Aim: Behçet’s disease (BD) is a chronic, inflammatory disease effecting multiple organs. Vascular involvement is a major cause of morbidity and mortality in BD patients. Though clinically well-defined, there is limited information related to disease pathogenesis and vascular incidences in this patient group. The aim of the current study is to investigate the unique metabolic signatures of BD patients with vascular involvement (VBD). Methods: Metabolomic profiling was performed on serum samples of 48 BD patients (18 with vascular involvement) and 40 healthy controls using gas chromatography-mass spectrometry (GC-MS) based untargeted metabolomics analysis. Multivariate and univariate statistical analyses were performed to find altered metabolites and pathways. Results: Untargeted metabolomics results showed that a total of 168 metabolites were identified. The comparison between the groups of BD, vascular involvement in BD and the healthy control group showed that altered amino acid and oxidative stress pathways, especially with glutathione synthesis could be an important stage for developing BD. Conclusion: In the present work, the untargeted metabolomics approach provided new molecular insights for a better understanding of BD pathogenesis and also developing vascular involvement in BD at the metabolite level. The results showed that vascular involvement in BD could be highly linked with amino acid metabolism and also the antioxidant system and these disease-related pathways could be evaluated with further experiments for diagnosis and prognosis of BD and also for vascular involvement in BD.

The stiffness of the tumor microenvironment (TME) is dynamic and drives metabolic reprogramming in cancer cells as a consequence of tumor progression. To demonstrate the possibility to modulate the mechano-metabolomic profile of breast cancers by tuning the mechanical property and dimensionality of extracellular matrices (ECMs), we cultured triple-negative MDA-MB-231 and luminal MCF-7 cells on 2D and in 3D hydrogels based on tyramine functionalized hyaluronic acid (HTA). Using high-throughput metabolomics analyses, we established that we can differentially regulate breast cancer mechano-metabolome. The stiff hydrogels resulted in upregulated lipid and amino acid metabolism along with increasing malignancy and chemoresistancy. Reprogramming in glucose metabolism is primarily observed in cells seeded on 2D hydrogels, whereas modifications in amino acid metabolism is predominant in cells embedded in 3D stiff hydrogels. These findings suggest that matrix stiffness and dimensions have decisive roles in reprogramming breast cancer metabolome, which is the hallmark of breast cancer development and progression.