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Selective targeting of microglia by quantum dots

<p>Abstract</p> <p>Background</p> <p>Microglia, the resident immune cells of the brain, have been implicated in brain injury and various neurological disorders. However, their precise roles in different pathophysiological situations remain enigmatic and may range from detrimental to protective. Targeting the delivery of biologically active compounds to microglia could help elucidate these roles and facilitate the therapeutic modulation of microglial functions in neurological diseases.</p> <p>Methods</p> <p>Here we employ primary cell cultures and stereotaxic injections into mouse brain to investigate the cell type specific localization of semiconductor quantum dots (QDs) in vitro and in vivo. Two potential receptors for QDs are identified using pharmacological inhibitors and neutralizing antibodies.</p> <p>Results</p> <p>In mixed primary cortical cultures, QDs were selectively taken up by microglia; this uptake was decreased by inhibitors of clathrin-dependent endocytosis, implicating the endosomal pathway as the major route of entry for QDs into microglia. Furthermore, inhibiting mannose receptors and macrophage scavenger receptors blocked the uptake of QDs by microglia, indicating that QD uptake occurs through microglia-specific receptor endocytosis. When injected into the brain, QDs were taken up primarily by microglia and with high efficiency. In primary cortical cultures, QDs conjugated to the toxin saporin depleted microglia in mixed primary cortical cultures, protecting neurons in these cultures against amyloid beta-induced neurotoxicity.</p> <p>Conclusions</p> <p>These findings demonstrate that QDs can be used to specifically label and modulate microglia in primary cortical cultures and in brain and may allow for the selective delivery of therapeutic agents to these cells.</p

Fibroblast functionality on novel Ti-30Ta nanotube array

In this study, the mechanical substrate and topographical surface properties of anodized Ti - 30Ta alloy were investigated using scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS) and contact angle measurement. The anodization process was performed in an electrolyte solution containing HE (48%) and H2SO4 (98%) in the volumetric ratios 1:9 with the addition of 5% dimethyl sulfoxide (DMSO) at 15 V, 25 V and 35 V for 20 and 40 min, producing a nanotube architecture when anodized at 35 V for 40 min. Human dermal fibroblasts (HDF, neonatal) were utilized to evaluate the biocompatibility of Ti - 30Ta nanotubes and Ti - 30Ta alloy after 1 and 3 days of culture. Cellular adhesion, proliferation, viability, cytoskeletal organization and morphology were investigated using fluorescence microscope imaging, biochemical assay and SEM imaging respectively. The results presented identify altered material properties and improved cellular interaction on Ti - 30Ta nanotubes as compared to Ti - 30 Ta alloy. (C) 2012 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Interaction between mesenchymal stem cells and Ti-30Ta alloy after surface treatment

In this study, in vitro cytocompatibility was investigated in the Ti-30Ta alloy after two kinds of surfaces treatments: alkaline and biomimetic treatment. Each condition was evaluated by scanning electron microscopy/energy-dispersive X-ray spectroscopy. Cellular adhesion, viability, protein expression, morphology, and differentiation were evaluated with Bone marrow stromal cells (MSCs) to investigate the short and long-term cellular response by fluorescence microscope imaging and colorimetric assays techniques. Two treatments exhibited similar results with respect to total protein content and enzyme activity as compared with alloy without treatment. However, it was observed improved of the biomineralization, bone matrix formation, enzyme activity, and MSCs functionality after biomimetic treatment. These results indicate that the biomimetic surface treatment has a high potential for enhanced osseointegration. © 2013 Wiley Periodicals, Inc

Intramolecular Acylation of Unactivated Pyridines or Arenes via Multiple C–H Functionalizations: Synthesis of All Four Azafluorenones and Fluorenones

An unprecedented intramolecular acylation of unactivated pyridines via multiple C­(sp³/sp²)–H functionalizations of a methyl, hydroxymethyl, or aldehyde group has been developed providing a general access to all four azafluorenones. The application of this protocol is further demonstrated to the synthesis of azafluorenone related fused nitrogen heterocycles and fluorenones. In addition, design and synthesis of a novel fluorene based organic emitter for potential use in organic light emitting devices (OLEDs) is also reported