving/culturing DH and demonstrate their utility for functional studies in vitro, compared to primary hepatocytes(PH) and HCC. PH and DH were prepared by portal vein collagenase perfusion from C57BL/6J mice. DH were subsequently subjected to FACS...
April 10, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28407767/e167k-polymorphism-of-tm6sf2-gene-affects-cell-cycle-of-hepatocellular-carcinoma-cell-hepa-1-6
#3
Shuixian Du, Linlin Lu, Yingxia Miao, Wenwen Jin, Changfei Li, Yongning Xin, Shiying Xuan
BACKGROUND: Some studties reported that the polymorphism of TM6SF2 gene E167K affects the occurrence and the progression of hepatocytes carcinoma (hepatocellular, HCC). In oeder to investigate the effects of the polymorphism of TM6SF2 gene E167K in the pathogenesis of HCC, we explored its influence on the cell cycle in hepatocellular carcinoma cell HEPA1-6. METHODS: HEPA 1-6 cells which could respectively overexpress TM6SF2 wild type and E167K variant were cultured and HEPA 1-6 cells with zero load plasmids were used as matched control...
April 13, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28402954/chaperone-mediated-autophagy-compensates-for-impaired-macroautophagy-in-the-cirrhotic-liver-to-promote-hepatocellular-carcinoma
#4
Srinivas Chava, Christine Lee, Yucel Aydin, Partha K Chandra, Asha Dash, Milad Chedid, Swan N Thung, Krzysztof Moroz, Tong Wu, Nabeen C Nayak, Srikanta Dash
Macroautophagy and chaperone-mediated autophagy (CMA) represent two major lysosomal degradation processes and often compensate for one another to facilitate cell survival. The aim of this study was to determine whether these autophagy pathways could compensate for one another to promote HCC cell survival in the cirrhotic liver. Analysis of normal liver tissue showed no expression of glypican-3 or p62 proteins, suggesting that macroautophagy is the major contributor to autophagic flux under non-pathological conditions...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28381798/gallic-acid-and-dodecyl-gallate-prevents-carbon-tetrachloride-induced-acute-and-chronic-hepatotoxicity-by-enhancing-hepatic-antioxidant-status-and-increasing-p53-expression
#5
Marlene Raimunda Andreola Perazzoli, Camila Katerin Perondi, Cesar Milton Baratto, Evelyn Winter, Tânia Beatriz Creczynski-Pasa, Claudriana Locatelli
Gallic acid (3,4,5-trihydroxybenzoic acid, GA), a natural phenolic acid has been reported as a strong antioxidant. Therefore the present study was designed to evaluate the effects of GA and dodecyl gallate (DGA) against acute and chronic carbon tetrachloride (CCl4)-induced hepatotoxicity. For acute model, rats were orally treated with GA and DGA for 7 d prior to CCl4 by intraperitoneally (i.p.) injection. For the chronic model, rats were orally treated with GA or DGA and CCl4 i.p. twice a week for four weeks...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28337887/up-regulation-of-mir-888-5p-in-hepatocellular-carcinoma-cell-lines-and-its-effect-on-malignant-characteristics-of-cells
#6
E Hao, J Yu, S Xie, W Zhang, G Wang
MicroRNA (miRNA) expression has been linked to the molecular pathogenesis of hepatocellular carcinoma (HCC). The aberrant expression of miRNA is involved in the processes of tumorigenesis and cancer progression. According to the latest research, miR-888-5p is associated with strong cancer-promoting effect. For instance, miR-888-5p is up-regulated in prostate cancer and breast cancer. Nevertheless, the role of miR-888-5p in HCC has not been investigated to date. In this study, we found that miR-888-5p levels in four HCC cell lines (SMMC7721, HepG2, Huh-7 and Bel7402) were significantly up-regulated compared with human hepatocyte cell line (HHL-5)...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28321271/parkin-in-cancer-mitophagy-related-unrelated-tasks
#7
EDITORIAL
Nabil Eid, Yoichi Kondo
Dysfunctional mitochondria may produce excessive reactive oxygen species, thus inducing DNA damage, which may be oncogenic if not repaired. As a major role of the PINK1-Parkin pathway involves selective autophagic clearance of damaged mitochondria via a process termed mitophagy, Parkin-mediated mitophagy may be a tumor-suppressive mechanism. As an alternative mechanism for tumor inhibition beyond mitophagy, Parkin has been reported to have other oncosuppressive functions such as DNA repair, negative regulation of cell proliferation and stimulation of p53 tumor suppressor function...
March 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28252653/endogenous-ampk-acts-as-a-detrimental-factor-in-fulminant-hepatitis-via-potentiating-jnk-dependent-hepatocyte-apoptosis
#8
Kai Hu, Xianqiong Gong, Qing Ai, Ling Lin, Jie Dai, Lu Cai, Rong Jiang, Pu Ge, Li Zhang
The energy sensor AMP-activated protein kinase (AMPK) is crucial for energy homeostasis. Recent studies have revealed that AMPK is involved in various energy-intensive pathological processes such as inflammation and apoptosis. The physiological functions of hepatic AMPK have been well studied, but the pathological significance of AMPK in liver disorders remains largely unknown. In the present study, the phosphorylation status and the roles of AMPK were investigated in mice with lipopolysaccharide (LPS)/d-galactosamine (D-Gal)-induced fulminant hepatitis...
March 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28212554/afb1-hepatocarcinogenesis-is-via-lipid-peroxidation-that-inhibits-dna-repair-sensitizes-mutation-susceptibility-and-induces-aldehyde-dna-adducts-at-p53-mutational-hotspot-codon-249
#9
Mao-Wen Weng, Hyun-Wook Lee, Bongkun Choi, Hsiang-Tsui Wang, Yu Hu, Manju Mehta, Dhimant Desai, Shantu Amin, Yi Zheng, Moon-Shong Tang
Aflatoxin B1 (AFB1) contamination in the food chain is a major cause of hepatocellular carcinoma (HCC). More than 60% of AFB1 related HCC carry p53 codon 249 mutations but the causal mechanism remains unclear. We found that 1) AFB1 induces two types of DNA adducts in human hepatocytes, AFB1-8,9-epoxide-deoxyguanosine (AFB1-E-dG) induced by AFB1-E and cyclic α-methyl-γ-hydroxy-1,N2-propano-dG (meth-OH-PdG) induced by lipid peroxidation generated acetaldehyde (Acet) and crotonaldehyde (Cro); 2) the level of meth-OH-PdG is >30 fold higher than the level of AFB1-E-dG; 3) AFB1, Acet, and Cro, but not AFB1-E, preferentially induce DNA damage at codon 249; 4) methylation at -CpG- sites enhances meth-OH-PdG formation at codon 249; and 5) repair of meth-OH-PdG at codon 249 is poor...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28166970/effects-of-intrauterine-growth-restriction-during-late-pregnancy-on-the-cell-apoptosis-and-related-gene-expression-in-ovine-fetal-liver
#10
Yingchun Liu, Chi Ma, Hui Li, Lingyao Li, Feng Gao, Changjin Ao
This study investigated the effect of intrauterine growth restriction (IUGR) during late pregnancy on the cell apoptosis and related gene expression in ovine fetal liver. Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: Restricted Group 1 (RG1, 0.18 MJ ME kg BW(-0.75) d(-1), n = 6), Restricted Group 2 (RG2, 0.33 MJ ME kg BW(-0.75) d(-1), n = 6) and a Control Group (CG, ad libitum, 0.67 MJ ME kg BW (-0.75) d (-1), n = 6). Fetuses were recovered at slaughter on d 140...
March 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28130345/the-piddosome-activates-p53-in-response-to-supernumerary-centrosomes
#11
Luca L Fava, Fabian Schuler, Valentina Sladky, Manuel D Haschka, Claudia Soratroi, Lisa Eiterer, Egon Demetz, Guenter Weiss, Stephan Geley, Erich A Nigg, Andreas Villunger
Centrosomes, the main microtubule-organizing centers in animal cells, are replicated exactly once during the cell division cycle to form the poles of the mitotic spindle. Supernumerary centrosomes can lead to aberrant cell division and have been causally linked to chromosomal instability and cancer. Here, we report that an increase in the number of mature centrosomes, generated by disrupting cytokinesis or forcing centrosome overduplication, triggers the activation of the PIDDosome multiprotein complex, leading to Caspase-2-mediated MDM2 cleavage, p53 stabilization, and p21-dependent cell cycle arrest...
January 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28121078/research-highlights
#12
(no author information available yet)
In this issue, we highlight work from Cecchinato et al. revealing a technique for restoring chemotaxis in HIV-infected Th17 cells, a study by Wei et al. showing that Yersinia pestis YopM is an E3 ligase that can regulate host inflammasomes, a paper by Prokesch et al. reporting that p53 regulates metabolic adaptation to starvation in normal hepatocytes and work from Singh et al. that shows that Salmonella acquires nutrients from host cells by hijacking chaperone-mediated autophagy.
January 2017: FEBS Journal
https://www.readbyqxmd.com/read/28119452/microrna-375-is-induced-in-cisplatin-nephrotoxicity-to-repress-hepatocyte-nuclear-factor-1-%C3%AE
#13
Jielu Hao, Qiang Lou, Qingqing Wei, Shuqin Mei, Lin Li, Guangyu Wu, Qing-Sheng Mi, Changlin Mei, Zheng Dong
Nephrotoxicity is a major adverse effect of cisplatin-mediated chemotherapy in cancer patients. The pathogenesis of cisplatin-induced nephrotoxicity remains largely unclear, making it difficult to design effective renoprotective approaches. Here, we have examined the role of microRNAs (miRNAs) in cisplatin-induced nephrotoxicity. We show that cisplatin nephrotoxicity was not affected by overall depletion of both beneficial and detrimental miRNAs from kidney proximal tubular cells in mice in which the miRNA-generating enzyme Dicer had been conditionally knocked out...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28088184/anti-hepatitis-b-virus-hbv-response-of-imiquimod-based-toll-like-receptor-7-ligand-in-hbv-positive-human-hepatocelluar-carcinoma-cell-line
#14
Dipanwita Das, Isha Sengupta, Neelakshi Sarkar, Ananya Pal, Debraj Saha, Manikankana Bandopadhyay, Chandrima Das, Jimmy Narayan, Shivaram Prasad Singh, Sekhar Chakrabarti, Runu Chakravarty
BACKGROUND: Toll like receptors (TLRs) play an important role in innate immunity and various studies suggest that TLRs play a crucial role in pathogenesis of hepatitis B virus (HBV) infection. The present study aims in looking into the status of crucial host and viral gene expression on inciting TLR7. METHODS: The transcription of TLR7 pathway signaling molecules and HBV DNA viral load were quantified by Real Time-PCR after stimulation of TLR7 with its imiquimod based ligand, R837...
January 14, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28075444/the-role-of-lncrna-malat1-in-the-regulation-of-hepatocyte-proliferation-during-liver-regeneration
#15
Cuicui Li, Lei Chang, Zhiquan Chen, Zhongzhong Liu, Yanfeng Wang, Qifa Ye
Exploring the biological functions of long non-coding RNAs (lncRNAs) has come to the foreground in recent years. Studies have indicated that the lncRNA metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) not only regulates tumorigenesis in hepatocellular carcinoma, but also controls cell cycle progression in hematopoietic cells. The present study was designed to investigate the biological role of lncRNA MALAT1 in liver regeneration. We carried out a series of assays during liver regeneration following 2/3 partial hepatectomy in mice...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28059455/acetoacetate-induces-hepatocytes-apoptosis-by-the-ros-mediated-mapks-pathway-in-ketotic-cows
#16
Xiliang Du, Zhen Shi, Zhicheng Peng, Chenxu Zhao, Yuming Zhang, Zhe Wang, Xiaobing Li, Guowen Liu, Xinwei Li
Dairy cows with ketosis are characterized by oxidative stress, hepatic damage, and hyperketonemia. Acetoacetate (AA) is the main component of ketone bodies in ketotic cows, and is associated with the above pathological process. However, the potential mechanism was not illuminated. Therefore, the aim of this study was to investigate the mechanism of AA-induced hepatic oxidative damage in ketotic cows. Compared with healthy cows, ketotic cows exhibited severe oxidative stress and hepatic damage. Moreover, the extent of hepatic damage and oxidative stress had a positive relationship with the AA levels...
January 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27956228/genome-wide-crispr-screen-identifies-regulators-of-mitogen-activated-protein-kinase-as-suppressors-of-liver-tumors-in-mice
#17
Chun-Qing Song, Yingxiang Li, Haiwei Mou, Jill Moore, Angela Park, Yotsawat Pomyen, Soren Hough, Zachary Kennedy, Andrew Fischer, Hao Yin, Daniel G Anderson, Darryl Conte, Lars Zender, Xin Wei Wang, Snorri Thorgeirsson, Zhiping Weng, Wen Xue
BACKGROUND & AIMS: It has been a challenge to identify liver tumor suppressors or oncogenes due to the genetic heterogeneity of these tumors. We performed a genome-wide screen to identify suppressors of liver tumor formation in mice, using CRISPR-mediated genome editing. METHODS: We performed a genome-wide CRISPR/Cas9-based knockout screen of P53-null mouse embryonic liver progenitor cells that overexpressed MYC. We infected p53(-/-);Myc;Cas9 hepatocytes with the mGeCKOa lentiviral library of 67,000 single-guide RNAs (sgRNAs), targeting 20,611 mouse genes, and transplanted the transduced cells subcutaneously into nude mice...
April 2017: Gastroenterology
https://www.readbyqxmd.com/read/27902328/hepatitis-c-virus-core-activates-proteasomal-activator-28%C3%AE-expression-via-upregulation-of-p53-levels-to-control-virus-propagation
#18
Juri Kwak, Indira Tiwari, Kyung Lib Jang
The proteasomal activator 28γ (PA28γ), frequently overexpressed in hepatocellular carcinoma, is believed to play several important roles in hepatitis C virus (HCV) replication and viral pathogenesis. However, the underlying mechanism for PA28γ overexpression in hepatocellular carcinoma 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...
January 2017: 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
#19
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
#20
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
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