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Exosomes derived from microRNA-540-3p overexpressing mesenchymal stem cells promote immune tolerance via the CD74/nuclear factor-kappaB pathway in cardiac allograft
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作者 Ji-Gang He Xin-Xin Wu +3 位作者 Si Li Dan Yan Gao-Peng Xiao Fu-Gang Mao 《World Journal of Stem Cells》 SCIE 2024年第12期1022-1046,共25页
BACKGROUND Heart transplantation is a crucial intervention for severe heart failure,yet the challenge of organ rejection is significant.Bone marrow mesenchymal stem cells(BMSCs)and their exosomes have demonstrated pot... BACKGROUND Heart transplantation is a crucial intervention for severe heart failure,yet the challenge of organ rejection is significant.Bone marrow mesenchymal stem cells(BMSCs)and their exosomes have demonstrated potential in modulating T cells,dendtitic cells(DCs),and cytokines to achieve immunomodulatory effects.DCs,as key antigen-presenting cells,play a critical role in shaping immune responses by influencing T-cell activation and cytokine production.Through this modulation,BMSCs and their exosomes enhance graft tolerance and prolonging survival.AIM To explore the immunomodulatory effects of exosomes derived from BMSCs overexpressing microRNA-540-3p(miR-540-3p)on cardiac allograft tolerance,focusing on how these exosomes modulating DCs and T cells activity through the CD74/nuclear factor-kappaB(NF-κB)pathway.METHODS Rat models were used to assess the impact of miR-540-3p-enhanced exosomes on immune tolerance in cardiac allografts.MiR-540-3p expression was manipulated in BMSCs,and derived exosomes were collected and administered to the rat models post-heart transplantation.The study monitored expression levels of major histocompatibility complex II,CD80,CD86,and CD274 in DCs,and quantified CD4^(+)and CD8^(+)T cells,T regulatory cells,and cytokine profiles.RESULTS Exosomes from miR-540-3p-overexpressing BMSCs lead to reduced expression of immune activation markers CD74 and NF-κB p65 in DCs and T cells.Rats treated with these exosomes showed decreased inflammation and improved cardiac function,indicated by lower levels of pro-inflammatory cytokines(interleukin-1β,interferon-γ)and higher levels of anti-inflammatory cytokines(interleukin-10,transforming growth factorβ1).Additionally,miR-540-3p skewed the profiles of DCs and T cells towards immune tolerance,increasing the ratio of T regulatory cells and shifting cytokine secretion to favor graft acceptance.CONCLUSION Exosomes derived from BMSCs overexpressing miR-540-3p significantly enhance immune tolerance and prolong cardiac allograft survival by modulating the CD74/NF-κB pathway,which regulates activities of DCs and T cells.These findings highlight a promising therapeutic strategy to improve heart transplantation outcomes and potentially reduce the need for prolonged immunosuppression. 展开更多
关键词 Bone marrow mesenchymal stem cells EXOSOMES MicroRNA-540-3p Cardiac allograft Immune tolerance
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红景天苷促进MC3T3-E1细胞成骨分化能力的体外实验
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作者 刘朝辉 韩晓谦 +2 位作者 段昕 郭鹏达 张云涛 《中国组织工程研究》 CAS 北大核心 2025年第2期231-237,共7页
背景:骨缺损可直接影响牙齿种植的成功率及种植体的长期稳定性。研究显示红景天苷可促进成骨细胞增殖、分化,但对于其成骨分化相关通路具体研究不多。目的:体外细胞实验研究红景天苷对MC3T3-E1细胞增殖和分化的影响,并探究其对相关基因... 背景:骨缺损可直接影响牙齿种植的成功率及种植体的长期稳定性。研究显示红景天苷可促进成骨细胞增殖、分化,但对于其成骨分化相关通路具体研究不多。目的:体外细胞实验研究红景天苷对MC3T3-E1细胞增殖和分化的影响,并探究其对相关基因和蛋白表达的影响。方法:采用CCK-8实验和碱性磷酸酶实验筛选红景天苷(0.5,1,5,10,50μmol/L)促进MC3T3-E1细胞增殖和分化的最佳浓度。实验分为4组:对照组、红景天苷组、红景天苷+LY294002组、LY294002组,分别用成骨诱导液、含10μmol/L红景天苷、10μmol/L红景天苷+10μmol/L LY294002、10μmol/L LY294002的成骨诱导液进行培养,观察红景天苷及PI3K/Akt信号通路抑制剂LY294002对成骨相关基因和蛋白表达的影响。结果与结论:①CCK-8实验和碱性磷酸酶实验显示:红景天苷促进MC3T3-E1细胞增殖的作用在10μmol/L时最显著;②与对照组相比,红景天苷可以促进矿化、促进细胞黏附、减少细胞死亡,提高Runx-2、骨钙素、骨桥蛋白的mRNA表达(P<0.01),提高Runx-2和p-Akt蛋白表达(P<0.01);而添加PI3K/Akt信号通路抑制剂LY294002则可逆转以上结果;③结果表明,红景天苷能促进MC3T3-E1细胞矿化,并能促进成骨相关基因、蛋白的表达,这可能与PI3K/Akt信号通路的激活有关。 展开更多
关键词 红景天苷 MC3t3-E1细胞 细胞分化 成骨 矿化 LY294002 PI3K/AKt信号通路
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黄芪甲苷可缓解MC3T3-E1细胞氧化应激损伤并促进成骨
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作者 张加豪 李嘉程 +3 位作者 温明韬 郭艳波 骆帝 李刚 《中国组织工程研究》 CAS 北大核心 2025年第17期3529-3536,共8页
背景:氧化应激是导致骨质疏松症的主要原因之一,减少氧化应激水平与增加抗氧化防御是治疗骨质疏松症的重要研究方向。研究证实黄芪甲苷具有抗骨质疏松作用,但其作用机制尚不明确。目的:探讨黄芪甲苷对氧化应激条件下MC3T3-E1细胞成骨的... 背景:氧化应激是导致骨质疏松症的主要原因之一,减少氧化应激水平与增加抗氧化防御是治疗骨质疏松症的重要研究方向。研究证实黄芪甲苷具有抗骨质疏松作用,但其作用机制尚不明确。目的:探讨黄芪甲苷对氧化应激条件下MC3T3-E1细胞成骨的作用。方法:将MC3T3-E1细胞分4组培养:对照组加入完全培养基,模型组加入含过氧化氢的完全培养基干预24 h后更换为完全培养基,黄芪甲苷组加入含过氧化氢、黄芪甲苷的完全培养基干预24 h后更换为含黄芪甲苷的完全培养基,抑制剂组加入含过氧化氢、黄芪甲苷、细胞外信号调节激酶(extracellular signal-regulated kinases,ERK)抑制剂的完全培养基干预24 h后更换为含黄芪甲苷、ERK抑制剂的完全培养基。过氧化氢干预48 h后,通过丙二醛含量检测黄芪甲苷对MC3T3-E1细胞氧化应激的缓解作用;过氧化氢干预48 h后进行成骨诱导培养,通过碱性磷酸酶染色、茜素红染色验证MC3T3-E1细胞成骨及矿化能力,通过RT-qPCR检测成骨相关基因的表达,Western blot检测成骨相关蛋白及ERK/腺苷酸激活蛋白激酶(AMP-activated protein kinase,AMPK)信号通路蛋白的表达。结果与结论:(1)模型组细胞内碱性磷酸酶含量与矿化结节形成均少于对照组(P<0.05),黄芪甲苷组细胞内碱性磷酸酶含量与矿化结节形成均多于模型组(P<0.05)。(2)与对照组比较,模型组细胞内丙二醛含量增加(P<0.05),骨钙素、RUNX2、Ⅰ型胶原蛋白的mRNA与蛋白表达均降低(P<0.05),AMPK mRNA与p-AMPK蛋白表达升高(P<0.05);与模型组比较,黄芪甲苷组细胞内丙二醛含量减少(P<0.05),骨钙素、RUNX2、Ⅰ型胶原蛋白的mRNA与蛋白表达均升高(P<0.05),ERK1/2、AMPK mRNA表达升高(P<0.05),p-AMPK、p-ERK1/2蛋白表达均升高(P<0.05);ERK抑制剂可部分抑制黄芪甲苷的上述作用。(3)结果表明,黄芪甲苷可通过激活ERK/AMPK信号通路促进氧化应激条件下MC3T3-E1细胞的成骨分化。 展开更多
关键词 黄芪甲苷 骨质疏松症 MC3t3-E1细胞 氧化应激 ERK/AMPK信号通路 成骨 工程化骨材料
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Research on Al^(3+) Tolerance among Different Buckwheat Genotypes
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作者 韩承华 黄凯丰 《Agricultural Science & Technology》 CAS 2010年第9期73-75,200,共4页
[Objective] The research aimed to select the buckwheat accessions with higher Al3+ tolerance.[Method]25 buckwheat accessions were used as materials,the Al3+ tolerance were studied by means of solution culture method... [Objective] The research aimed to select the buckwheat accessions with higher Al3+ tolerance.[Method]25 buckwheat accessions were used as materials,the Al3+ tolerance were studied by means of solution culture method in this research.The length of root was used to evaluate the degree of Al3+ tolerance.[Result]The root growth of some buckwheat accessions were significantly promoted under the concentration of 500 μmol/L,while high concentration of Al3+(1 000 μmol/L)inhibited the buckwheat roots growth.There were great variations of Al3+ tolerance among the different buckwheat genotypes.[Conclusion]Among the 25 buckwheat genotypes,L2081 and T442 had much higher Al3+ tolerance than the others,which could be used for research on the buckwheat breeding and the mechanism of the buckwheat Al3+ tolerance. 展开更多
关键词 BUCKWHEAt Al3 tolerance SEEDS
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初级纤毛介导成骨前体细胞系MC3T3-E1传代衰老减低成骨分化能力
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作者 高丰 王纪亮 +3 位作者 王洪波 杨永胜 刘源 付苏 《中国组织工程研究》 CAS 北大核心 2025年第18期3741-3746,共6页
背景:在大段骨缺损修复中,由于种子细胞传代等多种因素可引起成骨类细胞衰老,造成组织工程骨植入体内后成骨分化活性降低。近年来,初级纤毛介导细胞衰老的机制已被广泛研究,但“传代衰老-成骨活性减低”的初级纤毛相关机制尚未完全明了... 背景:在大段骨缺损修复中,由于种子细胞传代等多种因素可引起成骨类细胞衰老,造成组织工程骨植入体内后成骨分化活性降低。近年来,初级纤毛介导细胞衰老的机制已被广泛研究,但“传代衰老-成骨活性减低”的初级纤毛相关机制尚未完全明了。目的:探讨初级纤毛调控成骨性MC3T3-E1细胞传代衰老的可能机制。方法:成骨前体细胞系MC3T3-E1细胞传代至第10代(早期传代)及第40代(晚期传代),同时使用siRNA沉默IFT88阻碍初级纤毛生成,即将细胞分为第10代组、第40代组、第10代+siRNA IFT88-组、第40代+siRNA IFT88-组。各组细胞成骨诱导3 d,采用RT-PCR和Western blot检测衰老标志物CDKN2A(P16)的表达、成骨活性标志物骨形态发生蛋白2和碱性磷酸酶的表达、Hedgehog通路IHH的表达;茜素红染色和初级纤毛免疫荧光染色分析初级纤毛形态;对初级纤毛阳性率与IHH、骨形态发生蛋白2的表达进行Spearman相关性分析。结果与结论:①成骨诱导3 d,第40代组MC3T3-E1细胞的CDKN2A(P16)表达显著高于第10代组,而在siRNA IFT88-干预后差异消失;②第10代组的初级纤毛细胞阳性率高于第40代组,siRNA IFT88-则显著性抑制第10代与第40代细胞的初级纤毛表达;③第10代组MC3T3-E1细胞的碱性磷酸酶及骨形态发生蛋白2的转录活性和蛋白表达均高于第40代组,通过siRNA抑制初级纤毛表达后,上述差异减低或者消失;④初级纤毛细胞阳性率与IHH蛋白表达及骨形态发生蛋白2蛋白表达呈正相关。结果表明:初级纤毛介导了成骨性MC3T3-E1细胞的传代衰老,可调控成骨分化能力。 展开更多
关键词 MC3t3-E1细胞 初级纤毛 衰老 成骨分化 传代 骨形态发生蛋白2 HEDGEHOG通路 组织工程细胞
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Cellular strategies to induce immune tolerance after liver transplantation:Clinical perspectives
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作者 Ai-Wei Zhou Jing Jin Yuan Liu 《World Journal of Gastroenterology》 SCIE CAS 2024年第13期1791-1800,共10页
Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techni... Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management.However,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more attention.Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain normal.The approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced tolerance.The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up.No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation.With the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT recipients.Cellular strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells.The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical practice.Here,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients. 展开更多
关键词 Cellular therapy Induced tolerance Liver transplantation Regulatory t cells Regulatory dendritic cells
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Tumor-infiltrating T-Lymphocyte immunity-related immune tolerance and anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy for advanced hepatocellular carcinoma
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作者 Lingzhen Hu Zongren Wang +3 位作者 Yang Liao Xiaomeng Jiang Huojun Lian Zhuoying Lin 《Oncology and Translational Medicine》 CAS 2024年第4期162-170,共9页
Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes ... Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC. 展开更多
关键词 Anti–PD-1/PD-L1 treatment Combination therapy Hepatocellular carcinoma Immune tolerance tumor-infiltrating t lymphocyte immunity
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Maintaining immunological tolerance with Foxp3 被引量:3
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作者 Lauren E Mays Youhai H Chen 《Cell Research》 SCIE CAS CSCD 2007年第11期904-918,共15页
Central tolerance in the thymus is the primary mechanism for deleting autoreactive T cells. Despite this, escape of self-reactive T lymphocytes into the periphery reveals the threat of autoimmunity. To compensate for ... Central tolerance in the thymus is the primary mechanism for deleting autoreactive T cells. Despite this, escape of self-reactive T lymphocytes into the periphery reveals the threat of autoimmunity. To compensate for its imperfection, the thymus also produces a naturally occurring subset of Foxp3+ CD4+CD25+ regulatory T cells with suppressive function, capable of controlling autoreactive cells. Foxp3 (forkhead box P3), the lineage-specific marker for this subset of cells, is crucial to their thymic development and peripheral function, and yet the transcriptional program driven by Foxp3 was until now largely undefined. Emerging evidence has provided insight into its role: from the ability of Foxp3 to cooperate with other transcription factors such as NFAT, to the genome-wide characterization of target genes directly bound and regulated by Foxp3. Here we discuss the discovery of naturally occurring regulatory T cells-their phenotype, development, maintenance, and function-largely as they are defined by the lineage-specific marker, Foxp3. 展开更多
关键词 FOXP3 tolerance t cell SUPPRESSION regulatory cells
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Involvement of Apoptosis in 3-nitropropionic Acid-induced Ischemic Tolerance to Transient Focal Cerebral Ischemia in Rats 被引量:1
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作者 朱红灿 孙圣刚 +1 位作者 李红戈 童萼塘 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2004年第1期79-82,共4页
The involvement of apoptosis in mitochondrial toxin 3 nitropropionic acid (3 NPA) induced ischemic tolerance to transient focal cerebral ischemia in rats and the mechanism was investigated. 3 NPA at a dose of 20 m... The involvement of apoptosis in mitochondrial toxin 3 nitropropionic acid (3 NPA) induced ischemic tolerance to transient focal cerebral ischemia in rats and the mechanism was investigated. 3 NPA at a dose of 20 mg/kg or vehicle control was intraperitoneally into the rats. Three days later, rats were exposed to 2 h of middle cerebral artery occlusion followed by 24 h of reperfusion. Infarct volumes were assessed by 2,3,5 triphenyltetrazolinm chloride (TTC) staining 24 h after reperfusion. Neural cell apoptosis in cerebral ischemic penumbra was detected by terminal deoxynucleotidyl transferase mediated dUTP biotin in situ nick end labeling (TUNEL) and flow cytometry methods (FCM). The results showed that as compared to the vehicle treated group, pretreatment with 3 NPA could reduce the infarct volume by 23.3 % and decrease the number of TUNEL positive neural cells and apoptotic percentage by 47 % ( P< 0.05) and 44.9 % ( P< 0 01), respectively. It was concluded that the development of 3 NPA induced ischemic tolerance in brain might be related to the decreases in neural cell apoptosis. 展开更多
关键词 3-nitropropionic acid cerebral ischemic tolerance ischemic penumbra APOPtOSIS
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Effect of the C.–1388 A>G polymorphism in chicken heat shock transcription factor 3 gene on heat tolerance 被引量:1
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作者 ZHANG Wen-wu KONG Li-na +3 位作者 ZHANG De-xiang JI Cong-liang ZHANG Xi-quan LUO Qing-bin 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2015年第9期1808-1815,共8页
Heat stress is one of the main factors that inlfuence poultry production. Heat shock proteins (HSPs) are known to affect heat tolerance. The formation of HSPs is regulated by heat shock transcription factor 3 (HSF3) i... Heat stress is one of the main factors that inlfuence poultry production. Heat shock proteins (HSPs) are known to affect heat tolerance. The formation of HSPs is regulated by heat shock transcription factor 3 (HSF3) in chicken. A DNA pool was established for identifying single nucleotide polymorphisms (SNPs) of the chicken HSF3, and 13 SNPs were detected. The bioinformatic analysis showed that 8 SNPs had the capacity to alter the transcription activity of HSF3. The dual luciferase report gene assay showed that there was a signiifcant difference (P<0.01) in the Firelfy luciferase/Renil a luciferase ratio (F/R) of C.–1 703 A>G (S1) and C.–1 388 A>G (S4) sites at the 5′-untranslated region (UTR) of chicken HSF3. The elec-trophoretic mobility shift assay showed that the S4 site was a transcription binding factor. The analysis of the association of the S1 and S4 sites with heat tolerance index revealed that the S4 site was signiifcantly correlated with the CD3+T cel , corticosterone, and T3 levels in Lingshan chickens and with the heterophil/lymphocyte value in White Recessive Rock. These results showed that the S4 site at the 5′ UTR of chicken HSF3 might have an impact on heat tolerance in summer and could be used as a potential marker for the selection of chicken with heat tolerance in the future. 展开更多
关键词 CHICKEN heat shock factor 3 dual luciferase report gene heat tolerance
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Eu ^(3+) Improving Drought Tolerance But Decreasing ODAP Level in Grass Pea (Lathyrus Sativus L.) Seedlings 被引量:1
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作者 熊友才 邢更妹 +3 位作者 郑峥 王亚馥 李志孝 李凤民 《Journal of Rare Earths》 SCIE EI CAS CSCD 2005年第S1期502-507,共6页
Drought tolerance and toxicity variation of grass pea (Lathyrus Sativus L.) were studied in the presence and absence of earth element Eu 3+ under the pot-culture condition. The addition of exogenous Eu 3+ increases th... Drought tolerance and toxicity variation of grass pea (Lathyrus Sativus L.) were studied in the presence and absence of earth element Eu 3+ under the pot-culture condition. The addition of exogenous Eu 3+ increases the survival days (SD) and lowered the stomatal sensitivity of grass pea seedlings under the decreasing soil moisture from -0.2 MPa to -1 MPa, suggesting that Eu 3+ can improve the ability of grass pea seedlings to tolerate drought. But in this case, Eu 3+ is found to significantly inhibit the increase in contents of plant toxicity β-N-oxalyl-L-a, β-diaminopropionic acid (ODAP) level in leaves. Therefore, the results demonstrate that Eu 3+ application is a potential agronomic approach to improve drought tolerance while lowering the toxicity level in grass pea productivity. 展开更多
关键词 grass pea β-N-oxalyl-L-a β-diaminopropionic acid (ODAP) europium ion (Eu 3+) survival days stomatal sensitivity drought tolerance rare earths
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Development of Hybrid Rice Variety FY7206 with Blast Resistance Gene Pid3 and Cold Tolerance Gene Ctb1 被引量:2
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作者 XIE Hong-guang JIANG Jia-huang +6 位作者 ZHENG Yan-mei ZHU Yong-sheng WU Fang-xi LUO Xi CAI Qiu-hua ZHANG Jian-fu XIE Hua-an 《Rice science》 SCIE CSCD 2016年第5期266-273,共8页
Hybrid rice Fanyou 7206(FY7206), derived from the cross between a sterile line Fanyuan A and a restorer line Fuhui 7206, was bred by the Rice Research Institute, Fujian Academy of Agricultural Sciences, China. FY720... Hybrid rice Fanyou 7206(FY7206), derived from the cross between a sterile line Fanyuan A and a restorer line Fuhui 7206, was bred by the Rice Research Institute, Fujian Academy of Agricultural Sciences, China. FY7206 was characterized by moderate blast resistance, cold tolerance, as well as wide adaptability, and high yields. The blast resistance results indicated that the frequencies of blast races in race B, race C and the total resistance frequency for FY7206 were 95.5%, 100.0% and 97.2%, respectively. The disease resistance results showed that the leaf blast grade for FY7206 was level 1 and panicle blast was level 5. The indoor spray results indicated that FY7206 was resistant to 11 isolates of Magnorpathe oryzae. The blast resistance of FY7206 might be derived from the high expression of blast resistance gene Pid3. The results for simulated cold resistance in an artificial climate chamber indicated that the cold tolerance for FY7206 was moderate at the booting and flowering stages. The cold tolerance results also indicated that FY7206 could be tolerant to temperatures as low as 10 °C at the seedling stage. The q RT-PCR results showed that the expression of cold tolerance gene Ctb1 in FY7206 was relatively high. These results suggested that FY7206 is a hybrid indica rice variety with good comprehensive characteristics, including blast resistance and cold tolerance. 展开更多
关键词 hybrid rice blast resistance gene Pid3 cold tolerance gene Ctb1 yield breeding
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栀子苷调节PI3K/AKT/mTOR信号通路在动脉粥样硬化形成过程中对Th17/Treg功能的影响 被引量:3
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作者 吴佳 吴进 +1 位作者 肖凯 凌超 《中西医结合心脑血管病杂志》 2024年第5期817-822,共6页
目的:观察栀子苷对载脂蛋白E缺乏(ApoE^(-/-))小鼠Th17/调节性T(Treg)细胞失衡的影响及其作用机制。方法:将50只纯合子ApoE^(-/-)雌性小鼠随机分为对照组、模型组和栀子苷低剂量组、栀子苷中剂量组、栀子苷高剂量组。对照组小鼠喂养普... 目的:观察栀子苷对载脂蛋白E缺乏(ApoE^(-/-))小鼠Th17/调节性T(Treg)细胞失衡的影响及其作用机制。方法:将50只纯合子ApoE^(-/-)雌性小鼠随机分为对照组、模型组和栀子苷低剂量组、栀子苷中剂量组、栀子苷高剂量组。对照组小鼠喂养普通饲料,模型组和栀子苷组小鼠喂养高脂饲料。从第8周开始,栀子苷各剂量组每日灌胃栀子苷(25、50、100 mg/kg),连续8周。试验结束时,采用油红O染色评估主动脉及其根部动脉粥样硬化(AS)病变面积比。采用定量逆转录聚合酶链式反应(RT-PCR)分析主动脉组织肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-17A和IL-10 mRNA表达;采用流式细胞仪分析脾脏中Th17和Treg细胞百分比;蛋白免疫印迹法(Western Blot)检测主动脉组织磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路相关蛋白表达。结果:油红O染色病变显示,栀子苷中剂量组、栀子苷高剂量组病变百分比低于模型组(P<0.05)。与对照组比较,模型组主动脉TNF-α、IL-6和IL-17A mRNA表达水平升高(P<0.05);栀子苷各剂量组主动脉TNF-α、IL-6和IL-17A mRNA表达水平降低(P<0.05)。与对照组比较,模型组主动脉抗炎细胞因子IL-10 mRNA表达水平降低(P<0.05);栀子苷各剂量组主动脉抗炎细胞因子IL-10 mRNA表达水平升高(P<0.05)。与对照组比较,模型组小鼠脾脏中Th17细胞百分比升高,Treg细胞百分比降低(P<0.05)。栀子苷处理恢复了AS小鼠Th17和Treg细胞的平衡。栀子苷抑制PI3K的表达及AKT和mTOR的磷酸化,MHY1485(mTOR活化剂)减弱了栀子苷对T细胞分化的影响。结论:栀子苷抗AS作用机制可能与抑制PI3K/AKT/mTOR信号引起的Treg细胞增多和Th17细胞减少有关。 展开更多
关键词 动脉粥样硬化 栀子苷 载脂蛋白E缺乏 th17/调节性t细胞 磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKt)/哺乳动物雷帕霉素靶蛋白(mtOR)信号通路 小鼠 实验研究
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NLRP3炎症小体抑制剂MCC950通过抑制Th1/Th17和促进Tregs改善脓毒症小鼠器官损伤 被引量:1
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作者 叶玉妹 陈隆望 +1 位作者 张万里 王雪涛 《温州医科大学学报》 CAS 2024年第3期190-198,共9页
目的:探讨核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体抑制剂MCC950对脓毒症小鼠T细胞分化及器官损伤的影响。方法:将18只C57BL/6雄性小鼠随机分为假手术组(sham组)、脓毒症模型组(CLP组)和MCC950治疗组(MCC950组),每组6只。其中... 目的:探讨核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体抑制剂MCC950对脓毒症小鼠T细胞分化及器官损伤的影响。方法:将18只C57BL/6雄性小鼠随机分为假手术组(sham组)、脓毒症模型组(CLP组)和MCC950治疗组(MCC950组),每组6只。其中CLP组和MCC950组通过盲肠结扎穿孔(CLP)的方法制备脓毒症模型。MCC950组腹腔注射溶于0.5 mL 0.9%氯化钠溶液的MCC950(50 mg/kg),sham组和CLP组腹腔注射等体积的0.9%氯化钠溶液。CLP术后24 h收集小鼠血清及器官标本。HE染色法观察脓毒症小鼠肺脏、肾脏组织病理损伤程度,并计算生存率;Western blot法检测脾脏NLRP3蛋白含量;ELISA法检测小鼠血清和肺组织的细胞因子水平(IL-1β、IL-18、IL-1α、IL-6、TNF-α);分离脾脏获得脾脏淋巴细胞,采用流式细胞术检测辅助性T细胞(Th)1、Th17、调节性T细胞(Tregs)比例。结果:与sham组相比,CLP组小鼠肺组织炎性细胞浸润、水肿和肺泡壁增厚,肾小管刷状缘和上皮细胞减少,肾小球萎缩,肾小管成弥漫性扩张,大量炎性细胞浸润,脾脏NLRP3的蛋白表达上调(P<0.05),血清IL-1β、IL-18、IL-1α、IL-6、TNF-α水平均升高(P<0.05),肺组织中IL-1α、IL-6、TNF-α水平均升高(P<0.05),脾脏CD4^(+)IFN-γ^(+)Th1、CD4^(+)IL-17^(+)Th17、CD4^(+)CD25^(+)Foxp3^(+)Tregs比例均升高(P<0.05),小鼠7 d生存率为30%(P<0.05)。与CLP组相比,MCC950组小鼠肺组织炎性细胞浸润减轻,水肿减退,肾小管扩张不明显,炎性细胞浸润亦有所减轻,脾脏NLRP3的蛋白表达下调(P<0.05),血清IL-1β、IL-18、IL-1α、IL-6、TNF-α水平均降低(P<0.05),肺组织中IL-1α、IL-6、TNF-α水平均降低(P<0.05),脾脏CD4^(+)IFN-γ^(+)Th1、CD4^(+)IL-17^(+)Th17比例减少,CD4^(+)CD25^(+)Foxp3^(+)Tregs比例明显增加(P<0.05),小鼠7 d生存率显著提升(P<0.05)。结论:MCC950阻断NLRP3可改善脓毒症小鼠的器官损伤,其作用可能依赖于抑制Th1/Th17反应和促进Tregs反应。 展开更多
关键词 MCC950 NLRP3 脓毒症 t细胞分化 器官损伤
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NFAT3在充血性心力衰竭气虚血瘀证患者舌苔液中的表达及意义 被引量:1
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作者 张蕾 李小茜 何建成 《辽宁中医杂志》 CAS 北大核心 2024年第6期10-13,共4页
目的研究活化T细胞核因子3(nuclear factor of activated T-cells 3,NFAT3)在充血性心力衰竭(congestive heart failure,CHF)气虚血瘀证患者舌苔液中的表达及与临床指标相关性,初步拟定该证候的诊断界值。方法收集CHF气虚血瘀证患者及... 目的研究活化T细胞核因子3(nuclear factor of activated T-cells 3,NFAT3)在充血性心力衰竭(congestive heart failure,CHF)气虚血瘀证患者舌苔液中的表达及与临床指标相关性,初步拟定该证候的诊断界值。方法收集CHF气虚血瘀证患者及健康对照者各30例,酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测舌苔液中NFAT3的含量。结果NFAT3在CHF气虚血瘀证患者舌苔液的含量为(481.40±103.00)pg/mL,明显高于健康对照者舌苔液的含量[(237.90±156.50)pg/mL](P<0.01);且随着美国纽约心脏协会(New York Heart Association,NYHA)心功能分级的增加,CHF气虚血瘀证患者舌苔液中NFAT3含量不断升高(P<0.01);CHF气虚血瘀证患者舌苔液NFAT3与NYHA心功能分级呈正相关性(r=0.927,P<0.01),与B型脑钠肽(brain natriuretic peptide,BNP)(r=0.806,P<0.01)呈正相关性,与左室射血分数(left ventricular ejection fraction,LVEF)呈负相关性(r=-0.739,P<0.01)。绘制受试者操作特性曲线(receive operating characteristic,ROC)初步拟定舌苔液清中NFAT3诊断CHF气滞血瘀证的界值为363.37 pg/mL,曲线下面积为0.91。结论NFAT3能够反映CHF病情轻重程度,可为CHF气虚血瘀证提供客观化、量化的参考和依据。 展开更多
关键词 充血性心力衰竭 气虚血瘀证 舌苔液 活化t细胞核因子3 诊断界值
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(1-3)-β-D葡聚糖联合降钙素原、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究
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作者 黄强 王宇 +5 位作者 江渊 梁道斌 黄锐洁 秦小超 潘燕妮 和鹰 《中国真菌学杂志》 CSCD 2024年第1期21-24,29,共5页
目的探讨(1-3)-β-D葡聚糖联合降钙素原(procalcitonin,PCT)、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究。方法回顾性选取我院2020年1月—2022年6月住院的120例艾滋病患者为研究对象。依据实验室结果,将... 目的探讨(1-3)-β-D葡聚糖联合降钙素原(procalcitonin,PCT)、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究。方法回顾性选取我院2020年1月—2022年6月住院的120例艾滋病患者为研究对象。依据实验室结果,将其分为马尔尼菲篮状菌感染确诊组(血或组织液培育养出马尔尼菲篮状菌),简称A组(62例),及马尔尼菲篮状菌感染临床诊断组[根据临床症状、体征、血常规及(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞多指标诊断],简称B组(58例)。检测患者(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞的表达水平,采用受试者工作特征(receiver-operating characteristic,ROC)曲线下面积(area under the curve,AUC)评估上述指标联合检测对艾滋病患者感染马尔尼菲篮状菌的诊断效能。结果A组的(1-3)-β-D葡聚糖和PCT水平均高于B组,CD4^(+)T淋巴细胞个数低于B组(P<0.05);(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞联合检测的AUC为0.933,(1-3)-β-D葡聚糖单独检测的AUC是0.812,PCT单独检测的AUC为0.883,CD4^(+)T淋巴细胞单独检测的AUC是0.810,(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的AUC皆优于三项单独检测,表明(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的诊断价值皆优于单一指标诊断,且联合检测的特异度、约登指数分别为92.43%和0.580,均高于三项单独检测。结论(1-3)-β-D葡聚糖联合PCT和CD4^(+)T淋巴细胞多指标对艾滋病马尔尼菲篮状菌感染具有非常高的临床诊断价值,能够帮助医生分析出高危风险患者,及时制定治疗方案,同时也承担预后效果的判断依据,对治疗艾滋病马尔尼菲篮状菌感染具有非常重要的研究价值。 展开更多
关键词 (1-3)-β-D葡聚糖 PCt CD4^(+)t淋巴细胞 艾滋病 马尔尼菲篮状菌感染
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急性病毒性肝炎患者血清HDAC3和HDAC11表达与T细胞淋巴亚群的关系研究
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作者 武云慧 董敬超 +3 位作者 张雪棉 曹立华 苗亮 张继东 《中国急救复苏与灾害医学杂志》 2024年第11期1500-1503,1535,共5页
目的 探究急性病毒性肝炎(AVH)患者血清组蛋白脱乙酰酶3(HDAC3)和组蛋白脱乙酰酶11(HDAC11)表达水平与T细胞淋巴亚群的关系。方法 选取2022年1月—2023年6月在秦皇岛市第三医院就诊的120例AVH患者作为研究对象(AVH组),并选择同期的120... 目的 探究急性病毒性肝炎(AVH)患者血清组蛋白脱乙酰酶3(HDAC3)和组蛋白脱乙酰酶11(HDAC11)表达水平与T细胞淋巴亚群的关系。方法 选取2022年1月—2023年6月在秦皇岛市第三医院就诊的120例AVH患者作为研究对象(AVH组),并选择同期的120名体检健康者作为对照组。收集并比较两组的一般临床资料。检测两组血清中HDAC3、HDAC11、CD3^(+)、CD4^(+)和CD4^(+)/CD8^(+)水平。利用Pearson等级相关性分析AVH患者血清HDAC3、HDAC11水平与T细胞淋巴亚群的相关性。利用受试者工作特征(ROC)曲线分析血清HDAC3、HDAC11对诊断AVH的临床价值。结果 AVH组和对照组的年龄、性别和BMI无显著性差异(P>0.05)。与对照组相比,AVH组的丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素、三酰甘油、胆固醇、低密度胆固醇显著升高(P<0.05),而AVH组的高密度胆固醇显著降低(P<0.05)。AVH组患者的血清HDAC3和HDAC11表达水平均显著高于对照组(P<0.05),CD3^(+)、CD4^(+)和CD4^(+)/CD8^(+)均显著降低于对照组(P<0.05)。Pearson相关分析显示,AVH患者血清HDAC3水平与CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)均呈负相关(r=-0.458、-0.533、-0.462,均P<0.001),HDAC3表达水平与CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)均呈负相关(r=-0.473、-0.551、-0.422,均P<0.001)。ROC曲线显示,HDAC3、HDAC11及二者联合预测诊断AVH的曲线下面积(AUC)分别为0.921、0.941、0.988,血清HDAC3、HDAC11联合诊断AVH的临床应用价值高于单项指标诊断(Z_(二者联合-HDAC3)=3.672、P=0.000;Z_(二者联合-HDAC11)=3.078、P=0.002)。结论 AVH患者血清HDAC3和HDAC11表达水平升高,且与T淋巴细胞亚群存在相关性,HDAC3与HDAC11联合预测AVH的临床价值较高。 展开更多
关键词 急性病毒性肝炎 组蛋白脱乙酰酶3 组蛋白脱乙酰酶11 t淋巴细胞亚群 相关性
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附子理中汤联合骨髓间充质干细胞调控变应性鼻炎大鼠鼻黏膜T-bet和GATA3 mRNA表达的研究
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作者 滕磊 袁波 +5 位作者 李杨 施陈燕 鞠晗 董雪林 蔡蔚然 张治军 《现代中西医结合杂志》 CAS 2024年第19期2629-2633,2649,共6页
目的研究附子理中汤联合骨髓间充质干细胞(MSCs)对变应性鼻炎大鼠鼻黏膜T盒转录因子(T-bet)、锌指蛋白3(GATA3)mRNA表达的影响。方法将40只雄性SD大鼠随机分为5组,每组8只。对照组大鼠不造模、不干预;模型组、MSCs组、附子理中汤组、附... 目的研究附子理中汤联合骨髓间充质干细胞(MSCs)对变应性鼻炎大鼠鼻黏膜T盒转录因子(T-bet)、锌指蛋白3(GATA3)mRNA表达的影响。方法将40只雄性SD大鼠随机分为5组,每组8只。对照组大鼠不造模、不干预;模型组、MSCs组、附子理中汤组、附子理中汤+MSCs组大鼠均进行变应性鼻炎造模,其中模型组造模后不治疗,MSCs组造模后给予骨髓MSCs尾静脉注射1次,附子理中汤组造模后给予附子理中汤连续灌胃14 d,附子理中汤+MSCs组造模后给予骨髓MSCs尾静脉注射1次和附子理中汤连续灌胃14 d。比较各组大鼠干预前后的行为学积分;干预结束后ELISA法检测鼻腔灌洗液中白细胞介素-4(IL-4)、白细胞介素-13(IL-13)、干扰素-γ(IFN-γ)水平,qRT-PCR法检测鼻黏膜组织中T-bet和GATA3 mRNA表达情况。结果MSCs组、附子理中汤组和附子理中汤+MSCs组大鼠干预后行为学积分均明显低于干预前及模型组(P均<0.05),且附子理中汤+MSCs组大鼠干预后行为学积分均明显低于MSCs组和附子理中汤组(P均<0.05)。与对照组比较,模型组大鼠鼻腔灌洗液中IL-4、IL-13水平和鼻黏膜组织中GATA3 mRNA相对表达量均明显升高(P均<0.05),鼻腔灌洗液中IFN-γ水平和鼻黏膜组织中T-bet mRNA相对表达量均明显降低(P均<0.05)。与模型组比较,MSCs组、附子理中汤组和附子理中汤+MSCs组大鼠鼻腔灌洗液中IL-4、IL-13水平和鼻黏膜组织中GATA3 mRNA相对表达量均明显降低(P均<0.05),附子理中汤组和附子理中汤+MSCs组大鼠鼻腔灌洗液中IFN-γ水平和鼻黏膜组织中T-bet mRNA相对表达量均明显升高(P均<0.05),MSCs组大鼠鼻腔灌洗液中IFN-γ水平和鼻黏膜组织中T-bet mRNA相对表达量均无明显变化(P均>0.05);且附子理中汤+MSCs组大鼠鼻腔灌洗液中IL-4、IL-13水平和鼻黏膜组织中GATA3 mRNA相对表达量均明显低于MSCs组(P均<0.05),鼻腔灌洗液中IFN-γ水平和鼻黏膜组织中T-bet mRNA相对表达量均明显高于MSCs组(P均<0.05)。结论附子理中汤联合骨髓MSCs能上调T-bet mRNA和下调GATA3 mRNA表达,进而调节Th1/Th2细胞的平衡,抑制炎症反应,改善变应性鼻炎症状。 展开更多
关键词 变应性鼻炎 附子理中汤 骨髓间充质干细胞 转录因子 t盒转录因子 锌指蛋白3
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梅毒血清固定患者中NOD样受体蛋白3和Toll样受体4表达与Th1/Th2相关细胞因子的相关性研究
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作者 张燕 刘健 +1 位作者 黄富琴 王烜 《中国性科学》 2024年第8期136-140,共5页
目的探究梅毒血清固定患者中NOD样受体蛋白3(NLRP3)、Toll样受体4(TLR4)表达与辅助性T细胞1/辅助性T细胞2(Th1/Th2)相关细胞因子的相关性。方法选取2021年2月至2022年4月川北医学院附属三台医院收治的197例梅毒患者作为研究对象。将进... 目的探究梅毒血清固定患者中NOD样受体蛋白3(NLRP3)、Toll样受体4(TLR4)表达与辅助性T细胞1/辅助性T细胞2(Th1/Th2)相关细胞因子的相关性。方法选取2021年2月至2022年4月川北医学院附属三台医院收治的197例梅毒患者作为研究对象。将进行驱梅治疗后血清转阴者纳入转阴组(n=88),未进行驱梅治疗者纳入梅毒组(n=45),接受驱梅治疗后血清固定者纳入固定组(n=64)。另选取同期进行体检的健康人作为对照组(n=53)。采用实时荧光定量聚合酶链反应检测外周血单个核细胞(PBMCs)中NLRP3、TLR4 mRNA相对表达水平;采用酶联免疫吸附试验法检测Th1/Th2相关细胞因子的表达水平;采用Pearson法分析TLR4、NLRP3 mRNA与Th1/Th2相关细胞因子的相关性。结果各组PBMCs中TLR4、NLRP3 mRNA表达水平比较,梅毒组>转阴组>对照组>固定组,差异具有统计学意义(P<0.05);各组白介素(IL)-2、γ干扰素(IFN-γ)水平比较,对照组>转阴组>梅毒组>固定组,差异具有统计学意义(P<0.05);各组IL-1β、IL-4、IL-10及IL-18水平比较,对照组<转阴组<梅毒组<固定组,差异具有统计学意义(P<0.05);梅毒血清固定患者TLR4、NLRP3 mRNA表达与IFN-γ、IL-2呈正相关,与IL-1β、IL-4、IL-10、IL-18呈负相关(P<0.05)。结论梅毒血清固定患者NLRP3、TLR4 mRNA表达水平显著降低,且与Th1/Th2相关细胞因子密切相关。 展开更多
关键词 NOD样受体蛋白3 tOLL样受体4 梅毒血清固定 相关性 辅助性t细胞1/辅助性t细胞2相关细胞因子
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Effect of LaCl_3 on the chilling tolerance of rice seedlings
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作者 LI Meiru LIU Hongxian WANG Yirou South China Inst of Botany,Academia Sinica,Guangzhou 510650,China 《Chinese Rice Research Newsletter》 1997年第2期9-10,共2页
The rice variety Tesanai 2 is susceptible tochilling.Exposure of the seedlings grown at 28±1℃ and under a photo flux density(PFD)of30 μmol/m~2s to 1℃ and under a PFD of 150μmol/m~2s for 2 d caused a physiolog... The rice variety Tesanai 2 is susceptible tochilling.Exposure of the seedlings grown at 28±1℃ and under a photo flux density(PFD)of30 μmol/m~2s to 1℃ and under a PFD of 150μmol/m~2s for 2 d caused a physiological disor-der called chilling injury which reduced the sur-vival rate to 50%.The experimental results in- 展开更多
关键词 LA Effect of LaCl3 on the chilling tolerance of rice seedlings
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