Objective To explore the role of ethyl pyruvate (EP) on E-cadherin of airway epithelium and airway inflammation in a TDI-induced mouse asthma model. Methods 30 male BALB/c mice were randomly divided into control group , asthma group and EP group. On day 1 and 8 , mice in asthma group and EP group were treated with 0.3%TDI on the dorsum of both ears for sensitization. And on day 15 , 18 and 21 the mice underwent an aerosol inhalation of 3% TDI, and saline (100 mg/kg) was injected intraperitoneally 1 hour before inhalation. The control group underwent acetone and olive oil (AOO) sensitization on day 1 and 8, AOO challenge on day 15, 18 and 21. Saline (100 mg/kg) was injected intraperitoneally 1 hour before challenge. One hour before each challenge, mice were given EP (100mg/kg) or vehicle via intraperitoneal injection. On day 22, airway reactivity, IL-4 , IFN-γand IgE in the serum were detected , immunohistochemistry and WB were used to assess E-cadherin levels. Results Airway reactivity, IL-4, IFN-γin and IgE in the serum in asthma group are significantly higher than that in control group (P<0.05). Treatment with EP dramatically decreased airway hyperresponsiveness in TDI-challenged mice, as well as IL-4, IFN-γ and IgE (P < 0.05). E-cadherin in control group was distributed evenly at the connection of epithelial cells. E-cadherinin distribution was chaotic and its expression was decreased in asthma group. EP intervention can ameliorate the damage of E-cadherinin. Conclusions EP can ameliorate the destruction of E-cadherin in airway epithilum by TDI.

OBJECTIVE To investigate the effects and mechanism of luteolin on osteogenic repair of bone defects. METHODS The targets and potential pathways of luteolin in the treatment of bone defects were screened by network pharmacology method， and then the top 2 targets were selected by Hub gene screening for molecular docking verification， with binding energy as the evaluation standard. In vitro experiments were conducted on rat bone mesenchymal stem cells （BMSC） and rat umbilical vein endothelial cells （RUVEC）. Phenotypic validation was performed using alkaline phosphatase staining， alizarin red S staining， and in vitro angiogenesis experiments. Western blot assay was used to detect the protein expressions of phosphatidylinositol 3 kinase （PI3K） and protein kinase 1 （Akt1）， so as to validate the mechanism of luteolin on osteogenic differentiation of BMSC and angiogenesis of RUVEC in vitro. RESULTS The results of network pharmacology showed that the effects of luteolin on vascular formation and bone repair in bone defects were mainly related to Akt1， SRC， estrogen receptor 1， epidermal growth factor receptor， cyclooxygenase 2， matrix metalloproteinase 9 targets， and were closely related to PI3K-Akt signaling pathway. The results of molecular docking showed that luteolin binding to Akt1 and SRC proteins was stable. The results of in vitro experiments showed that luteolin could significantly improve the expressions and activities of alkaline phosphatase in BMSC， increased the number of calcium salt deposits and calcified nodules， and promoted calcification of BMSC. Compared with luteolin 0 μmol/L group， the angiogenesis ability of RUVEC was enhanced significantly in luteolin 1， 10 μmol/L groups， the length of blood vessels and the protein expressions of PI3K and Akt1 were significantly increased （P＜0.05 or P＜0.01）； the higherthe concentration， the better the effect. CONCLUSIONS Luteolin may play a role in promoting angiogenesis and bone repair at the fracture site by activating PI3K/Akt signaling pathway and promoting the protein expressions of PI3K and Akt1.