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6 个结果
  • 简介:Thismini-reviewpresentstheauthors'visiononthecurrentstatusandfuturetrendsinthedevelopmentofneuroprotectiveagentsworkingviaactivationofnuclearfactorerythroid2-relatedfactor2(Nrf2),andinparticular,viadisruptionofNrf2-Keaplinteraction.Therearetwoopposite'chemical'mechanismsunderlyingsuchactivation:thefirstoneisanon-specificcovalentmodificationofKeap1thiols,resultinginsideeffectsofvariedseverity,andthesecondoneistheshiftoftheNrf2-Kelch-likeECHassociatedprotein-1(Keap1)bindingequilibriuminthepresenceofacompetitiveandchemicallybenigndisplacementagent.Atthispoint,nodisplacementactivatorsexhibitsufficientbiologicalactivityincomparisonwithcommonNrf2activatorsworkingviaKeaplthiolmodification.Hence,thehopeintherapeuticsisnowlinkedtotheFDAapproveddimethylfumarate,whosederivative,monomethylfumarate,aswedemonstratedrecently,ismuchlesstoxicbutequallybiologicallypotentandanidealcandidateforclinicaltrialsrightnow.AnewlyemergingplayerisanuclearinhibitorofNrf2,BTBdomainandCNChomolog1(Bach1).ThecommerciallydevelopedBachlinhibitorsarecurrentlyunderinvestigationinourlaboratoryshowingpromisingresults.Inourviewpoint,theperfectfuturedrugwillpresentthecombinationofadisplacementactivatorandBachlinhibitortoinsuresafetyandefficiencyofNrf2activation.

  • 标签: 治疗 化学驱油剂 展望 基础 发展趋势 相关因子
  • 简介:肿瘤的一个重要特性就是肿瘤细胞的无限增殖,这一特性可以通过基因变异实现端粒长度的维持,从而解除细胞周期的限制来实现[1-2]。对黑色素瘤的研究表明,体细胞端粒长度的维持主要有两种机制:端粒酶依赖性机制(85%)和端粒酶非依赖性机制(15%)[3],后者依靠ATRX和DAXX变异介导的端粒替代延长机制(ALT)实现端粒的延长;

  • 标签: TERT 神经胶质瘤 端粒长度 非依赖性 启动子区域 高甲基化
  • 简介:目的探讨下调或过表达FOXR2对脑胶质瘤细胞增殖能力的影响。方法以正常脑组织标本为模板,PCR法克隆FOXR2基因,并构建FOXR2过表达质粒;Westernblot法检测FOXR2在胶质瘤细胞系中的表达水平。用慢病毒系统构建稳定下调及过表达FOXR2的脑胶质瘤细胞株;CCK8实验检测下调或过表达FOXR2对胶质瘤细胞增殖速率的影响。结果成功克隆FOXR2基因;WB检测结果显示稳定下调FOXR2的U251细胞株及过表达FOXR2的U87细胞株构建成功。CCK8实验结果表明,与对照组相比,96h后下调FOXR2的胶质瘤细胞增殖速率减少45.13%;相反,过表达FOXR2后,胶质瘤细胞的增殖速率可增加43.98%。结论转录因子FOXR2可促进胶质瘤细胞的增殖。

  • 标签: 脑胶质瘤 FOXR2 增殖
  • 简介:Heatshockprotein70(HSP70)maintainsCa~(2+)homeostasisinPC12cells,whichmayprotectagainstapoptosis;however,themechanismsofneuroprotectionareunclear.Therefore,inthisstudy,weexaminedCa~(2+)levelsinPC12cellstransfectedwithanexogenouslentiviralHSP70geneexpressionconstruct,andwesubsequentlysubjectedthecellstoischemia-hypoxia/reoxygenationinjury.HSP70overexpressionincreasedneuronalviabilityandATPaseactivity,anditdecreasedcellularreactiveoxygenspecieslevelsandintracellularCa~(2+)concentrationafterhypoxia/reoxygenation.HSP70overexpressionenhancedtheproteinandmRNAexpressionlevelsofsarcoplasmic/endoplasmicreticulumCa~(2+)-ATPase(SERCA),butitdecreasedtheproteinandmRNAlevelsofinositol1,4,5-trisphosphatereceptor(IP3R),therebyleadingtodecreasedintracellularCa~(2+)concentrationafterischemia-hypoxia/reoxygenation.TheseresultssuggestthatexogenousHSP70protectsagainstischemia-hypoxia/reoxygenationinjury,atleastinpart,bymaintainingcellularCa~(2+)homeostasis,byupregulatingSERCAexpressionandbydownregulatingIP_3Rexpression.

  • 标签: 缺氧/复氧损伤 热休克蛋白70 PC12细胞 神经保护作用 细胞内 钙稳态
  • 简介:Thestudyaimstoconfirmtheneuroregenerativeeffectsofbacterialmelanin(BM)oncentralnervoussysteminjuryusingaspecialstainingmethodbasedonthedetectionofCa~(2+)-dependentacidphosphataseactivity.Twenty-fourratswererandomlyassignedtoundergoeitherunilateraldestructionofsensorimotorcortex(groupI;n=12)orunilateralrubrospinaltracttransectionatthecervicallevel(C3–4)(groupⅡ;n=12).Ineachgroup,sixratswererandomlyselectedaftersurgerytoundergointramuscularinjectionofBMsolution(BMsubgroup)andtheremainingsixratswereintramuscularlyinjectedwithsaline(salinesubgroup).NeurologicaltestingconfirmedthatBMacceleratedtherecoveryofmotorfunctioninratsfrombothBMandsalinesubgroups.Twomonthsaftersurgery,Ca~(2+)-dependentacidphosphataseactivitydetectionincombinationwithChilingarian'scalciumadenosidetriphosphatemethodrevealedthatBMstimulatedthesproutingoffibersanddilatedthecapillariesinthebrainandspinalcord.TheseresultssuggestthatBMcanpromotetherecoveryofmotorfunctionofratswithcentralnervoussysteminjury;anddetectionofCa~(2+)-dependentacidphosphataseactivityisafastandeasymethodusedtostudytheregeneration-promotingeffectsofBMontheinjuredcentralnervoussystem.

  • 标签: 中枢神经系统损伤 酸性磷酸酶活性 活性检测 黑色素 依赖性 细菌性
  • 简介:目的:总结非接触式球囊标测系统指导下室性心律失常射频消融术患者的护理方法。方法:回顾分析在非接触式球囊标测系统指导下行室性心律失常射频消融术的2例患者的病例资料,并总结临床护理方法。结果:2例患者均在非接触式球囊标测系统指导下标测到心动过速的靶点,并成功进行射频消融治疗,术后恢复良好。结论:非接触式球囊标测系统是一种较新的技术,对疑难复杂心律失常的射频消融治疗有很好的指导作用,术中及围术期护理有其自身特点,合理的护理措施有利于手术的顺利进行和患者术后康复。

  • 标签: 非接触标测 室性心律失常 射频消融 护理