ABSTRACT
Bacterial infection is a common complication in bone defect surgery, in which infection by clinically resistant bacteria has been a challenge for the medical community. Given this emerging problem, the discovery of novel natural-type inhibitors of drug-resistant bacteria has become imperative. Brucine, present in the traditional Chinese herb Strychnine semen, is reported to exert analgesic and anti-inflammatory effects. Brucine's clinical application was limited because of its water solubility. We extracted high-purity BS by employing reflux extraction and crystallization, greatly improved its solubility, and evaluated its antimicrobial activity against E. coli and S. aureus. Importantly, we found that BS inhibited the drug-resistant strains significantly better than standard strains and achieved sterilization by disrupting the bacterial cell wall. Considering the safety concerns associated with the narrow therapeutic window of BS, a 3D BS-PLLA/PGA bone scaffold system was constructed with SLS technology and tested for its performance, bacteriostatic behaviors, and biocompatibility. The results have shown that the drug-loaded bone scaffolds had not only long-term, slow-controlled release with good cytocompatibility but also demonstrated significant antimicrobial activity in antimicrobial testing. The above results indicated that BS may be a potential drug candidate for the treatment of antibiotic-resistant bacterial infections and that scaffolds with enhanced antibacterial activity and mechanical properties may have potential applications in bone tissue engineering.
ABSTRACT
Electroacupuncture (EA) has been shown to enhance the recovery of symptoms in rheumatoid arthritis (RA); however, the underlying mechanism remains unclear. Both the pathogenesis of RA and the therapeutic effects of EA are closely associated with the metabolic activity of the brain. In this study, we investigated the effect of EA at the "Zusanli" acupoint (ST36) on a rat model of collagen-induced rheumatoid arthritis (CIA). The results demonstrated that EA effectively alleviated joint swelling, synovial hyperplasia, cartilage erosion, and bone destruction in CIA rats. Additionally, the metabolic kinetics study revealed a significant increase in the 13C enrichment of GABA2 and Glu4 in the midbrain of CIA rats treated with EA. Correlation network analysis showed that changes in Gln4 levels in the hippocampus were strongly associated with the severity of rheumatoid arthritis. Immunofluorescence staining of c-Fos in the midbrain's periaqueductal gray matter (PAG) and hippocampus demonstrated increased c-Fos expression in these regions following EA treatment. These findings suggest that GABAergic and glutamatergic neurons in the midbrain, along with astrocytes in the hippocampus, may play vital roles in the beneficial effects of EA on RA. Furthermore, the PAG and hippocampus brain regions hold potential as critical targets for future RA treatments. Overall, this study provides valuable insights into the specific mechanism of EA in treating RA by elucidating the perspective of cerebral metabolism.
