Role of mitogen-activated protein kinases in the iNOS production and cytokine secretion by salmonella enterica serovar Typhimurium porins.

Abstract The expression of inducible nitric oxide synthase (iNOS) is a critical factor in both physiological and pathological functions. The present study examined the role of mitogen-activated protein kinases (MAPKs) in the regulation of iNOS and proinflammatory cytokine production in RAW 264.7 cells in response to Salmonella enterica serovar Typhimurium porins. By use of Western blotting for iNOS detection and enzyme-linked immunosorbent assay (ELISA) for quantization of cytokine secretion, selective pharmacological inhibitors of MAPK pathways were tested for dissecting the molecular mechanisms underlying the mediation of these signaling in porins-stimulated murine macrophages. S. enterica serovar Typhimurium porins activated iNOS expression, NO production and interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) release. Treatment of cells with SB203580 and SP600125 (inhibitors of p38 and JNK, respectively) significantly affected porin-stimulated iNOS and NO production. Concomitant decrease in the proinflammatory cytokine secretion was detected. These data confirm the importance of the MAPKs cascade in macrophage activation by bacterial product opening up new strategies for therapy of septic shock

MODELLING AN ADEQUATE PROFILE FOR A MORE TARGETED WORK METHODOLOGY, WITH DEDICATED TECHNOLOGIES, FOR ELITE-LEVEL FOOTBALLERS: COMPARISON BETWEEN SUB 17 VS SUB 19, HIGHLIGHTS AND SHADOWS

Purpose: The aim of this study is to compare physical performance during official match (under 17 Championship Serie A and B, under 19Serie B) in two different professional football team and analyze which are the physical parameters that differentiates better under 17 (U-17) and under 19 (U-19) young elite-level football teams. Method: Forty-five (n=45) professional soccer players were analyzed (n=23 under 17; age 16.5±0.5 body weight 69.8±7.0 kg; height 177±8.0cm; fat mass 8.2±3.6 %) and (n=22 under 19; age 17±0.4 years, body weight 70.9±5.8 kg; height 180±5.3 cm; fat mass 8.9±3.6%),excluding goalkeepers, they have been analyzed during 50 official matches (2017-2018: 26 Matches U-17 and 24 Matches U-19 respectively) with K-GPS 20Hz (K-Sport Universal STATS, Montelabbate (PU), Italy).Results: Distance covered at very high intensity acceleration (D_A8, m) is significantly higher in U-19 vs U-17 (ES=1.14; p 3m/s²), are greater in U-19 respect to U-17, in the entire season, in fact this parameter is correlated with the development of strength and muscle mass (growth process).This underline the importance to strength training from young ages respecting physiological processes of development

Processing, Characterization, and Oxidation Resistance of Glass-Ceramic Coating on CoSb₃

Power generation based on thermoelectric (TE) materials is very attractive due to its low environmental impact and waste heat recovery. Thermoelectric materials based on cobalt triantimonide CoSb3 exhibit one of the highest energy conversion efficiencies, revealing thermoelectric figures of merit, ZTs > 1, but undergo oxidation above 380 °C and sublimation above 500 °C. In this work, a glass-ceramic coating was chosen to match the coefficient of thermal expansion (CTE) of the TE substrate 9.2 × 10−6 K−1 (200–400 °C), deposition temperature (max. 700 °C), and maximum working temperature (600 °C). Coating processing involved the production of glass powder and glass-ceramic sintering. The glass-ceramic and the coating/CoSb3 interface were systematically investigated by means of dilatometry, X-ray diffraction, and scanning and transmission electron microscopy. As a result, a coating with good substrate coverage and adherence was developed. Finally, oxidation tests were carried out at 500 and 600 °C in order to assess the protective properties of the glass-ceramic. Microstructural and chemical composition analysis indicated limited protective properties of the coating

Porins from Salmonella enterica serovar Typhimurium activate the transcription factors AP-1 and NF-kB through the Raf-1-mitogen activated protein kinase cascade

In this study we examined the ability of Salmonella enterica serovar Typhimurium porins to activate activating protein 1 (AP-1) and nuclear factor kappaB (NF-kappaB) through the mitogen-activated protein kinase (MAPK) cascade, and we identified the AP-1-induced protein subunits. Our results demonstrate that these enzymes may participate in cell signaling pathways leading to AP-1 and NF-kappaB activation following porin stimulation of cells. Raf-1 was phosphorylated in response to the treatment of U937 cells with porins; moreover, the porin-mediated increase in Raf-1 phosphorylation is accompanied by the phosphorylation of MAPK kinase 1/2 (MEK1/2), p38, extracellular-signal-regulated kinase 1/2, and c-Jun N-terminal kinase. We used three different inhibitors of phosphorylation pathways: 2'-amino-3'-methoxyflavone (PD-098059), a selective inhibitor of MEK1 activator and the MAPK cascade; 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580), a specific inhibitor of the p38 pathway; and 7beta-acetoxy-1alpha,6beta,9alpha-trihydroxy-8,13-epoxy-labd-14-en-11-one (forskolin), an inhibitor at the level of Raf-1 kinase. PD-098059 pretreatment of cells decreases AP-1 and NF-kappaB activation by lipopolysaccharide (LPS) but not by porins, and SB203580 pretreatment of cells decreases mainly AP-1 and NF-kappaB activation by porins; in contrast, forskolin pretreatment of cells does not affect AP-1 and NF-kappaB activation following either porin or LPS stimulation. Our data suggest that the p38 signaling pathway mainly regulates AP-1 and NF-kappaB activation in cells treated with S. enterica serovar Typhimurium porins. Antibody electrophoretic mobility shift assays showed that JunD and c-Fos binding is found in cells treated with porins, in cells treated with LPS, and in unstimulated cells. However, by 30 to 60 min of stimulation, a different complex including c-Jun appears in cells treated with porins or LPS, while the Fra-2 subunit is present only after porin stimulation. These data suggest different molecular mechanisms of activation induced by porins or by LPS

Glass-ceramic oxidation protective coatings for manganese- and magnesium-based thermoelectric silicides

Higher manganese silicide (HMS) and magnesium silicide are considered promising thermoelectric materials to generate electricity from waste-heat recovery. However, a critical issue is their stability over time and their oxidation resistance at temperatures above 500°C. Glass-based materials, due to their low electrical and thermal conductivity, are good candidates as protective coatings. In this work, MnSi1.74 and Mg2Si0.487Sn0.5Sb0.013 substrates, densified by spark plasma sintering, were coated with silica-based glass-ceramic materials in order to provide oxidation protection. The thermal cycling stability (from room temperature to 600°C in air) of as-sintered and glass-ceramic coated HMS was studied, with respect to changes in their chemical composition and electrical properties. The formation of a Si-deficient layer on the uncoated HMS, due to the reaction between HMS and oxygen at 600°C, led to a higher electrical resistivity as well as a reduced power factor. The coated samples did not show variations in electrical properties compared to the as-sintered one, thus demonstrating that the use of a glass-ceramic coating is an efficient oxidation protective system during cyclic working conditions. Moreover, a new silica-based glass-ceramic coating for magnesium silicide was designed in order to improve the long-term reliability of the thermoelectric module and its efficiency

Glass-ceramic oxidation protection of higher manganese silicide thermoelectrics

A higher manganese silicide (HMS) thermoelectric, with composition MnSi1.74, densified by spark plasma sintering, was successfully coated with a glass-ceramic, in order to be used at temperatures higher than 500°C. Compositional changes in both the HMS substrate and the glass-ceramic coating are reviewed and discussed with respect to the electrical properties of the uncoated and coated HMS before and after thermal cycles from RT to 600°C in air. The formation of a Si-deficient layer (MnSi) on the uncoated HMS surface is due to the reaction between the HMS and oxygen at 600°C, thus contributing to a lower power factor in comparison with the as-sintered HMS. Coated HMS samples (after thermal cycles RT-600°C) show a lower electrical resistivity and a significantly higher power factor in comparison with the uncoated ones. The glass-ceramic coating is self-reparable at 600°C, as demonstrated by the complete sealing of an induced scratch on its surface