Ferroptosis is a recently identified nonapoptotic form of cell death whose major markers are iron dependence and accumulation of lipid reactive oxygen species, accompanied by morphological changes such as shrunken mitochondria and increased membrane density. It appears to contribute to the death of tumors, ischemia-reperfusion, acute renal failure, and nervous system diseases, among others. The generative mechanism of ferroptosis includes iron overloading, lipid peroxidation, and downstream execution, while the regulatory mechanism involves the glutathione/glutathione peroxidase 4 pathway, as well as the mevalonate pathway and the transsulfuration pathway. In-depth research has continuously developed and enriched knowledge on the mechanism by which ferroptosis occurs. In recent years, reports of the noninterchangeable role played by selenium in glutathione peroxidase 4 and its function in suppressing ferroptosis and the discovery of ferroptosis suppressor protein 1, identified as a ferroptosis resistance factor parallel to the glutathione peroxidase 4 pathway, have expanded and deepened our understanding of the mechanism by which ferroptosis works. Ferroptosis has been reported in spinal cord injury animal model experiments, and the inhibition of ferroptosis could promote the recovery of neurological function. Here, we review the latest studies on mechanism by which ferroptosis occurs, focusing on the ferroptosis execution and the contents related to selenium and ferroptosis suppressor protein 1. In addition, we summarize the current research status of ferroptosis in spinal cord injury. The aim of this review is to better understand the mechanisms by which ferroptosis occurs and its role in the pathophysiological process of spinal cord injury, so as to provide a new idea and frame of reference for further exploration.
Objective: The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated.Methods: By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats.Results: The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis.Conclusion: In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.
Background: Cervical Pedicle Screw (CPS) placement is a challenging work due to the high risk of neurovascular complications. Although there have been several different free-hand or navigation assisted techniques for CPS placement, perforations may occur during screw insertion, especially lateral perforation. The objective of this manuscript is to describe a novel free-hand technique for subaxial CPS placement (C3–C7) and to evaluate if it decreases the chances of perforation. Methods: Thirty-two patients undergoing surgery with CPS instrumentation (C3–C7) at our institute between June 2017 and December 2018 were included in this study. All the patients had cervical trauma, and pedicle screw insertion was performed according to the free-hand “slide technique”. The lamina, lateral mass and facet joint of the target area were exposed and the optimal entry point was found on the lateral mass posterior surface. A pedicular probe was then inserted and gently advanced. During the pedicle probe insertion, the cortex of the medial margin of the pedicle acted as a slide to permit the safe insertion of the screw. If the pedicle screw pathway was intact, the screw of the appropriate size was carefully placed. Three-dimensional (3D) CT imaging reconstruction was performed in all the patients after surgery, and screw perforations were graded with the Gertzbein-Robbins classification. Results: Thirty-two patients who met the inclusion criteria were included in this study. A total of 257 CPSs (C3–7) were inserted, of which 41 CPSs were in C3, 61 CPSs were in C4, 55 CPSs were in C5, 53 CPSs were in C6, and 47 CPSs were in C7. The diameter and length of CPSs were 3.5 mm and 22–26 mm respectively. According to the Gertzbein-Robbins classification, grade 0, 231 screws; grade 1, 19 screws; and grade 2, 7 screws. No neurovascular complications occurred stemming from malpositioning of pedicle screws. Among perforated screws (26 screws), there were 16 lateral perforations, 5 medical perforations, and 4 inferior perforations. Conclusions: The initial usage result shows the “slide technique” is a safe, effective and cost-effective technique for pedicle screw placement in the cervical spine. This is the first report of such a technique, and further studies are needed.
Host immune dysregulation involves in the initiation and development of osteosarcoma (OS). However, the exact role of immune cells in OS remains unknown. We aimed to distinguish the molecular subtypes and establish a prognostic model in OS patients based on immunocyte infiltration. The gene expression profile and corresponding clinical feature of OS patients were obtained from TARGET and GSE21257 datasets. MCP-counter and univariate Cox regression analyses were applied to identify immune cell infiltration-related molecular subgroups. Functional enrichment analysis and immunocyte infiltration analysis were performed between two subgroups. Furthermore, Cox regression and LASSO analyses were performed to establish the prognostic model for the prediction of prognosis and metastasis in OS patients. The subgroup with low infiltration of monocytic lineage (ML) was related to bad prognosis in OS patients. 435 DEGs were screened between the two subgroups. Functional enrichment analysis revealed these DEGs were involved in immune- and inflammation-related pathways. Three important genes (including TERT, CCDC26, and IL2RA) were identified to establish the prognostic model. The risk model had good prognostic performance for the prediction of metastasis and overall survival in OS patients. A novel stratification system was established based on ML-related signature. The risk model could predict the metastasis and prognosis in OS patients. Our findings offered a novel sight for the prognosis and development of OS.
Background: Cervical Pedicle Screw(CPS) placement is a challenging work due to the high risk of neurovascular complications. Although there have been several different free-hand or navigation assisted techniques for CPS placement, perforations may occur during screw insertion, especially lateral perforation. The objective of this manuscript is to describe a novel free-hand technique for subaxial CPS placement (C3–C7) and to evaluate if it decreases the chances of perforation.Methods: Thirty-two patients undergoing surgery with CPS instrumentation (C3–C7) at our institute between June 2017 and December 2018 were included in this study. All the patients had cervical trauma, and pedicle screw insertion was performed according to the free-hand “slide technique”. The lamina, lateral mass and facet joint of the target area were exposed and the optimal entry point was found on the lateral mass posterior surface. A pedicular probe was then inserted and gently advanced. During the pedicle probe insertion, the cortex of the medial margin of the pedicle acted as a slide to permit the safe insertion of the screw. If the pedicle screw pathway was intact, the screw of the appropriate size was carefully placed. Three-dimensional (3D) CT imaging reconstruction was performed in all the patients after surgery, and screw perforations were graded with the Gertzbein-Robbins classification.Results: A total of 257 CPSs (C3-7) were inserted, of which 41 CPSs were in C3, 61 CPSs were in C4, 55 CPSs were in C5, 53 CPSs were in C6, and 47 CPSs were in C7. The diameter and length of CPSs were 3.5 mm and 22-26 mm respectively. According to the Gertzbein-Robbins classification, grade 0, 231 screws; grade 1, 19 screws; and grade 2, 7 screws. No neurovascular complications occurred stemming from malpositioning of pedicle screws. Among perforated screws (26 screws), there were 16 lateral perforations, 5 medical perforations, and 4 inferior perforations.Conclusions: The initial usage result shows the “slide technique” is a safe, effective and cost-effective technique for pedicle screw placement in the cervical spine. This is the first report of such a technique. We recommend its use though further studies are needed.
Background : Cervical Pedicle Screw(CPS) placement is a challenging work due to high risk of neurovascular complications. Although there have been a number of different free-hand or navigation assisted techniques for CPS placement, perforations always occur during screw insertion, especially lateral perforation. The objective of this research is to describe a novel free-hand technique for subaxial CPS placement (C3–C7) for improving security and decreasing the chances of perforation. Methods : Thirty-two patients undergoing surgery with CPS instrumentation (C3–C7) at our institute between June 2017 and December 2018 were included in the study. All the patients had cervical trauma, and pedicle screw insertion was made according to the free-hand “slide technique”. Lamina, lateral mass and facet joint of the target area were clearly exposed and the optimal entry point was found on the lateral mass posterior surface. A pedicular probe was then inserted and gently advanced. During the pedicle probe insertion, the cortex of the medial margin of the pedicle acted as a “slide” to permit safe insertion of the screw. If the pedicle screw pathway was intact, screw of appropriate size was carefully placed. Three-dimensional (3D) CT imaging reconstruction was performed in all the patients after surgery, and screw perforations were graded with the Gertzbein-Robbins classification. Results : A total of 257 CPSs (C3-7) were inserted, of which 41 CPSs in C3, 61 CPSs in C4, 55 CPSs in C5, 53 CPSs in C6, and 47 CPSs in C7. The diameter and length of CPSs were 3.5 mm and 22-26 mm respectively. According to the Gertzbein-Robbins classification, grade 0, 231 screws; grade 1, 19 screws; and grade 2, 7 screws. No neurovascular complications occurred stemming from malpositioning of pedicle screws. In perforated screws (26 screws), lateral perforations were 16, medical perforations were 5, and inferior perforations were 4. Conclusions : The initial usage result show the “slide technique” is a safe, effective and cost-effective technique for pedicle screw placement in the cervical spine. This is the first report of such technique, we recommend it to wide practical application though further studies are needed.