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Epigenetics liver

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https://www.readbyqxmd.com/read/28810182/selenium-increases-hepatic-dna-methylation-and-modulates-one-carbon-metabolism-in-the-liver-of-mice
#1
Bodo Speckmann, Sarah Schulz, Franziska Hiller, Deike Hesse, Fabian Schumacher, Burkhard Kleuser, Jürgen Geisel, Rima Obeid, Tilman Grune, Anna P Kipp
The average intake of the essential trace element selenium (Se) is below the recommendation in most European countries, possibly causing sub-optimal expression of selenoproteins. It is still unclear how a suboptimal Se status may affect health. To mimic this situation, mice were fed one of three physiologically relevant amounts of Se. We focused on the liver, the organ most sensitive to changes in the Se supply indicated by hepatic glutathione peroxidase activity. In addition, liver is the main organ for synthesis of methyl groups and glutathione via one-carbon metabolism...
July 9, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28808785/conserved-dna-methylation-combined-with-differential-frontal-cortex-and-cerebellar-expression-distinguishes-c9orf72-associated-and-sporadic-als-and-implicates-serpina1-in-disease
#2
Mark T W Ebbert, Christian A Ross, Luc J Pregent, Rebecca J Lank, Cheng Zhang, Rebecca B Katzman, Karen Jansen-West, Yuping Song, Edroaldo Lummertz da Rocha, Carla Palmucci, Pamela Desaro, Amelia E Robertson, Ana M Caputo, Dennis W Dickson, Kevin B Boylan, Rosa Rademakers, Tamas Ordog, Hu Li, Veronique V Belzil
We previously found C9orf72-associated (c9ALS) and sporadic amyotrophic lateral sclerosis (sALS) brain transcriptomes comprise thousands of defects, among which, some are likely key contributors to ALS pathogenesis. We have now generated complementary methylome data and combine these two data sets to perform a comprehensive "multi-omic" analysis to clarify the molecular mechanisms initiating RNA misregulation in ALS. We found that c9ALS and sALS patients have generally distinct but overlapping methylome profiles, and that the c9ALS- and sALS-affected genes and pathways have similar biological functions, indicating conserved pathobiology in disease...
August 14, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28798080/long-term-programming-effect-of-early-hypoxia-and-high-carbohydrate-diet-at-first-feeding-on-glucose-metabolism-in-rainbow-trout-juveniles
#3
Jingwei Liu, Karine Dias, Elisabeth Plagnes-Juan, Vincent Véron, Stéphane Panserat, Lucie Marandel
Environmental conditions experienced during early life play an important role in the long-term metabolic status of individuals. The present study investigated whether early hypoxia exposure (24 h, 2.5 mg·l(-1), 20% dissolved O2) during embryo stage alone (hypoxic history) or combined with a 5-day high carbohydrate diet (60%) stimulus at first-feeding (high carbohydrate diet history) can affect the glucose metabolism later in life, i.e. in fish juveniles. After 19 weeks of growth, we observed a decrease in final body weight in fish with a high carbohydrate diet history...
August 10, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28796629/hepatic-lipid-accumulation-and-nrf2-expression-following-perinatal-and-peripubertal-exposure-to-bisphenol-a-in-a-mouse-model-of-nonalcoholic-liver-disease
#4
Prajakta C Shimpi, Vijay R More, Maneesha Paranjpe, Ajay C Donepudi, Jaclyn M Goodrich, Dana C Dolinoy, Beverly Rubin, Angela L Slitt
BACKGROUND: Exposure to chemicals during critical windows of development may re-program liver for increased risk of nonalcoholic fatty liver disease (NAFLD). Bisphenol A (BPA), a plastics component, has been described to impart adverse effects during gestational and lactational exposure. Our work has pointed to nuclear factor E2-related factor 2 (Nrf2) being a modulator of hepatic lipid accumulation in models of NAFLD. OBJECTIVES: To determine if chemical exposure can prime liver for steatosis via modulation of NRF2 and epigenetic mechanisms...
August 4, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28778066/inhibition-of-lsd1-epigenetically-attenuates-oral-cancer-growth-and-metastasis
#5
Saqer F Alsaqer, Mustafa M Tashkandi, Vinay K Kartha, Ya-Ting Yang, Yazeed Alkheriji, Andrew Salama, Xaralabos Varelas, Maria Kukuruzinska, Stefano Monti, Manish V Bais
Lysine-specific demethylase 1 (LSD1) is a nuclear histone demethylase and a member of the amine oxidase (AO) family. LSD1 is a flavin-containing AO that specifically catalyzes the demethylation of mono- and di-methylated histone H3 lysine 4 through an FAD-dependent oxidative reaction. LSD1 is inappropriately upregulated in lung, liver, brain and esophageal cancers, where it promotes cancer initiation, progression, and metastasis. However, unlike other lysine-specific demethylases, the role and specific targets of LSD1 in oral squamous cell carcinoma (OSCC) pathogenesis remain unknown...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28759385/physical-activity-sedentary-behaviour-diet-and-cancer-an-update-and-emerging-new-evidence
#6
REVIEW
Jacqueline Kerr, Cheryl Anderson, Scott M Lippman
The lifestyle factors of physical activity, sedentary behaviour, and diet are increasingly being studied for their associations with cancer. Physical activity is inversely associated with and sedentary behaviour is positively (and independently) associated with an increased risk of more than ten types of cancer, including colorectal cancer (and advanced adenomas), endometrial cancers, and breast cancer. The most consistent dietary risk factor for premalignant and invasive breast cancer is alcohol, whether consumed during early or late adult life, even at low levels...
August 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28758427/genome-wide-dna-methylation-profiling-of-the-regenerative-mrl-mpj-mouse-and-two-normal-strains
#7
Bartosz Górnikiewicz, Anna Ronowicz, Piotr Madanecki, Paweł Sachadyn
AIM: We aimed to identify the pivotal differences in the DNA methylation profiles between the regeneration capable MRL/MpJ mouse and reference mouse strains. MATERIALS & METHODS: Global DNA methylation profiling was performed in ear pinnae, bone marrow, spleen, liver and heart from uninjured adult females of the MRL/MpJ and C57BL/6J and BALB/c. RESULTS & CONCLUSION: A number of differentially methylated regions (DMRs) distinguishing between the MRL/MpJ mouse and both references were identified...
July 31, 2017: Epigenomics
https://www.readbyqxmd.com/read/28756210/the-role-of-epigenomic-alterations-in-furan-induced-hepatobiliary-pathologies
#8
Aline de Conti, Frederick A Beland, Igor P Pogribny
Furan, a volatile heterocyclic organic chemical found in a wide spectrum of common human foods, is a liver toxicant and carcinogen in mice and rats. The carcinogenic effects of furan have been attributed to genotoxic and non-genotoxic mechanisms. Among the broad range of non-genotoxic alterations induced by furan, epigenetic alterations are of special interest because of their connection to all other non-genotoxic events. This review summarizes current evidence of alterations for epigenetic mechanisms, including cytosine DNA methylation, histone modifications, and microRNA expression, caused by furan exposure and highlights the role of these aberrations in furan-associated hepatobiliary pathologies...
July 26, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28754290/molecular-epigenetic-targets-for-liver-diseases-current-challenges-and-future-prospects
#9
REVIEW
Robert Zeidler, Bruno Leonardo de Freitas Soares, Augustinus Bader, Shibashish Giri
Advanced chemotherapy fails to treat liver cancer but recent progress in understanding epigenetic modifications have witnessed promising clinical outcomes. Epigenetic alteration is the alteration of epigenomes (surrounding histone proteins) without changing the DNA sequence. Such epigenetic mechanisms include histone modifications such as methylation, acetylation, phosphorylation and sumoylation followed by changes in the genomic architecture. Current studies involving the understanding of small RNA molecules such as noncoding RNA and microRNA in modulating the chromatin architecture are explained in depth here, along with effects of some novel compounds from recent preclinical and clinical evidence...
July 25, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28751453/maternal-modifiers-of-the-infant-gut-microbiota-metabolic-consequences
#10
Christopher M Mulligan, Jacob E Friedman
Transmission of metabolic diseases from mother to child is multifactorial and includes genetic, epigenetic, and environmental influences. Evidence in rodents, humans and non-human primates support the scientific premise that exposure to maternal obesity or high-fat diet during pregnancy creates a long-lasting metabolic signature on the infant innate immune system and the juvenile microbiota which predisposes the offspring to obesity and metabolic diseases. In neonates, gastrointestinal microbes introduced through the mother are noted for their ability to serve as direct inducers/regulators of the infant immune system...
July 27, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28747973/effect-of-ionizing-radiation-at-low-dose-on-transgenerational-carcinogenesis-by-epigenetic-regulation
#11
Lan Li, Jong-Hyun Kim, Hee-Tae Park, Jae-Hoon Lee, Min-Koo Park, Ji-Won Lee, Jeong-Chan Lee, Min-Jae Lee
The objective of this study was to determine the effect of ionizing radiation (IR) exposure of parents on carcinogenesis of the next generation focusing on the epigenetic perspective to clarify the relationship between radiation dose and carcinogenesis in F1 generation SD rats. F1 generations from pregnant rats (F0) who were exposed to gamma rays were divided into three groups according to the dose of radiation: 10 rad, 30 rad, and untreated. They were intraperitoneally injected with 50 mg/kg of diethylnitrosamine (DEN)...
June 2017: Laboratory Animal Research
https://www.readbyqxmd.com/read/28730461/low-salinity-affects-cellularity-dna-methylation-and-mrna-expression-of-igf1-in-the-liver-of-half-smooth-tongue-sole-cynoglossus-semilaevis
#12
Siping Li, Feng He, Haishen Wen, Jifang Li, Yufeng Si, Mingyuan Liu, Yajuan Huang, Lingcai Meng
Animal growth depends on feedback regulation of hormone levels and environmental conditions. Insulin-like growth factor-1 (Igf1) promotes cell growth and differentiation and represses apoptosis and is highly regulated by the environment. Moreover, animals modify physiological homeostasis under stressful conditions through epigenetics and genetic regulatory mechanisms. Therefore, a comprehensive understanding of the effects of salt on fish growth is needed. In this study, half smooth tongue sole (Cynoglossus semilaevis) were subjected to 15‰ salinity for 0, 7, and 60 days (D) to assess the effects of low salinity on liver cellularity and growth...
July 21, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28718980/an-endogenous-dna-adduct-as-a-prognostic-biomarker-for-hepatocarcinogenesis-and-its-prevention-by-theaphenon-e-in-mice
#13
Ying Fu, Shana Silverstein, Justine N McCutcheon, Marcin Dyba, Raghu G Nath, Monika Aggarwal, Heidi Coia, Angela Bai, Jishen Pan, Jiji Jiang, Bhaskar Kallakury, Hongkun Wang, Yu-Wen Zhang, Giuseppe Giaccone, Aiwu Ruth He, Fung-Lung Chung
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, mainly because of its poor prognosis. A valid mechanism-based prognostic biomarker is urgently needed. γ-hydroxy-1,N(2) -propanodeoxyguanosine (γ-OHPdG) is an endogenously formed mutagenic DNA adduct derived from lipid peroxidation (LPO). We examined the relationship of γ-OHPdG with hepatocarcinogenesis in two animal models and its potential role as a prognostic biomarker for recurrence in HCC patients. Bioassays were conducted in the Xeroderma pigmentosum group A knockout mice (Xpa(-/-) ), and the diethylnitrosamine (DEN)-injected mice, both prone to HCC development...
July 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28708602/development-of-hepatoma-derived-bidirectional-oval-like-cells-as-a-model-to-study-host-interactions-with-hepatitis-c-virus-during-differentiation
#14
Masahiko Ito, Suofeng Sun, Takasuke Fukuhara, Ryosuke Suzuki, Miho Tamai, Toyohiko Yamauchi, Kenji Nakashima, Yoh-Ichi Tagawa, Shigetoshi Okazaki, Yoshiharu Matsuura, Takaji Wakita, Tetsuro Suzuki
Directed differentiation of human stem cells including induced pluripotent stem cells into hepatic cells potentially leads to acquired susceptibility to hepatitis C virus (HCV) infection. However, cellular determinants that change their expression during cell reprogramming or hepatic differentiation and are pivotal for supporting the HCV life cycle remain unclear. In this study, by introducing a set of reprogramming factors, we established HuH-7-derived oval-like cell lines, Hdo-17 and -23, which possess features of bipotential liver precursors...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28706189/vertical-sleeve-gastrectomy-reverses-diet-induced-gene-regulatory-changes-impacting-lipid-metabolism
#15
Juan Du, Jingyan Tian, Lili Ding, Candi Trac, Brian Xia, Siming Sun, Dustin E Schones, Wendong Huang
Vertical sleeve gastrectomy (VSG) produces sustainable weight loss, remission of type 2 diabetes (T2D), and improvement of nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms underlying the metabolic benefits of VSG have remained elusive. According to our previous results, diet-induced obesity induces epigenetic modifications to chromatin in mouse liver. We demonstrate here that VSG in C57BL/6J wild-type male mice can reverse these chromatin modifications and thereby impact the expression of key metabolic genes...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696214/epigenetic-regulation-by-agonist-specific-aryl-hydrocarbon-receptor-recruitment-of-metastasis-associated-protein-2-selectively-induces-stanniocalcin-2-expression
#16
Aditya D Joshi, Ekram Hossain, Cornelis J Elferink
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates a plethora of target genes. Historically, the AhR has been studied as a regulator of xenobiotic metabolizing enzyme genes, notably cytochrome P4501A1 encoded by CYP1A1, in response to the exogenous prototypical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AhR activity depends on its binding to the xenobiotic response element (XRE) in partnership with the AhR nuclear translocator (Arnt). Recent studies identified stanniocalcin 2 (Stc2) as a novel AhR target gene responsive to the endogenous AhR agonist cinnabarinic acid (CA)...
September 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28694329/feminization-of-male-mouse-liver-by-persistent-growth-hormone-stimulation-activation-of-sex-biased-transcriptional-networks-and-dynamic-changes-in-chromatin-states
#17
Dana Lau-Corona, Alexander Suvorov, David J Waxman
Sex-dependent pituitary GH secretory profiles--pulsatile in males and persistent in females--regulate sex-biased, STAT5-dependent expression of hundreds of genes in mouse liver, imparting sex differences in hepatic drug/lipid metabolism and disease risk. Here we examine transcriptional and epigenetic changes induced by continuous-GH infusion (cGH) in male mice, which rapidly feminizes the temporal profile of liver STAT5 activity. cGH repressed 86% of male-biased genes and induced 68% of female-biased genes within 4-days; however, several highly female-specific genes showed weak or no feminization, even after 14-days cGH...
July 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28692045/impact-of-histone-demethylase-kdm3a-dependent-ap-1-transactivity-on-hepatotumorigenesis-induced-by-pi3k-activation
#18
T Nakatsuka, K Tateishi, Y Kudo, K Yamamoto, H Nakagawa, H Fujiwara, R Takahashi, K Miyabayashi, Y Asaoka, Y Tanaka, H Ijichi, Y Hirata, M Otsuka, M Kato, J Sakai, M Tachibana, H Aburatani, Y Shinkai, K Koike
Epigenetic gene regulation linked to oncogenic pathways is an important focus of cancer research. KDM3A, a histone H3 lysine 9 (H3K9) demethylase, is known to have a pro-tumorigenic function. Here, we showed that KDM3A contributes to liver tumor formation through the phosphatidylinositol 3-kinase (PI3K) pathway, which is often activated in hepatocellular carcinoma. Loss of Kdm3a attenuated tumor formation in Pik3ca transgenic (Tg) mouse livers. Transcriptome analysis of pre-cancerous liver tissues revealed that the expression of activator protein 1 (AP-1) target genes was induced by PI3K activation, but blunted upon Kdm3a ablation...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28683826/identification-and-characterization-of-a-foxa2-regulated-transcriptional-enhancer-at-a-type-2-diabetes-intronic-locus-that-controls-gckr-expression-in-liver-cells
#19
Maykel López Rodríguez, Dorota Kaminska, Kati Lappalainen, Jussi Pihlajamäki, Minna U Kaikkonen, Markku Laakso
BACKGROUND: Genome-wide association studies (GWAS) have identified more than 100 genetic loci associated with type 2 diabetes (T2D). However, the underlying biological mechanisms for many of these associations remain unknown. GWAS signals close to the glucokinase regulatory protein gene (GCKR) have been reported for lipid and glucose metabolism traits and the risk of T2D. We investigated the regulatory function of an intronic locus at GCKR represented by the lead single nucleotide polymorphism (SNP) rs780094...
July 6, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28667006/whole-genome-and-epigenomic-landscapes-of-etiologically-distinct-subtypes-of-cholangiocarcinoma
#20
Apinya Jusakul, Ioana Cutcutache, Chern Han Yong, Jing Quan Lim, Mi Ni Huang, Nisha Padmanabhan, Vishwa Nellore, Sarinya Kongpetch, Alvin Wei Tian Ng, Ley Moy Ng, Su Pin Choo, Swe Swe Myint, Raynoo Thanan, Sanjanaa Nagarajan, Weng Khong Lim, Cedric Chuan Young Ng, Arnoud Boot, Mo Liu, Choon Kiat Ong, Vikneswari Rajasegaran, Stefanus Lie, Alvin Soon Tiong Lim, Tse Hui Lim, Jing Tan, Jia Liang Loh, John R McPherson, Narong Khuntikeo, Vajaraphongsa Bhudhisawasdi, Puangrat Yongvanit, Sopit Wongkham, Yasushi Totoki, Hiromi Nakamura, Yasuhito Arai, Satoshi Yamasaki, Pierce K H Chow, Alexander Yaw Fui Chung, London Lucien Peng Jin Ooi, Kiat Hon Lim, Simona Dima, Dan G Duda, Irinel Popescu, Philippe Broet, Sen-Yung Hsieh, Ming-Chin Yu, Aldo Scarpa, Jiaming Lai, Di-Xian Luo, Andre Lopes Carvalho, André Luiz Vettore, Hyungjin Rhee, Young Nyun Park, Ludmil Alexandrov, Raluca Gordan, Steven G Rozen, Tatsuhiro Shibata, Chawalit Pairojkul, Bin Tean Teh, Patrick Tan
Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analysed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined four CCA clusters - Fluke-Positive CCAs (Clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations, conversely Fluke-Negative CCAs (Clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements...
June 30, 2017: Cancer Discovery
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