Modulating voltage-gated sodium channels to enhance differentiation and sensitize glioblastoma cells to chemotherapy.

BACKGROUND: Glioblastoma (GBM) stands as the most prevalent and aggressive form of adult gliomas. Despite the implementation of intensive therapeutic approaches involving surgery, radiation, and chemotherapy, Glioblastoma Stem Cells contribute to tumor recurrence and poor prognosis. The induction of Glioblastoma Stem Cells differentiation by manipulating the transcriptional machinery has emerged as a promising strategy for GBM treatment. Here, we explored an innovative approach by investigating the role of the depolarized resting membrane potential (RMP) observed in patient-derived GBM sphereforming cell (GSCs), which allows them to maintain a stemness profile when they reside in the G0 phase of the cell cycle. METHODS: We conducted molecular biology and electrophysiological experiments, both in vitro and in vivo, to examine the functional expression of the voltage-gated sodium channel (Nav) in GSCs, particularly focusing on its cell cycle-dependent functional expression. Nav activity was pharmacologically manipulated, and its effects on GSCs behavior were assessed by live imaging cell cycle analysis, self-renewal assays, and chemosensitivity assays. Mechanistic insights into the role of Nav in regulating GBM stemness were investigated through pathway analysis in vitro and through tumor proliferation assay in vivo. RESULTS: We demonstrated that Nav is functionally expressed by GSCs mainly during the G0 phase of the cell cycle, suggesting its pivotal role in modulating the RMP. The pharmacological blockade of Nav made GBM cells more susceptible to temozolomide (TMZ), a standard drug for this type of tumor, by inducing cell cycle re-entry from G0 phase to G1/S transition. Additionally, inhibition of Nav substantially influenced the self-renewal and multipotency features of GSCs, concomitantly enhancing their degree of differentiation. Finally, our data suggested that Nav positively regulates GBM stemness by depolarizing the RMP and suppressing the ERK signaling pathway. Of note, in vivo proliferation assessment confirmed the increased susceptibility to TMZ following pharmacological blockade of Nav. CONCLUSIONS: This insight positions Nav as a promising prognostic biomarker and therapeutic target for GBM patients, particularly in conjunction with temozolomide treatment.

Sexual and Reproductive Health and Education of Adolescents during COVID-19 Pandemic, Results from "Come Te La Passi?"-Survey in Bologna, Italy.

Social distancing measures adopted to face the COVID-19 pandemic had a detrimental impact on adolescent education and their interaction with peers and adults, secondary to the limitation of school and recreational activities, with repercussions on social and sexual life. The "Come te la passi?" ("How is it going?") study, performed in the Metropolitan City of Bologna (Italy), aimed at investigating the type of information sources adopted by adolescents for their sexual and reproductive health (SRH) knowledge and education, the age of their sexual debut, and the way in which the COVID-19 pandemic affected their relationships and sexual life in order to help local health care professionals and educators designing SRH education programs. A purposely designed online survey was administered during the COVID-19 pandemic to 378 high school students (age > 14 yo) in July 2021. Based on the study results, the most common source of SRH education was the web, followed by peers (friends). A total of 61.3% of 17-year-olds already had sexual intercourse, and 90% of 15-year-olds had experienced romantic or sexual attraction. For 58.2% of the adolescents, the COVID-19 pandemic had negative effects on their relationships/sexual life. The current research emphasizes the need to involve health care professionals and educators in structured programs to promote SRH education tailored to adolescents' needs and started from early ages.

Physical Well-Being of Children and Adolescents during the SARS-CoV-2 Pandemic: Findings from the "Come te la Passi?" Cross Sectional Survey in Bologna, Italy.

BACKGROUND: The COVID-19 had a strong impact on the physical and general well-being of the youngest. In Italy, citizens were forced to change their habits, especially during the national lockdown, causing increased levels of sedentary and unhealthy behaviors. "Come te la passi?" was a cross-sectional study aimed at investigating changes in the physical activity levels (PA) and well-being of children and adolescents in the City of Bologna. METHODS: An anonymous survey was administered to parents/guardians of children and adolescents aged 6-18 years. RESULTS: 1134 questionnaires were collected during June 2021; 457 (40.3%) were females, and the mean age was 13.0 ± 3.4 years. Regarding the general well-being perception, 61.3% of the participants reported concerns about the future, 46.3% reported sleep difficulties, and 72.8% reported experiencing attention difficulty, with higher percentages among adolescents. Considering the PA frequency, an overall reduction was found, with the percentage of those who rarely did PA and those who frequently did PA both increasing. No gender differences were found. CONCLUSIONS: Our findings suggest that the current pandemic has strongly impacted the well-being of children and adolescents. It appears to have primarily affected adolescents, with a significant reduction in PA levels, even after the end of the national lockdown.