Total saponins of Panax notoginseng （PNS） have been shown to ameliorate renal interstitial fibrosis. Ginsenoside Rg 1, a panaxatriol saponin, is one of the major active molecules from PNS. The present study was unde...Total saponins of Panax notoginseng （PNS） have been shown to ameliorate renal interstitial fibrosis. Ginsenoside Rg 1, a panaxatriol saponin, is one of the major active molecules from PNS. The present study was undertaken to investigate the effect of ginsenoside Rgl on renal fibrosis in rats with unilateral ureteral obstruction （UUO）. The rats were randomly divided into 3 groups： sham-operation （n=15）, UUO （n=15） and UUO with ginsenoside Rgl treatment （n=15, 50 mg per kg body weight, intraperitoneally （i.p.） injected）. The rats were sacrificed on Days 7 and 14 after the surgery. Histological examination demonstrated that ginsenoside Rgl significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition, u-smooth muscle actin （α-SMA） and E-cadherin are two markers of tubular epithelial-myofibroblast transition （TEMT）. Interestingly, ginsenoside Rgl notably decreased α-SMA expression and simultaneously enhanced E-cadherin expression. The messenger RNA （mRNA） of transforming growth factor-β1 （TGF-β1）, a key mediator to regulate TEMT, in the obstructed kidney increased dramatically, but was found to decrease significantly after administration of ginsenoside Rg 1. Further study showed that ginsenoside Rgl considerably decreased the levels of both active TGF-β1 and phosphorylated Smad2 （pSmad2）. Moreover, ginsenoside Rgl substantially suppressed the expression of thrombospondin-1 （TSP-1）, a cytokine which can promote the transcription of TGF-β1 mRNA and the activation of latent TGF-β1. These results suggest that ginsenoside Rgl inhibits renal interstitial fibrosis in rats with UUO. The mechanism might be partly related to the blocking of TEMT via suppressing the expression of TSP-1.展开更多
Astragalus mongholicus(AM)derived from the dry root ofAstragalus membranaceus Bge.var.mongolicus(Bge.)Hsiao is a widely used traditional Chinese medicine.The present study investigated the potential role of AM on rena...Astragalus mongholicus(AM)derived from the dry root ofAstragalus membranaceus Bge.var.mongolicus(Bge.)Hsiao is a widely used traditional Chinese medicine.The present study investigated the potential role of AM on renal fibrosis on a rat model of unilateral ureteral obstruction(UUO).We divided 48 Sprague-Dawley rats randomly into 4 groups:sham-operated group(Sham),untreated UUO group,AM-treated(10 g/(kg.d))UUO group,and losartan-treated(20 mg/(kg.d))UUO group as positive control.Haematoxylin&eosin(HE)and Masson staining were used to study the dynamic histological changes of the kidneys 7 and 14 d after operation.The expressions of fibronectin(FN),type I collagen(coil),hepatocyte growth factor(HGF),transforming growth factor-β1(TGF-β1),and eL-smooth muscle actin(α-SMA)were analyzed by real-time polymerase chain reaction(PCR),immunohistochemistry staining,and Western blot.Results show that,similar to losartan,AM alleviated the renal damage and decreased the deposition of FN and coil from UUO by reducing the expressions of TGF-β1 andα-SMA(P〈0.05),whereas HGF increased greatly with AM treatment(P〈0.05).Our findings reveal that AM could retard the progression of renal fibrosis.The renoprotective effect of AM might be related to inhibition ofmyofibroblast activation,inducing of HGF and reducing of TGF-β1 expression.展开更多
Objective： The effects of hydraulic pressure on renal tubular epithelial-myofibroblast transdifferentiation （TEMT） were investigated. Methods： We applied hydraulic pressure （50 cmH2O） to normal rat kidney tubula...Objective： The effects of hydraulic pressure on renal tubular epithelial-myofibroblast transdifferentiation （TEMT） were investigated. Methods： We applied hydraulic pressure （50 cmH2O） to normal rat kidney tubular epithelial cells （NRK52E） for different durations. Furthermore, different pressure magnitudes were applied to cells. The morphology, cytoskeleton, and expression ofmyofibroblastic marker protein and transforming growth factor-β1 （TGF-β1） of NRK52E cells were examined. Results Disorganized actin filaments and formation of curling clusters in actin were seen in the cytoplasm of pressurized cells. We verified that de novo expression α-smooth muscle actin induced by pressure, which indicated TEMT, was dependent on both the magnitude and duration of pressure. TGF-β1 expression was significantly upregulated under certain conditions, which implies that the induction of TEMT by hydraulic pressure is related with TGF-β1. Conclusion： We illustrate for the first time that hydraulic pressure can induce TEMT in a pressure magnitude- and duration-dependent manner, and that this TEMT is accompanied by TGF-β1 secretion.展开更多
BACKGROUND Bone marrow-derived mesenchymal stem cells(MSCs)show podocyte-protective effects in chronic kidney disease.Calycosin(CA),a phytoestrogen,is isolated from Astragalus membranaceus with a kidney-tonifying effe...BACKGROUND Bone marrow-derived mesenchymal stem cells(MSCs)show podocyte-protective effects in chronic kidney disease.Calycosin(CA),a phytoestrogen,is isolated from Astragalus membranaceus with a kidney-tonifying effect.CA preconditioning enhances the protective effect of MSCs against renal fibrosis in mice with unilateral ureteral occlusion.However,the protective effect and underlying mechanism of CA-pretreated MSCs(MSCsCA)on podocytes in adriamycin(ADR)-induced focal segmental glomerulosclerosis(FSGS)mice remain unclear.AIM To investigate whether CA enhances the role of MSCs in protecting against podocyte injury induced by ADR and the possible mechanism involved.METHODS ADR was used to induce FSGS in mice,and MSCs,CA,or MSCsCA were administered to mice.Their protective effect and possible mechanism of action on podocytes were observed by Western blot,immunohistochemistry,immunofluorescence,and real-time polymerase chain reaction.In vitro,ADR was used to stimulate mouse podocytes(MPC5)to induce injury,and the supernatants from MSC-,CA-,or MSCsCA-treated cells were collected to observe their protective effects on podocytes.Subsequently,the apoptosis of podocytes was detected in vivo and in vitro by Western blot,TUNEL assay,and immunofluorescence.Overexpression of Smad3,which is involved in apoptosis,was then induced to evaluate whether the MSCsCA-mediated podocyte protective effect is associated with Smad3 inhibition in MPC5 cells.RESULTS CA-pretreated MSCs enhanced the protective effect of MSCs against podocyte injury and the ability to inhibit podocyte apoptosis in ADR-induced FSGS mice and MPC5 cells.Expression of p-Smad3 was upregulated in mice with ADR-induced FSGS and MPC5 cells,which was reversed by MSCCA treatment more significantly than by MSCs or CA alone.When Smad3 was overexpressed in MPC5 cells,MSCsCA could not fulfill their potential to inhibit podocyte apoptosis.CONCLUSION MSCsCA enhance the protection of MSCs against ADR-induced podocyte apoptosis.The underlying mechanism may be related to MSCsCA-targeted inhibition of p-Smad3 in podocytes.展开更多
Segmentation of intracranial aneurysm(IA)from computed tomography angiography(CTA)images is of significant importance for quantitative assessment of IA and further surgical treatment.Manual segmentation of IA is a lab...Segmentation of intracranial aneurysm(IA)from computed tomography angiography(CTA)images is of significant importance for quantitative assessment of IA and further surgical treatment.Manual segmentation of IA is a labor-intensive,time-consuming job and suffers from inter-and intra-observer variabilities.Training deep neural networks usually requires a large amount of labeled data,while annotating data is very time-consuming for the IA segmentation task.This paper presents a novel weight-perceptual self-ensembling model for semi-supervised IA segmentation,which employs unlabeled data by encouraging the predictions of given perturbed input samples to be consistent.Considering that the quality of consistency targets is not comparable to each other,we introduce a novel sample weight perception module to quantify the quality of different consistency targets.Our proposed module can be used to evaluate the contributions of unlabeled samples during training to force the network to focus on those well-predicted samples.We have conducted both horizontal and vertical comparisons on the clinical intracranial aneurysm CTA image dataset.Experimental results show that our proposed method can improve at least 3%Dice coefficient over the fully-supervised baseline,and at least 1.7%over other state-of-the-art semi-supervised methods.展开更多
基金Project (No. 30170437) supported by the National Natural Science Foundation of China
文摘Total saponins of Panax notoginseng （PNS） have been shown to ameliorate renal interstitial fibrosis. Ginsenoside Rg 1, a panaxatriol saponin, is one of the major active molecules from PNS. The present study was undertaken to investigate the effect of ginsenoside Rgl on renal fibrosis in rats with unilateral ureteral obstruction （UUO）. The rats were randomly divided into 3 groups： sham-operation （n=15）, UUO （n=15） and UUO with ginsenoside Rgl treatment （n=15, 50 mg per kg body weight, intraperitoneally （i.p.） injected）. The rats were sacrificed on Days 7 and 14 after the surgery. Histological examination demonstrated that ginsenoside Rgl significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition, u-smooth muscle actin （α-SMA） and E-cadherin are two markers of tubular epithelial-myofibroblast transition （TEMT）. Interestingly, ginsenoside Rgl notably decreased α-SMA expression and simultaneously enhanced E-cadherin expression. The messenger RNA （mRNA） of transforming growth factor-β1 （TGF-β1）, a key mediator to regulate TEMT, in the obstructed kidney increased dramatically, but was found to decrease significantly after administration of ginsenoside Rg 1. Further study showed that ginsenoside Rgl considerably decreased the levels of both active TGF-β1 and phosphorylated Smad2 （pSmad2）. Moreover, ginsenoside Rgl substantially suppressed the expression of thrombospondin-1 （TSP-1）, a cytokine which can promote the transcription of TGF-β1 mRNA and the activation of latent TGF-β1. These results suggest that ginsenoside Rgl inhibits renal interstitial fibrosis in rats with UUO. The mechanism might be partly related to the blocking of TEMT via suppressing the expression of TSP-1.
基金Projec(No.30170437)supported by the National Natural Science Foundation of China
文摘Astragalus mongholicus(AM)derived from the dry root ofAstragalus membranaceus Bge.var.mongolicus(Bge.)Hsiao is a widely used traditional Chinese medicine.The present study investigated the potential role of AM on renal fibrosis on a rat model of unilateral ureteral obstruction(UUO).We divided 48 Sprague-Dawley rats randomly into 4 groups:sham-operated group(Sham),untreated UUO group,AM-treated(10 g/(kg.d))UUO group,and losartan-treated(20 mg/(kg.d))UUO group as positive control.Haematoxylin&eosin(HE)and Masson staining were used to study the dynamic histological changes of the kidneys 7 and 14 d after operation.The expressions of fibronectin(FN),type I collagen(coil),hepatocyte growth factor(HGF),transforming growth factor-β1(TGF-β1),and eL-smooth muscle actin(α-SMA)were analyzed by real-time polymerase chain reaction(PCR),immunohistochemistry staining,and Western blot.Results show that,similar to losartan,AM alleviated the renal damage and decreased the deposition of FN and coil from UUO by reducing the expressions of TGF-β1 andα-SMA(P〈0.05),whereas HGF increased greatly with AM treatment(P〈0.05).Our findings reveal that AM could retard the progression of renal fibrosis.The renoprotective effect of AM might be related to inhibition ofmyofibroblast activation,inducing of HGF and reducing of TGF-β1 expression.
基金Project (No. 2007CB947802) supported by National Basic Research Program of China
文摘Objective： The effects of hydraulic pressure on renal tubular epithelial-myofibroblast transdifferentiation （TEMT） were investigated. Methods： We applied hydraulic pressure （50 cmH2O） to normal rat kidney tubular epithelial cells （NRK52E） for different durations. Furthermore, different pressure magnitudes were applied to cells. The morphology, cytoskeleton, and expression ofmyofibroblastic marker protein and transforming growth factor-β1 （TGF-β1） of NRK52E cells were examined. Results Disorganized actin filaments and formation of curling clusters in actin were seen in the cytoplasm of pressurized cells. We verified that de novo expression α-smooth muscle actin induced by pressure, which indicated TEMT, was dependent on both the magnitude and duration of pressure. TGF-β1 expression was significantly upregulated under certain conditions, which implies that the induction of TEMT by hydraulic pressure is related with TGF-β1. Conclusion： We illustrate for the first time that hydraulic pressure can induce TEMT in a pressure magnitude- and duration-dependent manner, and that this TEMT is accompanied by TGF-β1 secretion.
基金the National Natural Science Foundation of China(General Program),No.82205002Science and Technology Project of Sichuan Province,No.2022YFS0621,No.21ZDYF0348,and No.2022NSFSC1459+1 种基金Luzhou-Southwest Medical University Science and Technology Strategic Cooperation Project,No.2021LZXNYD-P04Southwest Medical University of Affiliated Traditional Medicine Hospital Project,No.2022-CXTD-03.
文摘BACKGROUND Bone marrow-derived mesenchymal stem cells(MSCs)show podocyte-protective effects in chronic kidney disease.Calycosin(CA),a phytoestrogen,is isolated from Astragalus membranaceus with a kidney-tonifying effect.CA preconditioning enhances the protective effect of MSCs against renal fibrosis in mice with unilateral ureteral occlusion.However,the protective effect and underlying mechanism of CA-pretreated MSCs(MSCsCA)on podocytes in adriamycin(ADR)-induced focal segmental glomerulosclerosis(FSGS)mice remain unclear.AIM To investigate whether CA enhances the role of MSCs in protecting against podocyte injury induced by ADR and the possible mechanism involved.METHODS ADR was used to induce FSGS in mice,and MSCs,CA,or MSCsCA were administered to mice.Their protective effect and possible mechanism of action on podocytes were observed by Western blot,immunohistochemistry,immunofluorescence,and real-time polymerase chain reaction.In vitro,ADR was used to stimulate mouse podocytes(MPC5)to induce injury,and the supernatants from MSC-,CA-,or MSCsCA-treated cells were collected to observe their protective effects on podocytes.Subsequently,the apoptosis of podocytes was detected in vivo and in vitro by Western blot,TUNEL assay,and immunofluorescence.Overexpression of Smad3,which is involved in apoptosis,was then induced to evaluate whether the MSCsCA-mediated podocyte protective effect is associated with Smad3 inhibition in MPC5 cells.RESULTS CA-pretreated MSCs enhanced the protective effect of MSCs against podocyte injury and the ability to inhibit podocyte apoptosis in ADR-induced FSGS mice and MPC5 cells.Expression of p-Smad3 was upregulated in mice with ADR-induced FSGS and MPC5 cells,which was reversed by MSCCA treatment more significantly than by MSCs or CA alone.When Smad3 was overexpressed in MPC5 cells,MSCsCA could not fulfill their potential to inhibit podocyte apoptosis.CONCLUSION MSCsCA enhance the protection of MSCs against ADR-induced podocyte apoptosis.The underlying mechanism may be related to MSCsCA-targeted inhibition of p-Smad3 in podocytes.
基金supported by Shenzhen Fundamental Research Program of China under Grant Nos.JCYJ20200109110420626 and JCYJ20200109110208764the National Natural Science Foundation of China under Grant Nos.U1813204 and 61802385+1 种基金the Natural Science Foundation of Guangdong of China under Grant No.2021A1515012604the Clinical Research Project of Shenzhen Municiple Health Commission under Grant No.SZLY2017011.
文摘Segmentation of intracranial aneurysm(IA)from computed tomography angiography(CTA)images is of significant importance for quantitative assessment of IA and further surgical treatment.Manual segmentation of IA is a labor-intensive,time-consuming job and suffers from inter-and intra-observer variabilities.Training deep neural networks usually requires a large amount of labeled data,while annotating data is very time-consuming for the IA segmentation task.This paper presents a novel weight-perceptual self-ensembling model for semi-supervised IA segmentation,which employs unlabeled data by encouraging the predictions of given perturbed input samples to be consistent.Considering that the quality of consistency targets is not comparable to each other,we introduce a novel sample weight perception module to quantify the quality of different consistency targets.Our proposed module can be used to evaluate the contributions of unlabeled samples during training to force the network to focus on those well-predicted samples.We have conducted both horizontal and vertical comparisons on the clinical intracranial aneurysm CTA image dataset.Experimental results show that our proposed method can improve at least 3%Dice coefficient over the fully-supervised baseline,and at least 1.7%over other state-of-the-art semi-supervised methods.
