ABSTRACT
Objective To investigate the correlation between histone deacetylase 9 gene ( HDAC9 ) single nucleotide polymorphisms and ischemic stroke ( IS) subtypes. Methods A total of 202 patients with IS were enrolled prospectively. According to the Trial of Org 10172 in Acute Stroke Treatment ( TOAST) classification,the patients with IS were divided into large artery atherosclerotic stroke group (LAA,n=149) and the small-artery occlusive stroke group (SAO,n=53). A total of 201 age- and sex-matched healthy subjects over the same period were enrolled as the control group. Polymerase chain reaction-ligase detection reaction ( PCR-LDR ) was used to perform genotyping for HDAC9 gene rs11984041 and rs2107595 loci in all subjects. The correlation between genotype and IS was analyzed with multivariate logistic regression analysis. Results ( 1 ) In all the subjects detected, the genotype detected from rs11984041 loci was type CC,and 3 genotypes including CC,CT,and TT were detected from rs2107595 loci. (2) There were significant differences in dominance model (CT+TT,CC) genotypes and allele frequencies among the LAA, SAO, and control group dominance model ( CT +TT, CC ) and (χ2 =8. 635,P=0. 013, χ2 =10. 309,P=0. 006);and there were no significant differences in dominance model (CT+TT,CC) and allele frequencies among the 3 groups (after adjustment all P>0. 017). Compared with the control group,there were significant differences in the CC,CT,and TT genotypes and allele frequencies in the LAA group (χ2 =7. 446;P=0. 006). In the dominance models (CT+TT),there was significant difference in genotype frequencies between the LAA group ( 65. 1%,97/149 ) and the control group (52. 2%,105/201) (χ2 =5. 800;P=0. 016). (3) Multivariate logistic regression analysis showed that in addition to gender,hypertension,smoking,and high level of low-density lipoprotein,the dominance model CT+TT genotype was associated with the LAA type IS ( CT+TT genotype:OR,1. 909,95% CI 1. 055-3. 454,P =0. 033). Conclusion In addition to the risk factors for cerebrovascular disease such as gender,hypertension,smoking,and high level of low-density lipoprotein,HDAC9 gene polymorphisms may be associated with the LAA type IS. rs2107595 locus CT + TT genotype may be an independent risk factor for LAA type IS.
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ObjectiveTo explore the multidrug resistance(MDR) reversal activity of a novel compound liposome doxorubicin(PLD) and its mechanism.MethodsMTT assay was used to evaluate MDR reversal activity of PLD in P-gp expressing tumor cell lines,KBv200 and MCF-7/ADR.ResultsPLD had a strong reversal in vivo activity,recognized the strong reversal activity than verapamil reversal activity,in 5.0μmol/L concentration of multi-drug resistant cell KBv200 increased sensitivity to vincristine of 45 times.KBv200 PLD-dependent increased in intracellular concentration of rhodamine accumulation(0,2.5,5.0,10μmol/L).Mainly to its cardiac toxicity,bone marrow suppression and hair loss and other side effects were significantly reduced.ConclusionPLD was an efficient modulator,mainly through the continuous accumulation to tumor tissue,tumor local drug concentration,enhanced anti-tumor activity,
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Objective To observe the influence of bezafibrate on the apoptosis and expression of lectin-like oxidized low density lipoprotein receptor-1(LOX-1) mediated by oxidized low density lipoprotein(ox-LDL) in cultured human umbilical vein endothelial cells(HUVECs).Methodes The apoptosis of HUVECs mediated by ox-LDL were evaluated by flow cytometry and the expression of LOX-1 mRNA were detected by RT-PCR.Results Compared with the control group,ox-LDL could increase apoptosis and the expression of LOX-1(P<0.05),and Bezafibrate could decrease the apoptosis and the expression of LOX-1 in a concentration -dependent manner(P<0.05).Preincubation of HUVECs with polyinosinic acid for 2 hours,the apoptosis and the expression of LOX-1 decreased(P<0.05).Conclusions Bezafibrate inhibits the apoptosis of HUVECs mediated by ox-LDL by reducing the expression of LOX-1,which may be part of the reasons for bezafibrate to prevent and treat atherosclerosis.