Ferroptosis, a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation, is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury. Thus, in this study, bulk RNA sequencing data (GSE47681 and GSE5296) and single-cell RNA sequencing data (GSE162610) were acquired from gene expression databases. We then conducted differential analysis and immune infiltration analysis. Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms. Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes. Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells, confirming the high expression of Atf3 and Piezo1 in these cells. Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide. In a mouse model of T8 spinal cord injury, low-dose cycloheximide treatment was found to improve neurological function, decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase, and increase levels of the anti-inflammatory cytokine arginase 1. Correspondingly, the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia, while the expression of Acsl4 decreased. Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury, identify the key cell types and genes involved in ferroptosis after spinal cord injury, and validate the efficacy of potential drug therapies, pointing to new directions in the treatment of spinal cord injury.
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http://dx.doi.org/10.4103/NRR.NRR-D-24-00037 | DOI Listing |
J Vet Intern Med
January 2025
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Background: Clinical characteristics of cervical hydrated nucleus pulposus extrusion (HNPE) in dogs compared to other causes of cervical myelopathy are not well described.
Hypothesis/objectives: To evaluate for clinical characteristics and mechanical ventilation likelihood associated with HNPE compared to other causes of cervical myelopathy.
Animals: Three hundred seventy-seven client-owned dogs from 2010 to 2022.
Nutrients
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Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, University of Florence, 50139 Florence, Italy.
Background: Oxaliplatin-induced neuropathy (OIN) is a severe painful condition that strongly affects the patient's quality of life and cannot be counteracted by the available drugs or adjuvants. Thus, several efforts are devoted to discovering substances that can revert or reduce OIN, including natural compounds. The carob tree, L.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
The journal retracts the article titled "Long Coding RNA XIST Contributes to Neuronal Apoptosis through the Downregulation of AKT Phosphorylation and Is Negatively Regulated by miR-494 in Rat Spinal Cord Injury" [...
View Article and Find Full Text PDFInt J Mol Sci
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Department of Infectology, Rīga Stradiņš University, LV-1007 Riga, Latvia.
Forecasting the progression of the disease in the early inflammatory stage of the most prevalent type of multiple sclerosis (MS), referred to as relapsing-remitting multiple sclerosis (RRMS), is essential for making prompt treatment modifications, aimed to reduce clinical relapses and disability. In total, 58 patients with RRMS, having an Expanded Disability Status Scale (EDSS) score less than 4, were included in this study. Baseline magnetic resonance imaging (MRI) was performed, and brain and spinal cord lesions were evaluated.
View Article and Find Full Text PDFInt J Mol Sci
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Department of Orthopedic Surgery, E-Da Hospital, I-Shou University, Kaohsiung City 824, Taiwan.
Olfactory ensheathing cell (OEC) transplantation demonstrates promising therapeutic results in neurological disorders, such as spinal cord injury. The emerging cell-free secretome therapy compensates for the limitations of cell transplantation, such as low cell survival rates. However, the therapeutic benefits of the human OEC secretome remain unclear.
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