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
Adsorbents with high adsorption efficiency and excellent biosafety for biomedical applications are highly required.MXene is a promising candidate owning these advantages,yet pristine MXene faces dilemmas including insu...Adsorbents with high adsorption efficiency and excellent biosafety for biomedical applications are highly required.MXene is a promising candidate owning these advantages,yet pristine MXene faces dilemmas including insufficient utility of sur-face site as well as limited processibility.Here,we develop MXene-encapsulated porous microcapsules via microfluidics.The microcapsules have a biomass hydrogel shell that provides robust support for MXene in the core,by which the microcapsules are endowed with high MXene dosage and remarkable biosafety.Additionally,the MXene nanoflakes assemble into a three-dimensional network via metal ion-induced gelation,thereby avoiding restacking and significantly improving surface utiliza-tion.Moreover,a freeze-pretreatment of the microcapsules during preparation results in the formation of a macroporous structure in the shell,which can facilitate the diffusion of the target molecules.These features,combined with additional magneto-responsiveness rendered by the incorporation of magnetic nanoparticles,contribute to prominent performances of the microcapsules in cleaning uremia toxins including creatinine,urea,and uric acid.Thus,it is anticipated that the MXene-encapsulated microcapsules will be promising adsorbents in dialysis-related applications,and the combination of microfluidic encapsulation with metal ion gelation will provide a novel approach for construction of hybrid MXene materials with desired functions.展开更多
Chronic kidney disease （CKD） is a major disease that threatens human health. With the progression of CKD, the risk of cardiovascular death increases, which is associated with the elevated levels of uremic toxins （...Chronic kidney disease （CKD） is a major disease that threatens human health. With the progression of CKD, the risk of cardiovascular death increases, which is associated with the elevated levels of uremic toxins （UTs）. Representative toxins such as indoxyl sulfate and p-cresyl sulfate are involed in CKD progression and cardiovascular events inseparable from the key role of endothelial dysfunction. The therapeutic strategies of UTs are aimed at signaling pathways that target the levels and damage of toxins in modem medicine. There is a certain relevance between toxins and ＂turbid toxin＂ in the theory of Chinese medicine （CM）. CM treatments have been demonstrated to reduce the damage of gut-derived toxins to the heart, kidney and blood vessels. Modern medicine still lacks evidence-based therapies, so it is necessary to explore the treatments of CM.展开更多
At present,clinical interventions for chronic kidney disease are very limited,and most patients rely on dialysis to sustain their lives for a long time.However,studies on the gut—kidney axis have shown that the gut m...At present,clinical interventions for chronic kidney disease are very limited,and most patients rely on dialysis to sustain their lives for a long time.However,studies on the gut—kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease.This study showed that berberine,a natural drug with low oral availability,significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins,including p-cresol.Furthermore,berberine reduced the content of pcresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine—p-cresol pathway of the intestinal flora.Meanwhile,berberine increased the butyric acid producing bacteria and the butyric acid content in feces,while decreased the renal toxic trimethylamine N-oxide.These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut—kidney axis.展开更多
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.
基金National Key Research and Development Program of China,Grant/Award Number:2020YFA0908200Strategic Priority Research Program of Chinese Academy of Sciences,Grant/Award Number:XDB33030300+1 种基金National Natural Science Foundation of China,Grant/Award Number:32271383Youth Innovation Promotion Association of CAS,Grant/Award Number:2021007。
文摘Adsorbents with high adsorption efficiency and excellent biosafety for biomedical applications are highly required.MXene is a promising candidate owning these advantages,yet pristine MXene faces dilemmas including insufficient utility of sur-face site as well as limited processibility.Here,we develop MXene-encapsulated porous microcapsules via microfluidics.The microcapsules have a biomass hydrogel shell that provides robust support for MXene in the core,by which the microcapsules are endowed with high MXene dosage and remarkable biosafety.Additionally,the MXene nanoflakes assemble into a three-dimensional network via metal ion-induced gelation,thereby avoiding restacking and significantly improving surface utiliza-tion.Moreover,a freeze-pretreatment of the microcapsules during preparation results in the formation of a macroporous structure in the shell,which can facilitate the diffusion of the target molecules.These features,combined with additional magneto-responsiveness rendered by the incorporation of magnetic nanoparticles,contribute to prominent performances of the microcapsules in cleaning uremia toxins including creatinine,urea,and uric acid.Thus,it is anticipated that the MXene-encapsulated microcapsules will be promising adsorbents in dialysis-related applications,and the combination of microfluidic encapsulation with metal ion gelation will provide a novel approach for construction of hybrid MXene materials with desired functions.
基金Supported by the National Natural Science Foundation of China(No.81573791,81141122)
文摘Chronic kidney disease （CKD） is a major disease that threatens human health. With the progression of CKD, the risk of cardiovascular death increases, which is associated with the elevated levels of uremic toxins （UTs）. Representative toxins such as indoxyl sulfate and p-cresyl sulfate are involed in CKD progression and cardiovascular events inseparable from the key role of endothelial dysfunction. The therapeutic strategies of UTs are aimed at signaling pathways that target the levels and damage of toxins in modem medicine. There is a certain relevance between toxins and ＂turbid toxin＂ in the theory of Chinese medicine （CM）. CM treatments have been demonstrated to reduce the damage of gut-derived toxins to the heart, kidney and blood vessels. Modern medicine still lacks evidence-based therapies, so it is necessary to explore the treatments of CM.
基金supported by the National Key R&D Program of China(No.2022YFA0806400)the CAMS Innovation Fund for Medical Sciences(CIFMS+2 种基金Nos.2022-I2M-JB-011,2022-I2M-2-002,and 2021-I2M-1-007,China)National Natural Science Foundation of China(Nos.82173888 and 81973290)Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study(Z141102004414062,China)。
文摘At present,clinical interventions for chronic kidney disease are very limited,and most patients rely on dialysis to sustain their lives for a long time.However,studies on the gut—kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease.This study showed that berberine,a natural drug with low oral availability,significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins,including p-cresol.Furthermore,berberine reduced the content of pcresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine—p-cresol pathway of the intestinal flora.Meanwhile,berberine increased the butyric acid producing bacteria and the butyric acid content in feces,while decreased the renal toxic trimethylamine N-oxide.These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut—kidney axis.
