RESUMEN
Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults. The high levels of glucose trigger multiple intracellular oxidative stress pathways, such as POLDIP2, resulting in excessive reactive oxygen species (ROS) production and increased expression of vascular cell adhesion molecule-1 (VCAM-1), hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF), causing microvascular dysfunction. Dihydromyricetin (DMY) is a natural flavonoid small molecule antioxidant. However, it exhibits poor solubility in physiological environments, has a short half-life in vivo, and has low oral bioavailability. In this study, we present, for the first time, the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles (Fe-DMY NCPs), formed by combining DMY with low-toxicity iron ions. In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose, scavenge excess ROS, and improve pathological features of DR, such as retinal vascular leakage and neovascularization. Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H2O2 signaling pathway and downregulate vital vascular function indicators such as VCAM-1, HIF-1α, and VEGF. These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent, with the potential as a novel multimeric drug for DR therapy.
RESUMEN
Objective To investigate the effect of artesunate (ART) on T lymphocyte immune function in patients with lung cancer. Methods Fifteen healthy people (NC group) and twenty-one lung cancer patients (LC group) were randomly selected to collect their clinical information and isolate peripheral blood mononuclear cells (PBMCs). After 24 hour-treatment of PBMCs with ART, the median lethal concentration (LC50) and the optimal concentration of ART induced high expression of CD39 and CD279 in T cell membrane were determined by flow cytometry (FCM). Following the induction of ART with the best concentration, the expression levels of CD39 and CD279 on CD8+ and CD4+ T cells in NC group, and the expression levels of CD39, CD279, CD38, CD28, granzyme B (GrzB), perforin (PerF), interferon γ(IFN-γ) and interleukin-2 (IL-2) on CD8+ and CD4+ T cells in LC group were detected by FCM. Results LC50 and optimal concentration of ART were 522 µmol/L and 200 µmol/L, respectively. Compared with the NC group, the baseline expression levels of CD279 on CD8+ and CD4+ T cells in LC group was significantly higher. Moreover, the expression levels of CD39 increased significantly after inducing 200 µmol/L ART, in the CD8+ and CD4+ T cell of NC groups; In CD8+ and CD4+ T cells of LC group, the expression of CD39, CD279 and GrzB increased significantly, while that of IL-2 decreased markedly. No significant difference was detected in the expression levels of CD38, CD28, IFN-γ and PerF. The clinical factors that promote the expression of CD39 on CD8+ T cells induced by ART showed no radiotherapy. The clinical factors that promote the expression of CD279 on CD8+ T cells induced by ART include age>60 years old, lymphocyte count>1.26×109/L, NLR<5, radiotherapy, 0.29×109/L ≤monocyte count ≤0.95×109/L. Conclusion The expression of CD279 on T lymphocytes is higher in lung cancer patients; ART induces the upregulation of CD8+ and CD4+T cells CD39, CD279 and GrzB in lung cancer patients, thus regulating the immune function of T cell subsets.
