Immune-mediated mechanisms in acute osteofascial compartment syndrome: insights from multi-omics analysis

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: Feb. 5, 2025

Acute Osteofascial Compartment Syndrome (AOCS) stands as a critical surgical emergency, often secondary to various diseases. Its clinical manifestation arises from increased pressure within the fascial compartment, resulting in diminished tissue perfusion and consequential ischemic damage. Presently, diagnostics lack effective biological markers, patients face grim prognosis, experiencing muscle contractures, necrosis, amputations, renal failure, even mortality. The primary treatment, fasciotomy, poses infection risks potential nerve Hence, there is an urgent need for research elucidating AOCS's pathogenic mechanism exploring novel treatments. To address this, we established rat model of AOCS, extracting toe flexor muscles both experimental control groups. Employing second-generation high-throughput sequencing, obtained comprehensive mRNA, lncRNA, circRNA, miRNA data. Comparative analysis expression differences between AOCS groups, followed by in-depth examination, allowed us unravel intricacies occurrence multi-omics perspective. Our findings indicate that immune-mediated inflammatory disease, primarily involving immune cells, especially neutrophils. In addition, genes associated with ferroptosis, form regulated cell death, are found be upregulated model, non-coding RNAs playing role regulatory interactions. These results suggest neutrophils may undergo thereby enhancing inflammation responses which promotes disease progression. Furthermore, these reveal interactions molecules pathways significant deeper understanding pathogenesis development targeted therapeutic strategies.

Language: Английский

Study on the Mechanism of Artesunate in Modulating AR Epithelial Injury and Th2-Type Inflammatory Status

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 5329 - 5342

Published: April 1, 2025

To evaluate the therapeutic efficacy of Artesunate (ART) in a mouse model allergic rhinitis (AR) induced by house dust mite (HDM) and explore its underlying mechanism. Transcriptome sequencing (RNA-seq) analysis identified differentially expressed genes (DEGs) nasal mucosa between healthy mice, with Gene Set Enrichment Analysis (GSEA) revealing STING pathway activation. We established (HDM)-induced via intraperitoneal sensitization. was evaluated through dose-response testing (10-30 mg/kg), 30 mg/kg as optimal dose. Mice were stratified into four groups: normal control (NC), NC+ART, AR model, AR+ART-treated. Interventions administered intraperitoneally, followed systematic evaluation of: ① behavioral symptoms (sneezing/nasal scratching), ② histopathological changes lung tissues, ③ serum TH2 cytokine levels, ④ mucosal protein expression profiles. With increasing concentrations (10, 20, there significant improvement inflammatory status mice. The cGAS-STING signaling determines degree epithelial tissue damage systemic TH2-type inhibits pathway, protects mitochondrial structure improves status. This study presents new treatment approach for respiratory allergies clarifying how alleviates rhinitis, identifying effective dosage ranges, demonstrating potential developing ART- cGAS-STING-targeted therapies, ultimately advancing clinical translation.

Language: Английский