Correlation between variants of leukotriene A4 hydrolase gene and risk of ischemic stroke in population of southern Zhejiang Province / 中华神经科杂志

Objective To investigate the correlation between two single nucleotide polymorphisms of the leukotriene A4 hydrolase (LTA4H) gene (rs2660845 and rs2540493) and risk of ischemic stroke in population of southern Zhejiang Province.Methods A total of 300 ischemic stroke patients and 300 healthy controls,recruited from the Department of Neurology,Third Affiliated Hospital of Wenzhou Medical University between September 2010 and June 2013,were enrolled in this study.Two single nucleotide polymorphisms of the LTA4H gene (rs2660845 and rs2540493) were analyzed by polymerase chain reaction and matrix-assisted laser desorption/ionization time of flight,respectively.Sixty-seven patients and thirty controls were randomly selected (complete randomization) and detected the serum leukotriene B4 (LTB4)concentration by ELISA method.Results There was no evidence of association between the two variants of LTA4H gene and the risk of ischemic stroke or its TOAST (Trial of Org 10 172 in acute stroke treatment)subtypes (P ＞ 0.05).Analysis of LTB4 levels revealed that there was no statistically significant difference in serum LTB4 concentration between patients (n =67) and controls (n =30; 0.991 ± 0.305 vs 1.035 ± 0.498 ; P =0.692),and no statistically significant difference in LTB4 concentration was found among the three genotypes of rs2660845 as well (AG genotype vs AA genotype vs GG genotype:0.938 ± 0.269 vs 1.038 ± 0.268 vs 1.043 ± 0.383 ; P =0.401).Conclusion The present study suggests that there is no association between the two polymorphisms in the LTA4H gene and risk of ischemic stroke in population of southern Zhejiang Province.

Study on effect of COX-2 selective inhibitor celecoxib on inducing apoptosis of NB4 / 国际检验医学杂志

Objective To study the effects of COX-2 selective inhibitor celecoxib on the apoptosis of acute promyelocytic leuke-mia NB4 cell line,and to investigate its apoptosis mechanisms.Methods The expression of COX-2 mRNA in different cell lines was detected by reverse transcript polymerase chain reaction(RT-PCR).After treatment of NB4 with different doses of celecoxib,the in-hibition of NB4 growth was assayed by MTT,and the DNA fragmentation was examined by the DNA ladder test.The level of Bcl-2 protein expression was assayed by the flow cytometry.Results As compared with the no-medication treatment group,the DNA ladder fragments became more and more obvious after the treatment by different doses of celecoxib.The expression rates of Bcl-2 protein in the different doses of celecoxib groups (25,50,100 μmol/L)were (71.69 ±1.65 )%,(34.51 ±2.53)% and (29.28 ± 2.38)% respectively,compared with the Bcl-2 protein expression rate (85.34±2.89%)in the blank control group,the expression rate of Bcl-2 protein in different doses of celecoxib groups(50,100 μmol/L )was significantly decreased(P <0.05 ).Conclusion Celecoxib as COX-2 selective inhibitor could evidently induce the apoptosis of NB4 cells by down-regulating the expression of Bcl-2 protein in NB4 cells.

Neuroprotective effect of inhibition of soluble epoxide hydrolase on focal cerebral ischemia/reperfusion in Rats / 国际脑血管病杂志

Objective To investigate the neuroprotective effect of soluble epoxide hydrolase (sEH) inhibitor 12-(3-adamantan-l-yl-ureido) dodecanoic acid (AUDA) on focal cerebral ischemia/reperfusion in rats and its mechanisms.Methods Sixty male Sprague-Dawley rats were randomly divided into sham operation and saline control groups,as well as low-dose (0.157 ml/kg),medium-dose (0.235 ml/kg) and high-dose (0.314 ml/kg) AUDA groups (n =12 in each group).Four rats in each group were selected for infarct volume,cell apoptosis and p-Akt immunohistochemistry detection.A model of middle cerebral artery ischemia/ reperfusion was induced by the suture method.The corresponding dose AUDA or equal volume of saline was injected intraperitoneally before reperfusion in each AUDA group and the saline control group.Neurological deficit scores were performed at 24 h of reperfusion.2,3,5 triphenyltetrazolium chloride (TTC) staining was used to detect infarct volume.TdT-mediated dUTP nick end labeling (TUNEL) was used to detect apoptotic cells of brain tissue in the periinfarction area.Immunohistochemical method was used to detect p-Akt expression of brain tissue in the peri-infarction area.Results TTC staining showed no infarction was observed in the sham operation group.The infarction volumes in the saline control group as well as the low-dose,medlum-dose and high-dose AUDA groups were 254.146 ± 25.481,212.679 ± 7.514,150.188 ± 33.997,and 99.563 ± 3.415 mm3,respectively.There were significant differences (F =39.637,P =0.000).The each dose AUDA group was significant less than the control group (all P=0.000).The medium-dose AUDA group was significantly less than the low-dose AUDA group (P=0.002),and the high-dose AUDA group was also significantly less than the low-dose AUDA group (P =0.000) and medium-dose AUDA group (P =0.006).TUNEL staining showed that a small number of apoptotic cells (6.400 ± 1.477/high-power field) were observed in the sham operation group.The numbers of apoptotic cells in the saline control group as well as in the low-dose,medium-dose and high-dose AUDA groups were 57.550 ± 13.067,47.030 ± 8.423,34.530 ± 4.393 and 26.400 ± 2.683/high power field,respectively.Each dose AUDA group was significantly less than the saline control group (all P ＜0.01).The medium-dose and high-dose AUDA groups were significantly less than the low-dose AUDA group (P ＜ 0.01),and the high-dose AUDA group was also significantly less than the medium-dose AUDA group (P ＜0.01).Immunohistochemistry showed that only a few p-Akt-positive cells (3.325 ± 1.438/high power field) were observed in the sham operation group.The numbers of p-Akt-positive cells in the saline control group as well as the low-dose,medium-dose and high-dose AUDA groups were 9.450 ±2.531,16.400 ± 3.865,22.875 ± 7.974,and 29.300 ± 3.203/high-power field,respectively.Each dose AUDA group was significantly more than the saline control group (all P ＜0.01).The medium-dose and high-dose AUDA groups were significantly more than the low-dose AUDA group (all P ＜0.01).The high-dose AUDA group was also significantly more than the medium-dose AUDA group (P ＜ 0.01).Conclusions The inhibition of sEH may decrease neuronal apoptosis and reduce infarct volume in the peri-infarction area by upregulating the PI3K/Akt pathway.It has a neuroprotective effect for focal cerebral ischemia/reperfusion in rats.

The expression of cyclooxygenase-2 in breast cancer tissues and its clinicopathological significance / 中国医师进修杂志

Objective To investigate the expression of cyclooxygenase-2(COX-2)in breast cancer tissues,as well as the relationship between COX-2 and the clinicopathological features.Method The expression of COX-2 was detected in 60 cases of breast cancer tissues and 20 cases of breast normal tissues by using immunohistochemistry,and combined with clinicopathological information for analysis.Results The COX-2 expression rate was 65.0%(39/60)in breast cancer tissues and 10.0%(2/20)in breast normal tissues respectively.There was statistic difference between the two(P<0.01).The over expression of COX-2 was significantly correlated with TNM stages,lymphatic metastasis and the expression of epidermal growuth factor receptor-2(C-erbB-2)(P<0.05 or<0.01).Conclusion The expression of COX-2 in breast cancer tissues is significantly higher,which might play a fairly important role in tumorigenesis and progression of breast cancer.

Association of EPHX2 polymorphism G860A with hypertension in middle ages / 中国医师杂志

Objective To investigate the association between the EPHX2 polymorphism G860A and the risk of hypertension in mild ages. Methods In a hospital based case-control study, one common polymorphism C860A in EPHX2 gene in a case-control study of 100 hypertension and 300 age- and sex frequency - matched disease-free controls were genotyped in a Southern Chinese population. SAS 9. 13 was used toanalysis the polymorphism and hypertension risk. Results Genotype frequencies of EPHX2 G860Alocus between the cases and the controls were significantly different (P =0. 01). Compared with the most common 860GG genotype, the 860GA heterozygote had an increased risk of hypertension (adjusted OR =1.98; 95%CI = 1.19 -3.51), the AA homozygote had a further increased risk of hypertension (adjusted OR =2. 84; 95%CI = 1.01 -6. 11). There was a significant trend for an allele dose effect on risk of hypertension (P trend = 0. 03). Conclusions EPHX2 polymorphism G860A is associated with an increased risk of hypertension, and the 860A variant may be a marker for susceptibility to hypertension.

Relationship between cyclooxygenase-2 and vascular endothelial growth factor with liver sinusoidal capillarization of chronic hepatitis B / 中国基层医药

Objective To study the relationship between expression of cyclooxygenase-2 (COX-2) and vas-culax endothelial growth factor (VEGF) with liver sinusnidal capillarization (LSC) of chronic hepatitis B (CHB). Methods We studied liver biopsies from 200 patients with CHB COX-2 ,VEGF immunohistochemical stain were ob-served to accomplish relationship between expression of COX-2,VEGF and LSC. Results LSC occupy above 80% in the group. There were manifestation in mild-LSC (focal) , middle-LSC (sheet-shape) and severe-LSC (widespread). Electron microscope shown the laceration in the endothelium of sinuses and formation of basal lamina and budding for-mation lumen of blood vessel and fat-storing cell convert myofibroblast. Expression of COX-2, VEGF, Co-Ⅳ and retic-ulum, collagen and elastic fibers with mild or severe in LSC is manifest locking relate. Conclusion Increased ex-pression of COX-2 ,VEGF in liver tissue of CHB may facilitate LSC and hepatic fibrosis.

The expression of COX-2 and Survivin protein in gastric carcinoma and its clinical significance / 中国基层医药

Objective To investigate the expression and clinical significance of COX-2 and Survivin protein in gastric carcinoma.Methods In 76 gastric carcinoma specimen and 13 normal mucosa gastric specimen,the exprssion of COX-2 and Survivin protein were detectede by immunohistochemistry SP.The relationship between expression of COX-2 and Survivin protein and clinical pathological parameter were analyzed,also the relationship between COX-2 and Survivin protein.Results The positive expression rate of COX-2 and Survivin protein was 80.26% and 77.63%,and higher than those in normal gastric tissues (P＜0.01).The positive expression of COX-2 protein was negatively related to gender,age,cellular differentiation,serosa infiltration (P＞0.05),but associated with lymph node and TNM stage (P＜0.05).The positive expression of Survivin protein was not related to gender,age (P＞0.05),but associated with cellular differentiation,serosa infiltration,lymph node metastasis and TNM stage (P＜0.05),The expression of COX-2 protein was positively correlated with Survivin protein (P＜0.01).Conclusion COX-2,Survivin protein play an important role in the genesis and development of gastric carcinoma.The expression of Survivin and COX-2 protein may be the index of prognostic evaluation and determination of biological behavior in gastric carcinoma.

Research status of COX-2 and its inhibitor in breast cancer / 国际肿瘤学杂志

COX-2 is the rate-limiting enzyme in prostaglandin biosynthesis,which may promote the human tumorigenesis and tumor development through a variety of pathogenic mechanisms.The over expression of COX-2 in breast cancer is significantly correlated with the clinicopathological pammeters and prognosis.COX-2 inhibitors play anti-tumor effects through different mechanisms.Recent studies indicate that COX-2 inhibitors are effective both in breast cancer chemoprevention and treatment of breast cancer combined with cytotoxic drugs and aromatase inaetivators,and therefore may provide a potential new therapy of breast cancer prevention and treatment.