Daily Ards Research Analysis

ETHNOPHARMACOLOGICAL RELEVANCE: Xuanbai Chengqi Decoction (XCD), a classic formula from the Qing Dynasty treatise Wen Bing Tiao Bian, has traditionally been used in Traditional Chinese Medicine (TCM) to treat pulmonary infections with features of heat and obstruction. These historical indications coincide with the pathophysiology of severe pneumonia and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the molecular mechanisms, particularly epigenetic ones, remain unclear. AIM OF THE STUDY: To clarify the protective effects of XCD on lipopolysaccharide (LPS)-induced ALI and elucidate the underlying epigenetic mechanism centered on the EZH2/EGR1/TXNIP axis. MATERIALS AND METHODS: An ALI model was induced in mice by intraperitoneal injection of LPS. Additionally, a cellular model was established using LPS-stimulated J774A.1 macrophages. Lung histology, lung wet-to-dry (W/D) ratio, and cytokine levels (TNF-α, IL-6, IL-1β) were evaluated. Bioactive constituents were identified by UPLC-HRMS, and potential EZH2-binding compounds were predicted through molecular docking and molecular dynamics simulations. RNA-seq was used to identify key pathways. RT-qPCR, Western blotting, and immunofluorescence were performed to validate key molecular targets. Pharmacological inhibition with 3-deazaneplanocin A (DZNep) and EZH2-knockout mice were utilized to confirm the essential role of EZH2. RESULTS: XCD alleviated lung edema, inflammation, and cytokine release in ALI mice and reduced macrophage activation in vitro. Mechanistically, XCD elevated EZH2 expression and H3K27me3 levels, thereby epigenetically suppressing EGR1 and TXNIP transcription. This inhibition attenuated NLRP3 inflammasome activation and oxidative stress. Critically, these protective effects were abolished by pharmacological EZH2 inhibition or genetic knockout, establishing EZH2 as an indispensable mediator of XCD's therapeutic efficacy. Chemical profiling identified diverse bioactive constituents, including emodin, rutin, epicatechin, and polydatin. Computational analyses suggested that emodin and polydatin form stable complexes with EZH2's catalytic domain. CONCLUSIONS: XCD exerts protective effects against LPS-induced ALI by enhancing EZH2 expression, which epigenetically represses the EGR1/TXNIP pro-inflammatory pathway. Emodin and polydatin are identified as candidate bioactive constituents that may directly interact with EZH2. This study provides mechanistic support for the traditional use of XCD and identifies EZH2 activation as a potential therapeutic strategy for inflammatory lung diseases.

BACKGROUND: Pediatric acute respiratory distress syndrome (PARDS), often triggered by viral infections, is a life-threatening condition. Despite its severity, children demonstrate significantly better survival rates and superior lung repair compared to adults. However, the mechanisms underlying this age-specific advantage remain incompletely understood. PATIENTS AND METHODS: We conducted a pilot multi-omics study of influenza-associated PARDS integrating single-cell RNA sequencing (scRNA-seq) of pediatric lung tissue and bronchoalveolar lavage fluid (BALF), spatial transcriptomics, and plasma proteomics. Analyses were harmonized with the Human Lung Cell Atlas (HLCA) reference, reanalysis of public pediatric PARDS airway scRNA-seq, and contextual comparisons to adult lethal COVID-19 lung. RESULTS: Tissue scRNA-seq and spatial data indicated outcome-linked divergence in PARDS. Survivor showed spatially restricted repair with preserved alveolar type II (AT2) cells, AT2-to-alveolar type I (AT1) differentiation signatures, and higher KRT17, whereas fatal case and adults exhibited diffuse immune activation with pro-fibrotic and pro-apoptotic signaling. In BALF, KRT17-positive airway stress-repair epithelial cells (hillock-like) increased from the acute to recovery phase, and plasma proteomics showed higher circulating KRT17 in survivors. HLCA-based label transfer strengthened cell-type definitions and enabled pediatric-adult comparisons suggesting biological and developmental differences; the adult lethal COVID-19 atlas provided a benchmark with attenuated epithelial repair and prominent collagen CTHRC1-pathologic fibroblasts. Fibroblast programs were regionally compartmentalized, with injury-enriched CTHRC1 CONCLUSIONS: This pilot multi-omics case series outlines putative pediatric lung repair niches in influenza-associated PARDS. KRT17-positive transitional epithelium, preserved AT2 differentiation, and restoration of resident-like macrophages may align with recovery, whereas diffuse immune activation and CTHRC1-enriched fibroblast programs may accompany worse outcomes. HLCA-guided annotations and adult benchmarks indicate possible age-related differences, warranting validation in larger multi-center cohorts.

BACKGROUND: Extremely low birth weight (ELBW) infants, which weighing less than 1000 g, are at high risk of adverse neonatal outcomes, including intraventricular hemorrhage (IVH), respiratory distress syndrome, and long-term neurodevelopmental impairments. En caul cesarean section (ECCS) is often performed for delivery of ELBW infants to minimize potential damages to the skin, bones, and brain. Although a few studies reported that ECCS is a safe procedure for infants, there is limited research investigating the association between this procedure and neonatal IVH. This study aims to assess whether ECCS contributes to adverse effects during delivery, and association with the occurrence of neonatal IVH. METHODS: We retrospectively examined 252 ELBW infants delivered at our hospital from April 2015 to December 2023. Patients were divided into four groups according to delivery mode: successful ECCS, unsuccessful ECCS, non-trial ECCS, and vaginal delivery. The primary outcome was the incidence of IVH grade ≥ 3 during the neonatal period. The secondary outcomes were hemoglobin level of the infant, umbilical artery blood pH level, and maternal blood loss at delivery. RESULTS: No significant differences were observed in the median umbilical artery blood pH levels, Hb levels of infants at delivery, the amounts of maternal blood loss at delivery, incidence of IVH grade ≥ 3, intestinal perforation, or neonatal mortality between the group of patients who were attempted en caul cesarean delivery and the group of patients who were not. The incidence of IVH grade ≥ 3 was significantly lower in the group of successful ECCS compared with the other groups (4.8% vs. 15.8%, respectively; p < 0.05). The significant factors for IVH grade ≥ 3 identified on multivariate analysis were gestation week at delivery ≤ 24 weeks (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.33-6.62), steroid administration (OR 0.10, 95% CI 0.01-0.77) and successful ECCS (OR 0.29, 95% CI 0.09-0.87). CONCLUSION: ECCS for ELBW infants may reduce the risk of neonatal IVH grade ≥ 3, and does not contribute to anemia and hypoxia of infants at delivery.