Search Results (174)

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article

Wilms tumor (nephroblastoma), the most common pediatric renal malignancy, has a complex genetic and epigenetic landscape. While mutations in genes like WT1, CTNNB1, and WTX have been well characterized, accumulating evidence suggests that epigenetic dysregulation plays a pivotal role in WT pathogenesis. This review examines the various epigenetic mechanisms implicated in WT, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA-mediated regulation. We discuss how epigenetic mechanisms contribute to tumor initiation, progression, and heterogeneity and their implications for improved diagnosis and targeted therapy. We also highlight recent advances in epigenomic profiling, discuss the interplay between epigenetics and developmental gene expression programs, and evaluate potential therapeutic strategies targeting epigenetic regulators. Full article

Erythropoiesis, the process driving the differentiation of hematopoietic stem and progenitor cells to mature erythrocytes, unfolds through tightly orchestrated developmental stages, each defined by profound epigenetic remodeling. From the initial commitment of hematopoietic progenitors to the terminal enucleation of erythrocytes, dynamic changes in chromatin accessibility, transcription factor occupancy, and three-dimensional genome architecture govern lineage specification and stage-specific gene expression. Advances in our understanding of the regulatory genome have uncovered how non-coding elements, including enhancers, silencers, and insulators, shape the transcriptional landscape of erythroid cells. These elements work in concert with lineage-determining transcription factors to establish and maintain erythroid identity. Disruption of these epigenetic programs—whether by inherited mutations, somatic alterations, or environmental stress—can lead to a wide range of hematologic disorders. Importantly, this growing knowledge base has opened new therapeutic avenues, enabling the development of precision tools that target regulatory circuits to correct gene expression. These include epigenetic drugs, enhancer-targeted genome editing, and lineage-restricted gene therapies that leverage endogenous regulatory logic. As our understanding of erythroid epigenomics deepens, so too does our ability to design rational, cell-type-specific interventions for red blood cell disorders. Full article

The integration of artificial intelligence (AI) into next-generation sequencing (NGS) has revolutionized genomics, offering unprecedented advancements in data analysis, accuracy, and scalability. This review explores the synergistic relationship between AI and NGS, highlighting its transformative impact across genomic research and clinical applications. AI-driven tools, including machine learning and deep learning, enhance every aspect of NGS workflows—from experimental design and wet-lab automation to bioinformatics analysis of the generated raw data. Key applications of AI integration in NGS include variant calling, epigenomic profiling, transcriptomics, and single-cell sequencing, where AI models such as CNNs, RNNs, and hybrid architectures outperform traditional methods. In cancer research, AI enables precise tumor subtyping, biomarker discovery, and personalized therapy prediction, while in drug discovery, it accelerates target identification and repurposing. Despite these advancements, challenges persist, including data heterogeneity, model interpretability, and ethical concerns. This review also discusses the emerging role of AI in third-generation sequencing (TGS), addressing long-read-specific challenges, like fast and accurate basecalling, as well as epigenetic modification detection. Future directions should focus on implementing federated learning to address data privacy, advancing interpretable AI to improve clinical trust and developing unified frameworks for seamless integration of multi-modal omics data. By fostering interdisciplinary collaboration, AI promises to unlock new frontiers in precision medicine, making genomic insights more actionable and scalable. Full article

Age-related macular degeneration (AMD) is a common cause of blindness worldwide, and it is projected to affect several million individuals by 2040. The human retinal pigment epithelium (hRPE) degenerates in dry AMD, prompting the need to develop stem cell therapies to replace the lost tissue by autologous transplantation and restore the visual function. Nevertheless, the molecular factors behind the hRPE cell fate determination have not been elucidated. Here we identify all molecular determinants of the hRPE cell fate identity by comprehensive and unbiased screening of predicted pioneer factors in the human genome: such TFs mediate coordinated transitions in chromatin accessibility and transcriptional outcome along three major stages of the hRPE genesis. Furthermore, we compile a complete census of all transcription factor-specific binding sites by footprinting analysis of the human epigenome along the RPE developmental trajectory. Gene regulatory networks were found to be involved in cellular responses to glucose and hypoxia, RPE nitrosative stress, type II epithelial-to-mesenchymal transition (EMT), and type III tumorigenic EMT, providing routes for therapeutic intervention on pleiotropic targets dysregulated in AMD, diabetic retinopathy, and cancer progression. Genome editing technologies may leverage this repository to devise functional screenings of regulatory elements and pharmacogenomic therapies in complex diseases, paving the way for strategies in precision medicine. Full article

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor with a dismal prognosis despite advances in multimodal treatment. Conventional therapies fail to achieve durable responses due to GBM’s molecular heterogeneity and capacity to evade therapeutic pressures. Epigenetic alterations have emerged as critical contributors to GBM pathobiology, including aberrant DNA methylation, histone modifications, and non-coding RNA (ncRNA) dysregulation. These mechanisms drive oncogenesis, therapy resistance, and immune evasion. This scoping review evaluates the current state of knowledge on epigenetic modifications in GBM, synthesizing findings from original articles and preclinical and clinical trials published over the last decade. Particular attention is given to MGMT promoter hypermethylation status as a biomarker for temozolomide (TMZ) sensitivity, histone deacetylation and methylation as modulators of chromatin structure, and microRNAs as regulators of pathways such as apoptosis and angiogenesis. Therapeutically, epigenetic drugs, like DNA methyltransferase inhibitors (DNMTis) and histone deacetylase inhibitors (HDACis), appear as promising approaches in preclinical models and early trials. Emerging RNA-based therapies targeting dysregulated ncRNAs represent a novel approach to reprogram the tumor epigenome. Combination therapies, pairing epigenetic agents with immune checkpoint inhibitors or chemotherapy, are explored for their potential to enhance treatment response. Despite these advancements, challenges such as tumor heterogeneity, the blood–brain barrier (BBB), and off-target effects remain significant. Future directions emphasize integrative omics approaches to identify patient-specific targets and refine therapies. This article thus highlights the potential of epigenetics in reshaping GBM treatment paradigms. Full article

Metabolic reprogramming and epigenetic alterations are fundamental hallmarks of cancer cells, contributing to adaptation, progression, and resistance. In melanoma, high metabolic-epigenetic plasticity enables the rapid modulation of cell states in response to environmental and therapeutic pressures. Recent studies have highlighted a bidirectional crosstalk between cellular metabolism and epigenetic regulation. Epigenetic modifications influence the transcriptional control of metabolic genes, thereby shaping metabolic phenotypes. Conversely, specific metabolites are essential cofactors or substrates for epigenetic enzymes, directly modulating the epigenome. Understanding the intricate mechanisms of this interaction offers opportunities for the development of innovative tumor management that combines epigenetic, metabolic, and therapy interventions. In this review, we summarize the latest evidence on the role of the metabolism–epigenetics axis in melanoma and discuss its potential clinical implications, aiming to provide a comprehensive overview of metabolic/epigenetic interconnections. Full article

Male-factor infertility accounts for nearly half of all infertility cases, and mounting evidence points to oxidative stress as a pivotal driver of sperm dysfunction, genetic instability, and epigenetic dysregulation. In particular, the oxidative DNA lesion 8-hydroxy-2′-deoxyguanosine (8-OHdG) has emerged as a central mediator at the interface of DNA damage and epigenetic regulation. We discuss how this lesion can disrupt key epigenetic mechanisms such as DNA methylation, histone modifications, and small non-coding RNAs, thereby influencing fertilization outcomes, embryo development, and offspring health. We propose that the interplay between oxidative DNA damage and epigenetic reprogramming is further exacerbated by aging in both the paternal and maternal germlines, creating a “perfect storm” that increases the risk of heritable (epi)mutations. The consequences of unresolved oxidative lesions can thus persist beyond fertilization, contributing to transgenerational health risks. Finally, we explore the promise and potential pitfalls of antioxidant therapy as a strategy to mitigate sperm oxidative damage. While antioxidant supplementation may hold significant therapeutic value for men with subfertility experiencing elevated oxidative stress, a careful, personalized approach is essential to avoid reductive stress and unintended epigenetic disruptions. Recognizing the dual role of oxidative stress in shaping both the genome and the epigenome underscores the need for integrating redox biology into reproductive medicine, with the aim of improving fertility treatments and safeguarding the health of future generations. Full article

Spatial omics integrates molecular profiling with spatial tissue context, enabling high-resolution analysis of gene expression, protein interactions, and epigenetic modifications. This approach provides critical insights into disease mechanisms and therapeutic responses, with applications in cancer, neurology, and immunology. Spatial omics technologies, including spatial transcriptomics, proteomics, and epigenomics, facilitate the study of cellular heterogeneity, tissue organization, and cell–cell interactions within their native environments. Despite challenges in data complexity and integration, advancements in multi-omics pipelines and computational tools are enhancing data accuracy and biological interpretation. This review provides a comprehensive overview of key spatial omics technologies, their analytical methods, validation strategies, and clinical applications. By integrating spatially resolved molecular data with traditional omics, spatial omics is transforming precision medicine, biomarker discovery, and personalized therapy. Future research should focus on improving standardization, reproducibility, and multimodal data integration to fully realize the potential of spatial omics in clinical and translational research. Full article

Background: High-risk human papillomavirus (HPV) contributes to oropharyngeal cancers through mechanisms involving the deregulation of host cell functions by oncoproteins E6 and E7. Changes in the epigenome, particularly involving long non-coding RNAs (lncRNAs), are crucial for understanding HPV-related carcinogenesis. Methods: This study aimed to analyze the expression levels of lncRNAs in HPV-related head and neck squamous cell carcinoma (HNSCC) to determine their biological and clinical significance, addressing the current gap in clinically validated biomarkers for early screening and therapeutic interventions. Results: The study highlights the significant overexpression of the EGOT gene in HPV-positive HNSCC samples, suggesting its potential as a marker to distinguish between HPV-negative and HPV-positive cases. Furthermore, high EGOT expression correlates with better overall survival (OS) and indicates possible resistance to therapy, making it a valuable prognostic factor. Conclusions: These findings underscore the potential of incorporating EGOT expression analysis in clinical practice for improved patient stratification and treatment outcomes in HNSCC. Full article

Rheumatoid arthritis (RA) is a multifaceted autoimmune disease that is marked by a complex molecular profile influenced by an array of factors, including genetic, epigenetic, and environmental elements. Despite significant advancements in research, the precise etiology of RA remains elusive, presenting challenges in developing innovative therapeutic markers. This study takes an integrated multi-omics approach to uncover novel therapeutic markers for RA. By analyzing both transcriptomics and epigenomics datasets, we identified common gene candidates that span these two omics levels in patients diagnosed with RA. Remarkably, we discovered eighteen multi-evidence genes (MEGs) that are prevalent across transcriptomics and epigenomics, twelve of which have not been previously linked directly to RA. The bioinformatics analyses of the twelve novel MEGs revealed they are part of tightly interconnected protein–protein interaction networks directly related to RA-associated KEGG pathways and gene ontology terms. Furthermore, these novel MEGs exhibited direct interactions with miRNAs linked to RA, underscoring their critical role in the disease’s pathogenicity. Overall, this comprehensive bioinformatics approach opens avenues for identifying new candidate markers for RA, empowering researchers to validate these markers efficiently through experimental studies. By advancing our understanding of RA, we can pave the way for more effective therapies and improved patient outcomes. Full article

Heart failure (HF) is a complex, heterogeneous syndrome with rising prevalence and high morbidity and mortality. The pathophysiology and diverse etiologies of HF present significant challenges for developing effective therapies. Omics technologies—including genomics, proteomics, transcriptomics, metabolomics, and epigenomics—have reshaped our understanding of HF at the molecular level, uncovering new biomarkers and potential therapeutic targets. Omics also enable insights into individualized treatment responses, the risks of adverse drug effects, and patient stratification for clinical trials. This review explores how multi-omics can enhance heart failure drug discovery and development across all stages of the therapeutic pipeline: (1) target selection and lead identification, (2) preclinical studies, and (3) clinical trials. By integrating omics approaches throughout the drug development process, we can accelerate the discovery of more effective and personalized therapies for heart failure. Full article

This article reviews the impact of single-cell sequencing (SCS) on cancer biology research. SCS has revolutionized our understanding of cancer and tumor heterogeneity, clonal evolution, and the complex interplay between cancer cells and tumor microenvironment. SCS provides high-resolution profiling of individual cells in genomic, transcriptomic, and epigenomic landscapes, facilitating the detection of rare mutations, the characterization of cellular diversity, and the integration of molecular data with phenotypic traits. The integration of SCS with multi-omics has provided a multidimensional view of cellular states and regulatory mechanisms in cancer, uncovering novel regulatory mechanisms and therapeutic targets. Advances in computational tools, artificial intelligence (AI), and machine learning have been crucial in interpreting the vast amounts of data generated, leading to the identification of new biomarkers and the development of predictive models for patient stratification. Furthermore, there have been emerging technologies such as spatial transcriptomics and in situ sequencing, which promise to further enhance our understanding of tumor microenvironment organization and cellular interactions. As SCS and its related technologies continue to advance, they are expected to drive significant advances in personalized cancer diagnostics, prognosis, and therapy, ultimately improving patient outcomes in the era of precision oncology. Full article

S-adenosylmethionine (SAMe) is a key methyl donor that plays a critical role in a variety of cellular processes, such as DNA, RNA and protein methylation, essential for maintaining genomic stability, regulating gene expression and maintaining cellular homeostasis. The involvement of SAMe in cancer pathogenesis is multifaceted, as through its multiple cellular functions, it can influence tumor initiation, progression and therapeutic resistance. In addition, the connection of SAMe with polyamine synthesis and oxidative stress management further underscores its importance in cancer biology. Recent studies have highlighted the potential of SAMe as a biomarker for cancer diagnosis and prognosis. Furthermore, the therapeutic implications of SAMe are promising, with evidence suggesting that SAMe supplementation or modulation could improve the efficacy of existing cancer treatments by restoring proper methylation patterns and mitigating oxidative damage and protect against damage induced by chemotherapeutic drugs. Moreover, targeting methionine cycle enzymes to both regulate SAMe availability and SAMe-independent regulatory effects, particularly in methionine-dependent cancers such as colorectal and lung cancer, presents a promising therapeutic approach. Additionally, exploring epitranscriptomic regulations, such as m6A modifications, and their interaction with non-coding RNAs could enhance our understanding of tumor progression and resistance mechanisms. Precision medicine approaches integrating patient subtyping and combination therapies with chemotherapeutics, such as decitabine or doxorubicin, together with SAMe, can enhance chemosensitivity and modulate epigenomics, showing promising results that may improve treatment outcomes. This review comprehensively examines the various roles of SAMe in cancer pathogenesis, its potential as a diagnostic and prognostic marker, and its emerging therapeutic applications. While SAMe modulation holds significant promise, challenges such as bioavailability, patient stratification and context-dependent effects must be addressed before clinical implementation. In addition, better validation of the obtained results into specific cancer animal models would also help to bridge the gap between research and clinical practice. Full article