Oxaceprol

Down syndrome (DS) arises from a genetic anomaly characterized by an extra copy of chromosome 21 (exCh21). Despite high incidence of congenital diseases among DS patients, direct impacts of exCh21 remain elusive. Here, we established a robust DS model harnessing human-induced pluripotent stem cells (hiPSCs) from mosaic DS patient. These hiPSC lines encompassed both those with standard karyotype and those carrying an extra copy of exCh21, allowing to generate isogenic cell lines with a consistent genetic background. We unraveled that exCh21 inflicted disruption upon the cellular transcriptome, ushering in alterations in metabolic processes and triggering DNA damage. The impact of exCh21 was also manifested in profound modifications in chromatin accessibility patterns. Moreover, we identified two signature metabolites, 5-oxo-ETE and Calcitriol, whose biosynthesis is affected by exCh21. Notably, supplementation with 5-oxo-ETE promoted DNA damage, in stark contrast to the protective effect elicited by Calcitriol against such damage. We also found that exCh21 disrupted cardiogenesis, and that this impairment could be mitigated through supplementation with Calcitriol. Specifically, the deleterious effects of 5-oxo-ETE unfolded in the form of DNA damage induction and the repression of cardiogenesis. On the other hand, Calcitriol emerged as a potent activator of its nuclear receptor VDR, fostering amplified binding to chromatin and subsequent facilitation of gene transcription. Our findings provide a comprehensive understanding of exCh21’s metabolic implications within the context of Down syndrome, offering potential avenues for therapeutic interventions for Down syndrome treatment.

Auricularia cornea has garnered attention due to its nutrition, culinary applications, and promising commercial prospects. However, there is little information available regarding the metabolic profiling of various colors strains. In this study, 642 metabolites across 64 classes were identified by LC-MS/MS to understand the metabolic variations between white, pink and dark brown strains. Notably, prenol lipids, carboxylic acids and fatty acyls accounted for 46.8 % of the total. Comparative analysis revealed 17 shared differential metabolites (DMs) among them. ACP vs ACW exhibited 17 unique metabolites, including d-arginine and maleic acid, etc. ACP vs ACB showed 5 unique metabolites, with only PS(18:1(9Z)/0:0) demonstrating up-regulation. ACB vs ACW showed 8 unique metabolites, including 4-hydroxymandelic acid and 5'-methylthioadenosine, etc. KEGG enrichment analysis highlighted pathway variations, and MetPA analysis identified key-pathways influencing DMs accumulation in A. cornea. This pioneering metabolomics study offers insights into A. cornea metabolic profiling, potential applications, and guides further research.