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.

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.

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.

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.

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.

Baicalein from Scutellaria baicalensis influences miRNA expression in various cancers, affecting key signaling pathways (PI3K/AKT, Wnt/β-catenin, mTOR) and processes like tumor growth, apoptosis, and metastasis. miRNAs, as small non-coding RNAs, play crucial roles in the cancer pathogenesis-associated gene regulations. This study is aimed at systematically reviewing the effects of baicalein on miRNA expression in various cancers. A comprehensive systematic review was conducted following PRISMA guidelines to investigate the impact of baicalein on miRNA expression in cancer. Databases including PubMed, Scopus, and Web of Science were systematically searched using key search terms. Inclusion criteria encompassed studies reporting changes in miRNA expression following baicalein treatment in cancer cell lines and animal models. Data extraction and risk of bias assessment based on SYRCLE's risk of bias tool were performed to ensure methodological rigor and reliability of the findings. Fifteen studies meeting the inclusion criteria were included in the systematic review. Baicalein impacts miRNA expression in cancers like hepatocellular carcinoma, breast, cervical, ovarian, and gastric cancers, suggesting its potential as a multi-cancer therapeutic. Baicalein regulates tumor-related genes (HDAC10, MDM2, Bcl-2/Bax, and Cyclin E1) and signaling molecules (AKT, FOXO3α), affecting cell viability, apoptosis, and cell cycle, indicating targeted therapeutic potential. In vitro and in vivo studies show baicalein inhibits tumor growth, enhances apoptosis, and regulates cell proliferation, supporting its anticancer effects. Baicalein exhibits potential in modulating miRNA expression in cancer, offering avenues for therapeutic intervention. However, methodological rigor in future studies is essential to enhance the reliability and validity of findings. Comprehensive understanding of baicalein's effects on miRNA expression holds promise for developing novel cancer treatment strategies.

Given the high prevalence of cannabis use among people with HIV (PWH) and its potential to modulate immune responses and reduce inflammation, this systematic review examines preclinical evidence on how tetrahydrocannabinol (THC), a key compound in cannabis, affects gene and micro-RNA expression in simian immunodeficiency virus (SIV)-infected macaques and HIV-infected human cells. Through a comprehensive search, 19 studies were identified, primarily involving SIV-infected macaques, with a pooled sample size of 176, though methodological quality varied across the studies. Pathway analysis of differentially expressed genes (DEGs) and miRNAs associated with THC revealed enrichment in pathways related to inflammation, epithelial cell proliferation, and adhesion. Notably, some DEGs were targets of the differentially expressed miRNAs, suggesting that epigenetic regulation may contribute to THC's effects on gene function. These findings indicate that THC may help mitigate chronic immune activation in HIV infection by altering gene and miRNA expression, suggesting its potential immunomodulatory role. However, the evidence is constrained by small sample sizes and inconsistencies across studies. Further research employing advanced methodologies and larger cohorts is essential to confirm THC's potential as a complementary therapy for PWH and fully elucidate the underlying mechanisms, which could inform targeted interventions to harness its immunomodulatory effects.

Epigenetic aging biomarkers are used for evaluating morbidity and mortality, monitoring therapies, and direct-to-consumer testing. However, the influence of environmental exposures on epigenetic age acceleration (EAA), also known as epigenetic age deviation, has not been systematically evaluated. In this systematic review, we synthesized findings from human epidemiologic studies on chemical and climatic environmental exposures, particularly air pollution, chemicals, metals, climate, and cigarette smoke, and EAA. A total of 102 studies analyzing epigenetic data from over 180,000 subjects were evaluated. Overall, studies in each exposure category frequently included adult participants, used a variety of epigenetic clocks, analyzed whole blood samples, and had a low risk of bias. Exposure to air pollution (15/19 of studies; 79%), cigarette smoke (53/66; 80%), and synthetic and occupational chemicals (5/8; 63%) were notably associated with increased EAA. Results for essential and non-essential metal exposure were more equivocal: 7/13 studies (54%) reported increased EAA. One study reported increased EAA with greater temperature exposure. In summary, we identified environmental exposures, such as air pollution and cigarette smoke, that were strongly associated with increased EAA. Further research is needed with larger and more diverse samples and high-quality exposure assessment.

Cardiovascular diseases (CVDs) are the major contributor to global mortality and are gaining incremental attention following the COVID-19 outbreak. Epigenetic events such as DNA methylation, histone modifications, and non-coding RNAs have a significant impact on the incidence and onset of CVDs. Altered redox status is one of the major causative factors that regulate epigenetic pathways linked to CVDs. Various bioactive phytocompounds used in alternative therapies including Traditional Chinese Medicines (TCM) regulate redox balance and epigenetic phenomena linked to CVDs. Phytocompound-based medications are in the limelight for the development of cost-effective drugs with the least side effects, which will have immense therapeutic applications.

Background: Curcumin is a polyphenol compound with anticancer effects. We aimed to review the anti-neoplastic effects of curcumin on urogenital cancers, by regulating different microRNA expressions. Methods: A systematic search was conducted in Medline (PubMed), Embase, Scopus, and Web of Science up to the end of August 2024. All English, in vitro, and observational studies that evaluated the effect of curcumin on preventing or treating urogenital cancers through its impact on microRNA expression were included. In vivo or silico studies were excluded. Result: A total of 2549 records were found. Finally, 25 studies were included. Twelve studies assessed the effect of curcumin on prostate cancer, six studies on ovarian cancer, three studies on cervical cancer, three studies on bladder cancer, and one study on renal cancer. MicroRNAs are small noncoding RNAs that regulate the post-transcriptional pathways. They possess pivotal roles in different fundamental mechanisms in cells such as differentiation, migration, apoptosis, and proliferation. Curcumin exerts its anticancer effects on urogenital neoplasms by upregulating tumor suppressor microRNAs (miR-143, miR-145, miR-Let-7, miR-101, miR-3127, miR-3178, miR-1275, miR-3198, miR-1908, miR-770, miR-1247, miR-411, miR-34a, miR-383, miR-708, miR-483, miR-199a, miR-335, miR-503, miR-10b, miR-551a, miR-9, miR-203, miR-7110, miR-29b, and miR-126) and downregulating oncogenic microRNAs (miR-21, miR-210, miR-382, miR-654, miR-494, miR-193b, miR-671, miR-222, miR-23b, miR-664, miR-183, miR-214, miR-320a, miR-23a, miR-30a, miR-320d, miR-1285, miR-32, miR-181a, miR-205, miR-216a, miR-1246, and miR-106b). Conclusion: Cell proliferation is inhibited, and cell apoptosis is induced by curcumin in different urogenital cancers through suppressing oncogenic microRNAs or provoking tumor suppressor microRNAs.

Colorectal cancer (CRC) remains a global health challenge with limited treatment success due to drug resistance. Recent research highlights the potential of small molecules to modulate CRC by targeting epigenetics or autophagy pathways. This systematic review explores the epigenetic effect of small molecules on autophagy in CRC, aiming to identify novel therapeutic strategies.

Triple-negative breast cancer (TNBC) exhibits a proclivity for early recurrence and development of metastasis. Moreover, drug resistance tends to arise few months following chemotherapeutic regimen with agents such as Doxorubicin, Paclitaxel, Docetaxel, and Cisplatin. miR-200 family and miR-205 are considered key regulators of metastasis by regulating the Epithelial-to-mesenchymal transition (EMT) via inhibiting ZEB1. Therefore, these microRNAs may offer therapeutic applications. Moreover, they hold potential for inhibiting chemoresistance and increasing chemosensitivity. These microRNAs are suppressed in TNBC cells. Increasing their levels, however, can inhibit EMT and improve progression-free survival (PFS). Besides using direct miRNA therapy via viral vectors, some drugs like Acetaminophen, or Tamoxifen are deemed useful for TNBC due to their ability to upregulate these miRNAs. In this review, by conducting an advanced search on PubMed, Embase, and Medline and selecting pertinent studies, we aimed to explore the potential applications of these microRNAs in controlling EMT and overcoming chemoresistance.

Curcumin is known as a bioactive component that is found in the rhizomes of Curcuma longa. Curcumin is well known for its chemo-preventive and anticancer properties. However, its anticancer mechanism in colorectal cancer treatment is unclear, and some studies have shown that many microRNAs (miRs) could be potential targets for curcumin in colorectal cancer (CRC) treatment, so there is a need for their integration and clarification.

Antipsychotic medications are essential when treating schizophrenia spectrum and other psychotic disorders, but the efficacy and tolerability of these medications vary from person to person. This interindividual variation is likely mediated, at least in part, by epigenomic processes that have yet to be fully elucidated. Herein, we systematically identified and evaluated 65 studies that examine the influence of antipsychotic drugs on epigenomic changes, including global methylation (9 studies), genome-wide methylation (22 studies), candidate gene methylation (16 studies), and histone modification (18 studies). Our evaluation revealed that haloperidol was consistently associated with increased global hypermethylation, which corroborates with genome-wide analyses, mostly performed by methylation arrays. In contrast, clozapine seems to promote hypomethylation across the epigenome. Candidate-gene methylation studies reveal varying effects post-antipsychotic therapy. Some genes like Glra1 and Drd2 are frequently found to undergo hypermethylation, whereas other genes such as SLC6A4, DUSP6, and DTNBP1 are more likely to exhibit hypomethylation in promoter regions. In examining histone modifications, the literature suggests that clozapine changes histone methylation patterns in the prefrontal cortex, particularly elevating H3K4me3 at the Gad1 gene and affecting the transcription of genes like mGlu2 by modifying histone acetylation and interacting with HDAC2 enzymes. Risperidone and quetiapine, however, exhibit distinct impacts on histone marks across different brain regions and cell types, with risperidone reducing H3K27ac in the striatum and quetiapine modifying global H3K9me2 levels in the prefrontal cortex, suggesting antipsychotics demonstrate selective influence on histone modifications, which demonstrates a complex and targeted mode of action. While this review summarizes current knowledge, the intricate dynamics between antipsychotics and epigenetics clearly warrant more exhaustive exploration with the potential to redefine our understanding and treatment of psychiatric conditions. By deciphering the epigenetic changes associated with drug treatment and therapeutic outcomes, we can move closer to personalized medicine in psychiatry.

Adenomyosis can reduce the chance of clinical pregnancy in women undergoing assisted conception. Treatment with prolonged gonadotrophin-releasing hormone analogue (GnRHa) downregulation prior to IVF/ICSI has been postulated to improve pregnancy outcomes.

Epigenetic-mediated modifications, induced by adverse environmental conditions, significantly alter an organism's physiological mechanisms. Even after elimination of the stimulus, these epigenetic modifications can be inherited through mitosis, thereby triggering transgenerational epigenetics. Plastics, with their versatile properties, are indispensable in various aspects of daily life. However, due to mismanagement, plastics have become so ubiquitous in the environment that no ecosystem on Earth is free from micro-nanoplastics (MNPs). This situation has raised profound concerns regarding their potential impact on human health. Recently, both in vivo animal and in vitro human cellular models have shown the potential to identify the harmful effects of MNPs at the genome level. The emerging epigenetic impact of MNP exposure is characterized by short-term alterations in chromatin remodelling and miRNA modulation. However, to understand long-term epigenetic changes and potential transgenerational effects, substantial and more environmentally realistic exposure studies are needed. In the current review, the intricate epigenetic responses, including the NHL-2-EKL-1, NDK-1-KSR1/2, and WRT-3-ASP-2 cascades, wnt-signalling, and TGF- β signalling, established in model organisms such as C. elegans, mice, and human cell lines upon exposure to MNPs, were systematically examined. This comprehensive analysis aimed to predict human pathways by identifying human homologs using databases and algorithms. We are confident that various parallel miRNA pathways, specifically the KSR-ERK-MAPK pathway, FOXO-Insulin cascade, and GPX3-HIF-α in humans, may be influenced by MNP exposure. This influence may lead to disruptions in key metabolic and immune pathways, including glucose balance, apoptosis, cell proliferation, and angiogenesis. Therefore, we believe that these genes and pathways could serve as potential biomarkers for future studies. Additionally, this review emphasizes the origin, dispersion, and distribution of plastics, providing valuable insights into the complex relationship between plastics and human health while elaborating on the epigenetic impacts.