Objective:To investigate the potential targets and mechanisms of Draconis Sanguis(DS),a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl(D.Sanguis,Xue Jie),in the trea...Objective:To investigate the potential targets and mechanisms of Draconis Sanguis(DS),a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl(D.Sanguis,Xue Jie),in the treatment of myocardial infarction(MI).Methods:We explored the potential mechanisms of DS in the treatment of MI using network pharmacology,bioinformatic techniques,and transcriptomic analysis,followed by validation through in vivo and in vitro experiments.Results:Network pharmacology and bioinformatic analyses identified five genes(Fpr1,Glul,Mme,Mmp9,and Pla2g7)as potential targets for MI treatment.Moreover,DS significantly ameliorated cardiac function,inflammatory responses,and MI-induced myocardial fibrosis in vivo.Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI.Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene.Furthermore,DS reduced the expression of Pla2g7(P=.0009),NLRP3(P=.003),interleukin-18(P<.001),and interleukin-1b(P=.004)mRNAs in vivo.Conclusions:The results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response.This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.展开更多
Myocardial fibrosis(MF)is a common pathological hallmark of cardiovascular diseases,reflecting shared mechanisms in their progression.However,the lack of reliable MF models that accurately mimic its pathogenesis has h...Myocardial fibrosis(MF)is a common pathological hallmark of cardiovascular diseases,reflecting shared mechanisms in their progression.However,the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery,highlighting the urgent need for more effective therapeutic agents.Herein,a novel contractile three-dimensional(3D)myocardial tissue model integrating cardiomyocytes,cardiac-fibroblasts,and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease,and facilitate the screening of anti-MF compounds.The 3D myocardial tissue model exhibited precise,visualizable,and quantifiable contractile characteristics under hypoxia and drug interventions.76 compounds extracted from the resins of Toxicodendron vernicifluum,a traditional Chinese medicine with clear clinical benefits for fibrotic diseases,were screened for anti-fibrotic activity.Using an in vitro 3D oxygeneglucose deprivation(OGD)-treated myocardial tissue model instead of a twodimensional transforming growth factor-b treated cardiac-fibroblasts model,two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity,which was further validated in left anterior descending coronary artery ligation-induced MF mouse model.The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF,further stressing the great potential of regulating macrophages in the treatment of MF.展开更多
Background:The aim of the study was to investigate the changes in the periarterial capillary-free zone(paCFZ)after anti-vascular endothelial growth factor(VEGF)therapy in patients with branch retinal vein occlusion(BR...Background:The aim of the study was to investigate the changes in the periarterial capillary-free zone(paCFZ)after anti-vascular endothelial growth factor(VEGF)therapy in patients with branch retinal vein occlusion(BRVO)by widefield swept-source optical coherence tomography angiography(SS-OCTA)and assess their associations with clinical outcomes.Methods:In this retrospective observational study of 54 treatment-naive BRVO patients with macular edema,we reviewed the findings of 12×12 mm^(2)SS-OCTA at baseline,3,6,and 12 months after intravitreal ranibizumab injections.The paCFZ and major retinal artery areas were measured on SS-OCTA images.The paCFZ area to artery area(P/A)ratio was calculated.Results:The paCFZ areas and P/A ratios of first-and second-order arteries were significantly greater in BRVO eyes than in contralateral eyes(all P<0.01),but there were no differences in the first-and second-order artery areas(P=0.20 and 0.25,respectively).The paCFZ areas and P/A ratios decreased significantly at 3,6,and 12 months after anti-VEGF therapy(all P<0.01).The baseline P/A ratio was significantly correlated with the baseline best-corrected visual acuity(BCVA),central retinal thickness,and their improvements at 3,6,and 12 months(all P<0.05).Baseline BCVA and P/A ratios of first-and second-order arteries were independently associated with the final BCVA in multivariate linear regression.Conclusions:Wide-field SS-OCTA shows that anti-VEGF therapy can lead to a significant improvement in the paCFZ parameters in BRVO.Smaller baseline P/A ratios on SS-OCTA tend to predict better visual outcomes at 12 months after anti-VEGF therapy.展开更多
基金the National Natural Science Foundation of China(82222075).
文摘Objective:To investigate the potential targets and mechanisms of Draconis Sanguis(DS),a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl(D.Sanguis,Xue Jie),in the treatment of myocardial infarction(MI).Methods:We explored the potential mechanisms of DS in the treatment of MI using network pharmacology,bioinformatic techniques,and transcriptomic analysis,followed by validation through in vivo and in vitro experiments.Results:Network pharmacology and bioinformatic analyses identified five genes(Fpr1,Glul,Mme,Mmp9,and Pla2g7)as potential targets for MI treatment.Moreover,DS significantly ameliorated cardiac function,inflammatory responses,and MI-induced myocardial fibrosis in vivo.Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI.Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene.Furthermore,DS reduced the expression of Pla2g7(P=.0009),NLRP3(P=.003),interleukin-18(P<.001),and interleukin-1b(P=.004)mRNAs in vivo.Conclusions:The results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response.This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.
基金supported by grants from the National Natural Science Foundation of China(Nos.82222075,82374420,and 82174215)Key Research and Development Project of Shandong province(2021CXGC010507,China).
文摘Myocardial fibrosis(MF)is a common pathological hallmark of cardiovascular diseases,reflecting shared mechanisms in their progression.However,the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery,highlighting the urgent need for more effective therapeutic agents.Herein,a novel contractile three-dimensional(3D)myocardial tissue model integrating cardiomyocytes,cardiac-fibroblasts,and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease,and facilitate the screening of anti-MF compounds.The 3D myocardial tissue model exhibited precise,visualizable,and quantifiable contractile characteristics under hypoxia and drug interventions.76 compounds extracted from the resins of Toxicodendron vernicifluum,a traditional Chinese medicine with clear clinical benefits for fibrotic diseases,were screened for anti-fibrotic activity.Using an in vitro 3D oxygeneglucose deprivation(OGD)-treated myocardial tissue model instead of a twodimensional transforming growth factor-b treated cardiac-fibroblasts model,two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity,which was further validated in left anterior descending coronary artery ligation-induced MF mouse model.The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF,further stressing the great potential of regulating macrophages in the treatment of MF.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82101150,82171078)Shanghai clinical 3-year action plan-major clinical research(Grant Nos.SHDC2020CR2041B,SHDC2020CR5014-003)+1 种基金Shanghai Sailing Program(Grant No.21YF1405300)Shanghai Committee of Science and Technology(Grant Nos.20Y11911100,18411965100).
文摘Background:The aim of the study was to investigate the changes in the periarterial capillary-free zone(paCFZ)after anti-vascular endothelial growth factor(VEGF)therapy in patients with branch retinal vein occlusion(BRVO)by widefield swept-source optical coherence tomography angiography(SS-OCTA)and assess their associations with clinical outcomes.Methods:In this retrospective observational study of 54 treatment-naive BRVO patients with macular edema,we reviewed the findings of 12×12 mm^(2)SS-OCTA at baseline,3,6,and 12 months after intravitreal ranibizumab injections.The paCFZ and major retinal artery areas were measured on SS-OCTA images.The paCFZ area to artery area(P/A)ratio was calculated.Results:The paCFZ areas and P/A ratios of first-and second-order arteries were significantly greater in BRVO eyes than in contralateral eyes(all P<0.01),but there were no differences in the first-and second-order artery areas(P=0.20 and 0.25,respectively).The paCFZ areas and P/A ratios decreased significantly at 3,6,and 12 months after anti-VEGF therapy(all P<0.01).The baseline P/A ratio was significantly correlated with the baseline best-corrected visual acuity(BCVA),central retinal thickness,and their improvements at 3,6,and 12 months(all P<0.05).Baseline BCVA and P/A ratios of first-and second-order arteries were independently associated with the final BCVA in multivariate linear regression.Conclusions:Wide-field SS-OCTA shows that anti-VEGF therapy can lead to a significant improvement in the paCFZ parameters in BRVO.Smaller baseline P/A ratios on SS-OCTA tend to predict better visual outcomes at 12 months after anti-VEGF therapy.
