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Epigenetics liver

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https://www.readbyqxmd.com/read/28239993/maternal-betaine-supplementation-in-rats-induces-intergenerational-changes-in-hepatic-igf-1-expression-and-dna-methylation
#1
Nannan Zhao, Shu Yang, Yun Hu, Haibo Dong, Ruqian Zhao
SCOPE: Betaine is widely used in animal nutrition to promote growth. Here we aimed to investigate whether maternal betaine supplementation during pregnancy can exert multigenerational effects on growth across two generations and the possible epigenetic modifications associated to such effects. METHODS AND RESULTS: In this study, 3-month-old female Sprague-Dawley rats were fed diet supplemented with 1% betaine throughout the pregnancy and lactation. Betaine-supplemented dams produced bigger litter but smaller F1 pups at birth and weaning...
February 26, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28236308/prmt5-restricts-hepatitis-b-virus-replication-via-epigenetic-repression-of-cccdna-transcription-and-interference-with-pgrna-encapsidation
#2
Wen Zhang, Jieliang Chen, Min Wu, Xiaonan Zhang, Min Zhang, Lei Yue, Yaming Li, Jiangxia Liu, Baocun Li, Fang Shen, Yang Wang, Lu Bai, Ulrike Protzer, Massimo Levrero, Zhenghong Yuan
: Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. The covalently closed circular DNA (cccDNA) minichromosome, which serves as the template for the transcription of viral RNAs, plays a key role in viral persistence. While accumulating evidence suggests that cccDNA transcription is regulated by epigenetic machinery, particularly the acetylation of cccDNA-bound histone 3 (H3) and H4, the potential contributions of histone methylation and related host factors remain obscured...
February 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28226195/global-transcriptional-response-of-human-liver-cells-to-ethanol-stress-of-different-strength-reveals-hormetic-behavior
#3
Wolfgang Schmidt-Heck, Eva C Wönne, Thomas Hiller, Uwe Menzel, Dirk Koczan, Georg Damm, Daniel Seehofer, Fanny Knöspel, Nora Freyer, Reinhard Guthke, Steven Dooley, Katrin Zeilinger
BACKGROUND: The liver is the major site for alcohol metabolism in the body and therefore, the primary target organ for ethanol-induced toxicity. In this study, we investigated the in vitro response of human liver cells to different ethanol concentrations in a perfused bioartificial liver device that mimics the complex architecture of the natural organ. METHODS: Primary human liver cells were cultured in the bioartificial liver device and treated for 24 hours with medium containing 150 mM (low), 300 mM (medium) or 600 mM (high) ethanol, while a control culture was kept untreated...
February 22, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28219123/identification-of-core-gene-networks-and-hub-genes-associated-with-progression-of-nonalcoholic-fatty-liver-disease-by-rna-sequencing
#4
Kikuko Hotta, Masataka Kikuchi, Takuya Kitamoto, Aya Kitamoto, Yuji Ogawa, Yasushi Honda, Takaomi Kessoku, Kaori Kobayashi, Masato Yoneda, Kento Imajo, Wataru Tomeno, Akihiro Nakaya, Yutaka Suzuki, Satoru Saito, Atsushi Nakajima
AIM: Nonalcoholic fatty liver disease (NAFLD) progresses because of the interaction between numerous genes. Thus, we performed weighted gene co-expression network analysis to identify core gene networks and key genes associated with NAFLD progression. METHODS: We enrolled 39 patients with mild NAFLD (fibrosis stages 0 to 2) and 21 with advanced NAFLD (fibrosis stages 3 or 4). Total RNA was extracted from frozen liver biopsies, and sequenced to capture a large dynamic range of expression levels...
February 20, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28218475/profound-changes-in-mirna-expression-during-cancer-initiation-by-aflatoxin-b1-and-their-abrogation-by-the-chemopreventive-triterpenoid-cddo-im
#5
Merricka C Livingstone, Natalie M Johnson, Bill D Roebuck, Thomas W Kensler, John D Groopman
Aflatoxin B1 (AFB1 ) is a potent human and animal hepatocarcinogen. To investigate the effects of aflatoxin on miRNA expression during the initiation phase of carcinogenesis, next-generation sequencing was used to analyze liver tissues from F344 rats exposed to 200 µg/kg per day AFB1 for 4 weeks. A panel of miRNAs was identified that was upregulated with AFB1 treatment compared to controls: rno-miR-434-3p, rno-miR-411-5p, rno-miR-221-3p, rno-miR-127-3p, rno-miR-205, rno-miR-429, rno-miR-34a-5p, rno-miR-181c-3p, rno-miR-200b-3p, and rno-miR-541-5p...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28216439/role-of-thyroid-hormone-in-hepatic-gene-regulation-chromatin-remodeling-and-autophagy
#6
Brijesh Kumar Singh, Rohit Anthony Sinha, Kenji Ohba, Paul Michael Yen
Thyroid hormone (TH) actions on development and metabolism have been studied ever since the discovery of thyroxine almost a century ago. Initial studies focused on the physiological and biochemical actions of TH. Later, the cloning of the thyroid hormone receptor (THR) isoforms and the development of techniques enabled the study of TH regulation of complex cellular processes (such as gene transcription). Recently we found that TH activates secondary transcription factors such as FOXO1, to amplify gene transcription; and also is a potent inducer of autophagy that was critical for fatty acid β-oxidation in the liver...
February 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28206970/genetic-variation-in-long-noncoding-rnas-and-the-risk-of-nonalcoholic-fatty-liver-disease
#7
Silvia Sookoian, Cristian Rohr, Adrián Salatino, Hernán Dopazo, Tomas Fernandez Gianotti, Gustavo O Castaño, Carlos J Pirola
: The human transcriptome comprises a myriad of non protein-coding RNA species, including long noncoding RNAs (lncRNAs), which have a remarkable role in transcriptional and epigenetic regulation. We hypothesized that variants in lncRNAs influence the susceptibility to nonalcoholic fatty liver disease (NAFLD). Using next generation sequencing, we performed a survey of genetic variation associated with randomly selected lncRNA-genomic regions located within both experimentally validated and computationally predicted regulatory elements...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28202850/hypermethylation-of-the-n-myc-downstream-regulated-gene-2-promoter-in-peripheral-blood-mononuclear-cells-is-associated-with-liver-fibrosis-in-chronic-hepatitis-b
#8
Xin-Yuan Liu, Yu-Chen Fan, Shuai Gao, Jing Zhao, Feng Li, Jun Zhang, Kai Wang
DNA methylation is a fundamental epigenetic modification to regulate gene expression. N-Myc downstream-regulated gene (NDRG) 2 is a cytoplasmic protein and participates in the pathogenesis of liver fibrosis. In this study, the mRNA expression and methylation status of NDRG2 was evaluated in patients with chronic hepatitis B (CHB). The study included 143 CHB patients and 65 normal controls (NC). The mRNA expression of NDRG2 in peripheral blood mononuclear cells (PBMCs) was detected by quantitative real-time polymerase chain reaction...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28186961/combination-epigenetic-therapy-in-metastatic-colorectal-cancer-mcrc-with-subcutaneous-5-azacitidine-and-entinostat-a-phase-2-consortium-stand-up-2-cancer-study
#9
Nilofer S Azad, Anthony El-Khoueiry, Jun Yin, Ann L Oberg, Patrick Flynn, Douglas Adkins, Anup Sharma, Daniel J Weisenberger, Thomas Brown, Prakriti Medvari, Peter A Jones, Hariharan Easwaran, Ihab Kamel, Nathan Bahary, George Kim, Joel Picus, Henry C Pitot, Charles Erlichman, Ross Donehower, Hui Shen, Peter W Laird, Richard Piekarz, Stephen Baylin, Nita Ahuja
PURPOSE: Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies. EXPERIMENTAL DESIGN: We conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 75 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10...
February 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178526/crl4-dcaf8-ubiquitin-ligase-targets-histone-h3k79-and-promotes-h3k9-methylation-in-the-liver
#10
Gaofeng Li, Tong Ji, Jiang Chen, Yufei Fu, Lidan Hou, Yan Feng, Tingyue Zhang, Tianyu Song, Jie Zhao, Yoko Endo, Hui Lin, Xiujun Cai, Yong Cang
Transcription from chromosomes is regulated by posttranslational modifications to histones, such as methylation and ubiquitination. Monoubiquitination of histones H2A and H2B influences H3 methylation to reinforce the activation or repression of gene expression. Here, we provide evidence that H3 polyubiquitination represses transcription of fetal and cell-cycle genes in postnatal mouse liver by crosstalk with H3K9 methylation. We found that the CRL4 ubiquitin ligase targets H3 for polyubiquitination at K79 via the DCAF8 substrate receptor in hepatocytes...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28177898/maternal-dietary-zinc-supplementation-enhances-the-epigenetic-activated-antioxidant-ability-of-chick-embryos-from-maternal-normal-and-high-temperatures
#11
Yongwen Zhu, Xiudong Liao, Lin Lu, Wenxiang Li, Liyang Zhang, Cheng Ji, Xi Lin, Hsiao-Ching Liu, Jack Odle, Xugang Luo
The role of maternal dietary zinc supplementation in protecting the embryos from maternal hyperthermia-induced negative effects via epigenetic mechanisms was examined using an avian model (Gallus gallus). Broiler breeder hens were exposed to two maternal temperatures (21°C and 32°C) × three maternal dietary zinc treatments (zinc-unsupplemented control diet, the control diet + 110 mg zinc/kg inorganic or organic zinc) for 8 weeks. Maternal hyperthermia increased the embryonic mortality and induced oxidative damage evidenced by the elevated mRNA expressions of heat shock protein genes...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28174625/sex-and-age-differences-in-the-expression-of-liver-micrornas-during-the-life-span-of-f344-rats
#12
Joshua C Kwekel, Vikrant Vijay, Tao Han, Carrie L Moland, Varsha G Desai, James C Fuscoe
BACKGROUND: Physiological factors such as age and sex have been shown to be risk factors for adverse effects in the liver, including liver diseases and drug-induced liver injury. Previously, we have reported age- and sex-related significant differences in hepatic basal gene expression in rats during the life span that may be related to susceptibility to such adverse effects. However, the underlying mechanisms of the gene expression changes were not fully understood. In recent years, increasing evidence for epigenetic mechanisms of gene regulation has fueled interest in the role of microRNAs (miRNAs) in toxicogenomics and biomarker discovery...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28163185/genomic-characterization-and-dynamic-methylation-of-promoter-facilitates-transcriptional-regulation-of-h2a-variants-h2a-1-and-h2a-2-in-various-pathophysiological-states-of-hepatocyte
#13
Monica Tyagi, Divya Reddy, Sanjay Gupta
Differential expression of homomorphous variants of H2A family of histone H2A.1 and H2A.2 have been associated with hepatocellular carcinoma and maintenance of undifferentiated state of hepatocyte. However, not much is known about the transcriptional regulation of these H2A variants. The current study revealed the presence of 43bp 5'-regulatory region upstream of translation start site and a 26bp 3' stem loop conserved region for both the H2A.1 and H2A.2 variants. However, alignment of both H2A.1 and H2A.2 5'-untranslated region (UTR) sequences revealed no significant degree of homology between them despite the coding exon being very similar amongst the variants...
February 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28157489/cathepsin-h-mediated-degradation-of-hdac4-for-matrix-metalloproteinase-expression-in-hepatic-stellate-cells-implications-of-epigenetic-suppression-of-matrix-metalloproteinases-in-fibrosis-through-stabilization-of-class-iia-histone-deacetylases
#14
Zemin Yang, Yu Liu, Lan Qin, Pengfei Wu, Zanxian Xia, Mei Luo, Yilan Zeng, Hidekazu Tsukamoto, Zongyun Ju, Danmei Su, Han Kang, Zhixiong Xiao, Sujun Zheng, Zhongping Duan, Richard Hu, Qiang Wang, Stephen J Pandol, Yuan-Ping Han
In three-dimensional extracellular matrix, mesenchymal cells including hepatic stellate cells (HSCs) gain the ability to express matrix metalloproteinases (MMPs) on injury signals. In contrast, in myofibroblastic HSCs in fibrotic liver, many MMP genes are silenced into an epigenetically nonpermissive state. The mechanism by which the three-dimensional extracellular matrix confers the MMP genes into an epigenetically permissive state has not been well characterized. In continuation of previous work, we show here that the up-regulation of MMP genes is mediated through degradation of class IIa histone deacetylases (HDACs) by certain cysteine cathepsins (Cts)...
February 1, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28130850/demethylating-and-anti-hepatocarcinogenic-potential-of-hesperidin-a-natural-polyphenol-of-citrus-juices
#15
Zahira Fernández-Bedmar, Jaouad Anter, Angeles Alonso-Moraga, Juana Martín de Las Mulas, Yolanda Millán-Ruiz, Silvia Guil-Luna
Hepatocellular carcinoma (HCC) is a neoplasia representing the fifth most common malignancy worldwide and the third cause of death from cancer. Diets with high content in fruits and vegetables are widely recommended for their health-promoting properties, among them, the protection against diabetes, cancer and cardiovascular diseases. Hesperidin is the most important phenol in the orange fruit with well-known health benefits. Diet components have been used as possible modulator agents of DNA methylation in cancer cells and epigenetic therapy against their harmful effects could be a potential tool in chemotherapy...
January 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28129116/a-proof-of-concept-for-epigenetic-therapy-of-tissue-fibrosis-inhibition-of-liver-fibrosis-progression-by-3-deazaneplanocin-a
#16
Müjdat Zeybel, Saimir Luli, Laura Sabater, Timothy Hardy, Fiona Oakley, Jack Leslie, Agata Page, Eva Moran Salvador, Victoria Sharkey, Hidekazu Tsukamoto, David C K Chu, Uma Sharan Singh, Mirco Ponzoni, Patrizia Perri, Daniela Di Paolo, Edgar J Mendivil, Jelena Mann, Derek A Mann
The progression of fibrosis in chronic liver disease is dependent upon hepatic stellate cells (HSCs) transdifferentiating to a myofibroblast-like phenotype. This pivotal process is controlled by enzymes that regulate histone methylation and chromatin structure, which may be targets for developing anti-fibrotics. There is limited pre-clinical experimental support for the potential to therapeutically manipulate epigenetic regulators in fibrosis. In order to learn if epigenetic treatment can halt the progression of pre-established liver fibrosis, we treated mice with the histone methyltransferase inhibitor 3-deazaneplanocin A (DZNep) in a naked form or by selectively targeting HSC-derived myofibroblasts via an antibody-liposome-DZNep targeting vehicle...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28129115/hotair-epigenetically-modulates-pten-expression-via-microrna-29b-a-novel-mechanism-in-regulation-of-liver-fibrosis
#17
Fujun Yu, Bicheng Chen, Peihong Dong, Jianjian Zheng
Homeobox transcript antisense RNA (HOTAIR), as a long intergenic non-coding RNA (lincRNA), is upregulated in various cancers and involved in diverse cellular functions. However, its role in liver fibrosis is unclear. In this study, HOTAIR expression was upregulated in hepatic stellate cells (HSCs) in vivo and in vitro during liver fibrosis. HOTAIR knockdown suppressed HSC activation including α-smooth muscle actin (α-SMA) and typeIcollagen in vitro and in vivo. Both HSC proliferation and cell cycle were inhibited by HOTAIR knockdown...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28126648/maternal-consumption-of-low-isoflavone-soy-protein-isolate-alters-hepatic-gene-expression-and-liver-development-in-rat-offspring
#18
Sae Bom Won, Anna Han, Young Hye Kwon
In utero environment is known to affect fetal development. Especially, the distinct fetal programming of carcinogenesis was reported in offspring exposed to maternal diets containing soy protein isolate (SPI) or genistein. Therefore, we investigated whether maternal consumption of low-isoflavone SPI or genistein alters hepatic gene expression and liver development in rat offspring. Female Sprague-Dawley rats were fed a casein diet, a low-isoflavone SPI diet or a casein diet supplemented with genistein (250 mg/kg diet) for 2 weeks before mating and throughout pregnancy and lactation...
January 12, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28125731/correlated-5-hydroxymethylcytosine-5hmc-and-gene-expression-profiles-underpin-gene-and-organ-specific-epigenetic-regulation-in-adult-mouse-brain-and-liver
#19
I-Hsuan Lin, Yi-Fan Chen, Ming-Ta Hsu
BACKGROUND: DNA methylation is an epigenetic mechanism essential for gene regulation and vital for mammalian development. 5-hydroxymethylcytosine (5hmC) is the first oxidative product of the TET-mediated 5-methylcytosine (5mC) demethylation pathway. Aside from being a key intermediate in cytosine demethylation, 5hmC may have potential regulatory functions with emerging importance in mammalian biology. METHODS: Here, we investigate the global 5hmC enrichment in five brain structures, including cerebellum, cerebral cortex, hippocampus, hypothalamus and thalamus, as well as liver tissues from female and male adult mice by using chemical capture-based technique coupled with next-generation sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28111205/carcinogenic-risk-and-bisphenol-a-exposure-a-focus-on-molecular-aspects-in-endoderm-derived-glands
#20
Danila Cuomo, Immacolata Porreca, Gilda Cobellis, Roberta Tarallo, Giovanni Nassa, Geppino Falco, Antonio Nardone, Francesca Rizzo, Massimo Mallardo, Concetta Ambrosino
Epidemiological and experimental evidence associates the exposure to Bisphenol A with the increase of cancer risk in several organs, including prostate. BPA targets different pathways involved in carcinogenicity including the Nuclear Receptors (i.e. estrogen and androgen receptors), stress regulated proteins and, finally, epigenetic changes. Here, we analyse BPA-dependent carcinogenesis in endoderm-derived glands, thyroid, liver, pancreas and prostate focusing on cell signalling, DNA damage repair pathways and epigenetic modifications...
January 19, 2017: Molecular and Cellular Endocrinology
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