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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Management of ROS and Regulatory Cell Death in Myocardial Ischemia–Reperfusion Injury

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

Published: June 9, 2024

Language: Английский

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Gallic acid showed neuroprotection against endoplasmic reticulum stress in rats

Acta Cirúrgica Brasileira, Journal Year: 2025, Volume and Issue: 40

Published: Jan. 1, 2025

We aimed to investigate the role of gallic acid treatment on spinal cord tissues after injury (SCI) and its relationship with endoplasmic reticulum (ER) stress by histochemical, immunohistochemical, in-silico techniques. Thirty female Wistar albino rats were divided into three groups: sham, SCI, SCI+gallic acid. SCI was induced dropping a 15-g weight onto exposed T10-T11 segment. The group received 25 mg/kg intraperitoneally daily for one week. Histopathological, silico analyses performed. Histological analysis revealed improved neural cell survival tissue integrity in compared group. Caspase-12 expression significantly increased group, indicating elevated ER apoptosis. Gallic resulted marked reduction caspase-12 neurons, neuroglia, endothelial cells, suggesting decreased stress. exhibits significant neuroprotective effects against cellular damage rat model SCI. apoptotic immune-related pathways which showed regulating caspase-12. These results suggest that may be promising therapeutic agent mitigating secondary post-SCI.

Language: Английский

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Histone lactylation stimulated upregulation of PSMD14 alleviates neuron PANoptosis through deubiquitinating PKM/PKM2 to activate PINK1-mediated mitophagy after traumatic brain injury

Autophagy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 19

Published: Feb. 26, 2025

Alleviating the multiple types of programmed neuronal death caused by mechanical injury has been an impetus for designing neuro-therapeutical approaches after traumatic brain (TBI). The aim this study was to elucidate potential role PSMD14 (proteasome 26S subunit, non-ATPase 14) in neuron and specific mechanism through which it improves prognosis TBI patients. Here, we identified differential expression protein between controlled cortical impact (CCI) sham mouse groups LC-MS proteomic analysis found that significantly upregulated neurons qPCR western blot. suppressed stretch-induced PANoptosis improved motor ability learning performance CCI vivo. Mechanistically, PINK1 phosphorylation levels at Thr257 activated PINK1-mediated mitophagy deubiquitinating PKM/PKM2 (pyruvate kinase M1/2) maintain PKM stability. PSMD14-induced promoted mitochondrial homeostasis reduced ROS production, ultimately inhibited PANoptosis. upregulation due increase histone lactation modification level lactate treatment alleviated via increasing expression. Our findings suggest could be a therapeutic approach improving patients.Abbreviations: CCI: impact; CQ: chloroquine; DUBs: enzymes; H3K18la: H3 lysine 18 lactylation; IB: immunoblot; IHC: immunohistochemistry; IP: immunoprecipitation; MLKL: mixed lineage domain like pseudokinase; PI3K: phosphoinositide 3-kinase; PINK1: PTEN induced 1; PKM/PKM2: pyruvate M1/2; PSMD14: proteasome 14; ROS: reactive oxygen species; RIPK1: receptor interacting serine/threonine RIPK3: 3; TBI: injury.

Language: Английский

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Cycloastragenol promotes dorsal column axon regeneration in mice

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 3, 2025

Cycloastragenol (CAG) has a wide range of pharmacological effects, including anti-inflammatory, antiaging, antioxidative, and antitumorigenic properties. In addition, our previous study showed that CAG administration can promote axonal regeneration in peripheral neurons. However, whether activate axon central nervous system (CNS) remains unknown. Here, we established novel mouse model for visualizing spinal cord dorsal column involving the injection AAV2/9-Cre into lumbar 4/5 root ganglion (DRG) Rosa-tdTomato reporter mice. We then treated mice by intraperitoneal CAG. Our results injections significantly promoted growth vitro-cultured DRG axons as well over injury site (SCI) further indicate recovery sensory urinary function SCI Together, findings highlight therapeutic potential repair.

Language: Английский

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Trigonelline exerts its neuroprotective effects in experimental spinal cord injury through modulation of inflammation, apoptosis, and neurotrophic factors

Asian Pacific Journal of Tropical Biomedicine, Journal Year: 2025, Volume and Issue: 15(1), P. 34 - 42

Published: Jan. 1, 2025

Objective: To assess the protective effects of trigonelline against spinal cord injury (SCI) in rats. Methods: Rats (Sprague-Dawley, male) were randomly assigned to seven groups ( n =15 per group): normal, sham, SCI control (1% DMSO), methylprednisolone (30 mg/kg), and (50, 100, 200 mg/kg). received respective treatment daily for 28 days. was induced by using a temporary aneurysm clip. Behavioral, biochemical, histological analyses performed investigate neuroprotective effect trigonelline. Results: Trigonelline (100 mg/kg) effectively P <0.05) mitigated SCI-induced changes mechano-tactile sensation, allodynia, hyperalgesia, motor nerve conduction velocity. It notably downregulated apoptotic (Bax caspase-3) inflammatory (COX-II) markers, while upregulating Bcl-2 BDNF mRNA expression <0.05). Furthermore, alleviated alterations mitochondrial complex levels, resulting enhanced nicotinamide adenine dinucleotide dehydrogenase, succinate redox activity, cytochrome-C levels. Histological examination tissue indicated that significantly ameliorated damage caused SCI, thereby improving neuronal degeneration, cell infiltration, necrosis. Conclusions: shows properties rats reducing inflammation, stabilizing enzyme complexes, modulating neurotrophic factors. Thus, holds promise as potential agent.

Language: Английский

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Epidermal Mechanical Scratching-Induced ROS Exacerbates the Itch-Scratch Cycle via TRPA1 Activation on Mast Cells in Atopic Dermatitis

Journal of Investigative Dermatology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Unveiling the effects of Rosa canina oligosaccharide liposome on neuropathic pain and motor dysfunction following spinal cord injury in rats: relevance to its antioxidative effects

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

Published: Feb. 14, 2025

Background Spinal cord injury (SCI) is a leading cause of sensorimotor disorders, impacting millions people globally. The absence effective treatments and the side effects existing medications highlight need for innovative research into new therapeutic compounds. Purpose Given critical role oxidative stress in development SCI antioxidant properties oligosaccharides other neurological this study focuses on explores potential novel oligosaccharide nanoformulation derived from Rosa canina (Oligo-L). Materials methods Oligo-L was formulated using soy lecithin as phospholipid characterization included size, zeta potential, morphology, drug loading efficiency. Then 35 Wistar male rats were divided five groups Sham, SCI, (10 μL intrathecal injection 15, 30, 45 mg/mL). An aneurysm clip used to induce compression groups. Sensory-motor functions evaluated weekly 4 weeks tests such BBB scale, inclined plane, acetone drop, hot plate, von Frey, monitoring weight changes. Additionally, markers histological changes examined evaluate nitrite, glutathione, catalase, neuronal survival. Results discussion findings indicated that treatment led significant improvements neuropathic pain, motor function performance animals first week post-SCI. also enhanced catalase glutathione levels while reducing serum nitrite levels, contributing preservation. increased survival both ventral (motor neurons) dorsal (sensory horns spinal cord. Conclusion Overall, Oligo-L, characterized by its beneficial physicochemical properties, showed promising neuroprotective agent facilitated recovery sensory after SCI.

Language: Английский

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FOXO3-induced microRNA-128-3p promotes the progression of spinal cord injury in mice via regulating NLRP3 inflammasome-mediated pyroptosis

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

Published: Feb. 21, 2025

Spinal cord injury (SCI) remains a severe condition with an extremely high disability rate and complex pathophysiologic mechanisms. Pyroptosis, inflammatory form of cell death triggered by certain inflammasomes, has key role in variety diseases, including SCI. However, it is unclear whether microRNAs (miRNAs), novel regulators the SCI, are involved SCI-induced pyroptosis. Two GEO miRNA expression profiles (GSE158195 GSE90452) were downloaded, differentially expressed miRNAs analyzed bioinformatics methods. An vivo animal model vitro cellular SCI constructed female C57BL/6 mice BV-2 cells for studying possible roles FOXO3, miR-128-3p NLRP3-mediated pyroptosis Markers ROS, inflammation measured RT-qPCR, Western blotting, immunofluorescence, flow cytometry, enzyme-linked immunosorbent assays. Histopathological changes spinal tissue detected using hematoxylin eosin immunohistochemical. The Basso-Beattie-Bresnahan (BBB) score was used to evaluate motor function each group. Bioinformatics analysis GSE158195 GSE90452 datasets revealed significant downregulation miR-128-3p, phenomenon that consistently observed model. Functionally, upregulation improved functional behavioral recovery, relieved pathological injury, repressed oxidative stress, alleviated mouse models. We also confirmed Thioredoxin-interacting protein (TXNIP) target gene overexpression TXNIP can effectively reverse improvement Moreover, we found transcription factor FOXO3 facilitated expression, its resulted similar effects To best our knowledge, this first report demonstrating secondary through modulation pathway. Our results suggest FOXO3/miR-128-3p/TXNIP/NLRP3-mediated axis may be potential therapeutic

Language: Английский

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Activation of the Nrf2 Signaling Pathway by Tetrahydroberberine Suppresses Ferroptosis and Enhances Functional Recovery Following Spinal Cord Injury

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

Published: Feb. 26, 2025

Language: Английский

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