Результаты поиска

DNMT1 stabilizes MAPK10 via m5C RNA methylation to ameliorate hepatic steatosis and mitochondrial dysfunction in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents a highly prevalent metabolic disorder; however, the functional role of mito … trating that DNMT1 post-transcriptionally regulates MAPK10 expression and stability through m5C RNA methylation. We establish MAPK10 as a key metabolic protector against NAFLD, ameliorating hepatic steatosis, oxidative stress, and mitochondrial dysfunction. By integrating bioinformatics, molecular biology, and functional validation across in vivo and in vitro …

Cell-free DNA methylation profiling reveals injury types and severities in swine rotational and contusional models of traumatic brain injury.

Early diagnosis of traumatic brain injury (TBI) is crucial to guide treatment and improve recovery. Yet neuroimaging-the current gold standard for detection-cannot detect subtle biochemical changes and is insufficient to diagnose many TBI cases. Consequently, there is an urgent need for early, brain-associated biomarkers of TBI. Following injury, brain cells release cell-free DNA (cfDNA) into peripheral blood due to neurovascular disruption. DNA methylation patterns, which inform tissue specificity, could serve as biomarkers for TBI severity and progression. To test this hypothesis, we analyze…

Genomic regions exhibiting divergent DNA methylation patterns co-vary with loci associated with sexual signalling traits in a stick insect.

The evolution of signalling traits can affect local adaptation, mate choice and the development of reproductive isolation between diverging populations. While the genetic basis of many sexual signalling traits is well characterized, variation in these traits may also reflect regulatory mechanisms, including epigenetic marks. However, the extent to which epigenetic marks, particularly DNA methylation, are associated with signalling traits remains unclear. Here, we focus on epigenetic variation and cuticular hydrocarbons (CHCs), the latter being chemical traits that can be used for mate choice i…

The epigenetic role of ADRB3 DNA methylation in post-bariatric energy expenditure for women with obesity: a longitudinal observational study.

Bariatric surgery induces profound metabolic changes that may influence epigenetic mechanisms regulating genes involved in energy metabolism. Given the global burden of obesity on women’s health, understanding molecular responses to surgical treatment is essential. This study investigated the effect of Roux-en-Y gastric bypass (RYGB) on DNA methylation of the β-3 adrenergic receptor (ADRB3) gene and its influence on energy expenditure in women with obesity. Sixteen participants were evaluated before and six months after surgery, including measurements of body composition, resting metabolic rat…

The impact of arsenic exposure on DNA methylation in humans: building an epigenetic biomarker of exposure across three independent cohorts.

BACKGROUND: Inorganic arsenic (As) is a carcinogen and >200 million people worldwide are exposed to As through drinking water. Long-term As exposure increases the risk of chronic diseases including cancer and cardiovascular disease. While prior work has identified several genomic regions where DNA methylation (DNAm) is associated with As exposure, our knowledge remains limited. METHODS: We first evaluated the association of As exposure (measured in urine and drinking water) with DNAm (measured genome-wide in blood cells at >720 000 cytosine-phosphate-guanine (CpG) sites) among 1186 Bangladesh…

Multi-tissue DNA methylation analysis to identify an appropriate surrogate tissue for a unique neurological tissue specific to spina bifida.

BACKGROUND: Animal models suggest a role of epigenetic mechanisms, including DNA methylation, in neural tube closure; however, studies characterizing DNA methylation profiles in nervous system tissue from humans with spina bifida are limited. In this study, we assessed DNA methylation profiles in dural tissue of infants with spina bifida, collected at the time of surgical closure of the defect, and examined whether whole blood or buccal swab are appropriate surrogate tissues, as they are more practical to collect in large-scale epidemiological studies. DNA methylation was measured in dural tis…

Longitudinal study of genome-wide DNA methylation in individuals with and without post-acute symptoms following SARS-CoV-2 infection.

BACKGROUND: Symptoms following SARS-CoV-2 infection, referred to as Long-COVID, have been reported since the pandemic. We investigated whether COVID-19 or Long-COVID is associated with persistent genome-wide DNA methylation (DNAm) changes in whole blood using a longitudinal design. METHODS: DNAm was measured using the Illumina EPIC V2 platform (859,651 CpGs) in 297 adult participants (594 samples in total) from two Norwegian population-based cohorts, with samples collected pre-infection (2020) and during the pandemic (2023). Participants were classified as Long-COVID, COVID-19 (no persistent …

RON receptor tyrosine kinase regulates abiraterone resistance in prostate cancer via the methylation-dependent and independent dual functions of DNMT1.

Acquired resistance to the CYP17 inhibitor abiraterone is a critical challenge in the clinical treatment of metastatic prostate cancer; however, the mechanisms driving this resistance remain elusive. This study suggests that aberrant RON expression plays an important role in the development of acquired abiraterone resistance in prostate cancer cells. Increased RON expression was observed in most clinical tumor samples with an abiraterone-insensitive phenotype. In established prostate cancer cell lines, aberrant RON expression is associated with increased abiraterone resistance and enhanced mig

Epigenetic and metabolic signatures in systemic lupus erythematous: The impact of excess body weight on adipose tissue DNA methylation profile.

BACKGROUND & AIMS: The interaction between systemic lupus erythematosus (SLE), excess body weight, and epigenetic variation remains poorly understood. This study investigated the association between excess body weight and genome-wide DNA methylation profiles in subcutaneous adipose tissue (SAT) from patients with SLE. METHODS: In this cross-sectional study, 36 premenopausal women with SLE were classified as normal weight (NW,n = 16) or excess body weight (EBW, n = 20). Anthropometric, metabolic, dietary, and physical activity data were collected. Genome-wide DNA methylation in SAT was assesse…

Analgesic drug usage is associated with differential methylation in lower back and neuropathic pain patients in the Quebec pain registry.

Analgesic drugs, which modulate nociception through various cellular pathways, are extensively used in pain treatment. However, their utility in blocking pain signaling is offset by side effects and potential for misuse. The long-term effects of exposure to these drugs remain poorly understood and may involve epigenetic alterations to gene expression patterns, including differential methylation of gene regulatory regions. We hypothesized that individuals with pain conditions, enrolled in a longitudinal pain registry and exposed to different analgesic drugs, would later exhibit significant diff…

Epigenetic alterations in WDFY4 DNA methylation are linked to immunoinflammatory processes in rheumatoid arthritis: insights from a case-control study.

OBJECTIVE: This study examines the relationship between WDFY4 gene DNA methylation and clinical characteristics of rheumatoid arthritis (RA) through peripheral blood analysis. METHODS: Peripheral blood samples from 150 RA patients and 150 healthy controls were analyzed via targeted methylation sequencing. Generalized linear regression assessed associations between WDFY4 methylation haplotypes, CpG sites, and clinical markers, with adjustment for potential confounders. RESULTS: RA patients exhibited significantly reduced overall WDFY4 methylation levels compared to controls (0.865 ± 0.053 vs.…

Betaine-driven Keap1 methylation promotes p62-mediated autophagy and Nrf2 stabilization to alleviate glutathione-dependent redox dyshomeostasis in liver injury.

Nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates detoxification and antioxidant programs that protect the liver from chemical and metabolic stress. Nrf2 is restrained by Kelch-like ECH-associated protein 1 (Keap1), which can be removed through p62-mediated selective autophagy; however, nutritional cues that engage this pathway remain incompletely understood. This study provides evidence that betaine (trimethylglycine; BET) can regulate the Keap1-Nrf2 axis through modulation of Keap1. In biochemical and cellular assays, betaine was associated with methylation of Keap1 at Cys513 an…

PAX1/JAM3 methylation in cervical exfoliated cells: a robust diagnostic biomarker for cervical high-grade lesions associated with vaginal dysbiosis.

OBJECTIVE: This prospective single-center study aimed to investigate the clinical correlation between PAX1/JAM3 methylation (CISCER) assay and clinically evaluated vaginal microecological features in women referred for colposcopy, and to assess the potential complementary diagnostic value for detecting high-grade cervical lesions. METHODS: Participants were recruited from the Gynecologic Colposcopy Outpatient Clinic of Beijing Anzhen Hospital, Capital Medical University, from February 2024 to December 2024. The clinical performance of the CISCER assay and the vaginal microecology composition o…

Genome-Wide Analysis of DNA Methylation Profiles on Jining Grey Goat Uterus Associated with Prolificacy Using Whole-Genome Bisulfite Sequencing.

Litter size is a vital economic trait in goat production, and previous studies on its regulatory mechanisms mainly focus on ovarian tissues. The genome-wide DNA methylation landscape of the goat uterus and its association with prolificacy remain poorly understood. In this study, we performed whole-genome bisulfite sequencing (WGBS) on uterine tissues from high-prolificacy (HP) and low-prolificacy (LP) Jining Grey Goats to explore epigenetic regulatory mechanisms underlying litter size. A total of 880 differentially methylated regions (DMRs) and 274 differentially methylated genes (DMGs) were i…

The Effect of MEG3 Promoter Methylation on MEG3 Expression in Acute Myeloid Leukemia: Assessment by High-Resolution Melting (HRM) Analysis.

INTRODUCTION: Epigenetic mechanisms play a crucial role in regulating genome expression and are subject to dysregulation in leukemia, hence exerting a significant impact on the pathogenesis of this malignancy. Maternally expressed gene 3 (MEG3), a long non-coding RNA, has been identified as a tumor suppressor in many hematologic malignancies due to its frequent down-regulation. This study aimed to examine the expression and methylation status of MEG3 in patients diagnosed with acute myeloid leukemia by employing the High-Resolution Melting (HRM) method. MATERIALS AND METHODS: The study employ…

Association of prenatal exposure to opioids, cannabis, and polysubstance use with cord blood DNA methylation patterns in a multiancestry cohort.

Blood DNA methylation patterns are highly predictive of prenatal exposure to smoking, and differential methylation has been associated with maternal alcohol use. We extended this to determine whether DNA methylation patterns in cord blood are associated with prenatal exposure to opioids, cannabis, and polysubstance use. We also evaluated whether DNA methylation patterns have predictive utility. We examined 932 mother-child pairs in the Boston Birth Cohort between 1998 and 2020 with cord blood DNA methylation data. For each substance self-reported within 72 hr after birth, we performed an adjus…

Эпигенетические достижения в педиатрическом многоразовом склерозе: ДНК-метилирование примечательно участие Эпштейна-Барра заражённых вирусом и принимающих иммунных сетей.

СПРАВОЧНАЯ ИНФОРМАЦИЯ И ЦЕЛИ: Педиатрический множественный склероз (PedMS) предоставляет уникальную возможность для изучения патогенеза MS с учетом короткого интервала между воздействием на окружающую среду и возникновением заболеваний. Цель этого исследования состояла в том, чтобы выявить различные метилированные регионы (ДМР), которые способствуют взаимодействию между экологическими факторами и геномными факторами на ранних этапах заболевания. В этом многоцентровом исследовании мы проанализировали периферическую ДНК крови. 175 Итальянские предметы122 Пациенты педиатрии, 53 - здоровый контрол

Совпадение в аннотации оригинала
BACKGROUND AND OBJECTIVES: Pediatric-onset multiple sclerosis (PedMS) provides a unique opportunity to investigate MS pathogenesis because o … al blood DNA from 175 Italian subjects (122 PedMS patients, 53 healthy controls) using the Infinium Methylation EPIC Array v2. All patients were enrolled within 4 years of onset. The bioinformatic pipeline included batch effect correction, normalization, and differential methylation analysis adjusted for sex and inferred cell-type proportions. DMRs were detec …

N-Methylation of Legionaminic Acid in Legionella pneumophila Serogroup 1 LPS Affects Cell Surface Properties, Intracellular Growth, and Cytokine Response.

Legionella pneumophila is widely recognized as the principal organism responsible for Legionnaires' disease. Modifications of surface-exposed lipopolysaccharide in L. pneumophila are key determinants of bacterial adaptation to host cells. Using a mutant strain deficient in N-methylation of legionaminic acid and fluorescence-based biophysical analyses, it was demonstrated that N-methyl groups linked to the acetimidoylamino group of legionaminic acid modulate the physicochemical properties of the bacterial cell surface and influence the interaction of L. pneumophila with macrophages. Loss of N-m…

Preliminary Analysis of CpG, CHG and CHH Methylation in the Mitochondrial Control Region of Dogs With Malignant Mammary Gland Tumours.

Canine mammary tumours (CMTs) are one of the most frequently observed malignancies in female dogs. Many studies have investigated epigenetic changes in CMT at the nuclear level, yet the role of mtDNA methylation, particularly in the D-loop region, remains largely unexplored. Given the significant importance of the D-loop region in mtDNA replication and transcription, and the previous identification of CpG enrichment there, this preliminary study aimed to assess apparent methylation signals in the mitochondrial D-loop region. We examined CpG, CHG and CHH methylation contexts in matched tumour a…

Artificial Intelligence/Machine Learning-Driven cfDNA Methylation Blood Test for Early Cancer Detection in Military Personnel With Environmental Toxin Exposure.

INTRODUCTION: Military personnel face heightened cancer risks from exposure to burn-pit emissions, per- and polyfluoroalkyl substances (PFAS), jet fuel, and radiation. Veterans show elevated malignancy rates, and active-duty personnel remain vulnerable because of ongoing operational exposures, underscoring the need for early detection. Traditional screening methods are invasive and have limited sensitivity for early-stage disease. This study evaluates the feasibility of artificial intelligence/machine learning (AI/ML)-based cell-free DNA (cfDNA) methylation analysis for early cancer detection …