Bohou Xia

Triphenyl phosphate (TPhP) is a ubiquitous environmental contaminant and endocrine disruptor potentially associated with an increased risk of thyroid cancer (TC). However, whether TPhP directly contributes to TC remains unclear. This study integrated network toxicology and machine learning to investigate potential molecular associations between TPhP exposure and thyroid oncogenesis. By integrating multi-source databases and transcriptomic data, we constructed a TPhP–TC interaction network and established a TC risk prediction model using 127 machine learning algorithm combinations, identifying ten candidate hub genes. GO and KEGG enrichment analyses indicated that these genes are predominantly enriched in phosphorus metabolism, purine metabolism, and nuclear receptor signaling pathways, implying that TPhP may be linked to tumorigenesis through the disruption of metabolic reprogramming. SHAP analysis highlighted AHR and SLC20A2 as critical contributors to model performance. Molecular docking predicted stable binding between TPhP and all hub proteins in silico, with binding energies ranging from −9.2 to −6.6 kcal/mol. This study offers two computational contributions: (1) a quantifiable framework for predicting pollutant-associated TC risk and (2) systematic computational evidence for potential TPhP thyroid toxicity. These findings address a critical gap in understanding potential links between endocrine-disrupting chemical exposure and thyroid carcinogenesis, generating hypotheses for future experimental validation.

Polygonatum odoratum is a traditional medicinal food used for diabetes management, yet most studies have focused on its polysaccharides and largely overlooked its protein fraction. Here, we investigated the antidiabetic activity and potential mechanisms of a Polygonatum odoratum protein hydrolysate (POP) for the first time. POP was produced by simulated gastrointestinal digestion and consisted mainly of oligopeptides (β -cell injury, hepatic steatosis, and renal damage. POP also attenuated hepatic oxidative stress, as indicated by lower ROS and MDA levels and higher activities of antioxidant enzymes (SOD, CAT, and GSH-Px). Consistently, immunofluorescence indicated activation of the Nrf2/Keap1 pathway, with enhanced Nrf2 nuclear translocation and increased HO-1 expression. Therefore, POP improves glucose and lipid homeostasis and tissue damage in diabetic mice by enhancing Nrf2-dependent antioxidant defense mechanisms. These findings highlight the underexplored value of the P. odoratum protein fraction and support POP as a promising functional food ingredient for T2DM management.

Triple-negative breast cancer (TNBC) is a type of breast cancer characterized by high molecular heterogeneity. Owing to the lack of effective therapeutic strategies, patients with TNBC have a poor prognosis. Prunella vulgaris L. has the effects of reducing swelling, dissolving knots and treating breast carbuncles and mammary rocks. Modern pharmacological studies have reported that it can effectively inhibit the growth of breast cancer. The main active antitumor components of Prunella vulgaris are triterpenoids (PVT); however, the role and potential mechanism of PVT in TNBC remain unexplored. Our study aimed to further explore the inhibitory effects of PVT on TNBC and the associated mechanism. The results showed that 19 compounds associated with PVT were identified, 9 of which were triterpenoids. The percentages of ursolic acid and oleanolic acid in PVT were 34.51% and 11.32%, respectively. Triterpenes of Prunella vulgaris significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells and promoted their apoptosis in a concentration-dependent manner. PVT could also effectively downregulate the mRNA and protein expression levels of Ptp1b, Pi3k, Akt and mtor and upregulate the mRNA and protein expression levels of Il-24 in MDA-MB-231 cells. In mice with tumors of TNBC, PVT significantly reduced tumor growth and the expression levels of PTP1B, CXCL12, CXCR4, PI3K, AKT, mTOR and other proteins in TNBC tumor tissue and upregulated the expression of IL-24. This study showed that PVT played an anti-TNBC role by regulating the PTP1B/PI3K/AKT/mTOR signaling pathway and the IL-24/CXCL12/CXCR4 signaling axis.