Bisphenol A promotes colorectal cancer malignancy through CXCL8 upregulation associated with p38 MAPK activation: A potential link to type 2 diabetes mellitus comorbidity.

From Environmental Lead Exposure to Colorectal Cancer: Integrated Transcriptomic and Genetic Analyses Identify HMOX1 as a Prioritized Candidate.

Exploring the mechanism by which triphenyl phosphate promotes malignant phenotypes in bladder and kidney cancer through MMP9 based on bioinformatics analysis and experimental validation.

Background Bladder and kidney cancer burden rises globally, with environmental toxicants driving their progression. Methods We integrated global epidemiological analysis, single-cell transcriptomics, cell-cell communication analysis, epithelial subclustering, pseudotime inference, toxicological target prediction, survival modeling, cross-cohort validation, single-cell virtual knockout, spatial transcriptomic deconvolution, molecular docking/dynamics, CETSA, and in vitro assays to define a shared molecular interface linking triphenyl phosphate (TPP) to bladder and kidney cancer. Results Both malignancies exhibited age- and SDI-associated burden patterns. Single-cell profiling identified conserved epithelial, stromal, and immune ecosystems, with tumor epithelial cells occupying central positions in intercellular communication networks. Epithelial subclustering revealed a reproducible EMT-high subcluster 4 in both cancers, which localized to a terminal-like pseudotime state and was associated with poor survival. Predicted TPP targets intersected with subcluster 4 signatures and converged on extracellular matrix organization, adhesion, and leukocyte transendothelial migration pathways. Integrative survival modeling and multi-cohort validation identified MMP9 as a robust prognostic candidate associated with tumor progression. Importantly, single-cell virtual knockout of MMP9 revealed convergent remodeling of proliferative, inflammatory, hypoxia-related, and stress-response programs across bladder and renal cancer epithelial cells, highlighting conserved regulatory circuitry. Spatial transcriptomics further localized MMP9 to macrophage- and fibroblast-enriched niches in both tumor types. Structural modeling and CETSA supported an interaction between TPP and MMP9. Experimentally, TPP upregulated MMP9 at both mRNA and protein levels in T24 and 786-O cells; higher concentrations reduced viability, whereas lower concentrations enhanced migration and clonogenic growth. Conclusions TPP promotes the malignant phenotypes of bladder and kidney cancer via MMP9, which is validated by virtual knockout and in vitro experiments.

BDE47 exposure in lung adenocarcinoma: prognostic biomarkers, immune dysregulation, and mechanistic insights from toxicogenomic and docking studies

How BDE47 exposure may influence lung adenocarcinoma and highlights the need for environmental pollutant monitoring, while also offering potential biomarkers for cancer prognosis and treatment is revealed.

DEHP exposure induces cholesterol dysregulation and inflammatory signaling in human colonic epithelial cells: Implications for early colorectal carcinogenesis.

Di(2-ethylhexyl) phthalate (DEHP), a ubiquitous plasticizer and a classified Group 2B carcinogen, is associated with increased colorectal cancer (CRC) incidence, but its causal role and mechanisms are unclear. We investigated DEHP toxicity in human colonic epithelial cells (NCM460) using an integrated multi-omics approach. Phenotypic assays showed that low-dose (200 μM) exposure markedly inhibited cell migration by 32% independent of cytotoxicity within 48 h. Transcriptomics revealed a biphasic stress response: an early disruption of cholesterol metabolism and ABC transporters, followed by activation of pro-oncogenic pathways. Metabolomics confirmed concurrent redox imbalance and lipid/steroid dysregulation. Integrated analysis identified ABCA1, ABCG1, and SREBF1 as central regulatory nodes linking metabolic dysfunction to inflammatory and oncogenic pathways. The downregulation of ABCA1 and ABCG1 was validated at the mRNA level, a finding corroborated by their significant underexpression in clinical CRC tumors (TCGA database). Tumor tissues exhibited a 0.54-fold decrease in ABCA1 and a 0.47-fold decrease in ABCG1 compared to normal controls (p < 0.0001, n = 286). Moreover, ABCA1 knockdown phenocopied the inhibitory effect of DEHP on cell migration. In conclusion, these findings suggest that short-term DEHP exposure may disrupt intestinal epithelial homeostasis through a mechanism involving cholesterol transport impairment (SREBF1/ABCA1/ABCG1 axis), representing an early event in DEHP-associated colorectal pathogenesis.

FAP as a Clinical Biomarker: FAP+ CAFs Orchestrate an Immunosuppressive Stem Cell Niche via the COL1A1/2‐CD44 Axis in Colon Cancer

Background Colon cancer (CC) remains a leading cause of cancer‐related mortality worldwide, driven largely by the complex interactions within the tumor microenvironment (TME). Fibroblast activation protein (FAP) is highly expressed in cancer‐associated fibroblasts (CAFs) and is associated with poor prognosis, yet its role in coordinating immune evasion and cancer stemness remains to be fully elucidated. Methods We integrated multiomics data from TCGA and GEO databases, utilizing bulk RNA‐seq and single‐cell RNA‐seq (scRNA‐seq) analyses. Findings were validated via tissue microarray (TMA) immunohistochemistry (IHC). We further employed cell–cell communication analysis, pseudotime trajectory modeling, and the Connectivity Map (CMap) for drug sensitivity prediction and molecular docking. Results FAP was significantly upregulated in CC tissues and correlated with advanced clinical stages. scRNA‐seq confirmed that FAP is predominantly expressed in CAFs. Functional analysis revealed that FAP‐high tumors are enriched in extracellular matrix (ECM) remodeling and immunosuppressive pathways. Cell–cell communication analysis identified that FAP+ CAFs interact with T cells and cancer stem cells (CSCs) primarily through the COL1A1/2‐CD44 axis. Specifically, FAP+ CAFs promote the differentiation of naive T cells into regulatory T cells (Tregs) and are positively correlated with various stemness markers, including CD44, ABCG2, and BMI1. Based on these findings, we established a 14‐gene prognostic risk model with robust predictive accuracy (area under the curve [AUC] > 0.64) and identified AS604850 and LY364947 as potential therapeutic agents. Conclusion Our study demonstrates that FAP+ CAFs orchestrate a dual‐functional “immunosuppressive stem cell niche” via the COL1A1/2‐CD44 signaling axis. Targeting this FAP‐driven niche provides a promising strategy for overcoming immunotherapy resistance and improving clinical outcomes in CC.

Bisphenol A drives the comorbidity of non-alcoholic fatty liver disease and osteoarthritis by targeting RHOB: Integrated multi-omics, single-cell analysis, and experimental validation.

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.