Succinate is an intermediate of the citric acid cycle as well as an extracellular circulating molecule, whose receptor, G protein-coupled receptor-91 (GPR91), was recently identified and characterized in several tissues, including heart. Because some pathological conditions such as ischemia increase succinate blood levels, we investigated the role of this metabolite during a heart ischemic event, using human and rodent models. We found that succinate causes cardiac hypertrophy in a GPR91 dependent manner. GPR91 activation triggers the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), the expression of calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) and the translocation of histone deacetylase 5 (HDAC5) into the cytoplasm, which are hypertrophic-signaling events. Furthermore, we found that serum levels of succinate are increased in patients with cardiac hypertrophy associated with acute and chronic ischemic diseases. These results show for the first time that succinate plays an important role in cardiomyocyte hypertrophy through GPR91 activation, and extend our understanding of how ischemia can induce hypertrophic cardiomyopathy.
MWCNT and CNF are interesting NPs that possess great potential for applications in various fields such as water treatment, reinforcement materials and medical devices. However, the rapid dissemination of NPs can impact the environment and in the human health. Thus, the aim of this study was to evaluate the MWCNT and cotton CNF toxicological effects on freshwater green microalgae Chlorella vulgaris.
1 October 2014 in Journal of Petroleum Science and Engineering
Carbon nanotubes (CNTs) and nanofibers (CNFs) were synthesized on clinker and silica fume particles in order to create a low cost cementitious nanostructured material. The synthesis was carried out by an in situ chemical vapor deposition (CVD) process using converter dust, an industrial byproduct, as iron precursor. The use of these materials reduces the cost, with the objective of application in large-scale nanostructured cement production. The resulting products were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and thermogravimetric analysis (TGA) and were found to be polydisperse in size and to have defective microstructure. Some enhancement in the mechanical behavior of cement mortars was observed due to the addition of these nano-size materials. The contribution of these CNTs/CNFs to the mechanical strength of mortar specimens is similar to that of high quality CNTs incorporated in mortars by physical mixture.
Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. Despite the recent licensure of the CYD-TDV dengue vaccine in some countries, results from the vaccine’s phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.
1 April 2019 in Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology