Harmaline to Human Mitochondrial Caseinolytic Serine Protease Activation for Pediatric Diffuse Intrinsic Pontine Glioma Treatment.

Diffuse intrinsic pontine glioma (DIPG), affecting children aged 4-7 years, is a rare, aggressive tumor that originates in the pons and then spreads to nearby tissue. DIPG is the leading cause of death for pediatric brain tumors due to its infiltrative nature and inoperability. Radiotherapy has only a palliative effect on stabilizing symptoms. In silico and preclinical studies identified ONC201 as a cytotoxic agent against some human cancer cell lines, including DIPG ones. A single-crystal X-ray analysis of the complex of the human mitochondrial caseinolytic serine protease type C (hClpP) and ONC201 (PDB ID: 6DL7) allowed hClpP to be identified as its main target. The hyperactivation of hClpP causes damage to mitochondrial oxidative phosphorylation and cell death. In some DIPG patients receiving ONC201, an acquired resistance was observed. In this context, a wide program was initiated to discover original scaffolds for new hClpP activators to treat ONC201-non-responding patients. Harmaline, a small molecule belonging to the chemical class of ß-carboline, was identified through Fingerprints for Ligands and Proteins (FLAP), a structure-based virtual screening approach. Molecular dynamics simulations and a deep in vitro investigation showed interesting information on the interaction and activation of hClpP by harmaline.

Different In Silico Approaches Using Heterocyclic Derivatives against the Binding between Different Lineages of SARS-CoV-2 and ACE2.

Over the last few years, the study of the SARS-CoV-2 spike protein and its mutations has become essential in understanding how it interacts with human host receptors. Since the crystallized structure of the spike protein bound to the angiotensin-converting enzyme 2 (ACE2) receptor was released (PDB code 6M0J), in silico studies have been performed to understand the interactions between these two proteins. Specifically, in this study, heterocyclic compounds with different chemical characteristics were examined to highlight the possibility of interaction with the spike protein and the disruption of the interaction between ACE2 and the spike protein. Our results showed that these compounds interacted with the spike protein and interposed in the interaction zone with ACE2. Although further studies are needed, this work points to these heterocyclic push-pull compounds as possible agents capable of interacting with the spike protein, with the potential for the inhibition of spike protein-ACE2 binding.

Nutritional Intake of Young Italian High-Level Soccer Players: Under-Reporting is the Essential Outcome.

It is recognized that much of the dietary data on adolescents and athletes is prone to reporting error, mostly through under-reporting. Nevertheless, in the majority of studies assessing the nutritional intake of young soccer players under-reporting has not been taken into consideration. The purpose of this study was to assess the dietary intake of a sample of young male Italian high-level soccer players on two time points to evaluate the degree of under- reporting. Seventy-five male high level soccer players (age range: 15-17 years) completed 4-day food records on two separate occasions (T0; T1, 3 months after T0). Under-reporting was assessed by the ratio of reported estimated energy intake (EEI) to estimated energy expenditure (EEE). Forty- three subjects, whose food records were judged accurate enough both at T0 and T1, were included in the data analysis (inclusion rate 57.3%). No significant weight changes were documented between T0 and T1 and in the two weeks preceding both T0 and T1. Reported mean daily energy intake was significantly lower than mean estimated daily energy expenditure both at T0 and T1 (p < 0.001). The average EEI/EEE ratio was 0.75 + 0.2 both at T0 and T1. It was ≤ 80% in 27 subjects (62.8%) at T0 and in 23 (53.4%) at T1; it reached 50% in 4 subjects both at T0 and T1. The degree of under- reporting of the young soccer players was in line with the available data on this age group. This study emphasizes that under-reporting is a critical issue in the evaluation of young athletes dietary intake, which should be considered in the interpretation of data, particularly when energy inadequacies are reported. Further studies with uniformed methods are needed, in order to reduce the degree of under-reporting, obtain reliable data on the dietary intake of young soccer players and evaluate the efficacy of targeted nutrition education programs. Key pointsUnder-reporting is a critical issue in the evaluation of young athletes' dietary intake, which should be always considered in the interpretation of data.The young athletes' motivation and parents' co-operation are key points that should be enhanced in this kind of studies.The nutritional intakes of young Italian high-level soccer players are likely to be qualitative inadequate, due to excessive cholesterol and very poor fiber intakes.