Complejos metalosupramoleculares de Cu(I), Ag(I), Au(I), Pd(II) y Pt(II): síntesis, caracterización estructural y propiedades biológicas

En esta tesis se han desarrollado compuestos metalosupramoleculares de Cu(I), Ag(I), Au(I), Pd(II) y Pt(II) a partir de ligandos funcionalizados con fosfinas (bases de Schiff, tiosemicarbazonas y semicarbazona), que han permitido obtener información valiosa para la comprensión de los procesos de autoensamblaje en sistemas de esta naturaleza. Particularmente, se ha estudiado en detalle el proceso de desulfurización de un helicato clúster doble derivado de Ag(I) y tiosemicarbazona. La gran relevancia de algunos de estos iones metálicos a nivel biológico ha permitido evaluar de forma preliminar la aplicación de alguno de los complejos como posibles metalofármacos

Prothymosin α is phosphorylated by casein kinase-2

AbstractProthymosin α (ProTα) is a 12.5 kDa acidic polypeptide that is considered to have a nuclear function related to cell proliferation. Inspection of its amino acid sequence revealed the presence of sequences that may serve as targets for phosphorylation by casein kinase-2 (CK-2). ProTα isolated from calf thymocytes was phosphorylated in vitro by CK-2. The phosphorylation sites are Ser and Thr residues located among the first 14 amino acid residues in the ProTα sequence. Another site that is theoretically suitable for phosphorylation by CK-2, at the C-terminus of the polypeptide, is not, in fact, phosphorylated. Thymosin α1 (Tα1), a peptide whose sequence corresponds to the first 28 amino acids of ProTα, is also phosphorylated by CK-2 at the same phosphorylation sites as ProTα. In cultured splenic lymphocytes ProTα was phosphorylated at Thr residues located at positions 7, 12 and/or 13. Based on these observations we conclude that CK-2, or another cellular kinase with similar sequence specifity, is responsible for phosphorylation of ProTα in vivo

Design, development, and characterization of an idebenone-loaded poly-ε-caprolactone intravitreal implant as a new therapeutic approach for LHON treatment

Leber's Hereditary Optic Neuropathy (LHON) is a hereditary mitochondrial neurodegenerative disease of unclear etiology and lack of available therapeutic alternatives. The main goal of the current pilot study was based on the evaluation of the feasibility and characteristics of prolonged and controlled idebenone release from a PCL intravitreal implant. The design, development, and characterization of idebenone-loaded PCL implants prepared by an homogenization/extrusion/solvent evaporation method allowed the obtention of high PY, EE and LC values. In vitro characterization was completed by the assessment of mechanical and instrumental properties. The in vitro release of idebenone from the PCL implants was assessed and the implant erosion was monitored by the mass loss and surface morphology changes. DSC was used to estimate stability and interaction among implant’s components. The present work demonstrated the controlled and prolonged idebenone delivery from the PCL implants in an in vitro model. A consistent preclinical base was established, supporting the idea of idebenone-loaded PCL implants as a new strategy of long-term sustained intraocular delivery for the LHON treatmentRVF acknowledges the financial support of the FIDIS (Health Research Institute of Santiago de Compostela Foundation). This work was supported by the Spanish Ministry of Science, Innovation and Universities (RTI2018-099597-B-100)S

Enhancement in corneal permeability of riboflavin using cyclodextrin derivates complexes as a previous step to transepithelial cross-linking

Corneal cross-linking has been described as an effective treatment to slow the progression of keratoconus. The standard protocol entails corneal epithelial removal to allow the diffusion of riboflavin into the stroma. Although, de-epithelization can generate risks or complications that transepithelial cross-linking tries to solve or avoid. Different formulations were developed after verifying that hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobuthylether-β-cyclodextrin (SBEβCD) in a 20% concentration, increased the solubility of practically insoluble in water drugs such as riboflavin from 0.12 mg/mL to 0.35 mg/mL and 0.29 mg/mL respectively. These values were higher when chitosan and arginine were added to the formulation, showing solubility of 0.78 mg/mL when HPβCD concentration was not modified. Ex vivo corneal permeability was measured after having kept in contact bovine corneas with intact epithelium for 5 h with the 0.1 mg/mL riboflavin solution, the formulations developed and a reproduced nanoemulsion from another work. Riboflavin’s permeability was increased when cyclodextrins, chitosan, and arginine were part of the formulations, compared to the control drug solution. The best permeability coefficient was reached when riboflavin was combined with 40% (w/v) HPβCD, 0.5% (w/w) arginine, and 0.5% (w/w) chitosan. After having carried out toxicity studies as bovine corneal opacity and permeability (BCOP) and Heńs Egg Test - Chorioallantoic Membrane Test (HET-CAM) it was verified that both, the active ingredients and the excipients of the different formulations were not harmful without generating irritation, loss of transparency or corneal permeability alterations. The results show the great potential of the ocular developed solution for their use in transepithelial cross-linking for keratoconus treatmentS

La realidad aumentada en la docencia de ciencias de la salud. Nuevos caminos para la comprensión

[SPA] La evolución de las nuevas tecnologías y formatos electrónicos ha influido en las nuevas formas de enseñanza. La Realidad Aumentada (AR) es una variante de la realidad virtual en el que la imagen virtual se superpone con el mundo real. Creamos un libro con realidad aumentada (AR BOOK) una herramienta para los estudiantes y los instructores como parte del material docente. En esta primera parte, se centró en la anatomía de la extremidad inferior, el AR BOOK fue utilizado por los estudiantes de 1º de grado de podología de varias universidades españolas. 211 estudiantes fueron divididos en dos grupos: un grupo estudió con el AR BOOK y el otro con metodologías estándar. El conocimiento adquirido fue estadísticamente significativo (1,13 puntos en comparación con el grupo de la enseñanza tradicional, p <0,0001). Algunos datos coinciden con los resultados encontrados en otros estudios, lo que sugiere que el uso de las nuevas tecnologías debe ser considerado como una herramienta interesante para el proceso de enseñanza-aprendizaje con una serie de ventajas en términos de beneficios, el costo y/o la portabilidad.[ENG] The evolution of new technologies and electronic formats has also influenced on new forms of teaching. Augmented Reality (AR) is a variant of the virtual reality where the virtual image overlaps with the real world. Augmented reality book (AR BOOK) was created as a tool for both students and instructors as part of the teaching material. In this first part, focused on the anatomy of the lower limb, the AR BOOK was used by podiatry degree students. 211 students were divided in two groups: One group studied with the AR BOOK and the other one with standard methodologies. Acquired knowledge was statistically significant increased (1,13 points compared to the traditional teaching group; p<0.0001). Some data agree with results found herein, suggesting that the use of new technologies must be considered as a interesting tool for teaching-learning process with several advantages in terms of benefits, cost or portability

Supramolecular self-assembly of a symmetric imine ligand functionalized with a dansyl fluorophore moiety

The 20th International Electronic Conference on Synthetic Organic Chemistry session Polymer and Supramolecular ChemistryWe report the synthesis and characterization of a symmetric [N4] tetradentate imine-type ligand H2L that incorporates a dansyl fluorophore group in both ligand arms. Two binding domains separated by a short arene spacer and two bulky arms with an anti conformation make this organic molecule suitable as precursor of metallosupramolecular species such as helicates. The molecular structure of H2L has been analyzed by X-ray diffraction. This technique has revealed the formation of intermolecular hydrogen bond interactions that lead to the supramolecular self-assembly of ligand molecules in the solid state and the generation of oval-shaped channels in the 3D crystal packin

miR302a and 122 are deregulated in small extracellular vesicles from ARPE-19 cells cultured with H2O2

Age related macular degeneration (AMD) is a common retina-related disease leading to blindness. Little is known on the origin of the disease, but it is well documented that oxidative stress generated in the retinal pigment epithelium and choroid neovascularization are closely involved. The study of circulating miRNAs is opening new possibilities in terms of diagnosis and therapeutics. miRNAs can travel associated to lipoproteins or inside small Extracellular Vesicles (sEVs). A number of reports indicate a signifcant deregulation of circulating miRNAs in AMD and experimental approaches, but it is unclear whether sEVs present a signifcant miRNA cargo. The present work studies miRNA expression changes in sEVs released from ARPE-19 cells under oxidative conditions (i.e. hydrogen peroxide, H2O2). H2O2 increased sEVs release from ARPE-19 cells. Moreover, 218 miRNAs could be detected in control and H2O2 induced-sEVs. Interestingly, only two of them (hsa-miR-302a and hsa-miR-122) were signifcantly under-expressed in H2O2-induced sEVs. Results herein suggest that the down regulation of miRNAs 302a and 122 might be related with previous studies showing sEVs-induced neovascularization after oxidative challenge in ARPE-19 cells.Te present project was supported by internal funds from Universidad Católica de Valencia San Vicente Mártir (2018-128-001), Centro de Investigación Traslacional San Alberto Magno de la UCV (2019-128-001), and Conselleria de Educación, Investigación, Cultura y Deporte; Generalitat Valenciana (PROMETEO/2016/094). Oltra M and Vidal-Gil L, PhD training program fellowship UCV (EDUCV-PRE-2016-005 and EDUCVPRE-2015-006 Personal Investigador en Formación UCV, respectively).Medicin

Context-dependent impact of RAS oncogene expression on cellular reprogramming to pluripotency

Induction of pluripotency in somatic cells with defined genetic factors has been successfully used to investigate the mechanisms of disease initiation and progression. Cellular reprogramming and oncogenic transformation share common features; both involve undergoing a dramatic change in cell identity, and immortalization is a key step for cancer progression that enhances reprogramming. However, there are very few examples of complete successful reprogramming of tumor cells. Here we address the effect of expressing an active oncogene, RAS, on the process of reprogramming and found that, while combined expression with reprogramming factors enhanced dedifferentiation, expression within the context of neoplastic transformation impaired reprogramming. RAS induces expression changes that promote loss of cell identity and acquisition of stemness in a paracrine manner and these changes result in reprogramming when combined with reprogramming factors. When cells carry cooperating oncogenic defects, RAS drives cells into an incompatible cellular fate of malignancy.A.F. is an FPU predoctoral fellow from MECD; P.P. and J.M.V. are predoctoral fellows from Xunta de Galicia; F.T.-M. is a postdoctoral fellow from CONACYT (cvu 268632). M.C. is a ‘‘Miguel Servet II’’ investigator (CPII16/00015). Work in the laboratory of M.C. is funded by an ISCIII and EU-FEDER grant (PI14/00554). Work in the laboratory of A.V. is funded by Xunta de Galicia (ED431B 2016) and MINECO (MAT2017-89678-R; cofinanced with FEDER Funds)S

Pharmacokinetics of Intravitreal Anti-VEGF Drugs in Age-Related Macular Degeneration

Intravitreal administration of anti-vascular endothelial growth factor (VEGF) antibodies has become the standard treatment for Age-Related Macular Degeneration; however, the knowledge of their pharmacokinetics is limited. A comprehensive review of the preclinical and clinical pharmacokinetic data that were obtained in different studies with intravitreal bevacizumab, ranibizumab, and aflibercept has been conducted. Moreover, the factors that can influence the vitreous pharmacokinetics of these drugs, as well as the methods that were used in the studies for analytical determination, have been exposed. These anti-VEGF drugs present different charge and molecular weights, which play an important role in vitreous distribution and elimination. The pharmacokinetic parameters that were collected differ depending on the species that were involved in the studies and on physiological and pathological conditions, such as vitrectomy and lensectomy. Knowledge of the intravitreal pharmacokinetics of the anti-VEGF drugs that were used in clinical practice is of vital importance.This work was partially supported by the ISCIII (PI17/00940, RETICS Oftared, RD16/0008/0003 and RD12/0034/0017) cofunded by FEDER and by the Spanish Ministry of Science, Innovation and Universities (RTI2018-099597-B-100)S