Integrated metabolomics and transcriptomics analysis reveals new biomarkers and mechanistic insights on atrazine exposures in MCF­7 cells.

Atrazine (ATZ) is a widely used herbicide worldwide and is a long-suspected endocrine-disrupting chemical. However, most endocrine-disrupting toxicity studies on ATZ have been based on animal models and those investigating inner mechanisms have only focused on a few genes. Therefore, the possible link between ATZ and endocrine-disrupting toxicity is still unclear. In this study, multi-omics and molecular biology techniques were used to elucidate the possible molecular mechanisms underlying the effect of ATZ exposure on MCF-7 proliferation at environmentally relevant concentrations. Our study is the first report on ATZ-induced one carbon pool by folate metabolic disorder in MCF-7 cells. A concentration of 1 µM ATZ yielded the highest cell viability and was selected for further mechanistic studies. A total of 34 significantly changed metabolites were identified based on metabolomic analysis, including vitamins, amino acids, fatty acids, and corresponding derivatives. Folate and pyridoxal have potential as biomarkers of ATZ exposure. One carbon pool by folate metabolic pathway was identified based on metabolic pathway analysis of the significantly altered pathways. Moreover, FTCD and MTHFD related to this pathway were further identified based on transcriptomic analysis and protein assays. Folate and different forms of 5,6,7,8-tetrahydrofolate, which participate in purine synthesis and associate with methyl groups (SOPC, arachidonic acid, and L-tryptophan) in one carbon pool by the folate metabolic pathway, potentially promote MCF-7 cell proliferation. These findings on the key metabolites and regulation of the related differentially expressed genes in folate metabolism will shed light on the mechanism of MCF-7 cell proliferation after ATZ exposure. Overall, this study provides new insights into the mechanistic understanding of toxicity caused by endocrine-disrupting chemicals.

Appropriate Patient Selection Is Essential for the Success of Primary Closure After Laparoscopic Common Bile Duct Exploration.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is being increasingly used for management of common bile duct (CBD) stones. Primary CBD closure has been reported to have better short-term outcomes compared to T-tube placement. However, primary CBD closure cannot be performed in all patients. AIM: This study aims to evaluate the short- and long-term outcomes of LCBDE with primary CBD closure in appropriately selected patients and compare them with T-tube drainage. METHODS: Retrospective analysis of patients undergoing LCBDE in our department from June 2011 to October 2014 was performed. Primary closure was performed in 52 patients (group A), and a T-tube was placed in 33 patients (group B). Patient demographics, intraoperative findings, postoperative stay, complications, and long-term follow-up data were recorded and compared. RESULTS: The mean operating time was much longer in group A compared to group B (113.92 vs. 95.92 min, p = 0.032). The overall complication rate (9.6 vs. 6.3%, p = 0.701) and hospital stay (4 vs. 5.11 days, p = 0.088) were similar in both groups. No patient required conversion to the open procedure. Bile leakage was more frequent in group A (5.78 vs. 0%, p = 0.279), but this was not statistically significant. All three patients with bile leakage were treated successfully by conservative measures and gradual drain withdrawal. On long-term follow-up, recurrent stones were detected in two patients in group A. No patient was found to develop CBD stricture. CONCLUSION: LCBDE and primary CBD closure has excellent short- and long-term outcomes when performed in appropriately selected patients.