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.

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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.

简介：尽管有CD4+CD25+规章的T房间(Tregs)在过去的十年期间，在他们的临床的翻译以后的进步仍然保持停滞。增长证据建议那自然地发生的CD8+CD122+T房间也是有能力的Tregs禁止T房间回答并且象alloimmunity一样压制autoimmunity。事实上，他们是像记忆的Tregs类似于一个中央记忆T房间(T厘米)显型。位于他们的抑制下面的机制仍然不好被理解，尽管他们可以包括IL-10生产。我们最近证明了那个规划death-1(PD-1)表达式区分在之间规章并且存储器CD8+CD122+T房间和那CD8+CD122+Tregs经历更快的homeostatic增长并且比常规CD4+CD25+Tregs。这些调查结果可以为在诊所加速有效Treg治疗打开调查的一根新线。在这评论，我们在CD8+CD122+Treg在诊所研究并且讨论他们的显型，在autoimmunity和alloimmunity的镇压角色，功能的要求，行动的机制和潜在的应用。

简介：类型IIEpstein-Barr病毒(EBV)联系了象鼻咽的癌和non-Hodgkin的淋巴瘤那样的恶意一致地快速的潜伏的膜2A(LMP2A)蛋白质，它被建议了是为免疫疗法的一个理想的目标。在我们表明了的以前的研究，那使用的LMP2A蛋白质装载了树枝状的房间，在身体处理房间的最强大的抗原能得到特定、柔韧的反肿瘤在vitro的细胞的有免疫力的反应。在这份报纸，我们进一步调查了反肿瘤免疫者反应的T房间侧面。我们发现LMP2A特定的CD4+和CD8+T房间能被LMP2A蛋白质刺激装载树枝状的房间(DC)。Th1类型免疫者反应在有免疫力的反应是主导的由LMP2A特定的CD4+T房间调停了。有效地并且明确地忍受房间的CD8+细胞毒素的T房间罐头细胞溶解LMP2A。CD8+细胞毒素的T房间能也分泌细胞内部的IFN-的高水平，它显示这些房间是EBV-LMP2A特定的细胞毒素的T房间。总的来说，我们的研究证明了装载DC能得到的那LMP2A蛋白质是反肿瘤细胞的有免疫力的回答高效地。这研究对表示恶意的EBV-LMP2A为基于DC的免疫疗法提供一个基本原理。

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简介：AbstractCell-cell communication is the basis of physiological processes and cell signals. The disease occurs when the cells do not adequately communicate and the messages are blocked. With ligand-receptor interaction databases and single-cell RNA sequencing (scRNA-seq) databases, we can detect intercellular signaling and reconstruct the cell-cell communications among different cell types. This review summarized the computational approaches for analyzing the cell-cell communication based on scRNA-seq data and discussed its applications in carcinogenesis and COVID-19. We believe that this review will accelerate the scRNA-seq data deciphering and facilitate the cell-cell communication studies for complex physiological processes, such as carcinogenesis and SARS-CoV-2 infection.

简介：许多病毒的epitope在匹配MHC的个人的特定的T房间受体(TCR)被表明了在链包含保存氨基酸主题决定补充的区域3(CDR3)。然而，保存主题是否能也在TCR链被发现，不肯定。在以前的研究，我们开发了一个修改方法扩大cytomegalovirus(CMV)的百分比pp65在由在vitro的连续的肽刺激的PBMC的肽特定的CD8+T房间，它为察觉提供特定的T房间的足够的数字。在这研究，我们进一步分析了TCRV和V基因家庭的限制用法并且调查了pp65的CDR3基因顺序肽特定的CD8+T房间。CDR3spectratypes的分析建议了TCR链AV8，AV12，AV21，AV31家庭和TCR的一个限制用法链BV3，BV14，BV21，BV23，在施主CD8+T房间的BV11家庭由pp65肽刺激了。这些T房间的序列包含了类似的顺序(TX)在TCR链和L(XT)的CDR3区域的G(X)A在TCR的G(X)A链。

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简介：ＥＦＦＥＣＴＳＯＦＡＰＡＴＩＴＥＣＥＲＡＭＩＣＳＯＮＣＥＬＬＧＲＯＷＴＨＳＡＮＤＤＮＡＳＹＮＴＨＥＳＥＳＩＮＨＵＭＡＮＯＳＴＥＯＢＬＡＳＴＬＩＫＥＣＥＬＬＥＦＦＥＣＴＳＯＦＡＰＡＴＩＴＥＣＥＲＡＭＩＣＳＯＮＣＥＬＬＧＲＯＷＴＨＳＡＮＤＤＮＡＳＹＮＴＨ...

简介：Objectives:Toinvestigatetheeffectsofadenovirus-mediatedinduciblenitricoxidesynthasegenetransfectiononbladdertransitionalcellcarcinomaT24cells,andtoprovidenovelinsightsandapproachestoclinicaltherapiesagainstbladdertransitionalcellcarcinoma.Methods:Firstly,constructrecombinantadenovirusvectorpAd-iNOSofiNOS,followedbytransfectionofpAd-iNOSintoHECK293packagingcells.Thirdly,harvestrecombinantadenovirusrAd-iNOSafteramplificationandpurificationprocedures.Finally,transfecttherecombinantadenovirusrAd-iNOSintohumanbladdercarcinomaT24cellsandexaminetheeffectofrAd-iNOStransfectiononapoptosisofT24andpossiblemechanism.Results:Asshownbythisstudy,therecombinantadenovirusrAd-iNOSwasconstructedsuccessfully.Thevirustiterwas5.8×108PFU/mLandrecombinantwasverifiedbyPCRanalysis.TransfectionofadenovirusrAd-iNOSintoT24cellscouldinducesecretionofhighNOconcentration,P53proteinexpressionupregulation,aswellaspromotionofT24cellapoptosis.Conclusions:ThetransfectionofhumanbladdercarcinomaT24cellsfromrecombinantadenovirusrAdiNOSwasconfirmedtoinduceintracellulariNOSover-expression,highproductionofNO,up-regulationofintracellularP53expressionandpromotionofcellapoptosis.

简介：AbstractBackground:Pharmacological factors used to induce insulin resistance (IR) in in vitro models may not mimic the full in vivo features of type 2 diabetes mellitus (T2DM). This study aimed to examine the ability of diabetic serum (DS) to induce IR and investigate whether adipose-derived mesenchymal stem cell conditioned medium (ADMSC-CM) reverses DS-induced IR.Methods:DS was obtained from newly diagnosed T2DM patients. IR was induced in differentiated 3T3-L1 cells by employing dexamethasone, tumor necrosis factor alpha (TNF-α), palmitate and DS. Glucose uptake (2-[N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] amino]-2-deoxyglucose(2-NBDG) uptake assay), intracellular levels of reactive oxygen species (ROS), and superoxide radicals (O2-) (fluorescence microscopy and fluorometry) were analyzed in control and experimental samples. mRNA expression of key genes involved in glucose transport and inflammation were analyzed by using reverse transcription polymerase chain reaction (RT-PCR). Pro-inflammatory cytokines and phospho-insulin receptor substrate (IRS) (Ser-307) protein expression were analyzed by fluorescence activated cell sorter analysis. Statistical significance was determined by using one-way ANOVA followed by Tukey's multiple comparison tests.Results:ADMSC-CM significantly increased the DS-mediated decrease in 2-NBDG uptake (11.01 ± 0.50 vs. 7.20 ± 0.30, P < 0.01) and reduced DS-driven ROS (fluorescence count, 6.35 ± 0.46 vs. 9.80 ± 0.10, P < 0.01) and O2- (fluorescence count, 3.00 ± 0.10 vs. 4.60 ± 0.09, P < 0.01) production. Further, the ADMSC-CM restored DS-induced down regulation GLUT4 (1.52- fold, P < 0.05) as well as the up-regulation of PPARγ (0.35-fold, P < 0.01), and IKKβ (0.37-fold, P < 0.01) mRNA, and phospho-IRS (Ser-307) protein expression compared to the baseline (median fluorescence intensity, 88,192 ± 2720 vs. 65,450 ± 3111, P < 0.01). DS induced IR, similar to the traditionally used pharmacological factors, namely dexamethasone, TNF-α, and palmitate, which can be attributed to the significantly higher pro-inflammatory cytokines levels (TNF-α (2.28 ± 0.03 pg/mL vs. 2.38 ± 0.03 pg/mL, P < 0.01), interleukin 6 (IL)-6 (1.94 ± 0.02 pg/mL vs. 2.17 ± 0.04 pg/mL, P < 0.01), IL-17 (2.16 ± 0.02 pg/mL vs. 2.22 ± 0.002 pg/mL, P < 0.05), and interferon gamma (IFN-γ) (2.07 ± 0.02 pg/mL vs. 2.15 ± 0.04 pg/mL, P < 0.05)) in DS.Conclusions:DS can be explored as a novel inducer of IR in in vitro studies with further standardization, substituting the conventionally used pharmacological factors. Our findings also affirm the validity of ADMSC-CM as a prospective insulin sensitizer for T2DM therapy.

简介：AbstractBackground:Circular RNA ciRS-7 has been reported to be involved in the progression of various cancers. However, ciRS-7 expression and its role in clear cell renal cell carcinoma (ccRCC) progression remains unclear. This study aimed to investigate the effect of ciRS-7 expression on ccRCC and the related signaling pathway.Methods:ciRS-7 expression was analyzed using quantitative reverse transcription polymerase chain reaction in 87 pairs of ccRCC and matched adjacent normal tissues. The role of ciRS-7 in ccRCC cell proliferation and invasion was determined using the cell counting kit-8 and invasion assays, respectively. Potential mechanisms underlying the role of ciRS-7 in promoting ccRCC progression were explored by Western blotting. The relationship between the expression of ciRS-7 and features of ccRCC was analyzed by the Chi-square test and progression-free survival was determined using a Kaplan-Meier plot.Results:ciRS-7 was overexpressed in ccRCC tissues compared with that in matched adjacent normal tissues. In addition, ciRS-7 up-regulation was closely associated with tumor diameter (P = 0.050), clinical stage (P = 0.009), and distant metastasis (P = 0.007). ciRS-7 knockdown in 786O and 769P cells markedly inhibited their proliferative and invasive abilities. In addition, ciRS-7 inhibition reduced phosphorylated epidermal growth factor receptor (p-EGFR) and phosphorylated serine/threonine kinase (p-Akt) levels.Conclusions:ciRS-7 up-regulation could promote ccRCC cell proliferation and invasion, which may be related with the EGFR/Akt signaling pathway. ciRS-7 might be a potential ccRCC therapeutic target.

简介：Thedendriticcellsystemcontainsconventionaldendriticcells(DCs)andplasmacytoidpre-dendriticcells(pDCs).BothDCsandpDCsarebonemarrowderivedcells.AlthoughthecommonfunctionsofDCsareantigen-processingandT-lymphocyteactivation,theydifferinsurfacemarkers,migratorypatterns,andcytokineoutput.ThesedifferencescandeterminethefateoftheTcellstheyactivate.SeveralsubsetsofmatureDCshavebeendescribedinbothmouseandhumanandthedevelopmentalprocessesofthesespecializedDCsubsetshavebeenstudiedextensively.TheoriginalconceptthatallDCswereofmyeloidoriginwasquestionedbyseveralrecentstudies,whichdemonstratedthatinadditiontotheDCsderivedfrommyeloidprecursors,someDCscouldalsobeefficientlygeneratedfromlymphoid-restrictedprecursors.Moreover,ithasbeenshownrecentlythatbothconventionalDCsandpDCscanbegeneratedbytheFlt3expressinghemopoieticprogenitorsregardlessoftheirmyeloid-orlymphoid-origin.ThesefindingssuggestanearlydevelopmentalflexibilityofprecursorsforDCsandpDCs.ThisreviewsummarizessomerecentobservationsonthedevelopmentofDCsysteminbothhumanandmouse.

简介：今日任务蓓蒂买新手机时必须做哪些决定？会话A（赛门站在邮局里。）蓓蒂：赛门，所以我的手机出了什么问题啊？赛门：我不确定耶，蓓蒂。我看过电池，电池没问题，但你也知道这个手机很旧了。

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简介：Redbloodcells(RBC)’flickeringpresentthedynamicpropertiesofthecytomembrane.Itscomplexitycouldbeusedforaginganalysisortheevaluationforthestoragequality.Theflickeringactivityisakindofreversibleperpendicularmotionofthespecifiedpixel.Therefore,thecomplexityanalysisdependsonthereliabledetectionoftemporalvariationforthegray-scalevaluesfromeachpixelofthecells.Inthispaper,weimprovedourpreviousworkonthescreeningofthehorizontaldriftedcellswithasurfacebasedoncellregistrationmethodandtheeffectofGSMexposuretothedynamicpropertiesoftheRBCsintermsofmulti-scalesampleentropywaspresentedinthepaper.