Background: Inflammation and apoptosis play important roles in the initiation and progression of acute lung injury (ALI). Our previous study has shown that progranulin (PGRN) exerts lung protective effects during LPS-induced ALI. Here, we have investigated the potential roles of PGRN-targeting microRNAs (miRNAs) in regulating inflammation and apoptosis in ALI and have highlighted the important role of PGRN. Methods: LPS-induced lung injury and the protective roles of PGRN in ALI were first confirmed. The function of miR-34b-5p in ALI was determined by transfection of a miR-34b-5p mimic or inhibitor in intro and in vivo. Results: The PGRN level gradually increased and subsequently significantly decreased, reaching its lowest value by 24 h; PGRN was still elevated compared to the control. The change was accompanied by a release of inflammatory mediators and accumulation of inflammatory cells in the lungs. Using bioinformatics analysis and RT-PCR, we demonstrated that, among 12 putative miRNAs, the kinetics of the miR-34b-5p levels were closely associated with PGRN expression in the lung homogenates. The gain- and loss-of-function analysis, dual-luciferase reporter assays and rescue experiments confirmed that PGRN was ta functional target of miR-34b-5p. Intravenous injection of miR-34b-5p antagomir in vivo significantly inhibited miR-34b-5p up-regulation, reduced inflammatory cytokine release, decreased alveolar epithelial cell apoptosis, attenuated lung inflammation and improved survival by targeting PGRN during ALI. Conclusion: miR-34b-5p knockdown attenuates lung inflammation and apoptosis in an LPS-induced ALI mouse model by targeting PGRN. This study shows that miR-34b-5p and PGRN may be potential targets for ALI treatments. This article is protected by copyright. All rights reserved

Cigarette smoke can cause endoplasmic reticulum stress and induce apoptosis, both of which are important pathogenic factors contributing to chronic obstructive pulmonary disease. The aim of the present study was to produce a cigarette smoke extract (CSE)‑induced apoptosis human bronchial epithelial cell (HBEpC) model, to investigate the protective effects of resveratrol (RES). The role of oxygen‑regulated protein 150 (ORP150) in the RES‑induced activation of Sirtuin 1 (SIRT1) was additionally studied. Cultured HBEpCs were initially treated with CSE to induce apoptosis, followed by an incubation either with or without RES. Numerous techniques were used to evaluate the outcomes of the present study, including cell counting kit‑8 assay, quantitative polymerase chain reaction, western blotting, Hoechst 33342 staining and AnnexinV‑PI flow cytometry apoptosis analyses, and gene knockdown. It was identified that 24 h 2% CSE incubation induced apoptosis in HBEpC, accompanied by an overexpression of the apoptosis molecular markers CCAAT‑enhancer‑binding protein homologous protein, caspase 4 and caspase 3. Pre‑treatment of the cells with RES markedly alleviated the severity of apoptosis, as confirmed by apoptosis analyses and the expression levels of the apoptosis molecular markers. SIRT1 was shown to be overexpressed following RES treatment. However, following the gene knockdown of ORP150, the anti‑apoptotic effects of RES were significantly attenuated. The results of the present study demonstrate that RES may have a protective effect against CSE‑induced apoptosis, and a molecular pathway involving SIRT1 and ORP150 may be associated with the anti‑apoptotic functions of RES in HBEpC.

Purposes: To explore the value of metagenomic next-generation sequencing (mNGS) in diagnosing pneumocystis jiroveciipneumonia (PJP) in the immunocompromised patients.Methods: Data of 122 patients with PJP in an immunosuppressed state and 67 non-PJP patients were collected. The diagnostic efficacy of mNGS was compared with the conventional methods, including Gomori methenamine silver (GMS) staining and serum (1,3)-β-D-glucan (BDG). Changes of anti-microbial therapy for patients with PJP based on mNGS results were also reviewed.Results: The diagnostic sensitivity of mNGS to PJP was higher than that of GMS and BDG (100% vs. 15 and 74.5%, p < 0.001). The diagnostic specificity (91.%) was lower than that of GMS (100%), and similar with BDG (89.6%). In addition to P. jirovecii, mNGS revealed co-pathogens like human β-herpesvirus 5, human γ-pesvirus 4, and some other opportunistic pathogens. The reads of mNGS were remarkably higher in BALF than in blood samples. Initial antimicrobial treatment was modified in 89.3% patients based on the mNGS results, and 74 cases (60.7%) were treated with anti-P. jirovecii therapy.Conclusion: mNGS is highly efficient in diagnosing PJP and good at identifying pathogens in mixed infections.