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Environmental Research Apr 2024Ambient PM exposure has been recognized as a major health risk and related to aging, cardiovascular, respiratory and neurologic diseases, and cancer. However, underlying...
Ambient PM exposure has been recognized as a major health risk and related to aging, cardiovascular, respiratory and neurologic diseases, and cancer. However, underlying mechanism of epigenetic alteration and regulated pathways still remained unclear. The study on methylome effect of PM exposure was quite limited in Chinese population, and cohort-based study was absent. The study included blood-derived DNA methylation for 3365 Chinese participants from the NSPT cohort. We estimated individual PM exposure level of short-medium-, medium- and long-term, based on a validated prediction model. We preformed epigenome-wide association studies to estimate the links between PM exposure and DNA methylation change, as well as stratification and sensitive analysis to examined the robustness of the association models. A systematic review was conducted to obtain the previously published CpGs and examined for replication. We also conducted comparison on the DNA methylation variation corresponding to different time windows. We further conducted gene function analysis and pathway enrichment analysis to reveal related biological response. We identified a total of 177 CpGs and 107 DMRs associated with short-medium-term PM exposure, at a strict genome-wide significance (P < 5 × 10). The effect sizes on most CpGs tended to cease with the exposure of extended time scale. Associated markers and aligned genes were related to aging, immunity, inflammation and carcinogenesis. Enriched pathways were mostly involved in cell cycle and cell division, signal transduction, inflammatory pathway. Our study is the first EWAS on PM exposure conducted in large-scale Han Chinese cohort and identified associated DNA methylation change on CpGs and regions, as well as related gene functions and pathways.
Topics: Humans; Air Pollutants; Particulate Matter; Epigenome; DNA Methylation; China
PubMed: 38246299
DOI: 10.1016/j.envres.2024.118276 -
Epigenetics Dec 2023Research has recently begun to examine the potential intergenerational impacts of trauma on obesity. This scoping review examines the literature on the interactions... (Review)
Review
Research has recently begun to examine the potential intergenerational impacts of trauma on obesity. This scoping review examines the literature on the interactions between intergenerational trauma, epigenetics, and obesity in Indigenous populations. The review was conducted to identify what is known from the literature about how intergenerational trauma may epigenetically influence obesity in Indigenous populations. Following the PRISMA-ScR guidelines for scoping reviews, online databases were used to identify studies that included discussion of the four focus topics: trauma, epigenetics, obesity, and Indigeneity. The review resulted in six studies that examined those themes. The focus and findings of the selected studies varied from cultural to biological mechanisms and from discussion regarding trauma, epigenetics, obesity, or Indigeneity, but they support three broad statements. First, they support that obesity has genetic and epigenetic factors. Second, intergenerational trauma is prevalent in Indigenous communities. Finally, intergenerational trauma has cultural and biological influences on obesity. Current literature illustrates that intergenerational trauma has behavioural and epigenetic influences that can lead to increased obesity. This scoping review provides a preliminary map of the current literature and understandings of these topics. This review calls for continued studies regarding the connection between trauma, obesity, and epigenetics in Indigenous communities. Future research is vital for practice and policy surrounding individual and communal healing.
Topics: Humans; Historical Trauma; DNA Methylation; Indigenous Peoples; Obesity; Epigenesis, Genetic; Canada
PubMed: 37752750
DOI: 10.1080/15592294.2023.2260218 -
Gynecologic and Obstetric Investigation 2024This meta-analysis aimed to comprehensively evaluate the diagnostic use of erythrocyte membrane protein band 4.1like3 (EPB41L3) methylation detection in cervical cancer... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This meta-analysis aimed to comprehensively evaluate the diagnostic use of erythrocyte membrane protein band 4.1like3 (EPB41L3) methylation detection in cervical cancer (CC) and its precancerous lesions.
METHODS
CNKI, Wanfang, Cochrane Library, PubMed, and Ovid databases were searched using a combination of subject headings and free words. Pertinent data were retrieved after screening for inclusion and exclusion criteria, and the quality of the included studies was evaluated using QUADAS-2 criteria. The appropriate software was used for heterogeneity analysis and combined effect size calculation. Additionally, sensitivity analysis was used to evaluate the robustness of the combined results, and meta-regression and subgroup analysis were conducted to investigate the origins of heterogeneity.
RESULTS
This meta-analysis included six studies, including 525 healthy individuals, 182 cervical intraepithelial neoplasia 1 (CIN1) samples, 182 CIN2 samples, 281 CIN3 samples, and 226 CC samples. EPB41L3 methylation detection for CIN2 and above lesions demonstrated combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and the area under the curve of the comprehensive receiver operating characteristic curve of 0.67, 0.76, 3.19, 0.41, 7.60, and 0.80, respectively; CIN3 and above lesions demonstrated these evaluations at 0.73, 0.84, 4.35, 0.33, 23.94, and 0.90, respectively. Meta-regression analysis revealed that the population, time, sample type, detection method, literature quality, and sample size were not significant sources of heterogeneity affecting the combined diagnostic efficacy of CIN2 and above lesions (p > 0.05). Subgroup analysis revealed higher combined diagnostic values of CIN2 and above lesions in retrospective studies, tissue samples, and Chinese populations, with DORs of 41.03, 14.59, and 13.70, respectively.
CONCLUSION
EPB41L3 methylation demonstrated a relatively low diagnostic performance in CC and precancerous lesions. However, it merits further investigation as a potential biomarker. Integrating it with multiple gene detection, human papillomavirus testing, and ThinPrep liquid-based cytology test examination is recommended to explore improved diagnostic strategies for CC and its precancerous lesions.
Topics: Female; Humans; Uterine Cervical Neoplasms; Retrospective Studies; DNA Methylation; Uterine Cervical Dysplasia; Precancerous Conditions; Papillomavirus Infections; Early Detection of Cancer; Microfilament Proteins
PubMed: 38081153
DOI: 10.1159/000535563 -
Prevention Science : the Official... Oct 2023Biological age, measured via epigenetic clocks, offers a unique and useful tool for prevention scientists to explore the short- and long-term implications of age... (Review)
Review
Biological age, measured via epigenetic clocks, offers a unique and useful tool for prevention scientists to explore the short- and long-term implications of age deviations for health, development, and behavior. The use of epigenetic clocks in pediatric research is rapidly increasing, and there is a need to review the landscape of this work to understand the utility of these clocks for prevention scientists. We summarize the current state of the literature on the use of specific epigenetic clocks in childhood. Using systematic review methods, we identified studies published through February 2023 that used one of three epigenetic clocks as a measure of biological aging. These epigenetic clocks could either be used as a predictor of health outcomes or as a health outcome of interest. The database search identified 982 records, 908 of which were included in a title and abstract review. After full-text screening, 68 studies were eligible for inclusion. While findings were somewhat mixed, a majority of included studies found significant associations between the epigenetic clock used and the health outcome of interest or between an exposure and the epigenetic clock used. From these results, we propose the use of epigenetic clocks as a tool to understand how exposures impact biologic aging pathways and development in early life, as well as to monitor the effectiveness of preventive interventions that aim to reduce exposure and associated adverse health outcomes.
Topics: Child; Humans; Epigenesis, Genetic; DNA Methylation; Aging; Databases, Factual
PubMed: 37477807
DOI: 10.1007/s11121-023-01576-4 -
Translational Psychiatry Dec 2023Prenatal stress and poor maternal mental health are associated with adverse offspring outcomes; however, the biological mechanisms are unknown. Epigenetic modification... (Meta-Analysis)
Meta-Analysis
Prenatal stress and poor maternal mental health are associated with adverse offspring outcomes; however, the biological mechanisms are unknown. Epigenetic modification has linked maternal health with offspring development. Epigenome-wide association studies (EWAS) have examined offspring DNA methylation profiles for association with prenatal maternal mental health to elucidate mechanisms of these complex relationships. The objective of this study is to provide a comprehensive, systematic review of EWASs of infant epigenetic profiles and prenatal maternal anxiety, depression, or depression treatment. We conducted a systematic literature search following PRISMA guidelines for EWAS studies between prenatal maternal mental health and infant epigenetics through May 22, 2023. Of 645 identified articles, 20 fulfilled inclusion criteria. We assessed replication of CpG sites among studies, conducted gene enrichment analysis, and evaluated the articles for quality and risk of bias. We found one repeated CpG site among the maternal depression studies; however, nine pairs of overlapping differentially methylatd regions were reported in at least two maternal depression studies. Gene enrichment analysis found significant pathways for maternal depression but not for any other maternal mental health category. We found evidence that these EWAS present a medium to high risk of bias. Exposure to prenatal maternal depression and anxiety or treatment for such was not consistently associated with epigenetic changes in infants in this systematic review and meta-analysis. Small sample size, potential bias due to exposure misclassification and statistical challenges are critical to address in future efforts to explore epigenetic modification as a potential mechanism by which prenatal exposure to maternal mental health disorders leads to adverse infant outcomes.
Topics: Pregnancy; Infant; Female; Humans; Epigenome; Mental Health; DNA Methylation; Maternal Health; Epigenesis, Genetic
PubMed: 38062042
DOI: 10.1038/s41398-023-02620-1 -
BMC Neurology Mar 2024MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT...
BACKGROUND
MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated.
METHODS
To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included.
RESULTS
We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG's 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG's 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG's 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions.
CONCLUSION
The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.
Topics: Humans; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Glioma; Prognosis; Tumor Suppressor Proteins
PubMed: 38521933
DOI: 10.1186/s12883-024-03605-3 -
Journal of Applied Toxicology : JAT Jan 2024The International Agency for Research on Cancer has classified N-nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A... (Review)
Review
The International Agency for Research on Cancer has classified N-nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A of compounds that are probably harmful to humans. It is found in nature and tobacco smoke, along with its precursors, and is also synthesized endogenously in the human body. The oral or parenteral administration of a minimal quantity of NDEA results in severe liver and kidney organ damage. The NDEA required bioactivation by CYP450 enzyme to form DNA adduct in the alkylation mechanism. Thus, this bioactivation directs oxidative stress and injury to cells due to the higher formation of reactive oxygen species and alters antioxidant system in tissues, whereas free radical scavengers guard the membranes from NDEA-directed injury in many enzymes. This might be one of the reasons in the etiology of cancer that is not limited to a certain target organ but can affect various organs and organ systems. Although there are various possible approaches for the treatment of NDEA-induced cancer, their therapeutic outcomes are still very dismal. However, several precautions were considered to be taken during handling or working with NDEA, as it considered being the best way to lower down the occurrence of NDEA-directed cancers. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter the antioxidant line to cause malignancy in different parts of animal body along with its protective agents. Thus, revelation to constant, unpredictable stress situations even in common life may remarkably augment the toxic potential through the rise in the oxidative stress and damage of DNA.
PubMed: 38212177
DOI: 10.1002/jat.4574 -
Journal of Strength and Conditioning... Feb 2024Vasileva, F, Hristovski, R, Font-Lladó, R, Georgiev, G, Sacot, A, López-Ros, V, Calleja-González, J, Barretina-Ginesta, J, López-Bermejo, A, and Prats-Puig, A....
Vasileva, F, Hristovski, R, Font-Lladó, R, Georgiev, G, Sacot, A, López-Ros, V, Calleja-González, J, Barretina-Ginesta, J, López-Bermejo, A, and Prats-Puig, A. Physical exercise-induced DNA methylation in disease-related genes in healthy adults-A systematic review with bioinformatic analysis. J Strength Cond Res 38(2): 384-393, 2024-This study aimed to systematically review the existing literature regarding physical exercise (PE) and DNA methylation (DNAm) in healthy adults. Specific goals were to (a) identify differently methylated genes (DMGs) after PE intervention, their imprinting status, chromosome and genomic location, function, and related diseases; and (b) to screen for core genes and identify methylation changes of the core genes that can be modified by PE intervention. Our search identified 2,869 articles from which 8 were finally included. We identified 1851 DMGs ( p < 0.05) after PE intervention, although 45 of them were imprinted. Aerobic exercise (AE) seems to induce more DNA hypermethylation rather than hypomethylation, whereas anaerobic exercise (AN) seems to induce more DNA hypomethylation rather than hypermethylation. Aerobic exercise induced highest % of methylation changes on chromosome 6, whereas AN and mixed type (MT) on chromosome 1. Mixed type induced higher % of methylation changes close to transcription start site in comparison to AE and AN. After PE intervention, DMGs were mainly involved in fat metabolism, cell growth, and neuronal differentiation, whereas diseases regulated by those genes were mainly chronic diseases (metabolic, cardiovascular, neurodegenerative). Finally, 19 core genes were identified among DMGs, all related to protein metabolism. In conclusion, our findings may shed some light on the mechanisms explaining PE-induced health benefits such as the potential role that PE-induced DNAm may have in disease prevention and disease treatment.
Topics: Humans; Computational Biology; DNA; DNA Methylation; Exercise
PubMed: 38088908
DOI: 10.1519/JSC.0000000000004686 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... May 2024To summarize and elucidate the impact of ambient air pollution on biological aging among middle-aged and older adults. "Air pollution""Biological age""Epigenetic...
To summarize and elucidate the impact of ambient air pollution on biological aging among middle-aged and older adults. "Air pollution""Biological age""Epigenetic age""Biological aging"and"Epigenetic aging", as well as specific names of air pollutants and biological age were used as search keywords. This study searched the databases of PubMed and Web of Science for eligible English articles and CNKI, CQVIP, Wanfang, CBM, CSTP and other Chinese databases for eligible Chinese articles from inception until June 30, 2023. The language was limited to Chinese and English. Among the 14 included articles, five studies investigated the impact of air pollution on DNA methylation age using different algorithms, while six studies explored the relationship between air pollutants and telomere length. Six studies focused on frailty as an outcome, and an additional study revealed the relationship between fine particulate matter (PM) and its components with composite indicator age (KDM age). The results indicated that, although different forms of biological ages were susceptible to different ambient air pollutants at different degrees, previous studies had consistently found that the increased levels of PM and one of its major components, black carbon (BC), could significantly accelerate the biological aging of middle-aged and older adults. Similar trends were observed with nitrogen oxides (NO) and ozone (O) but with relatively limited evidence. Major air pollutants could accelerate the biological aging of middle-aged and older adults.
Topics: Humans; Air Pollution; Air Pollutants; Particulate Matter; Aging; Middle Aged; Aged; DNA Methylation; Epigenesis, Genetic; Environmental Exposure
PubMed: 38715498
DOI: 10.3760/cma.j.cn112150-20231009-00247 -
The British Journal of Oral &... Jun 2024Oral epithelial dysplasia (OED) is a premalignant condition that carries an appreciable risk of malignant progression. The current grading system for severity, as... (Meta-Analysis)
Meta-Analysis Review
Oral epithelial dysplasia (OED) is a premalignant condition that carries an appreciable risk of malignant progression. The current grading system for severity, as defined by the World Health Organization, is a valuable clinical tool, but further work is required to improve the accuracy of predicting OED malignant progression. This systematic review aimed to assess progress in prognostic biomarker discovery in OED over the past 16 years. The primary objective was to update the latest evidence on prognostic biomarkers that may predict malignant progression of OED, with strict inclusion criteria of studies with a longitudinal design and long-term follow-up data to enhance the robustness and translational clinical potential of the findings. Of 2829 studies identified through the searching of five databases, 20 met our inclusion criteria. These studies investigated a total of 32 biomarkers, 20 of which demonstrated significant potential to predict malignant progression of OED. Meta-analysis demonstrated the significant prognostic value of four biomarkers: podoplanin, EGFR expression, p16 methylation, and DNA aneuploidy. Our review has identified 20 reported biomarkers with prognostic potential to predict malignant progression in OED, but their translation into clinical practice remains elusive. Further research is required, and this should focus on validating the promising biomarkers identified in large cohort studies, with adherence to standardised reporting guidelines.
Topics: Humans; Prognosis; Disease Progression; Mouth Neoplasms; Biomarkers, Tumor; Precancerous Conditions; Mouth Mucosa; ErbB Receptors; DNA Methylation; Aneuploidy
PubMed: 38677951
DOI: 10.1016/j.bjoms.2024.03.001