受体,趋化因子

摘要： 目的 分析CC趋化因子受体7(CCR7)蛋白在肝细胞癌中的表达及临床意义.方法 选取2016年1月至2017年6月南阳市第一人民医院收治的52例肝细胞癌患者作为研究对象,对肝细胞癌组织及配对癌旁组织的CCR7表达水平进行测定,以及对CCR7表达与预后的关系及临床病理特征进行分析.结果 ①52例患者肝细胞癌组织中,CCR7阳性率高于配对癌旁组织(65.38％ vs.26.92％) (P＜0.05).②CCR7表达与性别、年龄、肝功能分级、肝硬化及乙肝病史无关(P＞0.05),而与甲胎蛋白(AFP)水平、包膜完整有关(P＜0.05).③CCR7高表达组中1年生存率及无复发率低于低表达组,差异无统计学意义(P＞0.05).CCR7高表达组3年生存率及无复发率低于低表达组,差异有统计学意义(P＜0.05).结论 CCR7的表达在肝细胞癌组织中明显升高,与AFP水平、包膜完整密切相关,其对患者3年生存率及复发率具有重要的评估价值.

摘要： 作为G蛋白偶联受体超家族的重要成员,CXC趋化因子受体1(CXCR1)是CXC趋化因子白细胞介素-8最重要且颇具亲和力的受体之一.CXCR1常表达于中性粒细胞、单核细胞、T细胞等细胞表面,并且可与CXC趋化因子配体(CXCL)6、CXCL7、CXCL8相结合.研究发现CXCR1在促进恶性肿瘤转移、化疗耐药以及维持肿瘤干细胞特性中发挥至关重要的作用,下调CXCR1表达能显著抑制恶性肿瘤的生物学特性.目前学术界将CXCR1视为恶性肿瘤的原癌基因,CXCR1有望成为恶性肿瘤诊断和治疗的潜在靶点.

摘要： 目的 探讨基质细胞衍生因子-1(SDF-1)、受体趋化因子(CXCR4)、微血管密度(MVD)联合检测在多发性骨髓瘤患者预后评估中的应用.方法 选取2015年4月至2018年6月在晋城大医院进行多发性骨髓瘤治疗的76例患者作为研究组,另选取同期30例骨髓象正常者作为对照组.比较两组SDF-1、CXCR4、MVD表达水平及相关关系,并分析年龄、性别、国际分期系统(ISS)分期、免疫球蛋白分型及SDF-1、CXCR4、MVD与患者预后之间的关联.结果 研究组SDF-1及CXCR4阳性程度均高于对照组(P均<0.05),且研究组MVD水平也高于对照组(P<0.05);研究组SDF-1及CXCR4表达与MVD水平呈正相关关系(P<0.05).分析患者预后影响因素表明,患者年龄、ISS分期、免疫球蛋白分型及SDF-1及CXCR4表达水平、MVD计数能够作为判断该疾病预后的因素.结论 SDF-1、CXCR4、MVD对多发性骨髓瘤病情的发展可能起一定的促进作用,且均为影响患者预后的因素,故通过检测患者体内SDF-1、CXCR4、MVD水平,可对其预后进行有效评估.%Objective To investigate the application of combined detection of stromal cell derived factor-1 ( SDF-1 ) , chemokine receptor 4 ( CXCR4 ) and microvessel density ( MVD ) in evaluating the prognosis of patients with multiple myeloma. Methods Seventy-six patients with multiple myeloma in Jincheng General Hospital from April 2015 to June 2018 were selected as study group, and 30 patients with normal bone marrow in the same period were selected as control group. The expression levels of SDF-1, CXCR4 and MVD and their correlations were compared between the two groups. The correlation of age, sex, international staging system ( ISS ) stage, immunoglobulin typing, SDF-1, CXCR4, MVD with prognosis was analyzed. Results The positive levels of SDF-1 and CXCR4 in study group were significantly higher than those in control group ( P<0. 05 ) , and the MVD level in study group was also significantly higher than that in control group ( P<0. 05 ) . The expression of SDF-1 and CXCR4 was positively correlated with MVD level in study group ( P<0. 05 ) . Analysis of prognostic factors showed that age, ISS stage, immunoglobulin typing, expression of SDF-1 and CXCR4, MVD count could be used as prognostic factors for multiple myeloma. Conclusions SDF-1, CXCR4 and MVD may play positive roles in promoting the development of multiple myeloma, and they are all factors affecting the prognosis. Therefore, the prognosis of patients can be effectively evaluated by detecting the levels of SDF-1, CXCR4 and MVD.

摘要： 趋化因子家族通过作用于跨G蛋白偶联受体来介导趋化因子的活性.趋化因子及其受体形成同源或异源二聚体的能力以及趋化因子与趋化因子受体之间的相互作用,使得趋化因子蛋白家族在很多方面具有目前尚未完全了解的可塑性及复杂性.趋化因子既是炎性反应中的必需调节剂又可以介导宿主对肿瘤的反应.大量数据表明,趋化因子及其受体影响大多数肿瘤的形成.因此,笔者将从趋化因子及其受体的信号转导开始,对其如何影响肿瘤细胞的增殖、凋亡、自噬及免疫浸润作一综述.%The chemokine family mediates the activity of chemokines by acting on G protein -coupled receptors.Because chemokines and their receptors have the ability to form homologous or heterodimers and the interaction between chemokines and chemokine receptors ,the chemokine family has many aspects that are not yet fully understood such as plasticity and complexity .Chemokines not only are essential regulators in the inflammatory response but also mediate the host 's response to tumor.Many studies have found that chemokines and their receptors affect the formation of most tumors .Therefore,this article will begin with the signal transduction of chemokines and their receptors,and summarize how they affect the proliferation ,apoptosis,autophagy and immune infiltration of tumor cells .

摘要： 目的 明确CXCR3在肝癌组织中的表达及其与患者总体生存情况的关系,并探讨靶向沉默CXCR3基因对肝癌细胞增殖的影响及其作用机制. 方法 采用免疫组织化学方法检测60例肝癌组织及相应癌旁组织中CXCR3表达情况,分析CXCR3在肝癌组织中的表达水平与肝癌患者临床病理学之间的相关性,并结合随访资料进行单因素Kaplan-Meier生存分析;采用慢病毒LV-CXCR3-shRNA病毒感染Huh7肝癌细胞,通过细胞计数试剂盒-8增殖实验及裸鼠荷瘤实验明确CXCR3缺失对肝癌细胞增殖的影响.计量资料的方差齐性检验用F检验,两两比较,方差齐者用t检验,方差不齐者用校正t检验,各组间率的比较用x2检验,多组等级资料的比较用Wilcoxon秩和检验. 结果 CXCR3在肝癌组织中高表达,且CXCR3高表达患者的总体生存率显著低于低表达患者.Huh7肝癌细胞内CXCR3基因被有效沉默后,Huh7细胞体外增殖能力明显受到抑制,裸鼠荷瘤生长速度减慢;且Huh7细胞内JAK-STAT通路活性降低,c-MYC与Bcl-xl蛋白水平下降;此外,CXCR3缺失可有效抑制白细胞介素6介导的JAK-STAT通路激活. 结论 CXCR3高表达提示患者生存率差;靶向沉默CXCR3基因可抑制肝癌细胞增殖,可能与JAK-STAT通路活性抑制有关.CXCR3有可能成为肝癌治疗的潜在靶点.%Objective To explicit,the expression of chemokine receptor 3 in HCC tissues and its relationship with overall survival of patients,and to explore the effect of targeted silencing CXCR3 gene on proliferation of hepatocellular carcinoma cells and its mechanism of action.Methods The expression of CXCR3 in 60 cases of hepatocellular carcinoma and its adjacent tissues were detected by immunohistochemistry.The clinicopathological correlations between the expression levels of CXCR3 in hepatoma tissues of liver cancer patients were analyzed and univariate Kaplan-Meier survival analysis was performed in combination with follow-up data.Huh7 hepatoma cells were infected with lentivirus LV-CXCR3-shRNA.The effects of CXCR3 deletion on proliferation of hepatoma cells were determined by CCK-8 assay and tumor-bearing nude mice experiment.Results CXCR3 was highly expressed in HCC tissues,and the overall survival rate (OS) of patients with high CXCR3 expression was significantly lower than that of patients with low expression.After the CXCR3 gene was successfully silenced in Huh7 hepatocellular carcinoma cells,the proliferation ability of Huh7 cells was significantly inhibited in vitro,and the tumor growth rate of nude mice was slowed down,and the activity of JAK-STAT pathway in Huh7 cells was decreased,and the levels of c-MYC and Bcl-xl protein were decreased.In addition,deletion of CXCR3 can effectively inhibit IL-6-mediated JAK-STAT pathway activation.Conclusion CXCR3 high expression indicated that the survival rate was poor,and the target silencing of CXCR3 gene could inhibit the proliferation of hepatocellular carcinoma cells and maybe related to inhibition of JAK-STAT pathway activity.CXCR3 may be a potential target for the treatment of hepatocellular carcinoma.

摘要： 目的 探讨中国汉族人群中趋化因子受体5(CXCR5)基因单核苷酸多态性(single nucleotide poly-morphism,SNP)与视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorders,NMOSD)发病的相关性.方法 纳入312例NM OSD患者以及487名年龄、性别相匹配的健康对照人群(HCs).从基因数据库中选出9个CXCR5基因多态性位点(rs11574667、rs523604、rs118182497、rs1623316、rs78146216、rs497916、rs598207、rs676925、rs581063),另一个位点rs10892301来源于系统性红斑狼疮(SLE)的研究.通过对2组等位基因、基因型频率及单倍型分析来探讨CXCR5基因SNP与NMOSD易感性的相关性.结果 NMOSD组与 HCs性别构成及年龄比较差异无统计学意义(均 P> 0.05).等位基因关联分析提示 rs11574667的次等位基因 C 与NMOSD易感性相关(OR=1.33,95% CI:1.01~1.75,P=0.03),经矫正性别及年龄的 Logistic回归分析结果显示,加性、显性及隐形模型中10个SNPs均与NMOSD易感性无关(P>0.05).单倍型分析提示 rs1574667-rs523604-rs118182497的单倍型C-G-G与NMOSD易感性相关(OR=1.50,95% CI:1.00~2.23,P=0.046).结论 中国汉族人群中CXCR5 SNP rs11574667的次等位基因C及 rs1574667-rs523604-rs118182497的单倍型C-G-G与NM OSD易感性相关.有关两者间确切关系尚需进一步研究.%Objective To investigate the genetic association between chemokine receptor-5(CXCR5) polymorphisms and neuromyelitis optica spectrum disorders(NMOSD)in a Han Chinese population.Methods We prospectively consecutively collected 312 patients with NMOSD,as well as 487 age-sex matched healthy controls(HCs).Ten single nucleotide polymorphisms(SNPs)were selected from 1000 Genomes Project (1KGP)database, including rs11574667, rs523604, rs118182497, rs1623316, rs78146216, rs497916, rs598207,rs676925,and rs581063.In addition,a SNPs named rs10892301 was selected from a previous study of another autoimmune disease SLE.The correlation between the CXCR5 SNPs and the susceptibility of NMOSD was investigated by analyzing the alleles,genotype frequencies and haplotypes of these two groups.Results There was no significant difference in gender or age between the patients and the HCs(Both P> 0.05).The allelic association analysis suggested that the minor allele C of rs11574667 was associated with the increased risk of NMOSD(OR=1.33,95% CI:1.01-1.75,P= 0.03).The logistic regression analyses adjusted by gender and age indicated that none of the SNPs was associated with the increased risk of NMOSD under additive, dominant or recessive model(P > 0.05).Haplotype analysis showed that C-G-G of rs1574667-rs523604-rs118182497 was associated with the risk of NMOSD(OR = 1.50,95% CI:1.00-2.23, P = 0.046). Conclusions Our study may suggest that the minor allele C of rs11574667 and haplotype C-G-G of rs1574667-rs523604-rs118182497 were associated with the risk of NMOSD.Further study is needed on the exact relationship between CXCR5 SNPs and NMOSD.

摘要： Objective To investigate the effect of cigarette smoke exposure on the expression of CC Chemokine receptor 7 (CCR7) and levels of Th1/Th2 cytokines in asthmatic rats.Methods Forty Wistar rats were randomly divided into four groups:control group,asthma group,smoke exposure group,asthmasmoke exposure group.The asthma group were sensitized with ovalbumin (OVA) and Aluminum hydroxide at day 1,8 and challenged with OVA at day 15 by atomization for 8 weeks.While control group was sensitized and challenged with normal saline instead of OVA.The smoke exposure group was sensitized and challenged with normal saline instead of OVA followed passive smoking for 8 weeks.The asthma-smoke exposure group was challenged with OVA followed passive smoking.The pathological changes of different groups were observed by HE-staining.CCR7 was semiquantitatively analyzed in lungs by immunohistochemistry.The concentration of CC chemokine ligand (CCL) 19,CCL21,interferon (IFN)-γ and interleukin (IL)-4 in peripheral blood and CCL19 and CCL21 in bronchoalveolar lavage fluid (BALF) were measured by enzymelinked immunosorbent (ELESA) assay.Results In asthma group,smoke exposure group and asthmasmoke exposure group,the various degrees of inflammatory reaction appeared in lung tissue and the asthmasmoke exposure group was with the most significant reaction.In the lung tissues of the rats from asthma group,smoke exposure group and asthma-smoke exposure group,the average optical density (AOD) of CCR7 were significantly higher than those in control group (0.350 ± 0.023,0.252 ± 0.022,0.400 ± 0.029 vs 0.180 ±0.020,all P ＜0.01).The AOD of CCR7 of asthma-smoke exposure group was much higher than both that in asthma group and in smoke exposure group (both P ＜ 0.01).In asthma group,smoke exposure group and asthma-smoke exposure group,the concentrations of both CCL19 and CCL21 in peripheral blood and BALF were significantly higher than that in control group (all P ＜ 0.01).The concentrations of both CCL19 and CCL21 in peripheral blood and BALF of asthma-smoke exposure group were significantly higher than the results in asthma group and in smoke exposure group (all P ＜0.01).The concentrations of IFN-γ in peripheral blood of asthma group and asthma-smoke exposure group were lower than those in control group [(33 ± 3),(17 ± 3) vs (70 ± 4) pg/ml],but asthma-smoke exposure group was much lower than the results in asthma group (all P ＜0.01).The concentration of IFN-γ in peripheral blood of smoke exposure group[(100 ± 5)pg/ml] was higher than that in control group and asthma-smoke exposure group (both P ＜ 0.01).In asthma group,smoke exposure group,asthma-smoke exposure group,the concentrations of IL-4 in peripheral blood were significantly higher than those in control group [(54 ±4),(42 ±4),(76 ±4) vs (30 ±4) pg/ml,all P ＜ 0.01].The concentrations of IL-4 in peripheral blood of asthma-smoke exposure group was significantly higher than those in asthma group and in smoke exposure group (both P ＜ 0.01).Conclusion Cigarette smoke could enhance the expression of CCR7 and its ligand,and it can also result in exacerbations of asthma by reducing the expression level of IFN-γ (the representative of Th1 cytokine) and increasing the expression level of IL-4 (the representative of Th2 cytokine).%目的 观察烟雾暴露对支气管哮喘(简称哮喘)大鼠肺组织CC趋化因子受体7(CCR7)和辅助性T细胞(Th1/Th2)细胞因子表达的影响.方法 40只雄性Wistar大鼠按随机数字表法随机分为对照组、哮喘组、烟雾暴露组和哮喘+烟雾暴露组各10只.哮喘组用卵清白蛋白(OVA)和氢氧化铝在第1、8天致敏,并于第15天雾化激发,持续8周,对照组以生理盐水代替OVA,烟雾暴露组以生理盐水代替OVA并给予8周香烟烟雾吸入处理,哮喘+烟雾暴露组每次先给予烟雾吸入再用OVA激发.HE染色观察其肺组织病理变化,免疫组织化学法测定肺组织CCR7表达(以阳性颗粒平均光密度表示),酶联免疫吸附试验(ELISA)检测支气管肺泡灌洗液(BALF)中CC趋化因子配体(CCL) 19和CCL21以及血浆中CCL19、CCL21、干扰素(IFN)-γ和白细胞介素(IL)-4的含量变化.结果 哮喘组、烟雾暴露组、哮喘+烟雾暴露组肺组织发生不同程度的炎症反应,其中哮喘+烟雾暴露组炎症反应最明显;哮喘组、烟雾暴露组、哮喘+烟雾暴露组肺组织CCR7表达均显著高于对照组(0.350±0.023、0.252±0.022、0.400±0.029比0.180±0.020),哮喘+烟雾暴露组CCR7表达均显著高于哮喘组和烟雾暴露组(均P＜0.01);哮喘组、烟雾暴露组、哮喘+烟雾暴露组BALF和血浆中CCL19和CCL21含量均显著高于对照组,哮喘+烟雾暴露组CCL19和CCL21含量均显著高于哮喘组和烟雾暴露组(均P＜0.01);哮喘组、哮喘+烟雾暴露组大鼠血浆中IFN-γ含量均显著低于对照组[(33±3)、(17±3)比(70±4)pg/ml],但哮喘+烟雾暴露组IFN-γ含量低于哮喘组,烟雾暴露组大鼠血浆中IFN-γ含量[(100 ±5) pg/ml]均显著高于对照组和哮喘+烟雾暴露组(均P＜0.01);哮喘组、烟雾暴露组、哮喘+烟雾暴露组大鼠血浆中IL-4含量均显著高于对照组[(54±4)、(42±4)、(76±4)比(30±4) pg/ml],哮喘+烟雾暴露组IL-4含量均显著高于哮喘组和烟雾暴露组(均P＜0.01).结论 烟雾暴露可增加CCR7及其配体CCL19和CCL21的表达,降低Th1细胞因子IFN-γ表达,增加Th2细胞因子IL-4表达,进一步加重哮喘.

摘要： Objective To investigate the relationship between C-C chemokine receptor type 2 (CCR2) and P38 mitogen-activated protein kinase (P38MAPK) signaling pathway in the spinal cord of rats and further clarify the mechanism of bone cancer pain (BCP).Methods A total of 92 healthy female SD rats, of which 60 were subjected to behavioral tests using a ciliary mechanical stimulation needle .SD rats were randomly divided into six groups:sham operation group (group S), bone cancer pain group (group B), sham operation +DMSO solvent group ( group SD ) , bone cancer pain +DMSO solvent group ( group BD) , sham operation +RS102895 CCR2 inhibitor group ( group SR ) , bone cancer pain +RS102895 CCR2 inhibitor group ( group BR ) , and Von Frey was used in the behavioral test .Another 32 SD rats were randomly divided into the following 8 groups (n=4):sham operation group (group S), bone cancer pain 5 d group (group B5), bone cancer pain 9 d group (group B9), bone cancer pain 14 d group (group B14), bone cancer pain +DMSO solvent group ( group BD ) , bone cancer pain +RS102895 CCR2 inhibitor 0.5 h group ( group BR0.5 h) , bone cancer pain +RS102895 CCR2 inhibitor 4 h group ( group BR4 h) , bone cancer pain +RS102895 CCR2 inhibitor 12 h group ( group BR12 h).Western blot was used to detect the expression of P38, p-P38 and CCR2 in spinal cord of rats.Results At day 5,7,9,14,21 post-injection,mechanical withdrawal thresholds of group S were (30.9 ±1.5),(31.9 ±1.2),(32.0 ±1.1), (31.6 ±1.5),(32.2 ±1.4)g respectively, the mechanical withdrawal thresholds of group B were ( 26.4 ± 0.7),(24.4 ±0.8),(21.4 ±0.8),(13.5 ±0.4),(9.9 ±0.2)g respectively,the mechanical withdrawal thresholds in group B decreased obviously versus group S , and the differences were statistically significant (t=-13.177,-16.660,-23.778, -35.574, -48.401,all P<0.01).At day 9 post-injection,the mechanical withdrawal thresholds in SD,BD,SR and BR groups were (32.4 ±1.7),(19.4 ±1.1), (32.1 ±1.3), (26.3 ±1.0) g respectively,the difference was statistically significant (F=224.681,P<0.01 ) ,and the mechanical withdrawal thresholds in group BD decreased obviously versus group SD ,while the mechanical withdrawal thresholds in group BR increased obviously versus group BD .The expression levels of p-P38 in spinal cord of group S, group B5, group B9 and group B14 were(0.08 ±0.03),(0.20 ±0.05), (0.40 ±0.17),(0.65 ±0.14)respectively,the expression levels of CCR2 were(0.08 ±0.04),(0.18 ± 0.05),(0.30 ±0.09),(0.58 ±0.07)respectively,the difference was statistically significant (F=19.123, 40.746,all P<0.01),and the expression of p-P38 and CCR2 in group B9 were showed a significant up-regulation versus group S .The expression levels of p-P38 in spinal cord of group BD , group BR0.5 h, group BR4 h and group BR12 h were ( 0.57 ±0.06 ) , ( 0.17 ±0.11 ) , ( 0.03 ±0.01 ) , ( 0.25 ±0.11 ) respectively,and the difference was statistically significant (F=29.582,P<0.01).The expression of p-P38 in group BR0.5 h, BR4 h, BR12 h showed a significant down-regulation versus group BD.Conclusion CCR2 in the spinal cord may be involved in the development of bone cancer pain by activating P 38MAPK signaling pathway in rats .%目的 探讨骨癌痛大鼠脊髓趋化因子受体2(CCR2)与P38丝裂原活化蛋白激酶(P38MAPK)信号通路的关系,进一步明确骨癌痛的发生机制.方法 健康雌性SD大鼠共92只,其中60只利用纤毛机械刺激针方法用于行为学试验,采用随机数字表法分为以下6组(n=10):假手术组(S组)、骨癌痛组(B组)、假手术+二甲亚砜(DMSO)溶剂组(SD组)、骨癌痛+DMSO组(BD组)、假手术+RS102895 CCR2抑制剂组(SR组)、骨癌痛+RS102895 CCR2抑制剂组(BR组).另外32只SD大鼠采用随机数字表法分为以下8组(n=4):假手术组(S组)、骨癌痛5 d组(B5组)、骨癌痛9 d组(B9组)、骨癌痛14 d组(B14组)、骨癌痛+DMSO溶剂组(BD组)、骨癌痛+RS102895 CCR2抑制剂后0.5 h组(BR0.5 h组)、骨癌痛+RS102895 CCR2抑制剂后4 h组(BR4h组)、骨癌痛+RS102895 CCR2抑制剂后12 h组(BR12 h组),通过蛋白质印迹法(Western Blot)检测大鼠脊髓P38蛋白、磷酸化的P38(p-P38)和CCR2的表达水平.结果 S组造模后5、7、9、14、21 d的机械缩足反应阈值分别为(30.9±1.5)、(31.9±1.2)、(32.0±1.1)、(31.6±1.5)、(32.2±1.4)g,B组分别为(26.4±0.7)、(24.4±0.8)、(21.4±0.8)、(13.5±0.4)、(9.9±0.2)g,与S组比较,B组造模后5、7、9、14、21 d时机械痛阈值降低,差异均有统计学意义(t=-13.177、-16.660、-23.778、-35.574、-48.401,均P<0.01).造模后第9天,SD组、BD组、SR组和BR组给药后4 h机械缩足反应阈值分别为(32.4±1.7)、(19.4±1.1)、(32.1±1.3)、(26.3±1.0)g,差异有统计学意义(F=224.681,P<0.01);与SD组比较,BD组机械痛阈值降低;与BD组比较,BR组机械痛阈值升高.S组、B5组、B9组、B14组大鼠脊髓p-P38表达水平分别为(0.08±0.03)、(0.20±0.05)、(0.40±0.17)、(0.65±0.14),CCR2表达水平分别为(0.08±0.04)、(0.18±0.05)、(0.30±0.09)、(0.58±0.07),差异均有统计学意义(F=19.123、40.746,均P<0.01);与S组比较,B9组大鼠脊髓p-P38和CCR2表达上调.造模后第9天,BD组、BR0.5 h组、BR4 h组和BR12 h组大鼠脊髓p-P38表达水平分别为(0.57±0.06)、(0.17±0.11)、(0.03±0.01)、(0.25±0.11),差异有统计学意义(F=29.582,P<0.01);与BD组比较,BR0.5 h组、BR4 h组、BR12 h组大鼠脊髓p-P38表达明显下调.结论 脊髓CCR2可能通过激活P38MAPK信号通路参与了大鼠骨癌痛痛觉过敏的发生.

摘要： 目的 探讨厄贝沙坦联合瑞舒伐他汀对合并心血管疾病的早期糖尿病肾病(DN)的治疗效果及对基质细胞衍生因子1/趋化因子受体4(SDF-1/CXCR4)表达的影响.方法 选取2016年1月至2017年12月临海市第二人民医院收治的的合并心血管疾病的早期DN患者130例为研究对象,采用随机数字表法分为三组,即厄贝沙坦组(对照1组,n＝43)、瑞舒伐他汀组(对照2组,n＝43)和厄贝沙坦联合瑞舒伐他汀组(观察组,n＝44),比较三组临床疗效,血压、血脂水平及SDF-1/CXCR4表达.结果 治疗后,观察组总有效率为93.18%(41/44),对照1组总有效率为69.77%(30/43),对照2组总有效率为74.42%(32/43),三组差异均有统计学意义(χ2＝12.341、10.106,均P＜0.05).治疗后,观察组收缩压(SBP)、舒张压(DBP)水平与对照1组、对照2组比较,差异均有统计学意义(F＝23.087、20.249,均P＜0.05).治疗后,观察组胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)与对照1组、对照2组比较,差异均有统计学意义(F＝18.408、15.623、14.852、9.845,均P＜0.05).治疗后,观察组SDF-1水平较治疗前显著提高且与对照1 组、对照2组比较,差异有统计学意义( F＝21.085,P＜0.05).治疗后,观察组CXCR4阳性率较治疗前显著提高,且与对照1组、对照2组比较,差异有统计学意义(F＝23.641,P＜0.05).结论 厄贝沙坦联合瑞舒伐他汀对合并心血管疾病的早期DN的临床疗效显著,可有效改善患者血压、血脂水平,显著提高SDF-1水平及CXCR4阳性率.%Objective To investigate the effect of irbesartan combined with resuvastatin on early diabetic nephropathy( DN) complicated with cardiovascular disease,and its influence on SDF -1/CXCR4 expression. Methods From January 2016 to December 2017,130 early DN patients complicated with cardiovascular disease in the Second People＇s Hospital of Linhai were selected as study objects,and according to the digital table,they were randomly divided into three groups: irbesartan group(control group 1,n＝43),resuvastatin group(control group 2,n＝43) and irbesartan combined with resuvastatin group (observation group,n＝44).The clinical efficacy,blood pres-sure,blood lipids and SDF -1/CXCR4 expression were compared among the three groups.Results After treatment,the total effective rate in the observation group was 93.18%(41/44 ),which in the control group 1 was 69.77%(30/43),which in the control group 2 was 74.42%(32/43),there was statistically significant difference among the three groups(χ2＝12.341,10.106,all P＜0.05).After treatment,the levels of SBP and DBP in the observation group had statistically significant differences compared with those in the control group 1 and control group 2( F＝23.087,20.249,all P＜0.05).After treatment,there were statistically significant differences in TC,TG,HDL-C and LDL-C between the observation group and control group 1,control group 2(F＝18.408,15.623,14.852,9.845,all P＜0.05).After treatment,the level of SDF -1 in the observation group was significantly higher than that before treatment,and which was also significantly higher than that in the control group 1 and control group 2(F＝21.085,P＜0.05).After treatment,the positive rate of CXCR4 in the observation group was significantly higher than that before treatment,and compared with that in the control group 1 and control group 2,the difference was statistically significant(F＝23.641,P＜0.05).Conclusion Irbesartan combined with resuvastatin in the treatment of early DN patients with cardiovascular disease has significant clinical efficacy,can effectively improve blood pressure and blood lipid levels,significantly improve the level of SDF -1 and CXCR4 positive rate.

摘要： 目的:探究甘肃省汉族人群CXC型趋化因子配体12(CXCL12)及其受体趋化因子受体4(CXCR4)rs2297630和rs2322864位点基因多态性与冠心病发病风险以及冠状动脉狭窄程度的相关性.方法:2017年11月至2018年6月在兰州大学第二医院住院治疗的302例无血缘关系的冠心病患者作为冠心病组,同期年龄、性别相匹配的302名无血缘关系的体检者作为健康对照组.应用竞争性等位基因特异性PCR法检测所有研究对象rs2297630和rs2322864位点的基因分型,并根据冠状动脉造影结果采用Gensini评分对患者冠状动脉狭窄程度进行评价.采用二元Logistic回归分析和多因素线性回归分析rs2297630和rs2322864基因多态性与冠心病发病风险和冠状动脉狭窄程度的相关性.结果:冠心病组与健康对照组rs2297630和rs2322864等位基因和基因型分布频率差异均具有统计学意义(均P0.05).结论:甘肃省汉族人群中CXCL12多态性位点rs2297630与冠心病的发病风险和冠状动脉狭窄程度相关,其受体CXCR4上的常见突变位点rs2322864也与冠心病的发病风险相关,但与冠状动脉狭窄程度不相关.

摘要： 本发明公开了一种分泌表达IL15RA‑IL15融合蛋白、CCL21趋化因子的嵌合抗原受体‑T细胞及应用。超级IL15能够促进T(尤其是记忆T)、NK、NKT细胞的活化和增殖，CCL‑21可以募集外周CCR7阳性的初始T细胞、记忆T细胞和DC(树突状细胞)进入淋巴组织或肿瘤病灶，进而激活机体内在的主动抗肿瘤免疫反应(如癌症记忆T细胞)，从而显著提高有效率和缓解率、降低治疗缓解后的复发率。

摘要： 提供用于合成细胞因子、趋化因子、生长因子、多肽激素及其受体结合拮抗剂的聚合物缀合物的方法，此缀合物通常保留高受体结合活性。根据本发明的方法来制备聚合物缀合物可减少或避免因聚合物附着在细胞因子、趋化因子、生长因子、多肽激素及其激动和拮抗类似物的受体结合区域而通常引起的对受体－配体相互作用的空间抑制作用。本发明也提供由这类方法所生产的缀合物和组合物。相对于那些通过传统聚合物偶联方法(其目标不在于避开细胞因子、趋化因子、生长因子和多肽激素的受体－结合结构域)所生产的缀合物，本发明的缀合物保持了更高的受体－结合活性。相对于未缀合的细胞因子、趋化因子、生长因子和多肽激素，本发明的缀合物也在体内和体外显示出延长的半衰期。本发明也提供含有这类缀合物和/或组合物的试剂盒，以及在不同的诊断、预防、治疗和生物加工应用中使用这类缀合物和组合物的方法。

摘要： 本发明涉及式(I)的趋化因子受体2b拮抗剂或其药学上可接受的盐。此类化合物可以拮抗趋化因子受体2b，有效地产生抗炎作用。

摘要： 本发明提供了促进家禽T细胞向靶器官迁移的关键趋化因子受体及其配体和受体及其配体的应用。主要包括CCR4、CCR5、CCR6、CCR7和CXCR4及其配体CCL17/CCL22、CCL3/CCL4、CCL20、CCL19/CCL21和CXCL12。利用定量PCR和转录组测序技术检测感染传染性法氏囊病毒家禽法氏囊器官中趋化因子受体及其配体基因表达变化，结果发现IBDV感染组中法氏囊组织T细胞趋化因子受体CCR4、CCR5、CCR6、CCR7和CXCR4及其配体基因表达量显著变化，在T细胞迁移中发挥重要作用。

摘要： 本公开涉及一种药物递送系统，包含神经营养剂、凋亡信号传导片段抑制剂(FAS)或FAS配体(FASL)抑制剂、肿瘤坏死因子‑α(TNF‑α)或TNF受体(TNFR)抑制剂、线粒体肽、寡核苷酸、趋化因子抑制剂、半胱氨酸‑天冬氨酸蛋白酶抑制剂，包括这些化合物的任何组合；以及任选的持续递送组分。这种类型的药物递送系统可用于治疗医学病症，例如遗传性或与年龄相关的脉络膜、视网膜、视神经疾患或视神经变性；耳部疾病；神经系统或CNS疾患；或相关病症；或与血管或血液循环的闭塞或阻塞有关的病症，例如中风、心肌或肾梗死。还描述了药物、制造药物的方法、试剂盒和其他相关产品或方法。

摘要： 本公开涉及一种药物递送系统，所述药物递送系统包含神经营养剂、凋亡信号传导片段抑制剂(FAS)或FAS配体(FASL)抑制剂、肿瘤坏死因子‑α(TNF‑α)或TNF受体(TNFR)抑制剂、线粒体肽、寡核苷酸、趋化因子抑制剂、或半胱氨酸‑天冬氨酸蛋白酶，包括这些化合物的任何组合；以及任选的持续递送组分。这种类型的药物递送系统可用于治疗医学病症，例如遗传性或与年龄相关的脉络膜、视网膜、视神经疾患或视神经变性；耳部疾病；神经系统或CNS疾患；或相关病症；或与血管或血液循环的闭塞或阻塞有关的病症，例如卒中、心肌或肾梗死。还描述了药物、制造药物的方法、试剂盒和其他相关产品或方法。

摘要： 已发现白细胞衍生趋化因子2(LECT2)与HCC病患的血管侵入程度的抑制调控有关。亦发现LECT2通过抑制MET及其他在HGF/MET路径中下游目标的磷酸化，而强烈地减少HCC细胞的生长、迁移及侵入。发现LECT2的HXXXD基序对于其肿瘤抑制机制是重要的。除了HCC以外，LECT2于其他癌症中减少Met酪氨酸磷酸化及肿瘤细胞侵入，例如肺癌、乳癌、及胃癌。基于上述新发现的LECT2的肿瘤抑制特性，描述用于预防、治疗或诊断肿瘤(例如HCC)的方法及组合物。

摘要： 本发明公开了一种方法，其通过检测应答刺激中某些mRNA的水平，用于确定患有克罗恩病的人是否可能对靶向TNFSF成员或细胞因子的治疗有应答。本发明还公开了一种评估克罗恩病治疗对人的效力的方法。此外，本发明公开了一种筛选用于克罗恩病的治疗中的化合物的方法。本发明还公开了一种随着时间监控克罗恩病患者疾病状态的方法。

摘要： 本发明提供了使用陪伴蛋白10(Cpn10)来调节Toll样受体信号传导和/或Toll样受体诱导性免疫调节剂分泌的方法。Cpn10可负性调节Toll样受体激动剂诱导的促炎细胞因子和趋化因子分泌，其实例分别为IL－6和RANTES。Cpn10可正性调节Toll样受体激动剂诱导的抗炎细胞因子和趋化因子分泌，其实例为IL－10。这些Cpn10的免疫调节活性可用于治疗促炎细胞因子和趋化因子过度分泌引起的疾病、紊乱和病症。本发明还涉及根据调节Toll样受体信号传导和/或Toll样受体诱导性免疫调节剂分泌的能力，生产、设计和/或筛选Cpn10激动剂和拮抗剂。

摘要： 本文公开了用于治疗和/或预防与E‑选择蛋白、半乳凝素‑3和/或CXCR4趋化因子受体活性相关的至少一种疾病、病症和/或病况的化合物、组合物和方法。例如，公开了E‑选择蛋白、半乳凝素‑3和/或CXCR4趋化因子受体的多聚体糖模拟物抑制剂以及它们的用于治疗和/或预防炎性疾病、纤维化和癌症的用途。