Search Results (1,344)

Microalgae, with their unparalleled capabilities for sunlight-driven growth, CO₂ fixation, and synthesis of diverse high-value compounds, represent sustainable cell factories for a circular bioeconomy. However, industrial deployment has been hindered by biological constraints and the inadequacy of conventional genetic tools. The advent of CRISPR-Cas systems initially provided precise gene editing via targeted DNA cleavage. This review argues that the true transformative potential lies in moving decisively beyond cutting to harness CRISPR as a versatile synthetic biology “Swiss Army Knife”. We synthesize the rapid evolution of CRISPR-derived tools—including transcriptional modulators (CRISPRa/i), epigenome editors, base/prime editors, multiplexed systems, and biosensor-integrated logic gates—and their revolutionary applications in microalgal engineering. These tools enable tunable gene expression, stable epigenetic reprogramming, DSB-free nucleotide-level precision editing, coordinated rewiring of complex metabolic networks, and dynamic, autonomous control in response to environmental cues. We critically evaluate their deployment to enhance photosynthesis, boost lipid/biofuel production, engineer high-value compound pathways (carotenoids, PUFAs, proteins), improve stress resilience, and optimize carbon utilization. Persistent challenges—species-specific tool optimization, delivery efficiency, genetic stability, scalability, and biosafety—are analyzed, alongside emerging solutions and future directions integrating AI, automation, and multi-omics. The strategic integration of this CRISPR toolkit unlocks the potential to engineer robust, high-productivity microalgal cell factories, finally realizing their promise as sustainable platforms for next-generation biomanufacturing. 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

Male-factor infertility accounts for approxiamately half of all infertility cases globally, yet therapeutic options remain limited for individuals with no retrievable spermatozoa, such as those with non-obstructive azoospermia (NOA). In recent years, artificial gametogenesis has emerged as a promising avenue for fertility restoration, driven by advances in two complementary strategies: organotypic in vitro spermatogenesis (IVS), which aims to complete spermatogenesis ex vivo using native testicular tissue, and in vitro gametogenesis (IVG), which seeks to generate male gametes de novo from pluripotent or reprogrammed somatic stem cells. To evaluate the current landscape and future potential of these approaches, a narrative, semi-systematic literature search was conducted in PubMed and Scopus for the period January 2010 to February 2025. Additionally, landmark studies published prior to 2010 that contributed foundational knowledge in spermatogenesis and testicular tissue modeling were reviewed to provide historical context. This narrative review synthesizes multidisciplinary evidence from cell biology, tissue engineering, and translational medicine to benchmark IVS and IVG technologies against species-specific developmental milestones, ranging from rodent models to non-human primates and emerging human systems. Key challenges—such as the reconstitution of the blood–testis barrier, stage-specific endocrine signaling, and epigenetic reprogramming—are discussed alongside critical performance metrics of various platforms, including air–liquid interface slice cultures, three-dimensional organoids, microfluidic “testis-on-chip” devices, and stem cell-derived gametogenic protocols. Particular attention is given to clinical applicability in contexts such as NOA, oncofertility preservation in prepubertal patients, genetic syndromes, and reprocutive scenarios involving same-sex or unpartnered individuals. Safety, regulatory, and ethical considerations are critically appraised, and a translational framework is outlined that emphasizes biomimetic scaffold design, multi-omics-guided media optimization, and rigorous genomic and epigenomic quality control. While the generation of functionally mature sperm in vitro remains unachieved, converging progress in animal models and early human systems suggests that clinically revelant IVS and IVG applications are approaching feasibility, offering a paradigm shift in reproductive medicine. Full article

Ulcerative colitis (UC), a subtype of inflammatory bowel disease (IBD), is a chronic, relapsing inflammatory condition that significantly impairs the patient’s quality of life. While biologics have transformed disease management, a substantial number of patients remain unresponsive or lose efficacy over time. Tofacitinib (TOFA), an oral Janus kinase (JAK) inhibitor, introduces a novel therapeutic class of small-molecule drugs with a unique oral administration route, offering enhanced patient convenience and broader accessibility compared to parenterally administered biologics. As the first oral treatment approved for moderate to severe UC in years, TOFA acts by modulating the JAK/STAT pathway, influencing critical inflammatory mediators such as IL-6, IL-17, and IFN-γ. However, response rates are variable and appear dose-dependent, with up to 60% of patients showing inadequate therapeutic outcomes. This review represents the first comprehensive synthesis focused specifically on biomarkers of TOFA response in UC. Drawing on multi-omics data—epigenomics, transcriptomics, proteomics, and cellular profiling, we highlight emerging predictors of responsiveness, including CpG methylation signatures (e.g., LRPAP1 and FGFR2), transcriptomic regulators (e.g., REG3A and CLDN3), immune and epithelial cell shifts, and the cationic transporter MATE1. TOFA demonstrates a dual mechanism by modulating immune responses while supporting epithelial barrier restoration. Despite being promising, TOFA’s dose-dependent efficacy and interpatient variability underscore the critical need for non-invasive, predictive biomarkers to guide personalized treatment. As the first review of its kind, this work establishes a basis for precision medicine approaches to optimize the clinical utility of TOFA in UC management. Full article

The epigenetic landscape plays a pivotal role in regulating the functions of both germ and somatic cells (Sertoli and Leydig cells) within the testis, which are essential for male fertility. While somatic cells support germ cell maturation and testosterone synthesis, the epigenetic regulation of germ cells is critical for proper spermatogenesis and function. Epigenetic modifications such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs (ncRNAs) are crucial for regulating gene expression that is essential for spermatogenesis and reproductive function. Although numerous studies have highlighted the significance of the epigenome and its implications for male reproductive health, a comprehensive overview of the existing literature and knowledge is lacking. This review aims to provide an in-depth analysis of the role of epigenetics in spermatogenesis and reproductive health, with a specific focus on DNA methylation, histone remodeling, and small noncoding RNAs (sncRNAs). Additionally, we examine the impact of lifestyle and environmental factors, such as diet, smoking, physical activity, and exposure to endocrine-disrupting chemicals, on the sperm epigenome. We emphasize how these factors influence fertility, embryonic development, and potential transgenerational inheritance. This review underscores how recent advances in the understanding of the epigenetic modulation of testicular function can inform the pathophysiology of male infertility, thereby paving the way for the development of targeted diagnostic and therapeutic strategies. Full article

Multiple metrics for read-level DNA methylation pattern analysis have provided new insights into DNA methylation modifications. However, the performance of these metrics and their relationship with DNA methylation ratios in identifying biologically meaningful regions have remained unclear. Here, we systematically benchmarked five read-level DNA methylation metrics using whole-genome bisulfite sequencing data from 59 individuals across six healthy tissue types and six tumor types. We found that DNA methylation concurrence (MCR) effectively captured tissue-specific features independent of the DNA methylation ratios. Regions that exhibited decreased MCR (MCDRs) in tumors were significantly enriched in promoter and intergenic regions and strongly overlapped with tumor-gained chromatin accessibility sites. The further analysis of histone modifications, including H3K4me3, H3K27ac, and H3K9ac, confirmed that MCDRs marked active gene regulatory elements. Motif enrichment analysis revealed a strong preference for CTCF binding within MCDRs. Additionally, 3D genome analysis supported a model in which MCDRs, independent of DNA methylation ratios, contribute to active gene regulation by facilitating CTCF binding and long-range chromatin interactions. Full article

Aberrant DNA methylation has been shown to be a fingerprint characteristic in human colorectal tumors. In this study, we hypothesize that investigating global DNA methylation could offer potential candidates for clinical application in CRC. The epigenome-wide association analysis was conducted in both the tumor area (N = 27) and the adjacent tumor-free (NAT) area (N = 15). We found 78,935 differentially methylated CpG sites (DMCs) (FDR < 0.05), 42,888 hypomethylated and 36,047 hypermethylation showing overall hypomethylation. Gene ontology and KEGG analysis of differentially methylated genes showed significant enrichment in developmental genes, as well as in genes involved in metabolic processes and the cell cycle, such as the TFGβ and cAMP signaling pathways. Through filtered analysis, we identified TNXB as the most epigenetically dysregulated gene, hypomethylated and downregulated in CRC (both with p < 0.001) and associated with poor overall survival. In the functional analysis, TNXB was epigenetically regulated in a dose-dependent manner, suggesting a potential role in CRC. The epigenetic dysregulation and functional role of TNXB in CRC could have clinical implications, serving as indicators of malignant potential, with adverse effects associated with disease origin and progression in CRC. Full article

Plants are constantly exposed to environmental stressors such as drought, salinity, and extreme temperatures, which threaten their growth and productivity. To counter these challenges, they employ complex molecular defense systems, including epigenetic modifications that regulate gene expression without altering the underlying DNA sequence. This review comprehensively examines the emerging roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as central signaling molecules orchestrating epigenetic changes in response to abiotic stress. In addition, biotic factors such as pathogen infection and microbial interactions are considered for their ability to trigger ROS/RNS generation and epigenetic remodeling. It explores how ROS and RNS influence DNA methylation, histone modifications, and small RNA pathways, thereby modulating chromatin structure and stress-responsive gene expression. Mechanistic insights into redox-mediated regulation of DNA methyltransferases, histone acetyltransferases, and microRNA expression are discussed in the context of plant stress resilience. The review also highlights cutting-edge epigenomic technologies such as whole-genome bisulfite sequencing (WGBS), chromatin immunoprecipitation sequencing (ChIP-seq), and small RNA sequencing, which are enabling precise mapping of stress-induced epigenetic landscapes. By integrating redox biology with epigenetics, this work provides a novel framework for engineering climate-resilient crops through the targeted manipulation of stress-responsive epigenomic signatures. Full article

Background/Objectives: This study investigated variations in DNA methylation patterns associated with chronic pain and propensity for recurrent pressure injuries (PrI) in persons with spinal cord injury (SCI). Methods: Whole blood was collected from 81 individuals with SCI. DNA methylation was quantified using Illumina genome-wide arrays (EPIC and EPICv2). Comprehensive clinical profiles collected included secondary health complications, in particular current PrI and chronic pain. Relationships between recurrent PrI and chronic pain and whether the co-occurrence of both traits was mediated by changes in DNA methylation were investigated using R packages limma, DMRcate and mCSEA. Results: Three differentially methylated positions (DMPs) (cg09867095, cg26559694, cg24890286) and one region in the micro-imprinted locus for BLCAP/NNAT are associated with chronic pain in persons with SCI. The study cohort was stratified by PrI status to identify any sites associated with chronic pain and while the same three sites and region were replicated in the group with no recurrent PrI, two novel, hypermethylated (cg21756558, cg26217441) sites and one region in the protein-coding gene FDFT1 were identified in the group with recurrent PrI. Gene enrichment and genes associated with specific promoters using MetaScape identified several shared disorders and ontology terms between independent phenotypes of pain and recurrent PrI and interactive sub-groups. Conclusions: DMR analysis using mCSEA identified several shared genes, promoter-associated regions and CGI associated with overall pain and PrI history, as well as sub-groups based on recurrent PrI history. These findings suggest that a much larger gene regulatory network is associated with each phenotype. These findings require further validation. Full article

Ischemic stroke is a complex, multifactorial disorder with a significant heritable component. Recent developments in genome-wide association studies (GWASs) have identified several common variants associated with clinical outcomes, stroke subtypes, and overall risk. Key loci implicated in biological pathways related to vascular integrity, lipid metabolism, inflammation, and atherogenesis include 9p21 (ANRIL), HDAC9, SORT1, and PITX2. Although polygenic risk scores (PRSs) hold promise for early risk prediction and stratification, their clinical utility remains limited by Eurocentric bias and missing heritability. Integrating multiomics approaches, such as functional genomics, transcriptomics, and epigenomics, enhances our understanding of stroke pathophysiology and paves the way for precision medicine. This review summarizes the current genetic landscape of ischemic stroke, emphasizing how evolving methodologies are shaping its prevention, diagnosis, and treatment. Full article

Class IIa histone deacetylases (HDACs) are pleiotropic regulators of various differentiation pathways and adaptive responses. They form complexes with other co-repressors and can bind to DNA by interacting with selected transcription factors, with members of the Myocyte Enhancer Factor-2 (MEF2) family being the best characterized. A notable feature of class IIa HDACs is the substitution of tyrosine for histidine in the catalytic site, which has occurred over the course of evolution and has a profound effect on the efficiency of catalysis against acetyl-lysine. Another distinctive feature of this family of “pseudoenzymes” is the regulated nucleus–cytoplasm shuttling associated with several non-histone proteins that have been identified as potential substrates, including proteins localized in the cytosol. Within the complexity of class IIa HDACs, several aspects deserve further investigation. In the following, I will discuss some of the recent advances in our knowledge of class IIa HDACs. Full article

Bipolar disorder (BD) is a multifactorial mental disease with a prevalence of 1–5% in adults, caused by complex interactions between genetic and environmental factors. Environmental factors contribute to gene expression alterations through epigenetic mechanisms without changing the underlying DNA sequences. Interactions between the gut microbiota (GM) and diverse external factors, such as nutritional composition, may induce epigenetic alterations and increase susceptibility to BD. While epigenetic mechanisms are involved in both the pathogenesis of BD and drug treatment responses, epigenetic marks could be employed as predictors and indicators of drug response. This review highlights recent studies on the potential role of epigenetic aberrations in the development and progression of BD. Next, we focus on drug response-related alterations in the epigenetic landscape, including DNA methylation, histone modifications, and non-coding RNAs. Afterward, we delve into the potential roles of GM-induced epigenetic changes in the pathogenesis of BD and GM-based therapeutic strategies aimed at improving BD outcomes through epigenetic modifications. We also discuss how BD drugs may exert beneficial effects through modulation of the GM and the epigenome. Finally, we consider future research strategies that could address existing challenges. Full article

Background: Epigenomic instability accelerates mutations in tumor suppressor genes and oncogenes, contributing to malignant transformation. Histone modifications, particularly methylation and acetylation, significantly influence tumor biology, with chromo-, bromo-, and Tudor domain-containing proteins mediating these changes. This study investigates how genes encoding these domain-containing proteins affect colorectal cancer (CRC) prognosis. Methods: Using CRC data from the GSE39582 and TCGA datasets, we identified domain-related genes via GeneCards and developed a prognostic signature using LASSO-COX regression. Patients were classified into high- and low-risk groups, and comparisons were made across survival, clinical features, immune cell infiltration, immunotherapy responses, and drug sensitivity predictions. Single-cell analysis assessed gene expression in different cell subsets. Results: Four domain-related genes (AKAP1, ORC1, CHAF1A, and UHRF2) were identified as a prognostic signature. Validation confirmed their prognostic value, with significant differences in survival, clinical features, immune patterns, and immunotherapy responses between the high- and low-risk groups. Drug sensitivity analysis revealed top candidates for CRC treatment. Single-cell analysis showed varied expression of these genes across cell subsets. Conclusions: This study presents a novel prognostic signature based on domain-related genes that can predict CRC severity and offer insights into immune dynamics, providing a promising tool for personalized risk assessment in CRC. Full article

Environmental xenobiotics, including heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, air pollutants, nano- and microplastics, mycotoxins, and phycotoxins, are widespread compounds that pose significant risks to human health. These substances, originating from industrial and agricultural activities, vehicle emissions, and household products, disrupt cellular homeostasis and contribute to a range of diseases, including cancer and neurodegenerative diseases, among others. Emerging evidence indicates that epigenetic alterations, such as abnormal deoxyribonucleic acid (DNA) methylation, aberrant histone modifications, and altered expression of non-coding ribonucleic acids (ncRNAs), may play a central role in mediating the toxic effects of environmental xenobiotics. Furthermore, exposure to these compounds during critical periods, such as embryogenesis and early postnatal stages, can induce long-lasting epigenetic alterations that increase susceptibility to diseases later in life. Moreover, modifications to the gamete epigenome can potentially lead to effects that persist across generations (transgenerational effects). Although these modifications represent significant health risks, many epigenetic alterations may be reversible through the removal of the xenobiotic trigger, offering potential for therapeutic intervention. This review explores the relationship between environmental xenobiotics and alterations in epigenetic signatures, focusing on how these changes impact human health, including their potential for transgenerational inheritance and their potential reversibility. Full article

Nanomaterials (NMs) are currently widely used in a wide range of industrial production and scientific applications, starting from molecular and medical diagnostics to agriculture. In the agricultural and food systems, NMs are now used in various ways, to improve the nutritional value of crops, detect microbial activity and inhibit biofilms, encapsulate and deliver pesticides, protect plants from chemical spoilage, as nanosensors and more. Despite these applications, NMs are described as “dual-face technologies”: they can also act as environmental contaminants. For instance, nanoplastics (NPs) dispersed in the environment can damage plants at different levels and undermine their viability. Epigenetic modifications induced by NMs have potentially wider and longer-term impacts on gene expression and plant functions. Therefore, it is important to verify whether plants are also affected by NMs on the molecular level, including epigenetic mechanisms and any induced variation on the epigenome. This review focusses on gene expression modulation and epigenetic alterations such as DNA methylation and the role of microRNAs and long non-coding RNAs (lncRNAs) induced in plants and crops by NMs and NPs. Full article