M6A methylation-regulated autophagy may be a new therapeutic target for intervertebral disc degeneration.

Degeneration of intervertebral discs is considered one of the most important causes of low back pain and disability. The intervertebral disc (IVD) is characterized by its susceptibility to various stressors that accelerate the senescence and apoptosis of nucleus pulposus cells, resulting in the loss of these cells and dysfunction of the intervertebral disc. Therefore, how to reduce the loss of nucleus pulposus cells under stress environment is the main problem in treating intervertebral disc degeneration. Autophagy is a kind of programmed cell death, which can provide energy by recycling substances in cells. It is considered to be an effective method to reduce the senescence and apoptosis of nucleus pulposus cells under stress. However, further research is needed on the mechanisms by which autophagy of nucleus pulposus cells is regulated under stress environments. M6A methylation, as the most extensive RNA modification in eukaryotic cells, participates in various cellular biological functions and is believed to be related to the regulation of autophagy under stress environments, may play a significant role in nucleus pulposus responding to stress. This article first summarizes the effects of various stressors on the death and autophagy of nucleus pulposus cells. Then, it summarizes the regulatory mechanism of m6A methylation on autophagy-related genes under stress and the role of these autophagy genes in nucleus pulposus cells. Finally, it proposes that the methylation modification of autophagy-related genes regulated by m6A may become a new treatment approach for intervertebral disc degeneration, providing new insights and ideas for the clinical treatment of intervertebral disc degeneration.

[Clinical research progress of spinal epidural lipomatosis].

Objective: To review the clinical research progress of spinal epidural lipomatosis (SEL). Methods: The clinical studies on SEL at home and abroad in recent years were extensively reviewed, and the pathogenesis, clinical and imaging manifestations, and treatment status of SEL were summarized and analyzed. Results: SEL is a disease characterized by compression of the spinal cord and nerve roots due to abnormal accumulation of epidural adipose tissue in the spinal canal. Its prevalence and diagnosis rate are low and the pathogenesis is not fully understood. MRI is the most sensitive and specific diagnostic test for SEL. Surgical decompression and removal of excess adipose tissue are the only options for patients with acute SEL or those who have failed conservative management, and conservative management should be considered for other patients. Conclusion: SEL is a rare disease and related research still needs to be improved. In the future, high-quality, multi-center and large-sample studies will be of great significance for evaluating the choice of treatment methods and effectiveness of SEL patients.

Tert-butyl hydroperoxide induces ferroptosis of bone mesenchymal stem cells by repressing the prominin2/BACH1/ROS axis.

Ferroptosis has been proven critical for survival following bone marrow mesenchymal stem cells (BMSCs) explantation. Suppression of ferroptosis in BMSCs will be a valid tactic to elevate the therapeutic potential of engrafted BMSCs. Prominin2 is a pentaspanin protein involved in mediating iron efflux and thus modulates resistance to ferroptosis, but its role in tert-butyl hydroperoxide (TBHP)-induced BMSCs ferroptosis remains elusive. We examined the biological effect of prominin2 in vitro and in vivo by using cell proliferation assay, iron assay, reactive oxygen species (ROS) examination, malondialdehyde assay, glutathione (GSH) examination, Western blot, quantitative reverse transcription-PCR, immunofluorescence staining assay, gene expression inhibition and activation, co-immunoprecipitation (CO-IP) assay, radiographic analysis, and histopathological analysis. Our study demonstrated that prominin2 activity was impaired in TBHP-induced BMSCs ferroptosis. We found that PROM2 (encoding the protein prominin2) activation delayed the onset of ferroptosis and PROM2 knockdown deteriorated the course of ferroptosis. CO-IP, Western blot, and immunofluorescence demonstrated that prominin2 exerts antiferroptosis effects by inhibiting BTB and CNC homology 1 (BACH1) that promotes ROS generation, and thus exerts potent antioxidant effects in oxidative stress (OS)-induced BMSCs ferroptosis, including elevating BMSCs' survival rate and enhancing GSH contents. BMSCs with PROM2 overexpression also partially delayed the progression of intervertebral disk degeneration in vivo, as illustrated by less loss of disk height and lower histological scores. Our findings revealed a mechanism that the prominin2/BACH1/ROS axis participates in BMSCs ferroptosis and the strengthening of this axis is promising to maintain BMSCs' survival after explantation.NEW & NOTEWORTHY We found that prominin2 might be a potential biomarker and is expected to be utilized to augment engrafted bone marrow mesenchymal stem cells (BMSCs) survival rate. The prominin2/BTB and CNC homology 1 (BACH1)/reactive oxygen species (ROS) axis, which participates in the regulation of BMSCs ferroptosis induced by tert-butyl hydroperoxide (TBHP), is uncovered in our study. The therapeutic targeting of the prominin2/BACH1/ROS axis components is promising to elevate the survival of transplanted BMSCs in clinical practice.

Novel perspective in transplantation therapy of mesenchymal stem cells: targeting the ferroptosis pathway. / 间å 质干细胞移植治疗的新视角：靶向铁死亡通路.

Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.