Evidence suggests that environmental exposures induce epigenetic modifications that can have long-lasting effects on multiple health outcomes, and an in-depth review of the epidemiological evidence is urgent. We aimed to comprehensively assess the associations between long-term exposure to air pollution and epigenetic changes in adults.

Ambient air pollution may accelerate biological aging, but the extent of its impact remains uncertain. Epigenetic clocks capture aging by comparing biological to chronological age, highlighting whether an individual is aging biologically faster (accelerating) or slower (decelerating) than expected. This systematic review and meta-analysis aimed to evaluate the association between long-term outdoor air pollution exposure [particulate matter (PM2.5, PM10), nitrogen dioxide (NO2), or black carbon (BC)] and epigenetic clocks. We systematically searched the databases of PubMed, Scopus, and Google Scholar until April 2025. Random-effects models were used to estimate beta coefficients for the association between air pollutants and epigenetic age acceleration (EAA). The study protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42024628148). Our meta-analysis included 18 studies with a combined sample size of 363,381 participants. Using the Horvath EAA, no significant associations were found for all pollutants [per 5 μg/m3 PM2.5: 0.523 y (95 %CI: -0.136, 1.182, p = 0.12); 5 μg/m3 PM10: 0.043 y (95 %CI: -0.281, 0.366, p = 0.80); 10 μg/m3 NO2: -0.078 y (95 %CI: -0.201, 0.044, p = 0.21); 0.5 μg/m3 BC: 0.268 y (95 %CI: -0.165, 0.701, p = 0.23)]. In a sensitivity analysis, when only including adult populations, the effect for a 5 µg/m3 increase in PM2.5 was more pronounced [0.740 y (95 %CI: -0.050, 1.529, p = 0.066)]. For PhenoAge EAA, inconsistent associations between pollutants and epigenetic aging were observed, which were driven by a single study. Finally, for GrimAge EAA, no associations with pollutant exposures were identified. In conclusion, this meta-analysis suggests a potential weak association between ambient particulate air pollution exposure and Horvath epigenetic age acceleration in adults; however, this currently lacks statistical significance. Other epigenetic clocks showed inconsistent or no associations. Additional high-quality longitudinal studies are needed to clarify the nature and strength of the potential link between air pollution exposure and epigenetic aging.

Dioxins, are highly potent environmental carcinogens. Their toxic effects are mediated primarily by the Aryl Hydrocarbon Receptor (AhR). A comprehensive understanding of how AhR-induced genetic and epigenetic alterations drive carcinogenesis, especially through effects on cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT) and transgenerational inheritance, remains imperative.

Tobacco use during pregnancy is a modifiable risk factor contributing to adverse birth outcomes. The placenta is the master regulator of fetal growth and development and contributes to the overall health of the pregnant person and fetus throughout pregnancy. The primary aim of our systematic review was to investigate the impact of tobacco product use during pregnancy on placental epigenetics. A secondary aim of the review was to investigate how tobacco-related alterations in the placental epigenome are associated with maternal and fetal health outcomes. Twenty papers were included in the review. All studies included investigated combustible cigarette smoking only and the majority (85 %) studied full term placentas. Using data from studies that included data on methylation changes in 30 or more CpG loci and/or genes, the three most common molecular pathways identified across all the genes were binding, catalytic activity, and transcription regulator activity. However, a large proportion of the genes were not assigned to a specific category. Additional research is needed to understand whether non-cigarette tobacco products also disrupt placenta epigenetics.

To systematically evaluate preclinical evidence on the protective effects of herbal interventions against toxicant-induced genetic and epigenetic alterations in animal models.

PARP inhibitors (PARPi) improve ovarian cancer (OC) outcomes, but resistance remains a major challenge without reliable prognostic biomarkers. This study identified epigenetic hallmarks of PARPi resistance by integrating 27 studies (22 preclinical, 5 clinical) from the past 15 years, and validating candidate genes using web-based bioinformatics tools and public microarray/RNA-seq datasets from non-relapsed, primary OC tissues. We hypothesised that early aberrant expression of these epigenetically altered, PARPi resistance-related genes in tumours may be linked to disease progression (PFS) and could serve as early biomarkers to be associated with PARPi resistance during first-line treatment. We confirmed epigenetic involvement in PARPi resistance across 36 genes linked to epigenetic modifications. Of these, 10 genes (n = 614-1435)-including RNASEH2B (HR=1.41), VHL (HR=1.26), ATM (HR=1.22), XRCC1 (HR=1.20), NRP1 (HR=1.16), KAT2B (HR=1.16), EZH2 (HR=1.15), CREBBP (HR=1.14), FZD10 (HR=0.87), and CARM1 (HR=0.86)-showed significant prognostic value for PFS (all: p < 0.05). This 10-gene signature remained collectively significant (HR 1.27, p = 0.014). RNA-seq validation showed differential expression of these genes, with highest fold-change overexpression in tumours for FZD10 (4.20), EZH2 (3.56), and CARM1 (1.61), and lowest in ATM (0.22), KAT2B (0.33), and NRP1 (0.44). GO and KEGG analyses revealed these genes are enriched in key resistance pathways, including impaired DNA repair, reduced replication stress, immune evasion, and stemness maintenance. This review with bioinformatic validation identified a 10-gene epigenetic signature associated with PARPi resistance and disease progression. These clinically actionable genes, aberrantly expressed before treatment, may serve as early biomarkers for risk stratification. Further validation in PARPi-sensitive and -resistant ovarian cancer cohorts is needed.

Lead (Pb) is a hazardous heavy metal frequently used because it is readily available and inexpensive. Due to contaminated soil, dust, and items like paints and batteries, lead exposure is still an issue of concern in many nations. There is no known safe threshold of exposure, and it can have serious adverse effects on human health. Exposure to lead has been linked to detrimental effects on the developing nervous system of both children and adults. Alzheimer's disease (AD) is the most prevalent type of dementia affecting adults over the age of 65, resulting in a decrease in memory and thinking skills. In this review, we describe the role of lead in exacerbating the build-up of hyperphosphorylated tau proteins and formation of amyloid-β (Aβ) plaques, major neurotoxicants which can impair neuronal function leading to AD. We highlight the effect of developmental and lifelong lead exposure on various gene expression changes resulting in the formation of the neurotoxicants responsible to AD. Understanding the mechanisms related to Aβ plaques and neurofibrillary tangles (NFTs) formation serves as a novel approach to identify biomarkers for lead-induced AD and developing therapeutic interventions. Lead exposure has been related to adverse effects on the developing neurological systems of both adults and children.

Ketamine antidepressant effects go beyond immediate receptor action, involving lasting transcriptional and epigenomic changes that support its rapid, long-lasting benefits. The present systematic review synthesized existing preclinical and clinical evidence on the epigenetic mechanisms of ketamine in the treatment of depression.

Epigenetics refers to heritable modifications in gene expression that do not involve changes to the DNA sequence. Among these, DNA methylation, histone modifications, and non-coding RNAs play a key role in regulating gene activity and are influenced by environmental factors, including exposure to psychoactive substances. In recent years, it has been hypothesized that such alterations may serve as molecular markers with forensic relevance. This systematic review aims to evaluate whether current evidence supports the use of drug-induced epigenetic changes as potential toxicological fingerprints in human subjects.

Cancer is a significant health burden throughout the world. Gliomas are a type of cancer with the origin of central nervous system. They are the most prevalent group of brain malignancies. Chemotherapy is an integral component of standard treatment strategies for this disease. Carmustine is regarded as one of the most effective chemotherapy drugs against different cancer types and, most importantly, Gliomas. However development of resistance to Carmustine has restricted its application. It is evidenced that non-coding RNAs, especially microRNAs (miRNAs, miRs), play significant roles in association with the occurrence of this phenomenon. In the present systematic study, the interaction mechanisms between non-coding RNAs And Carmustine in the modulation of sensitivity to this drug in cancer have been investigated. The search and analysis steps followed PRISMA guidelines. A comprehensive search was conducted across databases including PubMed, Scopus, and Web of Science. According to the opted criteria, a total of 12 studies were eligible for inclusion in the study. Up or downregulation of non-coding RNA expression levels effectively influences the biology of various signaling pathways in Glioblastoma cell lines or tumors. Eventually, these significant influences would be translated into an altered status of sensitivity to Carmustine. A deeper understanding of the underscored network of interactions could be potentially helpful for improving the efficacy of chemotherapy-based approaches against cancer.

Multidrug-resistant (MDR) Escherichia coli (E.coli) is a growing public health concern, largely driven by the overexpression of efflux pumps such as AcrAB-tolC. These efflux systems contribute to resistance against multiple antibiotic classes, including fluoroquinolones, β-lactams, and aminoglycosides. Despite the well-documented role of efflux pumps in resistance, inconsistencies in reported expression levels and regulatory mechanisms complicate the development of targeted therapies. This systematic review and meta-analysis aim to consolidate available evidence on acrAB-tolC expression patterns and evaluate the impact of efflux pump inhibitors (EPIs) on antibiotic susceptibility.

For centuries, Panax ginseng C.A. Meyer has been widely employed in traditional medicine, and its primary therapeutic constituents are a class of compounds known as ginsenosides. In particular, protopanaxadiol (PPD)-type ginsenosides exhibit potent anticancer properties, largely mediated through epigenetic mechanisms.

DNA methylation represents a crucial epigenetic mechanism orchestrating gene expression, cellular homeostasis, and the aging trajectory. Dysregulation of DNA methyltransferases (DNMTs)-the enzymes catalyzing this process-has been implicated in a wide spectrum of chronic conditions, including cancer, cardiovascular and metabolic disorders, and neurodegenerative diseases. Emerging evidence suggests that food-derived bioactive compounds can act as DNMT inhibitors, reshaping epigenetic landscapes. This systematic review, registered in PROSPERO (CRD42022320316), critically evaluated in vitro, in vivo animal, and ex vivo studies investigating the effects of dietary bioactives on DNMT expression and activity. A thorough search of PubMed up to 23 May, 2025, yielded 103 studies, of which 76 met the inclusion criteria. Eligible publications were original, peer-reviewed, and provided evidence from in vitro, in vivo animal, or ex vivo models. Frequently studied bioactives included epigallocatechin-3-gallate, curcumin, genistein, resveratrol, sulforaphane, and folate. Notably, nearly 90% of studies reported DNMT inhibition-often dose- and time-dependent. Approximately 21% defined minimal effective concentrations, predominantly for isolated compounds. Several studies described synergistic interactions between bioactives, and emerging data highlighted the gut microbiota's mediating role in epigenetic modulation. Despite promising outcomes, the predominance of preclinical evidence and variability in experimental protocols and dosing limit the immediate translational impact. Nonetheless, current findings underscore the promise of dietary DNMT modulators as foundational elements for precision nutrition strategies aimed at promoting healthy aging and mitigating age-associated disease risk. The potential application of DNA methylation age as a biomarker of biological aging has been increasingly supported by recent literature, reinforcing its relevance in future nutritional epigenetics research. Further well-designed clinical trials are warranted to assess long-term efficacy, safety, and bioavailability of these compounds and to validate their use in personalized epigenetic interventions using biological aging markers. This review was funded by the European Union-Next Generation EU, PNRR Project Age-It (DM 1557 11.10.2022), and the University of Padua SID Grant (2024DCTV1SIDPROGETTI-00194).

Cancer is one of the leading causes of mortality worldwide. Development of new methods or improving the efficiency of already existing methods is essential in the successful treatment of this disease. Topotecan, a chemotherapeutic drug, has been used to inhibit various cancer types. However, chemotherapy resistance to this drug in cancer has impeded its maximum performance. miRNAs and other non-coding RNAs play crucial roles in regulating this attribute. In this systematic review, we investigated the interaction mechanism between these molecules and Topotecan in the modulation of cancer sensitivity to this agent. This study was carried out according to PRISMA guidelines. PubMed, Scopus, and Web of Science databases were comprehensively searched, using our predefined search terms. Following a selective process based on strategic criteria, eleven studies were included in the analysis. Altered expression levels of non-coding RNAs, especially miRNAs, regulated the sensitivity of cancer cell lines and animal models, directly and indirectly, through affecting cascades of signaling molecules. This impact was recorded in a variety of cancer types, including retinoblastoma, renal cell carcinoma, colorectal cancer, cervical cancer, breast cancer, prostate cancer, and leukemia. The highlighted interactions potentially offer new opportunities for modifying therapeutic intervention utilizing chemotherapeutic agents.

This study attempts to summarize current knowledge about the carcinogenic potential of alternative tobacco products: electronic cigarettes (ECs), heat-not-burn (HnB) cigarettes and snus/nicotine pouches (NPs). We focus on determining the effect of such products on epigenetic alteration, especially for genes and pathways which are fundamental for cancer development.

Arterial hypertension affects >1.28 billion adults globally, remaining a leading cause of cardiovascular morbidity and mortality. Despite effective therapies, suboptimal blood pressure control persists, highlighting the need for precision approaches. Epigenetic biomarkers, particularly DNA methylation (DNAm), have emerged as potential tools to enhance risk stratification and personalize antihypertensive therapy, yet their clinical relevance remains uncertain. To systematically synthesize evidence on genetic and epigenetic biomarkers associated with hypertension, focusing on DNAm signatures, regulatory pathways, and translational potential, we conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, registered in PROSPERO (Chronic Renal Disease (CRD) 420251059256). PubMed, MEDLINE, Embase, and ScienceDirect were searched up to March 2025. Eligible studies investigated genetic or epigenetic markers, such as DNAm, single nucleotide polymorphisms, or chromatin modifications in adult hypertension populations. Data on study design, populations, biomarkers, analytical methods, and outcomes were extracted. Risk of bias was assessed using RoB 2 and Risk of Bias in Nonrandomized Studies of Interventions tool. Twelve studies were included, encompassing cross-sectional and longitudinal designs. DNAm signatures at loci including AGTR1, PHGDH, SLC7A11, Angiotensin-Converting Enzyme (ACE), and WNT3A were recurrently associated with blood pressure regulation. Transancestry genome-wide analyses identified methylation-enriched loci such as KCNK3, PDE3A, and PRDM6. However, no study demonstrated predictive value for clinical end points or robust replication across diverse populations. Methodological heterogeneity limited longitudinal data and underrepresentation of low- and middle-income countries were key limitations. Although epigenetic markers show promise for hypertension research, current evidence remains exploratory. Rigorous, longitudinal studies integrating clinical end points are essential for advancing toward clinical translation.

Doxorubicin (DOX), a cornerstone chemotherapeutic agent, is plagued by dose-dependent cardiotoxicity that compromises its clinical utility. Despite advances in understanding DOX-induced cardiotoxicity (DIC), effective interventions remain limited. Emerging evidence highlights Traditional Chinese Medicine (TCM) - with its multi-target epigenetic modulatory potential - as a promising therapeutic strategy.

Τhe epigenetic effects of glucocorticosteroids-also known as glucocorticoids-(GCs) on the human epigenome are under constant in-depth examination. During uncomplicated pregnancy, endogenous GCs are normally increased, this increase being increased in stressful maternal conditions, such GC excess potentially having a deleterious effect on the fetus. In addition, however, synthetic GCs have long been used during pregnancy, not only for lung maturation in pregnancies at risk for preterm birth but also therapeutically for a large number of maternal diseases. Although GCs can be administrated as treatment during pregnancy, exhaustive study of the genome as well as of the compound's epigenetic effects has called their use into question.

Extensive evidence highlights the role of epigenetic alterations in chemically induced carcinogenesis. Accordingly, this review focuses on the importance of epigenetics and exposure in bladder cancer. Specifically, we examined publications reporting epigenetic alterations associated with exposure to agents and occupations classified by the International Agency for Research on Cancer as having sufficient evidence for bladder cancer. This systematic review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of the PubMed database was performed for studies published up to March 2024. The inclusion criteria required the use of epigenetic studies in healthy populations exposed to carcinogenic agents or occupational exposures with sufficient evidence for bladder cancer, as classified by the International Agency for Research on Cancer, and was limited to articles written in English. We identified 23 studies examining epigenetic changes in healthy individuals exposed to 16 carcinogens or occupational exposures with established evidence of increased bladder cancer risk. These studies particularly emphasized DNA methylation analysis. Epigenetic responses associated with these exposures have been extensively studied and characterized. Although epigenetic disorders are increasingly considered critical in cancer assessments, there remain gaps in research addressing the epigenetic effects of many potential carcinogens in the human epithelium. Consequently, data on bladder cancer induction through epigenetic mechanisms are especially valuable.

Preeclampsia (PE) is a critical complication of pregnancy that affects 3% to 5% of all pregnancies and has been linked to aberrant placentation, causing severe maternal and fetal illness and death.