Identification and validation of biomarkers associated with mitochondrial dysfunction and ferroptosis in rat spinal cord injury DOI Creative Commons

Jihong Zhu,

Shuai Wang,

Yu Zhang

и другие.

Frontiers in Neurology, Год журнала: 2025, Номер 16

Опубликована: Март 17, 2025

Mitochondrial dysfunction and ferroptosis have been implicated in the pathophysiological processes following spinal cord injury (SCI), with evidence suggesting their interplay influences neuronal cell survival repair mechanisms. This study seeks to identify mitochondria- ferroptosis-related biomarkers through comprehensive bioinformatics analysis. Mitochondria- ferroptosis-associated differentially expressed genes (DEGs) were identified integration of differential expression analysis weighted gene co-expression network Two machine learning algorithms, least absolute shrinkage selection operator (LASSO) Boruta, employed isolate SCI-associated feature genes. Biomarkers subsequently by analyzing levels. An artificial neural (ANN) diagnostic model was constructed predict SCI likelihood based on these biomarkers. Further evaluations performed using enrichment analysis, immune infiltration profiling, molecular modulation assessment, drug prediction. The biomarkers' levels validated RT-qPCR. In this study, two biomarkers, Hcrt Cdca2, linked mitochondrial function SCI, found be highly samples. Tissue-specific from GTEx database revealed brain tissues. ANN model, accurately discriminated between control Enrichment highlighted several co-enriched pathways for including "ubiquitin-mediated proteolysis," "endocytosis," "neurotrophin signaling pathway." Immune Wilcoxon test, demonstrated significant differences T follicular helper levels, which lower samples compared controls. Notably, cells exhibited a positive correlation negative Cdca2. Furthermore, seven transcription factors, CEBPB, FOXC1, GATA2, as potential co-regulators Drug prediction stable interactions Cdca2 pinosylvin, zinc acetate dihydrate, hydroquinone, lucanthone, dasatinib. RT-qPCR validation confirmed patterns alignment dataset, showing statistically differences. identifies related providing new insights diagnosis mechanistic understanding SCI.

Язык: Английский

Cannabinoid receptor-2 attenuates neuroinflammation by promoting autophagy-mediated degradation of the NLRP3 inflammasome post spinal cord injury DOI Creative Commons
Fan Jiang,

Mingjie Xia,

Yanan Zhang

и другие.

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Сен. 26, 2022

Neuroinflammation following spinal cord injury (SCI) results in prolonged neurological damage and locomotor dysfunction. Polarization of microglia is vital to regulation neuroinflammation, although the underlying mechanisms have not yet been elucidated. Endocannabinoid receptor subtype 2 (CB2R) reported ameliorate neurodegeneration via immunomodulation activities. However, machinery context SCI remains unclear.A lipopolysaccharide-induced inflammation model a mouse were employed investigate regulatory role CB2R polarization response excess neuroinflammation. Markers autophagy measured by Western blot analysis, immunofluorescence, flow cytometry, enzyme-linked immunosorbent assays. Histological staining with hematoxylin eosin, Nissl, Luxol® fast blue was conducted using commercial kits. The function hindlimbs experimental mice evaluated Basso Mouse Scale, Louisville Swim footprint assay.The showed that promoted M2 differentiation, increased interleukin (IL)-10 expression, inhibited M1 differentiation decreased expression IL-1β IL-6. activation also ubiquitination NLRP3 inflammasome interacted autophagy-related proteins p62 microtubule-associated 1B light chain 3. Treatment activator JWH-133 reduced loss myelin, apoptosis neurons, glial scarring, leading improved functional recovery hindlimbs, while antagonist AM630 produced opposite results.Taken together, these suggested attenuated neuroinflammation targeting microglial promoting clearance, thereby facilitating post-SCI.

Язык: Английский

Процитировано

35
Targeted transplantation of engineered mitochondrial compound promotes functional recovery after spinal cord injury by enhancing macrophage phagocytosis DOI Creative Commons
Jiaqi Xu, Chaoran Shi,

Feifei Yuan

и другие.

Bioactive Materials, Год журнала: 2023, Номер 32, С. 427 - 444

Опубликована: Окт. 27, 2023

Mitochondria are crucial in sustaining and orchestrating cellular functions. Capitalizing on this, we explored mitochondrial transplantation as an innovative therapeutic strategy for acute spinal cord injury (SCI). In our study, developed engineered compound tailored to target macrophages within the SCI region. Sourced from IL-10-induced Mertkhi bone marrow-derived macrophages, conjugated a peptide sequence, cations-cysteine-alanine-glutamine-lysine (CAQK), with mitochondria, optimizing its targeting affinity site. Our data demonstrated that these compounds significantly enhanced macrophage phagocytosis of myelin debris, curtailed lipid buildup, ameliorated dysfunction, attenuated pro-inflammatory profiles both vitro vivo. The intravenously delivered targeted epicenter, being primary recipients. Critically, they promoted tissue regeneration bolstered functional recovery mice. This study heralds transformative approach SCI, spotlighting modulation activity, phagocytosis, phenotype.

Язык: Английский

Процитировано

19
Neurotrauma—From Injury to Repair: Clinical Perspectives, Cellular Mechanisms and Promoting Regeneration of the Injured Brain and Spinal Cord DOI Creative Commons
Andrew R. Stevens, Antonio Belli, Zubair Ahmed

и другие.

Biomedicines, Год журнала: 2024, Номер 12(3), С. 643 - 643

Опубликована: Март 13, 2024

Traumatic injury to the brain and spinal cord (neurotrauma) is a common event across populations often causes profound irreversible disability. Pathophysiological responses trauma exacerbate damage of an index injury, propagating loss function that central nervous system (CNS) cannot repair after initial resolved. The way in which lost consequence complex array mechanisms continue chronic phase post-injury prevent effective neural repair. This review summarises events traumatic (TBI) (SCI), comprising description current clinical management strategies, summary known cellular molecular secondary their role prevention A discussion emerging approaches promote neuroregeneration CNS presented. barriers promoting neurotrauma are pathways cell types occur on level. presents challenge traditional pharmacological targeting single pathways. It suggested novel multiple or using combinatorial therapies may yield sought-after recovery for future patients.

Язык: Английский

Процитировано

9
Zinc ions regulate mitochondrial quality control in neurons under oxidative stress and reduce PANoptosis in spinal cord injury models via the Lgals3-Bax pathway DOI

Mingyu Bai,

Yang Cui,

Zelin Sang

и другие.

Free Radical Biology and Medicine, Год журнала: 2024, Номер 221, С. 169 - 180

Опубликована: Май 21, 2024

Язык: Английский

Процитировано

8
Repair spinal cord injury with a versatile anti-oxidant and neural regenerative nanoplatform DOI Creative Commons

Heng Zhou,

Ziwei Li, Shuili Jing

и другие.

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 20, 2024

Abstract Spinal cord injury (SCI) often results in motor and sensory deficits, or even paralysis. Due to the role of cascade reaction, effect excessive reactive oxygen species (ROS) early middle stages SCI severely damage neurons, most antioxidants cannot consistently eliminate ROS at non-toxic doses, which leads a huge compromise antioxidant treatment SCI. Selenium nanoparticles (SeNPs) have excellent scavenging bioactivity, but toxicity control problem limits therapeutic window. Here, we propose synergistic strategy SeNPs encapsulated by ZIF-8 (SeNPs@ZIF-8) obtain activity. Three different spatial structures SeNPs@ZIF-8 were synthesized coated with ferrostatin-1, ferroptosis inhibitor (FSZ NPs), achieve enhanced anti-oxidant anti-ferroptosis activity without toxicity. FSZ NPs promoted maintenance mitochondrial homeostasis, thereby regulating expression inflammatory factors promoting polarization macrophages into M2 phenotype. In addition, presented strong abilities promote neuronal maturation axon growth through activating WNT4-dependent pathways, while prevented glial scar formation. The current study demonstrates powerful versatile bioactive functions for offers inspiration other neural diseases.

Язык: Английский

Процитировано

8
Engineering nanomedicines for neuroprotection and neuroregeneration in spinal cord injury DOI

Yaoyao Jiang,

Zhixia Chen, Jiawei Zhang

и другие.

Nano Today, Год журнала: 2025, Номер 61, С. 102643 - 102643

Опубликована: Янв. 20, 2025

Язык: Английский

Процитировано

1
Molecular Mechanisms and Clinical Application of Multipotent Stem Cells for Spinal Cord Injury DOI Creative Commons
Michał Szymoniuk, Jakub Litak, Leon Sakwa

и другие.

Cells, Год журнала: 2022, Номер 12(1), С. 120 - 120

Опубликована: Дек. 28, 2022

Spinal Cord Injury (SCI) is a common neurological disorder with devastating psychical and psychosocial sequelae. The majority of patients after SCI suffer from permanent disability caused by motor dysfunction, impaired sensation, neuropathic pain, spasticity as well urinary complications, small number experience complete recovery. Current standard treatment modalities the aim to prevent secondary injury provide limited recovery lost functions. Stem Cell Therapy (SCT) represents an emerging approach using differentiation, paracrine, self-renewal capabilities stem cells regenerate injured spinal cord. To date, multipotent including mesenchymal (MSCs), neural (NSCs), hematopoietic (HSCs) represent most investigated types for in preclinical clinical studies. microenvironment has significant impact on survival, proliferation, differentiation transplanted cells. Therefore, deep understanding pathophysiology molecular mechanisms through which act may help improve efficacy SCT find new therapeutic approaches such stem-cell-derived exosomes, gene-modified cells, scaffolds, nanomaterials. In this literature review, pathogenesis action MSCs, NSCs, HSCs are comprehensively described. Moreover, treatment, optimal protocol cell administration, recent based or combined also discussed.

Язык: Английский

Процитировано

27
Mitochondrial dysfunction as a target in spinal cord injury: intimate correlation between pathological processes and therapeutic approaches DOI Creative Commons

HéctorRamiro Quintá,

Julieta Schmidt

Neural Regeneration Research, Год журнала: 2023, Номер 18(10), С. 2161 - 2161

Опубликована: Янв. 1, 2023

Traumatic spinal cord injuries interrupt the connection of all axonal projections with their neuronal targets below and above lesion site. This interruption results in either temporary or permanent alterations locomotor, sensory, autonomic functions. Damage tissue prevents re-growth severed axons across reconnection targets. Therefore, absence spontaneous repair leads to sustained impairment voluntary control movement injury. For decades, regeneration have been considered opitome injury goal being damaged long motor sensory tracts a complex process that involves: (1) resealing injured axons; (2) reconstructing cytoskeletal structure inside (3) re-establishing healthy growth cones; (4) assembling cargos. These biological processes require an efficient production adenosine triphosphate, which is affected by mitochondrial dysfunction after From pathological standpoint, during secondary stage injury, homeostasis disrupted, mainly distal segments axons. result reduction triphosphate levels subsequent inactivation triphosphate-dependent ion pumps required for regulation concentrations reuptake neurotransmitters, such as glutamate. The consequences are calcium overload, reactive oxygen species formation, excitotoxicity. events intimately related activation necrotic apoptotic cell death programs, further exacerbate hallmark why restoring function early could represent potentially effective therapeutic intervention overcome failure produced review discusses most recent evidence linking context It also covers future mitochondria-targeted therapeutical approaches, antioxidant molecules, removing anchor proteins, increasing energetic metabolism through creatine treatment. approaches intended enhance functional recovery promoting regeneration-reconnection

Язык: Английский

Процитировано

15
Advances in molecular therapies for targeting pathophysiology in spinal cord injury DOI Creative Commons

Ha Neui Kim,

Madeline Rose McCrea,

Shuxin Li

и другие.

Expert Opinion on Therapeutic Targets, Год журнала: 2023, Номер 27(3), С. 171 - 187

Опубликована: Март 4, 2023

Introduction Spinal cord injury (SCI) affects 25,000–50,000 people around the world each year and there is no cure for SCI patients currently. The primary damages spinal tissues secondary mechanisms, including ischemia, apoptosis, inflammation, astrogliosis, further exacerbate lesions to cord. Recently, researchers have designed various therapeutic approaches by targeting its major cellular or molecular pathophysiology.Areas covered Some strategies shown promise in repairing injured functional recoveries, such as administering neuroprotective reagents, specific genes promote robust axon regeneration of disconnected fiber tracts, epigenetic factors enhance cell survival neural repair, facilitating neuronal relay pathways neuroplasticity restoration function after SCI. This review focuses on advances preclinical therapies reported recent years.Expert opinion Recent progress developing novel effective encouraging, but many challenges remain future design treatments, highly neuroprotectants early interventions, stimulating with synaptic reconnections among neurons, maximizing recovery lost functions combination strategies, translating most promising into human use.

Язык: Английский

Процитировано

13
Encapsulation of Selenium Nanoparticles and Metformin in Macrophage-Derived Cell Membranes for the Treatment of Spinal Cord Injury DOI

Xiaobang Liu,

Junpeng Sun,

Jiaqun Du

и другие.

ACS Biomaterials Science & Engineering, Год журнала: 2023, Номер 9(10), С. 5709 - 5723

Опубликована: Сен. 15, 2023

Spinal cord injury is an impact-induced disabling condition. A series of pathological changes after spinal (SCI) are usually associated with oxidative stress, inflammation, and apoptosis. These eventually lead to paralysis. The short half-life low bioavailability many drugs also limit the use in SCI. In this study, we designed nanovesicles derived from macrophages encapsulating selenium nanoparticles (SeNPs) metformin (SeNPs-Met-MVs) be used treatment can cross blood–spinal barrier (BSCB) deliver SeNPs Met site exert anti-inflammatory reactive oxygen species scavenging effects. Transmission electron microscopy (TEM) images showed that SeNPs-Met-MVs particle size was approximately 125 ± 5 nm. Drug release assays exhibited sustained encapsulation by macrophage cell membrane. cumulative 80% over 36 h. vitro cellular experiments vivo animal demonstrated decreased (ROS) malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) glutathione peroxidase (GSH-Px) activities, reduced expression inflammatory (TNF-α, IL-1β, IL-6) apoptotic (cleaved caspase-3) cytokines tissue addition, motor function mice significantly improved treatment. Therefore, have a promising future

Язык: Английский

Процитировано

13