ASCs-exosomes recover coupling efficiency and mitochondrial membrane potential in an in vitro model of ALS

The amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motoneurons death. Mutations in the superoxide dismutase 1 (SOD1) protein have been identified to be related to the disease. Beyond the different altered pathways, the mitochondrial dysfunction is one of the major features that leads to the selective death of motoneurons in ALS. The NSC-34 cell line, overexpressing human SOD1(G93A) mutant protein [NSC-34(G93A)], is considered an optimal in vitro model to study ALS. Here we investigated the energy metabolism in NSC-34(G93A) cells and in particular the effect of the mutated SOD1(G93A) protein on the mitochondrial respiratory capacity (complexes I-IV) by high resolution respirometry (HRR) and cytofluorimetry. We demonstrated that NSC-34(G93A) cells show a reduced mitochondrial oxidative capacity. In particular, we found significant impairment of the complex I-linked oxidative phosphorylation, reduced efficiency of the electron transfer system (ETS) associated with a higher rate of dissipative respiration, and a lower membrane potential. In order to rescue the effect of the mutated SOD1 gene on mitochondria impairment, we evaluated the efficacy of the exosomes, isolated from adipose-derived stem cells, administrated on the NSC-34(G93A) cells. These data show that ASCs-exosomes are able to restore complex I activity, coupling efficiency and mitochondrial membrane potential. Our results improve the knowledge about mitochondrial bioenergetic defects directly associated with the SOD1(G93A) mutation, and prove the efficacy of adipose-derived stem cells exosomes to rescue the function of mitochondria, indicating that these vesicles could represent a valuable approach to target mitochondrial dysfunction in ALS

Radiological Protection in Industries Involving NORM: A (Graded) Methodological Approach to Characterize the Exposure Situations

The interest in radiation protection in industrial sectors involving Naturally Occurring Radioactive Materials (NORM) is increasingly growing. This is due also to the recent implementation of the European Council Directive 59/2013/Euratom which in Italy and in the other European Union Member States extends the field of application to industrial sectors never involved before. This paper reports main results of a research project on radiation protection in industries involving NORM carried out in Italy aimed to provide useful tools for stakeholders to comply new legal obligations. The project activities were mainly focused on different aspects relevant to the NORM involving industries, accounting for the positive list reported in the Italian law. Firstly, the inventory of the industries currently operating in Italy in order to identify the industrial sectors with an important radiological impact on population and workers was updated. Based on this information, a general methodology was elaborated taking into account a graded approach. The first phase consists in the identification and characterization of the most critical exposure scenarios and of the radiological content of NORMs involved in the different phases of the industrial processes. In the second phase calculation methods were developed for dose estimation for workers and members of public. These tools require the use of existing and well tested calculation codes, and the development of a dedicated user-friendly software

Chronic cough in childhood: A systematic review for practical guidance by the Italian Society of Pediatric Allergy and Immunology

The current systematic review presented and discussed the most recent studies on pediatric chronic cough. In addition, the Italian Society of Pediatric Allergy and Immunology elaborated a comprehensive algorithm to guide the primary care approach to a pediatric patient with chronic cough.Several algorithms on chronic cough management have been adopted and validated in clinical practice; however, unlike the latter, we developed an algorithm focused on pediatric age, from birth until adulthood. Based on our findings, children and adolescents with chronic cough without cough pointers can be safely managed, initially using the watchful waiting approach and, successively, starting empirical treatment based on cough characteristics. Unlike other algorithms that suggest laboratory and instrumental investigations as a first step, this review highlighted the importance of a "wait and see" approach, consisting of parental reassurance and close clinical observation, also due to interprofessional collaboration and communication between general practitioners and specialists that guarantee better patient management, appropriate prescription behavior, and improved patient outcome. Moreover, the neonatal screening program provided by the Italian National Health System, which intercepts several diseases precociously, allowing to treat them in a very early stage, helps and supports a "wait and see" approach.Conversely, in the presence of cough pointers or persistence of cough, the patient should be tested and treated by the specialist. Further investigations and treatments will be based on cough etiology, aiming to intercept the underlying disease, prevent potentially irreversible tissue damage, and improve the general health of patients affected by chronic cough, as well as the quality of life of patients and their family. Further high-quality randomized controlled trials are needed to validate this algorithm's performance in real clinical practice

Acute cough in children and adolescents: A systematic review and a practical algorithm by the Italian Society of Pediatric Allergy and Immunology

The current systematic review presented and discussed the most recent studies on acute cough in pediatric age. After that, the Italian Society of Pediatric Allergy and Immunology elaborated a comprehensive algorithm to guide the primary care approach to pediatric patients, such as infants, children, and adolescents, with acute cough. An acute cough is usually consequent to upper respiratory tract infections and is self-resolving within a few weeks. However, an acute cough may be bothersome, and therefore remedies are requested, mainly by the parents. An acute cough may significantly affect the quality of life of patients and their family.Several algorithms for the management of acute cough have been adopted and validated in clinical practice; however, unlike the latter, we developed an algorithm focused on pediatric age, and, also, in accordance to the Italian National Health System, which regularly follows the child from birth to all lifelong. Based on our findings, infants from 6 months, children, and adolescents with acute cough without cough pointers can be safely managed using well-known medications, preferably non-sedative agents, such as levodropropizine and/or natural compounds, including honey, glycerol, and herb-derived components

The transcriptional profile of adipose-derived stromal cells (ASC) mirrors the whitening of adipose tissue with age

Multipotent stem cells persist within the stromal vascular fraction (SVF) of adipose tissue during adulthood. These cells, commonly referred to as adipose-derived stromal cells (ASC), have been extensively investigated over the past years as a promising therapeutic tool based on their regenerative and immunomodulatory properties. However, how ASC might mirror the age-related alteration of the fat they reside in remains unclear. Herein, we show that inguinal adipose tissue in mice turns from brown/beige- to white-like with age and resident ASC readily mirror these changes both at mRNA and microRNA transcriptional level. Mechanistically, our data suggest that these brown/age-related changes in ASC transcription rely on changes in the activity of E2F1 and NFkB transcription factors

La radioprotezione applicata alle industrie NORM: sviluppo di un sistema di strumenti metodologici, conoscitivi e formativi a sostegno degli stakeholders. Stato dell’arte del progetto di INAIL

Con il recepimento della Direttiva Europea 59/2013 EURATOM, la normativa italiana di radioprotezione ha introdotto nuovi obblighi per gli esercenti di diversi settori industriali “NORM”. Per sostenere l’assolvimento di tali obblighi che garantiscono la protezione di lavoratori e popolazione, dal 2019 è in corso un progetto di ricerca, nell’ambito del quale sono state realizzate diverse attività. Alcune di esse hanno avuto sviluppi anche in ambito internazionale, a testimonianza di quanto questa tematica sia di grande interesse. Lo scopo del presente lavoro è presentare i nuovi risultati del progetto, dall’aggiornamento del censimento dei settori NORM attualmente attivi in Italia, all’ applicazione e declinazione dell’approccio graduale per l’individuazione di situazioni di particolare interesse dal punto di vista della radioprotezione, fino allo sviluppo di metodologie operative e di calcolo applicate ad alcuni settori

Sviluppo di protocolli di campionamento e di valutazione della dose per settori industriali con presenza di NORM

Nell’ambito delle attività del progetto INAIL - BRIC ID 30 “Protocolli operativi e metodologie di calcolo per l’attuazione della nuova normativa di radioprotezione, recepimento della Direttiva 59/2013/Euratom, in settori industriali NORM di particolare impatto radiologico”, è stato sviluppato un approccio metodologico per gli adempimenti previsti dall’art. 22 del D.lgs. 101/2020. Una proposta di protocollo per la misura della concentrazione di attività delle matrici e per la valutazione della dose efficace per lavoratori e popolazione è stata elaborata per il settore della produzione di cemento e per l’industria dello zircone e zirconio

Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature.Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 +/- 26.9 yrs.; mean disease duration 8.9 +/- 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas.Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches.Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity