RESUMO
Periprosthetic joint infection (PJI) is a devastating complication. This study aimed to unravel the veil of the N6-methyladenine (m6A) modification in PJI. Synovium, synovial fluid, sonication fluid and bone samples were collected intraoperatively from Staphylococcus aureus PJI and aseptic failure (AF) patients. The overall m6A level was detected by the m6A RNA methylation quantification kit, and the expression of m6A-related genes was quantified by real-time PCR and Western blot. Finally, an epitranscriptomic microarray and bioinformatics analysis were performed. We showed that there was a significant difference in overall m6A level between the PJI group and the AF group (PJI group had a higher overall m6A level). The expression level of METTL3 was higher in the PJI group than that in the AF group. There were 2802 differential m6A-modified mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differential m6A-modified mRNAs were significantly enriched in the NOD-like receptor signaling pathway, Th17 cell differentiation and the IL-17 signaling pathway, which indicates that the m6A modification might be involved in the processes of infection and immune response, bone metabolism and programmed cell death in PJI. In summary, the present work demonstrated that m6A modification plays a role in PJI and might be a therapeutic target for developing effective treatment strategies.
RESUMO
Background: The relationship between Ankylosing Spondylitis (AS) and the risk of stroke is complex. Therefore, we utilized Two-Sample Mendelian randomization to examine the probable causal link between these two features. Methods: The genetic instruments linked to AS were chosen from a summary-level genetic data set from the FinnGen consortium in people of European ancestry (1462 cases and 164,682 controls). Stroke and its subtypes were selected as outcomes, and the MEGASTROKE consortium population was used to identify the genetic associations of AS on stroke (40,585 cases and 406,111 controls), ischemic stroke (IS) (34,217 cases and 406,111 controls), and its subtypes including large artery stroke (LAS) (4373 cases and 146,392 controls), small vessel stroke (SVS) (5386 cases and 192,662 controls), and cardioembolic stroke (CES) (7193 cases and 204,570 controls). Intracerebral hemorrhage (ICH) (1687 cases and 201,146 controls) data set from the FinnGen consortium was also used. To obtain the casual estimates, the inverse variant weighted (IVW) method was mainly used. By examining the heterogeneity and pleiotropy of particular single nucleotide polymorphisms (SNPs), the robustness of the results was also examined. Results: There was no evidence found to prove the correlation between genetically predicted AS and stroke (odds ratio [OR] 1.014; 95% confidence interval [CI] 0.999-1.031; P = 0.063), ICH (OR 1.030; 95% CI 0.995-1.067; P = 0.090), and IS (OR 1.013; 95% CI 0. 998-1.030; P = 0.090). In terms of the different subtypes of IS, there was strong evidence of positive causal inferences on CES (OR 1.051; 95% CI 1.022-1.081; P = 0.001), and suggestive evidence of positive causal inferences on LAS (OR 1.042; 95% CI 1.003-1.082; P = 0.033), while it was not significant for SVS (OR 1.010; 95% CI 0.975-1.047; P = 0.563). Conclusion: This study suggests that the possible causative impact of genetically predicted AS on stroke may be restricted to the CES and LAS subtypes.
