Autosomal dominant hyper-IgE syndrome (AD-HIES) is linked to dominant negative mutations of the STAT3 protein whose molecular basis for dysfunction is unclear and presenting with a variety of clinical manifestations with only supportive treatment. To establish the relationship between the impact of STAT3 mutations in different domains and the severity of the clinical manifestations, 105 STAT3 mutations were analyzed for their impact on protein stability, flexibility, function, and binding affinity using in Silico approaches. Our results showed that 73% of the studied mutations have an impact on the physicochemical properties of the protein, altering the stability, flexibility and function to varying degrees. In particular, mutations affecting the DNA binding domain (DBD) and the Src Homology 2 (SH2) have a significant impact on the protein structure and disrupt its interaction either with DNA or other STAT3 to form a heterodomain complex, leading to severe clinical phenotypes. Collectively, this study suggests that there is a close relationship between the domain involving the mutation, the degree of variation in the properties of the protein and the degree of loss of function ranging from partial loss to complete loss, explaining the variability of clinical manifestations between mild and severe.

Objective: This study investigates the relationship between vitamin D levels and asthma control in children. Methods: A total of 100 Moroccan children (2-16 years) with asthma were assessed for serum vitamin D levels using LC/MS-MS. Asthma control was evaluated according to the GINA guidelines and the C-ACT Test. Results: Among the participants, 69% had well-controlled asthma, while 31% exhibited partially controlled or uncontrolled asthma. Despite a high prevalence of vitamin D deficiency, no significant correlation was found between vitamin D levels and asthma control. Multivariate analysis, adjusting for age, BMI, and sex, confirmed that there was no significant association between vitamin D levels and asthma control (OR = 1.02; 95% CI: 0.90-1.16, P = .72). Conclusions: Children with asthma have a high incidence of vitamin D deficiency. However, the results are not consistently in favor of a correlation between vitamin D levels and the level of asthma control.

Fish allergy is a significant global health concern and often leads to persistent and potentially severe hypersensitivity reactions. The molecular heterogeneity of fish allergens poses challenges for developing broadly applicable immunotherapies. In this study, an integrated immunoinformatics pipeline was used to design a multi-epitope vaccine construct targeting three major fish allergens: parvalbumin, enolase, and aldolase. Predicted B-cell and T-cell epitopes were screened for immunogenicity, non-allergenicity, and lack of toxicity, and the selected peptides were assembled into a 432-amino acid chimeric construct using rationally chosen linkers to facilitate antigen processing. Computational analyses predicted the construct to exhibit favorable physicochemical properties, including stability, solubility, and a broad theoretical population coverage. Docking and molecular dynamics simulations suggested a potential interaction with Toll-like receptor 4, offering preliminary insight into possible innate immune engagement. As these findings are entirely in silico, they represent a theoretical framework; experimental validation is necessary to determine the construct’s biological behavior, safety, and immunological relevance.

Introduction: Immune checkpoint blockade targeting PD-1/PD-L1 has revolutionized cancer treatment; however, resistance remains a major clinical challenge. V-domain Immunoglobulin Suppressor of T cell Activation (VISTA), a B7 family member with high expression in tumor-infiltrating lymphocytes of ovarian cancer, has emerged as a promising alternative target for immunotherapeutic intervention. Materials and Methods: We performed in silico screening of 9,397 DrugBank compounds against PD-L1 and VISTA using AutoDock Vina. The top candidates based on docking scores were assessed through 100 ns molecular dynamics simulations, and binding free energies were calculated via MM-PBSA. Results: DB15637, DB12867, and DB06744 showed the strongest PD-L1 binding affinities (−7.33 to −7.87 kcal/mol) with average RMSD values of 8.89 Å, 8.94 Å, and 7.57 Å, respectively. DB00321 exhibited the highest affinity for VISTA (−7.31 kcal/mol) with an RMSD of 6.18 Å, maintaining stable interactions with key residues throughout the simulation. Discussion: The identified compounds demonstrated favorable docking scores, dynamic stability, and binding free energies, suggesting their potential as PD-L1 and VISTA inhibitors. Dual checkpoint targeting could enhance antitumor immune responses in ovarian cancer, where both proteins contribute to immune evasion. Conclusion: This in silico study identified promising candidates for PD-L1 and VISTA inhibition. These findings provide a computational basis for further experimental validation to confirm their therapeutic potential in the treatment of ovarian cancer.