Repair spinal cord injury with a versatile anti-oxidant and neural regenerative nanoplatform

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 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.

Language: Английский

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Transfer and fates of damaged mitochondria: role in health and disease

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: March 28, 2024

Intercellular communication is pivotal in mediating the transfer of mitochondria from donor to recipient cells. This process orchestrates various biological functions, including tissue repair, cell proliferation, differentiation and cancer invasion. Typically, dysfunctional depolarized are eliminated through intracellular or extracellular pathways. Nevertheless, increasing evidence suggests that intercellular damaged associated with pathogenesis diverse diseases. review investigates prevalent triggers mitochondrial damage underlying mechanisms transfer, elucidates role directional both physiological pathological contexts. Additionally, we propose potential previously unknown explore their prospective roles disease prevention therapy.

Language: Английский

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TRIM56 Modulates YBX1 Degradation to Ameliorate ZBP1‐Mediated Neuronal PANoptosis in Spinal Cord Injury

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Abstract Spinal cord injury (SCI) is a severe to the central nervous system, and its treatment always major medical challenge. Proinflammatory cell death considered an important factor affecting neuroinflammation prognosis after injury. PANoptosis, newly discovered type of proinflammatory death, regulates activation executioner molecules apoptosis, pyroptosis necroptosis through PANoptosome, providing new target for therapeutic intervention SCI. However, role regulatory mechanism in SCI are not yet elucidated. Here, based on proteomic data, YBX1 expression significantly increased neurons Guided by RIP‐seq, subsequent experiments reveal that promotes ZBP1 stabilizing Zbp1 mRNA, thereby aggravating ZBP1‐mediated PANoptosis. Furthermore, E3 ubiquitin ligase TRIM56 identified as endogenous inhibitor via molecular docking IP/MS analysis. Mechanistically, bound promoted ubiquitination, accelerating degradation. Taken together, these findings novel function regulating PANoptosis pathogenesis verified functions promote ubiquitin‐proteasomal degradation YBX1, insights into strategies.

Language: Английский

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Mitochondrial transplantation: a promising strategy for treating degenerative joint diseases

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 15, 2024

The prevalence of age-related degenerative joint diseases, particularly intervertebral disc degeneration and osteoarthritis, is increasing, thereby posing significant challenges for the elderly population. Mitochondrial dysfunction a critical factor in etiology progression these disorders. Therapeutic interventions that incorporate mitochondrial transplantation exhibit considerable promise by increasing numbers improving their functionality. Existing evidence suggests exogenous therapy improves clinical outcomes patients with diseases. This review elucidates abnormalities associated diseases examines mechanisms intercellular transfer artificial transplantation. Furthermore, therapeutic strategies are synthesized, concept engineered proposed.

Language: Английский

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The role of mitochondria in iron overload-induced damage

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 25, 2024

Iron overload is a pathological condition characterized by the abnormal accumulation of iron within body, which may result from excessive intake, disorders metabolism, or specific disease states. This can lead to significant health complications and pose life-threatening risks. The induce cellular stress, adversely affecting structure function mitochondria, thereby compromising overall organ function. Given critical role mitochondria in metabolism homeostasis, it imperative investigate how mitochondrial dysfunction induced contributes progression, as well explore mitochondrial-related pathways potential therapeutic targets for various disorders. review examines mechanisms are implicated overload-induced damage, including increased oxidative DNA disruptions energy metabolism. Additionally, addresses relationship between these processes forms programmed cell death, alterations dynamics. Furthermore, discusses strategies aimed at alleviating mitigating associated with patients targeting pathways.

Language: Английский

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Local delivery of mesenchymal stem cell-extruded nanovesicles through a bio-responsive scaffold for acute spinal cord injury treatment

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125222 - 125222

Published: Jan. 1, 2025

Language: Английский

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Glycosylated lysosomal membrane protein promotes tissue repair after spinal cord injury by reducing iron deposition and ferroptosis in microglia

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 22, 2025

Language: Английский

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O-GlcNAc transferase mediates O-GlcNAcylation of NLRP3 regulates pyroptosis in spinal cord injury

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111233 - 111233

Published: Jan. 1, 2025

Spinal cord injury (SCI) represents a severe disorder of the nervous system, imposing significant physical, psychological, and socioeconomic burdens on affected individuals society. We investigated implication O-linked β-N-acetylglucosamine (O-GlcNAcylation) in regulating pyroptosis related proteins at posttranslational level. PC12 cells were stimulated with lipopolysaccharide (LPS). The O-GlcNAcylation pathway was modified by manipulating expression O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA). Pro-inflammatory cytokine levels cell assessed. Co-immunoprecipitation (Co-IP) assays employed to investigate interaction between NLRP3 OGT. For vivo studies, an established SCI rat model utilized. Levels pro-inflammatory factors, inflammasome components, associated measured. Both OGT significantly elevated cells. Inhibition led marked reduction cytokines suppression pyroptosis. Furthermore, inhibition resulted downregulation its O-GlcNAcylation, while overexpression produced opposite effect. verified endogenous exogenous interactions Importantly, knockout mitigated progression animal model, suggesting protective role SCI. This study preliminarily proved that mechanism mediated participates action Targeting may be novel therapy method

Language: Английский

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Per2 deficiency in microglia alleviates motor dysfunction by inhibiting ferroptosis in spinal cord injury

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Microglia are specialized resident immune cells of the central nervous system parenchyma that mediate reactions such as inflammatory response to spinal cord injury (SCI) and play significant roles in exacerbating or alleviating disease progression. Previous studies have suggested ferroptosis, a newly discovered form regulated necrotic cell death, plays crucial role neuronal dysfunction loss following SCI; however, microglial ferroptosis SCI underlying mechanisms remain elusive. Here, we elucidate lipid droplets accumulate microglia facilitate after SCI. Notably, peaks at 3 days post-injury, which it decreases. Microglial Period 2 (Per2) expression is elevated vivo, this change highly synchronized with changes ferroptosis. Using conditional knockout mice, observed microglia-specific Per2 promoted neurological function recovery by suppressing In vitro, overexpression deficiency amplified mitigated respectively. RNA-seq analysis, found Gpx4 was downregulated Per2. Coimmunoprecipitation (Co-IP) demonstrated directly interacted PPARα further regulate Gpx4. Furthermore, degree decreased number increased treatment inhibitor, indicated reducing during acute phase may be beneficial for dysfunction. Overall, our results indicate determines susceptibility via PPARα-Gpx4 axis, suggest has potential therapeutic strategy alleviate motor inhibiting

Language: Английский

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Engineered hybrid exosomes responsive to reactive oxygen species target the treatment of spinal cord injury by repairing mitochondrial damage and promoting neuronal function recovery

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 160669 - 160669

Published: Feb. 1, 2025

Language: Английский

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