ThePI3K/AKTsignalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: Mechanisms and therapeutic opportunities

Cell Proliferation, Journal Year: 2022, Volume and Issue: 55(9)

Published: June 26, 2022

Abstract Objects Traumatic spinal cord injury (TSCI) causes neurological dysfunction below the injured segment of cord, which significantly impacts quality life in affected patients. The phosphoinositide 3kinase/serine‐threonine kinase (PI3K/AKT) signaling pathway offers a potential therapeutic target for inhibition secondary TSCI. This review summarizes updates concerning role PI3K/AKT Materials and Methods By searching articles related to TSCI field pathway, we summarized mechanisms pathway; also discuss current future treatment methods based on pathway. Results Early apoptosis autophagy after protect body against injury; prolonged inflammatory response leads accumulation pro‐inflammatory factors excessive apoptosis, as well surrounding normal nerve cells, thus aggravating subacute stage injury. Initial glial scar formation phase is protective mechanism TSCI, limits spread damage inflammation. However, mature tissue chronic hinders axon regeneration prevents recovery function. Activation can inhibit TSCI; inhibiting this reduce scar. Conclusion has an important function Inducing activation may be one strategies

Language: Английский

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Mesenchymal stem cells in the treatment of spinal cord injury: Mechanisms, current advances and future challenges

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 24, 2023

Spinal cord injury (SCI) has considerable impact on patient physical, mental, and financial health. Secondary SCI is associated with inflammation, vascular destruction, subsequent permanent damage to the nervous system. Mesenchymal stem cells (MSCs) have anti-inflammatory properties, promoting regeneration release neuro-nutrients, are a promising strategy for treatment of SCI. Preclinical studies shown that MSCs promote sensory motor function recovery in rats. In clinical trials, been reported improve American Injury Association (ASIA) scores. However, effectiveness treating patients remains controversial. tumorigenesis ensuring survival hostile environment challenging. this article we examine evidence pathophysiological changes occurring after We then review underlying mechanisms summarize potential application practice. Finally, highlight challenges surrounding use discuss future applications.

Language: Английский

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Multifunctional Conductive and Electrogenic Hydrogel Repaired Spinal Cord Injury via Immunoregulation and Enhancement of Neuronal Differentiation

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(21)

Published: Feb. 3, 2024

Abstract Spinal cord injury (SCI) is a refractory neurological disorder. Due to the complex pathological processes, especially secondary inflammatory cascade and lack of intrinsic regenerative capacity, it difficult recover function after SCI. Meanwhile, simulating conductive microenvironment spinal reconstructs electrical neural signal transmission interrupted by SCI facilitates repair. Therefore, double‐crosslinked hydrogel (BP@Hydrogel) containing black phosphorus nanoplates (BP) synthesized. When placed in rotating magnetic field (RMF), BP@Hydrogel can generate stable signals exhibit electrogenic characteristic. In vitro, shows satisfactory biocompatibility alleviate activation microglia. RMF, enhances anti‐inflammatory effects. wireless stimulation promotes differentiation stem cells (NSCs) into neurons, which associated with PI3K/AKT pathway. vivo, injectable elicit behavioral electrophysiological recovery complete transected mice alleviating inflammation facilitating endogenous NSCs form functional neurons synapses under RMF. The present research develops multifunctional for repair targeting multiple mechanisms including immunoregulation enhancement neuronal differentiation.

Language: Английский

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Baicalin ameliorates neuroinflammation by targeting TLR4/MD2 complex on microglia via PI3K/AKT/NF-κB signaling pathway

Neuropharmacology, Journal Year: 2025, Volume and Issue: 267, P. 110296 - 110296

Published: Jan. 9, 2025

Language: Английский

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The role of PI3K/Akt signalling pathway in spinal cord injury

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 156, P. 113881 - 113881

Published: Oct. 19, 2022

Language: Английский

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Pharmacological effects of salidroside on central nervous system diseases

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 156, P. 113746 - 113746

Published: Oct. 10, 2022

Language: Английский

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Oxidative stress following spinal cord injury: From molecular mechanisms to therapeutic targets

Journal of Neuroscience Research, Journal Year: 2023, Volume and Issue: 101(10), P. 1538 - 1554

Published: June 5, 2023

Abstract Spinal cord injury (SCI) is a medical condition that results from severe trauma to the central nervous system; it imposes great psychological and economic burdens on affected patients their families. The dynamic balance between reactive oxygen species (ROS) antioxidants essential for maintaining normal cellular physiological functions. As important intracellular signaling molecules, ROS regulate numerous activities, including vascular reactivity neuronal function. However, excessive can cause damage macromolecules, DNA, lipids, proteins; this eventually leads cell death. This review discusses mechanisms of oxidative stress in SCI describes some pathways after injury, with aim providing guidance development novel treatment strategies.

Language: Английский

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The Exosome-Mediated PI3K/Akt/mTOR Signaling Pathway in Neurological Diseases

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(3), P. 1006 - 1006

Published: March 21, 2023

As major public health concerns associated with a rapidly growing aging population, neurodegenerative diseases (NDDs) and neurological are important causes of disability mortality. Neurological affect millions people worldwide. Recent studies have indicated that apoptosis, inflammation, oxidative stress the main players NDDs critical roles in processes. During aforementioned inflammatory/apoptotic/oxidative procedures, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target rapamycin (mTOR) pathway plays crucial role. Considering functional structural aspects blood–brain barrier, drug delivery to central nervous system is relatively challenging. Exosomes nanoscale membrane-bound carriers can be secreted by cells carry several cargoes, including proteins, nucleic acids, lipids, metabolites. significantly take part intercellular communications due their specific features low immunogenicity, flexibility, great tissue/cell penetration capabilities. Due ability cross these nano-sized structures been introduced as proper vehicles for multiple studies. In present systematic review, we highlight potential therapeutic effects exosomes context targeting PI3K/Akt/mTOR signaling pathway.

Language: Английский

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Critical review on anti‐inflammation effects of saponins and their molecular mechanisms

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(4), P. 2007 - 2022

Published: Feb. 19, 2024

Abstract This review highlights the increasing interest in one of natural compounds called saponins, for their potential therapeutic applications addressing inflammation which is a key factor various chronic diseases. It delves into molecular mechanisms responsible anti‐inflammatory effects these amphiphilic compounds, prevalent plant‐based foods and marine organisms. Their structures vary with soap‐like properties influencing historical uses traditional medicine sparking renewed scientific interest. Recent research focuses on inflammatory diseases, unveiling actions such as NF‐κB MAPK pathway regulation COX/LOX enzyme inhibition. Saponin‐containing sources like Panax ginseng soybeans suggest novel therapies. The explores emerging role shaping gut microbiome, composition activity, contributing to effects. Specific examples, notoginseng Gynostemma pentaphyllum , illustrate intricate relationship between collective impact immune metabolic health. Despite promising findings, emphasizes need further comprehend behind interactions underscoring crucial balanced microbiome optimal health positioning saponins dietary interventions managing conditions.

Language: Английский

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Immune-defensive microspheres promote regeneration of the nucleus pulposus by targeted entrapment of the inflammatory cascade during intervertebral disc degeneration

Bioactive Materials, Journal Year: 2024, Volume and Issue: 37, P. 132 - 152

Published: March 21, 2024

Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration (IVDD). Effective antagonism or reduction of local inflammatory factors may help regulate IVDD microenvironment reshape extracellular matrix disc. This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology surface chemical modification methods by grafting neutrophil polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1 (TGF-β1) (T-NNPs) onto methacrylic gelatin anhydride microspheres (GM) via amide bonds. The nanoparticle-microsphere complex (GM@T-NNPs) sustained long-term release T-NNPs excellent cell-like functions, effectively bound to pro-inflammatory cytokines, improved kinetics TGF-β1, maintaining a 36 day-acting release. GM@T-NNPs significantly inhibited lipopolysaccharide-induced in nucleus pulposus cells vitro, downregulated expression metalloproteinase, upregulated collagen-II aggrecan. restored height structure biomechanical function rat model. integration biomimetic nano-drug delivery systems expands application materials provides new treatment strategy IVDD.

Language: Английский

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