ABSTRACT
The human protein-coding gene ILRUN (inflammation and lipid regulator with UBA-like and NBR1-like domain, previously C6orf106) is a recently-characterised inhibitor of the transcription regulators p300 and CREB-binding protein (CBP). Here we have utilised RNA-seq to define cellular pathways regulated by ILRUN in the context of severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) infection. We find that inhibition of ILRUN expression increases cellular expression of several members of the renin-angiotensin aldosterone system (RAAS), including the SARS-CoV-2 entry receptor angiotensin converting enzyme 2 (ACE2). Furthermore, inhibition of ILRUN results in increased SARS-CoV-2 replication. These data identify ILRUN as a novel inhibitor of SARS-CoV-2 replication and represents, to our knowledge, the first report of ILRUN as a regulator of the RAAS. SIGNIFICANCE STATEMENTThere is no doubt that the current rapid global spread of COVID-19 has had significant and far-reaching impacts on our health and economy and will continue to do so. Research in emerging infectious diseases, such as severe acute respiratory syndrome-associated coronavirus (SARS-CoV-2), is growing rapidly, with new breakthroughs in the understanding of host-virus interactions and the development of innovative and exciting therapeutic strategies and new knowledge and tools to better protect against the impacts of disease. The human protein-coding gene ILRUN is a recently-characterised inhibitor of the transcription regulators p300 and CREB-binding protein (CBP). Here we present the first evidence that ILRUN modulation has implications for SARS-CoV-2 infections. Virus infectivity assays confirmed that gene silencing of ILRUN had a proviral effect and increased SARS-CoV-2 replication, whilst over-expression of ILRUN inhibited SARS-CoV-2 production. Additionally, we observed that ILRUN also regulates the expression of key elements of the RAAS. These data have important implications for the development of antiviral strategies to deal with the current SARS-CoV-2 pandemic.
ABSTRACT
Aim To study the pharmacodynamics of antianxietic compound prescription capsule ( ACPC ) on acute stress in rats and the influence upon the ex-pression of ERK/CREB signal pathway and brain-de-rived neurotrophic factor ( BDNF) in the cerebral cor-tex and hippocampus of rats. Methods The elevated plus maze ( EPM ) test was applied to observe the effects of ACPC on acute stress rats administered 7 d low-, medium- and high-dose ( 0. 75 , 1. 5 , 3 g · kg-1 ) . The expression of ERK/CREB signal pathway and BDNF in the cerebral cortex and hippocampus of rats were studied by using Western blot method. Re-sults In EPM, high-dose of ACPC increased signifi-cantly the rat open arm time ( OT%) ( P<0 . 05 ) and the percentage of open arm entries ( OE%) ( P <0. 05). In Western blot, the medium-dose of ACPC reduced significantly p-ERK1/2 expression in hippo-campus ( P <0. 05 ) , and high-dose group decreased significantly the expression of p-ERK1/2 and p-CREB in the cortex and hippocampus of rats ( P <0. 05 ) . High-dose group increased significantly the expression of BDNF in the cortex and hippocampus of rats ( P<0. 05 , P<0. 01 ) . Conclusion ACPC has anti-anxie-ty effect in the model of EPM, and its mechanism may be related to the ERK/CREB signal pathway and in-creased BDNF expression.
ABSTRACT
This study was aimed to establish an HPLC method for simultaneous content determination of valtrate, acevaltrate, and their degradation products, which were baldrinal and 11-ethoxyviburtinal, in Valeriana jatamansi Jones. The separation and quantification of 4 constituents mentioned above were performed on an Agilent ZORBAX SB-C18 (4.6 mm×250 mm, 5 μm). The mobile phase consisted of water (A) - acetonitrile (B) with an optimized gradient program. The flow rate was 1 mL·min-1. The column temperature was set at 25℃. The wavelength was set at 241 nm. And the injection volume was 10μL. The results showed that among 14 different places of V. jatamansi, the 4 contents determined were different. The contents of valtrate, acevaltrate, and baldrinal in the Yunnan Baoshan Mount were the highest. And the content of 11-ethoxyviburtinal was the highest in Yunnan Dali. It was concluded that the method was with good precision, reproducibility and stability. And it was suitable for the determination of 4 valepotriates ingredients in V. jatamansi. It also provided references for the quality control and exploitation of V. jatamansi.
