Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprag...Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin.Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset.rMC-1 cells(rat Müller cell line)were treated with glyoxal for 24 h with or without ranibizumab.The expression levels of inwardly rectifying K^(+)channel 4.1(Kir4.1),aquaporin 4(AQP4),Dystrophin 71(Dp71),VEGF-A,glutamine synthetase(GS)and sodium-potassium-ATPase(Na^(+)-K^(+)-ATPase)were examined using Western blot.VEGF-A in the supernatant of the cell culture was detected with ELISA.The intracellular potassium and sodium levels were detected with specific indicators.Results:Compared with normal control,protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas,which were prevented by ranibizumab.The above changes were recapitulated in vitro.Similarly,the intracellular potassium level in glyoxal-treated rMC-1 cells was increased,while the intracellular sodium level and Na^(+)-K^(+)-ATPase protein level remained unchanged,compared with control.However,ranibizumab treatment decreased intracellular sodium,but not potassium.Conclusion:Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A.It also caused a reduction in intracellular osmotic pressure.展开更多
Let λ1,λ2,λ3,λ4 be non-zero real numbers, not all of the same sign, w real. Suppose that the ratios λ1/λ2,λ1/λ3 are irrational and algebraic. Then there are infinitely many solutions in primes pj, j = 1, 2,3,4...Let λ1,λ2,λ3,λ4 be non-zero real numbers, not all of the same sign, w real. Suppose that the ratios λ1/λ2,λ1/λ3 are irrational and algebraic. Then there are infinitely many solutions in primes pj, j = 1, 2,3,4, to the inequality |λ1p1 +λ2p^2/2 +λ3p^2/3+|λ4p^2/4+■(max{p1,p^2/2,p^2/3,p^2/4})-^5/64. This improves the earlier result.展开更多
基金supported by grants from the National Natural Science Foundation of China(81570852,81970810,81970811)National Major Scientific and Technological Special Project for“Significant New Drugs Development”during the Thirtieth Five-year Plan Period(2019ZX09301113).
文摘Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin.Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset.rMC-1 cells(rat Müller cell line)were treated with glyoxal for 24 h with or without ranibizumab.The expression levels of inwardly rectifying K^(+)channel 4.1(Kir4.1),aquaporin 4(AQP4),Dystrophin 71(Dp71),VEGF-A,glutamine synthetase(GS)and sodium-potassium-ATPase(Na^(+)-K^(+)-ATPase)were examined using Western blot.VEGF-A in the supernatant of the cell culture was detected with ELISA.The intracellular potassium and sodium levels were detected with specific indicators.Results:Compared with normal control,protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas,which were prevented by ranibizumab.The above changes were recapitulated in vitro.Similarly,the intracellular potassium level in glyoxal-treated rMC-1 cells was increased,while the intracellular sodium level and Na^(+)-K^(+)-ATPase protein level remained unchanged,compared with control.However,ranibizumab treatment decreased intracellular sodium,but not potassium.Conclusion:Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A.It also caused a reduction in intracellular osmotic pressure.
基金The authors thank the referees for their time and comments. This work was supported by the National Natural Science Foundation of China (Grant Nos. 11871193, 11471112)the Key Research Project of Henan Province Higher Education (No. 17A110009).
文摘Let λ1,λ2,λ3,λ4 be non-zero real numbers, not all of the same sign, w real. Suppose that the ratios λ1/λ2,λ1/λ3 are irrational and algebraic. Then there are infinitely many solutions in primes pj, j = 1, 2,3,4, to the inequality |λ1p1 +λ2p^2/2 +λ3p^2/3+|λ4p^2/4+■(max{p1,p^2/2,p^2/3,p^2/4})-^5/64. This improves the earlier result.
