Search Results (3,432)

Hair follicles are highly specialized mini-organs within the skin that drive the production of wool and cashmere, traits of major biological and economic importance in sheep and goats. Despite their microscopic size, hair follicles exhibit extraordinary regulatory complexity, integrating genetic programs with seasonal, endocrine, environmental, and epigenetic cues. Although transcriptional networks and signaling pathways underlying follicle morphogenesis and cycling have been extensively investigated, the post-transcriptional mechanisms that fine-tune these processes remain insufficiently understood. MicroRNAs (miRNAs) have emerged as pivotal post-transcriptional regulators that coordinate cell fate determination, lineage commitment, and tissue homeostasis. Growing evidence indicates that miRNAs play essential roles in hair follicle stem cell maintenance, proliferation, differentiation, apoptosis, and organ-level development, functioning through interconnected regulatory networks rather than isolated linear pathways. By modulating the expression of key follicle-determining genes and signaling components, miRNA-mediated regulation shapes follicle formation, cyclic regeneration, and fiber traits. In this review, we synthesize recent advances in miRNA research related to hair follicle biology, with a particular focus on wool- and cashmere-bearing mammals. We integrate findings across species to propose a systems-level framework in which miRNA networks interface with canonical signaling pathways and epigenetic mechanisms to orchestrate follicle development and regeneration. Conserved and species-specific regulatory principles are discussed to bridge fundamental follicle biology with practical applications in fiber production. Overall, this review highlights miRNAs as a critical yet previously underappreciated regulatory layer in hair follicle biology. A deeper understanding of miRNA-mediated control provides new conceptual insights into wool and cashmere development and offers a foundation for future molecular breeding and precision regulation strategies in livestock. Full article

The rapid expansion of cardiac imaging has substantially increased patient and occupational exposure to low-dose ionizing radiation. Evidence suggests that cumulative exposures below 100 mSv may contribute to long-term risks of cancer and non-cancer diseases, including cardiovascular disease. However, establishing causality at these dose levels is challenging, as epidemiological studies are limited by heterogeneous endpoints, uncertainties in dose reconstruction, and incomplete control of confounding factors. Molecular biomarkers offer a promising strategy to bridge the gap between radiation exposure and clinically manifest disease, enabling more precise individualized risk assessment and targeted preventive strategies. This review summarizes current evidence on genetic and epigenetic biomarkers for evaluating the biological effects of radiation in cardiac imaging and interventional cardiology and examines their potential role in risk stratification and occupational surveillance. Genetic markers—including γ-H2AX foci, micronucleus assays, and telomere length alterations—alongside epigenetic modifications such as DNA methylation changes and microRNA expression profiles provide sensitive indicators of radiation-induced cellular damage. Integrating biomarker profiling with individualized dosimetry and longitudinal follow-up may improve risk prediction, enhance occupational protection, and support safer, more sustainable imaging practices in contemporary cardiovascular care. Full article

Radiation-responsive promoters represent a functionally distinct class of transcriptional regulatory elements that translate genotoxic stress signals into quantifiable gene expression outputs. These promoters occupy a unique mechanistic position within the broader radiation biomarker landscape: rather than directly measuring molecular damage products, they report the cellular interpretation of radiation-induced stress through coordinated gene regulatory networks. This review provides a systematic analysis of five major classes of radiation-responsive promoters—microRNA (miRNA) promoters, tRNA-derived small RNA (tsRNA) promoters, acute-phase protein gene promoters, DNA repair gene promoters, and long non-coding RNA (lncRNA) promoters—with emphasis on their regulatory logic, dose-response characteristics, and current evidence for clinical deployment. We further describe four complementary screening strategies: homology-based conservation analysis, functional genomics and transcriptomics, epigenetic modification profiling, and synthetic biology promoter engineering. Applications spanning biosensor development, biological dosimetry, treatment response prediction, and radiation-guided gene therapy are evaluated within a two-track framework that distinguishes biomarker-oriented applications (Track A) from tool-oriented reporter gene systems (Track B). Critical appraisal of current limitations—including insufficient clinical-grade validation, absence of standardized dose-response curves, and reproducibility deficits—is integrated throughout. Future priorities include multi-center prospective validation studies, FAIR-compliant data infrastructure, AI-driven multi-omics integration, and point-of-care detection platforms. Radiation-responsive promoter biology holds significant potential for advancing precision radiotherapy and nuclear emergency medical response, contingent upon systematic closure of the current evidence gap relative to established gold-standard cytogenetic methods. Full article

Histone deacetylase 6 (HDAC6), a member of the class IIb HDAC family, plays a crucial role in epigenetic regulation and cytoskeletal dynamics, while participating in host anti-infective immune responses. However, its precise functions and mechanisms during Chlamydia muridarum (C. muridarum) infection remain incompletely defined. Our study demonstrated that C. muridarum respiratory infection upregulates HDAC6 expression at the infection site and in immune organs. Comparative analysis of wild-type (WT) and HDAC6-deficient (HDAC6^−/−) mice in this infection model revealed that HDAC6 deficiency exacerbates disease progression, including significant weight loss, severe pulmonary inflammation, and impaired C. muridarum clearance. Relative to WT mice, HDAC6^−/− mice exhibited elevated Signal Transducer and Activator of Transcription 6 (Stat6) and GATA Binding Protein 3 (Gata3) mRNA expression, enhanced pathological Th2 responses with increased IL-4 secretion, and no significant differences in protective Th1 or Th17 responses following C. muridarum infection. Concurrently, these mice displayed enhanced M2 macrophage polarization, as evidenced by upregulated CD206 and Arg-1 expression, whereas M1 marker expression remained unchanged. The vitro studies confirmed that HDAC6^−/− bone marrow-derived macrophages (BMDMs) promote M2 polarization, characterized by increased Arg-1, IL-10, and TGF-β production, and further co-culture experiments showed that C. muridarum -stimulated HDAC6^−/− BMDMs drive Th2 differentiation. These findings elucidate the critical role of HDAC6 in regulating Th2-M2 immune responses during C. muridarum respiratory infection and suggest targeted modulation of HDAC6 as a novel therapeutic strategy for chlamydial respiratory infection. Full article

The PRDM (PR domain-containing) family consists of transcriptional regulators characterized by a PR (PRDI-BF1 and RIZ homology) domain, a subtype of the SET domain, and a variable number of zinc finger motifs. Nineteen PRDM family members have been identified in both mice and humans, and increasing evidence supports their roles as epigenetic regulators in development and disease. PRDM proteins share a conserved structure, comprising an N-terminal PR domain with potential histone methyltransferase activity and C-terminal C2H2-type zinc fingers involved in protein–protein, protein–RNA, and protein–DNA interactions. Recent studies indicate that multiple PRDM family members are involved in the regulation of the neuro-motor system, including neural lineage specification, neuronal differentiation, motor function maintenance, and neuromuscular-related pathological processes. This review summarizes current evidence on the functions and regulatory mechanisms of PRDM family members in the neuro-motor system. Overall, PRDM family members act as important epigenetic regulators in the neuro-motor system. Clarifying their molecular mechanisms may contribute to a better understanding of neuro-motor regulation and provide a theoretical basis for future research in exercise and movement science. Full article

The safety of titanium dioxide (TiO₂), widely used in foods and personal care products, has been of on-going concern. Adverse effects of TiO₂ have been reported, suggesting risk to human health. To evaluate its potential epigenotoxicity, the effect of exposure to a TiO₂ product, to which humans could be exposed, on microRNA (miRNA) expression (a primary epigenetic mechanism) was investigated using human cell lines (Caco-2, HCT116 (colorectal) and HepG2, SNU387 (liver)) relevant to human exposure. The effect of TiO₂ nanomaterial exposure on expression levels of miRNA was determined using the TaqMan Array Human microRNA A+B Card Set v3.0 platform. Differentially expressed miRNAs were identified (SNU387 (n = 112), HepG2 (n = 97), Caco-2 (n = 94), and HCT116 (n = 53)). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional enrichment analysis of target genes provided insights into the roles of modulating pathways, which can be associated with diseases. Top 10 KEGG pathways in each cell line included MAPK signaling pathway, Axon guidance, cell cycle, Hippo signaling pathway, and Endocytosis. Findings from the study clearly demonstrate the impact of TiO₂ exposure on miRNA expression, supporting the potential involvement of this epigenetic mechanism in its biological responses. Hence, epigenetic studies are important for the complete assessment of the potential risk from exposure. Full article

Background: Gene expression and cellular identity are regulated by epigenetics that occurs through chromatin modifications, RNA changes, chromatin accessibility, and three-dimensional genome organization. Although DNA methylation has been the focus of most epigenetics studies in the past, other non-methyl epigenetic processes, including histone post-translational modifications (PTMs), epitranscriptomic marks, and chromatin remodeling, are dynamic, reversible, and context-dependent, and thus are difficult to accurately interrogate using endpoint sequencing-based assays, especially in heterogeneous tissues, developing systems, and therapeutic response environments. Scope and Approach: The present review discusses epigenetic modifications other than DNA methylation regarding sensor-based technologies that can measure live, dynamic, and spatially resolved measurements. Epigenetic sensors include any genetically encoded sensors (GECs) based on resonance energy transfer, CRISPR/dCas-derived sensors, or aptamer-based sensors, and hybrid biochemical/imaging sensors that can be used in live or semi-live settings. It lays emphasis on the technologies, which have been developed recently, that allow real-time kinetic measurements, working in three-dimensional and organoid models, and being applied to disease-relevant perturbations. On these platforms, performance properties such as specificity, sensitivity, spatial and temporal resolution, ability to perform dynamic versus locus-specific interrogation, and perturbed endogenous chromatin states are compared. Key Conclusions and Outlook: Together, these sensing strategies are complementary to the traditional methods of measuring epigenomics in that they show epigenetic dynamics unobservable with static measurements. We list the important technical issues, including specificity, quantitation, multiplexing, and chromatin perturbation, and report the barriers and solutions in development and design. Lastly, we provide a conceptual map of how live epigenetic sensing and multi-omics and translational models can be integrated, and how the two methodologies can be used to develop functional epigenetics and guide disease modeling and drug development. Full article

Oral squamous cell carcinoma (OSCC) remains a major global health burden due to aggressive invasion, early metastasis, therapeutic resistance, and poor long-term survival. Beyond tumor-intrinsic genetic and epigenetic alterations, accumulating evidence highlights the critical role of the tumor microenvironment in shaping OSCC progression and clinical outcomes. Cancer-associated fibroblasts (CAFs) and immune cells orchestrate tumor initiation, immune evasion, and recurrence through extracellular matrix remodeling, cytokine signaling, angiogenesis, and metabolic and redox regulation. Key oncogenic pathways, including EGFR/PI3K/AKT/mTOR, TGF-β, Wnt, and Notch, integrate with non-coding RNA networks to reinforce stemness, epithelial–mesenchymal transition, and therapy resistance. Moreover, PD-1/PD-L1-mediated immune escape, CAF-driven biomechanical remodeling, and metabolic reprogramming such as aerobic glycolysis and lipid metabolism contribute to OSCC heterogeneity. This review synthesizes current insights into OSCC across genomic, epigenetic, metabolic, and microenvironmental dimensions, emphasizing CAF biology, immune landscape reprogramming, and non-coding RNA regulation. We further discuss emerging biomarkers, liquid biopsy approaches, and targeted therapeutic strategies, providing a system-level framework for biomarker-guided stratification and precision combination therapies in OSCC. Full article

The hypothalamic–pituitary–adrenal (HPA) axis coordinates metabolic, immune, and behavioral responses to a changing environment. Its molecular effectors are the nuclear receptors for glucocorticoids and mineralocorticoids (the GRs/MRs), encoded by nr3c1/nr3c2. The MR serves as the high-affinity sensor of basal hormone concentrations, whereas the GR amplifies the stress response and mediates negative feedback. Despite their shared domain architecture, the receptors have diverged functionally: isoform composition, post-translational modifications, and the complement of co-regulators together determine which genes are activated or repressed in a given tissue at a given time. The regulation of the HPA axis activity is a major determinant of embryonic development. Pregnancy adds a placental control layer that meters maternal signals: 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in the syncytiotrophoblast inactivates cortisol, whereas 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) can regenerate it, and systemic buffering by transcortin (cortisol-binding globulin, CBG) limits the free hormone fraction. Under stress, inflammation, or hypoxia, this barrier weakens, exposing the fetus to stronger glucocorticoid pulses during windows of heightened vulnerability for brain and immune development. Such overexposure not only reshapes ongoing transcription but is also epigenetically inscribed: the methylation of alternative nr3c1 promoters, the remodeling of histones, and the shifts in ncRNA profiles recalibrate the axis sensitivity for the long term. At the phenotypic level, this manifests as variability in stress reactivity, cognitive and affective trajectories, and an immune and metabolic risk across later ontogeny. In this review, we integrate evidence on the structure and functions of the GR, the mechanisms of its post-translational and epigenetic regulation, and the role of the placenta, to provide a coherent framework for understanding the multifaceted consequences of prenatal stress and to identify potential targets for early prevention. Full article

Patients with Liver Hepatocellular carcinoma (LIHC) have a poor prognosis due to late-stage diagnosis and the limited efficacy of drug treatments. Dysregulation of nuclear pore complex (NPC) components, particularly nucleoporins (NUPs), may play a role in tumor progression. However, the specific role of NUP205 in LIHC has not been comprehensively investigated. We evaluated the expression, prognostic significance, epigenetic regulation, microRNA(miRNA) interactions, drug sensitivity, and biological functions of NUP205 in LIHC. Comprehensive bioinformatics analyses were performed using publicly available databases and web-based analysis platforms, including The Cancer Genome Atlas (TCGA), UALCAN, and the Kaplan–Meier Plotter (KM Plotter), among others. In vitro validation was performed using small interfering RNA (siRNA)-mediated knockdown of NUP205 in HepG2 cells, followed by quantitative reverse transcription PCR (RT-qPCR), apoptosis assay and wound-healing assay. NUP205 expression was significantly elevated in patients with LIHC and was associated with advanced clinicopathological features and poor prognosis. Promoter hypomethylation and miRNAs were identified as regulatory mechanisms influencing NUP205 expression. Increased NUP205 levels were associated with resistance to multiple chemotherapeutic agents. NUP205 knockdown significantly reduced messenger RNA (mRNA) expression in HepG2 and PLC/PRF/5 cells, and also reduced the expression of Transmembrane protein 209 (TMEM209) in HepG2 cells and improved sensitivity to doxorubicin. NUP205 expression was consistently associated with adverse clinicopathological features, poor prognosis, and altered drug sensitivity in LIHC. Integrative analyses suggest that NUP205 dysregulation may be linked to epigenetic and miRNA-associated regulatory mechanisms. These findings support NUP205 as a candidate prognostic biomarker and a potential regulatory factor in LIHC, warranting further mechanistic and protein-level validation. Further research is necessary to fully elucidate its underlying mechanisms and potential clinical applications. Full article

N6-methyladenosine (m⁶A) is a reversible RNA modification that dynamically regulates gene expression by modulating RNA stability, splicing, nuclear export, translation, and maturation—thereby orchestrating organismal development. In birds, including geese, the liver is a multi-functional organ central to metabolic regulation. Studies on the dynamic patterns of RNA m⁶A modifications during healthy liver growth and development remain limited. Here, we performed integrative methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) on liver tissues from geese at three biologically defined stages: post-hatch day 0 (0 week, P), fast growth (10 weeks, F), and sexual maturation (30 weeks, S). The level of m⁶A modification in total RNA extracted from liver tissues was higher in P than in F samples. Compared with other groups, the S group recorded the lowest m⁶A modification. In addition, 1641, 668, and 558 m⁶A peaks were differentially modified in the P, F, and S groups, respectively. The m⁶A peaks in the liver of the three groups were mainly enriched in the coding sequence and 3′ untranslated region. Moreover, integrated multi-omics analysis (MeRIP-seq and RNA-seq), combined with protein–protein interaction networks analysis, identified CDK1 as a core cell cycle regulator and IGF2BP3—a well-established m⁶A reader—as a consistently differentially expressed gene across all developmental stages. The m⁶A-regulated cell cycle, p53 signaling pathway, and pyrimidine metabolism pathway were identified in liver tissue as novel potential targets for controlling geese growth and metabolism. Together, these findings shed light on the dynamic regulation of RNA methylation during distinct growth phases in geese and advance our understanding of epigenetic mechanisms underlying poultry liver development. Full article

The gut–skin axis is increasingly implicated in psoriasis pathogenesis, yet the cross-compartment convergence of molecular programs remains incompletely defined. We constructed a conceptual “Triple-Hit” multi-omics framework by integrating five independent public datasets spanning gut microbial functional remodeling (shotgun metagenomics), systemic immune cell methylomes (PBMC and CD8+ T-cell EPIC 850K), and lesional skin regulatory layers (miRNA and bulk RNA-seq). In the gut compartment, functional profiles exhibited a selective reduction in microbial lipid catabolic potential, including decreased fatty acid degradation and a lowered composite lipid degradation score, alongside heterogeneous shifts across SCFA-associated metabolic pathways. Systemically, PBMC methylomes revealed widespread regional remodeling (45,396 DMRs) enriched for membrane-proximal signaling and cytoskeletal programs, while CD8+ T cells showed specific epigenetic alterations in lipid- and glycosphingolipid-associated loci, suggesting a systemic metabolic–epigenetic alignment. In the skin, we identified a compact miRNA signature (168 DE-miRNAs) and a mechanistically interpretable, directionality-constrained miRNA–mRNA bridge that aligns with an AMP-dominant inflammatory transcriptome, consistent with reduced post-transcriptional restraint. Collectively, these findings support a convergent multi-omics framework linking putative microbial metabolic remodeling, systemic immune priming, and cutaneous effector programs. This study provides a systems-level perspective on psoriasis pathogenesis, highlighting the metabolic–epigenetic–transcriptional convergence as a potential avenue for therapeutic intervention. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, driven by aggressive tumor biology, extensive intratumoral heterogeneity, and profound resistance to standard therapies. While recurrent genetic alterations such as KRAS mutations are central to PDAC initiation, growing evidence demonstrates that epigenetic dysregulation is a critical determinant of disease progression, cellular plasticity, immune evasion, and therapeutic failure. Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA regulation, shape transcriptional programs without altering the underlying DNA sequence, rendering them dynamic and potentially reversible therapeutic targets. This review provides a comprehensive overview of key epigenetic proteins implicated in PDAC, encompassing writers, readers, and erasers of chromatin marks. Aberrant activity of histone methyltransferases and acetyltransferases, bromodomain-containing proteins, histone deacetylases, and demethylases orchestrates transcriptional reprogramming that promotes epithelial–mesenchymal transition, stem-like phenotypes, metabolic adaptation, and resistance to chemotherapy and radiotherapy. In parallel, epigenetic alterations within the tumor microenvironment contribute to stromal activation and immune suppression, further limiting therapeutic efficacy. We summarize recent advances in pharmacological targeting of epigenetic regulators and discuss the rationale for combination strategies integrating epigenetic inhibitors with cytotoxic agents, targeted therapies, and immunotherapies. Emphasis is placed on emerging experimental platforms—including patient-derived organoids, co-culture systems, and in vivo models—combined with multi-omic profiling and computational approaches to identify biomarkers of response and optimize therapeutic design. Collectively, this review highlights epigenetic regulation as a central and actionable vulnerability in PDAC and outlines future directions toward biomarker-guided, personalized epigenetic therapies aimed at overcoming resistance and improving clinical outcomes. Full article

Seborrheic dermatitis (SD) is a chronic inflammatory skin disorder with a multifactorial pathogenesis involving immune dysregulation, oxidative stress, neuroendocrine signaling, and alterations of the epidermal barrier–lipid axis. Increasing molecular evidence indicates that SD is associated with both systemic and cutaneous abnormalities, including elevated β-endorphin levels, disturbed redox homeostasis, enhanced lipid peroxidation, dysregulated cytokine signaling, and genetic and epigenetic susceptibility factors. This systematic review was conducted in accordance with PRISMA guidelines. Comprehensive literature searches of PubMed, Scopus, and Web of Science identified eight studies that met the inclusion criteria. The included investigations comprised clinical case–control studies, genetic and epigenetic analyses, and multi-omics profiling of human blood and skin samples. Collectively, the findings demonstrate consistent systemic oxidative and neuroendocrine alterations alongside pronounced local immune activation characterized by Th1- and Th17-skewed responses, cytokine and stress-ligand upregulation, and activation of inflammatory signaling pathways. Genetic association signals and disease-specific microRNA profiles further implicate post-transcriptional regulation of immune and keratinocyte-related pathways in SD pathogenesis. Moreover, multi-omics studies revealed coordinated immune activation accompanied by impaired epidermal barrier function and altered lipid metabolism, supporting a dysregulated immune–barrier–lipid axis. Overall, SD emerges as a disorder driven by interconnected systemic and cutaneous molecular mechanisms. The identified pathways may represent promising directions for future biomarker research and targeted therapeutic development rather than established diagnostic or treatment strategies. Full article

Background: Collagen type V alpha 2 (COL5A2) is an important regulator of tumor progression and metastasis in various tumors. microRNAs (miRNAs), key post-transcriptional regulators of gene expression, can act as tumor suppressors or oncogenes. Dysregulated miRNA is closely associated with tumor development and progression. This study aimed to investigate COL5A2 expression across different tumors and to investigate its prognostic, immune cell infiltration, and miRNA associations. Methods: We used the TIMER database to assess COL5A2 expression across various tumor types and tumor-infiltrating immune cells. The UALCAN database was used to study the associations between COL5A2 expression and tumor stages, while overall survival results were obtained using the Kaplan–Meier plotter. We identified tumor suppressor miRNAs predicted to regulate COL5A2 expression in different tumors using the miRNet database and evaluated correlations between their expression levels, COL5A2 expression, and patient survival using the StarBase database. Results: COL5A2 was significantly upregulated in 12 tumors, and the upregulated COL5A2 expression was associated with altered immune cell infiltration and worse overall survival in lung and stomach adenocarcinoma. A total of 29 tumor suppressor miRNAs were identified as potential regulators of COL5A2 expression. We found that hsa-miR-101-3p and hsa-miR-29c-3p were downregulated in lung adenocarcinoma and negatively correlated with COL5A2 expression, and their downregulated expression was associated with unfavorable prognosis. Conclusions: COL5A2 and its regulatory miRNAs, hsa-miR-101-3p and hsa-miR-29c-3p, may represent potential diagnostic and prognostic biomarkers and modulators of the tumor immune microenvironment in lung adenocarcinoma. These results warrant further experimental validation and future evaluation in the context of Sustainable Development Goal (SDG) 3-aligned cancer control strategies. Full article