Objective To explore the expression of matrix metalloproteinase （MMP）-2 in patients with papillary thyroid cancer （PTC） recurrence or residuum and its value of clinical application. Methods The serums from 68 patients with thyroid disease underwent operation and 15 health examinations under stomachs empty from March 2009 to December2009 in this hospital were gathered. Sixty-eight patients with thyroid disease were divided into PTC with lymph node metastasis （LNM） group （n=19），PTC recurrence or residuum with LNM group （n=17），PTC without LNM group （n=10），and benign thyroid disease group （n=22） according to the postoperative pathological findings，15 health examinations as control group. The expression of MMP-2 of serum sample was detected by ELISA method. The difference of the expression of MMP-2 in each group was analyzed. Results The expressions of MMP-2 in the PTC recurrence or residuum with LNM group，PTC with LNM group，PTC without LNM group， benign thyroid disease group，and the control group were （1 724.00±762.24） ng/ml，（1 329.16±776.59） ng/ml，（1 489.61±546.53） ng/ml，（1 264.87±817.27） ng/ml，and （608.43±88.63） ng/ml，respectively. The expressions of MMP-2 in the PTC with LNM group and PTC recurrence or residuum with LNM group were significantly higher than those in the benign thyroid disease group （P＜0.05） and the control group （P＜0.05），respectively，which in the PTC without LNM group was significantly higher than that in the control group （P＜0.05）. There was no significant difference of MMP-2 expression of serum between the benign thyroid disease group and the control group （P＞0.05），which were no significant difference among the other threemalignant disease groups （P＞0.05）. The MMP-2 positive expression rates were 79%，76%，80%，41%，and 20% in the PTC with LNM，PTC recurrence or residue with LNM group，PTC without LNM group，benign thyroid disease group，and control group，respectively. The MMP-2 positive expressions rates of serums were not significantly different among three malignant disease groups （P＞0.05），but which were significantly higher than those of the benign thyroid disease group （P＜0.01） and control group （P＜0.01），respectively. Conclusions The MMP-2 level of serum can be used as an index to judge preoperative thyroid nodules，which can not be use to determine whether PTC metastasis or not.
ObjectiveTo investigate the expression of a disintegrin and metalloproteinase with thrombospondin typeⅠmotif (ADAMTS1) in colorectal cancer tissues, and to study the relationship with clinicopathological features and prognosis of it. MethodsExpression of ADAMTS1 was evaluated by immunohistochemistry (SP method) in 65 specimens, which obtained by resection from patients with colorectal cancer, including corresponding adjacent benign tissues. Chi-square test was used for analyzing the relationship between expression of ADAMTS1 and clinicopathological features of colorectal cancer tissues. Cox proportional hazard model was used to explore the relationship between expression of ADAMTS1, other clinicopathological parameters, and patients' survival situation. ResultsThe positive expression rate of ADAMTS1 was 40% (26/65) in the colorectal cancer tissues and 85% (55/65) in the adjacent benign tissues, which was significantly higher in adjacent benign tissues (χ2=27.546, P < 0.001). The positive expression rate of ADAMTS1 was significantly lower in the colorectal cancer tissues with lymph node metastasis than that of the colorectal cancer without lymph node metastasis (χ2=5.329, P=0.021). Results of survival analysis showed that median survival time were 27 months in the ADAMTS1-negative group and 70 months in the ADAMTS1-positive group respectively, and the survival situation was better in latter group (χ2=10.151, P=0.001). Results of multivariable prognostic analysis of Cox proportional hazard model showed that colorectal cancer withⅠ-Ⅱstage (RR=3.782, 95% CI:1.509-9.476, P=0.005), without lymph node metastasis (RR=3.107, 95% CI:1.186-8.138, P=0.021), and with positive-expression of ADAMTS1 (RR=2.020, 95% CI:1.071-3.809, P=0.030) had better survival situation. ConclusionsExpression of ADAMTS1 is down-regulated in colorectal cancer tissues and it is associated with lymph node metastasis. The prognosis of patients in ADAMTS1-positive group is better than that of ADAMTS1-negative group, suggesting that ADAMTS1 may be an independent prognostic factor in colorectal cancer.
Objective To investigate the expression of matrix metallo proteinase (MMP)-2 and MMP-9 in rats′optical nerves after extrusion wound. Methods We set up the model of rats with extrusion wound of the optical nerves, detected activity changes of MMP-2 and MMP-9 in the optical nerves by gelatin zymography, identified the attribute by Western blotting, and verified the expression of mRNA of MMP-2 and MMP-9 by reverse transcriptase-polymerase chain reaction (RT-PCR ). Results MMP-2 existed in normal optial nerves and optical nerves with extrusion wound, while MMP-9 was only detected in the latter. The expression of MMP-9 was the highest 1 day after the extrusion wound, while that of MMP-2 was the highest 7 days after the extrusion wound. Conclusions MMP-2 and MMP-9 may participate in the pathological recovery process of optical nerves after extrusion wound. The glial cells in the optical nerves may be one of the sources of MMP-2 and MMP-9. (Chin J Ocul Fundus Dis，2003，19：269-332)
Objective To investigate the plasma levels of soluble Fas receptor ( sFas) , soluble Fas ligand ( sFas-L) and matrix metalloproteinase-7 ( MMP-7) and their correlation with disease severity as well as the prognosis of septic patients.Methods The plasma levels of sFas, sFas-L, sFas / sFas-L ratio and MMP-7 were measured by enzyme-linked immunosorbent assay and compared between32 patients with sepsis and 24 age and sex matched healthy controls. Based on the 28-day outcome, the patients were divided into a survival group and a death group. The difference in sFas, sFas-L, sFas/ sFas-L ratio and MMP-7 between the survival group and the death group were compared.Results Compared with the healthy control group, the concentration of plasma sFas, sFas-L and MMP-7 were significantly increased in the septic patients ( P lt; 0. 01) . Elevated plasma sFas and sFas-L were both positive correlated with the APACHEⅡ score and SOFA score. Although a modest negative correlation was found between plasma MMP-7 and APACHEⅡ score and SOFA score, but this correlation did not reach statistical significance ( P gt;0. 05) . The septic patients who died had significantly higher sFas-L level and lower sFas / sFas-L ratio as compared with those who survived ( P lt;0. 05) . Conclusion Plasma sFas, sFas-L and MMP-7 are associated with the disease severity and can serve as potential markers for predicting the outcome in septic patients.
Objective To measure the level of circulating endothelial progenitor cells ( EPCs) in peripheral blood of patients with acute exacerbation of chronic obstructive pulmonary disease ( AECOPD) , and to explore the relationship between EPCs and severity markers of the disease and cardiovascular adverse outcome predictors.Methods Forty patients with COPD were recruited, including 27 at acute exacerbation phase and 13 with stable COPD from December 2010 to December 2011. Sixteen healthy nonsmokers were included as controls. Circulating EPCs were isolated by Ficoll density-gradient centrifugation and purified by Magnetic Activated Cell Sorting system. High-sensitivity C-reactive protein ( hsCRP) was estimated by using a latex immunoturbidimetric assay kit, and matrix metalloproteinase-9 ( MMP-9) was measured by enzymelinked immunosorbent assay ( ELISA) . Arterial blood gas analysis and echocardiograph were performed in the AECOPD patients. The correlations between circulating EPCs, lung function, and cardiovascular markers were investigated. Results Circulating EPCs were significantly lower in AECOPD and stable COPD patients compared with the healthy controls [ ( 5.1 ±2.6) ×103 /mL and ( 6.0 ±3.2) ×103 /mL vs. ( 9.0 ±4.3) × 103 /mL, Plt;0. 05] . EPCs had a weak correlation with hsCRP ( P = 0. 033) , but not with MMP-9. In the AECOPD patients, EPC counts were significantly inversely correlated with PASP ( pulmonary artery systolic pressure) and NT-proBNP ( amino-terminal pro-brain natriuretic peptide) levels, and positively with left ventricular ejection fraction. No correlations were found between EPCs and lung function, blood gas, hospital stays or smoking index. Conclusions Circulating EPCs were significantly lower in AECOPD patients compared with healthy controls, in which systemic inflammation might be involved. Decreased EPCs were correlated with cardiac dysfunction in patients with AECOPD, which may account for the increased cardiovascular risk in this population.
Objective To investigate the effects of heat injured keratinocytes (KC) supernatant on the expressions of collagen type I, collagen type III, and matrix metalloproteinase 1 (MMP-1) of dermal fibroblasts (Fb). Methods KC and Fb were isolated and cultured. Then the models of heat injured KC and Fb were reproduced in vitro, respectively. The heat injured and normal culture supernatant were collected respectively at 12 hours, and formulated as a 50% concentration of cell-conditioned medium. According to the culture medium, Fb at passage 3-5 was divided into 3 groups. Normal Fb was cultured with the conditioned medium containing 50% heat injured KC culture supernatant (group A), the conditioned medium containing 50% normal KC culture supernatant (group B), and DMEM (group C), respectively. The cells in 3 groups were collected at 24 hours. In addition， the cells in group A were collected at 0, 1, 2, 6, 12, 24, and 48 hours， respectively. Normal Fb was cultured with the conditioned medium containing 50% heat injured Fb culture supernatant. Then, the cells were collected at 0, 1, 2, 6, 12, 24, and 48 hours, respectively. The mRNA levels of the collagen type I, collagen type III, and MMP-1 of Fb were measured by real-time fluorescent quantitative PCR techniques. Results At 24 hours after cultured with supernatant of heat injured KC，mRNA relative expression levels of collagen type I, collagen type III, and MMP-1 in group A were significantly higher than those in groups B and C (P lt; 0.05). The mRNA relative expression levels of collagen type I, collagen type III, and MMP-1 in group A gradually increased with time going, showing significant differences between 0 hour and 2, 6, 12, 24, and 48 hours (P lt; 0.05); significant differences were found between different time points after 2 hours (P lt; 0.05). After Fb was treated with supernatant of heat injured Fb, the mRNA relative expression levels of MMP-1 gradually decreased with time going, showing significant differences between 0 hour and 1, 2, 6, 12, 24, and 24 hours (P lt; 0.05); after 2 hours of culture, significant differences were found among different time points (P lt; 0.05). Conclusion Heat injured KC supernatant may regulate the mRNA expressions of collagen type I, collagen type III, and MMP-1 of Fb.
ObjectiveTo investigate the expression of amniotic fluid levels and blood serum levels of matrix metalloproteinases-8 (MMP-8) and interleukin-6 (IL-6) in women with preterm delivery. MethodsBetween January 2010 and December 2012, we collected the amniotic fluid of 102 preterm pregnant women and 98 full term pregnant women and analyzed the MMP-8 levels and IL-6 levels in amniotic fluid and blood serum. Meanwhile, we also collected the amniotic fluid to do bacterial culture. ResultsThe amniotic fluid levels of MMP-8 in preterm pregnant women were higher than those in full term pregnant women [(320.45±59.88) vs (153.72±29.12) ng/mL, P<0.05], but there was no obvious discrepancy in the blood serum levels of MMP-8 in the two groups [(9.56±2.11) vs (9.42±2.01) ng/mL, P>0.05]. Both amniotic fluid levels and blood serum levels of IL-6 in preterm pregnant women were significantly higher than the full term pregnant women [(90.5±16.3] vs (20.6±12.5) μg/L, P<0.05; (159.2±20.4) vs (22.3±11.8) μg/L, P<0.05]. The positive bacterial culture rate of preterm pregnant women was higher than the full term pregnant women (8.8% vs 1.0%, P<0.05). ConclusionInfection is the most important reason for preterm pregnancy. MMP-8 level increases in the amniotic fluid, and the level of IL-6 in amniotic fluid and blood serum is a valuable clinical index for identifying premature delivery.
Objective To transfect bone marrow mesenchymal stem cells (BMSCs) of rats by recombinant adenovirus Ad-human matrix metalloproteinase 1 (hMMP-1) in vitro so as to lay the experimental foundation for the treatment of liver fibrosis with a combination of BMSCs and hMMP-1 gene transplantation. Methods BMSCs were isolated from bone marrow of 2-3 weeks old Sprague Dawley rats by whole bone marrow adherence method and identified, then transfected by recombinant adenovirus Ad-hMMP-1 carrying enhanced green fluorescent protein (EGFP) marker in vitro. The green fluorescent expression was observed by fluorescence microscope and the transfection efficiency was detected by flow cytometry to determine the optimum multiplicity of infection (MOI). BMSCs at passage 3 were divided into 3 groups: untransfected BMSCs group (group A), Ad-EGFP transfected BMSCs group (group B), and Ad-hMMP-1-EGFP transfected BMSCs group (group C); the gene and intracellular protein of hMMP-1 were detected by RT-PCR and Western blot; the ELISA assay was used to detect the supernatant protein expression, and the hMMP-1 activity was measured by fluorescent quantification kit. Results The green fluorescent was observed in BMSCs transfected by recombinant adenovirus at 24 hours after transfection; the fluorescence intensity was highest at 72 hours; and the optimum MOI was 200. The cells of 3 groups entered the logarithmic growth phase on the 3rd day and reached plateau phase on the 6th day by MTT assay; no significant difference was found in the cell proliferation rate among 3 groups (P gt; 0.05). RT-PCR, Western blot, and ELISA assay showed high expressions of the hMMP-1 gene and protein in group C, but no expression in groups A and B. The hMMP-1 activity was 1.24 nmol/(mg · min) in group C, but hMMP-1 activity was not detectable in groups A and B. Conclusion The exogenous hMMP-1 gene is successfully transfected into BMSCs of rats via recombinant adenovirus and can highly express, which lays the experimental foundation for the treatment of liver fibrosis with a combination of BMSCs and hMMP-1 gene transplantation.
Objective To observe the effect of epidermal growth factor (EGF) on the proliferation, adhesion, invasiveness and the activation of nuclear factor-κB (NF-κB), matrix metalloproteinases (MMPs) expression and explore related mechanisms in pancreatic cancer cells. Methods Cell invasion assay, proliferation assay and adhesion assay were used to examine the proliferation, adhesion and invasiveness of pancreatic cancer cells, respectively. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA), and MMPs protein and mRNA expressions were investigated by gelatin zymography, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Results EGF increased the invasiveness of pancreatic cancer cell in a dose-dependent manner (P＜0.05), but did not affect cell proliferation or adhesion. The expressions of MMP-9 mRNA and protein significantly increased after induction by EGF and were highest when EGF concentration was 50 ng/ml, while there was no effect on the expressions of MMP-2 mRNA and protein. Furthermore, NF-κB activity increased with increased concentration of EGF in a concentration-dependent manner (P＜0.05). In addition, NF-κB activity and the expressions of MMP-9 mRNA and protein by pretreatment with both pyrrolidine dithiocarbamate (PDTC) and EGF decreased when compared that by pretreatment with EGF alone. The invasiveness of pancreatic cancer cell by pretreatment with both PDTC and EGF decreased when compared that by pretreatment with EGF alone and nothing (P＜0.05).Conclusion The findings indicate that the NF-κB-mediated MMP-9 induction is essential for EGF-induced invasiveness in pancreatic cancer cells, which can be inhibited by PDTC.
Objectives To study the relationship between matrix metalloproteinase-9 (MMP-9) and hemorrhagic transformation (HT) in ischemic stroke patients and provide evidence for the further clinical studies, thrombolytic therapy selection, and application of MMP inhibitors to clinical practice to extend the windows for thrombolytic therapy. Methods The studies on relationship between MMP-9 and hemorrhagic transformation in ischemic stroke were identified, in which HT was followed-up based on plasma level of MMP-9 or comparison of plasma level of MMP-9 was conducted based on HT or not, regardless of language of publication and type of design. MEDLINE (1966-Jan. 2006), EMBASE (1966-Apr. 2006), CNKI (1977-Feb.2006), and Wanfang database (1989-2005) were searched and the references lists of eligible studies were manually searched. Two reviewers independently evaluated the quality of studies and extracted data. The data were analyzed using the RevMan 4.2. and SPSS11.0 softwares. Results Six trials fulfilled the inclusion criteria, including 558 patients, 130 of them developed hemorrhagic transformation. The heterogeneity between studies was statistically significant; (Plt;0.0001). We didn’t pool the data of studies of plasma MMP-9 level. Most of the studies showed that the plasma MMP-9 level in HT or in a certain type of HT was higher than that in non-HT patients. The result of subgroup analysis showed that the plasma MMP-9 level was independently associated with HT, summary OR=14.45, 95%CI (4.90, 43.65). Conclusions The values of plasma MMP-9 in HT or in a certain type of HT are higher than that in non-HT. MMP-9 may independently be a risk of hemorrhagic transformation. The sample size of the included studies is small. So the conclusions need to be confirmed with further studies.