Evaluation of anti-inflammatory activity of food compounds using zebrafish

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/128014The principal aim of this work was to optimize and apply a zebrafish experimental model for the screening of anti-inflammatory substances present in the Mediterranean diet. The zebrafish is an organism widely used in various fields of experimental biology. The inflammation is easily inducible, reproducible and visualized in their early stages of development. Specifically, the migration of neutrophils to the injured caudal fin, one of the first steps of the inflammatory response, is quantitatively measured by image analysis. The anti-inflammatory effect of natural compounds can be evaluated as a decrease of migration. Adverse effects triggered by inflammation are mainly mediated by reactive oxygen species. The anti-oxidant activity of compounds was evaluated in zebrafish embryo measuring their protective effect against tert-butyl hydroperoxide toxicity. Several phenolic compounds have been assayed. Our results showed that the compounds with the greatest decrease on neutrophil migration were chlorogenic acid and cyanidin. The activity of these two polyphenols was quite similar to that observed with anti-inflammatory drugs (indomethacin, piroxicam) and NADPH oxidase inhibitor compounds (dibenzoidolium, apocynin). The anti-inflammatory and the anti-oxidant activity of the assayed polyphenols did not show a clear correlation

Cardiovascular effects of PCB 126 (3,3',4,4',5-pentachlorobiphenyl) in zebrafish embryos and impact of co-exposure to redox modulating chemicals

The developing cardiovascular system of zebrafish is a sensitive target for many environmental pollutants, including dioxin-like compounds and pesticides. Some polychlorinated biphenyls (PCBs) can compromise the cardiovascular endothelial function by activating oxidative stress-sensitive signaling pathways. Therefore, we exposed zebrafish embryos to PCB126 or to several redox-modulating chemicals to study their ability to modulate the dysmorphogenesis produced by PCB126. PCB126 produced a concentration-dependent induction of pericardial edema and circulatory failure, and a concentration-dependent reduction of cardiac output and body length at 80 hours post fertilization (hpf). Among several modulators tested, the effects of PCB126 could be both positively and negatively modulated by different compounds; co-treatment with -tocopherol (vitamin E liposoluble) prevented the adverse effects of PCB126 in pericardial edema, whereas co-treatment with sodium nitroprusside (a vasodilator compound) significantly worsened PCB126 effects. Gene expression analysis showed an up-regulation of cyp1a, hsp70, and gstp1, indicative of PCB126 interaction with the aryl hydrocarbon receptor (AhR), while the transcription of antioxidant genes (sod1, sod2; cat and gpx1a) was not affected. Further studies are necessary to understand the role of oxidative stress in the developmental toxicity of low concentrations of PCB126 (25 nM). Our results give insights into the use of zebrafish embryos for exploring mechanisms underlying the oxidative potential of environmental pollutants

Epigallocatechin-3-gallate PEGylated poly(lactic-co-glycolic) acid nanoparticles mitigate striatal pathology and motor deficits in 3-nitropropionic acid intoxicated mice

AIM:To compare free and nanoparticle (NP)-encapsulated epigallocatechin-3-gallate (EGCG) for the treatment of Huntington’s disease (HD)-like symptoms in mice. MATERIALS & METHODS: EGCG was incorporated into PEGylated poly(lactic-co-glycolic) acid NPs with ascorbic acid (AA). HD-like striatal lesions and motor deficit were induced in mice by 3-nitropropionic acid-intoxication. EGCG and EGCG/AA NPs were co-administered and behavioral motor assessments and striatal histology performed after 5 days. RESULTS: EGCG/AA NPs were significantly more effective than free EGCG in reducing motor disturbances and depression-like behavior associated with 3-nitropropionic acid toxicity. EGCG/AA NPs treatment also mitigated neuroinflammation and prevented neuronal loss. CONCLUSION: NP encapsulation enhances therapeutic robustness of EGCG in this model of HD symptomatology. Together with our previous findings, this highlights the potential of EGCG/AA NPs in the symptomatic treatment of neurodegenerative diseases

La enseñanza de la Toxicología en Farmacia: los seminarios como herramienta para la evaluación continuada

Con la finalidad de adaptarnos al EEES, desarrollamos una herramienta que nos permitiera realizar un proceso de evaluación continua de la asignatura troncal de Toxicología. En el presente trabajo presentamos los resultados de este modelo en el que utilizamos los seminarios como elementos básicos de este proceso. Describimos cómo se estructuran y desarrollan estos seminarios, así como el modelo de evaluación de los mismos. Los seminarios fueron evaluados con una puntuación máxima del 30 % sobre la nota final de la signatura, y la participación en los mismos con un máximo del 10 %. Algunos de estos seminarios incorporaban evaluaciones realizadas antes del desarrollo de los mismos, que denominábamos «pre», y otras justo al final del desarrollo de los mismos, que denominábamos «post». Esta herramienta de evaluación continua se ha mostrado muy eficaz en lo que respecta al grado de participación y preparación de los alumnos. Además, ha supuesto un cambio significativo en el grado de implicación de los profesores, y una mejora de la comunicación alumno-profesor

Expression and Role of MicroRNAs from the miR-200 Family in the Tumor Formation and Metastatic Propensity of Pancreatic Cancer

MicroRNAs from the miR-200 family are commonly associated with the inhibition of the metastatic potential of cancer cells, following inhibition of ZEB transcription factors expression and epithelial-to-mesenchymal transition. However, previous studies performed in pancreatic adenocarcinoma revealed a more complex picture challenging this canonical model. To gain better insights into the role of miR-200 family members in this disease, we analyzed the expression of miR-200a, miR- 200b, miR-200c, miR-141, miR-429, and miR-205, and ZEB1, ZEB2, and CDH1 in pancreatic tumors and matching normal adjacent parenchyma and patient-derived xenografts. We found that miR-200a, miR-429, and miR-205 are frequently overex- pressed in pancreatic tumors, whereas CDH1 is downregulated, and ZEB1 and ZEB2 levels remain unchanged. Furthermore, we measured a positive correlation between miR-200 family mem- bers and CDH1 expression, and a negative correlation between ZEB1 and miR-200c, miR-141, and miR-205 expression, respec- tively. Interestingly, we identified significant changes in expres- sion of epithelial-to-mesenchymal transition regulators and miR-200 members in patient-derived xenografts. Lastly, func- tional studies revealed that miR-141 and miR-429 inhibit the tumorigenic potential of pancreatic cancer cells. Taken together, this comprehensive analysis strongly suggests that miRNAs from the miR-200 family, and in particular miR-429, may act as a tu- mor suppressor gene in pancreatic cancer

Prognostic value and risk stratification of residual disease in patients with incidental gallbladder cancer

Background and aim: given their poor prognosis, patients with residual disease (RD) in the re-resection specimen of an incidental gallbladder carcinoma (IGBC) could benefit from a better selection for surgical treatment. The Gallbladder Cancer Risk Score (GBRS) has been proposed to preoperatively identify RD risk more precisely than T-stage alone. The aim of this study was to assess the prognostic value of RD and to validate the GBRS in a retrospective series of patients. Material and methods: a prospectively collected database including 59 patients with IGBC diagnosed from December 1996 to November 2015 was retrospectively analyzed. Three locations of RD were established: local, regional, and distant. The effect of RD on overall survival (OS) was analyzed with the Kaplan-Meier method. To identify variables associated with the presence of RD, characteristics of patients with and without RD were compared using Fisher's exact test. The relative risk of RD associated with clinical and pathologic factors was studied with a univariate logistic regression analysis. Results: RD was found in 30 patients (50.8%). The presence of RD in any location was associated with worse OS (29% vs. 74.2%, p = 0.0001), even after an R0 resection (37.7% vs 74.2%, p = 0.003). There was no significant difference in survival between patients without RD and with local RD (74.2% vs 64.3%, p = 0.266), nor between patients with regional RD and distant RD (16.1% vs 20%, p = 0.411). After selecting patients in which R0 resection was achieved (n = 44), 5-year survival rate for patients without RD, local RD, and regional RD was, respectively, 74.2%, 75%, and 13.9% (p = 0.0001). The GBRS could be calculated in 25 cases (42.3%), and its usefulness to predict the presence of regional or distant RD (RDRD) was confirmed (80% in high-risk patients and 30% in intermediate risk p = 0.041). Conclusion: RDRD, but not local RD, represents a negative prognostic factor of OS. The GBRS was useful to preoperatively identify patients with high risk of RDRD. An R0 resection did not improve OS of patients with regional RD

Knowledge Integration Activities in the Pharmacy Degree. Application in the Toxicology Subject

Los autores agradecen el soporte a todos los miembros del Grupo de Innovación docente ORFILAObjetivos. Durante los últimos años, los profesores del Departamento de Farmacología, Toxicología y Química Terapéutica hemos puesto en marcha un conjunto de acciones docentes con el objetivo de promover en los alumnos del grado de Farmacia la mejora de capacidades de integración de los conocimientos de las materias impartidas, así como un modelo de evaluación continuada multidisciplinar y retroactivo que nos permita objetivar su consecución. Métodos. Para desarrollar estas acciones de integración y la posterior evaluación de las mismas, diversas asignaturas del Departamento se han coordinado y se han analizado los conocimientos necesarios para la comprensión de contenidos que se desarrollan en cursos posteriores. Dentro de la asignatura de Toxicología hemos desarrollado un conjunto de acciones que se han concretado fundamentalmente en el diseño, aplicación y, en algunos casos, evaluación de unas actividades de tipología diversa. Resultados. A fin de valorar el éxito de estas acciones, se han comparado los resultados obtenidos en un test de preguntas de integración a principio de curso con los resultados de otro test a final de curso. Los resultados obtenidos en los cuatro ítems comparados muestran una mejora significativa en una pregunta, una mejora relativa no significativa en otras dos y resultados similares en la última. Conclusiones. Podemos concluir que las acciones desarrolladas han conseguido parcialmente los objetivos propuestos. Consideramos que esta herramienta puede ser muy útil para promover una mayor coordinación entre los profesores, en el diseño de material didáctico conjunto y transversal y en modelos integrados de evaluación.Aim. During the last years the professors of the Department of Pharmacology, Toxicology and Therapeutic Chemistry have initiated a set of teaching actions with the aim of promoting the improvement of knowledge integration capacities corresponding to the subjects taught to students of Pharmacy degree; as well as a multidisciplinary and retroactive continuous evaluation model allowing to objectify its achievement. Methods. In order to develop these integration actions and their subsequent evaluation, several subjects of the Department have been coordinated and the knowledge necessary for understanding the contents of following courses have been analyzed. Within the subject of Toxicology, we have developed a set of actions based on the design, application and, in some cases, evaluation of a variety of activities. Results. In order to assess the success of these actions, we have compared the results obtained in a test of integration questions at the beginning of the course with the results of another test at the end of the course. The results obtained in the four items compared show a significant improvement in one question, a maintenance of results in another, and a non-significant relative improvement in the other two. Conclusions. We can conclude that the actions developed have partially achieved the proposed objectives. We consider that this tool can be very useful to promote greater coordination among teachers in the design of joint and transversal teaching materials and in integrated evaluation models.Este trabajo se enmarca en un proyecto de innovación docente de la Universidad de Barcelona (2015PID-UB-031

Open access simulation toolbox for the grid connection of offshore wind farms using multi-terminal HVDC networks

Decarbonisation of the European electricity system can become dauntingly costly due to transmission and distribution network issues arising from the integration of intermittent renewable generation sources. It is expected that wind energy will be the principal renewable source by 2050 and, as such, a number of initiatives in the academia and in the industry are being carried out to propose solutions to best accommodate the wind resource. This paper presents work carried out by DEMO 1 partners within the EU FP7 project BEST PATHS. A MATLAB/Simulink toolbox consisting of the necessary building blocks for the simulation and integration of offshore wind farms using enabling technologies such as multiterminal high-voltage direct-current grids is presented. To illustrate the toolbox capabilities, a number of system topologies is studied. System performance is assessed and measured against a set of key performance indicators. To ensure knowledge dissemination, the toolbox has been made available as open access in the BEST PATHS project website

Comparison of Migration Disturbance Potency of Epigallocatechin Gallate (EGCG) Synthetic Analogs and EGCG PEGylated PLGA Nanoparticles in Rat Neurospheres

Epigallocatechin gallate (EGCG), the main catechin of green tea, is described to have potential health benefits in several fields like oncology, neurology or cardiology. Currently, it is also under pre-clinical investigation as a potential therapeutic or preventive treatment during pregnancy against developmental adverse effects induced by toxic substances. However, the safety of EGCG during pregnancy is unclear due to its proven adverse effects on neural progenitor cells' (NPCs) migration. As lately several strategies have arisen to generate new therapeutic agents derived from EGCG, we have used the rat 'Neurosphere Assay' to characterize and compare the effects of EGCG structurally related compounds and EGCG PEGylated PLGA nanoparticles on a neurodevelopmental key event: NPCs migration. Compounds structurally-related to EGCG induce the same pattern of NPCs migration alterations (decreased migration distance, decreased formation of migration corona, chaotic orientation of cellular processes and decreased migration of neurons at higher concentrations). The potency of the compounds does not depend on the number of galloyl groups, and small structure variations can imply large potency differences. Due to their lower toxicity observed in vitro in NPCs, 4,4′-bis[(3,4,5-trihydroxybenzoyl)oxy]-1,1′-biphenyl and EGCG PEGylated PLGA nanoparticles are suggested as potential future therapeutic or preventive alternatives to EGCG during prenatal period

Epigallocatechin-3-gallate PEGylated poly(lactic-co-glycolic) acid nanoparticles mitigate striatal pathology and motor deficits in 3-nitropropionic acid intoxicated mice

Huntington's disease (HD) is a debilitating neurodegenerative disease that affects around 5-10/100,000 individuals in developed countries. It is caused by genetic alterations in the huntingtin (htt) gene. Efforts are being made to find treatments which will correct the genetic alterations or their pathophysiological consequences associated with HD,3 however none of these options are yet available to patients. Thus, therapies that address and ameliorate the symptomatology of HD, which include motor dysfunction and a wide range of behavioural disturbances, are also needed. Epigallocatechin-3-gallate (EGCG) is a powerful compound extracted from the green tea plant that may possess beneficial effects for HD patients, but whose therapeutic success is limited because of its chemical instability. Here, we show that protective encapsulation of EGCG rendered it much more efficient in attenuating motor deficits and depression-like behaviour in a mice model of HD-like neurodegeneration. Importantly, behavioural improvement was also associated with a reduction of neuronal damage. These results, together with our previous findings using nanoparticle-encapsulated EGCG in mouse models of Alzheimer's disease and epilepsy, highlight their potential effectiveness for symptomatic treatment of neurodegenerative diseases