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AIM: To investigate the guiding role of individualized medication adjustment based on CYP2C19 metabolic typing in the treatment of ischemic stroke with clopidogrel, and to provide reference for clinical individualized medication. METHODS: The total of 80 patients with ischemic stroke were divided into the individualized drug instruction group with gene detection (n=40) and the control group without gene detection (n=40) according to whether they received CYP2C19 gene detection. According to the metabolism of CYP2C19, the individualized medication instruction group was divided into slow metabolic type, intermediate metabolic type, fast metabolic type and ultra-fast metabolic type. Patients with fast and ultra-fast metabolites were given clopidogrel dose of 75 mg once a day. Patients with intermediate metabolic type were given double clopidogrel dose of 150 mg once a day. Patients with slow metabolism were given tigrillo dose of 90 mg twice a day or aspirin dose of 100 mg once a day. The control group received 75 mg clopidogrel once a day. All patients enrolled in the groups were followed up for 3 months by outpatients or telephone. The incidence of vascular events and mRS scale scores were compared between the two groups. RESULTS: The incidence of vascular events in the individualized drug instruction group was significantly lower than that in the control group, and the incidence of mRS score(0-1) was significantly higher than that in the control group, with statistically significant differences (P<0.05). CONCLUSION: The individualized medication for patients with ischemic stroke by CYP2C19 gene detection can significantly reduce the incidence of adverse vascular events and improve the prognosis and living ability of patients.
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Objective To explore the A2AR activation after traumatic brain injury mechanisms and the role of excessive tau protein phosphorylation.Methods With no specific mice experiment research of specific pathogens, position in the left parietal cortex in mice, by the method of controllable cortical against brain trauma model model, 15 min after injury in mice abdominal injection of A2AR specific inhibitors ZM241385 or use A2AR knockout mice, testing the brain neuron loss and tau protein phosphorylation level;Use specific agonists CGS21680 activate the original generation of nerve cells in the hippocampus and the A2AR human neuroblastoma cells, using immunocytochemistry and immunofluorescence test tua protein phosphorylation level of change, to observe axon transport function of mitochondria.Results Immunohistochemical results accumulation of optical density analysis showed that inhibition of A2AR activation can significantly reduce after cerebral trauma Ser404 tua protein loci phosphorylation levels, reduce excessive tua protein phosphorylation with nerve pathological change;A2AR activation after tua phosphorylation of proteins at a Ser404 site level increased significantly, nerve axons per unit length processes in the mitochondria number decreased significantly, resulting in axoplasmic transport dysfunction;To activate the original generation of nerve cells in the hippocampus and after the A2AR human neuroblastoma cells, tua protein phosphorylation Ser404 locus levels increased significantly.Conclusion A2AR activation after cerebral trauma has obvious influence on tua protein phosphorylation levels, may be a function by influencing the axoplasmic transport, eventually forming cognitive dysfunction.
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Aim To study the effect of IL-1β on pro-tein expression of vascular endothelial growth factor in glioma cells and plasma membrane microcapsule struc-ture protein caveolin-1 and plasma membrane vesicles in brain microvascular endothelial cells, and prelimi-narity discuss the possible mechanism of IL-1β opening blood tumor barrier. Methods The tumor barrier mod-el was established by transwell in vitro. The effect of IL-1β on the expression of VEGF in glioma cells and caveolin-1 in brain microvascular endothelial cells was dynamically monitored by Western blot. TEM was used to observe the number of plasma membrane vesicles of brain microvascular endothelial cells. Sodium fluores-cein leakage test was used to assess the permeability of blood tumor barrier after IL-1β. Results The tumor barrier model was successfully established by transwell in vitro. When IL-1β treated the model of blood tumor barrier,the expression of VEGF increased,and reached the peak at 60min,and recovered to the initial state at 120min. The permeability of the blood tumor barrier model was the highest at 60min. In addition,our re-sults also found that,the protein expression of plasma membrane microcapsule structure protein caveolin-1 and number of plasma membrane vesicles in brain mi-crocapsule endothelial cells reached peak at 60 min, subsequently reduced and returned to non drug state at 120min. Conclusion IL-1β increases blood tumor barrier permeability,which may be related to IL-1β in-creasing the number of plasma membrane vesicles through VEGF/ caveolin-1 pathway.
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Objective To investigate the effect of serum of esophageal squamous cell carcinoma (ESCC) patients with blood stasis syndrome (BSS) on proliferation and cycle of EC9706 cells, and to explore the action of blood micro-environment of ESCC patient with BSS on EC9706 cells. Methods Human EC9706 cells were cultured in an incubator with RPMI-1640 medium containing fetal bovine serum ( FBS) , at 37℃ and under 5% saturated humidity for 24 h. After EC9706 cells were starved in serum-free medium for another 24h, the three experimental groups were treated with serum of ESCC patients with BSS, serum of ESCC patients with spleen-qi deficiency syndrome (SQDS), and serum from healthy volunteers, respectively. Cell proliferation was determined by methyl thiazolyl tetrazolium ( MTT) assay, EC9706 cell morphology was observed under light microscope, and cell cycle was measured by flow cytometer (FCM). Results The serum concentrations of ESCC patients with BSS and ESCC patients with SQDS for obtaining 50 percent cell proliferation rates ( PI50) were 71.1 μL/mL and 118 μL/mL, respectively. And the proliferation of EC9706 cells in the both groups all arrived to the peak values at culturing hour 48. The light microscopy results showed that the feature of EC9706 cells in both groups presented as spindle-like or polygon-like shape, and cell count in BSS group was larger than SQDS group. FCM assay results for EC9706 cell cycle showed that the percentage of G1-phase EC9706 was decreased and the percentage of S-phase EC9706 was increased in BSS group as compared with those in SQDS group ( P<0.05). Conclusion Serum micro -environment in ESCC patients with BSS is more beneficial to EC9706 cells proliferation than ESCC patients with SQDS, and the mechanism may be related to the regulation of cell cycle.
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Purpose To explore the role of tumor necrosis factor-α( TNF-α) in the process of temozolomide ( TMZ) reduce glioma in-vasiveness and its possible mechanism. Methods C6 glioma cells of logarithmic phase were randomly divided into TMZ treatment (10, 30, 60, 120, 180, 240 min group) (n=15), dynamic monitoring content of TNF-αin the culture medium was measured by ra-dioimmunoassay, expression of p53 protein in C6 cells was detected with Western blotting method, and cell apoptosis was used with AnnexinV-FITC. A glioma invasiveness model was established in vitro and glioma invasiveness was determined by crystal violet stai-ning. Results For C6 cells, contents of TNF-αin the nutrient fluid and expressions of p53 protein in C6 cells obviously increased af-ter TMZ treatment and they achieved the peak at 120 min (P<0. 01), followed by decrease gradually. Glioma invasiveness was re-duced after TMZ acted on glioma in vitro. Conclusion TMZ can reduce glioma invasiveness by TNF-α, which this role may be is TMZ promote C6 cells release of TNF-α and increased TNF-α due to glioma cells apoptosis.
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Aim To assess the effect of heat shock factor-1(HSF1)and heat shock protein 70(HSP70)to tachyphylaxis by bradykinin in the opening blood-tumor barrier(BTB).Methods The C6 rat intracerebral glioma model was constructed by stereotactic implantation technique.Using western blotting method to continue monitoring the protein expression of HSF1 and HSP70 in tumor tissue after bradykinin acted on animals.The expression of occludin in tumor tissue were detected by immunohistochemistry method.Using Evans blue and electron microscope,respectively,detected the permeability and pathology of BTB after intracarotid infusion of bradykinin in C6 rats.Results Bradykinin increased the tight junction opening and the permeability of BTB in C6 animals,and the relative increments of EB were 5.19 ?g?g-1(0 min),5.06 ?g?g-1(5 min),11.35 ?g?g-1(10 min,P
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Aim To study the effects of HSP70 on hepatic ischemia-reperfusion injury after heat preconditioning in rats.Method To establish the models of the hepatic ischemia-reperfusion injury. 42 Wistar rats were randomly divided into 6 groups, (each group had 7 rats): normal group(N); quercetin injection group(Q); ischemia-reperfusion group(I); heat preconditioning 16 hours before ischemia-reperfusion group(H+I); quercetin injection before heat preconditioning group(Q+H+I); quercetin injection before ischemia-reperfusion group(Q+I).We detected the activity of serum enzyme of ALT,AST and the pathological changes of the liver;The expressions of HSP70 of the rats were observed by Western blotting. Results The expressions of HSP70 from high to low were:group H+I,group I,group Q+H+I,group Q+I,group Q,group N; The serum levels of ALT and AST from high to low were: group Q+I,group I,group Q+H+I,group H+I,group Q,group N;All groups had visibly hepatic histological changes respectively.Conclusion The protection of heat stress pretreatment from ischemia reperfusion injury was possibly performed by inducing the expression of HSP70.