713 research outputs found

    Sphingosine 1-phosphate receptors: do they have a therapeutic potential in cardiac fibrosis?

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    Sphingosine 1-phosphate (S1P) is a bioactive lipid that is characterized by a peculiar mechanism of action. In fact, S1P, which is produced inside the cell, can act as an intracellular mediator, whereas after its export outside the cell, it can act as ligand of specific G-protein coupled receptors, which were initially named endothelial differentiation gene (Edg) and eventually renamed sphingosine 1-phosphate receptors (S1PRs). Among the five S1PR subtypes, S1PR1, S1PR2 and S1PR3 isoforms show broad tissue gene expression, while S1PR4 is primarily expressed in immune system cells, and S1PR5 is expressed in the central nervous system. There is accumulating evidence for the important role of S1P as a mediator of many processes, such as angiogenesis, carcinogenesis and immunity, and, ultimately, fibrosis. After a tissue injury, the imbalance between the production of extracellular matrix (ECM) and its degradation, which occurs due to chronic inflammatory conditions, leads to an accumulation of ECM and, consequential, organ dysfunction. In these pathological conditions, many factors have been described to act as pro- and anti-fibrotic agents, including S1P. This bioactive lipid exhibits both pro- and anti-fibrotic effects, depending on its site of action. In this review, after a brief description of sphingolipid metabolism and signaling, we emphasize the involvement of the S1P/S1PR axis and the downstream signaling pathways in the development of fibrosis. The current knowledge of the therapeutic potential of S1PR subtype modulators in the treatment of the cardiac functions and fibrinogenesis are also examined

    Vitamin D and Sphingolipids: Role in Bone and Neural System

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    1-Alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) is known to play an important physiological role on growth and differentiation in a variety of nonmalignant and malignant cell types through classical actions, mediated by its specific receptor (VDR), and nongenomic actions resulting in the activation of specific signalling pathways. Due to the broad distribution of Vitamin D Receptor (VDR) in many tissues and the ability of 1,25(OH)2D3 to regulate fundamental processes, such as cell proliferation and differentiation, this steroid hormone has been suggested in the treatment of different diseases, from cancer to neurodegenerative diseases. In fact, structural 1,25(OH)2D3 analogues, with weaker collateral effects, have recently entered in clinical trials. Other interesting molecules due to their pleiotropic actions are the bioactive sphingolipids (SLs), in particular ceramide (Cer) and sphingosine 1-phosphate (S1P). Cells maintain a dynamic balance of these metabolites since Cer and sphingoid bases mediate cell death, while S1P exerts mitogenic effects and promotes differentiation of several cell types including osteogenic and neural cells. The biological actions of 1,25(OH)2D3 and SLs, in particular S1P, share many common effectors, including calcium regulation, growth factor expression, inflammatory cytokines, etc., but whether they could act synergistically is still unknown and deserves further investigation

    Correction to: Size‐Dependent Enforcement, Tax Evasion and Dimensional Trap

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    The article “Size‐Dependent Enforcement, Tax Evasion and Dimensional Trap”, written by Raffaella Coppier, Elisabetta Michetti and Luisa Scaccia, was originally published electronically on the publisher’s internet portal on 05 July 2023 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on 24 February 2024 to © The Author(s) 2024 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made

    IL MYCOARRAY: UN TEST RAPIDO PER LA DIAGNOSI SIEROLOGICA DI MICOSI ENDEMICHE

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    Introduzione Le micosi da funghi dimorfi, estremamente rare in Europa, sono rappresentate da casi di importazione, con l’eccezione della istoplasmosi per la quale sono stati segnalati anche casi autoctoni. La bassa frequenza, in combinazione con l’aspecificità delle manifestazioni cliniche, rende difficile una diagnosi rapida. Scopo del presente studio è la valutazione dell’utilizzo del saggio mycoarray (1) come strumento multiparametrico e rapido, a supporto della sierologia convenzionale, nella diagnosi di laboratorio delle micosi endemiche. Metodi Antigeni fungini (H. capsulatum, C. immitis, B. dermatitidis e P. brasiliensis), diluizioni scalari di anticorpi IgG e IgM e controlli sono stati deposti su vetrini microarray per mezzo di un sistema robotizzato ad alta precisione. I vetrini così ottenuti sono stati cimentati col siero, opportunamente diluito, e successivamente con anticorpi secondari marcati con fluorofori per rivelare l’avvenuta formazione degli immunocomplessi. Il segnale è stato acquisito mediante uno scanner, quantificato ed analizzato per mezzo di un apposito software. Risultati Il mycoarray ha mostrato elevate sensibilità e specificità: un primo studio retrospettivo, condotto su sieri da pazienti con diagnosi certa di istoplasmosi o di coccidioidomicosi, ha fornito risultati consistenti con i dati clinici e di laboratorio, acquisiti con la diagnostica di routine. Indagini su ulteriori campioni da casi clinici “sospetti”, analizzati con il mycoarray, hanno fornito risultati originali utili per la diagnosi definitiva di micosi endemica. Conclusioni Il mycoarray presenta una serie di peculiarità (miniaturizzazione, multiparametricità e rapidità di esecuzione) che lo rendono estremamente utile come strumento di laboratorio a sussidio del percorso convenzionale nella diagnosi di micosi primitive, specialmente in zone a bassa endemicità. Ringraziamenti Lavoro in parte supportato da MIUR, PRIN-200985J87J Bibliografia (1) Ardizzoni et al., (2011) New Microbiol, 34:307-16

    Elisabetta I come Cinzia: Una regina e il suo oceano

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    The defeat of the Spanish Armada in the Channel in 1588 turned ‘a weak and feeble woman’ into one of the most relevant characters of late 16th-century European history: Elizabeth I, the Tudor Queen, was considered a semi-divine creature whom the myth, by comparing her to Moon goddesses like Diana and Cinthia, had made known as Semper Eadem. The identification of the queen with Cinthia became more and more evident after the events occurred in 1588, when she was hailed as the moon goddess par excellence in a series of texts written by her contemporaries. It was in that period, the last decades of the 16th century, that Sir Walter Ralegh, courtier, poet and seaman, wrote The Poems to Cynthia: a collection of short poems where Elizabeth I, the lady of the seas, is addressed as his beloved. The role of Elizabeth as Cinthia is evident above all in Ralegh’s Last Book of the Ocean to Cynthia, an unfinished poem where the author, desperate for being in disgrace, appeals to her clemency and addresses her as the empress of the ocean.La sconfitta della flotta spagnola nelle acque della Manica nel 1588 trasformò una donna sola e fragile in una delle figure più rilevanti della storia europea di fine XVI secolo: Elisabetta I Tudor divenne per i suoi sudditi una creatura semidivina che il mito, accostandola alle divinità lunari Diana e Cinzia, avrebbe consegnato alla Storia come Semper Eadem. Pur essendo evidente già nei primi tempi del suo regno, l’identificazione della sovrana con Cinzia, la dea che governa i mari e i corsi d’acqua, si fa ancora più evidente dopo il 1588, quando si assiste ad una fioritura di testi che esaltano Elisabetta I come la dea lunare per eccellenza. Sempre in quegli anni di fine XVI secolo, Sir Walter Ralegh compone The Poems to Cynthia: letterato, cortigiano e uomo di mare, Ralegh dedicherà il suo amore ad Elisabetta come Cinzia, signora dei mari. Il legame tra Elisabetta e l’oceano è soprattutto evidente in Last Book of the Ocean to Cynthia, un poemetto incompiuto in cui il poeta, caduto in disgrazia, riunisce sotto il nome di Cinzia, la donna e la regina, l’amante e la dea, trasformando così Elisabetta in dea e imperatrice dei mari

    Elisabetta I come Cinzia. Una regina e il suo oceano.

    No full text
    La sconfitta della flotta spagnola nelle acque della Manica nel 1588 trasformò una donna sola e fragile in una delle figure più rilevanti della storia europea di fine XVI secolo: Elisabetta I Tudor divenne per i suoi sudditi una creatura semidivina che il mito, accostandola alle divinità lunari Diana e Cinzia, avrebbe consegnato alla Storia come Semper Eadem. Pur essendo evidente già nei primi tempi del suo regno, l’identificazione della sovrana con Cinzia, la dea che governa i mari e i corsi d’acqua, si fa ancora più evidente dopo il 1588, quando si assiste ad una fioritura di testi che esaltano Elisabetta I come la dea lunare per eccellenza. Sempre in quegli anni di fine XVI secolo, Sir Walter Raleigh compone ‘The Poems to Cynthia’: letterato, cortigiano e uomo di mare, Raleigh dedicherà il suo amore ad Elisabetta come Cinzia, signora dei mari. Il legame tra Elisabetta e l’oceano è soprattutto evidente in ‘Last Book of the Ocean to Cynthia’, un poemetto incompiuto in cui il poeta, caduto in disgrazia, riunisce sotto il nome di Cinzia, la donna e la regina, l’amante e la dea, trasformando così Elisabetta in dea e imperatrice dei mari.The defeat of the Spanish Armada in the Channel in 1588 turned ‘a weak and feeble woman’ into one of the most relevant characters of late 16th-century European history: Elizabeth I, the Tudor Queen, was considered a semi-divine creature whom the myth, by comparing her to Moon goddesses like Diana and Cinthia, had made known as Semper Eadem. The identification of the queen with Cinthia became more and more evident after the events occurred in 1588, when she was hailed as the moon goddess par excellence in a series of texts written by her contemporaries. It was in that period, the last decades of the 16th century, that Sir Walter Raleigh, courtier, poet and seaman, wrote ‘The Poems to Cynthia’: a collection of short poems where Elizabeth I, the lady of the seas, is addressed as his beloved. The role of Elizabeth as Cinthia is evident above all in Raleigh’s ‘Last Book of the Ocean to Cynthia’, an unfinished poem where the author, desperate for being in disgrace, appeals to her clemency and addresses her as the empress of the ocean

    Praxiphanes of Mytilene (called 'of Rhodes'). The Sources, Text and Translation

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    Nuova edizione dei frammenti di Prassifane di MItilene, detto di Rodi, con traduzione e note. Prassifane era uno dei filosofi di età ellenistica implicato in ruoli anche pubblici in merito ai quali abbiamo segnali di onori ricevuti (cittadinanza e prossenia). I frammenti superstiti permettono di ricostruire la personalità di un filosofo peripatetico, allievo di Teofrasto, che pur avendo acquisito fama come 'primo grammatico' ed essersi occupato di critica letteraria, di poeti, di poetica e di 'storia', non lasciò da parte interessi di etica e probabilmente di fisica. Importante la sua attività a Rodi, nel pieno III sec. a.C., in un periodo nel quale l'isola rivestì un ruolo particolarmente rilevante dal punto di vista politico, economico e culturale per il mondo ellenico.New Critical Edition of the sources related to Praxiphanes of Mytilene, called of Rhodes' (3rd BC), a Peripatetic philosopher, pupil of Theophrastus, whose entire works are lost. The new collection of fragments shows that he was a philosopher involved in public life, called 'first grammarian' and author of works on literary critics, on poetics, on poets, on history, on ethics and physics. He lived and worked in Rhodes in a special period when this island was an important economic, political and cultural centre of the Hellenic world

    The protein “mycoarray”: a novel serological assay for the laboratory diagnosis of primitive endemic mycoses

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    A protein microarray containing fungal antigens (the “mycoarray”) has been set up to provide rapid and appropriateserodiagnosis of primitive endemic mycoses, an important cause of morbidity and mortality in an increasingly highnumber of patients. The mycoarray consists of three antigen extracts (histoplasmin, coccidioidin and Coccidioides “TP”)and antibody dilution curves were spotted on microarray slides. The arrays were processed with coccidioidomycosisand histoplasmosis patients’ sera or with control sera and the occurring immunocomplexes were detected by indirectimmunofluorescence. In agreement with clinical and microbiological diagnosis, the results distinguished betweenhistoplasmosis and coccidioidomycosis patients. In addition, the assay could clearly discriminate between IgM andIgG antibody reactivity. No reactivity was ever observed in the arrays processed with negative control sera. Therefore,this pilot study demonstrates that the “mycoarray” is sensitive and specific enough to discriminate between healthyindividuals and patients with histoplasmosis or coccidioidomycosis. Because of miniaturization and multiparametricity,the new assay cuts costs and processing time. Thus, once clinically validated and implemented as a large-scale array,the “mycoarray” will be ready to be applied to the daily clinical practice
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