Colorectal cancer (CRC) continues to be a significant global health issue. Thymoquinone (TQ), a bioactive component of Nigella sativa, has shown anticancer capabilities by inducing apoptosis. This systematic review and meta-analysis aim to assess the impact of TQ on the levels of pro-apoptotic (BAX, CASP3) and anti-apoptotic (BCL2) markers in colorectal cancer cells.

Although microRNAs (miRNAs) are an active area of research in multiple sclerosis (MS) and have been proposed as potential biomarkers of treatment response, the evidence remains difficult to interpret. This systematic review examines the relationship between miRNA expression and response to disease-modifying therapies (DMTs) in adults with MS. The PubMed/MEDLINE and Web of Science databases were systematically searched from inception to 11 February 2026. Fifteen studies that compared miRNA expression between responders and non-responders or assessed changes in miRNA expression after DMT initiation were synthesized narratively by treatment group and outcome, in accordance with the 2020 PRISMA guidelines. After considering study design, treatment response definitions, and miRNA analytical methods, miR-548a-3p in fingolimod-treated patients and miR-223-3p, miR-23a/b-3p, and miR-27a/b-3p in dimethyl fumarate (DMF)-treated patients appeared the most promising miRNAs investigated; however, each was assessed in a single study and has not yet been validated in independent external cohorts. However, they were notable because they had been evaluated in clinically relevant settings: miR-548a-3p in relation to no evidence of disease activity-3 and receiver operating characteristic-based discrimination, and the DMF-associated miRNAs through baseline expression levels and early fold-change analyses. Although miR-23a-3p, miR-26a-5p, miR-146a-5p, miR-155, miR-34a-5p, miR-223-3p, miR-660-5p, and miR-326 had been reported in more than one study, most were investigated in different DMT or outcome contexts. Therefore, the existing literature correlating miRNA expression levels with treatment response provides valuable but limited and heterogeneous evidence. Thus, miRNAs should currently be considered exploratory biomarkers and require further independent validation before their use in clinical practice.

Kratom (Mitragyna speciosa) is a traditional Southeast Asian botanical long used for alleviating pain and boosting energy. Its chief bioactive compound, mitragynine (MG), exhibits both opioid-like and stimulant properties and has prompted interest in its potential role in pain management and opioid withdrawal support. However, its safety profile and underlying mechanisms remain incompletely understood. This systematic review critically synthesizes preclinical evidence on kratom's molecular, pharmacological, and epigenetic effects. Guided by PRISMA 2020 criteria, studies indexed in Scopus and Web of Science (2000-2024) were analyzed, focusing on receptor activity, intracellular signaling, and gene regulation in in vitro and in vivo models. Among 20 eligible studies, key findings indicate that kratom alkaloids engage μ-opioid, adrenergic, and serotonergic receptors; modulate dopaminergic and glutamatergic systems; and exert anti-inflammatory and analgesic effects. Under chronic exposure followed by withdrawal, MG was associated with reduced histone acetylation and increased HDAC2 expression, while Rab35 emerged as a potential withdrawal-associated biomarker. MG also inhibited cardiac ion channels and altered CYP450 enzyme expression, highlighting safety concerns related to cardiotoxicity and drug-drug interactions. Despite these mechanistic insights, limitations in pharmacokinetic data, standardized dosing, and long-term safety preclude clinical application. Future research should prioritize controlled human studies, omics-driven biomarker discovery, and evidence-based regulatory evaluation to clarify kratom's therapeutic potential and risk profile.

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.

Alcohol exposure affects immune regulation and tissue homeostasis. Antimicrobial peptides (AMPs) are essential components of innate immunity, not only defending against pathogens but also modulating processes such as inflammation. However, their tissue-specific regulation in response to alcohol remains poorly characterized, particularly in humans after acute intoxication. We evaluated the expression of AMPs in the peripheral blood of patients with alcohol use disorder (AUD, n = 9), individuals with acute alcohol consumption (AAC, n = 9), and controls using quantitative polymerase chain reaction (qPCR). Additionally, we analyzed AMP expression in selected tissues of mice exposed to chronic ethanol feeding (National Institute on Alcohol Abuse and Alcoholism model for 5 days) and performed a systematic review of AMP regulation in alcohol-related disorders (2005-2025; n = 36 studies, reflecting a limited and heterogeneous body of available evidence). Human cathelicidin antimicrobial peptide (LL-37), lipopolysaccharide-binding protein (LBP), and bactericidal/permeability-increasing protein (BPI) were significantly upregulated in patients with AUD, whereas LL-37 and LBP were significantly upregulated in AAC. In the livers of ethanol-fed mice, LEP2, LCN2, and LBP levels were markedly increased, whereas LL-37 and LEP1 were downregulated. Duodenal tissue exhibited upregulation of DEFB1. In adipose tissue, DEFA2 was significantly increased in peripheral depots, whereas only LCN2 was upregulated in brain tissue. The systematic review demonstrated complex, heterogeneous, and organ-dependent AMP regulation and also highlighted the paucity of human data on AAC, a gap that our study partially addresses. Our results are consistent with the hypothesis that selected AMPs may serve as candidate markers of organ damage or microbial translocation and as possible therapeutic targets, a hypothesis that requires confirmation in larger, adequately powered studies.

Prenatal and early childhood exposure to pesticides is a global concern, yet the genotoxic mechanisms potentially linking these exposures to adverse health outcomes remain incompletely characterized. We conducted a systematic review and random-effects meta-analysis of studies reporting primary DNA damage, cytogenetic damage, DNA methylation, or gene expression outcomes associated with prenatal and early childhood pesticide exposure. We searched four databases following PRISMA guidelines and assessed using risk of bias using the Newcastle-Ottawa Scale. Twenty-eight studies met inclusion criteria. Meta-analysis revealed substantial DNA damage in pesticide-exposed groups (Cohen's d = 4.85, 95%CI = 3.31-6.39), with stronger effects in maternal and cord blood than in children's blood. Cytogenetic damage showed consistent increases in agricultural versus urban areas, though with significant heterogeneity in effect magnitude. Pathway-specific gene expression analysis revealed significant downregulation of DNA damage/repair genes (-1.08, 95%CI:-1.20,-0.96) and distinct biological responses across inflammatory, oxidative stress, and cell signaling pathways. DNA methylation responses varied by pesticide class, with o,p'-DDT consistently associated with hypermethylation. Pronounced sex-specific effects and genetic susceptibility emerged as important effect modifiers. The evidence supports substantial genotoxic and epigenetic alterations following early-life pesticide exposure, highlighting mechanistic pathways that may underlie adverse health outcomes and reinforcing the need for precautionary policies during critical developmental windows.

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.