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Epigenetics liver

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https://www.readbyqxmd.com/read/27912059/microbiota-diurnal-rhythmicity-programs-host-transcriptome-oscillations
#1
Christoph A Thaiss, Maayan Levy, Tal Korem, Lenka Dohnalová, Hagit Shapiro, Diego A Jaitin, Eyal David, Deborah R Winter, Meital Gury-BenAri, Evgeny Tatirovsky, Timur Tuganbaev, Sara Federici, Niv Zmora, David Zeevi, Mally Dori-Bachash, Meirav Pevsner-Fischer, Elena Kartvelishvily, Alexander Brandis, Alon Harmelin, Oren Shibolet, Zamir Halpern, Kenya Honda, Ido Amit, Eran Segal, Eran Elinav
The intestinal microbiota undergoes diurnal compositional and functional oscillations that affect metabolic homeostasis, but the mechanisms by which the rhythmic microbiota influences host circadian activity remain elusive. Using integrated multi-omics and imaging approaches, we demonstrate that the gut microbiota features oscillating biogeographical localization and metabolome patterns that determine the rhythmic exposure of the intestinal epithelium to different bacterial species and their metabolites over the course of a day...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27911095/epigenetic-alterations-in-blood-mirror-age-associated-dna-methylation-and-gene-expression-changes-in-human-liver
#2
Madhusudhan Bysani, Alexander Perfilyev, Vanessa D de Mello, Tina Rönn, Emma Nilsson, Jussi Pihlajamäki, Charlotte Ling
AIM: To study the impact of aging on DNA methylation and mRNA expression in human liver. EXPERIMENTAL PROCEDURES: We analysed genome-wide DNA methylation and gene expression in human liver samples using Illumina 450K and HumanHT12 expression BeadChip arrays. RESULTS: DNA methylation analysis of ∼455,000 CpG sites in human liver revealed that age was significantly associated with altered DNA methylation of 20,396 CpG sites. Comparison of liver methylation data with published methylation data in other tissues showed that vast majority of the age-associated significant CpG sites overlapped between liver and blood, whereas a smaller overlap was found between liver and pancreatic islets or adipose tissue, respectively...
December 2, 2016: Epigenomics
https://www.readbyqxmd.com/read/27909741/the-role-of-epigenetic-modifiers-in-extended-cultures-of-functional-hepatocyte-like-cells-derived-from-human-neonatal-mesenchymal-stem-cells
#3
M Cipriano, J C Correia, S P Camões, N G Oliveira, P Cruz, H Cruz, M Castro, J L Ruas, J M Santos, J P Miranda
The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO)...
December 1, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27900050/molecular-alterations-in-the-carcinogenesis-and-progression-of-hepatocellular-carcinoma-tumor-factors-and-background-liver-factors
#4
Yoshikuni Inokawa, Kenichi Inaoka, Fuminori Sonohara, Masamichi Hayashi, Mitsuro Kanda, Shuji Nomoto
Although hepatocellular carcinoma (HCC) is associated with poor prognosis worldwide, the molecular mechanisms underlying the carcinogenesis and progression of this disease remain unclear. Several tumor characteristics have previously been demonstrated to be prognostic factors of survival following hepatic resection, or the recurrence of HCC or other types of cancer. Comparisons of normal tissues and HCC tumor tissues have revealed the presence of numerous molecular alterations in HCC, including genetic and epigenetic mechanisms, particularly mutations in certain genes and DNA methylation in the promoter regions of tumor-suppressor genes...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27893715/tgf%C3%AE-promotes-mesenchymal-phenotype-of-pancreatic-cancer-cells-in-part-through-epigenetic-activation-of-vav1
#5
P-H Huang, P-J Lu, L-Y Ding, P-C Chu, W-Y Hsu, C-S Chen, C-C Tsao, B-H Chen, C-T Lee, Y-S Shan, C-S Chen
The highly homeostasis-resistant nature of cancer cells leads to their escape from treatment and to liver metastasis, which in turn makes pancreatic ductal adenocarcinoma (PDAC) difficult to treat, especially the squamous/epithelial-to-mesenchymal transition (EMT)-like subtype. As the molecular mechanisms underlying tumour heterogeneity remain elusive, we investigated whether epigenetic regulation might explain inter-individual differences in the progression of specific subtypes. DNA methylation profiling performed on cancer tissues prior to chemo/radiotherapy identified one hypermethylated CpG site (CpG6882469) in the VAV1 gene body that was correlated with demethylation of two promoter CpGs (CpG6772370/CpG6772811) in both PDAC and peripheral blood...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27889327/epigenetics-in-non-alcoholic-fatty-liver-disease
#6
REVIEW
Jooho Lee, Yuri Kim, Simonetta Friso, Sang-Woon Choi
Non-alcoholic fatty liver disease (NAFLD), a common hepatic disorder ranging from simple steatosis through steatohepatitis to fibrosis and cirrhosis, is an emerging health concern. NAFLD is a pathologic condition characterized by the buildup of extra fat in liver cells that is not caused by alcohol consumption. Excess hepatic fat accumulation results from increased delivery of triglycerides (TG) to the liver or conversion of surplus carbohydrates to TG. Importantly, a subgroup of NAFLD results in hepatocellular injury and inflammation, which is referred to as non-alcoholic steatohepatitis (NASH), and may progress to irreversible cirrhosis and hepatocellular carcinoma (HCC)...
November 23, 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27869795/cd68-macrosialin-not-just-a-histochemical-marker
#7
Dimitry A Chistiakov, Murry C Killingsworth, Veronika A Myasoedova, Alexander N Orekhov, Yuri V Bobryshev
CD68 is a heavily glycosylated glycoprotein that is highly expressed in macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as a valuable cytochemical marker to immunostain monocyte/macrophages in the histochemical analysis of inflamed tissues, tumor tissues, and other immunohistopathological applications. CD68 alone or in combination with other cell markers of tumor-associated macrophages showed a good predictive value as a prognostic marker of survival in cancer patients. Lowression of CD68 was found in the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells, etc), and tumor cells...
November 21, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27860427/the-role-of-adipoq-methylation-in-experimental-non-alcoholic-fatty-liver-disease
#8
Wen Ji Chen, Bing Cai, Hui Ting Chen, Chuang Yu Cao, Yan Lei Du, Yu Yuan Li, Yu Qiang Nie, Yong Jian Zhou
AIM: To investigate the role of adiponectin gene (ADIPOQ) DNA methylation and curcumin in the intervention of non-alcoholic fatty liver disease (NAFLD). METHODS: Twenty-four Sprague-Dawley (SD) rats were divided into three groups: normal, NAFLD and curcumin groups. The genetic and epigenetic features of each rat were tested. RT-PCR and western blot were used to quantify the ADIPOQ mRNA and protein level respectively. Bisulfite sequencing PCR (BSP) was used to detect the extent of methylation in rat livers...
November 9, 2016: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/27858497/high-fat-diet-and-exercise-lead-to-a-disrupted-and-pathogenic-dna-methylome-in-mouse-liver
#9
Dan Zhou, Ryan A Hlady, Marissa J Schafer, Thomas A White, Chen Liu, Jeong-Hyeon Choi, Jordan D Miller, Lewis R Roberts, Nathan K LeBrasseur, Keith D Robertson
High-fat diet consumption and sedentary life style elevates risk for obesity, non-alcoholic fatty liver disease, and cancer. Exercise training conveys health benefits in populations with or without these chronic conditions. Diet and exercise regulate gene expression by mediating epigenetic mechanisms in many tissues; however, such effects are poorly documented in the liver, a central metabolic organ. To dissect the consequences of diet and exercise on the liver epigenome, we measured DNA methylation, using reduced representation bisulfite sequencing, and transcription, using RNA-seq, in mice maintained on a fast food diet with sedentary lifestyle or exercise, compared to control diet with and without exercise...
November 18, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27855367/the-epigenetically-regulated-microrna-378a-targets-tgf-%C3%AE-2-in-tgf-%C3%AE-1-treated-hepatic-stellate-cells
#10
Fujun Yu, Jianhuan Yang, Kate Huang, Xiaodong Pan, BiCheng Chen, Peihong Dong, Jianjian Zheng
BACKGROUND/AIMS: In liver fibrosis, the activation of hepatic stellate cells (HSCs) is considered as a pivotal event. It is well known that transforming growth factor-β1 (TGF-β1) is the main stimuli factor responsible for HSC activation. microRNAs (miRNAs), regulating various biological processes, have recently been shown to be involved in HSC activation. A recent study reported that deficiency of miR-378a contributes to cardiac fibrosis via TGF-β1-dependent paracrine mechanism. However, the involvement of miR-378a and its roles in TGF-β1-induced HSC activation remains largely unknown...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27843535/insights-for-hepatitis-c-virus-related-hepatocellular-carcinoma-genetic-biomarkers-early-diagnosis-and-therapeutic-intervention
#11
REVIEW
Wafaa M Ezzat, Khalda Sayed Amr
The current review explores the role of emerging molecular contributing factors in liver carcinogenesis on top of hepatitis C virus (HCV). Here we will try to discuss the role genetic and epigenetic factors in pathogenesis of hepatocellular carcinoma. Understanding the role of these factors will help in discovering the mystery of liver carcinogenesis on top of chronic HCV infection. Moreover, use of the studied molecular factors will provide the hepatologists with tailored diagnostic promising biomarkers and flatten the way for establishment of emerging molecular treatment based on exploring the molecular subscription of this aggressive liver cancer...
October 28, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27830358/curcumin-inhibits-growth-of-human-breast-cancer-cells-through-demethylation-of-dlc1-promoter
#12
Yufei Liu, Jun Zhou, Yuchang Hu, Junjie Wang, Chengfu Yuan
The heterogeneity of breast cancer makes it a challenging solid tumor to diagnose and treat. A tumor suppressor Deleted in Liver Cancer 1 (DLC1) has been reported to be down-regulated or even silenced in several kinds of cancer including breast cancer. Curcumin has been reported to modulate the growth of tumor cells through regulation of multiple cell signaling pathways and modulate epigenetic changes by CpG demethylation of many tumor suppressor genes. This study was designed to investigate the effect of curcumin on the expression of Deleted in Liver Cancer 1 (DLC1) in human breast cancer cell line MDA-MB-361 and the underlying mechanism in vitro and in vivo...
November 10, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27825936/new-insights-into-the-molecular-mechanisms-of-chemical-carcinogenesis-in-vivo-adduction-of-histone-h2b-by-a-reactive-metabolite-of-the-chemical-carcinogen-furan
#13
João Nunes, Inês L Martins, Catarina Charneira, Igor P Pogribny, Aline de Conti, Frederick A Beland, M Matilde Marques, Cristina C Jacob, Alexandra M M Antunes
Furan is a rodent hepatocarcinogen ubiquitously found in the environment and heat-processed foods. Furan undergoes cytochrome P450 2E1-catalyzed bioactivation to cis-2-butene-1,4-dial (BDA), which has been shown to form an electrophilic conjugate (GSH-BDA) with glutathione. Both BDA and GSH-BDA yield covalent adducts with lysine residues in proteins. Dose- and time-dependent epigenetic histone alterations have been observed in furan-treated rats. While the covalent modification of histones by chemical carcinogens has long been proposed, histone-carcinogen adducts have eluded detection in vivo...
November 5, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27824951/epigenetic-signatures-at-aqp3-and-socs3-engage-in-low-grade-inflammation-across-different-tissues
#14
Carola Marzi, Lesca M Holdt, Giovanni Fiorito, Pei-Chien Tsai, Anja Kretschmer, Simone Wahl, Simonetta Guarrera, Daniel Teupser, Tim D Spector, Licia Iacoviello, Carlotta Sacerdote, Konstantin Strauch, Serene Lee, Wolfgang E Thasler, Annette Peters, Barbara Thorand, Petra Wolf, Holger Prokisch, Rosario Tumino, Christian Gieger, Vittorio Krogh, Salvatore Panico, Jordana T Bell, Giuseppe Matullo, Melanie Waldenberger, Harald Grallert, Wolfgang Koenig
BACKGROUND: Elevated levels of C-reactive protein (CRP, determined by a high-sensitivity assay) indicate low-grade inflammation which is implicated in many age-related disorders. Epigenetic studies on CRP might discover molecular mechanisms underlying CRP regulation. We aimed to identify DNA methylation sites related to CRP concentrations in cells and tissues regulating low-grade inflammation. RESULTS: Genome-wide DNA methylation was measured in peripheral blood in 1,741 participants of the KORA F4 study using Illumina HumanMethylation450 BeadChip arrays...
2016: PloS One
https://www.readbyqxmd.com/read/27824486/novel-epigenetic-biomarkers-mediating-bisphenol-a-exposure-and-metabolic-phenotypes-in-female-mice
#15
Olivia S Anderson, Jung H Kim, Karen E Peterson, Brisa N Sanchez, Karilyn E Sant, Maureen A Sartor, Caren Weinhouse, Dana C Dolinoy
There is compelling evidence that epigenetic modifications link developmental environmental insults to adult disease susceptibility. Animal studies have associated perinatal bisphenol A (BPA) exposure to altered DNA methylation, but these studies are often limited to candidate gene and global non-loci specific approaches. Utilizing an epigenome-wide discovery platform, we elucidate epigenetic alterations in liver tissue from adult offspring (10 months) following perinatal BPA exposure at human physiologically relevant doses (50 ng, 50 μg, and 50 mg BPA/kg diet)...
November 8, 2016: Endocrinology
https://www.readbyqxmd.com/read/27805256/homocysteine-alcoholism-and-its-potential-epigenetic-mechanism
#16
REVIEW
Pradip K Kamat, Carissa J Mallonee, Akash K George, Suresh C Tyagi, Neetu Tyagi
Alcohol is the most socially accepted addictive drug. Alcohol consumption is associated with some health problems such as neurological, cognitive, behavioral deficits, cancer, heart, and liver disease. Mechanisms of alcohol-induced toxicity are presently not yet clear. One of the mechanisms underlying alcohol toxicity has to do with its interaction with amino acid homocysteine (Hcy), which has been linked with brain neurotoxicity. Elevated Hcy impairs with various physiological mechanisms in the body, especially metabolic pathways...
December 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27799657/lkb1-loss-links-serine-metabolism-to-dna-methylation-and-tumorigenesis
#17
Filippos Kottakis, Brandon N Nicolay, Ahlima Roumane, Rahul Karnik, Hongcang Gu, Julia M Nagle, Myriam Boukhali, Michele C Hayward, Yvonne Y Li, Ting Chen, Marc Liesa, Peter S Hammerman, Kwok Kin Wong, D Neil Hayes, Orian S Shirihai, Nicholas J Dyson, Wilhelm Haas, Alexander Meissner, Nabeel Bardeesy
Intermediary metabolism generates substrates for chromatin modification, enabling the potential coupling of metabolic and epigenetic states. Here we identify a network linking metabolic and epigenetic alterations that is central to oncogenic transformation downstream of the liver kinase B1 (LKB1, also known as STK11) tumour suppressor, an integrator of nutrient availability, metabolism and growth. By developing genetically engineered mouse models and primary pancreatic epithelial cells, and employing transcriptional, proteomics, and metabolic analyses, we find that oncogenic cooperation between LKB1 loss and KRAS activation is fuelled by pronounced mTOR-dependent induction of the serine-glycine-one-carbon pathway coupled to S-adenosylmethionine generation...
October 31, 2016: Nature
https://www.readbyqxmd.com/read/27795551/attenuation-of-diet-induced-obesity-and-induction-of-white-fat-browning-with-a-chemical-inhibitor-of-histone-deacetylases
#18
A Ferrari, E Fiorino, R Longo, S Barilla, N Mitro, G Cermenati, M Giudici, D Caruso, A Mai, U Guerrini, E De Fabiani, M Crestani
BACKGROUND/OBJECTIVES: In the last decade a strict link between epigenetics and metabolism has been demonstrated. Histone deacetylases (HDACs) have emerged as key epigenetic regulators involved in metabolic homeostasis in normal and pathologic conditions. Here we investigated the effect of the class I HDAC inhibitor MS-275 in a model of obesity induced by a high fat diet (HFD). METHODS: C57BL6/J male mice were fed HFD for 17 weeks and then randomized in two groups treated intraperitoneally with vehicle (DMSO) or with the class I selective HDAC inhibitor MS-275 every other day for 22 days...
October 31, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27793011/metastasis-suppressing-nid2-an-epigenetically-silenced-gene-in-the-pathogenesis-of-nasopharyngeal-carcinoma-and-esophageal-squamous-cell-carcinoma
#19
Annie Wai Yeeng Chai, Arthur Kwok Leung Cheung, Wei Dai, Josephine Mun Yee Ko, Joseph Chok Yan Ip, Kwok Wah Chan, Dora Lai-Wan Kwong, Wai Tong Ng, Anne Wing Mui Lee, Roger Kai Cheong Ngan, Chun Chung Yau, Stewart Yuk Tung, Victor Ho Fun Lee, Alfred King-Yin Lam, Suja Pillai, Simon Law, Maria Li Lung
Nidogen-2 (NID2) is a key component of the basement membrane that stabilizes the extracellular matrix (ECM) network. The aim of the study is to analyze the functional roles of NID2 in the pathogenesis of nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC). We performed genome-wide methylation profiling of NPC and ESCC and validated our findings using the methylation-sensitive high-resolution melting (MS-HRM) assay. Results showed that promoter methylation of NID2 was significantly higher in NPC and ESCC samples than in their adjacent non-cancer counterparts...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27781201/molecular-pathogenesis-of-hepatocellular-carcinoma
#20
Daniel Wai-Hung Ho, Regina Cheuk-Lam Lo, Lo-Kong Chan, Irene Oi-Lin Ng
The pathogenesis of hepatocellular carcinoma (HCC) is a multistep process involving the progressive accumulation of molecular alterations pinpointing different molecular and cellular events. The next-generation sequencing technology is facilitating the global and systematic evaluation of molecular landscapes in HCC. There is emerging evidence supporting the importance of cancer metabolism and tumor microenvironment in providing a favorable and supportive niche to expedite HCC development. Moreover, recent studies have identified distinct surface markers of cancer stem cell (CSC) in HCC, and they also put forward the profound involvement of altered signaling pathways and epigenetic modifications in CSCs, in addition to the concomitant drug resistance and metastasis...
October 2016: Liver Cancer
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