Galectin-3. One molecule for an alphabet of diseases, from A to Z

Galectin-3 (Gal-3) regulates basic cellular functions such as cell–cell and cell–matrix interactions, growth, proliferation, differentiation, and inflammation. It is not surprising, therefore, that this protein is involved in the pathogenesis of many relevant human diseases, including cancer, fibrosis, chronic inflammation and scarring affecting many different tissues. The papers published in the literature have progressively increased in number during the last decades, testifying the great interest given to this protein by numerous researchers involved in many different clinical contexts. Considering the crucial role exerted by Gal-3 in many different clinical conditions, Gal-3 is emerging as a new diagnostic, prognostic biomarker and as a new promising therapeutic target. The current review aims to extensively examine the studies published so far on the role of Gal-3 in all the clinical conditions and diseases, listed in alphabetical order, where it was analyzed

Graphene oxide nanoribbons induce autophagic vacuoles in neuroblastoma cell lines

Since graphene nanoparticles are attracting increasing interest in relation to medical applications, it is important to understand their potential effects on humans. In the present study, we prepared graphene oxide (GO) nanoribbons by oxidative unzipping of single-wall carbon nanotubes (SWCNTs) and analyzed their toxicity in two human neuroblastoma cell lines. Neuroblastoma is the most common solid neoplasia in children. The hallmark of these tumors is the high number of different clinical variables, ranging from highly metastatic, rapid progression and resistance to therapy to spontaneous regression or change into benign ganglioneuromas. Patients with neuroblastoma are grouped into different risk groups that are characterized by different prognosis and different clinical behavior. Relapse and mortality in high risk patients is very high in spite of new advances in chemotherapy. Cell lines, obtained from neuroblastomas have different genotypic and phenotypic features. The cell lines SK-N-BE(2) and SH-SY5Y have different genetic mutations and tumorigenicity. Cells were exposed to low doses of GO for different times in order to investigate whether GO was a good vehicle for biological molecules delivering individualized therapy. Cytotoxicity in both cell lines was studied by measuring cellular oxidative stress (ROS), mitochondria membrane potential, expression of lysosomial proteins and cell growth. GO uptake and cytoplasmic distribution of particles were studied by Transmission Electron Microscopy (TEM) for up to 72 h. The results show that GO at low concentrations increased ROS production and induced autophagy in both neuroblastoma cell lines within a few hours of exposure, events that, however, are not followed by growth arrest or death. For this reason, we suggest that the GO nanoparticle can be used for therapeutic delivery to the brain tissue with minimal effects on healthy cells

Data-driven clustering of combined Functional Motor Disorders based on the Italian registry

Functional Motor Disorders (FMDs) represent nosological entities with no clear phenotypic characterization, especially in patients with multiple (combined FMDs) motor manifestations. A data-driven approach using cluster analysis of clinical data has been proposed as an analytic method to obtain non-hierarchical unbiased classifications. The study aimed to identify clinical subtypes of combined FMDs using a data-driven approach to overcome possible limits related to "a priori" classifications and clinical overlapping

Cell-to-Cell Signaling Influences the Fate of Prostate Cancer Stem Cells and Their Potential to Generate More Aggressive Tumors

An increasing number of malignancies has been shown to be initiated and propelled by small subpopulations of cancer stem cells (CSC). However, whether tumor aggressiveness is driven by CSC and by what extent this property may be relevant within the tumor mass is still unsettled. To address this issue, we isolated a rare tumor cell population on the basis of its CD44+CD24− phenotype from the human androgen-independent prostate carcinoma cell line DU145 and established its CSC properties. The behavior of selected CSC was investigated with respect to the bulk DU145 cells. The injection of CSC in nude mice generated highly vascularized tumors infiltrating the adjacent tissues, showing high density of neuroendocrine cells and expressing low levels of E-cadherin and β-catenin as well as high levels of vimentin. On the contrary, when a comparable number of unsorted DU145 cells were injected the resulting tumors were less aggressive. To investigate the different features of tumors in vivo, the influence of differentiated tumor cells on CSC was examined in vitro by growing CSC in the absence or presence of conditioned medium from DU145 cells. CSC grown in permissive conditions differentiated into cell populations with features similar to those of cells held in aggressive tumors generated from CSC injection. Differently, conditioned medium induced CSC to differentiate into a cell phenotype comparable to cells of scarcely aggressive tumors originated from bulk DU145 cell injection. These findings show for the first time that CSC are able to generate differentiated cells expressing either highly or scarcely aggressive phenotype, thus influencing prostate cancer progression. The fate of CSC was determined by signals released from tumor environment. Moreover, using microarray analysis we selected some molecules which could be involved in this cell-to-cell signaling, hypothesizing their potential value for prognostic or therapeutic applications

The large area detector onboard the eXTP mission

The Large Area Detector (LAD) is the high-throughput, spectral-timing instrument onboard the eXTP mission, a flagship mission of the Chinese Academy of Sciences and the China National Space Administration, with a large European participation coordinated by Italy and Spain. The eXTP mission is currently performing its phase B study, with a target launch at the end-2027. The eXTP scientific payload includes four instruments (SFA, PFA, LAD and WFM) offering unprecedented simultaneous wide-band X-ray timing and polarimetry sensitivity. The LAD instrument is based on the design originally proposed for the LOFT mission. It envisages a deployed 3.2 m2 effective area in the 2-30 keV energy range, achieved through the technology of the large-area Silicon Drift Detectors - offering a spectral resolution of up to 200 eV FWHM at 6 keV - and of capillary plate collimators - limiting the field of view to about 1 degree. In this paper we will provide an overview of the LAD instrument design, its current status of development and anticipated performance

Clinical correlates of “pure” essential tremor: the TITAN study

BackgroundTo date, there are no large studies delineating the clinical correlates of “pure” essential tremor (ET) according to its new definition.MethodsFrom the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of “pure” ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum.ResultsOut of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) “pure” ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options.DiscussionThe findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of “pure” ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of “pure” ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies

Enabling planetary science across light-years. Ariel Definition Study Report

Ariel, the Atmospheric Remote-sensing Infrared Exoplanet Large-survey, was adopted as the fourth medium-class mission in ESA's Cosmic Vision programme to be launched in 2029. During its 4-year mission, Ariel will study what exoplanets are made of, how they formed and how they evolve, by surveying a diverse sample of about 1000 extrasolar planets, simultaneously in visible and infrared wavelengths. It is the first mission dedicated to measuring the chemical composition and thermal structures of hundreds of transiting exoplanets, enabling planetary science far beyond the boundaries of the Solar System. The payload consists of an off-axis Cassegrain telescope (primary mirror 1100 mm x 730 mm ellipse) and two separate instruments (FGS and AIRS) covering simultaneously 0.5-7.8 micron spectral range. The satellite is best placed into an L2 orbit to maximise the thermal stability and the field of regard. The payload module is passively cooled via a series of V-Groove radiators; the detectors for the AIRS are the only items that require active cooling via an active Ne JT cooler. The Ariel payload is developed by a consortium of more than 50 institutes from 16 ESA countries, which include the UK, France, Italy, Belgium, Poland, Spain, Austria, Denmark, Ireland, Portugal, Czech Republic, Hungary, the Netherlands, Sweden, Norway, Estonia, and a NASA contribution

Il saggio sociale di sconto nell'analisi costi-benefici per la gestione del rischio alluvionale: riflessioni sulle preferenze intertemporali

About the Flood Risk Management Plans (PGRA) the European Community (DIR. 2007/60; Regulation No. 1303/2013) introduces the need to provide an assessment of the prevention and mitigation measures for the hydraulic risk through a Cost-Benefit Analysis (CBA), (Cohesion Fund, 2014-2020). Indeed, the CBA helps identifying a priority ranking of structural and non-structural interventions to be implemented so to reduce the probability of flooding and the negative consequences for human health, the environment, cultural heritage and economic activities. In Cost-Benefit Analysis (CBA) application, the Social Discount Rate (SDR) covers a fundamental role in revealing the intergenerational concern and the willingness to pay for environmental protection and debt inheritance of a society into a specific territorial-time dimension. In particular, scientific research on the hydraulic risk area like the national and international guidelines demonstrates no agreement about the methodologies for estimating the SSS and the (SSS) value adopted in different territorial contexts. For this reason, this paper aims at investigating literature debates about SDR effectiveness on a value-based assessment and how it is applied in CBA analysis dealing with intergenerational environmental costs redistribution and human heath protections. The theoretical explanation is supported by applying CBA analysis to the real case study of Olbia city, where relevant flood events occurred in the last fifty years and, in particular, the last one in 2013, causing significant losses in economic welfare and human lives. First results from the empirical application show how the choice of the SSS and the time-frame of the interventions have a strong impact on the effectiveness of the strategic decisions from a social point of view. In particular, these two factors' influence is more evident in long-term scenarios due to intertemporal prices' cumulative and multiplicative effects, which reduce future values such as environmental and social benefits if discounted to date. Nell'ambito dei Piani di Gestione del Rischio Alluvioni (PGRA), la Comunità Europea (Dir. 2007/60; Regulation No. 1303/2013) ha introdotto la necessità della valutazione delle misure di prevenzione del rischio alluvioni sulla base di una Analisi Benefici-Costi (ACB), al fine di individuare una graduatoria di priorità degli interventi strutturali e non strutturali da attuarsi per ridurre la probabilità di inondazione e le conseguenze negative per la salute umana, l'ambiente, il patrimonio culturale e le attività economiche. Rispetto all'applicazione dell'ACB, la stima del Saggio Sociale di Sconto (SSS) rappresenta uno degli aspetti più critici per esprimere il valore delle preferenze intertemporali, la disponibilità a pagare per la tutela dell'ambiente e la qualità della vita, nonché il peso attribuito all'eredità del debito futuro intergenerazionale in una specifica dimensione spazio-temporale. In particolare, le applicazioni al settore del rischio idraulico così come le linee guida nazionali e internazionali mostrano come non vi sia ancora una convergenza di opinioni sulle metodologie da applicare per la stima del SSS e sul valore da adottare in differenti contesti territoriali. A partire da un'analisi della letteratura sul ruolo del SSS nelle ACB applicate al settore della prevenzione del rischio idraulico, il presente articolo propone un quadro ampio di casi di studio in differenti contesti geografici, che sottopone a una riflessione critica in merito agli aspetti teorici e operativi. Le riflessioni teoriche sono poi sperimentate attraverso un'applicazione dell'ACB alla città di Olbia, dove si sono verificate grandi alluvioni negli ultimi cinquant'anni, l'ultima delle quali nel 2013, che hanno causato perdite significative in termini di benessere economico e vite umane. I primi risultati ottenuti mostrano come la scelta del SSS, così come la temporalizzazione degli interventi, sia determinante per l'efficacia delle scelte dal punto di vista sociale, soprattutto in scenari di lungo periodo, a causa dell'effetto cumulato e moltiplicativo dei prezzi intertemporali che porta a ridurre i valori futuri, quali per esempio i benefici ambientali e sociali, se scontati all'attualità