Ricerc@Sapienza

Nanomaterials have gained a rapid increase in use in a variety of applications that pertain to many aspects of human life. The majority of these innovations are centered on medical applications and a range of industrial and environmental uses ranging from electronics to environmental remediation. Despite the advantages of NPs, the knowledge of their toxicological behavior and their interactions with the cellular machinery that determines cell fate is extremely limited.

Reactive oxygen species (ROS) are small oxygen-derived molecules that are used to control infections by phagocytic cells. In macrophages, the oxidative burst produced by the NOX2 NADPH-oxidase is essential to eradicate engulfed pathogens by both oxidative and non-oxidative killing. Indeed, while the superoxide anion (O2-) produced by NOX2, and the other ROS derived from its transformation, can directly target pathogens, ROS also contribute to activation of non-oxidative microbicidal effectors.

Background: PD-L1 is a membrane protein with inhibitory effects on immune responses, whose expression has been correlated with high aggressiveness and the propensity of melanoma to metastasize. The nitrobenzoxadiazole (NBD) NBDHEX and its analog MC3181 are endowed with strong antitumor activity towards melanoma and a significant ability to reduce its adhesion and invasiveness. Therefore, we investigated whether PD-L1 status could affect cell sensitivity to the cytotoxic effects of NBDs. We then evaluated the effects of NBDHEX on PD-L1 expression and autophagy in melanoma cells.

Viral egress and autophagy are two mechanisms that seem to be strictly connected in Herpesviruses's biology. Several data suggest that the autophagic machinery facilitates the egress of viral capsids and thus the production of new infectious particles. In the Herpesvirus family, viral nuclear egress is controlled and organized by a well conserved group of proteins named Nuclear Egress Complex (NEC).

Autophagy is a catabolic process strongly involved in the immune response, and its dysregulation contributes to the onset of several diseases including cancer. The human oncogenic gammaherpesviruses, EpsteinBarr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), manipulate autophagy, either during the de novo infection or during the lytic reactivation, in naturally latently-infected lymphoma cells.

The oncogenic gammaherpesvirus Epstein–Barr virus (EBV) immortalizes in vitro B lymphocytes into lymphoblastoid cell lines (LCLs), a model that gives the opportunity to explore the molecular mechanisms driving viral tumorigenesis. In this study, we addressed the potential of quercetin, a widely distributed flavonoid displaying antioxidant, anti-inflammatory, and anti-cancer properties, in preventing EBV-driven B cell immortalization.

HHV-6A and HHV-6B are ubiquitous human betaherpesviruses sharing more than 80% homology. HHV-6B is the most common cause of encephalitis in transplant patients and its primary infection may cause the exanthema subitum and febrile seizures in infants. HHV-6A and HHV-6B are able to infect several immune cell types such as T cells, monocytes and dendritic cells (DCs). In this study we found that HHV-6 B derived from patients affected by exanthema subitum impaired monocyte differentiation into DCs, as the infected cells acquired less CD1a DC marker and retained more CD14 monocyte marker.

Autophagy is a catabolic process whose activation may help cancer cells to adapt to cellular stress although, in some instances, it can induce cell death. Autophagy stimulation or inhibition has been considered an opportunity to treat cancer, especially in combination with anticancer therapies, although autophagy manipulation may be viewed as controversial. Thus, whether to induce or to inhibit autophagy may be the best option in the different cancer patients is still matter of debate.

Pancreatic cancer is one of the most aggressive cancers whose prognosis is worsened by the poor response to the current chemotherapies. In this study, we investigated the cytotoxic effect of Apigenin, against two pancreatic cell lines, namely Panc1 and PaCa44, harboring different p53 mutations. Apigenin is a flavonoid widely distributed in nature that displays anti-inflammatory and anticancer properties against a variety of cancers. Here we observed that Apigenin exerted a stronger cytotoxic effect against Panc1 cell line in comparison to PaCa44.

Neurotropic herpesviruses have been associated with the onset and progression of Alzheimer's disease, a common form of dementia that afflicts a large percentage of elderly individuals. Interestingly, among the neurotropic herpesviruses, herpes simplex virus-1, human herpesvirus-6A, and human herpesvirus-6B have been reported to infect several cell types present in the central nervous system and to dysregulate autophagy, a process required for homeostasis of cells, especially neurons.