Cyclohexadione-aniline conjugate inhibits proliferation of melanoma cells via upregulation of Mek 1/2 kinase activity

Purpose: To investigate the antiproliferative effect of cyclohexadione-aniline conjugate (CHAC) on melanoma cells, and the mechanism of action involved. Methods: Human melanoma cell lines (B16 F1 and A375) were used in this study. The cells were cultured in RPMI 1640 medium supplemented with 10 % fetal bovine serum (FBS) and 1 % penicillin/streptomycin at 37 °C in a humidified atmosphere of 5 % CO2 and 95 % air. After attaining 70 - 80 % confluency, the cells were treated with serum-free medium and graded concentrations of CHAC (10 – 60 μM) for 24 h. Normal cell culture without CHAC served as control group. B16 F1 and A375 cells were used in logarithmic growth phase in this study. Cell viability and apoptosis were assessed using 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphe¬nyltetrazolium bromide (MTT) and flow cytometric assays, respectively. Western blotting was used to assess the levels of protein expression of X linked inhibitor of apoptosis (XIAP), survivin, p-Erk 1/2, and p-Mek 1/2. Results: Treatment of B16 F1 and A375 cells with CHAC led to significant and concentrationdependent reductions in their viability (p < 0.05). The proliferation of B16 F1 cells decreased from 93.41 to 32.87 %, while that of A375 cells was reduced from 95.23 to 36.50 %. Treatment of B16 F1 cells with CHAC significantly and concentration-dependently increased the population of cells in G0/G1 phase, and significantly reduced cell proportion in S and G2/M phases (p < 0.05). It also significantly and concentration-dependently promoted apoptosis in B16 F1 cells (p < 0.05). CHAC treatment significantly and concentration-dependently down-regulated the expressions of XIAP and survivin proteins (p < 0.05). Exposure of B16 F1 cells to CHAC significantly and concentration-dependently upregulated the expression of p-Mek 1/2, but down-regulated p-Erk 1/2 protein expression (p < 0.05). Densitometric analysis revealed that the expression of p-Mek 1/2 was increased from 12 to 91 %. Conclusion: The results of this study indicate that CHAC inhibits the proliferation of melanoma cells via upregulation of Mek 1/2 kinase activity, and therefore may find application in the management of melanoma

The manufacturing and the application of polycrystalline diamond tools – A comprehensive review

Advanced materials such as titanium alloys and metal matrix composites are extensively used in the aerospace industry and biomedical engineering. They are difficult to machine because of the severe abrasion and high temperature at the tool/chip and tool/workpiece interfaces which cause severe tool wear and premature tool rejection. Compared with conventional cutting tools, polycrystalline diamond (PCD) tools are promising in machining refractory metals and hard-to-machine materials because of the outstanding mechanical properties of PCD. This paper reviewed the manufacturing and application of PCD cutting tools. The researches on manufacturing process of PCD tools and the application in cutting hard-to-machine materials were analysed, and the results and findings were comprehensively discussed. Two most widely used refining methods including abrasive grinding and electrical discharge grinding (EDG) as well as the defects caused by the processes were presented. The wear process of PCD tools in different industrial cutting methods and the wear mechanism of different PCD materials were explained in both micro-scale and macro-scale. Research directions and the trend of the application of PCD cutting tools were introduced

Sputtered Hydroxyapatite Nanocoatings on Novel Titanium Alloys for Biomedical Applications

Titanium and titanium alloys have been extensively studied for many applications in the area of bone tissue engineering. It was believed that the excellent properties of titanium alloys, e.g. lightweight, excellent corrosion resistance, high mechanical strength and low elastic modulus compared to other metallic biomaterials such as stainless steels and Cr-Co alloys, would provide enhanced stability for load-bearing implants. However, they usually lack sufficient osseointegration for implant longevity, and their biocompatibility is also an important concern in these applications due to the potential adverse reactions of metallic ions with the surrounding tissues once these metallic ions are released from the implant surfaces. One approach for consideration to improve the healing process is the application of a hydroxyapatite nanocoating onto the surface of biomedical devices and implants. Hydroxyapatite, with its excellent biocompatibility, and similar chemistry and structure to the mineral component of bone, provides a bioactive surface for direct bone formation and apposition with adjacent hard tissues. The deposition of a SiO2 interlayer between the implant surface and the hydroxyapatite nanocoating is necessary to further improve the biocompatibility of metal implants, as SiO2 has its own excellent compatibility with living tissues, and high chemical inertness, which lead to enhanced osteointegrative and functional properties of the system as a whole. Therefore, SiO2 and hydroxyapatite nanocoatings were deposited onto titanium alloys using electron beam evaporation and magnetron sputtering techniques, respectively, with different process parameters to optimize the deposition conditions and so achieve desired properties. Surface characteristics are essential due to their role in enhancing osseointegration. Surface morphology and microstructure were observed using a scanning electron micro-scope (SEM) and elemental analysis was performed by the energy dispersive X-ray spectroscopy method (EDS). The crystal structure was examined using X-ray diffractometer (XRD) to identify the phase components, while nanocoating thickness was measured using profilometer. This chapter is divided into five major parts. First is an overview of bone and bone implants, including their structure and mechanical properties. The second part highlights the importance of nanocoatings for bone implants longevity. Various coatings and surface modification techniques of titanium and its alloys are also elucidated. The advantages and drawbacks of each technique are reviewed. The last part focuses on the study of sputtered hydroxyapatite and SiO2 nanocoatings on titanium. A thorough discussion of the results is presented

Mechanical properties, in vitro corrosion and biocompatibility of newly developed biodegradable Mg-Zr-Sr-Ho alloys for biomedical applications

Our previous studies have demonstrated that Mg-Zr-Sr alloys can be anticipated as excellent biodegradable implant materials for load-bearing applications. In general, rare earth elements (REEs) are widely used in magnesium (Mg) alloys with the aim of enhancing the mechanical properties of Mg-based alloys. In this study, the REE holmium (Ho) was added to an Mg-1Zr-2Sr alloy at different concentrations of Mg1Zr2SrxHo alloys (x = 0, 1, 3, 5 wt. %) and the microstructure, mechanical properties, degradation behaviour and biocompatibility of the alloys were systematically investigated. The results indicate that the addition of Ho to Mg1Zr2Sr led to the formation of the intermetallic phases MgHo3, Mg2Ho and Mg17Sr2 which resulted in enhanced mechanical strength and decreased degradation rates of the Mg-Zr-Sr-Ho alloys. Furthermore, Ho addition (≤5 wt. %) to Mg-Zr-Sr alloys led to enhancement of cell adhesion and proliferation of osteoblast cells on the Mg-Zr-Sr-Ho alloys. The in vitro biodegradation and the biocompatibility of the Mg-Zr-Sr-Ho alloys were both influenced by the Ho concentration in the Mg alloys; Mg1Zr2Sr3Ho exhibited lower degradation rates than Mg1Zr2Sr and displayed the best biocompatibility compared with the other alloys

Zirconium, calcium, and strontium contents in magnesium based biodegradable alloys modulate the efficiency of implant-induced osseointegration

Development of new biodegradable implants and devices is necessary to meet the increasing needs of regenerative orthopedic procedures. An important consideration while formulating new implant materials is that they should physicochemically and biologically mimic bone-like properties. In earlier studies, we have developed and characterized magnesium based biodegradable alloys, in particular magnesium-zirconium (Mg-Zr) alloys. Here we have reported the biological properties of four Mg-Zr alloys containing different quantities of strontium or calcium. The alloys were implanted in small cavities made in femur bones of New Zealand White rabbits, and the quantitative and qualitative assessments of newly induced bone tissue were carried out. A total of 30 experimental animals, three for each implant type, were studied, and bone induction was assessed by histological, immunohistochemical and radiological methods; cavities in the femurs with no implants and observed for the same period of time were kept as controls. Our results showed that Mg-Zr alloys containing appropriate quantities of strontium were more efficient in inducing good quality mineralized bone than other alloys. Our results have been discussed in the context of physicochemical and biological properties of the alloys, and they could be very useful in determining the nature of future generations of biodegradable orthopedic implants

Fabrication of Ti14Nb4Sn Alloys for Bone Tissue Engineering Applications

In this paper, porous Ti14Nb4Sn alloys were fabricated using a space holder sintering method, resulting in a porosity of ~70%. Scanning electron microscopy (SEM) analyses revealed a combination of both macropore and micropore structures. The fabricated titanium alloy scaffolds exhibited a similar structure to that of natural bone, which is expected to improve bone implant longevity. Bacterial cells of Pseudomonas aeruginosa ATCC 9027 were employed for the in vitro test

Fabrication of Ti14Nb4Sn alloys for bone tissue engineering applications

In this paper, porous Ti14Nb4Sn alloys were fabricated using a space holder sintering method, resulting in a porosity of ~70%. Scanning electron microscopy (SEM) analyses revealed a combination of both macropore and micropore structures. The fabricated titanium alloy scaffolds exhibited a similar structure to that of natural bone, which is expected to improve bone implant longevity. Bacterial cells of Pseudomonas aeruginosa ATCC 9027 were employed for the in vitro test