Daily Ards Research Analysis

INTRODUCTION: Smoke inhalation injury (SII) is the most common cause of death in burn patients who are victims of fire. The inflammatory response to smoke inhalation is an important factor leading to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), so finding effective anti-inflammatory targets is the key to treating SII. Our previous study demonstrated that bone marrow mesenchymal stem cells (BMSCs) can regulate the M2-type polarization of alveolar macrophages, inhibit the inflammatory response, and have a good therapeutic effect on SII. However, the potential mechanism remains largely unknown. The immune checkpoint molecule CD200 is an important player in the immunomodulatory function of MSCs. However, whether CD200, as an immune molecule that targets macrophages, could be a new anti-inflammatory target for treating SII has not been reported. METHODS: To delineate the role of the immune checkpoint CD200 in this process, we employed an in vitro co-culture system of BMSCs and alveolar macrophages, employing siRNA-mediated knockdown to specifically inhibit CD200 expression in BMSCs. The effects of CD200 knockdown on macrophage polarization and associated molecular pathways were subsequently investigated. For in vivo validation, a rat model of smoke inhalation injury was established to evaluate the therapeutic efficacy of CD200-deficient BMSCs on lung injury and macrophage polarization. RESULTS: Our study revealed that BMSCs significantly promoted the M2-type polarization of alveolar macrophages. In contrast, the ability of BMSCs to promote the conversion of M1 to M2 macrophages was significantly diminished by knocking down CD200. These observations suggest that the regulatory effect of BMSCs on alveolar macrophage polarization is partly mediated through the CD200-CD200R pathway. Mechanistically, this regulation was associated with CD200-CD200R-mediated suppression of c-Jun N-terminal kinase (JNK) activity in alveolar macrophages. In vivo, we further confirmed that CD200 knockdown significantly downregulated the regulatory effect of BMSCs on M1/M2 macrophage polarization in rats with SII, which in turn attenuated the therapeutic effect of BMSCs on lung injury after smoke inhalation. DISCUSSION: Our findings identify the immune checkpoint molecule CD200 as an anti-inflammatory target in the regulation of alveolar macrophages by BMSCs and provide new insights for more effective and precise MSC-based cell therapy.

BACKGROUND: Metabolic reprogramming plays a critical role in various diseases, with particular emphasis on immune cell metabolism. However, the involvement of immune cells and metabolic reprogramming-related genes (MRRGs) in acute respiratory distress syndrome (ARDS) remains underexplored. This study aimed to investigate the molecular mechanisms underlying cell and metabolic reprogramming biomarkers in ARDS. METHODS: Using transcriptomic data from whole blood samples, candidate genes were identified through differential expression analysis and weighted gene co-expression network analysis (WGCNA) in conjunction with MRRGs. Machine learning techniques, expression analysis, and receiver operating characteristic (ROC) analysis were employed to identify potential biomarkers. An artificial neural network (ANN) model was developed and evaluated. Additionally, functional enrichment, regulatory network, and drug prediction analyses were performed. Single-cell analysis was conducted to examine the expression of biomarkers within specific cell populations. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used for biomarker validation in human whole blood samples. The functional validation of candidate biomarkers was performed in lipopolysaccharide (LPS)-induced ARDS mouse models (peripheral blood neutrophils and lung tissues) and THP-1-derived macrophages. RESULTS: Through machine learning algorithms, RPL14, SMARCD3, and TCN1 were identified as candidate biomarkers. ROC analysis demonstrated that the ANN model, incorporating these biomarkers, exhibited strong predictive power for ARDS onset. Enrichment analysis revealed that these genes were linked to various pathways, including the chemokine signaling pathway. The regulatory network analysis suggested that KLF9 may regulate both RPL14 and SMARCD3, with these genes playing a pivotal role in ARDS progression. Furthermore, selenium (CTD 00006731) and Cyclosporine A(CsA)(CTD 00007121) were identified as compounds targeting RPL14 and SMARCD3. Expression levels of the biomarkers varied across different stages of cell differentiation. RT-qPCR confirmed a significant upregulation of SMARCD3 and TCN1 in ARDS samples, aligning with dataset expression analysis results. Both CONCLUSION: SMARCD3 and TCN1 were identified as key biomarkers associated with immune cell and metabolic reprogramming in ARDS, while RPL14 was identified as a candidate biomarker through computational approaches, offering valuable insights for understanding the pathogenesis of the disease.

OBJECTIVES: Acute respiratory distress syndrome (ARDS) represents a significant complication in trauma patients. Yet the epidemiology of ARDS in trauma remains incompletely characterized. We sought to define trends in ARDS frequency and the effect of temporal, patient, and center-level factors on outcomes with the hypothesis that ARDS independently predicts mortality. DESIGN: Retrospective cohort study. SETTING: Hospitals submitting data to the American College of Surgeons National Trauma Data Bank. PATIENTS: Injured patients 18 years old or older from 2007 to 2019 on mechanical ventilation (MV) for greater than or equal to 2 days were included, and patients with ARDS were compared with those without ARDS. A subgroup with transfusion data was also identified. Multivariable logistic regression models by year adjusted for patient demographics, center characteristics, and blood products identified factors independently associated with ARDS diagnosis and 30-day hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 384,032 injured patients on MV, ARDS was documented in 29,359 (8 per 100 MV patients) with a significant decrease over the study period (22 in 2007 vs. 3 in 2019, p < 0.001). Patient-level risk factors independently associated with ARDS were blunt injury (odds ratio [OR] 1.25; 95% CI, 1.20-1.30), severe sepsis (OR 2.16; 95% CI, 2.06-2.27), ventilator-associated pneumonia (OR 2.91; 95% CI, 2.82-3.00), and acute kidney injury (AKI, OR 2.98; 95% CI, 2.85 to 3.12). In the transfusion subset, 24-hour plasma (OR 1.02; 95% CI, 1.01-1.04) and platelets (OR 1.03; 95% CI, 1.02-1.05) were independently associated with ARDS. Crude ARDS mortality increased over the study period (2007, 15.1% vs. 2019, 29.7%, p < 0.001), and after adjusting for significant differences, ARDS was independently associated with 30-day hospital mortality (OR 1.32; 95% CI, 1.27-1.37). Independent risk factors for 30-day mortality in patients with ARDS included head injury (OR 1.54; 95% CI, 1.43-1.66), severe sepsis (OR 1.48; 95% CI, 1.34-1.63), and AKI (OR 2.72; 95% CI, 2.50-2.96). Patients with ARDS managed in Prevention and Early Treatment of Acute Lung Injury and the Extracorporeal Life Support Organization centers were less likely to die (OR 0.78; 95% CI, 0.72-0.84). CONCLUSIONS: From 2007 to 2019, ARDS decreased significantly in trauma patients. Over the same time, mortality increased to nearly 30%, and after adjusting for other risks factors, ARDS was strongly associated with 30-day mortality. Future studies should examine modifiable patient and center-level factors to improve mortality in these high-risk patients.