简介：AbstractObjective:Mifepristone (RU486), one of the most common medications for artificial abortion, attenuates the immunoregulatory effects of progesterone. However, the specific immune regulatory mechanism of RU486 in abortion remains unknown. We intended to investigate the immunomodulatory effects of RU486 on abortion.Methods:Sixty female mice were divided into the control group (0 mg RU486) and RU486 group (2 mg/kg RU486). The uterus, peripheral blood, and spleen were obtained for isolation of specific cell types. The population and phenotype of immune cells in the decidua, peripheral blood, and spleen were analyzed using flow cytometry. Statistical differences between groups were determined using two-tailed t-test. For all statistical tests, P < 0.05 was considered statistically significant.Results:RU486 effectively induced abortion in pregnant mice, with a significantly higher number of decidual macrophages (dMφ) (control group = 25.55% ± 2.467%, RU486 group = 19.41% ± 1.423%; P < 0.05), especially the major histocompatibility complex IIhigh subset. No difference in Mφ number was observed in the spleen or peripheral blood. Moreover, the dMφ from mice with RU486-induced abortion displayed a remarkable activated phenotype, with increased expressions of inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin (IL)-12 but decreased expressions of arginase-1 and IL-10. We also found elevated levels of decidual CD4+ T-cells in the RU486 group that exhibited a higher level of the proinflammatory cytokine interferon-γ and a lower level of the anti-inflammatory cytokines, IL-4 and IL-10.Conclusions:We report a new mechanism of RU486-induced abortion via the regulation of innate cell Mφ activation and the adaptive response of CD4+ T-cells present in the decidua but not the periphery.

简介：GinsenosideRg1（Rg1）hasanti-agingandanti-neurodegenerativeeffects.However,themechanismsunderlyingtheseactionsremainunclear.TheaimofthepresentstudywastodeterminewhetherRg1affectshippocampalsurvivalandneuriteoutgrowthinvitroafterexposuretoamyloid-betapeptidefragment25–35(Aβ25–35),andtoexplorewhethertheextracellularsignal-regulatedkinase（ERK）andAktsignalingpathwaysareinvolvedinthesebiologicalprocesses.Weculturedhippocampalneuronsfromnewbornratsfor24hours,thenaddedRg1tothemediumforanother24hours,withorwithoutpharmacologicalinhibitorsofthemitogen-activatedproteinkinase（MAPK）familyorAktsignalingpathwaysforafurther24hours.Wethenimmunostainedtheneuronsforgrowthassociatedprotein-43,andmeasuredneuritelength.Inaseparateexperiment,weexposedculturedhippocampalneuronstoAβ25–35for30minutes,beforeaddingRg1for48hours,withorwithoutAktorMAPKinhibitors,andassessedneuronalsurvivalusingHoechst33258staining,andphosphorylationofERK1/2andAktbywesternblotanalysis.Rg1inducedneuriteoutgrowth,andthiseffectwasblockedbyAPI-2（Aktinhibitor）andPD98059（MAPK/ERKkinaseinhibitor）,butnotbySP600125orSB203580（inhibitorsofc-JunN-terminalkinaseandp38MAPK,respectively）.Consistentwiththiseffect,Rg1upregulatedthephosphorylationofAktandERK1/2;theseeffectswerereversedbyAPI-2andPD98059,respectively.Inaddition,Rg1significantlyreversedAβ25–35-inducedapoptosis;thiseffectwasblockedbyAPI-2andPD98059,butnotbySP600125orSB203580.Finally,Rg1significantlyreversedtheAβ25–35-induceddecreaseinAktandERK1/2phosphorylation,butAPI-2preventedthisreversal.OurresultsindicatethatRg1enhancesneuriteoutgrowthandprotectsagainstAβ25–35-induceddamage,andthatitsmechanismmayinvolvetheactivationofAktandERK1/2signaling.更多还原

简介：BACKGROUND:GenetherapyforParkinson'sdiseaseisbeingexploredasaneffectivestrategytorestoreandprotectthefunctionofneuronalcellsinthesubstantianigra.Regulationofgeneexpressionisnecessaryforgenetherapytoavoidadverseeffectsduetoexcessivesynthesisoftransgeneproducts.OBJECTIVE:Herewedevelopedrecombinantadeno-associatedvirus(AAV)asaviralvector-mediatedgeneregulationsystembasedonCrerecombinasefusedtothemutatedligand-bindingdomainoftheestrogenreceptor(CreERT2)+inducingagenttamoxifen.InducibleCrerecombinasewasusedtoreducetyrosinehydroxylasegeneexpressionandtopreventtheexcessiveincreaseindopamine.DESIGN,TIMEANDSETTING:Ageneticengineeringinvitrocomparativestudyandrandomizedcontrolledanimalexperiment.ThisstudywasconductedattheGeneTherapyCenter,JichiMedicalSchool,JapanfromJune2002toJune2004.METHODS:ToconstructarecombinantAAVvectorcarryingadopaminesynthasegene.ThetyrosinehydroxylasegenewasinsertedusingaloxPfragmentthatcouldberegulatedbyCrerecombinase.TherecombinantAAVvectorcarryingtheCreERT2genewasco-transducedwithHEK293cellsandthecorpusstriatuminaratmodelofParkinson'sdisease,withinducingagenttamoxifentoregulategeneexpression.MAINOUTCOMEMEASURES:ThelevelsofdopamineandaromaticL-aminoaciddecarboxylase(AADC)activityweredetectedinHEK293cellmediumandinthecorpusstriatuminaratmodelofParkinson'sdiseaseusinghigh-performanceliquidchromatography.ImmunofluorescencedoublestainingwasusedtoobservetyrosinehydroxylaseandCreorAADCco-expressioninHEK293cellmedium.ImmunohistochemicalstainingwasemployedtoobservetyrosinehydroxylaseandAADCexpressionandbehavioralchangesweremeasuredinParkinson'srats.RESULTS:TransfectedAAV-CreERT2andAAVexpressingdopaminesynthesisenzymescouldincreasethesynthesisofdopamineinHEK293mediumandParkinson'sratstriatum(P<0.01)andimprovetherotationalbehaviorofParkin

简介：AbstractObjective:Capsaicin (CPS) is a major component of the red pepper, and its anti-tumor property has been confirmed. However, the underlying mechanism of this anti-tumor effect has not been fully clarified, so we conducted this study to evaluate the role of mitochondrial fission and subsequent mitochondrial dysfunction in CPS-induced apoptosis of melanoma cells.Methods:Two melanoma cell lines and melanocytes were treated with CPS alone or in combination with ruthenium red (a transient receptor potential vanilloid 1 [TRPV] antagonist), Z-VAD-FMK (a pan-caspase inhibitor), or N-acetyl-L-cysteine (an antioxidant). Cell vitality was tested using a cell counting kit-8 assay. The expression levels of related proteins were examined by Western blotting. Apoptosis, intracellular reactive oxygen species, mitochondrial membrane potential, adenosine triphosphate levels, and mitochondrial dynamics were analyzed by flow cytometry, luminometry, and confocal laser microscopy, respectively, and compared between groups.Results:CPS treatment significantly inhibited the vitality of melanoma cells (For A2058 cells: 0 vs. 120 μmol/L: [100.00% ± 0%] vs. [51.02% ± 6.40%], P < 0.05; For WM35 cells: 0 vs. 120 μmol/L: [100.00% ± 0%] vs. [51.80% ± 3.45%], P < 0.05) but exerted less impact on normal melanocytes. CPS promoted melanoma cell apoptosis through TRPV channels and the caspase cascade. CPS treatment then led to TRPV channel-dependent mitochondrial dysfunction with an increase in reactive oxygen species generation (For A2058 cells: CPS vs. CPS+RR: [2.34 ± 0.30] vs. [1.34 ± 0.12], P < 0.05; For WM35 cells: CPS vs. CPS+RR: [2.25 ± 0.25] vs. [1.65 ± 0.13], P < 0.05), dissipation of the mitochondrial membrane potential (Control vs. CPS: [1.00 ± 0] vs. [0.61 ± 0.08], P < 0.05), and adenosine triphosphate reduction (P < 0.05). In addition, reactive oxygen species generation contributed to CPS-induced melanoma cell apoptosis. Mitochondrial fission was subsequently proved to connect CPS treatment to mitochondrial dysfunction, which was also TRPV channel-dependent, thereby inducing melanoma cell apoptosis.Conclusion:Our study highlights the role of mitochondrial fission and its related mitochondrial dysfunction in mediating the pro-apoptotic effect of CPS in melanoma. These findings deepen our understanding of the mechanisms underlying the anti-tumor activity of CPS and indicate the clinical relevancy of extending the use of this agent for cancer therapy.

简介：Itiswell-knownthatidiopathicthrombocytopenicpurpura(ITP)isanacquiredorgan-specificautoimmunehemorrhagicdiseaseanddysfunctionalcellularimmunityisconsideredimportantinthepathophysiologyofITP.However,polarizationpatternsandapoptosisprofilesofTlymphocytesremainunclear.Inthisstudy,weinvestigatedthepolarizationofTcellsubsets,theexpressionsofapoptoticproteinsFas/FasLonthesubsetsandthelevelofanti-apoptoticgenebcl-2andbaxmRNA.ItwasdemonstratedthattheratiosofTh1/Th2andTc1/Tc2inITPchildrenwereincreasedobviouslyandthattheaveragepercentageswereincreasedclearlyforTh1andTh2,butnotforTc1andTc2.InITPchildren,theenhancingexpressionsweredetectedforFasLonTh1andTc1andforFasonTh2andTc2.Withincreasinglevelofbcl-2mRNAanddecreasingexpressionofbaxmRNAinITPchildren,theratioofbcl-2/baxmRNAwasimprovedobviously,whichwaspositivecorrelatedwiththeratioofTh1/Th2.Takentogether,ourfindingsindicatethatITPisaTh1predominantdisease.ThispolarizationpatternofTcellsubsetsmightberelatedtothehighratioofbcl-2/baxmRNAandtheabnormalexpressionsofFasandFasLonTcellsubsets.Cellular&MolecularImmunology.

简介：Objective:Toinvestigatetherelationshipbetweenapoptosisandproliferatingcellnuclearantigen(PCNA)expressionofkeratinocytesinCondylomataacuminata(CA).Methods:PCNAexpressionwasobservedbyimmunohistochemistrytechnique(ABCmethod)in51CAspecimensand18normalspecimensofforeskinorvaginalmucosae.55specimens(40intheCAgroupand15inthecontrolgroup)wererandomlysampledforinsitulabelingofapoptoticcellsusingtheTUNELmethod.Results:PositiveexpressionofPCNAinCAandcontrolgroupswere90.2%and77.8%,respectively,andtheproliferationindexinCAgroupwassignificantlyhigherthanthatinthecontrolgroup(P<0.001).Thepositiverateofapoptosiswas42.5%intheCAgroupand53.3%inthecontrolgroup,andtherewerenosignificantdifferencesintheapoptoticindexandapoptosis-proliferationratiobetweentwogroups(P>0.05).Theproliferationindexshowedasignificantnegativecorrelationwiththeapoptosis-proliferationratio(r=-0.62,P=0.01)intheCAgroup.Conclusion:ItissuggestedthattheproliferativeappearanceofCAcouldbeduetotheimbalancebetweencellgrowthandcelldeathwhichiscausedbymoreproliferationandlessapoptosisinkeratinocytes.

简介：Theexpressionandfunctioningrowthandapoptosisoftherenin-angiotensinsystem(RAS)wasevaluatedinhumanglioblastoma.Reninandangiotensinogen(AGT)mRNAsandproteinswerefoundbyinsituhybridisationandimmunohistochemistryinglioblastomacells.Angiotensinogenwaspresentinglioblastomacysticfluids.Thus,humanglioblastomacellsproducereninandAGTandsecreteAGT.Humanglioblastomaandglioblastomacellsexpressedrenin,AGT,reninreceptor,AT(2)and/orAT(1)mRNAsandproteinsdeterminedbyRT-PCRand/

简介：这研究是在RGD-FasL和内在的机制导致的垂体腺瘤房间线GH3/MMQ/AtT20上调查细胞毒素的效果。Fas/DcR3mRNAs被RT-PCR检测，他们的表面表情被流动cytometry测量。RGD-FasL在肿瘤房间上施加的Cytotoxicity与MTT试金被测量，导致的apoptosis被agarose胶化电气泳动决定。房间周期和apoptosis被流动cytometry估计，PI染色。caspase8/9/3，Bcl-2，RANKL和JNK2的表情被西方的弄污检测。约13.7%GH3房间，25.5%MMQ房间，，22.2%AtT20房间表示船边交货23.9%GH3房间，24.1%MMQ房间，4.6%AtT20房间表示DcR3。肿瘤房间上的FasL/RGD-FasL的细胞毒素的效果都以一种剂量依赖者方式被拿。房间线MMQ/AtT20至于FasL显示出一样的敏感到RGD-FasL，当房间线GH3对RGD-FasL不太敏感时。房间周期分析显示RGD-FasL能在G0/G1阶段和G2/M阶段禁止房间。在与RGD-FasL对待的MMQ和AtT20房间，AI不与，在与RGD-FasL对待的GH3房间与FasL对待那显著地不同，AI比与FasL对待的低。当Bcl-2的与RGD-FasL在处理以后被减少时，caspase-8/9/3，RANKL和JNK2的表情被增加，建议RGD-FasL导致通过caspase激活的apoptosis。我们断定RGD-FasL能可能被看作垂体腺瘤的处理的一个新奇therapeutical候选人。

简介：Objective:Toexploretherelationshipbetweenneuronalapoptosisandhypoxiaortraumaticinjury.Methods:Ratneuronsprimarilyculturedinvitroweretreatedwithhypoxia(thehypoxiagroup)ortraumaticinjury(thetraumagroup).Theneuronalapoptosiswasevaluatedwithmicroscope,TUNEL(terminaldeoxynucleotidyltransferasemediatedx-dUTPnickendlabeling)staining,flowcytometry,agarosegetelectrophoresisandimmunohistochemistry.Results:Morphologicalchangesofapoptosisappearedinthetreatedneurons,andtheDNAfragmentationshowed“ladder”break.Theapoptoticindexwas10.8%inthehypoxiagroupand4.8%inthetraumagroup,whileitwasonly1.6%inthecontrolgroup.Theexpressionofapoptosis-associatedgenes(c-myc,fasandfasL)increased.Conclusions:Hypoxiaortraumaticinjurycaninduceneuronalapoptosis,anditsmolecularmechanismisprobablyrelatedtotheexpressionsofapoptosis-associatedgenes.

简介：Acetylcholinesterase(AChE)playsakeyroleinterminatingneurotransmissionatcholinergicsynapses.AChEisalsofoundintissuesdevoidofcholinergicresponses,indicatingitspotentialfunctionbeyondneurotransmission.IthasbeensuggestedthatAChEmayparticipateindevelopment,differentiation,andpathogenicprocessessuchasAlzheimer'sdiseaseandtumorigenesis.WeexaminedAChEexpressioninhumanlungfibroblastcellline(HLF)uponinductionofapoptosisbyUVorG418.AChEisinducedinallapoptoticcellsexaminedasdeterminedbycytochemicalstaining,immunologicalanalysis,affinity

简介：Apoptosis在众多的医药混乱的病原学或致病起一个枢轴的作用，并且这样，apoptotic房间指向可以实质地推进耐心的照顾。在我们为为apoptosis的新奇low-molecular-weight探针的探索，我们集中了于不平常的氨基酸纬-carboxyglutamic酸(Gla)，它在clotting因素的绑定起一个重要作用到否定地控告的phospholipid表面。基于Gla的alkyl-malonic酸主题，我们开发了并且现在介绍ML-10(2-(5-fluoro-pentyl)-2-methyl-malonic酸，MW=206Da)，apoptosis的小分子的察觉者的一个新奇家庭的原型的成员。ML-10被发现在apoptotic房间执行选择举起和累积，当从可行或坏死的房间被排除时。有caspase激活，Annexin-V绑定和mitochondrial膜潜力的混乱的apoptotic特点的ML-10举起相互关联。malonate一半被发现为在apoptosis察觉的ML-10功能关键。ML-10在早apoptosis对房间的特征的唯一的建筑群作出回应，包括膜潜力，房间膜和细胞质的永久使发酸，和膜正直的保藏的不可逆的损失。ML-10因此是迄今为止知道的最紧缩的apoptosis探查。由于它的氟的符号原子，ML-10对顺从与18F同位素标记收音机，向它为apoptosis的临床的正电子排放断层摄影术成像的潜在的未来使用。

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简介：AbstractBackground:Sweat secreted by eccrine sweat glands is transported to the skin surface through the lumen. The eccrine sweat gland develops from the initial solid bud to the final gland structure with a lumen, but how the lumen is formed and the mechanism of lumen formation have not yet been fully elucidated. This study aimed to investigate the mechanism of lumen formation of eccrine gland organoids (EGOs).Methods:Human eccrine sweat glands were isolated from the skin for tissue culture, and the primary cultured cells were collected and cultured in Matrigel for 14 days in vitro. EGOs at different development days were collected for hematoxylin and eosin (H&E) staining to observe morphological changes and for immunofluorescence staining of proliferation marker Ki67, cellular motility marker filamentous actin (F-actin), and autophagy marker LC3B. Western blotting was used to detect the expression of Ki67, F-actin, and LC3B. Moreover, apoptosis was detected using a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay kit, and the expression of poly (ADP-ribose) polymerase and Caspase-3 was detected by Western blot. In addition, 3-methyladenine (3MA) was used as an autophagy inhibitor to detect whether the formation of sweat glands can be effectively inhibited.Results:The results showed that a single gland cell proliferated rapidly and formed EGOs on day 4. The earliest lumen formation was observed on day 6. From day 8 to day 14, the rate of lumen formation in EGOs increased significantly. The immunofluorescence and Western blot analyses showed that the expression of Ki67 gradually decreased with the increase in days, while the F-actin expression level did not change. Notably, the expression of autophagy marker LC3B was detected in the interior cells of EGOs as the apoptosis signal of EGOs was negative. Compared with the control group, the autophagy inhibitor 3MA can effectively limit the formation rate of the lumen and reduce the inner diameter of EGOs.Conclusion:Using our model of eccrine gland 3D-reconstruction in Matrigel, we determined that autophagy rather than apoptosis plays a role in the lumen formation of EGOs.

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简介：<正>Immunologicaltolerancetoselfisessentialformaintainingtheintegrityoftheorgansystems,anditsbreakdownmayleadtothedevelopmentofautoimmunediseases.Tolerancetoselfismaintainedthroughseveralmechanisms,whichincludenegativeselection,functionalinactivation(anergy)andsuppressionofautoreactivelymphocytes.However,onlynegativeselectionpermanentlyremovesautoreactivecellsthroughapoptosis.WhileithaslongbeenknownthatnegativeselectionrequiresaTcellreceptor(TCR)signal,itisunclearwhetheradeathligandsignalisalsoinvolved.TRAIL,thetumornecrosisfactor(TNF)-relatedapoptosis-inducingligand,isanewlydescribedmemberoftheTNFfamily.Unlikeotherdeathligandsof

简介：肿瘤坏死因素相关的导致apoptosisligand(小道)是为anticancer的一个有希望的代理人治疗。能建立前列腺癌症(PCa)的敏感的小分子的鉴定房间到导致小道的apoptosis为PCa的指向的治疗是关键的。PC3，DU145，JAC-1，TsuPr1，和LNCaP房间与Andrographolide(Andro)被对待，小道，和apoptosis用AnnexinV/PI被测量两倍染色的方法。真实时间聚合酶链反应(PCR)和西方的污点分析被执行测量目标分子的表示层次。RNA干扰技术习惯于下面调整目标蛋白质的表示。我们建立了PCa的一个裸体老鼠异种皮移植模特儿，它被用来用流动cytometry在肿瘤房间测量caspase-3活动。在这研究研究，我们的结果证明Andro优先地在subtoxic集中增加了PCa房间的敏感到导致小道的apoptosis，并且规定机制与DR4的起来规定有关。另外，它也增加了p53表示并且在细胞导致了反应的氧种类(ROS)的产生。进一步的研究表明DR4抑制，p53表示，和ROS产生罐头显著地减少小道和Andro的联合在PCa房间导致的apoptosis。在结论，Andro通过ROS的产生和p53的起来规定增加PCa房间的敏感到导致小道的apoptosis然后支持与DR4的激活联系的PCa房间apoptosis。

简介：Manystudiesdemonstratethatconventionalanticancerdrugselevateintracellularlevelofreactiveoxygenspecies(ROS)andalterredox-homeostasisofcancercells.ItiswidelyacceptedthatanticancereffectofthesechemotherapeuticsisduetoinductionofoxidativestressandROS-mediatedapoptosisincancer.Ontheotherhand,theharmfulsideeffectsofconventionalanticancerchemotherapyarealsoduetoincreasedproductionofROSanddisruptionofredox-homeostasisofnormalcellsandtissues.ThisarticledescribesthemechanismsfortriggeringandmodulationofapoptosisthroughROS-dependentandROS-independentpathways.Wetrytoanswerthequestion:'Isitpossibletoinducehighlyspecificapoptosisonlyincancercells,withoutoverproductionofROS,aswellaswithoutharmfuleffectsonnormalcellsandtissues?'Thereviewalsosuggestsanewtherapeuticstrategyforselectivekillingofcancercells,withoutsignificantimpactonviabilityofnormalcellsandtissues,bycombininganticancerdrugswithredox-modulators,affectingspecificsignalingpathwaysandavoidingoxidativestress.

简介：有建议激活的apoptosis在呼喊的人的精子发信号否定地影响他们的授精潜力的证据的基本身体。然而，发信号的这apoptotic是否是与精子发生有关的未成功的apoptosis的一件遗物，仍然是争论的或如果它应该在导致stereotypical的成熟精子被认为是一条功能的preformed小径词法变化思考原子拆卸。探讨这个问题，apoptosis在密度坡度centrifugation充实的成熟、不成熟的呼喊的人的精子用betulinic酸被导致。apoptosis的执行被经由传播电子显微镜学观察极端词法的变化监视。在体的房间的apoptosis的典型词法符号与apoptotic身体，损害mitochondrial正直，原子信封的缺点，和原子破碎的形成包括血浆膜blebbing；这些形态学也在人的精子被观察了。另外，这些apoptotic特征在与成熟精子相比的不成熟的精子是更经常的。后面的betulinic酸处理，apoptosis相关的词法变化从健康施主在成熟精子被导致。这效果更不在不成熟的精子被读。而且在两部分，betulinic酸处理增加了反应acrosome的精子的百分比。我们的极端词法的学习的结果在成熟呼喊的人的精子证明apoptosis的功能的胜任。一个唯一的未成功的过程的理论可能为不成熟的精子仅仅是有效的。由刺激apoptosis的acrosome反应的正式就职可能使精子apoptosis的生物关联清楚些。

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简介：AbstractCell death occurs in various tissues and organs in the body. It is a physiological or pathological process that has different effects. It is of great significance in maintaining the morphological function of cells and clearing abnormal cells. Pyroptosis, apoptosis, and necrosis are all modes of cell death that have been studied extensively by many experts and scholars, including studies on their effects on the liver, kidney, the heart, other organs, and even the whole body. The heart, as the most important organ of the body, should be a particular focus. This review summarizes the mechanisms underlying the various cell death modes and the relationship between the various mechanisms and heart diseases. The current research status for heart therapy is discussed from the perspective of pathogenesis.