OBJECTIVE To determine whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus.METHODS Streptozotocin-induced diabetic mice were introduced,and th...OBJECTIVE To determine whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus.METHODS Streptozotocin-induced diabetic mice were introduced,and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated.RESULTS Berberine combined with canagliflozin(BC)increased reduction of fasting and postprandial blood glucose,diet,and water intake compared with berberine or canagliflozin alone.Interestingly,BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone.In addition,BC showed increased phosphorylated 5′AMP-activated protein kinase(pA MPK)expression and decreased tumor necrosis factor alpha(TNFα)levels in kidneys compared with berberine or canagliflozin alone.CONCLUSION These results indicated that BC is as tronger antidiabetic than berberine or canagliflozin alone with less negative side effectson the kidneys of diabetic mice.The antidiabetic effect is likely mediated by synergically promoting the expression of p AMPK and reducing the expression of TNFαin kidneys.This study first proved that canagliflozin combined withberberine is apromising treatment for diabetes mellitus.However,the exact mechanisms should be further investigated in future studies.展开更多
The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduc...The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated. Our results showed that berberine combined with canagliflozin(BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone. Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone. In addition, BC showed increased phosphorylated 5' AMP-activated protein kinase(p AMPK) expression and decreased tumor necrosis factor alpha(TNFα) levels in kidneys, compared with berberine or canagliflozin alone. These results indicated that BC was a stronger antidiabetic than berberine or canagliflozin alone with less negative side effects on the kidneys in the diabetic mice. The antidiabetic effect was likely to be mediated by synergically promoting the expression of p AMPK and reducing the expression of TNFα in kidneys. The present study represented the first report that canagliflozin combined with berberine was a promising treatment for diabetes mellitus. The exact underlying mechanisms of action should be investigated in future studies.展开更多
In this work, we developed a simple method to fabricate a thickness-based continuous stiffness gradient for biological studies. It was made by glass slides, polydimethylsiloxane （PDMS） pre-polymer, spacer and clips ...In this work, we developed a simple method to fabricate a thickness-based continuous stiffness gradient for biological studies. It was made by glass slides, polydimethylsiloxane （PDMS） pre-polymer, spacer and clips only, without any sophisticated equipment. It is easy to fabricate in any general biological and pharmaceutical laboratories. The stiffness gradient was characterized in terms of apparent Young＇s modulus by atomic force microscopy （AFM） and the Young＇s modulus along the gradient was found to be 8.5- 120 kPa, which is within the physiological relevant range. HeLa-C3 ceils were cultured on the gradient to study their morphological behavior according to the substrate stiffness. Furthermore, the drug efficiency of etoposide, an anti-cancer drug, was studied along the substrate stiffness gradient. It was found that HeLa-C3 cells cultured on the soft region of the gradient （8.5-11 kPa） are more sensitive to etoposide. We believe the proposed device could promote cell investigations and drug screenings on a substrate with comparable stiffness to the native tissue.展开更多
基金The project supported by National Natural Science Foundation of China(81373460)by the Natural Science Foundation of Guangdong Province(2014A030313744)
文摘OBJECTIVE To determine whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus.METHODS Streptozotocin-induced diabetic mice were introduced,and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated.RESULTS Berberine combined with canagliflozin(BC)increased reduction of fasting and postprandial blood glucose,diet,and water intake compared with berberine or canagliflozin alone.Interestingly,BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone.In addition,BC showed increased phosphorylated 5′AMP-activated protein kinase(pA MPK)expression and decreased tumor necrosis factor alpha(TNFα)levels in kidneys compared with berberine or canagliflozin alone.CONCLUSION These results indicated that BC is as tronger antidiabetic than berberine or canagliflozin alone with less negative side effectson the kidneys of diabetic mice.The antidiabetic effect is likely mediated by synergically promoting the expression of p AMPK and reducing the expression of TNFαin kidneys.This study first proved that canagliflozin combined withberberine is apromising treatment for diabetes mellitus.However,the exact mechanisms should be further investigated in future studies.
基金supported by National Natural Science Foundation of China(No.81373460)Natural Science Foundation of Guangdong Province(No.2014A030313744)+1 种基金Shenzhen Science and Technology R&D Foundation(SGLH20121008144756945)China Scholarship Council(201308440130)
文摘The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated. Our results showed that berberine combined with canagliflozin(BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone. Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone. In addition, BC showed increased phosphorylated 5' AMP-activated protein kinase(p AMPK) expression and decreased tumor necrosis factor alpha(TNFα) levels in kidneys, compared with berberine or canagliflozin alone. These results indicated that BC was a stronger antidiabetic than berberine or canagliflozin alone with less negative side effects on the kidneys in the diabetic mice. The antidiabetic effect was likely to be mediated by synergically promoting the expression of p AMPK and reducing the expression of TNFα in kidneys. The present study represented the first report that canagliflozin combined with berberine was a promising treatment for diabetes mellitus. The exact underlying mechanisms of action should be investigated in future studies.
基金supported by the Hong Kong Research Grant Council (GRF#16306115 and #16325116)HKUST SSTSP (#FP701)the National High Technology Research and Development Program of China (2013AA032204)
文摘In this work, we developed a simple method to fabricate a thickness-based continuous stiffness gradient for biological studies. It was made by glass slides, polydimethylsiloxane （PDMS） pre-polymer, spacer and clips only, without any sophisticated equipment. It is easy to fabricate in any general biological and pharmaceutical laboratories. The stiffness gradient was characterized in terms of apparent Young＇s modulus by atomic force microscopy （AFM） and the Young＇s modulus along the gradient was found to be 8.5- 120 kPa, which is within the physiological relevant range. HeLa-C3 ceils were cultured on the gradient to study their morphological behavior according to the substrate stiffness. Furthermore, the drug efficiency of etoposide, an anti-cancer drug, was studied along the substrate stiffness gradient. It was found that HeLa-C3 cells cultured on the soft region of the gradient （8.5-11 kPa） are more sensitive to etoposide. We believe the proposed device could promote cell investigations and drug screenings on a substrate with comparable stiffness to the native tissue.
