Tumor necrosis factor-α is a common cytokine that increases in inflammatory processes, slows the differentiation of bone formation, and induces osteodystrophy in the long-term inflammatory microenvironment. Our previous study confirmed that the Elongation protein 2 (ELP2) plays a significant role in osteogenesis and osteogenic differentiation, which is considered a drug discovery target in diseases related to bone formation and differentiation. In this study, we applied an in silico virtual screening method to select molecules that bind to the ELP2 protein from a chemical drug molecule library and obtained 95 candidates. Then, we included 11 candidates by observing the docking patterns and the noncovalent bonds. The binding affinity of the ELP2 protein with the candidate compounds was examined by SPR analysis, and 5 out of 11 compounds performed good binding affinity to the mouse ELP2 protein. After in vitro cell differentiation assay, candidates 2# and 5# were shown to reduce differentiation inhibition after tumor necrosis factor-α stimulation, allowing further optimization and development for potential clinical treatment of inflammation-mediated orthopedic diseases.
Background: In recent years, mitochondrial dysfunction has been extensively studied and published, but research in the effects of mitochondrial dysfunction on bone metabolism and related diseases is only just beginning. Furthermore, no studies have been carried out to systematically illustrate this area from a scientometric point of view. The goal of this research is to review existing knowledge and identify new trends and possible hotspots in this area.Methods: All publications related to the relationship between mitochondrial dysfunction and bone metabolism and related diseases during 2003 to 2022 are searched at the Web of Science Core Collection (WoSCC) on May 7, 2022. Four different analytical tools: VOSviewer 1.6.18, CiteSpace V 6.1, HistorCite (12.03.07) and Excel 2021 were used for the scientometric research.Results: The final analysis included 555 valid records in total. Journal of Biological Chemistry is the most famous journal in this field. China, the United States, and Korea are the most productive countries. Blanco FJ, and Sun L are the main researchers with significant academic influence. Current research hotspot are basic research on mitochondrial dysfunction and prevention or treatment of bone metabolism related diseases. Conclusion: The study of the consequences of mitochondrial dysfunction on bone metabolism and associated diseases is advancing rapidly. A number of prominent researchers have published extensive literature and are widely cited. Future research in this area will focus on oxidative stress, aging, gene expression, and the pathogenesis of bone metabolism-related diseases.
Open reduction internal fixation technique has been generally accepted for treatment of complex humeral fractures. Traditional proximal humeral locking plate design (PHILOS) have been reported in clinical or biomechanical researches, while presently the spiral plate design has been introduced improved biomechanical behavior over conventional designs. In order to objectively realize the multi-directional biomechanical performances and minimally invasive surgery for humeral plate designs, a current conceptual finite element analysis has been conducted with identical cross-sectional features for humeral plates. The conceptual lateral, and spiral humeral plate models were constructed for virtual reduction and fixation to the multiple fractures of the humerus. Mechanical load cases including axial compression, counterclockwise torsion and anterior bending have been applied for confirming the multi-directional structural stability and implant safety in biomechanical perspective. Results revealed that the lateral humeral plate model showed lower equivalent (von-Mises) stress under counterclockwise torsion, while the spiral humeral plate model performed greater rigidity and lower equivalent (von-Mises) stress under other loading cases. Four models represented similar structural stiffness under bending load. Under the different mechanical load cases, the spiral humeral plate model revealed comparable results with acceptable multi-directional biomechanical behavior. The concept of spiral humeral plate design is worth considering in practical application in clinics. Implant safety and stability should be further investigated by evidences in future mechanical tests and clinical observations.
The purpose of this case–control study was to examine possible links between NLRP3 gene polymorphisms and the risk of developing posttraumatic osteomyelitis (PTOM) in the Chinese population. A total of 306 patients with PTOM and 368 normal controls were genotyped for NLRP3 (rs35829419, rs10754558, rs7525979, rs4612666), ELP2 (rs1785929, rs1789547, rs1785928, rs12185396, rs681757, rs8299, rs2032206, rs559289), STAT3 (rs4796793, rs744166, rs1026916, rs2293152, rs1053004), CASP1 (rs501192, rs580253, rs556205, rs530537), NFKBIA (rs696), NFKB1 (rs4648068), CARD8 (rs204321), and CD14 (rs2569190) using the genotyping technique SNaPshot. The genotype distributions of NLRP3 gene rs10754558 (p = 0.047) and rs7525979 (p = 0.048) significantly differed between the patients and the healthy controls. Additionally, heterozygous models indicated a significant association between NLRP3 rs10754558 and the likelihood of developing PTOM (OR = 1.600, p = 0.039), as did recessive and homozygous models of NLRP3 rs7525979 (OR = 0.248, p = 0.019 and 0.239, p = 0.016, respectively). Collectively, our findings suggest that, in the Chinese population, the risk of developing PTOM was increased by the association between NLRP3 rs10754558 and rs7525979. Therefore, our findings may provide novel insights and guidance in the prevention and development of PTOM.
Introduction: The induced membrane technique (IMT) is a two-stage procedure dedicated to reconstruction of bone defects of the limbs. The aim of this study was to investigate the effect of IMT in the treatment of infected tibial bone defect. Patients and methods: A retrospective study was performed among the patients treated using IMT for infected tibial bone defect between 2017 and 2020. The complications were recorded, and the bone defect union and the functional results were evaluated by Paley method. All patients were followed up for at least one year. Results We included 12 patients (11 males) with a mean age of 44.5 years (range 19 to 65). The mean length of bone defect was 26.7 mm (range 10 to 60). The mean interval between the stage one and the stage two of the procedure was 11.8 weeks (range 4 to 32). At a mean follow-up of 18.08 months (range 12 to 32), bone union was achieved in all cases in a mean time of 8 months (range 5 to 16) without infection recurrence, where one patient received additional bone grafting. The joint function recovered well for the patients and the rate of functionally excellent and good results was 9/12. Conclusion IMT in the treatment of infected tibial bone defect offers the advantages of simple operation, rapid healing of bone defects, and low recurrence rate of infection.
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