Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance,preventing autoimmune responses,and minimizing tissue damage by regulating the duration and intensi...Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance,preventing autoimmune responses,and minimizing tissue damage by regulating the duration and intensity of the immune response.Furthermore,immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response.Based on substantial physiological analyses as well as preclinical and clinical studies,checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers.In the last few years,extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines(TCMs).The main advantage of TCMs and natural medicine is that they usually contain multiple active components,which can act on multiple targets at the same time,resulting in additive or synergistic effects.The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest.For example,Astragalus membranaceus polysaccharides can induce anti-PD-1 antibody responses in animals,and these antibodies can overcome the exhaustion of immune cells under tumor immune evasion.Furthermore,many other TCM molecules could also be novel and effective drug candidates for the treatment of cancers.Therefore,it is essential to assess the application of immune checkpoints in the development of new drugs and TCMs.In this review,we focus on research progress in the field of immune checkpoints based on three topics:(1)immune checkpoint targets and pathways,(2)development of novel immune checkpoint-based drugs,and(3)application of immune checkpoints in the development of TCMs.展开更多
Objective:Taxifolin is a natural flavonoid compound that can be isolated from onions,grapes,oranges and grapefruit.It also acts as a medicine food homology with extraordinary antioxidant and antiinflammatory activity....Objective:Taxifolin is a natural flavonoid compound that can be isolated from onions,grapes,oranges and grapefruit.It also acts as a medicine food homology with extraordinary antioxidant and antiinflammatory activity.This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction.Methods:Levels of interleukin(IL)-6,IL-1βand intracellular reactive oxygen species(ROS)were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide(LPS).Subsequently,the m RNA and protein levels of inducible nitric oxide synthase(i NOS),vascular endothelial growth factor(VEGF),cyclooxygenase(COX)-2,tumor necrosis factor(TNF)-a and the phosphorylation expression levels of the MAPK signal pathway were also evaluated.A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway.And then MAPK inhibitors were used to reveal the expression level of i NOS,VEGF,COX-2 and TNF-a in RAW264.7 cells.Results:It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin.Then,the m RNA and protein levels of i NOS,VEGF,COX-2 and TNF-a were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well.In silico analysis,taxifolin could form a relatively stable combination with MAPK signal pathway.MAPK inhibitors showed increasing or decreasing effect in the m RNA levels of i NOS,VEGF,COX-2 and TNF-a,which suggesting that taxifolin down-regulated i NOS,VEGF,COX-2 and TNF-a expressions were not entirely through the MAPK pathway.Conclusion:This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.展开更多
基金partly supported by National Natural Science Foundation of China for Key Projects(No.81430096,China)National New Drug Innovation(No.2017ZX09301062,China)Tianjin Science and Technology Plan Project(No.19YFSLQY00110,China)。
文摘Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance,preventing autoimmune responses,and minimizing tissue damage by regulating the duration and intensity of the immune response.Furthermore,immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response.Based on substantial physiological analyses as well as preclinical and clinical studies,checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers.In the last few years,extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines(TCMs).The main advantage of TCMs and natural medicine is that they usually contain multiple active components,which can act on multiple targets at the same time,resulting in additive or synergistic effects.The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest.For example,Astragalus membranaceus polysaccharides can induce anti-PD-1 antibody responses in animals,and these antibodies can overcome the exhaustion of immune cells under tumor immune evasion.Furthermore,many other TCM molecules could also be novel and effective drug candidates for the treatment of cancers.Therefore,it is essential to assess the application of immune checkpoints in the development of new drugs and TCMs.In this review,we focus on research progress in the field of immune checkpoints based on three topics:(1)immune checkpoint targets and pathways,(2)development of novel immune checkpoint-based drugs,and(3)application of immune checkpoints in the development of TCMs.
基金supported by Open and Selective Project of National Major New Drug Development Science and Technology Major Project in Tianjin,China(No.2017ZX09031062)National Major New Drug Innovation Project of China(No.2017ZX09101001)+4 种基金National Key Research and Development Project in Tianjin,China(No.2019YFA09005600)Open Research fund of State Key Laboratory of Drug Delivery Technology and Pharmacokinetics in TianjinChina(No.010161003)CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-020)Tianjin Key Training Project for‘Project+Team’(No.XC202030)。
文摘Objective:Taxifolin is a natural flavonoid compound that can be isolated from onions,grapes,oranges and grapefruit.It also acts as a medicine food homology with extraordinary antioxidant and antiinflammatory activity.This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction.Methods:Levels of interleukin(IL)-6,IL-1βand intracellular reactive oxygen species(ROS)were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide(LPS).Subsequently,the m RNA and protein levels of inducible nitric oxide synthase(i NOS),vascular endothelial growth factor(VEGF),cyclooxygenase(COX)-2,tumor necrosis factor(TNF)-a and the phosphorylation expression levels of the MAPK signal pathway were also evaluated.A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway.And then MAPK inhibitors were used to reveal the expression level of i NOS,VEGF,COX-2 and TNF-a in RAW264.7 cells.Results:It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin.Then,the m RNA and protein levels of i NOS,VEGF,COX-2 and TNF-a were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well.In silico analysis,taxifolin could form a relatively stable combination with MAPK signal pathway.MAPK inhibitors showed increasing or decreasing effect in the m RNA levels of i NOS,VEGF,COX-2 and TNF-a,which suggesting that taxifolin down-regulated i NOS,VEGF,COX-2 and TNF-a expressions were not entirely through the MAPK pathway.Conclusion:This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.
