Search Results (978)

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

Heart failure with preserved ejection fraction (HFpEF) is an increasingly common form of heart failure (HF) that is best understood as a systemic, multiorgan syndrome rather than a disease of left-ventricular filling alone. This review has three specific aims: first, to synthesize genetic and molecular pathways that are most relevant to non-ischemic HFpEF; second, to distinguish HFpEF-enriched mechanisms from evidence extrapolated from ischemic cardiomyopathy or HFrEF; and third, to consider translational implications for populations with high consanguinity, including the Kingdom of Saudi Arabia. The available evidence indicates that chronic inflammatory signaling involving CCL2, CCL5, TLR3, PTGS2/COX-2, IL-6/JAK/STAT3, NF-kB, and NLRP3 acts upstream of endothelial dysfunction, nitric-oxide/cGMP/PKG impairment, mitochondrial reactive oxygen species generation, and fibroblast activation. Extracellular-matrix regulators including ASPN, COL1A1, and MMP2 then amplify collagen deposition and myocardial stiffness, whereas mitochondrial genes and proteins such as ATP5C1 contribute to impaired oxidative phosphorylation, reduced ATP reserve, defective fatty-acid oxidation, and blunted mitophagy. Protein-quality-control pathways involving HSP90AA1, CCT2/CCT5, PSMA3, and stress-responsive STAT3 further link metabolic stress to proteotoxic injury. Epigenetic mechanisms, including DNA methylation and microRNAs such as miR-155, miR-1297, and miR-4649-3p, add a regulatory layer that may improve risk stratification but remains insufficiently validated for routine clinical use. In high-consanguinity settings, recessive cardiomyopathy variants can cluster in families and contribute to earlier NIHF presentations; however, population-level HFpEF-specific variant frequencies remain limited, and findings from HFrEF or dilated cardiomyopathy should be interpreted as candidate pathway evidence rather than definitive HFpEF markers. Translationally, SGLT2 inhibitors, mineralocorticoid-receptor antagonism, biomarker panels, and structured genetic evaluation provide the most clinically actionable bridge from molecular mechanisms to precision HFpEF care. Full article

Cynops orientalis, a member of the Salamandridae family, can regenerate severely injured limbs throughout its lifespan. The molecular mechanisms regulating limb regeneration in C. orientalis remain largely unknown. SERCA1 (sarcoplasmic/endoplasmic reticulum calcium ATPase 1) is a major sarco/endoplasmic reticulum calcium pump in skeletal muscle, and our previous transcriptomic sequencing results showed increased SERCA1 mRNA expression during the early stages of newt limb regeneration. In the present study, we investigated the role and regulatory mechanism of SERCA1 during newt limb regeneration by using a limb-amputation model, shRNA-mediated knockdown, Thapsigargin-mediated SERCA1 inhibition, miRNAomics analysis, dual-luciferase reporter assays and Agomir therapy. Knockdown of SERCA1 expression or suppression of SERCA1 activity impaired skeletal muscle cell dedifferentiation, disrupted AEC and blastema formation, reduced cell proliferation, and significantly delayed limb regeneration compared with control animals. Through miRNAomics analysis and in vitro dual-luciferase reporter assays, we identified miR-20487-5p as a negative regulator of SERCA1 expression in C. orientalis. In vivo treatment with miR-20487-5p Agomir down-regulated SERCA1 expression resulted in limb-regenerative defects. Mechanistically, shRNA-SERCA1 or miR-20487-5p Agomir treatment reduced ERK phosphorylation in regenerating limb tissue, suggesting an association between the miR-20487-5p/SERCA1 axis and MAPK/ERK activation. Taken together, our study supports the significant role of the miR-20487-5p/SERCA1/MAPK/ERK axis in early newt limb regeneration. This study expands the current understanding of molecular mechanisms initiating newt limb regeneration. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and significant neuropathological changes. Early and accurate diagnosis remains a major challenge, highlighting the need for reliable, minimally invasive biomarkers. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, have emerged as promising candidates. Their expression is altered in the brains of AD patients, reflecting disease-specific pathological processes, and they are detectable in peripheral biofluids. However, discrepancies in miRNA profiles between the brain and the circulation, and between patient populations remain a significant limitation, raising questions about their origin, transport across the blood–brain barrier, and their reliability in reflecting central nervous system pathology. This review provides a comprehensive overview of current research comparing miRNA expression profiles in brain tissue and blood in AD, with a focus on their biological relevance, mechanisms of release and transport, and diagnostic potential. We also discuss the challenges associated with cross-tissue variability, methodological inconsistencies, and the need for standardized approaches. Finally, we highlight future directions, including multi-tissue analyses and integration with other noninvasive modalities, to improve the clinical utility of miRNA-based biomarkers in AD. Full article

Metabolic syndrome (MeS) is a major risk factor for cardiovascular disease and is characterized by chronic low-grade inflammation, immune dysregulation, and metabolic abnormalities. However, the molecular mechanisms linking MeS to diabetic coronary artery disease (DMCAD) remain incompletely understood. Publicly available peripheral blood mononuclear cell (PBMC) transcriptomic datasets of MeS and DMCAD were analyzed using an integrative bioinformatics approach. Differentially expressed genes (DEGs) were identified using the limma package, followed by functional enrichment, protein–protein interaction (PPI) network construction, weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis (GSEA), and miRNA regulatory network analysis. Candidate genes were further evaluated using an independent type 2 diabetes mellitus (T2DM) dataset for external transcriptomic validation. Integrated analyses identified immune-inflammatory and immuno-metabolic pathways as central features of both MeS and DMCAD. Enrichment analyses highlighted cytokine signaling, leukocyte activation, chemotaxis, complement activation, oxidative stress, and vascular inflammatory responses. Network analyses identified CD86, CD33, CCR1, C5AR1, FPR1, CXCL16, and LILRA5 as key hub genes associated with immune regulation and cardiometabolic dysfunction. External transcriptomic validation supported the relevance of CD33, CD86, and LILRA5. miRNA network analysis identified members of the miR-17/92 family and miR-146a-5p as potential upstream regulators. TAM 2.0 enrichment analysis further linked these miRNAs to metabolic syndrome, diabetes mellitus, atherosclerosis, coronary heart disease, immune response, inflammation, and angiogenesis. Our findings suggest that coordinated immune-inflammatory and metabolic signaling networks contribute to the progression from MeS to DMCAD. The identified hub genes and miRNAs may serve as potential biomarkers and therapeutic targets for inflammation-driven cardiometabolic disease. Full article

Laccases (EC 1.10.3.2, LAC) are copper-containing glycoproteins involved in lignin biosynthesis, and as such, they play important roles in plant development and stress responses. In this study, a genome-wide analysis of the LAC gene family was performed in Pinus massoniana (Chinese red pine), identifying 78 PmaLAC genes, all predicted to encode cell membrane-localized proteins. These genes were unevenly distributed across eight chromosomes, with notable clusters on chromosomes 7 and 8, indicating gene duplication-driven expansion in P. massoniana. Phylogenetic analysis revealed that PmaLAC genes are classified into five subfamilies, reflecting the lineage-specific expansion and evolutionary divergence of gymnosperm LAC genes. Conserved motif and gene structure analyses showed high conservation among PmaLAC proteins. Promoter analysis identified numerous cis-acting elements related to hormone signaling, stress, and light responses. RNA-seq analysis revealed distinct tissue-specific expression patterns for PmaLAC gene family members. Moreover, degradome analysis combined with dual-luciferase assays supported the interaction between miR397c-9 and PmaLAC31, suggesting that miR397c-9 negatively regulates PmaLAC31 and indicating a potentially conserved miRNA-mediated regulatory mechanism. Overall, this study provides a systematic overview of the composition, evolution, and potential regulation mechanisms of the PmaLAC gene family in P. massoniana, providing a useful resource for future functional characterization of PmaLAC genes. Full article

The use of inhaled corticosteroids (ICs) could influence the respiratory microbiota. In animals with asthma it is, however, difficult to separate the immunomodulatory effects of ICs from their indirect effects via improvement of ventilation. Our objective was to determine if ICs alter the pulmonary microbiota independently from their effects on lung function, using a blinded, controlled trial in an experimental model of asthma exacerbation in horses. We treated horses with severe asthma with either bronchodilators alone, or in combination with ICs. Twelve horses in exacerbation received long-acting β2-agonist (LABA, salmeterol) or ICs/LABA (fluticasone/salmeterol) by inhalation, for 2 weeks. Lung function and bronchoalveolar lavages (BAL) were performed before and after treatment. 16S rRNA gene quantification and sequencing were performed on BAL fluid, using digital droplet PCR and the Illumina MiSeq platform. Data were processed using the software package mothur v. 1.44.2. In the LABA group, pulmonary bacterial load and the relative abundance of Actinobacteria and Verrucomicrobia phyla decreased with treatment (p < 0.05 for both), and β-diversity differed from baseline (p = 0.007). The relative abundance of families and genera belonging to the Bacteroidetes phylum increased with ICs/LABA (p < 0.05). Lung function significantly improved with both treatments, suggesting that treatment-related differences in pulmonary microbiota could be attributed in part to medication, not solely to change in ventilation. However, it is not clear if these changes are positive or detrimental to the lung environment. Furthermore, lung function following treatment was not perfectly identical between groups. Full article

Type 2 diabetes mellitus (T2DM) is a major driver of chronic kidney disease and cardiovascular morbidity worldwide. Extracellular vesicles (EVs), particularly exosomes, carry microRNAs (miRNAs) that reflect the pathophysiological state of their parent cells and represent promising non-invasive biomarkers. This review comprehensively examines the diagnostic and mechanistic roles of EV-derived miRNAs in diabetic nephropathy (DN) and cardiovascular diseases (CVDs) associated with T2DM. A PRISMA-guided literature search of PubMed, Scopus, Web of Science, and Embase identified 847 articles published between January 2020 and June 2026, of which 156 studies met the inclusion criteria. Several urinary exosomal miRNAs demonstrated significant diagnostic performance for DN, including miR-4534 (AUC = 0.786), miR-136-5p (sensitivity 72.2%, specificity 78.4%), and miR-142-3p. A meta-analysis of circulating miRNAs in diabetic kidney disease reported a pooled AUC of 0.79. In the cardiovascular setting, exosomal miR-155-5p (AUC = 0.901), miR-15a-3p (AUC = 0.874), and a four-miRNA panel (miR-433-3p/let-7b/miR-30-5p/miR-122-5p; AUC = 0.833) demonstrated strong diagnostic performance for ischemic heart disease and carotid atherosclerosis in T2DM. Mechanistically, key EV-associated miRNAs, including miR-21, miR-192, and the anti-fibrotic miR-29 family, participate in fibrosis, inflammation, oxidative stress, endothelial dysfunction, and cardiac remodeling pathways. EV-derived miRNAs therefore represent highly promising non-invasive biomarkers for the early diagnosis and monitoring of diabetic renal and cardiovascular complications. However, clinical translation requires standardized EV isolation and miRNA detection protocols, together with validation in large multicenter prospective cohorts. This review highlights the considerable diagnostic and translational potential of EV-derived miRNAs for precision medicine and liquid biopsy applications in T2DM complications. Full article