Carbon monoxide(CO),as a vital small molecule in signaling pathways,is found to be involved in ischemia-reperfusion injury(IRI) in renal transplantation.CO-releasing molecule-2(CORM-2),a CO-releasing molecule,is a typ...Carbon monoxide(CO),as a vital small molecule in signaling pathways,is found to be involved in ischemia-reperfusion injury(IRI) in renal transplantation.CO-releasing molecule-2(CORM-2),a CO-releasing molecule,is a type of metal carbonyl complexes which can quickly release CO in vivo.In this study,an in vitro oxidative stress injury model was established to examine the effect of CORM-2 pretreatment on the nuclear-cytoplasmic translocation of high mobility group box 1 protein(HMGB1) in mouse primary renal proximal tubular epithelial cells(RPTECs).Immunofluorescence staining showed that HMGB1 in the medium-and CORM-2-treated groups was predominantly localized in the nucleus of the cells,whereas higher amounts of HMGB1 translocated to the cytoplasm in the H2O2-and inactive CORM-2(i CORM-2)-treated groups.Western blotting of HMGB1 showed that the total amounts of cytoplasmic HMGB1 in the H2O2-treated(0.59±0.27) and i CORM-2-treated(0.57±0.22) groups were markedly higher than those in the medium-treated(0.19±0.05) and CORM-2-treated(0.21±0.10) groups(P<0.05).Co-immunoprecipitation showed that the levels of acetylated HMGB1 in the H2O2-treated(642.98±57.25) and i CORM-2-treated(342.11±131.25) groups were markedly increased as compared with the medium-treated(78.72±74.17) and CORM-2-treated(71.42±53.35) groups(P<0.05),and no significant difference was observed between the medium-treated and CORM-2-treated groups(P>0.05).In conclusion,our study demonstrated that in the in vitro oxidative stress injury model of primary RPTECs,CORM-2 can significantly inhibit the nuclear-cytoplasmic translocation of HMGB1,which is probably associated with the prevention of HMGB1 acetylation.展开更多
Background:Diabetic nephropathy(DN)is the most common complication of type 2 diabetes mellitus and the main cause of end-stage renal disease worldwide.Diagnostic biomarkers may allow early diagnosis and treatment of D...Background:Diabetic nephropathy(DN)is the most common complication of type 2 diabetes mellitus and the main cause of end-stage renal disease worldwide.Diagnostic biomarkers may allow early diagnosis and treatment of DN to reduce the prevalence and delay the development of DN.Kidney biopsy is the gold standard for diagnosing DN;however,its invasive character is its primary limitation.The machine learning approach provides a non-invasive and specific criterion for diagnosing DN,although traditional machine learning algorithms need to be improved to enhance diagnostic performance.Methods:We applied high-throughput RNA sequencing to obtain the genes related to DN tubular tissues and normal tubular tissues of mice.Then machine learning algorithms,random forest,LASSO logistic regression,and principal component analysis were used to identify key genes(CES1G,CYP4A14,NDUFA4,ABCC4,ACE).Then,the genetic algorithm-optimized backpropagation neural network(GA-BPNN)was used to improve the DN diagnostic model.Results:The AUC value of the GA-BPNN model in the training dataset was 0.83,and the AUC value of the model in the validation dataset was 0.81,while the AUC values of the SVM model in the training dataset and external validation dataset were 0.756 and 0.650,respectively.Thus,this GA-BPNN gave better values than the traditional SVM model.This diagnosis model may aim for personalized diagnosis and treatment of patients with DN.Immunohistochemical staining further confirmed that the tissue and cell expression of NADH dehydrogenase(ubiquinone)1 alpha subcomplex,4-like 2(NDUFA4L2)in tubular tissue in DN mice were decreased.Conclusion:The GA-BPNN model has better accuracy than the traditional SVM model and may provide an effective tool for diagnosing DN.展开更多
The exact solutions for the viscous fluid through a porous slit with linear absorption are obtained. The Stokes equation with non-homogeneous boundary conditions is solved to get the expressions for the velocity compo...The exact solutions for the viscous fluid through a porous slit with linear absorption are obtained. The Stokes equation with non-homogeneous boundary conditions is solved to get the expressions for the velocity components, pressure distribution, wall shear stress, fractional absorption, and leakage flux. The volume flow rate and mean flow rate are found to be useful in obtaining a convenient form of the longitudinal velocity component and pressure difference. The points of the maximum velocity components for a fixed axial distance are identified. The value of the linear absorption parameter is randomly chosen, and the rest available data of the rat kidney to the tabulate pressure drop and fractional absorption are incorporated. The effects of the linear absorption, uniform absorption, and flow rate parameters on the flow properties are discussed by graphs. It is found that forward flow occurs only if the volume flux per unit width is greater than the absorption velocity throughout the length of the slit, otherwise back flow may occur. The leakage flux increases with the increase in the linear absorption parameter. Streamlines are drawn to help the analysis of the flow behaviors during the absorption of the fluid flow through the renal tubule and purification of blood through an artificial kidney.展开更多
Background Hereditary renal tubular disease can cause hypercalciuria,acid-base imbalance,hypokalemia,hypomagnesemia,rickets,kidney stones,etc.If these diseases are not diagnosed or treated in time,they can cause kidne...Background Hereditary renal tubular disease can cause hypercalciuria,acid-base imbalance,hypokalemia,hypomagnesemia,rickets,kidney stones,etc.If these diseases are not diagnosed or treated in time,they can cause kidney damage and electrolyte disturbances,which can be detrimental to the maturation and development of the child.Glomerular involvement in renal tubular disease patients has only been considered recently.Methods We screened 71 papers(including experimental research,clinical research,etc.)about Dent's disease,Gitelman syndrome,and cystinosis from PubMed,and made reference.Results Glomerular disease was initially underestimated among the clinical signs of renal tubular disease or was treated merely as a consequence of the tubular damage.Renal tubular diseases affect glomerular podocytes through certain mechanisms resulting in functional damage,morphological changes,and glomerular lesions.Conclusions This article focuses on the progress of changes in glomerular podocyte function in Dent disease,Gitelman syndrome,and cystinosis for the purposes of facilitating clinically accurate diagnosis and scientific treatment and improving prognosis.展开更多
基金supported by the National Natural Science Foundation of China(No.81300574)
文摘Carbon monoxide(CO),as a vital small molecule in signaling pathways,is found to be involved in ischemia-reperfusion injury(IRI) in renal transplantation.CO-releasing molecule-2(CORM-2),a CO-releasing molecule,is a type of metal carbonyl complexes which can quickly release CO in vivo.In this study,an in vitro oxidative stress injury model was established to examine the effect of CORM-2 pretreatment on the nuclear-cytoplasmic translocation of high mobility group box 1 protein(HMGB1) in mouse primary renal proximal tubular epithelial cells(RPTECs).Immunofluorescence staining showed that HMGB1 in the medium-and CORM-2-treated groups was predominantly localized in the nucleus of the cells,whereas higher amounts of HMGB1 translocated to the cytoplasm in the H2O2-and inactive CORM-2(i CORM-2)-treated groups.Western blotting of HMGB1 showed that the total amounts of cytoplasmic HMGB1 in the H2O2-treated(0.59±0.27) and i CORM-2-treated(0.57±0.22) groups were markedly higher than those in the medium-treated(0.19±0.05) and CORM-2-treated(0.21±0.10) groups(P<0.05).Co-immunoprecipitation showed that the levels of acetylated HMGB1 in the H2O2-treated(642.98±57.25) and i CORM-2-treated(342.11±131.25) groups were markedly increased as compared with the medium-treated(78.72±74.17) and CORM-2-treated(71.42±53.35) groups(P<0.05),and no significant difference was observed between the medium-treated and CORM-2-treated groups(P>0.05).In conclusion,our study demonstrated that in the in vitro oxidative stress injury model of primary RPTECs,CORM-2 can significantly inhibit the nuclear-cytoplasmic translocation of HMGB1,which is probably associated with the prevention of HMGB1 acetylation.
基金the National Natural Science Foundation of China(Grant Number:81970631 to W.L.).
文摘Background:Diabetic nephropathy(DN)is the most common complication of type 2 diabetes mellitus and the main cause of end-stage renal disease worldwide.Diagnostic biomarkers may allow early diagnosis and treatment of DN to reduce the prevalence and delay the development of DN.Kidney biopsy is the gold standard for diagnosing DN;however,its invasive character is its primary limitation.The machine learning approach provides a non-invasive and specific criterion for diagnosing DN,although traditional machine learning algorithms need to be improved to enhance diagnostic performance.Methods:We applied high-throughput RNA sequencing to obtain the genes related to DN tubular tissues and normal tubular tissues of mice.Then machine learning algorithms,random forest,LASSO logistic regression,and principal component analysis were used to identify key genes(CES1G,CYP4A14,NDUFA4,ABCC4,ACE).Then,the genetic algorithm-optimized backpropagation neural network(GA-BPNN)was used to improve the DN diagnostic model.Results:The AUC value of the GA-BPNN model in the training dataset was 0.83,and the AUC value of the model in the validation dataset was 0.81,while the AUC values of the SVM model in the training dataset and external validation dataset were 0.756 and 0.650,respectively.Thus,this GA-BPNN gave better values than the traditional SVM model.This diagnosis model may aim for personalized diagnosis and treatment of patients with DN.Immunohistochemical staining further confirmed that the tissue and cell expression of NADH dehydrogenase(ubiquinone)1 alpha subcomplex,4-like 2(NDUFA4L2)in tubular tissue in DN mice were decreased.Conclusion:The GA-BPNN model has better accuracy than the traditional SVM model and may provide an effective tool for diagnosing DN.
文摘The exact solutions for the viscous fluid through a porous slit with linear absorption are obtained. The Stokes equation with non-homogeneous boundary conditions is solved to get the expressions for the velocity components, pressure distribution, wall shear stress, fractional absorption, and leakage flux. The volume flow rate and mean flow rate are found to be useful in obtaining a convenient form of the longitudinal velocity component and pressure difference. The points of the maximum velocity components for a fixed axial distance are identified. The value of the linear absorption parameter is randomly chosen, and the rest available data of the rat kidney to the tabulate pressure drop and fractional absorption are incorporated. The effects of the linear absorption, uniform absorption, and flow rate parameters on the flow properties are discussed by graphs. It is found that forward flow occurs only if the volume flux per unit width is greater than the absorption velocity throughout the length of the slit, otherwise back flow may occur. The leakage flux increases with the increase in the linear absorption parameter. Streamlines are drawn to help the analysis of the flow behaviors during the absorption of the fluid flow through the renal tubule and purification of blood through an artificial kidney.
文摘Background Hereditary renal tubular disease can cause hypercalciuria,acid-base imbalance,hypokalemia,hypomagnesemia,rickets,kidney stones,etc.If these diseases are not diagnosed or treated in time,they can cause kidney damage and electrolyte disturbances,which can be detrimental to the maturation and development of the child.Glomerular involvement in renal tubular disease patients has only been considered recently.Methods We screened 71 papers(including experimental research,clinical research,etc.)about Dent's disease,Gitelman syndrome,and cystinosis from PubMed,and made reference.Results Glomerular disease was initially underestimated among the clinical signs of renal tubular disease or was treated merely as a consequence of the tubular damage.Renal tubular diseases affect glomerular podocytes through certain mechanisms resulting in functional damage,morphological changes,and glomerular lesions.Conclusions This article focuses on the progress of changes in glomerular podocyte function in Dent disease,Gitelman syndrome,and cystinosis for the purposes of facilitating clinically accurate diagnosis and scientific treatment and improving prognosis.
