Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death,highlighting the urgent clinical need for effective therapies.Recently,tanshinoneⅡA has been iden...Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death,highlighting the urgent clinical need for effective therapies.Recently,tanshinoneⅡA has been identified as a promising therapeutic agent for myocardial infarction.However,efficient delivery remains a major issue that limits clinical translation.To address this problem,an injectable thermosensitive poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid-co-glycolic acid)gel(PLGA-PEG-PLGA)system encapsulating tanshinoneⅡA-loaded reactive oxygen species-sensitive microspheres(Gel-MS/tanshinoneⅡA)has been designed and synthesized in this study.The thermosensitive hydrogel exhibits good mechanical properties after reaching body temperature.Microspheres initially immobilized by the gel exhibit excellent reactive oxygen species-triggered release properties in a high-reactive oxygen species environment after myocardial infarction onset.As a result,encapsulated tanshinoneⅡA is effectively released into the infarcted myocardium,where it exerts local anti-pyroptotic and anti-inflammatory effects.Importantly,the combined advantages of this technique contribute to the mitigation of left ventricular remodeling and the restoration of cardiac function following tanshinoneⅡA.Therefore,this novel,precision-guided intra-tissue therapeutic system allows for customized local release of tanshinoneⅡA,presenting a promising alternative treatment strategy aimed at inducing beneficial ventricular remodeling in the post-infarct heart.展开更多
BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has sho...BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.展开更多
Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis (PF). It is considered as a promising therapeutic targe...Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis (PF). It is considered as a promising therapeutic target anti-PF. The well-documented against PF properties of Tanshinone IIA (Tan IIA) have been primarily attributed to its antioxidant and anti-inflammatory potency. Emerging evidence suggests that Tan IIA may target energy metabolism pathways, including glycolysis and tricarboxylic acid (TCA) cycle. However, the detailed and advanced mechanisms underlying the anti-PF activities remain obscure. In this study, we applied [U-13C]-glucose metabolic flux analysis (MFA) to examine metabolism flux disruption and modulation nodes of Tan IIA in PF. We identified that Tan IIA inhibited the glycolysis and TCA flux, thereby suppressing the production of transforming growth factor-β1 (TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro. We further revealed that Tan IIA inhibited the expression of key metabolic enzyme hexokinase 2 (HK2) by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1α (HIF-1α) pathway activities, which decreased the accumulation of abnormal metabolites. Notably, we demonstrated that Tan IIA inhibited ATP citrate lyase (ACLY) activity, which reduced the collagen synthesis pathway caused by cytosol citrate consumption. Further, these results were validated in a mouse model of bleomycin-induced PF. This study was novel in exploring the mechanism of the occurrence and development of Tan IIA in treating PF using 13C-MFA technology. It provided a novel understanding of the mechanism of Tan IIA against PF from the perspective of metabolic reprogramming.展开更多
[Objective]The aim was to extract tanshinone from Salvia miltiorrhiza Bge. dregs and to determine tanshinone components. [Method]Organic solvent method was adopted to extract tanshinone from S. miltiorrhiza dregs and ...[Objective]The aim was to extract tanshinone from Salvia miltiorrhiza Bge. dregs and to determine tanshinone components. [Method]Organic solvent method was adopted to extract tanshinone from S. miltiorrhiza dregs and TLC was used to determine the optimum extraction solvent. The components of tanshinone were measured with HPLC. [Result]Ether was the best solvent to extract tanshinone from S. miltiorrhiza dregs. After water immersion,dry dregs of S. miltiorrhiza and Panax notoginseng were extracted with ethanol to obtain fat-soluble extracts. Then with ether as the solvent for Soxhlet extraction,the yield of crude tanshinone was 2.17%. The HPLC detection showed that the contents of tanshinone Ⅱ A,methylene tanshinquinone,cryptotanshinone,tanshinone Ⅰ were 3.62%,1.02%,2.56%,2.75% respectively. [Conclusion]The components of tanshinone in S. miltiorrhiza dregs were basically the same as tanshinone in medicine S. miltiorrhiza. S. miltiorrhiza dregs could be used as a kind of tanshinone resource,which has the value of development and utilization.展开更多
基金supported by the National Natural Science Foundation of China(82104962,82104647,82274271)Scientific Research Project of Guangdong Provincial Administration of Traditional Chinese Medicine(20211070)+2 种基金Science and Technology Planning Project of Guangzhou(202102010301)Young Talents Support Project from China Association of Chinese Medicine(2019-QNRC2-C06)Team of Prevention and Treatment of Acute Myocardial Infarction with Chinese Medicine(2019KCXTD009)
文摘Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death,highlighting the urgent clinical need for effective therapies.Recently,tanshinoneⅡA has been identified as a promising therapeutic agent for myocardial infarction.However,efficient delivery remains a major issue that limits clinical translation.To address this problem,an injectable thermosensitive poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid-co-glycolic acid)gel(PLGA-PEG-PLGA)system encapsulating tanshinoneⅡA-loaded reactive oxygen species-sensitive microspheres(Gel-MS/tanshinoneⅡA)has been designed and synthesized in this study.The thermosensitive hydrogel exhibits good mechanical properties after reaching body temperature.Microspheres initially immobilized by the gel exhibit excellent reactive oxygen species-triggered release properties in a high-reactive oxygen species environment after myocardial infarction onset.As a result,encapsulated tanshinoneⅡA is effectively released into the infarcted myocardium,where it exerts local anti-pyroptotic and anti-inflammatory effects.Importantly,the combined advantages of this technique contribute to the mitigation of left ventricular remodeling and the restoration of cardiac function following tanshinoneⅡA.Therefore,this novel,precision-guided intra-tissue therapeutic system allows for customized local release of tanshinoneⅡA,presenting a promising alternative treatment strategy aimed at inducing beneficial ventricular remodeling in the post-infarct heart.
基金Supported by 2020 Guangxi Zhuang Autonomous Region Health Care Commission Self-Financing Research Projects,No.Z202000962023 Guangxi University Young and Middle-Aged Teachers’Basic Research Ability Improvement Project,No.2023KY0091+1 种基金National Natural Science Foundation of China,No.82260241the Natural Science Foundation of Guangxi Province,No.2015GXNSFAA139171 and No.2020GXNSFAA259053.
文摘BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.
基金supported by the National Natural Science Foundation of China(Grant No.:82174100).
文摘Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis (PF). It is considered as a promising therapeutic target anti-PF. The well-documented against PF properties of Tanshinone IIA (Tan IIA) have been primarily attributed to its antioxidant and anti-inflammatory potency. Emerging evidence suggests that Tan IIA may target energy metabolism pathways, including glycolysis and tricarboxylic acid (TCA) cycle. However, the detailed and advanced mechanisms underlying the anti-PF activities remain obscure. In this study, we applied [U-13C]-glucose metabolic flux analysis (MFA) to examine metabolism flux disruption and modulation nodes of Tan IIA in PF. We identified that Tan IIA inhibited the glycolysis and TCA flux, thereby suppressing the production of transforming growth factor-β1 (TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro. We further revealed that Tan IIA inhibited the expression of key metabolic enzyme hexokinase 2 (HK2) by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1α (HIF-1α) pathway activities, which decreased the accumulation of abnormal metabolites. Notably, we demonstrated that Tan IIA inhibited ATP citrate lyase (ACLY) activity, which reduced the collagen synthesis pathway caused by cytosol citrate consumption. Further, these results were validated in a mouse model of bleomycin-induced PF. This study was novel in exploring the mechanism of the occurrence and development of Tan IIA in treating PF using 13C-MFA technology. It provided a novel understanding of the mechanism of Tan IIA against PF from the perspective of metabolic reprogramming.
基金Supported by National Natural Science Foundation of China(30470055)Innovation Team Project of Liaoning Education Department (2007T006)~~
文摘[Objective]The aim was to extract tanshinone from Salvia miltiorrhiza Bge. dregs and to determine tanshinone components. [Method]Organic solvent method was adopted to extract tanshinone from S. miltiorrhiza dregs and TLC was used to determine the optimum extraction solvent. The components of tanshinone were measured with HPLC. [Result]Ether was the best solvent to extract tanshinone from S. miltiorrhiza dregs. After water immersion,dry dregs of S. miltiorrhiza and Panax notoginseng were extracted with ethanol to obtain fat-soluble extracts. Then with ether as the solvent for Soxhlet extraction,the yield of crude tanshinone was 2.17%. The HPLC detection showed that the contents of tanshinone Ⅱ A,methylene tanshinquinone,cryptotanshinone,tanshinone Ⅰ were 3.62%,1.02%,2.56%,2.75% respectively. [Conclusion]The components of tanshinone in S. miltiorrhiza dregs were basically the same as tanshinone in medicine S. miltiorrhiza. S. miltiorrhiza dregs could be used as a kind of tanshinone resource,which has the value of development and utilization.
文摘工程结构在制造工艺过程中或使用期间会产生裂纹,对结构断裂路径的预测和研究是防治工程安全问题发生的重要手段。在考虑裂纹尖端应力场常数项T应力的基础上对传统的最大周向应力准则(Maximum tangential stress criterion,MTS)和最小应变能密度因子准则(Minimum strain energy density criterion,SED)进行修正,采用Python语言对ABAQUS的前、后处理和有限元计算模块进行二次开发,通过计算最优解的粒子群算法(Particle swarm optimization,PSO)将修正后的准则编入裂纹自动扩展程序脚本中。利用上述二次开发程序对初始纯Ⅰ型裂纹的扩展路径进行模拟,结果表明:采用ABAQUS脚本程序模拟结果与相关文献实验结果吻合,表明了程序的有效性,进而实现考虑T应力的多种断裂准则对裂纹扩展路径的预测;当T应力值处于一定范围内时,修正的MTS准则无法预测裂纹发生的偏转现象,扩展路径呈直线,此时可采用修正的SED准则进行预测。
