Triclocarban and triclosan promote breast cancer progression in vitro and in vivo via activating G protein-coupled estrogen receptor signaling pathways.

Triclocarban (TCC) and triclosan (TCS) have been detected ubiquitously in human body and evoked increasing concerns. This study aimed to reveal the induction risks of TCC and TCS on triple negative breast cancer through non-genomic GPER-mediated signaling pathways. Molecular simulation indicated that TCC exhibited higher GPER binding affinity than TCS theoretically. Calcium mobilization assay displayed that TCC/TCS activated GPER signaling pathway with the lowest observed effective concentrations (LOEC) of 10 nM/100 nM. TCC and TCS also upregulated MMP-2/9, EGFR, MAPK3 but downregulated MAPK8 via GPER-mediated signaling pathway. Proliferation assay showed that TCC/TCS induced 4 T1 breast cancer cells proliferation with the LOEC of 100 nM/1000 nM. Wound-healing and transwell assays showed that TCC/TCS promoted 4 T1 cells migration in a concentration-dependent manner with the LOEC of 10 nM. The effects of TCC on breast cancer cells proliferation and migration were stronger than TCS and both were regulated by GPER. TCC/TCS induced migratory effects were more significantly than proliferative effect. Mechanism study showed that TCC/TCS downregulated the expression of epithelial marker (E-cadherin) but upregulated mesenchymal markers (snail and N-cadherin), which was reversed by GPER inhibitor G15. These biomarkers results indicated that TCC/TCS-induced 4 T1 cells migration was a classic epithelial to mesenchymal transition mechanism regulated by GPER signaling pathway. Orthotopic tumor model verified that TCC promoted breast cancer in-situ tumor growth and distal tissue metastasis via GPER-mediated signaling pathway at human-exposure level of 10 mg/kg/d. TCC-induced tissue metastasis of breast cancer was more significantly than in-situ tumor growth. Overall, we demonstrated for the first time that TCC/TCS could activate the GPER signaling pathways to induce breast cancer progression.

Co-Mn-Fe spinel-carbon composite catalysts enhanced persulfate activation for degradation of neonicotinoid insecticides: (Non) radical path identification, degradation pathway and toxicity analysis.

The extensive utilization of neonicotinoid insecticides (NNIs) in agricultural practices ultimately poses a significant threat to both the environment and human health. This work focuses on the efficient degradation and detoxification of the representative NNI, thiamethoxam (THX), and explores the underlying mechanism using a Co-Fe-Mn mixed spinel doped carbon composite catalyst activated persulfate. The findings demonstrate that the composite effectively degrades THX, achieving a degradation rate of 95% in 30 mins, while requiring only a fraction (one-sixteenth) of the oxidant dosage compared to pure carbon. The study aimed to examine the negative impact of reactive halogens on reactive oxygen species within a saline environment. The degradation byproducts were linked to the presence of two common electron-withdrawing groups, namely halogens and nitro in the THX molecule. It was hypothesized that the degradation process was primarily influenced by C-N bond breaking and hydroxylation occurring between the diazine oxide and 2-chlorothiazole rings. Consequently, dehalogenation and carbonylation processes facilitated the elimination of halogenated components and pharmacophores from the THX, leading to detoxification. In addition to the identified free radical pathway including SO4•-, •OH and O2•- contributed to THX degradation, the participation of non-radical pathways (1O2 and electron transfer) were also confirmed. The efficacy of detoxification was further validated through toxicity assessment, employing quantitative conformation relationship prediction and microbial culture utilizing Bacillus subtilis.

Formation and stability of Eucommia ulmoides Oliver seed oil-loaded inverse microemulsion formed by food-grade ingredients and its antioxidant activities.

Eucommia ulmoides Oliver seed oil (E.u oil) as a functional oil is rich in many natural active components such as α-linolenic acid (56% to 63%), vitamin E, aucubin, and so on. In this study, water-in-oil (W/O) microemulsions composed of Eucommia ulmoides Oliver seed oil, distilled water, a blend of Sorbitan monooleate 80 (Span 80) and Polysorbate (20) sorbitan monooleate (Tween 80), and propylene glycol were prepared for improving the compatibility of Eucommia ulmoides Oliver seed oil. Pseudoternary phase diagrams were built to illustrate the phase behavior of the microemulsions, based on hydrophilic-lipophilic balance values, cosurfactant type, the proportion of cosurfactant, and the changing environmental stress. Dynamic light scattering, transmission electron microscopy, and electrical conductivity measurements were performed to characterize the microstructural aspects. The optimum process conditions at which the Eucommia ulmoides Oliver seed oil-loaded microemulsion had good tolerance to pH and salinity were: Propylene glycol served as cosurfactant, water-Propylene glycol, and Span 80-Tween 80 ratios separately kept constant at 1:1 and 6:4. These microemulsions with narrow size distribution, nanoscale particle size (below 60 nm), transparent appearance had a wide range of oil phase content and free-radical scavenging capacity toward DPPH and ABTS radicals with half-maximal inhibitory concentration (IC50 ) values of 49.20 and 33.43 mg/mL, respectively. PRACTICAL APPLICATION: This nanostructure, environmental stability, and antioxidant activity of microemulsions containing Eucommia ulmoides Oliver seed oil is a potential delivery system as an alternative to α-linolenic acid and can be used for the delivery of peptides, proteins, antioxidants, and water-soluble nutrients.