Daily Ards Research Analysis

BACKGROUND: Acute lung injury (ALI) is a critical pathophysiological response in various respiratory diseases characterized by alveolar damage and excessive inflammation. It can progress to acute respiratory distress syndrome, with current treatments showing limited efficacy and considerable side effects. Psoralen (Pso), derived from Psoralea corylifolia l., has anti-inflammatory properties, but its role in ALI remains fully elucidated. PURPOSE: This study aimed to investigate the therapeutic effects of Pso on ALI, and to explore its therapeutic targets and mechanisms. METHODS: The therapeutic potential of Pso was assessed using a model of ALI induced by lipopolysaccharide (LPS). The direct target was investigated using alkynyl-Psoralen (A-Pso) for chemical proteomic analysis, and a series of molecular biology methods were used to explore the underlying mechanism. RESULTS: Pso treatment significantly alleviated LPS-induced lung injury in mice, targeted macrophages, and inhibited the LPS-induced activation of macrophages. Target-fishing experiments identified high-mobility group box-1 (HMGB1) as a direct target of Pso in macrophages. FTS and CETSA confirmed Pso binding to HMGB1, and LC-MS/MS analysis indicated a covalent interaction between Pso and Cys106 of HMGB1. Furthermore, Pso covalently targeted Cys106, affecting HMGB1 binding to TLR4 and downregulating the phosphorylation of NF-κB, indicating the inhibition of the TLR4/NF-κB signaling pathway both in macrophages and in lung tissues of ALI mice. These findings suggest that Pso exerts its therapeutic effects by covalently targeting HMGB1 in macrophages and modulating the TLR4/NF-κB signaling pathway. CONCLUSION: This study not only found that Pso improves LPS-induced ALI inflammation by targeting macrophages, but also verified that this mechanism of action is mainly caused by Pso covalently targeting Cys106 of HMGB1, inhibiting the HMGB1-TLR4 interaction, and thereby suppressing cytokine storm generation. As the first naturally derived HMGB1 covalent inhibitor with a clear binding site, Pso plays an important role in HMGB1 induced inflammatory diseases and is an active precursor for the development of new HMGB1 covalent inhibitors.

The administration of exogenous surfactant is essential for many premature infants to compensate for pulmonary immaturity and the absence of endogenous surfactant at birth. Exogenous surfactant delivery techniques are continually being refined to improve the management of these infants, with the goal of increasing therapeutic efficacy and decreasing the invasiveness of delivery protocols. Imaging is one of the tools available to achieve these goals. In this study, we established and applied an magnetic resonance imaging (MRI) protocol in a rabbit animal model to determine the intrapulmonary distribution of surfactant solution administered by the clinical reference method. The protocol was applied to an ex vivo model of isolated thorax from non-valued food industry by-products. The protocol made it possible to image surfactant biodistribution with isotropic spatial resolution in the millimeter range, to determine surfactant distribution between the main airways and distal lung regions where alveoli are present using automated segmentation techniques, and to quantitatively map the distribution of the administered surfactant solution.

BACKGROUND: Despite the high mortality and economic burden associated with the acute respiratory distress syndrome (ARDS), the role of chest radiograph (CXR) in ARDS diagnosis and prognosis remains uncertain. The purpose of this study is to elucidate clinical characteristics that distinguish ARDS patients from those without ARDS, especially in patients where CXRs are indicative of ARDS. METHODS: Secondary analysis of a prospective observational study with 454 postoperative septic patients under mechanical ventilation (MV). Patients were stratified in two groups depending on whether they met the Berlin criteria for ARDS. Primary outcome was identification of clinical characteristics differentiating patients with ARDS confirmed by CXR from non-ARDS patients. Secondary outcome was 60-day in-hospital mortality of postoperative sepsis-induced ARDS. RESULTS: One hundred thirty-nine patients (30.6%) had CXRs compatible with ARDS, although ARDS was confirmed in only 45 patients (9.9%). Emergency surgery (OR 6.6), abdominal source of infection (OR 6.0), pneumonia (OR 8.2), and higher lactate (OR 3.9) were clinical features associated with ARDS development confirmed by CXR. ARDS was an independent risk factor for 60-day mortality (OR 1.8). CONCLUSION: Although CXR criteria for ARDS diagnosis could be replaced in future definitions, its importance for ARDS diagnosis should not be underestimated.