Metformin enhanced the effect of pirfenidone on pulmonary fibrosis in mice.

BACKGROUND: The aim of the study is to observe the anti-inflammatory and antioxidative stress effects of metformin on bleomycin (BLM)-induced pulmonary fibrosis in mice. METHODS: Mice with BLM-induced pulmonary fibrosis were treated with pirfenidone, metformin, pirfenidone plus metformin and the NADPH oxidase 4 (NOX4) inhibitor diphenyleneiodonium chloride (DPI). Pathological changes and hydroxyproline (HPO) levels were examined in the lung tissue of mice with pulmonary fibrosis. Superoxide dismutase (SOD) activity and malonaldehyde (MDA) levels in lung tissue were determined. RESULTS: Compared with pirfenidone, pirfenidone plus metformin could reduce alveolar damage and collagen fibre deposition and alleviate BLM-induced pulmonary fibrosis. Lung HPO levels were significantly lower in the PFD + MET group than in the BLM group (p < 0.05). SOD levels in the lungs of mice were increased in the PFD + MET group than in the BLM group (p < 0.05). Metformin and pirfenidone plus metformin can reduce MDA levels (p < 0.05). Pirfenidone plus metformin could reduce HPO levels, increase SOD levels, and reduce MDA levels in the lungs of mice. There was a significant correlation between the HPO level and the Ashcroft score (r = 0.520, p < 0.001). CONCLUSION: Metformin enhanced the antifibrotic effects of pirfenidone on BLM-treated mice. Moreover, these findings provide an experimental basis for examining whether metformin can improve the antifibrotic effects of pirfenidone on patients with idiopathic pulmonary fibrosis (IPF). It has broad therapeutic prospects for patients with IPF.

Long non­coding RNA FGD5­AS1/microRNA­133a­3p upregulates aquaporin 1 to decrease the inflammatory response in LPS­induced sepsis.

Sepsis is a systemic inflammatory response syndrome caused by infections. The present study aimed to investigate the potential mechanism of FGD5­AS1 in sepsis and lipopolysaccharide (LPS)­induced inflammatory response. An animal model of sepsis was constructed. LPS was used to induce mice HL­1 cardiomyocytes to construct a cell model. The association between FGD5­AS1 and miR­133a­3p was investigated through animal and cell models. FGD5­AS1 overexpression was used to analyze the effect of FGD5­AS1 on inflammatory reaction. Tumor necrosis factor (TNF)­α, interleukin (IL)­1ß and IL­6 levels were detected by enzyme­linked immunosorbent assay and reverse transcription­quantitative polymerase chain reaction. The interaction of FGD5­AS1, miR­133a­3p and aquaporin 1 (AQP1) was detected by dual­luciferase reporter assay and microRNA (miRNA/miR) pull­down assay. Compared with the control group, the expression of FGD5­AS1 was decreased and the expression of miR­133a­3p was increased in the sepsis group. FGD5­AS1 overexpression increased LPS­induced expression of FGD5­AS1 and AQP1, decreased the expression of miR­133a­3p, and inhibited the expression of the inflammatory cytokines, TNF­α, IL­6 and IL­1ß. Dual­luciferase reporter and miRNA pull­down assays confirmed the interaction of FGD5­AS1, miR­133a­3p and AQP1. These results indicated that FGD5­AS1 is the competitive endogenous RNA of miR­133a­3p on AQP1, and thus FGD5­AS1 overexpression may be able to inhibit the inflammatory response in sepsis.

Application of metagenomic next-generation sequencing technology for difficult lung lesions in patients with haematological diseases.

BACKGROUND: The purpose of this study was to evaluate the diagnostic value of combined virtual bronchoscopic navigation (Direct Path), radial endobronchial ultrasound with guide-sheath (EBUS), ultrathin bronchoscopy, rapid on-site evaluation of cytology (ROSE), and metagenomic next-generation sequencing (mNGS) for difficult lung lesions in patients with haematological diseases. METHODS: In this study, lung specimens were obtained from patients with haematological diseases by transbronchial lung biopsy (TBLB) and bronchoalveolar lavage (BAL). The specimens were subjected to mNGS for sequencing of pathogenic microorganisms and sent to the laboratory for examination and pathological analysis. Additionally, the clinical data and pathogenic characteristics of the patients were analysed. The sensitivity and specificity of mNGS for sequencing pathogenic microorganisms were compared between TBLB and BAL specimens. RESULTS: In this study, the diagnosis of infectious pneumonia mainly included cytomegalovirus pneumonia, Pneumocystis jirovecii pneumonia (PCP), pulmonary aspergillosis, and tuberculosis. Some patients had non-infectious pulmonary complications, and the clinical and therapeutic outcomes were diagnosed as graft-versus-host disease (GVHD), idiopathic pneumonia syndrome (IPS), and delayed pulmonary toxicity syndrome (DPTS). The sensitivity of mNGS for pathogenic microbes in lung tissue is better than that of alveolar lavage fluid, whereas compared with alveolar lavage fluid, its specificity is reduced. CONCLUSIONS: The results of this study indicate that combined virtual bronchoscopic navigation (Direct Path), radial EBUS, ultrathin bronchoscopy, and ROSE of target control specimens reduce the risk of bleeding, and their combination with mNGS has high diagnostic value for difficult lung lesions in patients with haematological diseases, especially in the field of infection diagnosis. TBLB and BAL specimens have respective advantages in specificity and sensitivity for mNGS analysis.