The aim of the present study was to examine the effects of 3,5,4′-tri-O-acetylresveratrol on connexin 43 (Cx43) in acute lung injury (ALI) in rats induced by tracheal instillation of artificial seawater. Different doses (50, 150, and 450 mg/kg) of 3,5,4′-tri-O-acetylresveratrol were administered orally for 7 days before modeling. Four hours after seawater inhalation, histological changes, contents of TNF-α, IL-1β and IL-10, and the expression of Cx43 in lungs were detected. Besides, the gap junction communication in A549 cells and human umbilical vein endothelial cells (HUVECs) challenged by seawater was also evaluated. Histological changes, increased contents of inflammatory factors, upregulation in gene level, and deregulation in protein level of Cx43 in lungs stimulated by seawater were observed. On the other hand, pretreatment with 3,5,4′-tri-O-acetylresveratrol significantly inhibited infiltration of inflammation, development of pulmonary edema, and contents of inflammatory mediators in lungs. Above all, 3,5,4′-tri-O-acetylresveratrol upregulated the expression of Cx43 in both gene and protein levels, and its intermediate metabolite, resveratrol, also enhanced the gap junction communication in the two cell lines. The results of the present study suggested that administration of 3,5,4′-tri-O-acetylresveratrol may be beneficial for treatment of inflammatorycellsin lung.

There have been no major breakthroughs in the treatment of small-cell lung cancer (SCLC) in recent decades. It is thus essential to explore new or adjuvant treatment options for SCLC. Resveratrol (Res) is a natural antioxidant revealed to influence the entire process of cancer development. Accordingly, the present study used the SCLC cell line H446 to explore the antitumor mechanism of Res. Cells were treated with 40 µg/ml Res with or without pretreatment with the antioxidant N-acetyl-L-cysteine (NAC). H446 cell viability and apoptosis were assessed with MTT and flow cytometry, and the expression of cytochrome c and the PI3K/Akt/c-Myc pathway and the nuclear translocation of apoptosis inducing factor (AIF) were assessed by western blotting. In addition, the changes in ROS content and mitochondrial membrane potential were determined. The results revealed that Res inhibited H446 cell viability and induced apoptosis, increased cytochrome c expression, inhibited the expression of PI3K/Akt/c-Myc signaling pathway components, and promoted the translocation of AIF from the cytoplasm to the nucleus in H446 cells. However, NAC pretreatment reversed these changes to various extents. The results of the present study indicated that Res may inhibit the viability and promote the apoptosis of human SCLC H446 cells through the PI3K/Akt/c-Myc pathway and that oxidative stress and mitochondrial membrane potential depolarization may be involved in the aforementioned processes.

Abstract:Calorie restriction (CR) is one of the most effective nonpharmacological interventions protecting against cardiovascular disease, such as hypertension in the systemic circulation. However, whether CR could attenuate pulmonary arterial hypertension (PAH) is largely unknown. The PAH model was developed by subjecting the rats to a single subcutaneous injection of monocrotaline. CR lowered mean pulmonary arterial pressure (mPAP) and reduced vascular remodeling and right ventricular hypertrophy in PAH rats. Meanwhile, CR attenuated endothelial dysfunction as evidenced by increased relaxation in response to acetylcholine. The beneficial effects of CR were associated with restored sirtuin-1 (SIRT1) expression and endothelial nitric oxide synthase (eNOS) phosphorylation and reduced eNOS acetylation in pulmonary arteries of PAH rats. To further clarify the role of SIRT1 in the protective effects of CR, adenoviral vectors for overexpression of SIRT1 were administered intratracheally at 1 day before monocrotaline injection. Overexpression of SIRT1 exhibited similar beneficial effects on mPAP and endothelial function, and increased eNOS phosphorylation and reduced eNOS acetylation in the absence of CR. Moreover, SIRT1 overexpression attenuated the increase in mPAP in hypoxia-induced PAH animals. Overall, the present data demonstrate that CR may serve as an effective treatment of PAH, and targeting the SIRT1/eNOS pathway may improve treatment of PAH.

Background Lung cancer is the most common and lethal malignancy worldwide. TCTP is highly expressed in various cancers including lung cancer. Epithelial–mesenchymal transition (EMT) could increase cancer cell invasion. Whether TCTP’s expression is associated with EMT in lung adenocarcinoma is largely unknown. Methods Several Gene Expression Omnibus datasets were used to analyze the correlation between TCTP expression and overall survival of lung adenocarcinoma patients by Kaplan–Meier survival analysis. Then, 24 surgically removed fresh lung adenocarcinoma tissue samples and paired paracancer tissue samples were used to analyze the correlation between TCTP expression and tumor stage by immunohistochemical analysis. Furthermore, stable cell lines were generated using lentiviral transduction systems to knock down or overexpress TCTP in A549 cells. Cell migration and invasion were measured by scratch and transwell assays, and EMT marker proteins such as α-SMA, ZEB1, and E-cadherin were quantitated by Western blot. The expression levels of miR-200a, miR-141, and miR-429 were determined by real-time quantitative PCR, and their target genes were predicted by an online database miRTarBase. The interaction between TCTP and these genes was analyzed by String database and visualized by Cytoscape. Results TCTP was highly expressed in tumor tissues compared to paracancer tissues. The expression of TCTP was associated with shorter overall survival. TCTP knockdown experiment in A549 cells suggested that TCTP knockdown could decrease the migration and invasion of lung cancer cells, and the expression level of ZEB1 and α-SMA, but increase the expression of E-cadherin and p53. Vice versa, overexpression of TCTP could increase the migration and invasion of cancer cells, and the expression level of ZEB1 and α-SMA, but decrease the expression of E-cadherin and p53. Furthermore, we found the expression of miR-200a, miR-141, and miR-429 was associated with TCTP expression. Conclusion TCTP promotes EMT in lung adenocarcinoma, and this effect may be associated with miR-200 family members like miR-200a, miR-141, and miR-429.

Environmental pollution, especially particulate matter in the air, is a serious threat to human health. Long-term inhalation of particulate matter with a diameter < 2.5 μm (PM2.5) induced irreversible respiratory and lung injury. However, it is not clear whether temporary exposure to massive PM2.5 would result in epithelial damage and lung injury. More importantly, it is urgent to clarify the mechanisms of PM2.5 cytotoxicity and develop a defensive and therapeutic approach. In this study, we demonstrated that temporary exposure with PM2.5 induced lung epithelial cell apoptosis via promoting cytokines expression and inflammatory factors secretion. The cytotoxicity of PM2.5 could be alleviated by tussilagone (TSL), which is a natural compound isolated from the flower buds of Tussilago farfara. The mechanism study indicated that PM2.5 promoted the protein level of Hif-1α by reducing its degradation mediated by PHD2 binding, which furtherly activated NF-κB signaling and inflammatory response. Meanwhile, TSL administration facilitated the interaction of the Hif-1α/PHD2 complex and restored the Hif-1α protein level increased by PM2.5.When PHD2 was inhibited in epithelial cells, the protective function of TSL on PM2.5 cytotoxicity was attenuated and the expression of cytokines was retrieved.Expectedly, the in vivo study also suggested that temporary PM2.5 exposure led to acute lung injury. TSL treatment could effectively relieve the damage and decrease the expression of inflammatory cytokines by repressing Hif-1α level and NF-κB activation. Our findings provide a new therapeutic strategy for air pollution-related respiratory diseases, and TSL would be a potential preventive medicine for PM2.5 cytotoxicity.