Beneficial effect of a multistrain synbiotic prodefen® plus on the systemic and vascular alterations associated with metabolic syndrome in rats: The role of the neuronal nitric oxide synthase and protein kinase A

A high fat diet (HFD) intake is crucial for the development and progression of metabolic syndrome (MtS). Increasing evidence links gut dysbiosis with the metabolic and vascular alterations associated with MtS. Here we studied the use of a combination of various probiotic strains together with a prebiotic (synbiotic) in a commercially available Prodefen® Plus. MtS was induced by HFD (45%) in maleWistar rats. Half of the MtS animals received Prodefen® Plus for 4 weeks. At 12 weeks, we observed an increase in body weight, together with the presence of insulin resistance, liver steatosis, hypertriglyceridemia and hypertension in MtS rats. Prodefen® Plus supplementation did not a ect the body weight gain but ameliorated all the MtS-related symptoms. Moreover, the hypertension induced by HFD is caused by a diminished both nitric oxide (NO) functional role and release probably due to a diminished neuronal nitric oxide synthase (nNOS) activation by protein kinase A (PKA) pathway. Prodefen® Plus supplementation for 4 weeks recovered the NO function and release and the systolic blood pressure was returned to normotensive values as a result. Overall, supplementation with Prodefen® Plus could be considered an interesting non-pharmacological approach in MtS.This research was funded by Italfarmaco, S.A (L.O.U. 83; 0138/2018), CiberCV (Grant number: CB16/11/00286), the European Regional Development Grant (FEDER) (Comunidad de Madrid, Grant number B2017/BMD-3676), and R + D projects for young researchers, Universidad Autónoma de Madrid (Comunidad de Madrid (SI1-PJI-2019-00321). R.R.-D. received a fellowship from Juan de la Cierva Program (IJCI-2017-31399)

CD4 homologue in sea bass (Dicentrarchus labrax): molecular characterization and structural analysis

CD4 is a transmembrane glycoprotein fundamental for cell-mediated immunity. Its action as a T cell coreceptor increases the avidity of association between a T cell and an antigen-presenting cell by interacting with portions of the complex between MHC class II and TR molecules. In this paper we report the cDNA cloning, expression and structural analysis of a CD4 homologue from sea bass (Dicentrarchus labrax). The sea bass CD4 cDNA consists of 2071 bp that translates in one reading frame to give the entire molecule containing 480 amino acids. The analysis of the sequence shows the presence of four putative Ig-like domains and that some fundamental structural features, like a disulphide bond in domain D2 and the CXC signalling motif in the cytoplasmic tail, are conserved from sea bass to mammals. Real-time PCR analysis showed that very high levels of CD4 mRNA transcripts are present in thymus, followed by gut and gills. In vitro stimulation of head kidney leukocytes with LPS and PHA-L gave an increase of CD4 mRNA levels after 4 h and a decrease after 24 h. Homology modelling has been applied to create a 3D model of sea bass CD4 and to investigate its interaction with sea bass MHC-II. The analysis of the 3D complex between sea bass CD4 and sea bass MHC-II suggests that the absence of a disulfide bond in the CD4 D1 domain could make this molecule more flexible, inducing a different conformation and affecting the binding and the way of interaction between CD4 and MHC-II. Our results will add new insights into the sea bass T cell immune responses and will help in the identification of T cell subsets in teleost fishes to better understand the evolution of cell-mediated immunity from fish to mammals.L'articolo è disponibile sul sito dell'editore http://www.sciencedirect.com

Functional rewiring across spinal injuries via biomimetic nanofiber scaffolds

The regrowth of severed axons is fundamental to reestablish motor control after spinal-cord injury (SCI). Ongoing efforts to promote axonal regeneration after SCI have involved multiple strategies that have been only partially successful. Our study introduces an artificial carbon-nanotube based scaffold that, once implanted in SCI rats, improves motor function recovery. Confocal microscopy analysis plus fiber tracking by magnetic resonance imaging and neurotracer labeling of long-distance corticospinal axons suggest that recovery might be partly attributable to successful crossing of the lesion site by regenerating fibers. Since manipulating SCI microenvironment properties, such as mechanical and electrical ones, may promote biological responses, we propose this artificial scaffold as a prototype to exploit the physics governing spinal regenerative plasticity

Tuning the Reduction of Graphene Oxide Nanoflakes Differently Affects Neuronal Networks in the Zebrafish

The increasing engineering of biomedical devices and the design of drug-delivery platforms enriched by graphene-based components demand careful investigations of the impact of graphene-related materials (GRMs) on the nervous system. In addition, the enhanced diffusion of GRM-based products and technologies that might favor the dispersion in the environment of GRMs nanoparticles urgently requires the potential neurotoxicity of these compounds to be addressed. One of the challenges in providing definite evidence supporting the harmful or safe use of GRMs is addressing the variety of this family of materials, with GRMs differing for size and chemistry. Such a diversity impairs reaching a unique and predictive picture of the effects of GRMs on the nervous system. Here, by exploiting the thermal reduction of graphene oxide nanoflakes (GO) to generate materials with different oxygen/carbon ratios, we used a high-throughput analysis of early-stage zebrafish locomotor behavior to investigate if modifications of a specific GRM chemical property influenced how these nanomaterials affect vertebrate sensory-motor neurophysiology—exposing zebrafish to GO downregulated their swimming performance. Conversely, reduced GO (rGO) treatments boosted locomotor activity. We concluded that the tuning of single GRM chemical properties is sufficient to produce differential effects on nervous system physiology, likely interfering with different signaling pathways

El patrimonio cultural árabo-islámico en Madrid como herramienta para el conocimiento y reflexión sobre la historia y los usos de la memoria, la gestión ciudadana del patrimonio y la promoción de la diversidad y la inclusión

Este proyecto de innovación docente desarrollado durante el curso 2022-2023 ha planteado el diseño y ejecución de una serie de rutas urbanas y actividades relacionadas con el patrimonio árabo-islámico de Madrid, incluida la presencia musulmana en el Madrid actual, con el objetivo de darlo a conocer, ponerlo en valor y reflexionar sobre los procesos de narración de la historia y producción de memoria, para ponerlos en relación con la diversidad cultural y religiosa de la sociedad madrileña de hoy. Se trata de un proyecto interdisciplinar e interfacultativo.Depto. de Lingüística, Estudios Árabes, Hebreos y de Asia OrientalFac. de FilologíaFALSEsubmitte

Correlación entre el diagnóstico postoperatorio y anatomopatológico de apendicitis aguda en pacientes menores de 14 años en el H.N.C.A.S.E – Essalud Arequipa de enero a diciembre del 2019

La Apendicitis Aguda es el cuadro quirúrgico que constituye la urgencia más frecuente en Cirugía General. Su diagnóstico puede ser bastante esquivo aumentando la dificultad en la población pediátrica. El cirujano da un diagnóstico postquirúrgico sin embargo el gold estándar es dado por el patólogo. Algunas veces el diagnóstico postoperatorio es incorrecto, ocasionando un manejo inapropiado. OBJETIVO: Determinar la concordancia entre el diagnóstico postoperatorio y anatomopatológico de apendicitis aguda en pacientes menores de 14 años del H.N.C.A.S.E. en el año 2019. MÉTODOS: Estudio observacional, retrospectivo y transversal. La concordancia se midió con Kappa de Cohen. RESULTADOS: 105 casos cumplieron los criterios de selección. 54,3% fueron varones; la edad más frecuente fue 8 años con 15,2%. El tipo de apendicitis más frecuente en ambos informes fue la gangrenada. Sin embargo, al agruparlas en complicadas o no, fueron las no complicadas las más frecuentes. El valor Kappa obtenido fue de 0,54 (moderada); al agrupar los tipos en complicada o no, el valor de Kappa fue 0,67 (buena). CONCLUSIÓN: El grado de concordancia entre el diagnóstico postoperatorio y anatomopatológico fue moderada, y aumentó a buena al determinar si se trataba de apendicitis aguda complicada o no.Tesi

Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model

High-density lipoproteins (HDL) undergo adverse remodeling and loss of function in the presence of comorbidities. We assessed the potential of lipid-lowering approaches (diet and rosuvastatin) to rescue hypercholesterolemia-induced HDL dysfunction. Hypercholesterolemia was induced in 32 pigs for 10 days. Then, they randomly received one of the 30-day interventions: (I) hypercholesterolemic (HC) diet; (II) HC diet + rosuvastatin; (III) normocholesterolemic (NC) diet; (IV) NC diet + rosuvastatin. We determined cholesterol efflux capacity (CEC), antioxidant potential, HDL particle number, HDL apolipoprotein content, LDL oxidation, and lipid levels. Hypercholesterolemia time-dependently impaired HDL function (−62% CEC, −11% antioxidant index (AOI); p p p p < 0.0001). These parameters remained unchanged in animals on HC diet alone up to day 40, while AOI deteriorated up to day 25 (−30%). The switch to NC diet reversed HDL dysfunction, restored apolipoprotein M content and particle numbers, and normalized cholesterol levels at day 40. Rosuvastatin improved HDL, AOI, and apolipoprotein M content. Apolipoprotein A-I and apolipoprotein C-III remained unchanged. Lowering LDL-C levels with a low-fat diet rescues HDL CEC and antioxidant potential, while the addition of rosuvastatin enhances HDL antioxidant capacity in a pig model of hypercholesterolemia. Both strategies restore HDL-bound apolipoprotein M content

Graphene oxide prevents lateral amygdala dysfunctional synaptic plasticity and reverts long lasting anxiety behavior in rats

Engineered small graphene oxide (s-GO) sheets were previously shown to reversibly down-regulate glutamatergic synapses in the hippocampus of juvenile rats, disclosing an unexpected translational potential of these nanomaterials to target selective synapses in vivo. Synapses are anatomical specializations acting in the Central Nervous System (CNS) as functional interfaces among neurons. Dynamic changes in synaptic function, named synaptic plasticity, are crucial to learning and memory. More recently, pathological mechanisms involving dysfunctional synaptic plasticity were implicated in several brain diseases, from dementia to anxiety disorders. Hyper-excitability of glutamatergic neurons in the lateral nucleus of the amygdala complex (LA) is substantially involved in the storage of aversive memory induced by stressful events enabling post-traumatic stress disorder (PTSD). Here we translated in PTSD animal model the ability of s-GO, when stereotaxically administered to hamper LA glutamatergic transmission and to prevent the behavioral response featured in long-term aversive memory. We propose that s-GO, by interference with glutamatergic plasticity, impair LA-dependent memory retrieval related to PTSD.This work has received funding from the European Union Horizon 2020 Research and Innovation Programme under Grant Agreement numbers GrapheneCore2 (785219) and GrapheneCore3 (881603) and from the São Paulo Research Foundation (FAPESP) number 2016/18218–0. We would like to acknowledge the staff of the Electron Microscopy Unit at ICN2 for their expertise and assistance on the SEM. The ICN2 is funded by the CERCA programme, Generalitat de Catalunya, and is supported by the Severo Ochoa Centres of Excellence programme by the Spanish Research Agency (AEI, grant no. SEV-2017-0706)