Broad-spectrum downregulation of inflammatory cytokines by polydopamine nanoparticles to protect the injured spinal cord DOI Creative Commons
Dongdong Jiang, Yaping Ding, S. P. Hu

et al.

Acta Biomaterialia, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Acute neuroinflammation, which is notably characterized by a significant elevation in pro-inflammatory cytokines and chemokines, often rapidly develops following traumatic spinal cord injury exacerbates damage the lesion area. This study addresses limitations inherent strategies that regulate only single or few cytokines, are insufficient to counteract progression of secondary injuries. We explore use polydopamine nanoparticles as broad-spectrum immunomodulator, capable capturing adsorption wide range thereby effectively suppressing neuroinflammation. Leveraging their adhesive properties, these promptly reduce levels various excessive including IL-1α, IL-1β, IL-6, IL-10, IL-17A, IL-18, TNF-α, MCP-1, GRO/KC, M-CSF, MIP-3α, IFN-γ, primarily through physical adsorption. reduction cytokine contributes subsequent inhibition M1 microglia A1 astrocyte activation, aiding recovery motor functions vivo. In summary, represent versatile effective approach for modulating acute neuroinflammation By broadly down-regulating propose an innovative treating STATEMENT OF SIGNIFICANCE: The current demonstrated immunomodulatory potential mitigating injury. Both vitro vivo analyses revealed downregulation several key among panel 23 chemokines. underlying mechanisms governing interactions were elucidated comprehensive molecular dynamics simulations first time. Consequently, chemokines led activation both models. protected neurons within microenvironment, resulting improved locomotor functions. Overall, this underscores prominent therapeutic efficacy alleviating highlighting regulators intricate microenvironments.

Language: Английский

Regulating astrocyte phenotype by Lcn2 inhibition toward ischemic stroke therapy DOI

Ruhui Xiao,

Jingmei Pan,

Mu Yang

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 317, P. 123102 - 123102

Published: Jan. 16, 2025

Language: Английский

Citations

2
Microglial C/EBPβ-Fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recovery DOI Creative Commons
Jing Li, Yubing Yang, Chenguang Zhao

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 31, 2025

CAAT/Enhancer Binding Protein β (C/EBPβ) is associated with inflammatory responses in neurodegenerative pathologies, particularly the brain. However, regulatory role of C/EBPβ spinal cord injury and its impact on neurological recovery remain unknown. In this study, we observed significant upregulation microglia after mice was neuroinflammation. Knocking down attenuated pyroptosis, reduced production proinflammatory cytokines, inhibited neuronal apoptosis. Mechanistically, promoted transcription Fcgr1, which involved activating pyroptosis. both in-vivo in-vitro experiments, knocking Cebpb or pyroptosis inhibitor VX765 apoptosis improved mice. These findings indicate that functions as a key regulator participates pyroptosis-mediated neuroinflammation by Fcgr1 transcription.

Language: Английский

Citations

1
Amphiphilic pH-responsive core-shell nanoparticles can increase the performances of cellulose-based drug delivery systems DOI Creative Commons

Elisa Lacroce,

Giuseppe Nunziata,

Francesca Cianniello

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 283, P. 137659 - 137659

Published: Nov. 17, 2024

Language: Английский

Citations

6
Magnetically Active Bicontinuous Polymer Structures for Multiple Controlled Drug Delivery DOI

Elisa Lacroce,

Fabio Pizzetti,

Nicolás M. Barbosa Urrego

et al.

Macromolecular Bioscience, Journal Year: 2024, Volume and Issue: unknown

Published: May 11, 2024

Abstract The targeted delivery of drugs using wireless navigable magnetic robots allows the drug molecules to be controlled non only in time but also space, improving medical outcomes. main disadvantages behind their use lies low amount that can transported and single nature loaded (hydrophilic or hydrophobic). These considerations limit co‐delivery systems, now recognized very promising for many different pathologies. A bijel‐like structure is developed load release types In this work, ε‐caprolactone explored, which polymerize, forming hydrophobic domains (oil phase). After mixing with iron oxide nanoparticles (NPs), water dispersion creates a biphasic porous without phase separation. resulting device shows good performance both actuation as system.

Language: Английский

Citations

5
Amantadine modulates novel macrophage phenotypes to enhance neural repair following spinal cord injury DOI Creative Commons

Shijie Yang,

Beibei Yu, Qing Zhang

et al.

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

Published: Jan. 13, 2025

Spinal cord injury (SCI) triggers a complex inflammatory response that impedes neural repair and functional recovery. The modulation of macrophage phenotypes is thus considered promising therapeutic strategy to mitigate inflammation promote regeneration. We employed microarray single-cell RNA sequencing (scRNA-seq) investigate gene expression changes immune cell dynamics in mice following crush at 3 7 days post-injury (dpi). High-dimensional co-expression network analysis (hdWGCNA) slingshot trajectory were identify key modules differentiation pathways. Subsequently, immunofluorescence staining, flow cytometry, western blotting performed validate the identified effects amantadine on inflammation. To elucidate molecular mechanisms underlying transcriptional level, we followed by set enrichment (GSEA). results revealed pathways related phagocytosis activation are significantly involved post-injury, shedding light regulatory role macrophages SCI repair. further within injured spinal cord, conducted scRNA-Seq, identifying three distinct subtypes: border-associated (BAMs), (IMs), chemotaxis-inducing (CIMs). Trajectory suggested pathway from Il-1b+ IMs Mrc1+ BAMs, subsequently Arg1+ CIMs, indicating potential maturation process. Given importance these response, utilized docking hypothesize might modulate this Subsequent vitro vivo experiments demonstrated reduces facilitates transition BAMs likely through HIF-1α NF-κB This promotes regeneration enhances recovery SCI. Amantadine modulates SCI, early responses, function These findings highlight as treatment for provide foundation future translational research into its clinical applications.

Language: Английский

Citations

0
Multifunctional albumin-based hydrogel/microglia composites enhancing the therapeutic potential of neonatal microglia in complex spinal cord injuries and sealing dural rupture DOI
Shang Li, Yongxian Guo, Xiaoyu Zhou

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 321, P. 123327 - 123327

Published: April 11, 2025

Language: Английский

Citations

0
Nanomedicine-enabled next-generation therapeutics for spinal cord injury DOI
Min Ge,

Yuanqing Ding,

Tingting Hu

et al.

Materials Today, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Targeted therapy and deep learning insights into microglia modulation for spinal cord injury DOI Creative Commons

Emilia Petillo,

Valeria Veneruso,

Gianluca Gragnaniello

et al.

Materials Today Bio, Journal Year: 2024, Volume and Issue: 27, P. 101117 - 101117

Published: June 13, 2024

Spinal cord injury (SCI) is a devastating condition that can cause significant motor and sensory impairment. Microglia, the central nervous system's immune sentinels, are known to be promising therapeutic targets in both SCI neurodegenerative diseases. The most effective way deliver medications control microglial inflammation through nanovectors; however, because of variability morphology lack standardized techniques, it still difficult precisely measure their activation preclinical models. This problem especially important SCI, where intricacy glia response following traumatic events necessitates use sophisticated method automatically discern between various cell states vary over time space as secondary progresses. We address this issue by proposing deep learning-based technique for quantifying drug-loaded nanovector treatment model. Our uses convolutional neural network segment classify microglia based on morphological characteristics. approach's accuracy efficiency demonstrated evaluation collection histology pictures from injured intact spinal cords. robust computational has potential analyzing across neuropathologies demonstrating usefulness nanovectors modifying other neurological disorders. It ability speed development crucial sector providing objective compare options.

Language: Английский

Citations

3
Harnessing nanomedicine for modulating microglial states in the central nervous system disorders: Challenges and opportunities DOI Creative Commons
Haisong Li, Meng Guan, Ning-Ning Zhang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117011 - 117011

Published: June 24, 2024

Microglia are essential for maintaining homeostasis and responding to pathological events in the central nervous system (CNS). Their dynamic multidimensional states different environments pivotal factors various CNS disorders. However, therapeutic modulation of microglial is challenging due intricate balance these cells maintain environment blood-brain barrier's restriction drug delivery. Nanomedicine presents a promising avenue addressing challenges, offering method targeted efficient states. This review covers challenges faced potential use nanoparticle-based delivery systems. We provide an in-depth examination nanoparticle applications modulating range disorders, encompassing neurodegenerative autoimmune diseases, infections, traumatic injuries, stroke, tumors, chronic pain, psychiatric conditions. highlights recent advancements future prospects nanomedicine modulation, paving way research clinical interventions

Language: Английский

Citations

2
Beyond Traditional Medicine: EVs-Loaded Hydrogels as a Game Changer in Disease Therapeutics DOI Creative Commons
S.W. Du, Xiaohu Zhou, Bo Zheng

et al.

Gels, Journal Year: 2024, Volume and Issue: 10(3), P. 162 - 162

Published: Feb. 21, 2024

Extracellular vesicles (EVs), especially exosomes, have shown great therapeutic potential in the treatment of diseases, as they can target cells or tissues. However, effect EVs is limited due to susceptibility immune system clearance during transport vivo. Hydrogels become an ideal delivery platform for their good biocompatibility and porous structure. This article reviews preparation application EVs-loaded hydrogels a cell-free therapy strategy diseases. The also discusses challenges future outlook hydrogels.

Language: Английский

Citations

2