Hydrogel loaded with cerium-manganese nanoparticles and nerve growth factor enhances spinal cord injury repair by modulating immune microenvironment and promoting neuronal regeneration

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 20, 2025

Spinal cord injury (SCI) treatment remains a formidable challenge, as current therapeutic approaches provide only marginal relief and fail to reverse the underlying tissue damage. This study aims develop novel composite material combining enzymatic nanoparticles nerve growth factor (NGF) modulate immune microenvironment enhance SCI repair. CeMn (NP) NP-polyethylene glycol (PEG) nanozymes were synthesized via sol–gel reaction DSPE-mPEG modification. Transmission Electron Microscopy, Selected-Area Diffraction, X-ray Diffraction Photoelectron Spectroscopy confirmed their crystalline structure, mixed-valence states, redox properties. Size uniformity, biocompatibility, catalytic activity assessed hydrodynamic diameter, zeta potential, elemental analysis. The Lightgel/NGF/CeMn NP-PEG was characterized electron microscopy, compression testing, rheological analysis, NGF release kinetics, 30-day degradation studies. Both in vitro vivo experiments conducted evaluate effects of on SCI. successfully synthesized, exhibiting favorable physical At concentration 4 µg/mL, maintained cell viability demonstrated enhanced biological activity. It also showed superior mechanical properties an effective profile. Notably, significantly upregulated expression growth-associated proteins, reduced inflammatory cytokines, scavenged reactive oxygen species (ROS), promoted M2 macrophage polarization by inhibiting cyclic GMP-AMP synthase (cGAS)-stimulator interferon genes (STING) signaling pathway. In rat model, it facilitated functional recovery attenuated inflammation. shows significant promise for SCI, effectively eliminating ROS, promoting polarization, reducing pro-inflammatory supporting neuronal regeneration. These substantially motor function rats, positioning promising candidate future clinical applications.

Language: Английский

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NF-κB and JAK/STAT Signaling Pathways as Crucial Regulators of Neuroinflammation and Astrocyte Modulation in Spinal Cord Injury

Cells, Journal Year: 2024, Volume and Issue: 13(7), P. 581 - 581

Published: March 26, 2024

Spinal cord injury (SCI) leads to significant functional impairments below the level of injury, and astrocytes play a crucial role in pathophysiology SCI. Astrocytes undergo changes form glial scar after SCI, which has traditionally been viewed as barrier axonal regeneration recovery. activate intracellular signaling pathways, including nuclear factor κB (NF-κB) Janus kinase-signal transducers activators transcription (JAK/STAT), response external stimuli. NF-κB STAT3 are factors that pivotal initiating gene expression related astrogliosis. The JAK/STAT pathway is essential for managing secondary damage facilitating recovery processes post-SCI: inflammation, formation, astrocyte survival. activation production pro-inflammatory by astrocytes. pathways interconnected: release interleukin-6 (IL-6), interacts with IL-6 receptor initiates activation. By modulating responses, these offer promising avenues enhancing outcomes, illustrating need further investigation into their mechanisms therapeutic applications SCI treatment.

Language: Английский

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IL-11 promotes Ang II-induced autophagy inhibition and mitochondrial dysfunction in atrial fibroblasts

Open Life Sciences, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 1, 2025

Abstract This study aimed to investigate potential targets for the pathogenesis of atrial fibrillation facilitate development effective treatments. Atrial fibroblasts were isolated and stimulated with 1 μM angiotensin-II (Ang-II) 24 h. To increase interleukin 11 (IL-11) expression, overexpression plasmids transfected into fibroblasts. The role underlying mechanism IL-11 in examined by immunofluorescence, measurements reactive oxygen species (ROS) mitochondrial membrane (MMP), western blotting assays. Results demonstrated that was upregulated Ang-II-elicited Ang-II treatment increases alpha-smooth muscle actin (α-SMA), ROS MMP levels, p62 expression but decreases microtubule-associated protein light chain 3 II/I (LC3 II/I) Beclin-1 expressions These effects further amplified overexpression. Mechanistically, mammalian target rapamycin (mTOR) pathway enhanced Ang-II-induced fibroblasts, which elevated upregulation. facilitates Ang II-induced differentiation myofibroblasts promoting oxidative stress, dysfunction, autophagy inhibition through mTOR pathway.

Language: Английский

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Investigating the Potential Therapeutic Targeting of the JAK-STAT Pathway in Cerebrovascular Diseases: Opportunities and Challenges

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Language: Английский

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Neuroprotective effect and possible mechanism of edaravone in rat models of spinal cord injury: a systematic review and network meta-analysis

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

Published: April 7, 2025

The present review was developed to critically evaluate the neuroprotective effects of edaravone for experimental rat models spinal cord injury (SCI) and generalize possible mechanisms. Systematic searches were carried out on databases including PubMed, Embase, Web Science, Scopus, Cochrane Library from their inception March 2024. Controlled studies that assessed neurological roles rats following SCI selected. Basso, Beattie, Bresnahan (BBB) locomotor rating scale, residual white matter area, malondialdehyde (MDA) level systematically searched by two reviewers. Ten eligible publications included. Meta-analyses showed increased BBB scores in edaravone-treated compared with control ones. effect size gradually day 7 (seven studies, n = 246, weighted mean difference (WMD) 1.96, 95% confidence interval (CI) 1.23 2.68, P < 0.00001) 28 222, WMD 4.41, CI 3.19 5.63, after then maintained stably time. Meanwhile, treatment associated an amendment spared area a lowering MDA expression lesion area. subgroup analyses revealed treated exhibited superior recovery compression than contusion In network analyses, surface under cumulative ranking curve up dose 5-6 mg/(kg·d) edaravone, which it plateaued. Mechanism analysis suggested can ameliorate oxidative stress, mitigate neuroinflammation, counteract neuron apoptosis ferroptosis via multiple signaling pathways exert its effects. Collectively, protective systematic action mechanism, warrants further investigation research treatment. Nonetheless, light limitations included findings this should be interpreted caution. https://www.crd.york.ac.uk/PROSPERO/view/CRD42022374914.

Language: Английский

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Biomineralized MnO2 Nanoparticle-Constituted Hydrogels Promote Spinal Cord Injury Repair by Modulating Redox Microenvironment and Inhibiting Ferroptosis

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(8), P. 1057 - 1057

Published: Aug. 12, 2024

Spinal cord injury (SCI) is one of the most severe injuries, characterized by multiple positive feedback regulatory signaling networks formed oxidative stress and inflammation in microenvironment, leading to neuronal cell damage even death. Here, astragaloside IV (AS), known for its role ferroptosis, was encapsulated cavity apoferritin (HFn) after an situ biomineralization process involving MnO

Language: Английский

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Silencing of SH3BP2 Inhibits Microglia Activation Via the JAK/STAT Signaling in Spinal Cord Injury Models

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

Published: Nov. 15, 2024

Language: Английский

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Interleukin-11Rα2 in the hypothalamic arcuate nucleus affects depression-related behaviors and the AKT-BDNF pathway

Gene, Journal Year: 2024, Volume and Issue: 933, P. 148966 - 148966

Published: Sept. 26, 2024

Language: Английский

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Dual intervention of Boeravinone B and Chebulinic Acid mitigates BHT-Induced toxicity in HepG2 cells: modulating apoptosis and autophagy

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 28, 2024

Butylated Hydroxytoluene (BHT) is found to exert cellular toxicity through induction of oxidative stress although being used as antioxidant in many food products. This study investigates the protective effects two herbal compounds Boeravinone B (BB) and Chebulinic acid (CA) combination (B4C3 i.e. BB 4 µg/mL CA 3 µg/mL). Key findings revealed that BHT exerted ROS (234.47 a.u.) RNS (0.042 µM/mL), but B4C3 has significantly reduced it (115.46 a.u. 0.018 µM/mL respecctively). exposure raised activities enzymes such SOD (70.9%), CAT (7.08 units/mL), GPX (1.21 levels protein carbonyls (3.52 units/mg) lipid peroxides (418.34%). Whereas treatment with decreased (29.92%), (3.12 (0.36 (0.91 units/mg protein) (106.67%) during exposure. It was 20.56% cells were apoptotic while 73.83% autophagic treatment. However, proposed phytotherapy rescued from death supported cell growth which confirmed by RT-PCR analysis. Collectively, offered a significant protection against BHT-induced damage, suggesting its potential therapeutic agents for stress-related hepatotoxicity.

Language: Английский

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Identification of potential pathogenic genes for urolithiasis through multi-omics Mendelian randomization analysis

Urolithiasis, Journal Year: 2024, Volume and Issue: 53(1)

Published: Dec. 16, 2024

Language: Английский

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