Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

血清MMP2/TIMP2比值与老年2型糖尿病患者并发AS的相关性分析

目的探讨血清基质金属蛋白酶-2/金属蛋白酶组织抑制因子-2(MMP2/TIMP2)比值与老年2型糖尿病(T2DM)患者并发主动脉硬化(AS)之间的关系。方法回顾性分析2022年1月至2023年4月万宁市人民医院收治的180例初次诊断为T2DM的老年患者的临床资料,并根据是否并发AS[颈动脉-股动脉脉搏波传导速度(cfPWV)>10 m/s]分为AS组(n=69)和非AS组(n=111)。另选取同时期来院体检健康者采用倾向性评分法匹配90例为对照组。比较3组对象的一般资料、实验室指标以及血清MMP2、TIMP2水平和MMP2/TIMP2比值。采用Spearman相关分析探究老年T2DM患者cfPWV与各项指标的相关性。采用多因素logistic回归模型分析,老年T2DM患者并发AS的影响因素。绘制受试者工作特征(ROC)曲线,分析并比较MMP2/TIMP2比值与多指标联合检测对老年T2DM患者并发AS的诊断价值。结果非AS组稳态模型胰岛素抵抗指数(HOMA-IR)、血清三酰甘油(TG)、MMP2水平及MMP2/TIMP2比值高于对照组,血清TIMP2水平低于对照组,差异有统计学意义(P<0.05)。AS组年龄、合并高血压比例高于非AS组(P<0.05)。AS组HOMA-IR、血清TG、MMP2水平及MMP2/TIMP2比值高于对照组和非AS组,血清TIMP2水平低于对照组和非AS组,差异均有统计学意义(P<0.05)。相关性分析结果显示,非AS组患者的cfPWV与HOMA-IR、TC、LDL-C、MMP2、MMP2/TIMP2比值呈正相关(r=0.217、0.264、0.216、0.197、0.703,P<0.05),与TIMP2呈负相关(r=-0.524,P<0.01);AS组患者cfPWV与MMP2、MMP2/TIMP2比值呈正相关(r=0.659、0.857,P<0.01),与TIMP2呈负相关(r=-0.532,P<0.01)。logistic回归分析显示,年龄增长(OR=1.108,95%CI:1.022~1.201,P=0.012)、高血压病(OR=2.877,95%CI:1.174~7.051,P=0.021)及MMP2/TIMP2比值升高(OR=5.147,95%CI:2.392~11.074,P<0.001)是老年T2DM患者并发AS的的独立危险因素。ROC曲线分析结果显示,MMP2/TIMP2比值及多指标联合检测诊断老年T2DM患者并发AS的曲线下面积分别为0.850(95%CI:0.789~0.899,P<0.01)和0.886(95%CI:0.831~0.929,P<0.01),灵敏度分别为73.91%、82.61%,特异度分别为89.19%、82.88%,约登指数分别为0.631、0.655。多指标联合检测的诊断效能明显大于MMP2/TIMP2比值,差异具有统计学意义(Z=2.233,P=0.026)。MMP2/TIMP2比值诊断老年T2DM患者并发AS的最佳截断值为3.23。结论MMP2/TIMP2比值升高为老年T2DM患者并发AS的独立危险因素,对老年T2DM并发AS的诊断有辅助价值,多指标联合检测可提高诊断效能。

MMP2基因多态性与盐酸多奈哌齐治疗阿尔茨海默病的血药浓度和效果的关系

目的 探讨基质金属蛋白酶2(Matrix metalloproteinase 2,MMP2)基因单核苷酸多态性对盐酸多奈哌齐在阿尔茨海默病(Alzheimer′s disease, AD)中的血药浓度和治疗效果的影响。方法 选择2020年1月-2023年1月于徐州市东方人民医院老年精神科就诊治疗的97例AD患者为AD组,以同期进行体检的100名健康老年人为健康对照组。所有患者入院接受5 mg/d的盐酸多奈哌齐治疗,连续30 d,将盐酸多奈哌齐剂量增至10mg/d,连续150 d。治疗前后采用简明精神状况量表(Mini-mental state examination, MMSE)评估患者的认知功能,依据最后一次MMSE评分与第一次MMSE评分相比是否下降,分为应答组和未应答组。治疗6个月后采用高效液相色谱-串联质谱联用法测定两组血液中盐酸多奈哌齐血药浓度。采用实时定量PCR(Polymerase chain reaction, PCR)和限制性片段长度多态性分析检测血液中MMP2基因rs243865(C>T)、rs2285053(C>T)基因分型。结果 与健康对照组比较,AD组MMP2基因rs243865、rs2285053基因型分布,rs243865位点遗传模型差异无统计学意义(P>0.05),rs2285053位点显性模型差异有统计学意义(P<0.05)。经盐酸多奈哌齐治疗后,与未应答组比较,应答组MMP2基因rs243865基因型分布、遗传模型及隐性模型差异均无统计学意义(P>0.05),rs2285053基因型分布、相加模型、显性模型差异有统计学意义(P<0.05)。不同MMP2基因位点rs243865位点基因型AD患者的盐酸多奈哌齐血药浓度比较差异无统计学意义(P>0.05)。与rs2285053位点TT基因型AD患者比较,CC、CT基因型患者的盐酸多奈哌齐血药浓度增大,差异有统计学意义(P<0.05)。未应答组与应答组间盐酸多奈哌齐血药浓度差异无统计学意义(P>0.05)。结论 MMP2基因rs2285053位点变异与盐酸多奈哌齐治疗AD的血药浓度和疗效有关,对于临床治疗用药有一定指导价值。

替吉奥联合奥沙利铂对老年胃癌患者胃动力相关激素及基质金属蛋白酶-2、基质金属蛋白酶-9的影响

目的探讨替吉奥联合奥沙利铂对老年胃癌患者胃动力相关激素及基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)的影响。方法选取128例老年胃癌患者为研究对象,随机分成对照组(n=64)与观察组(n=64)。对照组给予替吉奥治疗,观察组给予替吉奥联合奥沙利铂治疗。观察2组的胃动力相关激素[胃动素(MTL)、血管活性肠肽(VIP)]、MMP-2与MMP-9、肿瘤标志物[癌胚抗原(CEA)、糖类抗原125(CA125)、糖类抗原19-9(CA19-9)]、临床疗效以及不良反应发生情况。分析胃动力相关激素与MMP-2、MMP-9及肿瘤标记物水平的相关性。结果治疗后,2组MTL低于治疗前,VIP高于治疗前,且观察组MTL低于对照组,VIP高于对照组,差异有统计学意义(P<0.05)。治疗后,2组MMP-2、MMP-9及CEA、CA125、CA19-9低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05)。观察组总有效率为70.31%,高于对照组的53.13%,差异有统计学意义(P<0.05)。2组不良反应发生率比较,差异无统计学意义(P>0.05)。MTL与MMP-2、MMP-9、CEA、CA125、CA19-9呈负相关(P<0.05);VIP与MMP-2、MMP-9、CEA、CA125、CA19-9呈正相关(P<0.05)。结论替吉奥联合奥沙利铂治疗老年胃癌患者的效果较好,且安全性较高。MTL、VIP与MMP-2、MMP-9及CEA、CA125、CA19-9在老年胃癌患者的疾病发展中起相互关联作用。

EGR-1和MMP-2在早期自然流产患者中的表达及临床意义

目的探讨早期生长反应因子(EGR-1)和基质金属蛋白酶-2(MMP-2)在早期自然流产患者绒毛中的表达及临床意义。方法采用RT-PCR和Westernblot检测20例早期自然流产患者(流产组)和20例正常早孕人工流产(对照组)绒毛组织中EGR-1和MMP-2的表达情况。结果流产组中EGR-1、MMP-2 mRNA和蛋白水平明显低于对照组,差异有统计学意义(P<0.05)。结论EGR-1和MMP-2在早孕绒毛组织中表达异常可能参与早期妊娠失败的发生。

子宫肌瘤组织中MMP-2、MLCK、VEGF及IGF-2表达及其临床意义

目的分析基质金属蛋白酶-2(MMP-2)、肌球蛋白轻链激酶(MLCK)、血管内皮生长因子(VEGF)、胰岛素样生长因子-2(IGF-2)在子宫肌瘤组织内的表达及临床意义。方法选取76例子宫肌瘤患者,收集其子宫肌瘤组织及正常子宫组织,采用免疫组织化学法测定MMP-2、MLCK、VEGF及IGF-2表达,统计对比两者的阳性率。结果子宫肌瘤组织中MMP-2、MLCK、VEGF及IGF-2阳性表达率分别为69.74%(53/76)、60.53%(46/76)、81.58%(62/76)、92.11%(70/76),高于正常子宫组织的15.79%(12/76)、10.53%(8/76)、17.11%(13/76)、30.26%(23/76),差异有统计学意义(P<0.05)。结论MMP-2、MLCK、VEGF及IGF-2在子宫肌瘤组织中呈异常的高表达,与疾病的发生与发展存在紧密联系。

输卵管阻塞性不孕患者血清TGF-β1、IL-2、MMP-9水平及临床意义

目的:分析输卵管阻塞性不孕患者血清转化生长因子-β1(TGF-β1)、白细胞介素-2(IL-2)、基质金属蛋白酶-9(MMP-9)水平变化及临床意义。方法:以本院2022年3月-2023年10月诊治的60例输卵管阻塞性不孕患者为病例组,正常妊娠分娩的女性50例为对照组。测定对比两组血清TGF-β1、IL-2、MMP-9水平,Pearson相关性分析血清指标间相关性,受试者工作特征(ROC)曲线分析血清指标诊断不孕效能,logistic多因素回归分析输卵管阻塞性不孕发生影响因素。结果:病例组术前血清TGF-β1(593.79±148.23 ng/L)、IL-2(3.90±0.75 ng/L)、MMP-9(384.88±86.87 ng/ml)水平均高于对照组(239.42±113.37 ng/L、3.09±0.84 ng/L、178.98±80.85 ng/ml),术后血清TGF-β1、IL-2、MMP-9水平较术前均下降,血清TGF-β1与IL-2、MMP-9,及IL-2与MMP-9均呈正相关(均P<0.05)。ROC曲线分析,诊断不孕TGF-β1曲线下面积(AUC)0.941、敏感度88.3%、特异度94.0%,IL-2 AUC 0.778、敏感度66.7%、特异度84.0%,MMP-9 AUC 0.946、敏感度88.3%、特异度86.0%,3指标联合诊断AUC为0.992,敏感度93.3%、特异度100.0%。logistic回归分析,血清TGF-β1、IL-2、MMP-9异常升高是输卵管阻塞性不孕发发生的危险因素(均P<0.05)。结论:输卵管阻塞性不孕患者血清TGF-β1、IL-2、MMP-9水平均高表达,且是不孕发生的危险因素,3者联合检测对输卵管阻塞性不孕有较高诊断价值。

朱琏抑制Ⅱ型针法干预盆腔炎性疾病后遗症大鼠的效果及其对前列腺素、VEGF、MMP2表达的影响

目的观察朱琏抑制Ⅱ型针法干预盆腔炎性疾病后遗症(SPID)大鼠的效果,并基于前列腺素(PG)F_(2α)、PGE_(2)、血管内皮生长因子(VEGF)及基质金属蛋白酶2(MMP2)探讨其作用机制。方法将55只雌性未孕SD大鼠随机分为空白组、模型组、西药组、普通针刺组(普针组)、朱琏抑制Ⅱ型针法组(针法组)。除空白组外,其他组采用宫内注射混合菌液联合机械损伤法制备SPID大鼠模型。造模成功后,给予西药组灌胃阿奇霉素治疗,给予普针组普通针刺治疗,给予针法组朱琏抑制Ⅱ型针法治疗,空白组与模型组不给予任何治疗。连续干预4周后,处死各组大鼠,观察各组大鼠子宫形态学及组织病理学改变,检测各组大鼠血清PGF_(2α)、PGE_(2)含量及子宫组织VEGF、MMP2蛋白表达水平。结果(1)模型组大部分大鼠子宫肿胀、充血、双侧形态不对称,盆腔组织广泛粘连且有积液;子宫组织可见大量炎症细胞浸润,组织结构紊乱,并出现轻微纤维化。各干预组大鼠子宫形态、子宫组织炎症优于模型组,针法组大鼠的改善更为明显。(2)与空白组相比,模型组及各干预组大鼠血清PGF_(2α)和PGE_(2)含量、子宫组织VEGF、MMP2的蛋白表达水平均升高(均P<0.05),针法组上述指标均低于普针组(均P<0.05),但与西药组的差异无统计学意义(均P>0.05)。结论朱琏抑制Ⅱ型针法可能通过降低血清PGF_(2α)、PGE_(2)含量,抑制VEGF、MMP2蛋白表达来发挥治疗SPID的作用,其效果优于普通针刺法,与西药干预效果相近。

血根碱对膀胱癌T24细胞增殖迁移的调控作用及其机制

目的 观察血根碱对膀胱癌T24细胞增殖迁移的调控作用,并探索可能的作用靶基因及作用机制。方法 培养膀胱癌T24细胞和人正常膀胱上皮细胞SV-HUC-1,分别分为实验组和对照组,实验组分别加入0.012 5、0.025、0.05、0.1、0.2、0.4、0.8、1.6μmol/L的血根碱,对照组培养基中不加血根碱,采用CCK-8试剂盒检测细胞增殖能力,并计算半数抑制浓度(IC_(50))。将T24细胞分为实验组和对照组,实验组给予血根碱,对照组不进行血根碱处理,采用Transwell小室实验检测细胞迁移能力。分别基于BATMAN、SwissTargetPrediction网络药理学数据库、TCGA数据库分析并筛选得到血根碱作用靶基因和膀胱癌治疗靶基因的交集靶基因,进行GO分析和KEGG功能富集分析,绘制蛋白质相互作用网络,筛选血根碱调控T24细胞的靶基因。采用GSEA_4.2.3进行靶基因集富集分析,以确定靶基因富集的相关通路。基于GEPIA网站和“survival”R软件包评估靶基因高表达组和低表达组的无进展间隔期、疾病特异性生存期、总生存期差异。将血根碱和靶基因蛋白结构进行分子对接,并计算结合能。采用实时荧光定量PCR法检测实验组和对照组细胞中的靶基因。结果 实验组T24细胞增殖能力和穿膜细胞数低于对照组(P均<0.05)。血根碱对T24细胞的IC_(50)为0.200 3μmol/L、对SV-HUC-1细胞的IC_(50)为0.709 9μmol/L。筛选出血根碱调控T24细胞的靶基因为基质金属蛋白酶(MMP)-2、MMP-9、前列腺素—内过氧化物合酶2(PTGS2)。MMP-2、MMP-9、PTGS2与调节上皮细胞增殖的通路有关。MMP-9高表达者疾病特异性生存期和总生存期低于低表达者(P均<0.05)。血根碱与MMP-2、MMP-9、PTGS2结合能分别为-8.8、-8.6、-10.0 kcal/mol。实验组PTGS2、MMP-2、MMP-9 mRNA表达低于对照组(P均<0.05)。结论 血根碱可在不影响SV-HUC-1细胞的浓度下抑制膀胱癌T24细胞的增殖迁移能力。血根碱对膀胱癌细胞增殖迁移能力的调控作用可能与调控MMP-2、MMP-9、PTGS2表达并影响上皮细胞增殖相关通路有关。

慢性阻塞性肺疾病患者外周血MMP2水平Meta分析

目的 评估外周血基质金属蛋白酶2(matrix metalloproteinase-2, MMP2)在慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)患者中的潜在作用。方法 在中国知网(CNKI)、中国生物医学文献服务系统、万方数据知识服务平台、维普网、PubMed和Embase数据库中检索建库至2021年11月的文献,确定与COPD和MMP2相关的合格文献。使用统计软件计算标准化平均差(standardized mean difference, SMD)及其95%CI以衡量各研究效应量大小。结果 此次Meta分析共纳入10篇研究,结果显示,与对照组比较,外国COPD组的外周血MMP2水平升高,差异有统计学意义(SMD=3.40,95%CI:0.70~6.10,I2=98%,P=0.01)。中国急性加重期COPD(acute exacerbation of chronic obstructive pulmonary disease, AECOPD)患者外周血MMP2水平高于对照组,差异有统计学意义(SMD=2.94,95%CI:2.02~3.86,I2=78%,P<0.001)。中国稳定期COPD患者外周血MMP2低于对照组,差异有统计学意义(SMD=-5.90,95%CI:-10.64~-1.16,I2=99%,P=0.01)。结论 外国COPD患者外周血MMP2水平升高。中国AECOPD患者外周血MMP2水平升高,中国稳定期COPD患者外周血MMP2水平下降。在中国COPD人群中,外周血MMP2可以作为监测COPD疾病进展的潜在生物学标志物。

Expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic stellate cells during rat hepatic fibrosis and its intervention by IL-10

AIM: To investigate the expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10).METHODS: Hepatic fibrosis was induced by CCl4administration and 60 male Sprague-Dawley rats were randomly divided into normal control group (group N, 8rats), CCl4-induced group (group C, 28 rats) and IL-10-treated group (group I, 24 rats). At the beginning of the 7th and 11th wk, rats in each group were routinely perfused with pronase E and type Ⅳ collagenase through portal vein catheter and the suspension was centrifuged by 11%Nycodenz density gradient to isolate hepatic stellate cells (HSCs). RT-PCR was used to analyze mRNA of MMP-2 and TIMP-1 from freshly isolated cells. Densitometric data were standardized with β-actin signals. Immunocytochemistry was performed to detect MMP-2 and TIMP-1 expression in HSC cultured for 72 h.RESULTS: Compared to group N in the 7th wk, MMP-2and TIMP-1 mRNA increased in group C (P= 0.001/0.001)and group I (P = 0.001/0.009). The level of MMP-2 and TIMP-1 mRNA in group I was significantly lower than that in group C (P= 0.001/0.001). In the 11th wk, MMP-2 mRNAin group I was still lower than that in group C (P = 0.005),but both dropped compared with that in the 7th week (P = 0.001/0.004). TIMP-1 mRNA in group I was still lower than that in group C (P= 0.001), and increased in group C (P = 0.001) while decreased in group I (P = 0.042)compared with that in the 7th wk. Same results were found by immunocytochemistry.CONCLUSION: Expression of MMP-2 and TIMP-1 is increased in hepatic fibrosis. IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression.

Relationship between matrix metalloproteinase-2 mRNA expression and clinicopathological and urokinase-type plasminogen activator system parameters and prognosis in human gastric cancer

AIM: To investigate the relationship between matrix metalloproteinase-2 (MMP-2) mRNA expression and clinicopathologic and urokinase-type plasminogen activator (uPA) system parameter and prognosis in human gastric cancer.METHODS: Expression of MMP-2 mRNA, uPA, and uPA-R mRNA in tumor tissues and ≥5 cm adjacent normal tissues from 67 cases of gastric cancer was studied using RTPCR and Northern blot respectively. Survival analyses were done using the Kaplan-Meier method. RESULTS: The expression rates of MMP-2 mRNA, uPA and uPA-R mRNA in tumor tissues (31%, 41%, and 51%, respectively) were significantly higher than those in ≥5 cm adjacent tissues (19%, 11%, and 9%; χ2 = 4.59, 43.58, and 53.24 respectively, P＜0.05, 0.0001, and 0.0001, respectively). Expression of MMP-2 mRNA was significantly correlated with lymph node metastasis (metastasis:61.9%, no metastasis: 39.1%, χ2= 7.61, P＜0.05), Lauren's classification of diffuse/mixed types: 54.2%, intestinal type: 26.3%, χ2 = 4.25, P＜0.05, expression of uPA and uPA-R mRNA (uPA+: 55.1%, uPA-: 22.2% and uPA-R+: 54.9%, uPA-R-: 18.8%, x2= 5.72 and 6.40 respectively, P＜0.05). Kaplan-Meier survival analysis of MMP-2 mRNA expression did not show significant difference in all 67 cases, but revealed an association of the expression of MMP-2 mRNA, uPA, and uPA-R mRNA with worse prognosis (P = 0.0083, 0.0160, and 0.0094, respectively). CONCLUSION: MMP-2 may play an important role in the development of invasion and metastasis of gastric cancer.

Suppression of matrix metalloproteinase-2 via RNA interference inhibits pancreatic carcinoma cell invasiveness and adhesion

AIM:To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line,BxPC-3.METHODS:RNAi was performed using the vector (pGPU6)-based small interference RNA (siRNA) plasmid gene silence system to specifically knock down MMP-2 expression in pancreatic cancer cell line,BxPC-3. Four groups of different specific target sequence in coding region of MMP-2 and one non-specific sequence were chosen to construct four experimental siRNA plasmids of pGPU6-1,pGPU6-2,pGPU6-3 and pGPU6-4,and one negative control siRNA plasmid of pGPU6 (-). MMP-2 expression was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) and flow cytometry,respectively. The abilities of adhesion and invasion were detected by cell adhesion assay and cell invasion assay using Transwell chambers.RESULTS:The expression of MMP-2 was inhibited and the inhibitory effects of different sequence varied. pGPU6-1 group had the most efficient inhibitory effect,followed by pGPU6-2 and pGPU6-3 groups.Invasiveness and adhesion were more significantly reduced in pGPU6-1,pGPU6-2 and pGPU6-3 groups as compared with pGPU6 (-) and blank control groups. However,no difference concerning cell proliferation and apoptosis was observed after transfection between experiment groups and control groups.CONCLUSION:RNAi against MMP-2 successfully inhibited the mRNA and protein expression of MMP-2 in the pancreatic cancer cell line,BxPC-3,leading to a potent suppression of tumor cell adhesion and invasion without affecting cell proliferation and apoptosis. These findings suggest that the RNAi approach towards MMP-2 may be an effective therapeutic strategy for the clinical management of pancreatic tumor.

Correlation of matrix metalloproteinase－2, －9, tissue inhibitor－1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis

This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The ex-pression of matrix metalloproteinase-2,-9 (MMP-2,MMP-9), tissue inhibitor-1 of matrix metalloprote inase(TIMP-1) , cell adhesion molecule 44 variant 6 (CD44v6) , HER2/neu and p53 was investigated in 154 pa-tients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP-2, MMP-9, TIMP-1,CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68. 18%, 98.05%,55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there wasclose positive relationship ( P < 0.05) between the expression of MMP-2 and MMP-9, TIMP-1 and CD44v6,HER2/neu and MMP-9, MMP-2 and p53. Up-regulation of MMP-2 was accompanied by advanced T stage( P < 0.01 ) . There was also a trend of MMP-2 expression being related with tumor metastasis. Increased ex-pression of HER2/neu was found in patients with tumor recurrence( P < 0.05 ) . The expression of TIMP-1 washigher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non-keratlnizing SCC than that in basaloid SCC ( P < 0.05 ) . These findings suggested that MMP-2 and MMP-9, HER2/neu andMMP-9, MMP-2 and p53 had a coordinate function in aggression of tumor; that MMP-2 had a more important function than MMP-9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker forpoor prognosis in HNSCC.

超声收缩期峰值血流速度、阻力指数与乳腺癌组织中Survivin、基质金属蛋白酶-11、人类表皮生长因子受体2关系研究

目的:探讨超声收缩期峰值血流速度(PSV)、阻力指数(RI)与乳腺癌组织中Survivin、基质金属蛋白酶-11(MMP-11)、人类表皮生长因子受体2(HER2)的关系。方法:选取60例乳腺癌患者作为观察组,另选择同期60例乳腺良性病变患者作为对照组。均行手术治疗,术前经超声检测,比较两组患者术前RI值、PSV值,免疫组化法检测术后癌组织中Survivin、MMP-11、HER2的表达,分析Survivin、MMP-11、HER2表达与超声RI、PSV值的关系。结果:观察组RI、PSV值高于对照组(均P<0.05)。观察组癌组织中Survivin、MMP-11、HER2表达阳性率高于对照组(均P<0.05)。不同病灶直径、临床分期患者RI、PSV值,不同病灶直径、临床分期及是否淋巴结转移患者癌组织中Survivin、MMP-11、HER2表达比较,差异有统计学意义(均P<0.05)。癌组织中Survivin、MMP-11、HER2表达与PSV、RI值呈正相关(均P<0.05)。结论:超声检测RI、PSV值对术前判断乳腺癌有一定价值,RI、PSV值与乳腺癌癌组织Survivin、MMP-11、HER2表达均相关,Survivin、MMP-11、HER2在乳腺癌的发生、发展过程中发挥重要作用。

Do different bariatric surgical procedures influence plasma levels of matrix metalloproteinase-2,-7,and-9 among patients with type 2 diabetes mellitus?

BACKGROUND Bariatric surgery is an efficient strategy for body weight and type 2 diabetes mellitus(T2 DM) management. Abnormal lipid deposition in visceral organs,especially the pancreas and liver, might cause beta-cell dysfunction and insulin resistance. Extracellular matrix(ECM) remodeling allows adipose expansion, and matrix metalloproteinases(MMPs) play essential roles in ECM construction.MMP-2 and MMP-9 are the substrates of MMP-7. Different studies have reported that MMP-2,-7, and-9 increase in patients with obesity and metabolic syndromes or T2 DM and are considered biomarkers in obesity and hyperglycemia patients.AIMTo prospectively investigate whether MMP-2, MMP-7, and MMP-9 differ after two bariatric surgeries: Gastric bypass(GB) and sleeve gastrectomy(SG).METHODS We performed GB in 23 and SG in 19 obese patients with T2 DM. We measured body weight, waist circumference, body mass index(BMI), and serum concentrations of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood sugar(FBS),hemoglobin A1 c(Hb A1 c), C-peptide, homeostasis model assessments of insulin resistance, and MMP-2, MMP-7, and MMP-9 levels at baseline and at 3, 12, and 24 mo post-operation.RESULTS Twenty-three patients aged 44.7 ± 9.7 years underwent GB, and 19 patients aged40.1 ± 9.1 years underwent SG. In the GB group, BMI decreased from 30.3 ± 3.4 to24.4 ± 2.4 kg/m2, Hb A1 c decreased from 9.2% ± 1.5% to 6.7% ± 1.4%, and FBS decreased from 171.6 ± 65.0 mg/d L to 117.7 ± 37.5 mg/d L 2 years post-operation(P < 0.001). However, the MMP-2, MMP-7, and MMP-9 levels pre-and post-GB were similar even 2 years post-operation(P = 0.107, 0.258, and 0.466,respectively). The SG group revealed similar results: BMI decreased from 36.2 ±5.1 to 26.9 ± 4.7 kg/m2, Hb A1 c decreased from 7.9% ± 1.7% to 5.8% ± 0.6%, and FBS decreased from 138.3 ± 55.6 mg/d L to 95.1 ± 3.1 mg/d L(P < 0.001). The serum MMP-2,-7, and-9 levels pre-and post-SG were not different(P = 0.083,0.869, and 0.1, respectively).CONCLUSION Improvements in obesity and T2 DM induced by bariatric surgery might be the result of MMP-2,-7, or-9 independent pathways.

Correlation of RECK with Matrix Metalloproteinase-2 in Regulation of Trophoblast Invasion of Early Pregnancy

To study the role of the reversion-inducing-cysteine-rich protein with Kazal motifs （RECK） gene and matrix metalloproteinase-2 （MMP-2） in the regulation of trophoblast invasion of early pregnancy. Immunohistochemistry, Western blot and gelatin zymography were used to detect the RECK protein expression localization, expression level and MMP-2 activation level in the placental tissues harvested from 52 normal pregnant women （27 in the early pregnancy, 25 in the term pregnancy）. Immunohistochemistry showed that RECK expression was found both in villous tissues of early pregnancy group and term pregnancy group and was mainly observed in cell membrane and cytoplasm of cytotrophoblasts and syneytiotrophoblasts. RECK expression increased with gestational time. RECK expression of early pregnancy group was significantly lower than that of term pregnancy group （P〈0.05）. RECK expression was significantly lower in cellular column （CC） with invasion ability. Western blot showed that the RECK protein expression in early pregnancy group was significantly lower than that in term pregnancy （P〈0.05）. The optical density values of RECK protein expression in early pregnancy group and term pregnancy group were 1.35±0.14 and 2.68±0.26, respectively, while MMP-2 activation ratio was contrary to RECK protein expression and decreased with the gestation time （P〈0.01）. The MMP-2 activation ratios of early pregnancy group and term pregnancy group were 0.46±0.05 and 0.10±0.02, respectively. The expression of the tumor inhibitory gene RECK was positively related with the invasion ability of trophoblasts, while the invasion gene MMP-2 was negatively related with the ability. The interaction between RECK and MMP-2 may play an important role in the regulation of the trophoblast invasion in early pregnancy.

2型糖尿病患者血清巨噬细胞炎症蛋白1α和基质金属蛋白酶9水平与甲状腺结节的相关性研究

目的探讨2型糖尿病(T_(2)DM)患者血清巨噬细胞炎症蛋白1α(MIP-1α)、基质金属蛋白酶9(MMP-9)水平与甲状腺结节的相关性。方法回顾性选取2021年10月至2023年3月于河北医科大学第三医院就诊的T_(2)DM患者154例,根据患者是否合并甲状腺结节分为甲状腺结节组(83例)和无甲状腺结节组(71例)。比较2组甲状腺功能、血糖、血脂、MIP-1α、MMP-9等指标。采用Logistic回归模型分析影响T_(2)DM患者出现甲状腺结节的因素;采用Pearson相关性检验分析T_(2)DM患者血清MIP-1α、MMP-9水平与其他因素的相关性;绘制受试者工作特征曲线分析血清MIP-1α、MMP-9水平对T_(2)DM患者出现甲状腺结节的预测价值。结果甲状腺结节组促甲状腺激素(TSH)、总三碘甲状腺原氨酸(TT_(3))、总甲状腺素(TT_(4))、稳态模型胰岛素抵抗指数(HOMA-IR)、稳态模型胰岛β细胞功能指数、空腹血糖、空腹胰岛素水平均高于无甲状腺结节组,胰岛素敏感指数(ISI)低于无甲状腺结节组(均P<0.05)。甲状腺结节组血清MIP-1α、MMP-9水平均高于无甲状腺结节组[(29±5)ng/L比(25±5)ng/L、(2.0±0.5)ng/L比(1.4±0.5)ng/L](均P<0.001)。Logistic回归分析结果显示,MIP-1α、MMP-9、TSH、TT_(3)、TT_(4)、空腹胰岛素、HOMA-IR和ISI均为T_(2)DM患者出现甲状腺结节的危险因素(均P<0.05)。Pearson相关性分析结果表明,T_(2)DM患者血清MIP-1α与MMP-9水平呈正相关(r=0.362,P<0.001)。血清MIP-1α、MMP-9水平与空腹胰岛素、TSH、HOMA-IR、TT_(3)、TT_(4)均呈正相关,与ISI呈负相关(均P<0.001)。MIP-1α、MMP-9水平联合检测预测T_(2)DM患者出现甲状腺结节的曲线下面积大于MIP-1α、MMP-9单独检测(均P<0.05)。结论血清MIP-1α、MMP-9水平与T_(2)DM患者出现甲状腺结节具有密切关系,对预测T_(2)DM患者甲状腺结节具有重要价值。

A single nucleotide polymorphism in the matrix metalloproteinase 2 promoter is closely associated with high risk of nasopharyngeal carcinoma in Cantonese from southern China

Matrix metalloproteinase 2(MMP2) has been shown to play an important role in several steps of cancer development.The-1306C/T polymorphism of the MMP2 gene displays a strikingly lower promoter activity than the T allele,and the CC genotype in the MMP2 promoter has been reported to associate with the development of several cancers.To assess the contribution of the MMP2-1306C/T polymorphism to the risk of nasopharyngeal carcinoma(NPC),we conducted a case-control study and analyzed MMP2 genotypes in 370 patients with NPC and 390 frequency-matched controls using real-time PCR-based TaqMan allele analysis.We found that subjects with the CC genotype had an increased risk(OR = 1.55,95% CI = 1.05-2.27) of developing NPC compared to those with the CT or TT genotypes.Furthermore,we found that the risk of NPC was markedly increased in subjects who were smokers(OR = 15.04,95% CI = 6.65-33.99),heavy smokers who smoked ≥20 pack-years(OR = 18.66,95% CI = 7.67-45.38),or young(<60 years) at diagnosis(OR = 1.52,95% CI = 1.01-2.29).Our results provide molecular epidemiological evidence that the MMP2-1306C/T promoter polymorphism is associated with NPC risk,and this association is especially noteworthy in heavy smokers.