Search Results (1,522)

Despite comprehensive and multi-modal therapy, outcomes for children and adolescents with rhabdomyosarcoma (RMS) have plateaued over the past four decades. This is not for a lack of progress in the basic and translational studies of RMS. Indeed, advances in animal models and/or patient tissue sample acquisition and analysis have improved our understanding of RMS biology. Large-scale sequencing efforts have generated transcriptomic, genomic, and epigenomic datasets that highlight the heterogeneity of RMS and have the potential to improve prognostication and the application of precision medicine in patients with RMS. However, few of these discoveries have been clinically translated, and limitations to the accessibility, uniformity, and application of these new models and datasets hinder their utility. Here, we discuss how advances in understanding RMS biology, optimization of preclinical models, and strategies for translating basic science discoveries to the clinic can potentially improve outcomes for patients with RMS. Full article

Metabolomics, representing the biochemical phenotype of cells or tissues, serves as an intrinsic factor underlying the differences in plant traits. Recent advances in multi-omics technologies have significantly deepened our understanding of plant metabolic diversity, enabling researchers to dissect complex biochemical networks at unprecedented levels of detail. This review explores the integration of metabolomics with genomics, transcriptomics, proteomics, epigenomics, microbiomics, and other omics approaches, emphasizing the power of these combined approaches in unraveling the molecular mechanisms underlying plant adaptation, stress resistance, and phenotypic variation. Through a critical analysis of representative case studies across diverse crops, we demonstrate how multi-omics strategies facilitate the identification of key metabolic pathways and regulatory networks for crop improvement. We also discuss current challenges in data integration, metabolite coverage, and the functional characterization of unknown compounds, and propose future directions for overcoming these limitations. Addressing these challenges will require both the enhanced resolution and sensitivity of analytical techniques, as well as more robust frameworks for data integration and interpretation. By overcoming these challenges, the convergence of metabolomics with other omics disciplines will continue to expand our understanding of plant biology, offering novel insights and innovation in crop breeding and sustainable agriculture. Full article

Vitamin D signaling via the vitamin D receptor (VDR) regulates calcium–phosphate homeostasis and extensive gene programs controlling cell proliferation, differentiation, immune tone, and metabolism. However, systemic use of the natural agonist 1α,25-dihydroxyvitamin D₃ (calcitriol) for extraskeletal indications is limited by dose-limiting hypercalcemia. This review summarizes VDR biology and the structural basis of ligand action, emphasizing how ligand-induced repositioning of helix 12 and altered coregulator recruitment can be exploited to engineer selective VDR modulators. We highlight medicinal chemistry strategies spanning secosteroidal analogs with side-chain or ring modifications and emerging non-seco scaffolds and discuss clinically established agents (e.g., calcipotriol and paricalcitol) alongside experimental “super-agonists”, partial agonists, and antagonists designed to widen the therapeutic window. Finally, we discuss current evidence for VDR targeting across cancer, metabolic disease, fibrosis, and immune-inflammatory disorders, including mechanisms of resistance such as dysregulated vitamin D metabolism and epigenetic repression. Structural and epigenomic insights are positioning next-generation VDR ligands as tissue- and pathway-biased therapeutics that may enable safer, mechanism-guided translation beyond bone and mineral indications. Full article

Background: Osteoporosis is a complex disorder involving bone loss and muscle degeneration. Multi-omics technologies provide novel insights into its molecular mechanisms and may support biomarker discovery, patient stratification, and therapeutic development. Objective: This scoping review aimed to synthesize current evidence on the application of multi-omics approaches in osteoporosis, focusing on molecular insights, methodological diversity, and translational potential. Methods: A literature search of PubMed, Embase, and Scopus retrieved 433 records using the keywords “osteoporosis,” “osteosarcopenia,” and “omics.” After removing duplicates and screening titles, abstracts, and full texts, 30 studies met the inclusion criteria. Data on study populations, biological samples, multi-omics techniques, and integration methods were extracted. Results: Studies employed transcriptomics, proteomics, metabolomics, lipidomics, epigenomics, and metagenomics, often combined in multi-omics analyses with computational modeling. Key pathways included osteoclast differentiation, immune regulation, ferroptosis, and microbiome–metabolite interactions. Multi-omics integration enabled the identification of molecular subtypes, candidate biomarkers, and potential therapeutic targets. Limitations included small or single-center cohorts, heterogeneous designs, and limited validation, restricting generalizability and clinical translation. Conclusions: Multi-omics approaches offer a powerful framework to uncover the molecular mechanisms underlying bone and muscle degeneration and to guide precision diagnostics and interventions. Future studies should prioritize large, multicenter, longitudinal designs integrating multi-omics data with clinical and functional validation to facilitate clinical application. Full article

Background/Objectives: Fire is a dominant ecological force in Mediterranean ecosystems, shaping the adaptive traits of forest species such as Pinus brutia. Prescribed burning (also called controlled burning) is the intentional, carefully planned use of fire under specific environmental conditions to manage vegetation and reduce wildfire risk. While morphological and physiological fire adaptations are well-documented, emerging evidence highlights the role of epigenetic mechanisms—such as DNA methylation and histone modifications—in mediating stress responses. Methods: This study investigates genome-wide epigenetic changes in P. brutia following a prescribed burning experiment on Chios Island, Greece. Using methylation-sensitive amplified polymorphism (MSAP) analysis, we compared temporal shifts on epigenetic profiles before and after fire exposure extracting DNA from the same trees. Results: A significant increase in polymorphic epiloci, epigenetic diversity indices, and private epigenetic bands after prescribed burning was revealed, suggesting a stress-induced reprogramming of the epigenome. Concurrent measurements of midday needle water potential indicated an exploratory association between water stress and epigenetic shifts. Furthermore, Fireline Intensity (FI) correlated with epigenetic diversity index signaling an immediate response of the tree. Conclusions: These findings support the hypothesis that fire stress induces epigenetic responses in P. brutia, potentially enhancing resilience to future environmental challenges. Further research is required to address the level of heritability of these epigenetic changes in next generation and connect these indexes with adaptation and sustainability of forest ecosystems. Full article

Background/Objectives: Methadone maintenance treatment (MMT) is one of the major pharmacotherapies for opioid use disorder. The underlying mechanisms of addiction and the treatment response are only partially understood. The study’s main goal was to identify differential DNA CpG methylation that occurred in response to MMT. Methods: Toward this goal, we have conducted a longitudinal epigenome-wide study of blood samples from 64 patients at the beginning and after 1–3 years of MMT, using a linear mixed model. Results: A total of 1881 differentially methylated probes (DMPs) were identified (FDR < 0.05), controlling for sex, age, estimates of blood cell proportions, and the first two principal components based on genome-wide SNP genotypes. Among the genes annotated to the top DMPs are DGLUCY, NXNL2, SOX10, and NPAS3. Several genes associated with substance use disorder were annotated by the identified DMPs, including ADORA2A, BDNF, CACNA1D, CREB1, CRHR1, CRY1, DNMT3B, GABRD, GNAS, GRIP1, OXR1, PRKACB, SCN2A, and SCN3A. The most overrepresented pathway is the small GTPase-mediated signal transduction pathway, and the most overrepresented process is the actin cytoskeleton organization. Conclusions: The study provides preliminary insight into the epigenetic effect of MMT. Future studies will have to confirm the DMPs, assess their impact on gene expression, and determine their clinical relevance. Full article

Interactions among plant roots, soil, and microorganisms in the rhizosphere regulate nutrient cycling, plant health, and ecosystem resilience. Recent advances in DNA sequencing and multi-omics are contributing to a shift from primarily descriptive surveys toward more mechanistic and predictive frameworks. This review synthesizes methodological developments and conceptual insights spanning microbial ecology, functional genomics, and agricultural applications. We first summarize DNA-based approaches—marker-gene sequencing, shotgun metagenomics, and quantitative nucleic acid assays—and then complementary omics layers, including metatranscriptomics, metaproteomics, metabolomics, epigenomics, ionomics, and phenomics. We next outline computational advances in data integration, network modeling, and visualization that help represent complex multi-layered datasets as biologically interpretable systems. Applications relevant to climate resilience and sustainable agriculture are discussed, including the design of synthetic microbial communities, the identification of biomarkers for soil health and stress tolerance, and case studies in which rhizosphere multi-omics informs crop breeding and soil management strategies. Overall, these developments underscore the potential of treating microbes as functional and, to some extent, manageable components of the plant holobiont. Looking ahead, we identify key research gaps involving standardized workflows, cross-scale causal inference, and real-time monitoring pipelines that integrate molecular diagnostics with remote sensing and edge–cloud analytics. By linking ecological mechanisms with translational practice, multi-omics frameworks may support the development of more sustainable, data-driven agriculture that better aligns productivity with environmental stewardship. Full article

Abiotic stresses such as drought, salinity, extreme temperatures, and heavy metal contamination severely limit global crop productivity and threaten food security. Plants have evolved epigenetic strategies, particularly DNA methylation, to perceive, adapt to, and memorize environmental challenges. This review systematically elucidates the dynamic regulatory mechanisms of DNA methylation—including establishment via RNA-directed DNA methylation (RdDM), maintenance by methyltransferases (MET1, CMT), and active removal by demethylases (ROS1)—in plant responses to diverse abiotic stresses. We highlight how stress-induced methylation reprogramming modulates gene expression, chromatin states, and physiological adaptations, contributing to both somatic and transgenerational stress memory. Furthermore, we discuss advanced detection technologies for profiling methylation patterns and evaluate their applications in epigenetic breeding, such as exploiting heritable epialleles, RdDM-based gene silencing, and methylation markers for heterosis prediction. Despite significant progress, translating epigenetic insights into predictable breeding tools remains challenging. Future efforts should focus on establishing causal links between methylation changes and stress phenotypes, improving epigenome editing precision, and integrating multi-omics approaches for the development of climate-resilient crops. This work provides a comprehensive epigenetic perspective for enhancing crop adaptability and sustainable agriculture. Full article

Pesticides are widely used in rice cultivation for pest control to guarantee crop productivity. Intensive use of these chemicals causes harmful effects on rice plants, such as physiological and biochemical stress responses. Such stress is often expressed as oxidative damage, disruption of metabolic balance, and a reduction in plant resilience to environmental challenges. In recent years, omic technologies (such as transcriptomics, epigenomics, proteomics, and metabolomics) have contributed to identifying molecular pathways affected by pesticide exposure. However, no comprehensive synthesis of rice-specific omic evidence currently exists, limiting translational applications. These omic studies revealed activation of detoxification-related enzymes and transporters, alongside changes in antioxidant defenses, hormone-mediated signaling, and membrane remodeling. This review presents current omic-based approaches used to investigate pesticide-induced stress in rice. It focuses on molecular responses including changes in gene expression, enzymatic detoxification, metabolic reprogramming, and stress signaling pathways. The review also highlights how multi-omic integration can contribute to a more holistic understanding of these stress responses, combining cross-layer evidence that connects gene regulation, protein activity, and metabolic remodeling. Despite these advancements, there are still challenges, particularly in the interpretation of complex datasets, the integration of multiple omic layers and the translation of results to real agricultural conditions. Finally, the review also discusses biotechnological approaches that may improve rice tolerance to pesticide exposure. In summary, the role of omic approaches to elucidate pesticide toxicity in rice and to contribute to more resilient crop production systems is critically reviewed. Full article

Adipose tissues (ATs) are dynamic and heterogeneous organs divided into three distinct categories, including white, beige, and brown ATs. Collectively, they contribute to systemic energy homeostasis in various ways. White adipocytes primarily store excess energy, whereas brown and beige adipocytes dissipate energy as heat through non-shivering thermogenesis. Recent advances in multi-omics technologies have transformed our understanding of adipocyte biology, enabling comprehensive interrogation of transcriptional, epigenetic, proteomic, and metabolomic networks that define adipocyte identity and function. Transcriptomic studies reveal distinct gene signatures underlying thermogenic activation and lineage commitment, while epigenomic profiling highlights regulatory elements that orchestrate adipocyte plasticity, particularly the inducible browning of white fat. Proteomic and metabolomic analyses further uncover mitochondrial remodeling, lipid turnover pathways, and metabolite, hormone interactions that regulate thermogenic capacity and metabolic health. Integrating these multi-layered datasets provides systems-level insights into the roles of environmental cues, such as diet and temperature, and endogenous factors, including hormonal signaling, circadian rhythms, and genetic background, in reshaping adipocyte phenotypes and influencing whole-body metabolism. Multi-omics approaches are increasingly identifying potential novel biomarkers and therapeutic targets aiming to enhance the activity of brown and beige adipocyte to combat obesity and metabolic disorders. Overall, these technologies provide a powerful framework for elucidating the complexity of ATs and advancing precision strategies for metabolic disease management and prevention. Full article

Population ageing and the growing burden of immune-mediated disease have prompted efforts to quantify immunosenescence with clinically usable biomarkers. Immune ageing clocks have been built from immunophenotyping, transcriptomics, proteomics, epigenomics and adaptive receptor repertoires, but heterogeneous task definitions, assay protocols and evaluation criteria limit comparability and translation. We review major immune data modalities and outline an end-to-end workflow from cohort design and assay standardisation to preprocessing, feature engineering, model development, validation and recalibration. We propose a task–modality–model taxonomy separating (i) chronological age clocks, (ii) outcome-anchored risk clocks and (iii) cell lineage/state clocks, while treating bulk blood transcriptomics (whole blood or PBMC) as a molecular-layer modality that can support either age-scale or outcome-anchored tasks depending on supervision. Across studies, common limitations include batch effects, compositional confounding, endpoint mismatch, scarce external validation and limited mechanistic anchoring. We conclude with priorities for the field, including multimodal integration, longitudinal designs with digital phenotypes, tissue- and cell-type-specific models, and pathway-grounded clocks that can be linked to interventions. Full article

Background/Objectives: Following centuries of systematic eradication, grey wolf (Canis lupus) populations across Europe have experienced a significant recovery over recent decades, which leads to concerns regarding, among others, anthropogenic hybridization. In Greece, the genetic status of the wolf population is largely unknown to date. Here, we genetically monitor and test for wolf–dog hybridization events in a recently established wolf population in the Parnitha Protected Area, in close vicinity to the capital city of Greece. Methods: One hundred and twenty-four wolf scat samples were genotyped at 20 canine-specific autosomal microsatellite loci and compared to available reference tissue samples from wolves and free-ranging dogs. Results: A minimum of 31 unique wolf individuals were identified, structured into at least three packs. No wolf–dog hybrids were detected in the study area. To validate the accuracy of the microsatellite analysis, an ancestry informative 93-SNP panel was applied to non-invasive wolf DNA samples from the study area, confirming the absence of hybrids among them. However, a possible wolf–dog hybrid was detected among reference wolf samples collected in Northern Greece, where individuals with atypical morphological traits are observed. The estimated census population size was in accordance with concurrently obtained camera trapping data, while heterozygosity values were low. Conclusions: This research represents the first systematic effort in Greece to genetically monitor wolves recently established in a protected area. It highlights the need for targeted management strategies based on genetic data to ensure balanced long-term conservation of wolves in peri-urban areas. Full article

Background/Objectives Sports-related musculoskeletal injuries remain a major challenge in physically active populations, with substantial interindividual variability in susceptibility and recovery that cannot be fully explained by biomechanics or genetics alone. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, provide a dynamic interface through which mechanical loading, inflammation, and metabolic signals regulate gene expression during tissue adaptation and repair. This narrative review synthesizes current evidence on “epigenetically active” dietary supplements and their potential relevance to sports injuries, focusing on methyl donors, polyphenols, omega-3 fatty acids, vitamin D, and redox-active nutrients. Methods Targeted searches of PubMed, Scopus, and Web of Science (2000–2026) were performed using epigenetics-, injury-, exercise-, and supplementation-related terms, prioritizing mechanistic and translational evidence. Results Available data indicate that these compounds can influence molecular mechanisms implicated in musculoskeletal recovery. However, human evidence is largely derived from peripheral tissues and indirect molecular markers, with limited clear linkage to clinically significant injury outcomes such as injury incidence, severity, or return-to-play timelines. Accordingly, these nutrients are best viewed as modulators of recovery-related biology rather than as direct therapeutic agents. Conclusions This review highlights a notable translational gap between mechanistic plausibility and clinical evidence and discusses practical implications for sports nutrition from a personalized perspective. Future research priorities include tissue-relevant epigenetic assessments, integration of multi-omics approaches, and longitudinal trials incorporating injury endpoints. Nutritional epigenomics, therefore, represents a promising avenue to support musculoskeletal health while underscoring the need for rigorous clinical validation. Full article

Periodontal disease is a chronic inflammatory condition that destroys tooth-supporting tissues, particularly the alveolar bone and the periodontal ligament, and effective regenerative therapies remain limited. While the role of metabolic–epigenomic crosstalk in determining cell fate is well established, the specific mechanism by which a tricarboxylic acid (TCA) cycle metabolite can modulate chromatin regulation to promote periodontal regeneration remains to be elucidated. The impact of one TCA cycle metabolite, alpha-ketoglutarate (α-KG), was examined in human periodontal ligament fibroblasts cultured under osteogenic induction and profiled by ALP assays, RT-qPCR, analyses of multiple histone modifications, ATAC-seq, and RNA-seq. α-KG increased ALP activity and upregulated genes associated with osteogenesis and the extracellular matrix (ECM). ATAC-seq revealed minimal genome-wide accessibility changes, whereas histone analyses showed reduced H3K27me3, consistent with an epigenetic mechanism that does not require extensive chromatin opening. The RNA-seq identified 14 upregulated α-KG-induced genes, including multiple components of the OGN-OMD-PLAP1/ASPN-ECM2 loci, supporting an osteogenic/ECM transcriptional program. In a mouse periodontal regeneration model, oral administration of α-KG enhanced alveolar bone regeneration and reduced H3K27me3 signals and collagen-rich tissue organization within the periodontal ligament space. These findings identify α-KG as a metabolite-driven epigenetic modulator that alleviates H3K27me3-mediated repression and supports periodontal regeneration. Full article

Oxygen (O₂) tension is a critical factor influencing in vitro development of pre-implantation embryos. The in vivo environment has lower O₂ tension (2–10%) than atmospheric air (~20%), along the female reproductive tract, from the oviducts (8–10%) to the uterus (2–5%), supporting development of early-stage embryos. As the female reproductive tract is inherently hypoxic, replicating low-O₂ conditions in vitro may enhance embryo development. In contrast, culturing embryos under non-physiological O₂ tension may impair stress adaptation and reduce developmental competence. Optimal O₂ tension likely varies with species and embryo stage, suggesting a single uniform O₂ tension throughout in vitro culture may not be ideal; conditions beneficial at one stage may be detrimental at another. Although atmospheric O₂ harms embryo development and redox balance, specific advantages of low (5%) or ultra-low (≤2%) O₂ remain uncertain, despite many studies documenting improved development under hypoxia. This review examines the current literature on effects of atmospheric, low, and ultra-low O₂ tension during in vitro embryo culture, emphasizing impacts on in vitro fertilization (IVF) outcomes, and the regulation of transcription and epigenomics during pre-implantation embryo development. Full article