Identifying potential therapeutic targets for ischemic stroke through immune infiltration analysis and construction of a programmed cell death‑related ceRNA network

Cui, Yiteng; Zhou, Xin; Meng, Pingping; Dong, Shanshan; Wang, Ziwei; Liu, Tongye; Liu, Xiaomin; Cui, Yunteng; Wang, Yuyang; Wang, Qiang

doi:10.3892/etm.2022.11616

Cited by 3 publications

(2 citation statements)

References 53 publications

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“…The corrplot of “R” ( 27 ) was used to create the heat maps related to invasive immune cells, and Cibersort ( 28 ) was utilized to examine the infiltration of immune cells.…”

Section: Methodsmentioning

confidence: 99%

Schizophrenia and cell senescence candidate genes screening, machine learning, diagnostic models, and drug prediction

Feng

Shen

et al. 2023

Front. Psychiatry

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BackgroundSchizophrenia (SC) is one of the most common psychiatric diseases. Its potential pathogenic genes and effective treatment methods are still unclear. Cell senescence has been confirmed in mental diseases. A link exists between cellular senescence and immunity, and immune-related problems affect suicide rates in individuals suffering from schizophrenia. Therefore, the aims of this study were to identify candidate genes based on cell senescence that can affect the diagnosis and treatment of schizophrenia.MethodsTwo data sets of schizophrenia were provided by the Gene Expression Omnibus (GEO) database, one was taken as training and the other as a validation group. The genes related to cell senescence were obtained from the CellAge database. DEGs were identified using the Limma package and weighted gene co-expression network analysis (WGCNA). The function enrichment analysis was conducted, followed by machine learning-based identification for least absolute shrinking and selection operators (LASSO) regression. Random Forest were used to identify candidate immune-related central genes and establish artificial neural networks for verification of the candidate genes. The receiver operating characteristic curve (ROC curve) was used for the diagnosis of schizophrenia. Immune cell infiltrates were constructed to study immune cell dysregulation in schizophrenia, and relevant drugs with candidate genes were collected from the DrugBank database.ResultsThirteen co-expression modules were screened for schizophrenia, of which 124 were the most relevant genes.There were 23 intersected genes of schizophrenia (including DEGs and the cellular senescence-related genes), and through machine learning six candidate genes were finally screened out. The diagnostic value was evaluated using the ROC curve data. Based on these results it was confirmed that these candidate genes have high diagnostic value.Two drugs related to candidate genes, Fostamatinib and Ritodine, were collected from the DrugBanks database.ConclusionSix potential candidate genes (SFN, KDM5B, MYLK, IRF3, IRF7, and ID1) had been identified, all of which had diagnostic significance. Fostamatinib might be a drug choice for patients with schizophrenia to develop immune thrombocytopenic purpura (ITP) after treatment, providing effective evidence for the pathogenesis and drug treatment of schizophrenia.

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“…The corrplot of “R” ( 27 ) was used to create the heat maps related to invasive immune cells, and Cibersort ( 28 ) was utilized to examine the infiltration of immune cells.…”

Section: Methodsmentioning

confidence: 99%

Schizophrenia and cell senescence candidate genes screening, machine learning, diagnostic models, and drug prediction

Feng

Shen

et al. 2023

Front. Psychiatry

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“…Biochemical and transcriptomic analyses of mediators of iron metabolism, antioxidant defenses, oxidative stress, and lipid peroxidation in experimental disease models, autopsy material, and induced pluripotent stem cell (iPSCs) derived from patients indicate that ferroptosis is a major mechanism of cell death in a wide range of neurologic disorders. These include Alzheimer disease (AD), 64,72,76-82 Parkinson disease (PD), 55,83-87 amyotrophic lateral sclerosis (ALS), 88-92 Huntington disease, 93-95 Friedreich ataxia, 96-98 multiple sclerosis, 99-101 ischemic stroke, 47,102-105 intracerebral hemorrhage, 106,107 traumatic brain injury, 108 spinal cord injury, 109,110 epilepsy, 111-113 and glioma, 114 among others. This topic has been extensively reviewed, 16-21,115,116 and only few concepts will be emphasized in this study.…”

Section: Role Of Ferroptosis In Neurologic Diseasementioning

confidence: 99%

What Is the Role of Ferroptosis in Neurodegeneration?

Benarroch

2023

Neurology

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Ferroptosis is a unique form of programmed cell death pathway that is mechanistically different from necrosis, apoptosis, or autophagy.1 Ferroptosis is induced by reactive oxygen species (ROS) originating from multiple sources, especially accumulation of free intracellular divalent iron (Fe2+), leading to peroxidation of polyunsaturated fatty acids (PUFAs) and resulting in membrane damage (Figure). One major trigger of ferroptosis is decreased availability of intracellular antioxidant enzymes, particularly glutathione peroxidases (GPXs).1-7 Because of its high lipid concentration and oxygen consumption rate, the nervous tissue is extremely vulnerable to oxidative damage and ferroptosis. With aging, iron accumulates in the brain, which predisposes to and exacerbates these processes.8 Iron promotes ferroptosis both directly and as a cofactor required for the activity of enzymes mediating redox reactions and lipid peroxidation.9,10 Epigenetic regulation can determine cell sensitivity to ferroptosis by affecting intracellular iron levels, oxidative stress, and lipid metabolism.11 Ferroptosis affects all cell types in the nervous system, including neurons, glial cells, and pericytes.12 Microglia are the primary iron-accumulating cells in disease.13,14 Recent evidence indicates that iron-laden microglia have a critical role in ferroptosis associated with neurodegeneration.15 Studies in vitro, in experimental disease models, and in human brain tissue indicate that iron accumulation, oxidative stress, and lipid peroxidation are major disease mechanisms in a wide range of neurologic disorders. These studies also suggest that the different components of the ferroptosis pathway are potential targets for therapeutic intervention. The mechanisms of ferroptosis and its role in neurologic disorders have been the subject of several recent comprehensive reviews.7,8,16-21 Some of these concepts pertinent to neurodegeneration will be emphasized in this study.

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Implications of the SNHG10/miR-665/RASSF5/NF-κB pathway in dihydromyricetin-mediated ischemic stroke protection

Zeng,

Xiao,

Zeng

et al. 2024

PeerJ

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Ischemic stroke (IS) remains a leading cause of disability and mortality worldwide, and inflammation and oxidative stress play significant roles in its pathogenesis. This study investigates the effects of dihydromyricetin (DHM) on IS using RT-qPCR and western blot with SH-SY5Y cells, focusing on its effects on the small nucleolar RNA host gene 10 (SNHG10)/microRNA (miR)-665/Ras association domain family member 5 (RASSF5) axis and nuclear factor-kappa B (NF-κB) signaling. In addition, the effects of the SNHG10/miR-665/RASSF5 axis on SH-SY5Y cell activity, apoptosis, oxidative stress, and inflammatory markers were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and enzyme-linked immunosorbent assays. Our results showed that, in response to oxygen-glucose deprivation/reperfusion (OGD/R), DHM treatment improved cell viability, reduced apoptosis, and attenuated neuroinflammation and oxidative stress in a dose-dependent manner (p < 0.05). Interestingly, lncRNA SNHG10 was overexpressed during OGD/R and suppressed by DHM. Through bioinformatics analysis and experimental validation, we identified miR-665 as a direct target of SNHG10 and RASSF5 as a direct target of miR-665. The protective effect of DHM against OGD/R injury was partially reversed by SNHG10 overexpression and further enhanced by co-transfection with the miR-665 mimic and si-RASSF5 (p < 0.05). This study identifies a novel mechanism of DHM against IS, which may act via modulation of the SNHG10/miR-665/RASSF5 axis and inactivation of NF-κB signaling, and offers a promising therapeutic target for IS.

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Identifying potential therapeutic targets for ischemic stroke through immune infiltration analysis and construction of a programmed cell death‑related ceRNA network

Cited by 3 publications

References 53 publications

Schizophrenia and cell senescence candidate genes screening, machine learning, diagnostic models, and drug prediction

Schizophrenia and cell senescence candidate genes screening, machine learning, diagnostic models, and drug prediction

What Is the Role of Ferroptosis in Neurodegeneration?

Implications of the SNHG10/miR-665/RASSF5/NF-κB pathway in dihydromyricetin-mediated ischemic stroke protection

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