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The interaction between programmed cell death protein 1 (PD-1) and its ligand PD-L1 plays a crucial role in tumor immune evasion, presenting a critical target for cancer immunotherapy. Despite being effective, current monoclonal antibodies present some drawbacks such as high costs, toxicity, and resistance development. Therefore, the development of small-molecule inhibitors is necessary, especially those derived from natural sources. In this study, benzosampangine is predicted as a promising PD-L1 inhibitor, with potential applications in cancer immunotherapy. Utilizing the high-resolution crystal structure of human PD-L1 (PDB ID: 5O45), we screened 511 natural compounds, identifying benzosampangine as a top candidate with exceptional inhibitory properties. Molecular docking predicted that benzosampangine exhibits a strong binding affinity for PD-L1 (−9.4 kcal/mol) compared with established controls such as CA-170 (−6.5 kcal/mol), BMS-202 (−8.6 kcal/mol), and pyrvinium (−8.9 kcal/mol). The compound's predicted binding efficacy is highlighted by robust interactions with key amino acids (ILE54, TYR56, GLN66, MET115, ILE116, SER117, ALA121, ASP122) within the active site, notably forming 3 Pi-sulfur interactions with MET115—an interaction absents in control inhibitors. In addition, ADMET profiling suggests that over the control molecules, benzosampangine has several key advantages, including favorable solubility, permeability, metabolic stability, and low toxicity, while adhering to Lipinski's rule of five. Molecular dynamic simulations predict the stability of the benzosampangine-PD-L1 complex, reinforcing its potential to sustain inhibition of the PD-1/PD-L1 pathway. MMGBSA analysis calculated a binding free energy (ΔGbind) of −39.39 kcal/mol for the benzosampangine-PD-L1 complex, with significant contributions from Coulombic, lipophilic, and Van der Waals interactions, validating the predicted docking results. This study investigates in silico benzosampangine, predicting its better molecular interactions and pharmacokinetic profile compared with several already known PD-L1 inhibitors. [ABSTRACT FROM AUTHOR]

Introduction: Nutrition plays an integral role in optimizing football players' performance during training sessions and matches and maintaining their overall health throughout the season. This study aimed to evaluate how well the dietary practices of professional and adolescent football players in Morocco during the competitive period met international macronutrient recommendations, and to explore the relationship between their nutritional status and aerobic performance, as measured by the Yo-Yo IRL1 test. Methods: A total of 277 footballers from Morocco's professional league, "Botola-Pro", were monitored over a seven-day (training microcycle) during the competitive period. The dietary intake was assessed through self-reported methods and 24-hour recalls. Relevant body composition was measured with bioelectrical impedance (BI), and aerobic performance was evaluated using the Yo-Yo IR test. Results: The results indicated significant variations in performance and nutritional status across different categories and age groups. The nutritional status of the players didn't match the UEFA recommendations (p < 0.001). We found that higher intake levels of carbohydrates and proteins were positively correlated with the total distance covered by the players (p < 0.001, r = 0.63, R2 = 0.4 for carbohydrates; p < 0.001, r = 0.59, R2 = 0.35 for proteins). Conversely, a higher proportion of energy derived from fats in the diet was negatively correlated with the distance covered (p < 0.001, r = −0.64, R2 = 0.41). Conclusion: These findings suggest that optimizing carbohydrates and protein intake while managing fat consumption is crucial for enhancing sporting performance. This information is essential for tailoring training programs and nutritional regimens based on the competition level. [ABSTRACT FROM AUTHOR]

This work focuses on the leaves and stems of Euphorbia nicaeensis All. to confirm its historical use by the Moroccan population. The phytochemical profile of the plant by HPLC-UV-MS/MS was identified for the first time, and the biological activities of each plant organ was evaluated separately by maceration and ultrasonic-assisted extraction. The evaluation of antioxidant activity based on DPPH assay and hydrogen peroxide scavenging assay showed that leaves could be used as a natural source of antioxidants as they provide a potent antioxidant effect (DPPH IC50 = 23.47±0.62 µg/ml), (H2O2 IC50 = 110.27 ± 3.59 µg/ml) compared to stems. These results were proven by HPLC-UV-MS/MS analysis and revealed that E. nicaeensis leaves are richer in phenolic compounds, especially quercetin and derivatives, known for their antioxidant properties. In contrast, the stems could be considered a potential anti-inflammatory agent considering their solid anti-inflammatory activity. The most potent effects were obtained at a concentration of 2 mg/ml, which induced 83.98% and 82.04% inhibition against bovine albumin and egg albumin denaturation, respectively, compared to the control. In addition, the stem phytochemical profile indicated the presence of some compounds with anti-inflammatory effects, such as fargesin and nuciferine. Likewise, the findings showed that ultrasound-assisted extraction was more effective than maceration. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus type 1 (HIV-1) infection varies substantially among individuals. One of the factors influencing viral infection is genetic variability. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is a genetic factor that has been correlated with different types of pathologies, including HIV-1. The MTHFR gene encodes the MTHFR enzyme, an essential factor in the folate metabolic pathway and in maintaining circulating folate and methionine at constant levels, thus preventing the homocysteine accumulation. Several studies have shown the role of folate on CD4+ T lymphocyte count among HIV-1 subjects. In this case-control study we aimed to determine the association between the MTHFR C677T polymorphism and HIV-1 infection susceptibility, AIDS development, and therapeutic outcome among Moroccans. The C677T polymorphism was genotyped by polymerase chain reaction followed by fragment length polymorphism digestion in 214 participants living with HIV-1 and 318 healthy controls. The results of the study revealed no statistically significant association between MTHFR C677T polymorphism and HIV-1 infection (P  > .05). After dividing HIV-1 subjects according to their AIDS status, no significant difference was observed between C677T polymorphism and AIDS development (P  > .05). Furthermore, regarding the treatment response outcome, as measured by HIV-1 RNA viral load and CD4+ T cell counts, no statistically significant association was found with MTHFR C677T polymorphism. We conclude that, in the genetic context of the Moroccan population, MTHFR C677T polymorphism does not affect HIV-1 infection susceptibility, AIDS development, or response to treatment. However, more studies should be done to investigate both genetic and nutritional aspects for more conclusive results. [ABSTRACT FROM AUTHOR]