Expression and effect of TLR4 in rats with diabetic nephropathy

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.

Ultrastructural features of gentamicin-induced glomerular damages in rabbits

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-10·d-1 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.

Optical coherence tomography of the living human kidney

Acute tubular necrosis(ATN)induced by ischemia is the most common insult to donor kidneysdestined for trarsplantation.ATN results from sweling and subsequent damage to cells lining thelkidney tubules.In this study,we demonstrate the capability of optical coherence tomography(OcT)to image the renal microst ructures of living human donor kidneys and potentially providea measure to det ermine the extent of A TN.We also found that Doppler-based OCT(i.e.,DOCT)reveals renal blood flow dynamics that is another major factor which could relate to post-transplant renal finction.All OCT/DoCT oberva tions were performed in a noninvasive,sterileand timely manner on intact human kidneys both prior to(er vivo)and following(in vivo)theirtransplantation.Our results indicate that this imaging model provides transplant surgeons withan objective visualization of the transplant lidneys prior and immediately post transplantation.

Focal Segmental Glomerulosclerosis in Côte d’Ivoire: Epidemiological, Clinical and Pathological Aspects

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 C&#244;te 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 C&#244;te 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.

Prenatal prednisone exposure disturbs fetal kidney development and its characteristics

Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary medication.Now,it is also recognized as an emerging environmental contaminant.Pregnantwomenmay be exposed to prednisone actively or passively throughmultiple pathways and cause developmental toxicity to the fetus.However,the impact of prenatal prednisone exposure(PPE)on fetal kidney development remains unclear.In this study,pregnant mice were administered prednisone intragastrically during full-term pregnancy with different doses(0.25,0.5,or 1 mg/(kg·day)),or at the dose of 1 mg/(kg·day)in different gestational days(GD)(GD0-9,GD10-18,or GD0-18).The pregnant mice were euthanized on GD18.HE staining revealed fetal kidney dysplasia,with an enlarged glomerular Bowman’s capsule space and a reduced capillary network in the PPE groups.The expression of the podocyte and the mesangial cell marker genes was significantly reduced in the PPE groups.However,overall gene expression in renal tubules and collecting ducts were markedly increased.All of the above effects were more pronounced in high-dose,full-term pregnancy,and female fetuses.Studies on the mechanism of the female fetal kidney have revealed that PPE reduced the expression of Six2,increased the expression of Hnf1β,Hnf4α,and Wnt9b,and inhibited the expression of glial cell line-derived neurotrophic factor(GDNF)and Notch signaling pathways.In conclusion,this study demonstrated that there is a sex difference in the developmental toxicity of PPE to the fetal kidney,and the time effect is manifested as full-term pregnancy>early pregnancy>mid-late pregnancy.

Genetic variation of mannose-binding protein associated with glomerular immune deposition in IgA nephropathy

OBJECTIVE: To investigate the relationship between codon 54 gene polymorphism of the host defense molecule, mannose-binding protein (MBP), and the patterns of glomerular immune deposition in IgA nephropathy (IgAN). METHODS: IgAN patients with different patterns of glomerular immune deposition were selected and divided into two groups. Group A consisted of 77 patients with glomerular IgA and C3 deposits, and Group AGM consisted of 70 patients with glomerular IgA, IgG, IgM, C3 and Clq deposits. Clinical features and laboratory relevant data of all patients were collected. One-hundred and forty healthy adults were recruited as normal controls. The MBP gene codon 54 GGC/GAC polymorphism was investigated by using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The genotype frequency of GGC/GAC heterozygotes was significantly higher in Group AGM as compared with that of Group A (41.4% vs 19.5%, P

he Spectrum of Biopsy-Proven Glomerular Disease in China： A Systematic Review

Background： Chronic kidney disease has become a leading public health concern in China, as it is associated with increased morbidity, mortality, and costs. However, the overall situation regarding common glomerular diseases in China remains unclear. Hence, the aim of this study was to assess the national profile of the common types ofglomerulonephritis in China. Methods： We searched Medline, Embase, Cochrane Library, CNKI, SinoMed, VIP, and Wanfang databases for English and Chinese language articles from inception to September 2017. We also collected potentially relevant studies and reviews using a manual search. The fbllowing words in combinations are as keywords： ＂renal biopsy＂, ＂kidney pathological diagnosis＂, and ＂spectrum of pathological types＂. Results： We identified 23 studies involving 176,355 patients from 15 provinces/cities in China. The detection rates of primary glomerulonephritis （PGN） and secondary glomerulonephritis （SGN） were 0.740 and 0.221, respectively. Over the past 30 years, the top five types of PGN were immunoglobulin A nephropathy （IgAN; 24.3%）, mesangial proliferative glomerulonephritis （MsPGN; 10.5%）, membranous nephropathy （MN; 12.6%）, minimal change disease （MCD; 9.8%）, and tbcal segmental glomerulosclerosis （FSGS; 4.6%）, and the top four types of SGN were lupus nephritis （LN; 8.6%）, Henoch-Sch6nlein purpura glomerulonephritis （4.1%）, hepatitis B virus-associated glomerulonephritis （HBV-GN; 2.6%）, and diabetic nephropathy （DN; 1.6%）. The proportion of MN, MCD, HBV-GN, and DN tended to increase, while those of IgAN, MsPGN, FSGS, and LN tended to drop. Conclusions： Although the incidence of SGN is increasing gradually, PGN is still the leading lbrm of kidney disease in patients undergoing renal biopsies in China. IgAN and LN are the most common types of PGN and SGN, respectively. Differences between regions are related to various factors such as nationality, environment, and diet. Furthermore, unified standards and norms for evahlating renal biopsies are urgently needed.

Glomerular chemokine expression and the effect of steroid and cyclophosphamide pulse therapy in human crescentic glomerulonephritis

OBJECTIVE: To study glomerular expression of C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha and beta (MIP-1alpha, MIP-1beta) and the effect of steroid and cyclophosphamide (CTX) intermittent intravenous pulse therapy on expression in patients with crescentic glomerulonephritis (CGN) to further investigate the underlying mechanism of the treatment. METHODS: Twelve patients with initial biopsy-proven CGN(2), 6 with lupus nephritis (lupus-CGN, LN-CGN) and 6 with vasculitis, (vasculitis-CGN, V-CGN) were enrolled in this study. They underwent an initial biopsy before steroid and CTX intermittent intravenous pulse therapy and were biopsied again one to three months later. Expression of MCP-1, MIP-1alpha, MIP-1beta, and CD68 in glomeruli with cellular and fibrocellular crescents were examined by immunohistochemical analysis in serial sections of renal biopsies. The effect of the pulse therapy on histopathological changes was also observed. RESULTS: Although steroid and CTX intermittent intravenous pulse therapy markedly reduced the degree of glomerular crescent formation both in LN-CGN and V-CGN, the effect of the therapy on glomerular chemokine expression was significantly different between LN-CGN and V-CGN. It was found that steroid and CTX intermittent intravenous pulse therapy reduced the expression of CD68, MCP-1, and MIP-1alpha, but had no effect on MIP-1beta in glomeruli with cellular crescents of patients with LN-CGN. In patients with V-CGN, the therapy also reduced the expression of CD68, but had no effect on MCP-1, MIP-1alpha, and MIP-1beta in glomeruli with cellular crescents. It was noted that the degree of glomerulosclerosis and tubular interstitial fibrosis increased more significantly at the second biopsy in V-CGN as compared to LN-CGN. CONCLUSIONS: The efficacy of steroid and CTX intermittent intravenous pulse therapy in CGN might be affected by reduction of glomerular chemokine expression. The different changes in glomerular expression of MCP-1 and MIP-1alpha in patients with LN-CGN and V-CGN after pulse therapy may correlate to different responses to treatment and prognosis.

Establishment and functional characterization of the reversibly immortalized mouse glomerular podocytes(imPODs)

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.

Three-dimensional structure of the antennal lobe in the Southern house mosquito Culex quinquefasciatus

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.

Targeted delivery of celastrol to glomerular endothelium and podocytes for chronic kidney disease treatment

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.

Epidemiology of biopsy-proven glomerular diseases in Chinese children: A scoping review

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.