The pivotal role of Inflammaging in the peritumoral tissue of Renal Cell Carcinoma: from potential regulating mechanisms to clinical significance

L'inflammaging, che comprende il processo di infiammazione cronica di basso grado e di senescenza cellulare, influisce sulla progressione del tumore attraverso il rilascio di un particolare fenotipo secretorio associato alla senescenza (SASP). Nel presente lavoro, abbiamo esplorato il ruolo dell'inflammaging nel contesto del carcinoma a cellule renali (RCC). È stata valutata mediante microscopia confocale l'espressione di proteine pro-infiammatorie (PTX3) e correlate al SASP (p21/CIP1/WAF1, p16/INK4a, IL-6) nel tessuto peritumorale (periRCC) e tumorale (RCC) di campioni renali prelevati da 10 pazienti sottoposti a nefrectomia radicale per RCC. Inoltre, è stata condotta un'analisi in vitro mediante western blotting e qPCR su cellule epiteliali del tubulo prossimale (RPTEC) in condizioni di ipossia e nelle linee cellulari di RCC. È stata osservata un'aumentata espressione di PTX3 e IL-6 nei tessuti periRCC e RCC, rispetto ai normali tessuti renali (p<0,001) e un aumento dell'espressione dei livelli di p21 e p16 dai tessuti sani a quelli periRCC (p<0,001) con la loro riduzione nei tessuti RCC (p<0,05). L'analisi in vitro ha mostrato che in condizioni dell’1% di ipossia, l'espressione di PTX3 e IL-6 è risultata significativamente e progressivamente aumentata nelle linee cellulari RPTEC e RCC in modo dipendente dal tempo. È interessante notare che l'espressione di p21 e p16 è apparsa aumentata nelle RPTEC in condizioni di ipossia mentre nelle linee cellulari di RCC i livelli di espressione di p21 sono risultati espressi in modo simile alle linee RPTEC in condizione basale mentre quelli di p16 sono risultati non rilevabili. Nel contesto dei meccanismi molecolari, è stato rilevato un aumento coordinato nel tempo dell’espressione genica di PTX3 e del miR-224-5p in condizioni ipossiche nelle linee e nei tessuti normali e tumorali di RCC. Inoltre, classificando i tessuti secondo il Fuhrman Grading, sono state rilevate differenze operative nello stato di senescenza dei tessuti RCC peritumorali rispetto ai tessuti tumorali. Sono stati osservati livelli più elevati di PTX3 e IL-6 e livelli ridotti degli inibitori del ciclo cellulare nei tumori ad alto grado (G3-G4) rispetto ai tumori a basso grado (G1-G2), sia nei tessuti periRCC che RCC. Questo studio apre la strada a una migliore comprensione dell'infiammazione come meccanismo alla base della progressione del RCC. La riduzione dell’espressione degli inibitori del ciclo cellulare e l'aumentata espressione di fattori pro-infiammatori appaiono come aspetti cruciali per la progressione del tumore e per il significato clinico della malattia.Chronic, low-grade inflammation and cell senescence, also named Inflammaging, impacts tumor progression via the secretion of senescence-associated secretory phenotype (SASP). Here, we explored the role of inflammaging in the context of Renal Cell Carcinoma (RCC). The expression of pro-inflammatory (PTX3) and SASP-related proteins (p21/ CIP1/WAF1, p16/INK4a, IL-6) in the peritumoral (periRCC) and tumoral (RCC) area of renal samples from 10 patients undergone radical nephrectomy for RCC was evaluated by confocal microscopy. Moreover, an in vitro analysis on normal renal proximal tubular epithelial cells (RPTECs) under hypoxia conditions and in RCC cell lines was conducted by western blotting and qPCR. An increased expression of PTX3 and IL-6 in both periRCC and RCC tissues, as compared to normal renal tissues (p<0.001) was observed, while an increased expression of p21 and p16 levels from normal to periRCC (p<0.001) and their reduction in RCC tissues (p <0.05) was also observed. The in vitro analysis showed that under conditions of 1% hypoxia, expression of PTX3 and IL-6 was significantly and progressively increased in RPTEC and RCC cell lines in a time-dependent manner. Interestingly, expression of p21 and p16 were upregulated in hypoxic RPTEC while in RCC cell lines, p21 was similarly expressed to RPTEC at baseline and p16 expresssion was undetectable. In the context of molecular mechanisms, a coordinate increase in the gene expression of PTX3 and miR-224-5p over time under hypoxic conditions in normal and in ccRCC cells and tissues was observed. Furthermore, classifying tissues according to Fuhrman Grading, operational differences in the senescence status of peritumoral vs. tumor core RCC tissues were detected. Higher levels of PTX3 and IL-6 and lower level of cell cycle inhibitors in high grade (G3-G4) than in low-grade tumors (G1- G2), both in periRCC and RCC tissues, were observed. This study paves the way to an improved understanding of inflammaging as a mechanism impacting ccRCC disease progression. The downregulation of cell cycle inhibitors and the increased expression of pro-inflammatory factors appear to be crucial for tumor progression and clinical significance of the disease

LE SCELTE E GLI ESITI IN RELAZIONE AL GENERE NEI DIVERSI CORSI DI STUDI DELL'UNIVERSITA' DI FOGGIA

Il presente lavoro mira all'acquisizione di conoscenze specifiche in ordine all'offerta formativa al fine di migliorare la programmazione didattica delle Facoltà dell'Università degli Studi di Foggia. Si analizzeranno: 1. le preferenze degli studenti distinti in base al genere per Facoltà e i diversi corsi di laurea; 2. la distribuzione degli immatricolati e laureati per Facoltà e corso di laurea dall'a.a. 1999 all'a.a. 2007; 3. la situazione occupazionale dei laureati dell'Università di Foggia.

Epidemic and timer-based message dissemination in VANETs: A performance comparison

Data dissemination is among the key functions of Vehicular Ad-Hoc Networks (VANETs), and it has attracted much attention in the past decade. We address distributed, efficient, and scalable algorithms in the context of VANETs adopting the paradigm. We introduce an epidemic algorithm for message dissemination. The algorithm, named EPIC, is based on few assumptions, and it is very simple to implement. It uses only local information at each node, broadcast communications, and timers. EPIC is designed with the goal to reach the highest number of vehicles “infected” by the message, without overloading the network. It is tested on different scenarios taken from VANET simulations based on real urban environments (Manhattan, Cologne, Luxembourg). We compare our algorithm with a standard-based solution that exploits the contention-based forwarding component of the ETSI GeoNetworking protocol. On the other hand, we adapt literature based on a connected cover set to assess the near-optimality of our proposed algorithm and gain insight into the best selection of relay nodes as the size of the graph over which messages are spread scales up. The performance evaluation shows the behavior of EPIC and allows us to optimize the protocol parameters to minimize delay and overhead

CD40 cross-linking induces migration of renal tumor cell through nuclear factor of activated T cells (NFAT) activation

CD40 crosslinking plays an important role in regulating cell migration, adhesion and proliferation in renal cell carcinoma (RCC). CD40/CD40L interaction on RCC cells activates different intracellular pathways but the molecular mechanisms leading to cell scattering are not yet clearly defined. Aim of our study was to investigate the main intracellular pathways activated by CD40 ligation and their specific involvement in RCC cell migration. CD40 ligation increased the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH (2)-terminal kinase (JNK) and p38 MAPK. Furthermore, CD40 crosslinking activated different transcriptional factors on RCC cell lines: AP-1, NFkB and some members of the Nuclear Factor of Activated T cells (NFAT) family. Interestingly, the specific inhibition of NFAT factors by cyclosporine A, completely blocked RCC cell motility induced by CD40 ligation. In tumor tissue, we observed a higher expression of NFAT factors and in particular an increased activation and nuclear migration of NFATc4 on RCC tumor tissues belonging to patients that developed metastases when compared to those who did not. Moreover, CD40-CD40L interaction induced a cytoskeleton reorganization and increased the expression of integrin β1 on RCC cell lines, and this effect was reversed by cyclosporine A and NFAT inhibition. These data suggest that CD40 ligation induces the activation of different intracellular signaling pathways, in particular the NFATs factors, that could represent a potential therapeutic target in the setting of patients with metastatic RCC

Modulation of complement activation by pentraxin-3 in prostate cancer.

Pentraxin 3 (PTX3) is an essential component of the innate immune system and a recognized modulator of Complement cascade. The role of Complement system in the pathogenesis of prostate cancer has been largely underestimated. The aim of our study was to investigate the role of PTX3 as possible modulator of Complement activation in the development of this neoplasia. We performed a single center cohort study; from January 2017 through December 2018, serum and prostate tissue samples were obtained from 620 patients undergoing prostate biopsy. A group of patients with benign prostatic hyperplasia (BPH) underwent a second biopsy within 12-36 months demonstrating the presence of a prostate cancer (Group A, n = 40) or confirming the diagnosis of BPH (Group B, N = 40). We measured tissue PTX3 protein expression together with complement activation by confocal microscopy in the first and second biopsy in group A and B patients. We confirmed that that PTX3 tissue expression in the first biopsy was increased in group A compared to group B patients. C1q deposits were extensively present in group A patients co-localizing and significantly correlating with PTX3 deposits; on the contrary, C1q/PTX3 deposits were negative in group B. Moreover, we found a significantly increased expression of C3a and C5a receptors within resident cells in group A patient. Interestingly, C1q/PTX3 deposits were not associated with activation of the terminal Complement complex C5b-9; moreover, we found a significant increase of Complement inhibitor CD59 in cancer tissue. Our data indicate that PTX3 might play a significant pathogenic role in the development of this neoplasia through recruitment of the early components of Complement cascade with hampered activation of terminal Complement pathway associated with the upregulation of CD59. This alteration might lead to the PTX3-mediated promotion of cellular proliferation, angiogenesis and insensitivity to apoptosis possible leading to cancer cell invasion and migration

Ultrasonic Cutting Device for Bone Surgery Based on a Cymbal Transducer

AbstractIn this study, we introduce a new prototype ultrasonic cutting device for bone surgery based on a class V flextensional cymbal transducer, configured for use in power ultrasonics applications, which removes many of the geometrical restrictions on the cutting tip of Langevin-based transducers. The benefit of incorporating a cymbal transducer is that since the cutting blade itself does not have to be tuned, blade design can focus more closely on delivering the best interaction with bone to provide a highly accurate cut. Small variations to the geometry of the blade do not affect the final resonance frequency. Also the ultrasonic device can be miniaturised to allow the design of devices for delicate orthopaedic procedures involving minimal-access surgery. The results show how the cymbal transducer, driven by a single piezoceramic disc, can excite sufficiently high vibration displacement amplitudes at lower driving voltages. This is achieved by adapting the configuration of the cymbal to remove the problem of epoxy layer debonding, and by optimising the cymbal end-cap and geometry through finite element modelling supported with experimental vibration characterisation. Preliminary characterisations of the resulting prototype ultrasonic bone cutting device, which operates at around 25kHz, illustrate the success of this novel device design

Ellipsis comprehension in the elderly population: an implicit relationship

reservedCon il termine ellissi si indicano diversi fenomeni linguistici in cui parte del materiale lessicale di una frase risulta mancante in quanto sott’inteso. Il suo contenuto può essere ricavato grazie al contesto grammaticale e/o discorsivo. In questa tesi ci si focalizzerà sulla comprensione di materiale ellittico appartenente al dominio nominale (NP), più precisamente quello collocato in posizione di oggetto, utilizzando un Truth Value Judgemente Task (TVJT). Gli studi di riferimento sono stati quelli di Wijnen, Roeper, & van der Meulen (2004) e di Tasinato & Sanfelici (in corso di pubblicazione). Lo scopo di questo lavoro è stato quello di provare a capire come avvenga la comprensione di NP ellissi in una popolazione anziana, al fine di poterla confrontare con quella di un gruppo di controllo di persone adulte (18-65); si è inoltre provato a comprendere se, in questo specifico task, vi siano interferenze legate ad altri parametri, quali il genere, il livello di istruzione e, infine, il tipo di costruzione elisa. In quest’ultimo caso si è trattato di capire se le ellissi nominali siano più facili da computare in costruzioni locali (ellissi coordinative) o non locali (ellissi discorsive). In generale, i dati ottenuti indicherebbero che gli anziani parlanti italiano L1 comprendono bene l’ellissi nominale, specialmente nelle condizioni di identità, mentre mostrano qualche difficoltà nelle condizioni di non identità, discostandosi dal campione di controllo e mostrando interpretazioni di tipo deittico. In aggiunta, non sembrano esserci interferenze dovute al genere o di livello di istruzione; al contrario, appare abbastanza consistente un effetto di località, in quanto le strutture non locali vengono interpretate con più difficoltà rispetto a quelle locali. È bene chiarire che, dato il ridotto numero di soggetti testati, quella rinvenuta è una possibile tendenza, e in quanto tale va necessariamente approfondito con una popolazione più ampia e diversificata per poter essere confermata

Intrusion detection systems for IoT. Opportunities and challenges offered by Edge Computing

Key components of current cybersecurity methods are the Intrusion Detection Systems (IDSs) were different techniques and architectures are applied to detect intrusions. IDSs can be based either on cross-checking monitored events with a database of known intrusion experiences, known as signature-based, or on learning the normal behavior of the system and reporting whether some anomalous events occur, named anomaly-based. This work is dedicated to the application to the Internet of Things (IoT) network where edge computing is used to support the IDS implementation. New challenges that arise when deploying an IDS in an edge scenario are identified and remedies are proposed. We focus on anomaly-based IDSs, showing the main techniques that can be leveraged to detect anomalies and we present machine learning techniques and their application in the context of an IDS, describing the expected advantages and disadvantages that a specific technique could cause