Cytokine Signaling in Diabetic Neuropathy: A Key Player in Peripheral Nerve Damage

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 589 - 589

Published: Feb. 28, 2025

Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes mellitus, characterized by progressive nerve damage driven chronic hyperglycemia and systemic inflammation. The pathophysiology DPN significantly influenced pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α. These cytokines promote oxidative stress, vascular dysfunction, neuronal degeneration activating important signaling pathways including NF-κB MAPK. While IL-6 promotes microenvironment, increasing neuropathic pain, TNF-α IL-1β worsen Schwann cell failure compromising axonal support causing demyelination. Immune infiltration TLR activation increase the inflammatory cascade in DPN, resulting persistent neuroinflammatory state that sustains injury. main characteristics are degeneration, decreased neurotrophic support, which weaken transmission susceptibility to damage. Advanced glycation end-products, TNF-α, CXCL10 examples biomarkers may be used for early diagnosis disease progression monitoring. Additionally, crucial molecular targets have been found using proteomic transcriptome techniques, enabling precision medicine treatment DPN. This review emphasizes importance cytokine pathogenesis how cytokine-targeted treatments might reduce inflammation, restore function, improve clinical outcomes diabetic patients.

Language: Английский

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Inflammation in the Peripheral Nervous System after Injury

Biomedicines, Journal Year: 2024, Volume and Issue: 12(6), P. 1256 - 1256

Published: June 5, 2024

Nerve injury is a common condition that occurs as result of trauma, iatrogenic injury, or long-lasting stimulation. Unlike the central nervous system (CNS), peripheral (PNS) has strong capacity for self-repair and regeneration. Peripheral nerve results in degeneration distal axons myelin sheaths. Macrophages Schwann cells (SCs) can phagocytose damaged cells. Wallerian (WD) makes whole axon structure degenerate, creating favorable regenerative environment new axons. After macrophages, neutrophils other are mobilized recruited to site necrotic debris. Pro-inflammatory anti-inflammatory factors involved inflammatory response provide microenvironment regeneration regulate effects inflammation on body through relevant signaling pathways. Previously, was thought be detrimental body, but further research shown appropriate promotes regeneration, formation. On contrary, excessive cause tissue damage pathological changes, even lead neurological diseases. Therefore, after various interact with cytokines chemokines promote repair by inhibiting negative harnessing positive specific ways at times. Understanding interaction between neuroinflammation provides several therapeutic ideas improve

Language: Английский

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Constructing Nerve Guidance Conduit using dECM‐Doped Conductive Hydrogel to Promote Peripheral Nerve Regeneration

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(38)

Published: April 12, 2024

Abstract Peripheral nerve injury often leads to the loss of neurological functions due slow regeneration rate and inefficient functional reconstruction. Current clinical treatments using guidance conduits (NGCs) still face challenges in providing a biomimetic microenvironment promote repair. Herein, decellularized extracellular matrix (dECM) is obtained from porcine Achilles tendon crosslinked with 3‐amino‐4‐methoxybenzoic acid grafted gelatin (PAMB‐G) obtain conductive hydrogels. Then, novel conduit developed by assembling poly(vinyl alcohol) (PVA) ECM@PAMB‐G hydrogel. This bioengineered ECM@PAMB‐G/PVA demonstrated excellent cytocompatibility, electrical conductivity, mechanical properties, biodegradability. In vitro experiments confirmed that hydrogel significantly promotes proliferation migration PC12 cells primary Schwann cells, as well growth dorsal root ganglion (DRG) axons. Furthermore, vivo studies rat sciatic model exhibited improvements axonal regeneration, cell migration, myelin sheath formation, recovery mediated conduit. work demonstrates synergistic effects cues enhancing peripheral regeneration. The shows potential an alternative autografts for supporting

Language: Английский

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A comprehensive review of hydrogel strategies for repairing peripheral nerve injuries

Brain‐X, Journal Year: 2025, Volume and Issue: 3(1)

Published: Feb. 8, 2025

Abstract As an etiological factor underlying physical and mental disability in humans, peripheral nerve injuries (PNIs) can induce pain, sensory impairment, disability. Despite their regenerative ability, nerves cannot self‐repair after severe defects. While grafting is the gold standard for treatment of PNIs, it limited by graft versus host reactions, surgical complications, donor nerves. field material science continues to develop, hydrogels have been proposed use PNI repair biomodification, targeted modification, or loading with biological factors cells. This article reviewed research advances used repair, including simple composite functionalized loaded Based on findings from these reviews, we determined that further clarification mechanisms action modulating cellular functions necessary. In addition, there a need explore synergistic effect novel other biological, physical, biochemical factors. clinical trials are still limited, scientific efforts expected promote application repair.

Language: Английский

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Entrectinib can induce nerve cell damage by inhibiting PI3K-AKT and TGF-β signaling pathways

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

Published: Feb. 13, 2025

Background The tyrosine receptor kinase inhibitor (TRKi) entrectinib is used to treat neurotrophic (NTRK) fusion-positive solid tumors and ROS1-positive patients. Despite its impressive efficacy against cancer, the clinical application still limited by central nervous system (CNS)-related toxicities. However, precise mechanism of such CNS-related toxicities remains elusive. Methods effect entrectinib-induced nerve cell damage was evaluated cells (PC12, HT22 SK-N-SH) based in vitro models. Various assays, including CCK-8, colony formation EdU incorporation assays were utilized estimate cellular viability proliferation ability. Cell apoptosis measured flow cytometry. Next, transcriptome sequencing technology performed identify differentially expressed genes (DEGs). Gene ontology (GO), kyoto encyclopedia genomes (KEGG) analysis gene set enrichment (GSEA) applied predict potential functions DEGs. Quantitative real time polymerase chain reaction (qRT-PCR) Western blotting measure expressions thrombospondin-1 (THBS1), TGF-β1, PI3K, AKT phosphorylated (p-AKT) entrectinib-treated cells. Additionally, we Preliminary observed validated whether THBS1 overexpression could rescue abnormalities PI3K-AKT TGF-β signaling pathways. Results Entrectinib significantly inhibited formation, induced apoptosis. Transcriptome qRT-PCR revealed that downregulated within treatment. KEGG GSEA also suggested directly caused proliferation-related pathway like pathway, apoptosis-related pathway. We further demonstrated THBS1, p-AKT entrectinib. Meanwhile, pretreatment with plasmids rescued from death Conclusion These results identified a critical role promoting downregulating expression while inhibiting Our findings will provide therapeutic targets for

Language: Английский

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Neuroplasticity and Nervous System Recovery: Cellular Mechanisms, Therapeutic Advances, and Future Prospects

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(4), P. 400 - 400

Published: April 15, 2025

Neuroplasticity, the ability of nervous system to adapt structurally and functionally in response environmental interactions injuries, is a cornerstone recovery central (CNS) peripheral systems (PNS). This review explores mechanisms underlying neuroplasticity, focusing on dynamic roles cellular molecular processes from injuries. Key players, including Schwann cells, oligodendrocytes, neural stem are highlighted for their contributions nerve repair, myelination, regeneration. Advances therapeutic interventions, such as electrical stimulation, bioluminescent optogenetics, innovative grafting techniques, discussed alongside potential enhance functional outcomes. The underpinnings plasticity, involving synaptic remodeling, homeostatic mechanisms, activity-dependent regulation gene expression, elucidated illustrate role learning, memory, injury repair. Integrating emerging technologies approaches with foundational understanding neuroplasticity offers pathway toward more effective strategies restoring functionality after injury.

Language: Английский

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Unraveling the immune system’s role in peripheral nerve regeneration: a pathway to enhanced healing

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

Published: Feb. 21, 2025

Peripheral nerve injury (PNI) represents a common challenge in clinical practice. In contrast to the central nervous system (CNS), peripheral (PNS) mature mammals possesses limited regenerative capacity. Upon occurrence of PNI, regeneration (PNR) is initiated, facilitated by activation immune microenvironment and intrinsic growth potential neurons. This process encompasses several key stages, including distal axon degeneration, myelin breakdown, clearance debris, inflammatory responses from non-neuronal cells, subsequent axonal regeneration. The response, recognized for its role clearing debris modulating local milieu, crucial initiating at proximal stump nerves. Nevertheless, precise mechanisms which response influences PNI strategies harness this augment remain elusive. article provides comprehensive overview diverse roles PNR presents insights into therapeutic strategies. Furthermore, examines immune-associated signaling pathways their impact on PNR, underscoring significance modulation enhancing patient outcomes with PNI. Ultimately, it encapsulates forecasts theoretical practical directions field.

Language: Английский

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How Advancing is Peripheral Nerve Regeneration Using Nanofiber Scaffolds? A Comprehensive Review of the Literature

International Journal of Nanomedicine, Journal Year: 2023, Volume and Issue: Volume 18, P. 6763 - 6779

Published: Nov. 1, 2023

Abstract: Peripheral nerve injuries present significant challenges in regenerative medicine, primarily due to inherent limitations the body’s natural healing processes. In response these and with aim of enhancing peripheral regeneration, nanofiber scaffolds have emerged as a promising advanced intervention. However, deeper understanding underlying mechanistic foundations that drive favorable contributions regeneration is essential. this comprehensive review, we make an exploration latent potential augmenting regeneration. This includes detailed introduction fabrication methods nanofibers, analysis intricate interactions between cellular entities, examination strategies related controlled release bioactive agents, assessment prospects for clinical translation, emerging trends, thorough considerations regarding biocompatibility safety. By comprehensively elucidating structural attributes multifaceted functional capacities scaffolds, offer prospective effective strategy treatment injury. Keywords: nanofiber, nanomedicine, tissue

Language: Английский

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Autophagy-targeting modulation to promote peripheral nerve regeneration

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(7), P. 1864 - 1882

Published: May 10, 2024

Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors intricate molecular mechanisms. Past studies have focused on that stimulate axonal outgrowth myelin regeneration. However, recent highlighted the pivotal role of autophagy in regeneration, particularly context injuries. Consequently, autophagy-targeting modulation has emerged as promising therapeutic approach to enhancing Our current understanding suggests activating facilitates rapid clearance damaged axons sheaths, thereby neuronal survival mitigating injury-induced oxidative stress inflammation. These actions collectively contribute creating favorable microenvironment for structural functional A range autophagy-inducing drugs interventions demonstrated beneficial effects alleviating neuropathy promoting preclinical models This review delves into regulation cell types involved summarizing potential can be harnessed promote this process. We hope our will offer novel insights perspectives exploitation pathways treatment neuropathies.

Language: Английский

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Mesenchymal stem cells’ “garbage bags” at work: Treating radial nerve injury with mesenchymal stem cell-derived exosomes

World Journal of Stem Cells, Journal Year: 2024, Volume and Issue: 16(5), P. 467 - 478

Published: May 23, 2024

Unlike central nervous system injuries, peripheral nerve injuries (PNIs) are often characterized by more or less successful axonal regeneration. However, structural and functional recovery is a senile process involving multifaceted cellular molecular processes. The contemporary treatment options limited, with surgical intervention as the gold-standard method; however, each option has its associated limitations, especially when injury severe large gap. Recent advancements in cell-based therapy cell-free approaches using stem cell-derived soluble insoluble components of cell secretome fast-emerging therapeutic to treating acute chronic PNI. recent pilot study leap forward field, which expected pave way for enormous, systematic, well-designed clinical trials assess efficacy mesenchymal exosomes bio-drug either alone part combinatorial approach, an attempt synergize best novel address complexity neural repair

Language: Английский

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