简介：Clusterinisa75-80kDaheterodimericglycoprotein,thatisproducedinmosttissuesbutwhichexactbiologicalroleisstillnotclear.Particularly,itsroleinprotectionorpromotionofapoptosisisheavilydisputed,sincedatasupportingbothviewshavebeenreportedinseveralindependentstudies.Toclarifythisissue,andalsotodeterminewhetherclusterinexpressionitselfmightbeaffectedbyapoptosis,inthepresentstudy,ratthymocytesweretreatedwithdexamethasone,-asyntheticglucocorticoidthatelicitsapoptosisinthymocytes-,andclusterinmRNAexpressionwasanalyzedbysemi-quantitativeRT-PCRbeforeandafterinductionofapoptosis.Interestingly,neitherthetreatmentwithdexamethasoneinvitronortriggeringofapoptosisinvivoup-regulatedclusterinexpression,opposingtheviewthatclusterinisinvolvedinapoptoticprocesses.Ontheotherhand,anewclusterinmRNAisoformwasdetectedandisolated,whoseexpressionwasrestrictedtofreshlyisolatedthymocytes.Thisnovelisoformlacksthepost-translationalproteolyticcleavagesiteandisthereforepredictedtoencodeamonomericprotein.Thebiologicalfunctionundernormalcircumstances,however,willneedfurtherinvestigationsforclarification.Whileapoptosiscouldnotmodulateclusterinexpression,activationofthymocyteswithconcanavalinAandinterleukin-2resultedinup-regulationofclusterinmRNAlevel,indicatingthatclusterinexpressionisratherunderthecontrolofcellactivation-mediatedratherthanapoptosis-inducedsignals.

简介：自我忍耐的损失和汽车反应的淋巴细胞的扩大是汽车免疫的基础。当保证的协调过程与非病理学的结果调整了细胞质和压力反应，Apoptosis和由吞噬细胞的apoptotic房间的快速的清理通常发生。在apoptotic房间的清理的缺点将贡献自我反应的淋巴细胞的产生，它驾驶象风湿性关节炎(RA)和全身的豺狼座erythematosus(SLE)那样的自体免疫的混乱。cytokines(IL-12，IL-23，和IL-27)和IL-10的IL-12家庭被吞噬细胞的巨噬细胞生产并且在对病原体的有免疫力的回答期间在介绍抗原的房间(APC)和受动器淋巴细胞的规定起关键作用。这些cytokines和他们的dysregulated活动的不恰当的表示强烈在几自体免疫的疾病的致病被含有。由吞噬细胞的APC的支持inflammatory和反煽动性的cytokines的生产精巧地作为内在的机制的部分在apoptotic房间的摄取期间被调整阻止煽动性的自体免疫的反应。怎么导出房间的信号调整的apoptoticcytokine生产糟糕被理解。由我们的组的最近的研究证明由激活的巨噬细胞的apoptotic房间的那个吞噬作用由激活一个新奇抄写抑压者导致IL-12p35基因表示的强壮的抑制，我们把它称为GC有约束力的蛋白质(GC-BP)，通过酷氨酸dephosphorylation。我们开始也正在理解位于apoptotic下面的分子的机制由吞噬细胞的IL-10的被触发房间的生产。阐明的这些研究愿望帮助一些新奇有免疫力的规章的机制并且与潜力探索对汽车抗原的有免疫力的回答的规定为自体免疫的混乱的处理发现新治疗学的目标。

简介：Anuranmetamorphosisinvolvessystematictransformationsofindividualorgansinathyroidhormone(TH)-dependentmanner.Morphologicalandcellularstudieshaveshownthattheremovaloflarvalorgans/tissuessuchthetailandthetadpoleintestinalepitheliumisthroughprogrammedcelldeathorapoptosis.RecentmolecularinvestigationssuggestthatTHregulatesmetamorphosisbyregulatingtargetgeneexpressionthroughthyroidhormonereceptors(TRs),whichareDNA-bindingtranscriptionfactors.CloningandcharacterizationofTHresponsegenesshowthatdiversegroupsofearlyresponsegenesareinducedbyTH.TheproductsoftheseTHresponsegenesarebelievedtodirectlyorindirectlyaffecttheexpressionand/orfunctionsofcelldeathgenes,whichareconservedatbothsequenceandfunctionlevelsindifferentanimalspecies.Amajorchallengeforfutureresearchliesatdeterminingthesignalingpathwaysleadingtotheactivationofapoptoticprocessesandwhetherdifferentdeathgenesareinvolvedintheregulationofapoptosisindifferenttissues/organstoeffecttissue-specifictransformations.

简介：AIM:Toidentifythosewithamicropapillarypattern,ascertainrelativefrequencyanddocumentclinicopathologicalcharacteristicsbyreviewinggastriccarcinomas.METHODS:Onehundredandfifty-onepatientsdiagnosedwithgastriccancerwhounderwentgastrectomywereretrospectivelystudiedandthepresenceofaregionalinvasivemicropapillarycomponentwasevaluatedbylightmicroscopy.Allavailablehematoxylin-eosin(HE)-stainedslideswerehistologicallyreviewedand5tumorswereselectedasp...

简介：<正>Althoughapoptosishasbeenrecentlydocumentedtotransmitimmunosuppressivesignals,theirsignificanceinallogeneictransplantationhasnotbeenreported.Inthepresentstudy,weinvestigatedtheinfluenceofdonorapoptoticsplenocytesonallograftsurvivalinaSDtoWistarratcardiactransplantmodel.Donorsplenocyteswereisolatedandirradiatedwithultraviolet(UV)toinduceapoptosisinvitro.5x107apoptotic,necroticoruntreateddonorspleencellsweretransfusedpreoperativelyandcardiacallogeneictransplantation

简介：Genisteiniseffectiveagainstamyloid-βtoxicity,buttheunderlyingmechanismsareunclear.Wehypothesizedthatgenisteinmayprotectneuronsbyinhibitingthemitochondrialapoptoticpathway,andtherebyplayaroleinthepreventionofAlzheimer'sdisease.AratmodelofAlzheimer'sdiseasewasestablishedbyintraperitonealinjectionofD-galactoseandintracerebralinjectionofamyloid-βpeptide(25–35).Inthegenisteintreatmentgroups,a7-daypretreatmentwithgenistein(10,30,90mg/kg)wasgivenpriortoestablishingAlzheimer'sdiseasemodel,for49consecutivedays.Terminaldeoxyribonucleotidyltransferase-mediateddUTPnickendlabelingassaydemonstratedareductioninapoptosisinthehippocampusofratstreatedwithgenistein.Westernblotanalysisshowedthatexpressionlevelsofcapase-3,Baxandcytochromecweredecreasedcomparedwiththemodelgroup.Furthermore,immunohistochemicalstainingrevealedreductionsincytochromecandBaximmunoreactivityintheserats.MorriswatermazerevealedasubstantialshorteningofescapelatencybygenisteininAlzheimer'sdiseaserats.Thesefindingssuggestthatgenisteindecreasesneuronallossinthehippocampus,andimproveslearningandmemoryability.Theneuroprotectiveeffectsofgenisteinareassociatedwiththeinhibitionofthemitochondrialapoptoticpathway,asshownbyitsabilitytoreducelevelsofcaspase-3,Baxandcytochromec.

简介：Age-relatedhearingloss(AHL),orpresbycusis,isthemostcommonneurodegenerativedisorderandtopcommunicationdeficitoftheagedpopulation.GeneticpredispositionisoneofthemajorfactorsinthedevelopmentofAHL.Generally,AHLisassociatedwithanage-dependentlossofsensoryhaircells,spiralganglionneuronsandstriavasculariscellsintheinnerear.Althoughthemechanismsleadingtogenetichearinglossarenotcompletelyunderstood,caspase-familyproteasesfunctionasimportantsignalsintheinnerearpathology.ItisnowacceptedthatmousemodelsarethebesttoolstostudythemechanismofgenetichearinglossorAHL.Here,weprovideabriefreviewofrecentstudiesonhearingimprovementinmousemodelsofAHLbyanti-apoptotictreatment.

简介：ObjectivesToinvestigatetheanti-apoptoticeffectsofmesenchymalstemcells(MSCs)onhypoxicinjuredcardiacmyocytesinvitro.MethodsMSCswereisolatedfrombonemarrowofSprague-Dawley(SD)rats,andcardiacmyocytesfromneonatalrats.Theratcardiacmyocyteswereco-culturedwithMSCsorMSC-conditionedmediainanoxia(95%N2+5%CO2)for72hours.CellapoptosiswasmeasuredbyHoechst33258staining.TheexpressionofBcl-2andBaxincardiacmyocyteswastestedbyWesternBlot.ResultsTheapoptoticratewas51.6%±2.4%whencardiacmyocyteswereculturedincontinuoushypoxiaandwassignificantlydecreasedwhencardiacmyocyteswerecoculturedwithMSCsorMSC-conditionedmedia(15.1%±5.4%and24.0%±4.2%respectively,P<0.001).ThedecreasedexpressionofBaxinthecardiacmyocyteswasgreatlyrelatedtothedecreasingofapoptosis,buttherewasnodifferenceinBcl-2expressionamongthesegroups.ConclusionsCo-culturedMSCsshowedsignificantanti-apoptoticeffectsoncardiacmyocytesincontinuoushypoxia.ThemechanismmaybetheinteractofcelltocellandparacrineofcytokineswhicheffectedtheexpressionofBaxinthecardiacmyocytes.

简介：·AIM:Toinvestigatethepossibleeffectsofintracameralbevacizumabonoxidativestressparametersandapoptosisincornealtissue.·METHODS:Intotal,30ratswereassignedrandomlyintothefollowingthreegroupsof10ratseach:ashamgroup(Group1;n=10),acontrolgroup[Group2;balancedsaltsolution(BSS)wasadministeredat0.01mL;n=10],andatreatmentgroup(Group3;bevacizumabwasadministeredat0.25mg/0.01mL;n=10).Thetotalantioxidantstatus(TAS)andthetotaloxidantstatus(TOS)inthecornealtissueandbloodsamplesweremeasured,andtheoxidativestressindex(OSI)wascalculated.Additionally,cornealtissuehistopathologywasevaluatedforcaspase-3and8stainingandapoptoticactivity.·RESULTS:Inthebloodsamples,theTAS,TOS,andOSIlevelswerenotsignificantlydifferent(allP>0.05).Comparedwiththeshamandcontrolgroups,theTOSandOSIlevelsinthecornealtissuesweresignificantlydifferentinthebevacizumabgroup(allP<0.05).Nostatisticallysignificantdifferenceswereobservedbetweentheshamandcontrolgroups(allP>0.05).However,comparedwiththeshamandcontrolgroups,greaterimmunohistochemicalstainingforcaspases-3and8andanelevatedlevelofapoptoticactivitywereobservedinthebevacizumabgroup.·CONCLUSION:Thisstudyrevealedthatintracameralbevacizumabinjectionsseemedtobesystemicallysafebutmayhaveelicitedlocaltoxiceffectsinthecornealtissue,asindicatedbytheoxidativestressparametersandhistopathologicalevaluations.

简介：Apoptotic房间转移被发现了能便于allograft的嫁接。然而，内在的机制尚待充分被理解。这里，我们证明施主apoptoticsplenocytes的静脉内的管理能由导致tolerogenic的产生支持胰腺的小岛嫁接树枝状的房间(Tol-DCs)和CD4+Foxp3+规章的T房间(Tregs)。在vivo，树枝状的房间(DC)或Tregs的清理由apoptotic房间管理阻止了有免疫力的忍耐的正式就职。用anti-CD25的Tregs的短暂消除，monoclonal抗体(mAb)在apoptoticsplenocytes的管理以后废除了Tol-DCs的产生。相互地，在用白喉毒素(DT)的CD11c数据终端就绪老鼠以内的DC的弄空与apoptoticsplenocytes的管理在接受者阻止了Tregs的产生。在二个房间之间的房间接触打的由直接要求，并且规划了死亡1ligand(PD-L1)的Tol-DCs的Tregs的正式就职在Tregs扩大起了重要作用。Apoptotic房间管理没能在IL-10-deficient和Smad3缺乏的老鼠导致Tol-DCs，建议那IL-10和转变生长factor-β；(TGF-β；)被需要处于tolerogenic状态维持DC。因此，我们证明Tol-DCs在他们的表面上并且相互地经由PD-L1支持Tregs的扩大Tregs便于Tol-DCs维持apoptotic房间经由secretingIL-10和TGF-β导致的移植忍耐；。

简介：以前的调查后退幸存由神经生长因素(NGF)和另外的neurotrophins发信号支持了多样的机制，但是所有建议机制有在普通retrogradely传给neuronal细胞身体的幸存信号的产生。我们报导在轴突发现被本地NGF发信号压制一个retrogradeapoptotic信号。从远侧的轴突的NGF退却独自是足够的激活pro-apoptotic抄写因素，c-jun，在房间身体。直接提供NGF给房间身体，从而恢复导致NGF的幸存的来源发信号，不能阻止NGF退却从远侧的轴突引起的c-jun激活。这是c-jun没在房间身体由于幸存信号的损失被激活的证据。而且，与用番红花作原料而制成的植物盐基堵住axonal运输禁止了建议retrogradely搬运的幸存的一个retrogradely搬运的pro-apoptotic信号，而非损失发信号的NGF剥夺引起的c-jun激活，引起的c-jun激活。另外的实验证明c-jun，pro-caspase-3劈开，和apoptosis的激活被蛋白质kinaseC禁止者，rottlerin和chelerythrine堵住，仅仅当适用于建议他们堵住轴突特定的pro-apoptotic信号的远侧的轴突时。rottlerin敏感的机制被发现调整肝糖synthasekinase3(GSK3)活动。siRNA的效果击倒，并且GSK3的药理学抑制建议GSK3为NGF剥夺引起的apoptosis被要求并且可以作为轴突apoptotic信号的一个retrograde搬运人工作。在被neurotrophins压制的轴突表明系统的retrograde死亡的存在为neurodevelopment并且为为neurodegenerative疾病和neurotrauma发现治疗有宽广含意。

简介：AIM:Toinvestigatetheanti-apoptoticcapabilityofthehepatitisBvirus(HBV)intheHepG2hepatomacelllineandtheunderlyingmechanisms.METHODS:CellviabilityandapoptosisweremeasuredbyMTTassayandflowcytometry,respectively.Targetedknockdownofmanganesesuperoxidedismutase(MnSOD),AMP-activatedproteinkinase(AMPK)andhepatitisBvirusXprotein(HBx)genesaswellasAMPKagonistAICARandantagonistcompoundCwereemployedtodeterminethecorrelationsofexpressionofthesegenes.RESULTS:HBVmarkedlyprotectedthehepatomacellsfromgrowthsuppressionandcelldeathintheconditionofserumdeprivation.AdecreaseofsuperoxideanionproductionaccompaniedwithanincreaseofMnSODexpressionandactivitywasfoundinHepG2.215cells.Moreover,AMPKactivationcontributedtotheup-regulationofMnSOD.HBxproteinwasidentifiedtoinducetheexpressionofAMPKandMnSOD.CONCLUSION:OurresultssuggestthatHBVsuppressesmitochondrialsuperoxidelevelandexertsanantiapoptoticeffectbyactivatingAMPK/MnSODsignalingpathway,whichmayprovideanovelpharmacologicalstrategytopreventHCC.

简介：ActivinA,amemberofthetransforminggrowthfactor-betasuperfamily,playsaneuroprotectiveroleinmultipleneurologicaldiseases.Endoplasmicreticulum(ER)stress-mediatedapoptoticandautophagiccelldeathisimplicatedinawiderangeofdiseases,includingcerebralischemiaandneurodegenerativediseases.ThapsigarginwasusedtoinducePC12celldeath,andActivinAwasusedforintervention.OurresultsshowedthatActivinAsignificantlyinhibitedmorphologicalchangesinthapsigargin-inducedapoptoticcells,andtheexpressionofapoptosis-associatedproteins[cleaved-caspase-12,C/EBPhomologousprotein(CHOP)andcleaved-caspase-3]andbiomarkersofautophagy(Beclin-1andlightchain3),anddownregulatedtheexpressionofthapsigargin-inducedERstress-associatedproteins[inositolrequiringenzyme-1(IRE1),tumornecrosisfactorreceptor-associatedfactor2(TRAF2),apoptosissignal-regulatingkinase1(ASK1),c-JunN-terminalkinase(JNK)andp38].Theinhibitionofthapsigargin-inducedcelldeathwasconcentration-dependent.ThesefindingssuggestthatadministrationofActivinAprotectsPC12cellsagainstERstress-mediatedapoptoticandautophagiccelldeathbyinhibitingtheactivationoftheIRE1-TRAF2-ASK1-JNK/p38cascade.

简介：我们以前报导了那ONO-AE-248，选择EP3受体收缩筋，没有apoptosis和坏死的典型特征，被显示了引起嗜中性的死亡。然而，嗜中性的死亡的机制是不清楚的。由使用西方的弄污，流动cytometry(FACS)和扫描显微镜学(CLSM)的共焦的激光，我们调查了嗜中性的死亡的细胞的信号transduction小径。研究结果证明ONO-AE-248导致的嗜中性的死亡没显示出apoptosis的词法变化并且没与p38-MAPK的caspase-3，caspase-8，和phosphorylation的活动被联系。然而，线粒体transmembrane潜力的缺陷在房间死亡的过程期间被发现了。这些调查结果建议ONO-AE-248导致了non-apoptoticneutrophils通过的规划房间死亡部分线粒体发信号transduction小径。

简介：Therearefewstudiesontheneuroprotectiveeffectsofsyringaldehydeinaratmodelofcerebralischemia.Thestudyaimedtoelucidatethemechanismsunderlyingtheneuroprotectiveeffectsofsyringaldehydeonischemicbraincells.Ratmodelsofcerebralischemiawereintraperitoneallyadministeredsyringaldehyde.At6and24hoursaftersyringaldehydeadministration,celldamageinthebrainofcerebralischemiaratswasobviouslyreduced,superoxidedismutaseactivityandnuclearrespiratoryfactor1expressioninthebraintissueweremarkedlyincreased,malondiadehydelevelwasobviouslydecreased,apoptosis-relatedcysteinepeptidasecaspase-3and-9immunoreactivitywasobviouslydecreased,andneurologicalfunctionwasmarkedlyimproved.Thesefindingssuggestthatsyringaldehydeexertsneuroprotectiveeffectsoncerebralischemiainjurythroughanti-oxidationandanti-apoptosis.

简介：AbstractObjective:Paclitaxel (PAC) is a chemotherapy drug and has an active role in the treatment of lung, breast, and ovarian cancers; however, its use causes increased levels of free radicals, leading to severe and irreversible organ damage. Thymus vulgaris is a species of flowering plant that contains various antioxidant chemical compounds. This study aimed to investigate the effect of T. vulgaris on PAC-induced oxidative damage in mice testis and sperm parameters.Methods:In this study, 40 BALB/c mice were divided into five groups: normal control (NC); positive control (20 mg/kg of PAC); and three treatment groups (4.5, 9, and 18 mg/kg doses of T. vulgaris extract + 20 mg/kg PAC). Treatments were administered intraperitoneally daily for 50 days. Finally, the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were measured using immunoassay method. Testicular stereological features and sperm parameters were also calculated. Antioxidant parameters were measured using nitrite oxide (NO) and perioxidation levels and ferric-reducing ability of plasma assay. The expressions of p53, caspase-3, Bax, and Bcl-2 were measured through real-time quantitative polymerase chain reaction.Results:T. vulgaris + PAC treatments at all doses significantly increased all parameters in NC and three treatment groups compared with the positive control group (20 mg/kg of PAC) (P < 0.05), except the LH, FSH, and NO levels, which were decreased. Further, significantly downregulated levels of p53, caspase-3, and Bax genes and upregulated levels of Bcl-2 gene expression were noted in NC and three treatment groups in comparison with the positive control group (P < 0.05).Conclusions:T. vulgaris administration attenuates the toxic effects of PAC on male reproductive parameters.

简介：调查recombinantcalreticulin(rCRT)的目的调停了antitumor免疫者反应。方法房间增长被MTT方法决定，apoptosis被DNA破碎和CRT表示评估，房间本地化是由西方的弄污，QT-RT-PCR和immunofluorescence的assayed试金。老鼠黑瘤房间线B16-F1与polyamine类似物后房被对待导致apoptosis并且与rCRT孵化了得到在膜，然后房间上涂的rCRT作为房间抗原习惯于有免疫力的BALB/c老鼠。使免疫的动物被实时B16-F1房间然后肿瘤产生比率重新质问，lactate脱氢酶版本试金被用来评估调停rCRT的免疫的antitumor效果。没有CRT的再分配，结果后房在房间以内导致了B16-F1房间的apoptosis。当与rCRT涂的B16-F1细胞被用作房间抗原接种动物时，老鼠在在vivo禁止相应肿瘤细胞的增长获得了能力。与积极控制组，作比较从那些的splenocytes接种老鼠对B16-F1房间明确地在他们的cytolytic效果上有明显的改进。在房间表面上涂的结论rCRT能提高apoptotic肿瘤的immunogenicity在老鼠的房间和调停的有效反肿瘤immunoresponse。

简介：Objective:Squamousesophagealcarcinomaishighlyprevalentindevelopingcountries,especiallyinChina.TuBeiMu(TBM),atraditionalfolkmedicine,hasbeenusedtotreatesophagealsquamouscellcarcinoma(ESCC)foralongterm.tubeimosideI(TBMS1)isthemaincomponentofTBM,exhibitinggreatanticancerpotential.Inthisstudy,weinvestigatedthemechanismofTBMS1cytotoxiceffectonEC109cells.Methods:Comparativenuclearproteomicapproachwasappliedinthecurrentstudyandweidentifiedseveralalteredproteinspots.Furtherbiochemicalstudieswerecarriedouttodetectthemitochondrialmembranepotential,cellcycleandcorrespondingproteins’expressionandlocation.Results:SubcellularproteomicstudyinthenucleusfromEC109cellsrevealedthatalteredproteinswereassociatedwithmitochondrialfunctionandcellproliferation.FurtherbiochemicalstudiesshowedthatTBMS1-inducedmoleculareventswererelatedtomitochondria-inducedintrinsicapoptosisandP21-cyclinB1/cdc2complex-relatedG2/Mcellcyclearrest.Conclusions:ConsideringtheconventionalapplicationofTBMinesophagealcancer,TBMS1thereforemayhaveagreatpotentialasachemotherapeuticdrugcandidateforESCC.

简介：新鲜的水息肉水螅属于门Cnidaria，它在bilaterians的外观前从后生动物的系分叉。以便在metazoans理解apoptosis的进化，我们开始阐明了在这个模型有机体的分子的细胞死亡机械。基于EST和整个水螅染色体集会，我们识别了15caspases。我们证明一个人在apoptosis期间被激活，四与N终端DED，卡片或DD领域有开始者caspases的特征，二在vitro经历autoprocessing。另外，我们描述七Bcl-2-like和二象Bak一样蛋白质。为大多数Bcl-2家庭蛋白质，我们观察了mitochondrial本地化。当在哺乳动物的房间表示了时，象HyBak一样1和2强烈导致的apoptosis。禁止的apoptosis与显示出特别强壮的保护的效果的HyBcl-2-like4在哺乳动物的房间由camptothecin劝诱了的六个Bcl-2家庭成员。这蛋白质也与象HyBak一样交往了1在酵母二混血儿的试金。在它的BH3领域的保存白氨酸的变化两个都与象HyBak一样废除了相互作用1并且anti-apoptotic效果。而且，我们BH-3-only描述新奇水螅蛋白质。这些之一与Bcl-2-like4交往了并且在哺乳动物的房间导致了apoptosis。我们的数据显示为房间死亡规定的一个复杂网络的进化在多细胞的组织的最早、最简单的水平产生了，它在此展出了一复杂性实质地高级比在protostome模型有机体Caenorhabditis和果蝇。

简介：