Результаты поиска

5-mC DNA methylation in neurodevelopment: from molecular mechanisms to therapeutic implications.

5-mC DNA methylation is a fundamental epigenetic modification that plays a crucial role in neurodevelopment and neurological disorders. This review synthesizes the current understanding of 5-mC DNA methylation in neural system development and its implications in neurodevelopmental disorders. During normal neural development, 5-mC methylation precisely regulates neural stem cell differentiation and neuronal maturation through DNA methyltransferases (DNMTs) and methyl-CpG-binding domain (MBD) proteins. Disruption of these methylation patterns contributes to various neurodevelopmental disorders. …

Methylation aberrations and genomic instability synergistically drive the evolution of intrahepatic cholangiocarcinoma.

AIMS & METHODS: DNA methylation and genomic instability are critical drivers of cancer initiation and malignant progression. However, the roles of methylation aberrations and genomic instability in malignant progression have not been thoroughly investigated in intrahepatic cholangiocarcinoma (ICC). To address this, we identified differentially methylated regions (DMRs) and somatic copy number alterations (SCNAs) from 341 ICC samples across various stages. RESULTS: Our findings revealed that stages IAIB, II, IIIA, and IIIB exhibited comparable methylation changes, whereas stage IV ICC showed a…

Comparative Analysis of CXCR5 Circulating DNA Methylation Levels in Autoimmune Rheumatic Diseases.

OBJECTIVE: To assess CXC chemokine receptor 5 (CXCR5) circulating DNA methylation differences in autoimmune rheumatic diseases and their relation with clinical features. METHODS: Targeted methylation sequencing was performed using peripheral blood from 164 rheumatoid arthritis (RA), 30 systemic lupus erythematosus (SLE), 30 ankylosing spondylitis (AS), 30 psoriatic arthritis (PsA), 24 Sjögren's syndrome (SS) patients, and 30 healthy controls (HC). RESULTS: Significant differences in CXCR5 cg19599951 methylation were found between RA and HC, as well as AS and SLE. RA patients exhibited higher…

Differential Methylation Patterns Predict HBsAg Seroconversion in Hepatitis B Virus Reactivation Patients.

BACKGROUND: Hepatitis B virus (HBV) modulates immune epigenetic landscape. Therefore, we investigated immune epigenetic landscape in HBsAg seroconverters and non-seroconverters. METHODS: Sixteen rHBV patients including seroconverters (SC, n = 7) and non-seroconverters (NSC, n = 9) at baseline and week 24 were recruited. Age matched naïve chronic hepatitis B patients (nCHBV, n = 7) and healthy controls (HC, n = 6) were also included. PBMCs and plasma were subjected to genome-methylation, gene-expression, immunophenotyping, functionality, and cytokines analysis using Reduced Representation Bisu…

DNA methylation patterns associated with prior tuberculosis infection in people with HIV.

Mechanisms by which prior tuberculosis (TB) increases long-term risk for cancer, cardiovascular, and neurological disorders remain unclear, particularly in people with HIV (PWH). This study investigated DNA methylation (DNAm) patterns and associated pathways in PWH with and without prior TB infection. DNAm was analyzed in blood samples from 30 PWH (10 with prior latent TB infection [LTBI], 10 with previous successfully treated active TB, and 10 with no TB) using the Illumina MethylationEPIC BeadChip covering over 850,000 CpG sites. Epigenetic age was estimated, and age acceleration was calcula…

A cell type enrichment analysis tool for brain DNA methylation data (CEAM).

DNA methylation (DNAm) signatures are highly cell type-specific, yet most epigenome-wide association studies (EWAS) are performed on bulk tissue, potentially obscuring critical cell type-specific patterns. Existing computational tools for detecting cell type-specific DNAm changes are often limited by the accuracy of cell type deconvolution algorithms. Here, we introduce CEAM (Cell-type Enrichment Analysis for Methylation), a robust and interpretable framework for cell type enrichment analysis in DNA methylation data. CEAM applies over-representation analysis with cell type-specific CpG panels …

Протеин TNFα, метилация ДНК, оценка выражений MRNA и miRNA в множестве склерозов.

КОЛИЧЕСТВО: Фактор некроза опухоли альфа (TNFα) является ключевым цитокином, вовлеченным в воспалительные и нейродегенеративные процессы, лежащие в основе множественных склерозов (MS). Его выражение четко регулируется эпигенетическими и посттранарными механизмами, включая стимулятор метилирования и деятельность МИРНА. Цель этого исследования заключается в изучении выражения, стимулятора метилирования и его регулирования с помощью miR-130a-3p у пациентов с релапсирующими излучающими (RR)MS, и в оценке как сыворотки, так и слюны как потенциальных диагностических биофильтров. МЕТОДЫ: Зачислены па

Совпадение в аннотации оригинала
BACKGROUND: Tumor necrosis factor alpha (TNFα) is a key cytokine involved in the inflammatory and neurodegenerative processes underlying multiple sclerosis (MS). Its expression is finely regulated by epigenetic and post-transcriptional mechanisms, including promoter methylation and miRNA activity. The objective of this study is to investigate TNFα expression…

Identification of Novel DNA Methylation Prognostic Biomarkers for AML With Normal Cytogenetics.

PURPOSE: AML is a hematologic cancer that is clinically heterogeneous, with a wide range of clinical outcomes. DNA methylation changes are a hallmark of AML but are not routinely used as a criterion for risk stratification. The aim of this study was to explore DNA methylation markers that could risk stratify patients with cytogenetically normal AML (CN-AML), currently classified as intermediate-risk. MATERIALS AND METHODS: DNA methylation profiles in whole blood samples from 77 patients with CN-AML in The Cancer Genome Atlas (LAML cohort) were analyzed. Individual 5'-cytosine-phosphate-guanin…

Odontogenic Myxomas Harbor Recurrent Copy Number Alterations and a Distinct Methylation Signature.

Odontogenic myxoma is a rare, benign, and locally aggressive tumor that develops in the tooth-bearing areas of the jaw. The molecular mechanisms underlying odontogenic myxomas are unknown and no diagnostic markers are available to date. The aim of this study was to analyze DNA methylation and copy number variations in odontogenic myxomas to identify new molecular signatures for diagnostic decision-making. We collected a cohort of 16 odontogenic myxomas from 2006 to 2021 located in the mandible (n = 10) and maxilla (n = 6) with available formalin-fixed paraffin-embedded or fresh frozen tumor ti…

[DNA Methylation Profiling in Aneurysm and Comorbid Atherosclerosis of the Ascending Aorta].

Atherosclerosis and aneurysm of the aorta are relatively common pathological conditions that remain asymptomatic for a long period of time and have life-threatening and disabling complications. DNA methylation profiling in several regions (a dilated area, a nondilated area, and an atherosclerotic plaque) of the ascending aorta was carried out in patients with aortic aneurysm. DNA methylation was analyzed by reduced representation bisulfite sequencing (RRBS). Differences in methylation level between dilated and normal aortic tissues were detected for two CpG sites of the NR2F1-AS1 gene (|Δβ| > …

Genome-wide DNA methylation and transcriptomic patterns of precancerous gastric cardia lesions.

BACKGROUND: Intestinal metaplasia (IM) and intraepithelial neoplasia (IEN) are considered precursors of gastric cardia cancer (GCC). Here, we investigated the histopathologic and molecular profiles of precancerous gastric cardia lesions (PGCLs) and biomarkers for risk stratification of gastric cardia IM. METHODS: We conducted a hospital-based evaluation (n = 4578) for PGCL profiles in high-incidence and non-high-incidence regions for GCC in China. We next performed 850K methylation arrays (n = 42) and RNA-seq (n = 44) in tissues with PGCLs. We then examined the protein expression of candidate…

Epigenetic DNA Methylation and Protein Homocysteinylation: Key Players in Hypertensive Renovascular Damage.

Hypertension has been a threat to the health of people, the mechanism of which, however, remains poorly understood. It is clinically related to loss of nephron function, glomerular sclerosis, or necrosis, resulting in renal functional declines. The mechanisms underlying hypertension's development and progression to organ damage, including hypertensive renal damage, remain to be fully elucidated. As a developing approach, epigenetics has been postulated to elucidate the phenomena that otherwise cannot be explained by genetic studies. The main epigenetic hallmarks, such as DNA methylation, histo…

Epigenetic regulation of mitochondrial fission and cardiac fibrosis via sFRP3 promoter methylation.

In the process of cardiac fibrosis, the balance between the Wnt/β-catenin signalling pathway and Wnt inhibitory factor genes plays an import … diac fibrosis. Using clinical samples and animal models, we investigated the role of sFRP3 promoter methylation in potentially enhancing cardiac fibrosis. We also attempted to characterize the underlying mechanisms using an isoprenaline-induced cardiac fibrosis mouse model and cultured primary cardiac fibroblasts. Hypermethylation of sFRP3 was associated with …

The association between neighborhood deprivation and DNA methylation in an autopsy cohort.

Previous research has found that living in a disadvantaged neighborhood is associated with poor health outcomes. Living in disadvantaged neighborhoods may alter inflammation and immune response in the body, which could be reflected in epigenetic mechanisms such as DNA methylation (DNAm). We used robust linear regression models to conduct an epigenome-wide association study examining the association between neighborhood deprivation (Area Deprivation Index; ADI), and DNAm in brain tissue from 159 donors enrolled in the Emory Goizueta Alzheimer's Disease Research Center (Georgia, USA). We found o…

The potential utility of cord blood DNA methylation in pediatric clinical practice.

Our understanding of the origins of noncommunicable diseases has evolved over the years with greater consideration given to the lasting influence exposures and experiences during the preconceptional and prenatal periods can have. Research highlights the associations of parental exposures (e.g., diet, obesity, gestational diabetes, lipid profile, toxic exposures and microbiome) with the infant/fetal methylome and suggest associations with infant, child and/or adolescent chronic health outcomes. Thus, epigenetics and specifically cord blood DNA methylation may have utility as biomarkers for dise…

Algae decomposition released dissolved organic matter subfractions on dark abiotic mercury methylation.

To understand the mechanism of dark abiotic mercury (Hg) methylation by algae-derived dissolved organic matter (DOM) and effectively manage the environmental risks of mercury methylation in aquaculture areas, we investigated the influence of subfractions of DOM released from algae (Ulothrix sp.) decomposition on mercury methylation. The results showed that the hydrophobic basic component (HOB) in DOM exhibited the most substantial promotion effect on Hg methylation. The methylmercury (MeHg) production in the HOB treatment increased significantly, while the production rate of MeHg (%MeHg repres…

Selenium-phosphorus modified biochar reduces mercury methylation and bioavailability in agricultural soil.

Biochar is a frequently employed for solidifying and stabilizing mercury (Hg) contamination in soil. However, it often results in an elevate … il mass ratio: 0.5 %) were conducted to investigate the impacts of these soil amendments on soil Hg methylation and bioavailability. Se and P co-modification substantially increased the surface area, pore volume, and Hg adsorption capacity of BC. BC treatment increased the simulated gastric acid-soluble Hg, organo-chelated Hg, and MeHg in the soil. Conversely …

Mercury Immobilization without Methylation in Sulfidogenic Systems Dominated by Sulfur Disproportionating Bacteria.

The sulfidogenic process mediated by sulfate-reducing bacteria (SRB) is not ideal for treating mercury (Hg)-bearing wastewater due to the risk of methylmercury (MeHg) production. Addressing this challenge, our study demonstrated that, under S0-rich conditions and without organic additives, sulfidogenic communities dominated by sulfur-disproportionating bacteria (SDB) can effectively remove Hg(II) and prevent MeHg production. Using various inocula, we successfully established biological sulfidogenic systems driven separately by SDB and SRB. Batch experiments revealed that SDB cultures completel

Exposure to air pollution is associated with DNA methylation changes in sperm.

Exposure to air pollutants has been associated with adverse health outcomes in adults and children who were prenatally exposed. In addition to reducing exposure to air pollutants, it is important to identify their biologic targets in order to mitigate the health consequences of exposure. One molecular change associated with prenatal exposure to air pollutants is DNA methylation (DNAm), which has been associated with changes in placenta and cord blood tissues at birth. However, little is known about how air pollution exposure impacts the sperm epigenome, which could provide important insights i…