Polydatin inhibited TNF-α-induced apoptosis of skeletal muscle cells through AKT-mediated p38 MAPK and NF-κB pathways.

Skeletal muscle atrophy severely impacts one's quality of life. The effects and mechanism of polydatin on skeletal muscle atrophy are unclear. This study investigated the effects and mechanism of polydatin on TNF-α-induced skeletal muscle cells. The skeletal muscle cell atrophy model was established by inducing C2C12 cells with TNF-α. Cell viability, IL-1ß levels and cell apoptosis were assessed. The mRNA and protein expression levels of apoptosis-related proteins were measured. Meanwhile, the binding of polydatin to AKT was analyzed by molecular docking. TNF-α reduced cell fusion and viability while up-regulated IL-1ß level and promoted cell apoptosis. TNF-α activated AKT, NF-κB, and p38 MAPK signaling pathways. Polydatin reversed these effects induced by TNF-α, with a low concentration being more effective. Polydatin was predicted to bind to GLY162, PHE161, GLU198, THR195 and GLU191 sites of AKT protein through van der Waals force and conventional hydrogen bonds. Overexpression of AKT led to increased phosphorylation levels of AKT, p38, and p65 proteins, as well as IL-1ß levels and cell apoptosis. Polydatin inhibited TNF-α-induced apoptosis of C2C12 cells by regulating NF-κB and p38 MAPK signaling pathways through AKT. This suggests that polydatin shows promise as a new drug for the treatment of skeletal muscle atrophy.

Modified Baihu decoction therapeutically remodels gut microbiota to inhibit acute gouty arthritis.

Background: Acute gouty arthritis (AGA) is the most common first symptom of gout, and the development of gout as a metabolic and immune inflammatory disease is also correlated with the gut microbiota. However, the mechanism of the effect of changes in the gut microbiota on AGA remains unclear. The intestinal flora can not only affect purine metabolism or regulate inflammation, but also influence the therapeutic effect of drugs on AGA. The aim of this study was to investigate the exact mechanism of modified Baihu decoction (MBD) in the treatment of AGA and whether it is related to the regulation of the structure of the intestinal flora. Methods: On the 21st day of MBD administration by continuous gavage, a rat acute gouty arthritis model was constructed using sodium urate (0.1 mL/rat, 50 mg/mL), and the ankle joint swelling was measured before and 4 h, 8 h, 24 h, and 48 h after the injection of sodium urate. After 48 h of sodium urate injection, serum, liver, kidney, ankle synovial tissue and feces were collected from rats. The collected samples were examined and analyzed using H&E, Elisa, Immunohistochemistry, Histopathology, 16S rDNA, and Biochemical analysis. To investigate the mechanism of MBD to alleviate AGA using pro-inflammatory factors and intestinal flora. Results: MBD (5.84, 35 g/kg) was administered orally to AGA rats and diclofenac sodium tablets (DS-tablets) were used as standard treatment control. Serum biochemical assessment confirmed that MBD is a safe drug for the treatment of AGA. In addition, our findings confirmed that MBD relieved AGA-related symptoms, such as toe swelling. Lowering serum levels of uric acid, IL-1ß, and TGF-ß1 immunohistochemical results also confirmed that MBD reduced the expression of inflammatory elements such as IL-1ß, NLRP3, ASC, and Caspase-1 in synovial tissue.Furthermore, compared with control group, the 16s rDNA sequencing of AGA rat faeces revealed an increase in the relative abundance of Lachnospiraceae, Muribaculaceae, and Bifidobacteriaceae species. While the relative abundance of Lactobacillaceae, Erysipelotrichaceae, Ruminococcaceae, Prevotellaceae and Enterobacteriaceae showed a relative decrease in species abundance. Of these, the reduction in species abundance of Enterobacteriaceae was associated with a reduction in amino acid metabolism and environmental perception. After MBD therapeutic intervention, the disturbance of the intestinal flora caused by AGA was restored. Conclusion: In summary, MBD is an effective agent for the treatment of AGA, with the potential mechanism being the regulation of intestinal flora to control inflammation. This would help to promote the therapeutic effect of MBD on AGA.

Effect of manual reduction and indirect decompression on thoracolumbar burst fracture: a comparison study.

OBJECTIVE: To evaluate the effect of manual reduction and indirect decompression on thoracolumbar burst fracture. METHODS: Sixty patients with thoracolumbar burst fracture who were hospitalized from January 2018 to October 2019 were selected and divided into an experimental group (33 cases) and control group (27 cases) according to different treatment methods. The experimental group was treated with manual reduction and indirect decompression, while the control group was not treated with manual reduction. The operation time and intraoperative blood loss were recorded. VAS score was used to evaluate the improvement of pain. The anterior height of the injured vertebra, wedge angle of the injured vertebral body, and encroachment ratio of the injured vertebral canal were used to evaluate the spinal canal decompression and fracture reduction. JOA score was used to evaluate the improvement of spinal function. RESULTS: There was no significant difference in operation time and intraoperative blood loss between the two groups. Compared with the control group, the VAS score and the wedge angle of the injured vertebral body of the experimental group 3 days after the operation and the last follow-up were significantly lower than that of the control group, and the difference was statistically significant. The ratio of the anterior height of the injured vertebra of the experimental group 3 days after the operation and the last follow-up was significantly higher than that of the control group, and the difference was statistically significant. The difference of the encroachment ratio of the injured vertebral canal between preoperation and 3 days after operation was significantly higher than that of the control group, and the difference was statistically significant. The bladder function of JOA 3 days after the operation of the experimental group was significantly higher than that of the control group, and the difference was statistically significant. And the rest aspect of JOA on 3 days after the operation and last follow-up of the experimental group has no significant difference compared with the control group. CONCLUSION: Manipulative reduction and indirect decompression can obtain a better clinical effect in the treatment of thoracolumbar burst fractures.