Caracterización de las especies de fosfolípidos en macrófagos de ratón por cromatografía líquida acoplada a espectometría de masas

La estimulación de los macrófagos peritoneales de ratón con zymosan provoca la liberación de ácido araquidónico por la enzima cPLA2. Ese ácido araquidónico liberado tiene dos destinos: la producción de eicosanoides, mediadores lipídicos en inflamación, y la reacilación en otras especies de fosfolípidos distintas de aquellas que lo contenían antes de la estimulación. Además de las reacciones de liberación de ácido araquidónico, la enzima transacilasa independiente de Coenzima A se encarga de transferir el ácido araquidónico desde las especies de fosfatidilcolina a las especies de fosfatidiletanolamina. La estimulación de los macrófagos peritoneales de ratón con zimosán provoca la disminución en los niveles de las especies de PC, al contrario que en las especies de PE, las cuales no sufren ese descenso debido a que se mantienen en un equilibrio entre las reacciones de desacilación y las de transacilación, por lo que no se aprecia liberación neta desde especies de PE.Departamento de Bioquímica, Biología Molecular y FisiologíaMáster en Investigación Biomédic

Reference values for spirometric variables for allegedly healthy workers

Introduction: Spirometry in workers exposed to air pollutants allows for early identification of lung function impairment. Reference values (RV) for spirometric variables (SV) obtained in Cuban workers (CW) are not available.Objective: To obtain adequate SV-specific RV adequate for supposedly healthy CW.Materials and methods: Retrospective, analytical study. Forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC ratio and 25-75% forced expiration fraction for FVC (FEF25-75) values were observed in 1 088 allegedly healthy, non-smoker workers from both sexes, aged between 20 - 65 years, assisted at the Instituto Nacional de la Salud de los Trabajadores (INSAT) in Havana (Cuba) between 2009 and 2015. RV were obtained for each sex as solutions of the regression function (RF) Y=α+β x age+χ x height+ε (Y: FVC, FSV1, FEV1/FVC, FEF25-75).Results: Advanced ages were associated with lower FVC and FEV1. Taller individuals showed higher FVC and FEV1. A RF including age and height implied a higher coefficient of determination r2 and lower estimation of ε error. Behavior of SV values predicted with the locally developed equation was less biased than those obtained with other foreign equations.Conclusions: Locally developed RV may be more effective for diagnosing lung diseases in CW.Introducción. La espirometría permite identificar de forma precoz el deterioro pulmonar en trabajadores expuestos a contaminantes laborales. No se tienen valores de referencia (VR) para variables espirométricas (VE) en trabajadores cubanos (TC).Objetivo. Obtener VR para VE en TC supuestamente sanos.Materiales y métodos. Estudio retrospectivo-analítico. Se obtuvo la capacidad vital forzada (CVF), el volumen espiratorio forzado en el primer segundo (VEF1), el cociente VEF1/CVF y la fracción de la espiración forzada al 25-75% de la CVF (FEF25-75) de 1 086 TC supuestamente sanos, no fumadores, de ambos sexos, con edades entre 20 y 65 años y atendidos en el Instituto Nacional de la Salud de los Trabajadores de La Habana, Cuba, entre 2009 y 2015. Los VR se obtuvieron para cada sexo de las funciones de regresión Y=α+β x Edad+χ x Talla+ε (Y=CVF, VEF1, VEF1/CVF, FEF25-75).Resultados. Edades avanzadas se asociaron con CVF y VEF1 disminuidos; la talla elevada se asoció con mayores CVF y VEF1; una FR construida se asoció con la edad, y la talla implicó un coeficiente r2 de determinación superior y un error menor. El comportamiento de la VE predicho con la ecuación desarrollada fue menos sesgado que el observado con otras importadas.Conclusiones. Los VR construidos localmente pueden ser más efectivos en el diagnóstico de las afecciones pulmonares de los TC

Aptamer-functionalized natural protein-based polymers as innovative biomaterials

Producción CientíficaBiomaterials science is one of the most rapidly evolving fields in biomedicine. However, although novel biomaterials have achieved well-defined goals, such as the production of devices with improved biocompatibility and mechanical properties, their development could be more ambitious. Indeed, the integration of active targeting strategies has been shown to allow spatiotemporal control of cell–material interactions, thus leading to more specific and better-performing devices. This manuscript reviews recent advances that have led to enhanced biomaterials resulting from the use of natural structural macromolecules. In this regard, several structural macromolecules have been adapted or modified using biohybrid approaches for use in both regenerative medicine and therapeutic delivery. The integration of structural and functional features and aptamer targeting, although still incipient, has already shown its ability and wide-reaching potential. In this review, we discuss aptamer-functionalized hybrid protein-based or polymeric biomaterials derived from structural macromolecules, with a focus on bioresponsive/bioactive systems.Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional - Fondo Social Europeo (Proyects MAT2016-79435-R, DTS19/00162, and PID2019-106386RB-I00)Junta de Castilla y León (Project VA317P18

Self-assembling ELR-based nanoparticles as smart drug-delivery systems modulating cellular growth via Akt

Producción CientíficaThis work investigates the physicochemical properties and in vitro accuracy of a genetically engineered drug delivery system based on elastin-like block recombinamers. The DNA recombinant technics allowed us to create this smart complex polymer containing bioactive sequences for internalization, lysosome activation under acidic pH and blockage of cellular growth by a small peptide inhibitor. The recombinant polymer reversibly self-assembled, when temperature was increased above 15°C, into nanoparticles with a diameter of 72 nm and negative surface charge. Furthermore, smart nanoparticles were showed to enter in the cells via clathrin-dependent endocytosis, and properly blocked phosphorylation and consequent activation of Akt kinase. This system provoked apoptosis-mediated cell death in breast and colorectal cancer cells, which possess higher expression levels of Akt, whereas non-cancerous cells, such as endothelial cells, fibroblasts and mesenchymal stem cells, were not affected. Hence, we conclude that the conformational complexity of this smart elastin-like recombinamer leads to achieve successful drug delivery in targeted cells and could be a promising approach as nanocarriers with bioactive peptides in order to modulate multiple cellular processes involved in different diseases.Ministerio de Economía, Industria y Competitividad (PCIN-2015-010, MAT2015-68901-R, MAT2016-79435-R and MAT2016-78903-R)Junta de Castilla y León (VA317P18)European Union (NMP-2014-646075

Genetically Engineered Elastin-based Biomaterials for Biomedical Applications

Producción CientíficaProtein-based polymers are some of the most promising candidates for a new generation of innovative biomaterials as recent advances in genetic-engineering and biotechnological techniques mean that protein-based biomaterials can be designed and constructed with a high degree of complexity and accuracy. Moreover, their sequences, which are derived from structural protein-based modules, can easily be modified to include bioactive motifs that improve their functions and material-host interactions, thereby satisfying fundamental biological requirements. The accuracy with which these advanced polypeptides can be produced, and their versatility, self-assembly behavior, stimuli-responsiveness and biocompatibility, means that they have attracted increasing attention for use in biomedical applications such as cell culture, tissue engineering, protein purification, surface engineering and controlled drug delivery. The biopolymers discussed in this review are elastin-derived protein-based polymers which are biologically inspired and biomimetic materials. This review will also focus on the design, synthesis and characterization of these genetically encoded polymers and their potential utility for controlled drug and gene delivery, as well as in tissue engineering and regenerative medicine.European Social Fund (ESF) and European Regional Development Fund (ERDF)EU (NMP-2014-646075, HEALTH-F4-2011-278557, PITN-GA-2012-317306 and MSCA-ITN-2014-642687)Ministerio de Economía, Industria y Competitividad (Projects MAT2015-68901-R, MAT2016-79435-R and MAT2016-78903-R)Junta de Castilla y León (programa de apoyo a proyectos de investigación - Ref. Projects VA244U13 and VA313U14

Nanomedicine for autophagy modulation in cancer therapy: a clinical perspective

In recent years, progress in nanotechnology provided new tools to treat cancer more effectively. Advances in biomaterials tailored for drug delivery have the potential to overcome the limited selectivity and side effects frequently associated with traditional therapeutic agents. While autophagy is pivotal in determining cell fate and adaptation to different challenges, and despite the fact that it is frequently dysregulated in cancer, antitumor therapeutic strategies leveraging on or targeting this process are scarce. This is due to many reasons, including the very contextual effects of autophagy in cancer, low bioavailability and non-targeted delivery of existing autophagy modulatory compounds. Conjugating the versatile characteristics of nanoparticles with autophagy modulators may render these drugs safer and more effective for cancer treatment. Here, we review current standing questions on the biology of autophagy in tumor progression, and precursory studies and the state-of-the-art in harnessing nanomaterials science to enhance the specificity and therapeutic potential of autophagy modulators.Work in the laboratories of the authors is funded by grants from the Italian Ministries for Health (Ricerca Corrente) to M.T., from Education, University and Research (MIUR; 000003_17_MAP_STRIP and FISR 2020-Covid FISR2020IP_03366) to R.S; and from the Spanish Ministerio de Ciencia e Innovación (PID2021-128106NA-I00). M.C. is currently a recipient of a Ramón y Cajal tenure track contract from the Spanish Ministry of Science and Innovation (RYC2021-031003-I) and was funded by “Maria Zambrano” contract from Spanish Ministry of Universities and Complutense University of Madrid. M.S-A is recipient of a Ramón y Cajal tenure track contract from the Spanish Ministry of Science and Innovation (RYC2020-029690-I)

How rotating ATP synthases can modulate membrane structure

F1Fo-ATP synthase (ATP synthase) is a central membrane protein that synthetizes most of the ATP in the cell through a rotational movement driven by a proton gradient across the hosting membrane. In mitochondria, ATP synthases can form dimers through specific interactions between some subunits of the protein. The dimeric form of ATP synthase provides the protein with a spontaneous curvature that sustain their arrangement at the rim of the high-curvature edges of mitochondrial membrane (cristae). Also, a direct interaction with cardiolipin, a lipid present in the inner mitochondrial membrane, induces the dimerization of ATP synthase molecules along cristae. The deletion of those biochemical interactions abolishes the protein dimerization producing an altered mitochondrial function and morphology. Mechanically, membrane bending is one of the key deformation modes by which mitochondrial membranes can be shaped. In particular, bending rigidity and spontaneous curvature are important physical factors for membrane remodelling. Here, we discuss a complementary mechanism whereby the rotatory movement of the ATP synthase might modify the mechanical properties of lipid bilayers and contribute to the formation and regulation of the membrane invaginations

Hip fracture rates and bisphosphonate consumption in Spain. An ecologic study

Producción CientíficaIntroduction Bisphosphonates are used worldwide to treat osteoporosis and, thus, to prevent fractures. Though they have been proven in clinical trials to avoid some fractures, their effectiveness in reducing hip fractures is unclear. The aim of the present study was to explore the relationship between bisphosphonate use and hip fracture trends in Spain. Methods For this purpose, an ecologic study spanning 2002 to 2008 was conducted in Spain. Consumption data were obtained from the Spanish Ministry of Health and Social Policy. The number of hip fractures was obtained from hospital discharges; annual hip fracture rates were determined and standardized using the Spanish 2002 population census. A linear regression was performed between fracture rate and use of bisphosphonates; R2 and Pearson correlation coefficient were calculated. Results From 2002 to 2008, dispensed prescriptions of bisphosphonates in Spain increased from 3.28 to 17.66 DDD/1,000 inhabitants per day. In the same period, the crude hip fracture rate increased from 2.85 to 3.02 cases per 1,000 inhabitants older than 50 years; however, when age standardized rates were estimated, the rate declined from 2.85 to 2.79. Analyzed by sex, the standardized rate for men slightly increased from 1.45 to 1.48, while for women the rate significantly dropped from 4.00 to 3.91.Conclusion A small effect of bisphosphonates on hip fracture rates can not be ruled out; however, other factors might partially explain this decline. Assuming this medication was the only cause for hip fracture rate reduction, the elevated medication cost to avoid a single hip fracture makes it necessary to explore less expensive intervention

Análisis y desarrollo de las competencias personales y profesionales del profesor tutor de TFG

Durante este curso hemos conseguido llevar a cabo sólo una parte de los objetivos que teníamos previstos. No obstante, hemos constatado la relevancia del tema que estamos trabajando en los foros a los que hemos asistido, por lo que nos ha animado a pedir una continuación del proyecto para el próximo curso. En primer lugar, hemos llevado a cabo una revisión bibliográfica acerca de las competencias personales y profesionales que debe tener un buen profesor de educación superior. Estas competencias son el punto de partida para desempeñar con eficacia la función de tutorizar un TFG. Las conclusiones de esta revisión apuntan a la consideración de tres dimensiones fundamentales: las competencias personales, las pedagógicas y las técnicas. Sobre estas dimensiones se ha empezado a construir un cuestionario de evaluación de competencias. Durante este curso se han confeccionado los ítems y se ha pasado la primera batería a profesores expertos en dirigir TFGs con el objeto de obtener la validez de contenido del instrumento. En el futuro nos queda aplicar el cuestionario a profesores y alumnos para llevar a cabo el trabajo psicométrico, así como diseñar el protocolo de actuación que mejore la actuación docente de los profesores que dirigen un TFG

Feasibility assessment of the interactive use of a Monte Carlo algorithm in treatment planning for intraoperative electron radiation therapy

This work analysed the feasibility of using a fast, customized Monte Carlo (MC) method to perform accurate computation of dose distributions during pre- and intraplanning of intraoperative electron radiation therapy (IOERT) procedures. The MC method that was implemented, which has been integrated into a specific innovative simulation and planning tool, is able to simulate the fate of thousands of particles per second, and it was the aim of this work to determine the level of interactivity that could be achieved. The planning workflow enabled calibration of the imaging and treatment equipment, as well as manipulation of the surgical frame and insertion of the protection shields around the organs at risk and other beam modifiers. In this way, the multidisciplinary team involved in IOERT has all the tools necessary to perform complex MC dosage simulations adapted to their equipment in an efficient and transparent way. To assess the accuracy and reliability of this MC technique, dose distributions for a monoenergetic source were compared with those obtained using a general-purpose software package used widely in medical physics applications. Once accuracy of the underlying simulator was confirmed, a clinical accelerator was modelled and experimental measurements in water were conducted. A comparison was made with the output from the simulator to identify the conditions under which accurate dose estimations could be obtained in less than 3 min, which is the threshold imposed to allow for interactive use of the tool in treatment planning. Finally, a clinically relevant scenario, namely early-stage breast cancer treatment, was simulated with pre- and intraoperative volumes to verify that it was feasible to use the MC tool intraoperatively and to adjust dose delivery based on the simulation output, without compromising accuracy. The workflow provided a satisfactory model of the treatment head and the imaging system, enabling proper configuration of the treatment planning system and providing good accuracy in the dosage simulation