简介：

简介：Accumulatingevidencefromepidemiologicalandexperimentalstudiesindicatethatobesity,anditsrelatedmetabolicconsequencesofinsulinresistanceandtype2diabetes,areassociatedwithacceleratedcognitivedecline(Yatesetal.,2012).Theetiologyofneurodegenerationinobesityisundoubtedlycomplex,withvascular,metabolic,inflammatory,andstructuralchangesalllikelytoplayarole(Yatesetal.,

简介：无

简介：Thenuclearreceptorsuperfamilyandthetranscriptionalfactorsassociatedwithcytokinesareinherentlydifferentfamiliesofsignalingmoleculesandactivategenetranscriptionbybindingtotheirrespectiveresponsiveelement.However,ithasbecomeincreasinglyclearfromourworksandothersthatnuclearreceptorsareimportantregulatorsofcytokineproductionandfunctionthroughcomplexandvariedinteractionsbetweenthesedistincttranscriptionalfactors.Thisreviewprovidesageneraloverviewofthemechanismofactionofnuclearreceptorsandtheirtranscriptionalcrosstalkwithtranscriptionalfactorsassociatedwithcytokinetransductionpathways.Oneofthemostimportantmechanisticaspectsisproteintoproteininteractionthroughadirectorco-regulator-mediatedindirectmanner.Suchcrosstalkiscruciallyinvolvedinphysiologicalandtherapeuticrolesofnuclearreceptorsandtheirligandsinimmunity,inflammationandcytokine-relatedtumors.Cellular&MolecularImmunology.2004;1(6):416-424.

简介：Objective:Despiteevidencethatestrogensandinsulinareinvolvedinthedevelopmentandprogressionofmanycancers,theirsynergisticroleinendometrialcarcinoma(EC)hasnotbeenanalyzedyet.Methods:Here,weinvestigatedhowestrogensactsynergisticallywithinsulintopromoteECprogression.Cellgrowthinvitroandinvivo,effectsofestradiolandinsulinonapoptosisandcellcycledistribution,andexpressionandactivationofestrogenreceptor(ER),insulinreceptor(InsR),andkeyproteinsinthePI3KandMAPKpathwayswereexaminedaftercombinedstimulationwithestradiolandinsulin.Results:ComparedtoECcellstreatedwithestradiolorinsulinalone,thosetreatedwithbothestradiolandinsulinexhibitedstrongerstimulation.EstradiolsignificantlyinducedphosphorylationofInsR-βandIRS-1,whereasinsulinsignificantlyinducedphosphorylationofER-α.Inaddition,treatmentwithbothinsulinandestradioltogethersignificantlyincreasedtheexpressionandphosphorylationofAkt,MAPK,andERK.Notably,InsR-βinhibitionhadalimitedeffectonestradiol-dependentproliferation,cellcycle,andapoptosis,whereasER-αinhibitionhadalimitedinsulin-dependenteffect,inECcelllines.InsulinandestradiolindividuallyandsynergisticallypromotedECxenograftgrowthinmice.Conclusions:EstrogenandinsulinplaysynergisticrolesinECcarcinogenesisandprogressionbyactivatingInsR-βandER-α,promotingacrosstalkbetweenthem,andtherebyresultingintheactivationofdownstreamPI3K/AktandMAPK/ERKsignalingpathways.

简介：在树枝状的房间(DC)和生来的杀手(NK)之间的相互的激活串音房间戏在对病毒和肿瘤调整有免疫力的防卫的一个枢轴的角色。生产cytokine能力，Th房间极化能力和chemokine表达式，移植和DC的stimulatory函数被激活的NK房间调整。相反地，天生并且NK房间的受动器功能与激活的DC要求靠近的相互作用。包括cytokines和前列腺素(PG)，房间联系膜的分子和可溶的调停人贡献在DC和NK房间之间的双向串音。最著名、学习得好的PG之一是PGE2。由许多房间类型生产了，PGE2被显示了由对免疫系统的所有部件起作用影响有免疫力、煽动性的回答的各种各样的方面。正在出现PGE2在DC和NK房间生物学起关键作用的证据。几研究证明了DC是它在正常有免疫力的反应并且在有免疫力的混乱期间的immunomodulatory行动的PGE2，而且一个目标的不仅来源。尽管NK房间看起来不能生产PGE2，他们被描述为强大的反应PGE2房间，当他们表示所有PGE2E-prostanoid(EP)受体。几NK房间功能(细胞溶解，移植，增长，cytokine生产)被PGE2影响。这评论在正常和immunopathological过程在有免疫力的规定上在DC-NK房间串音和它的随后的影响上加亮PGE2的效果。

简介：AbstractObjective:The maternal-fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus. The interaction between decidual γδ T cells and trophoblasts plays a pivotal role during successful pregnancy; however, their physiological functions in early-term human pregnancy are still not completely illustrated. This study was undertaken to illustrate the functional roles of CXCL16/CXCR6 to prevent pregnancy loss via the crosstalk between decidual γδ T cells and HTR8/SVneo trophoblast cells.Methods:The percentile of CXCR6+ γδ T cells in the peripheral blood from normal female and recurrent spontaneous abortion (RSA) patients was analyzed by flow cytometry. The expression of CXCR6 was detected in decidual immune cells via flow cytometry, and the expression of CXCL16 was analyzed in HTR8/SVneo trophoblast cells and lentivirus (LV)-HTR8/SVneo trophoblast cells via enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used to verify the expression of the CXCL16 gene in LV-HTR8/SVneo trophoblast cells. Expression of granzyme B and cytokines and proliferation of decidual γδ T cocultured with HTR8/SVneo trophoblast cells were analyzed by flow cytometry. Invasion of HTR8/SVneo trophoblast cells was assessed via Matrigel transwell assay. Adoptive transfer was induced in vivo further to illustrate that the normal expression of CXCL16/CXCR6 could prevent pregnancy loss.Results:The percentile of CXCR6+ γδ T cells in the peripheral blood from RSA patients was lower than normal pregnancies. The expression of CXCR6 was highest in the decidual γδ T cells among decidual immune cells, and the expression of CXCL16 increased as the amount of HTR8/SVneo trophoblast cells increased. Expression of granzyme B in the decidual γδ T cells was downregulated by cocultured with HTR8/SVneo cells dependent of CXCL16, and HTR8/SVneo trophoblast cells induced the Th2 cytokines production in the decidual γδ T cells. Both the expression of CXCR6 in the decidual γδ T cells and proliferation of the decidual γδ T cells were promoted by HTR8/SVneo trophoblast cells. On the other hand, decidual γδ T cells enhanced the invasion of HTR8/SVneo trophoblast cells and thus promoted embryo implantation. In vivo study was taken further and shown that low expression of CXCL16/CXCR6 results in pregnancy loss because of dialog disorder between decidual γδ T cells and trophoblasts.Conclusions:Low expression of CXCL16/CXCR6 results in pregnancy loss because of the dialog disorder between decidual γδ T cells and trophoblasts, and it showed a light on the effective strategy of adoptive transfer of CXCR6+ γδ T cells on the treatment of RSA. This observation provides a scientific basis on which a potential strategy can be applied to the early-detect and treatment of RSA.

简介：AbstractBackground:MicroRNAs are closely associated with the progression and outcomes of multiple human diseases, including sepsis. In this study, we examined the role of miR-23a in septic injury.MethodsLipopolysaccharide (LPS) was used to induce sepsis in a rat model and H9C2 and HK-2 cells. miR-23a expression was evaluated in rat myocardial and kidney tissues, as well as H9C2 and HK-2 cells. A miR-23a mimic was introduced into cells to identify the role of miR-23a in cell viability, apoptosis, and the secretion of inflammatory cytokines. Furthermore, the effect of Rho-associated kinase 1 (ROCK1), a miR-23a target, on cell damage was evaluated, and molecules involved in the underlying mechanism were identified.Results:In the rat model, miR-23a was poorly expressed in myocardial (sham vs. sepsis 1.00 ± 0.06 vs. 0.27 ± 0.03, P < 0.01) and kidney tissues (sham vs. sepsis 0.27 ± 0.03 vs. 1.00 ± 0.06, P < 0.01). Artificial overexpression of miR-23a resulted in increased proliferative activity (DNA replication rate: Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 34.13 ± 3.12 vs. 12.94 ± 1.21 vs. 13.31 ± 1.43 vs. 22.94 ± 2.26, P < 0.05; HK-2 cells: 15.17 ± 1.43 vs. 34.52 ± 3.46 vs. 35.19 ± 3.12 vs. 19.87 ± 1.52, P < 0.05), decreased cell apoptosis (Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 11.39 ± 1.04 vs. 32.57 ± 2.29 vs. 33.08 ± 3.12 vs. 21.63 ± 2.35, P < 0.05; HK-2 cells: 15.17 ± 1.43 vs. 34.52 ± 3.46 vs. 35.19 ± 3.12 vs. 19.87 ± 1.52, P < 0.05), and decreased production of inflammatory cytokines, including interleukin-6 (Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 59.61 ± 5.14 vs. 113.54 ± 12.30 vs. 116.51 ± 10.69 vs. 87.69 ± 2.97 ng/mL; P < 0.05, F = 12.67, HK-2 cells: 68.12 ± 6.44 vs. 139.65 ± 16.62 vs. 143.51 ± 13.64 vs. 100.82 ± 9.74 ng/mL, P < 0.05, F = 9.83) and tumor necrosis factor-α (Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 103.20 ± 10.31 vs. 169.67 ± 18.84 vs. 173.61 ± 15.91 vs. 133.36 ± 12.32 ng/mL, P < 0.05, F = 12.67, HK-2 cells: 132.51 ± 13.37 vs. 187.47 ± 16.74 vs. 143.51 ± 13.64 vs. 155.79 ± 15.31 ng/mL, P < 0.05, F = 9.83) in cells. However, ROCK1 was identified as a miR-23a target, and further up-regulation of ROCK1 mitigated the protective function of miR-23a in LPS-treated H9C2 and HK-2 cells. Moreover, ROCK1 suppressed sirtuin-1 (SIRT1) expression to promote the phosphorylation of nuclear factor-kappa B (NF-κB) p65, indicating the possible involvement of this signaling pathway in miR-23a-mediated events.Conclusion:Our results indicate that miR-23a could suppress LPS-induced cell damage and inflammatory cytokine secretion by binding to ROCK1, mediated through the potential participation of the SIRT1/NF-κB signaling pathway.