Development of multidrug resistance (MDR) is a continuous clinical challenge partially due to the overexpression of P-glycoprotein (P-gp) for chronic myelogenous leukemia (CML) patients. Herein, we evaluated the inhibitory potency of emodin, a natural anthraquinone derivative isolated from Rheum palmatum L, on P-gp in P-gp positive K562/ADM cells. Competition experiments combined with molecular docking analysis were utilized to investigate the binding modes between emodin and binding sites of P-gp. Emodin reversed adriamycin resistance in K562/ADM cells accompanied with the decrease of P-gp protein expression, further increasing the uptake of rhodamine123 in both K562/ADM and Caco-2 cells, indicating the inhibition of P-gp efflux function. Moreover, when incubated with emodin under different conditions where P-gp was inhibited, K562/ADM cells displayed increasing intracellular uptake of emodin, suggesting that emodin may be the potential substrate of P-gp. Importantly, rhodamine 123 could increase the Kintrinsic (Ki) value of emodin linearly, whereas, verapamil could not, implying that emodin competitively bound to the R site of P-gp and noncompetition existed between emodin and verapamil at the M site, in a good accordance with the results of molecular docking that emodin bound to the R site of P-gp with higher affinity. Based on our results, we suggest that emodin might be used to modulate P-gp function and expression.
A novel coronavirus (SARS-CoV-2) causing corona virus disease 2019 (COVID-19) has
attracted global attention due to its highly infectious and pathogenic properties. Most
of current studies focus on aerosols released from infected individuals, but the
presence of SARS-CoV-2 in wastewater also should be examined. In this review, we used
bibliometrics to statistically evaluate the importance of water-related issues in the
context of COVID-19. The results show that the levels and transmission possibilities of
SARS-CoV-2 in wastewater are the main concerns, followed by potential secondary
pollution by the intensive use of disinfectants, sludge disposal, and the personal
safety of workers. The presence of SARS-CoV-2 in wastewater requires more attention
during the COVID-19 pandemic. Thus, the most effective techniques, i.e.,
wastewater-based epidemiology and quantitative microbial risk assessment, for virus
surveillance in wastewater are systematically analyzed. We further explicitly review and
analyze the successful operation of a sewage treatment plant in Huoshenshan Hospital in
China as an example and reference for other sewage treatment systems to properly ensure
discharge safety and tackle the COVID-19 pandemic. This review offers deeper insight
into the prevention and control of SARS-CoV-2 and similar viruses in the post-COVID-19
era from a wastewater perspective.
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