Male infertility has become an increasingly severe global health issue, with its incidence significantly rising over the past few decades. This paper delves into the crucial role of epigenetics in male reproductive health, focusing particularly on the effects of DNA methylation, histone modifications, chromatin remodeling and non-coding RNAs regulation on spermatogenesis. Exposure to various environmental factors can cause sperm DNA damage, leading to epigenetic abnormalities. Among these factors, we have discussed heavy metals (including Zinc, Cadmium, Arsenic, Copper), phthalates, electromagnetic radiation, and temperature in detail. Notably, aberrations in DNA methylation are closely associated with various symptoms of male infertility, and histone modifications and chromatin remodeling are essential for sperm maturation and function. By synthesizing existing literature and experimental data, this narrative review investigates how environmental factors influence male reproductive health through epigenetic mechanisms, thus providing new theoretical foundations and practical guidelines for the early diagnosis and treatment of male infertility.

Epigenetic modifications, such as aberrant DNA methylation, histone alterations, non-coding RNA remodeling, and modulation of transcription factors, are pivotal in the pathogenesis of diverse malignancies. Reactive oxygen species (ROS) have the capacity to impact these epigenetic mechanisms, including DNA methylation, throughout the different stages of cancer development. Therefore, the aim of this review is to address the impact of.

Enhancer of zeste homolog 2 (EZH2) is a methyltransferase involved in cell cycle regulation, cell differentiation, and cell death and plays a role in modulating the immune response. Although it mainly functions by catalyzing the tri-methylation of H3 histone on K27 (H3K27), to inhibit the transcription of target genes, EZH2 can directly methylate several transcription factors or form complexes with them, regulating their functions. EZH2 expression/activity is often dysregulated in cancer, contributing to carcinogenesis and immune escape, thereby representing an important target in anti-cancer therapy. This review summarizes some of the mechanisms through which EZH2 regulates the expression and function of tumor suppressor genes and oncogenic molecules such as STAT3, mutant p53, and c-Myc and how it modulates the anti-cancer immune response. The influence of posttranslational modifications on EZH2 activity and stability and the possible strategies leading to its inhibition are also reviewed.

Doxorubicin (DOX), a cornerstone chemotherapeutic agent, effectively combats various malignancies but is marred by significant cardiovascular toxicity, including endothelial damage, chronic heart failure, and vascular remodeling. These adverse effects, mediated by oxidative stress, mitochondrial dysfunction, inflammatory pathways, and dysregulated autophagy, underscore the need for precise therapeutic strategies. Emerging research highlights the critical role of microRNAs (miRNAs) in DOX-induced vascular remodeling and cardiotoxicity. miRNAs, such as miR-21, miR-22, miR-25, miR-126, miR-140-5p, miR-330-5p, miR-146, miR-143, miR-375, miR-125b, miR-451, miR-34a-5p, and miR-9, influence signaling pathways like TGF-β/Smad, AMPKa/SIRT, NF-κB, mTOR, VEGF, and PI3K/AKT/Nrf2, impacting vascular homeostasis, angiogenesis, and endothelial-to-mesenchymal transition. Despite existing studies, gaps remain in understanding the full spectrum of miRNAs involved and their downstream effects on vascular remodeling. This review synthesizes the current knowledge on miRNA dysregulation during DOX exposure, focusing on their dual roles in cardiovascular pathology and tumor progression. Strategies to reduce DOX cardiotoxicity include modulating miRNA expression to restore signaling balance, targeting pro-inflammatory and pro-fibrotic pathways, and leveraging miRNA inhibitors or mimics. This review aims to organize and integrate the existing knowledge on the role of miRNAs in vascular remodeling, particularly in the contexts of DOX treatment and the progression of various cardiovascular diseases, including their potential involvement in tumor growth.

This review provides a comprehensive overview of the role of G9a/EHMT2, focusing on its structure and exploring the impact of its pharmacological and/or gene inhibition in various neurological diseases. In addition, we delve into the advancements in the design and synthesis of G9a/EHMT2 inhibitors, which hold promise not only as a treatment for neurodegeneration diseases but also for other conditions, such as cancer and malaria. Besides, we presented the discovery of dual therapeutic approaches based on G9a inhibition and different epigenetic enzymes like histone deacetylases, DNA methyltransferases, and other lysine methyltransferases. Hence, findings offer valuable insights into developing novel and promising therapeutic strategies targeting G9a/EHMT2 for managing these neurological conditions.

Cancer remains a leading cause of mortality globally and a major health burden, with chemotherapy often serving as the primary therapeutic option for patients with advanced-stage disease, partially compensating for the limitations of non-curative treatments. However, the emergence of chemotherapy resistance significantly limits its efficacy, posing a major clinical challenge. Moreover, heterogeneity of resistance mechanisms across cancer types complicates the development of universally effective diagnostic and therapeutic approaches. Understanding the molecular mechanisms of chemoresistance and identifying strategies to overcome it are current research focal points. This review provides a comprehensive analysis of the key molecular mechanisms underlying chemotherapy resistance, including drug efflux, enhanced DNA damage repair (DDR), apoptosis evasion, epigenetic modifications, altered intracellular drug metabolism, and the role of cancer stem cells (CSCs). We also examine specific causes of resistance in major cancer types and highlight various molecular targets involved in resistance. Finally, we discuss current strategies aiming at overcoming chemotherapy resistance, such as combination therapies, targeted treatments, and novel drug delivery systems, while proposing future directions for research in this evolving field. By addressing these molecular barriers, this review lays a foundation for the development of more effective cancer therapies aimed at mitigating chemotherapy resistance.

The oncoprotein c-Myc is expressed in all breast cancer subtypes, but its expression is higher in triple-negative breast cancer (TNBC) compared to estrogen receptor (ER+), progesterone receptor (PR+), or human epidermal growth factor receptor 2 (HER2+) positive tumors. The c-Myc gene is crucial for tumor progression and therapy resistance, impacting cell proliferation, differentiation, senescence, angiogenesis, immune evasion, metabolism, invasion, autophagy, apoptosis, chromosomal instability, and protein biosynthesis. Targeting c-Myc has emerged as a potential therapeutic strategy for TNBC, a highly aggressive and deadly breast cancer form. This review highlights c-Myc as a pharmacological target, discussing antitumor compounds in preclinical and clinical trials. Notably, the c-Myc inhibitor OMO-103 has shown promise in a Phase II clinical trial for advanced cancer patients. Further research is needed to develop new drugs targeting this gene, protein, or its pathways, and additional studies on cancer patients are encouraged.

Histone methylation, a crucial aspect of epigenetics, intricately involves specialized enzymes such as G9a, a histone methyltransferase (HMT) catalyzing the methylation of histone H3 lysine 9 (H3K9) and H3K27. Apart from histone modification, G9a regulates essential cellular processes such as deoxyribonucleic acid (DNA) replication, damage repair, and gene expression via modulating DNA methylation patterns. The dysregulation and overexpression of G9a are intricately linked to cancer initiation, progression, and metastasis, making it a compelling target for anticancer therapy. Moreover, aberrant levels of H3K9 dimethylation were identified in Alzheimer's disease (AD), broadening the scope of epigenetic implications across various pathologies. The quest for potent therapy has resulted in the identification of numerous G9a inhibitors/degraders, each demonstrating the potential to disrupt aberrant signaling pathways. This perspective provides valuable insights into the evolving potential and advancement of G9a modulators as promising candidates for treating a spectrum of diseases.

Ovarian cancer (OC) is one of the leading gynecological causes of death among women. The current standard treatment for OC is debulking surgery followed by platinum-based chemotherapy treatments; however, despite initial success to treatment many patients experience relapses. Currently, there are no available tests to predict sensitivity or resistance to chemotherapy. The aim of this review is to investigate the literature regarding prediction of chemotherapy resistance in patients with OC using gene expression patterns.

Leukemia is a type of blood cancer characterized by the uncontrolled growth of abnormal cells in the bone marrow, which replace normal blood cells and disrupt normal blood cell function. Timely and personalized interventions are crucial for disease management and improving survival rates. However, many patients experience relapse following conventional chemotherapy, and increasing treatment intensity often fails to improve outcomes due to mutated gene-induced drug resistance in leukemia cells. This article analyzes the association of gene mutations and drug resistance in leukemia. It explores genetic abnormalities in leukemia, highlighting recently identified mutations affecting signaling pathways, cell apoptosis, epigenetic regulation, histone modification, and splicing mechanisms. Additionally, the article discusses therapeutic strategies such as molecular targeting of gene mutations, alternative pathway targeting, and immunotherapy in leukemia. These approaches aim to combat specific drug-resistant mutations, providing potential avenues to mitigate leukemia relapse. Future research with these strategies holds promise for advancing leukemia treatment and addressing the challenges of drug-resistant mutations to improve patient outcomes.

Over the last decades, human infertility has become a major concern in public health, with severe societal and health consequences. Growing evidence shows that endocrine disruptors chemicals (EDCs) have been considered as risk factors of infertility. Their presence in our everyday life has become ubiquitous because of their universal use in food and beverage containers, personal care products, cosmetics, phytosanitary products. Exposure to these products has an impact on human reproductive health. Recent studies suggest that women are more exposed to EDCs than men due to higher chemical products use. The aim of this review is to understand the possible link between reproductive disorders and EDCs such as phthalates, bisphenol, dioxins, and pesticides. In women, the loss of endocrine balance leads to altered oocyte maturation, competency, anovulation and uterine disorders, endometriosis, premature ovarian insufficiency (POI) or embryonic defect and decreases the in vitro fertilization outcomes. In this review, we consider EDCs effects on the women's reproductive system, embryogenesis, with a focus on associated reproductive pathologies.

Silica nanoparticles (SiNPs) are widely used in biomedical fields, such as drug delivery, disease diagnosis, and molecular imaging. An increasing number of consumer products containing SiNPs are being used without supervision, and the toxicity of SiNPs to the human body is becoming a major problem. SiNPs contact the human body in various ways and cause damage to the structure and function of genetic material, potentially leading to carcinogenesis, teratogenicity and infertility. This review summarizes SiNPs-induced genetic and epigenetic toxicity, especially to germ cells, and explore their potential mechanisms. SiNPs cause genetic material damage mainly by inducing oxidative stress. Furtherly, the molecular mechanisms of epigenetic toxicity are discussed in detail for the first time. SiNPs alter DNA methylation, miRNA expression, histone modification and inhibit chromatin remodeling by regulating epigenetic-related enzymes and transcription factors. This review is beneficial for investigating potential solutions to avoid toxicity and provide guidance for better application of SiNPs in the biomedical field.

Multiple myeloma (MM), a hematological malignancy which affects the monoclonal plasma cells in the bone marrow, is in rising incidence around the world, accounting for approximately 2 % of newly diagnosed cancer cases in the US, Australia, and Western Europe. Despite the progress made in the last few years in the available therapeutic options (e.g. proteasome inhibitors, immunomodulatory drugs, tumor cell-targeting monoclonal antibodies, autologous stem cell transplantation, etc.), multiple myeloma is still regarded as incurable, and the prognosis for most patients is poor, as the disease becomes refractory to treatment throughout time. Antisense oligonucleotides (ASOs), designed to be complementary to selected messenger RNA (mRNA) sequences of specific genes involved in the pathogenesis of multiple myeloma (e.g. Bcl-2, Mcl-1, STAT3, IRF4, IL6, ILF2, HK2, c-MYC, etc.), represent a promising alternative to conventional treatments, and can be tailored according to the individual requirements of each patient. The main goal of antisense therapy for multiple myeloma consists in silencing the specific genes participating in the proliferation and survival of tumor cells via RNA cleavage or RNA blockage, thus preventing mRNA interactions with ribosomes and altering the process of protein translation. So far, pre-clinical and clinical studies showed promising results when Bcl-2 (Genasense), Mcl-1 (ISIS2048), STAT3 (ISIS345794) and IRF4 (ION251) were targeted using ASOs-based formulations. However, FDA approval has not been obtained yet for these products, mainly due to ethical and financial issues posed by customized therapies and insufficient information regarding their long-term toxicity. This review aims to provide a comprehensive insight into antisense oligonucleotides-based therapies, their potential chemical modifications, the mechanisms involved in ASOs-mediated gene silencing, potential systems for ASOs delivery, and the applications of ASOs in the treatment of multiple myeloma. The relevant genetic targets in ASOs-based MM therapies were described, and the research results obtained in the studies conducted so far were analyzed, with a focus on the ASOs formulations that were already included in clinical trials. In the end, current challenges, and future perspectives of antisense therapy for MM were also discussed.

The review presents literature data on the role of the ТР53 gene and ionizing radiation (IR) in the pathogenesis of acute myeloid leukemia (AML).The violation of ТР53 functioning as a promoter of AML induction under the influence of negative external factors (IR, chemotherapeutic agents) was analyzed. New directions of AML stratification are presented, which will allow to optimize the future therapy and extend the life expectancy of this category of patients.

Metals are common environmental pollutants. Acute and chronic exposures to non-essential toxic metals or excessive essential metals cause various diseases including cancer in humans. However, the underlying mechanisms have not been well understood. Long non-coding RNAs (lncRNAs) refer to RNA transcripts that have more than 200 nucleotides but do not have significant protein coding capacities. While lncRNAs were once considered transcription noise, they have become increasingly recognized as crucial players in various physiological and pathogenesis processes. The goal of this article is to review and discuss recent studies that show important roles of lncRNA dysregulations in metal toxicity and carcinogenesis.

Resveratrol (RSV) is a naturally occurring astragalus-like polyphenolic compound with remarkable weight loss properties. However, the mechanism of RSV in treating obesity is unclear. In this narrative review, we explored electronic databases (PubMed) for research articles from 2021 to the present using the keywords "resveratrol" and "obesity". This article explores the mechanisms involved in the alleviation of obesity-related metabolic disorders by RSV. RSV affects obesity by modulating mitochondrial function, insulin signaling, and gut microbiota, regulating lipid metabolism, inhibiting oxidative stress, and regulating epigenetic regulation. Administering RSV to pregnant animals exhibits maternal and first-generation offspring benefits, and RSV administration to lactating animals has long-term benefits, which involve the epigenetic modulations by RSV. A comprehensive understanding of the epigenetic mechanisms of RSV regulation could help in developing drugs suitable for pregnancy preparation groups, pregnant women, and nursing infants.

DNA methylation is a key epigenetic mechanism that regulates gene expression. Fatty acids, the building blocks of many essential lipids, play a crucial role in various biological events. Aberrant acetylation and methylation profiles are linked to a number of non-communicable diseases. Various fatty acids have been identified as potential 'epi-drugs' because of their ability to correct aberrant acetylation and methylation profiles in a number of non-communicable diseases, enhancing the value of their biochemical properties. This review summarizes the effects of selected saturated and unsaturated fatty acids and fatty-acid-rich food items on disease-associated DNA methylation profiles, aiming to justify the classification of fatty acids as DNA methylation modulators.

Aberrant elongation of proteins can lead to the activation of oncogenic signaling pathways, resulting in the dysregulation of oncogenic signaling pathways. Eukaryotic elongation factor 2 (eEF2) is an essential regulator of protein synthesis that precisely elongates nascent peptides in the protein elongation process. Although studies have linked aberrant eEF2 expression to various cancers, research has primarily focused on its structure, highlighting a need for deeper exploration into its molecular functions. In this review, recent advancements in the structure, guanosine triphosphatase (GTPase) activity, posttranslational modifications, regulatory factors, and inhibitors of eEF2 are summarized. These findings provide a comprehensive cognition on the critical role of eEF2 and its potential as a therapeutic target in cancer. Furthermore, this review highlights important unanswered questions that warrant investigation in future research.

The development of chemo-resistance remains a significant hurdle in effective cancer therapy. NRF1 and NRF2, key regulators of redox homeostasis, play crucial roles in the cellular response to oxidative stress, with implications for both tumor growth and resistance to chemotherapy. This study delves into the dualistic role of NRF2, exploring its protective functions in normal cells and its paradoxical support of tumor survival and drug resistance in cancerous cells. We investigate the interplay between the PERK/NRF signaling pathway, ER stress, autophagy, and the unfolded protein response, offering a mechanistic perspective on how these processes contribute to chemoresistance. Our findings suggest that targeting NRF signaling pathways may offer new avenues for overcoming resistance to chemotherapeutic agents, highlighting the importance of a nuanced approach to redox regulation in cancer treatment. This research provides a molecular basis for the development of NRF-targeted therapies, potentially enhancing the efficacy of existing cancer treatments and offering hope for more effective management of resistant tumors.

Epigenetics refers to heritable changes in gene expression or phenotypic changes that occur without changing the gene sequence. The main methods of epigenetics include non-coding RNA, histone modification, and DNA modification, which play an essential role in gene expression regulation and even the occurrence of diverse diseases. Naringenin, the aglycone form of naringin, is a natural flavonoid compound mainly found in fruits or plant derivatives such as citrus, tomatoes, and cherries. Naringenin and naringin exhibit a broad spectrum of biological activities and pharmacological effects, including anti-cancer, cardiovascular disease improving, anti-inflammatory, and anti-oxidant activities, all of which are advantageous for human health. Recent studies have uncovered that naringenin and naringin influence gene expression by modulating epigenetic pathways, including microRNA (miRNA) regulation. This mechanism plays a crucial role in the therapeutic potential for various diseases. This paper reviews the epigenetic researches on the physiological activities of naringenin and naringin. It highlights how these compounds can exert diverse effects through different signaling pathways, thereby ameliorating associated diseases. These findings provide valuable insights for the future applications of naringenin and naringin.