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Abstract Background Critical limb-threatening ischemia (CLTI) constitutes the most severe manifestation of peripheral artery disease, usually induced by atherosclerosis. CLTI patients suffer from high risk of amputation of the lower extremities and elevated mortality rates, while they have low options for surgical revascularization due to associated comorbidities. Alternatively, cell-based therapeutic strategies represent an effective and safe approach to promote revascularization. However, the variability seen in several factors such as cell combinations or doses applied, have limited their success in clinical trials, being necessary to reach a consensus regarding the optimal “cellular-cocktail” prior further application into the clinic. To achieve so, it is essential to understand the mechanisms by which these cells exert their regenerative properties. Herein, we have evaluated, for the first time, the regenerative and vasculogenic potential of a combination of endothelial colony forming cells (ECFCs) and mesenchymal stem cells (MSCs) isolated from adipose-tissue (AT), compared with ECFCs from umbilical cord blood (CB-ECFCs) and AT-MSCs, in a murine model of CLTI. Methods Balb-c nude mice (n:32) were distributed in four different groups (n:8/group): control shams, and ischemic mice (after femoral ligation) that received 50 µl of physiological serum alone or a cellular combination of AT-MSCs with either CB-ECFCs or AT-ECFCs. Follow-up of blood flow reperfusion and ischemic symptoms was carried out for 21 days, when mice were sacrificed to evaluate vascular density formation. Moreover, the long-term molecular changes in response to CLTI and both cell combinations were analyzed in a proteomic quantitative approach. Results AT-MSCs with either AT- or CB-ECFCs, promoted a significant recovery of blood flow in CLTI mice 21 days post-ischemia. Besides, they modulated the inflammatory and necrotic related processes, although the CB group presented the slowest ischemic progression along the assay. Moreover, many proteins involved in the repairing mechanisms promoted by cell treatments were identified. Conclusions The combination of AT-MSCs with AT-ECFCs or with CB-ECFCs promoted similar revascularization in CLTI mice, by restoring blood flow levels, together with the modulation of the inflammatory and necrotic processes, and reduction of muscle damage. The protein changes identified are representative of the molecular mechanisms involved in ECFCs and MSCs-induced revascularization (immune response, vascular repair, muscle regeneration, etc.).

Abstract Achieving sufficient coverage of regulatory phosphorylation sites by mass spectrometry (MS)-based phosphoproteomics for signaling pathway reconstitution is challenging, especially when analyzing tiny sample amounts. To address this, we present a hybrid data-independent acquisition (DIA) strategy (hybrid-DIA) that combines targeted and discovery proteomics through an Application Programming Interface (API) to dynamically intercalate DIA scans with accurate triggering of multiplexed tandem mass spectrometry (MSx) scans of predefined (phospho)peptide targets. By spiking-in heavy stable isotope labeled phosphopeptide standards covering seven major signaling pathways, we benchmark hybrid-DIA against state-of-the-art targeted MS methods (i.e., SureQuant) using EGF-stimulated HeLa cells and find the quantitative accuracy and sensitivity to be comparable while hybrid-DIA also profiles the global phosphoproteome. To demonstrate the robustness, sensitivity, and biomedical potential of hybrid-DIA, we profile chemotherapeutic agents in single colon carcinoma multicellular spheroids and evaluate the phospho-signaling difference of cancer cells in 2D vs 3D culture.

Abstract Triple negative breast cancer (TNBC) is known for being very aggressive, heterogeneous and highly metastatic. The standard of care treatment is still chemotherapy, with adjacent toxicity and low efficacy, highlighting the need for alternative and more effective therapeutic strategies. Edelfosine, an alkyl-lysophospholipid, has proved to be a promising therapy for several cancer types, upon delivery in lipid nanoparticles. Therefore, the objective of this work was to explore the potential of edelfosine for the treatment of TNBC. Edelfosine nanoemulsions (ET-NEs) composed by edelfosine, Miglyol 812 and phosphatidylcholine as excipients, due to their good safety profile, presented an average size of about 120 nm and a neutral zeta potential, and were stable in biorelevant media. The ability of ET-NEs to interrupt tumor growth in TNBC was demonstrated both in vitro, using a highly aggressive and invasive TNBC cell line, and in vivo, using zebrafish embryos. Importantly, ET-NEs were able to penetrate through the skin barrier of MDA-MB 231 xenografted zebrafish embryos, into the yolk sac, leading to an effective decrease of highly aggressive and invasive tumoral cells’ proliferation. Altogether the results demonstrate the potential of ET-NEs for the development of new therapeutic approaches for TNBC.

Transportation of perishable foodstuff is an engineering and commercial activity ruled by an international Agreement (the ATP) that needs an updated regulation. Before addressing such updating, some analyses are required about the physics of the problem, in order to identify the optimum use of the available technologies and the advantages represented by new methodologies that could be enabled soon. It is worth pointing out that manufacturers of ATP equipment follow quite closely the prescriptions given by this Agreement. So, optimizing those prescriptions will generate a general optimization trend in this sector. In this paper, a coherent analysis on these subjects is presented, and a new coefficient is proposed for qualifying ATP units, and some new tests are also proposed for measuring that coefficient in an efficient and inexpensive way. These goals are justified in this paper as a contribution from basic physics to a particular domain of Thermal Engineering. The paper is intended to be a bridge from Science to Technology, which is a must to get optimum results in exploiting technical knowledge.

La creciente evidencia científica de mindfulness permite su expansión en distintos contextos, entre ellos el contexto educativo. Sin embargo, unida a esta rápida expansión, existe la preocupación de que los profesionales que enseñen mindfulness no tengan la suficiente formación personal y no posean las competencias y las habilidades necesarias para desempeñar esta tarea. Este artículo se basa en la información obtenida a partir de una búsqueda realizada en diferentes bases de datos, y referida a los principales artículos y trabajos publicados sobre mindfulness dirigidos al profesorado. Se exponen aspectos relativos a la formación en mindfulness y a las competencias, las habilidades y los principios necesarios para que los profesores apliquen mindfulness en las aulas; también se exponen las principales dificultades encontradas, los factores que contribuyen al éxito y las sugerencias de mejora respecto a la puesta en práctica de estos programas.

Se estudia la conveniencia de incluir el concepto de histéresis en las disciplinas humanistas, así como la necesidad de incorporar el análisis de los fenómenos donde aquél participa. La histéresis se produce en los más diversos campos de la acción y el pensamiento humanos, y su estudio contribuiría a completar y perfeccionar la visión que tenemos de los mismos. Al realizar la inclusión que aquí se propone, se operan varios cambios de orden epistemológico, operativo y conceptual. En las disciplinas humanistas, los conceptos vienen asumiendo por tradición el papel de herramientas analíticas en bastante mayor medida que el de contenidos sobre los que efectuar el análisis. La histéresis manifiesta su alcance como hecho a analizar y también como herramienta de análisis, pero en el caso presente hemos tenido en cuenta más aspectos del segundo enfoque que del primero. De aquí que nos hayamos centrado en ubicar su campo epistemológico.

Achieving sufficient coverage of regulatory phosphorylation sites by mass spectrometry (MS)-based phosphoproteomics for signaling pathway reconstitution is challenging, especially when analyzing tiny sample amounts. To address this, we present a hybrid data-independent acquisition (DIA) strategy (hybrid-DIA) that combines targeted and discovery proteomics through an Application Programming Interface (API) to dynamically intercalate DIA scans with accurate triggering of multiplexed tandem mass spectrometry (MSx) scans of predefined (phospho)peptide targets. By spiking-in heavy stable isotope labeled phosphopeptide standards covering seven major signaling pathways, we benchmark hybrid-DIA against state-of-the-art targeted MS methods (i.e., SureQuant) using EGF-stimulated HeLa cells and find the quantitative accuracy and sensitivity to be comparable while hybrid-DIA also profiles the global phosphoproteome. To demonstrate the robustness, sensitivity, and biomedical potential of hybrid-DIA, we profile chemotherapeutic agents in single colon carcinoma multicellular spheroids and evaluate the phospho-signaling difference of cancer cells in 2D vs 3D culture. Standard mass spectrometry analyses often miss key targets required for phospho-signalling reconstruction. Here, authors present an intelligent data acquisition strategy that combines discovery and targeted analysis in one run and apply it to maximize the information from single spheroids drug screenings. [ABSTRACT FROM AUTHOR]