Astemizole

Contaminants of emerging concern (CECs) in estuaries have received increasing attention due to their potential environmental impacts. However, detailed analyses of the sources, transport mechanisms, and environmental consequences of these contaminants remain limited. This study applied non-target screening technology to comprehensively assess CECs in the Nandu River estuary. A total of 18,000 characteristic features were screened, revealing a greater number of hydrophobic features in seawater than in the estuary. Systematic classification identified 74, 195, and 48 compounds at Levels 1, 2, and 4 respectively, with primary classifications comprising pharmaceuticals (34 %), industrial materials (23 %), pesticides (18 %), and natural products (17 %). Semi-quantitative analysis employing external standards revealed elevated concentrations of 61 monitored contaminants in estuarine zones compared to offshore waters, with Climbazole exhibiting peak concentration levels. Ecological risk assessment identified 12 contaminants of emerging concern (CECs) requiring prioritized monitoring (with RQ > 1). A priority list was established based on the frequency of detection, bioaccumulation potential, persistence, toxicity and endocrine disruption potential of the compounds. 64 CECs were identified as high priority, consisting mainly of pesticides and pharmaceutical compounds. Pesticides originate primarily from upstream agricultural activities, decreasing in concentration downstream, whereas pharmaceuticals, industrial materials, and natural products are linked to domestic sewage. Tidal cycles play a crucial role in modulating the distribution and concentration of CECs within estuarine waters. This modulation is attributed to the dynamic interaction between terrestrial inputs and coastal influences, where high tides contribute significantly to the dilution of land-derived pollutants.

In this study, we utilized the yeast two-hybrid system to screen for proteins interacting with USP24. Out of 250 such proteins, functional enrichment analysis using MetaCore™ indicated that 33 of them were involved in lung cancer progression. We then investigated gene expression and survival rates of these 33 proteins in lung cancer patients and cell lines through TCGA databases, Kaplan-Meier Plotter databases, and RNA-seq profile from A549/A549-T24 cells. By employing the patients' survival rate and gene expression profile of these 33 USP24-interacting proteins as gene signatures, we identified 10 potential drugs for inhibiting lung cancer progression or drug resistance via drug repurposing strategy using the Connectivity Map (CMap) database. Of these 10 drugs, six showed similar indicators in Clinical Trials, while the other four candidates (15-delta prostaglandin J2, Astemizole, Trifluoperazine, and 1,4-chrysenequinone) were chosen to evaluate their effect on re-sensitizing cytotoxicity of Taxol and Gefitinib in drug-resistant cancer cells. Experiments demonstrated that treatment with USP24-i-101 and Astemizole alone significantly inhibited drug resistance and re-sensitized the cytotoxicity of Taxol and Gefitinib in drug-resistant lung cancer cells. Notably, combination therapy with USP24-i-101and Astemizole re-sensitized the cytotoxicity of Taxol and Gefitinib in drug-resistant lung cancer, which could benefit in inhibiting drug resistance during cancer therapy.