Objective: To observe the expression of TLR4 in kidney tissue of rats with diabetic nephropathy and discuss the role of TLR4 in the occurrence and development of the diabetic nephropathy. Methods: A total of 60 clean ...Objective: To observe the expression of TLR4 in kidney tissue of rats with diabetic nephropathy and discuss the role of TLR4 in the occurrence and development of the diabetic nephropathy. Methods: A total of 60 clean male SD rats were selected and randomly divided into the modeling group and control group after 1 week of breeding, including 30 rats in each group. Biochemical indices as well as the protein expression of TLR4 were observed and compared between two groups at 2 w, 4 w, 6 w, 8 w and 12 w after the modeling, and the correlation between TLR4 and each biochemical indexes was analyzed. Results: Rats in the modeling group had higher levels of blood glucose, 24-hour urine protein and blood urea nitrogen after the modeling, and showed the increase in the serum creatinine, kidney/body weight ratio, CRP and serum TNF-毩 at 4w after the modeling, with the significant difference compared to results of the control group ( P <0.05). The cross-section area and mean volume of glomerulus in the modeling group at 4 w, 6 w, 8 w and 12 w were significantly higher than those in the control group, with the statistically significant difference ( P <0.05). The expression of TLR4 at each time point in the control group was relatively low. Rats in the modeling group had the high expression of TLR4 in kidney's glomerular basement membrane, proximal convoluted tubule and renal interstitial area since 2 w, with the significant difference compared to the control group ( P <0.05). The expression in rats of the modeling group was higher than the one of the control group since the 2nd week. As the time flied, its expression increased, with the statistically significant difference between two groups ( P <0.05). There was certain correlation between the protein expression of TLR4 and the increased serum titer of 24hour urine protein excretion, serum creatinine, CRP and TNF-毩. Conclusions: TLR4 may activate the immuno-inflammatory reactions to play a role in the occurrence and development of the diabetic nephropathy.展开更多
In order to clarify whether gentamicin （GM） could damage the renal glomeruli,theultrastructural changes of the renal cortex were observed in rabbits after they received a singleinjection of 100 mg/kg GM or 100 mg...In order to clarify whether gentamicin （GM） could damage the renal glomeruli,theultrastructural changes of the renal cortex were observed in rabbits after they received a singleinjection of 100 mg/kg GM or 100 mg·kg<sup>-10</sup>·d<sup>-1</sup> GM for 3 consecutive days.The animals ofthe control group received equal amount of normal saline.It was found that some myelin figuresappeared in the epithelial cells of the proximal tubules as early as 1 h after a single GM injec-tion;severe swelling,degeneration,and obvious changes of the organelles were seen in the en-dothelial cells of the glomerular capillaries,the podocytes and the epithelial cells of the proxi-mal tubules 24 h after an injection of GM;and fusion of the processes of podocytes,thickeningof the glomerular membrane and necrosis of the epithelial cells of a part of the’proximal tubuleswere encountered 24h after the 3rd GM injection.These findings demonstrate that GM can in-jure not only the proximal tubules but also the glomeruli in rabbits.展开更多
Focal segmental glomerulosclerosis (FSGS) is characterized histologically by hyalinosis and sclerosis of glomeruli associated or not with podocyte involvement. The objective of our work was to clarify the epidemiologi...Focal segmental glomerulosclerosis (FSGS) is characterized histologically by hyalinosis and sclerosis of glomeruli associated or not with podocyte involvement. The objective of our work was to clarify the epidemiological aspects and histological variants of FSGS in Côte d’Ivoire. Materials and Methods: This was a descriptive retrospective study, conducted from January 2015 to December 2019 using the renal biopsy registers (RB) of the Pathological Anatomy and Cytology departments of the Teaching Hospital of Cocody and Bouake in collaboration with the Nephrology Services of Côte d'Ivoire and the sub-region. The biopsies underwent conventional histopathology and/or immunofluorescence techniques. The parameters analyzed were: frequency, age, gender, proteinuria, biopsy indications and histological aspects and the different correlations between histological aspects and socio-demographic characteristics. Results: FSGS represented 58.1% (n = 104) of glomerular nephropathies. The average age of patients was 32.1 ± 13.3 years, with extremes of 13 and 70 years. The sex ratio was equal to 1. Nephrotic syndrome (68.9%), chronic renal failure (14.3%) and acute renal failure (10.1%) were the main indications for renal biopsy (RB). The mean proteinuria at the time of diagnosis was 4 ± 3.7 g/24 h. It was massive (3.5 g/24 h) in 42.3% of patients. FSGS was primary in 29.8% (n = 31) and secondary in 70.2% (n = 73) of patients, of which 27.9% (n = 35) was due to HIV. According to the Columbia classification, 62.5% NOS type was found;23.1% collapsing type;7.7% tip lesion type;4.8% cell type and 1.9% perihilary type. Conclusion: FSGS is a complex heterogeneous entity. It affects young people in our context with a homogeneous gender distribution. Understanding its histogenesis is essential for optimal patient management.展开更多
Glomerular podocytes are highly specialized epithelial cells and play an essential role in establishing the selective permeability of the glomerular filtration barrier of kidney.Maintaining the viability and structura...Glomerular podocytes are highly specialized epithelial cells and play an essential role in establishing the selective permeability of the glomerular filtration barrier of kidney.Maintaining the viability and structural integrity of podocytes is critical to the clinical management of glomerular diseases,which requires a thorough understanding of podocyte cell biology.As mature podocytes lose proliferative capacity,a conditionally SV40 mutant tsA58-immortalized mouse podocyte line(designated as tsPC)was established from the Immortomouse over 20 years ago.However,the utility of the tsPC cells is hampered by the practical inconvenience of culturing these cells.In this study,we establish a user-friendly and reversibly-immortalized mouse podocyte line(designated as imPOD),on the basis of the tsPC cells by stably expressing the wildtype SV40 T-antigen,which is flanked with FRT sites.We show the imPOD cells exhibit long-term high proliferative activity,which can be effectively reversed by FLP recombinase.The imPOD cells express most podocyte-related markers,including WT-1,Nephrin,Tubulin and Vinculin,but not differentiation marker Synaptopodin.The imPOD cells do not form tumor-like masses in vivo.We further demonstrate that TGFb1 induces a podocyte injury-like response in the FLP-reverted imPOD cells by suppressing the expression of slit diaphragm-associated proteins P-Cadherin and ZO-1 and upregulating the expression of mesenchymal markers,a-SMA,Vimentin and Nestin,as well as fibrogenic factors CTGF and Col1a1.Collectively,our results strongly demonstrate that the newly engineered im-POD cells should be a valuable tool to study podocyte biology both under normal and under pathological conditions.展开更多
The etiology of chronic kidney disease(CKD)is complex and diverse,which could be briefly categorized to glomerular-or tubularoriginated.However,the final outcomes of CKD are mainly glomerular sclerosis,endothelial dys...The etiology of chronic kidney disease(CKD)is complex and diverse,which could be briefly categorized to glomerular-or tubularoriginated.However,the final outcomes of CKD are mainly glomerular sclerosis,endothelial dysfunction and injury,and chronic inflammation.Thus,targeted delivery of drugs to the glomeruli in order to ameliorate glomerular endothelial damage may help alleviate CKD and help enrich our knowledge.The herb tripterygium wilfordii shows therapeutic effect on kidney disease,and celastrol(CLT)is one of its active ingredients but with strong toxicity.Therefore,based on the unique structure and pathological characteristics of the glomerulus,we designed a targeted delivery system named peptides coupled CLT-phospholipid lipid nanoparticles(PC-PLNs)to efficiently deliver CLT to damaged endothelial cells and podocytes in the glomerulus for CKD treatment and research.PC-PLNs could effectively inhibit inflammation,reduce endothelial damage,alleviate CKD severity,and reduce the toxicity of CLT.We also studied the mechanism of CLT in the treatment of nephropathy and found that CLT can increase the level of NO by increasing eNOS while inhibiting the expression of VCAM-1,thus provides an anti-inflammatory effect.Therefore,our study not only offered an efficient CKD drug formulation for further development,but also provided new medical knowledge about CKD.展开更多
The Southern house mosquito Culex quinquefasciatus relies on its olfactory system to locate the human hosts for blood meals,by which several deadly diseases are transmitted.Olfactory sensory neurons(OSNs)housed in the...The Southern house mosquito Culex quinquefasciatus relies on its olfactory system to locate the human hosts for blood meals,by which several deadly diseases are transmitted.Olfactory sensory neurons(OSNs)housed in the sensilla on the olfactory appendages send their axons into the antennal lobes(ALs),the primary olfactory center in the brain,where the OSNs expressing the same olfactory receptors converge upon the same spherical structures known as glomeruli in the AL.The structure of the antennal lobe,that is,the spatial organization of the glomeruli,governs the insect's odor identification and discrimination.Drosophila studies have demonstrated the specific connections between receptors and glomeruli based on the 3D structure of the antennal lobe,deepening our understanding of the relationships between glomerular activities and behaviors,but as yet the structure of the Cx.quinquefasciatus antennal lobe remains unknown.We therefore constructed a 3D model of the Cx.quinquefasciatus antennal lobe using nc82 antibody staining,identifying 62 and 44 glomeruli in the female and male mosquito antennal lobe,respectively,with a significant sexual dimorphism in terms of the antennal lobe volume and glomerulus number.These results demonstrate the structural basis of mosquito odor coding and provide a platform for future studies of the mosquito olfactory signal processing mechanism.展开更多
Background: Glomerular disease is the leading cause of chronic kidney disease globally. No scoping review reports have focused on China’’s spectrum of glomerular diseases in children. This study aimed to systematica...Background: Glomerular disease is the leading cause of chronic kidney disease globally. No scoping review reports have focused on China’’s spectrum of glomerular diseases in children. This study aimed to systematically identify and describe retrospective studies on pediatric glomerular disease based on available data on sex, age, study period, and region.Methods: Six databases were systematically searched for relevant studies from initiation to December 2021 in PubMed, Embase, Web of Science, Global Health Library, Wangfang Database, and CNKI.Results: Thirty-four studies were identified in the scoping review, including 40,430 patients with biopsy-proven diagnoses. The proportion of boys was significantly higher than that of girls. In this study, 28,280 (70%) cases were primary glomerular disease, 10,547 (26.1%) cases were diagnosed as secondary glomerular disease, and 1146 (2.8%) cases were hereditary glomerular disease. Minimal change disease is the most common glomerular disease among children in China, followed by mesangial proliferative glomerulonephritis, IgA nephropathy, and purpura nephritis. We observed increments in glomerular diseases in periods 2 (2001–2010) and 3 (2011–2021). The proportion of major glomerular diseases varies significantly in the different regions of China.Conclusion: The spectrum of pediatric glomerular diseases varied across sex, age groups, study periods, and regions, and has changed considerably over the past 30 years.展开更多
文摘Objective: To observe the expression of TLR4 in kidney tissue of rats with diabetic nephropathy and discuss the role of TLR4 in the occurrence and development of the diabetic nephropathy. Methods: A total of 60 clean male SD rats were selected and randomly divided into the modeling group and control group after 1 week of breeding, including 30 rats in each group. Biochemical indices as well as the protein expression of TLR4 were observed and compared between two groups at 2 w, 4 w, 6 w, 8 w and 12 w after the modeling, and the correlation between TLR4 and each biochemical indexes was analyzed. Results: Rats in the modeling group had higher levels of blood glucose, 24-hour urine protein and blood urea nitrogen after the modeling, and showed the increase in the serum creatinine, kidney/body weight ratio, CRP and serum TNF-毩 at 4w after the modeling, with the significant difference compared to results of the control group ( P <0.05). The cross-section area and mean volume of glomerulus in the modeling group at 4 w, 6 w, 8 w and 12 w were significantly higher than those in the control group, with the statistically significant difference ( P <0.05). The expression of TLR4 at each time point in the control group was relatively low. Rats in the modeling group had the high expression of TLR4 in kidney's glomerular basement membrane, proximal convoluted tubule and renal interstitial area since 2 w, with the significant difference compared to the control group ( P <0.05). The expression in rats of the modeling group was higher than the one of the control group since the 2nd week. As the time flied, its expression increased, with the statistically significant difference between two groups ( P <0.05). There was certain correlation between the protein expression of TLR4 and the increased serum titer of 24hour urine protein excretion, serum creatinine, CRP and TNF-毩. Conclusions: TLR4 may activate the immuno-inflammatory reactions to play a role in the occurrence and development of the diabetic nephropathy.
文摘In order to clarify whether gentamicin （GM） could damage the renal glomeruli,theultrastructural changes of the renal cortex were observed in rabbits after they received a singleinjection of 100 mg/kg GM or 100 mg·kg<sup>-10</sup>·d<sup>-1</sup> GM for 3 consecutive days.The animals ofthe control group received equal amount of normal saline.It was found that some myelin figuresappeared in the epithelial cells of the proximal tubules as early as 1 h after a single GM injec-tion;severe swelling,degeneration,and obvious changes of the organelles were seen in the en-dothelial cells of the glomerular capillaries,the podocytes and the epithelial cells of the proxi-mal tubules 24 h after an injection of GM;and fusion of the processes of podocytes,thickeningof the glomerular membrane and necrosis of the epithelial cells of a part of the’proximal tubuleswere encountered 24h after the 3rd GM injection.These findings demonstrate that GM can in-jure not only the proximal tubules but also the glomeruli in rabbits.
文摘Focal segmental glomerulosclerosis (FSGS) is characterized histologically by hyalinosis and sclerosis of glomeruli associated or not with podocyte involvement. The objective of our work was to clarify the epidemiological aspects and histological variants of FSGS in Côte d’Ivoire. Materials and Methods: This was a descriptive retrospective study, conducted from January 2015 to December 2019 using the renal biopsy registers (RB) of the Pathological Anatomy and Cytology departments of the Teaching Hospital of Cocody and Bouake in collaboration with the Nephrology Services of Côte d'Ivoire and the sub-region. The biopsies underwent conventional histopathology and/or immunofluorescence techniques. The parameters analyzed were: frequency, age, gender, proteinuria, biopsy indications and histological aspects and the different correlations between histological aspects and socio-demographic characteristics. Results: FSGS represented 58.1% (n = 104) of glomerular nephropathies. The average age of patients was 32.1 ± 13.3 years, with extremes of 13 and 70 years. The sex ratio was equal to 1. Nephrotic syndrome (68.9%), chronic renal failure (14.3%) and acute renal failure (10.1%) were the main indications for renal biopsy (RB). The mean proteinuria at the time of diagnosis was 4 ± 3.7 g/24 h. It was massive (3.5 g/24 h) in 42.3% of patients. FSGS was primary in 29.8% (n = 31) and secondary in 70.2% (n = 73) of patients, of which 27.9% (n = 35) was due to HIV. According to the Columbia classification, 62.5% NOS type was found;23.1% collapsing type;7.7% tip lesion type;4.8% cell type and 1.9% perihilary type. Conclusion: FSGS is a complex heterogeneous entity. It affects young people in our context with a homogeneous gender distribution. Understanding its histogenesis is essential for optimal patient management.
基金The reported work was supported in part by research grants from the National Institutes of Health(CA226303 to TCH)the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906 to TCH)+1 种基金This project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430.
文摘Glomerular podocytes are highly specialized epithelial cells and play an essential role in establishing the selective permeability of the glomerular filtration barrier of kidney.Maintaining the viability and structural integrity of podocytes is critical to the clinical management of glomerular diseases,which requires a thorough understanding of podocyte cell biology.As mature podocytes lose proliferative capacity,a conditionally SV40 mutant tsA58-immortalized mouse podocyte line(designated as tsPC)was established from the Immortomouse over 20 years ago.However,the utility of the tsPC cells is hampered by the practical inconvenience of culturing these cells.In this study,we establish a user-friendly and reversibly-immortalized mouse podocyte line(designated as imPOD),on the basis of the tsPC cells by stably expressing the wildtype SV40 T-antigen,which is flanked with FRT sites.We show the imPOD cells exhibit long-term high proliferative activity,which can be effectively reversed by FLP recombinase.The imPOD cells express most podocyte-related markers,including WT-1,Nephrin,Tubulin and Vinculin,but not differentiation marker Synaptopodin.The imPOD cells do not form tumor-like masses in vivo.We further demonstrate that TGFb1 induces a podocyte injury-like response in the FLP-reverted imPOD cells by suppressing the expression of slit diaphragm-associated proteins P-Cadherin and ZO-1 and upregulating the expression of mesenchymal markers,a-SMA,Vimentin and Nestin,as well as fibrogenic factors CTGF and Col1a1.Collectively,our results strongly demonstrate that the newly engineered im-POD cells should be a valuable tool to study podocyte biology both under normal and under pathological conditions.
基金This work was supported by the Regional Innovation and Development Joint Fund(No.U20A20411)the National Science Fund for Excellent Young Scholars(No.82022070).
文摘The etiology of chronic kidney disease(CKD)is complex and diverse,which could be briefly categorized to glomerular-or tubularoriginated.However,the final outcomes of CKD are mainly glomerular sclerosis,endothelial dysfunction and injury,and chronic inflammation.Thus,targeted delivery of drugs to the glomeruli in order to ameliorate glomerular endothelial damage may help alleviate CKD and help enrich our knowledge.The herb tripterygium wilfordii shows therapeutic effect on kidney disease,and celastrol(CLT)is one of its active ingredients but with strong toxicity.Therefore,based on the unique structure and pathological characteristics of the glomerulus,we designed a targeted delivery system named peptides coupled CLT-phospholipid lipid nanoparticles(PC-PLNs)to efficiently deliver CLT to damaged endothelial cells and podocytes in the glomerulus for CKD treatment and research.PC-PLNs could effectively inhibit inflammation,reduce endothelial damage,alleviate CKD severity,and reduce the toxicity of CLT.We also studied the mechanism of CLT in the treatment of nephropathy and found that CLT can increase the level of NO by increasing eNOS while inhibiting the expression of VCAM-1,thus provides an anti-inflammatory effect.Therefore,our study not only offered an efficient CKD drug formulation for further development,but also provided new medical knowledge about CKD.
基金an award from the Alabama Agricultural Experiment Station(AAES)Multistate/Hatch Grants ALA08-045,ALA015-1-10026,and ALA015-1-16009 to N.L.NL,ZY,and FL conceived and designed the study.ZY and FL performed the experiments.NL prepared the materials.NL,ZY,and FL wrote the main manuscript.All authors reviewed the manuscript.
文摘The Southern house mosquito Culex quinquefasciatus relies on its olfactory system to locate the human hosts for blood meals,by which several deadly diseases are transmitted.Olfactory sensory neurons(OSNs)housed in the sensilla on the olfactory appendages send their axons into the antennal lobes(ALs),the primary olfactory center in the brain,where the OSNs expressing the same olfactory receptors converge upon the same spherical structures known as glomeruli in the AL.The structure of the antennal lobe,that is,the spatial organization of the glomeruli,governs the insect's odor identification and discrimination.Drosophila studies have demonstrated the specific connections between receptors and glomeruli based on the 3D structure of the antennal lobe,deepening our understanding of the relationships between glomerular activities and behaviors,but as yet the structure of the Cx.quinquefasciatus antennal lobe remains unknown.We therefore constructed a 3D model of the Cx.quinquefasciatus antennal lobe using nc82 antibody staining,identifying 62 and 44 glomeruli in the female and male mosquito antennal lobe,respectively,with a significant sexual dimorphism in terms of the antennal lobe volume and glomerulus number.These results demonstrate the structural basis of mosquito odor coding and provide a platform for future studies of the mosquito olfactory signal processing mechanism.
基金Pillar Program of National Science & Technology(Grant/Award Number: 2015BAI12B06)National key clinical specialty capacity building project(Grant/Award Number: 2019-542)。
文摘Background: Glomerular disease is the leading cause of chronic kidney disease globally. No scoping review reports have focused on China’’s spectrum of glomerular diseases in children. This study aimed to systematically identify and describe retrospective studies on pediatric glomerular disease based on available data on sex, age, study period, and region.Methods: Six databases were systematically searched for relevant studies from initiation to December 2021 in PubMed, Embase, Web of Science, Global Health Library, Wangfang Database, and CNKI.Results: Thirty-four studies were identified in the scoping review, including 40,430 patients with biopsy-proven diagnoses. The proportion of boys was significantly higher than that of girls. In this study, 28,280 (70%) cases were primary glomerular disease, 10,547 (26.1%) cases were diagnosed as secondary glomerular disease, and 1146 (2.8%) cases were hereditary glomerular disease. Minimal change disease is the most common glomerular disease among children in China, followed by mesangial proliferative glomerulonephritis, IgA nephropathy, and purpura nephritis. We observed increments in glomerular diseases in periods 2 (2001–2010) and 3 (2011–2021). The proportion of major glomerular diseases varies significantly in the different regions of China.Conclusion: The spectrum of pediatric glomerular diseases varied across sex, age groups, study periods, and regions, and has changed considerably over the past 30 years.
