Mounting evidence indicates that amyloid β protein（Aβ） exerts neurotoxicity by disrupting the blood-brain barrier（BBB） in Alzheimer＇s disease. Hyperoside has neuroprotective effects both in vitro and in vivo ag...Mounting evidence indicates that amyloid β protein（Aβ） exerts neurotoxicity by disrupting the blood-brain barrier（BBB） in Alzheimer＇s disease. Hyperoside has neuroprotective effects both in vitro and in vivo against Aβ. Our previous study found that hyperoside suppressed Aβ1-42-induced leakage of the BBB, however, the mechanism remains unclear. In this study, bEnd.3 cells were pretreated with 50, 200, or 500 μM hyperoside for 2 hours, and then exposed to Aβ1-42 for 24 hours. Cell viability was determined using 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide assay. Flow cytometry and terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay were used to analyze cell apoptosis. Western blot assay was carried out to analyze expression levels of Bax, Bcl-2, cytochrome c, caspase-3, caspse-8, caspase-9, caspase-12, occludin, claudin-5, zonula occludens-1, matrix metalloproteinase-2（MMP-2）, and MMP-9. Exposure to Aβ1-42 alone remarkably induced bEnd.3 cell apoptosis; increased ratios of cleaved caspase-9/caspase-9, Bax/Bcl-2, cleav ed caspase-8/caspase-8, and cleaved caspase-12/caspase-12; increased expression of cytochrome c and activity of caspase-3; diminished levels of zonula occludens-1, claudin-5, and occludin; and increased levels of MMP-2 and MMP-9. However, hyperoside pretreatment reversed these changes in a dose-dependent manner. Our findings confirm that hyperoside alleviates fibrillar Aβ1-42-induced BBB disruption, thus offering a feasible therapeutic application in Alzheimer＇s disease.展开更多
In meandering rivers, the flow pattern is highly complex, with specific characteristics at bends that are not observed along straight paths. A numerical model can be effectively used to predict such flow fields. Since...In meandering rivers, the flow pattern is highly complex, with specific characteristics at bends that are not observed along straight paths. A numerical model can be effectively used to predict such flow fields. Since river bends are not uniform-some are divergent and others convergent-in this study, after the SSIIM 3-D model was calibrated using the result of measurements along a uniform 180° bend with a width of 0.6 m, a similar but convergent 180v bend, 0.6 m to 0.45 m wide, was simulated using the SSI1M 3-D numerical model. Flow characteristics of the convergent 180° bend, including lengthwise and vertical velocity profiles, primary and secondary flows, lengthwise and widtbwise slopes of the water surface, and the helical flow strength, were compared with those of the uniform 180° bend. The verification results of the model show that the numerical model can effectively simulate the flow field in the uniform bend. In addition, this research indicates that, in a convergent channel, the maximum velocity path at a plane near the water surface crosses the channel＇s centerline at about a 30° to 40° cross-section, while in the uniform bend, this occurs at about the 50° cross-section. The varying range of the water surface elevation is wider in the convergent channel than in the uniform one, and the strength of the helical flow is generally greater in the uniform channel than in the convergent one. Also, unlike the uniform bend, the convergent bend exhibits no rotational cell against the main direction of secondary flow rotation at the 135° cross-section.展开更多
基金financially supported by the National Natural Science Foundation of China,No.81573771the Natural Science Foundation of Jiangsu Province of China,No.BK20151599
文摘Mounting evidence indicates that amyloid β protein（Aβ） exerts neurotoxicity by disrupting the blood-brain barrier（BBB） in Alzheimer＇s disease. Hyperoside has neuroprotective effects both in vitro and in vivo against Aβ. Our previous study found that hyperoside suppressed Aβ1-42-induced leakage of the BBB, however, the mechanism remains unclear. In this study, bEnd.3 cells were pretreated with 50, 200, or 500 μM hyperoside for 2 hours, and then exposed to Aβ1-42 for 24 hours. Cell viability was determined using 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide assay. Flow cytometry and terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay were used to analyze cell apoptosis. Western blot assay was carried out to analyze expression levels of Bax, Bcl-2, cytochrome c, caspase-3, caspse-8, caspase-9, caspase-12, occludin, claudin-5, zonula occludens-1, matrix metalloproteinase-2（MMP-2）, and MMP-9. Exposure to Aβ1-42 alone remarkably induced bEnd.3 cell apoptosis; increased ratios of cleaved caspase-9/caspase-9, Bax/Bcl-2, cleav ed caspase-8/caspase-8, and cleaved caspase-12/caspase-12; increased expression of cytochrome c and activity of caspase-3; diminished levels of zonula occludens-1, claudin-5, and occludin; and increased levels of MMP-2 and MMP-9. However, hyperoside pretreatment reversed these changes in a dose-dependent manner. Our findings confirm that hyperoside alleviates fibrillar Aβ1-42-induced BBB disruption, thus offering a feasible therapeutic application in Alzheimer＇s disease.
文摘In meandering rivers, the flow pattern is highly complex, with specific characteristics at bends that are not observed along straight paths. A numerical model can be effectively used to predict such flow fields. Since river bends are not uniform-some are divergent and others convergent-in this study, after the SSIIM 3-D model was calibrated using the result of measurements along a uniform 180° bend with a width of 0.6 m, a similar but convergent 180v bend, 0.6 m to 0.45 m wide, was simulated using the SSI1M 3-D numerical model. Flow characteristics of the convergent 180° bend, including lengthwise and vertical velocity profiles, primary and secondary flows, lengthwise and widtbwise slopes of the water surface, and the helical flow strength, were compared with those of the uniform 180° bend. The verification results of the model show that the numerical model can effectively simulate the flow field in the uniform bend. In addition, this research indicates that, in a convergent channel, the maximum velocity path at a plane near the water surface crosses the channel＇s centerline at about a 30° to 40° cross-section, while in the uniform bend, this occurs at about the 50° cross-section. The varying range of the water surface elevation is wider in the convergent channel than in the uniform one, and the strength of the helical flow is generally greater in the uniform channel than in the convergent one. Also, unlike the uniform bend, the convergent bend exhibits no rotational cell against the main direction of secondary flow rotation at the 135° cross-section.
