简介：BACKGROUND:Ithasbeenshownthatginsenoside,theeffectivecomponentofginseng,canenhanceexpressionofcholineacetyltransferase,aswellasbrain-derivedneurotrophicfactor(BDNF)anditsreceptortyrosinekinaseB(TrkB),incholinergicneuronsofthebasalforebrain.OBJECTIVE:ToqualitativelyandquantitativelyverifytheinfluenceofginsenosideonexpressionofBDNFanditsreceptor,TrkB,inthemedialseptumofagedrats,andtoprovideamolecularbasisforclinicalapplication.DESIGN,TIMEANDSETTING:Acontraststudy,whichwasperformedintheDepartmentofAnatomy,ChinaMedicalUniversity,andtheDepartmentofAnatomy,ShenyangMedicalCollegebetweenDecember2005andMay2007.MATERIALS:Thirty-five,healthy,female,SpragueDawleyratswereselectedforthisstudy.Ginsenoside(81%purity)wasprovidedbyJilinJi’anWantaiChineseMedicineFactory;anti-BDNFantibody,anti-TrkBantibody,andtheirkitswereprovidedbyWuhanBosterCompany.METHODS:Atotalof35ratsweredividedintothreegroups:young(fourmonthsold),aging(26monthsold),andginsenoside.Ratsintheginsenosidegroupwereadministeredginsenoside(25mg/kg/d)between17monthsand26months.MAINOUTCOMEMEASURES:ImmunohistochemistryandinsituhybridizationwereusedtomeasureexpressionofBDNFandTrkBinthemedialseptumofagedrats,andthedetectedresultswereexpressedasgrayvalues.RESULTS:①Qualitativedetection:usingmicroscopy,degenerativeneuronswerevisibleinthemedialseptumintheaginggroup.However,neuronalmorphologyintheginsenosidegroupwassimilartoneuronsintheyounggroup.②Quantitativedetection:themeangrayvalueofBDNF-positiveandTrkB-positiveproductsintheaginggroupweresignificantlyhigherthanintheyounggroup(t=3.346,4.169,P<0.01);however,themeangrayvalueintheginsenosidegroupwassignificantlylowerthanintheaginggroup(t=2.432,2.651,P<0.01).CONCLUSION:GinsenosidecanincreaseexpressionofBDNFandTrkBinth

简介：瞄准：在老鼠碳在Kupffer房间决定激活血小板的因素(PAF)合成和它的受体表示导致四氯化物的肝硬化。方法：Kupffer房间，从控制和导致CCl4的肝脏硬化症的老鼠的肝孤立，一夜间被放在没有浆液的媒介。PAF浸透绑定，ET-1浸透和比赛绑定是assayed。导致的PAF合成，PAF的mRNA表示，preproendothelin-1，endothelinA(希腊语字母的第七字)和endothelinB(ETB)受体也是的ET-1决定了。结果：PAF合成的双重的增加(1.42+/-0.14对0.66+/-0.04pg/mugDNA)并且膜界限PAF的1.48褶层增加(1.02+/-0.06对0.69+/-0.07pg/mugDNA)在肝脏硬化症的老鼠的激活的Kupffer房间被观察。到Kupffer房间的ET-1的申请在激活的Kupffer房间经由ETB受体，而是PAF合成在肝脏硬化症、正常的老鼠以一种集中依赖者方式导致了PAF合成在正常Kupffer房间是比那更有效的。在激活的Kupffer房间，PAF受体表示和PAF绑定能力显著地被提高。激活的Kupffer房间涨了[125I]-ET-1绑定能力，而是改变的两个都不受体的亲密关系，也不希腊语字母的第七字的表达式受体。结论：在导致CCl4的肝硬化期间的Kupffer房间是增加的PAF的主要来源。ET-1内长地涉及由paracrine经由ETB受体在激活的Kupffer房间刺激PAF合成。希腊语字母的第七字受体没出现在激活的Kupffer房间，它可以加重肝硬化的肝、额外的肝的复杂并发症。

简介：活动过度的雄激素受体(AR)活动仍然是前列腺癌症和电阻的发作和前进的一个关键决定因素到当前的治疗。管理的机制阉割抵抗前列腺癌症糟糕被理解，但是定义这些分子的事件是必要的以便从前列腺癌症影响死亡。杨等。表明知道是在治疗的overexpressed的那二lnc-RNAs抵抗前列腺癌症，PRNCR1(也作为PCAT8知道)并且PCGEM1，跳到AR提高ligand依赖、ligand独立的AR基因表示和这些相互作用的顺序包含了的前列腺癌症cells.1的增长到acetylatedAR和DOT1L的一个随后的协会的PRNCR1的绑定，为lncRNAPCGEM1的顺序的招募被要求到AR氨基的终点，它接着被遇见

简介：高血压生产为与疾病联系的死亡经常负责的pathophysiological变化。overactive高血压蛋白原酶血管收缩素系统在高血压和与高血压联系的目标机关损坏的发展起一个中央作用，是明显的。我们以前发现了新奇血管收缩素受体(AT1)vaccine-ATR12181在自发地高血压的老鼠(SHR)稀释了高血压(BP)的发展人的必要高血压的模型。我们的目的是决定高BP的这变细是否与由高血压的状态导致的目标机关损坏的预防被联系。SHR被在联合复杂的peptide-tetanus-toxoid的重复下的注射与Freund的助手从AT1A受体的extracelluar部分对肽(编码ATR12181)使免疫。64个星期长期的观察被执行。重复种痘导致了anti-ATR12181抗体的正式就职。在观察的结束，种牛痘表明的SHR降低肾损害的BP，减少的心脏的肥大和变细。在心和肾的c-fos和c-jun的mRNA层次在种牛痘的SHR被减少。因为自我抗原被使用，疫苗的安全被担心。然而，自体免疫的疾病的符号没在心和肾的节被观察。这些数据证明对AT1受体的细胞外的部分的域的那重复免疫能对高血压引起一个目标机关保护。对AT1受体的活跃免疫可以在高血压的治疗被看作有希望的新策略。

简介：AbstractIntroduction:Tripterygium glycosides (TGs) have been widely used in China to treat diabetic nephropathy (DN); however, proof of their use is scarce. The present study aimed to evaluate the effectiveness and safety of adding TGs to angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).Methods:By searching Embase, MEDLINE, Cochrane Library, SINOMED, China National Knowledge Infrastructure, VIP Information/Chinese Scientific Journals, and WANFANG databases, we identified previous studies that met the specific selection criteria and included them in the meta-analysis. Analyses were performed using Review Manager (version 5.3).Results:Nine randomized controlled trials were included in the final meta-analysis. Patients were compared before and after treatment with ACE inhibitors or ARBs plus TGs, or ACE inhibitors or ARBs alone. The results revealed that treatment with ACE inhibitors or ARBs plus TGs resulted in significantly greater reductions in 24-h urinary total protein (UTP) levels (trial duration <2 months, mean difference [MD]: -0.25; 95% confidence interval [CI]: -0.32, -0.18; trial duration between 2 and 6 months, MD: -0.39; 95% CI: -0.44, -0.33; trial duration >6 months, MD: -2.09; 95% CI: -2.89, -1.29) compared with treatment using ACE inhibitors or ARBs alone. Additionally, ACE inhibitors or ARBs plus TGs showed better results after longterm administration. Treatment with ACE inhibitors or ARBs plus TGs resulted in significantly greater reductions in serum creatinine (SCr) compared with ACE inhibitors or ARBs alone (MD: -9.87; 95% CI: -13.76, -5.97).Conclusion:In patients with DN, adding TGs to ACE inhibitors or ARBs significantly lowered both the 24-h UTP and SCr levels. Therefore, ACE inhibitors or ARBs plus TGs might improve the treatment of DN in patients.

简介：Thedevelopmentandplasticityofcentralauditorysystemcanbeinfluencedbythechangeofperipheralneuronalactivity.However,themolecularmechanismparticipatingintheprocessremainselusive.Brain-derivedneurotrophicfactor(BDNF)bindingwithitsfunctionalreceptortropomyosinreceptorkinaseB(TrkB)hasmultipleeffectsonneurons.Hereweusedaratmodelofauditorydeprivationbybilateralcochlearablation,toinvestigatethechangesinexpressionofBDNFandTrkBintheauditorycortexafterauditorydeprivationthatoccurredduringthecriticalperiodforthedevelopmentofcentralauditorysystem.Reversetranscription-quantitativepolymerasechainreaction(RTqPCR)andimmunohistochemistrymethodswereadoptedtodetectthemRNAandproteinexpressionlevelsofBDNFandTrkBintheauditorycortexat2,4,6and8weeksaftersurgery,respectively.ThechangeintheexpressionofBDNFandTrkBmRNAsandproteinsfollowedsimilartrend.Inthebilateralcochlearablationgroups,theBDNF-TrkBexpressionlevelinitiallydecreasedat2weeksbutincreasedat4weeksfollowedbythereductionat6and8weeksaftercochlearremoval,ascomparedtotheage-matchedshamcontrolgroups.Inconclusion,theBDNF-TrkBsignalingisinvolvedintheplasticityofauditorycortexinanactivity-dependentmanner.

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简介：AbstractObjective:This study was performed to investigate the effects of honokiol on the activation of transient receptor potential channel V1 (TRPV1) and the secretion of thymic stromal lymphopoietin (TSLP) in a human benign epidermal keratinocyte line (HaCaT).Methods:HaCaT keratinocytes were cultivated and divided into six groups: capsaicin-induced model control group, capsazepine control group, solvent control group, and three honokiol treatment groups (7.81, 15.63, and 31.25 mg/L of honokiol). The effect of honokiol on calcium (Ca2+) influx was measured by a Ca2+ fluorescence imaging system. The fluorescence intensity (F) of cells was measured. The rate of change in F (ΔF/F0) was calculated, and the ΔF/F0-time curve was constructed. HaCaT keratinocytes were stimulated with polyinosinic:polycytidylic acid, recombinant human tumor necrosis factor α, and recombinant human interleukin 4. Different concentrations of honokiol (15.63, 7.81, and 3.91 mg/L) were added to the cells in the respective honokiol groups; 20 mg/L of dexamethasone or 0.5% dimethyl sulfoxide was added to the cells in the positive control group or solvent control group. The TSLP concentration in the HaCaT keratinocytes of each group was detected by enzyme-linked immunosorbent assay. Statistical analysis was performed by one-way analysis of variance and Dunnett t test.Results:The capsaicin-induced Ca2+ fluorescence intensity in HaCaT keratinocytes was significantly inhibited in the 31.25 mg/L honokiol group; ΔF/F0 at 45 second was 0.76 in the model control group and 0 in the 31.25 mg/L honokiol group. The TSLP level in the 15.63 and 7.81 mg/L honokiol groups was lower than that in the solvent control group (t= 7.382, P= 0.003, and t= 2.766, P= 0.023, respectively), while the TSLP level in the 3.91 mg/L honokiol group was not significantly different from that in the solvent control group (t= 1.872, P= 0.124).Conclusions:Honokiol inhibited the Ca2+ influx induced by capsaicin (TRPV1 agonist) in HaCaT keratinocytes. Honokiol has an inhibitory effect on TSLP secretion in HaCaT keratinocytes.

简介：Twomajorapoptosispathwayshavebeendefinedinmammaliancells,theFas/TNF-R1deathreceptorpathwayandthemitochondriapathway.TheBcl-2familyproteinsconsistofbothanti-apoptosisandpro-apoptosismembersthatregulateapoptosis,mainlybycontrollingthereleaseofcytochromecandothermitochondrialapoptoticevents.However,deathsignalsmediatedbyFas/TNF-R1receptorscanusuallyactivatecaspasesdirectly,bypassingtheneedformitochondriaandescapingtheregulationbyBcl-2familyproteins.Bidisanovelpro-apoptosisBcl-2familyproteinthatisactivatedbycaspase8inresponsetoFas/TNF-R1deathreceptorsignals.ActivatedBidistranslocatedtomitochondriaandinducescytochromecrelease,whichinturnactivatesdownstreamcaspases.Suchaconnectionbetweenthetwoapoptosispathwayscouldbeimportantforinductionofapoptosisincertaintypesofcellsandresponsibleforthepathogenesisofanumberofhumandiseases.

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简介：多功能的cytokineinterleukin-1(IL-1)的生物活动被它的受体调停。这研究的目的是决定一个协会是否在1和2受体基因(IL1R1和IL1R2)和表示在mononuclear房间的subpopulations或可溶的IL-1受体的浆液层次上膜界限IL1Rs铺平的IL-1类型在单个核苷酸多型性(SNP)之间存在。这被观察有在SNPrs2234650的遗传型TT的健康个人:C>；T有在他们的表面上表示IL1R1的未经触动的CD14+单核白血球的一个更低的百分比。SNPrs4141134:T>；在IL1R2的C也与表示IL1R2的未经触动的CD3+T房间的百分比被联系了。而且，带SNPrs4141134的CC等位基因的个人:T>；C和SNPrs2071008的TT等位基因:T>；在IL1R2的G在刺激的lipopolysaccharide(LPS)在CD14+单核白血球的表面上有IL1R2s的更低的密度PBMC文化。在摘要，这研究证明IL-1受体基因多型性能是在免疫能力的房间上影响膜界限IL-1受体(IL1R)的表示的因素之一。

简介：BACKGROUND:Ithasbeenreportedthatperoxisomeproliferator-activatedreceptorγ(PPARγ)ishighlyexpressedinlungcancer,coloncancer,andgastriccancer,aswellasothertumors.OBJECTIVE:TostudyexpressionofPPARγinpituitaryadenomasandanalyzetheroleofPPARγinhormonaltypingofpituitaryadenomas.DESIGN,TIMEANDSETTING:Semi-quantitativeimmunohistochemistryofpathologicalspecimens.TheexperimentwasconductedattheDepartmentofNeurosurgery,WuxiSecondHospitalAffiliatedtoNanjingMedicalUniversitybetweenJanuary2002andMay2005.MATERIALS:Surgicalresectionsamplesofpituitaryadenomasfrom38cases(18maleand20female)wereanalyzed.Eightcasesweredeterminedtobeinvasivepituitaryadenomasand30caseswerenon-invasivepituitaryadenomas.Hormonalclassificationofthetypesofpituitaryadenomasrevealedsomatotrophicadenomasinsixcases,corticotrophicadenomainfivecases,prolactinomasin13cases,multi-hormonesecretingadenomasinsixcases,andeightcasesofadenomawithoutalteredendocrinefunction.Fiveautopsyspecimenswerecollectedduringthesameperiodfrompatientsofmatchingagethatdiedfromunrelateddiseasesandwereincludedasnormalanteriorpituitarycontrols.METHODS:Cellcountsforpositiveimmunohistochemicalsignalswererecordedfromhistopathologicalsections.Thepercentageofpositivecellswasreportedasasemi-quantitativeanalysis.MAINOUTCOMEMEASURES:TherateofPPARγpositivecellsindifferenttypesofadenomawasbasedonhormonallevelsandinvasivenessofpituitarytumorcells.RESULTS:AlltumorbiopsiesweredeterminedtoexpressPPARγTherateofPPARγ-positivecellsrangedbetween8%-65%inthepituitaryadenomas.Accordingtohormonaltype,PPARγexpressiondidnotvarybetweenthegroups.Inaddition,therewasnosignificantdifferenceinPPARγexpressionbetweenthenon-invasiveandinvasivepituitaryadenomas.CONCLUSIONS:HumanpituitaryadenomasexpressPPARγ,andthisexpressionisunrelatedto

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简介：ToexploretherelationshipbetweensubstanceP(SP)releasedfromperipheralnerveendingsandtheexpressionofepidermalgrowthfactor(EGF)andepidermalgrowthfactorreceptor(EGFR)duringwoundhealing.Methods:FiftyWistarratswererandomlydividedinto2groups,injurygroupandcapsaicingroup.Intheinjurygroup,afull-thicknessskinwoundonthebackoftheratwastaken.Thewoundedgeandgranulationtissuesweretakenonthe1st,3rd,6th,9th,12thdaysafterinjury,respectively.Inthecapsaicingroup,capsaicinwasinjectedsubcutaneouslyonthebackoftheratstodestroythesensorynervetopreventthesecretionofSP,thenawoundandsamplewasmadeinthesameway.ImmunohistochemistryandinsituhybridizationwereemployedtodetecttheexpressionofSP,EGF/EGFR,andEGFmRNA/EGFRmRNAinthegranulationtissues.Results:Intheinjurygroup,immunohistochemicalstainofSPandEGF/EGFRwaslocatedonthehairfolliclesandsebaceousglandsatthe1stday.AndthestainofSPwasobviousatthe3rddayinthegranulationtissues,thendecreasedgradually.EGF/EGFRwasatlowlevelatthe3rdday,thenincreasedgraduallyandreachedthepeakatthe9thday,thendeclined.Inthecapsaicingroup,theimmunohistochemicalstainofSPandEGF/EGFRwasfaintandwithoutobviouschangeduringthewoundhealingprocess.ThetendencyoftheEGFmRNA/EGFRmRNAexpressionwassimilartothatofEGF/EGFR.Conclusions:Duringwoundhealing,SPmaypromotethehealingprocessbyaffectingtheexpressionofEGF/EGFRinthegranuationtissues.

简介：AbstractBackground:Conventional treatment has limited efficacy in relapsed/refractory B-cell lymphoma. Since chimeric antigen receptor T-cell (CAR-T) technology has shown high safety and results in high remission rates, we investigated its efficacy and safety in B-cell lymphoma treatment and analyzed potential affecting factors to provide evidence for therapeutic strategies and applications.Methods:We searched databases including PubMed, Embase, and Cochrane up to July 2019. Meta-analysis 1 was conducted to study the efficacy of CAR-T cell for treating B-cell lymphoma, measuring the response rate and complete remission rate as outcomes. Sub-group analysis was performed for age, pathological type, target antigen, co-stimulatory molecule, and conditioning chemotherapy. Meta-analysis 2 was undertaken on the safety of the treatment with the incidence rate of toxicity (cytokine-releasing syndrome [CRS], neurotoxicity) as an outcome.Results:Seventeen studies were included in the systematic review and meta-analysis. It was found that CAR-T cells had good therapeutic effects in the following cases: B-cell lymphoma (patients ≥65 years old); diffuse large B-cell lymphoma pathological type; patients with treatment target antigen other than CD19; patients treated with co-stimulatory molecules other than CD28, including 4-1BB+CD28 or 4-1BB; and patients treated with cyclophosphamide/fludarabine pre-treatment protocol conditioning chemotherapy. Although the CRS and neurotoxicity incidences were high, most were reversible with minimal risk of death.Conclusion:CAR-T cell treatment is safe for clinical application; however, toxicity effects should be monitored.

简介：维生素D受体(VDR)多型性作为潜在的贡献者被学习了到多重硬化(MS)。然而，出版了研究关于学习设计和检测的效果的意义不同。这研究的目的是确定与在用元分析的MS的VDR多型性接近的TaqI，BsmI，ApaI和FokI联系的风险的大小。为系统的评论和元分析指南跟随比较喜欢的报导项目，我们进行了文学的系统的搜索和元分析。亚群分析被执行从选择学习特征检测异质的潜在的来源。概括风险的稳定性用敏感分析被评估。元分析从13盒子控制研究包括了3300个案例和3194控制的一个总数。没有重要协会，在TaqI和BsmI多型性和MS风险之间发现。在ApaI多型性和MS风险之间的协会是重要的在同型结合并且codominant模型(P=；0.013并且P=；0.031，分别地)，建议AAApaI遗传型可能是一个重要MS风险因素。出版年和年龄显著地影响了在TaqI多型性和MS之间的协会(P=；0.014并且P=；0.010，分别地)，它显示主要T等位基因的保护的效果。AAApaI和FFFokI遗传型是为MS的重要风险因素。在TaqI多型性和MS风险之间的协会被学习特征显著地影响。

简介：FTY720,asphingosine1-phosphatereceptormodulator,inducesamarkeddecreaseinthenumberofperipheralbloodlymphocytesandexertsimmunomodulatingactivityinvariousexperimentalallograftandautoimmunediseasemodels.Inthisstudy,weevaluatedtheeffectofFTY720anditsactivemetabolite,(S)-enantiomerofFTY720-phosphate[(S)-FTY720-P]onexperimentalautoimmuneencephalomyelitis(EAE)inratsandmice.ProphylacticadministrationofFTY720at0.1to1mg/kgalmostcompletelypreventedthedevelopmentofEAE,andtherapeutictreatmentwithFTY720significantlyinhibitedtheprogressionofEAEandEAE-associatedhistologicalchangeinthespinalcordsofLEWratsinducedbyimmunizationwithmyelinbasicprotein.ConsistentwithratEAE,thedevelopmentofproteolipidprotein-inducedEAEinSJL/JmicewasalmostcompletelypreventedandinfiltrationofCD4+TcellsintospinalcordwasdecreasedbyprophylactictreatmentwithFTY720and(S)-FTY720-P.WhenFTY720or(S)-FTY720-PwasgivenafterestablishmentofEAEinSJL/Jmice,therelapseofEAEwasmarkedlyinhibitedascomparedwithinterferon-β,andtheareaofdemyelinationandtheinfiltrationofCD4+TcellsweredecreasedinspinalcordsofEAEmice.SimilartherapeuticeffectbyFTY720wasobtainedinmyelinoligodendrocyteglycoprotein-inducedEAEinC57BL/6mice.TheseresultsindicatethatFTY720exhibitsnotonlyaprophylacticbutalsoatherapeuticeffectonEAEinratsandmice,andthattheeffectofFTY720onEAEappearstobeduetoareductionoftheinfiltrationofmyelinantigen-specificCD4+Tcellsintotheinflammationsite.