简介：AbstractBackground:Topoisomerase II alpha (TOP2A) has been reported to play a crucial role in the tumorigenesis of various cancer types. However, the biological role of TOP2A in gallbladder cancer (GBC) remains unknown. The current study aimed to explore the function and potential mechanism of TOP2A in GBC.Methods:Based on Gene Expression Profiling Interactive Analysis data, we found TOP2A was significantly up-regulated in GBC tissues and resulting in shorter overall survival. Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to detect the expression of TOP2A in 45 pairs of GBC tissues and adjacent non-tumor tissues. In vitro, cell proliferation, migration, and invasion ability were examined by cell counting kit-8 and transwell assay, respectively. Epithelial-mesenchymal transition (EMT) related and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway-related markers were measured by Western blotting. Xenograft model assay was performed to evaluate the effect of TOP2A in vivo.Results:TOP2A was found up-regulated in GBC (tumor vs. normal, 12.62 vs. 0.34) and correlated with the late tumor node metastasis stage (P = 0.0032), present of lymph node metastasis (P = 0.0273), and poor prognosis in GBC patients (log-rank P = 0.028). In vitro and in vivo assays showed that knockdown of TOP2A notably inhibited cell proliferation, migration, invasion, EMT process, and tumor growth in GBC. In addition, TOP2A down-regulation significantly decreased the protein levels of phosphor (p)-PI3K, p-Akt, and p-mTOR.Conclusion:Our study demonstrates that TOP2A was overexpressed in GBC and associated with poor prognosis in GBC patients. TOP2A promotes GBC cell proliferation, migration, invasion, EMT process, and tumor growth through activating PI3K/Akt/mTOR signaling pathway, and may serve as a novel prognostic biomarker and therapeutic target for GBC.

简介：Humanpolymorphonuclearleukocytes(PMN)havebeenreportedtocompletelylackofDNA-dependentproteinkinase(DNA-PK)whichiscomposedofKuproteinandthecatalyticsubunitDNA-PKcs,neededfornonhomologousend-joining(NHEJ)ofDNAdouble-strandbreaks.PromyelocyticHL-60cellsexpressavariantformofKuresultinginenhancedradiationsensitivity.ThisraisesthequestioniflowefficiencyofNHEJ,instrumentalforthecellularrepairofoxidativedamage,isanormalcharacteristicofmyeloiddifferentiation.HereweconfirmedthecompletelackofDNAPKinPMNproteinextracts,andtheexpressionofthetruncatedKu86variantforminHL-60.However,thisdegradationofDNA-PKwasshowntobeduetoaDNA-PK-degradingproteaseinPMNandHL-60.Inaddition,byusingaprotease-resistantwholecellassay,bothKu86andDNA-PKcscouldbedemonstratedinPMN,suggestingthepreviouslyreportedabsenceinPMNofDNA-PKtobeanartefact.ThelevelsofKu86andDNA-PKcsweremuchreducedinPMN,ascomparedwiththatofthelymphocytes,whereasHL-60displayedamarkedlyelevatedDNA-PKconcentration.Inconclusion,ourfindingsprovideevidenceofreduced,notdepletedexpressionofDNA-PKduringthematurestagesofmyeloiddifferentiation.

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简介：房间有大量的控制维持他们的完整并且阻止随机切换到另外一个一个生物状态。RafKinase禁止的蛋白质(RKIP)，phosphatidylethanolamine绑定蛋白质(PEBP)的一个成员家庭，表明工作维持“yinyang”或生物系统的平衡的串联的调节的人的一个新类是代表性的。RKIP禁止地图kinase(Raf-MEK-ERK)，表明串联的G联合蛋白质的受体(GPCR)kinase和NFkappaB。因为RKIP指向依赖于它磷酸化的状态的不同家族ases，RKIP也行动集成多重环境刺激开始的串音。RKIP的损失或弄空导致正常细胞的壅滞和罐头的混乱导致象癌症那样的chromosomal畸形和疾病状态。因为RKIP和PEBP家庭以前被考察了，这分析的目标是提供更改并且加亮一些RKIP的唯一的特征在细胞的发信号的过程的规定使它成为一个批评播放器。

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简介：Toexploretheroleofnuclearfactor-κB(NF-κB)inthesignalpathwayofproteinkinaseC(PKC)regulatingtheproliferationandapoptosisofTlymphocytesinasthma.Tlymphocyteswereisolatedfromtheasthmaticmodelofguineapigsandtheasthmaticpatients.EithertheTcellsstimulatedwithPMAaloneorthosestimulatedwithPMAtogetherwithpyrrolidinedithiocarbamate(PDTC)wereincubatedfor1and24h.TheproliferationofandthepresenceofNF-κBinthecellsincubatedfor1hwereobservedbyMTTandimmunohistochemicalstaining,respectivelyAndthecellsincubatedfor24hwereobservedfortheapoptosisbyTUNEL.Alltheassayswereparalleledwithcontrols,andallthedatawereanalyzedstatisticallywiththesoftwareSAS.ThepercentageofcellsofnuclearpositivestainingofNF-scBandtheproliferationofTlymphocytesfromasthmaticguineapigsandasthmaticpatientsstimulatedwithPMAweresignificantlyhigherthanthoseofTlymphocytesfromasthmaticguineapigsandasthmaticpatientsstimulatedwithoutPMArespectively(P<0.01)andthoseofTlymphocytesfromnormalcontrolguineapigsandnormalcontrolpersonsstimulatedwithPMArespectively(P<0.01),andweresignificantlyreducedbyPDTC(P<0.01).TheapoptosisindexofTlymphocytesfromasthmaticguineapigsandasthmaticpatientsstimulatedwithPMAweresignificantlylowerthanthoseofTlymphocytesfromasthmaticguineapigsandasthmaticpatientsstimulatedwithoutPMArespectively(P<0.01)andthoseofTlymphocytesfromnormalcontrolguineapigsandnormalcontrolpersonsstimulatedwithPMArespectively(P<0.01),andweresignificantlyinducedbyPDTC(P<0.01).ThereweregoodpositivecorrelationbetweenthepercentageofcellsofnuclearstainingofNF-κBofTlymphocytesandtheproliferationofTlymphocytes(r=0.51-0.72,P<0.001),andalsogoodnegativecorrelationbetweenthepercentageofcellsofnuclearstainingofNF-scBandtheapoptosisindexofTlymphocytes(r=-0.55-0.71,P

简介：BACKGROUND:ToevaluateandsummarizetheeffectsofcerebralperfusionandvascularreserveonthetreatmentofSICAS.Recently,researchonβ-amyloidproteinhasfocusedontheregulatoryeffectsofes-trogenorphytoestrogenonitsdeposition.However,therehavebeenonlyafewreportsondynamicchangesofβ-amyloidproteindepositioninhippocampusofovariectomizedrats.OBJECTIVE:Tomeasureβ-amyloidproteindepositioninthehippocampalformationofovariectomizedratsbyusingimmunohistochemistry;toobservetime-dependentdynamicchanges.DESIGN:Randomizedcontrolledanimalstudy.SETTING:ThirdXiangyaHospitalofCentralSouthUniversity.MATERIALS:TheexperimentwascarriedoutintheCentralLaboratoryoftheThirdXiangyaHospitalofCentralSouthUniversityfromNovember2005toDecember2006.FiftyhealthyfemaleSpragueDawley(SD)rats,weighing(293±10)g,wereprovidedbytheAnimalLaboratoryofXiangyaMedicalCollege,CentralSouthUniversity.Allratshadneitherachildbearinghistorynorhepaticorrenaldisease,orskeletaldeformity.β-amyloidproteinimmunohistochemicalkitwasprovidedbyWuhanBosterCompany.Theex-perimentwasinaccordancewithanimalethicsstandards.METHODS:Allratswererandomlydividedintofivegroups,includingnormalcontrolgroup(n=10),shamoperationgroup(n=10),andovariectomizedgroup(n=30).Afteranesthesiaintheovariectomizedgroup,thebilateralovarieswereseparatedandresected.Thesamevolumeoffatwasresectedintheshamoperationgroup.Ratsfromthenormalcontrolgroup,however,didnotreceiveanysurgicaltreatments.Ratsinthenormalcontrolgroupandshamoperationgroupweresacrificedbyanesthesia7weeksaftersurgery.Everytenratsfromtheovariectomizedgroupwasrespectivelysacrificedat7,15,and30weeksaftersurgery.Immunohistochemistrywasusedtodetectβ-amyloidproteindepositioninhippocampalsections.Cellcountingandgrayvaluemeasurementsservedtorecordthedynamicchangesin�

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简介：干扰素规章的因素(IRF)7被表明了是导致病毒的类型的一个主人管理者我干扰素生产(IFN)，并且它对病毒在天生的有免疫力的反应起一个中央作用。这里，我们识别了联系死亡的蛋白质kinase1(DAPK1)作为由双人脚踏车亲密关系纯化(龙头)的交往IRF7蛋白质。病毒的感染导致了DAPK1-IRF7和DAPK1-IRF3相互作用，DAPK1的overexpression提高了刺激干扰素的反应元素(ISRE)和IFN-β的导致病毒的激活；倡导者和IFNB1基因的表示。稀释的DAPK1击倒IFNB1和RIG-I表示的正式就职由病毒的感染或IFN-β被触发；，并且他们被病毒的复制提高。另外，病毒的感染或IFN-β；处理导致了DAPK1的表示。IFN-β；处理也由减少激活DAPK1它在丝氨酸308点的phosphorylation水平。有趣地，在导致病毒的发信号的DAPK1的参与独立于它的kinase活动。因此，我们的学习作为细胞的抗病毒的反应的一个重要管理者识别了DAPK1。

简介：Mitogenactivated-proteinkinases(MAPKs)areimportantcomponentsinsignaltransductionpathwaysrespondingtovariousbioticandabioticstresses.AnMAPKgene,OsMPK14(GenBankAccessionNo.GQ265780)fromrice(OryzasativaL.),wasclonedbyRT-PCR.Thefull-lengthcDNAofOsMPK14consistsof1660bpinsize,containinganopenreadingframeof1629bp,whichencodesa542-amino-acidpolypeptideandhasatypicalproteinkinasedomainandaphosphorylationactivationmotifTDY.SequencealignmentandanalysisrevealedthatOsMPK14waslocatedonricechromosome5,andcomposedofnineexonsandeightintronsinthecodingregion.Semi-quantitativeRT-PCRwasperformedtodetecttheexpressionpatternsofOsMPK14inriceshootsandrootsunderdarkness,drought,highsalinity,lowtemperatureandabscisicacidtreatments.TheOsMPK14mRNAwasinducedbyabscisicacid,lowtemperatureandhighsalinity,butweaklyinhibitedbydrought.Inaddition,theexpressionofOsMPK14wasup-regulatedinroots,butdown-regulatedinshootsbylight.TheresultsindicatethatOsMPK14couldbeimplicatedindiversericestimuli-responsivesignalingcascades,anditsexpressionmightberegulatedbymultiplefactors.

简介：目的Coptidis根茎(CR)，亚洲植物(包括的黄连属chinensisFranch)的弄干的根茎，被用来对待糖尿病mellitus几千年。我们探索了CR在骨胳的肌肉上直接扮演的可能性，为葡萄糖动态平衡负责的主要机关，并且激活5-AMP-activated蛋白质kinase(AMPK)，导致骨胳的肌肉的新陈代谢的改进的一个发信号的中间人。孤立的老鼠epitrochlearis和soleus肌肉在包含一篇CR水摘录(CE)的一个缓冲区被孵化的方法，和AMPK和相关事件的激活被检验。响应CE治疗的结果，在AMPK的催化子单元的Thr172的phosphorylation，为完整的kinase激活的必要的步，在两肌肉增加了。乙酰CoAcarboxylase(ACC)的Ser79的Phosphorylation，AMPK的内长的底层，附随地增加了。isoform特定的AMPK活动的分析表明CE两个都激活催化子单元的1和2isoforms。重要地，AMPKphosphorylation上的CE的最大的效果比berberine(BBR)的显著地大，显示CE的行动完全没被归功于到BBR。我们建议那CE的结论是在快抽动、慢抽动的骨胳的肌肉的AMPK的尖锐使活跃之物。

简介：AbstractBackground:Autophagy of alveolar macrophages is a crucial process in ischemia/reperfusion injury-induced acute lung injury (ALI). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent cells with the potential for repairing injured sites and regulating autophagy. This study was to investigate the influence of BM-MSCs on autophagy of macrophages in the oxygen-glucose deprivation/restoration (OGD/R) microenvironment and to explore the potential mechanism.Methods:We established a co-culture system of macrophages (RAW264.7) with BM-MSCs under OGD/R conditions in vitro. RAW264.7 cells were transfected with recombinant adenovirus (Ad-mCherry-GFP-LC3B) and autophagic status of RAW264.7 cells was observed under a fluorescence microscope. Autophagy-related proteins light chain 3 (LC3)-I, LC3-II, and p62 in RAW264.7 cells were detected by Western blotting. We used microarray expression analysis to identify the differently expressed genes between OGD/R treated macrophages and macrophages co-culture with BM-MSCs. We investigated the gene heme oxygenase-1 (HO-1), which is downstream of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.Results:The ratio of LC3-II/LC3-I of OGD/R treated RAW264.7 cells was increased (1.27 ± 0.20 vs. 0.44 ± 0.08, t = 6.67, P < 0.05), while the expression of p62 was decreased (0.77 ± 0.04 vs. 0.95 ± 0.10, t = 2.90, P < 0.05), and PI3K (0.40 ± 0.06 vs. 0.63 ± 0.10, t = 3.42, P < 0.05) and p-Akt/Akt ratio was also decreased (0.39 ± 0.02 vs. 0.58 ± 0.03, t = 9.13, P < 0.05). BM-MSCs reduced the LC3-II/LC3-I ratio of OGD/R treated RAW264.7 cells (0.68 ± 0.14 vs. 1.27 ± 0.20, t = 4.12, P < 0.05), up-regulated p62 expression (1.10 ± 0.20 vs. 0.77 ± 0.04, t = 2.80, P < 0.05), and up-regulated PI3K (0.54 ± 0.05 vs. 0.40 ± 0.06, t = 3.11, P < 0.05) and p-Akt/Akt ratios (0.52 ± 0.05 vs. 0.39 ± 0.02, t = 9.13, P < 0.05). A whole-genome microarray assay screened the differentially expressed gene HO-1, which is downstream of the PI3K/Akt signaling pathway, and the alteration of HO-1 mRNA and protein expression was consistent with the data on PI3K/Akt pathway.Conclusions:Our results suggest the existence of the PI3K/Akt/HO-1 signaling pathway in RAW264.7 cells under OGD/R circumstances in vitro, revealing the mechanism underlying BM-MSC-mediated regulation of autophagy and enriching the understanding of potential therapeutic targets for the treatment of ALI.

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简介：ThechronicinfectionofhepatitisBvirus(HBV)iscloselyrelatedtotheoccurrenceanddevelopmentofhepatocellularcarcinoma(HCC).AccumulatedevidencehasshownthatHBVXprotein(HBxprotein)isamultifunctionalregulatorwithacrucialroleinhepatocarcinogenesis.However,informationonthemechanismbywhichHBVinducesHCCislacking.ThisreviewfocusesonthepathologicalfunctionsofHBxinHBV-inducedhepatocarcinogenesis.Asatransactivator,HBxcanmodulatenuclearfactorkappa-light-chain-enhancerofactivatedBcells(NF-κB)andtranscriptionfactorAP-2.Moreover,HBxcanaffectregulatorynon-codingRNAs(ncRNAs)includingmicroRNAsandlongncRNAs(lncRNAs),suchasmiRNA-205andhighlyupregulatedinlivercancer(HULC),respectively.HBxisalsoinvolvedinepigeneticmodification,includingmethylationandacetylation.HBxinteractswithvarioussignal-transductionpathways,suchasproteinkinaseB/Akt,Wnt/β-catenin,signaltransducerandactivatoroftranscription,andNF-κBpathways.Moreover,HBxaffectscellularfatebyshiftingthebalancetowardcellsurvival.HBxmayleadtothelossofapoptoticfunctionsordirectlycontributestooncogenesisbyachievingtransformingfunctions,whichinducehepatocarcinogenesis.Additionally,HBxcanmodulateapoptosisandimmuneresponsebydirectorindirectinteractionwithhostfactors.WeconcludethatHBxhastensthedevelopmentofhepatoma.

简介：Fucoidan能通过有免疫力的激活治好锑敏感、锑抵抗的内脏的leishmaniasis。然而，位于这细胞的回答下面的发信号的事件仍然是uncharacterized。现在的学习表明fucoidan导致p38和ERK1/2和NF-κ的激活；在正常和利什曼原虫的BDNA绑定感染donovani的巨噬细胞由西方的弄污和electrophoretic活动性移动揭示了试金(EMSA)分别地。p38，ERK1/2或NF-κ的药理学抑制；B小径显著地稀释了导致fucoidan的支持inflammatorycytokine合成和可诱导的氮的氧化物synthase(iNOS)基因抄写，导致寄生虫清理的减小。为了译解，各种各样的蛋白质kinaseC(PKC)isoforms的调停fucoidan的寄生虫抑制，表示和功能的内在的机制被immunoblotting和酶活动试金评估。Fucoidan在PKC-α的表示和活动得到了增加；，在感染的巨噬细胞的-βI和-βIIisoforms。功能PKC-α击倒；并且-β；导致了p38和ERK1/2的downregulation，与IL-12和TNF-α的显著减小一起；在对待fucoidan的感染的巨噬细胞的生产。一起，这些结果建议fucoidan的药品效果被激活mitogen的蛋白质kinase(MAPK)的PKC依赖的激活调停/NF-κ；B小径，它最终导致氮的氧化物的生产(没有)并且解决疾病的支持inflammatorycytokines。

简介：Severalstudieshavedemonstratedthattheamountofbeta-amyloid(Aβ)proteininthebraincanbeloweredbydown-regulatingAβproduction,promotingAβdegradation,reducingAβoligomerizationordeposition,therebyalleviatingsymptomsofAlzheimer'sdisease.Curcuminhasbeenknowntobeaperoxisomeproliferatoractivatedreceptorgamma(PPARγ)agonistandcanobviouslyinhibitAβproductionandoligomerization.Thisstudyinvestigatedtheeffectsofcurcuminontheβ-siteAPPcleavingenzyme1(BACE1)activityandPPARγexpressioninhumanneuroblastomaSH-SY5Ycells,andvalidatedtheinhibitoryeffectsofcurcuminonAβ40/42expressioninthebrain.ResultsrevealedthatPPARγmRNAandproteinexpressioninthehumanneuroblastomaSH-SY5Ycellssignificantlyincreasedwithincreasingcurcuminconcentrationandtimecourse(P<0.05);BACE1mRNAandproteinexpressionandAβ40/42productionsignificantlydecreasedwithincreasingcurcuminconcentrationandtimecourse(P<0.05).ThechangesinPPARγandBACE1expressionduringAβproductioncouldbereversedbythePPARγantagonistGW9662.ThesefindingsindicatethatcurcuminreducedAβproductionbyactivatingPPARγexpressionandinhibitingBACE1expressioninaconcentration-andtime-dependentmanner.

简介：很多研究调查了外部煽动性的索引，包括根据痴呆的子类型的血浆cytokines和相关分子，然而并非在温和认知缺陷(媒体控制接口)。在这研究，我们使用了复合cytokine试金作为amnestic和non-amnestic与媒体控制接口subtyped在病人估计22cytokines的血浆层次，根据认知特征。当比较血浆生长因素，chemokines和cytokines的层次时，血浆单核白血球铺平趋化性的蛋白质3(MCP-3)，并且贝它神经生长因素(在这二的-NGF)组织，他们被发现比在non-amnestic媒体控制接口病人在amnestic媒体控制接口病人显著地更高级，在好久调整和性以后。这建议血浆MCP-3和-NGF可能在区分媒体控制接口的子类型是有用的。

简介：AbstractBackground:Circular RNAs (circRNAs) are considered to be important regulators in cancer biology. In this study, we focused on the effect of circRNA baculoviral inhibitor of apoptosis protein (IAP) repeat containing 6 (circBIRC6) on non-small cell lung cancer (NSCLC) progression.Methods:The NSCLC and adjacent non-tumor tissues were collected at Shanghai Ninth People's Hospital. Quantitative real-time polymerase chain reaction was conducted for assessing the levels of circBIRC6, amyloid beta precursor protein binding protein 2 (APPBP2) messenger RNA (mRNA), baculoviral IAP repeat containing 6 mRNA (BIRC6), and microRNA-217 (miR-217). Western blot assay was adopted for measuring the protein levels of APPBP2, E-cadherin, N-cadherin, and vimentin. Colony formation assay, transwell assay, and flow cytometry analysis were utilized for evaluating cell colony formation, metastasis, and apoptosis. Dualluciferase reporter assay and RNA immunoprecipitation assay were carried out to determine the interaction between miR-217 and circBIRC6 and APPBP2 in NSCLC tissues. The murine xenograft model assay was used to investigate the function of circBIRC6 in tumor formation in vivo. Differences were analyzed via Student's t test or one-way analysis of variance. Pearson's correlation coefficient analysis was used to analyze linear correlation.Results:CircBIRC6 was overexpressed in NSCLC tissues and cells. Knockdown of circBIRC6 repressed the colony formation and metastasis and facilitated apoptosis of NSCLC cells in vitro and restrained tumorigenesis in vivo. Mechanically, circBIRC6 functioned as miR-217 sponge to promote APPBP2 expression in NSCLC cells. MiR-217 inhibition rescued circBIRC6 knockdown-mediated effects on NSCLC cell colony formation, metastasis, and apoptosis. Overexpression of miR-217 inhibited the malignant phenotypes of NSCLC cells, while the effects were abrogated by elevating APPBP2.Conclusion:CircBIRC6 aggravated NSCLC cell progression by elevating APPBP2 via sponging miR-217, which might provide a fresh perspective on NSCLC therapy.

简介：AbstractBackground:The Nuclear Dbf2-related (NDR1) kinase is a member of the NDR/LATS family, which was a supplementary of Hippo pathway. However, whether NDR1 could inhibit glioblastoma (GBM) growth by phosphorylating Yes-associated protein (YAP) remains unknown. Meanwhile, the role of NDR1 in GBM was not clear. This study aimed to investigate the role of NDR1-YAP pathway in GBM.Methods:Bioinformation analysis and immunohistochemistry (IHC) were performed to identify the expression of NDR1 in GBM. The effect of NDR1 on cell proliferation and cell cycle was analyzed utilizing CCK-8, clone formation, immunofluorescence and flow cytometry, respectively. In addition, the xenograft tumor model was established as well. Protein interaction was examined by Co-immunoprecipitation and immunofluorescence to observe co-localization.Results:Bioinformation analysis and IHC of our patients’ tumor tissues showed that expression of NDR1 in tumor tissue was relatively lower than that in normal tissues and was positively related to a lower survival rate. NDR1 could markedly reduce the proliferation and colony formation of U87 and U251. Furthermore, the results of flow cytometry showed that NDR1 led to cell cycle arrest at the G1 phase. Tumor growth was also inhibited in xenograft nude mouse models in NDR1-overexpression group. Western blotting and immunofluorescence showed that NDR1 could integrate with and phosphorylate YAP at S127 site. Meanwhile, NDR1 could mediate apoptosis process.Conclusion:In summary, our findings point out that NDR1 functions as a tumor suppressor in GBM. NDR1 is identified as a novel regulator of YAP, which gives us an in-depth comprehension of the Hippo signaling pathway.