The pathophysiology of osteoarthritis(OA)is multifactorial,with the primary risk factors being obesity,age,environmental variables,and genetic predisposition.The available evidence suggests that genetic diversity does...The pathophysiology of osteoarthritis(OA)is multifactorial,with the primary risk factors being obesity,age,environmental variables,and genetic predisposition.The available evidence suggests that genetic diversity does not adequately account for all clinical characteristics and heterogeneity of OA.Genetics has emerged as a nascent and crucial area of research in OA.The epigenetic module presents a potential link between genetic and environmental risk factors and the susceptibility and pathogenesis of OA.As a critical epigenetic alteration,DNA methylation has been shown to have an important role in the etiology of OA and is a viable biomarker for predicting disease progression and medication response,as shown in this research.This review aims to update knowledge in the field of DNA methylation associated with OA to better identify the essential features of OA subtypes and pathological conditions,hence accelerating individualized treatment and precision medicine.展开更多
On the basis of data mining,systematic pharmacology,molecular docking,and experiment validation,the oxidative-inflammatory molecular targets of Coicis Semen in the therapy of osteoarthritis(OA)were explored.Methods:Th...On the basis of data mining,systematic pharmacology,molecular docking,and experiment validation,the oxidative-inflammatory molecular targets of Coicis Semen in the therapy of osteoarthritis(OA)were explored.Methods:The association rule analysis was effectively applied to highlight the correlation between Coicis Semen and oxidative inflammation indices.The random walk model was subsequently used to evaluate the clinical efficacy of Coicis Semen.Network pharmacology was used to predict network targets.The binding affinity of the active ingredient in Coicis Semen to the key target of OA was also successfully predicted.Results:Coicis Semen showed a significant reduction in oxidative-inflammatory indicators of OA.A total of 108 promising targets were predicted for the 24 bioactive compounds in Coicis Semen.Eight target genes were considered core target genes.The enrichment analysis predicts that Coicis Semen may activate the interleukin(IL)-17,mitogen-activated protein kinase(MAPK),and nuclear factor kappa B(NF-kappa B)signaling pathways.Molecular docking demonstrated that stigmasterol,2-monoolein,sitosterol,and sitosterol alpha1 had free binding energies to oxidative and inflammatory targets(MAPK1,Estrogen Receptor 1[ESR1],and Peroxisome Proliferator-Activated Receptor Alpha[PPARA]).Both clinical trials and in vitro cell experiments revealed that Coicis Semen could increase ESR1 and PPAR-αlevels while decreasing MAPK1 levels.Conclusions:Coicis Semen has a remarkable anti-OA effect.Precisely,the major components of Coicis Semen,including stigmasterol,sitosterol alpha1,sitosterol,and 2-monoolein,specifically inhibit MAPK1,ESR1,and PPARA to reduce the inflammatory response and oxidative damage in OA.展开更多
基金supported by the Anhui Famous Traditional Chinese Medicine Liu Jian Studio Construction Project(Traditional Chinese Medicine Development Secret[2018]No.11)the Ministry of Science and Technology National Key Research and Development Program Chinese Medicine Modernization Research Key Project(No.2018YFC1705204)+1 种基金Anhui Province Traditional Chinese Medicine Leading Talent Project(Traditional Chinese Medicine Development Secret[2018]No.23)the Anhui Key Research and Development Program Foreign Science and Technology Cooperation Project(No.201904b11020011).
文摘The pathophysiology of osteoarthritis(OA)is multifactorial,with the primary risk factors being obesity,age,environmental variables,and genetic predisposition.The available evidence suggests that genetic diversity does not adequately account for all clinical characteristics and heterogeneity of OA.Genetics has emerged as a nascent and crucial area of research in OA.The epigenetic module presents a potential link between genetic and environmental risk factors and the susceptibility and pathogenesis of OA.As a critical epigenetic alteration,DNA methylation has been shown to have an important role in the etiology of OA and is a viable biomarker for predicting disease progression and medication response,as shown in this research.This review aims to update knowledge in the field of DNA methylation associated with OA to better identify the essential features of OA subtypes and pathological conditions,hence accelerating individualized treatment and precision medicine.
基金supported by the Anhui Famous Traditional Chinese Medicine Liu Jian Studio Construction Project(Traditional Chinese Medicine Development Secret[2018]No.11)the Ministry of Science and Technology National Key Research and Development Program Chinese Medicine Modernization Research Key Project(No.2018YFC1705204)+2 种基金Anhui Province Traditional Chinese Medicine Leading Talent Project(Traditional Chinese Medicine Development Secret[2018]No.23)the Anhui key Research and Development Program Foreign Science and Technology Cooperation Project(No.201904b11020011)the Anhui Provincial Education Department Project(No.2022AH050449).
文摘On the basis of data mining,systematic pharmacology,molecular docking,and experiment validation,the oxidative-inflammatory molecular targets of Coicis Semen in the therapy of osteoarthritis(OA)were explored.Methods:The association rule analysis was effectively applied to highlight the correlation between Coicis Semen and oxidative inflammation indices.The random walk model was subsequently used to evaluate the clinical efficacy of Coicis Semen.Network pharmacology was used to predict network targets.The binding affinity of the active ingredient in Coicis Semen to the key target of OA was also successfully predicted.Results:Coicis Semen showed a significant reduction in oxidative-inflammatory indicators of OA.A total of 108 promising targets were predicted for the 24 bioactive compounds in Coicis Semen.Eight target genes were considered core target genes.The enrichment analysis predicts that Coicis Semen may activate the interleukin(IL)-17,mitogen-activated protein kinase(MAPK),and nuclear factor kappa B(NF-kappa B)signaling pathways.Molecular docking demonstrated that stigmasterol,2-monoolein,sitosterol,and sitosterol alpha1 had free binding energies to oxidative and inflammatory targets(MAPK1,Estrogen Receptor 1[ESR1],and Peroxisome Proliferator-Activated Receptor Alpha[PPARA]).Both clinical trials and in vitro cell experiments revealed that Coicis Semen could increase ESR1 and PPAR-αlevels while decreasing MAPK1 levels.Conclusions:Coicis Semen has a remarkable anti-OA effect.Precisely,the major components of Coicis Semen,including stigmasterol,sitosterol alpha1,sitosterol,and 2-monoolein,specifically inhibit MAPK1,ESR1,and PPARA to reduce the inflammatory response and oxidative damage in OA.
