Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells

Accumulating evidence suggests that natural bioactive compounds, alone or in combination with traditional chemotherapeutic agents, could be used as potential therapies to fight cancer. In this study, we employed four natural bioactive compounds (curcumin, resveratrol, melatonin, and silibinin) and studied their role in redox control and ability to promote apoptosis in androgen sensitive and insensitive prostate cancer cells. Here is shown that curcumin and resveratrol promote ROS production and induce apoptosis in LNCaP and PC-3. An increase in reactive species is a trigger event in curcumin-induced apoptosis and a consequence of resveratrol effects on other pathways within these cells. Moreover, here we demonstrated that these four compounds affect differently one of the main intracellular redox regulator, the thioredoxin system. Exposure to curcumin and resveratrol promoted TRX1 oxidation and altered its subcellular location. Furthermore, resveratrol diminished TRX1 levels in PC-3 cells and increased the expression of its inhibitor TXNIP. Conversly, melatonin and silibinin only worked as cytostatic agents, reducing ROS levels and showing preventive effects against TRX oxidation. All together, this work explores the effect of compounds currently tested as chemo-preventive agents in prostate cancer therapy, on the TRX1 redox state and function. Our work shows the importance that the TRX system might have within the differences found in their mechanisms of action. These bioactive compounds trigger different responses and affect ROS production and redox systems in prostate cancer cells, suggesting the key role that redox-related pathways might play in processes like differentiation or survival in prostate cancer. Keywords: Thioredoxin, Thioredoxin reductase, TXNIP, Prostate cancer, Redox signaling, Apoptosi

Comunicación entre el personal sanitario y el paciente afásico

Comunicación oral presentada en la Segunda Conferencia Internacional de Comunicación en Salud, celebrada el 23 de octubre de 2015 en la Universidad Carlos III de MadridIntroducción: la afasia es la pérdida de capacidad de expresión debida a una lesión temporal o crónica de los centros temporales. Se calcula que en España hay unos 300.000 casos. Las limitaciones varían dependiendo del área dañada, viéndose afectada su capacidad para hablar, leer, escribir o comprender. Objetivos: Conocer los principales errores que comete el personal sanitario al comunicarse con el paciente afásico. Mostrar alternativas de comunicación entre paciente y personal sanitario. Fomentar la comunicación interprofesional. Metodología: se realiza una búsqueda bibliográfica en las bases de datos Dialnet, Lilacs, Medline y Cuiden Plus con las palabras “comunicación” “paciente” “afasia” para artículos a texto completo publicados en los últimos diez años. Resultados: la búsqueda ofreció resultados, que después proceso de selección se redujeron a cuatro artículos. Resultados: la bibliografía sobre la temática del estudio es escasa, la mayoría de los estudios se centran en el ámbito logopédico. Los profesionales que a diario se relacionan conel paciente afásico, carecen de formación en habilidades comunicativas, consecuencia de esro es que nos enfrentamos a una comunicación personal-paciente ineficaz reflejada en frustración en ambos. Se evidencia la necesidad de futuras líneas de investigación sobre este tema, con el fin, de mejorar la calidad de vida del enfermo afásico; así como fomentar el dialogo entre logopedas y el resto de profesionales sanitarios

Automatic pre-alignment of multimodality rat brain images using principal axes transformation

Abstract of: AMI Annual Conference 2006, March 25-29The use of small animal studies of different modalities isnowadays widespread, since functional studies like positron emission tomography (PET) or single photon emission computed tomography (SPECT) are better analyzed when mapped to the underlying anatomical structure coming from magnetic resonance imaging (MRI) or computed tomography (CT). The different positioning of the animals in the scanners results in the need for automated image registration methods. One important drawback of the existing algorithms is their limited capture range: if case of large initial misregistration (large translations and rotations) the optimization may not converge to the right solution, and the images do not become correctly coregistered. To avoid this problem we propose the use of a pre-alignment step based on the principal axes transformation.Publicad

Biomarkers and inorganic proxies in the paleoenvironmental reconstruction of mires: The importance of landscape in Las Conchas (Asturias, Northern Spain)

We determined the lipid distributions (n-alkanes, n-alkan-2-ones, n-alkanoic acids), total organic carbon (TOC), total nitrogen (TN), Ca/Mg and ash content in Las Conchas mire, a 3.2 m deep bryophyte-dominated mire in Northern Spain covering 8000 cal yr BP. Bog conditions developed in the bottom 20 cm of the profile, and good preservation of organic matter (OM) was inferred from n-alkanoic acid distribution, with the exception of the uppermost 20 cm (last ca. 200 yr). Microbial synthesis of long chain saturated fatty acids from primary OM likely produced a dominance of short chain n-alkanoic acids with a bimodal distribution, as well as the lack of correspondence between the n-alkane and n-alkanoic acid profiles in the upper 20 cm. This was accompanied by an increase in ash content, a decrease in TOC and variation in n-alkane ratios, thereby suggesting significant changes in the mire, namely drainage and transformation to a meadow, in the last ca. 200 yr. The distribution of n-alkan-2-ones indicated an increase in bacterial source from the bottom of the record to 94 cm, whereas their distribution in the upper part could be attributed mainly to plant input and/or the microbial oxidation of n-alkanes. The different n-alkane proxies showed variations, which we interpreted in terms of changes in vegetation (Sphagnum vs. non-Sphagnum dominated phases) during the last 8000 cal yr BP. C23 was the most abundant homolog throughout most of the record, thereby suggesting dominant humid conditions alternating with short drier phases. However, such humid conditions were not linked to paleoclimatic variation but rather to geomorphological characteristics: Las Conchas mire, at the base of the Cuera Range, receives continuous runoff—even during drier periods—which is not necessarily accompanied by additional mineral input to peat, producing the development of Sphagnum moss typical of waterlogged ecotopes and damp habitats. Thus, although geochemical proxies indicated an ombrotrophic regime in the mire, geomorphological characteristics may make a considerable contribution to environmental conditions

Co-planar PET/CT for small animal imaging

Proceeding of: 2005 IEEE Nuclear Science Symposium Conference Record, Puerto Rico, October 23 - 29, 2005A small animal PET/CT system based on a common rotating gantry is proposed. The PET detection subsystem is composed of two detector modules based on MLS arrays and four flat panel type PS PMT. The CT subsystem consists in a micro focus X ray tube and a semiconductor X ray detector. Space for opposed PET detectors and the CT scanner have been allocated on the same plane in such a way that the trans axial and axial centers are common for both systems. Shielding elements have been placed around the detectors to avoid cross modality contamination. The gantry can rotate 370 degrees to provide complete data sets for the CT image reconstruction algorithm that is based on the cone beam geometry. PET image reconstruction is implemented using FBP (2D and 3D) and OSEM. Sequential acquisition protocols minimize the scan duration, and CT information can be used to implement PET imaging corrections. The coplanar configuration of this system provides intrinsically co registered data sets, and it is not necessary to reposition the animal to perform any modality imaging, avoiding undesired animal or additional accessories movements. An additional advantage is the compactness of the system that saves space and allows a direct visual monitoring of the animal during the scanPart of this work is founded by the IM3 network (G03/185 Ministerio de Sanidad), with grants from the Ministerio de Educación y Ciencia, project TEC2004-07052-C02-01, and Ministerio de Industria, Turismo y Comercio project FIT-330101-2004-3. J.J. Vaquero has support from the “Ramón y Cajal” Program, Ministerio de Educación y Cienci

Efficient preclinical treatment of cortical T cell acute lymphoblastic leukemia with T lymphocytes secreting anti-CD1a T cell engagers

BACKGROUND: The dismal clinical outcome of relapsed/refractory (R/R) T cell acute lymphoblastic leukemia (T-ALL) highlights the need for innovative targeted therapies. Although chimeric antigen receptor (CAR)-engineered T cells have revolutionized the treatment of B cell malignancies, their clinical implementation in T-ALL is in its infancy. CD1a represents a safe target for cortical T-ALL (coT-ALL) patients, and fratricide-resistant CD1a-directed CAR T cells have been preclinically validated as an immunotherapeutic strategy for R/R coT-ALL. Nonetheless, T-ALL relapses are commonly very aggressive and hyperleukocytic, posing a challenge to recover sufficient non-leukemic effector T cells from leukapheresis in R/R T-ALL patients. METHODS: We carried out a comprehensive study using robust in vitro and in vivo assays comparing the efficacy of engineered T cells either expressing a second-generation CD1a-CAR or secreting CD1a x CD3 T cell-engaging Antibodies (CD1a-STAb). RESULTS: We show that CD1a-T cell engagers bind to cell surface expressed CD1a and CD3 and induce specific T cell activation. Recruitment of bystander T cells endows CD1a-STAbs with an enhanced in vitro cytotoxicity than CD1a-CAR T cells at lower effector:target ratios. CD1a-STAb T cells are as effective as CD1a-CAR T cells in cutting-edge in vivo T-ALL patient-derived xenograft models. CONCLUSIONS: Our data suggest that CD1a-STAb T cells could be an alternative to CD1a-CAR T cells in coT-ALL patients with aggressive and hyperleukocytic relapses with limited numbers of non-leukemic effector T cellsResearch in LA-V laboratory is funded by the Spanish Ministry of Science and Innovation (PID2020-117323RB-100 and PDC2021-121711-100), and the Carlos III Health Institute (DTS20/00089), with European Regional Development Fund (FEDER) cofinancing; the Spanish Association Against Cancer (AECC PROYE19084ALVA) and the CRIS Cancer Foundation (FCRIS-2018-0042 and FCRIS2021-0090). Research in PM laboratory is supported by CERCA/Generalitat de Catalunya and Fundació Josep Carreras-Obra Social la Caixa for core support; 'la Caixa' Foundation under the agreement LCF/PR/HR19/52160011; the European Research Council grant (ERC-PoC-957466); the Spanish Ministry of Science and Innovation (PID2019-108160RB-I00); and the ISCIII-RICORS within the Next Generation EU program (plan de Recuperación, Transformación y Resilencia). MLT is supported by Spanish Ministry of Science and Innovation (PID2019-105623RB-I00) and the Spanish Association Against Cancer (CICPF18030TORI). PP is supported by Carlos III Health Institute (PI21-01834), with FEDER cofinancing and Fundación Ramón Areces. NT was supported by an FPU PhD fellowship from Spain's Ministerio de Universidades (FPU19/00039). OH was supported by an industrial PhD fellowship from the Comunidad de Madrid (IND2020/BMD-17668). LD-A was supported by a Rio Hortega fellowship from the Carlos III Health Institute (CM20/00004). VMD is supported by the Torres Quevedo subprogram of the State Research Agency of the Ministry of Science, Innovation and Universities (Ref. PTQ2020-011056). DSM is partially founded by a Sara Borrell fellowship from Carlos III Health Institute (CD19/00013

Intervención Educativa para mejorar la calidad del Diagnóstico de la Malaria en la red de Laboratorios de Luanda, República de Angola

Introducción: La malaria continúa siendo uno de los más importantes problemas de salud  pública a nivel mundial que afecta con énfasis al continente africano y a Angola. Objetivos: Evaluar el nivel de conocimientos teóricos y prácticos en el diagnóstico de la malaria de un grupo de técnicos en Luanda antes y después de una intervención educativa. Material y Métodos: Entre abril y julio de 2013 se realizó un estudio experimental con grupo de control en 120 técnicos de la red de salud de Luanda; se hicieron dos evaluaciones teóricas y prácticas: una, al comienzo y otra, 3 meses después de una intervención educativa. Se incluyó un grupo adicional de control de 120 técnicos que fueron evaluados al mismo tiempo y en quienes no se hizo intervención. Los entrenamientos fueron de 10  días cumplimentando un programa de clases prácticas y teóricas. Resultados: Después de los entrenamientos en el grupo de Intervención, las notas ascendieron tras la segunda evaluación; mientras que en el grupo de control las calificaciones se mantuvieron sin cambios. Se observó que en el grupo de Intervención la probabilidad de estar desaprobado fue 129 veces mayor en la evaluación inicial para las pruebas teóricas y 108 veces mayor en los exámenes prácticos. Finalmente fueron identificados los principales aspectos en que fallaron los técnicos evaluados en los grupos de intervención y control. Conclusiones: Se demostró una mejoría en los conocimientos teóricos y prácticos de los técnicos de laboratorio dedicados al diagnóstico de la malaria después de la intervención educativa.Palabras clave: Malaria, conocimientos teóricos, evaluación práctica, diagnóstico microscópico.ABSTRACTIntroduction: The malaria still is one of the most important public health problems worldwide, specially the Africa as well as in Angola. Objectives: The aim was to evaluate the level of theoretical and practical knowledge in malaria diagnosis of a large group of technicians in Luanda before and after of an educational intervention. Material and Methods: Between April and July of 2013 an experimental study with a control group was carried out in 120 technicians from Luanda. The evaluations were applied previous and after (three months) of an educational intervention.  Another additional group of 120 technicians (control group) were evaluated too at the same period of time, but intervention was not made on them. Trainings were made during 10 days by completing a program with practical and theoretical classes. Results: after the trainings in the intervention group the scores increased in the theoretical and practical evaluations; while in the control group the scores of evaluations did not change after final evaluations. In the Intervention group the rate of disapproval was 129 times higher in the first evaluation than in final evaluation and this odd was 108 times higher in practical evaluations. Finally, the main topics with errors were identified in the evaluations from the beginning in the intervention and the control groups. Conclusions: In this study carried out in Luanda, Angola, an improvement of the evaluations was showed in theoretical and practical knowledge of the technicians after intervention in the network of laboratories of the capital province of the country.Keywords: Malaria, practical evaluation, theoretical knowledge, microscopic diagnosis. 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Comprehensive characterization of a novel, oncogenic and targetable SEPTIN6::ABL2 fusion in T-ALL

S