OBJECTIVE To explore mecha⁃nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net⁃work pharmacology combined with in vitro experi⁃ment.METHODS Drug targets were predicted using ...OBJECTIVE To explore mecha⁃nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net⁃work pharmacology combined with in vitro experi⁃ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data⁃bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100μmol·L^(-1))on P-gp activity were monitored in hCMEC/D3 in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans⁃mission regulation,neurotransmitter receptor activity,protein kinase regulation activity,G proteincoupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig⁃naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi⁃cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu⁃lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro⁃tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer⁃ence basis for further exploration of the mecha⁃nisms of imperatorin on regulating P-gp in BBB.展开更多
OBJECTIVE To evaluate the effects of Tong-Qiao-Huo-Xue decoction(TQHXD)on the bloodbrain barrier(BBB)permeability and the expressions of related proteins on the rats;and to analyse the constituents in the cerebrospina...OBJECTIVE To evaluate the effects of Tong-Qiao-Huo-Xue decoction(TQHXD)on the bloodbrain barrier(BBB)permeability and the expressions of related proteins on the rats;and to analyse the constituents in the cerebrospinal fluid on the rats with cerebral ischemic injury.METHODS Cerebral ischemia rats were induced by middle cerebral artery occlusion(MCAO).Adult male sprague-dawley(SD)rats were randomly divided into seven groups:sham-group;model group;nimodipine(NMP)-treated group and nao mai tai(NMT)-treated group were set as positive drug control groups;TQHXD-treated group(3,6 and 12g·kg-1body weight);The neurological function of rats was estimated by neurological defect scoring after the 1,7and 15 dafter administration.Histological structure of the brain in rats were observed by hematoxylin and eosin(H&E)staining.Ultramicrostructural features of hippocampus neurons and the opening of tight junction(TJ)of BBB in rats were observed by transmission electron microscope(TEM).Western blotting was performed to detect the expression of ZO-1,occludin,claudin-5,AQP-4 and MMP-9 in BBB after cerebral ischemia injury.Component analysis experiments:adult male SD rats were randomly divided into four groups:Distilled water was administered intragastrically sham-operated rats;Distilled water was administered intragastrically model rats by MCAO;TQHXD was administered intragatrically to rats in sham-operated group;TQHXD was administered intragestrically to rats in model group by MCAO.GC and HPLC was used to detect three compounds,namely,muscone,ligustilide and hydroxysafflor yellow A,in rats cerebrospinal fluid(CSF)after oral administration of TQHXD.Finally,samples of cerebrospinal fluid of rats in each group were compared with single medicine so as to explicit the three compounds come from which herb.RESULTS TQHXD significantly reduced the neurological defect scores.Histological examination indicated that dense neuropil and largely surviving neurons had been seen in TQHXD-treated rats.TEM observation revealed that TQHXD could significantly inhibit the damage of hippocampal neurons and reduce the opening of TJ.The decreased protein expression levels of claudin-5,occludin,ZO-1 and the increased protein expression levels of AQP-4 and MMP-9in cerebral ischemia tissue were significantly prevented by treatment of TQHXD.Analysis of experimental results showed that muscone,ligustilide and hydroxysafflor yellow A could penetrate the BBB into the CSF,and the content of the model group was lower than that of sham group after intragastric administration of TQHXD.CONCLUSION These results demonstrated that TQHXD may act as a potential neuroprotective agent against BBB damage for cerebral ischemia through protecting of hippocampus neurons,reducing the opening of TJ and decreasing the permeability of BBB by up-regulating ZO-1,occludin,claudin-5 expressions,down-regulating AQP-4 and MMP-9 expressions.The effect of TQHXD on the decrease of the opening of TJ also reduced the content of muscone,ligustilide and hydroxysafflor yellow A in cerebrospinal fluid.展开更多
OBJECTIVE Tissue plasminogen activator(tPA) is the only approved pharmaco.logical therapy for acute brain ischaemia;however,a major limitation of tPA is the haemorrhagic trans.formation that follows tPA treatment.Here...OBJECTIVE Tissue plasminogen activator(tPA) is the only approved pharmaco.logical therapy for acute brain ischaemia;however,a major limitation of tPA is the haemorrhagic trans.formation that follows tPA treatment.Here,we determined whether nicotinamide mononucleotide(NMN),a key intermediate of nicotinamide adenine dinucleotide biosynthesis,affects tPA-induced haemorrhagic transformation.METHODS Middle cerebral artery occlusion(MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h.When the filament was removed for reperfusion,tPA was infused via the tail vein.A single dose of NMN was injected i.p.(300 mg·kg^(-1)).Mice were killed at 24 h post ischaemia,and their brains were evaluated for brain infarction,oedema,haemoglobin content,apoptosis,neuroinflammation,blood-brain barrier(BBB) permeability,the expression of tight junction proteins(TJPs) and the activity/expression of MMPs.RESULTS In the mice infused with tPA at 5 h post ischaemia,there were significant increases in mortality,brain infarction,brain oedema,brain haemoglobin level,neural apoptosis,Iba-1 staining(microglia activation) and myeloperoxidase staining(neutrophil infiltration).All these tPA-induced alterations were significantly prevented by NMN administration.Mechanistically,the delayed tPA treatment increased BBB permeability by downregulating TJPs,including claudin-1,occludin and zonula occludens-1,and enhancing the activities and protein expression of MMP9 and MMP2.Similarly,NMN administration partly blocked these tPAinduced molecular changes.CONCLUSION Our results demonstrate that NMN ameliorates tPAinduced haemorrhagic transformation in brain ischaemia by maintaining the integrity of the BBB.展开更多
OBJECTIVE Scalp mechanical stimulation, like combing, is one of the useful methods to keep brain health, which was historically recorded in traditional Chinese medicine thousand years ago. For the brain care, it is co...OBJECTIVE Scalp mechanical stimulation, like combing, is one of the useful methods to keep brain health, which was historically recorded in traditional Chinese medicine thousand years ago. For the brain care, it is considered to promote cerebrovascular circulation to prevent alopecia,headache, neurasthenia, insomnia, memory deficits. However, few study was reported on its effect and how the scalp mechanical stimulation works on vascular functions. Therefore, in this study, we try to illustrate the effect of combing on the cerebrovascular. METHODS In vivo, the anesthetized mice have been used to observe the effects of scalp mechanical stimulation. Infrared thermal imaging has been used to measure the skin temperature;vasodilation has been evaluated by retro-orbital injection of FITC-dextran 150 ku;the permeability of Blood-Brain Barrier(BBB) was analyzed by confocal microscopy of FITC-dextran 40 ku extravasation and a spectrofluorometric assay of Even Blue extravasation.RESLUTS We found that scalp mechanical stimulation rather than on the back can maintain the body temperature, especially raise the temperature in the ears. Accordingly, a moderate vasodilatation of auricles′ capillaries(≤ 8 μm) was observed, the phenomenon of which did not occur combing on the back. Furthermore, the permeability of BBB was promoted by the assays of small molecular extravasation. In addition, in vivo imaging, the small molecular of FITC-dextran(40 ku) was found to transport far away from the blood vessels into the brain parenchyma with the lapse of time. CONCLUSION Scalp mechanical stimulation can work on vasodilatation of auricles and promotion of BBB under a biological condition. Combing, as a daily behavior, simple but may yield novel insights into neuroprotection.展开更多
Aim To investigate the protection effect of the compatibility of baicalin and geniposide （7 ： 3 ） on blood-brain barrier （BBB） damage and the mechanism of down-regulating the expression of AQP-4 protein in cere- ...Aim To investigate the protection effect of the compatibility of baicalin and geniposide （7 ： 3 ） on blood-brain barrier （BBB） damage and the mechanism of down-regulating the expression of AQP-4 protein in cere- bral ischemia reperfusion injury （CIRI） rats. Method： 100 rats were divided into 5 groups： sham, CIRI model group, baicalin and geniposide （7 ： 3） （30 mg · kg^-1 ,60 mg · kg^-1） group, allyl chloride （0. 0021 ml· kg^-1）group. The model of CIRI made by improved suture method, Neural function defect, morphology and number of neurons in cerebral cortex was observed by Nissl staining; tested the contental change of P-gp and Na＋ , K＋-ATP enzymes of brain tissue, the contental change of S100β, Glucose, pyruvic acid and lactic acid of plasma by ELISA; the dry wet weight and Evans Blue （EB） tracing method served BBB permeabilitical changes; immunohis- tochemistry staining and semi-quantitation analysis were performed to detect the AQP-4 and GFAP in cerebra ische- mia; the expression of AQP-4 in cerebra hippocampus was determined by RT-qPCR and Western blot; pathological change was observed in brain issueby HE staining; observed the changes of brain tissue ultrastructure usingtrans- mission electron microscope with Lanthanum nitrate tracer ; monitored the size and location of the ischemia injury in brain regions with magnetic resonance imaging （MRI）. Results Compared with CIRI group, baicalin and genipo- side group can restore nerve function defect; increase the number of Nissl positive cells in cerebral cortex; weaken Na＋ ,K＋-ATP enzyme dynamic, reduce the content of S10013 Glucose and P-gp, reduce the content of water and volume EB in brain, elevated the7content of pyruvic acid and pyruvic acid; remarkable attenuation of AQP-4 and GFAP over-expression in the brain; remarkable attenuation of AQP-4 mRNA expression in hippocampus; The mor- phology is became clear, eased lumen of blood vessel compression deformation, loose organization, lessened cell volume and edema; Reduction of lanthanum particles into the blood vessels and the cells, reduce the vascular endo- thelial cell edema. Conclusion Baicalin and geniposide （7 ： 3 ） can reduce the permeability of blood brain barri- er, and has a protective effect on the brain edema induced by CIRI.展开更多
Following ischemic stroke, blood-brain barrier （BBB） is disrupted and is further aggravated with the corresponding incidence of hyperlipidemia. BBB breakdown promotes inflammation infiltration into the brain, which ...Following ischemic stroke, blood-brain barrier （BBB） is disrupted and is further aggravated with the corresponding incidence of hyperlipidemia. BBB breakdown promotes inflammation infiltration into the brain, which exacerbates cerebral ischemic injury as a result. Here, we report that 10-O-（N,N-dimethylaminoethyl）-ginkgolide B methanesulfonate （XQ-1H） , a novel analog of ginkgolide B, alleviates BBB breakdown in hyperlipidemic rats and protects endothelial cells against inflammatory response. Middle cerebral artery occlusion （MCAO） modeled is- chemic stroke in rats. Before surgery, these rats were fed a cholesterol-rich diet to induce an experimental hyperlip- idemic condition. Additionally, lipopolysaccharide （LPS） incubation with rat brain microvessel endothelial cells （rBMECs） was applied to mimic hyperlipidemia-induced inflammatory injury of BBB. The results indicated more severe infarct size, increased BBB permeability, excessive secretion of pro-inflammatory cytokines, and exaggerated inflammation infiltration of the brain in hyperlipidemic rats following MCAO when compared to rats fed with normal diet. XQ-1H protected BBB integrity, lessoned brain edema and inflammation penetration, down- regulated MMP- 9 and VCMA-1 expressions, and extenuated ischemic infarction. XQ-1H alleviated LPS-induced inflammatory re- sponse in rBMECs, characterized by promoting cell viability, inhibiting TNF-α, IL-1β, and IL-6 releasing, and downregulating NF-KB inflammatory signal and down- stream proteins, such as VCAM-1 and iNOS. In conclusion, the present study shows that XQ-1H stabilizes BBB function following ischemic stroke in hyperlipidemic rats, and the possible mechanisms may be related to inflammation inhibition.展开更多
Aquaporin-4 （AQP-4）, a water-channel protein,is highly expressed in the brain, which is important ele- ments in the formation of brain edema and plays an important role in the rapid transmembrane transport. AQP-4 ex...Aquaporin-4 （AQP-4）, a water-channel protein,is highly expressed in the brain, which is important ele- ments in the formation of brain edema and plays an important role in the rapid transmembrane transport. AQP-4 ex- pression up-regulates after ischemia-reperfusion injury in rats, making the astrocytic endfeet swelling, with the con- sequence of the injury of blood-brain barrier（BBB） , increasing the permeability of BBB, render too much water in the blood flow to the brain parenchyma, which results in cytotoxic edema, disordering the stability of the central nervous system. In addintion, the increased permeability of BBB is one of the important reasons for the cerebral stroke, therefore, it is essential that research the relationship between AQP-4 with BBB further and restore the blood-brain barrier injury be a new strategy for the prevention and treatment of stroke, worthy of further research.展开更多
Rectifying circuit,as a crucial component for converting alternating current into direct current,plays a pivotal role in energy harvesting microsystems.Traditional silicon-based or germanium-based rectifier diodes hin...Rectifying circuit,as a crucial component for converting alternating current into direct current,plays a pivotal role in energy harvesting microsystems.Traditional silicon-based or germanium-based rectifier diodes hinder system integration due to their specific manufacturing processes.Conversely,metal oxide diodes,with their simple fabrication techniques,offer advantages for system integration.The oxygen vacancy defect of oxide semiconductor will greatly affect the electrical performance of the device,so the performance of the diode can be effectively controlled by adjusting the oxygen vacancy concentration.This study centers on optimizing the performance of diodes by modulating the oxygen vacancy concentration within InGaZnO films through control of oxygen flows during the sputtering process.Experimental results demonstrate that the diode exhibits a forward current density of 43.82 A·cm^(−2),with a rectification ratio of 6.94×10^(4),efficiently rectifying input sine signals with 1 kHz frequency and 5 V magnitude.These results demonstrate its potential in energy conversion and management.By adjusting the oxygen vacancy,a methodology is provided for optimizing the performance of rectifying diodes.展开更多
OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was ...OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery occlusion.Brain water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were measured.RESULTS After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral hemisphere.Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and Occludin.These results suggest that CKLF1 is involved in BBB disruption after reperfusion.CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein.展开更多
The purpose of this study was to develop a quantitative structure–property relationship(QSPR) model based on the enhanced replacement method(ERM) and support vector machine(SVM) to predict the blood-to-brain barrier ...The purpose of this study was to develop a quantitative structure–property relationship(QSPR) model based on the enhanced replacement method(ERM) and support vector machine(SVM) to predict the blood-to-brain barrier partitioning behavior(log BB) of various drugs and organic compounds. Different molecular descriptors were calculated using a dragon package to represent the molecular structures of the compounds studied. The enhanced replacement method(ERM) was used to select the variables and construct the SVM model. The correlation coefficient, R^2, between experimental results and predicted log BB was 0.878 and 0.986, respectively. The results obtained demonstrated that, for all compounds, the log BB values estimated by SVM agreed with the experimental data, demonstrating that SVM is an effective method for model development, and can be used as a powerful chemometric tool in QSPR studies.展开更多
To improve the safety of trains running in an undesirable wind environment,a novel louver-type wind barrier is proposed and further studied in this research using a scaled wind tunnel simulation with 1:40 scale models...To improve the safety of trains running in an undesirable wind environment,a novel louver-type wind barrier is proposed and further studied in this research using a scaled wind tunnel simulation with 1:40 scale models.Based on the aerodynamic performance of the train-bridge system,the parameters of the louver-type wind barrier are optimized.Compared to the case without a wind barrier,it is apparent that the wind barrier improves the running safety of trains,since the maximum reduction of the moment coefficient of the train reaches 58%using the louver-type wind barrier,larger than that achieved with conventional wind barriers(fence-type and grid-type).A louver-type wind barrier has more blade layers,and the rotation angle of the adjustable blade of the louver-type wind barrier is 90–180°(which induces the flow towards the deck surface),which is more favorable for the aerodynamic performance of the train.Comparing the 60°,90°and 120°wind fairings of the louver-type wind barrier blade,the blunt fairing is disadvantageous to the operational safety of the train.展开更多
The thermal barrier coatings with NiCrAlY alloy bonding layer, NiCrAlY Y 2O 3 stabilized ZrO 2 transition layer and Y 2O 3 stabilized ZrO 2 ceramic layer are prepared on nickel alloy substrates using the plasma spray ...The thermal barrier coatings with NiCrAlY alloy bonding layer, NiCrAlY Y 2O 3 stabilized ZrO 2 transition layer and Y 2O 3 stabilized ZrO 2 ceramic layer are prepared on nickel alloy substrates using the plasma spray technique. The relationship among the composition, structure and property of the coatings are investiga ted by means of optical microscope, scanning electronic microscope and the experiments of thermal shock resistance cycling and high temperature oxidation resistance. The results show that the structure design of introdu cing a transition layer between Ni alloy substrate and ZrO 2 ceramic coating guarantees the high quality and properties of the coatings; ZrO 2 coatings doped with a little SiO 2 possesses better thermal shock resistance and more excellent hot corrosion resistance as compared with ZrO 2 coating materials without SiO 2 ;the improvement in performance of ZrO 2 coating doped with SiO 2 is due to forming more dense coating structure by self closing effects of the flaws and pores in the ZrO 2 coatings.展开更多
Wind barriers are commonly adopted to prevent the effects of wind on high-speed railway trains,but their wind-proofing effects are greatly affected by substructures.To investigate the effects of wind barriers on the a...Wind barriers are commonly adopted to prevent the effects of wind on high-speed railway trains,but their wind-proofing effects are greatly affected by substructures.To investigate the effects of wind barriers on the aerodynamic characteristic of road-rail same-story truss bridge-train systems,wind tunnel experiments were carried out using a 1:50 scale model.Taking a wind barrier with a porosity of 30%as an example,the aerodynamic characteristics of the bridge train system under different wind barrier layouts(single-sided and double-sided),positions(inside and outside)and heights(2.5 m,3.0 m,3.5 m and 4.0 m)were tested.The results indicate that the downstream inside wind barrier has almost no effect on the aerodynamic characteristics of the train-bridge system,but the downstream outside wind barrier increases the drag coefficient of the bridge and reduces both the lift coefficient and drag coefficient of the train due to its effect on the trains wind pressure distribution,especially on the trains leeward surface.When the wind barriers are arranged on the outside,their effects on the drag coefficient of the bridge and shielding effect on the train are greater than when they are arranged on the inside.As the height of the wind barrier increases,the drag coefficient of the bridge also gradually increases,and the lift coefficient and drag coefficient of the train gradually decrease,but the degree of variation of the aerodynamic coefficient with the height is slightly different due to the different wind barrier layouts.When 3.0 m high double-sided wind barriers are arranged on the outside of the truss bridge,the drag coefficient of the bridge only increases by 12%,while the drag coefficient of the train decreases by 55%.展开更多
基金Natural Science Foundation of Hebei Province(H2022206456)Natural Sci⁃ence Foundation of Hebei Province(H2021206449)+1 种基金Undergraduate Innovative Experiment Program of Hebei Medical University(USIP2022173)Undergraduate Innovative Experiment Program of Hebei Medical University(USIP2023107)。
文摘OBJECTIVE To explore mecha⁃nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net⁃work pharmacology combined with in vitro experi⁃ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data⁃bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100μmol·L^(-1))on P-gp activity were monitored in hCMEC/D3 in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans⁃mission regulation,neurotransmitter receptor activity,protein kinase regulation activity,G proteincoupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig⁃naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi⁃cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu⁃lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro⁃tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer⁃ence basis for further exploration of the mecha⁃nisms of imperatorin on regulating P-gp in BBB.
基金The project supported by National Natural Science Foundation of China(81374005)″Twelfth Five Year″National Science and Technology Support Program(2012BAI26B03)
文摘OBJECTIVE To evaluate the effects of Tong-Qiao-Huo-Xue decoction(TQHXD)on the bloodbrain barrier(BBB)permeability and the expressions of related proteins on the rats;and to analyse the constituents in the cerebrospinal fluid on the rats with cerebral ischemic injury.METHODS Cerebral ischemia rats were induced by middle cerebral artery occlusion(MCAO).Adult male sprague-dawley(SD)rats were randomly divided into seven groups:sham-group;model group;nimodipine(NMP)-treated group and nao mai tai(NMT)-treated group were set as positive drug control groups;TQHXD-treated group(3,6 and 12g·kg-1body weight);The neurological function of rats was estimated by neurological defect scoring after the 1,7and 15 dafter administration.Histological structure of the brain in rats were observed by hematoxylin and eosin(H&E)staining.Ultramicrostructural features of hippocampus neurons and the opening of tight junction(TJ)of BBB in rats were observed by transmission electron microscope(TEM).Western blotting was performed to detect the expression of ZO-1,occludin,claudin-5,AQP-4 and MMP-9 in BBB after cerebral ischemia injury.Component analysis experiments:adult male SD rats were randomly divided into four groups:Distilled water was administered intragastrically sham-operated rats;Distilled water was administered intragastrically model rats by MCAO;TQHXD was administered intragatrically to rats in sham-operated group;TQHXD was administered intragestrically to rats in model group by MCAO.GC and HPLC was used to detect three compounds,namely,muscone,ligustilide and hydroxysafflor yellow A,in rats cerebrospinal fluid(CSF)after oral administration of TQHXD.Finally,samples of cerebrospinal fluid of rats in each group were compared with single medicine so as to explicit the three compounds come from which herb.RESULTS TQHXD significantly reduced the neurological defect scores.Histological examination indicated that dense neuropil and largely surviving neurons had been seen in TQHXD-treated rats.TEM observation revealed that TQHXD could significantly inhibit the damage of hippocampal neurons and reduce the opening of TJ.The decreased protein expression levels of claudin-5,occludin,ZO-1 and the increased protein expression levels of AQP-4 and MMP-9in cerebral ischemia tissue were significantly prevented by treatment of TQHXD.Analysis of experimental results showed that muscone,ligustilide and hydroxysafflor yellow A could penetrate the BBB into the CSF,and the content of the model group was lower than that of sham group after intragastric administration of TQHXD.CONCLUSION These results demonstrated that TQHXD may act as a potential neuroprotective agent against BBB damage for cerebral ischemia through protecting of hippocampus neurons,reducing the opening of TJ and decreasing the permeability of BBB by up-regulating ZO-1,occludin,claudin-5 expressions,down-regulating AQP-4 and MMP-9 expressions.The effect of TQHXD on the decrease of the opening of TJ also reduced the content of muscone,ligustilide and hydroxysafflor yellow A in cerebrospinal fluid.
基金supported by National Natural Science Foundation of China(8142204981473208+3 种基金816734858137341481130061) National 863 Plan Young Scientist Program of China(2015AA020943)
文摘OBJECTIVE Tissue plasminogen activator(tPA) is the only approved pharmaco.logical therapy for acute brain ischaemia;however,a major limitation of tPA is the haemorrhagic trans.formation that follows tPA treatment.Here,we determined whether nicotinamide mononucleotide(NMN),a key intermediate of nicotinamide adenine dinucleotide biosynthesis,affects tPA-induced haemorrhagic transformation.METHODS Middle cerebral artery occlusion(MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h.When the filament was removed for reperfusion,tPA was infused via the tail vein.A single dose of NMN was injected i.p.(300 mg·kg^(-1)).Mice were killed at 24 h post ischaemia,and their brains were evaluated for brain infarction,oedema,haemoglobin content,apoptosis,neuroinflammation,blood-brain barrier(BBB) permeability,the expression of tight junction proteins(TJPs) and the activity/expression of MMPs.RESULTS In the mice infused with tPA at 5 h post ischaemia,there were significant increases in mortality,brain infarction,brain oedema,brain haemoglobin level,neural apoptosis,Iba-1 staining(microglia activation) and myeloperoxidase staining(neutrophil infiltration).All these tPA-induced alterations were significantly prevented by NMN administration.Mechanistically,the delayed tPA treatment increased BBB permeability by downregulating TJPs,including claudin-1,occludin and zonula occludens-1,and enhancing the activities and protein expression of MMP9 and MMP2.Similarly,NMN administration partly blocked these tPAinduced molecular changes.CONCLUSION Our results demonstrate that NMN ameliorates tPAinduced haemorrhagic transformation in brain ischaemia by maintaining the integrity of the BBB.
文摘OBJECTIVE Scalp mechanical stimulation, like combing, is one of the useful methods to keep brain health, which was historically recorded in traditional Chinese medicine thousand years ago. For the brain care, it is considered to promote cerebrovascular circulation to prevent alopecia,headache, neurasthenia, insomnia, memory deficits. However, few study was reported on its effect and how the scalp mechanical stimulation works on vascular functions. Therefore, in this study, we try to illustrate the effect of combing on the cerebrovascular. METHODS In vivo, the anesthetized mice have been used to observe the effects of scalp mechanical stimulation. Infrared thermal imaging has been used to measure the skin temperature;vasodilation has been evaluated by retro-orbital injection of FITC-dextran 150 ku;the permeability of Blood-Brain Barrier(BBB) was analyzed by confocal microscopy of FITC-dextran 40 ku extravasation and a spectrofluorometric assay of Even Blue extravasation.RESLUTS We found that scalp mechanical stimulation rather than on the back can maintain the body temperature, especially raise the temperature in the ears. Accordingly, a moderate vasodilatation of auricles′ capillaries(≤ 8 μm) was observed, the phenomenon of which did not occur combing on the back. Furthermore, the permeability of BBB was promoted by the assays of small molecular extravasation. In addition, in vivo imaging, the small molecular of FITC-dextran(40 ku) was found to transport far away from the blood vessels into the brain parenchyma with the lapse of time. CONCLUSION Scalp mechanical stimulation can work on vasodilatation of auricles and promotion of BBB under a biological condition. Combing, as a daily behavior, simple but may yield novel insights into neuroprotection.
文摘Aim To investigate the protection effect of the compatibility of baicalin and geniposide （7 ： 3 ） on blood-brain barrier （BBB） damage and the mechanism of down-regulating the expression of AQP-4 protein in cere- bral ischemia reperfusion injury （CIRI） rats. Method： 100 rats were divided into 5 groups： sham, CIRI model group, baicalin and geniposide （7 ： 3） （30 mg · kg^-1 ,60 mg · kg^-1） group, allyl chloride （0. 0021 ml· kg^-1）group. The model of CIRI made by improved suture method, Neural function defect, morphology and number of neurons in cerebral cortex was observed by Nissl staining; tested the contental change of P-gp and Na＋ , K＋-ATP enzymes of brain tissue, the contental change of S100β, Glucose, pyruvic acid and lactic acid of plasma by ELISA; the dry wet weight and Evans Blue （EB） tracing method served BBB permeabilitical changes; immunohis- tochemistry staining and semi-quantitation analysis were performed to detect the AQP-4 and GFAP in cerebra ische- mia; the expression of AQP-4 in cerebra hippocampus was determined by RT-qPCR and Western blot; pathological change was observed in brain issueby HE staining; observed the changes of brain tissue ultrastructure usingtrans- mission electron microscope with Lanthanum nitrate tracer ; monitored the size and location of the ischemia injury in brain regions with magnetic resonance imaging （MRI）. Results Compared with CIRI group, baicalin and genipo- side group can restore nerve function defect; increase the number of Nissl positive cells in cerebral cortex; weaken Na＋ ,K＋-ATP enzyme dynamic, reduce the content of S10013 Glucose and P-gp, reduce the content of water and volume EB in brain, elevated the7content of pyruvic acid and pyruvic acid; remarkable attenuation of AQP-4 and GFAP over-expression in the brain; remarkable attenuation of AQP-4 mRNA expression in hippocampus; The mor- phology is became clear, eased lumen of blood vessel compression deformation, loose organization, lessened cell volume and edema; Reduction of lanthanum particles into the blood vessels and the cells, reduce the vascular endo- thelial cell edema. Conclusion Baicalin and geniposide （7 ： 3 ） can reduce the permeability of blood brain barri- er, and has a protective effect on the brain edema induced by CIRI.
文摘Following ischemic stroke, blood-brain barrier （BBB） is disrupted and is further aggravated with the corresponding incidence of hyperlipidemia. BBB breakdown promotes inflammation infiltration into the brain, which exacerbates cerebral ischemic injury as a result. Here, we report that 10-O-（N,N-dimethylaminoethyl）-ginkgolide B methanesulfonate （XQ-1H） , a novel analog of ginkgolide B, alleviates BBB breakdown in hyperlipidemic rats and protects endothelial cells against inflammatory response. Middle cerebral artery occlusion （MCAO） modeled is- chemic stroke in rats. Before surgery, these rats were fed a cholesterol-rich diet to induce an experimental hyperlip- idemic condition. Additionally, lipopolysaccharide （LPS） incubation with rat brain microvessel endothelial cells （rBMECs） was applied to mimic hyperlipidemia-induced inflammatory injury of BBB. The results indicated more severe infarct size, increased BBB permeability, excessive secretion of pro-inflammatory cytokines, and exaggerated inflammation infiltration of the brain in hyperlipidemic rats following MCAO when compared to rats fed with normal diet. XQ-1H protected BBB integrity, lessoned brain edema and inflammation penetration, down- regulated MMP- 9 and VCMA-1 expressions, and extenuated ischemic infarction. XQ-1H alleviated LPS-induced inflammatory re- sponse in rBMECs, characterized by promoting cell viability, inhibiting TNF-α, IL-1β, and IL-6 releasing, and downregulating NF-KB inflammatory signal and down- stream proteins, such as VCAM-1 and iNOS. In conclusion, the present study shows that XQ-1H stabilizes BBB function following ischemic stroke in hyperlipidemic rats, and the possible mechanisms may be related to inflammation inhibition.
文摘Aquaporin-4 （AQP-4）, a water-channel protein,is highly expressed in the brain, which is important ele- ments in the formation of brain edema and plays an important role in the rapid transmembrane transport. AQP-4 ex- pression up-regulates after ischemia-reperfusion injury in rats, making the astrocytic endfeet swelling, with the con- sequence of the injury of blood-brain barrier（BBB） , increasing the permeability of BBB, render too much water in the blood flow to the brain parenchyma, which results in cytotoxic edema, disordering the stability of the central nervous system. In addintion, the increased permeability of BBB is one of the important reasons for the cerebral stroke, therefore, it is essential that research the relationship between AQP-4 with BBB further and restore the blood-brain barrier injury be a new strategy for the prevention and treatment of stroke, worthy of further research.
文摘Rectifying circuit,as a crucial component for converting alternating current into direct current,plays a pivotal role in energy harvesting microsystems.Traditional silicon-based or germanium-based rectifier diodes hinder system integration due to their specific manufacturing processes.Conversely,metal oxide diodes,with their simple fabrication techniques,offer advantages for system integration.The oxygen vacancy defect of oxide semiconductor will greatly affect the electrical performance of the device,so the performance of the diode can be effectively controlled by adjusting the oxygen vacancy concentration.This study centers on optimizing the performance of diodes by modulating the oxygen vacancy concentration within InGaZnO films through control of oxygen flows during the sputtering process.Experimental results demonstrate that the diode exhibits a forward current density of 43.82 A·cm^(−2),with a rectification ratio of 6.94×10^(4),efficiently rectifying input sine signals with 1 kHz frequency and 5 V magnitude.These results demonstrate its potential in energy conversion and management.By adjusting the oxygen vacancy,a methodology is provided for optimizing the performance of rectifying diodes.
基金The project supported by National Natural Science Foundation of China(81302760)the Chinese Postdoctoral Science Foundation Project(2013M542510)
文摘OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery occlusion.Brain water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were measured.RESULTS After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral hemisphere.Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and Occludin.These results suggest that CKLF1 is involved in BBB disruption after reperfusion.CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein.
文摘The purpose of this study was to develop a quantitative structure–property relationship(QSPR) model based on the enhanced replacement method(ERM) and support vector machine(SVM) to predict the blood-to-brain barrier partitioning behavior(log BB) of various drugs and organic compounds. Different molecular descriptors were calculated using a dragon package to represent the molecular structures of the compounds studied. The enhanced replacement method(ERM) was used to select the variables and construct the SVM model. The correlation coefficient, R^2, between experimental results and predicted log BB was 0.878 and 0.986, respectively. The results obtained demonstrated that, for all compounds, the log BB values estimated by SVM agreed with the experimental data, demonstrating that SVM is an effective method for model development, and can be used as a powerful chemometric tool in QSPR studies.
基金Project(2017T001-G)supported by the Science and Technology Research and Development Program of China Railway CorporationProject(2017YFB1201204)supported by the National Key Research and Development Program of China+2 种基金Project(U1534206)supported by the National Natural Science Foundation of ChinaProject(2015CX006)supported by the Innovation-driven Plan in Central South University,ChinaProject(2017zzts521)supported by the Fundamental Research Funds for the Central Universities,China
文摘To improve the safety of trains running in an undesirable wind environment,a novel louver-type wind barrier is proposed and further studied in this research using a scaled wind tunnel simulation with 1:40 scale models.Based on the aerodynamic performance of the train-bridge system,the parameters of the louver-type wind barrier are optimized.Compared to the case without a wind barrier,it is apparent that the wind barrier improves the running safety of trains,since the maximum reduction of the moment coefficient of the train reaches 58%using the louver-type wind barrier,larger than that achieved with conventional wind barriers(fence-type and grid-type).A louver-type wind barrier has more blade layers,and the rotation angle of the adjustable blade of the louver-type wind barrier is 90–180°(which induces the flow towards the deck surface),which is more favorable for the aerodynamic performance of the train.Comparing the 60°,90°and 120°wind fairings of the louver-type wind barrier blade,the blunt fairing is disadvantageous to the operational safety of the train.
文摘The thermal barrier coatings with NiCrAlY alloy bonding layer, NiCrAlY Y 2O 3 stabilized ZrO 2 transition layer and Y 2O 3 stabilized ZrO 2 ceramic layer are prepared on nickel alloy substrates using the plasma spray technique. The relationship among the composition, structure and property of the coatings are investiga ted by means of optical microscope, scanning electronic microscope and the experiments of thermal shock resistance cycling and high temperature oxidation resistance. The results show that the structure design of introdu cing a transition layer between Ni alloy substrate and ZrO 2 ceramic coating guarantees the high quality and properties of the coatings; ZrO 2 coatings doped with a little SiO 2 possesses better thermal shock resistance and more excellent hot corrosion resistance as compared with ZrO 2 coating materials without SiO 2 ;the improvement in performance of ZrO 2 coating doped with SiO 2 is due to forming more dense coating structure by self closing effects of the flaws and pores in the ZrO 2 coatings.
基金Projects(52078504,51822803,51925808) supported by the National Natural Science Foundation of ChinaProject(2021RC3016) supported by the Science and Technology Innovation Program of Hunan Province,China。
文摘Wind barriers are commonly adopted to prevent the effects of wind on high-speed railway trains,but their wind-proofing effects are greatly affected by substructures.To investigate the effects of wind barriers on the aerodynamic characteristic of road-rail same-story truss bridge-train systems,wind tunnel experiments were carried out using a 1:50 scale model.Taking a wind barrier with a porosity of 30%as an example,the aerodynamic characteristics of the bridge train system under different wind barrier layouts(single-sided and double-sided),positions(inside and outside)and heights(2.5 m,3.0 m,3.5 m and 4.0 m)were tested.The results indicate that the downstream inside wind barrier has almost no effect on the aerodynamic characteristics of the train-bridge system,but the downstream outside wind barrier increases the drag coefficient of the bridge and reduces both the lift coefficient and drag coefficient of the train due to its effect on the trains wind pressure distribution,especially on the trains leeward surface.When the wind barriers are arranged on the outside,their effects on the drag coefficient of the bridge and shielding effect on the train are greater than when they are arranged on the inside.As the height of the wind barrier increases,the drag coefficient of the bridge also gradually increases,and the lift coefficient and drag coefficient of the train gradually decrease,but the degree of variation of the aerodynamic coefficient with the height is slightly different due to the different wind barrier layouts.When 3.0 m high double-sided wind barriers are arranged on the outside of the truss bridge,the drag coefficient of the bridge only increases by 12%,while the drag coefficient of the train decreases by 55%.
