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Clinical Epigenetics

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https://www.readbyqxmd.com/read/28932321/identification-and-characterization-of-interferon-signaling-related-micrornas-in-occult-hepatitis-b-virus-infection
#1
Yiying Wang, Peifu Zhu, Jing Qiu, Jie Wang, Huijuan Zhu, Yinwei Zhu, Lige Zhang, Jie Zhu, Xingxiang Liu, Chen Dong
BACKGROUND: Occult hepatitis B virus infection (OBI) is an important risk factor of liver cirrhosis and hepatocellular carcinoma. Type 1 interferon (IFN) signaling-related miRNAs were significantly associated with hepatitis B virus (HBV) infection. However, the characteristics of serum IFN signaling-related miRNAs in OBI remain unclear. Therefore, this study aimed to analyze the expression levels of serum IFN signaling-related miRNAs in OBI and to evaluate their potential values for OBI diagnosis...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28932320/epigenetic-clocks-for-gestational-age-statistical-and-study-design-considerations
#2
Andrew J Simpkin, Matthew Suderman, Laura D Howe
In this letter to the editor, we highlight some concerns with a recently published method to estimate gestational age at delivery from DNA methylation data. We conduct novel analyses to highlight the implications of different choices in study design and statistical methods for the prediction of phenotypes from methylation data.
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28932319/dna-hypomethylation-of-a-transcription-factor-binding-site-within-the-promoter-of-a-gout-risk-gene-nrbp1-upregulates-its-expression-by-inhibition-of-tfap2a-binding
#3
Zaihua Zhu, Weida Meng, Peiru Liu, Xiaoxia Zhu, Yun Liu, Hejian Zou
BACKGROUND: Genome-wide association studies (GWASs) have identified dozens of loci associated with gout, but for most cases, the risk genes and the underlying molecular mechanisms contributing to these associations are unknown. This study sought to understand the molecular mechanism of a common genetic variant, rs780093, in the development of gout, both in vitro and in vivo. RESULTS: Nuclear receptor binding protein 1 (NRBP1), as a gout risk gene, and its regulatory region, 72 bp upstream of the transcription start site, designated as B1, were identified through integrative analyses of genome-wide genotype and DNA methylation data...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28904641/histone-code-and-long-non-coding-rnas-lncrnas-aberrations-in-lung-cancer-implications-in-the-therapy-response
#4
REVIEW
Abril Marcela Herrera-Solorio, Leonel Armas-López, Oscar Arrieta, Joaquín Zúñiga, Patricia Piña-Sánchez, Federico Ávila-Moreno
Respiratory diseases hold several genome, epigenome, and transcriptional aberrations as a cause of the accumulated damage promoted by, among others, environmental risk factors. Such aberrations can also come about as an adaptive response when faced with therapeutic oncological drugs. In epigenetic terms, aberrations in DNA methylation patterns, histone code marks balance, and/or chromatin-remodeling complexes recruitment, among Polycomb Repressive Complex-2 (PRC2) versus Trithorax (TRX) Activator Complex, have been proposed to be affected by several previously characterized functional long non-coding RNAs (lncRNAs)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28883895/alterations-of-sorbin-and-sh3-domain-containing-3-sorbs3-in-human-skeletal-muscle-following-roux-en-y-gastric-bypass-surgery
#5
Samantha E Day, Luis A Garcia, Richard L Coletta, Latoya E Campbell, Tonya R Benjamin, Elena A De Filippis, James A Madura, Lawrence J Mandarino, Lori R Roust, Dawn K Coletta
BACKGROUND: Obesity is a disease that is caused by genetic and environmental factors. However, epigenetic mechanisms of obesity are less well known. DNA methylation provides a mechanism whereby environmental factors can influence gene transcription. The aim of our study was to investigate skeletal muscle DNA methylation of sorbin and SH3 domain containing 3 (SORBS3) with weight loss induced by Roux-en-Y gastric bypass (RYGB). RESULTS: Previously, we had shown increased methylation (5...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28883894/epigenetic-regulation-of-inflammation-in-localized-aggressive-periodontitis
#6
L M Shaddox, A F Mullersman, H Huang, S M Wallet, T Langaee, I Aukhil
BACKGROUND: We have previously demonstrated a Toll-like receptor (TLR)-mediated hyper-responsive phenotype in our cohort of localized aggressive periodontitis (LAP) individuals. However, mechanisms related to this phenotype are still not clear in the literature. The objective of this cross-sectional study is to examine the role of epigenetic regulation, specifically DNA methylation status of genes in the TLR pathway in this cohort. Peripheral blood was collected from 20 LAP patients and 20 healthy unrelated controls...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28883893/the-association-between-alu-hypomethylation-and-severity-of-type-2-diabetes-mellitus
#7
Jirapan Thongsroy, Maturada Patchsung, Apiwat Mutirangura
BACKGROUND: Cellular senescence due to genomic instability is believed to be one of the mechanisms causing health problems in diabetes mellitus (DM). Low methylation levels of Alu elements or Alu hypomethylation, an epigenomic event causing genomic instability, were commonly found in aging people and patients with aging phenotypes, such as osteoporosis. RESULTS: We investigate Alu methylation levels of white blood cells of type 2 DM, pre-DM, and control. The DM group possess the lowest Alu methylation (P < 0...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28878843/prognostic-relevance-of-an-epigenetic-biomarker-panel-in-sentinel-lymph-nodes-from-colon-cancer-patients
#8
Guro E Lind, Marianne Guriby, Terje Ahlquist, Israr Hussain, Marine Jeanmougin, Kjetil Søreide, Hartwig Kørner, Ragnhild A Lothe, Oddmund Nordgård
BACKGROUND: Patients with early colorectal cancer (stages I-II) generally have a good prognosis, but a subgroup of 15-20% experiences relapse and eventually die of disease. Occult metastases have been suggested as a marker for increased risk of recurrence in patients with node-negative disease. Using a previously identified, highly accurate epigenetic biomarker panel for early detection of colorectal tumors, we aimed at evaluating the prognostic value of occult metastases in sentinel lymph nodes of colon cancer patients...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28878842/efficacy-of-ezh2-inhibitory-drugs-in-human-papillomavirus-positive-and-human-papillomavirus-negative-oropharyngeal-squamous-cell-carcinomas
#9
Cameron D Lindsay, Morris A Kostiuk, Jeff Harris, Daniel A O'Connell, Hadi Seikaly, Vincent L Biron
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with rates of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) dramatically increasing. The overexpression of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for the trimethylation at lysine 27 of histone 3 (H3K27me3), is associated with a poor clinical prognosis and aggressive HPV-positive phenotypes. METHODS: We utilized three EZH2 pathway inhibitors, GSK-343, DZNeP, and EPZ-5687, and tested their efficacy in two HPV-positive and two HPV-negative OPSCC cell lines...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28861129/genome-wide-dna-methylation-analysis-in-blood-cells-from-patients-with-werner-syndrome
#10
T Guastafierro, M G Bacalini, A Marcoccia, D Gentilini, S Pisoni, A M Di Blasio, A Corsi, C Franceschi, D Raimondo, A Spanò, P Garagnani, F Bondanini
BACKGROUND: Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified. RESULTS: To address whether epigenetic changes can be associated with Werner syndrome phenotype, we analysed genome-wide DNA methylation profile using the Infinium MethylationEPIC BeadChip in the whole blood from three patients affected by Werner syndrome compared with three age- and sex-matched healthy controls...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28861128/pyrosequencing-quantified-methylation-level-of-mir-124-predicts-shorter-survival-for-patients-with-myelodysplastic-syndrome
#11
Hong Wang, Tong-Tong Zhang, Song Jin, Hong Liu, Xiang Zhang, Chang-Geng Ruan, De-Pei Wu, Yue Han, Xiao-Qin Wang
BACKGROUND: Aberrant CpG island methylation has been increasingly recognized as a common event in myelodysplastic syndrome (MDS). To date, most of the previous studies of miR-124 in MDS have focused on epigenetic changes and little is known about the underlying mechanism through which miR-124 regulates CDK6 expression. RESULTS: In the present study, we employed pyrosequencing analysis to quantify the methylation levels of upstream regions of the miR-124 genes (miR-124-1, miR-124-2 and miR-124-3) in 56 primary MDS patients...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28855972/epigenetic-response-of-imprinted-domains-during-carcinogenesis
#12
Corey L Bretz, Ingeborg M Langohr, Joomyeong Kim
BACKGROUND: Imprinted domains have been identified as targets for aberrant DNA methylation during carcinogenesis, but it remains unclear when these epigenetic alterations occur and how they contribute to tumor progression. Epigenetic instability at key cis-regulatory elements within imprinted domains can concomitantly activate proto-oncogenes and turn off tumor suppressor genes. Thus, to further characterize the epigenetic response of imprinted domains during carcinogenesis, we compared the stability of DNA methylation at a variety of cis-regulatory elements within imprinted domains in two fundamentally different mouse tumors, benign and malignant, induced by the KrasG12D mutation...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28855971/the-effect-of-nipped-b-like-nipbl-haploinsufficiency-on-genome-wide-cohesin-binding-and-target-gene-expression-modeling-cornelia-de-lange-syndrome
#13
Daniel A Newkirk, Yen-Yun Chen, Richard Chien, Weihua Zeng, Jacob Biesinger, Ebony Flowers, Shimako Kawauchi, Rosaysela Santos, Anne L Calof, Arthur D Lander, Xiaohui Xie, Kyoko Yokomori
BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder frequently associated with heterozygous loss-of-function mutations of Nipped-B-like (NIPBL), the human homolog of Drosophila Nipped-B. NIPBL loads cohesin onto chromatin. Cohesin mediates sister chromatid cohesion important for mitosis but is also increasingly recognized as a regulator of gene expression. In CdLS patient cells and animal models, expression changes of multiple genes with little or no sister chromatid cohesion defect suggests that disruption of gene regulation underlies this disorder...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28852427/seven-cpg-based-prognostic-signature-coupled-with-gene-expression-predicts-survival-of-oral-squamous-cell-carcinoma
#14
Sipeng Shen, Guanrong Wang, Qianwen Shi, Ruyang Zhang, Yang Zhao, Yongyue Wei, Feng Chen, David C Christiani
BACKGROUND: DNA methylation has started a recent revolution in genomics biology by identifying key biomarkers for multiple cancers, including oral squamous cell carcinoma (OSCC), the most common head and neck squamous cell carcinoma. METHODS: A multi-stage screening strategy was used to identify DNA-methylation-based signatures for OSCC prognosis. We used The Cancer Genome Atlas (TCGA) data as training set which were validated in two independent datasets from Gene Expression Omnibus (GEO)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28824732/the-impact-of-methylation-quantitative-trait-loci-mqtls-on-active-smoking-related-dna-methylation-changes
#15
Xu Gao, Hauke Thomsen, Yan Zhang, Lutz Philipp Breitling, Hermann Brenner
BACKGROUND: Methylation quantitative trait loci (mQTLs) are the genetic variants that may affect the DNA methylation patterns of CpG sites. However, their roles in influencing the disturbances of smoking-related epigenetic changes have not been well established. This study was conducted to address whether mQTLs exist in the vicinity of smoking-related CpG sites (± 50 kb) and to examine their associations with smoking exposure and all-cause mortality in older adults. RESULTS: We obtained DNA methylation profiles in whole blood samples by Illumina Infinium Human Methylation 450 BeadChip array of two independent subsamples of the ESTHER study (discovery set, n = 581; validation set, n = 368) and their corresponding genotyping data using the Illumina Infinium OncoArray BeadChip...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28824731/altered-epigenetic-features-in-circulating-nucleosomes-in-idiopathic-pulmonary-fibrosis
#16
J Guiot, I Struman, V Chavez, M Henket, M Herzog, K Scoubeau, N Hardat, B Bondue, J L Corhay, C Moermans, R Louis
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disorder of unknown origin with a highly variable and unpredictable clinical course. Polymorphisms and environmentally induced epigenetic variations seem to determine individual susceptibility to the development of lung fibrosis. METHODS: We have studied circulating epitopes on cell-free nucleosomes (cfnucleosomes) in 50 IPF patients. We have compared untreated IPF (n = 23) with IPF receiving antifibrotic therapy (n = 27) and healthy subjects (HS) (n = 27)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28814982/cord-blood-dna-methylation-and-adiposity-measures-in-early-and-mid-childhood
#17
Jacob K Kresovich, Yinan Zheng, Andres Cardenas, Brian T Joyce, Sheryl L Rifas-Shiman, Emily Oken, Matthew W Gillman, Marie-France Hivert, Andrea A Baccarelli, Lifang Hou
BACKGROUND: Excess adiposity in childhood is associated with numerous adverse health outcomes. As this condition is difficult to treat once present, identification of risk early in life can help inform and implement strategies to prevent the onset of the condition. We performed an epigenome-wide association study to prospectively investigate the relationship between cord blood DNA methylation and adiposity measurements in childhood. METHODS: We measured genome-wide DNA methylation from 478 children in cord blood and measured overall and central adiposity via skinfold caliper measurements in early (range 3...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28814981/cpg-location-and-methylation-level-are-crucial-factors-for-the-early-detection-of-oral-squamous-cell-carcinoma-in-brushing-samples-using-bisulfite-sequencing-of-a-13-gene-panel
#18
Luca Morandi, Davide Gissi, Achille Tarsitano, Sofia Asioli, Andrea Gabusi, Claudio Marchetti, Lucio Montebugnoli, Maria Pia Foschini
BACKGROUND: Oral squamous cell carcinoma (OSCC) is usually diagnosed at an advanced stage and is commonly preceded by oral premalignant lesions. The mortality rates have remained unchanged (50% within 5 years after diagnosis), and it is related to tobacco smoking and alcohol intake. Novel molecular markers for early diagnosis are urgently needed. The purpose of this study was to evaluate the diagnostic value of methylation level in a set of 18 genes by bisulfite next-generation sequencing...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28814980/cooperative-effect-of-chidamide-and-chemotherapeutic-drugs-induce-apoptosis-by-dna-damage-accumulation-and-repair-defects-in-acute-myeloid-leukemia-stem-and-progenitor-cells
#19
Yin Li, Yan Wang, Yong Zhou, Jie Li, Kai Chen, Leisi Zhang, Manman Deng, Suqi Deng, Peng Li, Bing Xu
BACKGROUND: Many conventional chemotherapeutic drugs are known to be involved in DNA damage, thus ultimately leading to apoptosis of leukemic cells. However, they fail to completely eliminate leukemia stem cells (LSCs) due to their higher DNA repair capacity of cancer stem cells than that of bulk cancer cells, which becomes the root of drug resistance and leukemia recurrence. A new strategy to eliminate LSCs in acute myeloid leukemia (AML) is therefore urgently needed. RESULTS: We report that a low-dose chidamide, a novel orally active benzamide-type histone deacetylase (HDAC) inhibitor, which selectively targets HDACs 1, 2, 3, and 10, could enhance the cytotoxicity of DNA-damaging agents (daunorubicin, idarubicin, and cytarabine) in CD34(+)CD38(-) KG1α cells, CD34(+)CD38(-) Kasumi cells, and primary refractory or relapsed AML CD34(+) cells, reflected by the inhibition of cell proliferation, induction of apoptosis, and increase of cell cycle arrest in vitro...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28811844/lsd1-dual-function-in-mediating-epigenetic-corruption-of-the-vitamin-d-signaling-in-prostate-cancer
#20
Sebastiano Battaglia, Ellen Karasik, Bryan Gillard, Jennifer Williams, Trisha Winchester, Michael T Moser, Dominic J Smiraglia, Barbara A Foster
BACKGROUND: Lysine-specific demethylase 1A (LSD1) is a key regulator of the androgen (AR) and estrogen receptors (ER), and LSD1 levels correlate with tumor aggressiveness. Here, we demonstrate that LSD1 regulates vitamin D receptor (VDR) activity and is a mediator of 1,25(OH)2-D3 (vitamin D) action in prostate cancer (PCa). METHODS: Athymic nude mice were xenografted with CWR22 cells and monitored weekly after testosterone pellet removal. Expression of LSD1 and VDR (IHC) were correlated with tumor growth using log-rank test...
2017: Clinical Epigenetics
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