MicroRNAs in vascular smooth muscle cells: Mechanisms, therapeutic potential, and advances in delivery systems

Life Sciences, Год журнала: 2025, Номер unknown, С. 123424 - 123424

Опубликована: Янв. 1, 2025

Язык: Английский

---

Altered microRNA Expression Correlates with Reduced TLR2/4-Dependent Periodontal Inflammation and Bone Resorption Induced by Polymicrobial Infection

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 12, 2025

ABSTRACT Periodontitis (PD) is a polymicrobial dysbiotic immuno-inflammatory disease. Toll-like receptors (TLRs) are present on gingival epithelial cells and recognize pathogen-associated molecular patterns (PAMPs) pathogenic bacteria, induce the secretion of proinflammatory cytokines, initiate innate adaptive antigen-specific immune responses to eradicate invading microbes. Since PD chronic inflammatory disease, TLR2/TLR4 plays vital role in disease pathogenesis maintaining periodontium during health. Many factors modulate TLR-mediated signaling pathway, including specific miRNAs. The study was designed characterize function TLR2/4 miRNA profile after polybacterial infection with Streptococcus gordonii, Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia C57BL6/J wild-type, TLR2 −/− , TLR4 mice (n=16/group) using RT-qPCR. selection 15 dominant miRNAs for RT-qPCR analysis based prior NanoString global expression profiling response monobacterial infection. Polybacterial infections established colonization induction bacterial-specific IgG. A significant reduction alveolar bone resorption (ABR) inflammation observed mandibles compared wild-type ( p <0.0001). Periodontal bacteria disseminated from tissue multiple organs (heart, lungs, brain, kidney) limited heart F. nucleatum ), lungs P. gingivalis kidney T. ) mice. diagnostic potential assessed by receiver operating characteristic (ROC) curves. Among miRNAs, three were upregulated mice, two seven Notably, anti-inflammatory miR-146a-5p consistently all Additionally, miR-15a-5p let-7c-5p downregulated Multi-species oral bacterial alters pathways modulating several biomarker periodontium. IMPORTANCE most prevalent immuno-infectious multispecies cavity. (TLR) provide first line defense, one best-characterized pathogens-detection systems play recognizing microbial products. Multispecies periodontal S. induced inflammation, whereas did not increase ABR deficient investigated, miR-146a - 5p, miR-146a-5p, miR-30c-5p, sham-infected controls. uniquely among different groups. (miR-146a, miR-15-a-5p, let-7c-5p) could be markers TLRs-mediated periodontitis.

Язык: Английский

---

Prognostic factors of MINOCA and their possible mechanisms

Preventive Medicine Reports, Год журнала: 2024, Номер 39, С. 102643 - 102643

Опубликована: Фев. 4, 2024

Despite not showing substantial stenosis of coronary arteries, Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) presents myocardial ischemia injury, thus having a grave prognosis and high risk long-term complications. This necessitates increased clinical attention exploration its root causes to prevent similar crisis.

Язык: Английский

---

In silico analysis of hub genes and regulatory networks implicates the putamen in non-motor Parkinson’s disease disorders

Egyptian Journal of Medical Human Genetics, Год журнала: 2025, Номер 26(1)

Опубликована: Янв. 20, 2025

Abstract Background Parkinson’s disease (PD) is a neurodegenerative condition marked by the gradual degeneration of dopaminergic neurons in substantia nigra, leading to depletion nigra as well and decreased activity putamen. This study aims identify role putamen non-motor PD symptoms potential therapeutic target PD. Methods Transcriptome profiles (dataset number: GSE205450, obtained from postmortem caudate samples forty controls thirty-five patients) were retrieved Gene Expression Omnibus (GEO) database. Specifically, we focused on data for patients. Differential gene expression analysis was carried out using with Limma, filtering genes |logFC|> 1 (fold change) p < 0.05 ( -value). Protein–Protein Interaction networks constructed stringDB (combined score > 0.7) analyzed Cytoscape hub based various topological measures (EPC, MCC, MNC, Degree, EcCentricity). Enrichment conducted Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG). Also, transcription factor (TF)-hub networks, miRNA-hub association JASPAR database, Tarbase DisGeNET via NetworkAnalyst platform, respectively. Results Seven genes, namely SST , NPY IL6 PVALB ALB NTS TH identified Notable miRNAs included hsa-mir-34a-5p, hsa-mir-15a-5p, hsa-mir-424-5p, hsa-mir-19b-3p while key factors include GATA2, CREB1, FOXC1, FOXL1, TID1, NFKB1, YY1, SPIB, GATA3, STAT3 . Conclusions Our findings revealed close associations between such major depressive disorder, mood disorders schizophrenia. These may provide new direction developing therapy wet lab research encouraged.

Язык: Английский

---

Clinical significance analysis of microRNA-199a-3p in gingival crevicular fluid for patients with chronic periodontitis

Molecular and Cellular Probes, Год журнала: 2025, Номер 80, С. 102015 - 102015

Опубликована: Фев. 12, 2025

Язык: Английский

---

Machine learning-based transcriptmics analysis reveals BMX, GRB10, and GADD45A as crucial biomarkers and therapeutic targets in sepsis

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 31, 2025

Sepsis is a life-threatening condition characterized by dysregulated host response to infection, resulting in high mortality rates and complex clinical management. This study leverages transcriptomics machine learning (ML) identify critical biomarkers therapeutic targets sepsis. Analyzing microarray data from the Gene Expression Omnibus (GEO) datasets GSE28750, GSE26440, GSE13205, GSE9960, we discovered three pivotal that BMX (bone marrow tyrosine kinase gene on chromosome X), GRB10 (growth factor receptor bound protein 10), GADD45A arrest DNA damage inducible alpha), exhibiting exceptional diagnostic accuracy (AUC >0.9). Functional enrichment analyses revealed these genes play key roles reactive oxygen species metabolism immune regulation. Specifically, was positively correlated with eosinophils inversely associated activated NK cells, CD8 T memory CD4 cells. showed positive correlations eosinophils, mast neutrophils, while linked M2 macrophages. Additionally, constructed comprehensive mRNA-miRNA-lncRNA regulatory network, identifying interactions may drive sepsis pathogenesis. Molecular docking dynamics simulations validated Bendroflumethiazide, Cianidanol, Hexamidine as promising agents targeting biomarkers. In conclusion, this integrated approach provides profound insights into molecular mechanisms underlying sepsis, pinpointing BMX, GRB10, targets. These findings significantly enhance our understanding of pathophysiology lay groundwork for developing personalized strategies aimed at improving patient outcomes.

Язык: Английский

---

Human umbilical cord mesenchymal stem cell-derived exosomal miR-199a-3p inhibits the MAPK4/NF-κB signaling pathway to relieve osteoarthritis

World Journal of Stem Cells, Год журнала: 2025, Номер 17(4)

Опубликована: Апрель 21, 2025

There is currently no effective treatment for osteoarthritis (OA), which the most common joint disorder leading to disability. Although human umbilical cord mesenchymal stem cells (hUC-MSCs) are promising OA treatments, their use limited by condition itself, and understanding of underlying mechanisms lacking. To explore specific molecular mechanism hUC-MSC-derived exosomal miR-199a-3p improves OA. Sodium iodoacetate was injected into rat articulations construct an animal model Interleukin (IL)-1β used induce chondrocytes (CHON-001) chondrocyte model. Exosomes in hUC-MSCs were isolated using Ribo™ Exosome Isolation Reagent. Real-time reverse transcriptase-polymerase chain reaction western blotting detect expression related genes proteins, damage CHON-001 articular cartilage tissue evaluated enzyme-linked immunosorbent assay, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling staining hematoxylin eosin staining. exosomes (hUC-MSC-Exos) inhibited IL-1β-induced inflammatory cytokines, namely, IL-6, IL-8 tumor necrosis factor-α. hUC-MSC-Exos also improved viability but apoptosis cells, pathological alleviated development vivo. Mechanistically, downregulated mitogen-activated protein kinase 4 delivering miR-199a-3p, thereby inhibiting activation nuclear factor-kappaB signaling pathway, alleviating inflammation apoptosis, ultimately improving alleviates 4/nuclear pathway. The present findings suggest that delivery may be a novel strategy

Язык: Английский

---

Investigating the regulation of the miR-199a-3p/TGF-β/Smad signaling pathway by BSHXF drug-containing serum combined with ADSCs for delaying intervertebral disc degeneration

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 28, 2025

Intervertebral disc degeneration (IDD) significantly contributes to low back pain (LBP), yet effective treatment options are scarce. BSHXF, a classical traditional Chinese medicine formula, demonstrates dual pharmacological actions: tonifying kidneys, strengthening bones, activating blood circulation, and resolving stasis. It has been widely used in IDD management. Given its potential, combining BSHXF with miRNA regulation stem cell therapy may enhance therapeutic outcomes by targeting molecular cellular pathways underlying pathogenesis. is recognized as one of the primary causes pain, interventions for this condition remain limited. This study explores role drug-containing serum combined adipose-derived cells (ADSCs) slowing progression via miR-199a-3p/TGF-β/Smad signaling pathway. By comprehensively investigating synergistic effects combination therapy, we aim propose novel multi-target strategy that addresses complex pathogenesis IDD. employed vivo vitro models. An model was induced rat caudal intervertebral discs through needle puncture, while an oxidative stress-induced ADSCs injury created using tert-butyl hydroperoxide (T-BHP). Cell viability measured CCK-8 assay. cycle distribution mitochondrial reactive oxygen species (ROS) levels were assessed flow cytometry. Cellular senescence SA-β-galactosidase staining. Lactate dehydrogenase (LDH) activity quantified evaluate damage. Differentiation into nucleus pulposus-like immunofluorescence double staining CD73 COL2A1. ELISA measure inflammatory cytokines (TNF-α, IL-1β, IL-4, IL-10) supernatants. miR-199a-3p expression determined RT-qPCR. Western blotting quantify COL2A1, SOX9, ACAN protein levels, reflecting differentiation extracellular matrix (ECM) synthesis capacity. assess pathway analyzing expressions TGF-β1, Smad2, Smad3, their phosphorylated forms, P-Smad2 P-Smad3. In experiments histopathological hematoxylin-eosin (HE) Safranin O-Fast Green Immunohistochemistry (IHC) analyzed COL1A1 COL2A1 levels. RT-qPCR expression. P-Smad2, P-Smad3 evaluation. Our experimental results demonstrated containing alleviated T-BHP-induced stress, improved microenvironment, promoted proliferation, decelerated senescence. Further mechanistic analysis revealed activated TGF-β/Smad pathway, driving restoring normal progression. Overexpression inhibited leading ECM degradation elevated factors IL-1β). contrast, restored downregulating overexpression exacerbated IDD, characterized reduced expression, increased fibrosis. intervention markedly attenuated reducing fibrosis, effectively collagen promote cells. exerted protective alleviating stress damage, improving delaying senescence, enhancing functions. first reveal exacerbates fibrosis degeneration. thereby structure function. integrated approach offers demonstrating significant potential.

Язык: Английский

---

miR-205-3p Inhibits Porphyromonas Gingivalis Lipopolysaccharide-Induced Human Umbilical Vein Endothelial Cells Inflammation and Apoptosis by Targeting PRMT5

Archives of Oral Biology, Год журнала: 2025, Номер 175, С. 106276 - 106276

Опубликована: Апрель 29, 2025

Язык: Английский

---

miRNA Differential Expression Profile Analysis and Identification of Potential Key Genes in Active Tuberculosis

Journal of Cellular and Molecular Medicine, Год журнала: 2025, Номер 29(10)

Опубликована: Май 1, 2025

ABSTRACT Tuberculosis (TB), caused by Mycobacterium TB (MTB), remains a significant global health issue, particularly in developing nations. MicroRNAs (miRNAs) are non‐coding RNAs (ncRNAs) that modulate immune responses and play pivotal role the pathogenesis of MTB altering host defences. Insights into regulatory functions these miRNAs have revealed mechanisms through which evades surveillance establishes persistent infections, highlighting critical miRNA networks pathogenesis. The purpose this study was to analyse expression plasma from patients, predict target genes, construct elucidate roles Plasma samples three patients with active healthy controls were analysed using high‐throughput small RNA sequencing. DEMs identified DESeq2, genes predicted via TargetScan miRWalk. Protein–protein interaction (PPI) constructed STRING Cytoscape. Functional enrichment analyses performed Gene Ontology (GO) KEGG databases. A total 23 identified, including 17 upregulated 6 downregulated miRNAs. hsa‐miR‐15a‐5p emerged as most significantly miRNA. PPI network analysis highlighted CCND1, CDK6 CCND2 central potentially regulated miR‐15a‐5p. GO pathways related cell cycle regulation, kinase activity protein complex formation, suggesting their involvement This identifies its key components landscape TB. These findings offer new insights molecular propose potential biomarkers therapeutic targets for future research.

Язык: Английский

---