BackgroundRecent studies have proved that autophagy dysfunction in proinflammatory cells is involved in tissue damage and an excessive inflammatory response in sepsis. In the present study, we identified that the human antimicrobial peptide LL-37 facilitates resistance to DNase II-induced mitochondrial DNA (mtDNA) degradation and subsequent autophagy.Material/MethodsWe found higher serum levels of LL-37 in patients with severe sepsis compared to that in patients with mild sepsis. Neutrophils isolated from mice with sepsis after treatment with Cramp-mtDNA produced an excess of proinflammatory cytokines, including IL-1β, IL-6, IL-8, MMP-8, and TNF-α. Cramp-mtDNA in the lung samples from model animals with sepsis was detected by immunohistochemical staining.ResultsExogenous delivery of Cramp-mtDNA complex significantly exacerbated lung inflammation but the antibody against Cramp-mtDNA attenuated the excessive inflammatory response in LPS-induced acute lung injury. The expression of proinflammatory cytokines in lungs was upregulated and downregulated after treatment with the complex and antibody, respectively. LC-3 expression in 16HBE cells increased after LPS induction, irrespective of stimulation with LL-37.ConclusionsThese data show that LL-37 treatment worsens local inflammation in sepsis-induced acute lung injury by preventing mtDNA degradation-induced autophagy.
Human adenovirus (HAdV) is one of the most common respiratory pathogens affecting children. HAdV infection has high morbidity and mortality, and it may lead to severe complications and long-term pulmonary sequelae. However, the pathogenesis of pediatric HAdV-7-induced sepsis remains unclear. The analysis of DNA methylation profiles in peripheral blood is attracting increasing attention as an effective method for investigating the pathogenesis of various diseases and identifying biomarkers of disease progression. Here, we performed reduced representation bisulfite sequencing to analyze DNA methylation in peripheral blood samples collected from 11 children with HAdV-7-induced sepsis and 5 healthy children. The Metilene software was used to analyze differential methylation in the two groups. We also performed functional enrichment analysis of the genes with differentially methylated regions (DMRs). We detected 1,138 DMRs between the two groups. Additionally, 122 DMRs were detected between the HAdV-7-induced sepsis survivor and non-survivor groups. After screening based on biological and clinical significance, we found that a group of genes (KCNQ1OT1, KPNB1, GRB10, HOXA5, HOXA4, and BCL9L) with differential methylation played an essential role in Wnt signaling. Additionally, genes related to the Wnt/β-catenin signaling pathway, such as MEG3, GNAS-AS1, and GNAS, exhibited differential methylation in the survivor and non-survivor groups. Our data suggest that specific patterns of DNA methylation are associated with the occurrence and progression of HAdV-7-induced sepsis. Wnt signaling was also affected by the changes in methylation. Thus, we identified potential biomarkers and therapeutic targets for pediatric HAdV-7-induced sepsis.
Pulmonary Agenesis (PA) is a rare congenital malformation of lung development, and patients with comorbid Pulmonary Hypertension (PH) have substantially increased morbidity and mortality risks. We describe five pediatric cases born with unilateral PA who developed PH. By integrating our findings with those of 7 previously published case reports, we aim to provide a more complete description of disease features, prognosis, and the most effective treatment strategies. We found that male PA patients and those with right-side agenesis were more likely to develop PH. Moreover, half of these comorbid patients had congenital heart disease with left-to-right shunt. Early diagnosis and treatment, including surgical and medical interventions, are critical for preservation of cardiopulmonary function. All PA cases should receive regular cardiopulmonary function tests starting at an early age.
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