elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.This study aimed to screen a novel TCM prescription against DR from patents and eluc...elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.This study aimed to screen a novel TCM prescription against DR from patents and elucidate its medication rule and molecular mechanism using data mining,network pharmacology,molecular docking and molecular dynamics(MD)simulation.Method:TCM prescriptions for treating DR was collected from patents and a novel TCM prescription was identified using data mining.Subsequently,the mechanism of the novel TCM prescription against DR was explored by constructing a network of core TCMs-core active ingredients-core targets-core pathways.Finally,molecular docking and MD simulation were employed to validate the findings from network pharmacology.Result:The TCMs of the collected prescriptions primarily possessed bitter and cold properties with heat-clearing and supplementing effects,attributed to the liver,lung and kidney channels.Notably,a novel TCM prescription for treating DR was identified,composed of Lycii Fructus,Chrysanthemi Flos,Astragali Radix and Angelicae Sinensis Radix.Twenty core active ingredients and ten core targets of the novel TCM prescription for treating DR were screened.Moreover,the novel TCM prescription played a crucial role for treating DR by inhibiting inflammatory response,oxidative stress,retinal pigment epithelium cell apoptosis and retinal neovascularization through various pathways,such as the AGE-RAGE signaling pathway in diabetic complications and the MAPK signaling pathway.Finally,molecular docking and MD simulation demonstrated that almost all core active ingredients exhibited satisfactory binding energies to core targets.Conclusions:This study identified a novel TCM prescription and unveiled its multi-component,multi-target and multi-pathway characteristics for treating DR.These findings provide a scientific basis and novel insights into the development of drugs for DR prevention and treatment.展开更多
Engineering of smart building molecules is key basis in designing intelligent drug delivery systems.As an emerging sophisticated delivery system strategy,the powerful functions of peptide drug conjugates(PDCs)are attr...Engineering of smart building molecules is key basis in designing intelligent drug delivery systems.As an emerging sophisticated delivery system strategy,the powerful functions of peptide drug conjugates(PDCs)are attributed to a smart linker and multifunctional peptide domain.Peptides exhibit a wide range of functions and properties,including easy chemical synthesis and versatile modification,tunable biocompatibility,diversified self-assembled nanostructures,specific recognition/binding,and deep penetration of the cell membrane/extracellular matrix.In addition,various types of linkers enable PDCs to release drugs responsively according to the disease microen-vironment or treatment needs.Owing to these inherent advantages,PDCs have been widely explored for drug delivery.Herein,the latest developments in functional peptides and linkers commonly used to construct smart PDCs are reviewed.The purpose is to bring widespread attention to PDC design strategies and their contribution to fighting various diseases,as well as to provide guidance for research on intelligent PDC drug delivery systems.展开更多
Gas therapy has been proven to be a promising and advantageous treatment option for cancers.Studies have shown that nitric oxide(NO)is one of the smallest structurally significant gas molecules with great potential to...Gas therapy has been proven to be a promising and advantageous treatment option for cancers.Studies have shown that nitric oxide(NO)is one of the smallest structurally significant gas molecules with great potential to suppress cancer.However,there is controversy and concern about its use as it exhibits the opposite physiological effects based on its levels in the tumor.Therefore,the anti-cancer mechanism of NO is the key to cancer treatment,and rationally designed NO delivery systems are crucial to the success of NO biomedical applications.This review summarizes the endogenous production of NO,its physiological mechanisms of action,the application of NO in cancer treatment,and nano-delivery systems for delivering NO donors.Moreover,it briefly reviews challenges in delivering NO from different nanoparticles and the issues associated with its combination treatment strategies.The advantages and challenges of various NO delivery platforms are recapitulated for possible transformation into clinical applications.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82104701)Science Fund Program for Outstanding Young Scholars in Universities of Anhui Province(Grant No.2022AH030064)+3 种基金Key Project at Central Government Level:the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(Grant No.2060302)Foundation of Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application(Grant No.2021KFKT10)China Agriculture Research System of MOF and MARA(Grant No.CARS-21)Talent Support Program of Anhui University of Chinese Medicine(Grant No.2020rcyb007).
文摘elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.This study aimed to screen a novel TCM prescription against DR from patents and elucidate its medication rule and molecular mechanism using data mining,network pharmacology,molecular docking and molecular dynamics(MD)simulation.Method:TCM prescriptions for treating DR was collected from patents and a novel TCM prescription was identified using data mining.Subsequently,the mechanism of the novel TCM prescription against DR was explored by constructing a network of core TCMs-core active ingredients-core targets-core pathways.Finally,molecular docking and MD simulation were employed to validate the findings from network pharmacology.Result:The TCMs of the collected prescriptions primarily possessed bitter and cold properties with heat-clearing and supplementing effects,attributed to the liver,lung and kidney channels.Notably,a novel TCM prescription for treating DR was identified,composed of Lycii Fructus,Chrysanthemi Flos,Astragali Radix and Angelicae Sinensis Radix.Twenty core active ingredients and ten core targets of the novel TCM prescription for treating DR were screened.Moreover,the novel TCM prescription played a crucial role for treating DR by inhibiting inflammatory response,oxidative stress,retinal pigment epithelium cell apoptosis and retinal neovascularization through various pathways,such as the AGE-RAGE signaling pathway in diabetic complications and the MAPK signaling pathway.Finally,molecular docking and MD simulation demonstrated that almost all core active ingredients exhibited satisfactory binding energies to core targets.Conclusions:This study identified a novel TCM prescription and unveiled its multi-component,multi-target and multi-pathway characteristics for treating DR.These findings provide a scientific basis and novel insights into the development of drugs for DR prevention and treatment.
基金supported by National Natural Science Foundation of China(No.82173992,81773662,81973488,81804100)National Key R&D program of China(2018YFC1706905)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX_201491).
文摘Engineering of smart building molecules is key basis in designing intelligent drug delivery systems.As an emerging sophisticated delivery system strategy,the powerful functions of peptide drug conjugates(PDCs)are attributed to a smart linker and multifunctional peptide domain.Peptides exhibit a wide range of functions and properties,including easy chemical synthesis and versatile modification,tunable biocompatibility,diversified self-assembled nanostructures,specific recognition/binding,and deep penetration of the cell membrane/extracellular matrix.In addition,various types of linkers enable PDCs to release drugs responsively according to the disease microen-vironment or treatment needs.Owing to these inherent advantages,PDCs have been widely explored for drug delivery.Herein,the latest developments in functional peptides and linkers commonly used to construct smart PDCs are reviewed.The purpose is to bring widespread attention to PDC design strategies and their contribution to fighting various diseases,as well as to provide guidance for research on intelligent PDC drug delivery systems.
基金supported by the Foundation of Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application(No.2021KFKT04,China)the National Natural Science Foundation of China(No.81973488,China)College Students Innovation Project for the R&D of Novel Drugs(No.J1310032,China)。
文摘Gas therapy has been proven to be a promising and advantageous treatment option for cancers.Studies have shown that nitric oxide(NO)is one of the smallest structurally significant gas molecules with great potential to suppress cancer.However,there is controversy and concern about its use as it exhibits the opposite physiological effects based on its levels in the tumor.Therefore,the anti-cancer mechanism of NO is the key to cancer treatment,and rationally designed NO delivery systems are crucial to the success of NO biomedical applications.This review summarizes the endogenous production of NO,its physiological mechanisms of action,the application of NO in cancer treatment,and nano-delivery systems for delivering NO donors.Moreover,it briefly reviews challenges in delivering NO from different nanoparticles and the issues associated with its combination treatment strategies.The advantages and challenges of various NO delivery platforms are recapitulated for possible transformation into clinical applications.