Safety and Immunogenicity of a Malaria Vaccine, Plasmodium falciparum AMA-1/MSP-1 Chimeric Protein Formulated in Montanide ISA 720 in Healthy Adults

The P. falciparum chimeric protein 2.9 (PfCP-2.9) consisting of the sequences of MSP1-19 and AMA-1 (III) is a malaria vaccine candidate that was found to induce inhibitory antibodies in rabbits and monkeys. This was a phase I randomized, single-blind, placebo-controlled, dose-escalation study to evaluate the safety and immunogenicity of the PfCP-2.9 formulated with a novel adjuvant Montanide ISA720. Fifty-two subjects were randomly assigned to 4 dose groups of 10 participants, each receiving the test vaccine of 20, 50, 100, or 200 µg respectively, and 1 placebo group of 12 participants receiving the adjuvant only.The vaccine formulation was shown to be safe and well-tolerated, and none of the participants withdrew. The total incidence of local adverse events (AEs) was 75%, distributed among 58% of the placebo group and 80% of those vaccinated. Among the vaccinated, 65% had events that were mild and 15% experienced moderate AEs. Almost all systemic adverse reactions observed in this study were graded as mild and required no therapy. The participants receiving the test vaccine developed detectable antibody responses which were boosted by the repeated vaccinations. Sixty percent of the vaccinated participants had high ELISA titers (>1∶10,000) of antigen-specific antibodies which could also recognize native parasite proteins in an immunofluorescence assay (IFA).This study is the first clinical trial for this candidate and builds on previous investigations supporting PfCP-2.9/ISA720 as a promising blood-stage malaria vaccine. Results demonstrate safety, tolerability (particularly at the lower doses tested) and immunogenicity of the formulation. Further clinical development is ongoing to explore optimizing the dose and schedule of the formulation to decrease reactogenicity without compromising immunogenicity.

Bioactive films on metallic surfaces for osteoconduction

A fast and effective electrochemical method was developed to make a dense calcium phosphate films on titanium and stainless steel for hard tissue replacement. The surfaces of titanium and stainless steel were cathodically treated in an electrochemical cell. By controlling the treatment parameters, a film of 100-nm thickness was deposited on the metal surface in several minutes. The thin film was amorphous calcium phosphate containing octacalcium phosphate nuclei, and also dense and ductile. The treated metals were able to induce bioactive calcium phosphate deposition after immersion in simulated body fluid (SBF) for only 1 and 2 days. In vivo study was conducted by implanting the treated specimens of titanium and stainless steel in dog's femur cavity. The treated metallic surfaces showed good ability of osteoconduction. This surface treatment method call be potentially used to enhance bioactivity of any type of metallic surfaces. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 88A: 481-490, 200

Antioxidant and immunomodulatory activities of Oviductus ranae in mice

Oviductus ranae (OR) is a traditional Chinese medicine, which was first recorded in the Compendium of Materia Medica in the Ming Dynasty. OR contains high amounts of proteins and elicits therapeutic effects on neurasthenia, insomnia, and respiratory symptoms, which are related to oxidative stress and immunodeficiency. This study aimed to obtain the potential of OR for the development of functional food possessing antioxidant and immune-enhancement functions in the same dose. In antioxidant evaluation, OR can significantly decrease malondialdehyde and protein carbonyls (P < 0.05, P < 0.01) and significantly increase total superoxide dismutase and glutathione in a dose-dependent manner (P< 0.05, P < 0.01) against ethanol-induced oxidative stress in mice at 0.1, 1.0, and 3.0 g/kg BW. In immunomodulatory evaluation, OR could significantly enhance the phagocytosis of liver macrophages (P < 0.05, P < 0.01), delayed-type hypersensitivity response (P < 0.05, P < 0.01), hemolytic activity (P < 0.05), antibody-producing cells (P < 0.05), and natural killer cell activity (P < 0.05) in the same dose range described in antioxidant evaluation compared with those in the normal control. OR slightly influenced lymphocyte proliferation, peritoneal macrophage phagocytosis, and immune organ indices in mice. Thus, 3.0 g/kg BW OR showed potential for the development of functional food with antioxidant and immune-enhancement activities

Safety Evaluation, in Vitro and in Vivo Antioxidant Activity of the Flavonoid-Rich Extract from Maydis stigma

This study aimed to assess the acute toxicity and safety of flavonoid-rich extract from Maydis stigma (FMS) in mice. The in vitro antioxidant activity of FMS was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethyl-benzthiazoline-6-sulphonate) (ABTS) scavenging assays. Furthermore, the in vivo antioxidant of FMS against ethanol-induced oxidative damage in mice was determined by analysis of the serum total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA) content, liver tissue glutathione (GSH) content, and protein carbonyl (PC) content in liver tissue. The oral administration of FMS at doses of 30 g/kg did not cause death in mice, and there were no significant biologically adverse effects in mice. These results indicated that the median lethal dose (LD50) is higher than this dose. The IC50 values of FMS for the DPPH and ABTS scavenging activity were 50.73 and 0.23 mg/mL, respectively. Meanwhile, FMS could significantly enhance T-SOD activity, reduce MDA content in the serum, increase GSH content, and decrease PC content in the liver tissue at the tested doses (25, 50, 100, 200 mg/kg·day). These results indicate that FMS can be generally regarded as safe and used potentially as a bioactive source of natural antioxidants

Polarization Converter with Controllable Birefringence Based on Hybrid All-Dielectric-Graphene Metasurface

Abstract Previous studies on hybrid dielectric-graphene metasurfaces have been used to implement induced transparency devices, while exhibiting high Q-factors based on trapped magnetic resonances. Typically, the transparency windows are single wavelength and less appropriate for polarization conversion structures. In this work, a quarter-wave plate based on a hybrid silicon-graphene metasurface with controllable birefringence is numerically designed. The phenomena of trapped magnetic mode resonance and high Q-factors are modulated by inserting graphene between silicon and silica. This results in a broader transmission wavelength in comparison to the all-dielectric structure without graphene. The birefringence tunability is based on the dimensions of silicon and the Fermi energy of graphene. Consequently, a linear-to-circular polarization conversion is achieved at a high degree of 96%, in the near-infrared. Moreover, the polarization state of the scattered light is switchable between right and left hand circular polarizations, based on an external gate biasing voltage. Unlike in plasmonic metasurfaces, these achievements demonstrate an efficient structure that is free from radiative and ohmic losses. Furthermore, the ultrathin thickness and the compactness of the structure are demonstrated as key components in realizing integrable and CMOS compatible photonic sensors

Localized Surface Plasmon Resonance Dependence on Misaligned Truncated Ag Nanoprism Dimer

Abstract Misaligned edge-to-edge dimers are the common products during the preparation of Ag nanoprism dimers using self-assembly method. However, in the self-assembly method, Ag nanoprisms are easily truncated because they are easy to oxidize in an acidic environment. In this work, modeling a truncated Ag nanoprism on a misaligned edge-to-edge dimer provides a better understanding of the effects of the truncation and misalignment on localized surface plasmon resonance (LSPR) of the dimer. The resonant wavelength and intensity of the dimer are flexibly modulated by changing the misalignment length of the dimer. As the misalignment length increases, a stronger peak at the shorter wavelength and a weaker one at the longer wavelength are observed. The resonant wavelengths and intensities of the two peaks are also flexibly tuned by adjusting the truncated length of the Ag nanoprism in the dimer. The results are numerically demonstrated based on the finite element method (FEM) and show promising potential for nanoswitch, multi-channel tunable biosensor and other nanodevice applications

The cooperation of enamelin and amelogenin in controlling octacalcium phosphate crystal morphology.

Enamel matrix proteins, including the most abundant amelogenin and lesser amounts of enamelin, ameloblastin, and proteinases, play vital roles in controlling crystal nucleation and growth during enamel formation. The cooperative action between amelogenin and the 32-kDa enamelin is critical to regulating the growth morphology of octacalcium phosphate crystals. Using biophysical methods, we investigated the interaction between the 32-kDa enamelin and recombinant pig amelogenin 148 (rP148) at pH 6.5 in phosphate-buffered saline (PBS). Dynamic light scattering results showed a trend of increasing particle size in the mixture with the addition of enamelin to amelogenin. Upon addition of the 32-kDa enamelin, the shift and intensity decrease in the ellipticity minima of rP148 in the circular dichroism spectra of rP148 illustrated a direct interaction between the 2 proteins. In the fluorescence spectra, the maximum emission of rP148 was blue shifted from 335 to 333 nm in the presence of enamelin as a result of complexation of the 2 proteins. Our results demonstrate that the 32-kDa enamelin has a close association with amelogenin at pH 6.5 in PBS buffer. Our present study provides novel insights into the possible cooperation between enamelin and amelogenin in macromolecular coassembly and in controlling enamel mineral formation.Enamel matrix proteins, including the most abundant amelogenin and lesser amounts of enamelin, ameloblastin, and proteinases, play vital roles in controlling crystal nucleation and growth during enamel formation. The cooperative action between amelogenin and the 32-kDa enamelin is critical to regulating the growth morphology of octacalcium phosphate crystals. Using biophysical methods, we investigated the interaction between the 32-kDa enamelin and recombinant pig amelogenin 148 (rP148) at pH 6.5 in phosphate-buffered saline (PBS). Dynamic light scattering results showed a trend of increasing particle size in the mixture with the addition of enamelin to amelogenin. Upon addition of the 32-kDa enamelin, the shift and intensity decrease in the ellipticity minima of rP148 in the circular dichroism spectra of rP148 illustrated a direct interaction between the 2 proteins. In the fluorescence spectra, the maximum emission of rP148 was blue shifted from 335 to 333 nm in the presence of enamelin as a result of complexation of the 2 proteins. Our results demonstrate that the 32-kDa enamelin has a close association with amelogenin at pH 6.5 in PBS buffer. Our present study provides novel insights into the possible cooperation between enamelin and amelogenin in macromolecular coassembly and in controlling enamel mineral formation