AIM:To examine whether rs2472493 and rs248032 in the ABCA1 gene,rs3785176 in the PMM2 gene,and rs11827818 in the ARHGEF12 gene contribute to primary open angle glaucoma(POAG)in an Iranian population.METHODS:Totally 82...AIM:To examine whether rs2472493 and rs248032 in the ABCA1 gene,rs3785176 in the PMM2 gene,and rs11827818 in the ARHGEF12 gene contribute to primary open angle glaucoma(POAG)in an Iranian population.METHODS:Totally 82 POAG patients and 172 healthy controls were enrolled.The selected gene polymorphisms were analyzed using TaqMan SNP Genotyping Assay using deoxyribonucleic acid(DNA)extracted from blood samples.Allelic and genotypic frequencies were evaluated using the Chi-square test.The association between the genotypes of single nucleotide polymorphisms(SNPs)and POAG was assessed using multiple logistic regression models.The linkage disequilibrium and haplotype block structure were assessed using the Haploview 4.2 software.RESULTS:The results showed a significant association between allele frequencies of rs2472493 in the ABCA1 gene locus and POAG[odds ratio(OR)=1.58,95%confidence intervals(CI)=1.04-2.39,P=0.031].The rs3785176 in the PMM2 gene was also associated with POAG in additive and over dominant genotypes.Moreover,haplotype analysis showed a significant association of two estimated haplotypes of rs2472493/rs2487032 with POAG.The AA haplotype showed a reduction in POAG risk(OR=0.41,95%CI=0.202-0.834,P=0.012),while the GG haplotype was associated with the disease.In addition,this study could not discover any association between genotype and allele frequency of rs248032 in the ABCA1 gene,and rs11827818 in ARHGEF12 gene and POAG.CONCLUSION:rs2472493 in the ABCA1 gene can be considered a genetic susceptibility locus for POAG.The haplotype constructed with ABCA1 gene SNPs(rs2472493/rs2487032)is associated with POAG.展开更多
Background:Diterpenoid esters are considered to be the main toxic components and bioactive constituents of Euphorbia lathyris L.(EL).Euphorbia factors L1(EF1),L2(EF2),and L3(EF3),the main diterpenoid esters of EL,have...Background:Diterpenoid esters are considered to be the main toxic components and bioactive constituents of Euphorbia lathyris L.(EL).Euphorbia factors L1(EF1),L2(EF2),and L3(EF3),the main diterpenoid esters of EL,have been found to cause intestinal diarrhea and induce intestinal inflammation in mice.This research aimed to explore the effects of major diterpenoid esters from EL on intestinal inflammation,as well as to clarify their possible targets and molecular mechanisms in vivo and vitro.Methods:Caco-2 cells and BALB/c mice were intervened with EFL1,EFL2,and EFL3,respectively.The expressions of TLR4,NLRP3,NF-κB p65,LXRα,ABCA1,TNF-αand IL-1βwere measured by Real-time PCR and ELISA.Cholesterol efflux levels were examined using cholesterol efflux kit.Flow cytometry was applied to detect lipid rafts abundance.Confocal microscopy was applied to investigate co-localization of lipid rafts and TLR4.Results:Our results revealed that EFL1,EFL2,and EFL3 inhibited LXRα,ABCA1 expression,and cholesterol efflux,promoted colocalization of TLR4 and lipid rafts,and up-regulated TLR4,NLRP3,NF-κB p65,TNF-αand IL-1βexpressions.Conclusion:These findings reveal that the mechanisms by which EFL1,EFL2,and EFL3 induce intestinal inflammation may be associated with LXRα/ABCA1-regulated lipid rafts and TLR4-mediated pathways.展开更多
目的探讨模型兔颈动脉粥样硬化斑块三磷酸腺苷结合盒运转体A1(ATP bindingcassette A1,AB-CA1)、视黄酸X受体(Retinoid X recepter,RXRα)表达机制及辛伐他丁对其表达的影响。方法32只新西兰大白兔,分为4组,空白对照组8只(A组),余24只...目的探讨模型兔颈动脉粥样硬化斑块三磷酸腺苷结合盒运转体A1(ATP bindingcassette A1,AB-CA1)、视黄酸X受体(Retinoid X recepter,RXRα)表达机制及辛伐他丁对其表达的影响。方法32只新西兰大白兔,分为4组,空白对照组8只(A组),余24只于兔右侧颈动脉放置改良的硅橡胶圈加1%高胆固醇喂养的方法建立粥样硬化斑块性颈动脉狭窄动物模型。颈动脉狭窄模型无干预对照组8只(B组);小剂量辛伐他丁治疗组8只(辛伐他丁每天2.5mg/kg每天1次;C组);大剂量辛伐他丁治疗组8只(辛伐他丁5mg/kg,每日1次,D组)。辛伐他丁干预前后检测兔模型静脉血的TG、TC、LDL及HDL水平,干预4周后处死动物取右侧颈动脉狭窄段及对侧相应段血管,以Western Blot法测定其ABCA1、RXRα蛋白质表达量。结果与A组比较,B、C、D组的ABCA1、RXRα蛋白质表达水平下调(P<0.05);辛伐他丁治疗4周后,与B组比较,C、D组ABCA1、RXRα蛋白质表达水平均有所上调(P<0.05);与C组比较,D组的ABCA1、RXRα蛋白质表达水平下调无统计学意义(P>0.05);与B组比较,C、D组的血脂水平显著下降(P<0.05)。结论ABCA1、RXRα蛋白表达下调可能参与颈动脉粥样硬化形成的机制,辛伐他丁可能通过上调ABCA1、RXRα蛋白质表达的机制,而有益于抗动脉粥样硬化斑块形成作用。展开更多
基金Supported by the Noor Ophthalmology Research Center and Shahroud University of Medical Sciences(No.9449)Shahroud University of Medical Sciences(No.9449)Shahroud Eye Cohort Study is supported by the Noor Ophthalmology Research Center and Shahroud University of Medical Sciences(No.8737).
文摘AIM:To examine whether rs2472493 and rs248032 in the ABCA1 gene,rs3785176 in the PMM2 gene,and rs11827818 in the ARHGEF12 gene contribute to primary open angle glaucoma(POAG)in an Iranian population.METHODS:Totally 82 POAG patients and 172 healthy controls were enrolled.The selected gene polymorphisms were analyzed using TaqMan SNP Genotyping Assay using deoxyribonucleic acid(DNA)extracted from blood samples.Allelic and genotypic frequencies were evaluated using the Chi-square test.The association between the genotypes of single nucleotide polymorphisms(SNPs)and POAG was assessed using multiple logistic regression models.The linkage disequilibrium and haplotype block structure were assessed using the Haploview 4.2 software.RESULTS:The results showed a significant association between allele frequencies of rs2472493 in the ABCA1 gene locus and POAG[odds ratio(OR)=1.58,95%confidence intervals(CI)=1.04-2.39,P=0.031].The rs3785176 in the PMM2 gene was also associated with POAG in additive and over dominant genotypes.Moreover,haplotype analysis showed a significant association of two estimated haplotypes of rs2472493/rs2487032 with POAG.The AA haplotype showed a reduction in POAG risk(OR=0.41,95%CI=0.202-0.834,P=0.012),while the GG haplotype was associated with the disease.In addition,this study could not discover any association between genotype and allele frequency of rs248032 in the ABCA1 gene,and rs11827818 in ARHGEF12 gene and POAG.CONCLUSION:rs2472493 in the ABCA1 gene can be considered a genetic susceptibility locus for POAG.The haplotype constructed with ABCA1 gene SNPs(rs2472493/rs2487032)is associated with POAG.
基金supported by the National Natural Science Foundation of China(Grant no.82074021,82374040)the Beijing Nova Program(Grant no.20240484548).
文摘Background:Diterpenoid esters are considered to be the main toxic components and bioactive constituents of Euphorbia lathyris L.(EL).Euphorbia factors L1(EF1),L2(EF2),and L3(EF3),the main diterpenoid esters of EL,have been found to cause intestinal diarrhea and induce intestinal inflammation in mice.This research aimed to explore the effects of major diterpenoid esters from EL on intestinal inflammation,as well as to clarify their possible targets and molecular mechanisms in vivo and vitro.Methods:Caco-2 cells and BALB/c mice were intervened with EFL1,EFL2,and EFL3,respectively.The expressions of TLR4,NLRP3,NF-κB p65,LXRα,ABCA1,TNF-αand IL-1βwere measured by Real-time PCR and ELISA.Cholesterol efflux levels were examined using cholesterol efflux kit.Flow cytometry was applied to detect lipid rafts abundance.Confocal microscopy was applied to investigate co-localization of lipid rafts and TLR4.Results:Our results revealed that EFL1,EFL2,and EFL3 inhibited LXRα,ABCA1 expression,and cholesterol efflux,promoted colocalization of TLR4 and lipid rafts,and up-regulated TLR4,NLRP3,NF-κB p65,TNF-αand IL-1βexpressions.Conclusion:These findings reveal that the mechanisms by which EFL1,EFL2,and EFL3 induce intestinal inflammation may be associated with LXRα/ABCA1-regulated lipid rafts and TLR4-mediated pathways.
