Objective： To investigate the effect of the Uremic Clearance Granule （UCG, 尿毒清颗粒）, a Chinese patent medicine, on tubular epithelial-to-mesenchymal transition （EMT） in a unilateral ureteral obstruction （UUO...Objective： To investigate the effect of the Uremic Clearance Granule （UCG, 尿毒清颗粒）, a Chinese patent medicine, on tubular epithelial-to-mesenchymal transition （EMT） in a unilateral ureteral obstruction （UUO） model in vivo and transforming growth factor （TGF）- 131 induced EMT of HK-2 cells in vitro. Methods： In vivo study, 50 Sprague Dawley rats were divided into three groups： a sham operation group （n=10）, a UUO group （n=20）, and a UUO with UCG treatment group （n=20）. The UCG was given at a dose of 4.5 g/kg body weight per day by gavage after surgery. In vitro study, HK-2 cells were cultured in 10% fetal bovine serum （FBS）, 10% healthy rat serum, 10% FBS and TGF-13 1 （10 ng/mL）, 10% healthy rat serum and TGF-13 1, or 10% rat serum containing the uremic clearance granule and TGF-13 1. The expression of the epithelial marker E-cadherin and the mesenchymal markers vimentin and e^-smooth muscle actin （ot-SMA） in kidney tissues and HK-2 cells were investigated by Western blot analysis and immunofluorescence staining. Results： The rats of the UUO group showed obvious tubulointerstitial fibrosis, compared with the sham operation group rats. Tubulointerstitial fibrosis score was reduced by 17.5%± 1.1% at day 7 and by 20.0%_＋ 1.2% at day 14 in the UCG-treated group, compared with the UUO group. The UCG could maintained expression of E-cadherin and suppressed expression of vimentin and α-SMA in kidney tissues of UUO rats at days 7 and 14, as determined by Western blot analysis and immunofluorescence staining. Rat serum containing the UCG partially inhibited TGF- β 1-induced fibroblast phenotype of HK-2 cells and maintained the epithelial morphology of HK-2 cells in vitro. This occurred partially through a reduction of vimentin expression and an increase of E-cadherin expression. Conclusion： These results suggest that the UCG prevents tubular EMT and may be a promising agent for treating tubulointerstitial fibrosis.展开更多
The role of beta2-microglobulin(β2M) in dialysisrelated amyloidosis as a specific amyloid precursor was defined in the 1980 s. Studies in those years were largely related to β2M amyloidosis. In 2005, for what was pr...The role of beta2-microglobulin(β2M) in dialysisrelated amyloidosis as a specific amyloid precursor was defined in the 1980 s. Studies in those years were largely related to β2M amyloidosis. In 2005, for what was probably the first time in the available literature, we provided data about the association betweenβ2M and early-onset atherosclerosis in hemodialysis patients without co-morbidities. In recent years, the role of uremic toxins in uremic atherosclerosis and the interest in β2M as a marker of cardiovascular(CV) and/or mortality risk have grown. In the current literature,clinical studies suggest that β2M is an independent, significant predictor of mortality, not only in dialysis patients, but also in predialysis patients and in the highrisk portion of the general population, and it seems to be a factor strongly linked to the presence and severity of CV disease. It is still unknown whether β2M is only a uremic toxin marker or if it also has an active role in vascular damage, but data support that it may reflect an increased burden of systemic atherosclerosis in a setting of underlying chronic kidney disease. Thus, although there have been some inconsistencies among the various analyses relating to β2M, it promises to be a novel risk marker of kidney function in the awareness and detection of high-risk patients. However, more research is required to establish the pathophysiological relationships between retained uremic toxins and further biochemical modifications in the uremic milieu to get answers to the questions of why and how. In this review, the recent literature about the changing role of β2M in uremic patients will be examined.展开更多
Hemolytic uremic syndrome （HUS） is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and patho-genetic classifications. New findings in genetics and, in ...Hemolytic uremic syndrome （HUS） is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and patho-genetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the comple-ment proteins are clearly involved in all types of thrombotic microangiopathy： typical HUS, atypical HUS and thrombotic thrombocytopenic purpura （TTP）. Fur-thermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic as-pects of this rare disease, examining both “traditional therapy” （including plasma therapy, kidney and kidney-liver transplantation） and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 mono-clonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases Ⅰ and Ⅱ. They include anti-C5 antibodies, which are more purifed, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.展开更多
Chronic kidney disease （CKD） patients are endangered with the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the fatalities. Cardiovascular calcifcations af...Chronic kidney disease （CKD） patients are endangered with the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the fatalities. Cardiovascular calcifcations affect most of the CKD patients. Most of this calcification is related to disturbed renal phosphate handling. Fibroblast growth factor 23 and klotho defciency were incriminated in the pathogenesis of vascular calcification through different mechanisms including their effects on endothelium and arterial wall smooth muscle cells. In addition, deficient klotho gene expression, a constant feature of CKD, pro-motes vascular pathology and shares in progression of the CKD. The role of gut in the etio-pathogenesis of systemic infammation and vascular calcifcation is a newly discovered mechanism. This review will cover the medical history, prevalence, pathogenesis, clinical relevance, different tools used to diagnose, the ideal timing to prevent or to withhold the progression of vascular cal-cification and the different medications and medical procedures that can help to prolong the survival of CKD patients.展开更多
基金Supported by the National Basic Research Program of China(No.2011CB944004)the Program of the National Natural Science Foundation of China(No.30971377)the Science and Technology Project of Beijing,China(No.D09050704310904)
文摘Objective： To investigate the effect of the Uremic Clearance Granule （UCG, 尿毒清颗粒）, a Chinese patent medicine, on tubular epithelial-to-mesenchymal transition （EMT） in a unilateral ureteral obstruction （UUO） model in vivo and transforming growth factor （TGF）- 131 induced EMT of HK-2 cells in vitro. Methods： In vivo study, 50 Sprague Dawley rats were divided into three groups： a sham operation group （n=10）, a UUO group （n=20）, and a UUO with UCG treatment group （n=20）. The UCG was given at a dose of 4.5 g/kg body weight per day by gavage after surgery. In vitro study, HK-2 cells were cultured in 10% fetal bovine serum （FBS）, 10% healthy rat serum, 10% FBS and TGF-13 1 （10 ng/mL）, 10% healthy rat serum and TGF-13 1, or 10% rat serum containing the uremic clearance granule and TGF-13 1. The expression of the epithelial marker E-cadherin and the mesenchymal markers vimentin and e^-smooth muscle actin （ot-SMA） in kidney tissues and HK-2 cells were investigated by Western blot analysis and immunofluorescence staining. Results： The rats of the UUO group showed obvious tubulointerstitial fibrosis, compared with the sham operation group rats. Tubulointerstitial fibrosis score was reduced by 17.5%± 1.1% at day 7 and by 20.0%_＋ 1.2% at day 14 in the UCG-treated group, compared with the UUO group. The UCG could maintained expression of E-cadherin and suppressed expression of vimentin and α-SMA in kidney tissues of UUO rats at days 7 and 14, as determined by Western blot analysis and immunofluorescence staining. Rat serum containing the UCG partially inhibited TGF- β 1-induced fibroblast phenotype of HK-2 cells and maintained the epithelial morphology of HK-2 cells in vitro. This occurred partially through a reduction of vimentin expression and an increase of E-cadherin expression. Conclusion： These results suggest that the UCG prevents tubular EMT and may be a promising agent for treating tubulointerstitial fibrosis.
文摘The role of beta2-microglobulin(β2M) in dialysisrelated amyloidosis as a specific amyloid precursor was defined in the 1980 s. Studies in those years were largely related to β2M amyloidosis. In 2005, for what was probably the first time in the available literature, we provided data about the association betweenβ2M and early-onset atherosclerosis in hemodialysis patients without co-morbidities. In recent years, the role of uremic toxins in uremic atherosclerosis and the interest in β2M as a marker of cardiovascular(CV) and/or mortality risk have grown. In the current literature,clinical studies suggest that β2M is an independent, significant predictor of mortality, not only in dialysis patients, but also in predialysis patients and in the highrisk portion of the general population, and it seems to be a factor strongly linked to the presence and severity of CV disease. It is still unknown whether β2M is only a uremic toxin marker or if it also has an active role in vascular damage, but data support that it may reflect an increased burden of systemic atherosclerosis in a setting of underlying chronic kidney disease. Thus, although there have been some inconsistencies among the various analyses relating to β2M, it promises to be a novel risk marker of kidney function in the awareness and detection of high-risk patients. However, more research is required to establish the pathophysiological relationships between retained uremic toxins and further biochemical modifications in the uremic milieu to get answers to the questions of why and how. In this review, the recent literature about the changing role of β2M in uremic patients will be examined.
文摘Hemolytic uremic syndrome （HUS） is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and patho-genetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the comple-ment proteins are clearly involved in all types of thrombotic microangiopathy： typical HUS, atypical HUS and thrombotic thrombocytopenic purpura （TTP）. Fur-thermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic as-pects of this rare disease, examining both “traditional therapy” （including plasma therapy, kidney and kidney-liver transplantation） and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 mono-clonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases Ⅰ and Ⅱ. They include anti-C5 antibodies, which are more purifed, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.
文摘Chronic kidney disease （CKD） patients are endangered with the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the fatalities. Cardiovascular calcifcations affect most of the CKD patients. Most of this calcification is related to disturbed renal phosphate handling. Fibroblast growth factor 23 and klotho defciency were incriminated in the pathogenesis of vascular calcification through different mechanisms including their effects on endothelium and arterial wall smooth muscle cells. In addition, deficient klotho gene expression, a constant feature of CKD, pro-motes vascular pathology and shares in progression of the CKD. The role of gut in the etio-pathogenesis of systemic infammation and vascular calcifcation is a newly discovered mechanism. This review will cover the medical history, prevalence, pathogenesis, clinical relevance, different tools used to diagnose, the ideal timing to prevent or to withhold the progression of vascular cal-cification and the different medications and medical procedures that can help to prolong the survival of CKD patients.
