Porous SiO(2)/pHEMA biocomposites were synthesized in situ by incorporating silica nanoparticles with a hydroxyethyl methacrylate (HEMA) monomer, following a UV-induced photopolymerization. The nanostructure of the composites was characterized and the resulting physical properties were examined. The release kinetics of the model molecule-vitamin B12-and the hemocompatibility of the porous SiO(2)/pHEMA composites were investigated. Heterogeneous reaction kinetics is proposed to be the formation mechanism of the nanoporosity in the pHEMA matrix as a result of incorporating silica nanoparticles following photopolymerization. Experimental results also demonstrated that the incorporation of the silica nanoparticles into the pHEMA matrix not only enhanced the mechanical property but also maintained a good hemocompatibility of the resulting biocomposites. In addition, it was observed that the drug release profile of the composites (in the form of a membrane) can be precisely regulated from a two-stage pattern to one-stage pattern by varying the concentration of both the SiO(2) nanoparticles and HEMA monomer during synthesis. The permeability of the model drug was enhanced by two orders of magnitude from 4.22 x 10(-7 )cm(2)/h to 3.92 x 10(-5 )cm(2)/h by controlling the micro-to-nanostructure of the composites. The platelet adhesion experiment demonstrated low aggregation of the platelets on the surface of the biocomposite membranes, indicating a promising antithrombotic property.
A novel Cu‐pHEMA hybrid was successfully prepared by in situ photopolymerization of 2‐hydroxyethyl methacrylate (HEMA) monomer in the presence of Cu(II) copper ions, following an in situ chemical reduction. Experimental observations indicate that intermolecular interactions such as the coupling force and hydrogen bonding between the Cu and the hydroxyl groups further stabilize the hybrid structure to a considerable extent. Localization of the metallic copper particles within the pHEMA network structure as a result of those intermolecular interactions gives rise to the formation of discretely distributed nanocrystallites with particle sizes ranging from 5 to 25 nm in diameter. A crystallographic change of the Cu nanophase from an amorphous‐like to a crystalline structure is observed as the H2O:HEMA molar ratio increases, upon synthesis, accompanied with an increase in the particle size. A relatively slow and sustained release of the Cu (in the form of cupric ions) from the hybrids was measured for a time period of about 10 days, which also illustrates a Cu(II)‐induced proliferation of the endothelial cells over a relatively small range of release rate of the Cu from the hybrids. Such a new type of Cu‐loaded hybrid hydrogel is expected to be compatible and may be considered as a candidate biomaterial for biomedical/therapeutic uses.
Alzheimer’s disease (AD) is characterized by the accumulation of neurotoxic amyloid-β (Aβ) peptides consisting of 39-43 amino acids, proteolytically derived fragments of the amyloid-β protein precursor (AβPP), and the accumulation of the hyperphosphorylated microtubule-associated protein tau. Inhibiting Aβ production may reduce neurodegeneration and cognitive dysfunction associated with AD. We have previously used an AβPP-firefly luciferase enzyme complementation assay to conduct a high throughput screen of a compound library for inhibitors of AβPP dimerization, and identified a compound that reduces Aβ levels. In the present study, we have identified an analog, compound Y10, which also reduced Aβ. Initial kinase profiling assays identified the receptor tyrosine kinase cKit as a putative Y10 target. To elucidate the precise mechanism involved, AβPP phosphorylation was examined by IP-western blotting. We found that Y10 inhibits cKit phosphorylation and increases AβPP phosphorylation mainly on tyrosine residue Y743, according to AβPP751 numbering. A known cKit inhibitor and siRNA specific to cKit were also found to increase AβPP phosphorylation and lower Aβ levels. We also investigated a cKit downstream signaling molecule, the Shp2 phosphatase, and found that known Shp2 inhibitors and siRNA specific to Shp2 also increase AβPP phosphorylation, suggesting that the cKit signaling pathway is also involved in AβPP phosphorylation and Aβ production. We further found that inhibitors of both cKit and Shp2 enhance AβPP surface localization. Thus, regulation of AβPP phosphorylation by small molecules should be considered as a novel therapeutic intervention for AD.
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