Skin is the first line of defence between the human body and the outside world, and it is constantly exposed to external injuries and wounds for a variety of reasons. Collagen is a structural protein of the extracellular matrix and an important component of the dermis. As a wound dressing, collagen not only provides nutrients to wounds but also enhances the immune response in the pre-healing phase, making it an excellent biomaterial for healing. In this study, we used electrospinning and freeze-drying technology to prepare a Bovine Achilles Tendon Collagen (BATC) electrospun composite membrane and a BATC freeze-dried composite membrane using BATC as a substrate supplemented with 16.7% Polyethylene oxide (PEO) and 0.2% Kukoamine B (KuB). The physicochemical properties and biocompatibility of the BATC composite membrane were verified via scanning electron microscopy, Fourier-transform infrared spectroscopy, and DSC analysis and by measuring the DPPH radical-scavenging capacity, water absorption, water retention, in vitro drug release, and extract cytotoxicity. The BATC composite membrane was found to have a significant effect on skin wound healing, especially in the middle stage of healing, in a mouse full-thickness skin injury model. The BATC/PEO/KuB electrospun composite membrane (EBPK) had the best capacity for promoting wound healing and can be used as a wound dressing for in-depth research and development, and KuB, a monomer component with a clear structure and mechanism of action, can be used as a candidate component of composite dressings.
Free bacterial lipopolysaccharide (LPS) is generally removed from the bloodstream through hepatic uptake via TLR4, the LPS pattern recognition receptor, but mechanisms for internalization and clearance of conjugated LPS are less clear. Kukoamine B (KB) is a novel cationic alkaloid that interferes with LPS binding to TLR4. In this study, KB accelerated blood clearance of LPS. KB also enhanced LPS distribution in the hepatic tissues of C57 BL/6 mice, along with LPS uptake in primary hepatocytes and HepG2 cells. By contrast, KB inhibited LPS internalization in Kupffer and RAW 264.7 cells. Loss of TLR4 did not affect LPS uptake into KB-treated hepatocytes. We also detected selective upregulation of the asialoglycoprotein receptor (ASGPR) upon KB treatment, and ASGPR colocalized with KB in cultured hepatocytes. Molecular docking showed that KB bound to ASGPR in a manner similar to GalNAc, a known ASGPR agonist. GalNAc dose-dependently reduced KB internalization, suggesting it competes with KB for ASGPR binding, and ASGPR knockdown also impaired LPS uptake into hepatocytes. Finally, while KB enhanced LPS uptake, it was protective against LPS-induced inflammation and hepatocyte injury. Our study provides a new mechanism for conjugated LPS hepatic uptake induced by the LPS neutralizer KB and mediated by membrane ASGPR binding.
危险品化学品经营许可证（带存储）