简介：AbstractObjective:Liver cancer stem cells (CSCs) are the culprits of hepatocellular carcinoma metastasis and recurrence. Only by eliminating tumor stem cells can malignant tumors be fundamentally cured. This study aimed to identify the role and underlying mechanism of aberrant Collagen Type XIV Alpha 1 Chain (COL14A1) overexpression in liver CSCs, and improve understanding of the molecular basis of hepatocellular carcinoma metastasis and recurrence.Methods:First, quantitative real-time polymerase chain reaction was used to confirm aberrant high-expression of COL14A1 in liver CSCs. Next, interference experiments were performed to determine the key role of COL14A1. To explore the mechanism of COL14A1 overexpression in liver CSCs, putative microRNA (miRNAs) targeting COL14A1 were analyzed using the miRTarBase database. Next, quantitative real-time polymerase chain reaction, western blotting, and luciferase reporter assays were performed to verify the interaction between miR-7108-3p and COL14A1. Lastly, key target proteins of the COL14A1-extracellular-regulated signal kinase (ERK) signaling pathway were identified through western blotting analysis. This study was approved by the Ethics Committee of Shanghai Fourth People’s Hospital, Tongji University School of Medicine, China (approval No. 2019tjdx17) on February 21, 2019.Results:COL14A1 is abnormally highly expressed in liver CSCs, which is necessary for liver CSCs to maintain their self-renewal capability. Mechanistically, COL14A1 is post-transcriptionally regulated by miR-7108-3p in a negative manner. Low expression of miR-7108-3p increased translation of COL14A1, which subsequently activated ERK signaling, ultimately maintaining the self-renewal and stem cell-like properties of liver CSCs.Conclusion:COL14A1, which is negatively regulated by miR-7108-3p, was found to play a crucial role in maintaining the self-renewal and stem cell-like properties of liver CSCs through activation of ERK signaling.

简介：信号变换器的七个成员和抄写(STAT)的使活跃之物抄写因素的家庭被特定的酷氨酸残余的磷酸化响应许多不同cytokines和生长因素激活。STAT1和STAT3基因是激活的STAT的特定的目标1和3分别地，响应干扰素(STAT1)或ligands导致这些unphosphorylatedSTAT(U-STATs)的层次的大增加那活跃gp130，例如IL-6(STAT3)。由从那些不同的新奇机制的U-STATs开车基因表示由phosphorylatedSTAT(P-STAT)使用了暗淡ers。在这评论，我们在基因表示的抄写和规定讨论U-STATs的角色。

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简介：Informationsharinginprocurementoccursinrichandvariedindustrycontextsinwhichmanagerialdecisionsaremadeandorganizationalstrategyisformulated.Weexplorehowinformationsharingoughttoworkinprocurementcontextsmatinvolveinvestmentsininter-organizationalinformationsystems(IOS)andcollaborativeplanning,forecastingandreplenishment(CPFR)practices.Howandunderwhatcircumstancesdoesafirmthatplaystheroleofasupplychainbuyerdecidetoshareinformationonkeyvariables,suchaspoint-of-saleconsumerdemanddatawithitssupplier,upthesupplychain?Thisisakeyissuethatcrossestheboundarybetweensupplychainmanagementandinformationsystems(IS)management.Theanswersthatweprovidearebasedonouruseofagame-theoreticsignalingmodelofbuyerandsupplierstrategyinthepresenceofuncertaintiesaboutfinalconsumerdemand.Wealsoexploretheconnectionbetweenoperationalcoststhatareassociatedwiththefirm'sinformationsharingandinformationwithholdingstrategies.Ourresultsprovidenormativeguidancetosupplychainbuyersabouthowtointerpretdifferentdemanduncertaintyscenariostoimprovetheirdecisionsandgeneratehighvalue.FromtheISmanagementperspective,weshowtheimpactsonthefirmofdifferentinformationsharingapproachesthataremadepossiblebypresentdaytechnologies.

简介：AbstractBackground:Cerebral cavernous malformations (CCMs), a major neurosurgical condition, characterized by abnormally dilated intracranial capillaries, result in increased susceptibility to stroke. KRIT1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3) have been identified as causes of CCMs in which at least one of them is disrupted in most familial cases. Our goal is to identify potential biomarkers and genetic modifiers of CCMs, using a global comparative omics approach across several in vitro studies and multiple in vivo animal models. We hypothesize that through analysis of the CSC utilizing various omics, we can identify potential biomarkers and genetic modifiers, by systemically evaluating effectors and binding partners of the CSC as well as second layer interactors.Methods:We utilize a comparative omics approach analyzing multiple CCMs deficient animal models across nine independent studies at the genomic, transcriptomic, and proteomic levels to dissect alterations in various signaling cascades.Results:Our analysis revealed a large set of genes that were validated across multiple independent studies, suggesting an important role for these identified genes in CCM pathogenesis.Conclusion:This is currently one of the largest comparative omics analysis of CCM deficiencies across multiple models, allowing us to investigate global alterations among multiple signaling cascades involved in both angiogenic and non-angiogenic events and to also identify potential biomarker candidates of CCMs, which can be used for new therapeutic strategies.

简介：转变生长因素(TGF)-尾家庭成员是多功能的cytokines在细胞上得到他们的效果包括endothelial和墙壁的细胞，经由特定的类型我和类型IIserine/threoninekinase受体和细胞内部的Smad抄写因素。为表明小径部件的TGF-尾家庭的猛烈老鼠模型在合适的蛋黄囊angiogenesis揭示了他们的批评重要性。在人的基因研究在这些发信号的部件连接了变化到象世袭出血性的毛细管扩张，主要肺的高血压和Marfan症候群那样的特定的心血管的症候群。在这评论，我们在我们TGF-尾受体在脉管的生物学和疾病发信号的角色的理解的现在的最近的进展，并且讨论这怎么可以被申请治疗。

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简介：Wnt/尾-catenin调整与肿瘤有关的细胞的功能开始和前进，房间增长，区别，幸存，和粘附。尾-Catenin独立的Wnt小径被建议了调整房间极性和移植，包括转移。在这评论，我们在肿瘤前进讨论catenin依赖的尾-和独立人士发信号小径的可能的角色，与他们Rho家庭GTPases，改变的细胞骨架，和与房间房间粘附和cilia/ciliogenesis的关系的规定上的一个重音。

简介：Newneuronsaregeneratedandintegrateintoexistingcircuitrywithinthehippocampaldentategyrusandtheolfactorybulbofmostmammals(GageandTemple,2013).Neurogenesisinthehippocampuspersiststhroughadulthood,andwhileitsfunctionandimportanceremainsunclear,itappearstoberequiredintheformationofspecifictypesof

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简介：ThemolecularmechanismsforNF-κBsignalingtransductionandtranscriptionhavebeenthemostattractivesubjectsforbothbasicresearchandpharmaceuticalindustriesduetoitsimportantrolesinbothphysiologicalandpathogenesis,particularlythecloseassociationofdysregulatedNF-κBwithtumorgenesisandinflammation.SeveralnovelintracellularmoleculareventsthatregulateNF-κBactivityhavebeendescribedrecently,includingthediscoveryofanalternativesignalingpathwaythatappearsinducingaspecificsubsetgenesinvolvedinadoptiveimmuneresponse.Multi-levelandmulti-dimensionalregulationofNF-κBactivitybyphosphorylationandacetylationmodificationshaveunveiledandbecamethehottesttargetsforpotentiallytissuespecificmolecularinterventions.AnotheremergingmechanismforNF-κB-responsivegene'sregulationwhereNF-κBparticipatesthetranscriptionalregulationindependentofitscognateregulatorybindingsitewithinthetargetgene'spromoterbutfacilitatingthetransactionactivityofotherinvolvedtranscriptionfactors,thatimplicatedannoveltranscriptionalactivitiesforNF-κB.Thus,thecurrentreviewwillfocusontheserecentprogressesthathavebeenmadeonNF-κBsignalingtransductionandtranscription.Cellular&MolecularImmunology.2004;1(6):425-435.

简介：<正>ThesusceptibilityofprimaryBcellstoFas(APO-1,CD95)-mediatedapoptosisisregulatedbysignalsderivedfromadditionalsurfacereceptors.CD40engagementproducesupregulationofFasexpressionandinducesmarkedsensitivitytoFas-inducedcelldeath,whereasBcellantigenreceptor(BCR)engagementinhibitsFaskillingandtherebyproducesFas-resistance,eveninotherwisesusceptible,CD40-stimulatedtargets.BCRsignalingforinducibleFas-resistancedevelopsoveraperiodof12hoursanddependson

简介：AIMTodeterminetheroleofcorticotropinreleasingfactorreceptor(CRF2)inepithelialpermeabilityandenterocytecelldifferentiation.METHODSForthispurpose,weusedratSpragueDawleyandvariouscoloncarcinomacelllines(SW620,HCT8R,HT-29andCaco-2celllines).ExpressionofCRF2proteinwasanalyzedbyfluorescentimmunolabelinginnormalratcolonandthenbywesternblotindissociatedcolonicepithelialcellsandinthelysatesofcoloncarcinomacelllinesorduringtheearlydifferentiationofHT-29cells(tenfirstdays).ToassesstheimpactofCRF2signalingoncoloniccelldifferentiation,HT-29andCaco-2cellswereexposedtoUrocortin3recombinantproteins(Ucn3,100nmol/L).Insomeexperiments,cellswerepre-exposedtotheastressin2b(A2b)aCRF2antagonistinordertoinhibittheactionofUcn3.Intestinalcelldifferentiationwasfirstanalyzedbyfunctionalassays:thetrans-cellularpermeabilityandthepara-cellularpermeabilityweredeterminedbyDextran-FITCintakeandmeasureofthetransepithelialelectricalresistancerespectively.Morphologicalmodificationsassociatedtoepithelialdysfunctionwereanalyzedbyconfocalmicroscopyafterfluorescentlabelingofactin(phaloidin-TRITC)andintercellularadhesionproteinssuchasE-cadherin,p120ctn,occludinandZO-1.Theestablishmentofmatureadherensjunctions(AJ)wasmonitoredbyfollowingthedistributionofAJproteinsinlipidraftfractions,afterseparationofcelllysatesonsucrosegradients.Finally,themRNAandtheproteinexpressionlevelsofcharacteristicmarkersofintestinalepithelialcell(IEC)differentiationsuchasthetranscriptionalfactorkrüppel-likefactor4(KLF4)orthedipeptidylpeptidaseIV(DPPIV)wereperformedbyRT-PCRandwesternblotrespectively.ThespecificactivitiesofDPPIVandalkalinephosphatase(AP)enzymesweredeterminedbyacolorimetricmethod.RESULTSCRF2proteinispreferentiallyexpressedinundifferentiatedepithelialcellsfromthecryptsofcolonandinhumancoloncarcinoma

简介：转变生长因素--尾除了Smads利用大量的细胞内部的发信号小径调整细胞的功能的一个宽数组。这些不在经典中，non-Smad小径被占据ligand的受体直接激活到增强，稀释，或不那样调制下游地细胞的回答。这些non-Smad小径包括地图kinase小径，象Rho一样GTPase发信号小径，和phosphatidylinositol-3-kinase/AKT小径的各种各样的分支。这评论在non-Smad小径的分子、生物化学的机制的理解集中于最近的进展。另外，这些non-Smad小径的功能也被讨论。

简介：摘要丝裂原活化蛋白激酶(mitogen-activated protein kinase，MAPK)信号转导通路是调节细胞生长和存活的关键途径，异常的MAPK信号能促进癌症的发生发展，也决定了癌症的治疗反应。胃癌是中国常见消化道恶性肿瘤之一；近年来研究发现，在胃癌中存在诸多细胞信号传导通路的调控异常。细胞外信号调节激酶(extracellular signal-regulated kinase，ERK)信号通路是MAPK家族中的一条重要信号通路，该信号通路通过整合传递细胞外信号至细胞及其核内控制细胞的生长、凋亡和分化等。MAPK/ERK信号通路的异常激活可导致细胞丧失凋亡和分化能力，引发细胞异常增殖和恶性转化，促进胃癌的恶性表型；相反，阻断MAPK/ERK信号通路的相关组分则可逆转这一过程。本文结合国内外最新研究报道，对近年来在胃癌研究中发现MAPK/ERK信号通路的激活或失活在促进或抑制胃癌细胞恶性表型的重要作用及其相关的分子机制加以综述。

简介：AbstractBone morphogenetic protein belongs to transcription growth factor superfamily β; bone morphogenetic protein signal pathway regulates cell proliferation, differentiation, and apoptosis among different tissues. Cerebrovascular system supplies sufficient oxygen and blood into brain to maintain its normal function. The disorder of cerebrovascular system will result into serious cerebrovascular diseases, which is gradually becoming a major threat to human health in modern society. In recent decades, many studies have revealed the underlying biology and mechanism of bone morphogenetic protein signal pathway played in cerebrovascular system. This review will discuss the relationship between the two aspects, aiming to provide new perspective for non-invasive treatment and basic research of cerebrovascular diseases.

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简介：Cytokineslikeinterferons(IFNs)playacentralroleinregulatinginnateandspecificimmunitiesagainstthepathogensandneoplasticcells.AnumberofsignalingpathwaysareinducedinresponsetoIFNinvariouscells.OneclassicmechanismemployedbyIFNsistheJAK-STATsignalingpathwayforinducingcellularresponses.Herewedescribethenon-STATpathwaysthatparticipateinIFN-inducedresponses.Inparticular,wewillfocusontheroleplayedbytranscriptionfactorC/EBP-βinmediatingtheseresponses.

简介：Thefibroblastgrowthfactorreceptor(FGFR)familyplaysimportantrolesinregulatingcellgrowth,proliferation,survival,differentiationandangiogenesis.DeregulationoftheFGF/FGFRsignalingpathwayhasbeenassociatedwithmultipledevelopmentsyndromesandcancers,andthustherapeuticstrategiestargetingFGFsandFGFRinhumancancerarecurrentlybeingexplored.However,fewstudiesontheFGF/FGFRpathwayhavebeenconductedinsarcoma,whichhasapooroutcomewithtraditionaltreatmentssuchassurgery,chemotherapy,andradiotherapy.Hence,inthepresentreview,weprovideanoverviewoftheroleoftheFGF/FGFRpathwaysignalinsarcomaandFGFRinhibitors,whichmightbenewtargetsforthetreatmentofsarcomasaccordingtorecentresearch.

简介：昆虫长是最丰富的草食动物，并且植物发展了复杂机制对他们的攻击保卫。特别地，植物能察觉与昆虫herbivory联系的织物损坏的特定的模式。某植物种类能在昆虫察觉某些elicitors在喂期间进入创伤，并且很快激活一系列缠绕的发信号的小径安排各种各样的防御代谢物的生合成的口头的分泌物(OS)。激活Mitogen的蛋白质kinases(MAPK)，对所有优核质普通，涉及许多细胞的进程的组织，包括开发和压力回答。在植物，至少二MAPK，水杨酸导致酸的蛋白质kinase(SIPK)和导致创伤的蛋白质kinase(WIPK)，被伤害或昆虫OS很快激活；重要地，用在MAPK发信号损害的转基因或变异的植物的基因研究显示MAPK在调整植物激素的导致herbivory的动力学起关键作用，例如jasmonic酸，乙烯和水杨酸酸，和MAPK也为草食动物的transcriptional激活被要求防御代谢物的防卫相关的基因和累积。在这评论，我们在在植物抵抗理解MAPK的功能到昆虫草食动物总结最近的开发。