ArticleBMC neurology2025
Exploring the pathophysiological relationship between bisphenol A exposure and ischemic stroke risk using network toxicology and machine learning.
Article in BMC neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Closing the Translational Gap: Closed-Loop AI Discovery Frameworks for Experimental Validation and Clinical Implementation in Cancer Therapeutics.Cancer medicine · 2026Review
- Bisphenol A exacerbates dry eye disease via the CASP1/GSDMD-mediated pyroptotic axis: network toxicology, mendelian randomization, and experimental validation.Frontiers in pharmacology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo explore the molecular mechanisms by which bisphenol A (BPA) exposure contributes to ischemic stroke (IS) risk via the induction of cellular senescence, using an integrative approach combining network toxicology, transcriptomics, and machine learning.
methodsBPA’s chemical properties and target genes were retrieved from PubChem, ChEMBL, STITCH, and SwissTargetPrediction databases, with toxicity validated via ProTox-3. Ischemic stroke (IS)-related differentially expressed genes (DEGs) were identified from merged GEO datasets (GSE16561, GSE37857) and validated in GSE58294. Cellular senescence-related genes (CSRGs) were obtained from CellAge. The intersection of BPA target genes, IS-DEGs, and CSRGs (BPA-CSRG-IS intergenes) was analyzed using protein-protein interaction (PPI) networks and machine learning algorithms (random forest, LASSO) to screen hub genes, with SHAP analysis applied to evaluate the optimal model. A risk prediction model was constructed via logistic regression and validated externally. Additionally, immune cell infiltration analysis, single-sample gene set enrichment analysis (ssGSEA), miRNA-TF-mRNA regulatory network construction, and molecular docking were performed to explore underlying mechanisms.
resultsBPA was confirmed to cross the blood-brain barrier and interact with 2,985 target genes. Merged IS datasets identified 708 DEGs, enriched in immune-related pathways. Intersection analysis yielded 17 BPA-CSRG-IS intergenes, with 2 hub genes (MMP9, HDAC1) identified via machine learning (KNN model, AUC = 0.940) and SHAP analysis (MMP9 as the top contributor). The risk model based on MMP9 and HDAC1 showed robust performance (training set AUC = 0.830; validation set AUC = 0.946). IS patients exhibited elevated immune cell infiltration (e.g., CD8 + T cells, M0 macrophages), with MMP9 and HDAC1 strongly correlated with immune cell subsets. ssGSEA revealed hub genes regulate pathways related to neuroinflammation, BBB disruption, and cellular senescence. Molecular docking confirmed strong binding affinity between BPA and MMP9 (–7.2 kcal/mol) or HDAC1 (–7.7 kcal/mol).
conclusionThis study identifies MMP9 and HDAC1 as key hub genes mediating BPA-induced IS via cellular senescence, highlighting their roles in regulating the “senescence-inflammation” cascade and immune cell infiltration. These findings provide mechanistic insights into BPA’s neurotoxicity and potential biomarkers/targets for IS prevention and treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.