Nicotinamide

The persistent challenge of diabetic wound healing arises from chronic inflammation, which disrupts the immunometabolic microenvironment. This dysregulated microenvironment exhibits remarkable chirality, but how the stereochemical specificity governs host immunometabolism networks remains elusive. In this study, we engineered chiral gold nanoparticles (L/D-AuNPs) to modulate immunometabolic interactions, thereby significantly promoting diabetic wound healing. To align with the chiral characteristics of the vimentin intermediate filaments (VIFs), L/D-AuNPs with mirror-symmetric windmill-like configurations were synthesized using a seed-mediated growth method. In diabetic murine wounds, L-AuNPs demonstrated superior therapeutic efficacy, enhancing wound healing rate by 29 % compared to the control group. Mechanistic studies revealed that L-AuNPs upregulated the expression of the intermediate filaments vimentin, enhancing fibroblast migration. Concomitant mechanotransduction activated the TGF-β/Slug signaling axis, driving nicotinamide metabolic reprogramming in fibroblasts, which subsequently polarized macrophages toward an anti-inflammatory M2 phenotype. This immunometabolic crosstalk was further validated by single-cell transcriptomic profiling of diabetic patient skin specimens. Based on this finding, we combined L-AuNPs with exogenous nicotinamide, which further accelerated wound regeneration through a significant synergistic effect. This study reveals that chiral AuNPs can promote tissue repair by modulating immunometabolic interactions, providing a novel therapeutic strategy for diabetic wound healing.

Colorectal cancer (CRC) is a highly prevalent disease that represents a major global health burden. Ferroptosis has gained significant attention in recent years as a potential target for cancer therapy. Meanwhile, microRNAs (miRNAs) have emerged as key regulators of gene expression, with the potential to influence various cellular pathways and functions, including those involved in cancer development and treatment. In this study, we employed a systems biology approach to leverage the FerrDb database and to identify key genes involved in the ferroptosis pathway. Then, we utilized the NCBI Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) associated with ferroptosis in CRC. The miRNet platform was used to identify miRNAs that target ferroptosis-associated genes in CRC. Additionally, we explored the Therapeutic Target Database (TTD) and Drug Gene Interaction Database (DGIdb) to identify approved drugs that could potentially modulate the identified targets. Our analysis identified EZH2, G6PD, PARP1, RRM2, SCD, and SLC7A11 as key suppressor genes that are dysregulated in CRC and are also recognized as approved drug targets. Furthermore, we identified hsa-miR-423-5p, hsa-miR-93-5p, hsa-miR-15a-5p, miR-103a-3p, and hsa-miR-16-5p as the five top miRNAs that show the highest number of connections to genes involved in the ferroptosis pathway. Interestingly, we also found that medications such as prasterone, tazemetostat, isoxyl, gemcitabine, ponsegromab, scx-2023, and nicotinamide could potentially be used in combination with the identified miRNAs to target ferroptosis in CRC. To further validate the stability and reliability of the predicted protein-ligand interactions, molecular dynamics (MD) simulations and MM-PBSA analyses were performed on selected top-ranking complexes, which confirmed their stable and favorable binding and supported the robustness of our docking results. These findings suggest that targeting these miRNAs and their associated genes, along with using the identified drugs, could be a promising strategy for CRC treatment, leveraging the potential of ferroptosis-inducing therapies.