A Two-Photon Probe Based on Naphthalimide-Styrene Fluorophore for the In Vivo Tracking of Cellular Senescence

Cellular senescence is a state of stable cell cycle arrest that can negatively affect the regenerative capacities of tissues and can contribute to inflammation and the progression of various aging-related diseases. Advances in the in vivo detection of cellular senescence are still crucial to monitor the action of senolytic drugs and to assess the early onset or accumulation of senescent cells. Here, we describe a naphthalimide-styrene-based probe (HeckGal) for the detection of cellular senescence both in vitro and in vivo. HeckGal is hydrolyzed by the increased lysosomal β-galactosidase activity of senescent cells, resulting in fluorescence emission. The probe was validated in vitro using normal human fibroblasts and various cancer cell lines undergoing senescence induced by different stress stimuli. Remarkably, HeckGal was also validated in vivo in an orthotopic breast cancer mouse model treated with senescence-inducing chemotherapy and in a renal fibrosis mouse model. In all cases, HeckGal allowed the unambiguous detection of senescence in vitro as well as in tissues and tumors in vivo. This work is expected to provide a potential technology for senescence detection in aged or damaged tissues

Combined kinetic analysis of SARS-CoV-2 RNAemia, N-antigenemia and virus-specific antibodies in critically ill adult COVID-19 patients

Combined kinetic analysis of plasma SARS‐CoV‐2 RNAemia, Nucleocapsid (N)‐antigenemia and virus‐specific antibodies may help ascertain the role of antibodies in preventing virus dissemination in COVID‐19 patients. We performed this analysis in a cohort of 71 consecutive critically ill COVID‐19 patients (49 male; median age, 65 years) using RT‐PCR assay, lateral flow immunochromatography method and receptor binding domain (RBD) and N‐based immunoassays. A total of 338 plasma specimens collected at a median of 12 days after symptoms onset were available for analyses. SARS‐ CoV‐2 RNAemia and N‐antigenemia were detected in 37 and 43 specimens from 26 (36.5%) and 30 (42.2%) patients, respectively. Free RNA was the main biological form of SARS‐CoV‐2 found in plasma. The detection rate for both viral components was associated with viral load at the upper respiratory tract. Median time to SARS‐CoV‐2‐RBD antibody detection was 14 days (range, 4-38) from onset of symptoms. Decreasing antibody levels were observed in parallel to increasing levels of both RNAemia and N‐antigenemia, yet overall a fairly modest inverse correlation (Rho = −0.35; P < 0.001) was seen between virus RNAemia and SARS‐CoV‐2‐RBD antibody levels. The data cast doubts on a major involvement of antibodies in virus clearance from the bloodstream within the timeframe examined

LPS-TLR4 Pathway mediates ductular cell expansion in alcoholic hepatitis.

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there are no effective therapies. Patients with AH show impaired hepatocyte proliferation, expansion of inefficient ductular cells and high lipopolysaccharide (LPS) levels. It is unknown whether LPS mediates ductular cell expansion. We performed transcriptome studies and identified keratin 23 (KRT23) as a new ductular cell marker. KRT23 expression correlated with mortality and LPS serum levels. LPS-TLR4 pathway role in ductular cell expansion was assessed in human and mouse progenitor cells, liver slices and liver injured TLR4 KO mice. In AH patients, ductular cell expansion correlated with portal hypertension and collagen expression. Functional studies in ductular cells showed that KRT23 regulates collagen expression. These results support a role for LPS-TLR4 pathway in promoting ductular reaction in AH. Maneuvers aimed at decreasing LPS serum levels in AH patients could have beneficial effects by preventing ductular reaction development

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Marco activo de recursos de innovación docente: Madrid

Una guía de espacios e instituciones para actividades educativas complementarias en enseñanza secundaria y Formación Profesional

Red “Universidad, género, docencia e igualdad”

La Red de investigación en docencia universitaria “Universidad, docencia, genero e igualdad” persigue avanzar en la calidad e innovación de las enseñanzas universitarias a partir de la inclusión de la perspectiva de género. Se busca dar cumplimiento a las directrices generales de los nuevos planes de estudio respecto del principio de igualdad de oportunidades entre hombres y mujeres en la formación universitaria (Real Decreto 1393/2007. BOE nº 260, 30 de octubre de 2007). En la quinta edición de la Red, y dada su composición multidisciplinar, se ha trabajado en tres líneas de investigación: 1) mantenimiento del “Portal web con recursos docentes con perspectiva de género”, proyecto financiado por el Instituto de la Mujer (PACUI, 2012) e iniciado en el curso 2012-2013; 2) desarrollo de la primera versión de “iLengUA”, una herramienta informática para un discurso inclusivo e igualitario; y 3) diseño de una Guía de recomendaciones para la inclusión de la perspectiva de género en la docencia universitaria