Plasmodium Infection Modulates Host Inflammatory Response through circRNAs during the Intracellular Stage in Red Blood Cells

ACS Infectious Diseases, Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

The integration of RNA- and DNA-based assays enables the investigation disease dynamics, specifically assessing role asymptomatic or subclinical infections in malaria transmission. Circular RNAs (circRNAs), a distinct category noncoding RNAs, are implicated numerous pathogenic mechanisms. As now, research has yet to explore circRNAs' function infection. findings revealed that Plasmodium infection upregulated 60 circRNAs downregulated 71 BALB/c mice. We selected 11 differentially expressed (DE) according prediction target miRNA-mRNA coding protein, these were further confirmed by validation experiments. IRESfinder, GO, KEGG evaluations indicated 7 DE possess protein-coding potential enriched MAPK signaling cascade. In P.y17XL-infected mouse models, substantiated dynamic characteristics correlated with inflammation, NF-κB cascades activated, also contributing inflammatory reaction during This study establishes Plasmodium-induced circRNA expression as novel mechanism which parasite modulates host immune signaling, advancing understanding Plasmodium–host cell interactions. addition, 42 found normal mice, 25 discovered excluding 1238 shared changes profile host, altered involved response possibly regulates reverse splicing pre-mRNA m6A modification RNA, inducing production host.

Язык: Английский

Analysis of shared pathogenic mechanisms and drug targets in myocardial infarction and gastric cancer based on transcriptomics and machine learning

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 21, 2025

Background Recent studies have suggested a potential association between gastric cancer (GC) and myocardial infarction (MI), with shared pathogenic factors. This study aimed to identify these common factors pharmacologic targets. Methods Data from the IEU Open GWAS project were used. Two-sample Mendelian randomization (MR) analysis was used explore causal link MI GC. Transcriptome identified differentially expressed genes, followed by enrichment analysis. Drug target MR eQTLs validated associations GC, Steiger direction test confirmed their direction. The random forest Lasso algorithms genes diagnostic value, leading nomogram construction. performance of model evaluated via ROC, calibration, decision curves. Correlations immune cell infiltration analyzed. Results linked increased GC risk ( OR =1.112, P =0.04). Seventy-four which are related mainly ubiquitin-dependent proteasome pathways, commonly Nine consistently associated eight had value. built on strong predictive AUC =0.950, validation set =0.957). Immune revealed significant correlations several cells, such as T macrophages, neutrophils, B dendritic cells. Conclusion is an developing both share constructed based 8 value good performance.

Язык: Английский

LncRNA NR_045147 modulates osteogenic differentiation and migration in PDLSCs via ITGB3BP degradation and mitochondrial dysfunction

Stem Cells Translational Medicine, Год журнала: 2024, Номер unknown

Опубликована: Дек. 14, 2024

Abstract Periodontitis is an inflammation of the alveolar bone and soft tissue surrounding teeth. Although mesenchymal stem cells (MSCs) have been implicated in periodontal regeneration, mechanisms by which they promote osteogenesis remain unclear. We examined whether epigenetic modifications mediated long-noncoding RNA (lncRNA) NR_045147, plays a crucial role cancer, influence osteogenic differentiation ligament (PDLSCs). Alkaline phosphatase staining, alizarin red western blotting were used to detect effects NR_045147 on PDLSC differentiation. Scratch migration transwell chemotaxis assays evaluate migration. Mitochondrial function was evaluated via Seahorse XF analysis measure changes cellular respiration upon manipulation expression. Ubiquitination performed examine protein stability degradation pathways affected NR_045147–MDM2 interaction. An vivo nude rat calvarial defect model established gene-edited PDLSCs re-implanted NR_045147. significantly reduced ability both vitro vivo. Under inflammatory conditions, loss rescued osteogenesis. blocked expression integrin beta3-binding (ITGB3BP). Mechanistically, promoted ITGB3BP-MDM2 interaction, thus increasing ITGB3BP ubiquitination degradation. regulated mitochondrial upregulation efficiently their ability. Concluding, downregulation enhances migration, connects metabolism functional outcomes respiration, promotes mediating its interaction with MDM2.

Язык: Английский