Comparison of Cellular Uptake and Inflammatory Response via Toll-Like Receptor 4 to Lipopolysaccharide and Titanium Dioxide Nanoparticles

The innate immune response is the earliest cellular response to infectious agents and mediates the interactions between microbes and cells. Toll-like receptors (TLRs) play an important role in these interactions. We have already shown that TLRs are involved with the uptake of titanium dioxide nanoparticles (TiO₂ NPs) and promote inflammatory responses. In this paper, we compared role of cellular uptake and inflammatory response via TLR 4 to lipopolysaccharide (LPS) and TiO₂ NPs. In the case of LPS, LPS binds to LPS binding protein (LBP) and CD 14, and then this complex binds to TLR 4. In the case of TiO₂ NPs, the necessity of LBP and CD 14 to induce the inflammatory response and for uptake by cells was investigated using over-expression, antibody blocking, and siRNA knockdown experiments. Our results suggested that for cellular uptake of TiO₂ NPs, TLR 4 did not form a complex with LBP and CD 14. In the TiO₂ NP-mediated inflammatory response, TLR 4 acted as the signaling receptor without protein complex of LPS, LBP and CD 14. The results suggested that character of TiO₂ NPs might be similar to the complex of LPS, LBP and CD 14. These results are important for development of safer nanomaterials.     

Genotoxicity of nano/microparticles in in vitro micronuclei, in vivo comet and mutation assay systems

Background

Recently, manufactured nano/microparticles such as fullerenes (C₆₀), carbon black (CB) and ceramic fiber are being widely used because of their desirable properties in industrial, medical and cosmetic fields. However, there are few data on these particles in mammalian mutagenesis and carcinogenesis. To examine genotoxic effects by C₆₀, CB and kaolin, an in vitro micronuclei (MN) test was conducted with human lung cancer cell line, A549 cells. In addition, DNA damage and mutations were analyzed by in vivo assay systems using male C57BL/6J or gpt delta transgenic mice which were intratracheally instilled with single or multiple doses of 0.2 mg per animal of particles.

Results

In in vitro genotoxic analysis, increased MN frequencies were observed in A549 cells treated with C₆₀, CB and kaolin in a dose-dependent manner. These three nano/microparticles also induced DNA damage in the lungs of C57BL/6J mice measured by comet assay. Moreover, single or multiple instillations of C₆₀ and kaolin, increased either or both of gpt and Spi^- mutant frequencies in the lungs of gpt delta transgenic mice. Mutation spectra analysis showed transversions were predominant, and more than 60% of the base substitutions occurred at G:C base pairs in the gpt genes. The G:C to C:G transversion was commonly increased by these particle instillations.

Conclusion

Manufactured nano/microparticles, CB, C₆₀ and kaolin, were shown to be genotoxic in in vitro and in vivo assay systems.     

Molecular dynamic simulation of heterogeneity and chemical states of fluorine in amorphous alkaline earth silicate systems

Chemical states of fluorine in fluorosilicate glasses in the system MF₂-MO-SiO₂ (M = Ca, Sr and Ba; SiO₂ content < 60 mol%) have been investigated by molecular dynamic (MD) simulations with a perfect ionic two-body potential. Comparison of the results with those derived by X-ray photoelectron spectra of the actual glasses demonstrates that MD simulations reproduce well the bonding states of fluorine in the systems as well as the formation of M-F clusters. The MD generated structure of imaginary glasses, or glasses not obtained by the conventional melt-quench technique, with 70 mol% SiO₂ indicates that an acidic environment induces a greater amount of F---Si bonds. Their M-F pair correlation functions plotted against normalized M-F distances suggest that relative ion positions in the clusters are very similar.     

Microassembly of semiconductor three-dimensional photonic crystals

Electronic devices and their highly integrated components formed from semiconductor crystals contain complex three-dimensional (3D) arrangements of elements and wiring. Photonic crystals, being analogous to semiconductor crystals, are expected to require a 3D structure to form successful optoelectronic devices. Here, we report a novel fabrication technology for a semiconductor 3D photonic crystal by uniting integrated circuit processing technology with micromanipulation. Four- to twenty-layered (five periods) crystals, including one with a controlled defect, for infrared wavelengths of 3-4.5 microm, were integrated at predetermined positions on a chip (structural error <50 nm). Numerical calculations revealed that a transmission peak observed at the upper frequency edge of the bandgap originated from the excitation of a resonant guided mode in the defective layers. Despite their importance, detailed discussions on the defective modes of 3D photonic crystals for such short wavelengths have not been reported before. This technology offers great potential for the production of optical wavelength photonic crystal devices.     

Functionalized Bilayer Membranes as Artificial Transaminase: Modification of the Active Site and Its Consequence in Catalytic Efficiency

The transamination reaction of l-phenylalanine with pyruvate as catalyzed by the artificial transaminase formed with synthetic bilayer aggregates was examined in aqueous media under mild kinetic conditions. Each catalyst system was constructed with a combination of a synthetic peptide lipid, a hydrophobic vitamin B₆ derivative, and metal ions. Modification of the active site in the present artificial transaminase was performed by changing a combination of molecular components constituting the catalytic system. While the catalytic activity was scarcely influenced by differences in aggregate structure, single- or multi-walled bilayer, and in copper-(II) concentration, molecular structures of the hydrophobic vitamin B₆ and an amino acid residue of the peptide lipid had significant effects on the reactivity.     

In Vitro and in Vivo Characteristics of Fluorapatite-Forming Calcium Phosphate Cements

This study reports for the first time in vitro and in vivo properties of fluorapatite (FA)-forming calcium phosphate cements (CPCs). The experimental cements contained from (0 to 3.1) mass % of F, corresponding to presence of FA at levels of approximately (0 to 87) mass %. The crystallinity of the apatitic cement product increased greatly with the FA content. When implanted subcutaneously in rats, the in vivo resorption rate decreased significantly with increasing FA content. The cement with the highest FA content was not resorbed in soft tissue, making it the first known biocompatible and bioinert CPC. These bioinert CPCs might be useful for applications where slow or no resorption of the implant is required to achieve the desired clinical outcome.     

Performance of surface ionic conduction single chamber fuel cell prepared by the sol gel method

The performance of surface ionic conduction single chamber fuel cell (SIC‐SCFC) prepared by the sol gel method was studied on electric characteristics due to the differences of the operating temperature and humidity, the electrode distance and electrolyte film depth, and multiple cells with the series and parallel connections. The SIC–SCFC was arranged the both anode of Pt and cathode of Au on the boehmite electrolyte. The open circuit voltage (OCV) of single cell achieved a maximum of 530mV in the dry gas mixtures of O₂/H₂=50% in room temperature operation, and but it became decrease as over 60%. The OCV was maintained the constant value between operating temperatures of 30°C to 80°C, and but it was decreased sharply at over 90°C because a humidity on the cell became lower as increasing operating temperature. Then, the cell property was improved to 120°C by adding to the humidity of 70% using a humidifier. The electrode distance and the electrolyte film depth of SIC‐SCFC found to be contributed to the reductions of the cell resistance and the surface roughness on the electrode, respectively. Moreover, the power property of SIC‐SCFC was significantly improved by cell stacks comprised of the series or parallel connection of a cell.     

A bag carrier for continuous intravenous hyperalimentation

We designed a new bag-carrier device system for continuous intravenous hyperalimentation. The patient carries it on his shoulder and can both walk up and down stairs and go out. The use of this device is simple and easy, and was found to increase the patient's opportunity to engage in physical activity.