Aug 2026· Reproductive Sciences· 0 citations· 44 references
Medicine
TL;DR
This study elucidates potential molecular links between BPA exposure and GDM, highlighting immune-metabolic dysregulation and identified core genes that may serve as biomarkers or therapeutic targets, thereby advancing precision environmental health strategies for pregnancy.
BACKGROUND
Tris(1,3-dichloro-2-propyl) phosphate (TDCPP), a widely used organophosphate flame retardant, has been increasingly recognized as a potential environmental risk factor for human cancers. However, its potential association with hepatocellular carcinoma (HCC) and the underlying molecular mechanisms remain largely unclear.
METHODS
An integrative network toxicology and multi-omics approach was employed to explore the potential computational link between TDCPP‑related targets and HCC transcriptomic changes. TDCPP-associated targets were collected from public databases and intersected with differentially expressed genes from The Cancer Genome Atlas (TCGA). Weighted gene co-expression network analysis (WGCNA) and machine learning algorithms were applied to identify candidate genes. Functional enrichment, immune infiltration, single-cell RNA sequencing, and molecular docking analyses were subsequently performed.
RESULTS
A total of six candidate genes were identified, among which ADAMTS13 exhibited strong discriminative performance in the predictive models. Functional analyses suggested that these genes may be involved in pathways related to extracellular matrix organization, immune regulation, and tumor microenvironment remodeling. Immune infiltration and single-cell analyses indicated a potential association between ADAMTS13 expression and tumor microenvironment characteristics. Molecular docking analysis further suggested a potential interaction between TDCPP and ADAMTS13 at the structural level.
CONCLUSIONS
These findings suggest a computational association between TDCPP-related targets and HCC transcriptomic changes, with ADAMTS13 emerging as a computationally prioritized candidate gene for further experimental investigation. This study provides a hypothesis-generating framework for understanding possible molecular links between environmental contaminants and hepatocarcinogenesis, but does not establish causality or confirm actual TDCPP exposure in the analyzed patient cohorts.
BACKGROUND
This study focuses on exploring the co-morbid mechanisms by which Bisphenol A (BPA) induces non-alcoholic fatty liver disease (NAFLD) and osteoarthritis (OA).
METHOD
This study identified potential BPA targets utilizing the SwissTargetPrediction database. These targets were integrated with genes associated with NAFLD and OA, which were screened via Weighted Gene Co-expression Network Analysis and differential gene expression analysis. To elucidate the underlying biological mechanisms, functional enrichment and immune infiltration analyses were conducted. Core genes associated with comorbidity were pinpointed via machine learning. The interactions and cellular localization were further validated by molecular docking, molecular dynamics simulations, and single-cell transcriptomics. Finally, in vitro experiments were employed to verify the effects on chondrocyte function, and hepatic lipid metabolism.
RESULTS
Functional enrichment analysis indicates that BPA-induced NAFLD and OA comorbidity pathways are enriched in muscle cell proliferation, DNA metabolism, and inflammation pathways. RHOB has been identified as a core gene, participating in disease progression by regulating signaling pathways such as Hippo and IL-17. Single-cell sequencing revealed that RHOB is primarily expressed in hepatocytes and cholangiocytes in NAFLD, while enriching in HomC and EC cell clusters in OA. In vitro experiments confirmed that BPA exposure suppresses RHOB expression, thereby promoting lipid accumulation in hepatocytes and impairing chondrocyte function. Concurrently, rescue experiments demonstrated that its overexpression significantly reversed these pathological states.
CONCLUSION
BPA exposure drives the co-morbidity of OA and NAFLD by inhibiting RHOB. Consequently, limiting BPA exposure or modulating the RHOB pathway represents a viable approach for intervening in related diseases.
The comorbidity of psoriasis and inflammatory bowel disease (IBD) is well-established, yet the shared molecular mechanisms, particularly the role of apoptosis, remain insufficiently explored. This study aims to identify key apoptosis-related genes that link these two diseases.
Microarray data from the GEO database were analyzed. We identified differentially expressed genes (DEGs) using the limma package and constructed co-expression networks via Weighted Gene Co-expression Network Analysis (WGCNA) to find disease-associated modules. Functional enrichment analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways was performed using the clusterProfiler package. Key apoptosis-related genes were refined by applying machine learning algorithms, including Least Absolute Shrinkage and Selection Operator and Random Forest. Immune cell infiltration between diseased and control samples was assessed using single-sample GSEA (ssGSEA).
Our integrated analysis identified three central apoptosis-related genes: CCL2, XK, and PRKAR2B. Gene set enrichment analysis indicated their involvement in critical biological processes and signaling pathways. Furthermore, correlation analysis revealed that these genes have strong associations with specific immune cell infiltration patterns, suggesting a potential mechanism linking apoptosis and immune dysregulation in both psoriasis and IBD.
This study identifies CCL2, XK, and PRKAR2B as pivotal genes bridging psoriasis and IBD through apoptosis-related mechanisms. These findings shed light on the shared molecular underpinnings of these comorbid conditions and highlight potential targets for future therapeutic strategies.
Qing Wei, Zhen-Qi Huang, Shaozhang Hou et al.· Indian Journal of Dermatolog...· 0 citations
INTRODUCTION
This study aimed to screen and validate such biomarkers to clarify the role of vascular endothelial injury (VEI) in the pathogenesis of gestational diabetes mellitus (GDM) and provide clues for future diagnostic and mechanistic studies.
METHODS
VEI scores were calculated using a published VEI-related gene set. VEI-correlated gene modules were classified by weighted gene co-expression network analysis (WGCNA), with module genes subjected to GO/KEGG enrichment analysis and intersected with differentially expressed genes (DEGs) from the GSE70493 dataset. Core genes were filtered using three machine learning algorithms, including random forest, LASSO regression, and SVM-RFE, followed by analyses of diagnostic performance, hallmark pathway correlations, and immune infiltration associations.
RESULTS
DEGs were enriched in endoplasmic reticulum protein localization, oxidative stress, and mitochondrial pathways and overlapped with the yellow gene module. Machine learning identified COX7B, GLRX5, and OR52H1 as the candidate biomarkers for GDM. These genes showed favorable diagnostic performance and distinct correlations with hallmark pathways and immune infiltration features, suggesting their potential involvement in VEI-related molecular changes in GDM.
DISCUSSION
This study identified VEI-related hub genes in GDM but is limited by its reliance on a single dataset, a small validation sample, and the lack of experimental validation, warranting further confirmation.
CONCLUSION
COX7B, GLRX5, and OR52H1 were identified as VEI-associated diagnostic biomarkers in GDM. These findings support the involvement of VEI-related molecular alterations in GDM but should be regarded as hypothesis-generating, requiring further validation in larger clinical cohorts and experimental models.
Yue-Ping Wang, Weiwei Feng· Current Medicinal Chemistry· 0 citations
BPA-induced CXCL8 upregulation is associated with CRC malignant progression and enhanced p38 MAPK signaling, and TEAD4 may function as an upstream transcriptional regulator of CXCL8, although its direct regulation by BPA remains unclear.
Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) is used as a nonreactive brominated flame retardant used in industrial products, particularly in flexible polyvinyl chloride and rigid and flexible polyurethane foams. Although TBPH exposure poses potential health risks, its association with atherosclerosis remains poorly understood.
This study integrated network toxicology, machine learning, molecular docking, and molecular dynamics (MD) simulations to elucidate the influence of TBPH on high-fat diet–induced atherosclerosis.
TBPH exhibited significant predicted toxicity across multiple organs. In total, 167 potential TBPH targets and 690 atherosclerosis-associated targets were identified, with 108 overlapping targets obtained through intersectional analysis. A PPI network was constructed based on these 108 overlapping genes, and the top 20 hub genes were identified. In a parallel independent analysis using a public transcriptomic dataset, 111 differentially expressed genes (DEGs) were identified by comparing atherosclerotic and normal tissues. Subsequent intersection analysis of the 108 overlapping targets and 111 DEGs identified candidate genes that were both TBPH-related and differentially expressed in atherosclerosis. Public transcriptomic data showed higher matrix metalloproteinase 9 (MMP9) level in atherosclerotic tissues. The corresponding receiver operating characteristic (ROC) curve yielded an AUC of 0.806 (95% confidence interval [CI]: 0.698–0.914). Molecular docking and MD simulations indicated favorable predicted binding modes and computational stability between TBPH and MMP9. In vivo experiments further demonstrated an association between TBPH exposure, increased MMP9 expression, and high–fat diet–induced atherosclerotic lesions.
These findings suggest that TBPH may be associated with high-fat diet–induced atherosclerosis progression through the dysregulation of key mediators, providing insight into environmental pollutant–driven disease development.
Huichao Pan, Dong Wang, Sheng-Guang Chen et al.· Frontiers in Pharmacology· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
