Molybdenum disulfide nanosheets promote the plasmid-mediated conjugative transfer of antibiotic resistance genes.

The environmental safety of nanoscale molybdenum disulfide (MoS2) has attracted considerable attention, but its influence on the horizontal migration of antibiotic resistance genes and the ecological risks entailed have not been reported. This study addressed the influence of exposure to MoS2 at different concentrations up to 100 mg/L on the conjugative transfer of antibiotic resistance genes carried by RP4 plasmids with two strains of Escherichia coli. As a result, MoS2 facilitated RP4 plasmid-mediated conjugative transfer in a dose-dependent manner. The conjugation of RP4 plasmids was enhanced as much as 7-fold. The promoting effect is mainly attributable to increased membrane permeability, oxidative stress induced by reactive oxygen species, changes in extracellular polymer secretion and differential expression of the genes involved in horizontal gene transfer. The data highlight the distinct dose dependence of the conjugative transfer of antibiotic resistance genes and the need to improve awareness of the ecological and health risks of nanoscale transition metal dichalcogenides.

Low concentrations of 17ß-estradiol exacerbate tamoxifen resistance in breast cancer treatment through membrane estrogen receptor-mediated signaling pathways.

The present study aims to discover the influences of tamoxifen and 17ß-estradiol (E2) on tamoxifen-resistant (TamR) patients in vitro. Herein, we established a stabilized TamR MCF-7 cell line at 1 µM via gradient concentrations of tamoxifen cultivation. The expression changes of four ER subtypes (ERα66, ERß, ERα36 and GPR30) were found to bring about tamoxifen resistance. Moreover, the generation of tamoxifen resistance involved in apoptosis escape via a reactive oxygen species-regulated p53 signaling pathway. Interestingly, E2 at environmental concentrations (0.1-10 nM) could activate the expression of both ERα36 and GPR30, and then stimulate the phosphorylation of ERK1/2 and Akt, resulting in cell growth promotion. Cell migration and invasion promotion, apoptosis inhibition, and cell cycle G1-S progression are involved in such proliferative effects. Conversely, the application of specific antagonists of ERα36 and GPR30 could restore tamoxifen's sensitivity as well as partially offset E2-mediated proliferation. In short, overexpression of ERα36 and GPR30 not only ablate tamoxifen responsiveness but also could promote tumor progression of TamR breast cancer under estrogen conditions. These results provided novel insights into underlying mechanisms of tamoxifen resistance and the negative effects of steroid estrogens at environmental concentrations on TamR MCF-7 cells, thus generating new thoughts for future management of ER-positive breast cancer.

Double-dose responses of Scenedesmus capricornus microalgae exposed to humic acid.

Dissolved organic matter (DOM) has been found to attenuate the ecotoxicity of various environmental pollutants, but research on its own toxic effects in aquatic ecosystems has been very limited. Herein, the toxic effects of humic acid (HA), a represent DOM typically found in natural waters, on the freshwater alga Scenedesmus capricornus were investigated. As result, HA exerted a double-dose effect on the growth of Scenedesmus capricornus. At HA concentrations below 2.0 mgC/L, the growth of Scenedesmus capricornus was slightly promoted, as was the synthesis of chlorophyll and macromolecules in the algae. Moreover, S. capricornus can maintain its growth by secreting fulvic acid as a nutrient carbon source. However, the growth of Scenedesmus capricornus was significantly inhibited when HA was beyond 2.0 mgC/L. The main mechanisms of humic acid's toxicity were membrane damage and oxidative stress. Particularly, when the oxidative stress exceeds the algae's carrying capacity, the synthesis of EPS is greatly inhibited and HA damage results. Taken together, DOM may have both positive and negative effects on aquatic ecosystems.

Quercetin exerts bidirectional regulation effects on the efficacy of tamoxifen in estrogen receptor-positive breast cancer therapy: An in vitro study.

Tamoxifen was widely applied in the therapy of estrogen receptor (ER)-positive breast cancer. With the purpose of determining the potential impacts of quercetin on its effectiveness, MCF-7 cells were selected as the in vitro model and several cellular biological behaviors (ie, cell proliferation, migration, invasion, cycle, apoptosis, and oxidative stress) were investigated. As results, quercetin showed contrasting dose-response to cellular behaviors dependent on the ROS-regulated p53 signaling pathways. In detail, quercetin promoted cell proliferation and inhibited cell apoptosis at low concentrations, whereas high-concentration resulted in apoptosis induction. Moreover, quercetin at a low concentration significantly inhibited tamoxifen-induced antiproliferation in MCF-7 cells, whereas high concentrations enhanced cell apoptosis in a synergetic manner. The real-time quantitative polymerase chain reaction analysis further implied that quercetin exerted its dual roles in tamoxifen-induced antiproliferative effects by regulated the gene expression involved in cell metastasis, cycle, and apoptosis through the ER pathways. Our present study provides a considerable support to the combination of quercetin and tamoxifen on human ER-positive breast carcinoma management.