Breast cancer remains the most prevalent cancer in females. The triple negative subtype of breast cancer is associated with higher recurrence rates and poorer prognosis, lack of effective targeted therapy options, and frequently becoming unresponsive to chemotherapy. This study investigates the in vitro anti-cancer potential of our previously in silico-discovered cryptides, from Penaeus vannamei, against MCF-7, MCF-7-CR, and MDA-MB-231 cancer cell lines. Five cryptides-AD4, AD7, AD8, AD11, and AD12-were tested using the MTT assay, revealing selective toxicity against cancer cells. The lowest and highest calculated IC₅₀ values were for AD12 against MCF-7-CR (∼4.6 μM) and MDA-MB-231 (∼20 μM), respectively. Mechanistic studies showed that the cytotoxicity mediated by cryptides, AD7 and AD8, induced loss of mitochondrial membrane potential, release of mitochondrial cytochrome C, and cleavage of caspases that were associated with BAX activation in MCF-7 and MDA-MB-231 cells. Furthermore, our results showed that both MCF-7 and MDA-MB-231 cells treated with AD7 or AD8 exhibited nuclei condensation, activation of Caspase 3/7, leading to apoptotic cell death associated with intrinsic apoptotic cell signaling mechanism. However, further investigation showed that both AD7 and AD8 peptides promoted up-regulation of FAS and p53 in MCF-7 cells while down-regulated the expression of both FAS and p53 in MDA-MB-231 cells, suggesting cell-type dependent apoptotic cell signaling mechanisms. Moreover, both AD7 and AD8 demonstrated cytotoxic and disintegration effects in 3D cancer model. This study highlights the anticancer potential of marine-derived cryptides against challenging breast cancer subtypes, including triple-negative breast cancer (TNBC), with selective cytotoxicity and potential to overcome resistance and recurrence.

2024-11-01·Journal of Pharmacological and Toxicological Methods

Evaluation of 4 quantification methods for monitoring 16 antidepressant drugs and their metabolites in human plasma by LC-MS/MS

Article

作者: Li, Jiao ; Zhao, Mengqiang ; Yu, Jing ; Zhao, Yuanyuan ; Wang, Lingjiao ; Xu, Hongtao ; Zhou, Chunhua ; Song, Yang

BACKGROUNDTherapeutic drug monitoring for antidepressants (ADs) is vital due to the potentially serious consequences and disputes related to medical events. Therefore, we created a quick and convenient analysis way for separation and quantification of ADs.METHODSTo ensure quantitative stability, we divided the 16 ADs or their metabolites into 4 pools (AD1-AD4), considering the hospital frequency that the clinician prescribed, the physicochemical properties of medicines, and the calibration range of selected ADs. After precipitation with methanol, the analytes were eluted for at least 3.5 min on a BEH C₁₈ analytical column by different gradient elution methods.RESULTSThe LLOQ and LOD were 1.25-10 ng/mL and 0.42-5 ng/mL, respectively. High precision (<12 %) and accuracy (87.07-111.47 %) were demonstrated by quality control samples both within and between days. All the compounds were stable at room temperature and within -80 °C.CONCLUSIONThe method is of wide clinical and laboratory interest due to simpler sample cleanup, shorter chromatographic run times, and wider calibration range compared to other methods.

2024-10-14·International Journal of Phytoremediation

Lead stabilization and remediation strategy with soil amendment in situ immobilization in contaminated range lands

Article

作者: Imran

In situ immobilization is a potential approach that can be used to remediate low-to-medium levels of heavy-metal in contaminated-soil. There is little known about how modifications to soil characteristics may affect Pb's release from soil. The four different amendments, triple-superphosphate and attapulgite were combined in Ad-1; zeolite and triple-superphosphate were in Ad-2; hydroxyapatite and humus were in Ad-3; and nano-carbon. These amendments are mostly made of phyllosilicate minerals, humus, base minerals, and nano-carbon, respectively. Results revealed that the test amendments' maximal Pb-adsorption capacity varied from 7.47 to 17.67 mg g^-1. Surface precipitation and ion-exchange were found to be the main mechanisms for Pb-adsorption by Ad-1 and Ad-2, while Ad-3 and Ad-4 were promising among the all, according to analysis of the modifications both before and after Pb loading. When the pH dropped (7-1) or the ion-strength rose (0-0.2 M), there was a discernible rise in the Pb-desorption percentages from the amendments. It was determined that Ad-3 and Ad-4 were more effective in situ immobilizing lead in contaminated-soils because of their high adsorption capacities (12.82 and 17.67 mg g^-1) and low-desorption percentages (4.46-6.23%) at ion-strengths of 0.01-0.1 mol L^-1 and pH levels ranging from 5 to 7.

100 项与 AD-4 相关的药物交易

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