Moxibustion is the main alternative medicine treatment that has been beneficial to diabetic peripheral neuropathy (DPN), a common complication secondary to diabetic microvascular injury. However, the underlying protective mechanism of moxibustion against neuroinflammation remains unclear. We hypothesized that moxibustion treats DPN by regulating the balance of nuclear factor-2 erythroid-related factor-2 (Nrf2)-nuclear factor-kappa light chain enhancer of B cells (NF-кB). In vivo, diabetes was induced in rats by injecting streptozotocin (STZ; 60 mg/kg; i.p.). Moxibustion was then applied to “Zusanli” (ST 36), “Guanyuan” (BL 26), and “Yishu” (EX-B 3) acupuncture points. Nerve conduction was detected. Serum interleukin (IL)-1β, IL-6, and IL-8 levels were determined through enzyme-linked immunosorbent assay. NF-κB and Nrf2 proteins were examined through immunoblot analysis. The mRNA of NF-κB and Nrf2 was evaluated through RT-PCR. We found that the conduction velocity and amplitude of the action potentials of sciatic nerve conduction were reduced in the DPN model group but were rescued by moxibustion treatment. Moxibustion also improved the effect of DPN on other parameters, including ultrastructural changes, NF-κB and Nrf2 expression in the sciatic nerve, and serum IL-1β, IL-6, and IL-8 levels. Our data suggested that moxibustion may alleviate neuroinflammation by inhibiting NF-κB and by activating Nrf2. Moxibustion may also provide therapeutic effects for patients with DPN by simultaneously targeting Nrf2 and NF-κB.

Purpose: This study aimed to evaluate the causal association between lipid phenotypes mediated by drug targets and bone mineral density using a two-sample Mendelian randomization approach. Methods: Mendelian randomization analysis was conducted utilizing publicly available pooled-level GWAS data for lipid traits. Instrumental variables were selected based on specific lipid-lowering targets, and inverse variance weighting, weighted median, and MR Egger methods were employed. Sensitivity analyses were performed to ensure the robustness of the results. Results:This study aimed to investigate the association between LDL cholesterol levels mediated by specific genes and bone mineral density (BMD) outcomes. Firstly, HMGCR-mediated LDL cholesterol showed a significant association with both H-BMD (β = -0.086, 95%CI: 0.117 to 0.055, p = 5.420 × 10^-8 ) and TB-BMD (β = 0.193, 95%CI: 0.288 to 0.098, p = 7.350× 10^-5 ). APOB-mediated LDL cholesterol demonstrated suggestive associations with FA-BMD (β = 0.210, 95%CI: 0.044 to 0.376, p = 0.013) and H-BMD (β = -0.032, 95%CI: -0.061 to -0.004, p = 0.027). Similarly, CETP-mediated LDL cholesterol showed suggestive relationships with FA-BMD (β = 0.315, 95%CI: 0.102 to 0.528, p = 0.004) and H-BMD (β = 0.055, 95%CI: -0.092 to -0.018, p = 0.027). LDLR-mediated LDL cholesterol was associated with H-BMD (β = -0.022, 95%CI: 0.041 to 0.003, p = 0.025) and LS-BMD (β = 0.124, 95%CI: 0.017 to 0.231, p = 0.023). However, no substantial evidence was found for an association between PCSK9-mediated LDL cholesterol, NPC1L1-mediated LDL cholesterol, and BMD outcomes. Conclusion: Our study provides significant findings supporting the protective effect of HMGCR inhibitors on BMD. Associations were also observed between APOB, CETP, and LDLR-mediated LDL cholesterol and BMD at different skeletal sites. These results contribute to our understanding of the relationship between cholesterol-related genes and bone health, suggesting potential therapeutic targets for improving bone density.