Search Results (702)

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

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

Epstein–Barr virus (EBV) is a highly prevalent oncogenic virus that establishes persistent infection in most of the human population and is strongly associated with several lymphoid and epithelial malignancies, particularly nasopharyngeal carcinoma, gastric carcinoma, and lymphoepithelial carcinoma. This review summarizes current knowledge on the relationship between EBV infection and apoptosis regulation in epithelial cancers, with emphasis on how viral persistence may contribute to tumor cell survival and therapeutic resistance. The manuscript reviews evidence on EBV genome organization, latent and lytic infection programs, the epidemiology of EBV-associated epithelial tumors, and the main intrinsic and extrinsic apoptotic pathways. It then discusses how viral proteins, including latent membrane proteins, Epstein–Barr nuclear antigen 1 (EBNA1), BHRF1, and BARF1, as well as EBV-encoded microRNAs, modulate key apoptotic regulators such as p53, Bcl-2 family members, death receptor pathways, and caspases. Current evidence indicates that EBV can promote apoptosis resistance through coordinated effects on mitochondrial and death receptor-mediated cell death. Understanding these mechanisms may help clarify the contribution of EBV to epithelial oncogenesis and support therapeutic strategies aimed at restoring apoptotic sensitivity in EBV-associated tumors. 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

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

Uridine diphosphate glucuronosyltransferase 2B (UGT2B) enzymes constitute a critical subgroup of phase II metabolizing enzymes that modulate the clearance of steroid hormones, carcinogens, and numerous anticancer agents, thereby influencing cancer susceptibility, progression, and therapeutic outcomes. This review provides a comprehensive synthesis of the genetic, regulatory, and functional roles of UGT2B family members, particularly UGT2B4, UGT2B7, UGT2B10, UGT2B15, UGT2B17, and UGT2B28, in oncogenesis and cancer treatment. We summarize evidence from molecular, epidemiological, pharmacogenetic, and clinical studies demonstrating how UGT2B expression patterns, polymorphisms, copy number variations, epigenetic regulation, and microRNA-mediated control shape intratumoral hormone homeostasis, carcinogen detoxification, and drug resistance across multiple malignancies, including prostate, breast, lung, colorectal, hematological, and hormone-dependent cancers. UGT2B enzymes metabolize several widely used anticancer drugs and active metabolites, thereby affecting pharmacokinetics, efficacy, and toxicity. Understanding the context-specific roles of UGT2B family members offers a compelling opportunity for therapeutic exploitation. In particular, rational combination strategies incorporating UGT2B inhibitors or modulators alongside standard anticancer agents may enhance drug effectiveness without increasing dosage, while simultaneously enabling the dose reduction of the partner agent to mitigate dose-dependent toxicities. Such approaches are especially relevant for therapies with narrow therapeutic indices. Overall, this review highlights UGT2B enzymes as multifunctional determinants of cancer risk and treatment response and underscores their promise as biomarkers and actionable targets for precision oncology and optimized combination regimens. Full article

Objective: This study aims to explore the effects of exercise on gut microbiota and short-chain fatty acid (SCFA) metabolism, as well as its relationships with joint degeneration. Methods: To explore the impact of exercise on obesity-associated osteoarthritis (OA), rats were fed a high-fat/high-sucrose (HFS) diet with or without exercise. Histological staining and micro-computed tomography (micro-CT) were used to assess the effects of exercise on articular cartilage and subchondral bone. 16S rRNA sequencing and Gas Chromatography–Mass Spectrometry (GC-MS) were performed to analyze alteration in fecal gut microbiota and serum SCFAs. Results: Exercise prevented articular cartilage degeneration and subchondral bone loss in the HFS diet with exercise (HE) group compared to the HFS-diet control sedentary (HS) group. Gut microbiota analysis revealed that exercise reduced the relative abundances of families Lachnospiraceae, Ruminococcaceae, genera Ruminococcus, Colidextribacter, Caproiciproducens, and the unidentified genus of Lachnospiraceae, while increased the relative abundance of genus Akkermansia. Metabolomic analysis indicated exercise prevented AA reduction in the HE group. In addition, the level of AA was negatively correlated with OA severity and with the abundances of families Lachnospiraceae and Ruminococcaceae, genus Colidextribacter and the unidentified genus of Lachnospiraceae. Conclusions: Exercise effectively preserves the integrity of the cartilage–subchondral bone unit. The observed modifications in gut microbiota and AA levels following exercise intervention may be associated with the protective mechanisms against obesity-associated OA. 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

Aberrant expression of multiple microRNAs has been reported in gastric cancer. In particular, microRNA-597 has been associated with poor survival rates but is not yet well characterized. Seventy-five clinical samples, four cell lines, and two patient-derived organoids were evaluated for the expression of microRNA-597 and its target genes. microRNA-597 was transiently transfected for analysis of cell migration, invasion, wound healing, colony formation, and cell viability, and its regulation by long non-coding RNAs was explored using the TCGA-STAD and LncBook tools. In clinical samples, low expression of microRNA-597 was associated with the intestinal subtype (p = 0.002) and stages III and IV (p = 0.048). All functional readouts were reduced after microRNA-597 transfection, including colony formation, in patient-derived organoids. Among target genes, RUNX1 was directly regulated by microRNA-597. Other cell invasion genes were dependent on RUNX1 as a hub for regulation. Analysis of the Intersection between long non-coding RNAs co-expressed with RUNX1 and those with the highest microRNA-597 prediction binding identified KCNQ1OT1 as the top transcript. Silencing of KCNQ1OT1 and co-expression in clinical samples suggest the existence of a KCNQ1OT1/microRNA-597/RUNX1 network. The results indicate that microRNA-597 directly suppresses RUNX1, while KCNQ1OT1 modulates this interaction. Our approach enabled the simultaneous analysis of dysregulation in three families of transcripts in gastric cancer progression. Full article

Spermatogenesis is a highly coordinated biological process in which diploid spermatogonia undergo mitotic expansion, meiotic division, and terminal differentiation into haploid spermatozoa. This process is tightly regulated by intrinsic germ cell programs and extrinsic signals from Sertoli cells within the seminiferous epithelium. Among the signaling pathways governing male germ cell development, all-trans retinoic acid (RA), a bioactive metabolite of vitamin A, has emerged as a master regulator of meiotic initiation and spermatogonial differentiation in mammals. RA functions through nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which regulate transcriptional networks essential for germ cell progression, including the activation of Stimulated by Retinoic Acid 8 (STRA8), a key determinant of meiotic entry. Intratesticular RA homeostasis is maintained by a balance between synthesis via aldehyde dehydrogenase (ALDH) enzymes and degradation by cytochrome P450 family 26 (CYP26) enzymes, ensuring precise temporal and spatial control of germ cell development. While rodent models have defined core mechanisms of RA signaling, the canine testis provides a valuable comparative and translational system due to its physiological similarity to human spermatogenesis and relevance to reproductive management. Recent studies highlight conserved RA signaling pathways in dogs, including receptor-mediated transcriptional regulation, feedback control of RA metabolism, and post-transcriptional modulation via microRNAs. Importantly, pharmacological manipulation of RA signaling can reversibly disrupt spermatogenesis, supporting its potential applications in non-hormonal male contraception. This review integrates molecular, developmental, pharmacological, and comparative evidence and presents RA signaling as a central regulatory axis of spermatogenesis with important translational applications. Full article

Soil cadmium (Cd) pollution has emerged as one of the key environmental issues threatening the safety of agricultural products worldwide, yet clean and low-cost intervention strategies that reduce Cd accumulation in edible crops without disrupting agricultural production remain scarce. Grafting onto tolerant rootstocks represents an emerging clean agronomic technology that achieves in situ Cd risk reduction within a single growing season. However, the molecular mechanisms by which rootstocks regulate scion phenotypes remain poorly understood. MicroRNAs (miRNAs) act as critical long-distance signals in plants, yet their roles in rootstock-mediated growth promotion and Cd reduction remain largely unclear. In this study, we used Solanum torvum as rootstock and purple eggplant (Solanum melongena) as scion to investigate growth, fruit quality, Cd accumulation, and miRNA-mediated regulatory mechanisms. Grafting significantly increased plant height (by 18%), stem diameter (by 12%), and yield without obvious effects on fruit quality. Under Cd stress, the Cd content in grafted eggplant fruits was reduced by 76%, whereas leaf potassium (K), calcium (Ca), and magnesium (Mg) contents were elevated by 21%, 17%, and 10%, respectively. High-throughput sequencing and quantitative real-time polymerase chain reaction identified five key differentially expressed miRNAs, including miR164a and miR166b, four of which were related to Cd stress. Gene Ontology (GO) enrichment analyzes that their target genes were mainly involved in hormone signal transduction and ion transport. Further validation suggested that grafting improved growth and reduced Cd accumulation by regulating genes of the NAC, SPL, and HD-ZIP III families. These results suggested that suitable rootstocks can enhance crop productivity and reduce toxic metal accumulation in edible parts through miRNA-mediated regulation. Full article

HD-ZIP III genes encode important transcription factors that play a crucial role in plant development and are regulated by microRNAs (miRNA). Although previous studies have examined the functions of rice HD-ZIP III genes using overexpression lines, the developmental consequences of increased expression of the rice OSHB3 gene under native regulatory conditions remain unclear. In this study, we isolated a gain-of-function mutant carrying mutations in the miRNA target site of the OSHB3 gene, a member of the HD-ZIP III family, and examined its morphology at multiple developmental stages. Gene expression was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization. Our results reveal that ectopic expression of the OSHB3 gene is associated with the differentiation pattern of meristems in rice and that a correlation exists between OSHB3 expression levels and phenotypic severity in the mutants. These findings highlight the importance of precise spatial and quantitative regulation of HD-ZIP III genes in rice development. Full article

Crohn’s disease (CD) is a chronic immune-mediated inflammatory disorder characterized by transmural inflammation and a progressive course that frequently leads to structural complications such as intestinal fibrosis. Fibrostenosing disease represents a major clinical challenge, affecting up to 50% of patients over time and often requiring surgical intervention. Despite advances in anti-inflammatory therapies, no effective treatments currently exist to prevent or reverse established fibrosis. Intestinal fibrosis arises from a dysregulated tissue remodeling process driven by excessive extracellular matrix deposition and persistent activation of mesenchymal cells, particularly fibroblasts and myofibroblasts. This process is orchestrated through complex interactions between immune and non-immune cells and mediated by key signaling pathways, including transforming growth factor beta (TGF-β1) and the TL1A/DR3 axis. Genetic susceptibility, notably variants in NOD2 and other fibrosis-related genes, contributes not only to disease risk but also to phenotype progression. Epigenetic mechanisms, particularly microRNAs such as the miR-29 and miR-200 families, further modulate fibrogenesis and represent promising non-invasive biomarkers. Additionally, intestinal dysbiosis and specific microbial signatures, including reduced short-chain fatty acid-producing bacteria and the presence of adherent-invasive Escherichia coli, play a critical role in promoting fibrotic pathways. Mesenteric adipose tissue, especially creeping fat, also contributes to fibrosis through immune and metabolic signaling. Emerging biomarkers related to collagen metabolism and advances in molecular profiling are improving early detection strategies. Novel therapeutic approaches targeting fibrogenic pathways, including anti-TL1A agents, show promising preliminary results. A deeper understanding of these mechanisms is essential to develop effective antifibrotic therapies and improve long-term outcomes in CD. Full article

Exosomal microRNAs (miRNAs) are key mediators of intercellular communication in the breast cancer tumor microenvironment (TME), facilitating bidirectional signaling between malignant cells and the desmoplastic stroma. This review explores current evidence on their dual roles as drivers of stromal remodeling and as circulating biomarkers of therapeutic resistance across major breast cancer subtypes, including triple-negative breast cancer (TNBC), hormone receptor-positive (ER+/PR+) disease, and HER2-amplified tumors. We outline how miR-9, miR-21, and miR-181 family members promote cancer-associated fibroblast (CAF) activation, increase extracellular matrix (ECM) stiffness, and sustain a reverse Warburg phenotype. We then detail subtype-specific resistance mechanisms: miR-181 family members suppress BCLAF1 to block doxorubicin-induced apoptosis; miR-221/222 downregulates ESR1 and p27Kip1 to confer tamoxifen resistance; miR-155 impairs homologous recombination in TNBC; and miR-1246 sustains PI3K/AKT signaling in HER2-positive disease. We also evaluate circulating exosomal miRNA panels as liquid biopsy tools for predicting chemotherapy response and tracking resistance emergence. Finally, we discuss therapeutic strategies including antagomirs, miRNA replacement therapy and engineered exosome platforms, and address key challenges such as assay standardization and regulatory hurdles, that must be overcome for clinical translation. Full article