Prostate cancer begins as an androgen-responsive disease. However, subsequent accumulation of multiple sequential genetic and epigenetic alterations transforms the disease into an aggressive, castration-resistant pros...Prostate cancer begins as an androgen-responsive disease. However, subsequent accumulation of multiple sequential genetic and epigenetic alterations transforms the disease into an aggressive, castration-resistant prostate cancer (CRPC). The monoallelic Androgen Receptor (AR) is associated with the onset, growth and development of Prostate cancer. The AR is a ligand-dependent transcription factor, and the targeting of androgen- and AR-signaling axis remains the primary therapeutic option for Prostate cancer (PCa) treatment. A durable and functional disruption of AR signaling pathways combining both traditional and novel therapeutics is likely to provide better treatment options for CRPC. Recent work has indicated that expression of AR is modulated at the posttranscriptional level by regulatory miRNAs. Due to a relatively long 3’ untranslated region (UTR) of AR mRNA, the posttranscription expression is likely to be regulated by hundreds of miRNAs in normal as well as in disease state. The main objective of the article is to offer a thought-provoking concept of “andro-miRs” and their potential application in AR gene expression targeting. This new paradigm for targeting constitutively active AR and its tumor specific splicing isoforms using andro-miRs may pave the way for a novel adjunctive therapy and improved treatment of CRPC.展开更多
Porcine reproductive and respiratory syndrome virus(PRRSV) continues to cause significant economic loss worldwide and remains a serious threat to the pork industry. Currently, vaccination strategies provide limited pr...Porcine reproductive and respiratory syndrome virus(PRRSV) continues to cause significant economic loss worldwide and remains a serious threat to the pork industry. Currently, vaccination strategies provide limited protection against PRRSV infection, and consequently, new antiviral strategies are urgently required. Andrographolide(Andro) and its derivative potassium dehydrographolide succinate(PDS) have been used clinically in China and other Asian countries as therapies for inflammation-related diseases, including bacterial and viral infections, for decades. Here, we demonstrate that Andro and PDS exhibit robust activity against PRRSV replication in Marc-145 cells and primary porcine alveolar macrophages(PAMs). The two compounds exhibited broad-spectrum inhibitory activities in vitro against clinically circulating type 2 PRRSV GD-HD, XH-GD, and NADC30-like HNhx strains in China. The EC_(50)values of Andro against three tested PRRSV strain infections in Marc-145 cells ranged from 11.7 to 15.3 lmol/L, with selectivity indexes ranging from 8.3 to10.8, while the EC_(50)values of PDS ranged from 57.1 to 85.4 lmol/L, with selectivity indexes ranging from 344 to 515.Mechanistically, the anti-PRRSV activity of the two compounds is closely associated with their potent suppression on NFj B activation and enhanced oxidative stress induced by PRRSV infection. Further mechanistic investigations revealed that PDS, but not Andro, is able to directly interact with PRRSV particles. Taken together, our findings suggest that Andro and PDS are promising PRRSV inhibitors in vitro and deserves further in vivo studies in swine.展开更多
1.我们是法官,头顶着国徽,肩扛着天平,绝不能在我们手中办一件错案。——大连“铁法官”谭彦We judges,national emblem on a cap and balance on shoulders,ab-solutely can’t handle a case wrong in our hands.2.用力去做只能达到称...1.我们是法官,头顶着国徽,肩扛着天平,绝不能在我们手中办一件错案。——大连“铁法官”谭彦We judges,national emblem on a cap and balance on shoulders,ab-solutely can’t handle a case wrong in our hands.2.用力去做只能达到称职,用心去做才能达到优秀。——北京“岗位作贡献,真情为他人”展开更多
The kaolinitic claystane is widespread in coal measures of the Taiyuan Formation ofUpper Carboniferous Series in Shanxi Province. It is discovered thai some kaolinitic claystone consists mainly of a coarse mineral as ...The kaolinitic claystane is widespread in coal measures of the Taiyuan Formation ofUpper Carboniferous Series in Shanxi Province. It is discovered thai some kaolinitic claystone consists mainly of a coarse mineral as was determined by various methods. The results manifest that it is not kaolinite, but a kaolinite-diekite interstratified mineral.展开更多
文摘Prostate cancer begins as an androgen-responsive disease. However, subsequent accumulation of multiple sequential genetic and epigenetic alterations transforms the disease into an aggressive, castration-resistant prostate cancer (CRPC). The monoallelic Androgen Receptor (AR) is associated with the onset, growth and development of Prostate cancer. The AR is a ligand-dependent transcription factor, and the targeting of androgen- and AR-signaling axis remains the primary therapeutic option for Prostate cancer (PCa) treatment. A durable and functional disruption of AR signaling pathways combining both traditional and novel therapeutics is likely to provide better treatment options for CRPC. Recent work has indicated that expression of AR is modulated at the posttranscriptional level by regulatory miRNAs. Due to a relatively long 3’ untranslated region (UTR) of AR mRNA, the posttranscription expression is likely to be regulated by hundreds of miRNAs in normal as well as in disease state. The main objective of the article is to offer a thought-provoking concept of “andro-miRs” and their potential application in AR gene expression targeting. This new paradigm for targeting constitutively active AR and its tumor specific splicing isoforms using andro-miRs may pave the way for a novel adjunctive therapy and improved treatment of CRPC.
基金This work was funded by the National Key Research and Development Program of China(Grant 2017YFD0501404)the National Natural Science Foundation of China(Grant 31872521)+1 种基金the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(Grant 2019BT02N054)the Basic Research&Applying Basic Research Foundation of Guangdong Province(Grant 2019B1515210007)。
文摘Porcine reproductive and respiratory syndrome virus(PRRSV) continues to cause significant economic loss worldwide and remains a serious threat to the pork industry. Currently, vaccination strategies provide limited protection against PRRSV infection, and consequently, new antiviral strategies are urgently required. Andrographolide(Andro) and its derivative potassium dehydrographolide succinate(PDS) have been used clinically in China and other Asian countries as therapies for inflammation-related diseases, including bacterial and viral infections, for decades. Here, we demonstrate that Andro and PDS exhibit robust activity against PRRSV replication in Marc-145 cells and primary porcine alveolar macrophages(PAMs). The two compounds exhibited broad-spectrum inhibitory activities in vitro against clinically circulating type 2 PRRSV GD-HD, XH-GD, and NADC30-like HNhx strains in China. The EC_(50)values of Andro against three tested PRRSV strain infections in Marc-145 cells ranged from 11.7 to 15.3 lmol/L, with selectivity indexes ranging from 8.3 to10.8, while the EC_(50)values of PDS ranged from 57.1 to 85.4 lmol/L, with selectivity indexes ranging from 344 to 515.Mechanistically, the anti-PRRSV activity of the two compounds is closely associated with their potent suppression on NFj B activation and enhanced oxidative stress induced by PRRSV infection. Further mechanistic investigations revealed that PDS, but not Andro, is able to directly interact with PRRSV particles. Taken together, our findings suggest that Andro and PDS are promising PRRSV inhibitors in vitro and deserves further in vivo studies in swine.
基金National Natural Science Fund of China(No.30772824)University Doctor Fund of Ministry of Education, China(No.200805410004)+2 种基金Hunan Provincial Natural Science Fund of China (No.07JJ3049)Scientific Research Fund of Hunan Provincial Science and Technology Department,China(No.2009FJ3001 )Hunan Provincial Master’s Innovation Fund in 2008(2008 No.28)~~
文摘1.我们是法官,头顶着国徽,肩扛着天平,绝不能在我们手中办一件错案。——大连“铁法官”谭彦We judges,national emblem on a cap and balance on shoulders,ab-solutely can’t handle a case wrong in our hands.2.用力去做只能达到称职,用心去做才能达到优秀。——北京“岗位作贡献,真情为他人”
文摘The kaolinitic claystane is widespread in coal measures of the Taiyuan Formation ofUpper Carboniferous Series in Shanxi Province. It is discovered thai some kaolinitic claystone consists mainly of a coarse mineral as was determined by various methods. The results manifest that it is not kaolinite, but a kaolinite-diekite interstratified mineral.
