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Воздействие окисляющего стресса Gene Protein, экспрессии и метилирования ДНК на множественный склероз: многомерное исследование менделий.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Окисляющий стресс (ОС) связан с развитием множественного склероза (MS), однако причинно-следственная связь с точки зрения генетической патофизиологии остается неясной. Мы использовали менделианскую случайность (MR) и анализ совместной локализации для изучения взаимосвязи между генами ОС и MS с использованием комплексного подхода, основанного на мультиомике. МЕТОДЫ: Мы получили данные по результатам исследования, проведенного в рамках всей ассоциации по геному (GWAS) MS, из Международного консорциума по многоразовым склерозовым генетикам (этап обнаружения) и исследования

Совпадение в аннотации оригинала
BACKGROUND: Oxidative stress (OS) is linked to the development of multiple sclerosis (MS), but the causal relationship in terms of genetic p … by Level 1 evidence. The CR1 gene shows an association with MS risk, evidenced by Level 3 support. Methylation at cg24718015 and cg17833746 in the STAT3 gene correlates with reduced expression of STAT3. At the protein level, high circulating levels of STAT3 are inversely associated with MS risk (OR: 0.43, 95% CI, 0.33-0.54). Elevated levels of TNFRSF1A are a …

Exercise promotes skeletal muscle growth in adolescents via modulating Mettl3-mediated m6A methylation of MyoD in muscle satellite cells.

BACKGROUND: Exercise exerts positive impacts on skeletal muscle health and homeostasis. Emerging evidence suggests that m6A methylation is involved in various physiological processes. However, the impact of exercise on adolescent skeletal muscle growth and the underlying epigenetic mechanisms remain poorly understood. METHODS: The lower-limb skeletal muscles were harvested from exercise and control groups to compare the skeletal muscle growth in adolescents. mRNA sequencing was conducted to explore the mechanisms underlying enhanced skeletal muscle growth following exercise. The effects and m…

Placental PFAS concentrations are associated with perturbations of placental DNA methylation at loci with important roles on cardiometabolic health.

The placenta is crucial for fetal development, is affected by PFAS toxicity, and evidence is accumulating that gestational PFAS perturb the epigenetic activity of the placenta. Gestational PFAS exposure is can adversely affect offspring, yet individual and cumulative impacts of PFAS on the placental epigenome remain underexplored. Here, we conducted an epigenome-wide association study (EWAS) to examine the relationships between placental PFAS levels and DNA methylation in a cohort of mother-infant dyads in Arkansas. We measured 17 PFAS in human placental tissues and quantified placental DNA me…

Association of Methylenetetrahydrofolate Reductase rs1801133 Gene Polymorphism with Cancer Risk and Septin 9 Methylation in Patients with Colorectal Cancer.

PURPOSE: Colorectal cancer (CRC) is one of the most common malignancies, with a high incidence and mortality worldwide. Methylated Septin 9 (mSEPT9) has been used clinically as an auxiliary tool for CRC screening. The aim of the present study was to investigate the association of the methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphism with the risk of CRC and the methylation status of Septin 9 in CRC. METHODS: Information of 540 patients with a confirmed diagnosis of CRC and with a physical examination were utilized to assess the association of the MTHFR rs1801133 polymorphism …

Correlation between the RNA Expression and the DNA Methylation of Estrogen Receptor Genes in Normal and Malignant Human Tissues.

Estrogen plays a multifaceted function in humans via interacting with the estrogen receptors ERα, ERβ, and G protein-coupled estrogen recept … strogen receptors through gene expression profiling interactive analysis (GEPIA). The status of DNA methylation of estrogen receptor genes from TCGA were analyzed through the software Wanderer and cBioPortal. The MethSurv tool was utilized to estimate the relevance between specific cytosine-guanine (CG) methylation and tumor survival. The expression profile a …

Variations in DNA methylation and the role of regulatory factors in rice (Oryza sativa) response to lunar orbit stressors.

Deep space flight imposes higher levels of damage on biological organisms; however, its specific effects on rice remain unclear. To investigate the variations in DNA methylation under deep space flight conditions, this study examined rice seeds carried by Chang'e-5. After 23 days of lunar orbital flight, the samples were planted in an artificial climate chamber and subjected to transcriptome and DNA methylation sequencing during the tillering and heading stages. The methylation patterns in the rice genome exhibited variability in response to lunar orbital stressors. DNA methylation alters the …

NALCN Promoter Methylation as a Biomarker for Metastatic Risk in a Cohort of Non-Small Cell Lung Cancer Patients.

Liquid biopsy enables real-time monitoring of tumor development and response to therapy through the analysis of CTCs and ctDNA. NALCN is a sodium leak channel that is frequently involved in tumor evolution and immunity and acts as a tumor suppressor. Deletion of NALCN has been shown to increase cancer metastasis and the number of CTCs in peripheral blood. In this study, we investigated for the first time NALCN promoter methylation in (a) Aza-treated cell lines (A549, TE671, BT20, and MDA-MB-468), (b) paired NSCLC tissues (n = 22), and (c) plasma cell-free DNA (ctDNA) from patients with NSCLC (…

RNA methyltransferase NSUN2-mediated m5C methylation promotes Cr(VI)-induced malignant transformation and lung cancer by accelerating metabolism reprogramming.

Hexavalent chromium [Cr(VI)], one common environmental contaminant, has long been recognized as a carcinogen associated with lung cancer, but roles and mechanisms of Cr(VI)-induced epigenetic dysregulations in carcinogenesis remain to be investigated. In this study, we identified that RNA m5C methyltransferase NSUN2 was significantly upregulated in Cr(VI)-transformed cells and lung tissues of Cr(VI)-exposed mice. Inhibition of NSUN2 reduced cell proliferation, migration, colony formation and tube formation abilities. We found NSUN2-mediated m5C modification induced metabolic reprogramming and

Clinical value of the MGMT promoter methylation score in IDHmt low-grade glioma for predicting benefit from temozolomide treatment.

BACKGROUND: Diffuse IDH mutant low-grade gliomas (IDHmt LGG) (World Health Organization grade 2) typically affect young adults. The outcome is variable, with survival ranging from 5 to over 20 years. The timing and choice of initial treatments after surgery remain controversial. In particular, radiotherapy is associated with early and late cognitive toxicity. Over 90% of IDHmt LGG exhibit some degree of promoter methylation of the repair gene O(6)-methylguanine-DNA methytransferase (MGMTp) that when expressed blunts the effect of alkylating agent chemotherapy, for example, temozolomide (TMZ). …

Transcriptomic Profiling Reveals Sex-Specific Epigenetic Dynamics Involving kdm6b and H3K27 Methylation in Cerebral Ischemia-Induced Neurogenesis and Recovery.

Cerebral ischemic stroke ranks among the leading causes of death and disability worldwide. A significant challenge, beyond the lack of effective therapies, is the frequent oversight of sex as a vital factor in stroke research. This study focuses on elucidating the sex-specific epigenetic mechanisms that contribute to neural damage and recovery in cerebral ischemia. In our previously reported study, we demonstrated that following ischemia-induced cerebral artery occlusion (ICAO), female striatal tissue exhibited an early reinstatement of H3K9me2 marks on the promoters of inflammatory genes comp

Maternal Undernutrition Affects Fetal Thymus DNA Methylation, Gene Expression, and, Thereby, Metabolism and Immunopoiesis in Wagyu (Japanese Black) Cattle.

We aimed to determine the effects of maternal nutrient restriction (MNR) on the DNA methylation and gene expression patterns associated with metabolism and immunopoiesis in the thymuses of fetal Wagyu cattle. Pregnant cows were allocated to two groups: a low-nutrition (LN; 60% nutritional requirement; n = 5) and a high-nutrition (HN; 120% nutritional requirement, n = 6) group, until 8.5 months of gestation. Whole-genome bisulfite sequencing (WGBS) and RNA sequencing were used to analyze DNA methylation and gene expression, while capillary electrophoresis-Fourier transform mass spectrometry ass…

DNA methylation as a possible mechanism linking childhood adversity and health: results from a 2-sample mendelian randomization study.

Childhood adversity is an important risk factor for adverse health across the life course. Epigenetic modifications, such as DNA methylation (DNAm), are a hypothesized mechanism linking adversity to disease susceptibility. Yet, few studies have determined whether adversity-related DNAm alterations are causally related to future health outcomes or if their developmental timing plays a role in these relationships. Here, we used 2-sample mendelian randomization to obtain stronger causal inferences about the association between adversity-associated DNAm loci across development (ie, birth, childhoo…

DNA methylation profiling of labial salivary gland tissues revealed hypomethylation of B-cell-related genes in primary Sjögren's syndrome.

The objective of this epigenetic study was to investigate the cellular proportions based on DNA methylation signatures and pathways of differentially methylated genes in labial salivary gland (LSG) tissues of individuals with Sjögren's syndrome (SS). Two methylation array datasets from the Gene Expression Omnibus repository (GSE166373 and GSE110007) were utilized, consisting of 159 LSG tissues from 77 SS cases and 82 non-SS controls. The raw data underwent analysis using the Chip Analysis Methylation Pipeline (ChAMP) in R statistical tool, which identified differential methylation probes and r…

Associations of altered leukocyte DDR1 promoter methylation and childhood trauma with bipolar disorder and suicidal behavior in euthymic patients.

Altered DNA methylation (DNAm) patterns of discoidin domain receptor 1 (DDR1) have been found in the blood and brain of patients with schizophrenia (SCZ) and the brain of patients with bipolar disorder (BD). Childhood trauma (CT) is associated with changes in DNAm that in turn are related to suicidal behavior (SB) in patients with several psychiatric disorders. Here, using MassARRAY® technology, we studied 128 patients diagnosed with BD in remission and 141 healthy controls (HCs) to compare leukocyte DDR1 promoter DNAm patterns between patients and HCs and between patients with and without SB.…

Systemic inflammation, oxidative damage and neurocognition predict telomere length in a transdiagnostic sample stratified by global DNA methylation levels.

Epigenetic mechanisms contribute to the maintenance of both type 2 diabetes mellitus (T2DM) and psychiatric disorders. Emerging evidence suggests that molecular pathways and neurocognitive performance regulate epigenetic dynamics in these disorders. The current combined and transdiagnostic study investigated whether inflammatory, oxidative stress, adhesion molecule, neurocognitive and functional performance are significant predictors of telomere dynamics in a sample stratified by global DNA methylation levels. Peripheral blood inflammation, oxidative stress and adhesion molecule biomarkers and…

Epigenome-wide association study identifies neonatal DNA methylation associated with two-year attention problems in children born very preterm.

Prior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age. DNA methylation was measured from bu…

Epigenome-wide association study of DNA methylation in maternal blood leukocytes with BMI in pregnancy and gestational weight gain.

OBJECTIVES: We aimed to discover CpG sites with differential DNA methylation in peripheral blood leukocytes associated with body mass index (BMI) in pregnancy and gestational weight gain (GWG) in women of European and South Asian ancestry. Furthermore, we aimed to investigate how the identified sites were associated with methylation quantitative trait loci, gene ontology, and cardiometabolic parameters. METHODS: In the Epigenetics in pregnancy (EPIPREG) sample we quantified maternal DNA methylation in peripheral blood leukocytes in gestational week 28 with Illumina's MethylationEPIC BeadChip.…

Anaerobic benzene oxidation in Geotalea daltonii involves activation by methylation and is regulated by the transition state regulator AbrB.

UNLABELLED: Benzene is a widespread groundwater contaminant that persists under anoxic conditions. The aim of this study was to more accurat … tion of benzene to the G. daltonii whole-cell lysate resulted in toluene formation, indicating that methylation of benzene was occurring. Complementation of σ54- (deficient) E. coli transformed with the bss operon restored its ability to grow in the presence of toluene, revealing bss to be regulated by σ54. Binding sites for σ70 and the transition state regul …

Prenatal exposures and cell type proportions are main drivers of FKBP5 DNA methylation in maltreated and non-maltreated children.

DNA methylation in peripheral tissues may be a relevant biomarker of risk for developing mental disorders after exposure to early life adversity. Genes involved in HPA axis regulation, such as FKBP5, might play a key role. In this study, we aimed to identify the main drivers of salivary FKBP5 methylation in a cohort of 162 maltreated and non-maltreated children aged 3-5 years at two measurement timepoints. We combined data from a targeted bisulfite sequencing approach for fine-mapping 49 CpGs in regulatory regions of FKBP5 and epigenetic scores for exposure to alcohol, cigarette smoke, and glu…

One Carbon to Rule Them All: Formaldehyde is a One-Carbon Signal Connecting One-Carbon Metabolism and Epigenetic Methylation.

Formaldehyde is commonly thought of as an environmental toxin or laboratory fixation reagent, but there is a growing appreciation for its broader physiological contributions as a naturally generated one-carbon metabolite across all kingdoms of life. In this In Focus article, we summarize emerging advances in the field that show how formaldehyde plays diverse roles as a one-carbon signal in DNA damage, one-carbon metabolism, and epigenetic regulation.