Tuning the Cytotoxicity of Bis-Phosphino-Amines Ruthenium(II) Para-Cymene Complexes for Clinical Development in Breast Cancer

Despite some limitations such as long-term side effects or the potential presence of intrinsic or acquired resistance, platinum compounds are key therapeutic components for the treatment of several solid tumors. To overcome these limitations, maintaining the same efficacy, organometallic ruthenium(II) compounds have been proposed as a viable alternative to platinum agents as they have a more favorable toxicity profile and represent an ideal template for both, high-throughput and rational drug design. To support the preclinical development of bis-phoshino-amine ruthenium compounds in the treatment of breast cancer, we carried out chemical modifications in the structure of these derivatives with the aim of designing less toxic and more efficient therapeutic agents. We report new bis-phoshino-amine ligands and the synthesis of their ruthenium counterparts. The novel ligands and compounds were fully characterized, water stability analyzed, and their in vitro cytotoxicity against a panel of tumor cell lines representative of different breast cancer subtypes was evaluated. The mechanism of action of the lead compound of the series was explored. In vivo toxicity was also assessed. The results obtained in this article might pave the way for the clinical development of these compounds in breast cancer therapyMinisterio de Ciencia e Innovación y Agencia Estatal de la Investigación, Spain (Grant Nos. PID2020-117788RB-I00, PID2020- 113661GB-I00, CTQ2017-84131-R and RED2018-102387-T Programa Redes Consolider), and Instituto de Salud Carlos III grant number PI16/01121. Alberto Ocaña’s lab is supported by the Instituto de Salud Carlos III (ISCIII, PI19/00808); CRIS Cancer Foundation, ACEPAIN, and Diputación de Albacete

Synthesis, characterization, and antibacterial activities of a heteroscorpionate derivative platinum complex against methicillin-resistant Staphylococcus aureus

Staphylococcus aureus is one of the species with the greatest clinical importance and greatest impact on public health. In fact, methicillin-resistant S. aureus (MRSA) is considered a pandemic pathogen, being essential to develop effective medicines and combat its rapid spread. This study aimed to foster the translation of clinical research outcomes based on metallodrugs into clinical practice for the treatment of MRSA. Bearing in mind the promising anti-Gram-positive effect of the heteroscorpionate ligand 1,1’-(2-(4-isopropylphenyl)ethane-1,1-diyl)bis(3,5-dimethyl-1H-pyrazole) (2P), we propose the coordination of this compound to platinum as a clinical strategy with the ultimate aim of overcoming resistance in the treatment of MRSA. Therefore, the novel metallodrug 2P-Pt were synthetized, fully characterized and its antibacterial effect against the planktonic and biofilm state of S. aureus evaluated. In this sense, three different strains of S. aureus were studied, one collection strain of S. aureus sensitive to methicillin and two clinical MRSA strains. To appraise the antibacterial activity, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC) were determined. Moreover, successful outcomes on the development of biofilm in a wound-like medium were obtained. The mechanism of action for 2P-Pt was proposed by measuring the MIC and MBC with EDTA (cation mediated mechanism) and DMSO (exogenous oxidative stress mechanism). Moreover, to shed light on the plausible antistaphylococcal mechanism of this novel platinum agent, additional experiments using transmission electron microscopy were carried out. 2P-Pt inhibited the growth and eradicated the three strains evaluated in the planktonic state. Another point worth stressing is the inhibition in the growth of MRSA biofilm even in a wounded medium. The results of this work support this novel agent as a promising therapeutic alternative for preventing infections caused by MRSA

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil. El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país. La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica. Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas

Inflexibilidad psicológica e impacto clínico: adaptación del Cuestionario de Aceptación y Acción-II en una muestra de pacientes en tratamiento de hemodiálisis.

Few studies have investigated the role psychological inflexibility (PI) could have in the context of chronic renal failure. The primary objective of this study was to analyse the psychometric features, the reliability and the validity of the Spanish version of the Acceptance and Action Questionnaire-II (AAQ-II) adapted to the context of patients undergoing haemodialysis (HD). The secondary objective was to assess the relationship between PI and parameters related to the adherence to treatment and quality of life in these types of patients. Prospective cross-sectional study with patients on haemodialysis (n=186). The fat tissue index (15.56±5.72 vs. 18.99±8.91, P=.033), phosphorus levels (3.92±1.24 vs. 4.66±1.38; P=.001) and interdialytic weight gain (1.56±0.69 vs. 1.89±0.93, P=.016) were higher in patients with a higher PI score. Phosphorus levels (P=.013) significantly explained the variability of PI levels. PI was also shown as a significant predictor (P=.026) of the variability of phosphorus levels. The adaptation of the AAQ-II questionnaire to the HD context led to a valid and reliable measurement of PI in these types of patients and our results also seem to support the relationship between PI and health and quality of life parameters in patients with chronic conditions

El asma : información y autocuidados

Tít. tomado de la cub.Se ofrece información sobre cómo el asma incide en el aparato respiratorio y los autocuidados a los que deben someterse las personas afectadas, el tratamiento y consejos para el manejo de las crisis asmáticas. También se analiza su incidencia en la vida cotidiana y la escuela, así como su relación con el deporte, las excursiones y salidas al campo.ES

Screening and preliminary biochemical and biological studies of [RuCl(p-cymene)(N, N-bis(diphenylphosphino)-isopropylamine)][BF4] in Breast Cancer Models

Breast cancer is the second leading cause of cancer death worldwide. Despite progress in drug discovery, identification of the correct population is the limiting factor to develop new compounds in the clinical setting. Therefore, the aim of this study is to evaluate the effects of a new metallodrug, [RuCl(p-cymene)(N,N-bis(diphenylphosphino)-isopropylamine)][BF4] (pnpRu-14), as a lead pnp-Ru compound by screening and preliminary biochemical and biological studies in different breast cancer subtypes. The results show that complex pnpRu-14 is much more effective in promoting in vitro cytotoxic effects on HER2+ and RH+/HER2- breast cancer than the reference metallodrugs cisplatin, carboplatin, or RAPTA-C. It is important to highlight that pnpRu-14 shows an impressive cytotoxicity against BT474 cells. Caspase-dependent apoptosis is the mechanism of action for these compounds. In addition, treatment of SKBR3, BT474, T47D, and MCF7 cancer cells with pnpRu-14 caused an accumulation of cells in the G0/G1 phase cells. The human serum albumin, DNA, and H1 histones binding properties of the lead compound are reported. Pharmacokinetic and biodistribution studies show a quick absorption of pnpRu-14 in serum with no significant accumulation in any of the tested organs. This work provides evidence to support the preclinical and clinical development of pnpRu-14 in breast cancer. Copyright © 2019 American Chemical Society.The authors gratefully acknowledge financial support from the Ministerio de Economı́a y Competitividad (MINECO), Spain (grant nos. CTQ2017-84131-R, CTQ2016-81797-REDC) 350 Programa Redes Consolider CTQ2016-78793-P, CTQ2017-86936-P, the Instituto de Salud Carlos III (PI16/01121), ACEPAIN, Diputación de Albacete, CIBERONC, and CRIS Cancer Foundation (to A.O.) and JJCC Castilla-La Mancha (grant no. SBPLY/17/180501/000262), as well as AGAUR (Gen. Catalunya, 2017 SGR 1051). ED thanks AECC for financial support.Peer reviewe

Equipos docentes y nuevas identidades académicas : en educación superior

Resumen basado en el de la publicaciónLa noción de equipos docentes en Educación Superior define una práctica de coordinación docente, bien para el logro de determinados propósitos transversales, bien en un sentido mucho más estricto, en el despliegue coordinado de una Titulación. Se aborda la pregunta de por qué y sobre qué ha de coordinarse el profesorado universitario, como reto fundamental a la cultura organizativa docente, basada en el ejercicio individual del profesorado y en la fragmentación de tareas, de responsabilidades y del conocimiento. Los cambios apuntados en las diversas contribuciones obedecen a las transformaciones que se están dando en la universidad española como consecuencia de nuevas demandas socio-formativas, las cuales generan nuevas necesidades, funciones y estructuras. Ello da lugar a nuevas identidades académicas. Lo anterior, nos sitúa en un contexto interpretativo de calado más amplio, el de la reconstrucción de las identidades académicas en relación a las funciones ejercidas dentro de ella.MadridBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

Equipos docentes y nuevas identidades académicas : en educación superior

Resumen basado en el de la publicaciónLa noción de equipos docentes en Educación Superior define una práctica de coordinación docente, bien para el logro de determinados propósitos transversales, bien en un sentido mucho más estricto, en el despliegue coordinado de una Titulación. Se aborda la pregunta de por qué y sobre qué ha de coordinarse el profesorado universitario, como reto fundamental a la cultura organizativa docente, basada en el ejercicio individual del profesorado y en la fragmentación de tareas, de responsabilidades y del conocimiento. Los cambios apuntados en las diversas contribuciones obedecen a las transformaciones que se están dando en la universidad española como consecuencia de nuevas demandas socio-formativas, las cuales generan nuevas necesidades, funciones y estructuras. Ello da lugar a nuevas identidades académicas. Lo anterior, nos sitúa en un contexto interpretativo de calado más amplio, el de la reconstrucción de las identidades académicas en relación a las funciones ejercidas dentro de ella.MadridBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]