Succinate causes pathological cardiomyocyte hypertrophy through GPR91 activation

Background\ud 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.\ud \ud \ud Results\ud 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.\ud \ud \ud Conclusions\ud 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.CAPESFAPEMIG (Pronex)INCT- Carbon NanotubesCNPqHHM

Using Converter Dust to Produce Low Cost Cementitious Composites by in situ Carbon Nanotube and Nanofiber Synthesis

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

Antileishmanial activity of fullerol and its liposomal formulation in experimental models of visceral leishmaniasis

Visceral leishmaniasis (VL) is a systemic parasitic disease that leads to high rates of morbidity and mortality in humans worldwide. There is a great need to develop new drugs and novel strategies to make chemotherapy for this disease more efficacious and well tolerated. Recent reports on the immunomodulatory effects and the low toxicity of the spherical carbon nanostructure fullerol led us to investigate in vitro and in vivo antileishmanial activity in free and encapsulated forms in liposomes. When assayed against intramacrophagic Leishmania amastigotes, fullerol showed a dose-dependent reduction of the infection index with IC50 of 0.042 mg/mL. When given daily by i.p. route for 20 days (0.05 mg/kg/d) in a murine model of acute VL, fullerol promoted significant reduction in the liver parasite load. To improve the delivery of fullerol to the infection sites, liposomal formulations were prepared by the dehydration-rehydration method. When evaluated in the acute VL model, liposomal fullerol (Lip-Ful) formulations given i.p. at 0.05 and 0.2 mg/kg with 4-days intervals were more effective than the free form, with significant parasite reductions in both liver and spleen. Lip-Ful at 0.2 mg/kg promoted complete parasite elimination in the liver. The antileishmanial activity of Lip-Ful was further confirmed in a chronic model of VL. Lip-Ful was also found to induce secretion of pro-inflammatory TNF-α, IFN-γ and IL-1β cytokines. In conclusion, this work reports for the first time the antileishmanial activity of fullerol and introduces an innovative approach for treatment of VL based on the association of this nanostructure with liposomes

HDR brachytherapy decreases proliferation rate and cellular progression of a radioresistant human squamous cell carcinoma in vitro

<p><b>Purpose:</b> To investigate the effects of high dose rate (HDR) brachytherapy on cellular progression of a radioresistant human squamous cell carcinoma in vitro, based on clinical parameters.</p> <p><b>Materials and methods:</b> An acrylic platform was designed to attach tissue culture flasks and assure source positioning during irradiation. At exponential phase, A431cells, a human squamous cell carcinoma, were irradiated twice up to 1100 cGy. Cellular proliferation was assessed by Trypan blue exclusion assay and survival fraction was calculated by clonogenic assay. DNA content analysis and cell cycle phases were assessed by flow cytometry and gel electrophoresis, respectively. Cellular death patterns were measured by HOPI double-staining method.</p> <p><b>Results:</b> Significant decreasing cellular proliferation rate (<i>p</i> < 0.05) as well as reduced survival fraction (<i>p</i> < 0.001) in irradiated cells were observed. Moreover, increased percentage of cells arrested in the G₂/M phase (32.3 ± 1.5%) in the irradiated group as compared with untreated cells (8.22 ± 1.2%) was detected. Also, a significant (<i>p</i> < 0.0001) nuclei shrinking in irradiated cells without evidence of necrosis or apoptosis was found.</p> <p><b>Conclusion:</b> HDR brachytherapy led to a decreased proliferation rate and cell survival and also hampered cellular progression to mitosis suggesting that tumor cell death mainly occurred due to mitotic death and G₂/M cell cycle arrest.</p

Universal saturation behavior in the transient optical response of plasmonic structures

We perform ultrafast pump-probe spectroscopy of plasmonic structures beyond the perturbative excitation regime. As a prototypical system we choose gold nanorods dispersed in water, which display both longitudinal and transverse plasmon resonances. A broadband investigation reveals a complex scenario for the saturation of the transient optical response as a function of the pump fluence, with strong dependence on the probe wavelength. In particular, we observed stronger saturation effects for the high energy transverse plasmonic resonance as compared to the low energy longitudinal one. This behavior is well captured by a three-temperature model and is understood in terms of the nonlinearity of the Fermi-smearing mechanism, presiding over the optical nonlinearity of noble metal nanomaterials. Our results highlight a universal saturation dynamics in the transient optical response of plasmon-enhanced photonic structures excited by intense light beams, with potential impact on many applications, from the all-optical modulation of light to photovoltaics and photocatalysis