Novel organic semiconducting small molecules for X-ray detection

L’elettronica organica ha trovato negli anni recenti diverse applicazioni, anche in dispositivi di uso quotidiano, come ad esempio gli schermi OLED (Organic Light Emitting Diode). I semiconduttori organici possono essere depositati con tecniche a basso costo, anche su scala industriale, e su grandi aree, fattore, quest’ultimo, che li rende particolarmente adatti alla fabbricazione di sensori di radiazioni ionizzanti. Il lavoro presentato riguarda la realizzazione di transistor organici a film sottile e la loro caratterizzazione, come transistor e come sensori di raggi X. In particolare, l’obiettivo di questo progetto sperimentale è il confronto delle sensibilità di due tipi di dispositivi fabbricati da soluzioni delle molecole diF-TES-ADT (5,11-bis(triethylsilylethynyl)anthradithiophene) e diF-TEG-ADT (5,11-bis(triethylgermylethynyl)anthradithiophene), appartenenti alla classe degli eteroaceni sostituiti. Nella prima molecola sono presenti due gruppi funzionali identici in cui è contenuto un atomo di silicio, mentre nell'altra essi contengono un atomo di germanio, caratterizzato da un numero atomico più alto. In questo lavoro viene dimostrato che il numero atomico più alto, grazie al maggiore coefficiente di assorbimento per la radiazione X, comporta una sensibilità più alta per il sensore di razioni ionizzanti, come confermato dai risultati ottenuti

Thrombo-Inflammatory Extracellular Vesicles 2.0

: In the complex field of cell-to-cell communication and physiological regulation, there is a remarkable category of tiny messengers called extracellular vesicles (EVs) [...]

Up-regulation of proinflammatory mediators induced by monocyte/macrophage derived microparticles in human airway epithelial cells involves an NF-κB mediated pathway, and is inhibited by peroxisome proliferator activated receptor γ-agonists

Microparticles (MP) are phospholipid vesicles shed by cells upon activation or during apoptosis. MP range in size from 50 nm to 1 µm (Hugel et al., 2005). Evidence gathered over the past several years has demonstrated that MP are involved in numerous physiological processes, including blood coagulation and inflammation. Because of the presence of negatively charged phospholipids on the outer leaflet of MP, these structures have been long attributed a role in blood coagulation, a process that requires the assembly of multimolecular complexes on the surface of negatively charged phospholipid membranes. More recently, however, it has become evident that MP also carry other components of the parental cell besides the phospholipids, which greatly broaden the spectrum of their potential effects as intercellular mediators (Hugel et al., 2005). For example, the presence on monocyte-derived MP of tissue factor (TF), an essential cofactor for the initiation of blood coagulation (Satta et al., 1994), adds to their role in blood coagulation and thrombus formation (Celi et al., 2004). The role of leukocyte- and endothelial cell-derived MP in inflammation has also been extensively investigated. MP released by stimulated polymorphonuclear leukocytes, for example, up-regulate IL-6 and IL-8 synthesis by endothelial cells (Mesri and Altieri, 1998), while MP derived from T-lymphocytes and monocytes induce the synthesis of matrix metalloproteinases and cytokines by synovial fibroblasts (Distler et al., 2005). We have previously demonstrated that the stimulation of human monocytes/macrophages with the calcium ionophore, A23187, or with histamine, causes MP shedding, and that incubation of these MP with airway epithelial cells results in upregulation of proinflammatory mediator synthesis, including interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1), thus potentially contributing to airway inflammation (Cerri et al., 2006). However, the molecular bases of these events are not known. Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Three isoforms of PPAR have been identified to date: α, β/δ and γ. Originally identified for their role on lipid and glucose regulation, PPAR have more recently been implicated in the regulation of other phenomena, including inflammation (Straus and Glass, 2007). PPAR-α is expressed, among other cell types, by alveolar and bronchial epithelial cells and its activation results in downregulation of proinflammatory mediators production, at least in part through suppression of NF-κB transcriptional activity (Hetzel et al., 2003) (Arnold and Konig, 2006). Accordingly, PPAR-γ are currently being considered as potential novel therapeutic targets in Chronic Obstructive Pulmonary Disease (COPD) (Remels et al., 2008). Here, we demonstrate that the effect of monocytes/macrophage-derived MP on airway epithelial cell inflammation is mediated through NF-κB activation and is inhibited by PPAR-γ stimulation

A model for the transition to the circular economy

The relevanceof circular economy has significantly grown in the last years, thanks to the spread of sustainability principles among companies, policy makers and practitioners.The European Union has given an important impulsetothe dissemination of circular economyin business practice, with the introduction of the Regulation on taxonomy for sustainable activities. It is a regulation for the classification of sustainable economic activities, aimed at creating a common language for investors, which favoursventures that have a significant positive impact on the climate and the environment. Starting from the theoretical backgroundoffered by the so-called “R”Framework, the paper attempts to close the gap between scholarsand practitioners,providingreal cases of implementation of circular economy.Since there is no European database of circular economy interventions, the proposed cases have been selected according to their degree of innovation, their potential impact on the environment or their real possibility of implementation by companies

Le microparticelle: un possibile nuovo biomarcatore in patologie umane

Le malattie polmonari interstiziali sono un gruppo eterogeneo di malattie in cui si evidenziano profonde alterazioni della struttura del parenchima polmonare, in particolar modo della membrana alveolo-capillare, con accumulo vistoso di tessuto connettivo fibroso. La deposizione di tessuto connettivo fibroso altera sostanzialmente le caratteristiche del tessuto, trasformando il delicato stroma elastico del polmone in una cicatrice che può occupare porzioni crescenti dell’alveolo fino a determinarne la completa obliterazione. La coagulazione e il danno da stress ossidativo/nitrossidativo sembrano avere un ruolo chiave nella patogenesi delle malattie polmonari interstiziali. Numerosi studi hanno evidenziato attivazione della cascata coagulativa nelle polmoniti interstiziali fibrosanti, con evidenza di aumentata espressione di fattore tissutale (TF), fattore VII (FVII) e fattore X (FX). Di recente è stato proposto che il FXa, la forma attiva dello zimogeno FX, a seguito del legame con i recettori PAR1 posti sui fibroblasti, causa l’attivazione di TGF-β, snodo centrale per mediare la conversione dei fibroblasti in miofibroblasti; sono proprio i miofibroblasti attivati a mediare la deposizione di collagene. Per quanto riguarda lo stresso ossidativo vari studi evidenziano l’alterazione del normale equilibrio tra sostanze ossidanti e il sistema di difesa antiossidante nelle malattie polmonari interstiziali. Le microparticelle, chiamate anche ectosomi e microvescicole, sono frammenti di membrana rilasciati virtualmente da tutte le cellule eucariotiche; sono presenti nel sangue periferico di individui sani, ma i loro livelli aumentano in pazienti con numerose malattie, tra cui malattie infiammatorie, autoimmuni, aterosclerosi e disordini coagulativi. Le microparticelle hanno il potenziale per esercitare un'attività procoagulante sia attraverso l'espressione sulla loro superficie di fosfolipidi carichi negativamente, essenziali per l’assemblaggio del complesso della protrombinasi, che attraverso l’espressione di TF. Essendo le microparticelle vescicole con attività procoagulante e potendo quindi contribuire alla conversione del FX in FXa, il presente progetto di tesi si propone di indagare il potenziale ruolo delle MP nella patogenesi delle malattie polmonari interstiziali. Lo studio si è composto di due parti, una ex-vivo e una in-vitro. Nella parte ex-vivo, sono state quantificate le microparticelle esprimenti TF sulla loro superficie nel liquido di lavaggio bronco-alveolare di soggetti affetti da malattie polmonari interstiziali di varia gravità e da soggetti affetti d’altre patologie a carico dell’apparato respiratorio. I risultati hanno evidenziato che la concentrazione di microparticelle esprimenti TF è significativamente aumentata nel bronco lavaggio alveolare di pazienti con malattie polmonari interstiziali rispetto ai controlli. Per lo studio in-vitro è stata utilizzata una linea cellulare tumorale delle vie aeree, le A549. La produzione di microparticelle esprimenti TF è stata valutata in condizioni basali e a seguito di stimolazione con stress-ossidativo (una noxa notoriamente implicata nella patogenesi della fibrosi polmonare). Per quanto riguarda il modello in-vitro i risultati mostrano che le A549 sottoposte a stress ossidativo evidenziano un aumento significativo di MP esprimenti TF. L’aumentato livello di TF non è determinato da un aumento della trascrizione genica, visto che i livelli trascrizionali di mRNA del TF non sono modulati dal trattamento con stress ossidativo ma probabilmente da un aumento delle MP procoagulanti, potenzialmente responsabili dell’attivazione in situ del FX. I risultati ottenuti sono coerenti con le ipotesi fissate e confermano che l'epitelio delle vie aeree è responsabile della generazione di microparticelle esprimenti TF che partecipano alla attivazione del FX in FXa, contribuendo così alla patogenesi delle malattie polmonari interstiziali

Old and Promising Markers Related to Autophagy in Traumatic Brain Injury

Traumatic brain injury (TBI) is one of the first causes of death and disability in the world. Because of the lack of macroscopical or histologic evidence of the damage, the forensic diagnosis of TBI could be particularly difficult. Considering that the activation of autophagy in the brain after a TBI is well documented in literature, the aim of this review is to find all autophagy immunohistological protein markers that are modified after TBI to propose a method to diagnose this eventuality in the brain of trauma victims. A systematic literature review on PubMed following PRISMA 2020 guidelines has enabled the identification of 241 articles. In all, 21 of these were enrolled to identify 24 markers that could be divided into two groups. The first consisted of well-known markers that could be considered for a first diagnosis of TBI. The second consisted of new markers recently proposed in the literature that could be used in combination with the markers of the first group to define the elapsed time between trauma and death. However, the use of these markers has to be validated in the future in human tissue by further studies, and the influence of other diseases affecting the victims before death should be explored

miR-19a and miR-20a and tissue factor expression in activated human peripheral blood mononuclear cells

Background and Aims. To investigate the behaviour of miR-19a and miR-20a, two microRNAs involved in posttranscriptional modulation of TF expression in peripheral blood mononuclear cells (PBMCs) exposed to high glucose (HG) and lipopolysaccharide (LPS), and to evaluate the involvement of angiotensin II in that process. Methods. TF Procoagulant Activity (PCA, one-stage clotting assay), antigen (Ag, ELISA), and miR-19a and miR-20a levels (specific TaqMan® MicroRNA Assays) were evaluated in PBMCs exposed to high glucose (HG, 50 mM), LPS (100 ng/mL), and Olmesartan (OLM, 10−6 M), an angiotensin II type 1 receptor antagonist. Results. HG increased TF expression and decreased both miRs as compared to control glucose conditions (11.1 mM). In HG-activated PBMCs, LPS stimulated TF expression and downregulated miR-20a, an effect reverted by OLM (10−6 M); miR-19a expression was unchanged by LPS in both CG and HG conditions. Conclusions. miR-19a and miR-20a are inhibited by inflammatory stimuli active on TF expression and their response differs by the stimulus under investigation; angiotensin II may participate in that mechanism

Rapid shedding of proinflammatory microparticles by human mononuclear cells exposed to cigarette smoke is dependent on Ca(2+) mobilization.

Microparticles are membrane vesicles shed by cells upon activation and apoptosis. Agonists capable of inducing microparticle generation include cytokines, bacterial products, P-selectin, histamine. Cigarette smoke extract has also been recognized as an agonist involved in microparticle generation with an apoptosis-dependent mechanism. We investigated the possibility that cigarette smoke extract induces the rapid generation of proinflammatory microparticles by human mononuclear cells with a calcium-dependent mechanism.Human mononuclear cells were exposed to cigarette smoke extract. [Ca(2+)]i mobilization was assessed with the fluorescent probe Fluo-4 NW. Microparticles were quantified with a prothrombinase assay and by flow cytometry. Normal human bronchial epithelial cells and A549 alveolar cells were incubated with cigarette smoke extract-induced microparticles and the generation of ICAM-1, IL-8, and MCP-1 was assessed by ELISA.Exposure to cigarette smoke extract induced a rapid increase in [Ca(2+)]i mobilization. Microparticle generation was also increased. EGTA, verapamil and the calmodulin inhibitor, W-7, inhibited microparticle generation. Incubation of lung epithelial cells with cigarette smoke extract-induced microparticles increased the expression of proinflammatory mediators.Exposure of mononuclear cells to cigarette smoke extract causes a rapid shedding of microparticles with a proinflammatory potential that might add to the mechanisms of disease from tobacco use

The effect of high glucose on the inhibitory action of C21, a selective AT2R agonist, of LPS-stimulated tissue factor expression in human mononuclear cells

Background: Intimate links connect tissue factor (TF), the principal initiator of the clotting cascade, to inflammation, a cross-talk amplified by locally generated Angiotensin (AT) II, the effector arm of the Renin Angiotensin System (RAS). C21, a selective AT2R agonist, downregulates the transcriptional expression of TF in LPS-activated peripheral blood mononuclear cell(PBMC)s implying the existence of ATII type 2 receptor (AT2R)s whose stimulation attenuates inflammation-mediated procoagulant responses. High glucose, by activating key signalling pathways and increasing the cellular content of RAS components, augments TF expression and potentiates the inhibitory effect of AT1R antagonists. It is unknown, however, the impact of that stimulus on AT2R-mediated TF inhibition, an information useful to understand more precisely the role of that signal transduction pathway in the inflammation-mediated coagulation process. TF antigen (ELISA), procoagulant activity (PCA, 1-stage clotting assay) and TF-mRNA (real-time polymerase chain reaction) were assessed in PBMCs activated by LPS, a pro-inflammatory and procoagulant stimulus, exposed to either normal (N) or HG concentrations (5.5 and 50 mM respectively). Results: HG upregulated TF expression, an effect abolished by BAY 11-7082, a NFκB inhibitor. C21 inhibited LPS-stimulated PCA, TFAg and mRNA to an extent independent of glucose concentration but the response to Olmesartan, an AT1R antagonist, was quite evidently potentiated by HG. Conclusions: HG stimulates LPS-induced TF expression through mechanisms completely dependent upon NFkB activation. Both AT2R-stimulation and AT1R-blockade downregulate inflammation-mediated procoagulant response in PBMCs but HG impacts differently on the two different signal transduction pathway

PARTICULATE MATTER-INDUCED PROCOAGULANT MICROPARTICLE GENERATION BY HUMAN MONONUCLEAR CELLS: A POSSIBLE NOVEL LINK BETWEEN AIRBORNE POLLUTANTS AND CARDIOVASCULAR DISEASES

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