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Objective To investigate the effects of cyclinA2 and its inhibitor p21 on alveolar development in bronchopulmonary dysplasia (BPD) neonatal rats.Methods Eighty newborn rats were randomly divided into a model group (FiO2 =80％-85％) and a control group (FiO2 =21％).The degree of alveolar development was evaluated by radial alveolar count (RAC) and alveolar septal thickness.The distribution and expression of cyclinA2 and p21 were detected by immunohistochemistry and Western blot.Results The RAC value of the model group was lower than that of the control group from 3 days.The thickness of the alveolar seprum was higher than that of the control group from 7 days (P ＜0.05).The expression of p21 protein in the model group began to increase from 3d,peaked on 14d,and lasted for 21d.The expression of cyclinA2 protein in model group was higher than that in control group at 14d and 21d (P ＜0.05).There was a negative correlation between RAC and p21 protein expression in model group (r =-0.5966,P ＜0.01),and no correlation with cyclinA2 (r=0.7276,P＞0.05);there was no correlation between RAC and p21 in the control group (r =-0.2929,P ＞ 0.05),and positively correlated with cyclinA2 (r =0.8476,P ＜ 0.01).The alveolar septal thickness of the model group and the control group were both positively correlated with p 21 (r =0.4291,P＜0.05;r=0.4447,P ＜0.05),and negatively correlated with cyclinA2 (r=-0.6814,P ＜0.01;r=-0.7636,P ＜0.01).Conclusion The imbalance of cell cycle regulatory protein cyclinA2 and its inhibitor p21 expression in neonatal rats exposed to hyperoxia may be one of the related factors that interfere with the development of BPD alveoli.
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Objective · To design and synthesize a series of benzenesulfonamide derivatives, test their inhibitory activity to CDK2-cyclinA2 kinase, and investigate the structure-activity relationship. Methods · Virtual screening was executed via computer-aided drug design according to the ATP binding site in CDK2-cyclinA2 protein crystal. A series of benzenesulfonamide derivatives were designed and synthesized on the basis of the interaction modes between the lead compound and the CDK2-cyclinA2. The biological evaluation of compounds was made through the CDK2-cyclinA2 in-vitro kinase activity detection system. Results · Twenty-nine new benzenesulfonamide compounds were prepared, and their inhibitory activity to CDK2-cyclinA2 was elicited. WZ-026 had the highest inhibitory parameter, which half maximal inhibitory concentration (IC50) was 3.81 μmol/L. Conclusion · By multipurpose utilization of virtual screening, chemical synthesis, and biological activity test, a benzenesulfonamide compound WZ-026 was found, which has great inhibitory activity towards CDK2-cyclinA2. Preliminary structure-activity relationship of compounds was obtained.
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Objective To investigate the association between the rs769236 polymorphism at the 5′-UTR region of CyclinA2 gene and the susceptibility of colorectal cancer (CRC) .Methods A case-control study was carried out on the Chinese Han population , the rs769236 polymorphism of CyclinA2 were analyzed by PCR restriction fragment length polymorphism (PCR-RFLP)in 150 CRC cases and 150 healthy controls .The association between CRC risk and the SNP (rs769236) was estimated by an unconditional logis-tic regression model .Results Compared with GG wild genotype ,variant genotypes(GA+AA) carriers had a significantly increased risk of CRC[adjusted odds ratio (OR)=1 .92 ,95% confidence interval(CI)=1 .10 -3 .36] .Conclusion The current results sug-gested that the SNP(rs769236) of CyclinA2 is significantly associated with the increased risk of CRC ,the variant genotypes(GA+AA) are the independent risk factors of CRC in Chinese Han population .