Bioinformatic analysis to explore key genes associated with brain ischemia–reperfusion injury in rats

Hong, Kui; Zhang, Xiaoli; Cheng, Lin; Fan, Yanxia; Xiao, Shuping; Ma, Yupo; Feng, Guangkun

doi:10.1080/00207454.2019.1595615

Cited by 10 publications

(6 citation statements)

References 42 publications

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“…Although various bioinformatics analyses of reperfusion in other organs and animals have been performed, a systematic and thorough analysis of cardiac IR in human hearts is still lacking (17,18). Therefore, in this study, a co-expression correlation network was constructed using the expression data from the gene expression omnibus (GEO) database.…”

Section: Introductionmentioning

confidence: 99%

Investigation of the underlying hub genes and mechanisms of reperfusion injury in patients undergoing coronary artery bypass graft surgery by integrated bioinformatic analyses

Shen¹,

Lu²,

Wei³

et al. 2019

Ann. Transl. Med.

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Background: Although coronary artery bypass graft (CABG) surgery is the main method to revascularize the occluded coronary vessels in coronary artery diseases, the full benefits of the operation are mitigated by ischemia-reperfusion (IR) injury. Although many studies have been devoted to reducing IR injury in animal models, the translation of this research into the clinical field has been disappointing. Our study aimed to explore the underlying hub genes and mechanisms of IR injury.Methods: A weighted gene co-expression network analysis (WGCNA) was executed based on the expression profiles in patients undergoing CABG surgery (GSE29396). Functional annotation and proteinprotein interaction (PPI) network construction were executed within the modules of interest. Potential hub genes were predicted, combining both intramodular connectivity (IC) and degrees. Meanwhile, potential transcription factors (TFs) and microRNAs (miRNAs) were predicted by corresponding bioinformatics tools.Results: A total of 336 differentially expressed genes (DEGs) were identified. DEGs were mainly enriched in neutrophil activity and immune response. Within the modules of interest, 5 upregulated hub genes (IL-6, CXCL8, IL-1β, MYC, PTGS-2) and 6 downregulated hub genes (C3, TIMP1, VSIG4, SERPING1, CD163, and HP) were predicted. Predicted miRNAs (hsa-miR-333-5p, hsa-miR-26b-5p, hsa-miR-124-3p, hsa-miR-16-5p, hsa-miR-98-5p, hsa-miR-17-5p, hsa-miR-93-5p) and TF (STAT1) might have regulated gene expression in the most positively related module, while hsa-miR-333-5p and HSF-1 were predicted to regulate the genes within the most negatively related module.Conclusions: Our study illustrates an overview of gene expression changes in human atrial samples from patients undergoing CABG surgery and might help translate future research into clinical work.

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Section: Introductionmentioning

confidence: 99%

Investigation of the underlying hub genes and mechanisms of reperfusion injury in patients undergoing coronary artery bypass graft surgery by integrated bioinformatic analyses

Shen¹,

Lu²,

Wei³

et al. 2019

Ann. Transl. Med.

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“…Repetitive hypoxia/reoxygenation is an important aspect of OSA pathogenesis, creating a condition similar to ischemia/reperfusion (I/R). There is evidence suggesting a role for miR125a in I/R [ 40 ]. Furthermore, miR125a has been shown to protect rat myocardium against I/R injuries through urocortin [ 40 ] and increased levels of miR125a may represent a response to combat such injuries [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating levels of miR125a, miR126, and miR146a-5p in patients with obstructive sleep apnea and their relation with markers of endothelial dysfunction

Fadaei,

Fallah,

Moradi

et al. 2023

PLoS ONE

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Background obstructive sleep apnea (OSA) is a prevalent sleep disorder that is associated with increased risk factors for cardiovascular diseases (CVDs). Oxidative stress, insulin resistance, inflammation, and endothelial dysfunction are increased in OSA patients and microRNAs (miRs) are regulatory elements that influence these pathological mechanisms. miR125a, miR126, and miR146a-5p play a role in these pathological mechanisms and have not been evaluated in patients with OSA. Method This case-control study was performed on 90 OSA patients and 34 controls. Circulating levels of miR125a, miR126, and miR146a-5 were determined using real-time PCR, and serum levels of hsCRP, ICAM-1, and VCAM-1 were evaluated using ELISA kits. Results miR125a and miR146a were elevated in patients with OSA compared to controls while miR126 decreased significantly. All three miRs indicated a remarkable difference between the mild-OSA group compared to the severe-OSA group. Furthermore, patients with OSA showed elevated levels of hsCRP, ICAM-1, and VCAM-1. Multiple linear regression indicated an independent association of miR125a with ICAM-1 and hsCRP, miR126 associated with VCAM-1 and total cholesterol, and miR146a-5p represented an association with apnea-hypopnea index and ICAM-1. Furthermore, miR146a-5p illustrated a good diagnostic ability to differentiate between OSA and controls. Conclusions Circulating miR125a, miR126, and miR146a-5p fluctuations in patients with OSA and their relations with markers of endothelial dysfunction provide in vivo evidence and suggest a potential role for these miRs with endothelial dysfunction in patients with OSA.

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“…Furthermore, we observed a low expression of Atf3 in OGD/R cells. Several publications have demonstrated the role of Atf3 in regulating the progression of ischemia–reperfusion injury (Ke et al, 2019; Lin & Cheng, 2018). In the study of IS, knockdown of Atf3 could induce cerebral infarction and neurological deterioration in IS mice, and resulted in increased neuronal apoptosis and an inflammatory response, suggesting the potential protective effect of Atf3 in IS (Wang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV alleviates neuronal ferroptosis in ischemic stroke by regulating fat mass and obesity‐associated—N6‐methyladenosine—acyl‐CoA synthetase long‐chain family member 4 axis

Jin

Gao

Guo

et al. 2023

Journal of Neurochemistry

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Ischemic stroke (IS) is a detrimental neurological disease with limited treatment options. Astragaloside IV (As-IV) was a promising bioactive constituent in the treatment of IS. However, the functional mechanism remains unclear. Here, IS cell and mouse models were established by oxygen glucose deprivation/re-oxygenation (OGD/R) and middle cerebral artery occlusion (MCAO). Quantitative reverse transcription PCR (RT-qPCR), Western blotting, or Immunofluorescence staining measured related gene and protein expression of cells or mice brain tissues, and the results revealed altered expression of acyl-CoA synthetase long-chain family member 4 (Acsl4), fat mass and obesity-associated (Fto), and activation transcription factor 3 (Atf3) after treatment with As-IV. Then, increased N 6 -methyladenosine (m 6 A) levels caused OGD/R or MCAO were reduced by As-IV according to the data from methylated RNA immunoprecipitation (MeRIP)-qPCR and dot blot assays. Moreover, through a series of functional experiments such as observing mitochondrial changes under transmission electron microscopy (TEM), evaluating cell viability by cell counting kit-8 (CCK-8), analyzing infract area of brain tissues by 2,3,5-triphenyltetrazolium chloride (TTC) staining, measuring levels of malondialdehyde (MDA), lactate dehydrogenase (LDH), Fe 2+ , solute carrier family 7 member 11 (Slc7a11) and glutathione peroxidase 4 (Gpx4) and concentration of glutathione (GSH), we found that Fto knockdown, Acsl4 overexpression or Atf3 knockdown promoted the viability of OGD/R cells, inhibited cell ferroptosis, reduced infract size, while As-IV treatment or Fto overexpression reversed these changes. In mechanism, the interplays of YTH N 6 -methyladenosine RNAbinding protein 3 (Ythdf3)/Acsl4 and Atf3/Fto were analyzed by RNA-pull down, RNA Zhenglong Jin and Wenying Gao are co-first authors.

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Bioinformatic analysis to explore key genes associated with brain ischemia–reperfusion injury in rats

Cited by 10 publications

References 42 publications

Investigation of the underlying hub genes and mechanisms of reperfusion injury in patients undergoing coronary artery bypass graft surgery by integrated bioinformatic analyses

Investigation of the underlying hub genes and mechanisms of reperfusion injury in patients undergoing coronary artery bypass graft surgery by integrated bioinformatic analyses

Circulating levels of miR125a, miR126, and miR146a-5p in patients with obstructive sleep apnea and their relation with markers of endothelial dysfunction

Astragaloside IV alleviates neuronal ferroptosis in ischemic stroke by regulating fat mass and obesity‐associated—N6‐methyladenosine—acyl‐CoA synthetase long‐chain family member 4 axis

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