Degradation performance of the digital coralline hydroxyapatite artificial bone scaffold in vitro

背景:前期实验成功制备了数字化珊瑚羟基磷灰石人工骨支架材料,并已证实其具有良好的理化性能和生物相容性。目的:评价数字化珊瑚羟基磷灰石人工骨的体外降解性能。方法:将珊瑚羟基磷灰石与左旋-聚乳酸分别以3∶1和4∶1的质量比混合,制备数字化珊瑚羟基磷灰石人工骨支架材料试件。将两种数字化人工骨支架材料、珊瑚羟基磷灰石及左旋-聚乳酸分别置于初始p H值为7.4的50 m L模拟体液中,在37℃恒温箱中降解16周,动态观察溶液p H值、钙及磷离子浓度,以及材料降解率、抗压强度及微观结构变化。结果与结论:降解16周时,两种数字化人工骨组的p H值维持在7.34-7.36,高于左旋-聚乳酸组(P3∶1数字化人工骨组>左旋-聚乳酸组>4∶1数字化人工骨组;两种数字化人工骨微孔结构增多,孔隙率升高,孔径增大,说明数字化珊瑚羟基磷灰石人工骨支架具有良好的降解性能。BACKGROUND: We have successfully prepared the digital coralline hydroxyapatite artificial bone scaffold in previous experiments, and it has good physicochemical properties and biocompatibility. OBJECTIVE: To evaluate the in vitro degradation performance of the digital coralline hydroxyapatite artificial bone. METHODS: We used the mixtures of coralline hydroxyapatite and L-polylactic acid at the mass ratio of 3:1 and 4:1 as raw materials to prepare the digital coralline hydroxyapatite artificial bone scafflold specimens, and then they were immersed in the 50 m L stimulated body fluid with the initial p H value of 7.4 in an incubator at 37 ℃ for degradation. After 16 weeks of degradation, the p H value, calcium and phosphate ion concentration, degradation rate, compressive strength and changes of microstructure were dynamically observed. RESULTS AND CONCLUSION: At the 16 th weeks of degradation, the p H values in the two kinds of digital artificial bone groups maintained at 7.34-7.36, which were higher than that in the L-polylactic acid group(P 3:1 digital artificial bone group > L-polylactic acid group > 4:1 digital artificial bone group. The cellular structure, porosity and pore size in the two kinds of digital artificial bone groups were all increased. These results show that the prepared digital coralline hydroxyapatite artificial bone scaffold has good degradation propertyies.福建省教育厅科技项目(JA12416);; 福建省自然科学基金青年创新项目(2013D013);; 漳州职业技术学院院级科研项目(ZZY1204)~

Oncogenic potential of Cyclin Kinase Subunit-2 in cholangiocarcinoma

National Nature Science Foundation of China [81101502]; young foundation from the Health Department of Fujian Province, China [2011-2-58]Background Cyclin kinase subunit-2 (Cks2), a member of the human Cks family, plays an important role in the regulation of meiosis and mitosis; and its abnormal expression is usually associated with carcinogenesis. However, its exact functions and molecular mechanisms remain unclear. Aims To observe Cks2 expression in cholangiocarcinoma and explore its role in the carcinogenesis of cholangiocarcinoma and possible mechanism. Methods Cks2 expression in cholangiocarcinoma was detected with immunostaining and RT-PCR. MTT, colony formation, immunofluorescence, flow cytometry and Western blotting were performed to explore the role of Cks2 in cholangiocarcinoma and possible mechanism. Results Cks2 was significantly elevated in cholangiocarcinoma tissues and its over-expression was associated with poor differentiation, CA19-9 and poor prognosis. Furthermore, Cks2 down-regulation inhibited cholangiocarcinoma cell proliferation and colony formation in vitro, and the growth of cholangiocarcinoma xenografts in animals; especially, enhanced the sensitivity of cholangiocarcinoma cells to chemotherapy. We further found that Cks2 knockdown induced cholangiocarcinoma cell cycle arrest in G2/M phase through down-regulation of Cyclin A and Cyclin B1 and Bax up-regulation and activation, mitochondrial membrane permeabilization and caspase-3 activation, which resulted in facilitating cholangiocarcinoma apoptosis. Conclusions These findings suggest that Cks2 may serve as an independent prognostic factor in patients with cholangiocarcinoma, and play an important role in the carcinogenesis of cholangiocarcinoma by facilitating cell cycle progression and Bax-mediated mitochondrial caspase-dependent apoptosis

Oncogenic Activity of Retinoic Acid Receptor gamma Is Exhibited through Activation of the Akt/NF-kappa B and Wnt/beta-Catenin Pathways in Cholangiocarcinoma

National Nature Science Foundation of China [81101502]; Youth Foundation of Fujian Health Department, China [2011-2-58]Aberrant expression and function of retinoic acid receptor gamma (RAR gamma) are often involved in the progression of several cancers. However, the role of RAR gamma in cholangiocarcinoma (CCA), chemoresistant bile duct carcinoma with a poor prognosis, remains unclear. In the present study, we found that RAR gamma was frequently overexpressed in human CCA specimens. Its overexpression was associated with poor differentiation, lymph node metastasis, high serum carbohydrate antigen 19-9 level, and poor prognosis of CCA. Downregulation of RAR gamma reduced CCA cell proliferation, migration, invasion, and colony formation ability in vitro and tumorigenic potential in nude mice. RAR gamma knockdown resulted in upregulation of cell cycle inhibitor P21, as well as down-regulation of cyclin D1, proliferating cell nuclear antigen, and matrix metallopeptidase 9, in parallel with suppression of the Akt/NF-kappa B pathway. Furthermore, overexpression of RAR gamma contributed to the multidrug chemoresistance of CCA cells, at least in part due to upregulation of P glycoprotein via activation of the Wnt/beta-catenin pathway. Molecular mechanism studies revealed that RAR gamma interacted with beta-catenin and led to beta-catenin nuclear translocation. Taken together, our results suggested that RAR gamma plays an important role in the proliferation, metastasis, and chemoresistance of CCA through simultaneous activation of the Akt/NF-kappa B and Wnt/beta-catenin pathways, serving as a potential molecular target for CCA treatment