EXPRESSION OF MATRIX METALLOPROTEINASE-7 AND FAS LIGAND: THEIR APOPTOSIS-INDUCING EFFECT ON GASTRIC CANCER CELLS

Objective: To investigate the expression of matrix metalloproteinase-7 (MMP-7) and Fas ligand (FasL) in gastric cancer and explore their role in progression of gastric cancer. Methods: Formalin-fixed paraffin and embedded tissues of primary gastric cancer and adjacent non-tumor mucosa from 113 cases were evaluated for MMP-7, FasL and Capase-3 expression by streptavidin-peroxidase (S-P) immunohistochemistry. The expression of the first two proteins in cancer cells of primary foci was compared with clinicopathological parameters of tumors. We also observed the correlation of MMP-7 and FasL expression with Caspase-3 expression in cancer cells of primary foci. Results: MMP-7 positive immunostaining was less frequently detected in adjacent epithelial cells than in cancer cells of primary foci of gastric cancer (P<0.05, 29.2% vs 69.0%), and so was FasL (P<0.05, 34.5% vs 54.0%). MMP-7 expression was associated with tumor size, Borrmann抯 classification, invasive depth, metastasis and TNM staging (P<0.05), but not with growth pattern, Lauren抯 classification, or histological classification (P>0.05). FasL expression was correlated with tumor size, invasive depth, metastasis, Lauren抯 classification, histological classification (P<0.05), while not with Borrmann抯 classification, TNM staging or growth pattern (P>0.05). Cancer cells of primary foci expressed less Caspase-3 than their adjacent epithelial cells (P<0.05, 32.7% vs 50.4%). There was an obvious correlation between FasL, MMP-7 and Caspase-3 expression in cancer cells of primary foci (P<0.05). Co-expression of MMP-7 and FasL paralleled with Caspase-3 expression in cancer cells of primary foci (P<0.05). Conclusion: MMP-7 and FasL expression was up-regulated in gastric carcinogenesis and was principally involved in progression of gastric cancer. FasL expression could reflect the differentiation of gastric cancer cells and underlie the molecular mechanisms of different pathways of gastric tumorigenesis. Co-expression of MMP-7 and FasL could have apoptosis-inducing effect on gastric cancer cells.

血清C反应蛋白与白蛋白比值、尿基质金属蛋白-7及微量白蛋白对髋关节置换术后假体感染的预测价值

目的:分析血清C反应蛋白与白蛋白比值(CRP/ALB)、尿基质金属蛋白-7(MMP-7)及微量白蛋白(MA)对髋关节置换术后假体感染的预测价值。方法:纳入髋关节置换手术患者共187例为研究对象,随访患者90 d的感染情况,其中28例术后假体感染患者设为感染组,159例未感染患者设为对照组。对2组患者资料进行单因素分析,对有统计学意义的因素行Logistic多因素分析,分析髋关节置换术后假体感染的危险因素,并分析CRP/ALB、MMP-7、MA对髋关节置换术后假体感染的预测价值。结果:感染组患者BMI水平、患部手术史发生率、手术时间、术后第1天引流量、术后总引流量、住院时间、激素使用史发生率、低蛋白血症、贫血、白细胞尿、C反应蛋白(CRP)水平、CRP/ALB水平、MMP-7水平、MA水平、免疫抑制剂使用史发生率均高于对照组,差异有统计学意义(P<0.05);Logistic分析结果显示,CRP/ALB≥2.5、MMP-7≥22μg·g^(-1)、MA≥15 mg·L^(-1)均为髋关节置换术后假体感染的危险因素(P<0.05);CRP/ALB、MMP-7、MA对髋关节置换术后假体感染均有一定的预测价值,但三项联合的预测价值高于其他单项预测。结论:CRP/ALB≥2.5、MMP-7≥22μg·g^(-1)、MA≥15 mg·L^(-1)均为髋关节置换术后假体感染的危险因素,且三者联合应用对髋关节置换术后假体感染有较佳的预测价值。

Expression of Matrix Metalloproteinase-7 in Serous Ovarian Tumors

Objective:To explore the expression of matrix metalloproteinase-7 in serous ovarian tumors. Methods: Expression of MMP- 1 in 6 normal ovaries, 12 serous cystadenomas of ovary, 6 borderline cystadenomas of ovary, and 22 serous cystadenocarcinomas of ovary were studied by immunohistoc/temical SP staining. Results: No expression of MMP- 1 was detected in normal ovaries. In most serous ovarian tumors, expression of MMP-7 was detected in both the cytoplasm of tumor cells and stroma, although it was reported in other tumors that MMP- 7 was mainly expressed in the cytoplasm of tumor cells. The expression level of MMP-7 in the cytoplasm of tumor cells was statistically insignificant between serous cystadenomas of ovary, borderline cystadenomas of ovary, and serous cystadenocarcinomas of ovary. But in the stroma, the expression level of MMP-7 in borderline cystadenomas of ovary and serous cystadenocarcinomas of ovary was significantly higher than that in serous cystadenomas of ovary (P<0. 05). In borderline cystadenomas and serous cystadenocarcinomas of ovary, expression of MMP-7 could also be detected in the nuclei of some tumor cells. Conclusion: MMP-7 may play an important role in the progression of serous ovarian tumors.

小鼠基质重塑相关7(MXRA7)基因产物在肝内互作蛋白质的鉴定（英文）

基质重塑相关7(matrix remodeling associated 7,MXRA7)基因于2002年被命名,但无论在人类或其他动物体系,该基因或其蛋白质产物的功能均未知。直至我们最近的研究表明,该基因可能参与眼睛发育或肝损伤及修复。在本研究中,应用酵母双杂交策略,用小鼠MXRA7诱饵载体对小鼠肝cDNA文库进行筛选,发现23种蛋白质(MUP1, Cpt1a, Mat1a, aldh1l1, Cytb, H2-K1, Psmb1, marc2, Atp5j2, Sec24D, Trf, Rdh7, Apoe, Glud1, Gmfb, Alb, Hdlbp, Pzp, Etnk2, Nrn1, Serpina1a, Apoa2, GNMT)可能直接或间接地与MXRA7蛋白发生相互作用。其中,主要尿蛋白1(major urinary protein,MUP1)或其同家族蛋白质占所有候选克隆的1/6,提示其很可能是小鼠肝内与MXRA7蛋白有较强相互作用的蛋白质。通过基因重组在Hepa 1-6肝癌细胞系中同时过表达MXRA7和MUP1蛋白,荧光染色证明这两种蛋白质在细胞内共定位,应用抗MXRA7或MUP1的抗体进行Pull-down检测,则证明二者共同存在于细胞裂解液中。另外,重组MXRA7蛋白和MUP1蛋白在无任何其他蛋白质的缓冲液体系中直接形成复合体。因此,至少在小鼠肝组织体系中,MXRA7蛋白可能通过与MUP1等蛋白质的相互作用而发挥作用。

Prospective study of MMP7 serum levels in the diagnosis of cholangiocarcinoma

AIM: To determine whether the serum level of matrix metalloproteinase-7 (MMP7) has the potential to diagnosis cholangiocarcinoma from benign biliary tract diseases. METHODS: This study was performed according to the PRoBE (a prospective-specimen-collection, retrospectiveblinded-evaluation) design. A total of 187 patients with obstructive jaundice were consecutively enrolled. After the diagnostic status of these patients was ascertained, their levels of serum MMP7 were assayed and compared with serum carbohydrate antigen 19-9 (CA19-9). This was conducted in a blinded case (cholangiocarcinoma)control (benign biliary tract disease) setup. RESULTS: MMP7 and CA19-9 serum levels were significantly elevated in cholangiocarcinoma patients (P < 0.001). The area under the curve (AUC) from a receiver operating characteristic (ROC) curve analysis for thediagnosis of cholangiocarcinoma, using MMP7 was more accurate than CA19-9 (AUC = 0.84, 95% CI: 0.778-0.903 for MMP7 and AUC = 0.79, 95% CI: 0.708-0.868 for CA19-9). The sensitivity and specificity of serum MMP7 (cut-off value of 5.5 ng/mL) was 75% and 78%, respectively, while the sensitivity and specificity of serum CA19-9 (cut-off value of 100 U/mL) was 68% and 87%, respectively. CONCLUSION: Serum values of MMP7 and CA19-9 appear to be useful biomarkers for differentiating cholangiocarcinoma from benign biliary tract obstructive diseases.

Pygopus 2 promotes kidney cancer OS-RC-2 cells proliferation and invasion in vitro and in vivo

Objective:Human Pygopus 2(Pygo2)was recently discovered to be a component of the Wnt signaling pathway required for b-catenin/Tcf-mediated transcription.But the role of Pygo2 in malignant cell proliferation and invasion has not yet been determined.Methods:Lentivirus-mediated small interfering RNA(siRNA)and vector-based overexpression were used to study the function of Pygo2 in OS-RC-2 cells.The resulted cells were subject to Western blotting assay,MTT assay,colony formation and cell invasion assays.Furthermore,renal cell carcinoma(RCC)models were established in BALB/c nude mice inoculated with OS-RC-2 cells.Immunohistochemistry(IHC)staining of matrix metalloproteinase-7(MMP-7),matrix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF)was performed in tumor tissue.Results:Pygo2 gene was successful knocked down and overexpressed in RCC OS-RC-2 cells by using an shRNA and overexpressing vector,respectively.Overexpression of Pygo2 effectively promoted cell proliferation,colony formation and invasion in vitro.Knockdown of Pygo2 obviously inhibited xenograft tumor growth in nude mice.In addition,overexpression of Pygo2 increased the levels of MMP-7,MMP-9 and VEGF in the xenograft tumors.Conclusion:Pygo2 has a role in promoting cell proliferation,invasion and metastasis,and may regulate angiogenesis via the Wnt/b-catenin signaling pathway.

血清C反应蛋白与白蛋白比值、尿基质金属蛋白-7及微量白蛋白与上尿路结石术后感染的关系

目的探讨血清C反应蛋白(CRP)与白蛋白(Alb)比值(CRP/Alb)、尿基质金属蛋白-7(MMP-7)及微量白蛋白(mAlb)与上尿路结石输尿管软镜碎石术(FUL)后感染的关系及预测价值。方法选取2021年10月至2022年10月郑州大学第一附属医院FUL术后发生尿路感染的上尿路结石患者54例,作为研究组,另选同期、同年龄段FUL术后未发生尿路感染的上尿路结石患者54例,作为对照组。比较两组一般资料、手术前后血清常规炎性因子[降钙素原(PCT)、白细胞介素-6(IL-6)]、CRP/Alb水平及尿MMP-7、mAlb水平,分析研究组血清CRP/Alb、尿MMP-7、mAlb与常规炎性因子的相关性,并比较不同感染程度患者手术前后血清CRP/Alb水平及尿MMP-7、mAlb水平,分析血清CRP/Alb水平及尿MMP-7、mAlb水平与感染程度的相关性,及预测FUL术后尿路感染的价值,并与血清常规炎性因子预测价值进行比较,采用Spearman/Pearson相关系数分析研究组术后血清CRP/Alb、尿MMP-7、mAlb与常规炎性因子、感染程度的相关性。结果研究组术后血清CRP/Alb、尿MMP-7、mAlb及血清PCT、IL-6水平均高于对照组[(3.20±0.51)、(72.18±16.94)pg/ml、(70.86±14.63)mg/L、(3.28±0.89)ng/ml、(75.19±15.63)ng/L比(1.86±0.45)、(48.61±11.50)pg/ml、(55.43±11.59)mg/L、(1.22±0.37)ng/ml、(24.17±6.17)ng/L,P<0.05];研究组术后血清CRP/Alb、尿MMP-7、mAlb水平与血清PCT(r=0.512、0.467、0.398)、IL-6(r=0.608、0.551、0.473)水平均呈正相关(P<0.05);重度感染患者术后血清CRP/Alb及尿MMP-7、mAlb水平均高于中度感染、轻度感染患者[(3.97±0.55)、(87.71±16.29)pg/ml、(81.72±14.55)mg/L比(3.39±0.52)、(73.26±15.75)pg/ml、(71.42±13.76)mg/L和(2.46±0.49)、(59.47±13.88)pg/ml、(62.13±12.53)mg/L](P<0.05),中度感染患者均高于轻度感染患者[(3.39±0.52)、(73.26±15.75)pg/ml、(71.42±13.76)mg/L比(2.46±0.49)、(59.47±13.88)pg/ml、(62.13±12.53)mg/L,P<0.05];研究组术后血清CRP/Alb、尿MMP-7、mAlb水平与感染程度呈正相关(r=0.751、0.756、0.723,P<0.05);术后血清CRP/Alb、尿MMP-7、mAlb预测FUL术后尿路感染的曲线下面积(AUC)分别为0.804、0.784、0.848,血清CRP/Alb、尿MMP-7、mAlb联合预测的AUC为0.952,大于血清PCT、IL-6联合预测的AUC(P<0.05)。结论上尿路结石FUL术后发生尿路感染患者术后早期血清CRP/Alb水平及尿MMP-7、mAlb水平在预测术后尿路感染发生风险方面具有较高预测效能。

血清基质金属蛋白酶7与膀胱癌的诊断及预后关系分析

目的探讨血清基质金属蛋白酶7（matrix metalloproteinase-7，MMP-7）检测在膀胱癌诊断和预后中的意义。方法选取77例膀胱癌患者和65例健康体检人群为研究对象。用ELISA方法测定血清MMP-7的水平。结果膀胱癌组血清MMP-7水平高于正常对照组[3．1（0-32．1）ng／ml vs 1．0（0.2-2．6）ng／ml，X^2=9．29，P=0．0023]；膀胱癌患者血清MMP-7水平与淋巴结转移（X^2=10．49，P〈0．01）和病理分期（X^2=4．55，P=0．033）有关。血清MMP-7水平的ROC曲线下面积为0．810，诊断膀胱癌的灵敏度为83．6％，特异度为77．4％。高MMP-7水平的膀胱癌患者的生存率显著低于低MMP-7水平的膀胱癌患者（X^2=3．88，P=0．0488）。结论MMP-7可能与膀胱癌的发生、发展和转移有关，血清MMP-7是膀胱癌的良好的诊断与预后指标。

压力性尿失禁患者盆底组织中MMP-7与TIMP-3的表达研究

目的:探讨女性压力性尿失禁(SUI)患者阴道壁结缔组织中基质金属蛋白酶-7(MMP-7)和基质金属蛋白酶组织抑制物-3(TIMP-3)的表达与SUI发病的关系。方法:30例有完整随访资料的女性SUI患者的阴道壁结缔组织标本为研究组(SUI组),30例有完整随访资料的女性POP患者的阴道壁结缔组织标本为研究对照组(POP组),30例无SUI和POP妇女为对照组,分别染色显示MMP-7和TIMP-3表达的情况。结果:SUI组患者的MMP-7均较对照组显著升高,差异有统计学意义(P<0.05),TIMP-3显著下降,差异有统计学意义(P<0.05)。MMP-7与TIMP-3在A组和B组之间的差异无统计学意义(P>0.05)。结论:MMP-7升高对胶原纤维的降解增加,TIMP-3下降对胶原纤维降解的抑制作用减弱,使得总体上对胶原纤维的降解增强,导致组织弹性降低,可能在SUI的发生过程中起重要作用。

肾结石术后尿路感染Wnt/β-catenin通路基因和MMP-7表达

目的探讨肾结石术后尿路感染Wnt/β-catenin通路基因和基质金属蛋白-7(MMP-7)的表达。方法选择儋州市人民医院泌尿外科2018年1月-2020年1月收治肾结石经皮肾镜取石术(PCNL)术后尿路感染患者62例作为感染组,同期医院肾结石PCNL术后未发生尿路感染的患者60例作为非感染组。采用实时荧光定量聚合酶链式法对两组患者外周血Wnt/β-catenin通路基因Wnt1、β-catenin相对表达水平进行检测,采用酶联免疫吸附法检测患者尿中MMP-7水平,分析尿MMP-7对于肾结石术后尿路感染的诊断价值。结果62例尿液标本共检出病原菌60株,其中革兰阴性菌42株,占70.00%,革兰阳性菌16株,占26.67%,真菌2株,占3.33%,大肠埃希菌检出率最高,共26株,占43.33%;感染组血液Wnt-1、β-catenin在mRNA上的相对表达及尿MMP-7表达水平高于非感染组(P<0.05);重度感染组Wnt-1、β-catenin、MMP-7水平高于中度感染组及轻度感染组,中度感染组Wnt-1、β-catenin、MMP-7水平高于轻度感染组(P<0.05);受试者工作特征曲线(ROC)分析结果表明,尿中MMP-7水平对于肾结石患者术后尿路感染诊断曲线下面积为0.773,P=0.002。结论肾结石术后尿路感染以大肠埃希菌为主,病原可能通过Wnt/β-catenin通路及MMP-7通路引发感染,尿MMP-7水平对其具有良好的诊断价值。

Effects of Weipixiao(胃痞消)on Wnt Pathway-Associated Proteins in Gastric Mucosal Epithelial Cells from Rats with Gastric Precancerous Lesions*

Objective： To study the effects of Weipixiao （胃痞消, WPX） on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions （GPL）. Methods： Sprague Dawley rats were randomly divided into control, model, vitacoenzyme （0.2 g·kg-l·day-1）, WPX high-dose （H-WPX, 15 g·kg-l·day-1）, WPX medium-dose （M-WPX, 7.5 g·kg-1·day-1） and WPX low-dose （L-WPX, 3.75 g·kg-l·day-1） groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-protein- coupled receptor 5 （Lgr5）, matrix metalloproteinase-7 （MMP-7）, Wntl, Wnt3a, and 13 -catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software. Results： Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wntl, Wnt3a and 13 -catenin than those of the control group （P〈0.01）. Interestingly, we also observed Lgr5＋ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wntl, and 13-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups （P〈0.05）. A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups （P〉0.05）. Conclusion： Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wntl, β -catenin and the aberrant activation of Wnt/β -catenin pathway.