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Epigenetics liver

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https://www.readbyqxmd.com/read/29143892/update-in-the-therapy-of-advanced-neuroendocrine-tumors
#1
REVIEW
Inbal Uri, Shani Avniel-Polak, David J Gross, Simona Grozinsky-Glasberg
Neuroendocrine tumors (NETs) are rare neoplasms, with an estimated annual incidence of ~ 6.9/100,000. NETs arise throughout the body from cells of the diffuse endocrine system. More than half originate from endocrine cells of the gastrointestinal tract and the pancreas, thus being referred to as gastroenteropancreatic NETs (GEP-NETs). The only treatment that offers a cure is surgery; however, most patients are diagnosed with metastatic disease, and curative surgery is usually not an option. These patients can be offered long-term systemic treatment, for both symptomatic relief and tumor growth suppression...
November 16, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29130343/defining-baseline-epigenetic-landscapes-in-the-rat-liver
#2
John P Thomson, Raffaele Ottaviano, Roland Buesen, Jonathan G Moggs, Michael Schwarz, Richard R Meehan
Characterization of the hepatic epigenome following exposure to chemicals and therapeutic drugs provides novel insights into toxicological and pharmacological mechanisms, however appreciation of genome-wide inter- and intra-strain baseline epigenetic variation, particularly in under-characterized species such as the rat is limited. Material & methods: To enhance the utility of epigenomic endpoints safety assessment, we map both DNA modifications (5-methyl-cytosine and 5-hydroxymethyl-cytosine) and enhancer related chromatin marks (H3K4me1 and H3K27ac) across multiple male and female rat livers for two important outbred laboratory rat strains (Sprague-Dawley and Wistar)...
November 13, 2017: Epigenomics
https://www.readbyqxmd.com/read/29127188/epigenetically-mediated-inhibition-of-s-adenosylhomocysteine-hydrolase-and-the-associated-dysregulation-of-1-carbon-metabolism-in-nonalcoholic-steatohepatitis-and-hepatocellular-carcinoma
#3
Igor P Pogribny, Kostiantyn Dreval, Iryna Kindrat, Stepan Melnyk, Leandro Jimenez, Aline de Conti, Volodymyr Tryndyak, Marta Pogribna, Juliana Festa Ortega, S Jill James, Ivan Rusyn, Frederick A Beland
The substantial rise in the prevalence of nonalcoholic steatohepatitis (NASH), an advanced form of nonalcoholic fatty liver disease, and the strong association between NASH and the development of hepatocellular carcinoma indicate the urgent need for a better understanding of the underlying mechanisms. In the present study, by using the Stelic animal model of NASH and NASH-derived liver carcinogenesis, we investigated the role of the folate-dependent 1-carbon metabolism in the pathogenesis of NASH. We demonstrated that advanced NASH and NASH-related liver carcinogenesis are characterized by a significant dysregulation of 1-carbon homeostasis, with diminished expression of key 1-carbon metabolism genes, especially a marked inhibition of the S-adenosylhomocysteine hydrolase (Ahcy) gene and an increased level of S-adenosyl-l-homocysteine (SAH)...
November 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29122391/genetics-and-epigenetics-of-nafld-and-nash-clinical-impact
#4
REVIEW
Mohammed Eslam, Luca Valenti, Stefano Romeo
Non-alcoholic fatty liver disease (NAFLD) is now recognised as the most common liver disease worldwide. It encompasses a broad spectrum of conditions, from simple steatosis, through non-alcoholic steatohepatitis, to fibrosis and ultimately cirrhosis and hepatocellular carcinoma. A hallmark of NAFLD is the substantial inter-patient variation in disease progression. NAFLD is considered a complex disease trait such that interactions between the environment and a susceptible polygenic host background determine disease phenotype and influence progression...
November 2, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29119508/endogenous-molecular-cellular-network-cancer-theory-a-systems-biology-approach
#5
Gaowei Wang, Ruoshi Yuan, Xiaomei Zhu, Ping Ao
In light of ever apparent limitation of the current dominant cancer mutation theory, a quantitative hypothesis for cancer genesis and progression, endogenous molecular-cellular network hypothesis has been proposed from the systems biology perspective, now for more than 10 years. It was intended to include both the genetic and epigenetic causes to understand cancer. Its development enters the stage of meaningful interaction with experimental and clinical data and the limitation of the traditional cancer mutation theory becomes more evident...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29115507/cytochrome-p450-1a1-and-1b1-promoter-cpg-island-methylation-regulates-rat-liver-injury-induced-by-isoniazid
#6
Yanhui Li, Yuhong Li, Guoying Zheng, Lingyan Zhu, Jishun Wang, Shasha Mu, Qi Ren, Fumin Feng
DNA methylation is an important component of epigenetics that is involved in the occurrence and development of a variety of diseases. The present study aimed to clarify the relationship between cytochrome P450 (CYP)1A1 and CYP1B1 promoter CpG island methylation and isoniazid‑induced liver injury in rats, and to explore the possible mechanism, rats were given an intragastric dose of isoniazid (55 mg·kg‑1·d‑1). High performance liquid chromatography was used to analyze the DNA methylation level of the whole genome in liver tissue...
October 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29113254/epigenetic-analysis-of-fhl1-tumor-suppressor-gene-in-human-liver-cancer
#7
Jun Wang, Fang Huang, Jian Huang, Jindan Kong, Shenglan Liu, Jun Jin
Liver cancer is one of the most common types of cancer among human malignancies. Four and a half LIM domains 1 (FHL1), as a tumor suppressor gene, is frequently downregulated in multiple types of human cancer. However, the role and specific mechanisms of FHL1 as a tumor suppressor in liver cancer are poorly understood. The present study aimed to investigate the role and associated mechanisms of FHL1 in human liver cancer. The level of FHL1 mRNA in hepatocellular carcinoma (HCC) tissue specimens and cell lines derived from the human liver was determined using reverse transcription polymerase chain reaction and western blot analysis...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29109731/gm-csf-monocyte-derived-cells-and-langerhans-cells-as-part-of-the-dendritic-cell-family
#8
REVIEW
Manfred B Lutz, Herbert Strobl, Gerold Schuler, Nikolaus Romani
Dendritic cells (DCs) and macrophages (Mph) share many characteristics as components of the innate immune system. The criteria to classify the multitude of subsets within the mononuclear phagocyte system are currently phenotype, ontogeny, transcription patterns, epigenetic adaptations, and function. More recently, ontogenetic, transcriptional, and proteomic research approaches uncovered major developmental differences between Flt3L-dependent conventional DCs as compared with Mphs and monocyte-derived DCs (MoDCs), the latter mainly generated in vitro from murine bone marrow-derived DCs (BM-DCs) or human CD14(+) peripheral blood monocytes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29108216/-research-advances-in-the-role-of-the-hippo-signaling-pathway-in-pathogenesis-of-liver-cancer
#9
L Yuan, Z W Li
The Hippo signaling pathway consists of four core components in mammals, i.e., Mst1/2, WW45, Mob1, and LATS1/2, which can inhibit the transcriptional coactivator YAP from entering the nucleus, maintain the balance between cell proliferation and apoptosis, control organ size, and maintain homeostasis. If the core components of the Hippo signaling pathway are inactivated due to gene mutation or epigenetic alterations, YAP is overexpressed and activated in the nucleus, which then induces excessive cell proliferation and inhibits cell apoptosis...
October 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29101051/histone-methyltransferase-g9a-modulates-hepatic-insulin-signaling-via-regulating-hmga1
#10
Weili Xue, Jin Huang, Hong Chen, Yu Zhang, Xiuqin Zhu, Jianshuang Li, Wenquan Zhang, Yangmian Yuan, Yan Wang, Ling Zheng, Kun Huang
Hepatic insulin sensitivity is critical for glucose homeostasis, and insulin resistance is a fundamental syndrome found in various metabolic disorders, including obesity and type 2 diabetes. Despite considerable studies on the mechanisms of hepatic insulin resistance, the link between epigenetic regulation and the development of insulin resistance remains elusive. Here, we reported that G9a/EHMT2, a histone methyltransferase, was markedly decreased in the liver of db/db mice and high-fat diet (HFD)-fed mice...
October 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29094699/two-independent-modes-of-chromatin-organization-revealed-by-cohesin-removal
#11
Wibke Schwarzer, Nezar Abdennur, Anton Goloborodko, Aleksandra Pekowska, Geoffrey Fudenberg, Yann Loe-Mie, Nuno A Fonseca, Wolfgang Huber, Christian H Haering, Leonid Mirny, Francois Spitz
Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes...
November 2, 2017: Nature
https://www.readbyqxmd.com/read/29080344/bile-acids-and-cancer-direct-and-environmental-dependent-effects
#12
Agostino Di Ciaula, David Q-H Wang, Emilio Molina-Molina, Raquel Lunardi Baccetto, Giuseppe Calamita, Vincenzo O Palmieri, Piero Portincasa
Bile acids (BAs) regulate the absorption of fat-soluble vitamins, cholesterol and lipids but have also a key role as singalling molecules and in the modulation of epithelial cell proliferation, gene expression and metabolism. These homeostatic pathways, when disrupted, are able to promote local inflammation, systemic metabolic disorders and, ultimately, cancer. The effect of hydrophobic BAs, in particular, can be linked with cancer in several digestive (mainly oesophagus, stomach, liver, pancreas, biliary tract, colon) and extra-digestive organs (i...
October 28, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/29079534/epigenetic-reprogramming-in-liver-fibrosis-and-cancer
#13
Caroline L Wilson, Derek A Mann, Lee A Borthwick
Novel insights into the epigenetic control of chronic liver diseases are now emerging. Recent advances in our understanding of the critical roles of DNA methylation, histone modifications and ncRNA may now be exploited to improve management of fibrosis/cirrhosis and cancer. Furthermore, improved technologies for the detection of epigenetic markers from patients' blood and tissues will vastly improve diagnosis, treatment options and prognostic tracking. The aim of this review is to present recent findings from the field of liver epigenetics and to explore their potential for translation into therapeutics to prevent disease promoting epigenome reprogramming and reverse epigenetic changes...
October 25, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29073595/epigenetically-regulated-microrna-9-5p-suppresses-the-activation-of-hepatic-stellate-cells-via-tgfbr1-and-tgfbr2
#14
Fujun Yu, BiCheng Chen, XuFei Fan, Guojun Li, Peihong Dong, Jianjian Zheng
BACKGROUND/AIMS: Recently, microRNAs (miRNAs) have been demonstrated to act as regulators of activation of hepatic stellate cells (HSCs). It is well known that the main profibrogenic inducer transforming growth factor-β1 (TGF-β1) contributes to HSC activation, which is a key event in liver fibrosis. Increasing studies show that miR-9-5p is down-regulated in liver fibrosis and restoration of miR-9-5p limits HSC activation. However, the role of miR-9-5p in TGF-β1-induced HSC activation is still not clear...
October 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29059699/identification-of-the-genomic-region-under-epigenetic-regulation-during-nonalcoholic-fatty-liver-disease-progression
#15
Kikuko Hotta, Takuya Kitamoto, Aya Kitamoto, Yuji Ogawa, Yasushi Honda, Takaomi Kessoku, Masato Yoneda, Kento Imajo, Wataru Tomeno, Satoru Saito, Atsushi Nakajima
AIM: The progression of nonalcoholic fatty liver disease (NAFLD) is affected by epigenetics. We performed co-methylation and differentially methylated region (DMR) analyses to identify the genomic region that is under epigenetic regulation during NAFLD progression. METHODS: We collected liver biopsy specimens from 60 Japanese patients with NAFLD and classified these into mild (fibrosis stages 0-2) or advanced (fibrosis stages 3-4) NAFLD. We performed genome-wide DNA methylation analysis and identified the differentially methylated CpGs between mild and advanced NAFLD...
October 23, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29057387/toward-solving-the-etiological-mystery-of-primary-biliary-cholangitis
#16
Atsushi Tanakaa, Patrick Sc Leung, Howard A Young, M Eric Gershwin
Primary biliary cholangitis (PBC) is considered a model autoimmune disease due to its signature AMA autoantibody, female predominance and relatively specific portal infiltration and cholestasis. The identification and cloning of the major mitochondrial autoantigens, recognized by AMA, have served as an immunologic platform to identify the earliest events involved in loss of tolerance. Despite the relative high concordance rate in identical twins, genome wide association studies have not proven clinically useful and have led to suggestions of epigenetic events...
June 2017: Hepatol Commun
https://www.readbyqxmd.com/read/29056005/-epigenetics-and-liver-fibrogenesis
#17
Y Q Zhang, J S Guo
Epigenetic modification refers to a variety of regulating processes that may induce the changes in gene expression without altering DNA sequence. Epigenetic mechanisms including DNA methylation, histone modification, and regulatory non-coding RNAs are involved in hepatic stellate cell activation and liver fibrogenesis. A deep understanding of epigenetic mechanisms in liver fibrosis helps to identify new markers and therapies for liver fibrosis.
August 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29054136/combined-methylome-and-transcriptome-analysis-during-rat-hepatic-stellate-cell-activation
#18
Eva Schumacher, Silke Götze, Claus Kordes, Vladimir Benes, Dieter Häussinger
Hepatic stellate cells (HSC) are mesenchymal stem cells (MSC) of the liver. They are unique among MSC, since HSC remain in a quiescent, retinoid-storing state in the normal liver but become activated after liver injury and contribute to tissue repair. The epigenetic mechanisms accompanying the transition of HSC from a quiescent to an activated state are in the focus of the present study. We investigated the methylome and transcriptome during this process and observed profound changes. While the promoter methylation correlated negatively with gene expression, the gene body methylation revealed no clear correlation...
October 20, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29045830/in%C3%A2-vivo-suppression-of-hiv-rebound-by-didehydro-cortistatin-a-a-block-and-lock-strategy-for-hiv-1-treatment
#19
Cari F Kessing, Christopher C Nixon, Chuan Li, Perry Tsai, Hiroshi Takata, Guillaume Mousseau, Phong T Ho, Jenna B Honeycutt, Mohammad Fallahi, Lydie Trautmann, J Victor Garcia, Susana T Valente
HIV-1 Tat activates viral transcription and limited Tat transactivation correlates with latency establishment. We postulated a "block-and-lock" functional cure approach based on properties of the Tat inhibitor didehydro-Cortistatin A (dCA). HIV-1 transcriptional inhibitors could block ongoing viremia during antiretroviral therapy (ART), locking the HIV promoter in persistent latency. We investigated this hypothesis in human CD4(+) T cells isolated from aviremic individuals. Combining dCA with ART accelerates HIV-1 suppression and prevents viral rebound after treatment interruption, even during strong cellular activation...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29030699/prematurity-and-biliary-atresia-a-30-year-observational-study
#20
Natalie Durkin, Maesha Deheragoda, Mark Davenport
AIM OF STUDY: The diagnosis of biliary atresia (BA) remains challenging and delay can lead to significant morbidity with time to surgery a key factor in determining outcome. Prematurity may impact on outcome potentially delaying diagnosis. We sought to assess whether the premature BA infants (PBA) have a delayed time to surgery and as such, worse outcomes? METHODS: Review of a single-centre prospectively maintained database. Prematurity was defined as delivery < 37/40 gestation...
December 2017: Pediatric Surgery International
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