Objects: Traumatic spinal cord injury (TSCI) causes neurological dysfunction below the injured segment of the spinal cord, which significantly impacts the quality of life in affected patients. The phosphoinositide 3kinase/serine-threonine kinase (PI3K/AKT) signaling pathway offers a potential therapeutic target for the inhibition of secondary TSCI. This review summarizes updates concerning the role of the PI3K/AKT pathway in TSCI.Materials and Methods: By searching articles related to the TSCI field and the PI3K/AKT signaling pathway, we summarized the mechanisms of secondary TSCI and the PI3K/AKT signaling pathway; we also discuss current and potential future treatment methods for TSCI based on the PI3K/AKT signaling pathway.Results: Early apoptosis and autophagy after TSCI protect the body against injury; a prolonged inflammatory response leads to the accumulation of pro-inflammatory factors and excessive apoptosis, as well as excessive autophagy in the surrounding normal nerve cells, thus aggravating TSCI in the subacute stage of secondary injury. Initial glial scar formation in the subacute phase is a protective mechanism for TSCI, which limits the spread of damage and inflammation. However, mature scar tissue in the chronic phase hinders axon regeneration and prevents the recovery of nerve function. Activation of PI3K/AKT signaling pathway can inhibit the inflammatory response and apoptosis in the subacute phase after secondary TSCI; inhibiting this pathway in the chronic phase can reduce the formation of glial scar. Conclusion:The PI3K/AKT signaling pathway has an important role in the recovery of spinal cord function after secondary injury. Inducing the activation of PI3K/AKT signaling pathway in the subacute phase of secondary injury and inhibiting this pathway in the chronic phase may be one of the potential strategies for the treatment of TSCI.Xuegang He, Ying Li and Bo Deng contributed equally to this study.

Intervertebral disc degeneration (IVDD) is a common musculoskeletal degenerative disease worldwide, of which the main clinical manifestation is low back pain (LBP); approximately, 80% of people suffer from it in their lifetime. Currently, the pathogenesis of IVDD is unclear, and modern treatments can only alleviate its symptoms but cannot inhibit or reverse its progression. However, in recent years, targeted therapy has led to new therapeutic strategies. Cysteine-containing aspartate proteolytic enzymes (caspases) are a family of proteases present in the cytoplasm. They are evolutionarily conserved and are involved in cell growth, differentiation, and apoptotic death of eukaryotic cells. In recent years, it has been confirmed to be involved in the pathogenesis of various diseases, mainly by regulating cell apoptosis and inflammatory response. With continuous research on the pathogenesis and pathological process of IVDD, an increasing number of studies have shown that caspases are closely related to the IVDD process, especially in the intervertebral disc (IVD) cell apoptosis and inflammatory response. Therefore, herein we study the role of caspases in IVDD with respect to the structure of caspases and the related signaling pathways involved. This would help explore the strategy of regulating the activity of the caspases involved and develop caspase inhibitors to prevent and treat IVDD. The aim of this review was to identify the caspases involved in IVDD which could be potential targets for the treatment of IVDD.

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STUDY DESIGN: Explanatory or mechanistic studies OBJECTIVES: Programmed cell death (PCD) in the development of spinal cord injury (SCI) is complicated, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis and autophagy. It is necessary to make clear the expression levels of PCD and potential molecular targets after SCI for formulating relevant treatment strategies. SETTING: Key Laboratory of Orthopedics Disease of Gansu Province, Lanzhou, Gansu，China METHODS: Download the rats SCI expression matrix GSE45006, ssGSEA method was used to analyze the PCD in SCI. Then the related differentially expressed genes (DEGs) were identified, and the gene ontology (GO) and pathway analysis, protein-protein interaction (PPI) network construction and hub genes were identified. Finally, the correlation between hub genes and PCD was analyzed. RESULTS: Apoptosis, necroptosis, pyroptosis, ferroptosis and autophagy increased significantly in the acute SCI, and then decreased gradually in the subacute and chronic stages; cuproptosis in acute SCI decreased significantly, and then gradually increased. In addition, we also screened 116 DEGs during the development of SCI. GO and pathway analysis showed that DEGs was related to mitosis and cell cycle. The identified hub genes are closely related to cell apoptosis, necroptosis, pyroptosis, ferroptosis after injury and autophagy CONCLUSIONS: PCD occurs differently in different stages after SCI. To inhibit apoptosis, necroptosis, pyroptosis, ferroptosis after injury and induce autophagy may be the therapeutic strategy. In addition, intervention therapy based on related hub genes may be the therapeutic target of SCI.