Journal of Drug Delivery Science and Technology, Год журнала: 2025, Номер unknown, С. 107058 - 107058
Опубликована: Май 1, 2025
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Янв. 8, 2024
Abstract Ischemia-reperfusion (I/R) injury paradoxically occurs during reperfusion following ischemia, exacerbating the initial tissue damage. The limited understanding of intricate mechanisms underlying I/R hinders development effective therapeutic interventions. Wnt signaling pathway exhibits extensive crosstalk with various other pathways, forming a network system pathways involved in injury. This review article elucidates signaling, as well complex interplay between and including Notch, phosphatidylinositol 3-kinase/protein kinase B, transforming growth factor-β, nuclear factor kappa, bone morphogenetic protein, N-methyl-D-aspartic acid receptor-Ca 2+ -Activin A, Hippo-Yes-associated toll-like receptor 4/toll-interleukine-1 domain-containing adapter-inducing interferon-β, hepatocyte factor/mesenchymal-epithelial transition factor. In particular, we delve into their respective contributions to key pathological processes, apoptosis, inflammatory response, oxidative stress, extracellular matrix remodeling, angiogenesis, cell hypertrophy, fibrosis, ferroptosis, neurogenesis, blood-brain barrier damage Our comprehensive analysis reveals that activation canonical promotes organ recovery, while non-canonical exacerbates Moreover, explore novel approaches based on these mechanistic findings, incorporating evidence from animal experiments, current standards, clinical trials. objective this is provide deeper insights roles its I/R-mediated processes dysfunction, facilitate innovative agents for
Язык: Английский
Процитировано
188
Neuropharmacology, Год журнала: 2025, Номер 267, С. 110296 - 110296
Опубликована: Янв. 9, 2025
Язык: Английский
Процитировано
2
Frontiers in Pharmacology, Год журнала: 2025, Номер 16
Опубликована: Фев. 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
Язык: Английский
Процитировано
1
Molecular Neurobiology, Год журнала: 2023, Номер 60(9), С. 5292 - 5308
Опубликована: Июнь 7, 2023
Язык: Английский
Процитировано
22
Bioactive Materials, Год журнала: 2023, Номер 29, С. 36 - 49
Опубликована: Июнь 28, 2023
Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)-mediated neurovascular unit formation. However, effects of central nerve system-derived MECs on neovascularization and neurogenesis, potential signaling involved therein, are unclear. Here, we established a primary cord-derived (SCMECs) isolation with high yield purity describe differences brain-derived (BMECs) their therapeutic SCI. Transcriptomics proteomics revealed differentially expressed genes proteins in SCMECs were angiogenesis, immunity, metabolism, adhesion molecular was only pathway enriched top 10 KEGG analysis. BMECs could be induced angiogenesis by different stiffness stimulation PEG hydrogels elastic modulus 50-1650 Pa for 50-300 BMECs, respectively. Moreover, promoted or NSC (SNSC/BNSC) proliferation, migration, differentiation at levels. At certain dose, combination NeuroRegen scaffold, showed higher effectiveness promotion vascular reconstruction. The underlying mechanism this phenomenon may through VEGF/AKT/eNOS- pathway, consequently accelerated neuronal functional recovery SCI rats compared BMECs. Our findings suggested promising role restoring vascularization neural regeneration.
Язык: Английский
Процитировано
21
Bioactive Materials, Год журнала: 2023, Номер 31, С. 563 - 577
Опубликована: Сен. 17, 2023
Decellularized extracellular matrix (dECM), with its distinct biological properties, has gained significant attention as a natural biomaterial. Leveraging potentials, we successfully developed three-dimensional matrix-based oriented nerve graft by encapsulating fibrous scaffold multilayered conformationally intact and biologically active human bone marrow mesenchymal stem cell-derived decellularized (hBMSC-dECM). Convincingly, the hBMSC-dECM group exhibited comparable functional recoveries to autograft postoperative week 12. In comprehensive analysis, molecular regulations in were more intricate nuanced compared group. Nevertheless, both groups displayed similar regulatory processes terms of vascularization matrix. Notably, demonstrated sustained high levels regulation axon myelin regeneration at 12, while immunomodulation returned normal after peaking 2. Collectively, our findings illustrated satisfactory construction cell-matrixed that established microenvironment conducive regeneration, elucidated patterns characteristics associated different repair modes.
Язык: Английский
Процитировано
20
Experimental Neurology, Год журнала: 2024, Номер 375, С. 114739 - 114739
Опубликована: Фев. 22, 2024
Spinal cord injury (SCI) is a disorder of the central nervous system resulting from various factors such as trauma, inflammation, tumors, and other etiologies. This condition leads to impairment in motor, sensory, autonomic functions below level injury. Limitations current therapeutic approaches prompt an investigation into angiogenesis through persistent local expression proangiogenic factors. Here, we investigated whether overexpression adeno-associated virus (AAV)-mediated vascular endothelial growth factor A (VEGFA) mouse SCI promoted locomotor function recovery, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was mechanistically involved. Three weeks before SCI, AAV-VEGFA injected at T10 induce VEGFA overexpression. Neurofunctional, histological, biochemical assessments were done determine tissue damage and/or recovery neuromuscular behavioral impairments. Daily injections PI3K/Akt inhibitor LY294002 made assess possible mechanism. dramatically improved ameliorated pathological caused by SCI. Improved motor-evoked potentials hindlimbs more spinal CD31-positive microvessels observed AAV-VEGFA-overexpressing mice. reduced PI3K Akt phosphorylation levels attenuated AAV-VEGFA-related improvements. In conclusion, sustained AAV-mediated can significantly promote ameliorate after contusion model activation signaling pathway.
Язык: Английский
Процитировано
9
Molecular Neurobiology, Год журнала: 2024, Номер unknown
Опубликована: Авг. 2, 2024
Язык: Английский
Процитировано
8
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(21), С. 11638 - 11638
Опубликована: Окт. 30, 2024
Neuroinflammation, characterised by the activation of immune cells in central nervous system (CNS), plays a dual role both protecting against and contributing to progression neurodegenerative diseases, such as Alzheimer's disease (AD) multiple sclerosis (MS). This review explores phosphoinositide 3-kinase (PI3K), key enzyme involved cellular survival, proliferation, inflammatory responses, within context neuroinflammation. Two PI3K isoforms interest, PI3Kγ PI3Kδ, are specific regulation CNS cells, microglia, astrocytes, neurons, oligodendrocytes, influencing pathways, Akt, mTOR, NF-κB, that control cytokine production, cell activation, neuroprotection. The dysregulation signalling is implicated chronic neuroinflammation, exacerbation diseases. Preclinical studies show promise targeting neuronal disorders using inhibitors, AS605240 (PI3Kγ) idelalisib (PI3Kδ), which have reduced inflammation, microglial death vivo models AD. However, clinical translation these inhibitors faces challenges, including blood-brain barrier (BBB) permeability, isoform specificity, long-term safety concerns. highlights therapeutic potential modulation neuroinflammatory identifying gaps current research, particularly need for brain-penetrating isoform-specific inhibitors. These findings underscore importance future research develop targeted therapies can effectively modulate activity provide neuroprotection disorders.
Язык: Английский
Процитировано
8
Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 176, С. 116938 - 116938
Опубликована: Июнь 14, 2024
Spinal cord injury (SCI) is a serious and disabling central nervous system injury. Its complex pathological mechanism can lead to sensory motor dysfunction. It has been reported that signaling pathway plays key role in the process neuronal recovery of SCI. Such as PI3K/Akt, MAPK, NF-κB, Wnt/β-catenin pathways. According reports, various stimuli cytokines activate these pathways related SCI pathology, thereby participating regulation processes such inflammation response, cell apoptosis, oxidative stress, glial scar formation after Activation or inhibition relevant delay inflammatory reduce prevent formation, improve microenvironment SCI, promote neural function recovery. Based on they may be potential targets for treatment Therefore, understanding its inhibitors beneficial development therapeutic new drugs. This paper mainly summarizes pathophysiological involved pathogenesis, specific inhibitors/activators treatment. In addition, this review also discusses deficiencies defects research. hoped study provide reference future research pathogenesis theoretical basis biotherapy.
Язык: Английский
Процитировано
6