ABSTRACT
Chronic cerebral hypoperfusion (CCH) is a common pathological change of central nervous system diseases and is closely associated with cognitive impairment. A number of studies have shown that inflammation is involved in the pathogenesis and progression of CCH-induced cognitive impairment. In the condition of CCH, the activation of inflammatory response in the brain can lead to a variety of pathological injuries, such as white matter lesions, blood-brain barrier destruction, degeneration and necrosis of hippocampal neurons, etc. Therefore, inhibition of inflammatory response is expected to provide a new therapeutic target for CCH-induced cognitive impairment. This article reviews the mechanism of inflammation in CCH-induced cognitive impairment.
ABSTRACT
OBJECTIVE: To observe the status of protein kinase B(Akt) signaling pathway in Akt phosphorylation induced by free silica(SiO_2) in mouse monocyte macrophage cell RAW264.7, and the role of Akt signaling pathway in early inflammatory response of silicosis. METHODS: i) RAW264.7 cells were routinely cultured and divided into SiO_2 stimulation groups at 5 different time points, and were stimulated for 15, 30, 60, 120 and 240 minutes with SiO_2 suspension with a final concentration of 100 mg/L, and a control group without SiO_2 treatment. At the end of treatment, the cells were collected and the expression of phospho-(Ser/Thr) Akt(p-Akt) was detected by Western blotting to select the optimal time of treatment. ii) RAW264.7 cells were divided into control group(no treatment), SiO_2 exposure group(previous concentration of 100 mg/L SiO_2 suspension) and intervention group(pre-treated with Akt activation inhibitor deguelin for one hour and then treated with 100 mg/L SiO_2 suspension), samples were collected after incubation for 60 minutes. The p-Akt expression and distribution in cells were detected by cellular immunofluorescence assay, the relative expression of p-Akt in cells was detected by Western blotting, and the levels of tumor necrosis factor-α(TNF-α) and transforming growth factor-β1(TGF-β1) in the supernatant of cells were detected by enzyme-linked immunosorbent assay. RESULTS: i) The optimal treatment time of RAW264.7 cells for SiO_2 exposure model was 60 minutes in vitro. ii) The results of cellular immunofluorescence assay showed that Akt phosphorylation was activated in RAW264.7 cells after stimulant with SiO_2, and the fluorescence of p-Akt was enhanced in the SiO_2 exposure group than the control group, and in the intervention group it was relatively weaker than the SiO_2 exposure group. The relative expression of p-Akt as well as the levels of TNF-α and TGF-β1 in the SiO_2 exposure group and the intervention group were higher than that in the control group(P<0.05), and the above three idexes in the intervention group were lower than the SiO_2 exposure group(P<0.05). CONCLUSION: Akt signaling pathway is involved in the process of SiO_2-induced macrophages phosphorylation, and participates in the early inflammatory response of silicosis.
ABSTRACT
Objective:To explore the effects of HIF-1α on the growth of transplanted oral cancer and on the expression of CEACAM1 and VEGF-C in the tumor.Methods:Nude mouse model of oral cancer was established by transplantation of Tca8113 cells respectively treated by HIF-1α siRNA and negative control siRNA subcutaneously into right axillary region of nude mice.3 weeks after transplantation the mice were sacrificed,the tumor volum and weight were measured.The tumor tissue was examined by ELISA method for the detection HIF-1α protein expression,by real-time quantitative PCR and western blot for the detection of mRNA and protein expression of HIF-1α,CEACAM1 and VEGF-C respectively.Results:The volume and weight of the transplanted tumor in HIF-1 α siRNA group were significantly less than those in the control group(P＜0.05),CEACAM1 and VEGF-C mRNA and protein were down-regulate in HIF-1α siRNA group (P＜0.05).Conclusion:HIF-1α expression is positively related to the expression of CEACAM1 and VEGF-C in the regulation of oral tumor growth.