Functionalization of Ruthenium(II) terpyridine complexes with cyclic RGD peptides to target integrin receptors in cancer cells

The lack of selectivity for cancer cells and the resulting negative impact on healthy tissue is a severe drawback of actual cancer chemotherapy. Tethering of cytotoxic drugs to targeting vectors such as peptides, which recognize receptors overexpressed on the surface of tumor cells, is one possible strategy to overcome such a problem. The pentapeptide cyc(RGDfK) targets the integrin receptor αvβ3, important for tumor growth and metastasis formation. In this work, two terpyridine based Ru(II) complexes were prepared and for the first time conjugated to cyc(RGDfK) via amide bond formation resulting in a monomeric and a dimeric bioconjugate. Both Ru(II) complexes bind strongly and selectively to integrin αvβ3, with the dimeric molecule displaying a 20-fold higher affinity to the receptor than the monomeric one. However, the cytotoxicity of the complexes and related bioconjugates against human A549 and SKOV-3 cell lines is still not sufficient for application as anticancer agents. Nevertheless, considering the high selectivity for integrin receptor αvβ3, the synthesis of Ru-based bioconjugates with cyc(RGDfK) paves a promising way towards the design of effective targeted anticancer agents

Exploring the C^N^C theme: Synthesis and biological properties of tridentate cyclometalated gold(III) complexes

A family of cyclometalated Au(III) complexes featuring a tridentate CNC scaffold has been synthesized and characterized. Microwave assisted synthesis of the ligands has also been exploited and optimized. The biological properties of the thus formed compounds have been studied in cancer cells and demonstrate generally moderate antiproliferative effects. Initial mechanistic insights have also been gained on the gold complex [Au(CNC)(GluS)] (3), and support the idea that the thioredoxin system may be a target for this family of compounds together with other relevant intracellular thiol-containing molecules. (C) 2017 Elsevier Ltd. All rights reserved

Disruption of vitamin A homeostasis by the biocide tetrakis(hydroxymethyl) phosphonium sulphate in pregnant rabbits

The biocide tetrakis(hydroxymethyl)phosphonium sulphate (THPS) and other members of the tetrakis(hydroxymethyl) phosphonium salts (THPX) family are associated with liver toxicity in several mammalian species and teratogenicity in rabbits. Malformations include skeletal changes and abnormalities in eye development and are very similar to those seen with vitamin A deficiency or excess. For this reason, it was hypothesized that teratogenicity of THPS(X) might be attributed to disturbances in retinol availability and/or metabolism as a result of maternal toxicity, for example, either due to insufficient dietary intake by the mothers or due to liver toxicity. Therefore, in the present study, liver toxicity and vitamin A homeostasis were studied in pregnant rabbits that were exposed to 13.8 or 46.0 mg/kg THPS during organogenesis and in precision-cut liver slices of rats and rabbits exposed to 0-70 mu M THPS. Results show that in vivo exposure to THPS leads to a marked reduction of food intake, increased plasma concentrations of gamma-glutamytransferase, degenerative changes in the liver and to changes in retinoid content in liver and plasma in the rabbits during organogenesis. In addition, THPS, both in vivo and ex vivo, caused a change in expression of proteins related to vitamin A metabolism and transport. Together, these observations could explain the birth defects observed in earlier teratogenicity studies

On the toxicity and transport mechanisms of cisplatin in kidney tissues in comparison to a gold-based cytotoxic agent

Mechanisms of toxicity and cellular transport of anticancer metallodrugs, including platinum-based agents, have not yet been fully elucidated. Here, we studied the toxic effects and accumulation mechanisms of cisplatin in healthy rat kidneys ex vivo, using the Precision Cut Tissue Slices (PCTS) method. In addition, for the first time, we investigated the nephrotoxic effects of an experimental anticancer cyclometallated complex [Au(pyb-H)(PTA)Cl]PF6 (PTA = 1,3,5-triazaphosphaadamantane). The viability of the kidney slices after metallodrug treatment was evaluated by ATP content determination and histomorphology analysis. A concentration dependent decrease in viability of PCKS was observed after exposure to cisplatin or the Au(III) complex, which correlated with the increase in slice content of Pt and Au, respectively. Metal accumulation in kidney slices was analysed by ICP-MS. The involvement of OCTs and MATE transporters in the accumulation of both metal compounds in kidneys was evaluated co-incubating the tissues with cimitedine, inhibitor of OCT and MATE. Studies of mRNA expression of the markers KIM-1, villin, p53 and Bax showed that cisplatin damages proximal tubules, whereas the Au(III) complex preferentially affects the distal tubules. However, no effect of cimetidine on the toxicity or accumulation of cisplatin and the Au(III) complex was observed. The effect of temperature on metallodrug accumulation in kidneys suggests the involvement of a carrier-mediated uptake process, other than OCT2, for cisplatin; while carrier-mediated excretion was suggested in the cases of the Au(III) complex

Red de seguimiento del Grado en Criminología on line

La red tenía por objeto llevar a cabo un especial seguimiento del grupo on line del Grado en Criminología que se imparte en la titulación y para el que son necesarios esfuerzos de coordinación adicionales y métodos docentes específicos a la docencia no presencial. Así, la red ha constituido un espacio de reflexión sobre docencia no presencial, que ha dado como resultado la adopción e implementación de acciones de mejora

“Influencia en la aplicación de la metodología en el proceso de aprendizaje en estudiantes del nivel medio ciclo básico de los Institutos Nacionales, muestra representativa de los municipios de Cuyotenango, San Gabriel, Sto. Domingo, San Bernandino, Samayac y San Francisco Zapotitlán del departamento de Suchitepéquez”.

El desarrollo de una nación está determinado por los niveles educativos alcanzados, así como la influencia que tienen cada uno de los elementos que se desarrollan y llevan a la educación a cada uno de los lugares del país. Un elemento indispensable dentro del rol educativo es, el docente quien tiene como papel fundamental la aplicación de metodologías para que estas sean absorbidas y luego reflejadas en el proceso de aprendizaje del alumno. Por ello debe mantenerse de forma activa y actualizada, conociendo los procesos actuales, para que con dedicación y esmero impartan sus clases y así el alumno pueda llevar a cabo lo aprendido siendo de manera significativa y con sentido común. El presente informe es del seminario sobre “Influencia en la aplicación de la metodología constructivista en el proceso de aprendizaje de estudiantes del nivel medio ciclo básico de los Institutos Nacionales de Educación Básica, muestra representativa de los municipios de Cuyotenango, San Gabriel, Sto. Domingo, San Bernandino, Samayac y San Francisco Zapotitlán del departamento de Suchitepéquez”. A través del cual se pudo conocer ciertos factores presentes en la educación así como la influencia que estos tienen, además de evidenciar necesidades palpables dentro de las instituciones educativas, para con ello tratar de proponer alternativas que permitan mejorar la calidad educativa. El informe está estructurado en V capítulos; El informe está estructurado en V capítulos; el capítulo I contiene el diseño de investigación dentro del cual están: el problema de investigación, definición del problema, planteamiento del problema, justificación, definición de unidad de análisis, delimitación del problema, objetivos e hipótesis