Zinc regulates a specific subpopulation of VEGFA + microglia to improve the hypoxic microenvironment for functional recovery after spinal cord injury.

INTRODUCTION: Spinal cord injury (SCI) is a central nervous system injury that is primarily traumatic and manifests as autonomic dysfunction below the level of injury. Our previous studies have found that zinc ions have important effects on the nervous system and nerve repair, promoting autophagy and reducing inflammatory responses. However, the role of zinc ions in vascular regeneration is unclear. AIMS: We investigated the effect of zinc ions after spinal cord injury from the perspective of a hypoxic microenvironment, and elucidated the role of VEGF-A secreted by microglia for vascular regeneration after spinal cord injury, providing new ideas for the treatment of spinal cord injury. RESULTS: Zinc promotes functional recovery after spinal cord injury by regulating VEGF-A secretion from microglia. On the one hand, VEGF-A secreted by microglia promotes angiogenesis through the PI3K/AKT/Bcl-2 pathway and improves the hypoxic microenvironment after spinal cord injury. On the other hand, VEGF-A secreted by microglia was positively correlated with platelet endothelial cell adhesion molecule-1 (CD31), and zinc could increase the association between microglia and blood vessels. CONCLUSION: Zinc promoted microglia secretion of VEGF-A, increased vascular endothelial cell proliferation and migration through the PI3K/AKT/Bcl-2 pathway, and inhibited microglia apoptosis.

Cytokine Regulation and Fast Inflammation Resolution in Early Rheumatoid Arthritis by Cerium-Modified Gold Nanoclusters.

Rheumatoid arthritis (RA) is an incurable chronic disorder that may induce autoinflammation and serious pain in the joints. Early diagnosis and treatment are important for RA prognosis. However, there is a lack of effective and objective diagnostic approaches. Levels of several immunity cytokines were found to change for patients with early RA, including IL-6, TNF-α, and IL-17 in serum. We assumed a combined change of these cytokines could predict early RA, and a total of 37 outpatients were found. After these patients with early symptoms had been followed for more than one year, 32 clinical cases of RA were diagnosed. The accuracy rate of the current method is >86%. We assumed the symptom relief could be achieved by regulating these cytokines and serum lipid-associated indicators. Thereafter, (R)-dihydrolipoic acid (R-DHLA)-stabilized gold nanoclusters (AuNCs) without (R-DHLA-AuNCs) and with cerium modification (R-DHLA-AuNCs-Ce) were employed for treatment of the RA rat model in vitro and in vivo. R-DHLA-AuNCs-Ce exhibited extraordinary reactive oxygen species-scavenging and anti-inflammation effects by regulating macrophage polarization, which was found to be more effective than methotrexate. The inflammation response of the joint microenvironment was also reduced with an exciting efficiency. By complex analysis of the pro-inflammatory cytokines and activity period indicators in vivo and in vitro, we concluded that macrophage-mediated inflammation exacerbated autoimmunity, which fully relieved the symptoms after administration of R-DHLA-AuNCs-Ce to RA rats.