Search Results (985)

Chronic hepatitis B virus (CHB) infection remains a major cause of hepatocellular carcinoma (HCC), yet the premalignant microenvironment that links to HBV-associated HCC (HBV-HCC) is still poorly defined. This review synthesizes evidence that HBV-infected hepatocytes function as signaling hubs that, through microRNA (miRNA)-regulated crosstalk with Kupffer cells, liver sinusoidal endothelial cells, hepatic stellate cells and cancer-associated fibroblasts (CAFs), progressively remodel the liver from an antiviral tissue into a premalignant and early tumor microenvironment. Across the HBV-HCC continuum, a core set of dysregulated miRNAs, including miR-21, miR-29a/b, miR-122, miR-146a, miR-155, miR-200a, miR-126, miR-210 and the miR-130/301 family, coordinates transition from innate antiviral responses to HSC activation, extracellular matrix deposition, mechanotransduction, angiogenesis, chronic inflammation and cancer-associated CAF programing. By mapping these stage-specific miRNA networks onto acute infection, CHB, early fibrogenesis, advanced fibrosis and CAF-rich dysplastic states, the review reframes HBV-HCC pathogenesis as a sequence of miRNA-guided hepatocyte–stromal states rather than a purely hepatocyte-intrinsic process. This perspective suggests that composite, cell-type-resolved miRNA signatures in serum or liver tissue could serve as biomarkers for identifying CHB patients who are entering a premalignant microenvironment before conventional surveillance markers become abnormal. It further highlights miRNA hubs that couple antiviral, fibrogenic, angiogenic and CAF-associated signaling as potential therapeutic targets for reprograming the HBV-driven premalignant microenvironment, with the long-term goal of intercepting HBV-HCC development at earlier, microenvironmentally defined stages. Full article

Postmenopausal ovarian hormone deficiency (OHD) contributes to overactive bladder (OAB) through oxidative stress, mitochondrial dysfunction, and dysregulated estrogen receptor (ER) signaling. This study investigated whether estradiol (E2) alleviates dysfunction by modulating the ER/Smad/miRNA-200/KLF4/mTOR signaling pathway to restore mitochondrial quality control. Thirty female Sprague-Dawley rats were initially allocated to Sham, Ovariectomy (OVX) and OVX + E2 group; after attrition during the 12-month protocol, six surviving animals per group were included in the principal analyses. The OVX + E2 group received daily intramuscular E2 (IM, 30 μg/kg/day) for one month. Bladder function was assessed via micturition volume and frequency by metabolic cages, cystometrograms, and contractility assays. Mechanisms were analyzed using immunofluorescence, Western blotting, transmission electron microscopy (TEM), and miRNA sequencing. OVX rats exhibited significant overactivity and compromised contractility, accompanied by upregulated ERα and downregulated ERβ/GPER. Molecularly, OHD was associated with the upregulation of the miRNA-200 family (miRNA-200a-3p, miRNA-200b-3p and miRNA-200b-5p), which was accompanied by reduced levels of KLF4 and autophagy proteins (ATG7, ATG12 and Beclin-1), as well as elevated p-mTOR expression. TEM revealed the accumulation of damaged mitochondria with ultrastructural features associated with impaired mitophagy. However, E2 treatment ameliorated these abnormalities. These improvements were associated with the restoration of TGF-β/Smad signaling, downregulation of selected miRNA-200 family members, recovery of KLF4 level, and increased expression of autophagy-related markers, accompanied by improved mitochondrial ultrastructural integrity. This cellular restoration might be correlated with improved urodynamic parameters. E2 might exert therapeutic effects by improving mitochondrial quality, potentially via the ER/Smad/miRNA-200/KLF4 signaling pathway. These findings provided mechanistic insights into estrogen-mediated protection and highlight this proposed signaling pathway as a therapeutic target for postmenopausal OAB. Full article

Fibrosis emerges when normally self-limiting tissue repair fails to resolve and overlapping phases of injury, stromal activation, extracellular matrix (ECM) deposition and remodelling become sustained. MicroRNAs (miRNAs) shape this transition by coordinating signalling, cell-state and matrix programmes. Functionally, pro-fibrotic fibro-miRs amplify fibrogenic pathways, whereas anti-fibrotic miRNAs restrain fibroblast activation and ECM production; the miR-29 family is a principal member of the latter group. This review examines miR-29 family organisation, the regulation of miR-29b by transforming growth factor-β (TGF-β)/Smad and additional transcriptional and inflammatory inputs, and the molecular targets through which miR-29b controls collagen synthesis, processing and crosslinking. Direct canonical targets are distinguished from experimentally supported, predicted and indirect pathway components. Evidence is evaluated across fibroblasts and myofibroblasts, epithelial and endothelial cells, and pulmonary, hepatic, renal, cardiac, dermal and ocular fibrosis models. Therapeutic translation is considered in relation to miR-29b mimics and agomirs, local and tissue-targeted delivery, pharmacokinetics, dose control, off-target repression, immune activation and long-term safety. Overall, miR-29b remains a credible network-level anti-fibrotic candidate, but successful translation requires cell- and disease-specific target validation, selective delivery and preservation of physiological wound repair. Full article

Background: Autophagy is a process that diversely impacts the stages of both tumor initiation and progression. Elucidating the molecular mechanisms underlying autophagy and its role in tumorigenesis is a key component of anticancer strategies in both prostate cancer and other malignancies. Because advanced prostate cancer frequently exploits enhanced autophagy as a defense mechanism against therapy-induced stress (e.g., from abiraterone), the pharmacological modulation of miRNA levels presents a tremendous opportunity to block the tumor’s escape route and overcome drug resistance. Methods: A comprehensive literature review was conducted to evaluate the molecular pathways determining cancer cell survival and death. The analysis focused on the dual nature of autophagy (functioning as a ‘double-edged sword’) within the tumor microenvironment, microRNA (miRNA) regulatory networks, and the efficacy of synergistic therapeutic strategies in overcoming treatment resistance. Results: The primary focus of this paper is the dual and complex role of autophagy, which serves, on the one hand, as a cellular protective shield against metabolic stress—thereby facilitating metastasis—and, on the other hand, as a potential pathway leading to autophagic cell death. The progression of this crucial process is regulated by intricate interactions (crosstalk) with apoptotic pathways, mediated by Bcl-2 family proteins, key kinases (such as mTOR, JNK, and DAPK), and transcription factors, such as p53. Furthermore, the autophagic machinery is precisely regulated by specific miRNA molecules (e.g., miR-21, miR-141, and miR-375). These not only act as crucial intracellular modulators of autophagy but also serve as promising circulating biomarkers, enabling the monitoring of this process’s activity throughout disease progression. Conclusions: Autophagy, and in particular its modulation via miRNA signaling networks, represents a major and highly promising translational target. By directly impairing this autophagic survival mechanism, ‘double-hit’ combination therapies—integrating autophagy inhibitors (such as hydroxychloroquine or VPS34 inhibitors) with standard antiandrogen or cytotoxic agents—demonstrate promising preclinical potential in overcoming treatment resistance and favorably modulating the immune microenvironment in advanced prostate cancer. Full article

PBU (N-phenyl-N′-thiazolylurea) promotes callus induction and adventitious bud differentiation in eucalyptus, but the miRNA-mediated regulatory mechanisms underlying these effects remain unclear. In this study, calli of Eucalyptus urophylla × E. grandis clone DH32-29 with distinct phenotypes were cultured at four PBU concentrations (0, 0.1, 1 and 5 mg L⁻¹) and analyzed by small-RNA sequencing, targeted metabolomics, and qRT-PCR validation. A total of 114 common differentially expressed miRNAs were identified, targeting 610 mRNAs. Functional enrichment analysis revealed that these targets were predominantly associated with lignin metabolism, phenylpropanoid metabolism, biotin metabolism, tryptophan metabolism, protein processing in the endoplasmic reticulum, and galactose metabolism. Metabolomic profiling detected 3029 metabolites, with differential metabolites enriched in the ABC transporter pathway, galloyl sugar biosynthesis, and cofactor biosynthesis. Key miRNA families, including miR164, miR165/166, and miR396, exhibited PBU concentration-dependent expression patterns and were predicted, based on in silico target prediction and qRT-PCR co-expression, to be potentially associated with target genes involved in lignin biosynthesis, ROS-related metabolism, and cytokinin homeostasis; these regulatory relationships remain to be experimentally validated. Among the tested concentrations, 1 mg L⁻¹ PBU was the dosage associated with the strongest reprogramming of secondary metabolism and with metabolic signatures suggestive of better preserved redox homeostasis; future work will build on this reference dataset with quantitative regeneration phenotyping and direct redox measurements to confirm this candidate optimum. These findings provide new insights into PBU-mediated in vitro regeneration in eucalyptus and offer a molecular basis for optimizing regeneration systems in E. urophylla × E. grandis. These findings provide new insights into the miRNA-metabolite regulatory network underlying phenylurea-mediated callus differentiation in woody plants. Full article

Cancer stem cells (CSCs) drive therapeutic resistance, metastasis, and tumor recurrence through reversible transitions among stem-like, differentiated, epithelial, and mesenchymal states, which are sustained by interconnected epigenetic mechanisms. To our knowledge, this is the first review to integrate curcumin-mediated regulation of DNA methylation, chromatin remodeling, and non-coding RNAs within a single CSC plasticity framework and to propose the concept of an “epigenetic collapse of CSC plasticity” as a mechanistic explanation for how curcumin may weaken stemness, state switching, and adaptive treatment resistance. Evidence was critically evaluated through structured searches of PubMed/MEDLINE, Scopus, Web of Science Core Collection, Google Scholar, and citation tracking, while direct curcumin–epigenetic evidence was distinguished from independent CSC evidence and inferential mechanistic links. Curcumin has been reported to modulate DNMT1 and locus-specific DNA methylation; regulate HDACs, p300/CBP, EZH2, H3K27me3, and BMI1; and alter selected microRNA, long non-coding RNA, and circular RNA pathways, with comparatively stronger evidence involving the miR-34 family, miR-200c, miR-21, H19, and circHN1. However, current evidence is constrained by the predominance of bulk cancer-cell models, heterogeneous formulations and exposure conditions, and the scarcity of epigenetic rescue experiments combined with rigorous functional CSC assays. By unifying previously fragmented epigenetic evidence, this review advances a new evidence-weighted model in which curcumin may suppress CSC persistence not through a single molecular target, but by destabilizing the multilayer epigenetic circuitry that enables plasticity. Curcumin should therefore be regarded as a context-dependent, multilayer epigenetic modulator rather than an established CSC-eradicating therapy, and its translational relevance requires validation in prospectively defined CSC models with pharmacologically justified delivery and exposure conditions. Full article

Background/Objectives: Citrus sinensis, Olea europaea var. sylvestris, Populus nigra, Prunus dulcis, and Punica granatum are economically and medicinally important perennial plant species. Carotenoid cleavage oxygenase (CCO) genes encode key enzymes involved in carotenoid degradation and play essential roles in plant growth, development, and responses to environmental stresses. In this study, a comprehensive genome-wide comparative analysis of the CCO gene family was conducted in C. sinensis, O. europaea var. sylvestris, P. nigra, P. dulcis, and P. granatum to investigate their structural diversity, evolutionary relationships, and potential biological functions. Methods: Chromosomal distribution, phylogenetic relationships, gene structure, conserved protein motifs, homology modeling, subcellular localization, cis-regulatory elements, and miRNA interactions were analyzed. Results: A total of 12, 23, 22, 11, and 17 CCO genes were identified in C. sinensis, O. europaea var. sylvestris, P. nigra, P. dulcis, and P. granatum, respectively. Most CCO proteins were acidic, and genes were concentrated on specific chromosomes. Phylogenetic analysis grouped CCO genes into three main clades. Gene structure analysis revealed intronless and intron-containing genes of varying lengths. Some CCO proteins possessed all conserved motifs, while others lacked certain motifs or had multiple copies. β-sheets were the predominant secondary structural elements, and CCO proteins were predicted to be localized in chloroplasts, mitochondria, peroxisomes, the cytoplasm, and the nucleus. Stress-related cis-elements and miRNAs were identified. Conclusions: These findings provide valuable insights into the diversity and evolutionary characteristics of the CCO gene family and suggest that CCO genes may contribute to plant stress responses and metabolic processes. Overall, this study provides a comprehensive comparative analysis of the CCO gene family in these five perennial plant species and offers a valuable genomic resource for future functional characterization, comparative genomic studies, and molecular breeding applications. Full article

Soil salinization has become a major global abiotic threat restricting sustainable viticulture, especially in coastal and inland saline–alkali zones. Unlike cereal crops mainly suffering from sodium toxicity, grapevine (Vitis vinifera L.) is a typical chloride-sensitive woody perennial, subjected to superimposed damages of osmotic stress, ionic imbalance and secondary oxidative injury under saline conditions which severely suppress vegetative growth and degrade berry quality. This review systematically summarizes the multi-layered physiological adaptive mechanisms of grapevine against salt stress, including ion homeostasis maintained by salt overly sensitive (SOS), Na⁺/H⁺ exchanger (NHX) and chloride channel (CLC) transporter families, active accumulation of osmoprotectants, synergistic enzymatic and non-enzymatic antioxidant systems, and phytohormone crosstalk networks formed by endogenous phytohormones (abscisic acid, ABA; jasmonic acid, JA; salicylic acid, SA; brassinosteroid, BR) and small signaling molecules. We further elaborate comprehensive molecular regulatory cascades governing salt tolerance, covering core functional genes for ion transport, master transcription factor families WRKY, MYB, APETALA2/Ethylene Response Factor (AP2/ERF), NAC, basic helix–loop–helix (bHLH) and emerging epigenetic regulatory layers mediated by deoxyribonucleic acid (DNA) methylation, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). In addition, we integrate four categories of field mitigation strategies for saline vineyards: germplasm improvement via salt-tolerant rootstock grafting, rhizosphere soil basal amendment, exogenous biostimulant regulation, and precision agronomic optimization. Current experimental systems do not fully recapitulate complex field combined-stress conditions, as most studies rely on laboratory single-salt stress simulation. Meanwhile, multi-omics, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) gene editing and high-throughput phenotyping tools provide promising approaches to deepen our understanding of grape salt tolerance. This review constructs a comprehensive theoretical framework linking physiological responses, molecular regulatory networks and practical field technologies, offering systematic theoretical references and technical guidance for salt-tolerant germplasm innovation and environmentally sustainable viticulture on saline soils. Full article

Field cancerization describes molecular alterations occurring in histologically normal tissues surrounding tumors that may contribute to cancer initiation and progression. In prostate cancer (PCa), the molecular characteristics of peritumoral tissue (PTT) remain incompletely understood. Because microRNAs (miRNAs) play key roles in gene regulation, tumor progression, and microenvironmental remodeling, we investigated miRNA expression patterns and regulatory networks across benign tissue (BT), PTT, and tumor tissue (TT). Small RNA sequencing was performed on matched formalin-fixed paraffin-embedded samples from 40 patients with PCa. Differential expression analysis was conducted using DESeq2, adjusting for age and Gleason grade, while functional enrichment analysis and weighted gene co-expression network analysis (WGCNA) were used to identify dysregulated pathways and conserved miRNA modules. PTT exhibited a molecular profile intermediate between BT and TT, consistent with a field cancerization effect. Compared with BT, 102 miRNAs were differentially expressed in TT and 57 in PTT, with 39 miRNAs (68% of the PTT-associated miRNAs) overlapping the tumor signature. Shared dysregulated pathways included PI3K–Akt, p53, and HIF-1 signaling; whereas, PTT showed additional enrichment in pathways related to epigenetic regulation (Polycomb Repressive Complex) and cellular stress responses (mitophagy, protein processing in ER) exclusively through up-regulated miRNAs; no pathways were uniquely enriched from down-regulated miRNAs in PTT. WGCNA identified conserved miRNA modules enriched for members of the let-7, miR-200, miR-103/107, and miR-106a~363 families, which have established roles in epithelial–mesenchymal transition, tumor progression, and microenvironmental remodeling. Collectively, these findings demonstrate that histologically benign peritumoral tissues harbor tumor-associated miRNA programs and regulatory networks that closely resemble those observed in prostate tumors, providing molecular evidence of field cancerization in PCa and identifying potential miRNA-mediated mechanisms relevant to disease progression and biomarker development. Full article

Background: MicroRNAs are key post-transcriptional regulators of gene expression and contribute to cancer progression, tumor heterogeneity, and context-dependent regulatory rewiring. However, most computational approaches rely on sequence-based target prediction or bulk expression association and are not designed to jointly model regulatory priors, expression context, and heterogeneous cancer states, particularly when matched single-cell microRNA/mRNA co-profiling data are scarce. Methods: We developed a context-aware graph transformer framework for microRNA–gene regulatory analysis across biological resolutions. The framework represents microRNAs, genes, and biological contexts as a heterogeneous graph, where contexts correspond to individual cells in single-cell data and tumor samples or subtype-defined profiles in bulk cohorts. Heterogeneous graph transformer learning generated regulatory embeddings, Bayesian topology optimization refined candidate microRNA–gene interactions, and a dominance-based competition layer with Dominance Share scoring identified master regulators and cooperative target modules. Results: We applied miR-CellMap to matched single-cell miRNA/mRNA co-sequencing data from K562 leukemia cells and paired bulk cancer datasets spanning pan-cancer and subtype-specific cohorts, including breast, colon, glioblastoma, lower-grade glioma, and ovarian cancer. The framework identified recurrent and dataset-specific miRNA regulatory programs, including regulators such as miR-186-5p, miR-214-3p, miR-27a-3p, and let-7 family members. Embedding-derived context analysis showed that predicted miRNA target programs were consistently closer to observed context-specific gene programs than random matched gene programs across all seven datasets. Dominance Share analysis further identified cooperative target modules and co-repressed target programs, supporting the use of miR-CellMap for interpretable cancer-focused miRNA regulatory discovery. Conclusions: This framework provides an interpretable strategy for mapping conserved, cancer-specific, and context-dependent microRNA–gene regulatory programs across single-cell and bulk cancer datasets. Full article

GDSL esterase/lipases (GELPs) are important regulators of plant growth and development, lipid metabolism, and stress responses. However, their genomic characteristics and expression patterns have not been systematically characterized for Juglans mandshurica, a woody oil crop species of significant ecological and economic value. Here, we identified 61 JmGELP genes in J. mandshurica through genome-wide analysis. Phylogenetic analysis classified them into seven major clades, and variations in gene structure and conserved motifs suggested potential functional divergence. Promoter cis-acting element analysis revealed widespread enrichment of motifs responsive to light, phytohormones, and abiotic stresses. Transcriptomic sequencing and qRT-PCR validation revealed distinct tissue-specific and seed development stage-specific expression patterns of JmGELP members, as well as their differential responses to various stress and hormone treatments. Gene Ontology (GO) annotation and protein–protein interaction (PPI) network analyses further supported their involvement in lipid metabolism. In silico analyses of transcription factor binding sites, miRNA targets, and molecular docking predicted that JmGELP-3, -38, and -41 have distinct transcriptional and post-transcriptional regulatory networks and potentially divergent substrate preferences. This study provides the first comprehensive characterization of the GELP family in J. mandshurica, identifying candidate genes that may inform future germplasm improvement and stress-resistance breeding in Juglans species. Full article

Background: Thoracic aortic aneurysm (TAA) is a potentially life-threatening degenerative disease whose principal danger arises from progressive aortic dilation with the attendant risk of rupture and dissection and which is characterized by extracellular matrix breakdown, smooth muscle loss, and endothelial dysfunction. Caveolae, plasma membrane microdomains built from caveolins (CAV1-3) and cavins (CAVIN1-4), govern nitric oxide (NO) signaling, endocytosis, and mechanotransduction. We hypothesized that downregulation of caveolae-associated genes, driven in part by microRNAs, contributes to endothelial failure and vascular remodeling in TAA. Methods: Normalized transcriptomic expression values for five caveolae-associated genes were retrieved from the GSE26155 dataset (43 TAA and 43 control aortas) using GEO2R. Differential expression was assessed for CAV1, CAV2, CAV3, CAVIN1, and CAVIN2, and Spearman correlation with Deming regression explored inter-gene relationships. Functional enrichment (Enrichr) and experimentally validated microRNA-target interactions (miRTarBase) were used to infer regulatory and mechanistic networks. CpG island mapping and gene-gene interactome construction (GeneMANIA) complemented the analyses. Results: CAV1 and CAV2 were downregulated in TAA at nominal significance (CAV1, p = 0.0225; CAV2, p = 0.0361); after Benjamini–Hochberg correction across the five candidate genes both differences attenuated to a consistent trend (q approximately 0.09), while the two caveolins were strongly co-expressed (Spearman r = 0.527, p < 0.001; Deming CAV2 = 1.881 × CAV1-0.892), indicating coordinated transcriptional regulation. Network analysis linked both genes to NOS3, NOSTRIN, EGFR, HRAS, and RAC1, consistent with impaired endothelial nitric oxide and GTPase signaling. Gene Ontology enrichment highlighted endothelial proliferation, nitric oxide metabolism, calcium homeostasis, vesicle organization, and MAPK regulation. Database-supported analysis (miRTarBase) identified miR-93-5p, miR-199a-3p, miR-203a-3p, and the miR-29 family as experimentally validated candidate repressors of CAV1/CAV2. Conclusions: This integrative transcriptomic and microRNA analysis identifies coordinated CAV1 and CAV2 downregulation as a candidate molecular event in thoracic aortic aneurysm, associated with caveolar loss, endothelial dysfunction, and disrupted nitric oxide homeostasis. The CAV1/CAV2-microRNA axis represents a candidate mechanistic signature warranting further investigation as a potential therapeutic target in aortic disease. Full article

MicroRNAs (miRNAs) are central regulators of gene expression and play pivotal roles in plant antiviral defense. In Cucurbitaceae, a globally important crop family including cucumber, melon, and watermelon, viral pathogens such as CGMMV, CMV, and ZYMV represent major constraints on productivity. However, the regulatory complexity of miRNA-mediated antiviral responses in these species remains incompletely understood. This review provides an integrated overview of recent advances in miRNA-guided antiviral immunity in Cucurbitaceae, highlighting the dynamic reprogramming of small RNA pathways upon viral infection. Conserved miRNA families act as key regulatory hubs, controlling development, hormone signaling, and defense responses, while viral suppressors interfere with RNA silencing machinery, reshaping host regulatory networks. Emerging evidence further reveals multilayered interactions between miRNAs and other non-coding RNAs, including lncRNAs and circRNAs, indicating complex cross-talk that fine-tunes antiviral responses in a species- and virus-specific manner. Importantly, miRNAs exhibit a dual role by contributing both to antiviral defense and to symptom development. Advances in artificial miRNAs and RNA-based technologies underscore their potential for engineering durable virus resistance. Overall, miRNA-centered regulatory networks represent a promising target for next-generation crop protection strategies in Cucurbitaceae. Full article

Objective: Exercise training helps preserve skeletal muscle health during aging. However, the molecular responses to different exercise modalities in older adults remain unclear. This study reanalyzed human skeletal muscle transcriptomes to compare signatures associated with combined training, resistance training, and high-intensity interval training. Method: We analyzed the older adult subset of GSE97084. This subset included 46 skeletal muscle RNA-seq samples from 23 participants with paired biopsies before and after training. The dataset included seven paired participants in the combined group, eight in the resistance training (RT) group, and eight in the high-intensity interval training (HIIT) group. We performed paired differential expression analysis, GO/KEGG enrichment analysis, GSEA, WGCNA, PPI analysis, regulatory network analysis, and transcriptome-inferred microenvironment signature analysis. Results: The within-modality paired comparisons identified 264 DEGs in the combined group, 297 DEGs in the RT group, and 1098 DEGs in the HIIT group. A total of 62 DEGs were shared across all three modalities. Combined training was mainly linked to extracellular matrix (ECM) organization, vascular regulation, and mitochondrial oxidative metabolism. RT showed prominent collagen, ECM, integrin, focal adhesion, and structural remodeling signatures. HIIT showed the broadest DEG profile under the current threshold. HIIT was characterized by vascular endothelial, angiogenic, ECM/adhesion, oxidative phosphorylation, and immune-related microenvironment signatures. WGCNA and PPI analyses identified candidate hub gene patterns. ECM and basement membrane genes were more prominent after combined training and RT. Vascular endothelial genes were more evident after HIIT. Regulatory network analysis highlighted miR-29 family members as database-supported candidate regulators of ECM-related hub genes. Transcriptome-inferred microenvironment analysis suggested increased endothelial-related signatures across all modalities. This analysis also suggested increased fibroblast/stromal signatures after RT and HIIT and increased macrophage-related signatures after HIIT. Conclusions: Different exercise modalities were associated with partially overlapping but distinct transcriptomic signatures in aged human skeletal muscle. Combined training and RT were mainly related to ECM, stromal, and structural remodeling signatures. HIIT showed broader vascular endothelial and microenvironment-related signatures. These findings should be interpreted as exploratory because this reanalysis used a modest older adult subset from a single public bulk RNA-seq dataset and lacked an independent validation cohort. Larger studies and complementary experimental validation are needed before drawing definitive conclusions about exercise-modality-specific responses in aged human skeletal muscle. Full article

Background and Objectives: Early diagnosis of acute myocardial infarction (AMI) remains challenging due to the “diagnostic blind window” of conventional protein biomarkers and the limited sensitivity of electrocardiograms in non ST-segment elevation myocardial infarction (NSTEMI). Cardiospecific circulating microRNAs, specifically the microRNA-208 (miR-208) family, have emerged as promising candidates to bridge this gap. This systematic review and meta-analysis evaluated the diagnostic accuracy of circulating miR-208 and outlines a proposed conceptual framework to guide its clinical translation. Materials and Methods: PubMed and Embase were systematically searched up to June 24th, 2026, for clinical studies evaluating the diagnostic performance of circulating miR-208a and/or miR-208b against standard reference definitions for AMI. Risk-of-bias assessment using the QUADAS-2 tool was performed independently by two reviewers. Pooled sensitivity and specificity were estimated using bivariate random effects modeling, and sources of heterogeneity were explored via subgroup analyses. Results: Forty-one studies enrolling 6306 participants were included in the qualitative synthesis, of which 14 were eligible for meta-analysis. The pooled sensitivity and specificity of circulating miR-208 for AMI detection were 0.89 (95% CI: 0.81–0.94) and 0.90 (95% CI: 0.83–0.94), respectively. Marked between-study heterogeneity was observed. Subgroup analyses revealed significantly higher diagnostic accuracy in isolated STEMI (sensitivity: 0.95) or NSTEMI (sensitivity: 0.93) cohorts compared to mixed chest pain populations (sensitivity: 0.65; p < 0.0001). Specificity dropped from 0.90 with healthy controls to 0.80 when using non-AMI controls (p = 0.002), indicating spectrum bias. Funnel plots suggested prominent small-study effects. Conclusions: Circulating miR-208 exhibits a powerful biological signal for the early detection of cardiomyocyte injury, but its standalone clinical utility is constrained by methodological heterogeneity and publication bias. Rather than an immediate clinical tool, future prospective translation requires evaluating this biomarker within the standardized miAMI framework—conceptually prioritizing future investigation of the hyper-acute (<2 h) window, absolute quantification to resolve normalization variability, and integration into multi-marker point-of-care panels. Full article