SEPHS1 attenuates intervertebral disc degeneration by delaying nucleus pulposus cell senescence through the Hippo-Yap/Taz pathway.

Nucleus pulposus cell (NPC) senescence is a major cause of intervertebral disc degeneration (IVDD). Oxidative stress and reactive oxygen species (ROS) play critical roles in regulating cell senescence. Selenophosphate synthetase 1 (SEPHS1) was reported to play an important role in mitigating oxidative stress in an osteoarthritis (OA) model by reducing the production of ROS, thereby, delaying the occurrence and development of osteoarthritis. In this study, we explored the, hitherto unknown, role of SEPHS1 in IVDD in vitro and in vivo using an interleukin-1ß (IL-1ß)-induced NPC senescence model and a rat needle puncture IVDD model, respectively. SEPHS1 delayed NPC senescence in vitro by reducing ROS production. Age-related dysfunction was also ameliorated by the overexpression of SEPHS1 and inhibition of the Hippo-Yap/Taz signaling pathway. In vivo experiments revealed that the overexpression of SEPHS1 and inhibition of Hippo-Yap/Taz alleviated IVDD in rats. Moreover, a selenium (Se)-deficient diet and lack of SEPHS1 synergistically aggravated IVDD progression. Taken together, our results demonstrate that SEPHS1 plays a significant role in NPC senescence. Overexpression of SEPHS1 and inhibition of Hippo-Yap/Taz can delay NPC senescence, restore the balance of extracellular matrix metabolism, and attenuate IVDD. SEPHS1 could be a promising therapeutic target for IVDD.NEW & NOTEWORTHY Selenophosphate synthetase 1 (SEPHS1) deficiency leads to an increase in reactive oxygen species levels and in the subsequent activation of the Hippo-Yap/Taz signaling pathway. In the rat model of intervertebral disc degeneration (IVDD), overexpression of SEPHS1 and inhibition of Hippo-YAP/Taz mitigated the progression of disc degeneration indicating the involvement of SEPHS1 in IVDD. SEPHS1 is a promising therapeutic target for IVDD.

Ginsenoside Rg1 Regulates Immune Microenvironment and Neurological Recovery After Spinal Cord Injury Through MYCBP2 Delivery via Neuronal Cell-Derived Extracellular Vesicles.

Spinal cord injury (SCI) is a severe neurological condition that frequently leads to significant sensory, motor, and autonomic dysfunction. This study sought to delineate the potential mechanistic underpinnings of extracellular vesicles (EVs) derived from ginsenoside Rg1-pretreated neuronal cells (Rg1-EVs) in ameliorating SCI. These results demonstrated that treatment with Rg1-EVs substantially improved motor function in spinal cord-injured mice. Rg1-EVs enhance microglial polarization toward the M2 phenotype and repressed oxidative stress, thereby altering immune responses and decreasing inflammatory cytokine secretion. Moreover, Rg1-EVs substantially diminish reactive oxygen species accumulation and enhanced neural tissue repair by regulating mitochondrial function. Proteomic profiling highlighted a significant enrichment of MYCBP2 in Rg1-EVs, and functional assays confirmed that MYCBP2 knockdown counteracted the beneficial effects of Rg1-EVs in vitro and in vivo. Mechanistically, MYCBP2 is implicated in the ubiquitination and degradation of S100A9, thereby promoting microglial M2-phenotype polarization and reducing oxidative stress. Overall, these findings substantiated the pivotal role of Rg1-EVs in neuronal protection and functional recovery following SCI through MYCBP2-mediated ubiquitination of S100A9. This research offers novel mechanistic insights into therapeutic strategies against SCI and supports the clinical potential of Rg1-EVs.

Clinical Guidelines for the Surgical Management of Chronic Lateral Ankle Instability: A Consensus Reached by Systematic Review of the Available Data.

BACKGROUND: The surgical management of chronic lateral ankle instability (CLAI) has evolved since the 1930s, but for the past 50 years, the modified Broström technique of ligament repair has been the gold standard. However, with the development of arthroscopic techniques, significant variation remains regarding when and how CLAI is treated operatively, which graft is the optimal choice, and which other controversial factors should be considered. PURPOSE: To develop clinical guidelines on the surgical treatment of CLAI and provide standardized guidelines for indications, surgical techniques, rehabilitation strategies, and assessment measures for patients with CLAI. STUDY DESIGN: A consensus statement of the Chinese Society of Sports Medicine. METHODS: A total of 14 physicians were queried for their input on guidelines for the surgical management of CLAI. After 9 clinical topics were proposed, a comprehensive systematic search of the literature published since 1980 was performed for each topic through use of China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), PubMed, Web of Science, EMBASE, and the Cochrane Library. The recommendations and statements were drafted, discussed, and finalized by all authors. The recommendations were graded as grade 1 (strong) or 2 (weak) based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) concept. Based on the input from 28 external specialists independent from the authors, the clinical guidelines were modified and finalized. RESULTS: A total of 9 topics were covered with regard to the following clinical areas: surgical indications, surgical techniques, whether to address intra-articular lesions, rehabilitation strategies, and assessments. Among the 9 topics, 6 recommendations were rated as strong and 3 recommendations were rated as weak. Each topic included a statement about how the recommendation was graded. CONCLUSION: This guideline provides recommendations for the surgical management of CLAI based on the evidence. We believe that this guideline will provide a useful tool for physicians in the decision-making process for the surgical treatment of patients with CLAI.