ABSTRACT
Diabetic ulcer is recognized as a chronic nonhealing wound, often associated with bacterial infection and tissue necrosis, which seriously affect patients' health and quality of life. The traditional treatment methods exist some problems, such as bacterial resistance and secondary trauma, so it is urgent to find new methods to meet the requirements of diabetic ulcer treatment. In this study, we prepared a drug delivery system (DFO@CuS nanoparticles) based on hollow copper sulfide (CuS) nanoparticles loaded with deferoxamine (DFO), which realized the synergistic therapy of promoting angiogenesis and photothermal antibacterial. The morphological structure and particle size distribution of DFO@CuS nanoparticles were characterized by transmission electron microscopy and particle size analyzer, respectively. The antibacterial effect of DFO@CuS nanoparticles was evaluated by the plate coating method. The effects of DFO@CuS nanoparticles on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evaluated by CCK-8 (cell counting kit-8) assay, cell scratch assay, and tube formation assay. The results showed that DFO@CuS nanoparticles were hollow and spherical in shape with an average particle size of (200.9 ± 8.6) nm. DFO@CuS nanoparticles could effectively inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) under near-infrared (NIR) light irradiation. DFO@CuS nanoparticles showed negligible cytotoxicity and effective acceleration of cell migration and tube formation in a certain concentration range. In conclusion, the prepared DFO@CuS nanoparticles exhibit good photothermal antibacterial properties and pro-angiogenic effects, providing a basis for their application in the treatment of diabetic ulcer.
ABSTRACT
Hypoxia-inducible factors (HIFs) are one of the primary transcription factors regulating oxygen balance, and their stability is determined by the hydroxylation state of the prolyl hydroxylase domain (PHD) that is sensitive to oxygen. In recent years, studies have shown that HIFs-prolyl hydroxylases (PHDs) oxygen-sensing pathway is involved in the process of cellular ferroptosis. Ferroptosis, a new type of cell death, different from necrosis, apoptosis, necrotizing apoptosis, and pyroptosis, is essentially a programmed death caused by the accumulation of iron-dependent lipid peroxides in cells. This paper focuses on the role and mechanism of the HIFs-PHDs oxygen-sensing pathway in cellular ferroptosis involved in nerve diseases, tumors, lung injury, and chemical nerve damage from three aspects of iron metabolism, lipid metabolism, and glutathione (GSH) synthesis/metabolism. This review will provide a theoretical basis and new ideas for the development of novel drugs targeting the HIFs-PHDs oxygen-sensing pathway and capable of regulating ferroptosis for the treatment of diseases related to ferroptosis such as nervous system diseases and tumors.
Subject(s)
Apoptosis , Basic Helix-Loop-Helix Transcription Factors , Ferroptosis , Oxygen , Prolyl HydroxylasesABSTRACT
This study aims to establish a novel gene-activated matrix that mimics the structure and function of extracellular matrix (ECM-m-GAM). The structure, mechanical property and release profile were also characterized. Firstly, the liposome/DNA lipoplex (LPD) was modified with cell penetrating peptide TAT. The obtained TAT-LPD was then mixed with RGD grafting hyaluronic acid solution. After addition of the matrix metalloproteinase (MMPs) sensitive crosslinker (HS-MMP-SH), hyaluronic acid was crosslinked and TAT-LPD was encapsulated in the subsequently formed hydrogel. As a result, the cell adhesion factor RGD, MMPs sensitive substrate and the efficient gene transfer vector TAT-LPD were all integrated in the hyaluronic acid hydrogel, which was named as ECM-m-GAM. The release profile of DNA from ECM-m-GAM in different release medium was evaluated with PicoGreen kits. The results suggested that the mean diameter of the spherical TAT-LPD was (263.0 ±4.30) nm. TAT-LPD was successfully encapsulated in ECM-m-GAM, which had the typical porous network structure of hydrogels. The mechanical strength of GAM was enhanced with the increasing of hyaluronic acid content. When the content was 4%, the elastic modulus of GAM reached 1 600 Pa. The highly elastic GAM may be suitable for implantation and tissue regeneration. The DNA release showed significant MMPs sensitive property. Especially, the released DNA still existed in form of nanoparticles. Bone marrow mesenchymal stem cells (BMSCs) were successfully transfected with GAM and the green fluorescent protein was expressed. The results have laid a solid foundation for future study of the cell transfection and tissue regeneration.
ABSTRACT
<p><b>AIM</b>To simulate the inhalation of the C21H27NO and C29H41NO4 molecules, the effective components of methadone and buprenorphine, into carbon nanotubes, and discuss the feasibility of the loading of methadone and buprenorphine into carbon nanotubes.</p><p><b>METHODS</b>The MM + force-field based molecular dynamics (MD) method uas used.</p><p><b>RESULTS</b>The ends-opened carbon nanotubes with diameter larger than 1 or 1.25 nm can initiatively inhale the C21H27 NO or C29H41NO4 molecule, and both two molecules have higher potential energy at the open ends of the carbon tubes than that at the middle of the tubes; the present single-walled nanotubes are very suitable for the loading of methadone and buprenorphine.</p><p><b>CONCLUSION</b>It is possible to make sustained-release detoxification agents with methadone- or buprenorphine-loaded carbon nanotubes.</p>