Dual Drug Loaded Nanotheranostic Platforms as a Novel Synergistic Approach to Improve Pancreatic Cancer Treatment

This study focuses on the development of theranostic, dual drug-loaded nanocarriers to propose a proof-of-principle therapeutic approach in the treatment of pancreatic ductal adenocarcinoma (PDAC). The nanoconstructs consist of a core of zinc oxide nanocrystals doped with gadolinium, useful as a potential contrast agent in magnetic resonance imaging applications. After functionalizing their surface with amino-propyl groups, the physical adsorption of two hydrophobic drugs is performed: Vismodegib and Sorafenib. Their synergistic use might improve PDAC treatment and stroma depletion when co-delivered in the tumor microenvironment for future in vivo applications. To enhance the nanoconstructs’ biostability, the ensemble is coated by a lipid bilayer and a tumor targeting peptide is incorporated on the outer shell surface. As a first proof of concept, the resulting nanoconstructs are tested against two pancreatic cancer cell lines, showing a modest increase in treatment efficacy compared to the free drug counterparts and proving to spare healthy pancreatic cells. In a second testing set, the dual-drug loaded nanoconstructs are tested on both cell lines previously sensitized to a firstline chemotherapeutic drug, Gemcitabine, showing an improved treatment response. From these preliminary results, the nanotheranostic platforms might constitute a good starting point for future PDAC therapy and diagnosis studies

Determination of 234U and 238U Activities in Soil by Liquid Scintillation and High-Resolution Alpha Spectrometry

Uranium is a radioactive element with a special presence in the rocks, waters, sediments, soils, and plants at the state of Chihuahua. The activity ratio of 238U/234U is used to explain the uranium transport by surface water and its deposition in arid environments. In this work, the activity concentration of natural U isotopes is determined by PERALS liquid scintillation and high-resolution alpha spectrometry (AS, Canberra camera 7401VR) in the Environmental Radiological Surveillance Laboratory (LVRA) at CIMAV, Chihuahua. Uranium is extracted from soils through the scintillating liquid extractor URAEX for PERALS, with chemical recovery (CR) of 80 - 85 %, and through the ion exchange resin UTEVA + electrode position by the Hallstadius method, with CR of 85 - 90 %, for AS. The procedures of 234U and 238U activity concentration (AC) determination in soils were validated by their application to the certified reference material IAEA-375. The resulting values were in the reference range of the certified or informative values. Both procedures were applied to 6 representative soil samples, with AC of the same order of magnitude or greater, and similar CR and compatible results. Both procedures are satisfactory for the purposes of LVRA research and in general

Comparative study of the primary cilia in thyrocytes of adult mammals

Since their discovery in different human tissues by Zimmermann in 1898, primary cilia have been found in the vast majority of cell types in vertebrates. Primary cilia are considered to be cellular antennae that occupy an ideal cellular location for the interpretation of information both from the environment and from other cells. To date, in mammalian thyroid gland, primary cilia have been found in the thyrocytes of humans and dogs (fetuses and adults) and in rat embryos. The present study investigated whether the existence of this organelle in follicular cells is a general event in the postnatal thyroid gland of different mammals, using both immunolabeling by immunofluorescence and electron microscopy. Furthermore, we aimed to analyse the presence of primary cilia in various thyroid cell lines. According to our results, primary cilia are present in the adult thyroid gland of most mammal species we studied (human, pig, guinea pig and rabbit), usually as a single copy per follicular cell. Strikingly, they were not found in rat or mouse thyroid tissues. Similarly, cilia were also observed in all human thyroid cell lines tested, both normal and neoplastic follicular cells, but not in cultured thyrocytes of rat origin. We hypothesize that primary cilia could be involved in the regulation of normal thyroid function through specific signaling pathways. Nevertheless, further studies are needed to shed light on the permanence of these organelles in the thyroid gland of most species during postnatal life.Junta de Andalucía. Consejería de Innovación, Ciencia y Empresa CTS-439/2011Junta de Andalucía. Consejería de Innovación, Ciencia y Empresa CTS-229/2011Junta de Andalucía. Consejería de Salud PI-0051-201

Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation

The main aim was to evaluate changes in urea cycle enzymes in NAFLD patients and in two preclinical animal models mimicking this entity. Seventeen liver specimens from NAFLD patients were included for immunohistochemistry and gene expression analyses. Three-hundred-and-eighty-two biopsy-proven NAFLD patients were genotyped for rs1047891, a functional variant located in carbamoyl phosphate synthetase-1 (CPS1) gene. Two preclinical models were employed to analyse CPS1 by immunohistochemistry, a choline deficient high-fat diet model (CDA-HFD) and a high fat diet LDLr knockout model (LDLr −/−). A significant downregulation in mRNA was observed in CPS1 and ornithine transcarbamylase (OTC1) in simple steatosis and NASH-fibrosis patients versus controls. Further, age, obesity (BMI > 30 kg/m), diabetes mellitus and ALT werefound to be risk factors whereas A-allele from CPS1 was a protective factor from liver fibrosis. CPS1 hepatic expression was diminished in parallel with the increase of fibrosis, and its levels reverted up to normality after changing diet in CDA-HFD mice. In conclusion, liver fibrosis and steatosis were associated with a reduction in both gene and protein expression patterns of mitochondrial urea cycle enzymes. A-allele from a variant on CPS1 may protect from fibrosis development. CPS1 expression is restored in a preclinical model when the main trigger of the liver damage disappears.The research leading to these results has received funding from the Consejería de Salud de la Junta de Andalucía under grant agreement PC-0148-2016-0148 and PE-0451-2018 and Instituto de Salud Carlos III under grant agreements CD21/00095, PI16/01842, PI19/01404, PI19/00589, IFI18/00041, FI20/00201, CD18/00126 and EHD18PI04/2021. Rocío Gallego-Durán has received the Andrew K Burroughs Fellowship from European Association for the Study of the Liver (EASL), Aprendizaje de Nuevas Tecnologías fellowship from Asociación Española para el Estudio del Hígado (AEEH) and CIBERehd Grant to support researcher’s mobility

Modelado eficiente de obstáculos en guía de onda rectangular para simuladores comerciales utilizando código Verilog-A

This paper reports the modelling of classical obstacles (post, iris, screw, etc.) within rectangular waveguide in terms of electrical lumped elements equivalent circuit using Verilog-A language code. This ability, allows making possible the enabling of the digital computer interaction and simulation using standard CAD simulation tools. Furthermore, the paper shows the simplicity and friendly technique of modelling passive microwave devices using Verilog-A code. Several examples have been studied under different commercial simulators: Agilent ADS and GENESYS. A comparison between the results obtained from Verilog-A based simulations and full 3-D electromagnetic simulation is shown, too

Experimental validation of multipactor effect for ferrite materials used in L- and S-band nonreciprocal microwave components

This paper reports on the experimental measurement of power threshold levels for the multipactor effect between samples of ferrite material typically used in the practical implementation of L- and S-band circulators and isolators. For this purposes, a new family of wideband, nonreciprocal rectangular waveguide structures loaded with ferrites has been designed with a full-wave electromagnetic simulation tool. The design also includes the required magnetostatic field biasing circuits. The multipactor breakdown power levels have also been predicted with an accurate electron tracking code using measured values for the secondary electron yield (SEY) coefficient. The measured results agree well with simulations, thereby fully validating the experimental campaign.This work was supported by European Space Agency (ESA) through research project "Novel Investigation in Multipactor Effect in Ferrite and other Dielectrics used in High Power RF Space Hardware" (ref. AO 1-7551/13/NL/GLC), and by MINECO (Spanish Government) under R&D projects TEC2016-75934-C4-1-R, TEC2016-75934-C4-2-R and the ERDF co-funded project TEC2014-55463-C3-3-P

Nutrition and physical activity programs for obesity treatment (PRONAF study). methodological approach of the project

Este trabajo aborda la metodología seguida para llevar a cabo el proyecto de investigación PRONAF (Clinical Trials Gov.: number NCT01116856.) Background: At present, scientific consensus exists on the multifactorial etiopatogenia of obesity. Both professionals and researchers agree that treatment must also have a multifactorial approach, including diet, physical activity, pharmacology and/or surgical treatment. These two last ones should be reserved for those cases of morbid obesities or in case of failure of the previous ones. The aim of the PRONAF study is to determine what type of exercise combined with caloric restriction is the most appropriate to be included in overweigth and obesity intervention programs, and the aim of this paper is to describe the design and the evaluation methods used to carry out the PRONAF study. Methods/design: One-hundred nineteen overweight (46 males) and 120 obese (61 males) subjects aged 18–50 years were randomly assigned to a strength training group, an endurance training group, a combined strength + endurance training group or a diet and physical activity recommendations group. The intervention period was 22 weeks (in all cases 3 times/wk of training for 22 weeks and 2 weeks for pre and post evaluation). All subjects followed a hypocaloric diet (25-30% less energy intake than the daily energy expenditure estimated by accelerometry). 29–34% of the total energy intake came from fat, 14–20% from protein, and 50–55% from carbohydrates. The mayor outcome variables assesed were, biochemical and inflamatory markers, body composition, energy balance, physical fitness, nutritional habits, genetic profile and quality of life. 180 (75.3%) subjects finished the study, with a dropout rate of 24.7%. Dropout reasons included: personal reasons 17 (28.8%), low adherence to exercise 3 (5.1%), low adherence to diet 6 (10.2%), job change 6 (10.2%), and lost interest 27 (45.8%). Discussion: Feasibility of the study has been proven, with a low dropout rate which corresponds to the estimated sample size. Transfer of knowledge is foreseen as a spin-off, in order that overweight and obese subjects can benefit from the results. The aim is to transfer it to sports centres. Effectiveness on individual health-related parameter in order to determine the most effective training programme will be analysed in forthcoming publications

Proyecto Escritiva

Memoria ID-0132. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2015-2016

Diseño y desarrollo de un modelo de portafolio para la evaluación de competencias en el Grado de Estudios Portugueses y Brasileños

Memoria ID-0205. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2014-2015

Proyecto Escritiva

Memoria ID-0180. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2016-2017