Molecular docking studies on rocaglamide, a traditional Chinese medicine for periodontitis

Purpose: To undertake an in silico assessment of rocaglamide as a potential drug therapy forperiodontitis (dental arthritis).Method: Lamarckian algorithm-based automated docking approach using AutoDock4.2 tool wasapplied for calculating the best possible binding mode of rocaglamide to IL-23p19 and IL-17, the targets of anti-inflammatory drugs in periodontal disease.Results: The top two interactions of rocaglamide with IL-17 (ΔG = -5.45 and -4.83 kcal/mol) were more spontaneous, and the physical interactions (two hydrogen bonds and one π-πbond) generated in the two IL-17- rocaglamide complexes were higher in number than in IL-23p14-rocaglamide complexes.Conclusion: In silico analysis of rocaglamide, a known antimicrobial and anti-inflammatory agent, is a promising natural candidate for periodontitis therapy, and should be further subjected to in vitro and in vivo anti-periodontitis investigations.Keywords: Periodontitis, Inflammation, Rocaglamide, Molecular docking, Lamarckian algorithm, IL- 23p19, IL-1

Iterative Learning Control of a Nonlinear Aeroelastic System despite Gust Load

The development of a control strategy appropriate for the suppression of aeroelastic vibration of a two-dimensional nonlinear wing section based on iterative learning control (ILC) theory is described. Structural stiffness in pitch degree of freedom is represented by nonlinear polynomials. The uncontrolled aeroelastic model exhibits limit cycle oscillations beyond a critical value of the free-stream velocity. Using a single trailing-edge control surface as the control input, a ILC law under alignment condition is developed to ensure convergence of state tracking error. A novel Barrier Lyapunov Function (BLF) is incorporated in the proposed Barrier Composite Energy Function (BCEF) approach. Numerical simulation results clearly demonstrate the effectiveness of the control strategy toward suppressing aeroelastic vibration in the presence of parameter uncertainties and triangular, sinusoidal, and graded gust loads

Gold-Sensitized Silicon/ZnO Core/Shell Nanowire Array for Solar Water Splitting

Solar water splitting represents one of the most promising strategies in the quest for clean and renewable energy. However, low conversion efficiency, use of sacrificial agents, and external bias for current water splitting system limit its practical application. Here, a gold-sensitized Si/ZnOcore/shell nanowire photoelectrochemical (PEC) cell is reported for efficient solar water oxidation. We demonstrated gold-sensitized n-Si/n-ZnO nanowire arrays exhibited higher energy conversion efficiency than gold-sensitized p-Si/n-ZnO nanowire arrays due to the favorable energy-band alignment characteristics. Without any assistance from an external electrical source and sacrificial reagents, gold-sensitized n-Si/n-ZnO core/shell nanowire array photoanode achieved unbiased water splitting under simulated solar light illumination. This method opens a promising venue to cost-efficient production of solar fuels

Immunoproteomic Analysis of Human Serological Antibody Responses to Vaccination with Whole-Cell Pertussis Vaccine (WCV)

BACKGROUND: Pertussis (whooping cough) caused by Bordetella pertussis (B.p), continues to be a serious public health threat. Vaccination is the most economical and effective strategy for preventing and controlling pertussis. However, few systematic investigations of actual human immune responses to pertussis vaccines have been performed. Therefore, we utilized a combination of two-dimensional electrophoresis (2-DE), immunoblotting, and mass spectrometry to reveal the entire antigenic proteome of whole-cell pertussis vaccine (WCV) targeted by the human immune system as a first step toward evaluating the repertoire of human humoral immune responses against WCV. METHODOLOGY/PRINCIPAL FINDINGS: Immunoproteomic profiling of total membrane enriched proteins and extracellular proteins of Chinese WCV strain 58003 identified a total of 30 immunoreactive proteins. Seven are known pertussis antigens including Pertactin, Serum resistance protein, chaperonin GroEL and two OMP porins. Sixteen have been documented to be immunogenic in other pathogens but not in B.p, and the immunogenicity of the last seven proteins was found for the first time. Furthermore, by comparison of the human and murine immunoproteomes of B.p, with the exception of four human immunoreactive proteins that were also reactive with mouse immune sera, a unique group of antigens including more than 20 novel immunoreactive proteins that uniquely reacted with human immune serum was confirmed. CONCLUSIONS/SIGNIFICANCE: This study is the first time that the repertoire of human serum antibody responses against WCV was comprehensively investigated, and a small number of previously unidentified antigens of WCV were also found by means of the classic immunoproteomic strategy. Further research on these newly identified predominant antigens of B.p exclusively against humans will not only remarkably accelerate the development of diagnostic biomarkers and subunit vaccines but also provide detailed insight into human immunity mechanisms against WCV. In particular, this work highlights the heterogeneity of the B.p immunoreactivity patterns of the mouse model and the human host

A Novel Nanobody Specific for Respiratory Surfactant Protein A has Potential for Lung Targeting

Lung-targeting drugs are thought to be potential therapies of refractory lung diseases by maximizing local drug concentrations in the lung to avoid systemic circulation. However, a major limitation in developing lung-targeted drugs is the acquirement of lung-specific ligands. Pulmonary surfactant protein A (SPA) is predominantly synthesized by type II alveolar epithelial cells, and may serve as a potential lung-targeting ligand. Here, we generated recombinant rat pulmonary SPA (rSPA) as an antigen and immunized an alpaca to produce two nanobodies (the smallest naturally occurring antibodies) specific for rSPA, designated Nb6 and Nb17. To assess these nanobodies\u27 potential for lung targeting, we evaluated their specificity to lung tissue and toxicity in mice. Using immunohistochemistry, we demonstrated that these anti-rSPA nanobodies selectively bound to rat lungs with high affinity. Furthermore, we intravenously injected fluorescein isothiocyanate-Nb17 in nude mice and observed its preferential accumulation in the lung to other tissues, suggesting high affinity of the nanobody for the lung. Studying acute and chronic toxicity of Nb17 revealed its safety in rats without causing apparent histological alterations. Collectively, we have generated and characterized lung-specific nanobodies, which may be applicable for lung drug delivery

Draft genome sequence of the Tibetan antelope

The Tibetan antelope (Pantholops hodgsonii) is endemic to the extremely inhospitable high-altitude environment of the Qinghai-Tibetan Plateau, a region that has a low partial pressure of oxygen and high ultraviolet radiation. Here we generate a draft genome of this artiodactyl and use it to detect the potential genetic bases of highland adaptation. Compared with other plain-dwelling mammals, the genome of the Tibetan antelope shows signals of adaptive evolution and gene-family expansion in genes associated with energy metabolism and oxygen transmission. Both the highland American pika, and the Tibetan antelope have signals of positive selection for genes involved in DNA repair and the production of ATPase. Genes associated with hypoxia seem to have experienced convergent evolution. Thus, our study suggests that common genetic mechanisms might have been utilized to enable high-altitude adaptation

Antrodia camphorata Mycelia Exert Anti-liver Cancer Effects and Inhibit STAT3 Signaling in vitro and in vivo

Hepatocellular carcinoma (HCC), the major form of primary liver cancer, is a common cause of cancer-related death worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in HCC and has been proposed as a chemotherapeutic target for HCC. Antrodia camphorata (AC), a medicinal mushroom unique to Taiwan, is traditionally used for treating HCC. Whereas natural AC is scarce, cultured AC mycelia are becoming alternatives. In this study, we investigated the anti-HCC effects of the ethyl acetate fraction of an ethanolic extract of AC mycelia (EEAC), particularly exploring the involvement of STAT3 signaling in these effects. We found that EEAC reduced cell viability, induced apoptosis, and retarded migration and invasion in cultured HepG2 and SMMC-7721 cells. Immunoblotting results showed that EEAC downregulated protein levels of phosphorylated and total STAT3 and JAK2 (an upstream kinase of STAT3) in HCC cells. Real-time PCR analyses showed that STAT3, but not JAK2, mRNA levels were decreased by EEAC. EEAC also lowered the protein level of nuclear STAT3, decreased the transcriptional activity of STAT3, and downregulated protein levels of STAT3-targeted molecules, including anti-apoptotic proteins Bcl-xL and Bcl-2, and invasion-related proteins MMP-2 and MMP-9. Over-activation of STAT3 in HCC cells diminished the cytotoxic effects of EEAC. In SMMC-7721 cell-bearing mice, EEAC (100 mg/kg, i.g. for 18 days) significantly inhibited tumor growth. Consistent with our in vitro data, EEAC induced apoptosis and suppressed JAK2/STAT3 activation/phosphorylation in the tumors. Taken together, EEAC exerts anti-HCC effects both in vitro and in vivo; and inhibition of STAT3 signaling is, at least in part, responsible for these effects. We did not observe significant toxicity of EEAC in normal human liver-derived cells, nude mice and rats. Our results provide a pharmacological basis for developing EEAC as a safe and effective agent for HCC management

Mitochondrial Protection and Anti-aging Activity of Astragalus Polysaccharides and Their Potential Mechanism

The current study was performed to investigate mitochondrial protection and anti-aging activity of Astragalus polysaccharides (APS) and the potential underlying mechanism. Lipid peroxidation of liver and brain mitochondria was induced by Fe2+–Vit C in vitro. Thiobarbituric acid (TBA) colorimetry was used to measure the content of thiobarbituric acid reactive substances (TBARS). Mouse liver mitochondrial permeability transition (PT) was induced by calcium overload in vitro and spectrophotometry was used to measure it. The scavenging activities of APS on superoxide anion (O2•−) and hydroxyl radical (•OH), which were produced by reduced nicotinamide adenine dinucleotide (NADH)—N-Methylphenazonium methyl sulfate (PMS) and hydrogen peroxide (H2O2)–Fe2+ system respectively, were measured by 4-nitrobluetetrazolium chloride (NBT) reduction and Fenton reaction colorimetry respectively. The Na2S2O3 titration method was used to measure the scavenging activities of APS on H2O2. APS could inhibit TBARS production, protect mitochondria from PT, and scavenge O2•−, •OH and H2O2 significantly in a concentration-dependent manner respectively. The back of the neck of mice was injected subcutaneously with D-galactose to induce aging at a dose of 100 mg/kg/d for seven weeks. Moreover, the activities of catalase (CAT), surperoxide dismutase (SOD) and glutathione peroxidase (GPx) and anti-hydroxyl radical which were assayed by using commercial monitoring kits were increased significantly in vivo by APS. According to this research, APS protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting mitochondrial PT and increasing the activities of antioxidases. Therefore, APS has the effect of promoting health