Involvement of selected circulating ncRNAs in the regulation of cognitive dysfunction induced by anesthesia.

Post-operative cognitive dysfunction (POCD) refers to the functional impairment of the nervous system caused by prolonged exposure to anesthetics. It is known that prolonged exposure to anesthetics may increase the risk for the development of several cognitive impairments. The drugs used to induce general anesthesia are generally safe, owing to the CNS's direct and/or indirect self-protective activity against drug-induced damages.

Direct cleavage of caspase-8 by herpes simplex virus 1 tegument protein US11.

The HSV-1 tegument protein Us11 counteracts the antiviral defense mechanisms by precluding the host protein shutoff. Previous works demonstrated that Us11 prevents heat-and staurosporine-induced apoptosis and inhibits autophagy. Therefore, in the present study, we investigated the hypothesis that HSV-1, through Us11, could recruit caspase-8, a key enzyme regulating programmed cell death.

Cancer-Related Intracellular Signalling Pathways Activated by DOXorubicin/Cyclodextrin-Graphene-Based Nanomaterials.

In the last decade, nanotechnological progress has generated new opportunities to improve the safety and efficacy of conventional anticancer therapies. Compared with other carriers, graphene nanoplatforms possess numerous tunable functionalities for the loading of multiple bioactive compounds, although their biocompatibility is still a debated concern. Recently, we have investigated the modulation of genes involved in cancer-associated canonical pathways induced by graphene engineered with cyclodextrins (GCD).

Single cell-derived spheroids capture the self-renewing subpopulations of metastatic ovarian cancer.

High Grade Serous Ovarian cancer (HGSOC) is a major unmet need in oncology, due to its precocious dissemination and the lack of meaningful human models for the investigation of disease pathogenesis in a patient-specific manner. To overcome this roadblock, we present a new method to isolate and grow single cells directly from patients' metastatic ascites, establishing the conditions for propagating them as 3D cultures that we refer to as single cell-derived metastatic ovarian cancer spheroids (sMOCS). By single cell RNA sequencing (scRNAseq) we define the cellular composition of metastatic ascites and trace its propagation in 2D and 3D culture paradigms, finding that sMOCS retain and amplify key subpopulations from the original patients' samples and recapitulate features of the original metastasis that do not emerge from classical 2D culture, including retention of individual patients' specificities.

TAp63 regulates bone remodeling by modulating the expression of TNFRSF11B/Osteoprotegerin.

MSC, mesenchymal stem cells; OPG, osteoprotegerin; RUNX2, Run-trelated transcription factor 2.

GLS2 is transcriptionally regulated by p73 and contributes to neuronal differentiation.

The amino acid Glutamine is converted into Glutamate by a deamidation reaction catalyzed by the enzyme Glutaminase (GLS). Two isoforms of this enzyme have been described, and the GLS2 isoform is regulated by the tumor suppressor gene p53. Here, we show that the p53 family member TAp73 also drives the expression of GLS2.

Relative expression of TAp73 and ΔNp73 isoforms.

The transcription factor p73 belongs to the p53 family of tumour suppressors and similar to other family members, transcribed as different isoforms with opposing pro- and anti-apoptotic functions. Unlike p53, p73 mutations are extremely rare in cancers. Instead, the pro-apoptotic activities of transcriptionally active p73 isoforms are commonly inhibited by over-expression of the dominant negative p73 isoforms.

p63 in tooth development.

Recent findings have shown that the development of teeth involves a complex sequence of molecular events in which the p53 family member p63 is involved. Indeed, mice lacking p63 do not have teeth and humans bearing mutations in p63 suffer developmental syndromes that affect tooth morphology and number. Several isoforms of p63 have been described: the use of two different promoters produces longer TAp63 isoforms, or shorter, 5' truncated isoforms known as ΔNp63.

p73 in Cancer.

p73 is a tumor suppressor belonging to the p53 family of transcription factors. Distinct isoforms are transcribed from the p73 locus. The use of 2 promoters at the N-terminus allows the expression of an isoform containing (TAp73) or not containing (ΔNp73) a complete N-terminal transactivation domain, with the latter isoform capable of a dominant negative effect over the former.

p73: a multifunctional protein in neurobiology.

p73, a transcription factor of the p53 family, plays a key role in many biological processes including neuronal development. Indeed, mice deficient for both TAp73 and ΔNp73 isoforms display neuronal pathologies, including hydrocephalus and hippocampal dysgenesis, with defects in the CA1-CA3 pyramidal cell layers and the dentate gyrus. TAp73 expression increases in parallel with neuronal differentiation and its ectopic expression induces neurite outgrowth and expression of neuronal markers in neuroblastoma cell lines and neural stem cells, suggesting that it has a pro-differentiation role.