Inhibition of APE1 Expression Enhances the Antitumor Activity of Olaparib in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that is prone to recurrence and metastasis. Because of the lack of expression of estrogen receptor (ER) and progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in TNBC, treatment methods are greatly limited. In this study, the proliferation inhibition and apoptosis-inducing effects of PARP1 inhibitors in TNBC breast cancer cells and in vivo xenograft animal models were examined to investigate the molecular role of APE1 in PARP1-targeted therapy. In TNBC patients, the expression of APE1 and PARP1 were positively correlated, and high expression of APE1 and PARP1 was associated with poor survival of TNBC. Our results indicated that knockdown APE1 could increase the sensitivity of olaparib in the treatment of TNBC. In conclusion, the results of this study will not only clarify the molecular role of APE1 in PARP1-targeted therapy for TNBC but also provide a theoretical basis for the future clinical application of targeting APE1 and PARP1 in the treatment of refractory TNBC.

Simultaneous Determination and Health Risk Assessment of Four High Detection Rate Pesticide Residues in Pu'er Tea from Yunnan, China.

Four pesticides with a high detection rate in Pu'er tea have been determined by a QuEChERS (quick, easy, cheap, effective, rugged, safe) method with multiwalled carbon nanotubes (MWCNTs), and combined ultrahigh-performance liquid chromatography-triple quadrupole linear ion trap-tandem mass spectrometry (UHPLC-QTRAP-MS/MS). MWCNs have been compared with other common purification materials, and found to be superior. The matrix effect was systematically studied, and the results show that the MWCNs can quickly and effectively reduce matrix interference values, which were in the range from -17.8 to 13.8. The coefficients (R2) were greater than 0.99, with the limit of quantification ranging from 0.1 to 0.5 µg/kg, and the recovery rate ranging from 74.8% to 105.0%, while the relative standard deviation (RSD) ranged from 3.9% to 6.6%. A total of 300 samples, taken from three areas in which Yunnan Pu'er tea was most commonly produced, tested for four pesticides. The results show that the detection rate of tolfenpyrad in Pu'er tea was 35.7%, which is higher than other pesticides, and the lowest was indoxacarb, with 5.2%. The residual concentrations of chlorpyrifos, triazophos, tolfenpyrad and indoxacarb ranged from 1.10 to 5.28, 0.014 to 0.103, 1.02 to 51.8, and 1.07 to 4.89 mg/kg, respectively. By comparing with China's pesticide residue limits in tea (GB 2763-2021), the over standard rates of chlorpyrifos, tolfenpyrad, and indoxacarb were 4.35%, 0.87% and 0%, respectively. The risk assessment result obtained with the hazard quotient (HQ) method shows that the HQ of the four pesticides was far less than one, indicating that the risk is considered acceptable for the four pesticides in Pu'er tea. The largest HQ was found for tolfenpyrad, 0.0135, and the smallest was found for indoxacarb, 0.000757, but more attention should be paid to tolfenpyrad in daily diets in the future, because its detection rate, and residual and residual median were all relatively high.