Gene DNA Methylation Research Articles

Constructing mRNA-meth-miRNA single-sample networks to reveal the molecular interaction patterns induced by lunar orbital stressors in rice (Oryzasativa).

To explore the bio-effects during Moon exploration missions, we utilized the Chang'E 5 probe to carry the seeds of Oryza. Sativa L., which were later returned to Earth after 23 days in lunar orbit and planted in an artificial climate chamber. Compared to the control group, rice seeds that underwent spaceflight showed inhibited growth and development when planted on the ground. Then we collected samples and employed RNA sequencing (RNA-Seq) and whole-genome bisulfite sequencing (WGBS) in the tillering and heading stages of rice. To gain a comprehensive understanding of the dysregulation in molecular interaction patterns during Moon exploration, a bioinformatics pipeline based on mRNA-meth-miRNA Single-Sample Networks (SSNs) was developed. Specifically, we constructed four SSNs for each sample at the mRNA, DNA methylation (promoter and gene bodies), and miRNA levels. By combining with the Protein-Protein Interaction (PPI) network, SSNs can character individual-specific gene interaction patterns. Under spaceflight conditions, distinct interaction patterns emerge across various omics levels. However, the molecules driving changes at each omics level predominantly regulate consistent biological functions, such as metabolic processes, DNA damage and repair, cell cycle, developmental processes, etc. In the tillering stage, pathways such as ubiquitin mediated proteolysis, nucleotide excision repair, and nucleotide metabolism are significantly enriched. Moreover, we identified 18 genes that played key/hub roles in the dysregulation of multi-omics molecular interaction patterns, and observed their involvement in regulating the above biological processes. As aforementioned, our multi-omics SSNs method can reveal the molecular interaction patterns under deep space exploration.

Mendelian Randomization Reveals Potential Causal Relationships Between DNA Damage Repair-Related Genes and Inflammatory Bowel Disease.

DNA damage repair (DDR) plays a key role in maintaining genomic stability and developing inflammatory bowel disease (IBD). However, no report about the causal association between DDR and IBD exists. Whether DDR-related genes are the precise causal association to IBD in etiology remains unclear. Herein, we employed a multi-omics summary data-based Mendelian randomization (SMR) approach to ascertain the potential causal effects of DDR-related genes in IBD. Methods: Summary statistics from expression quantitative trait loci (eQTL), DNA methylation QTL (mQTL), and protein QTL (pQTL) on European descent were included. The GWAS summarized data for IBD and its two subtypes, Crohn's disease (CD) and ulcerative colitis (UC), were acquired from the FinnGen study. We elected from genetic variants located within or near 2000 DDR-related genes in cis, which are closely associated with DDR-related gene changes. Variants were selected as instrumental variables (IVs) and assessed for causality with IBD and its subtypes using both SMR and two-sample MR (TSMR) approaches. Colocalization analysis was employed to evaluate whether a single genetic variant simultaneously influences two traits, thereby validating the pleiotropy hypothesis. Results: We identified seven DDR-related genes (Arid5b, Cox5a, Erbb2, Ube2l3, Gpx1, H2bcl2, and Mapk3), 33 DNA methylation genes, and two DDR-related proteins (CD274 and FCGR2A) which were all causally associated with IBD and its subtypes. Beyond causality, we integrated the multi-omics data between mQTL-eQTL and conducted druggability values. We found that DNA methylation of Erbb2 and Gpx1 significantly impacted their gene expression levels offering insights into the potential regulatory mechanisms of risk variants on IBD. Meanwhile, CD247 and FCGR2A could serve as targets for potential pharmacological interventions in IBD. Conclusions: Our study demonstrates the causal role of DDR in IBD based on the data-driven MR. Moreover, we found potential regulatory mechanisms of risk variants on IBD and potential pharmacological targets.

Identification of Potential Intervention Targets Involved in Prior Exercise that Attenuates Peripheral Neuropathic Pain by Integrating Transcriptome and Whole-genome Bisulfite Sequencing Analyses.

Changes in DNA methylation and subsequent alterations in gene expression have opened a new direction in research related to the pathogenesis of peripheral neuropathic pain (PNP). This study aimed to reveal epigenetic perturbations underlying DNA methylation in the dorsal root ganglion (DRG) of rats with peripheral nerve injury in response to prior exercise and identify potential target genes involved. Male Sprague-Dawley rats were divided into three groups, namely, chronic constriction injury (CCI) of the sciatic nerve, CCI with prior 6-week swimming training (CCI_Ex), and sham operated (Sham). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were used as the main observation indicators to evaluate behavioral changes associated with pain. In this study, 6-week swimming training before CCI prevented later chronic pain. In particular, CCI rats with prior exercise showed a significant increase in the MWT and TWL of the injured lateral hind paw compared with CCI rats without exercise on days 14, 21, and 28 after CCI. Whole-genome bisulfite sequencing from the injured lumbar (L4-L6) DRGs on the 28th day after surgery was detected. We also generated DNA methylation maps of the two comparisons (sham group vs. CCI and CCI groups vs. CCI_Ex group), and 396 overlapping differentially methylated region-related genes were found between the two comparisons. Moreover, we integrated RNA sequencing to understand the mechanism by which differential DNA methylation after CCI may influence gene expression. Finally, Ryr1 and Xirp2 were identified through association analysis of two omics and quantitative reverse-transcription polymerase chain reaction, respectively. The methylation levels of Ryr1 and Xirp2 were upregulated with a corresponding increase in their mRNA expression in the DRGs of CCI rats, whereas prior exercise downregulated Ryr1 methylation and restore its expression level. Functional enrichment analysis of both omics found that the calcium signaling pathway was significantly enriched. Therefore, the potential intervention targets (Ryr1 and Xirp2) in L4-L6 DRGs may be involved in prior exercise that attenuates PNP induced by CCI. This study provides crucial insights into the epigenetic regulation of PNP responses to prior exercise.

Chromosome-scale telomere to telomere genome assembly of common crystalwort (Riccia sorocarpa Bisch.)

Riccia sorocarpa Bisch., commonly known as common crystalwort, is a plant belonging to the Marchantiales order with a cosmopolitan distribution among a wide range of habitats: fields, gardens, waste ground, on paths, cliff tops, and thin soil over rocks or by water bodies. However, research into the genetic aspects of this species is limited. In this study, the chromosome-scale telomere-to-telomere genome of R. sorocarpa was assembled exclusively by Oxford Nanopore long-read sequencing and Pore-C technology. A high-quality chromosomal-scale assembly was obtained with a final genome size of 376.690 Mbp, contig N50 of 49.132 Mbp and 97.02% of the assembled contigs associated with the eight chromosomes. Genome assembly completeness was confirmed by BUSCO analysis accounting 91.8%. Among 27,626 total genes, 23,562 (85.29%) were functionally annotated. Moreover, collinearity of Marchantiales was analyzed as well as gene family evolution and DNA methylation profile. The availability of this genome, which is the second telomere-to-telomere liverwort assembly, opens up new avenues for in-depth analysis of R. sorocarpa genetic diversity and genomic characteristics.

PFAS Exposure and Male Reproductive Health: Implications for Sperm Epigenetics.

Per- and polyfluoroalkyl substances (PFASs) are persistent environmental contaminants found in human tissues and persist in the environment, posing significant risks to reproductive health. This review examines the impact of PFAS exposure on male reproductive health, with a focus on sperm epigenetics. PFASs disrupt endocrine function by altering key reproductive hormones and impairing sperm motility, quality, and viability. Epidemiologic and animal studies highlight inconsistent yet concerning associations between PFAS exposure and semen parameters, as well as altered gene expression and DNA methylation patterns. Moreover, PFAS exposure during critical windows of development has been linked to differential impacts on male versus female pubertal development, cognitive outcomes, and reproductive physiology, emphasizing the complexity of PFAS interactions. This comprehensive analysis highlights the need for continued research into the mechanisms by which PFASs influence reproductive health and development with potential implications for sperm epigenetics. The review emphasizes the importance of understanding the epigenetic mechanisms behind these disruptions, particularly DNA methylation and its role in heritable changes. Investigating the epigenetic modifications driven by PFAS exposure is crucial for elucidating the mechanisms by which these chemicals influence reproductive health. Future research should focus on understanding these epigenetic changes in both immediate fertility outcomes and transgenerational health risks.

Peripheral Blood ABCG1 Gene DNA Methylation: Mediating the Relationship between Dietary Intake of Methyl Donor Nutrients and Stroke Risk

Dysregulation of methyl donor nutrients interferes with DNA methylation and is associated with neurological diseases. ABCG1 gene regulates cholesterol to HDL-C, maintains lipid homeostasis, and has been linked to both methyl nutrition and neurological risks. The aim was to investigate whether there is an effect of ABCG1 DNA methylation on the relationship between intake of methyl donor nutrients and the risk of stroke occurrence. We hypothesize that the intake of methyl donor nutrients may influence stroke occurrence by modulating the methylation status of ABCG1. This study utilized a case-control design and selected 52 stroke patients along with 52 healthy controls from Northwest China. Dietary information was collected using a FFQ, and methylation levels were measured at 29 CpG sites of the ABCG1 gene. A significant linear trend was found between dietary intake of the methyl donor nutrient choline and CpG_19.20 methylation of the ABCG1 gene (β = -0.037, P = 0.033). Additionally, a significant association was observed between CpG_19.20 methylation and the risk of stroke (OR 2.325, 95% CI 1.210 - 4.466). Mediation analysis revealed that choline intake indirectly influenced stroke occurrence through its effect on CpG_19.20 methylation levels in the ABCG1 gene (β = -0.015, SE = 0.013, 95% CI = [-0.053, -0.001]). We found that DNA methylation at specific CpG sites of the peripheral blood ABCG1 gene mediates the association between dietary methyl donor nutrient intake and stroke risk in an adult population from Northwest China. New insights are provided on the prevention and treatment of stroke.

Understanding the Genetic and Environmental Factors Contributing to Type 1 Diabetes

Introduction: Complex autoimmune illness type 1 diabetes (T1D) is affected by epigenetic, environmental, and hereditary elements. Good preventative and treatment plans depend on an awareness of these connections. The relationships among epigenetic changes in T1D development, environmental exposures, and genetic predispositions are examined in this work. Methodology: From June 2022 until June 2024, Lady Reading Hospital (LRH) in Peshawar carried out a case-control study there were 88 individuals in all, 44 healthy controls and 44 diagnosed T1D patients. Data on demographic and clinical traits, family history, and environmental exposures as well as on With an eye toward non-HLA loci (PTPN22, INS) and HLA class II alleles (DR3-DQ2, DR4-DQ8), genetic study Examined were particular gene DNA methylation patterns (PTPN2, FOXP3). Chi-square tests, t-tests, odds ratios, and logistic regression comprised the statistical analyses. Results: T1D patients had significantly higher frequencies of DR3-DQ2 (63.6%) and DR4-DQ8 (59.1%) compared to controls (22.7% and 27.3%, p < 0.001). T1D patients (45.5% and 40.9%) also more often had non-HLA loci PTPN22 and INS than controls (18.2% and 13.6%, p = 0.01). T1D was substantially correlated with environmental elements including enteroviral infections (50.0% vs. 18.2%, p = 0.002), early exposure to cow's milk (59.1% vs. 31.8%, p = 0.01), gluten (54.5% vs. 27.3%, p = 0.01), and changed gut microbiota (68.2% vs. 31.8%, p In T1D patients, epigenetic analysis identified hypermethylation of PTPN2 (60.0% vs. 20.0%, p = 0.01) and hypomethylation of FOXP3 (50.0% vs. 10.0%, p = 0.02). Conclusion: This work validates in T1D the functions of epigenetic changes, environmental triggers, and genetic predisposition. The interactions among these elements underline the multifaceted character of T1D and imply that thorough interventions should target environmental as well as genetic elements.

The Effect of EGFR DNA Methylation on the Incident of Endometriosis

Endometriosis is a gynecological condition characterized by the development of endometrial tissue outside the uterus, often leading to pain and infertility. We explore the relationship between endometriosis and the effects of DNA methylation on the Epidermal Growth Factor Receptor (EGFR) gene. DNA methylation, an epigenetic mechanism, involves adding a methyl group to cytosine bases followed by guanine in CpG islands, thereby influencing gene expression through hypermethylation or hypomethylation. In endometriosis, methylation patterns on specific genes can lead to transcriptional changes, impacting inflammatory processes and hormonal functions, such as estrogen, that support the growth of ectopic tissue. Variations in the EGFR gene's DNA methylation are linked to elevated cellular activity and expression, which aids in the pathophysiology of endometriosis. These findings highlight the potential of DNA methylation as a therapeutic target in treating endometriosis, offering hope for improved patient outcomes.

Second Generation DNA Methylation Age Predicts Cognitive Change in Midlife: The Moderating Role of Childhood Socioeconomic Status.

DNA methylation age (DNAmAge) surpasses chronological age in its ability to predict age-related morbidities and mortality. This study analyzed data from 287 middle-aged twins in the Louisville Twin Study (mean age 51.9 years ± 7.03) to investigate the effect of DNAmAge acceleration on change in IQ (ΔIQ) between childhood and midlife, while testing childhood socioeconomic status (SES) as a moderator of the relationship. DNAmAge was estimated with five commonly used algorithms (Horvath, Horvath Skin and Blood, GrimAge, and PhenoAge). A factor analysis of these measures produced a two-factor structure which we identified as first generation and second generation measures. Results of genetically informed, quasi-causal regression models indicated that accelerated second generation DNAmAge predicted more negative ΔIQ from childhood to midlife, after accounting for genetic and environmental confounds shared by twins. The relationship between DNAmAge and ΔIQ was moderated by childhood SES, with a stronger effect observed among twins from low SES backgrounds. Second generation DNAmAge measures trained to estimate phenotypic biological age show promise in their predictive value for cognitive decline in midlife. Our genetically informed twin design suggested that DNAmAge may represent a biological pathway through which early-life socioeconomic disadvantage impacts midlife cognitive health.

Integration of gene expression and DNA methylation data using MLA-GNN for liver cancer biomarker mining

The early symptoms of hepatocellular carcinoma patients are often subtle and easily overlooked. By the time patients exhibit noticeable symptoms, the disease has typically progressed to middle or late stages, missing optimal treatment opportunities. Therefore, discovering biomarkers is essential for elucidating their functions for the early diagnosis and prevention. In practical research, challenges such as high-dimensional features, low sample size, and the complexity of gene interactions impact the reliability of biomarker discovery and disease diagnosis when using single-omics approaches. To address these challenges, we thus propose, Multi-level attention graph neural network (MLA-GNN) model for analyzing integrated multi-omics data related to liver cancer. The proposed protocol are using feature selection strategy by removing the noise and redundant information from gene expression and DNA methylation data. Additionally, it employs the Cartesian product method to integrate multi-omics datasets. The study also analyzes gene interactions using WGCNA and identifies potential genes through the MLA-GNN model, offering innovative approaches to resolve these issues. Furthermore, this paper identifies FOXL2 as a promising liver cancer marker through gene ontology and survival analysis. Validation using box plots showed that the expression of the gene FOXL2 was higher in patients with hepatocellular carcinoma than in normal individuals. The drug sensitivity correlation and molecular docking results of FOXL2 with the liver cancer-targeting agent lenvatinib emphasized its potential role in hepatocellular carcinoma treatment and highlighted the importance of FOXL2 in hepatocellular carcinoma treatment.

Religion, spirituality, and DNA methylation in HPA-axis genes among Hispanic/Latino adults.

Investigate associations between religion and spirituality (R&S) and DNA methylation of four HPA-axis genes (i.e. 14 CpG sites) among 992 adults from the Hispanic Community Health Study/Study of Latinos cohorts. We assessed 1) the association between R&S measures and mean percent methylation overall and stratified by nativity status (US-born or immigrant) and 2) if interactions between R&S and methylation differed by nativity status. Among individuals with the FKBP5 CC genotype, increased spirituality scores were associated with significantly lower methylation levels among immigrants, compared to US-born participants. Organizational religiosity (e.g. service attendance) was associated with increased FKBP5 (CC genotype) methylation among immigrants. R&S may influence HPA-axis functioning differently based on nativity status; a finding that could offer insight into mechanisms leading to health disparities.

Distinct microbiome dysbiosis and epigenetic anomaly in esophageal adenocarcinoma and its underlying Barrett’s esophagus

Interaction between host genotoxic changes and mucosa-associated microbiome (MAM) dysbiosis may have a role in various digestive cancers. We investigated MAM in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) progression sequence and its association with host genotoxic changes. 16S rRNA gene sequencing was performed in three different groups of biopsies from nonneoplastic BE from patients without cancer (N, normal group; n = 47) and with EAC (ADJ, adjacent group; n = 27). Endoscopic biopsies were also obtained from EAC tissues (T, tumor group; n = 22). Results were correlated with TP53 mutation, telomere length and DNA methylation of candidate genes (N33, DPYS, SLC16A12, miR124A3 and miR34bc). Genome-wide DNA methylation examined by reduced representation bisulfite sequencing (RRBS) was available for 32 samples (n = 12 for N, n = 12 for ADJ and n = 22 for T groups). Lower microbial alpha diversity measures were observed in ADJ/T groups relative to N group and associated with higher mean Z score DNA methylation of candidate genes. Specific genera (n = 16) with significant change between ADJ/T groups relative to N group occurred mostly in ADJ group (13/16) and half of them (8/16) were associated with DNA methylation status. Integrated MAM and genome-wide methylation analysis demonstrated that hyper-methylated sites, associated with lower alpha diversity measures dominantly occurred within near the transcription start site, codifying genes were involved in metabolic processes. Our result shows that microbial dysbiosis in EAC mostly occurs in adjacent BE and such dysbiosis was associated with DNA methylation status, offering support for a pathogenic role of interaction between host genotoxic changes and MAM in this tumor type.

Modulation of MSH2 gene expression and DNA global methylation in diethyl-nitrosamine induced hepatic fibrosis mouse model by cisplatin- anthocyanins combination

Novel therapeutic approaches targeting the molecular pathways of hepatocellular carcinoma (HCC) development are highly demanded. We aimed at studying the effect of cisplatin alone and combined with cranberry extract on global DNA methylation and the MSH2 gene expression in diethyl-nitrosamine (DEN)-induced hepatic fibrosis model, as a landmark in HCC development pathway in mice. Forty male albino mice were divided into 2 groups: Group I (n=10): control, Group II (n=30): mice were injected intraperitoneal with DEN and sub-classified into 3 equal groups; IIa: untreated, IIb: intraperitoneal cisplatin, IIc: intraperitoneal cisplatin + oral cranberry-derived anthocyanin. Histopathological examination of liver, assessment of global DNA methylation and MSH2 gene expression were done. MSH2 gene expression was significantly decreased in DEN-group as compared to the control group, but significantly increased by cisplatin alone and furthermore when anthocyanin was added (p<0.001). Global DNA methylation significantly increased in DEN-group, significant decrease in cisplatin-group and further decrease when anthocyanin was added (p<0.001). A significant negative correlation was observed between global DNA methylation and MSH2 gene expression among all the studied groups (p<0.001). Histopathological examination showed improvement of liver fibrosis when anthocyanin was added to cisplatin. Improvement of histopathological findings of DEN-induced hepatic fibrosis by cranberry-derived anthocyanins was associated with global DNA hypomethylation and increased MSH2 expression. Further studies are warranted to confirm the applicability of adding anthocyanins to liver fibrosis and HCC treatment regimen.

Maternal high-fat diet orchestrates offspring hepatic cholesterol metabolism via MEF2A hypermethylation-mediated CYP7A1 suppression

BackgroundMaternal overnutrition, prevalent among women of childbearing age, significantly impacts offspring health throughout their lifetime. While DNA methylation of metabolic-related genes mediates the transmission of detrimental effects from maternal high-fat diet (HFD), its role in programming hepatic cholesterol metabolism in offspring, particularly during weaning, remains elusive.MethodsFemale C57BL/6 J mice were administered a HFD or control diet, before and during, gestation and lactation. Hepatic cholesterol metabolism genes in the liver of offspring were evaluated in terms of their expression. The potential regulator of cholesterol metabolism in the offspring’s liver was identified, and the function of the targeted transcription factor was evaluated through in vitro experiments. The methylation level of the target transcription factor was assessed using the MassARRAY EpiTYPER platform. To determine whether transcription factor expression is influenced by DNA methylation, in vitro experiments were performed using 5-azacitidine and Lucia luciferase activity assays.ResultsHere, we demonstrate that maternal HFD results in higher body weight and hypercholesterolemia in the offspring as early as weaning age. Maternal HFD feeding exacerbates hepatic cholesterol accumulation in offspring primarily by inhibiting cholesterol elimination to bile acids, with a significant decrease of hepatic cholesterol 7α-hydroxylase (CYP7A1). RNA-seq analysis identified myocyte enhancer factor 2A (MEF2A) as a key transcription factor in the offspring liver, which was significantly downregulated in offspring of HFD-fed dams. MEF2A knockdown led to CYP7A1 downregulation and lipid accumulation in HepG2 cells, while MEF2A overexpression reversed this effect. Dual luciferase reporter assays confirmed direct modulation of CYP7A1 transcription by MEF2A. Furthermore, the reduced MEF2A expression was attributed to DNA hypermethylation in the Mef2a promoter region. This epigenetic modification manifested as early as the fetal stage.ConclusionsThis study provides novel insights into how maternal HFD orchestrates hepatic cholesterol metabolism via MEF2A hypermethylation-mediated CYP7A1 suppression in offspring at weaning.

Long-read sequencing of hundreds of diverse brains provides insight into the impact of structural variation on gene expression and DNA methylation.

Structural variants (SVs) drive gene expression in the human brain and are causative of many neurological conditions. However, most existing genetic studies have been based on short-read sequencing methods, which capture fewer than half of the SVs present in any one individual. Long-read sequencing (LRS) enhances our ability to detect disease-associated and functionally relevant structural variants (SVs); however, its application in large-scale genomic studies has been limited by challenges in sample preparation and high costs. Here, we leverage a new scalable wet-lab protocol and computational pipeline for whole-genome Oxford Nanopore Technologies sequencing and apply it to neurologically normal control samples from the North American Brain Expression Consortium (NABEC) (European ancestry) and Human Brain Collection Core (HBCC) (African or African admixed ancestry) cohorts. Through this work, we present a publicly available long-read resource from 351 human brain samples (median N50: 27 Kbp and at an average depth of ∼40x genome coverage). We discover approximately 234,905 SVs and produce locally phased assemblies that cover 95% of all protein-coding genes in GRCh38. Utilizing matched expression datasets for these samples, we apply quantitative trait locus (QTL) analyses and identify SVs that impact gene expression in post-mortem frontal cortex brain tissue. Further, we determine haplotype- specific methylation signatures at millions of CpGs and, with this data, identify cis-acting SVs. In summary, these results highlight that large-scale LRS can identify complex regulatory mechanisms in the brain that were inaccessible using previous approaches. We believe this new resource provides a critical step toward understanding the biological effects of genetic variation in the human brain.

An Epigenetic Locus Associated with Loss of Smell in COVID-19.

Loss of smell, also known as anosmia, is a prevalent and often prolonged symptom following infection with SARS-CoV-2. While many patients regain olfactory function within weeks, a significant portion experience persistent anosmia lasting over a year post-infection. The underlying mechanisms responsible for this sensory deficit remain largely uncharacterized. Previous studies, including genome-wide association studies (GWAS), have identified genetic variants near the UGT2A1 and UGT2A2 genes that are linked to anosmia in COVID-19 patients. However, the role of epigenetic changes in the development and persistence of smell loss has not been well explored. In this study, we aimed to investigate epigenetic alterations in the form of DNA methylation in the UGT1A1 gene, which is a locus associated with olfactory dysfunction in COVID-19 patients. We analysed DNA methylation patterns in blood samples from two carefully matched cohorts of 20 COVID-19 patients each, which are differentiated by their olfactory function-those with normal smell (normosmia) and those suffering from smell loss (anosmia). The cohorts were matched for age and sex to minimize potential confounding factors. Using quantitative analysis, we found significantly lower levels of DNA methylation in the UGT1A1 locus in the anosmia group compared to the normosmia group, with a 14% decrease in median methylation values in patients with smell loss (p < 0.0001). These findings highlight potential epigenomic alterations in the UGT1A1 gene that may contribute to the pathogenesis of anosmia following COVID-19 infection. Our results suggest that the methylation status at this locus could serve as a biomarker for olfactory dysfunction in affected individuals. This study is among the first to describe epigenetic changes associated with smell loss in COVID-19, providing a foundation for future research into targeted interventions and potential therapeutic strategies aimed at reversing persistent anosmia. Further investigations involving larger cohorts and additional loci may help elucidate the complex interaction between genetic, epigenetic, and environmental factors influencing long-term sensory impairment post-COVID-19.

Placental expression and methylation of angiogenic factors in assisted reproductive technology pregnancies from India.

This study aims to examine the gene expression and DNA methylation patterns of angiogenic factors in the placentae of Indian women who underwent assisted reproductive technology (ART) procedures and their association with maternal one-carbon metabolites and birth outcome. Placental gene expression and DNA methylation of angiogenic factors (VEGF, PlGF, FLT-1, KDR) in Indian women who underwent ART procedures (n = 64) and women who conceived naturally (Non-ART) (n = 93) was investigated using RT-qPCR and Epitect Methyl-II PCR assay kits. Maternal plasma one-carbon metabolites were assessed by CMIA technology. Gene expression of FLT-1 and KDR was higher (p < 0.05) in the ART placentae. Placental global DNA methylation levels were higher (p < 0.01) and DNA methylation levels of VEGF promoter were lower (p < 0.05) in ART compared to non-ART women. Maternal plasma folate and vitamin B12 levels were higher (p < 0.01) in the ART group. Gene expression of PlGF was negatively associated with maternal plasma folate (p < 0.05) whereas KDR was positively associated with maternal plasma homocysteine (p < 0.05). Gene expression of KDR was positively associated with chest circumference of the baby (p < 0.05). Hypomethylation of VEGF and increased expression of FLT-1 and KDR was observed in the placentae of women who underwent ART procedure.

MTHFR Gene Polymorphisms and DNA Methylation in Idiopathic Spontaneous Preterm Birth

Background and Objectives: Preterm birth (PTB) is a complex condition with various contributing factors, including genetic and epigenetic influences such as DNA methylation. Methylenetetrahydrofolate reductase (MTHFR) plays a critical role in DNA methylation and the remethylation of homocysteine. This study aimed to investigate the association between maternal MTHFR C677T and A1298C polymorphisms, LINE-1 DNA methylation levels, and the risk of idiopathic spontaneous preterm birth (SPTB) in Caucasian women from Croatia and Slovenia. Materials and Methods: A total of 50 women with SPTB (&lt;34 weeks of gestation) and 50 control women were included in the study. MTHFR polymorphisms were analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and LINE-1 DNA methylation levels were quantified using the MethyLight method. Results: The study found no significant differences in MTHFR C677T and A1298C polymorphisms’ genotype or allele frequencies between women with SPTB and controls. Additionally, no statistical significance of LINE-1 DNA methylation was found between the genotypes of the MTHFR polymorphisms analyzed. Conclusions: The study suggests no conclusive association between MTHFR C677T and A1298C polymorphisms, LINE-1 DNA methylation, and SPTB in Croatian and Slovenian women. Considering prior evidence connecting MTHFR polymorphisms, hyperhomocysteinemia, and PTB, the lack of homocysteine measurements and unassessed impact of folate or vitamin B supplementation limit the conclusions.

DNA hypermethylation of tumor suppressor genes among oral squamous cell carcinoma patients: a prominent diagnostic biomarker.

Oral Squamous Cell Carcinoma is a globally revealing form of oral malignancy. Epigenetics, which studies genetic modifications in gene expression without altering the sequence of DNA, is crucial for understanding OSCC. Key epigenetic modifications such as histone modifications, DNA methylation, and microRNA regulation play significant roles in Oral carcinoma. Aberrant methylation of DNA of tumor suppressor genes which leads to their inactivation, promoting cancer development, and specific methylation patterns are emerging as biomarkers for early OSCC detection.Current treatments like surgery, radiotherapy, and chemotherapy often fall short, prompting research into epigenetic therapies. Agents like DNMT and HDAC inhibitors demonstrate the potential for reversing aberrant epigenetic patterns, perhaps reactivating silenced TSGs, and suppressing oncogenes. Despite early promise, the development of effective combination medicines and the identification of reliable biomarkers continue to present challenges.In OSCC, resistance to therapy is also influenced by epigenetic processes. Aberrant DNA methylation and changes in histone modifications impact genes involved in medication metabolism and the survival of cells. Enhancing treatment efficacy and overcoming medication resistance may be possible by recognizing and focusing on these processes. This review explores the interplay between epigenetic changes and OSCC, their role in the disease's initiation and progression, and their impact on diagnosis and treatment. It also discusses the potential of epigenetic drugs (epi-drugs) to improve diagnostic precision and treatment outcomes.

Evaluation of ALKBH2 and ALKBH3 gene regulation in patients with adult T-cell leukemia/lymphoma

BackgroundHuman T-cell leukemia virus type 1 (HTLV-1) is an oncogenic virus that causes malignant adult T-cell leukemia/lymphoma (ATL). Patients infected with HTLV-1 are considered HTLV-1 carriers, and a small proportion of patients progress to life-threatening ATL after a long asymptomatic phase. No antiviral agent or preventive vaccine specific for HTLV-1 infection is established in current situation. For development of countermeasures to combat HTLV-1 infection and ATL, it is essential to expand our knowledge about their pathogenesis. Recently, AlkB homolog (ALKBH) family have been shown to participate in the oncogenesis of various cancer types.MethodsTo investigate the potential role of ALKBH family members in the pathogenesis of ATL, we analyzed their gene expression dynamics in HTLV-1-infected T-cell lines and peripheral blood mononuclear cell-derived clinical specimens obtained from asymptomatic HTLV-1 carriers and patients with acute-type ATL. Epigenetic analysis was performed to dissect the mechanisms of ALKBH3 gene regulation using cultivated cells and a public dataset.ResultsThe mRNA expression levels of ALKBH2 and ALKBH3 were significantly or suggestively decreased in asymptomatic HTLV-1 carriers, but reverted in acute-type ATL patients, correlating with HTLV-1 basic leucine zipper factor gene expression. Intriguingly, the pre-mRNA expression of ALKBH2 and ALKBH3 was significantly suppressed in patients infected with HTLV-1, but not in healthy controls. Epigenetic analysis was performed to dissect the mechanisms of ALKBH3 gene regulation. In vitro analysis suggested a possible relationship between DNA methylation and ALKBH3 gene expression. Investigation of a public dataset revealed that specific CpG sites exhibited characteristically regulated methylation states in HTLV-1-infected T-cell subsets.ConclusionWe discovered dynamically regulated patterns of ALKBH2 and ALKBH3 gene expression in patients infected with HTLV-1, and specific CpG sites epigenetically regulated by HTLV-1 infection. This study provides novel insights into HTLV-1 infection and contributes to the elucidation of ATL pathogenesis.