New Findings
What is the central question of this study?The aim was to investigate the role of μ‐opioid receptors in acute respiratory distress syndrome and whether their protective effect is mediated via the PI3K/Akt signalling pathway.
What is the main finding and its importance?Our findings show that activation of μ‐opioid receptors ameliorates lung injury, and the effects are reversed by the PI3K inhibitor, wortmannin.
Abstract
The main pathology of acute respiratory distress syndrome (ARDS) is the accumulation of inflammatory cells in the lung and increased permeability of vascular endothelial cells. The μ‐opioid receptor (MOR) is a G‐protein‐coupled receptor, which stimulates angiogenesis and vascular endothelial cell proliferation. In addition, the MOR inhibits cell apoptosis via the PI3K/Akt signalling pathway. In this study, we aimed to explore the contribution of the MOR in ARDS and whether its effects are mediated via PI3K/Akt signalling. An ARDS model was established by intratracheal instillation of 5 mg kg−1 lipopolysaccharide (LPS). Lung injury was confirmed by Haematoxylin and Eosin staining, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity and vascular cell adhesion molecule 1 expression. Lung inflammation was determined by assessment of interleukin‐1β and tumour necrosis factor‐α concentrations. The protein level of p‐Akt was detected by western blot. Endomorphin‐1‐activated MORs attenuated LPS‐induced lung injury, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity, interleukin‐1β and tumour necrosis factor‐α levels and vascular cell adhesion molecule 1 expression, and elevated LPS‐induced decreased p‐Akt expression. However, the protective effect of MOR activation on lung injury was reversed by the PI3K inhibitor, wortmannin. In conclusion, MOR involvement in LPS‐induced ARDS is via the PI3K/Akt pathway.
Introduction: Quercetin has been reported to have anti-tumor activity of a wide range of cancers, including breast, lung, colon, prostate. Here, we investigated the protective role of quercetin in glioblastoma (GBM), which causes higher risk of morbidity and mortality, and explored the anti-tumor effects of quercetin on GBM using the U87MG and T98G cells and GBM mouse models.
Methods: Cell viability and colony formation assays were performed by CCK-8 and clone formation assays. GBM xenograft mouse model was established to evaluate the tumor burden of mice treated with or without quercetin. To investigate spontaneous locomotor activity and survival rate of mice, orthotopic transplantation was performed through brain stereotaxic injection of U87 cells. Seahorse and Western blot were performed to examine the alteration of glycolytic metabolism GBM.
Results: We found that quercetin administration inhibited GBM cell proliferation and promoted cell apoptosis in vitro. Quercetin suppressed GBM growth, restored spontaneous locomotor activity and improved survival rate without toxicity to peripheral organs in vivo. Moreover, quercetin inhibited glycolytic metabolism in tumor tissue.
Discussion/Conclusion: Mechanistically, quercetin inhibited proliferation and angiogenesis, promoted cancer cell apoptosis, and finally improved locomotor activity and survival by inhibiting the glycolytic metabolism in GBM tissues, suggesting that quercetin is a potential drug for the treatment of GBM.
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