104 research outputs found
Ruolo della proteina Sam68 nella regolazione degli eventi biologici in cellule neoplastiche
No full textSam68, una proteina che lega l’RNA, è coinvolta in vari aspetti del metabolismo degli mRNA, tra cui lo splicing, l’esportazione dal nucleo e la traduzione; la sua struttura le consente di interagire con proteine coinvolte nella trasduzione del segnale attivata dai recettori per i fattori di crescita. A sostegno dell’ormai accreditato ruolo oncogenico, diversi studi ne documentano la frequente iper-espressione in carcinomi alla prostata, alla mammella e al rene; tuttavia i meccanismi molecolari attraverso i quali Sam68 promuove la trasformazione neoplastica sono ancora poco conosciuti. In questo contesto si inserisce l’attività di ricerca da me svolta: in particolare ho voluto analizzare il ruolo di Sam68 nella trasformazione mediata da ALK., la cui variante oncogenica NPM/ALK, gioca un ruolo centrale nella patogenesi del linfoma anaplastico a grandi cellule (ALCL). Ho potuto osservare che:1) l’attività di ALK è in grado di modulare la fosforilazione di Sam68 con un meccanismo p60src-dipendente 2) la down-regolazione di Sam68 determina una drastica inibizione delle capacità migratorie e proliferative, ed una sensibilizzazione al cisplatino delle cellule NPM/ALK positive derivanti da ALCL 3) in seguito ad attivazione di ALK, ho potuto osservare l’associazione tra Sam68 e Vav1, un fattore di scambio per nucleotidi, la cui attivazione è estremamente importante nella trasduzione dei segnali trasformanti ALK-mediati. Questi dati hanno trovato riscontro anche in cellule di mesotelioma maligno (MM) della pleura, in cui la down-regolazione di Sam68 è strettamente correlata ad una drastica riduzione delle capacità migratorie e dei livelli di espressione del trascritto CD44v5, la cui espressione è riscontrabile durante la fase invasiva di molti tumori. Infine, il trattamento con cisplatino induce nelle cellule derivate da MM una rilocalizzazione di Sam68 dal nucleo al citoplasma, suggerendo per questa proteina un ruolo fondamentale nella risposta allo stress genotossico
Los intereses tutelables y la dimensión de los perjuicios reparables en el Derecho francés de la responsabilidad civil extracontractual
No full textIn Tort Law, it is said that an individual mustrepair the damage he causes. What is the extention of this maxim? Is this affirmation accurate? What is considered damage for Law?Jean-Sebastién Borghetti answers this and other questions as understood by French Law, seeking to delimit the French system of civil liability. In that sense, through this article, the author proposes that not all affronts constitute a damage as understood by Law, and that not every damage can be repaired.En la Responsabilidad Civil, se afirma que todoaquel que causa un perjuicio debe repararlo. ¿Cuál es el alcance de esta máxima? ¿Qué tan exacta es esta afirmación? ¿Qué es un perjuicio para el Derecho?Jean-Sebastién Borghetti responde estas y otras preguntas desde el Derecho francés, buscando delimitar el sistema francés de la responsabilidad civil. En ese sentido, a través del presente artículo, el autor propone que no todo agravio constituye un perjuicio para elDerecho, y que no todo perjuicio es reparable
Legally protectable assets and the dimension of reparable damages in French Tort Law
Get PDFIn Tort Law, it is said that an individual mustrepair the damage he causes. What is the extention of this maxim? Is this affirmation accurate? What is considered damage for Law?Jean-Sebastién Borghetti answers this and other questions as understood by French Law, seeking to delimit the French system of civil liability. In that sense, through this article, the author proposes that not all affronts constitute a damage as understood by Law, and that not every damage can be repaired.En la Responsabilidad Civil, se afirma que todoaquel que causa un perjuicio debe repararlo. ¿Cuál es el alcance de esta máxima? ¿Qué tan exacta es esta afirmación? ¿Qué es un perjuicio para el Derecho?Jean-Sebastién Borghetti responde estas y otras preguntas desde el Derecho francés, buscando delimitar el sistema francés de la responsabilidad civil. En ese sentido, a través del presente artículo, el autor propone que no todo agravio constituye un perjuicio para elDerecho, y que no todo perjuicio es reparable
In vitro characterization of PRRSV isolates with different in vivo virulence using monocyte-derived macrophages
Get PDFThe recent emergence of highly pathogenic porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) strains has caused severe economic losses. The biological elements defining virulence and pathogenicity are still unclear. In vitro characteristics using natural target cells of PRRSV provide important information to understand the basis of virulence at the cellular level, and provide a mean to reduce animal experimentations to achieve this goal. Here, we compared PRRSV strains from two geographically different regions, with varying in vivo characteristics, in terms of their interactions with monocyte-derived macrophages (MDMs). The strains included Lena and BOR59 from Belarus, and ILI6 from Russia, as well as PR11 and PR40, both from Italy. As a reference, we used a cell culture-adapted version of Lelystad, LVP. MDMs were pre-treated with IFNγ, IL-4 or IFNβ, in order to understand responses in polarized and antiviral MDMs. In general, independent of the geographical origin, the strains with high virulence infected a higher percentage of MDMs and replicated to higher titers. These virulence-dependent differences were most pronounced when the MDMs had been treated with IFNβ. Differentiation between intermediate and low virulent PRRSV was difficult, due to variations between different experiments, but LVP differed clearly from all field strains. IFNα and IL-10 were not detected in any experiment, but PR40 induced TNF and IL-1β. Taken together, these results validate the MDM model to understand pathogenicity factors of PRRSV and confirm the importance of the escape from type I and II IFN-mediated effects for PRRSV virulence
Impact of maternally derived immunity on piglets’ immune response and protection against porcine circovirus type 2 (PCV2) after vaccination against PCV2 at different age
Get PDFBACKGROUND:
This study was aimed at evaluating the clinical protection, the level of Porcine circovirus type 2 (PCV2) viremia and the immune response (antibodies and IFN-γ secreting cells (SC)) in piglets derived from PCV2 vaccinated sows and themselves vaccinated against PCV2 at different age, namely at 4, 6 and 8 weeks. The cohort study has been carried out over three subsequent production cycles (replicates). At the start/enrolment, 46 gilts were considered at first mating, bled and vaccinated. At the first, second and third farrowing, dams were bled and re-vaccinated at the subsequent mating after weaning piglets. Overall 400 piglets at each farrowing (first, second and third) were randomly allocated in three different groups (100 piglets/group) based on the timing of vaccination (4, 6 or 8 weeks of age). A fourth group was kept non-vaccinated (controls). Piglets were vaccinated intramuscularly with one dose (2 mL) of a commercial PCV2a-based subunit vaccine (Porcilis® PCV). Twenty animals per group were bled at weaning and from vaccination to slaughter every 4 weeks for the detection of PCV2 viremia, humoral and cell-mediated immune responses. Clinical signs and individual treatments (morbidity), mortality, and body weight of all piglets were recorded.
RESULTS:
All vaccination schemes (4, 6 and 8 weeks of age) were able to induce an antibody response and IFN-γ SC. The highest clinical and virological protection sustained by immune reactivity was observed in pigs vaccinated at 6 weeks of age. Overall, repeated PCV2 vaccination in sows at mating and the subsequent higher levels of maternally derived antibodies did not significantly interfere with the induction of both humoral and cell-mediated immunity in their piglets after vaccination.
CONCLUSIONS:
The combination of vaccination in sows at mating and in piglets at 6 weeks of age was more effective for controlling PCV2 natural infection, than other vaccination schemas, thus sustaining that some interference of MDA with the induction of an efficient immune response could be considered. In conclusion, optimal vaccination strategy needs to balance the levels of passive immunity, the management practices and timing of infection
Phenotypic modulation of porcine CD14+ monocytes, natural killer/natural killer T cells and CD8αβ+ T cell subsets by an antibody-derived killer peptide (KP)
No full textA highly pathogenic porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) strongly modulates cellular innate and adaptive immune subsets upon experimental infection
Get PDFHighly pathogenic (HP) PRRSV isolates have been discovered within both PRRSV-1 and PRRSV-2 genotypes and
investigated in recent years especially for their ability to cause extremely severe disease in conventional pig
herds. The exacerbation of general and respiratory clinical signs has been attributed not only to an efficient
replication (virulence) but also to the ability to dysregulate viral recognition and induce mechanisms of immune
evasion or immune enhancement of humoral and cellular anti-viral responses differently from non-HP PRRSV
isolates in terms of intensity and temporal onset. Thus, the understanding of the immunopathogenesis of HP
PRRSV is a major concern for the study of virus biology and development of efficacious vaccines. The present
study aims at addressing the modulation of relevant immune cell subsets by flow cytometry in the blood of 4-
week-old pigs experimentally infected with the recently discovered PR40/2014 HP PRRSV-1.1 strain phenotypically
characterized in Canelli et al. (2017) compared to pigs infected with a non-HP PRRSV isolate (PR11/
2014) and uninfected controls. PR40 infected animals showed an early and marked reduction of pro-inflammatory
CD172α+ CD14+CD16+ and CD14+CD163+ monocytes and TCRγδ+CD8α+/CD8α- lymphocytes
when pigs were most infected, possibly due to a recruitment sustaining an acute inflammatory response in
target tissues. The prolonged increased CD3+CD16+ NKT cell levels may sustain peripheral inflammation and/
or the anti-viral response. The late reduction (potential depletion) of γ/δ T lymphocytes and CD3+CD4+CD8α-
naïve Th lymphocytes paralleled with the delayed increase of CD3+CD4+CD8α+ memory and CD3+CD4-
CD8α/β+cytotoxic T lymphocytes. In addition, PR40 infection showed an early depletion of activated
CD4+CD25+ T lymphocytes and Tregs together with an intense and lasting depletion of CD21+ B lymphocytes.
Overall, these features demonstrate that the more severe clinical signs observed upon infection with the
HP PR40 strain are sustained by remarkable changes in the peripheral blood distribution of immune cells and
provide further insights into the immune regulation/immunopathogenesis induced by PRRSV-1 subtype 1
European isolates
Immunoregulatory signal FoxP3, cytokine gene expression and IFN-γ cell responsiveness upon porcine reproductive and respiratory syndrome virus (PRRSV) natural infection
No full textThe study aims at evaluating gene expression of pro-inflammatory (IL-1β, IL-8, TNF-α), pro-immune (IFN-γ), anti-inflammatory (IL-10) cytokines and of the immunoregulatory signal FoxP3 in association with PRRSV-specific IFN-γ secreting cell (SC) responsiveness upon PRRSV natural infection. Forty PRRSV-negative pigs were assigned to two groups: 20 pigs were vaccinated at 3 weeks of age (weaning) against PRRSV (V-PRRSV) with a modified live virus vaccine (MLV) and 20 pigs were kept non-vaccinated (NV) as controls. Blood samples were collected at 3 (vaccination), 6, 8, 10, 12, 14, and 16 weeks of age. Natural infection occurred from 8 weeks of age onward in both groups and viremia lasted 8 weeks. In the early phase of infection, pro-inflammatory cytokines (IL-1β, IL-8, TNF-α) showed a delayed increase concomitant with the peak of viremia in both groups. In both groups, IL-10 peaked at 12 weeks in association with the increase of pro-inflammatory cytokines. Conversely, in vaccinated pigs (V-PRRSV), IFN-γ showed higher gene expression during the early phase of infection and a more intense secreting cell (SC) response in the late phase. Differently, gene expression of the transcription factor FoxP3, expressed by T regulatory lymphocytes (Tregs), increased significantly in controls only and was associated with the rise of the viral load. Moreover, FoxP3 levels remained significantly higher during the late phase of infection and paralleled with lower levels of IFN-γ SC detected by ELISPOT. The expression/production of immunoregulatory signals involved in Treg activation could be a promising marker to study the immunobiology of PRRSV infection
Universal testing for COVID-19 in patients undergoing cancer treatment during the second outbreak in Brescia
Get PDFBackground: The impact of coronavirus disease 2019 (COVID-19) has been overwhelming on patients with cancer, who may be at higher risk of developing severe disease. During the second COVID-19 outbreak in Italy, we planned universal microbiologic screening for patients scheduled for antineoplastic treatment. Methods: All patients with planned active treatment at Brescia University Radiation Oncology Department were screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA with repeated nasopharyngeal swabs (NPS) from October 31, 2020. Treatment continuation, suspension, or delay was modulated for patients testing positive according to clinical presentation. Results: From October 31, 2020, to February 6, 2021, 636 patients were enrolled and 1243 NPS were performed, of which 28 (2.25%) were positive. The infection rate was 2.52%; 81.3% of the patients with a positive NPS were asymptomatic, 2 had mild disease, and 1 severe disease that led to death. All patients already on treatment with mild or asymptomatic COVID-19 carried on the therapy with no or minimal delay. Median delay for patients with infection detected before treatment start was 16.5 days. Conclusions: Detected incidence of COVID-19 was lower during the second outbreak in our patients (2.52% vs 3.23%), despite the extensive testing schedule, and substantiates the high rate of asymptomatic infections and the low mortality among patients with COVID-19 (6.3% vs 38.5% during the first outbreak). Universal SARS-CoV-2 screening for all patients with planned treatment might allow early identification of patients with COVID-19, resulting in timely management that could improve clinical outcomes and prevent spread of the infection
- …
