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.

Probiotics exert a diverse range of immunomodulatory effects on the human gut immune system. These mechanisms encompass strengthening the intestinal mucosal barrier, inhibiting pathogen adhesion and colonization, stimulating immune modulation, and fostering the production of beneficial substances. As a result, probiotics hold significant potential in the prevention and treatment of various conditions, including inflammatory bowel disease and colorectal cancer. A pivotal mechanism by which probiotics achieve these effects is through modulating the expression of host miRNAs. miRNAs, non-coding RNA molecules, are vital regulators of fundamental biological processes like cell growth, differentiation, and apoptosis. By interacting with mRNAs, miRNAs can either promote their degradation or repress their translation, thereby regulating gene expression post-transcriptionally and modulating the immune system. This review provides a comprehensive overview of how probiotics modulate gut immune responses by altering miRNA expression levels, both upregulating and downregulating specific miRNAs. It further delves into how this modulation impacts the host's resistance to pathogens and susceptibility to diseases, offering a theoretical foundation and practical insights for the clinical utilization of probiotics in disease prevention and therapy.

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.

Diabetes mellitus is a complex disease in terms of its causes and pathophysiological processes, it produces a significant impact on health and leads to complications that are difficult to manage.

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.

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.

Despite osteoarthritis (OA) being recognised for over a century as a debilitating disease that affects millions, there are huge gaps in our understanding of the underlying pathophysiology that drives this disease. Present day studies that focussed on ubiquitination (Ub) and ubiquitylation-like (Ubl) modification related mechanisms have brought light into the possibility of attenuating OA development by targeting these specific proteins in chondrocytes. In the present review, we discuss recent advances in studies involving Ub ligases and deubiquitinating enzymes (DUBs) which are of importance in the development of OA, and may offer potential therapeutic strategies for OA. Such targets may involve attenuating proteases such as matrix metalloproteinases (MMP) 1, 8, 13, 4 and several A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) that are well known for their roles in cartilage breakdown. Ligases such as ubiquitin-conjugating enzymes (E2) and ubiquitin-ligating enzymes (E3) that are involved in extracellular matrix (ECM) degradation in OA and of their pathogenesis would be discussed. In addition to catabolic and degenerative downstream effects of Ub and DUBs in OA, inflammatory mechanisms most notably involving nuclear factor-kappa B (NF-κB) signalling pathways regulated through Ub and using various targeting molecules would also be highlighted. Challenges, gaps and insights from clinical trials will provide valuable guidance for future investigations on targeting ubiquitin-proteosome system (UPS) as a therapeutic option for OA.

Cytosine (DNA) methylation plays important roles in silencing transposable elements, plant development, genomic imprinting, stress responses, and maintenance of genome stability. To better understand the functions of this epigenetic modification, several tools have been developed to manipulate DNA methylation levels. These tools include mutants of DNA methylation writers and readers, targeted manipulation of locus-specific methylation, and the use of chemical inhibitors. Here, we summarize the effects of commonly used cytidine analog chemical inhibitors, represented by zebularine, 5-azacytidine, and their related compounds, on plants. These analogs are incorporated into chromosomal DNA, where they block the activity of the replicative CG DNA methyltransferase 1 (MET1). This leads to manifold alterations in the plant epigenome, modified developmental programs, or suppression of hybridization barriers. We also highlight the DNA-damaging effects of cytidine analogs, particularly the formation of stable DNA-protein crosslinks between DNA and MET1. This phenomenon sheds new light on specific phenotypes observed upon treatment with cytidine analogs. In conclusion, cytidine analogs are a vital tool for plant genome research and have the potential to open new promising avenues for applications in plant biotechnology and breeding.

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.

Glioblastoma (GBM) is a very deadly type of brain tumor with a poor prognosis and a short survival rate. Recent advancements in understanding GBM's molecular and genetic characteristics have led to the development of various therapeutic and diagnostic strategies. Key elements such as microRNAs, lncRNAs, exosomes, angiogenesis, and chromatin modifications are highlighted, alongside significant epigenetic alterations that impact therapy and diagnosis. Despite these advancements, molecular classifications have not improved patient outcomes due to intratumoral diversity complicating targeted therapies. In this article, it is tried to emphasize the potential of investigating the epigenetic landscape of GBM, particularly identifying patients with diffuse hypermethylation at gene promoters associated with better outcomes. Integrating epigenetic and genetic data has enhanced the identification of glioma subtypes with high diagnostic precision. The reversibility of epigenetic changes offers promising therapeutic prospects, as recent insights into the "epigenetic orchestra" suggest new avenues for innovative treatment modalities for this challenging cancer. In this review article, we focus on the roles of translational elements and their alterations in the context of GBM diagnosis and therapy.