简介：Ahallmarkofallformsofneurodegenerativediseasesisimpairmentofneuronalfunctions,andinmanycasesneuronalcelldeath.Althoughtheetiologyofneurodegenerativediseasesmaybedistinct,differentdiseasesdisplayasimilarpathogenesis,forexampleabnormalimmunitywithinthecentralnervoussystem(CNS),activationofmacrophage/microgliaandtheinvolvementofproinflammatorycytokines.Recentstudiesshowthatneuronsinaneurodegenerativestateundergoahighlyregulatedprogrammedcelldeath,alsocalledapoptosis.TNF-relatedapoptosis-inducingligand(TRAIL),amemberoftheTNFfamily,hasbeenshowntobeinvolvedinapoptosisduringmanydiseases.Asonememberofadeathligandfamily,TRAILwasoriginallythoughttotargetonlytumorcellsandwasnotpresentinCNS.However,recentdatashowedthatTRAILwasunregulatedinHIV-1-infectedandimmune-activatedmacrophages,amajordiseaseinducingcellduringHIV-1-associateddementia(HAD).TRAILisalsoinducedonneuronbyβ-amyloidprotein,animportantpathogenforAlzheimer'sdisease.Inthisreview,wesummarizethepossiblecommonaspectsthatTRAILinvolvedthoseneurodegenerativediseases,TRAILinducedapoptosissignalingintheCNScells,andspecificroleofTRAILinindividualdiseases.Cellular&MolecularImmunology.2005;2(2):113-122.

简介：Objective:Toinvestigatetheexpressionofmatrixmetalloproteinase-7(MMP-7)andFasligand(FasL)ingastriccancerandexploretheirroleinprogressionofgastriccancer.Methods:Formalin-fixedparaffinandembeddedtissuesofprimarygastriccancerandadjacentnon-tumormucosafrom113caseswereevaluatedforMMP-7,FasLandCapase-3expressionbystreptavidin-peroxidase(S-P)immunohistochemistry.Theexpressionofthefirsttwoproteinsincancercellsofprimaryfociwascomparedwithclinicopathologicalparametersoftumors.WealsoobservedthecorrelationofMMP-7andFasLexpressionwithCaspase-3expressionincancercellsofprimaryfoci.Results:MMP-7positiveimmunostainingwaslessfrequentlydetectedinadjacentepithelialcellsthanincancercellsofprimaryfociofgastriccancer(P<0.05,29.2%vs69.0%),andsowasFasL(P<0.05,34.5%vs54.0%).MMP-7expressionwasassociatedwithtumorsize,Borrmann'sclassification,invasivedepth,metastasisandTNMstaging(P<0.05),butnotwithgrowthpattern,Lauren'sclassification,orhistologicalclassification(P>0.05).FasLexpressionwascorrelatedwithtumorsize,invasivedepth,metastasis,Lauren'sclassification,histologicalclassification(P<0.05),whilenotwithBorrmann'sclassification,TNMstagingorgrowthpattern(P>0.05).CancercellsofprimaryfociexpressedlessCaspase-3thantheiradjacentepithelialcells(P<0.05,32.7%vs50.4%).TherewasanobviouscorrelationbetweenFasL,MMP-7andCaspase-3expressionincancercellsofprimaryfoci(P<0.05).Co-expressionofMMP-7andFasLparalleledwithCaspase-3expressionincancercellsofprimaryfoci(P<0.05).Conclusion:MMP-7andFasLexpressionwasup-regulatedingastriccarcinogenesisandwasprincipallyinvolvedinprogressionofgastriccancer.FasLexpressioncouldreflectthedifferentiationofgastriccancercellsandunderliethemolecularmechanismsofdifferentpathwaysofgastrictumorigenesis.Co-expressionofMMP-7andFasLcouldhaveapoptosis-inducingeffe

简介：AIM:TOexplorethefeasibilityofenhancingapoptosis-inducingeffectsofchemotherapeuticdrugsonhumangastriccancercellsbystabletransfectionofextrinsicSmacgene.METHODS:AfterSmacgenewastransferredintogastriccancercelllineMKN-45,subclonecellswereobtainedbypersistentG418selection.CellularSmacgeneexpressionwasdeterminedbyRT-PCRandWesternblotting.Aftertreatmentwithmitomycin(MMC)asanapoptoticinducer,invitrocellgrowthactivitieswereinvestigatedbytrypanblue-stainingmethodandMI-Icolorimetry.Cellapoptosisanditsratesweredeterminedbyelectronicmicroscopy,annexinV-FITCandpropidiumiodidestainingflowcytometry.Cellularcaspase-3proteinexpressionanditsactivitieswereassayedbyWesternblottingandcolorimetry.RESULTS:WhencomparedwithMKN-45cells,theselectedsubclonecelllineMKN-45/SmachadsignificantlyhigherSmacmRNA(3.12±0.21vs0.82:1:0.14,t=7.52,P<0.01)andproteinlevels(4.02±0.24vs0.98:1:0.11,t=8.32,P<0.01).Aftertreatmentwith10μg/mLMMCfor6-24h,growthinhibitionrateofMKN-45/Smac(15.8±1.2-54.8±2.9%)wassignificantlyhigherthanthatofMKN-45(5.8±0.4-24.0±1.5%,t=6.42,P<0.01).PartialMKN-45/Smaccancercellspresentedcharacteristicmorphologicalchangesofapoptosisundertheelectronicmicroscopewithanapoptosisrateof36.4=1=2.1%,whichwassignificantlyhigherthanthatofMKN-45(15.2±0.8%,t=9.25,P<0,01).ComparedwithMKN-45,caspase-3expressionlevelsinMKN-45/Smacwereimprovedsignificantly(3.39±0.42vs0.96:1:0.14,t=8.63,P<0.01),whileitsactivitieswere3.25timesasmanyasthoseofMKN-45(0.364±0.010vs0.112:1:0.007,t=6.34,P<0.01).CONCLUSION:StabletransfectionofextrinsicSmacgeneanditsover-expressioningasbiccancercelllinecansignificantlyenhancecellularcaspase-3expressionandactivities,ameliorateapoptosis-inducingeffectsofmitomycinConcancercells,whichisanovelstrategytoimprovechemotherapeuticeffectsongastriccancer.

简介：AbstractObjective:Structural abnormalities and dysfunction of the placenta contribute to pregnancy-related complications, such as preeclampsia. Syncytin-A (synA) has been reported to be expressed in the placenta. The contribution of synA to developmental abnormalities and dysfunction of the placenta remains elusive. In this study, we aimed to explore the role of synA in placental development and functions.Methods:SynA-knockout mice were generated using the CRISPR-Cas9 method, and the phenotypes of the placenta and fetus of synA-knockout mice were observed. Real-time quantitative polymerase chain reaction (PCR) and routine PCR were employed to detect the genotypes of the offspring. CD31 immunohistochemistry was used to evaluate the vessel density of the placenta, and the protein levels of key molecules were measured by western blotting.Results:SynA knockout caused fetal death. Furthermore, synA-knockout mice showed placental developmental abnormalities, indicated by a thinner labyrinth layer, thicker spongiotrophoblast layer, lower blood vessel density, and significantly higher numbers of apoptotic trophoblasts, when compared with wild-type littermates. Mechanistically, synA ablation induced apoptosis-inducing factor (AIF) cleavage and nuclear localization and promoted placental trophoblast apoptosis. In addition, synA knockout increased the calpain1 protein levels. The calpain1 inhibitor calpeptin blocked synA knockout-induced AIF cleavage, partially restoring the placental structural abnormalities of synA-knockout mice.Conclusions:SynA knockout leads to placental developmental abnormalities by inducing trophoblastic apoptosis via the calpain1-AIF pathway.

简介：AIMTo在透镜调查Aquaporin-1(AQP-1)的角色上皮的房间(LEC)和它的潜在的目标基因。AQP-1明确地在眼睛的LEC被表示并且为透镜动态平衡和透明性维护是重要的。此处，在LEC的AQP-1表示被调查在奔流formation.METHODSLECs与它的潜在的角色联合在房间幸存上评估它的影响是有带AQP-1的lentivirus的transfected小介入RNA(siRNA)。实时聚合酶链反应(PCR)并且西方的弄污被进行从不同的组在LEC检测AQP-1表示。同时，房间数kit-8(CCK-8)试金和流动cytometry被执行测量LEC增长和apoptosis，respectively.RESULTSAQP-1表示显著地在LEC被减少，两个都在mRNA和蛋白质铺平(P<；0.05)，在siRNA处理以后。减少的房间生存能力被CCK-8试金与siRNA干扰在LEC检测，与控制房间相比(P<；0.05)。apoptosis率显著地在siRNA干扰以后在房间增加了(P<；0.05).CONCLUSIONThe减少了在规定下面的房间生存能力追随者AQP-1大部分由于它LEC的apoptosis的正式就职。AQP-1减小可能在LEC导致生理的功能的变化，它可能与奔流的出现和发展被联系。

简介：AbstractBackground:Pulmonary arterial hypertension (PH) is a progressive disease with limited therapeutic options, ultimately leading to right heart failure and death. Recent findings indicate the role of the Warburg effect (aerobic glycolysis) in the development of PH. However, the effect of the glycolysis inhibitor 3-bromopyruvate (3-BrPA) on the pathogenesis of PH has not been well investigated. This study aimed to determine whether 3-BrPA inhibits PH and its possible mechanism.Methods:PH was induced in adult Sprague-Dawley rats by a single intraperitoneal injection of monocrotaline (MCT). 3-BrPA, or phosphate-buffered saline (PBS) was administered via intraperitoneal injection every other day from the first day of MCT-injection to 4 weeks of follow-up, and indices such as right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), pulmonary arteriolar remodeling indicated by percent media thickness (% MT), lactate levels and glucose consumption, were evaluated. Pulmonary arteriolar remodeling and right ventricular hypertrophy were observed in hematoxylin-eosin-stained lung sections. Western blotting, immunohistochemistry, and/or immunofluorescence analyses were used to measure the expression of relevant proteins. A cytochrome C release apoptosis assay and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining were used to measure cell apoptosis.Results:MCT-induced PH showed a significant increase in glucose consumption (0 vs. 4 weeks: 0.87 ± 0.23 vs. 2.94 ± 0.47, P = 0.0042) and lactate production (0 vs. 4 weeks: 4.19 ± 0.34 vs. 8.06 ± 0.67, P = 0.0004). Treatment with 3-BrPA resulted in a concomitant reduction in glucose consumption (1.10 ± 0.35 vs. 3.25 ± 0.47, P = 0.0063), lactate production (5.09 ± 0.55 vs. 8.06 ± 0.67, P= 0.0065), MCT-induced increase in RVSP (39.70 ± 2.94 vs. 58.85 ± 2.32, P= 0.0004), pulmonary vascular remodeling (% MT, 43.45% ± 1.41% vs. 63.66% ± 1.78%, P < 0.0001), and right ventricular hypertrophy (RVHI, 38.57% ± 2.69% vs. 62.61% ± 1.57%, P < 0.0001) when compared with those of the PBS-treated group. 3-BrPA, a hexokinase 2 inhibitor, exerted its beneficial effect on PH by decreasing aerobic glycolysis and was also associated with inhibiting the expression of glucose transporter protein-1, inducing apoptosis, and suppressing inflammation.Conclusions:3-BrPA might have a potential beneficial effect on the PH treatment.

简介：CleavageofchromosomalDNAintooligonucleosomalsizefragmentsisanintegralpartofapoptosis.ElegantbiochemicalworkidentifiedtheDNAfragmentationfactor(DFF)asamajorapoptoticendonucleaseforDNAfragmentationinvitroGeneticstudiesinmicesupporttheimportenceofDFFinDNAfragmentationandpossiblyinapoptosisinvivo.RecentworkalsosuggeststheexistenceofadditionalendonucleasesforDNAdegradation.Understandingtherolesofindividualendonucleasesinapoptosis,andhowtheymightcoordinatetodegradeDNAindifferenttissuesduringnormaldevelopmentandhomeostasis,aswellasinvariousdiseasedstates,willbeamajorresearchfocusinthenearfuture.

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简介：<正>Apoptosisisahighlyregulatedphysiologicalprocesscriticalindevelopmentandtissuehomeostasis.Abnormalapoptosiscanleadtodiseaseconditionsincludingneurodegeneration,autoimmunityandcancer.DNAfragmentationisanintegralpartofapoptosisandhaslongbeensuspectedtobeofcriticalimportanceincleaninguppotentiallyantigenicDNAandgeneticmaterialcapableofinducingneoplasmictransformationinneighboringcells.DirectevidenceforthisfunctionofDNAfragmentationhowever,isstilllacking.TheidentificationofaheterodimericDNAfragmentationfactor45and40(DFF45andDFF40,alsocalledICADforInhibitorofCaspaseActivatedDNaseandCADforCaspaseActivatedDNaserespectively)aswellas

简介：Objective:Toobservehumanneuronalapoptosissecondarytotraumaticbraininjury,andtoelucidateitsregulativemechanismandthechangeofexpressionofapoptosis-relatedgenes.Methods:Specimensofbrainwerecollectedfromcasesoftraumaticbraininjuryinhumans.Thehistologicalandcellularmorphologywasexaminedbylightandelectronmicroscopy.TheextentofDNAinjurytocorticalneuronswasdetectedbyusingTUNEL.ByinsituhybridisationandimmunohistochemistrythemRNAchangesandproteinexpressionofBcl-2,Bax,p53,andcaspase3p20subunitwereobserved.Results:Apoptoticneuronsappearedfollowingtraumaticbraininjury,peakedat24hoursandlastedfor7days.Innormalbraintissueactivatedcaspase3wasrare,butashorttimeaftertraumaitbecameactivated.Theactivitypeakedat20-28hoursandremainedhigherthannormalfor5-7days.TherewasnoexpressionofBcl-2mRNAandBcl-2proteininnormalbraintissuebut8hoursafterinjurytheirexpressionbecameevidentandthenincreased,peakedat2-3daysandremainedhigherthannormalfor5-7days.TheprimaryexpressionofBax-mRNAandBaxproteinwashighinnormalbraintissue.At20-28hourstheyincreasedandremainedhighfor2-3days;onthe7thdaystheyreturnedtoanormallevel.Innormalbraintissue,p53mRNAandP53wereminimallyexpressed.Increasedexpressionwasdetectedatthe8thhour,anddecreasedat20-28hoursbutstillremainedhigherthannormalonthe5thday.Conclusions:Followingtraumaticinjurytothehumanbrain,apoptoticneuronsappeararoundthefocusoftrauma.ThemRNAandproteinexpressionofBcl-2,Baxandp53andtheactivityofcaspase3enzymeareincreased.

简介：Inordertodeterminetheroleofalginate-derivedoligosaccharides(ADO)indroughtstressresistanceoftomato(Ly-copersiconesculentumMiller)seedlings,theleaveswereexposedtodifferentconcentrationsofADO(0.05%,0.10%,0.20%,0.30%and0.50%)afterdroughtstresswassimulatedbyexposingtherootsto0.6molL-1PEG-6000solutionfor6h.Changesinbiomass,electrolyteleakageandmalondialdehyde(MDA),freeproline,totalsolublesugars(TSS)andabscisicacid(ABA),theenzymeactivitiesofcatalase(CAT),superoxidedismutase(SOD),peroxidase(POD)andphenylalanineammonia-lyase(PAL)weremeasuredtoinvestigatetheeffectsofADOtreatment.TheresultsshowedthatthetreatmentwithanADOconcentrationof0.20%exhibitedthehighestperformanceofdroughtstressresistanceinthetomatoseedlingsbydecreasingtheelectrolyteleakageandtheconcentrationofMDA,increasingthecontentsoffreeproline,TSSandABA,andincreasingtheactivitiesofCAT,SOD,PODandPALaftertreatmentwithADO.Itissuggestedthatchangesinelectrolyteleakage,MDA,osmoticsolutes,ABA,anti-oxidativeenzymeandPALactivitieswereresponsiblefortheincreaseddroughtstressresistanceintomatoseedlings.Toourbestknowledge,thisisthefirstreportoftheeffectofADOtreatmentonenhancingthedroughtstressresistanceoftomatoseedlings.

简介：Thechiralclusters(μ3-S)MCoW(CO)8[η^5-C5H4C(O)OCH3][M=Ru(2),Fe(3)]weresynthesizedbyasymmetricinductionofN-benzylcinchoniumchlorideasphase-transfercatalyst(PTC).ThemostsuitableamountofPTCis70mol%.Cluster3wasdeterminedbysinglecrystalX-raydiffractionanalysis.Thebesteeofthechiralclusterisover20%.

简介：Ring-closingmetathesisreactionsinvolvingdiallyldiphenylsilaneanddiallyloxydiphenylsilaneweresuccessfullyperformedbyusingonly0.01molorevenlessofGrubbscatalyst1.Theeffectsofreactionparameters,suchassolvents,temperatureandconcentrationofthecatalystarediscussed.

简介：Wehaveidentifiedseveralkeyeventsinthymocyteapoptosisoverthepastfewyears,includingarequiredroleforproteasomefunctionandtheproductionofROS.WhileweourdataestablishedthatproteasomefunctionandROSproductionarerequiredforapoptosisinthymocytes,wehadnotestablishedtheorderofeventsleadingfromtheprimaryapoptoticstimulustotheactivationofcaspases.Recently,wehavedemonstratedthatbothTcellreceptorinducedapoptosisandglucocorticoidinducedapoptosissignalthymocytestodiethroughactivationoftheproteasomeandthiseventisupstreamoftheproductionofROS.

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简介：Weisolatedandpurifiedmitochondriafrommouseliversandspinachleaves.WhenaddedintoeggextractsofXenopuslaevis,theycausednucleiofmouselivertoundergoapoptoticchanges.Chromatincondensation,marginationandDNAladderwereobserved.Afterincubatingisolatedmitochondriainsomehypotonicsolutions,andcentrifugingthesemixturesatmghspeed,wegotmitochondrialsupernatants.Itwasfoundthatintheabsenceofcytosolicfactor,thesupernatantalonewasabletoinduceapoptoticchangesinnuclei.Theeffectivecomponentswerepartlyofprotein.DNAfragmentationwaspartlyinhibitedbycaspaseinhibitorsAC-DEVD-CHOandAC-YVAD-CHO.Meanwhile,caspaseinhibitorsfullyblockedchromatincondensation.Primarycharacterizationofthenuclearendonuclease(s)inducedbymitochondrialsupernatantswasalsoconducted.ItwasfoundthatthisendonucleaseisdifferentfromendonucleaseG,cytochromec-inducednuclease,orCa^2+-activatedendonuclease.

简介：OurpreviousstudyshowedthattwoMKN45variants,namelyMKN45Lm-andMKN45Lm+selectedbylamininadhesioninvitro,haddifferentabilitiesofinvasionandmetastasisinvivo(inoculatedinnudemice)andinvitro(inBoydenchamber),alsohaddifferentexpressionofcysteineproteinase.Inthepresentstudy,weinvestigatedthecellapoptosisofthisMKN45variantsbyTUNELandFACSmethods.Theresultswereshownsignificantdifferentofcellapoptosisinthiscellsublines.TheMKN45Lm-cellshadasmallsubdiploidypeak(3.5%)inDNAcontentanalyzedbyflowcytometry,

简介：肺上皮是在各种各样的肺疾病的肺损坏的主要地点。上皮的房间apoptosis被认为是在各种各样的肺疾病的起始的事件。发信号的Apoptosis古典主义地由二条原则小径组成。一个人是从死亡受体结扎的一条直接小径到caspase串联激活和房间死亡。象药，放射，传染代理人和反应的氧种类那样的压力触发的另外的小径被线粒体调停。Endoplasmic蜂窝胃也被显示了是细胞器调停apoptosis.Epithelial房间死亡被改变过程跟随，它由组成上皮并且成纤维细胞激活，cytokine生产，凝结小径的激活，neoangiogenesis，re-epithelialization和fibrosis.Epithelial和间充质的相互作用在这些过程起重要作用。apoptosis由新奇策略发信号和它的规定的进一步的理解可以对各种各样的肺疾病导致有效治疗。我们在apoptosis发信号的理解考察最近的进展并且在肺改变讨论apoptosis的参与。

简介：从一只使免疫的dipteran昆虫的一抗菌剂活动部分，Bactrocera背面由prepurification，离子交换层析，胶化过滤层析和反向阶段的高效液体层析(HPLC)是，被孤立并且净化。最后的净化的部分在聪明的系统HPLC上被检查并且被认为是纯部分。Theresults物理并且生物检验表明这部分是热对克积极的细菌的生长的稳定、显示出的强壮的活动。它拥有antibicrobial肽性质并且值得进一步的调查。

简介：Apoptosiscanbetriggeredbyavarietyofstimuliincludingdeathfactors,anti-cancerdrugsandfactor-deprivation.Theseapoptoticcellsareswiftlyphagocytosedbymacrophagestopreventthereleaseofnoxiousorinflammatorymaterialsfromdyingcells.ThemolecularanalysisofFasligand(adeathfactor)-inducedapoptosisindicatedthatacascadeofproteases(caspases)isactivatedduringthisprocess,whicheventuallyactivatesaspecificDNase(caspase-activatedDNase).CADexistsasacomplexwithitsinhibitor(ICAD)inproliferatingcells.Whenthecellsaretriggeredtoapoptosis,caspases,inparticularcaspase3,inthedownstreamofthecaspasecascadecleaveICAD,whichreleasesCADtocauseDNAdegradationinnuclei.