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.

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.

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.

Small interfering RNA (siRNA) holds promise as a therapeutic approach for various diseases, yet challenges persist in achieving efficient delivery, biodistribution, and minimizing off-target effects. Lipidic nanoformulations are being developed to address these hurdles, but the optimal dose for preclinical investigations remains unclear. This systematic review and meta-analysis aims to determine the optimal dose of nanoformulated siRNA and explore factors influencing dose and biodistribution, informing future research in this field. A comprehensive search across four electronic databases identified 25 potential studies, with 15 selected for meta-analysis after screening. Quality assessment was conducted using SYRCLE's risk of bias tool modified for animal studies based on research question. Study found an average siRNA dose of 1.513 ± 0.377 mg/kg with mean downregulation of 65.79 % achieved, with siRNA-LNPs mainly accumulating in the liver. While individual factors showed no significant correlation, a positive association between dose and downregulation was observed, alongside other influencing factors. Extrapolating intravenous doses to potential oral doses, we suggest an initial oral dose range of 1.5 to 8 mg/kg, considering siRNA-LNPs bioavailability. These findings contribute to advancing RNA interference research and encourage further exploration of siRNA-based treatments in personalized medicine.

The issue of MeHg contamination is a significant concern due to its detrimental impact on the environment. This study aimed to thoroughly investigate the effects of MeHg on neurodevelopmental biomarkers, as there is a lack of systematic reviews in this area. We conducted a comprehensive search of three databases (PubMed, Scopus, and Web of Science) and found 522 records, which were then meticulously reviewed by two independent reviewers. A total of 66 studies were included, with biomarkers related to oxidative stress, neurotransmission, inflammation, epigenetics, and apoptosis being the most prominent. The results of both in vitro and in vivo models indicate that antioxidant enzymes and other oxidative stress-related markers are indeed, altered following MeHg exposure. Moreover, MeHg exposure causes significant disruptions to neurotransmitter levels, activities of neurotransmitter synthesis enzymes, receptor densities, and proteins involved in synaptic function. Proinflammatory biomarkers are consistently overexpressed in both MeHg-treated cells and the brains of exposed rats. Furthermore, studies on DNA methylation and biomarker activity suggest that MeHg exposure may lead to neurotoxicity and neurodevelopmental issues via perturbations to epigenetic markers and the apoptosis pathway.

Exposure to pesticides is a risk factor for various diseases, yet its association with biological aging remains unclear. We aimed to systematically investigate the relationship between pesticide exposure and biological aging.

Paraoxonase (PON) proteins have various hydrolytic activities. The PON family is able to detoxify oxidized low-density lipoprotein. Additionally, differentiation of monocytes into macrophages, as the first stage in the development of atherosclerosis, is suppressed by PON 1. The effects of polyphenols including curcumin on PON1 have been investigated in studies. In this study, our main goal is to investigate curcumin's effect on PON1 protein levels, gene expression, and enzyme activity in animal interventional studies.

Endometriosis (EM), also known as Zhengjia in traditional Chinese medicine, is a common disease that significantly impacts women's health. An integrated treatment approach combining traditional Chinese medicine (TCM) and western medicine has demonstrated significant clinical efficacy in the management of this condition. Specifically, it has been effective in addressing blood circulation and other diseases. MicroRNAs (miRNAs), which are molecules important in gene regulation, have been implicated in various physiologic and pathologic processes. In this review, we systematically summarized the potential mechanisms underlying the integrated EM treatment, with a focus on the role of microRNAs (miRNAs). Current research suggests that integrated TCM and western medicine treatment may exert their therapeutic effects on EM by influencing the expression of miRNAs. Through miRNA modulation, such a treatment approach may inhibit the growth of ectopic lesions and alleviate clinical symptoms. This review will shed light on the specific miRNAs that have been implicated in the integrated treatment of EM, as well as their potential mechanisms of action. By consolidating the existing evidence, we aim to provide clinicians and researchers with a clearer understanding of the therapeutic benefits of the integrated approach and potentially identify new avenues for improving clinical treatment outcomes. Ultimately, this review will contribute to the growing body of knowledge in this field, providing a basis for further research and the development of more targeted and efficient treatment strategies for EM.

Seventy percent of breast cancer patients have an active estrogen receptor. Tamoxifen interferes with estrogen's ability to bind to cancer cells. The most challenging aspect of tamoxifen, however, is that breast cancer cells become resistant to its effects. Some studies have shown that alterations in miRNA expression contribute significantly to drug resistance in breast cancer. Therefore, the present systematic review aims to investigate miRNAs that significantly influence the response to tamoxifen treatment. The present study follows the PRISMA instructions. The Web of Science, PubMed, and Scopus databases were searched to retrieve English articles. The searches were conducted up to September 11, 2022. The search strategy included the terms "Tamoxifen", "Breast Neoplasm", and "MicroRNA". The inclusion criteria of this study are English, original, and experimental studies investigating miRNAs that are effective in the treatment efficacy of tamoxifen. A total of 565 articles were retrieved. After screening, 75 studies met our inclusion criteria. This systematic review study examined 105 miRNAs, of which 44 have a positive effect, and 47 miRNAs inhibit tamoxifen function. Fourteen miRNAs have a controversial effect, ie, some studies show positive and negative effects. The study of miRNAs affecting tamoxifen function in breast cancer patients may facilitate the identification of individuals at higher risk of disease recurrence. Conversely, it can potentially utilize appropriate interventions to defeat drug resistance effectively.

The advent of immune checkpoint inhibitors (ICIs) has represented a breakthrough in the treatment of many cancers, although a high number of patients fail to respond to ICIs, which is partially due to the ability of tumor cells to evade immune system surveillance. Non-coding microRNAs (miRNAs) have been shown to modulate the immune evasion of tumor cells, and there is thus growing interest in elucidating whether these miRNAs could be targetable or proposed as novel biomarkers for prognosis and treatment response to ICIs. We therefore performed an extensive literature analysis to evaluate the clinical utility of miRNAs with a confirmed direct relationship with treatment response to ICIs. As a result of this systematic review, we have stratified the miRNA landscape into (i) miRNAs whose levels directly modulate response to ICIs, (ii) miRNAs whose expression is modulated by ICIs, and (iii) miRNAs that directly elicit toxic effects or participate in immune-related adverse events (irAEs) caused by ICIs.