Nanotheranostics with microRNA: Application in radiotherapy

The authors acknowledge the funding of project IBEROS, Instituto de Bioingeniería en Red para el Envejecimiento Saludable, POCTEP/0245-BEROS-1-E, PROGRAMA INTERREG 2014-2020, to FEDER within the cooperation region of Galiza/Spain and North of Portugal. SS is grateful for the financial support of Fundação para a Ciência e Tecnologia (grant reference: SFRH/BD/138271/2018).info:eu-repo/semantics/publishedVersio

Nanotheranostics with gold nanoparticles applied to Radiotherapy

Sílvia Soares is grateful for the financial support of Fundação para a Ciência e Tecnologia (grant reference: SFRH/BD/138271/2018) and thanks the kind collaboration of all those involved in the radiotherapy service at Centro Hospitalar Universitário de São João for carrying out radiotherapy treatments.info:eu-repo/semantics/publishedVersio

Gold nanoparticles as therapeutic agent for radiotherapy of PC3 prostate cancer cell line

Radiotherapy (RT) is a therapeutic modality that deliver a precise dose of ionizing radiation in a specific tumour volume, promoting the irradiation of tumor cells with as minimal damage as possible in surrounding normal tissues. Besides the evolution of equipment and technology, this therapy still has some problems related with radioresistance, which consequently increase the recurrence at 5 years. Over the years, gold nanoparticles (AuNP) have attracted a lot of interest in cancer therapies due their unique chemical, optical and physical properties. So, it was synthetized two different types of AuNPs spherical (AuNPsp) and rods (AuNPr) for treat human prostate cancer cell line (PC3) and it was observed cell behavior when treated cells were irradiated with three fractions of 2,5 Gy. AuNPs were characterized using UV-Vis and TEM to confirm their size and shape. After, cells were treated with different concentrations of AuNPs from 0 to 1.0 mM during 24h. The results showed that none of the forms of AuNPs show signals of cytotoxicity until 1.0 mM, with exception of 1mM of AuNPr, where cells exhibit cytotoxicity around ~10%. Taken all together, AuNPsp and AuNPr demonstrated be effective to reduce the cell viability when associated to RT. Comparing both structures, AuNPr demonstrated a higher dose-dependency with and without radiation and under irradiation the inhibition of cell growth is higher when compared to control (no treatment). These results demonstrate for the first time the possibility of different forms of AuNPs can be used as potential radiosensitizer for prostate cancer cells.Sílvia Soares is grateful for the financial support of Fundação para a Ciência e Tecnologia (grant reference SFRH/BD/138271/2018 and thanks the kind collaboration of all those involved in the radiotherapy service at Centro Hospitalar Universitário de São João for carrying out radiotherapy treatmentsinfo:eu-repo/semantics/publishedVersio

Interacción entre receptores d2 y a2a. Toma de decisiones basada en el esfuerzo mediante un Programa de Razón Progresiva en ratas

Uno de los síntomas motivacionales característicos de la depresión y que supone un mayor problema para la realización de tareas cotidianas, es la anergia. Este síntoma supone una disminución del vigor y el esfuerzo que el sujeto está dispuesto a realizar para conseguir un objetivo. Las bases neurales de la anergia pueden estudiarse en el laboratorio mediante modelos animales, induciéndose a través de antagonistas dopaminérgicos. En el presente estudio, analizamos los efectos de la manipulación farmacológica del sistema dopaminérgico mediante el antagonismo de los receptores D2 (eticlopride). Como tratamiento que revierta estos síntomas administraremos MSX3, un antagonista de los receptores de adenosina A2a, los cuales están colocalizados con los receptores D2 y tienen efectos opuestos a éstos. Para evaluar los efectos conductuales de estas manipulaciones utilizamos un paradigma operante en el que el animal debe realizar cada vez más esfuerzo (apretando un mayor número de veces una palanca, Programa de Razón Progresiva, PROG) para conseguir una comida más apetecible, o tiene la opción de comer libremente otro tipo de comida menos sabrosa pero de libre acceso (chow). Los resultados demuestran que fármacos que interfieren con la transmisión de DA reducen el nivel de esfuerzo que el animal está dispuesto a realizar cuando tiene opciones menos costosas. Los antagonistas A2a revierten estos efectos y tienen potencial como fármacos para el tratamiento de la anergia en la depresión y en otras patologías como el Parkinson o el síndrome de fatiga crónica.People with depression not only display alterations in mood or affect, but also can show profound motivational impairments such as anergia. Mesolimbic dopamine (DA) is involved in behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. DA receptors are colocalized with adenosine receptors but have opposite effects in the intracellular cascade. Thus, adenosine receptors can be a target for therapeutical approaches. In the present study, we used a progressive ratio (PROG)/chow feeding concurrent choice task. With this task, rats can lever press on a pr og schedule reinforced by a preferred high-carbohydrate food pellet, or alternatively approach and consume the less preferred but concurrently available laboratory chow. The DA D2 antagonist eticlopride reduced highest ratio achieved but did not reduce chow intake. In contrast, the A2a antagonist MSX3 coadministrated with eticlopride reversed the effects of the interference with DA transmission

Gold nanorods as radiosensitizer agents on PC3 cells

Different structures of gold nanoparticles (AuNPs) are being extensively used in Radiotherapy (RT) because gold increased the sensitivity to radiation due to its high atomic number that can absorb high-energy gamma rays or X-rays and emit photoelectrons, Auger electrons, Compton electrons, and fluorescence photons.1 Gold nanorods (AuNPr) are gold nanoparticles with a rod shape, used to enhance the effect of ionizing radiation.2 After synthesized, the effect of the AuNPr on radiosensitization using megavoltage energies RT was evaluated for in PC3 prostate cancer cell line (PCa). Cells were incubated with different concentrations of AuNPr (0-1.0 mM) during 24h, then subjected to irradiation of 2,5 Gy per fraction, for 3 days, using a PRIMUS linear accelerator with 6 MV photon beam. After RT treatments, cell viability was analysed using PrestoBlue assay (Invitrogen), cell migration was explored doing the in vitro wound healing assay, and colonies assay was evaluated by microscopy. In this work, we found that the AuNPr displays a radiosensitization effect and it is dose dependent in PC3 cell line. These results are supported by decrease of viability and number of colonies produced.info:eu-repo/semantics/publishedVersio

El ejercicio forzado previene la anergia inducida por la depleción de dopamina. Estudios comparando la selección entre actividad física o la ingesta de alimentos dulces

Disfunciones relacionadas con el esfuerzo como la anergia y la fatiga son síntomas centrales de la depresión y otros trastornos. El sistema dopaminérgico (DA) mesolímbico desempeña un papel crítico en la activación de la conducta. Sin embargo, se ha demostrado que la depleción da no cambia la preferencia cuando no se requiere realizar esfuerzo en la adquisición del reforzador. Aun así, cuando una concentración alta de sucrosa requiere trabajo, los roedores con depleción da reducen el esfuerzo necesario para obtener la concentración preferida pero aún así compensan consumiendo sucrosa menos dulce de libre acceso. En el presente estudio, hemos desarrollado una tarea en un laberinto en T para ratones que nos permita evaluar la preferencia entre tres diferentes tipos de reforzadores situados cada uno en uno de los brazos: actividad física como la condición de refuerzo que requiere un alto esfuerzo, un plato con bolitas de sucrosa de libre acceso, y un agujero en el que se localiza un olor neutro. Los ratones muestran preferencia, de manera innata, por el ejercicio físico y esto es dependiente de las condiciones homeostáticas del animal (si está hambriento o saciado). Por otro lado, observamos un incremento de la preferencia por rodar en la rueda de actividad cuando la comida dulce se devalúa (se le añade un sabor amargo). Los animales que reciben tetrabenazina, un depletor DA que inhibe de manera reversible el transportador vesicular de monoaminas de tipo 2 (VMAT2), demostraron reducir su preferencia por el ejercicio físico, pero aumentaron el consumo de sucrosa de libre acceso. Así pues la reducción de DA produce síntomas de anergia (falta de energía) aunque no de anhedonia (falta de apreciación de las propiedades gustativas apetecibles de la sucrosa).Effort-related dysfunctions such as anergia and fatigue are core symptoms of depression and other disorders. Dopamine (DA) systems play a critical role in behavioral activation. However, previous studies have shown that DA depletion does not change sucrose consumption or preference when no effort is involved in procuring this reinforcer. Nevertheless, when the preferred sucrose concentration requires work, rodents with DA depletions reduce the work output for the preferred highly concentrated sucrose drink but compensate by consuming more of the less sweet but freely available sucrose fluid. In the present studies, we have developed mice T-maze tasks for the assessment of preference between three different type of reinforcers: engagement in physical activity as the high effort reinforcing condition, a dish with freely available sucrose pellets, and a non-social (neutral) odor in the third arm. Mice show an important preference by the physical exercise, and this preference depends on the animal’s homeostatic conditions (satiety or hunger). Moreover, preference for the running wheel increases when the sweet food is devalued. In the present studies, tetrabenozine, a selective and reversible vesicular monoamine transporter-2 (VMAT2) inhibitor reduced preference for physical exercise, but increased sucrose consumption. Thus the reduction of DA produces symptoms of anergy (lack of energy) but not anhedonia (lack of enjoyement of the sucrose taste)

POLÍTICA, EDUCAÇÃO E PESQUISA: ENTREVISTA COM O PROFESSOR DR. JOÃO ROBERTO MARTINS FILHO, DA UNIVERSIDADE FEDERAL DE SÃO CARLOS

Entrevista com o Prof. Dr. João Roberto Martins Filh

Análisis de la producción científica en Economía Financiera: 1995-2006

The present work analyzes the development of scientific production in the economics of finance between 1995 and 2006. Research in capital structure was identified as the most productive line during this period. The most significant contributions and seminal papers in this area are discussed, as are the main research lines that remain open.En el presente trabajo se analiza la evolución de la producción científica en economía financiera entre los años 1995 y 2006. Se ha concluido que la línea de investigación que más publicaciones ha recibido ha sido la estructura de capital de la empresa. A continuación se ha estudiado, para esta línea, y para el período analizado, los trabajos sobre los que se ha fundamentado la investigación actual, las aportaciones científicas más relevantes y las principales líneas de investigación que siguen abiertas