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p53 hepatocyte

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https://www.readbyqxmd.com/read/29218508/use-of-huh6-and-other-human-derived-hepatoma-lines-for-the-detection-of-genotoxins-a-new-hope-for-laboratory-animals
#1
Monika Waldherr, Miroslav Mišík, Franziska Ferk, Jana Tomc, Bojana Žegura, Metka Filipič, Wolfgang Mikulits, Sören Mai, Oskar Haas, Wolfgang W Huber, Elisabeth Haslinger, Siegfried Knasmüller
Cell lines which are currently used in genotoxicity tests lack enzymes which activate/detoxify mutagens. Therefore, rodent-derived liver preparations are used which reflect their metabolism in humans only partly; as a consequence misleading results are often obtained. Previous findings suggest that certain liver cell lines express phase I/II enzymes and detect promutagens without activation; however, their use is hampered by different shortcomings. The aim of this study was the identification of a suitable cell line...
December 7, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29159818/c-ebp%C3%AE-dependent-pre-neoplastic-tumor-foci-are-the-origin-of-hepatocellular-carcinoma-and-aggressive-pediatric-liver-cancer
#2
Ashley Cast, Leila Valanejad, Mary Wright, Phuong Nguyen, Anita Gupta, Liqin Zhu, Soona Shin, Nikolai Timchenko
Recent publications show that classic hepatoblastoma (HBL) is the result of failure of hepatic stem cells to differentiate into hepatocytes; while hepatocellular carcinoma (HCC) is caused by the de-differentiation of hepatocytes into Cancer Stem Cells (CSCs). However, the mechanisms of aggressive HBL and mechanisms that cause de-differentiation of hepatocytes into CSCs are unknown. We found that, similar to HCC but opposite to classic HBL, aggressive HBL is the result of de-differentiation of hepatocytes into CSCs...
November 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29156683/shycd-induces-ape1-ref-1-subcellular-localization-to-regulate-the-p53-apoptosis-signaling-pathway-in-the-prevention-and-treatment-of-acute-on-chronic-liver-failure
#3
Jianxin Diao, Haiye Li, Wei Huang, Wenxiao Ma, Huan Dai, Yawei Liu, Ming Wang, He Yu Hua, Jinying Ou, Xiaomin Sun, Xuegang Sun, Yungao Yang
Background & Aims: San huang yin chi decoction(SHYCD) is derived from the yin chen hao decoction, a well-known and canonical Chinese medicine formula from the "Treatise on Febrile Diseases". Over the past decade, SHYCD has been used to treat and prevent the liver cirrhosis and liver failure. In the present study, we investigated the effects of SHYCD for acute on chronic liver failure(ACLF) and explored its potential mechanism. an ACLF rat model, which induced by carbon tetrachloride (CCl4) combined with D-galactosamine (D-GalN) and lipopolysaccharide(LPS), was used and confirmed by B-ultrasound analysis...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29068287/hepatitis-b-virus-x-protein-suppresses-all-trans-retinoic-acid-induced-apoptosis-in-human-hepatocytes-by-repressing-p14-expression-via-dna-methylation
#4
Jung-Hye Choi, Hyerin Jeong, Kyung Lib Jang
All-trans retinoic acid (ATRA), the most biologically active metabolite of vitamin A, is known to activate p14 expression via promoter hypermethylation to induce p53-dependent apoptosis in human hepatocytes. In this study, we found that the oncogenic hepatitis B virus (HBV) X protein (HBx) of HBV, derived from both overexpression and 1.2-mer replicon systems, suppresses ATRA-induced apoptosis in p53-positive human hepatocytes. For this effect, HBx upregulated both protein and enzyme activity levels of DNA methyltransferase 1, 3a and 3b, in the presence of ATRA and thereby inhibited p14 expression via promoter hypermethylation, resulting in inactivation of the p14-mouse double minute 2 pathway and subsequent downregulation of p53 levels...
November 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29032040/effects-of-dietary-ginkgo-biloba-leaf-extract-on-growth-performance-plasma-biochemical-parameters-fish-composition-immune-responses-liver-histology-and-immune-and-apoptosis-related-genes-expression-of-hybrid-grouper-epinephelus-lanceolatus%C3%A2-%C3%A3-epinephelus-fuscoguttatus%C3%A2
#5
Xiaohong Tan, Zhenzhu Sun, Qingying Liu, Huaqun Ye, Cuiyun Zou, Chaoxia Ye, Anli Wang, Heizhao Lin
For thousands of years, leaves from the Ginkgo biloba tree have been a common treatment in Chinese medicine. The present study was conducted to investigate the effects of dietary ginkgo biloba leaf extract (GBE) supplementation on growth performance, plasma biochemical parameters, fish composition, immune responses, liver histology, and immune and apoptosis-related genes expression of hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀) fed high lipid diets. A basal diet supplemented with GBE at 0, 0...
October 12, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29027248/ursodeoxycholic-acid-protects-cardiomyocytes-against-cobalt-chloride-induced-hypoxia-by-regulating-transcriptional-mediator-of-cells-stress-hypoxia-inducible-factor-1%C3%AE-and-p53-protein
#6
Anis Syamimi Mohamed, Noorul Izzati Hanafi, Siti Hamimah Sheikh Abdul Kadir, Julina Md Noor, Narimah Abdul Hamid Hasani, Sharaniza Ab Rahim, Rosfaiizah Siran
In hepatocytes, ursodeoxycholic acid (UDCA) activates cell signalling pathways such as p53, intracellular calcium ([Ca(2+) ]i ), and sphingosine-1-phosphate (S1P)-receptor via Gαi -coupled-receptor. Recently, UDCA has been shown to protect the heart against hypoxia-reoxygenation injury. However, it is not clear whether UDCA cardioprotection against hypoxia acts through a transcriptional mediator of cells stress, HIF-1α and p53. Therefore, in here, we aimed to investigate whether UDCA could protect cardiomyocytes (CMs) against hypoxia by regulating expression of HIF-1α, p53, [Ca(2+) ]i , and S1P-Gαi -coupled-receptor...
October 12, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29018245/transient-postnatal-overfeeding-causes-liver-stress-induced-premature-senescence-in-adult-mice
#7
Catherine Yzydorczyk, Na Li, Hassib Chehade, Dolores Mosig, Mickael Bidho, Basile Keshavjee, Jean Baptiste Armengaud, Katya Nardou, Benazir Siddeek, Mohamed Benahmed, Catherine Vergely, Umberto Simeoni
Unbalanced nutrition early in life is increasingly recognized as an important factor in the development of chronic, non-communicable diseases at adulthood, including metabolic diseases. We aimed to determine whether transient postnatal overfeeding (OF) leads to liver stress-induced premature senescence (SIPS) of hepatocytes in association with liver structure and hepatic function alterations. Litters sizes of male C57BL/6 mice were adjusted to 9 pups (normal feeding, NF) or reduced to 3 pups during the lactation period to induce transient postnatal OF...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28993697/n-terminal-gelsolin-fragment-potentiates-trail-mediated-death-in-resistant-hepatoma-cells
#8
Keith Meyer, Young-Chan Kwon, Ratna B Ray, Ranjit Ray
TNF-α related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells, without damaging normal cells. TRAIL receptors facilitate induction of apoptosis for selective elimination of malignant cells. However, some cancer cells have developed resistances to TRAIL which limits anticancer potential. Gelsolin, a multifunctional actin-binding protein, mediates cell death involving the TRAIL receptors in the hepatic stellate cell line, LX2. Here, we have shown that conditioned medium (CM) containing gelsolin fragments or an N-terminal gelsolin fragment (amino acid residues 1-70) in the presence of TRAIL impairs cell viability of TRAIL resistant transformed human hepatocytes (HepG2)...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28991164/differential-expression-profile-of-lncrnas-from-primary-human-hepatocytes-following-deet-and-fipronil-exposure
#9
Robert D Mitchell Iii, Andrew D Wallace, Ernest Hodgson, R Michael Roe
While the synthesis and use of new chemical compounds is at an all-time high, the study of their potential impact on human health is quickly falling behind, and new methods are needed to assess their impact. We chose to examine the effects of two common environmental chemicals, the insect repellent N,N-diethyl-m-toluamide (DEET) and the insecticide fluocyanobenpyrazole (fipronil), on transcript levels of long non-protein coding RNAs (lncRNAs) in primary human hepatocytes using a global RNA-Seq approach. While lncRNAs are believed to play a critical role in numerous important biological processes, many still remain uncharacterized, and their functions and modes of action remain largely unclear, especially in relation to environmental chemicals...
October 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28981157/effects-of-melatonin-on-fatty-liver-disease-the-role-of-nr4a1-dna-pkcs-p53-pathway-mitochondrial-fission-and-mitophagy
#10
Hao Zhou, Wenjuan Du, Ye Li, Chen Shi, Nan Hu, Sai Ma, Weihu Wang, Jun Ren
Mitochondrial dysfunction has been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) through poorly defined mechanisms. Melatonin supplementation has been found to protect liver function in diabetes and obesity. Here, we intensively explored the role and mechanism of melatonin in the development of NAFLD. We demonstrated that the onset of diet-induced NAFLD greatly caused NR4A1 upregulation in hepatocytes, leading to the activation of DNA-PKcs and p53. On the one hand, p53 aided Drp1 migration in the mitochondria and consequently drove mitochondrial fission...
October 5, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28978056/vitamin-d-deficiency-causes-insulin-resistance-by-provoking-oxidative-stress-in-hepatocytes
#11
Sha Tao, Qi Yuan, Li Mao, Feng-Li Chen, Feng Ji, Zhao-Hui Cui
Vitamin D deficiency could cause insulin resistance. However, the underlying mechanisms are unclear. The 1α-Hydroxylase ["1α(OH)ase"] is a key enzyme for activate vitamin D3 synthesis. Here, we show that 1α(OH)ase stable knockdown by targeted shRNA led to vitamin D3 depletion in L02 hepatocytes. 1α(OH)ase silence also inhibited insulin-induced downstream signaling (IRS-1, ERK and AKT) transduction and glucose transporter 4 expression. Further, 1α(OH)ase shRNA in L02 hepatocytes led to significant reactive oxygen species production, p53-p21 activation and DNA damages...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968425/gene-expression-profiling-of-hepatocarcinogenesis-in-a-mouse-model-of-chronic-hepatitis-b
#12
Takuto Nosaka, Tatsushi Naito, Katsushi Hiramatsu, Masahiro Ohtani, Tomoyuki Nemoto, Hiroyuki Marusawa, Ning Ma, Yusuke Hiraku, Shosuke Kawanishi, Taro Yamashita, Shuichi Kaneko, Yasunari Nakamoto
BACKGROUND: Hepatocellular carcinoma (HCC) is a common complication of chronic viral hepatitis. In support of this notion, we have reported that hepatitis B surface antigen (HBsAg)-specific CD8+ T lymphocytes critically contribute to inducing chronic liver cell injury that exerts high carcinogenic potential in a hepatitis B virus (HBV) transgenic mouse model. The dynamics of the molecular signatures responsible for hepatocellular carcinogenesis are not fully understood. The current study was designed to determine the serial changes in gene expression profiles in a model of chronic immune-mediated hepatitis...
2017: PloS One
https://www.readbyqxmd.com/read/28954565/endometrial-serous-carcinoma-with-clear-cell-change-frequency-and-immunohistochemical-analysis
#13
Nosaibah Hariri, Morad Qarmali, Oluwole Fadare
The diagnostic distinction between endometrial serous carcinoma (ESC) and endometrial clear-cell carcinoma (CCC) may occasionally be problematic, and one potentially contributing factor is the finding of clear cells in otherwise classic cases of ESC. This study aimed to define the frequency of this finding and comparatively assessed the immunophenotype of the clear cells. A review of 56 cases of ESC identified 8 (14.28%) with clear cells, representing 1% to 20% (median 7.5) of tumoral volume in these cases...
September 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28919777/synaptotagmin-7-is-overexpressed-in-hepatocellular-carcinoma-and-regulates-hepatocellular-carcinoma-cell-proliferation-via-chk1-p53-signaling
#14
Hao Jin, Geliang Xu, Qiang Zhang, Qing Pang, Meifang Fang
BACKGROUND: Synaptotagmin-7 (Syt-7) is a member of the synaptotagmin (Syt) family, which plays an important role in many physiological and pathological processes. However, to the best of our knowledge, there is no study describing its function in tumors, particularly in hepatocellular carcinoma (HCC). Therefore, in this study, we examined the role of Syt-7 in HCC and attempted to elucidate its underlying mechanism. MATERIALS AND METHODS: We examined the expression levels of Syt-7 in HCC cell lines and normal hepatocytes by real-time quantitative polymerase chain reaction analysis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28918601/effects-of-phoxim-induced-hepatotoxicity-on-sd-rats-and-the-protection-of-vitamin-e
#15
Jing Zhang, Wentao Song, Yuecheng Sun, Anshan Shan
Currently, public pay more attention to the adverse effect of organophosphate pesticides on human and animal health and on the environment in developing nations. Vitamin E may protect the hepatocyte and increase the function of liver. The study was to investigate the effects of phoxim-induced hepatotoxicity on Sprague Dawley (SD) rats and the protection of vitamin E. SD rats received by gavage 180 mg kg(-1) (per body weight) of phoxim, 200 mg kg(-1) (per body weight) of vitamin E, and phoxim + vitamin E...
November 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28910492/p53-mediated-regulation-of-bile-acid-disposition-attenuates-cholic-acid-induced-cholestasis-in-mice
#16
Pan Chen, Dongshun Li, Yixin Chen, Jiahong Sun, Kaili Fu, Lihuan Guan, Huizhen Zhang, Yiming Jiang, Xi Li, Xuezhen Zeng, Xiao Chen, Min Huang, Huichang Bi
BACKGROUND AND PURPOSE: The tumour suppressor p53 is traditionally recognized as a surveillance molecule to preserve genome integrity. Recent studies have demonstrated that it contributes to metabolic diseases. Here, we investigated the role of p53 in the regulation of bile acid disposition and cholestasis. EXPERIMENTAL APPROACH: The bile acid disposition-related gene expression profile affected by p53 activation was assessed in mouse primary hepatocytes with p53 depletion and in Trp53-null mice...
September 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28886428/tris-2-chloroethyl-phosphate-induces-senescence-like-phenotype-of-hepatocytes-via-the-p21-waf1-cip1-rb-pathway-in-a-p53-independent-manner
#17
Wenjuan Zhang, Youjian Zhang, Jian Hou, Tian Xu, Wenjun Yin, Wei Xiong, Wenhong Lu, Hongyan Zheng, Jun Chen, Jing Yuan
Tris (2-chloroethyl) phosphate (TCEP) has been widely used as a plasticizer and flame retardant. TCEP as a potential carcinogen is often detected in the occupational and nature environments. To investigate effects of TCEP on human hepatocytes, we assessed cell growth rate, cellular membrane integrity, senescence-associated β-galactosidase (SA-β-Gal) activity and analyzed expression of regulators involved in the p53-p21(Waf1/Cip1)-Rb pathway in TCEP-treated L02 cells. The results showed TCEP increased the percentage of SA-β-Gal positive cells, decreased IL-6 levels, down-regulated the regulators of p38MAPK-NF-κB pathways, but up-regulated the regulators of p21(Waf1/Cip1)-Rb pathway in L02 cells...
August 31, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28821164/cape-gooseberry-physalis-peruviana-juice-as-a-modulator-agent-for-hepatocellular-carcinoma-linked-apoptosis-and-cell-cycle-arrest
#18
Hanaa A Hassan, Hanaa M Serag, Makwan S Qadir, Mohamed Fawzy Ramadan
BACKGROUND: Cape gooseberry (Physalis peruviana) fruit is highly nutritious with high content of health-promoting compounds including minerals, phenolic compounds, as well as vitamins A and C. Physalis peruviana fruits were used as mutagenic, antispasmodic, anticoagulant, and antileucemis agents. OBJECTIVE: The objective of the present work was to study the role of cape gooseberry juice (CG) as a natural modulator agent for adverse aspects associated with hepatocellular carcinoma (HCC)...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28818686/methyleugenol-and-selected-oxidative-metabolites-affect-dna-damage-signalling-pathways-and-induce-apoptosis-in-human-colon-tumour-ht29-cells
#19
Isabel Anna Maria Groh, Melanie Esselen
Previously the food carcinogen methyleugenol was found to be cytotoxic and genotoxic in multiple cell lines and in primary hepatocytes. In this study, the question addressed was whether methyleugenol and the selected oxidative metabolites, 1'-hydroxymethyleugenol, methyleugenol-2',3'-epoxide and 3'-oxomethylisoeugenol trigger a DNA damage response in the human colon carcinoma HT29 cell line. Most notably investigations by flow cytometry revealed that the metabolites induce an accumulation of HT29 cells in the G2 phase of the cell cycle...
August 14, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28808340/kr%C3%A3-ppel-like-factor-6-is-a-transcriptional-activator-of-autophagy-in-acute-liver-injury
#20
Svenja Sydor, Paul Manka, Jan Best, Sami Jafoui, Jan-Peter Sowa, Miguel Eugenio Zoubek, Virginia Hernandez-Gea, Francisco Javier Cubero, Julia Kälsch, Diana Vetter, Maria Isabel Fiel, Yujin Hoshida, C Billie Bian, Leonard J Nelson, Han Moshage, Klaas Nico Faber, Andreas Paul, Hideo A Baba, Guido Gerken, Scott L Friedman, Ali Canbay, Lars P Bechmann
Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)-treated mice...
August 14, 2017: Scientific Reports
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