Selenium nanoparticles activate selenoproteins to mitigate septic lung injury through miR-20b-mediated RORγt/STAT3/Th17 axis inhibition and enhanced mitochondrial transfer in BMSCs

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 20, 2025

Sepsis-induced acute lung injury (ALI) remains a critical clinical challenge with complex inflammatory pathogenesis. While bone marrow mesenchymal stem cells (BMSCs) demonstrate therapeutic potential through anti-inflammatory and cytoprotective effects, their age-related functional decline limits utility. This study developed chitosan-functionalized selenium nanoparticles (SeNPs@CS, 100 nm) to rejuvenate BMSCs miR-20b-mediated selenoprotein biosynthesis. Mechanistic investigations revealed that SeNPs@CS-treated exhibited enhanced mitochondrial transfer capacity, delivering mitochondria damaged alveolar epithelial (AECII) for cellular repair. Concurrently, miR-20b upregulation suppressed the RORγt/STAT3/Th17 axis, reducing pro-inflammatory Th17 cell differentiation in CD4+ T lymphocytes. The dual-target mechanism integrates immunomodulation via pathway inhibition rejuvenation therapy, representing paradigm-shifting approach ALI management. These engineered mitigated markers murine models, demonstrating superior efficacy conventional BMSC therapies. Our findings establish SeNPs@CS-modified as novel platform combining nanotechnology-enhanced engineering precision immunometabolic regulation, providing new avenues treatment of sepsis-induced ALI.

Language: Английский

Time-Varying Effects of Glucocorticoid Treatment in Critically III Patients with Severe Fever with Thrombocytopenia Syndrome: An Inverse Probability of Treatment Weighting Analysis

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 5311 - 5327

Published: April 1, 2025

To evaluate the efficacy of glucocorticoid treatment in critically ill patients with severe fever thrombocytopenia syndrome (SFTS) and to assess whether use increases risk fungal infections. A retrospective cohort study was conducted involving confirmed SFTS from a tertiary hospital. After applying Inverse Probability Treatment Weights (IPTW), multivariable Cox regression logistic analyses were utilized impact glucocorticoids on 28-day mortality rate Additionally, landmark analysis time-varying employed effects across different time intervals. The included 112 SFTS, comprising 67 (GC) group 45 non-glucocorticoid (non-GC) group. While did not significantly alter overall (aHR 0.92, 95% CI 0.44-1.93, P = 0.828), it associated notable reduction within first 7 days hospitalization 0.35, 0.15-0.82, 0.016) an increased between 28 4.92, 1.30-18.67, 0.019). Furthermore, linked higher developing infections (aOR 15.22, 4.04-57.38, < 0.001). vary depending disease stage, suggesting that timing administration is crucial. warrants careful consideration when prescribing this population.

Language: Английский

Sepsis-induced immunosuppression: mechanisms, biomarkers and immunotherapy

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 29, 2025

Sepsis, a life-threatening organ dysfunction resulting from dysregulated host response to infection, initiates complex immune that varies over time, characterized by sustained excessive inflammation and immunosuppression. Sepsis-induced immunosuppression is now recognized as major cause of septic death, identifying effective strategies counteract it poses significant challenge. This results the disruption homeostasis, abnormal death effector cells, hyperproliferation suppressor release anti-inflammatory cytokines, expression checkpoints. Preclinical studies targeting immunosuppression, particularly with checkpoint inhibitors, have shown promise in reversing immunocyte dysfunctions establishing resistance pathogens. Here, our review highlights mechanisms sepsis-induced current diagnostic biomarkers, well immune-enhancing evaluated patients therapeutics under investigation.

Language: Английский