简介:AbstractBackground:Despite improvements in disease diagnosis, treatment, and prognosis, breast cancer is still a leading cause of cancer death for women. Compelling evidence suggests that targeting cancer stem cells (CSCs) have a crucial impact on overcoming the current shortcomings of chemotherapy and radiotherapy. In the present study, we aimed to study the effects of T cells and a critical anti-tumor cytokine, interferon-gamma (IFN-γ), on breast cancer stem cells.Methods:BALB/c mice and BALB/c nude mice were subcutaneously injected with 4T1 tumor cells. Tumor growth and pulmonary metastasis were assessed. ALDEFLOURTM assays were performed to identify aldehyde dehydrogenasebright (ALDHbr) tumor cells. ALDHbr cells as well as T cells from tumor-bearing BALB/c mice were analyzed using flow cytometry. The effects of CD8+ T cells on ALDHbr tumor cells were assessed in vitro and in vivo. The expression profiles of ALDHbr and ALDHdim 4T1 tumor cells were determined. The levels of plasma IFN-γ were measured by enzyme-linked immunosorbent assay, and their associations with the percentages of ALDHbr tumor cells were evaluated. The effects of IFN-γ on ALDH expression and the malignancy of 4T1 tumor cells were analyzed in vitro.Results:There were fewer metastatic nodules in tumor-bearing BALB/c mice than those in tumor-bearing BALB/c nude mice (25.40 vs. 54.67, P < 0.050). CD8+ T cells decreased the percentages of ALDHbr 4T1 tumor cells in vitro (control vs. effector to target ratio of 1:1, 10.15% vs. 5.76%, P < 0.050) and in vivo (control vs. CD8+ T cell depletion, 10.15% vs. 21.75%, P < 0.001). The functions of upregulated genes in ALDHbr 4T1 tumor cells were enriched in the pathway of response to IFN-γ. The levels of plasma IFN-γ decreased gradually in tumor-bearing BALB/c mice, while the percentages of ALDHbr tumor cells in primary tumors increased. IFN-γ at a concentration of 26.68 ng/mL decreased the percentages of ALDHbr 4T1 tumor cells (22.88% vs. 9.88%, P < 0.050) and the protein levels of aldehyde dehydrogenase 1 family member A1 in 4T1 tumor cells (0.86 vs. 0.49, P < 0.050) and inhibited the abilities of sphere formation (sphere diameter <200 μm, 159.50 vs. 72.0; ≥200 μm, 127.0 vs. 59.0; both P < 0.050) and invasion (89.67 vs. 67.67, P < 0.001) of 4T1 tumor cells.Conclusion:CD8+ T cells and IFN-γ decreased CSC numbers in a 4T1 mouse model of breast cancer. The application of IFN-γ may be a potential strategy for reducing CSCs in breast cancer.
简介:·AIM:Toexploretheeffectofimmunizationwithcopolymer-1(COP-1)andretinalstemcells(RSCs)transplantationoninterferon-gamma(IFN-γ)levelsinaratexperimentalglaucomamodel.·METHODS:Anexperimentalglaucomawasinducedbyargonlaserphotocoagulationoftheepiscleralveinsandlimbalplexusintherighteyeofrats.Immediatelyfollowingglaucomainduction,ratswereimmunizedwithCOP-1.RSCswereculturedandtransplantedintravitreallyintotheeyesofglaucomamodelanimals1weekpost-lasertreatment.Sixexperimentalgroupswereused:COP-1/RSC,PBS/RSC,COP-1/PBS,PBS/PBS,glaucomamodelgroup,andanormalcontrolgroup.TheconcentrationofIFN-γinaqueoushumor(AH)andserumwasmeasuredbyenzyme-linkedimmunosorbentassay(ELISA)ineachofthesixgroups.Retinalganglioncell(RGC)survivalwasassessedbyquantifyingapoptosisusingHoechststaining.·RESULTS:ConcentrationsofIFN-γinAHandserumofratsthathadundergoneglaucomainductionwerehigherthanthoseofnon-inducedcontrolrats.TheconcentrationsofIFN-γinAHandserumoftheCOP-1/RSCstreatedgroupweredeterminedtobe2371.9ng/Land710.9ng/L,respectively,whichweresignificantlylowerthanthoseintheothertreatedgroups(P<0.05).Infact,IFN-γlevelsinthedualtreatedgroupwerereducedtobackgroundlevels.TheCOP-1/RSCgrouphadlowernumberofapoptoticRGCsthantheotherthreeexperimentalgroups(P<0.05).·CONCLUSION:ThereducedlevelsofIFN-γinAHandserumoftheCOP-1/RSCgroupmayberelatedtosynergisticeffectsbetweenRSCstransplantationandCOP-1immunemodulation.ItislikelythatthelowerlevelsofIFN-γpreventedRGCsglaucomatousapoptosis.·
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简介:TheGAMMAparadigmisrecentlyproposedbyBanatreandMetayertodescribethesystematicconstructionofparallelprogramswithoutintroducingartificialsequentiality.ThispaperpresentstwosynchronousexecutionmodelsforGAMMAanddiscusseshowtoimplementthemonMasParMP-1,amassivelydataparallelcomputer.TheresultsshowthatGAMMAparadigncanbeimplementedverynaturallyondataparallelmachines,andveryhighlevellanguage,suchasGAMMAinwhichparallelismisleftimplicit,issuitableforspecifyingmassivelyparallelapplications.
简介:Cytokineslikeinterferons(IFNs)playacentralroleinregulatinginnateandspecificimmunitiesagainstthepathogensandneoplasticcells.AnumberofsignalingpathwaysareinducedinresponsetoIFNinvariouscells.OneclassicmechanismemployedbyIFNsistheJAK-STATsignalingpathwayforinducingcellularresponses.Herewedescribethenon-STATpathwaysthatparticipateinIFN-inducedresponses.Inparticular,wewillfocusontheroleplayedbytranscriptionfactorC/EBP-βinmediatingtheseresponses.
简介:TheeffectofstressdistributionduetothechangesofthedistalscrewalignmentinrelationtotheGammanailandthefemoralshaftisthoroughlystudiedinthispaper.FailureoftheGammanailcompositeoccursthroughthecranialapertureofthedistalscrewsandtheinsertionholeforthelagscrewduetononunion,delayed-unionandcontinuedweight-bearing.Athree-dimensionalfiniteelementmodelwasusedtostudythefracturedfemur,theGammanail,thelagscrewandthedistallockingscrews.ThefirstandtheseconddistalscrewswereinsertedintotheGammanailinfourdifferentconfigurations.WefoundthatthestressoftheGammanailcompositewassubstantiallyreducedwiththetwoscrewsconfiguredintheanteriortoposteriordirection.Thisalignmentcanbeargreaterloadinginthemoredemandingfracturetypes.Inthesubtrochantericfractureorthecomminutedfracturesattheproximalfemur,theoptimalalignmentofthetwodistalscrewswasintheanteriortoposteriordirection.
简介:客观:在人的hepatocellular癌(HCC)在HLA医生表示上调查干扰素(IFN)的管理效果。方法:房间衬里的在4种HCC的HLA医生的表示,HHCC,SMMC-7721,BEL-7402,HCC-9204和一个正常的肝房间衬里QZG在被IFN-或IFN-的不同剂量刺激前后与immunohistochemicalABC和ELISA方法被检测。结果:仅仅SMMC-7721房间的小部分表示了另外的房间线的HLA医生,和所有是在有IFN-或IFN-的刺激前否定的HLA医生。HLA医生表示在刺激以后5根房间线在所有被提高,并且它与IFN的剂量被相关。QZG房间不比HCC房间明显。IFN-的效果比IFN-的更明显。结论:IFN能在HCC房间提高HLA医生表示。
简介:树枝状的房间(DC)在造血的房间的一张次要的人口,生产类型我干扰素(IFN)和另外的cytokines并且为天生的免疫是必要的。他们也是有势力抗原演讲者并且调整适应免疫。在DC子类型血浆之中似细胞的DC(pDC)生产类型的最高的数量我IFN。另外,象IL-12和IL-10那样的支持inflammatory和反煽动性的cytokines响应象发信号的受体(TLR)一样并且在病毒的感染之上的代价在DC被导致。在IRF家庭的蛋白质控制DC活动的许多方面。IRF-8和IRF-4为DC开发是必要的。他们差别控制四个DC子集的开发。IRF-8-/-老鼠大部分缺乏pDC和CD8alpha+DC,当IRF-4-/-老鼠缺乏CD4+DC时。IRF-8-/-,IRF4-/-,两倍猛烈老鼠有仅仅很少CD8a-CD4-DC那缺乏MHCII。IRF蛋白质也控制类型我在DC的IFN正式就职。IRF-7,在TLR发信号之上激活不仅在pDC,而且在常规DC(cDC)为IFN正式就职被要求,non-DC房间打字。IRF-3贡献在成纤维细胞感应的IFN,在在DC感应的IFN是非必需的。我们的最近的证据揭示那种类型我在DC感应的IFN非常依赖于IRF-8,它在DC在IFN基因正式就职的反馈阶段行动。类型我在pDC感应的IFN被MyD88调停依赖发信号小径,并且不同于在另外的房间采用的小径,它主要依靠TLR3和RIG-I家庭蛋白质。另外的支持inflammatorycytokines以一种IRF-5依赖方式被生产。然而,IRF-5没为IFN正式就职被要求,建议为类型的正式就职的分开的机制的存在我IFN和其它支持inflammatorycytokines。激活的DC接着生产的IFN和另外的cytokines预付DC成熟并且改变DC的显型和功能。这些过程也是可能的被IRF家庭蛋白质管理。
简介:Objective:Todetecttheexistenceofimmunetoleranceinducedbygamma-rayirradiation.Methods:Peritonealcellswereharvestedfrommicesubjectedto5Gy60Cogamma-raytotalbodyirradiationat3d,7d,15dand30d,thentheircounts,morphologicalchangesandIL-12geneexpressionwereinvestigated.Results:Afterirradiation,theperitonealcellsweresharplyreduced,thecellmorphologyshiftedfromround-liketopolymorphicandfusiformwithsomeprocesses,expressionofIL-12p35wasseriouslysuppressed,whilethatofIL-12p40greatlyenhanced.Conclusion:Ourdatahighlysuggestthatthegamma-rayirradiationcouldpotentiallyinducedendriticcell(DC)commitmentandimmunetolerance.
简介:TheserviceprovidedbytheGC(GammaCameras)intheNuclearMedicinedepartmentsfailsbecauseoftheirbreakdown,generallyduetotheassociatedelectronicsandnottothephysicaldetectioncomponents.Forthisreason,itwasdecidedtodevelopanelectronicsystemthatallowstherecoveryandoptimizationofdisusedGC,startingwiththedesignofthepreamplifierforaPMT(photomultipliertube).Thecircuitwasdesignedandsimulatedandthelistofcomponentsnecessaryfortheconstructionofthepreamplifierwasgenerated,aswellastheprintedcircuitboardwasdesignedforitsassembly.Bysimulatingthepreamplifierthisworkedinlinearmode.Thisdeterminesthattheamplitudeoftheoutputsignalisproportionaltotheamountofchargedeliveredbythedetector.ThiscardallowsanautomaticadjustmentofthesignalsofthePMTasdothemodernGC.
简介:客观干扰素(IFN)和ribavirin(RBV)的联合是为丙肝的标准治疗病毒(HCV)感染。HCV遗传型2a对治疗证明了更顺从,但是它的功效是还有限的。这研究试图在HCV遗传型2a感染的一种情况中调查差的反应的机制。方法:我们从一个病人分析了HCVRNA的动态变化,与HCV遗传型2a感染了,显示出差的virological回答到是的IFN/RBV判定了12在由HCV的治疗的开始以后的星期克隆定序。然后,我们构造了subgenomic日语有人性化的Gaussia的暴发性的hepatitis-1(JFH1)replicon和不同妄想的replicons酶基因。妄想的replicons从subgenomicJFH1replicon,NS5A区域被病人顺序从pre/posttreatment在代替被导出,并且到IFN的妄想的replicons危险性被相对Gausia酶活动评估。预告的处理HCV定序的结果显得几乎一致,并且quasispecies变化是进一步的在12星期治疗以后简化的更多。而且,quasispecies变化似乎相对,在NS5A更多样化为IFN反应关键的一个区域,和每妄想的replicons展出了不同反应到IFN。结论在长期的感染的功课期间,HCV人口似乎被使适应病人免疫学的系统,并且推进被IFN/RBV治疗的联合选择,显示quasispecies可以完全与IFN的与那些不同的目标由另外的药的增加消除了。另外,到IFN的妄想的replicon的各不同的反应与氨基酸变化在或在在长期的感染和IFN/RBV治疗期间决定NS5A的区域(ISDR)的IFN敏感附近有关是最可能的。
简介:AbstractEffective prophylactic and therapeutic interventions are urgentlyneeded to address the coronavirus disease 2019 (COVID-19) pandemic. Various antiviral drugs have recently been tested. Type I interferon (IFN) is a regulatory protein involved in the innate immune response, with broad-spectrum antiviral activities and the ability to directly block viral replication and support the immune response to eliminate virus infection. Insufficient virus-induced type I IFN production is characteristic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, because SARS-CoV-2 suppresses the IFN response by interacting with essential IFN signaling pathways. Exogenous type I IFN is recommended for treating COVID-19. Unexpectedly however, angiotensin converting enzyme-2 (ACE2) receptor, which acts as a SARS-CoV-2 receptor, was shown to be stimulated by IFN, raising doubts about the suitability of IFN use. However, further studies have excluded concerns regarding IFN administration. Type I IFNs, including IFN-α1b, have been used clinically as antiviral drugs for many years and have shown strong antiviral activity against SARS-CoV-2 in vitro. Preliminary clinical studies of type I IFNs, especially when delivered via aerosol inhalation, have demonstrated efficacy for the treatment and prevention of COVID-19. Randomized controlled trials of IFN for COVID-19 treatment are ongoing.