Search Results (712)

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

Potato (Solanum tuberosum L.) is the world’s fourth-largest staple crop. Alkaline salt stress is a major abiotic stress factor that severely limits the growth, yield, and quality of potatoes; however, little is known about the molecular basis of potatoes’ response to alkaline salt stress or the stress-alleviation mechanism mediated by 24-epibrassinoside. In this study, we conducted a genome-wide identification of the potato miR482 family and analyzed its response patterns under alkaline salt stress and 24-epibrassinoside-mediated stress relief. We identified a total of 9 mature stu-miR482 sequences and 5 precursor sequences; all precursors form typical stable hairpin structures and exhibit high evolutionary conservation among Solanaceae plants. Promoter analysis revealed multiple cis-acting elements in the promoter region associated with light signaling, plant hormones, and stress signaling. A total of 64 potential target genes were predicted, encompassing transcription factors, disease resistance, and signal transduction-related genes, forming a complex regulatory network. Phenotypic analysis confirmed that EBR significantly alleviates the growth inhibition in potatoes induced by alkaline salt stress. qRT-PCR analysis indicated that stu-miR482a-5p is the primary stress-responsive member in leaves; stu-miR482d-3p/5p exhibited the strongest regulatory response to EBR in roots; in potato stolons, all members of the miR482 family were significantly upregulated under alkaline salt stress, with stu-miR482d-5p showing extremely significant upregulation across all treatment groups. In summary, this study represents the first systematic characterization of the potato miR482 family, revealing its tissue differential functions in alkaline salt stress and EBR-mediated stress relief. Full article

Background/Objectives: As important post-transcriptional and epigenetic regulators of gene expression, miRNAs play a pivotal role in modulating host–virus interactions. While prior reviews have addressed either direct miRNA–HIV genome interactions or miRNA-mediated immune modulation in isolation, the integrated dual functionality of these molecules has not been systematically characterized. This review aimed to comprehensively explore how miRNAs that target the HIV-1 genome simultaneously modulate key innate and adaptive host immune signaling pathways. The conceptual novelty of this study is determined not by the identification of previously unknown miRNA-target gene pairs, but by the systemic integration of two regulatory levels (direct inhibition of the viral genome and modulation of the host cell immune signaling pathways) within a unified analytical framework. Such an integrated approach reveals a proviral regulatory network that remains non-obvious when each of these levels is examined separately. Methods: A narrative review was conducted using PubMed, Scopus, Web of Science, and Google Scholar (all years through 2025). In Stage 1, publications reporting experimentally confirmed interactions between host miRNAs and the HIV-1 genome were identified, yielding a curated set of 15 miRNAs. In Stage 2, target genes for each miRNA were retrieved from miRTarBase, TarBase (experimentally validated) and TargetScan 8.0 (in silico predicted). In Stage 3, target genes were manually mapped to key immune signaling pathways (TLR, NF-κB, JAK-STAT). In Stage 4, targeted literature searches were performed for each miRNA–target gene pair to identify direct experimental evidence of interaction. All stages were performed by two independent researchers, with discrepancies resolved by a third. Results: Fifteen host miRNAs with experimentally confirmed binding to the HIV-1 genome were identified, targeting viral genes including nef, pol, vpr, gag, env, vif, and the 3′-UTR. Thirteen of these miRNAs were found to regulate components of major immune pathways. miR-92a-3p, miR-29a/b-3p, miR-150-5p, and miR-125b-5p emerged as the most pleiotropic regulators, simultaneously suppressing TLR signaling (TLR3, TLR7, TLR8, MyD88, TRAF3/6, IRAK1/4), NF-κB components (REL, RELA, NFKB1), JAK-STAT effectors (STAT1–3, STAT5A/B, JAK2), and negative regulators of cytokine signaling (SOCS and PIAS family proteins). miR-133b and miR-196b-5p were found to selectively regulate SOCS/PIAS proteins without involvement in other analyzed pathways, suggesting potential for selective therapeutic targeting. Conclusions: The analyzed miRNAs exhibit functional dualism, acting as direct post-transcriptional suppressors of the HIV-1 genome while simultaneously functioning as epigenetic modulators of host immune signaling. These two modes of action are not independent but together form a conceptual framework of a self-reinforcing proviral regulatory network that, based on the synthesis of published evidence, is proposed to promote viral latency and immune evasion. The identified miRNAs represent promising, albeit complex, targets for novel therapeutic strategies aimed at eliminating latent HIV reservoirs. 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

Heterosis utilization is an effective strategy to improve crop yield, stress resistance, and quality, and has been widely used in crop breeding. Soybean is an important oil and protein crop worldwide with heterosis, but the genetic basis of soybean heterosis remains largely unclear. Whole-transcriptome analysis provides a new technical approach to explore the molecular mechanism of heterosis. In this study, HYBSOY2, a registered soybean hybrid variety with the strongest heterosis in China, together with its female parent JLCMS47A, maintainer line JLCMS47B, and male parent JLR2, were used as experimental material. Whole-transcriptome sequencing was performed using RNA extracted from seedling leaves. After mapping high-quality reads to the soybean reference genome, 57 co-expressed differentially expressed genes (DEGs) were identified in HYBSOY2 compared with both JLCMS47B and JLR2. GO and KEGG enrichment analyses shows that these DEGs were mainly enriched in ADP binding, oxidoreductase activity, fatty acid elongation, and pyruvate metabolism. A total of 787 transcription factors were identified between HYBSOY2 and its parents, most of which shows parental expression-level dominance, with the MYB family accounting for the highest proportion. In addition, 10 differentially expressed lncRNAs were detected between HYBSOY2 and its parents. In the comparison between HYBSOY2 and JLCMS47B, 18 differentially expressed miRNAs were identified, among which up-regulated miR396d functions in promoting leaf development and enhancing drought tolerance. In the comparison between HYBSOY2 and JLR2, 20 differentially expressed miRNAs were found, including down-regulated miR172c which is involved in flowering promotion. A total of 12 DEGs were further verified by qRT-PCR, which may be closely related to soybean heterosis. This study provides a comprehensive transcriptomic profile at the seedling stage of the hybrid soybean and offers valuable information for hybrid soybean breeding. These results lay a foundation for further revealing the molecular mechanism underlying soybean heterosis. Full article

Argonaute (AGO) proteins are central components of RNA silencing. While OsAGO18 is a known defense factor in antiviral immunity, its involvement in basal development and its transcriptomic behavior during fungal stress remains to be fully elucidated. In this study, based on its specific dual-localization in chloroplasts and processing bodies (P-bodies), we investigated the pleiotropic effects of OsAGO18 through transcriptomic network analysis of rice responding to the blast fungus Magnaporthe oryzae B.C. Couch. Our analysis revealed that the OsAGO18-mediated co-expression network is highly correlated with ribosome biogenesis and cell wall organization. Notably, the analyzed datasets reveal that this growth-related network is significantly suppressed upon M. oryzae challenge, highlighting a transcriptomic shift in OsAGO18 during the growth-to-defense transition. Phenotypic evaluations demonstrated that OsAGO18 overexpression accelerates early seedling growth and primary root elongation by promoting endogenous indole-3-acetic acid (IAA) accumulation, whereas ago18 mutants maintain basal growth rates without significant IAA fluctuations, reflecting robust genetic compensation within the highly redundant AGO family. Mechanistically, our integrated analysis suggests that OsAGO18 acts as a putative molecular decoy to sequester miR396d, thereby relieving the repression of the Growth-Regulating Factor OsGRF6 and triggering downstream auxin-dependent cascades. Collectively, our findings highlight OsAGO18 as a pivotal regulator of early seedling development and characterize its transcriptomic responsiveness to biotic stress, providing a plausible molecular link between post-transcriptional RNA regulation and rice growth coordination. 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

Silver Pomfret is increasingly threatened by many diseases under intensive artificial culturing conditions, yet conserved host biomarkers across different infections remain poorly defined. In this study, we integrated transcriptomic datasets from independent infections with Cryptocaryon irritans, Nocardia seriolae, and Photobacterium damselae subsp. damselae to identify shared host-response genes. By combining differential expression analysis with weighted gene co-expression network analysis, we prioritized six candidate genes associated with cross-pathogen infection responses. Random Forest and support vector machine analysis further supported their classification potential across the three infection models. Phylogenetic and structural analyses provided additional evidence for the conserved annotation of these proteins. GSVA-based signature analysis supported the cross-pathogen discriminatory capacity of the six-gene panel and suggested context-dependent contributions of individual genes across infection models. Immune signature analysis indicated distinct host immune response patterns under different pathogenic challenges, and candidate genes showed positive associations with inferred T cell-related signatures. Upstream regulatory prediction identified CTCF and the miR-17/20/93 family as potential regulators of these genes. Quantitative real-time PCR of the kidney further highlighted canx, rnd3, and angptl4 as the most robust infection-responsive candidates, with consistent temporal expression patterns observed from 0 to 24 h post-infection. These findings suggest a potential cross-pathogen host-response pattern in Silver Pomfret and provide preliminary support for future exploration of molecular markers for disease monitoring in aquaculture. 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

Banana productivity is severely limited by drought, yet the molecular basis of drought adaptation and endophyte-mediated stress alleviation remains poorly understood. Here, we performed a genome-wide analysis of the SQUAMOSA promoter-binding protein-like (SPL) transcription factor family in Musa acuminata and examined their transcriptional responses to drought stress and Serendipita indica inoculation. We identified 38 MaSPL genes, all encoding proteins with the conserved SBP domain and predicted nuclear localization. Phylogenetic, motif, gene structure, and collinearity analyses indicated that MaSPL genes are evolutionarily conserved, unevenly distributed across chromosomes, and expanded primarily through segmental duplication under purifying selection. Promoter analysis showed several cis-acting elements and transcription factor binding sites related to light, phytohormone, and stress signaling. Ten MaSPL genes were predicted as putative targets of miR156. qRT-PCR analysis showed that drought stress markedly downregulated the tested MaSPL genes, whereas miR156a expression increased, supporting an inverse regulatory relationship. Under drought, S. indica inoculation enhanced expression of most tested MaSPLs, restoring transcript accumulation while reducing miR156a to near-basal levels. Notable responses were observed in members of the MaSPL2, MaSPL9, and MaSPL13, respectively. S. indica improves drought tolerance by enhancing antioxidant defenses, reducing oxidative stress, and preserving photosynthetic and osmotic stability. Taken together, our results demonstrate that S. indica confers drought resilience in banana by counteracting drought-induced repression of MaSPL genes via the miR156–SPL module and by strengthening key physiological defense mechanisms. Full article

Yellow fever (YF) is an infectious disease caused by the yellow fever virus (YFV), an arbovirus of the Flaviviridae family. It is transmitted through the bite of infected mosquitoes of the Culicidae family and affects both humans and non-human primates (NHPs). This study aimed to investigate the sylvatic Culicidae fauna and the occurrence of natural YFV infection in a microregion of southern Santa Catarina, Brazil, an area recently affected by a sylvatic YF outbreak. Entomological collections were conducted between January and February 2023 in five municipalities with confirmed viral circulation. Natural YFV infection was assessed using RT-LAMP. A total of 4352 female culicids were collected, representing at least 32 species, including several key sylvatic YFV vectors. Haemagogus leucocelaenus was identified in all sampled municipalities, whereas Haemagogus (Haemagogus) janthinomys Dyar, 1921, historically considered the primary vector of sylvatic YFV in Brazil, was not detected. Mosquitoes from the genera Aedes Meigen, 1818; Haemagogus Williston, 1896; Psorophora Robineau-Desvoidy, 1827; and Sabethes Robineau-Desvoidy, 1827 were tested for YFV. Only one pool, composed of Sabethes albiprivus, tested positive, yielding a minimum infection rate (MIR) of 11.6. This is the first record of natural YFV infection in Sa. albiprivus in southern Brazil, and only the third record globally, highlighting its potential role as a secondary vector in maintaining viral circulation in sylvatic environments. Based on species presence and abundance, Hg. leucocelaenus is likely to have acted as the primary YFV vector in the study area. The composition of the culicid fauna, coupled with the detection of YFV in sylvatic vectors, indicates an ongoing epidemiological risk. These findings underscore the need to strengthen entomological surveillance and expand YF vaccination coverage in affected and neighbouring regions. Full article

MicroRNAs (miRNAs) play important roles in the regulation of gene expression and are frequently dysregulated in cancer. Among them, the miR-196 family has been implicated in multiple malignancies, including colorectal cancer (CRC), but the isoform-specific transcriptional effects of miR-196A and miR-196B remain poorly understood. In this study, we generated miR-196A and miR-196B knockout SW48 CRC cell lines using CRISPR-based genome editing and performed RNA sequencing to investigate the transcriptional consequences of individual miR-196 isoform deletion. Transcriptomic analysis revealed widespread gene expression changes in both knockout models and demonstrated distinct clustering patterns between parental SW48 cells and miR-196-deficient cells. Functional enrichment analysis indicated that the altered genes were associated with biological processes related to cytoskeletal organization, intracellular transport, protein folding, and metabolic regulation. Notably, both shared and isoform-specific transcriptional alterations were observed, suggesting that miR-196A and miR-196B contribute to partially overlapping but distinct regulatory networks in CRC cells. Collectively, these findings provide a comprehensive transcriptomic overview of miR-196 isoform deletion in colorectal cancer cells and highlight potential isoform-dependent transcriptional programs that may contribute to CRC biology. Full article