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pmid:36062187
Inflammation and Oxidative Stress Role of S100A12 as a Potential Diagnostic and Therapeutic Biomarker in Acute Myocardial Infarction.
Jian Xie · Changjun Luo · Binhai Mo · Yunhua Lin · Guoqing Liu · Xiantao Wang · Lang Li
Oxidative medicine and cellular longevity · 2022 doi:10.1155/2022/2633123
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Numerous studies have indicated that S100A12 may has an essential role in the occurrence and development of AMI, and in-depth studies are currently lacking. The purpose of this study is to investigate the effect of S100A12 on inflammation and oxidative stress and to determine its clinical applicability in AMI. Here, AMI datasets used to explore the expression pattern of S100A12 in AMI were derived from the Gene Expression Omnibus (GEO) database. The pooled standard average deviation (SMD) was calculated to further determine S100A12 expression. The overlapping differentially expressed genes (DEGs) contained in all included datasets were recognized by the GEO2R tool. Then, functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were carried out to determine the molecular function of overlapping DEGs. Gene set enrichment analysis (GSEA) was conducted to determine unrevealed mechanisms of S100A12. Summary receiver operating characteristic (SROC) curve analysis and receiver operating characteristic (ROC) curve analysis were carried out to identify the diagnostic capabilities of S100A12. Moreover, we screened miRNAs targeting S100A12 using three online databases (miRWalk, TargetScan, and miRDB). In addition, by comprehensively using enzyme-linked immunosorbent assay (ELISA), real-time quantitative PCR (RT-qPCR), Western blotting (WB) methods, etc., we used the AC16 cells to validate the expression and underlying mechanism of S100A12. In our study, five datasets related to AMI, GSE24519, GSE60993, GSE66360, GSE97320, and GSE48060 were included; 412 overlapping DEGs were identified. Protein-protein interaction (PPI) network and functional analyses showed that S100A12 was a pivotal gene related to inflammation and oxidative stress. Then, S100A12 overexpression was identified based on the included datasets. The pooled standard average deviation (SMD) also showed that S100A12 was upregulated in AMI (SMD = 1.36, 95% CI: 0.70-2.03, p = 0.024). The SROC curve analysis result suggested that S100A12 had remarkable diagnostic ability in AMI (AUC = 0.90, 95% CI: 0.87-0.92). And nine miRNAs targeting S100A12 were also identified. Additionally, the overexpression of S100A12 was further confirmed that it maybe promote inflammation and oxidative stress in AMI through comprehensive in vitro experiments. In summary, our study suggests that overexpressed S100A12 may be a latent diagnostic biomarker and therapeutic target of AMI that induces excessive inflammation and oxidative stress. Nine miRNAs targeting S100A12 may play a crucial role in AMI, but further studies are still needed. 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In addition, by comprehensively using enzyme-linked immunosorbent assay (ELISA), real-time quantitative PCR (RT-qPCR", "RT–qPCR), enzyme-linked immunosorbent assay (ELISA), Western blotting (WB) methods, and other i", "rmore, real-time quantitative PCR (RT–qPCR), enzyme-linked immunosorbent assay (ELISA), Western blotting (WB) methods, and"], "order_basis": "paper_text_order:1522", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["t assay (ELISA), real-time quantitative PCR (RT-qPCR), Western blotting (WB) methods, etc., we us", "ssay (ELISA), real-time quantitative PCR (RT-qPCR), Western blotting (WB) methods, etc., we us", "g enzyme-linked immunosorbent assay (ELISA), real-time quantitative PCR (RT-qPCR), Western blotting (WB) methods, et", "Furthermore, real-time quantitative PCR (RT–qPCR), enzyme-linked immunosorbent assay (ELISA),"], "order_basis": "paper_text_order:1565", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["LISA), real-time quantitative PCR (RT-qPCR), Western blotting (WB) methods, etc., we used the AC16 cells t", ", enzyme-linked immunosorbent assay (ELISA), Western blotting (WB) methods, and other in vitro experiments"], "order_basis": "paper_text_order:1603", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["ry Table 1: the S100A12-specific sequence of knockdown and overexpression in this study.Click here"], "order_basis": "paper_text_order:6939", "id": "assay:4"}, {"role": "analysis", "definition_id": "meta_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["random_effects_pool"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["As the included data were continuous variables, Stata 14 software was applied to calculate the pooled standard mean deviation (SMD). 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