Jue Wang, Yingci Xia, Wenxuan Zheng, Wenqin Yuan, Yunying Huang, Yuntao Zhang, Qiong Huang, Kelong Ai
This study reveals that GS eumelanin regulates coagulation homeostasis through its nanostructure and intestinal metabolites. Our results provide a nutritional basis for using natural eumelanin as a functional food ingredient to help manage the risk of postoperative bleeding.
Myocardial infarction causes persistent mitochondrial and metabolic dysfunction that drives adverse cardiac remodeling. Here we develop NAD+-genipin nanomedicine for metabolic balance (NGB), a physiologically adaptive nanomedicine with staged intracellular release. In a mouse myocardial infarction model, NGB preferentially accumulates in ischemic myocardium, rapidly replenishes nicotinamide adenine dinucleotide (NAD+) and subsequently provides mitochondria-associated sustained NAD+-genipin exposure. This phase-linked delivery limits early mitochondrial stress, apoptosis and inflammation and later restores coordination between oxidative phosphorylation, glycolysis and fatty-acid utilization. Mechanistically, NGB supports sirtuin-1-associated oxidative metabolism and suppresses sustained upregulation of the mitochondrial uncoupling protein 2 (UCP2). In hypoxic cardiomyocytes, UCP2 knockdown plus NAD+ supplementation partially reproduces the NGB metabolic phenotype, whereas UCP2 overexpression and sirtuin 1 inhibition reverse distinct components of NGB-mediated respiratory and glycolytic recovery. NGB thereby reduces fibrosis and ventricular remodeling and preserves cardiac function, supporting temporally coordinated metabolic intervention after myocardial infarction.