This paper reports the results of 24 cases of bone defect resulting from bone tumor or tumor condition excision, and of posterior spinal fusion, treated by human bone matrix gelatin. The success rate of bone defect re...This paper reports the results of 24 cases of bone defect resulting from bone tumor or tumor condition excision, and of posterior spinal fusion, treated by human bone matrix gelatin. The success rate of bone defect repair and spinal fusion is 91. 67 %. The results suggest that human bone matrix gelatin has. excellent osteoinductive effect and is ideal substitute for bone autografts.展开更多
AIM: To establish a novel, sensitive and high-throughput gelatinolytic assay to define new inhibitors and compare domain deletion mutants of gelatinase B/matrix metalloproteinase (MMP)-9. METHODS: Fluorogenic Dye-quen...AIM: To establish a novel, sensitive and high-throughput gelatinolytic assay to define new inhibitors and compare domain deletion mutants of gelatinase B/matrix metalloproteinase (MMP)-9. METHODS: Fluorogenic Dye-quenched (DQ)TM-gelatin was used as a substrate and biochemical parameters (substrate and enzyme concentrations, DMSO solvent concentrations) were optimized to establish a highthroughput assay system. Various small-sized libraries (ChemDiv, InterBioScreen and ChemBridge) of hetero-cyclic, drug-like substances were tested and compared with prototypic inhibitors. RESULTS: First, we designed a test system with gelatin as a natural substrate. Second, the assay was validated by selecting a novel pyrimidine-2,4,6-trione (barbitu- rate) inhibitor. Third, and in line with present structural data on collagenolysis, it was found that deletion of the O-glycosylated region significantly decreased gelatinolytic activity (kcat/kM ± 40% less than full-length MMP-9). CONCLUSION: The DQTM-gelatin assay is useful in high-throughput drug screening and exosite targeting. We demonstrate that flexibility between the catalytic and hemopexin domain is functionally critical for gelatinolysis.展开更多
Objective To investigate whether the calcium channel blocker amlodipine could inhibit macrophage matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expression and secretion. Methods Peritoneal m...Objective To investigate whether the calcium channel blocker amlodipine could inhibit macrophage matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expression and secretion. Methods Peritoneal macrophages were isolated from BALB/C mice and incubated with low (5μg/L ), middle (15μg/L) and high (305μg/L) concentrations of amlodipine, or in the medium alone (controls) for 24 hours, and the expression and secretion of MMP-2 and MM-9 of the cells were analyzed by RT-PCR and gelatin zymography. Results Compared with controls, amlodipine at low concentration had no significant effects on the expression and secretion of either MMP-2 and MMP-9 (P>0.05) at middle concentrationit it could inhibited MMP-2 and MMP-9 expressions completely and significantly reduced the secretion of MMP-9 (P<0.05); but it had no effect on the secretion of MMP-2. At high concentration it also inhibited MMP-2 and MMP-9 expression completely. Conclusion Amlodipine at 15 ig/L inhibited the expression of MMP-2 and MMP-9 and reduced the secretion of MMP-9, suggesting that amlodipine may stabilize atherosclerotic plaque.展开更多
文摘This paper reports the results of 24 cases of bone defect resulting from bone tumor or tumor condition excision, and of posterior spinal fusion, treated by human bone matrix gelatin. The success rate of bone defect repair and spinal fusion is 91. 67 %. The results suggest that human bone matrix gelatin has. excellent osteoinductive effect and is ideal substitute for bone autografts.
基金Supported by A postdoctoral fellowship (Van den Steen PE) and a research assistantship (Geurts N) of the Fund for Scientific Research,Belgium (FWO-Vlaanderen)
文摘AIM: To establish a novel, sensitive and high-throughput gelatinolytic assay to define new inhibitors and compare domain deletion mutants of gelatinase B/matrix metalloproteinase (MMP)-9. METHODS: Fluorogenic Dye-quenched (DQ)TM-gelatin was used as a substrate and biochemical parameters (substrate and enzyme concentrations, DMSO solvent concentrations) were optimized to establish a highthroughput assay system. Various small-sized libraries (ChemDiv, InterBioScreen and ChemBridge) of hetero-cyclic, drug-like substances were tested and compared with prototypic inhibitors. RESULTS: First, we designed a test system with gelatin as a natural substrate. Second, the assay was validated by selecting a novel pyrimidine-2,4,6-trione (barbitu- rate) inhibitor. Third, and in line with present structural data on collagenolysis, it was found that deletion of the O-glycosylated region significantly decreased gelatinolytic activity (kcat/kM ± 40% less than full-length MMP-9). CONCLUSION: The DQTM-gelatin assay is useful in high-throughput drug screening and exosite targeting. We demonstrate that flexibility between the catalytic and hemopexin domain is functionally critical for gelatinolysis.
文摘Objective To investigate whether the calcium channel blocker amlodipine could inhibit macrophage matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expression and secretion. Methods Peritoneal macrophages were isolated from BALB/C mice and incubated with low (5μg/L ), middle (15μg/L) and high (305μg/L) concentrations of amlodipine, or in the medium alone (controls) for 24 hours, and the expression and secretion of MMP-2 and MM-9 of the cells were analyzed by RT-PCR and gelatin zymography. Results Compared with controls, amlodipine at low concentration had no significant effects on the expression and secretion of either MMP-2 and MMP-9 (P>0.05) at middle concentrationit it could inhibited MMP-2 and MMP-9 expressions completely and significantly reduced the secretion of MMP-9 (P<0.05); but it had no effect on the secretion of MMP-2. At high concentration it also inhibited MMP-2 and MMP-9 expression completely. Conclusion Amlodipine at 15 ig/L inhibited the expression of MMP-2 and MMP-9 and reduced the secretion of MMP-9, suggesting that amlodipine may stabilize atherosclerotic plaque.
