简介:Suppressorofcytokinesignaling3(SOCS3)wasreportedasafeedbackinhibitorofcytokinereceptorsignalingbyinhibitingtheJAK-STATsignaltransductionpathway.Wesoughttotesttheanti-endotoxicsepticshockeffectofliposomemediatedgenedeliveryofSOCS3inalethalendotoxicshockmousemodel.BALB/cmicewereinjectedintraperitoneallywith200μgpcDNA3.1-SOCS3cationicliposomes,whilepcDNA3.1-IL-10andemptyvectoraspositiveandnegativecontrolrespectively.Forty-eighthoursaftergenedelivery,micewerechallengedwith4μgofE.coli0127:B8LPSand18mgD-GalNadministeredi.p.90minlater,serumTNF-αlevelwasdetermined.Survivaloverthenext48hwasevaluated.Peritonealmacrophagesfromsurvivalmicewerestimulatedinvitrowith1μg/mlLPSfor18h,andthesupernatantswereharvestedfordeterminationoftheamountofTNF-α.WefoundthatgenedeliveryofSOCS3significantlyincreasethemousesurvivalratefrom27.8±9.6%ofcontrolgroupto61.1±9.6%(p<0.01).Incomparisonwithcontrolgroup(218±13pg/ml)andshamdeliverygroup(219±22pg/ml),genedeliveryofSOCS3reducedthelevelofserumTNF-α(68±9pg/ml)significantly(p<0.01).Furthermore,genedeliveryofSOCS3displayedthecapacityofpreventionoftoleranceofperitonealmacrophagestoLPS.ThesefindingssuggestthatgenedeliveryofSOCS3mediatedbyliposomeisapromisingapproachforendotoxicsepticshocktreatment.Cellular&MolecularImmunology.
简介:ToclarifytheroleofAPOBEC3G(A3G)incellulardefenseagainsthepatitisBvirus(HBV),theexpressionofA3GinnormalhumanliverandtheregulationoftheA3Gexpressioninhep-atomacellline(HuH-7)wereinvestigated.ExpressionlevelofAPOBEC3smRNAinhumanliverwasdeterminedbyRT-PCR.HuH-7andHepG2cellsweretreatedwithvariousconcentrationsofIFN-α(0U/ml,100U/ml,500U/ml,1000U/ml)for12h.ThemRNAlevelsweremeasuredbyaquantitativeRT-PCR,theresultswerenormalizedrelativetothespecimenswithoutIFN-αstimulation.TotalproteinofHuH-7cellstreatedwithvariousconcentrationsofIFN-αfor48hwassubjectedtoWesternblotanalysis.Forreportergeneassay,HuH-7cellsweretransfectedwiththereporterplasmidscontainingIRF-Esitesanditsmutantswithdifferentlengths.Thenthecellsweretreatedwithorwithout1200U/mlIFN-aforadditional12h(1000U/ml)after24hoftransfection,andthecelllysatewaspreparedandassayedforluciferaseactivity.ItwasfoundthatnormalhumanliverexpressedthemRNAofA3G.A3GmRNAexpressioninHuH-7andHepG2cellswereup-regulatedbyIFN-αstimulationinadose-depen-dentmanner.WesternblotanalysisindicatedthatA3GproteinexpressionwasalsoenhancedbyIFN-αstimulation.SequenceanalysisshowedtheexistenceofputativesitesofIFNregulatoryfactorelement(IRF-E)in5'regionofA3Ggeneupstreamtheinitiationcodon.IFN-αstimulationresultsin6-to8-foldincreaseinluciferaseactivityincellstransfectedwiththeplasmidcontainingIRF-Esitesofthe5'upstreamsequences,whereasluciferaseactivitydidnotchangeincellstransfectedwiththeplasmidcontainingmutantIRF-EsitesorwithoutIRF-Esites.Asaconclusion,A3Gareexpressedinnormalhumanliver.A3Gexpressionwasup-regulatedbyIFN-αstimulationinhepatomacellsandcouldbeinvolvedinhostdefensemechanismsagainstHBV.ERF-Esitein5'regionofAP0BEC3Ggeneupstreamtheinitiationcodonplaysanimportantroleinthisp
简介:从生物体的能量消耗最小化原则来讲,生理意义上的基因表达调控多发生在转录水平,尤其是转录伊始不难理解--这样可以避免进行无用的转录过程和mRNA的剪切工作,从而避免了大量的资源浪费.相应地,目前被人们所熟悉的基因表达调控位点几乎都集中在基因的5'端,即转录调控的主要作用位置.然而基因不只有5'端序列,其3'端序列以长度推测亦应富含信息量.目前普遍被接受的一种观点是,基因的3'端,尤其是3'非翻译区涉及了基因转录后水平的调控过程,主要参与mRNA的稳定性、基因表达的定位以及翻译效率等生理进程的调控,具体可能在干细胞增殖分化、性别决定、神经元发生、血红细胞生成等过程中发挥作用.
简介:当病人的基牙相对完好且不适于种植修复时,树脂粘结桥(RBFPDs)是一种值得考虑的修复方法。但是,由于长跨度树脂粘结桥较单桥体树脂粘结桥的修复成功率低,对于2个或更多牙齿缺失的病例,传统树脂粘结桥修复的预后不佳。通过使用改良的非刚性连接体可以减少基牙间与固位体脱粘有关的有害应力,从而很好的提高长跨度树脂粘结桥的成功率。对于这样的长跨度修复体,应使主固位体至少包绕基牙3个面或者预备对称的轴向沟槽以达到辅助固位的目的。连接体应允许基牙间水平向和垂直向运动,这样固位体会具有更好的抗力形和固位形,应力减少,而且辅固位体不会脱粘。非刚性连接体自上而下的就位方式和阴型一主固位体的联合应用对于修复体的成功是至关重要的。如果由于主固位体遭受大载荷而脱粘,修复体可以被容易的取下并重新粘结。
简介:临床上患者和牙医越来越重视天然牙根的保留,利用完善根管治疗过的牙根做桩冠修复,越来越普遍[1].前牙牙冠缺失,不仅影响切割和发音功能,而且影响面部外形美观.利用桩钉插入根管内得以获得固位的桩冠修复,特别是烤瓷桩冠的修复,不仅固位良好,颜色和形态均能接近天然牙.但是,如果在桩冠制作的过程中,桩钉选择不当,桩钉加工技术欠缺,或者因外部因素,如外伤,咬合创伤等,均可造成桩钉的折断或脱落.临床上常采用取出断端桩钉,重新修复.当断面发生在根中1/3处,根内部分牢固,X线片显示根内部分较长(大于5mm),且临床上又难以取出时,作者认为可以不取出断端,采用桩钉两端凹凸相嵌的办法,进行桩冠修复.
简介:Objective:AllelicpolymorphismsofCCR5△32、CCR2b-64I,CX3CR1-249I280MandSDF1-3’AassociatedwithHIV-1infectionanddiseaseprogressionwereinvestigatedinindigenousUygurpopulationsfromtheXinjiangUygurAutonomousRegionofChina.Mithods:Thestudypopulationcomprised316healthyUygursubjectswithanagerangeof1-80yearsold,fromwhomwholeperipheralbloodsampleswerecollectedandnonewereHIV-1seropositive.GenomicDNAsampleswerepurifiedusingaQiagenBloodKit.GenotypingoftheaforementionedfouralleleswasperformedusingPCRorPCR/RFLPassay,andfurtherconfirmedbydirectDNAsequencing.Results:TheallelicfrequenciesinChineseUygurpopulationwereasfollows:3.48%forCCR5△32;19.45%forCCR2b-64I;13.8%forCX3CRI-249I280Mhaplotype,and20.41%forSDFI-3’A.MutantalleledistributionsamongUygurpopulationswereinaccordancewiththeHardy-Weinbergequilibrium.NostatisticaldifferencewasfoundbetweenthefrequencyofthethreeHIVcoreceptorsandtheirrespectiveligandgenes.Conclusion:ThefrequencyofSDF1-3’AandCX3CR1-249I280MhaplotypemorecloselymatchedthehanChinese.ThefequencyofCCR5△32inUygurpopulationswasbetweenCaucasianandHanfrequencies,themorecloselymatchingthefrequencyinMedi-Asiapeople.NogeneticlinkagebetweenanytwoofthethreeHIVcoreceptorgeneswasfound,butobviousgeneticlinkagesexistedbetweenCX3CR1-249IandCX3CR1-280M,withevenhigherlinkagedegreesthanCaucasianpeople.