scholarly journals DNA methylation in the inflammatory genes after neurosurgery and diagnostic ability of post-operative delirium

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takehiko Yamanashi ◽  
Takaaki Nagao ◽  
Nadia E. Wahba ◽  
Pedro S. Marra ◽  
Kaitlyn J. Crutchley ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Postoperative Delirium ◽  
Potential Role ◽  
Area Under The Curve ◽  
Diagnostic Ability ◽  
Cpg Sites ◽  
Post Surgery ◽  
Auc Value ◽  
Epic Array

AbstractThe pathophysiological mechanisms of postoperative delirium (POD) are still not clear, and no reliable biomarker is available to differentiate those with and without POD. Pre- and post-surgery blood from epilepsy subjects undergoing neurosurgery were collected. DNA methylation (DNAm) levels of the TNF gene, IL1B gene, and IL6 gene by the Illumina EPIC array method, and DNAm levels of the TNF gene by pyrosequencing, were analyzed. Blood from 37 subjects were analyzed by the EPIC array method, and blood from 27 subjects were analyzed by pyrosequencing. Several CpGs in the TNF gene in preoperative blood showed a negative correlation between their DNAm and age both in the POD group and in the non-POD group. However, these negative correlations were observed only in the POD group after neurosurgery. Neurosurgery significantly altered DNAm levels at 17 out of 24 CpG sites on the TNF gene, 8 out of 14 CpG sites on the IL1B gene, and 4 out of 14 CpG sites on the IL6 gene. Furthermore, it was found that the Inflammatory Methylation Index (IMI), which was based on the post-surgery DNAm levels at the selected five CpG sites, can be a potential detection tool for delirium with moderate accuracy; area under the curve (AUC) value was 0.84. The moderate accuracy of this IMI was replicated using another cohort from our previous study, in which the AUC was 0.79. Our findings provide further evidence of the potential role of epigenetics and inflammation in the pathophysiology of delirium.

DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease

2018 ◽  
Vol 32 (10) ◽  
pp. 5215-5226 ◽  
Author(s):  
Benjamin P. Larkin ◽  
Sarah J. Glastras ◽  
Hui Chen ◽  
Carol A. Pollock ◽  
Sonia Saad
Keyword(s):  
Chronic Kidney Disease ◽  
Dna Methylation ◽  
Kidney Disease ◽  
Potential Role ◽  
Demethylating Agents

scholarly journals DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Monica del C. Gomez-Alonso ◽  
Anja Kretschmer ◽  
Rory Wilson ◽  
Liliane Pfeiffer ◽  
Ville Karhunen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lipid Metabolism ◽  
Population Based ◽  
Total Serum ◽  
Resonance Spectroscopy ◽  
Metabolic Disturbances ◽  
Cpg Sites ◽  
Gene Transcripts

Abstract Background The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances. Results We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value < 4.7 × 10−10), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures, gene transcription, and metabolic measure ratios and were additionally linked to obesity or previous myocardial infarction, extending previously reported observations. Conclusion Our study provides evidence of a link between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses, thus offering in-depth insights into well-known associations of DNA methylation with total serum lipids. The results support detailed profiling of lipid metabolism to improve the molecular understanding of dyslipidemia and related disease mechanisms.

scholarly journals Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in Hepatocarcinogenesis

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jing Shen ◽  
Shuang Wang ◽  
Abby B. Siegel ◽  
Helen Remotti ◽  
Qiao Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Potential Role ◽  
Dna Hypermethylation ◽  
Two Phase ◽  
Genome Wide ◽  
Phase Study ◽  
A Genome ◽  
Genome Wide Expression ◽  
Inactive Chromatin

Background.Previous studies, including ours, have examined the regulation of microRNAs (miRNAs) by DNA methylation, but whether this regulation occurs at a genome-wide level in hepatocellular carcinoma (HCC) is unclear.Subjects/Methods.Using a two-phase study design, we conducted genome-wide screening for DNA methylation and miRNA expression to explore the potential role of methylation alterations in miRNAs regulation.Results.We found that expressions of 25 miRNAs were statistically significantly different between tumor and nontumor tissues and perfectly differentiated HCC tumor from nontumor. Six miRNAs were overexpressed, and 19 were repressed in tumors. Among 133 miRNAs with inverse correlations between methylation and expression, 8 miRNAs (6%) showed statistically significant differences in expression between tumor and nontumor tissues. Six miRNAs were validated in 56 additional paired HCC tissues, and significant inverse correlations were observed for miR-125b and miR-199a, which is consistent with the inactive chromatin pattern found in HepG2 cells.Conclusion.These data suggest that the expressions of miR-125b and miR-199a are dramatically regulated by DNA hypermethylation that plays a key role in hepatocarcinogenesis.

scholarly journals The Reprimo-Like Gene Is an Epigenetic-Mediated Tumor Suppressor and a Candidate Biomarker for the Non-Invasive Detection of Gastric Cancer

2020 ◽  
Vol 21 (24) ◽  
pp. 9472
Author(s):  
María Alarcón ◽  
Wilda Olivares ◽  
Miguel Córdova-Delgado ◽  
Matías Muñoz-Medel ◽  
Tomas de Mayo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Cancer Biology ◽  
Area Under The Curve ◽  
Soft Agar ◽  
Poor Overall Survival ◽  
Clinicopathologic Characteristics ◽  
Non Invasive

Reprimo-like (RPRML) is an uncharacterized member of the Reprimo gene family. Here, we evaluated the role of RPRML and whether its regulation by DNA methylation is a potential non-invasive biomarker of gastric cancer. RPRML expression was evaluated by immunohistochemistry in 90 patients with gastric cancer and associated with clinicopathologic characteristics and outcomes. The role of RPRML in cancer biology was investigated in vitro, through RPRML ectopic overexpression. Functional experiments included colony formation, soft agar, MTS, and Ki67 immunofluorescence assays. DNA methylation-mediated silencing was evaluated by the 5-azacytidine assay and direct bisulfite sequencing. Non-invasive detection of circulating methylated RPRML DNA was assessed in 25 gastric cancer cases and 25 age- and sex-balanced cancer-free controls by the MethyLight assay. Downregulation of RPRML protein expression was associated with poor overall survival in advanced gastric cancer. RPRML overexpression significantly inhibited clonogenic capacity, anchorage-independent growth, and proliferation in vitro. Circulating methylated RPRML DNA distinguished patients with gastric cancer from controls with an area under the curve of 0.726. The in vitro overexpression results and the poor patient survival associated with lower RPRML levels suggest that RPRML plays a tumor-suppressive role in the stomach. Circulating methylated RPRML DNA may serve as a biomarker for the non-invasive detection of gastric cancer.

scholarly journals Biotic Stress-Induced Priming and De-Priming of Transcriptional Memory in Arabidopsis and Apple

Epigenomes ◽  
2019 ◽  
Vol 3 (1) ◽  
pp. 3 ◽  
Author(s):  
Kay Gully ◽  
Jean-Marc Celton ◽  
Alexandre Degrave ◽  
Sandra Pelletier ◽  
Marie-Noelle Brisset ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Potential Role ◽  
Defense Responses ◽  
Pathogen Resistance ◽  
Growth Conditions ◽  
Treatment Level ◽  
Transcriptional Memory ◽  
Pre Treatment

Under natural growth conditions, plants experience various and repetitive biotic and abiotic stresses. Salicylic acid (SA) is a key phytohormone involved in the response to biotic challenges. Application of synthetic SA analogues can efficiently prime defense responses, and leads to improved pathogen resistance. Because SA analogues can result in long-term priming and memory, we identified genes for which expression was affected by the SA analogue and explored the role of DNA methylation in this memorization process. We show that treatments with an SA analogue can lead to long-term transcriptional memory of particular genes in Arabidopsis. We found that subsequent challenging of such plants with a bacterial elicitor reverted this transcriptional memory, bringing their expression back to the original pre-treatment level. We also made very similar observations in apple (Malus domestica), suggesting that this expression pattern is highly conserved in plants. Finally, we found a potential role for DNA methylation in the observed transcriptional memory behavior. We show that plants defective in DNA methylation pathways displayed a different memory behavior. Our work improves our understanding of the role of transcriptional memory in priming, and has important implication concerning the application of SA analogues in agricultural settings.

852. Potential Role of Amygdaloid Histone DNA Methylation Mechanisms in Anxiety and Alcohol Drinking Behaviors

2017 ◽  
Vol 81 (10) ◽  
pp. S345
Author(s):  
Tiffani Berkel ◽  
Huaibo Zhang ◽  
Evan Kyzar ◽  
Tara Teppen ◽  
Harish Krishnan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alcohol Drinking ◽  
Potential Role ◽  
Drinking Behaviors

scholarly journals Remember or not? For how long can a clonal plant remember drought stress?

2021 ◽  
Author(s):  
Jiaxin Quan ◽  
Zuzana Münzbergová ◽  
Vit Latzel
Keyword(s):  
Dna Methylation ◽  
Drought Stress ◽  
Environmental Conditions ◽  
Potential Role ◽  
Clonal Plant ◽  
Control Environment ◽  
Stress Memory ◽  
Limited Memory ◽  
Parental Plant

Stress can be remembered by plants in a form of ‘stress memory’ that can alter future phenotypes of previously stressed plants and even phenotypes of their offspring. It was shown that DNA methylation is among the mechanisms mediating the memory. It is not known for how long the memory is kept by plants. If the memory is long lasting, it can become maladaptive in situations when parental-offspring environment differ. We investigated for how long can a parental plant “remember” that it experienced a stress and pass the memory to its clonal offspring. We grew parental plants of three genotypes of Trifolium repens for five months either in control conditions or in control conditions that were interrupted with drought pulses applied for two months in four different time-slots. We also treated half of the parental plants with 5-azacytidine (5-azaC) to test for the potential role of DNA methylation in the stress memory. Then, we transplanted parental cuttings (ramets) individually to control environment and allowed them to produce offspring ramets for two months. The drought stress experienced by parents affected phenotypes of offspring ramets. Such a memory resulted in enhanced number of offspring side branches originating from plants that experienced drought stress maximally 6 weeks before their transplantation to control environment. We did not find any transgenerational memory in offspring of plants that experienced drought stress later than 6 weeks before their transplantation. 5-azaC also reduced the effect of transgenerational memory on offspring ramets. We confirmed that drought stress can trigger transgenerational memory in T. repens that is very likely mediated by DNA methylation. Most importantly, the memory was time limited and was gradually erased. We conclude that the time limited memory on environmental stress can be adaptive as climate tends to be variable and parental-offspring environmental conditions often do not match.

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