The Role of Resveratrol on Spinal Cord Injury: from Bench to Bedside.

Spinal cord injury (SCI) is a severe and disabling injury of the central nervous system, with complex pathological mechanisms leading to sensory and motor dysfunction. Pathological processes, such as oxidative stress, inflammatory response, apoptosis, and glial scarring are important factors that aggravate SCI. Therefore, the inhibition of these pathological processes may contribute to the treatment of SCI. Currently, the pathogenesis of SCI remains under investigation as SCI treatment has not progressed considerably. Resveratrol, a natural polyphenol with anti-inflammatory and antioxidant properties, is considered a potential therapeutic drug for various diseases and plays a beneficial role in nerve damage. Preclinical studies have confirmed that signaling pathways are closely related to the pathological processes in SCI, and resveratrol is believed to exert therapeutic effects in SCI by activating the related signaling pathways. Based on current research on the pathways of resveratrol and its role in SCI, resveratrol may be a potentially effective treatment for SCI. This review summarizes the role of resveratrol in promoting the recovery of nerve function by regulating oxidative stress, inflammation, apoptosis, and glial scar formation in SCI through various mechanisms and pathways, as well as the deficiency of resveratrol in SCI research and the current and anticipated research trends of resveratrol. In addition, this review provides a background for further studies on the molecular mechanisms of SCI and the development of potential therapeutic agents. This information could also help clinicians understand the known mechanisms of action of resveratrol and provide better treatment options for patients with SCI.

SIAH1 promotes senescence and apoptosis of nucleus pulposus cells to exacerbate disc degeneration through ubiquitinating XIAP.

BACKGROUND: Using clinical samples and database analysis, this study aimed to investigate the signaling pathways that mediated degeneration of nucleus pulposus cells (NPCs) in patients with intervertebral disc degeneration (IDD). METHODS: NPCs were extracted from enucleated intervertebral discs of IDD patients, and the senescence, apoptosis, and extracellular matrix (ECM) synthesis levels of cells were confirmed by ß-galactosidase (SA-ß-gal), Western blot, and measurement of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH). The microarray expression profile of GSE56081 was downloaded to screen differentially expressed mRNAs. CO-IP and ubiquitination assays were used to determine the targeted regulation of XIAP by SIAH1. Methylation of mRNA was verified by m6A RIP and actinomycin D assays. RESULTS: NPCs extracted from the enucleated intervertebral discs of IDD patients exhibited marked senescence, apoptosis, elevated levels of inflammation, and decreased ECM synthesis. The expression of SIAH1 was significantly elevated in NPCs of IDD patients, and SIAH1 knockdown reversed senescence, apoptosis, elevated levels of inflammation, and decreased ECM synthesis in NPCs of IDD patients. CO-IP and ubiquitination assays indicated that SIAH1 can target and ubiquitinate XIAP. Besides, MeRIP-qPCR and actinomycin experiments showed that METTL3-mediated m6A can methylate SIAH1 mRNA. CONCLUSION: In IDD patients, SIAH1 can target and ubiquitinate XIAP, thereby mediating senescence, apoptosis, increased inflammation, and decreased ECM synthesis of NPCs, while METTL3-mediated m6A can methylate SIAH1 mRNA, producing harmful effects.