COVID-19 vaccine acceptance among medical students in Romania.

Vaccination against COVID-19 is a highly debated subject that brings confusion due to contradictory information coming from the scientific community and the media. Our aim was to focus on a homogeneous group of students in the healthcare field to assess their intention to vaccinate and the drivers behind this decision. A cross-sectional study was performed in the spring of 2021 in a Medical University in Romania. 725 of the undergraduates that completed an online questionnaire regarding their intention to vaccinate against COVID-19 were included in the study. Univariable analysis and logistic regression were performed on several variables to analyze factors affecting the willingness to vaccinate against COVID-19. In our study sample, 93.1% of students presented a strong intention to vaccinate, out of which the highest proportion belonged to subjects studying general medicine (96%). On logistic regression, we identified the following predictor factors: previous infection with coronavirus, prior vaccination refusal, VAX score, scientifically oriented sources of information and preference for RNA-based technology. Medical students have an increased willingness towards vaccination. Even for them, a highly educated and informed group of subjects, the general attitude towards vaccinations has a strong impact on the choice of COVID-19 vaccination.

Unbalancing p53/Mdm2/IGF-1R axis by Mdm2 activation restrains the IGF-1-dependent invasive phenotype of skin melanoma.

Melanoma tumors usually retain wild-type p53; however, its tumor-suppressor activity is functionally disabled, most commonly through an inactivating interaction with mouse double-minute 2 homolog (Mdm2), indicating p53 release from this complex as a potential therapeutic approach. P53 and the tumor-promoter insulin-like growth factor type 1 receptor (IGF-1R) compete as substrates for the E3 ubiquitin ligase Mdm2, making their relative abundance intricately linked. Hence we investigated the effects of pharmacological Mdm2 release from the Mdm2/p53 complex on the expression and function of the IGF-1R. Nutlin-3 treatment increased IGF-1R/Mdm2 association with enhanced IGF-1R ubiquitination and a dual functional outcome: receptor downregulation and selective downstream signaling activation confined to the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. This Nutlin-3 functional selectivity translated into IGF-1-mediated bioactivities with biphasic effects on the proliferative and metastatic phenotype: an early increase and late decrease in the number of proliferative and migratory cells, while the invasiveness was completely inhibited following Nutlin-3 treatment through an impaired IGF-1-mediated matrix metalloproteinases type 2 activation mechanism. Taken together, these experiments reveal the biased agonistic properties of Nutlin-3 for the mitogen-activated protein kinase pathway, mediated by Mdm2 through IGF-1R ubiquitination and provide fundamental insights into destabilizing p53/Mdm2/IGF-1R circuitry that could be developed for therapeutic gain.