Silencing of CD40 in vivo reduces progression of experimental atherogenesis through an NF-kappa B/miR-125b axis and reveals new potential mediators in the pathogenesis of atherosclerosis
ATHEROSCLEROSIS
Authors: Hueso, Miguel; De Ramon, Laura; Navarro, Estanislao; Ripoll, Elia; Cruzado, Josep M.; Grinyo, Josep M.; Torras, Joan
Abstract
Background and aims: CD40/CD40L signaling exerts a critical role in the development of atherosclerosis, and microRNAs (miRNAs) are key regulators in vascular inflammation and plaque formation. In this work, we investigated mRNA/miRNA expression during progression of atherosclerotic lesions through CD40 silencing. Methods: We silenced CD40 with a specific siRNA in ApoE(-/-) mice and compared expression of mRNA/miRNA in ascending aorta with scrambled treated mice. Results: siRNA-CD40 treated mice significantly reduced the extension and severity of atherosclerotic lesions, as well as the number of F4/80(+), galectin-3(+) macrophages and NF-kappa B+ cells in the intima. Genome-wide mRNA/miRNA profiling allowed the identification of transcripts, which were significantly upregulated during atherosclerosis; among them, miR-125b and miR-30a, Xpr1, a regulator of macrophage differentiation, Taf3, a core transcription factor and the NF-kappa B activator Ikk beta, whereas, the NF-kappa B inhibitor Ikba was downregulated during disease progression. All those changes were reversed upon CD40 silencing. Interestingly, TAF3, XPR1 and miR-125b were also overexpressed in human atherosclerotic plaques. Murine Taf3 and Xpr1 were detected in the perivascular adipose tissue (PVAT), and Taf3 also in intimal foam cells. Finally, expression of miR-125b was regulated by the CD40-NF-kappa B signaling axis in RAW264.7 macrophages. Conclusions: CD40 silencing with a specific siRNA ameliorates progression of experimental atherosclerosis in ApoE(-/-) mice, and evidences a role for NF-kappa B, Taf3, Xpr1, and miR-125b in the pathogenesis of atherosclerosis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Tantalum carbide products from chemically-activated combustion synthesis reactions
CERAMICS INTERNATIONAL
Authors: Musa, Clara; Licheri, Roberta; Montinaro, Selena; Orru, Roberto; Cao, Giacomo
Abstract
A rapid route based on the use of small amounts of polytetrafluoroethylene to chemically activate and sustain the combustion synthesis reaction for the formation of TaC from its elements is successfully exploited in this work. Other than a reaction booster, the polymer is found to play also a role as a carbon source, so that part of graphite can be replaced by Teflon to produce a single phase material. A relevant importance in the activation of the synthesis reaction is provided by the intermediate phase TaF3, whose formation is clearly evidenced, along with that of Ta2C, by combustion front quenching experiments. Additive free TaC products with relative density up to about 98% and grains size less than 5 mu m are finally obtained when combustion synthesized powders are processed for 20 min at 1800 degrees C by Spark Plasma Sintering. A further increase in the sintering temperature to 2050 degrees C and/or the dwell time to 30 min is found to negatively affect product densification. This outcome is mainly ascribed to the significant grains coarsening (above 20 gm) correspondingly observed as well as to other vapor-phase generating events, which could be more easily induced when powders are exposed to higher temperature conditions.