Previous studies have shown that the inhibitory effect of betulinic acid (BA) on specificity protein 1 (Sp1) expression is involved in the prevention of cancer progression, but the mechanism of this effect remains to be delineated. In this study, we determined that BA treatment in HeLa cells increased the sumoylation of Sp1 by inhibiting sentrin-specific protease 1 expression. The subsequent recruitment of E3 ubiquitin-protein ligase RING finger protein 4 resulted in ubiquitin-mediated degradation in a 26S-proteosome-dependent pathway. In addition, both BA treatment and mithramycin A (MMA) treatment inhibited lung tumor growth and down-regulated Sp1 protein expression in Kras G12D -induced lung cancers of bitransgenic mice. In gene expression profiles of Kras G12D -induced lung cancers in bitransgenic mice with and without Sp1 inhibition, 542 genes were affected by MMA treatment. One of the gene products, cyclin A2, which was involved in the S and G 2 /M phase transition during cell cycle progression, was investigated in detail because its expression was regulated by Sp1. The down-regulation of cyclin A2 by BA treatment resulted in decreased retinoblastoma protein phosphorylation and cell cycle G 2 /M arrest. The BA-mediated cellular Sp1 degradation and antitumor effect were also confirmed in a xenograft mouse model by using H1299 cells. The knockdown of Sp1 in lung cancer cells attenuated the tumor-suppressive effect of BA. Taken together, the results of this study clarify the mechanism of BA-mediated Sp1 degradation and identify a pivotal role for Sp1 in the BA-induced repression of lung cancer growth.
Laser cladding technology was adopted to fabricate hydroxyapatite(HAP) and calcium phosphate compound coating according to the feature that a metallurgical bonding can be formed by laser cladding process. Compared with CO2laser, Nd-YAG laser has different wavelength(the former is 1.06μm and the latter is 10.06μm). Metal and ceramic material has quite different absorbance ability towards them and thus they can generate different laser cladding products by these two laser surface processings with different wavelength. This paper presents a new process and mechanism analysis to obtain bioceramic composite coating on Ti6Al4V substrate by Nd-YAG laser cladding. A bioceramic composite coating including HAP,Ca2P2O7,Ca3(PO4)2and calcium titanates and was successfully obtained by Nd-YAG laser cladding with pre-depositing mixed powders of CaHPO4•2H2O and CaCO3directly on Ti6Al4V substrate. Nd-YAG laser transmits mixed powders of CaHPO4•2H2O and CaCO3and the laser power is absorbed by Ti6Al4V substrate to produce a thin layer of molten region. There are mainly two kinds of chemical reaction systems in the coating during laser cladding processing. When CaHPO4•2H2O and CaCO3react together, they make calcium phosphate bioceramic products; The microstructure of the bioceramic composite coating is even and minute because of the rapid solidification in laser processing. A chemical metallergical bonding is formed between the boceramic composite coating and Ti6Al4V substrate. It can also be expected that Nd-YAG laser cladding technology can be used as a further modification procedure to enhance HAp/metal interface property.
In recent years there has been increasing interest concerning the synthesis of hollow materials in nanometer to micrometer dimensions. Hollow hydroxyapatite(HAP) microspheres with pores on their surfaces were prepared by a Li-Ca-B glass in situ immersion conversion process in an aqueous phosphate solution at 37°C. The chemical reaction ability of the Li-Ca-B glass was studied by immersing the glass in SBF solution, and the phases of the reaction product were identified by the XRD method. The morphology, composition, phases and thermal property of the hollow HAP microspheres were investigated using by chemical analysis, SEM ,and XRD . The microphere wall consisted of calcium deficient hydroxyapatite (CDHAP) crystals only. Furthermore, the formation mechanism of the hollow HAP microsphere was also discussed.
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