In Vitro and In Vivo Response of Zinc-Containing Mesoporous Bioactive Glasses in a Sheep Animal Model

Zinc-enriched mesoporous bioactive glasses (MBGs) are bioceramics with potential antibacterial and osteogenic properties. However, few assays have been performed to study these properties in animal models.In this study, MBGs enriched with up to 5% ZnO were synthesized, physicochemically characterized, and evaluated for their osteogenic activity both in vitro and in vivo. The ZnO MBGs showed excellent textural properties despite ZnO incorporation. However, the release of Zn2+ ions inhibited the mineralization process when immersed in simulated body fluid. In vitro assays showed significantly highe r values of viability and expression of early markers of celldifferentiation and angiogenesis in a ZnO-content-dependent manner. The next step was to study the osteogenic potential in a sheep bone defect model. Despite their excellent textural properties and cellular response in vitro, the ZnO MBGs were not able to integrate into the bone tissue, which can be explained in terms of inhibition of the mineralization process caused by Zn2+ ions. This work highlights the need to develop nanostructured materials for bone regeneration that can mineralize to interact with bone tissue and induce the processes of implant acceptance, cell colonization by osteogenic cells, and regeneration of lost bone tissue

Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum Stress

We have evaluated cardiac function and fibrosis in infarcted male Wistar rats treated with MitoQ (50 mg/kg/day) or vehicle for 4 weeks. A cohort of patients admitted with a first episode of acute MI were also analyzed with cardiac magnetic resonance and T1 mapping during admission and at a 12-month follow-up. Infarcted animals presented cardiac hypertrophy and a reduction in the left ventricular ejection fraction (LVEF) and E- and A-waves (E/A) ratio when compared to controls. Myocardial infarction (MI) rats also showed cardiac fibrosis and endoplasmic reticulum (ER) stress activation. Binding immunoglobulin protein (BiP) levels, a marker of ER stress, were correlated with collagen I levels. MitoQ reduced oxidative stress and prevented all these changes without affecting the infarct size. The LVEF and E/A ratio in patients with MI were 57.6 ± 7.9% and 0.96 ± 0.34, respectively. No major changes in cardiac function, extracellular volume fraction (ECV), or LV mass were observed at follow-up. Interestingly, the myeloperoxidase (MPO) levels were associated with the ECV in basal conditions. BiP staining and collagen content were also higher in cardiac samples from autopsies of patients who had suffered an MI than in those who had died from other causes. These results show the interactions between mitochondrial oxidative stress and ER stress, which can result in the development of diffuse fibrosis in the context of MI

Injectable mesoporous bioactive nanoparticles regenerate bone tissue under osteoporosis conditions

The osteogenic capability of mesoporous bioactive nanoparticles (MBNPs) in the SiO2–CaO system has been assessed in vivo using an osteoporotic rabbit model. MBNPs have been prepared using a double template method, resulting in spherical nanoparticles with a porous core-shell structure that has a high surface area and the ability to incorporate the anti-osteoporotic drug ipriflavone. In vitro expression of the pro-inflammatory genes NF-κB1, IL-6, TNF-α, P38 and NOS2 in RAW-264.7 macrophages, indicates that these nanoparticles do not show adverse inflammatory effects. An injectable system has been prepared by suspending MBNPs in a hyaluronic acid-based hydrogel, which has been injected intraosseously into cavitary bone defects in osteoporotic rabbits. The histological analyses evidenced that MBNPs promote bone regeneration with a moderate inflammatory response. The incorporation of ipriflavone into these nanoparticles resulted in a higher presence of osteoblasts and enhanced angiogenesis at the defect site, but without showing significant differences in terms of new bone formation

Valvulitis: un nuevo criterio ecocardiográfico para el diagnóstico de endocarditis infecciosa de bioprótesis de válvula aórtica

Introduction and objectives: Diffuse homogeneous hypoechoic leaflet thickening, with a wavy leaflet motion documented by transesophageal echocardiography (TEE), has been described in some cases of prosthetic valve endocarditis (PVE) involving aortic bioprosthesis (AoBio-PVE). This echocardiographic finding has been termed valvulitis. We aimed to estimate the prevalence of valvulitis, precisely describe its echocardiographic characteristics, and determine their clinical significance in patients with AoBio-PVE. Methods: From 2011 to 2022, 388 consecutive patients with infective endocarditis (IE) admitted to a tertiary care hospital were prospectively included in a multipurpose database. For this study, all patients with AoBio-PVE (n = 86) were selected, and their TEE images were thoroughly evaluated by 3 independent cardiologists to identify all cases of valvulitis. Results: The prevalence of isolated valvulitis was 12.8%, and 20.9% of patients had valvulitis accompanied by other classic echocardiographic findings of IE. A total of 9 out of 11 patients with isolated valvulitis had significant valve stenosis, whereas significant aortic valve regurgitation was documented in only 1 patient. Compared with the other patients with AoBio-PVE, cardiac surgery was less frequently performed in patients with isolated valvulitis (27.3% vs 62.7%, P = .017). In 4 out of 5 patients with valve stenosis who did not undergo surgery but underwent follow-up TEE, valve gradients significantly improved with appropriate antibiotic therapy. Conclusions: Valvulitis can be the only echocardiographic finding in infected AoBio and needs to be identified by imaging specialists for early diagnosis. However, this entity is a diagnostic challenge and additional imaging techniques might be required to confirm the diagnosis. Larger series are needed.Introducción y objetivos: En pacientes con endocarditis de válvula prótesica sobre bioprótesis aórtica (EVP-AoBio) se ha descrito un engrosamiento difuso homogéneo e hipoecoico de las valvas, por ecocardiografía transesofágica (ETE), con movimiento ondulante de estas. Este hallazgo ha sido denominado valvulitis. Nuestro objetivo es estimar la prevalencia de valvulitis en pacientes con EVP-AoBio, describir con precisión sus características ecocardiográficas y determinar su significado clínico. Métodos: Desde 2011 hasta 2022, se incluyó en una base de datos multipropósito a 388 pacientes consecutivos con endocarditis de un hospital terciario. Para este estudio, se seleccionó a todos los pacientes con EVP-AoBio (n = 86), cuyas imágenes de ETE 3 cardiólogos revisaron de manera independiente para identificar casos de valvulitis. Resultados: La prevalencia de valvulitis aislada fue del 12,8%, y el 20,9% de los pacientes presentaron valvulitis acompañada de otros hallazgos ecocardiográficos clásicos de endocarditis. De 11 pacientes con valvulitis aislada, 9 tenían estenosis valvular significativa, mientras que solo 1 caso mostró insuficiencia valvular significativa. Se practicó cirugía cardiaca con menos frecuencia que en otros sujetos con EVP-AoBio (el 27,3 frente al 62,7%; p = 0,017). En 4 de 5 pacientes con estenosis valvular que no fueron operados, se observó una mejora significativa en los gradientes tras un tratamiento antibiótico. Conclusiones: La valvulitis puede ser el único hallazgo ecocardiográfico en la endocarditis infecciosa sobre bioprótesis de válvula aórtica y es necesario que los especialistas en imagen la reconozcan para un diagnóstico temprano. Sin embargo, supone un reto diagnóstico y pueden ser necesarias técnicas de imagen adicionales. Se necesitan series más amplias.Sin financiación5.9 Q1 JCR 20221.991 Q1 SJR 2023No data IDR 2022UE

Role of Telomere Length in Survival of Patients with Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Diseases

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‐RocheDepto. de Bioquímica y Biología MolecularDepto. de CirugíaFac. de FarmaciaFac. de MedicinaTRUEpu

Mesoporous bioactive glass/epsilon-polycaprolactone scaffolds promote bone regeneration in osteoporotic sheep

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.Depto. de Bioquímica y Biología MolecularDepto. de Química en Ciencias FarmacéuticasFac. de Ciencias QuímicasFac. de FarmaciaTRUEpu

Incorporation of art in the teaching of Medicine

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.Through the study and analysis of works of art that manifest topics related to Medicine, we want to teach the student to observe and perceive, develop critical analysis, consider differential diagnoses, in short, practice medicine with greater success. The analysis of these works of art has also allowed them to have a historical perspective of Medicine, enrich their humanistic training, increase creativity, critical judgment and teamwork.Depto. de Medicina Legal, Psiquiatría y PatologíaFac. de MedicinaFALSEsubmitte

CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel essential gene in prostate cancer metastasis

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 MadridMinisterio de Ciencia e Innovación (España)Sección Deptal. de Bioquímica y Biología Molecular (Veterinaria)Sección Deptal. de Bioquímica y Biología Molecular (Farmacia)Fac. de VeterinariaTRUEpu