Inadequate vascularization is a major challenge in tissue engineering and can lead to the failure of tissue defect repair. Currently, the use of nanomaterials has emerged as a critical strategy for tissue engineering. Nanoparticles can be utilized as additives in composite materials to enhance the development of bone tissue engineering. Niobium (Nb), a transition metal element with notable biocompatibility, has potential in angiogenesis. However, the effect of Nb nanoparticles (a form of niobium in the nanoparticle state) on endothelial cell behavior remains unclear. This study focused on the effect of Nb nanoparticles on the differentiation of tip cells and its in-depth regulatory mechanism. Our results revealed that Nb nanoparticles promoted angiogenesis at an early stage and increased bone regeneration in calvarial bone defects. In addition, Nb nanoparticles activated tip cell differentiation and thereby promoted cell migration and tube formation. Furthermore, we verified that Nb nanoparticles promoted endothelial tip cell formation by activating YAP. Nb nanoparticles regulates YAP through the newly identified upstream regulatory molecules FOXA1 and PAK4. When FOXA1 or PAK4 was inhibited, YAP expression and tip cell activation were inhibited. Thus, Nb nanoparticles promoted angiogenesis by activating endothelial tip cells, and the FOXA1-PAK4-YAP signaling cascade regulated this process. The insights garnered from this study suggest a strategy for tissue engineering and lay a theoretical foundation for the expanded application of Nb nanoparticles in this field.
Li Ying,Wang Lei,Cao Yan,Lu Hujing,Zhou Jiawen,Zhao Panpan,Guan Xinying,Dong Zibo
Neuropathy is a common chronic complication of type 1 diabetes mellitus (T1D), an autoimmune disease in which neuroinflammation is considered a key pathological mechanism. P21-activated kinase 4 (PAK4) is a significant factor in this neuroinflammatory process. Higenamine hydrochloride (HGN) possesses anti-inflammatory properties. This study investigated the effects of HGN on T1D and its potential regulation of neuroinflammation via PAK4. We established a T1D mouse model using an intraperitoneal injection of streptozotocin (STZ), followed by HGN administration. The PAK4 inhibitor PF3758309 was given 2 weeks before the experiment ended. Pathological alterations in brain tissues were examined through Nissl and H&E staining. Cognitive function and behavior were assessed using the Morris water maze, elevated plus maze, and open field tests. Molecular docking, cellular thermal shift analysis (CETSA), drug affinity responsive target stability (DARTS) assays, immunofluorescence, and immunoblotting were employed to investigate the binding of HGN to PAK4, its nuclear translocation, and microglial polarization. HGN mitigated brain damage, memory loss, anxiety, and behavioral dysfunction. It also reduced the levels of proinflammatory cytokines (TNF-α and IL-1β) and markers (CD16b, CD11b, and iNOS). Mechanistically, HGN increased PAK4 stability and inhibited M1 polarization via the CRTC2-CREB pathway. PF3758309 diminished the protective effects of HGN and elevated the serum levels of brain damage indicators (S100β and NSE) and inflammatory factors. HGN effectively reduces neuroinflammation and neurological dysfunction in T1D by targeting PAK4, suggesting its potential as a therapeutic agent for diabetes-related complications. Graphical
危险品化学品经营许可证（带存储）