The prokineticin receptor agonist Bv8 decreases IL-10 and IL-4 production in mice splenocytes by activating prokineticin receptor-1

<p>Abstract</p> <p>Background</p> <p>Bv8, prokineticin-1, or endocrine gland-vascular endothelial growth factor, and prokineticin-2 are recently isolated peptide agonists of two G protein-coupled receptors, prokineticin receptor-1 (PROKR 1) and PROKR 2, and have been described as affecting a number of myeloid cell functions. We evaluated the impact of Bv8 on lymphoid cells by investigating its ability to modulate T cell cytokine balance in mouse.</p> <p>Results</p> <p>The production of T-helper1 cytokines (IL-2, IFN-γ and IL-1β), the T-helper 2 cytokine IL-4, and the anti-inflammatory cytokine IL-10 by mouse splenocytes was evaluated after polyclonal stimulation or immunisation with the keyhole limpet hemocyanin protein antigen by measuring cytokine levels. When added <it>in vitro </it>to Con-A-stimulated splenocytes, Bv8 significantly increased IL-1β and decreased IL-4 and IL-10; IL-2 and IFN-γ were not affected. Similar results were obtained when Bv8 was administered <it>in vivo</it>. In KLH-immunised mice, splenocytes restimulated <it>in vitro </it>with KLH and Bv8 produced significantly smaller amounts of IL-4 and IL-10. KLH-induced IL-10 and IL-4 production was also significantly blunted in animals administered Bv8 <it>in vivo </it>at the time of KLH immunisation or two weeks later. The Bv8-induced effects were lost in mice lacking the PROKR 1 gene, thus indicating that PROKR 1 is the receptor involved in the modulation of cytokines.</p> <p>Conclusion</p> <p>These findings indicate that Bv8/prokineticin-1 is a novel modulator of lymphoid functions, and may be a suitable target for new immunopharmacological strategies.</p

hArtes: Hardware-Software Codesign for Heterogeneous Multicore Platforms

Developing heterogeneous multicore platforms requires choosing the best hardware configuration for mapping the application, and modifying that application so that different parts execute on the most appropriate hardware component. The hArtes toolchain provides the option of automatic or semi-automatic support for this mapping. During test and validation on several computation-intensive applications, hArtes achieved substantial speedups and drastically reduced development times

Potential therapeutic effect of curcumin loaded hyalurosomes against inflammatory and oxidative processes involved in the pathogenesis of rheumatoid arthritis: The use of fibroblast-like synovial cells cultured in synovial fluid

In the present work curcumin loaded hyalurosomes were proposed as innovative systems for the treatment of rheumatoid arthritis. Vesicles were prepared using a one-step and environmentally friendly method. Aiming at finding the most suitable formulation in terms of size, surface charge and stability on storage, an extensive pre-formulation study was performed using different type and amount of phospholipids. Curcumin loaded vesicles prepared with 180 mg/ml of Phospholipon 90G (P90G) and immobilized with sodium hyaluronate (2 mg/ml) were selected because of their small size (189 nm), homogeneous dispersion (PI 0.24), negative charge (−35 mV), suitable ability to incorporate high amount of curcumin (E% ∼88%) and great stability on storage. The in vitro study using fibroblast-like synovial cells cultured in synovial fluid, demonstrated the ability of these vesicles to downregulate the production of anti-apoptotic proteins IAP1 and IAP2 and stimulate the production of IL-10, while the production of IL-6 and IL-15 and reactive oxygen species was reduced, confirming their suitability in counteracting pathogenesis of rheumatoid arthritis

In Vitro Activity of the Arylaminoartemisinin GC012 against Helicobacter pylori and Its Effects on Biofilm

This study evaluated the in vitro activity of the arylaminoartemisinin GC012, readily obtained from dihydroartemisinin (DHA), against clinical strains of Helicobacter pylori (H. pylori) with different antibiotic susceptibilities in the planktonic and sessile state. The activity was assessed in terms of bacteriostatic and bactericidal potential. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by the broth microdilution method. After treatment with GC012, all bacterial strains showed significantly lower MIC and MBC values compared to those of DHA. The effect of combination of GC012 with antibiotics was examined using the checkerboard method. GC012 displayed synergistic interactions with metronidazole, clarithromycin, and amoxicillin in all the strains. The antibiofilm activity was evaluated via crystal violet staining, AlamarBlue&reg; assay, colony-forming unit count, and fluorescence microscopy. At &frac12; MIC and &frac14; MIC concentration, both GC012 and DHA inhibited biofilm formation, but only GC012 showed a minimal biofilm eradication concentration (MBEC) on mature biofilm. Furthermore, both compounds induced structural changes in the bacterial membrane, as observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). It is thereby demonstrated that GC012 has the potential to be efficacious against H. pylori infection

Nanoincorporation of curcumin in polymer-glycerosomes and evaluation of their in vitro-in vivo suitability as pulmonary delivery systems

The aim of this work was to deliver curcumin into the lungs by incorporating it into innovative vesicles obtained using phospholipids and high concentrations of glycerol (50%, v/v), so called glycerosomes, which were then combined with two polymers: sodium hyaluronate and trimethyl chitosan to form polymer-glycerosomes. These systems were prepared without the use of organic solvents or acidic solutions and their physico-chemical properties were fully characterized. Cryogenic transmission electron microscopy and small-angle X-ray scattering showed that both glycerosomes and polymer-glycerosomes were spherical, mainly unilamellar and of nanometric size (65-112 nm). The vesicles were readily nebulized with the largest amount of curcumin being found in the latest stages of the Next Generation Impactor™. In vitro results revealed the high biocompatibility of samples especially those containing the polymers. Curcumin loaded vesicles were also able to protect in vitro A549 cells stressed with hydrogen peroxide, restoring healthy conditions, not only by directly scavenging free radicals but also by indirectly inhibiting the production of cytokine IL6 and IL8. Moreover, in vivo results in rats showed the high capacity of these formulations to favour the curcumin accumulation in the lungs confirming their potential use as a target system for the treatment of pulmonary diseases

Evaluation of anti-GHS-R Mab specificity.

<p>A. Western blot of analysis of a selected brain region (hypothalamus) and a non-brain GHS-R bearing tissue (heart) showing a single band of the predicted molecular weight for GHSR at 48 kDa B. Immunoprecipitation of rat cortical (C) and hippocampal (H) primary neurons lysates with Mab 1D8B2 and commercial polyclonal antibody. Lysates from rat hippocampal and cortical neurons after nine days in vitro were immunoprecipitated with Mab (8 µg) or polyclonal antibody (CTRL), resolved and transferred to nitrocellulose membranes. The western blot analysis were performed with the polyclonal antibody when the monoclonal was used for immunoprecipitation and the other way around, both immunoprecipitation analysis clearly showed a 48 kD band corresponding to the predicted size of GHS-R. β-actin was used as a loading control. Sizes (kD) of molecular mass markers are indicated on the right.</p