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The incorporation of cobalt ions into the composition of bioactive glasses has emerged as a strategy of interest for bone regeneration purposes. In the present work, we have designed a set of bioactive mesoporous glasses SiO2 -CaO-P2 O5 -CoO (Co-MBGs) with different amounts of cobalt. The physicochemi- cal changes introduced by the Co2 + ion, the in vitro effects of Co-MBGs on preosteoblasts and endothelial cells and their in vivo behaviour using them as bone grafts in a sheep model were studied. The results show that Co2 + ions neither destroy mesoporous ordering nor inhibit in vitro bioactive behaviour, ex- erting a dual role as network former and modifier for CoO concentrations above 3 % mol. On the other hand, the activity of Co-MBGs on MC3T3-E1 preosteoblasts and HUVEC vascular endothelial cells is de- pendent on the concentration of CoO present in the glass. For low Co-MBGs concentrations (1mg/ml) cell viability is not affected, while the expression of osteogenic (ALP, RUNX2 and OC) and angiogenic (VEGF) genes is stimulated. For Co-MBGs concentration of 5 mg/ml, cell viability decreases as a function of the CoO content. In vivo studies show that the incorporation of Co2 + ions to the MBGs improves the bone regeneration activity of these materials, despite the deleterious effect that this ion has on bone-forming cells for any of the Co-MBG compositions studied. This contradictory effect is explained by the marked increase in angiogenesis that takes place inside the bone defect, leading, Ministerio de Ciencia e Innovación (España), Depto. de Química en Ciencias Farmacéuticas, Fac. de Farmacia, TRUE, pub

Credit authorship contribution statement: Maria Rodrigo-Faus: Writing – review & editing, Writing – original draft, Visualization, Validation, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Africa Vincelle-Nieto: Writing – original draft, Visualization, Software, Methodology, Formal analysis. Natalia Vidal: Resources. Javier Puente: Resources. Melchor Saiz-Pardo: Resources, Investigation. Alejandra Lopez-Garcia: Resources, Methodology, Investigation. Marina Mendiburu-Eliçabe: Visualization, Formal analysis, Data curation. Nerea Palao: Visualization, Conceptualization. Cristina Baquero: Methodology. Paula Linzoain-Agos: Investigation, Methodology, Writing – review & editing. Angel M. Cuesta: Visualization, Methodology. Hui-Qi Qu: Visualization, Methodology, Formal analysis, Data curation. Hakon Hakonarson: Supervision, Conceptualization. Monica Musteanu: Validation, Supervision, Resources, Methodology. Armando ReyesPalomares: Writing – review & editing, Visualization, Validation, Methodology, Formal analysis, Data curation, Conceptualization. Almudena Porras: Writing – review & editing, Supervision, Conceptualization. Paloma Bragado: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Alvaro Gutierrez-Uzquiza: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Software, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization., Due to the limited effectiveness of current treatments, the survival rate of patients with metastatic castration-resistant prostate cancer (mCRPC) is significantly reduced. Consequently, it is imperative to identify novel therapeutic targets for managing these patients. Since the invasive ability of cells is crucial for establishing and maintaining metastasis, the aim of this study was to identify the essential regulators of invasive abilities of mCRPC cells by conducting two independent high-throughput CRISPR/Cas9 screenings. Furthermore, some of the top hits were validated using siRNA technology, with protein arginine methyltransferase 7 (PRMT7) emerging as the most promising candidate. We demonstrated that its inhibition or depletion via genetic or pharmacological approaches significantly reduces invasive, migratory and proliferative abilities of mCRPC cells in vitro. Moreover, we confirmed that PRMT7 ablation reduces cell dissemination in chicken chorioallantoic membrane and mouse xenograft assays. Molecularly, PRMT7 reprograms the expression of several adhesion molecules by methylating various transcription factors, such as FoxK1, resulting in the loss of adhesion from the primary tumor and increased motility of mCRPC cells. Furthermore, PRMT7 higher expression correlates with tumor aggressivity and poor overall survival in prostate cancer patients. Thus, this study demonstrates that PRMT7 is a potential therapeutic target and potential biomarker for mPCa., Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades (España), Sección Deptal. de Bioquímica y Biología Molecular (Veterinaria), Sección Deptal. de Bioquímica y Biología Molecular (Farmacia), Fac. de Veterinaria, TRUE, pub

Interstitial lung diseases (ILDs) constitute a group of more than 200 disorders, with idiopathic pulmonary fibrosis (IPF) being one of the most frequent. Telomere length (TL) shortening causes loss of function of the lung parenchyma. However, little is known about its role as a prognostic factor in ILD patients. With the aim of investigating the role of TL and telomerase activity in the prognosis of patients affected by ILDs, we analysed lung tissue samples from 61 patients. We measured relative TL and telomerase activity by conventional procedures. Both clinical and molecular parameters were associated with overall survival by the Kaplan–Meier method. Patients with IPF had poorer prognosis than patients with other ILDs (p = 0.034). When patients were classified according to TL, those with shortened telomeres reported lower overall survival (p = 0.085); differences reached statistical significance after excluding ILD patients who developed cancer (p = 0.021). In a Cox regression analysis, TL behaved as a risk-modifying variable for death associated with rheumatic disease (RD) co-occurrence (p = 0.029). Also, in patients without cancer, ferritin was significantly increased in cases with RD and IPF co-occurrence (p = 0.032). In relation to telomerase activity, no significant differences were detected. In conclusion, TL in lung tissue emerges as a prognostic factor in ILD patients. Specifically, in cases with RD and IPF co-occurrence, TL can be considered as a risk-modifying variable for death., Neumomadrid (Sociedad Madrileña de Neumología y Cirugía Torácica), Cátedra EPID Futuro UAM-Roche, Depto. de Cirugía, Fac. de Medicina, TRUE, pub

Mediante el estudio y análisis de obras de arte que manifiestan temas relacionados con la Medicina queremos enseñar al estudiante a observar y percibir, desarrollar el análisis critico, plantearse diagnósticos diferenciales en suma ejercer la medicina con mayor éxito. El análisis de estas obras de arte les ha permitido también tener una perspectiva histórica de la Medicina, enriquecer su formación humanística, aumentar la creatividad, el juicio critico y el trabajo en equipo.

Carlos Ferrera,1 Isidre Vilacosta,1 Beatriz Cabeza,2 Javier Cobiella,3 Isaac Martínez,4 Melchor Saiz-Pardo Sanz,5 Ana Bustos,2 Francisco Javier Serrano,4 Luis Maroto3 1Department of Cardiology, Hospital Clínico San Carlos, Madrid, Spain; 2Department of Radiology, Hospital Clínico San Carlos, Madrid, Spain; 3Department of Cardiac Surgery, Hospital Clínico San Carlos, Madrid, Spain; 4Department of Vascular Surgery, Hospital Clínico San Carlos, Madrid, Spain; 5Pathology Department, Hospital Clínico San Carlos, Madrid, SpainCorrespondence: Carlos FerreraDepartment of Cardiology, Hospital Clínico San Carlos, Calle Profesor Martín Lagos S/N, Madrid 28040, SpainTel +34 91 330 3149Fax +34 91 330 3142Email carlosferreraduran@gmail.comAbstract: Aortic intramural hematoma (AIH) is an entity within the acute aortic syndrome. Combination of a priori probability, clinical history, laboratory blood test and imaging techniques are the basis for diagnosis of AIH. This review is focused on all aspects related to diagnosis of patients with AIH, from clinical to imaging and analytical.Keywords: aortic intramural hematoma, acute aortic syndrome, diagnosis

Macroporous scaffolds made of a SiO2-CaO-P2O5 mesoporous bioactive glass (MBG) and epolycaprolactone (PCL) have been prepared by robocasting. These scaffolds showed an excellent in vitro biocompatibility in contact with osteoblast like cells (Saos 2) and osteoclasts derived from RAW 264.7 macrophages. In vivo studies were carried out by implantation into cavitary defects drilled in osteoporotic sheep. The scaffolds evidenced excellent bone regeneration properties, promoting new bone formation at both the peripheral and the inner parts of the scaffolds, thick trabeculae, high vascularization and high presence of osteoblasts and osteoclasts. In order to evaluate the effects of the local release of an antiosteoporotic drug, 1% (%wt) of zoledronic acid was incorporated to the scaffolds. The scaffolds loaded with zoledronic acid induced apoptosis in Saos 2 cells, impeded osteoclast differentiation in a time dependent manner and inhibited bone healing, promoting an intense inflammatory response in osteoporotic sheep., Ministerio de Economía y Competitividad (España), European Commission, Depto. de Bioquímica y Biología Molecular, Depto. de Química en Ciencias Farmacéuticas, Fac. de Ciencias Químicas, Fac. de Farmacia, TRUE, pub