The surface modification of long carbon fiber reinforced polyether ether ketone with bioactive composite hydrogel for effective osteogenicity.

Long carbon fiber reinforced polyether ether ketone (LCFRPEEK) is fabricated using a three-dimensional (3D) needle-punched method in our previous work, which is considered as a potential orthopedic implant due to its high mechanical strength and isotropic properties, as well as having an elastic modulus similar to human cortical bone. However, the LCFRPEEK has inferior integration with bone tissue, limiting its clinical application. Thus, a facile surface modification method, using gelatin methacrylate/polyacrylamide composite hydrogel coating (GelMA/PAAM) loading with dexamethasone (Dex) on our newly-developed LCFRPEEK composite via concentrated sulfuric acid sulfonating and ultraviolet (UV) irradiation grafting methods, has been developed to tackle the problem. The results demonstrate that the GelMA/PAAM/Dex coating modified sulfonated LCFRPEEK (SCP/GP/Dex) has a hydrophilicity surface, a long-term Dex release capability and forms more bone-like apatite nodules in SBF. The SCP/GP/Dex also displays enhanced cytocompatibility and osteogenic differentiation in terms of rat bone marrow mesenchymal stem cells (rBMSCs) responses in vitro assay. The in vivo rat cranial defect assay confirms that SCP/GP/Dex boosts bone regeneration/osseointegration, which significantly improves osteogenic fixation between the implant and bone tissue. Therefore, the newly-developed LCFRPEEK modified via GelMA/PAAM/Dex bioactive coating exhibits improved biocompatibility and osteogenic integration capability, which has the basis for an orthopedic implant for clinical application.

Integrated Network Pharmacology and Metabolomics Analysis of the Therapeutic Effects of Zi Dian Fang on Immune Thrombocytopenic Purpura.

Current hormone-based treatments for immune thrombocytopenic purpura (ITP) are associated with potentially serious adverse reactions. Zi Dian Fang (ZDF) is a multi-target Traditional Chinese Medicine (TCM) used to treat both the symptoms and root causes of ITP, with fewer side effects than hormone-based treatments. This study analysis of the therapeutic effects of ZDF on ITP from three aspects: platelet proliferation, immunoregulation, and inflammation. After detection of 52 chemical constituents of ZDF by UPLC-Q-TOF/MS, The main targets and pathways affected by ZDF were screened by network pharmacology and verified by Western blot and ELISA. Meanwhile, metabolomics analysis were applied to a mouse model of ITP to identify and screen endogenous terminal metabolites differentially regulated by ZDF. Integrated network pharmacology and metabolomics analysis of the therapeutic effects of ZDF on ITP may be as follows: ZDF counteracts ITP symptoms mainly by inhibiting Ras/MAPKs (Ras/Mitogen-activated protein kinases) pathway, and the expression of upstream protein (Ras) and downstream protein (p-ERK, p-JNK, p-p38) were inhibited, which affects the content of effect index associated with proliferation (Thrombopoietin, TPO; Granulocyte-macrophage colony stimulating factor, GM-CSF), inflammation (Tumor necrosis factor-α, TNF-α; Interleukin-6, IL-6), immune (Interleukin-2, IL-2; Interferon-gamma, IFN-γ; Interleukin-4, IL-4), so that the body's arginine, Δ12-prostaglandin j2 (Δ12-PGJ2), 9-cis-Retinoic Acid, sphingosine-1-phosphate (S1P), oleic acid amide and other 12 endogenous metabolites significantly changes. Considering the established safety profile, the present study suggests ZDF may be a useful alternative to hormone-based therapies for the treatment of ITP.

Research on the hepatotoxicity mechanism of citrate-modified silver nanoparticles based on metabolomics and proteomics.

Citrate-modified silver nanoparticles (AgNP-cit) have received extensive attention due to their excellent antimicrobial properties. However, these particles tend to migrate in vivo, thereby entering the blood circulatory system in granular form and accumulating in the liver, causing toxic reactions. However, the mechanism underlying AgNP-cit toxicity is not yet clear. Thus, we adopted a tandem mass tag (TMT)-labeled quantitative proteomics and metabolomics approach to identify proteins and small molecule metabolites associated with AgNP-cit-induced liver damage and constructed interaction networks between the differentially expressed proteins and metabolites to explain the AgNP-cit toxicity mechanism. AgNP-cit resulted in abnormal purine metabolism mainly by affecting xanthine and other key metabolites along with pyruvate kinase and other bodily proteins, leading to oxidative stress. AgNP-cit regulated the metabolism of amino acids and glycerol phospholipids through glycerol phospholipids, CYP450 enzymes and other key proteins, causing liver inflammation. Via alanine, isoleucine, L-serine dehydratase/L-threonine deaminase and other proteins, AgNP-cit altered the metabolism of glycine, serine and threonine, cysteine and methionine, affecting oxidation and deamination, and ultimately leading to liver damage. This work clearly explains toxic reactions induced by AgNP-cit from three perspectives, oxidative stress, inflammatory response, and oxidation and deamination, thus providing an experimental basis for the safe application of nanomaterials.