Table_2_Identification of canonical pyroptosis-related genes, associated regulation axis, and related traditional Chinese medicine in spinal cord injury.XLSX

Neuroinflammation plays an important role in spinal cord injury (SCI), and pyroptosis is inflammatory-related programmed cell death. Although neuroinflammation induced by pyroptosis has been reported in SCI, there is a lack of systematic research on SCI pyroptosis and its regulation mechanism. The purpose of this study was to systematically analyze the expression of pyroptosis-related genes (PRGs) in different SCI models and associated regulation axis by bioinformatics methods. We downloaded raw counts data of seven high-throughput sequencings and two microarray datasets from the GEO database, classified by species (rat and mouse) and SCI modes (moderate contusive model, aneurysm clip impact-compression model, and hemisection model), including mRNAs, miRNAs, lncRNAs, and circRNAs, basically covering the acute, subacute and chronic stages of SCI. We performed differential analysis by R (DEseq2) or GEO2R and found that the AIM2/NLRC4/NLRP3 inflammasome-related genes, GSDMD, IL1B, and IL18, were highly expressed in SCI. Based on the canonical NLRP3 inflammasome-mediated pyroptosis-related genes (NLRP3/PRGs), we constructed transcription factors (TFs)–NLRP3/PRGs, miRNAs- Nlrp3/PRGs and lncRNAs/circRNAs/mRNAs–miRNA- Nlrp3/PRGs (ceRNA) networks. In addition, we also predicted Traditional Chinese medicine (TCM) and small, drug-like molecules with NLRP3/PRGs as potential targets. Finally, 39 up-regulated TFs were identified, which may regulate at least two of NLRP3/PRGs. A total of 7 down-regulated miRNAs were identified which could regulate Nlrp3/PRGs. ceRNA networks were constructed including 23 lncRNAs, 3 cicrRNAs, 6 mRNAs, and 44 miRNAs. A total of 24 herbs were identified which may with two NLRP3/PRGs as potential targets. It is expected to provide new ideas and therapeutic targets for the treatment of SCI.

脊髓损伤（SCI）中神经炎症发挥着至关重要的作用，而焦亡是一种与炎症相关的程序性细胞死亡。尽管已有关于SCI中由焦亡诱导的神经炎症的报道，但对于SCI焦亡及其调控机制的系统研究尚显不足。本研究旨在通过生物信息学方法，系统地分析不同SCI模型中焦亡相关基因（PRGs）的表达及其相关调控轴。我们从GEO数据库中下载了七组高通量测序数据和两组微阵列数据集的原始计数数据，这些数据按照物种（大鼠和小鼠）和SCI模式（中度挫裂模型、动脉瘤夹夹闭压缩模型和半切模型）进行分类，包括mRNA、miRNA、lncRNA和circRNA，基本涵盖了SCI的急性、亚急性和慢性阶段。我们通过R（DEseq2）或GEO2R进行了差异分析，发现AIM2/NLRC4/NLRP3炎症小体相关基因、GSDMD、IL1B和IL18在SCI中高表达。基于经典的NLRP3炎症小体介导的焦亡相关基因（NLRP3/PRGs），我们构建了转录因子（TFs）-NLRP3/PRGs、miRNA-Nlrp3/PRGs以及lncRNAs/circRNAs/mRNA-miRNA-Nlrp3/PRGs（ceRNA）网络。此外，我们还预测了以NLRP3/PRGs为潜在靶点的传统中药（TCM）和小型、类似药物的分子。最终，我们鉴定出39个上调的TFs，它们可能调控至少两个NLRP3/PRGs。共鉴定出7个下调的miRNAs，它们可以调控Nlrp3/PRGs。构建了包含23个lncRNA、3个cicrRNA、6个mRNA和44个miRNA的ceRNA网络。共鉴定出24种草药，它们可能与两个NLRP3/PRGs作为潜在靶点。本研究有望为SCI的治疗提供新的思路和靶点。