No abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a second-generation antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and Ad-ACE2-transduced mice. Tmprss2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cells, however, such antiviral efficacy was lacking in human lung cells and organoids. Accordingly, enzalutamide showed no antiviral activity due to the AR-independent TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 regulatory locus in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19 through reducing TMPRSS2 expression in lung cells.

Sulfur dioxide (SO 2 ), ammonia (NH 3 ), hydrogen sulfide (H 2 S), nitrogen dioxide (NO 2 ), and nitric oxide (NO) are toxic gases from industrial exhaust, which could lead to acid rain, air pollution, health hazards, or corrosion of buildings. Removal of toxic gas is necessary for mitigating damage on human health, improving air quality, conforming to government regulations, and reusing in industry. However, capture of toxic gases with high efficiency, high selectivity, high sustainability, and low cost is still very challenging. Deep eutectic solvents (DESs) are novel green and designable solvents with high biocompatibility, high degradability, and low cost. Capturing toxic gases (e.g., SO 2 , NH 3 , H 2 S, NO 2 , and NO) by DESs is promising and environmentally friendly, which has attracted much attention. Here, we review the capture of SO 2 , NH 3 , H 2 S, NO 2 , and NO by DESs. CO 2 capture by DESs is not included because several reviews on that topic have been published.

that BRG1 inhibition is a promising approach against PTENmutant prostate tumors in preclinical models.

No abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat due to the lack of effective drugs or vaccines against SARS-CoV-2. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a relatively new antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry into host cells, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and SARS-CoV-2-infected Ad-ACE2-transduced Tmprss2 knockout (Tmprss2-KO) and wild-type (WT) mice. TMPRSS2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cancer cells (LNCaP) but not in human lung cancer cells or patient-derived lung organoids. Although Tmprss2 knockout effectively blocked SARS-CoV-2 infection in ACE2-transduced mice, enzalutamide showed no antiviral activity due to the AR independence of TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19.

1While cancer is commonly perceived as a disease of dedifferentiation, the hallmark of early stage prostate 2 cancer is paradoxically the loss of more plastic basal cells and the abnormal proliferation of more 3 differentiated secretory luminal cells. However, the mechanism of prostate cancer pro-luminal 4 differentiation is largely unknown. Through integrating analysis of the transcription factors (TFs) from 806 5 human prostate cancers, we have identified that ERG highly correlated with prostate cancer luminal 6subtyping. ERG overexpression in luminal epithelial cells inhibits its normal plasticity to transdifferentiate 7into basal lineage and ERG supersedes PTEN-loss which favors basal differentiation. ERG knock-out 8 disrupted prostate cell luminal differentiation, whereas AR knock-out had no such effects. Trp63 is a known 9 master regulator of prostate basal lineage. Through analysis of 3D chromatin architecture, we found that 10 ERG binds and inhibits the enhancer activity and chromatin looping of a Trp63 distal enhancer, thereby 11 silencing its gene expression. Specific deletion of the distal ERG binding site resulted in the loss of ERG-12 mediated inhibition of basal differentiation. Thus, ERG orchestrates chromatin interactions and regulates 13 prostate cell lineage toward pro-luminal program, as its fundamental role on lineage differentiation in 14 prostate cancer initiation. 15 16