Objective The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation.Autophagy is a catabolic process responsible for maintaining cellular homeos...Objective The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation.Autophagy is a catabolic process responsible for maintaining cellular homeostasis.In recent years,autophagy has been demonstrated to play an important role in neuroinflammation.Resolvin D1(RvD1)is a promising therapeutic mediator that has been shown to exert substantial anti-inflammatory and proresolving activities.However,whether RvD1-mediated resolution of inflammation in microglia is related to autophagy regulation needs further investigation.The present study aimed to explore the effect of RvD1 on microglial autophagy and its corresponding pathways.Methods Mouse microglial cells(BV-2)were cultured,treated with RvD1,and examined by Western blotting,confocal immunofluorescence microscopy,transmission electron microscopy,and flow cytometry.Results RvD1 promoted autophagy in both BV-2 cells and mouse primary microglia by favoring the maturation of autophagosomes and their fusion with lysosomes.Importantly,RvD1 had no significant effect on the activation of mammalian target of rapamycin(mTOR)signaling.Furthermore,RvD1-induced mTOR-independent autophagy was confirmed by observing reduced cytoplasmic calcium levels and suppressed calcium/calmodulin-dependent protein kinase II(CaMK II)activation.Moreover,by downregulating ATG5,the increased phagocytic activity induced by RvD1 was demonstrated to be tightly controlled by ATG5-dependent autophagy.Conclusion The present work identified a previously unreported mechanism responsible for the role of RvD1 in microglial autophagy,highlighting its therapeutic potential against neuroinflammation.展开更多
A novel and sensitive HPLC-UV method has been developed for the simultaneous determination of twelve major compounds in Longdan Xiegan Pill.The chemical profile of the twelve compounds,including geniposidic acid(1),...A novel and sensitive HPLC-UV method has been developed for the simultaneous determination of twelve major compounds in Longdan Xiegan Pill.The chemical profile of the twelve compounds,including geniposidic acid(1),geniposide(2),gentiopicroside(3),liquiritin(4),crocin(5),baicalin(6),wogonoside(7),baicalein(8),glycyrrhizic acid(9),wogonin(10),oroxylin A(11)and aristolochic acid A(12),was acquired using high-performance liquid chromatography-diode array detector coupled with an electrospray tandem mass spectrometer(HPLC-DAD-ESI-MS).The analysis was performed on a Dikma Platisil ODS C18 column(250 mm×4.6 mm,5 μm)with a gradient solvent system of acetonitrile-0.1% aqueous formic acid.The validation was carried out and the linearities(r〉0.9996),repeatability(RSD〈1.8%),intra-and inter-day precision(RSD〈1.3%),and recoveries(ranging from 96.6% to 103.4%)were acceptable.The limits of detection(LOD)of these compounds ranged from 0.29 to 4.17 ng.Aristolochic acid A,which is the toxic ingredient,was not detected in all the batches of Longdan Xiegan Pill.Furthermore,hierarchical cluster analysis was used to evaluate the variation of the herbal prescription.The proposed method is simple,effective and suitable for the quality control of this traditional Chinese medicine(TCM).展开更多
The mechanism of deuteron formation in neutron-induced reactions is studied within the framework of the isospin-dependent quantum molecular dynamics model,using the GEMINI code.The influence of the n+p→d reaction cha...The mechanism of deuteron formation in neutron-induced reactions is studied within the framework of the isospin-dependent quantum molecular dynamics model,using the GEMINI code.The influence of the n+p→d reaction channel is investigated by analyzing the deuteron production cross sections in the neutron-induced reactions12C(n,d),16O(n,d),and 28Si(n,d),with incident energies of 20-100 MeV.By including the n+p→d reaction channel when modeling the collision,the deuteron production cross sections increase,optimizing the cross-section results and bringing them closer to the experimental data values.This indicates that the n+p→d reaction channel is an important mechanism for enhancing deuteron production.展开更多
基金the National Natural Science Foundation of China(No.81902016).
文摘Objective The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation.Autophagy is a catabolic process responsible for maintaining cellular homeostasis.In recent years,autophagy has been demonstrated to play an important role in neuroinflammation.Resolvin D1(RvD1)is a promising therapeutic mediator that has been shown to exert substantial anti-inflammatory and proresolving activities.However,whether RvD1-mediated resolution of inflammation in microglia is related to autophagy regulation needs further investigation.The present study aimed to explore the effect of RvD1 on microglial autophagy and its corresponding pathways.Methods Mouse microglial cells(BV-2)were cultured,treated with RvD1,and examined by Western blotting,confocal immunofluorescence microscopy,transmission electron microscopy,and flow cytometry.Results RvD1 promoted autophagy in both BV-2 cells and mouse primary microglia by favoring the maturation of autophagosomes and their fusion with lysosomes.Importantly,RvD1 had no significant effect on the activation of mammalian target of rapamycin(mTOR)signaling.Furthermore,RvD1-induced mTOR-independent autophagy was confirmed by observing reduced cytoplasmic calcium levels and suppressed calcium/calmodulin-dependent protein kinase II(CaMK II)activation.Moreover,by downregulating ATG5,the increased phagocytic activity induced by RvD1 was demonstrated to be tightly controlled by ATG5-dependent autophagy.Conclusion The present work identified a previously unreported mechanism responsible for the role of RvD1 in microglial autophagy,highlighting its therapeutic potential against neuroinflammation.
基金supported by program NCET Foundation,NSFC(30725045)the Special Program for New Drug Innovation of the Ministry of Science and Technology,China(2009ZX09311-001,2008ZX09101-Z-029)+1 种基金Shanghai Leading Academic Discipline Project(B906)by the Scientific Foundation of Shanghai,China(07DZ19728,09DZ1975700,09DZ1971500)
文摘A novel and sensitive HPLC-UV method has been developed for the simultaneous determination of twelve major compounds in Longdan Xiegan Pill.The chemical profile of the twelve compounds,including geniposidic acid(1),geniposide(2),gentiopicroside(3),liquiritin(4),crocin(5),baicalin(6),wogonoside(7),baicalein(8),glycyrrhizic acid(9),wogonin(10),oroxylin A(11)and aristolochic acid A(12),was acquired using high-performance liquid chromatography-diode array detector coupled with an electrospray tandem mass spectrometer(HPLC-DAD-ESI-MS).The analysis was performed on a Dikma Platisil ODS C18 column(250 mm×4.6 mm,5 μm)with a gradient solvent system of acetonitrile-0.1% aqueous formic acid.The validation was carried out and the linearities(r〉0.9996),repeatability(RSD〈1.8%),intra-and inter-day precision(RSD〈1.3%),and recoveries(ranging from 96.6% to 103.4%)were acceptable.The limits of detection(LOD)of these compounds ranged from 0.29 to 4.17 ng.Aristolochic acid A,which is the toxic ingredient,was not detected in all the batches of Longdan Xiegan Pill.Furthermore,hierarchical cluster analysis was used to evaluate the variation of the herbal prescription.The proposed method is simple,effective and suitable for the quality control of this traditional Chinese medicine(TCM).
基金the National Natural Science Foundation of China(Nos.11875328 and U1832182)the Natural Science Foundation of Guangdong Province+1 种基金China(No.18zxxt65)Fundamental Research Funds for the Central Universities(19lgpy306and 18lgpy87)。
文摘The mechanism of deuteron formation in neutron-induced reactions is studied within the framework of the isospin-dependent quantum molecular dynamics model,using the GEMINI code.The influence of the n+p→d reaction channel is investigated by analyzing the deuteron production cross sections in the neutron-induced reactions12C(n,d),16O(n,d),and 28Si(n,d),with incident energies of 20-100 MeV.By including the n+p→d reaction channel when modeling the collision,the deuteron production cross sections increase,optimizing the cross-section results and bringing them closer to the experimental data values.This indicates that the n+p→d reaction channel is an important mechanism for enhancing deuteron production.