Annual Report 2018

Memoria Científica del año 2018

Osteogenic effects of simvastatin-loaded mesoporous titania thin films

The use of statins in the field of bone regeneration is under current investigation due to the existing demand for non-toxic anabolic agents capable of enhancing bone formation in cases of substantial loss. Simvastatin, a coenzyme currently prescribed in clinics to inhibit cholesterol biosynthesis, has been proven to promote osteogenic differentiation by stimulating bone formation and inhibiting osteoclasts activity. We present the loading of simvastatin in mesoporous TiO2 thin films toward combining the pro-osteogenic properties of this molecule with the demonstrated bioactivity of titania. TiO2 thin films processing and characterization were carried out, as well as evaluation of MC3T3-E1 pre-osteoblasts viability when directly incubated with different concentrations of simvastatin, followed by the analysis of osteogenic activity promoted by simvastatin upon loading in the thin films. The accessible porosity of 36% quantified on the 95 ± 5 nm thick mesoporous thin films, together with pore diameters of 5.5 nm, necks between pores of 2.8 nm and interpore distances of 12 ± 2 nm allow the loading of the simvastatin molecule, as confirmed by FTIR spectroscopy. Simvastatin was found to promote MC3T3-E1 pre-osteoblasts viability at concentrations ≤0.01 g l−1, with a cytotoxicity threshold of 0.05 g l−1. We additionally found that film loadings with 0.001 g l−1 simvastatin promotes statistically higher MC3T3-E1 pre-osteoblast proliferation whereas a higher concentration of 0.01 g l−1 leads to statistically higher osteogenic activity (ALP synthesis), after 21 days of incubation, as compared to unloaded films. These results demonstrate the potential of simvastatin local administration based on bioactive mesoporous thin films to promote pro-osteogenic properties. By focusing this strategy on the coating of metallic prostheses, the supply of simvastatin to the target tissue can be favored and risks of systemic side effects will be reduced while enhancing the osteointegration of the implants.Fil: Lopez Alvarez, Miriam. Universidad de Vigo; EspañaFil: López Puente, Vanesa. Universidad de Vigo; EspañaFil: Rodriguez Valencia, Cosme. Universidad de Vigo; EspañaFil: Angelome, Paula Cecilia. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Liz Marzan, Luis M. Ikerbasque; EspañaFil: Serra, Julia. Universidad de Vigo; EspañaFil: Pastoriza Santos, Isabel. Universidad de Vigo; EspañaFil: Gonzalez, Pio. Universidad de Vigo; Españ

Serum levels of il-8, il-10, il-13, ifnγ and tnfα in pediatric patients with acute infection with different dengue virus serotypes

Dengue is an acute febrile disease caused by four dengue virus (DENV) serotypes whose prevalence in the Americas has quintupled between 2003 and 2013. The immune response against the infection with dengue virus involves cellular and humoral factors. We performed an observational and cross-sectional study to evaluate the levels of interleukins of the innate immune response (IL-8, TNFα), TH1 response (IFNγ), TH2 (IL-13) and regulatory (IL-10) in serum of patients during the acute phase of infection with the DENV1, DENV3 and DENV4 serotypes

Niveles séricos de il-8, il-10, il-13, ifnγ y tnfα en pacientes pediátricos con infección aguda por diferentes serotipos de virus dengue

Dengue is an acute febrile disease caused by four dengue virus (DENV) serotypes whose prevalence in the Americas has quintupled between 2003 and 2013. The immune response against the infection with dengue virus involves cellular and humoral factors. We performed an observational and cross-sectional study to evaluate the levels of interleukins of the innate immune response (IL-8, TNFα), TH1 response (IFNγ), TH2 (IL-13) and regulatory (IL-10) in serum of patients during the acute phase of infection with the DENV1, DENV3 and DENV4 serotypes.El dengue es una enfermedad aguda febril causada por cuatro serotipos del virus dengue (DENV) cuya prevalencia en las Américas se ha quintuplicado entre 2003 y 2013. La respuesta inmune contra la infección del virus del dengue involucra la participación de factores celulares y humorales. Se realizó una investigación de corte transversal observacional para evaluar los niveles de interleucinas de la respuesta inmune innata (IL-8, TNFα), de respuesta TH1 (IFNγ), TH2 (IL-13) y regulatoria (IL-10) en suero de pacientes durante la fase aguda de infección por los serotipos DENV1, DENV3 y DENV4

El arte del color: colorantes naturales, tintes y pigmentos laca

El objetivo general del proyecto propuesto ha sido desarrollar una metodología que sirva de apoyo a las prácticas de laboratorio realizadas por los alumnos para las asignaturas que integran en sus competencias el estudio de tintes, pigmentos lacas y métodos extracción de colorantes y de tinción. Basándose en la relación que existe entre los fenómenos físicos y químicos implicados en los métodos desarrollados con la obtención del pigmento laca y tinte. Además del estudio de la influencia de diferentes elementos como mordientes, soportes inorgánicos y variables como el pH y la T

Filamin a expression negatively regulates Sphingosine-1-phosphate-induced NF-κB activation in melanoma cells by inhibition o Akt signaling

Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that regulates many processes in inflammation and cancer. S1P is a ligand for five G-protein-coupled receptors, S1PR1 to -5, and also has important intracellular actions. Previously, we showed that intracellular S1P is involved in tumor necrosis factor alpha (TNF)-induced NF-κB activation in melanoma cell lines that express filamin A (FLNA). Here, we show that extracellular S1P activates NF-κB only in melanoma cells that lack FLNA. In these cells, S1P, but not TNF, promotes IκB kinase (IKK) and p65 phosphorylation, IκBα degradation, p65 nuclear translocation, and NF-κB reporter activity. NF-κB activation induced by S1P was mediated via S1PR1 and S1PR2. Exogenous S1P enhanced the phosphorylation of protein kinase Cδ (PKCδ), and its downregulation reduced S1P-induced the phosphorylation of IKK and p65. In addition, silencing of Bcl10 also inhibited S1P-induced IKK phosphorylation. Surprisingly, S1P reduced Akt activation in melanoma cells that express FLNA, whereas in the absence of FLNA, high phosphorylation levels of Akt were maintained, enabling S1P-mediated NF-κB signaling. In accord, inhibition of Akt suppressed S1P-mediated IKK and p65 phosphorylation and degradation of IκBα. Hence, these results support a negative role of FLNA in S1P-mediated NF-κB activation in melanoma cells through modulation of Akt.Fil: Campos, Ludmila Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Rodriguez, Yamila Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Machado Leopoldino, Andreia. Virginia Commonwealth University. School of Medicine; Estados Unidos. Universidade de Sao Paulo; BrasilFil: Hait, Nitai C.. Virginia Commonwealth University. School of Medicine; Estados UnidosFil: Lopez Bergami, Pablo Roberto. Universidad Maimonides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castro, Melina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Sanchez, Emilse Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Maceyka, Michael. Virginia Commonwealth University. School of Medicine; Estados UnidosFil: Spiegel, Sarah. Virginia Commonwealth University School Of Medicine;Fil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin

Mitochondrial genetic diversity of Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) associated with cassava in Lao PDR

Cassava Mosaic Disease (CMD) caused by Sri Lankan cassava mosaic virus (SLCMV), has rapidly spread in Southeast Asia (SEA) since 2016. Recently it has been documented in Lao PDR. Previous reports have identified whitefly species of B. tabaci as potential vectors of CMD in SEA, but their occurrence and distribution in cassava fields is not well known. We conducted a countrywide survey in Lao PDR for adult whiteflies in cassava fields, and determined the abundance and genetic diversity of the B. tabaci species complex using mitochondrial cytochrome oxidase I (mtCOI) sequencing. In order to expedite the process, PCR amplifications were performed directly on whitefly adults without DNA extraction, and mtCOI sequences obtained using nanopore portable-sequencing technology. Low whitefly abundances and two cryptic species of the B. tabaci complex, Asia II 1 and Asia II 6, were identified. This is the first work on abundance and genetic identification of whiteflies associated with cassava in Lao PDR. This study indicates currently only a secondary role for Asia II in spreading CMD or as a pest. Routine monitoring and transmission studies on Asia II 6 should be carried out to establish its potential role as a vector of SLCMV in this region

The Fluid Aspect of the Mediterranean Diet in the Prevention and Management of Cardiovascular Disease and Diabetes: The Role of Polyphenol Content in Moderate Consumption of Wine and Olive Oil

A growing interest has emerged in the beneficial effects of plant-based diets for the prevention of cardiovascular disease, diabetes and obesity. The Mediterranean diet, one of the most widely evaluated dietary patterns in scientific literature, includes in its nutrients two fluid foods: olive oil, as the main source of fats, and a low-to-moderate consumption of wine, mainly red, particularly during meals. Current mechanisms underlying the beneficial effects of the Mediterranean diet include a reduction in inflammatory and oxidative stress markers, improvement in lipid profile, insulin sensitivity and endothelial function, as well as antithrombotic properties. Most of these effects are attributable to bioactive ingredients including polyphenols, mono- and poly-unsaturated fatty acids. Polyphenols are a heterogeneous group of phytochemicals containing phenol rings. The principal classes of red wine polyphenols include flavonols (quercetin and myricetin), flavanols (catechin and epicatechin), anthocyanin and stilbenes (resveratrol). Olive oil has at least 30 phenolic compounds. Among them, the main are simple phenols (tyrosol and hydroxytyrosol), secoroids and lignans. The present narrative review focuses on phenols, part of red wine and virgin olive oil, discussing the evidence of their effects on lipids, blood pressure, atheromatous plaque and glucose metabolism

Gene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients

Introduction: there are limited findings available on KIT-negative GIST-like (KNGL) population. Also, KIT expression may be post-transcriptionally regulated by miRNA221 and miRNA222. Hence, the aim of this study is to characterize KNGL population, by differential gene expression, and to analyze miRNA221/222 expression and their prognostic value in KNGL patients. Methods: KIT, PDGFRA, DOG1, IGF1R, MIR221 and MIR222 expression levels were determined by qRT-PCR. We also analyzed KIT and PDGFRA mutations, DOG1 expression, by immunohistochemistry, along with clinical and pathological data. Disease-free survival (DFS) and overall survival (OS) differences were calculated using Log-rank test. Results: hierarchical cluster analyses from gene expression data identified two groups: group I had KIT, DOG1 and PDGFRA overexpression and IGF1R underexpression and group II had overexpression of IGF1R and low expression of KIT, DOG1 and PDGFRA. Group II had a significant worse OS (p = 0.013) in all the series, and showed a tendency for worse OS (p = 0.11), when analyzed only the localized cases. MiRNA222 expression was significantly lower in a control subset of KIT-positive GIST (p < 0.001). OS was significantly worse in KNGL cases with higher expression of MIR221 (p = 0.028) or MIR222 (p = 0.014). Conclusions: we identified two distinct KNGL subsets, with a different prognostic value. Increased levels of miRNA221/222, which are associated with worse OS, could explain the absence of KIT protein expression of most KNGL tumors