Autoimmune disease management presents a significant challenge to medical science. Environmental factors potentially increase the risk of developing inflammatory and autoimmune diseases, such as multiple sclerosis, rh...Autoimmune disease management presents a significant challenge to medical science. Environmental factors potentially increase the risk of developing inflammatory and autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and lupus. Among various environmental stresses, cigarette smoke and hypoxia have both been reported to lead to an enhanced risk of inflammatory and autoimmune diseases. In this review, we shed light on all reported mechanisms whereby cigarette smoke and a hypoxic environment can induce inflammatory and autoimmune diseases and discuss how hypoxic conditions influence the cigarette smoke-induced threat of inflammatory and autoimmune disease development. Cigarette smoke and hypoxia both lead to increased oxidative stress and production of reactive oxygen species and other free radicals, which have various effects including the generation of autoreactive pro-inflammatory T cells and autoantibodies, reductions in T regulatory(Treg) cell activity, and enhanced expression of pro-inflammatory mediators [e.g., interleukin-6(IL-6), interleukin-4(IL-4) and interleukin-8(IL-8)]. Accordingly, smoking and hypoxic environments may synergistically act as potent environmental risk factors for inflammatory and autoimmune diseases. To our knowledge, no studies have reported the direct association of cigarette smoke and hypoxic environments with the risk of developing inflammatory and autoimmune diseases. Future studies exploring the risk of autoimmune disease development in smokers at high altitudes, particularly military personnel and mountaineers who are not acclimatized to high-altitude regions, are required to obtain a better understanding of disease risk as well as its management.展开更多
Objective:To explore natural compounds as potential inhibitors against main protease(Mpro)of SARS-CoV-2.Methods:In the current study,systematic molecular docking analysis was conducted using AutoDock 4.2 to determine ...Objective:To explore natural compounds as potential inhibitors against main protease(Mpro)of SARS-CoV-2.Methods:In the current study,systematic molecular docking analysis was conducted using AutoDock 4.2 to determine the binding affinities and interactions between natural compounds and Mpro.Selected natural compounds were further validated using a combination of molecular dynamic(MD)simulations and molecular mechanic Poisson-Boltzmann surface area(MM/PBSA)free energy c alculation s.Results:Out of twenty natural compounds,four natural metabolites namely,amentoflavone,guggulsterone,puerarin,and piperine were found to have strong interaction with Mpro of SARS-CoV-2 based on docking analysis.During MD simulations,all four natural compounds bound to Mpro at 50 ns and MM/G/P/BSA free energy calculations showed that all four shortlisted ligands had stable and favorable energies with strong binding to Mpro protein.Conclusions:Guggulsterone is a potential inhibitor of COVID-19 main protease Mpro.Further in vitro and pre-clinical studies are needed.展开更多
文摘Autoimmune disease management presents a significant challenge to medical science. Environmental factors potentially increase the risk of developing inflammatory and autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and lupus. Among various environmental stresses, cigarette smoke and hypoxia have both been reported to lead to an enhanced risk of inflammatory and autoimmune diseases. In this review, we shed light on all reported mechanisms whereby cigarette smoke and a hypoxic environment can induce inflammatory and autoimmune diseases and discuss how hypoxic conditions influence the cigarette smoke-induced threat of inflammatory and autoimmune disease development. Cigarette smoke and hypoxia both lead to increased oxidative stress and production of reactive oxygen species and other free radicals, which have various effects including the generation of autoreactive pro-inflammatory T cells and autoantibodies, reductions in T regulatory(Treg) cell activity, and enhanced expression of pro-inflammatory mediators [e.g., interleukin-6(IL-6), interleukin-4(IL-4) and interleukin-8(IL-8)]. Accordingly, smoking and hypoxic environments may synergistically act as potent environmental risk factors for inflammatory and autoimmune diseases. To our knowledge, no studies have reported the direct association of cigarette smoke and hypoxic environments with the risk of developing inflammatory and autoimmune diseases. Future studies exploring the risk of autoimmune disease development in smokers at high altitudes, particularly military personnel and mountaineers who are not acclimatized to high-altitude regions, are required to obtain a better understanding of disease risk as well as its management.
文摘Objective:To explore natural compounds as potential inhibitors against main protease(Mpro)of SARS-CoV-2.Methods:In the current study,systematic molecular docking analysis was conducted using AutoDock 4.2 to determine the binding affinities and interactions between natural compounds and Mpro.Selected natural compounds were further validated using a combination of molecular dynamic(MD)simulations and molecular mechanic Poisson-Boltzmann surface area(MM/PBSA)free energy c alculation s.Results:Out of twenty natural compounds,four natural metabolites namely,amentoflavone,guggulsterone,puerarin,and piperine were found to have strong interaction with Mpro of SARS-CoV-2 based on docking analysis.During MD simulations,all four natural compounds bound to Mpro at 50 ns and MM/G/P/BSA free energy calculations showed that all four shortlisted ligands had stable and favorable energies with strong binding to Mpro protein.Conclusions:Guggulsterone is a potential inhibitor of COVID-19 main protease Mpro.Further in vitro and pre-clinical studies are needed.
