The incidence of pulmonary fibrosis (PF), a progressively fatal disease, has increased in recent years. However, there are no effective medicines available. Previous results have shown that sinensetin probably has some curative effects on PF. Therefore, this paper aims to predict the targets of sinensetin using a network pharmacology method and to confirm its effects and functional targets in PF using a mouse PF model. First, network pharmacology analysis showed that sinensetin has 105 functional targets, and 1,698 gene targets closely relate to PF. The intersection of the functional targets and gene targets produced 52 targets for the treatment of PF with sinensetin. The PPIs (protein–protein interactions) led to several potential key target genes, including MAPK1, EGFR, SRC, and PTGS2. The results of GO and KEGG analyses suggested the crucial function of apoptosis in PF and its involvement in the PI3K signaling pathway. Subsequently, we tested the molecular docking of sinensetin with the PI3K protein using the AutoDock4 software. The results showed that sinensetin could fit well into several binding sites of the PI3K protein. Furthermore, we constructed a PF mouse model through one-off intratracheal instillation of bleomycin and then intragastrically administered different concentrations of sinensetin to the model mice. Twenty-eight days later, the mice were sacrificed, and the lung tissues, serum, and bronchoalveolar lavage fluid (BALF) were collected. The in vivo tests showed that the body weight of model mice increased slightly compared with that of PF mice after intragastric sinensetin. HE and Masson staining suggested a certain extent of reduction in the pathology of lung tissues. The expression of collagens I and III, as well as hydroxyproline in the lung tissues, was reduced to a certain extent. IL-6 levels in the serum and BALF decreased markedly. The expression of vimentin and α-SMA in pulmonary tissues decreased. Cell apoptosis, as well as P-PI3K and P-AKT levels, in lung tissues also reduced. In summary, network pharmacology and in vivo test results suggest sinensetin causes an effective delay in the progression of pulmonary fibrosis, and the functional mechanism is likely related to PI3K-AKT signaling.

BackgroundChronic obstructive pulmonary disease (COPD) is considered related to chronic systemic inflammation. Renin angiotensin system (RAS) inhibitor, exerting an anti-inflammatory action in many systems, has been demonstrated relevant to the pathogenesis of COPD. However, the association between RAS inhibitor use and prognosis of patients with COPD remains controversial. Therefore, we conducted a meta-analysis and systematic review to summarise current evidence.Material and methodsDatabases, including Medline, Embase, Web of Science and Cochran Library, were searched for eligible studies by the end of 30 September 2022. Observational studies or randomised controlled trials (RCTs) that investigated the association of RAS inhibitor use with prognosis of COPD (mortality or risk of acute exacerbation) were selected. The Newcastle-Ottawa Scale was used for quality assessment of observational studies, while the Cochrane risk-of-bias tool was used to assess the quality of RCTs. Statistical analyses were performed using Stata V.15. We selected relative risk (RR) with 95% CI as the effect measure. Heterogeneity was assessed by I-squared (I2) statistics. The funnel plot was used for visual assessment of publication bias.ResultsA total of 20 studies with 5 51 649 subjects were included in the meta-analysis. The overall analysis indicated that RAS inhibitor use decreased the risk of death in patients with COPD (RR: 0.69, 95% CI: 0.61 to 0.78). Subgroup analyses were conducted according to comorbidities, race and type of RAS inhibitors, and the results kept consistent. However, in the pooled analysis of prospective studies, RAS inhibitor use did not significantly decrease the mortality (RR: 0.89, 95% CI: 0.78 to 1.02). Additionally, the risk of exacerbations of COPD did not decrease in patients who were prescribed RAS inhibitors (RR: 0.99, 95% CI: 0.80 to 1.23). The funnel plot indicated significant publication bias.ConclusionRAS inhibitor use seemed to be associated with a reduction of mortality in patients with COPD. However, the available evidence is weak due to potential biases from retrospective studies and the heterogeneity across included studies.

Background: Non-small cell lung cancer (NSCLC) is a disease with quite grave prognosis. This study explored the diagnostic efficiency of miR-126-5p and miR-34c-3p in serum extracellular vesicles (EVs) in NSCLC patients.Methods: Serum EVs were extracted from NSCLC patients and healthy people and verified. The expression of miR-126-5p and miR-34c-3p in serum EVs were tested. Correlation of miR-126-5p and miR-34c-3p expression and diagnosis, prognosis and pathological characteristics (age, gender, tumor size, clinical stage, and lymph node metastasis) of NSCLC patients was analyzed. The downstream targets of miR-126-5p and miR-34c-3p were predicted and their roles in diagnosis and prognosis of NSCLC patients were evaluated.Results: miR-126-5p and miR-34c-3p were poorly expressed in serum EVs of NSCLC patients and their low expressions were associated with clinical stage, lymph node metastasis and prognosis of NSCLC patients and could be used as biomarkers for diagnosis. As the common target genes of miR-126-5p and miR-34c-3p, LYPLA1 and CDK6 were highly expressed in serum EVs and were associated with poor prognosis in NSCLC patients.Conclusion: Lowly expressed miR-126-5p and miR-34c-3p in serum EVs of NSCLC patients can serve as biomarkers for diagnosis and are linked with prognosis. As common targets of miR-126-5p and miR-34c-3p, LYPLA1 and CDK6 are also associated with poor prognosis in NSCLC patients.