A novel and rapid approach for the synthesis of biocompatible and highly stable Fe3O4/SiO2 and Fe3O4/C core/shell nanocubes and nanorods

Core/shell nanostructures of MNPs/inorganic materials have attracted enormous research interest due to their promising applications in bio-medicine, energy, electronics, the environment, etc. Although several approaches are available for the synthesis of these core/shell nanostructures, the use of large quantities of surfactants, multi-step synthesis procedures and long reaction times still remain as challenges to be overcome for industrial applications. In this study, a novel one-pot sonochemical approach was developed for the synthesis of core/shell iron oxide/silica and iron oxide/carbon nanostructures in aqueous medium. Interestingly, the total reaction time for the synthesis of the core/shell nanostructures is found to be shorter than for other reported methods. Moreover, transmission electron microscopy indicated that the sonochemical technique produces a uniform core/shell with a highly crystalline cubic structure. However, rod-like shaped nanostructures were obtained in the absence of ultrasound. The biocompatibility of the Fe3O4/SiO2 and Fe3O4/C nanocubes and nanorods was investigated and compared with iron oxide nanostructures in in vitro quantification of TK-6 and THP-1 cell viability using a CCK-8 assay. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.

Micromagnet Conductors for High-Resolution Separation of Magnetically Driven Beads and Cells at Multiple Frequencies

We demonstrate a separation method for complex mixture of superparamagnetic beads using half-disk pathways, under an in-plane rotating magnetic field, which is highly sensitive to the bead size and magnetic susceptibility. The non-linear dynamics of the beads moving along the half-disk pathways at multiple frequencies can be divided into three regimes: a phase-locked regime at low driving frequencies, a phase-slipping regime above the first critical frequency fc1, and a phase-insulated regime above the second critical frequency fc2 in which the beads just hop at the gaps between two half-disks. Hence, based on the dynamical motions, the beads with varied sizes or heterogenic magnetic properties can be separated efficiently. Furthermore, a bio-selective separation of bead plus human monocytic leukemia (THP-1) cell complexes from bare beads has been achieved due to the increased drag force on the complexes, resulting in a decreased critical frequency. © 2010-2012 IEEE.

Immunomodulating Hydrogels as Stealth Platform for Drug Delivery Applications

Non-targeted persistent immune activation or suppression by different drug delivery platforms can cause adverse and chronic physiological effects including cancer and arthritis. Therefore, non-toxic materials that do not trigger an immunogenic response during delivery are crucial for safe and effective in vivo treatment. Hydrogels are excellent candidates that can be engineered to control immune responses by modulating biomolecule release/adsorption, improving regeneration of lymphoid tissues, and enhancing function during antigen presentation. This review discusses the aspects of hydrogel-based systems used as drug delivery platforms for various diseases. A detailed investigation on different immunomodulation strategies for various delivery options and deliberate upon the outlook of such drug delivery platforms are conducted

ATC induces insulin secretion via cADPR/NAADP-dependent Ca²⁺ signals in pancreatic β cell.

<p><b>(A</b>) Representative tracing of the Ca²⁺ response to ATC (400 μM), Arginine (400 μM) (AG), Thiazolidine-2-carboxylic acid (400 μM) (T2C) and T2C + Arg treatments. <b>(B)</b> Representative tracing of the Ca²⁺ response to ATC (400 μM) and OTC (1 mM) treatments. <b>(C)</b> Comparisons of NAADP formation among ATC, OTC, Arg, T2C and T2C + AG treatment. <b>(D)</b> Comparisons of cADPR formation among ATC, OTC, Arg, T2C and T2C + Arg treatment. <b>(E)</b> Comparisons of insulin secretion among ATC, OTC, Arg, T2C and T2C + AG treatment. <b>(F)</b> Blood glucose levels in vehicle (<i>closed circle</i>, <i>n</i> = 5)- and ATC (5 mg/kg; <i>open circle</i>, <i>n</i> = 5, 10 mg/kg; <i>closed triangle</i>, <i>n</i> = 5, 20 mg/kg; <i>open triangle</i>, <i>n</i> = 5)-treated <i>db</i>/<i>db</i> mice following intraperitoneal injection of glucose after overnight fasting. <b>(G)</b> Plasma insulin levels during intraperitoneal glucose tolerance testing in vehicle (<i>closed circle</i>, <i>n</i> = 5)- and ATC (5 mg/kg; <i>open circle</i>, <i>n</i> = 5, 10 mg/kg; <i>closed triangle</i>, <i>n</i> = 5, 20 mg/kg; <i>open triangle</i>, <i>n</i> = 5)-treated <i>db</i>/<i>db</i> mice. *, P<0.05 versus CON level. #, P<0.05 versus ATC treated level. All data are expressed as the Mean ± SEM.</p

ATC-induced Ca²⁺ signals, cADPR and NAADP production, and insulin secretion in pancreatic β cell from wild-type (WT) and CD38 knock-out (KO) mice.

<p><b>(A)</b> Representative tracings of the Ca²⁺ response to ATC in pancreatic β cell prepared from WT and CD38 KO mice. <b>(B and C)</b> ATC-stimulated NAADP and cADPR formation in WT and CD38 KO mice. <b>(D and E)</b> ATC-stimulated cAMP and NO formation in WT and CD38 KO mice. <b>(F)</b> ATC-stimulated insulin secretion in WT and CD38 KO mice. *, P<0.05 versus CON level. #, P<0.05 versus ATC treated level. All data are expressed as the Mean ± SEM.</p

ATC-induced NAADP and cADPR formation in a cAMP-dependent manner in pancreatic β cell.

<p><b>(A)</b> Effect of H89 (10 μM) on ATC-induced Ca²⁺ signals. <b>(B)</b> Effect of Ca²⁺ second messenger inhibitors on ATC-induced cAMP formation. <b>(C and D)</b> Effect of H89 and Rp-cAMP (100 μM) on ATC-induced cADPR and NAADP formation. <b>(E)</b> Effect of Ca²⁺ second messenger inhibitors and cAMP antagonist on ATC-induced GSH formation. <b>(F-H)</b> Effect of GSH inhibitor, Diehtyl Maleate (DEM) (50 μM) on ATC-induced formation of cAMP, cADPR and NAADP. <b>(I)</b> Inhibitory effect of cAMP antagonists or DEM on ATC-induced insulin secretion. *, P<0.05 versus CON level. #, P<0.05 versus ATC treated level. All data are expressed as the Mean ± SEM.</p

Schematic representation of ATC-induced insulin secretion via cADPR and NAADP production as well as role of NO in pancreatic β cell.

<p>Arginine Thiazolidine Carboxylate (ATC) enters and is divided into TC and arginine. TC contributes for Glutathione (GSH) formation, which stimulates adenylyl cyclase, resulting in the production of cAMP. cAMP/PKA activates NSE to produce NAADP, releasing Ca²⁺ from lysosome-related acidic organelles. NAADP-mediated increase of intracellular Ca²⁺ levels results in the activation of NOS. At this moment, arginine is provided as a substrate for Nitric Oxide syntase (NOS). Resulting Nitric Oxide (NO) synthesis activate guanylyl cyclase (GC)/protein kinase G (PKG). PKG activates CD38 to produce cADPR. cADPR-mediated Ca²⁺ release from the ER Ca²⁺ stores. cADPR-mediated Ca²⁺ release regulates the Ca²⁺ influx through store-operated Ca²⁺ entry (SOCE), resulting in insulin secretion in pancreatic β cells. GLP-1, an insulin secretion inducing hormone, also uses similar Ca²⁺ signalling pathway for insulin secretion in pancreatic β cells.</p

Arginine Thiazolidine Carboxylate Stimulates Insulin Secretion through Production of Ca²⁺-Mobilizing Second Messengers NAADP and cADPR in Pancreatic Islets

<div><p>Oxothiazolidine carboxylic acid is a prodrug of cysteine that acts as an anti-diabetic agent via insulin secretion and the formation of the Ca²⁺-mobilizing second messenger, cyclic ADP-ribose (cADPR). Here we show that a hybrid compound, arginine thiazolidine carboxylate (ATC), increases cytoplasmic Ca²⁺ in pancreatic β-cells, and that the ATC-induced Ca²⁺ signals result from the sequential formation of two Ca²⁺-mobilizing second messengers: nicotinic acid adenine dinucleotide phosphate (NAADP) and cADPR. Our data demonstrate that ATC has potent insulin-releasing properties, due to the additive action of its two components; thiazolidine carboxylate (TC) and _L-arginine. TC increases glutathione (GSH) levels, resulting in cAMP production, followed by a cascade pathway of NAADP/nitric oxide (NO)/cGMP/cADPR synthesis. _L-arginine serves as the substrate for NO synthase (NOS), which results in cADPR synthesis via cGMP formation. Neuronal NOS is specifically activated in pancreatic β-cells upon ATC treatment. These results suggest that ATC is an ideal candidate as an anti-diabetic, capable of modulating the physiological Ca²⁺ signalling pathway to stimulate insulin secretion.</p></div

nNOS plays a major role in ATC-induced Ca²⁺ signaling and insulin secretion in pancreatic β cell.

<p><b>(A)</b> Effect of nNOS inhibitor, ARL17477 (30 μM) and iNOS inhibitor, 1400W (100 μM) on ATC-induced Ca²⁺ signals. <b>(B-D)</b> Effect of nNOS and iNOS inhibitors on ATC-induced NO, cADPR, NAADP formation. <b>(E)</b> Effect of nNOS knock down (KD) on ATC-induced NO formation. <b>(inset)</b> Representative immunoblots for quantifications of nNOS protein expression in pancreatic β cell after infection with lentiviral particles expressing scrambled or nNOS-specific short hairpin (shRNA). <b>(F)</b> Effect of nNOS KD on ATC-induced Ca²⁺ signal. <b>(G and H)</b> Effects of nNOS KD on ATC-induced cADPR and NAADP formation. <b>(I)</b> Effect of nNOS inhibitors and nNOS KD on ATC-induced insulin secretion. *, P<0.05 versus CON level. #, P<0.05 versus ATC treated level. All data are expressed as the Mean ± SEM.</p

ATC-induced NAADP and cADPR formation and involvement of SOCE in ATC-induced Ca²⁺ signaling in pancreatic β cell.

<p><b>(A)</b> Time course of NAADP and cADPR production following ATC treatment <b>(B)</b> Effect of Ca²⁺ second messenger inhibitors on ATC-induced Ca²⁺ signals. XesC (2 μM), Ned19 (100 μM) and 8-Br-cADPR (100 μM) were used. <b>(C)</b> Representative tracings of the Ca²⁺ response to ATC in the absence and presence of extracellular Ca²⁺. <b>(D)</b> Representative tracings of the Ca²⁺ response to ATC in the presence of SKF 96365 (10 μM) <b>(E and F)</b> Effect of Ca²⁺ second messenger inhibitors on ATC-induced cADPR and NAADP formation. <b>(G)</b> Effect of Ca²⁺ second messenger inhibitors on ATC-induced insulin secretion. *, P<0.05 versus CON level. #, P<0.05 versus ATC treated level. All data are expressed as the Mean ± SEM.</p