The Xinjiang autonomous region, located in west China, has a unique ethnic structure and a well-developed livestock industry. People in this region have a high risk of exposure to antibiotics, but the exposure level to antibiotics in relation to dietary determinants is unknown. In this study, 18 antibiotics, including four human antibiotics (HAs), four veterinary antibiotics (VAs), and 10 preferred veterinary antibiotics (PVAs) were detected in the urine of approximately half of the 873 adults in Xinjiang, including Han Chinese (24.6%), Hui (25.1%), Uighur (24.6%), and Kazakh (25.7%). Logistic regression was used to analyze the association between antibiotic exposure levels and adult diet and water intake. The detection percentage of antibiotics in the urine of adults in Xinjiang ranged from 0.1% to 30.1%, with a total detection percentage of all antibiotics of 49.8%. HAs, VAs and PVAs were detected in 12.3%, 10.3%, and 40.5%, respectively. Fluoroquinolones were the antibiotics with the highest detection percentage (30.1%) and tetracyclines were the antibiotics with the highest detected concentration (17 ng/mL). Adults who regularly ate pork, consumed fruit daily, and did not prefer a plant-based diet were associated with thiamphenicol, norfloxacin, and fluoroquinolones, respectively. These results indicated that adults in the Xinjiang autonomous region were extensively exposed to multiple antibiotics, and some types of food were potential sources of exposure. Special attention should be paid to the health effects of antibiotic exposure in humans in the future.

Background: Although previous studies have shown an association between clinically used antibiotics and type 2 diabetes, the relationship between antibiotic exposure from food and drinking water and type 2 diabetes in middle-aged and older adults is unclear. ObjectivE: This study was aimed at exploring the relationship between antibiotic exposures from different sources and type 2 diabetes in middle-aged and older people, through urinary antibiotic biomonitoring. MethodS: A total of 525 adults who were 45–75 years of age were recruited from Xinjiang in 2019. The total urinary concentrations of 18 antibiotics in five classes (tetracyclines, fluoroquinolones, macrolides, sulfonamides and chloramphenicol) commonly used in daily life were measured via isotope dilution ultraperformance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry. The antibiotics included four human antibiotics, four veterinary antibiotics and ten preferred veterinary antibiotics. The hazard quotient (HQ) of each antibiotic and the hazard index (HI) based on the mode of antibiotic use and effect endpoint classification were also calculated. Type 2 diabetes was defined on the basis of international levels. Results: The overall detection rate of the 18 antibiotics in middle-aged and older adults was 51.0%. The concentration, daily exposure dose, HQ, and HI were relatively high in participants with type 2 diabetes. After model adjustment for covariates, participants with HI > 1 for microbial effects (OR = 3.442, 95%CI: 1.423–8.327), HI > 1 for preferred veterinary antibiotic use (OR = 3.348, 95%CI: 1.386–8.083), HQ > 1 for norfloxacin (OR = 10.511, 96%CI: 1.571–70.344) and HQ > 1 for ciprofloxacin (OR = 6.565, 95%CI: 1.676–25.715) had a higher risk of developing type 2 diabetes mellitus. Conclusions: Certain antibiotic exposures, mainly those from sources associated with food and drinking water, generate health risks and are associated with type 2 diabetes in middle-aged and older adults. Because of this study’s cross-sectional design, additional prospective studies and experimental studies are needed to validate these findings.

Despite the known antitumor properties of echinacoside (ECH), its specific role and mechanism in hepatocellular carcinoma (HCC) require in-depth exploration. Our study aimed to decipher the mechanism of ECH against HCC through a multi-disciplinary strategy. We first identified tumor protein p53 (TP53) as a key mediator and ferroptosis as a critical process, through network pharmacology and enrichment analyses. The direct interaction between ECH and TP53 was validated by molecular docking and dynamics simulations. In vitro assessments demonstrated that ECH suppresses HCC proliferation by activating ferroptosis, marked by increased intracellular Fe²⁺, lipid peroxidation (LPO), and malondialdehyde (MDA), alongside reduced glutathione (GSH). The ferroptosis inhibitor ferrostatin-1 notably attenuated ECH’s effects, confirming ferroptosis as the primary mode of cell death. Further mechanistic investigation revealed that ECH acts through the TP53/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4) pathway. These results collectively identify ECH as a promising ferroptosis-inducing agent for HCC therapy via TP53 activation.

An effectual remedy for hepatocellular carcinoma (HCC) and knowledge of the mechanism are urgently needed. Researchers have found that CPhGs, an extract from Cistanche tubulosa (Schenk) Wight, had better antitumor effects, but its mechanism is still unknown. In the present study, using an H22 tumor-bearing mouse as a model, we investigated the antitumor effects of CPhGs and the effect of CPhGs on autophagy and apoptosis. Besides, we also discussed the role of autophagy with the help of HCQ and rapamycin. Our results show that CPhGs inhibit tumor growth and induce apoptosis and autophagy of tumor tissue. TUNEL staining displayed that tumor apoptosis rate increased after the intervention of CPhGs, and immunohistochemistry and western blot showed that cleaved-PARP and cleaved-caspase 3 were upregulated after the intervention of CPhGs, and these results were most pronounced in the high-dose group. Autophagy results revealed that CPhGs increased the number of autophagosomes, increased the level of LC3B-II, and decreased the level of p62. Finally, our results showed that excessive autophagy suppresses tumor growth, whereas inhibition of autophagy does the opposite, which indicated that CPhGs induced autophagic death in H22 hepatoma-bearing mice. These data altogether confirmed the involvement of apoptosis and autophagy in CPhGs treatment for HCC.

DCPMU, a major demethylated metabolite of diuron, is an environmentally persistent contaminant with potential endocrine-disrupting and carcinogenic relevance, yet its mechanistic association with prostate cancer remains unclear. This study investigated DCPMU-related mechanisms in prostate cancer by integrating network toxicology, molecular modeling, bulk transcriptomics, single-cell and spatial transcriptomics, and virtual perturbation analysis. Differentially expressed genes from TCGA-PRAD were intersected with DCPMU-associated and prostate cancer-related targets. Functional enrichment, machine learning screening, and external GEO validation identified seven candidate hub genes: APOBEC3G, SCGB1A1, PTGS1, CA12, CES1, FOLH1, and NOS1. Molecular docking showed favorable DCPMU binding to these proteins, and molecular dynamics simulations further supported stable interactions with PTGS1, CA12, CES1, and FOLH1. Single-cell analysis of GSE141445 revealed cell-type-specific expression, with FOLH1 and CA12 enriched in epithelial cells, CES1 in fibroblasts, and PTGS1 in mast cells. Spatial transcriptomics from GSE181294 showed tumor-enriched FOLH1 expression and increased Core4 module activity in malignant regions. Virtual knockout analysis suggested that FOLH1 perturbation was associated with predicted downstream transcriptional changes, with PTGS1 showing marked perturbation responsiveness. Overall, our integrative analyses suggest that DCPMU exposure is associated with epithelial malignancy, inflammatory metabolism, xenobiotic handling, and tumor-microenvironment remodeling, particularly within malignant epithelial niches. These hypothesis-generating findings require experimental validation to establish any causal role in prostate cancer progression.