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The aim of this study was to investigate the association between coronary heart disease (CHD) and ferroptosis, furthermore, to identify the relevant genes and potential diagnostic biomarkers by bioinformatics analysis. We analyzed the CHD dataset GSE23561 from the gene expression omnibus database (http://www.ncbi.nlm.nih.gov/geo) and iron-death-related genes from the FerrDb database (http://www.zhounan.org/ferrdb/). By intersecting bioinformatics-identified differentially expressed genes with iron-death-related genes in FerrDb, we identified CHD associated genes linked to ferroptosis. These genes underwent gene ontology, Kyoto encyclopedia of genes and genomes pathway enrichment, and disease ontology analyses. Using LASSO logistic regression, we selected diagnostic biomarkers for coronary artery disease from these ferroptosis-related genes. Meta-analysis validated these biomarkers, followed by population sample validation recruited from our institution. This study has shown that genes associated with ferroptosis include PRKAA2, NOX4, GLS2, and G6PD. Further data analysis and meta-analysis revealed that NOX4 gene expression was significantly upregulated in patients with CHD (P<.05), which may be related to coronary atherosclerosis and myocardial injury. Additionally, the upregulation of NOX4 expression was validated through RT-PCR. The study identified 122 ferroptosis-associated genes, emphasizing their roles in oxidative stress, cellular membrane functions, and cardiovascular diseases. LASSO regression pinpointed 4 diagnostic biomarkers: PRKAA2, NOX4, GLS2, and G6PD, notably with elevated NOX4 expression in CHD patients. Meta-analysis and experimental validation confirmed NOX4's significance in CHD, providing insights into its mechanisms and implications for early diagnosis and treatment strategies.

Regulated cell death (RCD) is essential to both physiological homeostasis and numerous diseases. FerrDb is a curated database for ferroptosis regulators and ferroptosis-disease associations. Though widely used, FerrDb is limited by its singular focus on ferroptosis. The field of cell death is rapidly expanding, marked by continuous discovery of novel RCD modalities. The need for a high-quality database that encompasses the entire spectrum of RCD is urgent, but none exists. Here, we introduce FerrDb V3, an upgraded version featuring extensive enhancements in content and functionality. Remarkably, it expands from the focus on ferroptosis to 22 RCD modalities. RCD regulators and RCD-disease associations were manually curated from >20 000 articles. Database content was additionally enriched by public resources. A conversational intelligent assistant that enables users to explore the database through natural language queries was created. A suite of web-based analytical utilities tailored for RCD research was developed. The web interface was updated accordingly to offer a seamless user experience. In conclusion, FerrDb V3 has evolved into a comprehensive resource and a valuable research tool for the RCD research community. FerrDb V3 is freely accessible at https://www.zhounan.org/ferrdb/.

Ferroptosis is a mode of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation. It is closely linked to the pathophysiological processes in many diseases. Since our publication of the first ferroptosis database in 2020 (FerrDb V1), many new findings have been published. To keep up with the rapid progress in ferroptosis research and to provide timely and high-quality data, here we present the successor, FerrDb V2. It contains 1001 ferroptosis regulators and 143 ferroptosis-disease associations manually curated from 3288 articles. Specifically, there are 621 gene regulators, of which 264 are drivers, 238 are suppressors, 9 are markers, and 110 are unclassified genes; and there are 380 substance regulators, with 201 inducers and 179 inhibitors. Compared to FerrDb V1, curated articles increase by >300%, ferroptosis regulators increase by 175%, and ferroptosis-disease associations increase by 50.5%. Circular RNA and pseudogene are novel regulators in FerrDb V2, and the percentage of non-coding RNA increases from 7.3% to 13.6%. External gene-related data were integrated, enabling thought-provoking and gene-oriented analysis in FerrDb V2. In conclusion, FerrDb V2 will help to acquire deeper insights into ferroptosis. FerrDb V2 is freely accessible at http://www.zhounan.org/ferrdb/.

Ferroptosis is a mode of regulated cell death that depends on iron. Cells die from the toxic accumulation of lipid reactive oxygen species. Ferroptosis is tightly linked to a variety of human diseases, such as cancers and degenerative diseases. The ferroptotic process is complicated and consists of a wide range of metabolites and biomolecules. Although great progress has been achieved, the mechanism of ferroptosis remains enigmatic. We have currently entered an era of extensive knowledge advancement, and thus, it is important to find ways to organize and utilize data efficiently. We have observed a high-quality knowledge base of ferroptosis research is lacking. In this study, we downloaded 784 ferroptosis articles from the PubMed database. Ferroptosis regulators and markers and associated diseases were extracted from these articles and annotated. In summary, 253 regulators (including 108 drivers, 69 suppressors, 35 inducers and 41 inhibitors), 111 markers and 95 ferroptosis-disease associations were found. We then developed FerrDb, the first manually curated database for regulators and markers of ferroptosis and ferroptosis-disease associations. The database has a user-friendly interface, and it will be updated every 6 months to offer long-term service. FerrDb is expected to help researchers acquire insights into ferroptosis.
Database URL: http://www.zhounan.org/ferrdb.