The inhibitory effects of Cinnamomum cassia bark-derived material on nitric oxide (NO) production in RAW 264.7 cells was determined through the evaluation of NO production and expression of inducible nitric oxide and compared to the effects of three commercially available compounds, cinnamyl alcohol, cinnamic acid, and eugenol. The biologically active constituents of C. cassia extract were characterized as trans-cinnamaldehyde by spectral analysis. The inhibitory effects varied with both chemical and concentration used. Potent inhibitory effects of cinnamaldehyde against NO production were 81.5 and 71.7% at 1.0 and 0.5 microg/microL, respectively, and a 41.2% inhibitory effect was revealed at 0.1 microg/microL. However, little or no activity was observed for cinnamic acid and eugenol. Suppression effects of cinnamaldehyde on inducible nitric oxide synthase expression were revealed by Western blot analysis. As a naturally occurring therapeutic agent, trans-cinnamaldehyde could be useful for developing new types of NO inhibitors.
Key Points• Donor treatment with agonistic DR3 antibody induces selective expansion of Tregs and reduced activation of conventional T cells.• T cells from DR3 antibodytreated donors result in reduced acute GVHD and preserved GVT effects. numbers of Tregs and were less proliferative to allogeneic stimuli. In vivo GVHD studies confirmed that Tregs from aDR3-treated donors expanded robustly and higher frequencies of Tregs within donor CD4 1 T cells were maintained, resulting in improved survival. Conventional T cells derived from aDR3-treated donors showed reduced activation and proliferation. Serum levels of proinflammatory cytokines (IFNg, IL-1b, and TNFa) and infiltration of donor T cells into GVHD target tissues (gastrointestinal tract and liver) were decreased. T cells from aDR3-treated donors retained graft-vs-tumor (GVT) effects. In conclusion, a single dose of aDR3 alleviates acute GVHD while preserving GVT effects by selectively expanding and maintaining donor Tregs. This novel strategy will facilitate the clinical application of Treg-based therapies. (Blood. 2015; 126(4):546-557)
CD4Foxp3 regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft-versus-host disease (GVHD) in murine models of allogeneic hematopoietic stem cell transplantation. We recently demonstrated that a single treatment of the agonistic antibody to DR3 (death receptor 3, αDR3) to donor mice resulted in the expansion of donor-derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated. In this study, we comprehensively analyzed the immunophenotype of Treg after DR3 signal activation, demonstrating that DR3-activated Treg (DR3-Treg) had an activated/mature phenotype. Furthermore, the CD25Foxp3 subpopulation in DR3-Treg showed stronger suppressive effects in vivo. Prophylactic treatment of αDR3 to recipient mice expanded recipient-derived Treg and reduced the severity of GVHD, whereas DR3 activation in mice with ongoing GVHD further promoted donor T-cell activation/proliferation. These data suggest that the function of DR3 signaling was highly dependent on the activation status of the T cells. In conclusion, our data demonstrated that DR3 signaling affects the function of Treg and T-cell activation after alloantigen exposure in a time-dependent manner. These observations provide important information for future clinical testing using human DR3 signal modulation and highlight the critical effect of the state of T-cell activation on clinical outcomes after activation of DR3.
The present work addresses Au(III) extraction from chloride media using phosphonium-based ionic liquid (Cyphos IL 109) as a novel anion exchanger diluted in xylene. Gold(III) is extracted into the organic phase as [P 66614 + ][AuCl 4 − ] and can easily be stripped by reduction to Au(I) with CS(NH 2 ) 2 /HCl or Na 2 S 2 O 3 . A series of extraction-stripping cycles show a possible recirculation of used solvent without loss of performance, as far as the extraction of gold(III) from HCl/Cl − media is concerned. Au(III) was quantitatively (99.4%) extracted from 0.1 mol L −1 HCl initially containing 100 mg L −1 Au(III) with 0.8 g L −1 Cyphos IL 109 with two counter-current stages at O/A = 1, whereas total stripping as Au(I) with 0.02 mol L −1 CS(NH 2 ) 2 in 5% HCl or 0.02 mol L −1 Na 2 S 2 O 3 also needed two counter-current stages, at O/A = 3. Simulations of counter-current modes reveal Cyphos IL 109 can be considered a promising new extractant for complete recovery of Au(III) from Cl − media in pilot scale.
The reduction of MoO 2 powder by hydrogen is one of the most important steps for manufacturing ferromolybdenum alloy and molybdenum powder. The results of experiments on the kinetics of this reaction are presented in this paper. The experiments were carried out under nonisothermal condition in hydrogen atmosphere using TGA equipment. The nonisothermal experiments were carried out at various linear heating rates up to 1273 K. It was found that the reduction reaction is very fast under the whole heating rate until the reduction ratio of MoO 2 approaches to about 0.92. The reduction ratio of MoO 2 was about 0.98 after finishing the reduction reaction at a heating rate of 4 K/min. Kinetics of the reaction was analyzed from the dynamic TGA data by means of Coats and Redfern equation. The nucleation and growth model yielded a satisfactory fit to these experimental data.
This study deals with the reduction of tin oxide by hydrogen in the temperature range of 773$1023 K and the hydrogen partial pressure of 30:4$101:3 kPa. It aims to investigate the kinetics of the reaction between tin oxide and hydrogen. The hydrogen reduction of tin oxide is to be related with the efforts to extract tin metal with decreasing the emission of carbon dioxide which causes global warming. The experiments were carried out under isothermal condition in hydrogen atmosphere using TGA equipment. The reduction rate of tin oxide to tin metal by hydrogen was found to be relatively fast under the whole conditions until the reduction ratio of SnO 2 approaches to about 0.95. As an example, at 1023 K under a hydrogen partial pressure of 101.3 kPa, almost 100% of tin oxide was reduced to tin metal in 10 min. The nucleation and growth model yielded a satisfactory fit to these experimental data. The reaction was first order with respect to hydrogen partial pressure and had an activation energy of 62.5 kJ/mol (15.0 kcal/mol).
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