Neovasculature in 3D-PLGA/nHAp Scaffolds for Murine Critical Sized Bone Defect Regeneration by Photoacoustic Imaging: A Preliminary Study

Abstract: Reconstruction of large bone defects remains a challenge in the orthopaedic clinic. Genetic modification of biomaterial scaffold provides the opportunity to control the cellular microenvironment by inducing expression of tissue inductive factors to promote angiogenesis and osteogenesis. Angiogenesis in tissue-engineering scaffolds is essential for supplying oxygen and nutrients to the cells, removing waste products, and ultimately functionalizing implanted scaffolds. However, it was difficult to visualize and measure angiogenesis in three-dimensional (3D) scaffolds or new bone in bone tissue engineering in vivo and non-invasively. Photoacoustic microscopy (PAM) is a novel imaging modality that can acquire volumetric data in a non-invasive manner. In this study, we fabricated lentivirus-mediated genetic modification of 3D-PLGA/nHAp scaffold (PH), which can deliver recombinant lentivirus carrying cytokine gene-pdgfb (LV-pdgfb). In vitro, the modified scaffolds (PHp) continuously released bioactive LV-pdgfb particles for up to 5 days, and expressed PDGF-BB and significantly promoted migration of bone marrow-derived MSCs (BMSCs). In vivo, we detected that there were significant increasing of expressing of pdgfb and angiogenesis related genes. In this preliminary study, by using acoustic-resolution PAM (AR-PAM) and optical-resolution PAM (OR-PAM), we have investigated the blood vessels pattern in mouse calvaria in vivo. We have confirmed that PAM is a useful tool in evaluating neovasculature in bone tissue. In the future, we will quantify the neovasculature in 3D-scaffold which assisted bone regeneration by PAM scanning, and correlate the neovasculature with new bone regeneration in a murine calvarial critical bone defect model in the future work

A Novel LMP1 Antibody Synergizes with Mitomycin C to Inhibit Nasopharyngeal Carcinoma Growth in Vivo Through Inducing Apoptosis and Downregulating Vascular Endothelial Growth Factor

Combined therapy emerges as an attractive strategy for cancer treatment. The aim of this study was to investigate the inhibitory effects of mitomycin C (MMC) combined with a novel antibody fragment (Fab) targeting latent membrane protein 1 (LMP1) on nasopharyngeal carcinoma (NPC) xenograft nude mice. The inhibitory rates of MMC (2 mg/kg), Fab (4 mg/kg), MMC (2 mg/kg) + Fab (4 mg/kg), and MMC (1 mg/kg) + Fab (4 mg/kg) were 20.1%, 7.3%, 42.5% and 40.5%, respectively. Flow cytometry analysis showed that the apoptotic rate of xenograft tumor cells in the MMC and Fab combination group was 28 ± 4.12%, significantly higher than the MMC (2 mg/kg) group (P < 0.01). Immunohistochemical staining showed that VEGF expression in NPC xenografts was significantly inhibited in the combination group compared to the Fab (4 mg/kg) group (P < 0.05). In conclusion, both MMC and Fab could inhibit NPC xenograft tumor growth in vivo and combination therapy showed apparent synergistic anti-tumor effects, which may be due to the induction of tumor cell apoptosis and the downregulation of VEGF expression. These results suggest that the novel combined therapy utilizing traditional chemotherapeutics and antibody-targeted therapy could be a promising strategy for the treatment of NPC

Experimental Quantum Simulation of Dynamic Localization on Curved Photonic Lattices

Dynamic localization, which originates from the phenomena of particle evolution suppression under an externally applied AC electric field, has been simulated by suppressed light evolution in periodically-curved photonic arrays. However, experimental studies on their quantitative dynamic transport properties and application for quantum information processing are rare. Here we fabricate one-dimensional and hexagonal two-dimensional arrays, both with sinusoidal curvature. We successfully observe the suppressed single-photon evolution patterns, and for the first time measure the variances to study their transport properties. For one-dimensional arrays, the measured variances match both the analytical electric field calculation and the quantum walk Hamiltonian engineering approach. For hexagonal arrays, as anisotropic effective couplings in four directions are mutually dependent, the analytical approach suffers, while quantum walk conveniently incorporates all anisotropic coupling coefficients in the Hamiltonian and solves its exponential as a whole, yielding consistent variances with our experimental results. Furthermore, we implement a nearly complete localization to show that it can preserve both the initial injection and the wave-packet after some evolution, acting as a memory of a flexible time scale in integrated photonics. We demonstrate a useful quantum simulation of dynamic localization for studying their anisotropic transport properties, and a promising application of dynamic localization as a building block for quantum information processing in integrated photonics.Comment: 4 figure

Anti-Malarial Drug Artesunate Attenuates Experimental Allergic Asthma via Inhibition of the Phosphoinositide 3-Kinase/Akt Pathway

, and has been shown to inhibit PI3K/Akt activity. We hypothesized that artesunate may attenuate allergic asthma via inhibition of the PI3K/Akt signaling pathway.Female BALB/c mice sensitized and challenged with ovalbumin (OVA) developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Artesunate dose-dependently inhibited OVA-induced increases in total and eosinophil counts, IL-4, IL-5, IL-13 and eotaxin levels in bronchoalveolar lavage fluid. It attenuated OVA-induced lung tissue eosinophilia and airway mucus production, mRNA expression of E-selectin, IL-17, IL-33 and Muc5ac in lung tissues, and airway hyperresponsiveness to methacholine. In normal human bronchial epithelial cells, artesunate blocked epidermal growth factor-induced phosphorylation of Akt and its downstream substrates tuberin, p70S6 kinase and 4E-binding protein 1, and transactivation of NF-κB. Similarly, artesunate blocked the phosphorylation of Akt and its downstream substrates in lung tissues from OVA-challenged mice. Anti-inflammatory effect of artesunate was further confirmed in a house dust mite mouse asthma model.Artesunate ameliorates experimental allergic airway inflammation probably via negative regulation of PI3K/Akt pathway and the downstream NF-κB activity. These findings provide a novel therapeutic value for artesunate in the treatment of allergic asthma