Detection of urinary exosomal HSD11B2 mRNA expression: a useful novel tool for the diagnostic approach of dysfunctional 11β-HSD2-related hypertension

Apparent mineralocorticoid excess (AME) is an autosomal recessive disorder caused by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme deficiency, traditionally assessed by measuring either the urinary cortisol metabolites ratio (tetrahydrocortisol+allotetrahydrocortisol/tetrahydrocortisone, THF+5αTHF/THE) or the urinary cortisol/cortisone (F/E) ratio. Exosomal mRNA is an emerging diagnostic tool due to its stability in body fluids and its biological regulatory function. It is unknown whether urinary exosomal HSD11B2 mRNA is related to steroid ratio or the HSD11B2 662 C>G genotype (corresponding to a 221 A>G substitution) in patients with AME and essential hypertension (EH)

Systems engineering approach for eco-comparison among power-train configurations of hybrid bus

This paper aims to realize an eco-comparison among power-train configurations of hybrid busses in terms of performance, fuel consumption and CO2 emission. The present study has been carried out in the context of the international research program PLACIS (PLAteforme Collaborative d’Ingénierie Systèmes). In this work, experimental data of a pure electric power-train, evaluated in a dedicated laboratory of Istituto Motori – the National Research Council of Italy, have been used to carry out a pre-design phase of the modelling procedure. From that point on, in order to optimize the powertrain performance, a series hybrid vehicles configuration and a parallel one have been modeled and simulated on DYMOLA-MODELICA environment. The vehicle that has been taken into account, as reference for the comparison, is a “RENAULT-Master” minibus. Power-trains have been modeled with a backward-forward configuration in order to have a physical approach to the problem, respecting the required performances. The study has been developed with System Engineering approach that aims to manage the complexity of systems with a multidisciplinary proposal

Proteomic analysis of urinary extracellular vesicles highlights specific signatures for patients with primary aldosteronism

BackgroundUrinary extracellular vesicles (uEVs) can be released by different cell types facing the urogenital tract and are involved in cellular trafficking, differentiation and survival. UEVs can be easily detected in urine and provide pathophysiological information “in vivo” without the need of a biopsy. Based on these premises, we hypothesized that uEVs proteomic profile may serve as a valuable tool in the differential characterization between Essential Hypertension (EH) and primary aldosteronism (PA).MethodsPatients with essential hypertension (EH) and PA were enrolled in the study (EH= 12, PA=24: 11 Bilateral Primary Aldosteronism subtype (BPA) and 13 Aldosterone Producing Adenoma (APA)). Clinical and biochemical parameters were available for all the subjects. UEVs were isolated from urine by ultracentrifugation and analysed by Transmission Electron Microscopy (TEM) and nanotrack particle analysis (NTA). UEVs protein content was investigated through an untargeted MS-based approach. Statistical and network analysis was performed to identify potential candidates for the identification and classification of PA.ResultsMS analysis provided more than 300 protein identifications. Exosomal markers CD9 and CD63 were detected in all samples. Several molecules characterizing EH vs PA patients as well as BPA and APA subtypes were identified after statistical elaboration and filtering of the results. In particular, some key proteins involved in water reabsorption mechanisms, such as AQP1 and AQP2, were among the best candidates for discriminating EH vs PA, as well as A1AG1 (AGP1).ConclusionThrough this proteomic approach, we identified uEVs molecular indicators that can improve PA characterization and help in the gain of insights of the pathophysiological features of this disease. In particular, PA was characterized by a reduction of AQP1 and AQP2 expression as compared with EH