Progetto di un sistema di pagamento per telefonia mobile

La grande disponibilità di telefoni mobili (e altri dispositivi mobili) sta aprendo sempre più la strada verso i servizi di m-commerce (commercio mobile). Il punto focale per lo sviluppo di questi servizi è costituito dalla sicurezza con cui le merci acquistate possono essere pagate (m-payment). I problemi di sicurezza riguardano principalmente il dispositivo mobile, l'interfaccia radio, l'infrastruttura di rete dell'operatore mobile ed il tipo di applicazione di m-commerce. Il lavoro di tesi svolto consiste nel progettare ed implementare un sistema di pagamento per telefonia mobile che permetta di risolvere i problemi di sicurezza sopra citati, analizzando in particolar modo il caso in cui il merchant utilizzi una macchina (simulata da un sistema Asterisk) per la vendita dei propri biglietti

The C-X-C Motif Chemokine Ligand 1 Sustains Breast Cancer Stem Cell Self-Renewal and Promotes Tumor Progression and Immune Escape Programs

Breast cancer (BC) mortality is mainly due to metastatic disease, which is primarily driven by cancer stem cells (CSC). The chemokine C-X-C motif ligand-1 (CXCL1) is involved in BC metastasis, but the question of whether it regulates breast cancer stem cell (BCSC) behavior is yet to be explored. Here, we demonstrate that BCSCs express CXCR2 and produce CXCL1, which stimulates their proliferation and self-renewal, and that CXCL1 blockade inhibits both BCSC proliferation and mammosphere formation efficiency. CXCL1 amplifies its own production and remarkably induces both tumor-promoting and immunosuppressive factors, including SPP1/OPN, ACKR3/CXCR7, TLR4, TNFSF10/TRAIL and CCL18 and, to a lesser extent, immunostimulatory cytokines, including IL15, while it downregulates CCL2, CCL28, and CXCR4. CXCL1 downregulates TWIST2 and SNAI2, while it boosts TWIST1 expression in association with the loss of E-Cadherin, ultimately promoting BCSC epithelial-mesenchymal transition. Bioinformatic analyses of transcriptional data obtained from BC samples of 1,084 patients, reveals that CXCL1 expressing BCs mostly belong to the Triple-Negative (TN) subtype, and that BC expression of CXCL1 strongly correlates with that of pro-angiogenic and cancer promoting genes, such as CXCL2-3-5-6, FGFBP1, BCL11A, PI3, B3GNT5, BBOX1, and PTX3, suggesting that the CXCL1 signaling cascade is part of a broader tumor-promoting signaling network. Our findings reveal that CXCL1 functions as an autocrine growth factor for BCSCs and elicits primarily tumor progression and immune escape programs. Targeting the CXCL1/CXCR2 axis could restrain the BCSC compartment and improve the treatment of aggressive BC

Looking for Nano- and Microplastics in Meiofauna Using Advanced Methodologies

: Meiofauna (body size within 30–1000 µm) are the community of microscopic invertebrates that live at the bottom of marine and freshwater ecosystems and play a key role in the food webs of these environments. Several studies have addressed the adverse effects of anthropic stressors on meiofauna; however, data on the presence and impact of plastic debris in wild meiofaunal organisms are scant. Since the amount of microplastic waste in sediments may surge rapidly, ascertaining the ingestion of these xenobiotics by the abundant micrometazoan community is necessary to understand their potential accumulation in aquatic food webs and their hazard to the health of the ecosystem. The absence of documentation in this regard may be due to the difficulty in detecting the small size of the plastic fragments meiofauna may potentially ingest. To overcome this difficulty, we developed an integrated approach based on different microscopic/spectroscopic techniques suitable for detecting plastic particles of sizes down to 200 nm.Meiofauna (body size within 30–1000 m) are the community of microscopic invertebrates that live at the bottom of marine and freshwater ecosystems and play a key role in the food webs of these environments. Several studies have addressed the adverse effects of anthropic stressors on meiofauna; however, data on the presence and impact of plastic debris in wild meiofaunal organisms are scant. Since the amount of microplastic waste in sediments may surge rapidly, ascertaining the ingestion of these xenobiotics by the abundant micrometazoan community is necessary to understand their potential accumulation in aquatic food webs and their hazard to the health of the ecosystem. The absence of documentation in this regard may be due to the difficulty in detecting the small size of the plastic fragments meiofauna may potentially ingest. To overcome this difficulty, we developed an integrated approach based on different microscopic/spectroscopic techniques suitable for detecting plastic particles of sizes down to 200 nm

Interleukin-30 feeds breast cancer stem cells via CXCL10 and IL23 autocrine loops and shapes immune contexture and host outcome

Background Breast cancer (BC) progression to metastatic disease is the leading cause of death in women worldwide. Metastasis is driven by cancer stem cells (CSCs) and signals from their microenvironment. Interleukin (IL) 30 promotes BC progression, and its expression correlates with disease recurrence and mortality. Whether it acts by regulating BCSCs is unknown and could have significant therapeutic implications. Methods Human (h) and murine (m) BCSCs were tested for their production of and response to IL30 by using flow cytometry, confocal microscopy, proliferation and sphere-formation assays, and PCR array. Immunocompetent mice were used to investigate the role of BCSC-derived IL30 on tumor development and host outcome. TCGA PanCancer and Oncomine databases provided gene expression data from 1084 and 75 hBC samples, respectively, and immunostaining unveiled the BCSC microenvironment. Results hBCSCs constitutively expressed IL30 as a membrane-anchored glycoprotein. Blocking IL30 hindered their proliferation and self-renewal efficiency, which were boosted by IL30 overexpression. IL30 regulation of immunity gene expression in human and murine BCSCs shared a significant induction of IL23 and CXCL10. Both immunoregulatory mediators stimulated BCSC proliferation and self-renewal, while their selective blockade dramatically hindered IL30-dependent BCSC proliferation and mammosphere formation. Orthotopic implantation of IL30-overexpressing mBCSCs, in syngeneic mice, gave rise to poorly differentiated and highly proliferating MYC + KLF4 + LAG3 + tumors, which expressed CXCL10 and IL23, and were infiltrated by myeloid-derived cells, Foxp3 + T regulatory cells and NKp46 + RORÎ 3t + type 3 innate lymphoid cells, resulting in increased metastasis and reduced survival. In tumor tissues from patients with BC, expression of IL30 overlapped with that of CXCL10 and IL23, and ranked beyond the 95th percentile in a Triple-Negative enriched BC collection from the Oncomine Platform. CIBERSORTx highlighted a defective dendritic cell, CD4 + T and Î 3δT lymphocyte content and a prominent LAG3 expression in IL30 high versus IL30 low human BC samples from the TCGA PanCancer collection. Conclusions Constitutive expression of membrane-bound IL30 regulates BCSC viability by juxtacrine signals and via second-level mediators, mainly CXCL10 and IL23. Their autocrine loops mediate much of the CSC growth factor activity of IL30, while their paracrine effect contributes to IL30 shaping of immune contexture. IL30-related immune subversion, which also emerged from computational analyses, strongly suggests that targeting IL30 can restrain the BCSC compartment and counteract BC progression

Physical Activity and Exercise Addiction During the Covid-19 Pandemic in Italy

© 2022, The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, to view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Severe restrictive measures were implemented globally to limit the spread of the Covid-19 pandemic leading to significant lifestyle changes and impacting on both the physical and the mental health of citizens. Caught by the fear of getting sick, some individuals have adopted behaviors which favored the development of exercise addiction (EA). Our aim was to evaluate physical activity habits and the risk of EA in the general Italian population during phase 1 of the lockdown. The role of appearance anxiety (AA), self-compassion, and use of performance and image enhancing drugs (PIEDs) as predictors of EA development were investigated. A comparison between physically active subjects with the inactive ones was also included. Between April and May 2020, an online survey was conducted across Italy. Nine hundred thirty-six answers were collected. The rate of EA in the physically active sample (782 subjects) was 4.1%. The physically active group showed higher SCS scores and a greater use of PIEDs. Of the physically active participants, 84.2% reported variations in their fitness routine. Perceived benefit of exercising resulted significantly higher in those with EA. Subjects with EA reported stronger motivation in engaging in physical activity as for “physical wellness,” “psychological well-being,” and “sexual attractiveness and confidence in relationship.” A higher level of AA, a lower level of self-compassion, and a higher perceived benefit of exercising during lockdown were all significant predictors for the presence of EA. Our findings suggest that the fear of getting sick from Covid-19, combined with radical changes in the lifestyles induced by the lockdown and individual personological characteristics, can favor the development of EA and related phenomena in the general population.Peer reviewedFinal Published versio

CD95 death-inducing signaling complex formation and internalization occur in lipid rafts of type I and type II cells

We investigated the membrane localization of CD95 in type I and type II cells, which differ in their ability to recruit and activate caspase-8. We found that CD95 was preferentially located in lipid rafts of type I cells, while it was present both in raft and non-raft plasma membrane sub-domains of type II cells. After stimulation, CD95 located in phospholipid-rich plasma membrane was recruited to lipid rafts in both types of cells. Similarly, CD95 cross-linking resulted in caspase-independent translocation of FADD/MORT1 and caspase-8 to the lipid rafts, which was prevented by a death domain-defective receptor. CD95 internalization was then rapid in type I and delayed in type II cells and showed a substantial correlation with the kinetics of Fas-associated death domain (FADD) and caspase-8 recruitment to lipid rafts. Finally, electron microscopy analysis showed that after CD95 stimulation lipid rafts aggregated in large clusters that were internalized in endosomal vesicles, where caspase-8 underwent massive processing. Taken together, our data demonstrate that CD95 death-inducing signaling complex formation and internalization in type I and type II cells occur in lipid rafts, which are a major site of caspase-8 activation. © 2004 WILEY-VCH Verlag GmbH & Co. KGaA

MiR-221 promotes stemness of breast cancer cells by targeting DNMT3b

Cancer stem cells (CSCs) are a small part of the heterogeneous tumor cell population possessing self-renewal and multilineage differentiation potential as well as a great ability to sustain tumorigenesis. The molecular pathways underlying CSC phenotype are not yet well characterized. MicroRNAs (miRs) are small noncoding RNAs that play a powerful role in biological processes. Early studies have linked miRs to the control of self-renewal and differentiation in normal and cancer stem cells. We aimed to study the functional role of miRs in human breast cancer stem cells (BCSCs), also named mammospheres. We found that miR-221 was upregulated in BCSCs compared to their differentiated counterpart. Similarly, mammospheres from T47D cells had an increased level of miR-221 compared to differentiated cells. Transfection of miR-221 in T47D cells increased the number of mammospheres and the expression of stem cell markers. Among miR-221's targets, we identified DNMT3b. Furthermore, in BCSCs we found that DNMT3b repressed the expression of various stemness genes, such as Nanog and Oct 3/4, acting on the methylation of their promoters, partially reverting the effect of miR-221 on stemness. We hypothesize that miR-221 contributes to breast cancer tumorigenicity by regulating stemness, at least in part through the control of DNMT3b expression

Colorectal cancer development is affected by the ECM molecule EMILIN-2 hinging on macrophage polarization via the TLR-4/MyD88 pathway

Background Colorectal cancer is one of the most frequent and deadly tumors. Among the key regulators of CRC growth and progression, the microenvironment has emerged as a crucial player and as a possible route for the development of new therapeutic opportunities. More specifically, the extracellular matrix acts directly on cancer cells and indirectly affecting the behavior of stromal and inflammatory cells, as well as the bioavailability of growth factors. Among the ECM molecules, EMILIN-2 is frequently down-regulated by methylation in CRC and the purpose of this study was to verify the impact of EMILIN-2 loss in CRC development and its possible value as a prognostic biomarker. Methods The AOM/DSS CRC protocol was applied to Emilin-2 null and wild type mice. Tumor development was monitored by endoscopy, the molecular analyses performed by IHC, IF and WB and the immune subpopulations characterized by flow cytometry. Ex vivo cultures of monocyte/macrophages from the murine models were used to verify the molecular pathways. Publicly available datasets were exploited to determine the CRC patients' expression profile; Spearman's correlation analyses and Cox regression were applied to evaluate the association with the inflammatory response; the clinical outcome was predicted by Kaplan-Meier survival curves. Pearson correlation analyses were also applied to a cohort of patients enrolled in our Institute. Results In preclinical settings, loss of EMILIN-2 associated with an increased number of tumor lesions upon AOM/DSS treatment. In addition, in the early stages of the disease, the Emilin-2 knockout mice displayed a myeloid-derived suppressor cells-rich infiltrate. Instead, in the late stages, lack of EMILIN-2 associated with a decreased number of M1 macrophages, resulting in a higher percentage of the tumor-promoting M2 macrophages. Mechanistically, EMILIN-2 triggered the activation of the Toll-like Receptor 4/MyD88/NF-kappa B pathway, instrumental for the polarization of macrophages towards the M1 phenotype. Accordingly, dataset and immunofluorescence analyses indicated that low EMILIN-2 expression levels correlated with an increased M2/M1 ratio and with poor CRC patients' prognosis. Conclusions These novel results indicate that EMILIN-2 is a key regulator of the tumor-associated inflammatory environment and may represent a promising prognostic biomarker for CRC patients