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Objective To verify the association of a disintegrin and metalloproteinase domain 33 (ADAM33) polymorphisms in childhood asthma susceptibility and severity in patients with moderate and severe asthma.Methods A total of 144 controls and 110 asthmatic patients were recruited for this hospitalbased case-control study.Two polymorphic sites (V4,T2) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method.The gene-gene interactions were analyzed with the multifactor dimensionality reduction (MDR) software.Results The allele frequencies of three SNPs (V4,T2) of ADAM33 in childhood asthma group were significantly higher than control group (P ＜ 0.01,OR =2.36 ～ 2.96,95％ CI:1.56-1.78 ～ 3.56-4.94).For the SNPs V4,GC genotype frequencies of both moderate and severe groups were significantly higher from the control group (P ＜ 0.05) ; the CC genotype frequencies in severe group were significantly higher than control group (P ＜ 0.05) ; the genotype GA of T2 locus in severe group and AA genotype frequencies in moderate group were significantly higher than control group (P ＜0.01 ～0.05) ; there were no significant differences for both allele and genotype frequencies of S2 locus between the childhood asthma and control group (P ＞ 0.05).By MDR analysis,the best interaction model was the four-factor model that the V4,T2 genotypes were the subgroup to predict asthma risk.Conclusions Our results highlight the role of ADAM33 as a susceptibility gene for childhood asthma,and the interactions among ADAM33 V4 and T2 are also associated with childhood asthma.
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Objective To investigate the learning and memory functions,expression changes of disintegrin and metalloprotease 10 (ADAM10) mRNA in hippocampus in the aged rats with chronic cerebral hypoperfusion as well as the effect of atorvastatin on them.Methods A total of 72 rats were randomly divided into sham operation,cerebral hypoperfusion and atorvastatin treatment groups.A permanent bilateral common carotid artery occlusion (2VO)model was induced.Atorvastatin 10 mg/(kg · d) was administered orally after procedure in the atorvastatin treatment group.Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of ADAM10 mRNA in bilateral hippoocampus at 1,2,4,and 16 weeks after modeling,Results Two weeks after modeling,the learning and memory functions were decreased significantly in the cerebral hypoperfusion group compared to the sham operation group (P ＜ 0.05).At 4 and 16 weeks after modeling,they were further decreased (P ＜0.01); there were no significant differences in the learning and memory functions at 1,2,and 3 weeks after modeling between the atorvastatin treatment group and the cerebral hypoperfusion group,however,they were improved significantly at 16 weeks compared to the cerebral hypoperfusion group (P＜0.01).The expression of ADAM10 mRNA in hippocampus at different time points after modeling in the cerebral hypoperfusion group was down-regulated by 22％,43％,35％,and 50％,respectively compared to the sham operation group (all P ＜0.05).The expression of ADAM 10 mRNA in hippocampus at 2 weeks in the atorvastatin treatment group was higher than 22％ in the cerebral hypoperfusion group (P＜0.05).There were not significant differences at other time points.Conelusions Chronic cerebral hypoperfusion results in the down-regulation of the expression of ADAM10 mRNA in hippocampus in the aged rats,and atorvastatin may inhibit down-regulation of the expression of ADAM10 mRNA at early stage.
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Objective To study the effects of hypoxia and reoxygenation on expression of a disintegrin and metalloprotease10(ADAM10),?-amyloid precursor protein cleaving enzyme(BACE1) mRNA in SH-SY5Y cells.Methods SH-SY5Y cells were grouped into hypoxic and control groups.The hypoxic cells were incubated in hypoxic condition(95%N_2,5%CO_2) for 12 hours and 24 hours,and then cells were reoxygenated for 0 hours,12 hours and 24 hours.The expression of ADAM10,BACE1 mRNA were tested respectively at different time points after reoxygenation by RT-PCR.Control groups were incubated in normal conditions,seeded and treated at the same time with the hypoxic cells.Results The expression of ADAM10 mRNA was down-regulated by 19.8%,41.4% and 64.6%(P=0.005,0.038,0.001) at different time after reoxygenation with 12 hours hypoxia and down-regulated by 30.1%,75.9% and 86.5%(P=0.009,0.005,0.043)after reoxygenation with 24 hours hypoxia.The expression of BACE1 mRNA was up-regulated by 31.5% and 35.1%(P=0.028,0.005)only at 12 hours and 24 hours points after reoxygenation with 24 hours hypoxia.Conclusion Hypoxia and reoxygenation might alter the expression of ADAM10 and BACE1,which demonstrates that the vascular factors should make the amyloid precursor protein easy to be processed by ?-secrease pathway,thus to involve the pathology of Alzheimer's disease.
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Objective:To study the effect of endogenous IL-1? on the expression of matrix metalloproteinases (MMPs) and COX2 in dental pulp cells. Methods:Human dental pulp cells were treated with human recombinant IL-1? at 1 nmol/L in serum-free medium for 18 h. Then the cells were collected and total RNA was isolated, MMPs and COX2 mRNA expression was assessed by semiquantitative RT-PCR. Results:IL-1? at 1 nmol/L induced the expression of COX2 and MMP-1 mRNA in human dental pulp cells. Conclusion:IL-1? may contribute to stimulating expression of MMPs and COX2 in the dental pulp during pulpitis.
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AIM: To investigate the ability of Chinese cobra snake venom-metalloproteinase(MT) to induce the histamine release from human mast cells and its potential mechanisms.METHODS: MT was purified from the snake venom by using heparin agarose and Superdex75 chromatography.Mast cells were dispersed from human lung, colon and tonsil tissues after digestion with collagenase and hyaluronidase.The dispersed mast cells were then challenged with MT,stimulus and control in LP4 tubes for 15 min at 37 ℃.A glass fibre-based fluorometric assay was used to measure histamine in the supernatants of dispersed mast cells.RESULTS: MT induced a dose-dependent release of histamine from human colon,lung and tonsil mast cells.As low as 0.03(mg/L) of MT was able to stimulate significant histamine release from human colon mast cells,but a minimum of 0.3 or 30 mg/L of MT was required to stimulate a similar level of histamine release from lung or tonsil mast cells,respectively.The release of histamine from colon and lung mast cells in response to MT was maximized at 12 min following the addition of the stimulus.This was quite different from the picture of the peak histamine release from tonsil mast cells,in which histamine release was maximized at 8 min following the addition of MT.Pretreatment of cells with metabolic inhibitors and pertussis toxin reduced dramatically histamine release from human colon,lung and tonsil mast cells by MT.In exogenous Ca~(2+) and Mg~(2+) free experiments,the release of histamine induced by MT was significantly decreased.CONCLUSION: Cobra snake venom MT induces human mast cells to release histamine through a G-protein-related mechanism,which may contribute to the pathogenesis of venomous snake bite.
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Bone morphogenetic protein-1(BMP-1) and its related molecules are members of metalloendoproteinase astacin family, including BMP-1, mTLD, mTLL-1 and mTLL-2. Even though all of them lack of the ability to induce bone or cartilage formation directly, they play key roles in numerable activities in ECM from embryo to adult, then affect the procedure and the result of osteogenesis and bone remodeling directly or indirectly. They are critical in maturation and deposition of some major collagen types, and in regulating the signaling of some growth factors in TGF-? superfamily by degradation of TGF-? inhibitor such as Chordin. The investigations about tissue distribution of BMP-1 and its related proteinases and also gene knock-out studies strongly indicate that they play key roles in osteogenesis and bone development.