Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the pre...Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of drugs.Ginkgolide B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke recovery.However,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a challenge.Herein,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes stably.The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)rats.Compared to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion.Low levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and angiogenesis.In addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway.Thus,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.展开更多
GdCl_3 reacts with CH_3C_6H_4Li at a molar ratio of 2:1 in tetra- hydyofuran(THF)to yield an interesting compound [Li·4THF][GdCl_4·2THF]; its X-ray crystal structure shows the molecule to be an ion-pair.
Tb3＋-doped Ca2BO3C1 compounds with different charge compensation approaches are synthesized by a hightemperature solid-state reaction method, and the luminescent properties and Commission Internationale de l＇Eclaira...Tb3＋-doped Ca2BO3C1 compounds with different charge compensation approaches are synthesized by a hightemperature solid-state reaction method, and the luminescent properties and Commission Internationale de l＇Eclairage （CIE） chromaticity coordinates are systematically characterized. Ca2BO3Cl：Tb3＋ can produce green emission under 376 nm radiation excitation. With codoped A＋ （A = Li, Na, K） as charge compensators, the relative emission intensities of Ca2BO3Cl：Tb3＋ are enhanced by about 1.61, 1.97, and 1.81 times compared with those of the direct charge balance, which is considered to be due to the effect of the difference in ion radius on the crystal field. The CIE chromaticity coordinates of Ca2BO3CI：Tb3＋, A＋ （A = Li, Na, K） are （0.335, 0.584）, （0.335, 0.585）, and （0.335, 0.585）, corresponding to the hues of green. Therefore, A＋ （A = Li, Na, K） may be the optimal charge compensator for Ca2BO3Cl：Tb3＋.展开更多
基金This research was funded by the National Natural Science Foundation of China(No.81773911,81690263 and 81573616)the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20180101).
文摘Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of drugs.Ginkgolide B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke recovery.However,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a challenge.Herein,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes stably.The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)rats.Compared to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion.Low levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and angiogenesis.In addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway.Thus,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.
文摘GdCl_3 reacts with CH_3C_6H_4Li at a molar ratio of 2:1 in tetra- hydyofuran(THF)to yield an interesting compound [Li·4THF][GdCl_4·2THF]; its X-ray crystal structure shows the molecule to be an ion-pair.
基金supported by the National Basic Research Program of China(Grant No.2010CB327704)the National Natural Science Foundation of China(Grant No.51272022)+3 种基金the New Century Excellent Talents in University,China(Grant No.NCET-10-0220)the Research Fund for the Doctoral Program of Higher Education,China(Grant No.20120009130005)the Excellent Doctor's Science and Technology Innovation Foundation of Beijing Jiaotong University,China(Grant No.2011YJS073)the Fundamental Research Funds for the Central Universities(Grant No.2012JBZ001)
文摘Tb3＋-doped Ca2BO3C1 compounds with different charge compensation approaches are synthesized by a hightemperature solid-state reaction method, and the luminescent properties and Commission Internationale de l＇Eclairage （CIE） chromaticity coordinates are systematically characterized. Ca2BO3Cl：Tb3＋ can produce green emission under 376 nm radiation excitation. With codoped A＋ （A = Li, Na, K） as charge compensators, the relative emission intensities of Ca2BO3Cl：Tb3＋ are enhanced by about 1.61, 1.97, and 1.81 times compared with those of the direct charge balance, which is considered to be due to the effect of the difference in ion radius on the crystal field. The CIE chromaticity coordinates of Ca2BO3CI：Tb3＋, A＋ （A = Li, Na, K） are （0.335, 0.584）, （0.335, 0.585）, and （0.335, 0.585）, corresponding to the hues of green. Therefore, A＋ （A = Li, Na, K） may be the optimal charge compensator for Ca2BO3Cl：Tb3＋.
