Molecular docking and molecular dynamics study Lianhua Qingwen granules (LHQW) treats COVID-19 by inhibiting inflammatory response and regulating cell survival.

Purpose: 2019 Coronavirus disease (COVID-19) is endangering health of populations worldwide. Latest research has proved that Lianhua Qingwen granules (LHQW) can reduce tissue damage caused by inflammatory reactions and relieve patients' clinical symptoms. However, the mechanism of LHQW treats COVID-19 is currently lacking. Therefore, we employed computer simulations to investigate the mechanism of LHQW treats COVID-19 by modulating inflammatory response. Methods: We employed bioinformatics to screen active ingredients in LHQW and intersection gene targets. PPI, GO and KEGG was used to analyze relationship of intersection gene targets. Molecular dynamics simulations validated the binding stability of active ingredients and target proteins. Binding free energy, radius of gyration and the solvent accessible surface area were analyzed by supercomputer platform. Results: COVID-19 had 4628 gene targets, LHQW had 1409 gene targets, intersection gene targets were 415. Bioinformatics analysis showed that intersection targets were closely related to inflammation and immunomodulatory. Molecular docking suggested that active ingredients (including: licopyranocoumarin, Glycyrol and 3-3-Oxopropanoic acid) in LHQW played a role in treating COVID-19 by acting on CSF2, CXCL8, CCR5, NLRP3, IFNG and TNF. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets. Conclusion: The mechanism of active ingredients in LHQW treats COVID-19 was investigated by computer simulations. We found that active ingredients in LHQW not only reduce cell damage and tissue destruction by inhibiting the inflammatory response through CSF2, CXCL8, CCR5 and IFNG, but also regulate cell survival and growth through NLRP3 and TNF thereby reducing apoptosis.

miR­494­3p promotes the progression of endometrial cancer by regulating the PTEN/PI3K/AKT pathway.

MicroRNAs (miRs) are essential regulators in the development and progression of cancer. The role of miR-494-3p in endometrial cancer (EC) has not yet been investigated. In the present study, the expression levels of miR­494­3p were significantly upregulated in EC tissues compared with adjacent normal tissues. Furthermore, upregulation of miR­494­3p in patients with EC indicated poorer prognosis; miR­494­3p overexpression significantly promoted the proliferation, migration and invasion of HHUA and JEC cells in vitro. Consistently, inhibition of miR­494­3p in HHUA cells significantly suppressed tumor growth in vivo in a xenograft model. Additionally, phosphatase and tensin homolog (PTEN) was revealed to be a direct target of miR­494­3p in EC cells. Furthermore, overexpression of miR­494­3p inhibited PTEN expression and consequently activated the downstream phosphoinositide 3­kinase/protein kinase B (PI3K/AKT) signialing pathway. Restoration of PTEN or inhibition of PI3K/AKT pathway also abolished miR­494­3p­mediated proliferation, migration and invasion of HHUA and JEC cells. In summary, the results of the present study revealed the importance of the miR­494­3p/PTEN/PI3K/AKT axis in the progression of EC, which may provide novel insight into potential therapeutic targets for the treatment of EC.