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The present study aimed to investigate the changes in the expression levels and activity of mast cell chymase in the process of burn wound healing in a hamster model of deep second-degree burn. The hamster model was established by exposing a ~3 cm diameter area of bare skin to hot water (75°C) for 0, 6, 8, 10 or 12 sec. Tissue specimens were collected 24 h after burning and histological analysis revealed that hot water contact for 12 sec was required to produce a deep second-degree burn. Quantitative polymerase chain reaction and a radioimmunoassay were used to the determine changes in chymase mRNA expression levels and activity. The mRNA expression levels and activity of chymase were increased in the burn wound tissues when compared with the normal skin. However, no statistically significant differences were observed in mast cell chymase activity amongst the various post-burn stages. Chymase mRNA expression levels peaked at day 1 post-burn, subsequently decreasing at days 3 and 7 post-burn and finally increasing again at day 14 post-burn. In summary, a hamster model of deep second-degree burn can be created by bringing the skin into contact with water at 75°C for 12 sec. Furthermore, the mRNA expression levels and activity of chymase in the burn wound tissues increased when compared with those in normal skin tissues. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effect of different concentrations of mast cell chymase on the transforming growth factor (TGF)-β1/Smad signaling pathway in skin fibroblasts. Cultured skin fibroblasts were treated with various concentrations of chymase for different time periods. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to assess the rate of cell proliferation. In addition, protein expression in the fibroblasts was measured using western blot analysis. Chymase was shown to enhance the proliferation of skin fibroblasts following incubation for 48, 72 and 96 h (P<0.01). Furthermore, high concentrations of mast cell chymase were shown to enhance the mRNA and protein expression levels of TGF-β1 after long-term (≥6 h) incubation. In addition, high concentrations of mast cell chymase increased P-Smad2/3 and Smad2/3 protein expression. By contrast, low concentrations of mast cell chymase increased Smad7 protein expression. Therefore, the results demonstrated that high concentrations of mast cell chymase facilitated the transduction of the TGF-β1/Smad signaling pathway in skin fibroblasts. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the anti-tumor mechanisms of gambogic acid (GA) on NCI-H1993 xenografts in vivo. Non-small cell lung carcinoma NCI-H1993 cells, which harbor a MET gene amplification, were subcutaneously injected into athymic nude mice. The mice were randomly assigned to treatment with 10, 20 or 30 mg/kg GA for 3 weeks. At the end of the efficacy study, all the mice were sacrificed and the tumor tissues were subjected to western blot analysis and immunohistochemical (IHC) staining. GA inhibited NCI-H1993 xenograft tumor growth in a dose-dependent manner. Western blot analysis demonstrated that expression of phosphorylated (p)-MET and its downstream signaling molecules p-AKT and p-ERK1/2 were significantly inhibited by GA. IHC analysis of Ki-67 expression demonstrated that GA treatment resulted in dose-dependent inhibition of tumor cell proliferation. GA exerted antitumor effects on NCI-H1993 xenografts in vivo by direct regulation of the MET signaling pathway. Theses antitumor effects were primarily a result of its anti-proliferation function. [ABSTRACT FROM AUTHOR]