Caracterización energética de la unión de 1,3,6- naftalén trisulfonato al factor de crecimiento para fibroblastos ácido humano: implicaciones para su uso como agente anti-angiogénico

The equilibrium interaction of anti-cancer agent 1,3,6-naphatalene trisulfonate with human acidic fi broblast growthfactor has been studied by calorimetry. The affi nity decreases with increasing ionic strength. At pH 7.0 and 0.15 MNaCl concentration, a binding constant of the protein with the ligand was estimated in the 102 – 103 M-1 range, anaffi nity two orders of magnitude lower than that of aFGF with heparin. The interaction is enthalpically driven, andthe entropy change is unfavorable. A small heat capacity change with an unusual positive value of 90 cal K-1mol-1 wasdetermined from the temperature dependence of the enthalpies. Changes in accessible apolar and polar surface areasin the interaction were calculated from the thermodynamic data obtained and parametric equations in the literature.The results were compared with those measured from NMR data. The study includes structural bioenergetic considerationsabout the possible use of 1,3,6-naphatalene trisulfonate as an anti-angiogenic agent itself, or as a lead for thedevelopment of anti-angiogenic drugs.Se ha estudiado, mediante calorimetría isotérmica de reacción, la interacción del agente anticancerígeno 1,3,6-naftaléntrisulfonato con el factor de crecimiento para fi broblastos ácido humano. La afi nidad decrece con el aumento de lafuerza iónica. A pH 7,0 y NaCl 0,15 M, la constante de unión de la proteína con el ligando se encuentra en el rango102 – 103 M-1, una afi nidad dos órdenes de magnitud menor que la del FGFa por heparina. El cambio de entalpíafavorece la interacción, siendo el cambio de entropía desfavorable. De la dependencia del cambio de entalpía con latemperatura se calculó un pequeño cambio en la capacidad calorífi ca del proceso, con un valor excepcionalmentepositivo de 90 cal K-1mol-1. A partir de los datos termodinámicos medidos y de ecuaciones paramétricas establecidasen la literatura, se calcularon cambios en la superfi cie accesible al disolvente, tanto polar como apolar, que acompañana la interacción. Los resultados se compararon con los medidos mediante resonancia magnética nuclear. Elestudio incluye consideraciones de bioenergética estructural sobre el posible uso de 1,3,6-naftalén trisulfonato comoagente antiangiogénico o como molécula líder para el desarrollo de fármacos anti-angiogénicos

Metabolic Targets of Coenzyme Q10 in Mitochondria

This work was supported by grants from Ministerio de Ciencia e Innovacion, Spain, and the ERDF (RTI2018-093503-B-100), the Muscular Dystrophy Association (MDA-602322). C.M.Q. is supported by the Department of Defense (DOD) grant PR190511. A.H.-G. and P.G.-G. are `FPU fellows' from the Ministerio de Universidades, Spain. S.L.-H. is supported by the "becas de colaboracion" from the Ministerio de Universidades, Spain. E.B.-C. is supported by the Consejeria de Salud, Junta de Andalucia, Spain.We thank Stacy Kelly Aguirre for the English editing. Figures created with BioRender.com.Coenzyme Q10 (CoQ(10)) is classically viewed as an important endogenous antioxidant and key component of the mitochondrial respiratory chain. For this second function, CoQ molecules seem to be dynamically segmented in a pool attached and engulfed by the super-complexes I + III, and a free pool available for complex II or any other mitochondrial enzyme that uses CoQ as a cofactor. This CoQ-free pool is, therefore, used by enzymes that link the mitochondrial respiratory chain to other pathways, such as the pyrimidine de novo biosynthesis, fatty acid beta-oxidation and amino acid catabolism, glycine metabolism, proline, glyoxylate and arginine metabolism, and sulfide oxidation metabolism. Some of these mitochondrial pathways are also connected to metabolic pathways in other compartments of the cell and, consequently, CoQ could indirectly modulate metabolic pathways located outside the mitochondria. Thus, we review the most relevant findings in all these metabolic functions of CoQ and their relations with the pathomechanisms of some metabolic diseases, highlighting some future perspectives and potential therapeutic implications.Spanish GovernmentEuropean Commission RTI2018-093503-B-100Muscular Dystrophy Association MDA-602322United States Department of Defense PR190511Ministerio de Universidades, SpainJunta de Andaluci

Electrocatalytic self-assembled multilayer structures based on thiolated Fc-DAB dendrimers: Determination of heavy metal ions by enzymatic inhibition

The development of sensitive and rapid inhibition-based biosensors for monitoring trace levels of heavy metals such as lead and copper ions in environmental samples is of high interest. In this work, we describe the fabrication of HRP sensitive peroxide biosensors based on ferrocenyl thiolated DAB dendrimers as bonding-layer between electrodeposited and colloidal gold nanoparticles and compare their electrocatalytic properties with those of thiolated DAB homologues. The complete electrochemical, kinetic and analytical characterization of these new heavy metals’ inhibition-biosensors are investigate

Health education in primary school: Alicante city (Spain) teachers’ opinions

Objetivo: Explorar la opinión del profesorado de educación primaria de la ciudad de Alicante sobre las actividades de salud realizadas en la escuela. Método: Estudio exploratorio mediante análisis de contenido cualitativo. Se formaron tres grupos de discusión (8-9 participantes) con profesorado de educación primaria (14 mujeres y 11 hombres) procedentes de 14 escuelas públicas y 7 concertadas de la ciudad de Alicante. La información se obtuvo preguntando a los/las participantes sobre las actividades de salud realizadas en el aula o en el centro escolar. Resultados: El profesorado diferenció las actividades que forman parte de las programaciones escolares de educación para la salud de las que proceden de programas de otras instituciones públicas o privadas. Consideró que los programas externos son impuestos, no tienen continuidad y responden a modas pasajeras. Aunque mostró una actitud más favorable y comprometida con las actividades y programaciones escolares, identificó la educación para la salud como una tarea secundaria. En su opinión, incrementar su formación en salud, implicar a los padres y las madres, profesionales sanitarios y la administración educativa fomentaría la educación para la salud en la escuela. Conclusiones: El profesorado muestra una opinión más favorable y un mayor compromiso hacia las actividades de salud que complementan y facilitan su tarea educativa. Su programación docente y opinión deben tenerse en cuenta para maximizar la eficiencia de las actividades de promoción y educación para la salud promovidas por instituciones, compañías y fundaciones externas a la escuela.Objective: This study explores the opinions of primary school teachers about health activities carried out in schools in Alicante city (Spain). Methods: An exploratory study was conducted through qualitative content analysis. Three focus groups were conducted with 25 primary school teachers (14 women and 11 men) working in 14 public and 7 private schools in the city of Alicante. Participants were asked about the health activities carried on in their schools. Results: Teachers distinguished between health education activities promoted by the school and those included in external programmes promoted by public and private institutions. External programmes were considered as impositions, lacking continuity and chosen according to passing fads. Although teachers demonstrated a more positive attitude towards activities arising from their own initiative, they identified health education as a secondary task. Teachers considered that improving their own health education training and promoting the involvement of parents, health professionals and public institutions were the most appropriate ways to promote health education in the school. Conclusion: Teachers showed a more positive opinion and greater commitment towards health activities that complement and facilitate their teaching tasks. Their didactic programme and opinion should be taken into account to maximise the efficiency of the health promotion and education activities promoted by external organisations.Este trabajo ha sido financiado por la Escuela Valenciana de Estudios en Salud (EVES) de la Generalitat Valenciana nº 044/2006

A new role of the Rac-GAP β2-chimaerin in cell adhesion reveals opposite functions in breast cancer initiation and tumor progression

β2-chimaerin is a Rac1-specific negative regulator and a candidate tumor suppressor in breast cancer but its precise function in mammary tumorigenesis in vivo is unknown. Here, we study for the first time the role of β2-chimaerin in breast cancer using a mouse model and describe an unforeseen role for this protein in epithelial cell-cell adhesion. We demonstrate that expression of β2-chimaerin in breast cancer epithelial cells reduces E-cadherin protein levels, thus loosening cell-cell contacts. In vivo, genetic ablation of β2-chimaerin in the MMTV-Neu/ErbB2 mice accelerates tumor onset, but delays tumor progression. Finally, analysis of clinical databases revealed an inverse correlation between β2-chimaerin and E-cadherin gene expressions in Her2+ breast tumors. Furthermore, breast cancer patients with low β2-chimaerin expression have reduced relapse free survival but develop metastasis at similar times. Overall, our data redefine the role of β2-chimaerin as tumor suppressor and provide the first in vivo evidence of a dual function in breast cancer, suppressing tumor initiation but favoring tumor progression