ADPKD is an inherited systemic disorder that predominantly affects the kidney, but may affect other organs including liver, pancreas, brain, and arterial blood vessel. APKPD occurs worldwide affecting about 1 in 500 -...ADPKD is an inherited systemic disorder that predominantly affects the kidney, but may affect other organs including liver, pancreas, brain, and arterial blood vessel. APKPD occurs worldwide affecting about 1 in 500 - 1000 people. Hypertension is the most common manifestation of ADPKD and the major contributor to renal disease progression. A definite diagnosis of ADPKD relies on image testing. Renal ultrasound is commonly used because of its cost effectiveness.展开更多
Objectives:To assess the safety,feasibility and clinical benefits of LCD and OCD for the treatment of ADPKD.Methods:Databases articles comparing LCD and OCD in treating PKD were collected through March 2019.After scre...Objectives:To assess the safety,feasibility and clinical benefits of LCD and OCD for the treatment of ADPKD.Methods:Databases articles comparing LCD and OCD in treating PKD were collected through March 2019.After screening for inclusion and data extraction,meta-analysis was performed by the RevMan 5.3 software.Results:A total of 9 studies involving 761 patients were finally included,with 362 cases in LCD group and 399 cases in OCD group.LCD was associated with a shorter operative time(MD=-36.24,95%CI:-44.20^-28.28,P<0.00001)and postoperative hospital stay(MD=-4.04,95%CI:-5.13^-2.95,P<0.00001).Besides,LCD had an earlier time to postoperative ambulation(MD=-14.90,95%CI:-16.33^-13.48,P<0.00001)and earlier time to first flatus(MD=-1.52 days,95%CI:-1.65^-1.40,P<0.00001;MD=-10.76 hours,95%CI:-12.71^-8.81,P<0.00001).In addition,LCD had a lower intraoperative blood loss(MD=-159.81,95%CI:-243.32^-76.31,P=0.0002)and lower analgesic dosage(MD=-56.62,95%CI:-84.16^-29.08,P<0.0001).There showed no statistically significant difference between the two groups in Scr,Bun,systolic and diastolic blood pressure(all P>0.05).Conclusions:Current evidence demonstrated a shorter postoperative hospital stay,lower blood loss,less postoperative pain,and other advantages.LCD may therefore be a feasible and safe surgical approach of ADPKD.展开更多
OBJECTIVE Autosomal dominant polycystic kidney disease(ADPKD) is a common.monogenetic disease characterized by progressive development of renal cysts.Thereis still further need for effective therapy.Based on our preci...OBJECTIVE Autosomal dominant polycystic kidney disease(ADPKD) is a common.monogenetic disease characterized by progressive development of renal cysts.Thereis still further need for effective therapy.Based on our precious study that Ganoderma triterpenes(GT),which is the major secondary metabolites of Ganoderma lucidum,is able to attenuate renal cyst development.The aim of this study was to investigate the effect of a monomer,Ganoderic acid A(GA-A) that was purified from the GT,which has been reported to exhibit antinociceptive,antioxidative,hepatoproctive and anti.cancer activities,to have a potent anti-cyst effect in ADPKD.METHODS We first evaluated the potential cytotoxicity of GA-A on MDCK cells using a CCK-8 assay.Then we used MDCK cyst model,cultivated MDCK cells in vitro to form fluid-filled cysts surrounded by monolayer cells.MDCK cells were co-incu.bated with 10 μmol·L^(-1) FSK with or without GA-A(25 μg·mL-1) and equal concentration GT as positive control from day 0 to day 6 to investigate the inhibitory effect of GA-A on cyst formation.And to further investigate the inhibitory effect of GA-A on cyst enlargement,MDCK cysts were treated with different concentration of GA-A(6.25,25 and 100 μg·mL-1) from day 5 to day 12.Next we used an embryonic kidney cyst model,wile-type mice kidneys were taken out on embryonic day 13.5 to form renal cysts stimulated with 8-Br-cAMP to prove the renal cyst inhibition at organ level.Meanwhile,we explored the possible mechanisms underlying GA-A inhibition on renal cyst development using MDCK cells treated with 10 μmol·L^(-1) FSK co-incubated with GA-A(25 μg·mL-1) and equal concentration GT.Several key components of Ras/MAPK pathway was evaluated by Western blot,the protein expression of H-ras,B-raf,p-ERK,Egr-1 and c-fos was evaluated.RESULTS MDCK cell viability was not affected by GA-A that were used ofincreasing concentrations up to 200 μg·mL^(-1).GA-A had no significant influence on cyst formation,but inhibited cyst enlargement dose-dependently and the inhibitory effect is significantly better than that of the same concentration of GT which proved that GA-A may be an effective monomer from GT.And after washing out GA-A on day 8,MDCK cysts regrew to a large size,suggesting that the inhibitory effect of GA-A on MDCK cyst enlargement was reversible.GA-A inhibited embryonic kidney cyst development significantly in a dose-dependent and reversible manner proving GA-A cyst inhibition at organ level,which is also more effective than equal concentration GT.Treatment of MDCK cells with FSK caused a significant elevation of H-ras,B-raf,p-ERK,Egr-1 and c-fos signaling molecules,while treatment with GA-A reduced the level of H-ras,B-raf,p-ERK,Egr-1 and c-fos expression.GA-A downregulated Ras/MAPK signaling pathway could contribute to its inhibitory effect on cyst development.CONCLUSION Ganoderic acid A from Ganoderma lucidum retard ADPKD renal cyst development via down-regulating Ras/MAPK signaling pathway.展开更多
文摘ADPKD is an inherited systemic disorder that predominantly affects the kidney, but may affect other organs including liver, pancreas, brain, and arterial blood vessel. APKPD occurs worldwide affecting about 1 in 500 - 1000 people. Hypertension is the most common manifestation of ADPKD and the major contributor to renal disease progression. A definite diagnosis of ADPKD relies on image testing. Renal ultrasound is commonly used because of its cost effectiveness.
文摘Objectives:To assess the safety,feasibility and clinical benefits of LCD and OCD for the treatment of ADPKD.Methods:Databases articles comparing LCD and OCD in treating PKD were collected through March 2019.After screening for inclusion and data extraction,meta-analysis was performed by the RevMan 5.3 software.Results:A total of 9 studies involving 761 patients were finally included,with 362 cases in LCD group and 399 cases in OCD group.LCD was associated with a shorter operative time(MD=-36.24,95%CI:-44.20^-28.28,P<0.00001)and postoperative hospital stay(MD=-4.04,95%CI:-5.13^-2.95,P<0.00001).Besides,LCD had an earlier time to postoperative ambulation(MD=-14.90,95%CI:-16.33^-13.48,P<0.00001)and earlier time to first flatus(MD=-1.52 days,95%CI:-1.65^-1.40,P<0.00001;MD=-10.76 hours,95%CI:-12.71^-8.81,P<0.00001).In addition,LCD had a lower intraoperative blood loss(MD=-159.81,95%CI:-243.32^-76.31,P=0.0002)and lower analgesic dosage(MD=-56.62,95%CI:-84.16^-29.08,P<0.0001).There showed no statistically significant difference between the two groups in Scr,Bun,systolic and diastolic blood pressure(all P>0.05).Conclusions:Current evidence demonstrated a shorter postoperative hospital stay,lower blood loss,less postoperative pain,and other advantages.LCD may therefore be a feasible and safe surgical approach of ADPKD.
基金supported by National Natural Science Foundation of China
文摘OBJECTIVE Autosomal dominant polycystic kidney disease(ADPKD) is a common.monogenetic disease characterized by progressive development of renal cysts.Thereis still further need for effective therapy.Based on our precious study that Ganoderma triterpenes(GT),which is the major secondary metabolites of Ganoderma lucidum,is able to attenuate renal cyst development.The aim of this study was to investigate the effect of a monomer,Ganoderic acid A(GA-A) that was purified from the GT,which has been reported to exhibit antinociceptive,antioxidative,hepatoproctive and anti.cancer activities,to have a potent anti-cyst effect in ADPKD.METHODS We first evaluated the potential cytotoxicity of GA-A on MDCK cells using a CCK-8 assay.Then we used MDCK cyst model,cultivated MDCK cells in vitro to form fluid-filled cysts surrounded by monolayer cells.MDCK cells were co-incu.bated with 10 μmol·L^(-1) FSK with or without GA-A(25 μg·mL-1) and equal concentration GT as positive control from day 0 to day 6 to investigate the inhibitory effect of GA-A on cyst formation.And to further investigate the inhibitory effect of GA-A on cyst enlargement,MDCK cysts were treated with different concentration of GA-A(6.25,25 and 100 μg·mL-1) from day 5 to day 12.Next we used an embryonic kidney cyst model,wile-type mice kidneys were taken out on embryonic day 13.5 to form renal cysts stimulated with 8-Br-cAMP to prove the renal cyst inhibition at organ level.Meanwhile,we explored the possible mechanisms underlying GA-A inhibition on renal cyst development using MDCK cells treated with 10 μmol·L^(-1) FSK co-incubated with GA-A(25 μg·mL-1) and equal concentration GT.Several key components of Ras/MAPK pathway was evaluated by Western blot,the protein expression of H-ras,B-raf,p-ERK,Egr-1 and c-fos was evaluated.RESULTS MDCK cell viability was not affected by GA-A that were used ofincreasing concentrations up to 200 μg·mL^(-1).GA-A had no significant influence on cyst formation,but inhibited cyst enlargement dose-dependently and the inhibitory effect is significantly better than that of the same concentration of GT which proved that GA-A may be an effective monomer from GT.And after washing out GA-A on day 8,MDCK cysts regrew to a large size,suggesting that the inhibitory effect of GA-A on MDCK cyst enlargement was reversible.GA-A inhibited embryonic kidney cyst development significantly in a dose-dependent and reversible manner proving GA-A cyst inhibition at organ level,which is also more effective than equal concentration GT.Treatment of MDCK cells with FSK caused a significant elevation of H-ras,B-raf,p-ERK,Egr-1 and c-fos signaling molecules,while treatment with GA-A reduced the level of H-ras,B-raf,p-ERK,Egr-1 and c-fos expression.GA-A downregulated Ras/MAPK signaling pathway could contribute to its inhibitory effect on cyst development.CONCLUSION Ganoderic acid A from Ganoderma lucidum retard ADPKD renal cyst development via down-regulating Ras/MAPK signaling pathway.
