Resveratrol Upregulates miR‐124‐3p Expression to Target DAPK1, Regulating the NLRP3/Caspase‐1/GSDMD Pathway to Inhibit Pyroptosis and Alleviate Spinal Cord Injury

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(2)

Published: Jan. 1, 2025

ABSTRACT Currently, an effective treatment for spinal cord injury (SCI) is not available. Due to the irreversible primary associated with SCI, prevention and of secondary are very important. In stage, pyroptosis exacerbates deterioration injury, inhibiting beneficial recovery from SCI. The aim this study was clarify role resveratrol (RES) antipyroptotic mechanisms RES miR‐124‐3p in SCI lay a theoretical foundation clinical provide new therapeutic approaches. Using cell staining related molecular protein detection techniques assess DAPK1, effects on were investigated, injured repair rats evaluated using tissue functional experiments. vitro, DAPK1 interacts NLRP3, exerting pyroptotic effect through NLRP3/Caspase‐1/GSDMD pathway knockdown inhibits pyroptosis. miR‐124‐3P negatively regulates level reduced increased expression reduces expression, affecting vivo, GSDMD‐N levels promotes recovery, thus Therefore, we concluded that increases miR‐124‐3p, which targets pathway, alleviates

Language: Английский

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Pre-treated Mesenchymal Stem Cell-Derived Exosomes: A New Perspective for Accelerating Spinal Cord Injury Repair

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 992, P. 177349 - 177349

Published: Feb. 5, 2025

Spinal cord injury (SCI) is a devastating event for the central nervous system (CNS), often resulting in loss of sensory and motor functions. It profoundly affects both physiological psychological well-being patients, reducing their quality life while also imposing significant economic pressure on families healthcare system. Due to complex pathophysiology SCI, effective treatments promoting recovery remain scarce. Mesenchymal stem cell-derived exosomes (MSC-Exos) offer advantages such as low immunogenicity, good biocompatibility, ability cross blood-spinal barrier (BSCB). In preclinical studies, they have progressively shown efficacy SCI repair functional recovery. However, yield insufficient targeting MSC-Exos limit therapeutic efficacy. Currently, genetic engineering other preprocessing techniques are being employed optimize properties exosomes, thereby enhancing potential. Therefore, this paper provides an overview biogenesis exosomes. summarizes current approaches optimizing exosome performance. Additionally, it details mechanisms through which optimized provide neuroprotection explores potential combined involving hydrogels.

Language: Английский

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Sirtuin1 in Spinal Cord Injury: Regulatory Mechanisms, Microenvironment Remodeling and Therapeutic Potential

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(2)

Published: Feb. 1, 2025

ABSTRACT Background Spinal cord injury (SCI) is a complex central nervous system disorder characterized by multifaceted pathological processes, including inflammation, oxidative stress, programmed cell death, autophagy, and mitochondrial dysfunction. Sirtuin 1 (Sirt1), critical NAD + ‐dependent deacetylase, has emerged as promising therapeutic target for SCI repair due to its potential protect neurons, regulate glial vascular cells, optimize the microenvironment. However, regulatory roles of Sirt1 in are challenging, effects vary depending on activation timing, expression levels, types. Methods A systematic literature review was conducted using PubMed, Scopus, Web Science identify studies investigating SCI. Relevant publications were analyzed synthesize current evidence Sirt1's mechanisms, effects, challenges repair. Results exerts broad across diverse processes types post‐SCI. It promotes neuronal survival axonal regeneration, modulates astrocytes microglia resolve supports oligodendrocyte‐mediated myelination, enhances endothelial function. Proper may mitigate secondary injury, whereas excessive or prolonged could impair inflammatory resolution disrupt cellular homeostasis. This highlights therapies, but include optimizing spatiotemporal addressing dual different Conclusion Targeting represents viable strategy repair, given regulation neuroprotection, immunomodulation, tissue remodeling. translating these findings into therapies requires resolving issues such type‐specific delivery, precise dosage control. provides theoretical foundation practical insights advancing Sirt1‐based treatments

Language: Английский

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Magnetic stimulation techniques for the treatment of central nervous system lesions: a narrative review

Advanced technology in neuroscience ., Journal Year: 2025, Volume and Issue: 2(1), P. 34 - 46

Published: Feb. 6, 2025

Neuromodulation has experienced significant growth in recent years. This technique modulates the activity of central or peripheral nervous system via electrical magnetic fields. It can be applied to nerves, spinal cord, brain. Historically, cord stimulation been used for chronic pain management, with electrodes surgically placed around a method known as epidural stimulation. Recently, this improved treatment injuries. In brain, deep brain targets basal ganglia and is primarily treat Parkinson’s disease. Over time, less invasive methods, such transcutaneous nerve (including repetitive stimulation), have emerged. Transcutaneous operates similarly but stimulates skin surface, whereas uses fields noninvasively induce currents. Repetitive clinically decades, particularly target specific cortical areas Although neurostimulation techniques long clinically, precise mechanisms involved only recently partially understood. review aims explore role treating pathologies, focus on its cellular molecular mechanisms. The comprehensive literature underscores evolving clinical research settings, highlighting continuous advancement these technologies neurological disorders suggesting potential revolution patients neurodegenerative traumatic diseases.

Language: Английский

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Cuproptosis and its potential role in musculoskeletal disease

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 11, 2025

Cuproptosis, a recently identified form of copper-dependent cell death, arises from intracellular copper dyshomeostasis. As an essential trace element, plays critical role in bioenergetic metabolism, redox regulation, and synaptic transmission. However, excessive exerts cytotoxic effects through multiple pathways, including increased reactive oxygen species (ROS) production, apoptotic cascade activation, necrotic membrane rupture, inflammatory responses, mitochondrial dysfunction. Distinct other death mechanisms, cuproptosis is characterized by ion binding to acetylated respiratory chain proteins, leading pathogenic protein aggregation, iron-sulfur cluster depletion, cellular collapse. Emerging evidence underscores aberrant accumulation resultant proteotoxic stress as pivotal contributors the pathogenesis musculoskeletal pathologies, osteoporosis, osteoarthritis, sarcopenia, osteosarcoma, intervertebral disc degeneration, spinal cord injury, biofilm-associated orthopedic infections. Understanding spatiotemporal regulation may provide novel opportunities for advancing diagnostic therapeutic approaches medicine. This review synthesizes current insights into molecular mechanisms cuproptosis, its diseases, potential biomarker-driven interventions.

Language: Английский

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Machine learning-driven prediction model for cuproptosis-related genes in spinal cord injury: construction and experimental validation

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: April 23, 2025

Introduction Spinal cord injury (SCI) severely affects the central nervous system. Copper homeostasis is closely related to mitochondrial regulation, and cuproptosis a novel form of cell death associated with metabolism. This study aimed explore relationship between SCI construct prediction models. Methods Gene expression data patient samples from GSE151371 dataset were analyzed. The differential correlation 13 cuproptosis-related genes (CRGs) non-SCI identified, ssGSEA algorithm was used for immunological infiltration analysis. Unsupervised clustering performed based on differentially expressed CRGs, followed by weighted gene co-expression network analysis (WGCNA) enrichment Three machine learning models (RF, LASSO, SVM) constructed screen candidate genes, Nomogram model verification. Animal experiments carried out an rat model, including behavioral scoring, histological staining, electron microscopic observation, qRT-PCR. Results Seven CRGs showed samples, there significant differences in immune levels. divided 38 into two clusters (Cluster C1 Cluster C2). WGCNA identified key modules clusters, involvement pathways such as Ribosome HIF-1 signaling pathway. Four (SLC31A1, DBT, DLST, LIAS) obtained models, SLC31A1 performing best (AUC = 0.958). confirmed decrease scores rats group, pathological changes tissue sections, model. Discussion revealed close association cuproptosis. Abnormal four function, energy metabolism, oxidative stress, response, which detrimental recovery neurological function SCI. However, this has some limitations, unidentified SRGs, small sample size. Future research requires more vitro vivo deeply regulatory mechanisms develop intervention methods.

Language: Английский

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Identification of Autophagy-Related Genes in Patients with Acute Spinal Cord Injury and Analysis of Potential Therapeutic Targets

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 16, 2024

Language: Английский

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