Background: Vitamin D is essential for overall health, wellbeing and immune system. hypervitaminosis D led to many deleterious effects and increased mortality. This study aimed evaluate the immunomodulatory potential of eugenol (volatile phenolic constituent of clove essential oil obtained from Eugenia caryophyllata) against inflammation induced by vitamin D toxicity. Methods: Vitamin D (100 mg/kg) was orally administered into male albino rats followed by an oral administration of eugenol (100 mg/kg) for two months. Result: Histological results showed Vitamin D intoxication cause distinct alterations such as loss of lobular architecture, fibrosis and necrosis, treatment of eugenol with injected of Vitamin D showed improvement in the histological features of liver tissues. The study showed that a significant upregulation in the TNF-α, IL-2 and iNOS genes expression levels caused by Vitamin D compared to the control group. eugenol treatment caused a significant decreased TNF-α, IL-2 and iNOS activity and down-regulated gene expression levels. In Conclusion, hepatoprotective effects of eugenol through inhibiting pro-inflammation by vitamin D toxicity and increase the activity of the antioxidant defense system.

Background/Objectives: Synovial sarcoma (SS) is a rare and aggressive soft-tissue malignancy characterized by complex molecular alterations and poor prognosis, highlighting the need for targeted immunotherapeutic strategies. This study aimed to design a rational multi-epitope vaccine targeting the FKBP10 oncoprotein to elicit effective immune responses against SS. Methods: Transcriptomic data from the GEO dataset GSE144190, comprising 10 tumor and 9 normal tissue samples, were analyzed to identify differentially expressed genes (DEGs). Results: Our findings revealed significantly upregulated FKBP10 with a log2 fold change of 3.55, baseMean expression of 1521.84, and adjusted p-value of 8.37 × 10⁻²⁶. Mutational analysis across 7782 sarcoma samples indicated a low alteration frequency of ~1.5%, primarily missense variants. Functional mapping showed FKBP10 as a hub interacting with multiple collagen chains and chaperone proteins, implicating its role in extracellular matrix organization and protein folding. Linear B-cell epitope prediction identified 17 epitopes (6–21 amino acids), while T-cell mapping yielded 10 MHC class I and 9 MHC class II high-affinity epitopes, all antigenic (VaxiJen > 0.5) and non-allergenic. A multi-epitope vaccine was constructed incorporating a 50S ribosomal protein L22 adjuvant, linkers, and a 6× histidine tag. Physicochemical analysis showed a molecular weight of 36.43 kDa, pI 6.97, instability index 31.79, aliphatic index 64.88, and GRAVY −0.509, indicating stability and hydrophilicity. Structural modeling validated 82.5% residues in favored regions. Molecular docking revealed strong binding with TLR4 (−9.7 kcal/mol) and TLR9 (−9.4 kcal/mol), and 200 ns molecular dynamics simulations confirmed stable RMSD trajectories, low RMSF at binding residues (<4 Å), persistent hydrogen bonding, compact radius of gyration (38–42 Å for TLR4; ~20 Å for TLR9), favorable total energy (−1400 to −1500 kcal/mol for TLR4; −650 to −720 kcal/mol for TLR9), and stable SASA (~52,000–54,000 Ų). Conclusions: These findings demonstrate that the FKBP10 multi-epitope vaccine is structurally stable, immunogenic, and capable of engaging key innate immune receptors, supporting its potential as a promising immunotherapeutic candidate for synovial sarcoma.

Background/Objectives: Methionine adenosyltransferase 2A (MAT2A) has emerged as a promising therapeutic target in cancers harboring methylthioadenosine phosphorylase (MTAP) deletion. However, the development of potent, drug-like MAT2A inhibitors with favorable pharmacokinetic profiles remains challenging. This study aimed to design, synthesize, and evaluate a library of benzofuran-based oxadiazole derivatives as novel MAT2A inhibitors and to elucidate their molecular basis of action through integrated computational studies. Methods: A series of benzofuran-based oxadiazole derivatives (10a–10j and 16–19) was designed, synthesized, and characterized by ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry (HRMS). All compounds were evaluated for MAT2A inhibitory activity, with AZ-28 used as the reference inhibitor. The most active compounds were subjected to molecular docking, 200 ns molecular dynamics (MD) simulations, density functional theory (DFT) calculations, and in silico ADME/toxicity prediction. No preregistration was applicable, and no animals were used in this study. Results: The synthesized compounds exhibited a broad range of MAT2A inhibition, with IC₅₀ values from 0.0116 ± 0.0020 to 28.77 ± 1.79 μM, benchmarked against AZ-28 (IC₅₀ = 0.0419 ± 0.0032 μM). Compounds 10g (IC₅₀ = 0.0116 ± 0.0020 μM), 10a (IC₅₀ = 0.0883 ± 0.0060 μM), and 19 (IC₅₀ = 0.158 ± 0.015 μM) were the most potent. Docking revealed favorable binding orientations within the MAT2A active site, supported by hydrogen-bonding and hydrophobic interactions. MD simulations showed stable protein–ligand complexes with favorable RMSD profiles, and binding free-energy calculations supported complex stability. DFT analyses (HOMO–LUMO and MEP) provided insight into electronic properties and reactive sites. Furthermore, in silico ADME and toxicity assessments provided preliminary insights into the drug-likeness and pharmacokinetic properties of the studied compounds. Nevertheless, these computational predictions remain preliminary and require experimental validation. Conclusions: Compounds 10g, 10a, and 19 are promising MAT2A inhibitors, with 10g identified as the most favorable lead. These computational predictions remain preliminary and require experimental validation. Further pharmacokinetic, toxicological, and in vivo studies of 10g are warranted.