Neuroprotective effects of SOX5 against ischemic stroke by regulating VEGF/PI3K/AKT pathway

Zhang, W; Wu, Yuqin; Chen, Hong; Yu, Dan; Zhao, Jinfeng; Chen, Jing

doi:10.1016/j.gene.2020.145148

Cited by 25 publications

(16 citation statements)

References 36 publications

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“…In this study, we found that the expression of IL1β, IL6, TNF-α, and CXCL2 was increased during the early stage of AIS ( Figure 8 ) but decreased after treatment. We also observed that pro-inflammatory signaling pathways, such as p38 MAPK, Erk1/2, and PI3K/Akt, were activated during AIS, which was supported by previous studies ( Liu et al, 2009 ; Lok et al, 2015 ; Fann et al, 2018 ; Zhang et al, 2021 ).…”

Section: Discussionsupporting

confidence: 91%

Serum Extracellular Vesicle–Derived miR-124-3p as a Diagnostic and Predictive Marker for Early-Stage Acute Ischemic Stroke

Zheng

Zhao

et al. 2021

Front. Mol. Biosci.

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Background: A delay in the diagnosis of acute ischemic stroke (AIS) reduces the eligibility and outcome of patients for thrombolytic therapy. Therefore, early diagnosis and treatment of AIS are crucial. The present study evaluated the sensitivity and accuracy of serum extracellular vesicle (EV)-derived miR-124-3p in the diagnosis and prediction of AIS.Methods: An miRNA expression profile was downloaded from Gene Expression Omnibus (GEO) database and analyzed by R software. EVs were harvested from the serum of AIS patients using a total exosome isolation kit and characterized by Western blotting, a transmission electron microscope, and the nanoparticle tracking analysis. BV2 microglia were pre-stimulated with lipopolysaccharide (LPS), followed by miR-124-3p treatment for 24 h and subsequent analysis of viability, apoptosis, and migration (scratch assay), and Western blotting. The relative expression of the selected genes was assessed by qRT-PCR. The phosphorylation of Erk1/2, PI3K/Akt, and p38MAPK in BV2 microglia cells was evaluated by Western blotting, while the luciferase reporter gene assay detected the correlation between key genes involved in the pro-inflammatory signaling pathways and miR-124-3p.Results:hsa-miR-124-3p was downregulated in AIS serum compared to the non-AIS serum (p < 0.05), and the gene expression of has-miR-124-3p in EVs was negatively correlated with serum pro-inflammatory cytokines and the NIHSS (p < 0.05). In addition, miR-124-3p promoted the viability and inhibited the apoptosis of LPS-induced BV2 microglia. Furthermore, miR-124-3p reduced the phosphorylation of Erk1/2, PI3K/Akt, and p38MAPK, and promoted the migration in LPS-induced BV2 microglia (p < 0.05).Conclusion: Serum EV-derived miR-124-3p serves as a diagnostic and predictive marker for early-stage AIS.

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Section: Discussionsupporting

confidence: 91%

Serum Extracellular Vesicle–Derived miR-124-3p as a Diagnostic and Predictive Marker for Early-Stage Acute Ischemic Stroke

Zheng

Zhao

et al. 2021

Front. Mol. Biosci.

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“…PIK3CA codes for the p110 subunit of the phosphatidylinositol 3-kinases (PI3Ks), and its mutations decrease cell apoptosis and increase the activity of downstream PI3Ks. It is known that activation of PI3K/AKT promotes repair of neural injury due to ischemic stroke [48,49] and angiogenesis in the hypoxic environment in vitro [50]. Consequently, it protects the rat brain from inflammation resulting from ischemia-reperfusion injury [51].…”

Section: Discussionmentioning

confidence: 99%

[Retracted] A Network Pharmacology to Explore the Mechanism of Calculus Bovis in the Treatment of Ischemic Stroke

Liu

Chen

et al. 2021

BioMed Research International

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Background. Calculus Bovis is a valuable Chinese medicine, which is widely used in the clinical treatment of ischemic stroke. The present study is aimed at investigating its target and the mechanism involved in ischemic stroke treatment by network pharmacology. Methods. Effective compounds of Calculus Bovis were collected using methods of network pharmacology and using the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Potential compound targets were searched in the TCMSP and SwissTargetPrediction databases. Ischemic stroke-related disease targets were searched in the Drugbank, DisGeNet, OMIM, and TTD databases. These two types of targets were uploaded to the STRING database, and a network of their interaction (PPI) was built with its characteristics calculated, aiming to reveal a number of key targets. Hub genes were selected using a plug-in of the Cytoscape software, and Gene Ontology (GO) biological processes and pathway enrichment analyses of Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted using the clusterProfiler package of R language. Results. Among 12 compounds, deoxycorticosterone, methyl cholate, and biliverdin were potentially effective components. A total of 344 Calculus Bovis compound targets and 590 ischemic stroke targets were found with 92 overlapping targets, including hub genes such as TP53, AKT, PIK2CA, MAPK3, MMP9, and MMP2. Biological functions of Calculus Bovis are associated with protein hydrolyzation, phosphorylation of serine/threonine residues of protein substrates, peptide bond hydrolyzation of peptides and proteins, hydrolyzation of intracellular second messengers, antioxidation and reduction, RNA transcription, and other biological processes. Conclusion. Calculus Bovis may play a role in ischemic stroke by activating PI3K-AKT and MAPK signaling pathways, which are involved in regulating inflammatory response, cell apoptosis, and proliferation.

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“…PI3K/Akt pathway can not only prevent nerve injury, but also promote neuronal survival. Its effect of repairing nerve injury was positively correlated to VEGF expression 66 . Lv et al have found that mice with ischemic stroke can promote the activation of glial cells and inhibit neuroinflammation by activating PI3K/Akt/NF-κB signaling pathway 67 .…”

Section: Discussionmentioning

confidence: 90%

Uncovering the Mechanism of Chuanhong Stroke Capsule in the Treatment of Stroke Based on Network Pharmacology and Molecular Docking Technology

Wang

Zhao

Kan

et al. 2022

Natural Product Communications

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Background and Objective: Chuanhong Stroke Capsule (CHSC) has good clinical efficacy in the treatment of cerebral ischemic stroke (CIS) patients. This study aimed to investigate the pharmacological mechanisms of CHSC in treating CIS using bioinformatics. Methods: The active compounds of CHSC were screened by searching Traditional Chinese Medicine System Pharmacological Database and Analysis Platform (TCMSP), Swiss absorption, distribution, metabolism, and excretion (ADME), PubMed, and China National Knowledge Infrastructure (CNKI) databases. Besides, the potential targets of active compounds were obtained through TCMSP and Swiss Target Prediction databases. CIS targets were obtained from GeneCards, Online Mendelian Inheritance in Man (OMIM), and Gene Expression Omnibus (GEO) databases. CHSC-CIS intersection targets were identified by matching the two, and prediction and analysis of biological functions and pathways of intersection targets was used the enrichments of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, protein–protein interaction (PPI) network, herb-target, and compound-target network of CHSC-CIS were constructed by Cytoscape3.7.2, and herb-compound-pathway network was drawn with Sankey diagram. Finally, AutoDock was used for molecular docking verification, and identifying the active binding sites in target proteins. Results: A total of 293 putative targets were obtained from 62 active compounds in CHSC. Among them, 209 targets were related to CIS. PPI network showed that the top 16 key targets were RELA, JUN, FOS, MAPK1, AKT1, etc. KEGG pathway enrichment analysis demonstrated that CHSC was enriched in PI3K-Akt, MAPK, and TNF signaling pathways. In addition, GO enrichment analysis showed the significant enrichment of CHSC in the following categories: kinase binding, cellular response to nitrogen compound, etc. Network topology analysis showed that quercetin, luteolin, kaempferol, etc., were the key components in CHSC. Finally, molecular docking studies suggested that the active components in CHSC had a good binding ability with the key targets. Conclusions: Our study demonstrated that CHSC exerted the effect in treating CIS by the characteristics of multi-target and multi-pathway, thereby providing a theoretical basis for further study of the effective components and mechanism of CHSC in the treatment of CIS.

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Neuroprotective effects of SOX5 against ischemic stroke by regulating VEGF/PI3K/AKT pathway

Cited by 25 publications

References 36 publications

Serum Extracellular Vesicle–Derived miR-124-3p as a Diagnostic and Predictive Marker for Early-Stage Acute Ischemic Stroke

Serum Extracellular Vesicle–Derived miR-124-3p as a Diagnostic and Predictive Marker for Early-Stage Acute Ischemic Stroke

[Retracted] A Network Pharmacology to Explore the Mechanism of Calculus Bovis in the Treatment of Ischemic Stroke

Uncovering the Mechanism of Chuanhong Stroke Capsule in the Treatment of Stroke Based on Network Pharmacology and Molecular Docking Technology

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