Epigenetics is currently considered the investigation of inheritable changes in gene expression that do not rely on DNA sequence alteration. Significant epigenetic procedures are involved, such as DNA methylations, histone modifications, and non-coding RNA actions. It is confirmed through several investigations that epigenetic changes are associated with the formation, development, and metastasis of various cancers, such as colorectal cancer (CRC). The difference between epigenetic changes and genetic mutations is that the former could be reversed or prevented; therefore, cancer treatment and prevention could be achieved by restoring abnormal epigenetic events within the neoplastic cells. These treatments, consequently, cause the anti-tumour effects augmentation, drug resistance reduction, and host immune response stimulation. In this article, we begin our survey by exploring basic epigenetic mechanisms to understand epigenetic tools and strategies for treating colorectal cancer in monotherapy and combination with chemotherapy or immunotherapy.

Over the past half-century, significant strides have been made to identify key risk factors, genetic mechanisms, and treatments for atherosclerosis. Yet, coronary artery disease (CAD) remains a leading global public health challenge. While the heritability of CAD is well-documented, there is increasing focus on the role of environmental exposures, such as smoking, air pollution, and heavy metals, on global CAD risk. Recent research has shed light on the interplay between genetic variation and environmental factors, offering insights into gene-environment (GxE) interactions. Moreover, emerging evidence suggests that environmental toxicants can profoundly impact the epigenome, altering gene regulation beyond the genetic sequence itself, revealing novel mechanisms underlying disease. Epigenetic changes - such as modifications in DNA methylation, chromatin structure, and non-coding RNA function - are now recognized as key molecular determinants of atherosclerosis. These observations have created a foundational paradigm that environment, genetics, and epigenetic mechanisms influence risk through a highly complex interaction regulating cellular phenotype, pathology, and disease progression. In this review, we explore the mechanisms by which environmental exposures influence the epigenome and contribute to the regulation of atherosclerotic disease. Additionally, we examine the transgenerational epigenetic effects of these exposures on disease risk. Advancing our understanding of these mechanisms is essential for informing public health strategies aimed at mitigating harmful environmental exposures and reducing the global burden of cardiovascular disease.

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related death globally, impacting both genders equally. The increasing global mortality rates from CRC are strongly linked to contemporary dietary habits, characterized by excessive meat consumption, alcohol intake, and insufficient physical activity. Thus, there is an unprecedented need to develop less hazardous and new therapies for CRC. CRC affects a substantial global population. The main treatments for CRC include chemotherapy and surgical intervention. Nonetheless, the advancement of innovative, safer, and more effective pharmaceuticals for CRC therapy is of paramount importance due to the widespread adverse effects and the dynamic nature of drug resistance. A growing amount of research suggests that natural chemicals may effectively battle CRC and, in certain cases, serve as alternatives to chemotherapeutics. Evidence suggests that miRNAs control important cancer features, including the maintenance of proliferative signals. These features also involve evasion of growth inhibition, resistance to cell death, and immortalization of replication. Additionally, miRNAs play a role in angiogenesis, invasion, and metastasis. Numerous compounds, including those exhibiting cytotoxic and apoptogenic properties against different malignancies, such as CRC, are sourced from diverse marine and medicinal plants. These chemicals stimulate several signaling pathways originating from different phytochemical families. This article evaluates the existing understanding of the anti-CRC capabilities of several phytochemical substances. Furthermore, their impact on several signaling pathways associated with cancer is examined. This article also highlights the potential of medicinal plants as a source of promising anti-CRC chemicals through modulating miRNA expression and the role of nanoparticle-based miRNA therapeutics in enhancing CRC treatment by improving tumor targeting and minimizing off-target effects.

Malignant tumors are non-communicable diseases that impact human health and quality of life. Identifying and targeting the underlying genetic drivers is a challenge. Heme oxygenase-1 (HO-1), a stress-inducible enzyme also known as heat shock protein 32, plays a crucial role in maintaining cellular homeostasis. It mitigates oxidative stress-induced damage and exhibits anti-apoptotic properties. HO-1 is expressed in a wide range of malignancies and is associated with tumor growth. However, the precise role of HO-1 in tumor development remains controversial. Drugs, both naturally occurring and chemically synthesized, can inhibit tumor growth by modulating HO-1 expression in cancer cells. The present review aimed to discuss biological functions of HO-1 pharmacological therapies targeting HO-1.

RNA modifications, collectively known as epitranscriptomic modifications, have emerged as critical regulators of gene expression, cellular adaptation, and therapeutic resistance. This review explores the pharmacological potential of targeting RNA modifications, including N6-methyladenosine (m6A) and 5-methylcytosine (m5C), as strategies to overcome drug resistance in cancer. We examine key regulatory enzymes, writers, erasers, and readers-and their roles in modulating RNA stability, translation, and splicing. Advances in combination therapies, integrating RNA modification modulators with conventional chemotherapies and immune checkpoint inhibitors, have shown promising outcomes in reversing multidrug resistance (MDR). Emerging RNA-targeting technologies, such as CRISPR/Cas13 systems and advanced RNA sequencing platforms, further enable precision manipulation of RNA molecules, opening new therapeutic frontiers. However, several challenges persist, including issues related to pharmacokinetics, acquired resistance, and the complexity of epitranscriptomic networks. This review underscores the need for innovative delivery systems, such as lipid nanoparticles and tissue-specific targeting strategies, and highlights the dynamic nature of RNA modifications in response to environmental and therapeutic stress. Ongoing research into non-coding RNA modifications and the interplay between epitranscriptomics and epigenetics offers exciting possibilities for developing novel RNA-targeting therapies. The continued evolution of RNA-based technologies will be crucial in advancing precision medicine, addressing drug resistance, and improving clinical outcomes across multiple diseases.

Liver cancer ranks as the second leading cause of cancer-related deaths globally, which remains a significant public health concern. The development of liver cancer is associated with several signaling pathways, particularly metabolic reprogramming. Protein S-palmitoylation, a type of lipid post-translational modification (PTM), involves the reversible attachment of palmitic acid to a cysteine residue through a thioester bond. This modification is found in a wide range of proteins, including enzymes, cancer promoters, tumor suppressors, and transcription factors. The palmitoylation process is catalyzed by the zinc finger DHHC-type containing (ZDHHC) protein family, while the reverse process, depalmitoylation, is facilitated by palmitoyl-protein thioesterases (PPTs). Dysregulation of palmitoylation has been linked to various cancer hallmark functions, cancer metabolism, and tumor microenvironment regulation. Currently, membrane palmitoylated protein (MPP) and PPT1 have been identified as prognostic markers and potential therapeutic targets in liver cancer. In this review, we summarize recent advances in understanding the effects of palmitoylation on liver cancer development, metastasis, and prognosis prediction, and explore potential therapeutic strategies for managing liver cancer.

Skeletal muscle atrophy is commonly present in various pathological states, posing a huge burden on society and patients. Increased protein hydrolysis, decreased protein synthesis, inflammatory response, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) are all important molecular mechanisms involved in the occurrence and development of skeletal muscle atrophy. The potential mechanisms of ERS and UPR in skeletal muscle atrophy are extremely complex and have not yet been fully elucidated. This article elucidates the molecular mechanisms of ERS and UPR, and discusses their effects on different types of muscle atrophy (muscle atrophy caused by disuse, cachexia, chronic kidney disease (CKD), diabetes mellitus (DM), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), spinal and bulbar muscular atrophy (SBMA), aging, sarcopenia, obesity, and starvation), and explores the preventive and therapeutic strategies targeting ERS and UPR in skeletal muscle atrophy, including inhibitor therapy and drug therapy. This review aims to emphasize the importance of endoplasmic reticulum (ER) in maintaining skeletal muscle homeostasis, which helps us further understand the molecular mechanisms of skeletal muscle atrophy and provides new ideas and insights for the development of effective therapeutic drugs and preventive measures for skeletal muscle atrophy.

Proteins are responsible for a vast majority of various cellular effector processes. α-crystallin is one of the most important proteins in the lens of the eye, which acts as a molecular chaperone that keeps the lens transparent and refractive. α-crystallin is categorized as an intrinsically disordered protein (IDP), devoid of a stable three-dimensional structure, in contrast to conventional globular proteins. Because of its structural flexibility, it can stop denatured proteins from aggregating and building up within the lens over time. α-crystallin's dynamic quaternary structure, which allows it to exist in a variety of oligomeric forms, from dimers to massive assemblies, improves its chaperone function and flexibility. Its intrinsically disordered nature enables it to interact with a variety of client proteins due to its large non-polar and polar residue content and lack of a hydrophobic core. Furthermore, under physiological stress, osmolytes like sorbitol, TMAO, and urea are essential in regulating the stability and function of α-crystallin. Post-translational modifications (PTMs) such as glycation, in which reducing sugars combine with amino groups on the protein to generate advanced glycation end-products, impair α-crystallin's ability to function. These AGEs can cross-link α-crystallin molecules to prevent protein aggregation, changing their structure and decreasing their chaperone action. Because of their raised blood glucose levels, diabetics have an increased chance of developing cataracts as a result of this process. Comprehending how glycation and other PTMs affect α-crystallin is crucial for formulating treatment plans to maintain lens transparency and fight cataracts linked to aging and metabolic disorders.

Colorectal cancer (CRC) remains the second most lethal cancer worldwide, with incidence rates expected to rise substantially by 2040. Although biomarker-driven therapies have improved treatment, responses to standard chemotherapeutics, such as 5-fluorouracil (5-FU), oxaliplatin, and irinotecan, vary considerably. This clinical heterogeneity emphasizes the urgent need for novel biomarkers that can guide therapeutic decisions and overcome chemoresistance. microRNAs (miRNAs) have emerged as key post-transcriptional regulators that critically influence chemotherapy responses. miRNAs orchestrate post-transcriptional gene regulation and modulate diverse pathways linked to chemoresistance. They influence drug transport by regulating ABC transporters and affect metabolic enzymes like thymidylate synthase (TYMS). These activities shape responses to standard CRC chemotherapy agents. Furthermore, miRNAs can regulate the epithelial-mesenchymal transition (EMT). The miR-200 family (e.g., miR-200c and miR-141) can reverse EMT phenotypes, restoring chemosensitivity. Additionally, miRNAs like miR-19a and miR-625-3p show predictive value for chemotherapy outcomes. Despite these promising findings, the clinical translation of miRNA-based biomarkers faces challenges, including methodological inconsistencies and the dynamic nature of miRNA expression, influenced by the tumor microenvironment. This review highlights the critical role of miRNAs in elucidating chemoresistance mechanisms and their promise as biomarkers and therapeutic targets in CRC, paving the way for a new era of precision oncology.

The use of plastics, valued for its affordability, durability, and convenience, has grown significantly with the advancement of industry. Paradoxically, these very properties of plastics have also led to significant environmental challenges. Plastics are highly resistant to decomposition, resulting in their accumulation on land, where they eventually enter aquatic environments, due to natural processes or human activities. Among these plastics, microplastics, which are tiny plastic particles, are particularly concerning when they enter aquatic ecosystems, including rivers and seas. Their small size makes them easily ingestible by aquatic organisms, either by mistake or through natural feeding behaviors, which poses serious risks. Moreover, microplastics readily adsorb other pollutants present in aquatic environments, creating pollutant complexes that can have a synergistic impact, magnifying their harmful effects compared to microplastics or pollutants acting alone. As a result, extensive research has focused on understanding the effects of microplastics on aquatic organisms. Numerous studies have demonstrated that aquatic organisms exposed to microplastics, either alone or in combination with other pollutants, exhibit abnormal hatching, development, and growth. Additionally, many genes, particularly those associated with the antioxidant system, display abnormal expression patterns in these conditions. In this review, we examine these impacts, by discussing specific studies that explore changes in phenotype and gene expression in aquatic organisms exposed to microplastics, both independently and in combination with adsorbed pollutants.

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by insulin resistance and beta cell dysfunction, resulting in hyperglycemia. Olive oil, a cornerstone of the Mediterranean diet, has attracted considerable attention due to its potential health benefits, including reducing the risk of developing T2DM. This literature review aims to critically examine and synthesize existing research regarding the impact of olive oil on the expression of genes relevant to T2DM. This paper also seeks to provide an immunological and genetic perspective on the signaling pathways of the main components of extra virgin olive oil. Key bioactive components of olive oil, such as oleic acid and phenolic compounds, were identified as modulators of insulin signaling. These compounds enhanced the insulin signaling pathway, improved lipid metabolism, and reduced oxidative stress by decreasing reactive oxygen species (ROS) production. Additionally, they were shown to alleviate inflammation by inhibiting the NF-κB pathway and downregulating pro-inflammatory cytokines and enzymes. Furthermore, these bioactive compounds were observed to mitigate endoplasmic reticulum (ER) stress by downregulating stress markers, thereby protecting beta cells from apoptosis and preserving their function. In summary, olive oil, particularly its bioactive constituents, has been demonstrated to enhance insulin sensitivity, protect beta cell function, and reduce inflammation and oxidative stress by modulating key genes involved in these processes. These findings underscore olive oil's therapeutic potential in managing T2DM. However, further research, including well-designed human clinical trials, is required to fully elucidate the role of olive oil in personalized nutrition strategies for the prevention and treatment of T2DM.

The pathophysiology of neurodevelopmental disorders is associated with multiple genetic and environmental risk factors. Epigenetics, owing to its potential to recover global gene expression changes associated with disease conditions, is a crucial target to address neurodevelopmental disorders influenced by genetic and environmental factors. Here, we discuss the discovery of selective inhibitors of lysine-specific demethylase 1 (LSD1) enzyme activity and their therapeutic potential for neurodevelopmental disorders through epigenetic regulation in the brain. Conventional LSD1 inhibitors not only inhibit LSD1 enzymatic activity but also interfere with LSD1-cofactor complex formation, thus leading to hematological side effects. Notably, investigations on the structure-activity relationship have revealed (aminocyclopropyl)benzamide and (aminocyclopropyl)thiophene carboxamide derivatives as novel series of LSD1 inhibitors with fewer hematological side effects. Subsequently, we discovered T-448 and TAK-418 (clinical candidate) that selectively and potently inhibit LSD1 enzymatic activity without disrupting the LSD1-cofactor complex, resulting in potent epigenetic modulation without significant hematological toxicity risks in rodents. T-448 and TAK-418, at doses that achieved almost complete LSD1 occupancy in the brain, improved behavioral abnormalities in multiple rodent models of neurodevelopmental disorders. Furthermore, comprehensive RNA expression analyses revealed that, although gene expression abnormalities exhibited limited commonality across disease models, TAK-418 normalized each aberrant gene expression pattern in these rodent models. A positron emission tomography tracer was discovered to potentially measure the occupancy of TAK-418 at the LSD1 active site in the brain to improve the translatability of its preclinical efficacy to therapeutic effects in humans. TAK-418-type LSD1 inhibitors may offer novel treatment options for neurodevelopmental disorders.

Pulmonary arterial hypertension (PAH) is a devastating disorder characterized by elevated pulmonary vascular resistance and pulmonary artery pressure, resulting from a multitude of etiological factors. If left untreated, PAH progressively leads to right heart failure and is associated with high mortality. The etiology of PAH is multifactorial, encompassing both congenital genetic predispositions and acquired secondary influences. Epigenetics, which refers to the regulation of gene expression through chromosomal alterations that do not involve changes in the DNA sequence, has garnered significant attention in PAH research. This includes mechanisms such as DNA methylation, histone modification, and RNA modification. Aberrant epigenetic modifications have been closely linked to the dysregulated proliferation and apoptosis of pulmonary artery smooth muscle cells and endothelial cells, suggesting that these alterations may serve as pivotal drivers of the pathophysiological changes observed in PAH. This review examines the potential impact of epigenetic alterations on the pathogenesis of PAH, highlighting their promise as therapeutic targets. Furthermore, we explore emerging therapeutic strategies and compounds aimed at modulating these epigenetic markers, and discusses their potential applications in both preclinical models and clinical trials. As our understanding of epigenetics deepens, it holds the potential to unlock novel avenues for the precise, individualized treatment of PAH, offering a new frontier in the fight against this debilitating disease.

Paclitaxel (PTX) is extensively used to treat various cancers, including those of the breast, ovary, lung, esophagus, stomach, pancreas, and neck. However, despite its effectiveness in clinical settings, patients often experience cancer recurrence due to the emergence of resistance to PTX. The mechanisms underlying this resistance in cancer cells exposed to PTX involve modifications in β-tubulin, the primary target molecule associated with mitosis, the activation of pathways that facilitate drug efflux, and the dysregulation of apoptosis-related proteins. Long non-coding RNAs (lncRNAs), which are RNA molecules exceeding 200 nucleotides in length and lacking protein-coding capabilities, play various regulatory roles in cellular functions. A growing body of evidence underscores the role of lncRNAs in cancer progression and their involvement in PTX resistance across different cancer types. As a result, lncRNAs have been identified as promising therapeutic targets for overcoming drug resistance in cancer therapies. This review aims to provide an overview of the current knowledge regarding lncRNAs and their contributions to resistance mechanisms to promote further research in this field. A summary of key lncRNAs and their related pathways associated with PTX resistance will be presented.

Ischemic heart disease (IHD), especially acute myocardial infarction (AMI), has a high mortality rate and poses a great threat to human health. When myocardial infarction occurs, the structure and function of the myocardium are significantly damaged, and its metabolisms switch from oxidative phosphorylation to glycolysis, producing lactate. Lactylation, as a newly discovered post-translational modification (PMT) in recent years, is involved in the regulation of gene expression, and cell proliferation. Emerging studies have revealed that lactate and lactylation modifications participate in inflammation and cardiac repair, and play an important role in cardiovascular diseases, such as myocardial infarction, myocardial fibrosis, and heart failure. Therefore, in this review, we discuss how glucose metabolism, glycolytic end-product lactate, and lactylation potentially interact with pathological processes, including inflammation, cardiac fibrosis, and heart failure. And targeting glycolysis and lactylation modification could provide a promising future for cardiovascular diseases.

One of the most dangerous characteristics of bacteria is their propensity to form biofilms and their resistance to the drugs used in clinical practice today. The total number of genes that can be categorized as virulence genes ranges from a few hundred to more than a thousand. The bacteria employ a variety of mechanisms to regulate the expression of these genes in a coordinated manner during infection. The search for new agents with anti-virulence capacity is therefore crucial. Nanotechnology provides safe platforms for targeted therapies to combat a broad spectrum of microbial infections. As a new class of innovative materials, carbon-based nanomaterials (CBNs), which include carbon dots, carbon nanotubes, graphene, and fullerenes can have strong antibacterial activity. Exposure to CBNs has been shown to affect bacterial gene expression patterns. This study investigated the effect of CBNs on the repression of specific genes related to bacterial virulence/pathogenicity.

The excision of introns from pre-mRNA is a crucial process in the expression of the majority of genes. Alternative splicing allows a single gene to generate diverse mRNA and protein products. Aberrant RNA splicing is recognized as a molecular characteristic present in almost all types of tumors. Therefore, identifying cancer-specific subtypes from aberrant processing offers new opportunities for therapeutic development. Numerous splicing modulators, each utilizing different mechanisms, have been developed as promising anticancer therapies, some of which are in clinical trials. In this review, we summarize the splice-altered signatures of cancer cell transcriptomes and the contributions of splicing aberrations to tumorigenesis and progression. Especially, we discuss current and emerging RNA splicing-targeted strategies for cancer therapy, including pharmacological approaches and splice-switching antisense oligonucleotides (ASOs). Finally, we address the challenges and opportunities in translating these findings into clinical practice.

Bladder cancer (BC) is a major global health issue with a high recurrence rate and limited effective treatments. Over the past few years, it has become evident that miRNAs play a role in the carcinogenesis process, particularly in regulating genes that promote cancer cell proliferation and invasion. This review focuses on the extent to which natural products can act as potential miRNA modulators for the management of bladder cancer. Polyphenols, flavonoids, and other phytochemicals are natural compounds found to have inherent potential to modulate miRNAs and reform the oncogenic properties of bladder cancer cells regulating cell growth and death. In integration with the current cancer treatment regimes, such natural agents may safely substitute for the traditional chemical chemotherapeutic agents of the conventional approaches. To this end, this review presents the existing knowledge of natural compounds as regulators of miRNA, their mechanisms for the management of BC, the role of their nanoparticles, and future novel therapies. The use of these compounds is not only a therapeutic practice for the conditions of bladder cancer, but it also upholds new avenues for creativity.

Dysregulation of epigenetic regulation is observed in numerous tumor cells. The therapeutic effects of natural products on tumors were investigated through a comprehensive analysis of active ingredients derived from various structured natural products. The analysis focuses on regulating key enzymes involved in epigenetic control. To study the modulation of these enzymes for tumor treatment, the structural characteristics of natural products that impact tumorigenesis were identified. The presence of specific patterns suggests that compounds sharing structural similarities can potentially induce therapeutic effects on identical tumors through modulation of distinct modifying enzymes. Structurally analogous natural products can likewise achieve therapeutic effects across diverse tumor types via their interaction with a common epigenetic enzyme. There exist numerous flavonoids with the capability to modulate METTL3, thereby influencing the development of various tumors. The normalization process was implemented to account for a common phenomenon, wherein structurally distinct compounds effectively target the same tumor by modulating a shared key enzyme. By summarizing, valuable insights into the role of compound-epigenetic enzymes in tumor development have been obtained. This discovery establishes a crucial scientific foundation for the prevention and treatment of tumor development through the utilization of structurally similar natural active ingredients.

The B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) protein of the polycomb complex is an essential mediator of the epigenetic transcriptional silencing by the chromatin structure. It has been reported to be crucial for homeostasis of the stem cells and tumorigenesis. Though years of investigation have clarified Bmi-1's transcriptional regulation, post-translational modifications, and functions in controlling cellular bioenergetics, pathologies, and DNA damage response, the full potential of this protein with so many diverse roles are still unfulfilled. Bmi-1 is overexpressed in many human malignancies. Unraveling the Bmi-1's precise functional role in head and neck cancers can be attractive for mechanisms-based developmental therapeutics. This review attempts to synthesize the current knowledge on Bmi-1 with an emphasis on the role that Bmi-1 plays in oral cancer progression and evaluates how this can be used in advancing clinical treatment strategies for head and neck cancer. Bmi-1 is a promising target for therapy because it has been linked to a stemness and oncogenesis signature. However, to use Bmi-1 as a prognostic marker and a therapeutic target in the long run, new methods are imperative for further characterization of the physiological roles of Bmi-1. Current biological insights of Bmi-1 as a master regulator of stem cell self-renewal have emerged as a prominent player in cancer stem cell (CSC) biology. Bmi-1+ cells mediate chemoresistance and metastasis. On the other hand, inhibiting Bmi-1 rescinds CSC function and re-sensitizes cancer cells to chemotherapy. Therefore, elucidating therapeutic approaches targeting Bmi-1 can be leveraged to further research analysis to advance clinical treatment strategies for head and neck cancer.