Dendrobii Caulis Mixture-containing Serum Protects Mice from Podocyte Injury Induced by High Glucose / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Dendrobium mixture （DMix）-containing serum on high glucose-induced podocyte injury in mice. MethodThe MPC5 mouse glomerular podocytes were cultured in vitro， and the optimal glucose concentration for modeling， modeling time， and concentration of DMix-containing serum for administration were determined. The cells were classified into normal （5.5 mmol·L-1 glucose+10% blank serum）， model （30 mmol·L-1 glucose+10% blank serum）， DMix-containing serum （30 mmol·L-1 glucose+10% DMix-containing serum）， ferroptosis inhibitor （Fer-1， 30 mmol·L-1 glucose+10% blank serum+1 μmol·L-1 Fer-1） groups. The corresponding kits were used to measure the levels of Fe2+ and lactate dehydrogenase （LDH） in cells. Enzyme-linked immunosorbent assay was employed to determine the content of glutathione （GSH） and lipid peroxide （LPO） in cells. Fluorescence probe was used to measure the reactive oxygen species （ROS） level. Real-time fluorescence quantitative polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels， respectively， of Wilms' tumor-1 （WT-1）， desmin， long chain acyl-CoA synthase 4 （ACSL4）， and glutathione peroxidase 4 （GPX4） in podocytes. ResultCompared with the blank group， the intervention with 30 mmol·L-1 glucose for 48 h reduced podocyte viability （P<0.01）， and the 10% DMix-containing serum showed the most significant improvement in podocyte viability （P<0.01）. Compared with the normal group， the model group presented elevated levels of Fe2+， LDH， LPO， and ROS， lowered GSH level， up-regulated mRNA and protein levels of desmin and ACSL4， and down-regulated mRNA and protein levels of WT-1 and GPX4 （P<0.01）. Compared with the model group， the DMix-containing serum lowered the Fe2+， LDH， LPO， and ROS levels， elevated the GSH level， down-regulated the mRNA and protein levels of desmin and ACSL4， and up-regulated the mRNA and protein levels of WT-1 and GPX4 in podocytes （P<0.05， P<0.01）. ConclusionDMix-containing serum exerts a protective effect on high glucose-induced podocyte injury by inhibiting ferroptosis.

TCM Treatment of Podocyte Injury in IgA Nephropathy Based on Multiple TCM Theories： A Review / 中国实验方剂学杂志

IgA nephropathy is the most common primary glomerular disease in China. Its clinical manifestations are mainly proteinuria， hematuria， hypertension， edema， hyperuricemia， etc. Most patients have hidden onset. 30%-40% of patients develop into end stage renal disease 10-20 years after diagnosis and rely on dialysis or kidney transplantation to maintain their lives， which is extremely harmful. Proteinuria is a common clinical manifestation of this disease， and most patients have small-to-moderate amounts of proteinuria， while 10%-24% of patients have large amounts of proteinuria. Proteinuria is the main risk factor affecting the progression of renal function in IgA nephropathy. Podocytes are the terminal part of the glomerular filtration barrier， and various factors can affect the fusion and detachment of podocyte processes that occur after podocyte injury. They are common histological lesions in IgA nephropathy and are key factors leading to proteinuria and the continuous progression of the disease. At present， Western medicine lacks targeted treatment for podocyte injury， with limited intervention methods. Drugs such as glucocorticoids are often used for treatment， and there are many adverse reactions. Based on the physiological function of podocytes， pathological and physiological changes after injury， and histological morphology of this disease， it is believed that it is closely related to traditional Chinese medicine's "Xuanfu Theory" "Kidney Collateral Syndrome" "Collateral Disease Theory"， and "Dry Blood Theory". More and more studies have shown that traditional Chinese medicine， which has the characteristics of multiple links， pathways， and targets， has a significant therapeutic effect on podocyte injury in IgA nephropathy. It can protect podocytes and reduce proteinuria and has good application and research prospects. This article systematically summarizes the mechanism and morphological changes of podocyte injury in IgA nephropathy， the understanding of podocyte injury in traditional Chinese medicine theory， and the research progress in traditional Chinese medicine treatment of podocyte injury in IgA nephropathy， so as to provide a reference for further research and application of traditional Chinese medicine intervention in podocyte injury in IgA nephropathy.

Progress on the mechanism of rituximab in the treatment of primary nephrotic syndrome / 国际儿科学杂志

In recent years, rituximab(RTX) has been increasingly used in the treatment of refractory primary nephrotic syndrome in children, and has achieved positive effects.Experimental evidence suggests that RTX may exert its therapeutic effects by directly acting on B cells and T cells, interfering with the interaction between B cells and T cells, and directly protecting podocytes.However, the number of studies on the mechanism of RTX in the treatment of nephrotic syndrome is limited and there is no definitive evidence, so there is no consensus in the academic community.This article summarizes experimental research results and reasonable speculations put forward by many scholars in recent years, and summarizes the significance of the research on the mechanism of RTX and the existing research gaps in this field, in order to provide theoretical guidance for the clinical application of RTX.

Role of suPAR in the Pathogenesis of Podocyte Injury of Primary Focal Segmental Glomerulosclerosis / 中山大学学报(医学科学版)

ObjectiveThis study aims to investigate the role of suPAR in the pathogenesis of podocyte injury in FSGS. Methods① The sera of primary FSGS patients （17 cases） were collected. Healthy volunteers （10 cases） and patients with other types of primary nephrotic syndrome （10 cases） were set as normal and disease controls. SuPAR levels were detected by ELISA； ② Podocytes were stimulated by suPAR in vitro， and cells were collected to analyze apoptosis by flow cytometry and for RNAseq analysis； ③ Differentially expressed genes （DEGs） were screened from RNAseq data. Both up-regulated and down-regulated genes were analyzed by KEGG and GO enrichment analysis. Heat map was used to show expression of genes related to podocyte focal adhesion， slit diaphragm and actin dynamics and endocytosis. Differentially expressed genes were verified by qPCR. Results① The level of suPAR in FSGS patients was significantly increased， and that in other nephrotic syndrome（NS） patients was also significantly increased； ② suPAR stimulation significantly altered the transcriptome pattern of human podocytes. A total of 272 up-regulated genes and 288 down-regulated genes were screened； ③ KEGG and GO enrichment analysis of up-regulated and down-regulated genes showed that Focal adhesion and DNA replication and DNA repair related pathways were significantly down-regulated； ④ suPAR did not increase podocyte apoptosis. ConclusionThe level of suPAR is significantly increased in patients with primary FSGS. SuPAR may promote podocyte injury by interfering with genomic homeostasis and disrupting focal adhesion， slit diaphragm， actin dynamics and endocytosis-related functional molecules of podocytes.

Effects and mechanisms of total flavones of Abelmoschus manihot in improving insulin resistance and podocyte epithelial-mesenchymal transition in diabetic kidney disease based on IRS1/PI3K/Akt pathway / 中国中药杂志

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.

Role of podocyte injury signaling pathway in steroid-resistant nephrotic syndrome and research progress in traditional Chinese medicine intervention / 中国中药杂志

As one of the main diseases leading to end-stage renal disease, steroid-resistant nephrotic syndrome(SRNS) can cause serious complications such as infection. Without effective control, this disease can further lead to the malignant development of the renal function, bringing serious social and economic burdens. As previously reported, the formation of SRNS is mostly related to the podocyte injury in the body, i.e., the injury of glomerular visceral epithelial cells. Phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, nuclear transcription factor-κB(NF-κB) signaling pathway, mammalian target of rapamycin(mTOR)/adenosine monophosphate(AMP)-activated protein kinase(AMPK), transforming growth factor(TGF)-β1/Smads, and other signaling pathways are classical signaling pathways related to podocyte injury. By regulating the expression of signaling pathways, podocyte injury can be intervened to improve the adhesion between podocyte foot processes and glomerular basement membrane and promote the function of podocytes, thereby alleviating the clinical symptoms of SRNS. Through the literature review, traditional Chinese medicine(TCM) has unique advantages and an important role in intervening in podocyte injury. In the intervention in podocyte injury, TCM, by virtue of multi-target and multi-pathway role, can regulate and intervene in podocyte injury in many ways, alleviate the clinical symptoms of SRNS, and interfere with the progress of SRNS, reflecting the unique advantages of TCM. On the other hand, TCM can directly or indirectly inhibit podocyte injury by regulating the above signaling pathways, which can not only promote the effect of hormones and immunosuppressants and shorten the course of treatment, but also reduce the toxic and side effects caused by various hormones and immunosuppressants to exert the advantages of small side effects and low price of TCM. This article reviewed TCM in the treatment of SRNS by interfering with podocyte injury-related signaling pathways and is expected to provide a reference for the in-depth study of TCM in the treatment of SRNS, as well as a theoretical basis and a new direction for the clinical application of TCM to shorten the course of treatment of SRNS and delay the progression to end-stage renal disease.

Ang-(1-7) attenuates podocyte injury induced by high glucose in vitro

ABSTRACT Objective: The incidence of diabetic nephropathy (DN) is gradually increasing worldwide. Podocyte injury, such as podocyte apoptosis and loss of the slit diaphragm (SD)-specific markers are early pathogenic features of DN. Materials and methods: The cultured mouse podocytes were separated into a high glucose-treated (HG, 30mM) group to mimic DN in vitro, a low glucose-treated (LG, 5mM) group as a control and HG+ angiotensin-(1-7)(Ang-(1-7)) and HG+Ang-(1-7) + D-Ala7-Ang-(1-7) (A779, Ang-(1-7)/Mas receptor antagonist) experimental groups. The Cell Counting Kit-8 (CCK-8) method and flow cytometry was used to detect podocyte activity and podocyte apoptosis respectively. The expression of angiotensin type 1 receptor (AT1R), Mas receptor (MasR) and podocyte-specific markers were examined by q-PCR and Western blot, respectively. Results: The results showed that the decrease in podocyte activity; the increase in podocyte apoptosis; the decreased mRNA and protein expression of nephrin, podocin, WT-1 and MasR; and the upregulated expression of AT1R induced by HG could be reversed by Ang-(1-7). However, these effects were blocked by A779. The possible mechanisms of the Ang-(1-7)-mediated effect depended on MasR. In addition, the protective effect of Ang-(1-7) on podocyte activity was dose-dependent and most obvious at 10 µM. A779 had the greatest antagonistic action against Ang-(1-7) at a concentration of 10 μM. Conclusion: This study reveals that binding of Ang-(1-7) to its specific receptor MasR may counteract the effects of Ang II mediated by AT1R to significantly attenuate podocyte injury induced by high glucose. Ang-(1-7)/MasR targeting in podocytes may be a therapeutic approach to attenuate renal injury in DN.

Searching for potential biomarkers reflecting early injury and progressive of podocytes in nephropathy based on cellular metabolomics combined with ROC analysis / 药学学报

The pathogenesis of the nephrotic syndrome is complex and the pathological types are diverse, so the minor symptoms in its early phases are difficult to detect. Renal biopsy is the gold indicator for the diagnosis of renal pathology and progression, but poor patient compliance shows, and the optimal treatment time is often delayed. Therefore, the discovery of biomarkers for early diagnosis and disease progression monitoring is of great clinical significance. In this study, doxorubicin-injured podocyte models were used to simulate human kidney disease at different stages of progression. LC-MS-based metabolomic technology combined with statistical methods was used to screen and identify the potential biomarkers associated with early injury or progression of podocytes. The results of cell viability, apoptosis tests and podocyte structural protein analysis showed that the model was successfully constructed, and the degree of podocyte injury was significantly different between the two modeling methods. According to VIP > 1 and P < 0.05 based on the orthogonal partial least squares discriminant analysis (OPLS-DA) model, nine differential metabolites reflecting early podocyte injury and twelve differential metabolites reflecting the injury progression were screened, respectively. ROC analysis was adopted to focus on the potential biomarkers that can reflecting the early podocyte injury including L-tryptophan, guanosine triphosphate (GTP), 5′-thymidylic acid (dTMP) and thymidine, and the biomarkers reflecting the injury progression of podocytes composed of L-phenylalanine, L-tyrosine acid, uridine 5′-diphosphate (UDP) and guanosine 5′-diphosphate (GDP) AUC > 0.85. It indicated that these eight metabolites may have high sensitivity and diagnostic ability. This study provides a reference for the research on biomarkers of progressive diseases.

Traditional Chinese Medicine Intervention in Membranous Nephropathy Based on Podocyte Injury： A Review / 中国实验方剂学杂志

Membranous nephropathy， an autoimmune kidney disease with glomerular podocyte injury as the core mechanism， is a common pathological type of adult nephrotic syndrome and has become the main cause of end-stage renal disease in China. Podocytes are terminally differentiated cells that play an important role in maintaining the structural and functional stability of glomeruli and are molecular barriers for protein filtration. Glomerular filtration membrane injury induced by podocyte injury is an important cause of massive proteinuria. Persistent or aggravated proteinuria may prolong the course of membranous nephropathy. It is believed that podocyte destruction in membranous nephropathy is mainly related to oxidative stress， autophagy dysregulation， abnormal expression of podocyte marker proteins， chronic inflammation， epithelial-mesenchymal cell transdifferentiation， and so on. At present， western medicine mostly uses immunosuppressants and hormones for treatment according to its pathological stage， but there are certain adverse reactions. Traditional Chinese medicine （TCM） has made some achievements in the prevention and treatment of membranous nephropathy. In recent years， studies have found that many Chinese medicines can affect the occurrence and development of membranous nephropathy in different links by acting on multiple targets in the human body， with manifest advantages. This paper overviewed the podocyte injury mechanism in membranous nephropathy and summarized the treatment of membranous nephropathy with Chinese medicine monomers， compounds， and Chinese patent medicines in intervening related target pathways， aiming to provide a basis for the clinical treatment， basic research， and targeted drug development of TCM against membranous nephropathy.

Astragaloside IV improves podocyte injury and mitochondrial dysfunction induced by high glucose and inhibits Notch pathway activation / 西安交通大学学报(医学版)

【Objective】 To investigate the protection of astragaloside IV from high glucose induced podocyte injury and mitochondrial dysfunction and its molecular mechanisms. 【Methods】 The model of podocyte injury induced by high glucose (30 mmol/L glucose) was established, and the model cells were treated with low, medium and high doses of astragaloside IV respectively; cell activity was detected by CCK-8. Apoptosis was detected by TUNEL staining. Mitochondrial membrane potential was detected by JC-1 fluorescence probe. ATP content was detected by the kit. The expression levels of apoptosis and podocyte injury related proteins and Notch pathway related proteins were detected by Western blotting. 【Results】 Compared with the control group, cell activity was decreased, apoptosis level was increased (P<0.05), anti-apoptotic protein (Bcl2) expression was decreased, and apoptosis protein (Bax, cleaved-caspase 9, cleaved-caspase 3) expressions were increased (all P<0.05) in HG group. Compared with HG group, HG+AS-IV improved cell activity and apoptosis level induced by high glucose (P<0.05), increased expression of anti-apoptotic protein (Bcl2), and decreased expressions of apoptotic protein (Bax, cleaved-caspase 9, and cleaved-caspase 3) (all P<0.05). Compared with the control group, mitochondrial dysfunction occurred in HG group, JC-1 monomer content increased, and ATP content decreased (all P<0.05). Compared with HG group, HG+AS-IV improved mitochondrial dysfunction, increased JC-1 polymer content and ATP content (P<0.05). In addition, compared with the control group, the expression of Notch pathway-related protein was decreased in HG group (P<0.05). Compared with HG group, Notch pathway-related protein expression was increased in HG+AS-IV group (all P<0.05). Molecular docking results showed that AS-IV could bind Notch1. 【Conclusion】 Astragaloside IV can improve podocyte injury and mitochondrial dysfunction induced by high glucose, possibly by inhibiting Notch pathway activation.

A case of podocyte infolding glomerulopathy / 中华肾脏病杂志

Podocyte infolding glomerulopathy (PIG) is a pathologic type of podocyte glomerulopathy reported recently. The characteristic is that the ultrastructure related to podocytes, such as microspheres and microtubules, are folded into the glomerular basement membrane (GBM) under electron microscope. At present, there are few reports about this disease at home and abroad, and most of them are concentrated in Japan. The clinical characteristics and pathogenesis of PIG are still unclear. In this paper, we report a case of clinical manifestations of nephrotic syndrome, renal biopsy indicated PIG, after the treatment of glucocorticoid, hydroxychloroquine and tacrolimus, the patient's clinical symptoms were relieved and urinary protein decreased.

Clinicopathological features analysis of focal segmental glomerulosclerosis after kidney transplantation / 器官移植

Objective To investigate the clinicopathological features of recurrent and de novo focal segmental glomerulosclerosis (FSGS) after kidney transplantation. Methods Thirty-four recipients pathologically diagnosed with FSGS by renal allograft biopsy were enrolled in this clinical trial. According to the detection of primary diseases of renal allografts and circulating permeability factors, 34 recipients were divided into the recurrent FSGS group (n=12) and de novo FSGS group (n=22). The differences of clinical indexes and the degree of pathological injury of renal allografts were compared between two groups. Results There was no significant difference in the mesangial hyperplasia score, glomerulosclerosis rate, renal tubular atrophy score, interstitial fibrosis score and podocyte proliferation rate between two groups (all P > 0.05). In the recurrent FSGS group, segmental glomerulosclerosis rate of the recipients was 0.10 (0.08, 0.27), lower than 0.19 (0.13, 0.33) in the de novo FSGS group (P < 0.05). No significant difference was found in the incidence of antibody-mediated rejection, drug-induced renal tubular injury and BK virus infection between two groups (all P > 0.05). The incidence of T cell-mediated rejection in the recurrent FSGS group was 17%, lower than 55% in the de novo FSGS group (P < 0.05). Immunohistochemical staining showed that the infiltrating inflammatory cells in the renal allografts were mainly T lymphocytes. The positive rates of C4d deposition in peripheral capillaries between the recurrent and de novo FSGS groups were 33% (4/12) and 32% (7/22), with no significant difference (P > 0.05). Immunofluorescence results revealed IgM deposition in the segmental glomerulosclerosis area of renal allografts in most cases. Electron microscopy showed extensive fusion or segmental distribution of podocytes in the glomerulus of renal allografts. Conclusions The degree of renal functional injury and the incidence of T cell-mediated rejection in the recurrent FSGS group are lower than those in the de novo FSGS group. Comprehensive analysis of preoperative and postoperative clinical manifestations, laboratory testing and pathological examination of kidney transplant recipients contribute to early diagnosis and treatment of recurrent and de novo FSGS.

Progress of glomerular injury in type Ⅰ cardiorenal syndrome / 国际儿科学杂志

Type Ⅰ cardiorenal syndrome is a common disease syndrome in clinic.Cardiac surgery and acute heart failure caused by various causes are common causes of type Ⅰ cardiorenal syndrome.More recognized pathogenesis includes overactivation of sympathetic nervous system and renin-angiotensin-aldosterone system, renal ischemia-reperfusion, inflammatory response and oxidative stress.In the current research, most of the renal injuries caused by type Ⅰ cardiorenal syndrome are related to renal tubular epithelial injury, but there are few reports on glomerular injury.With the continuous in-depth study, more and more people realize that glomerular injury plays an important role in the occurrence and progress of acute renal injury.This paper mainly reviews the research progress and future research direction of glomerular injury in type Ⅰ cardiorenal syndrome.

Hyperbilirubinemia induced oxidative stress resulting in glomerular injury in rats / 中华危重病急救医学

Objective:To observe the effect of hyperbilirubinemia on glomerulus of rats, and to explore its dose-response and mechanism.Methods:Twenty-four adult male Sprague-Dawley (SD) rats were divided into four groups according to the random number table method, with 6 rats in each group. Hyperbilirubinemia rat model was reproduced by intraperitoneal injection of bilirubin once every 12 hours for 4 times, at doses of 50, 100, and 200 mg/kg in low, medium, and high dose bilirubin group (LB group, MB group, HB group), respectively. The rats in negative control group (NC group) were given the same solvent without bilirubin powder. Urine was collected 24 hours after administration, and total protein (TP) level was detected. Then the rats were sacrificed, the blood was collected by cardiac puncture, and the total bilirubin (TBil) and direct bilirubin (DBil) levels were measured by automatic biochemical analyzer. The renal tissue was collected and stained with periodic acid-Schiff (PAS) staine, the glomerular morphology was observed under light microscope, and the glomerular injury score was performed. Podocyte morphology was observed by transmission electron microscopy after uranium acetate and lead citrate double staining. The activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) were determined by colorimetric method. The expression level of podocyte specific marker Wilms tumor protein-1 (WT-1) was determined by Western blotting.Results:With the increase of bilirubin dose, the contents of 24-hour urine TP, blood TBil, blood DBil and MDA content in kidney tissue were gradually increased, and the SOD activity and WT-1 expression in kidney tissue were gradually decreased. The differences between LB group, MB group, HB group and NC group were statistically significant [24-hour urine TP (mg): 24.85±2.22, 52.57±3.66, 56.84±3.49 vs. 7.50±1.33; blood TBil (μmol/L): 37.75±2.19, 81.37±2.13, 125.13±9.96 vs. 5.53±0.41; blood DBil (μmol/L): 15.50±1.96, 37.88±1.05, 64.53±2.89 vs. 2.38±0.35; kidney MDA (μmol/g): 3.14±0.65, 5.01±0.28, 7.50±1.08 vs. 2.30±0.20; kidney SOD (kU/g): 95.91±10.43, 57.06±15.90, 37.12±11.72 vs. 113.91±12.16; kidney WT-1 protein (WT-1/GAPDH): 0.280±0.006, 0.239±0.006, 0.198±0.001 vs. 0.361±0.005; all P < 0.05]. It was shown under light microscope that uneven thickness of mesangial membrane and basement membrane of the glomerulus, and some of them were accompanied by hyperplasia and widening. The glomerular injury score increased with the increase in bilirubin dose. The differences between LB group, MB group, HB group and NC group were statistically significant (17.50±1.05, 25.00±1.41, 34.00±1.41 vs. 11.67±0.82, all P < 0.05). Transmission electron microscopy showed that with the increase of bilirubin dose, the damage of glomerular podocytes was aggravated. Conclusions:Hyperbilirubinemia induced damage to glomerulus in a dose-dependent manner. In the lethal dose range, the higher the dose, the stronger the damage, which might be related to the oxidative stress promoted by bilirubin and the damage of glomerular podocytes.

Mechanism of adrenocorticotropic hormone in the treatment of nephrotic syndrome / 中华实用儿科临床杂志

In recent years, it has been demonstrated in some studies that adrenocorticotropic hormone (ACTH) is effective in the treatment of certain steroid-resistant nephrotic syndrome, including membranous nephropathy, focal segmental glomerular sclerosis, minimal change nephropathy and so forth.ACTH can effectively relieve proteinuria and protect renal function, suggesting that there may be other mechanisms in addition to the adrenocorticotropic effect.This article mainly introduces the biological characteristics of ACTH, in combination with the clinical and basic studies on the treatment of nephrotic syndrome by ACTH, and clarifies several possible mechanisms, in an attempt to provide basis for clinical application.

Effect of Danggui Buxuetang on Podocyte Pyroptosis in Diabetic Kidney Disease Rats： An Exploration Based on TXNIP/NLRP3/GSDMD Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Danggui Buxuetang on podocyte pyroptosis in diabetic kidney disease （DKD） rats and to explore the possible mechanism of its prevention and treatment of DKD and podocyte pyroptosis. MethodEight of the 50 male SD rats were randomly classified into a normal group， and the remaining 42 were fed a high-glucose and high-fat diet for six weeks and then intraperitoneally injected with 35 mg·kg-1 streptozotocin （STZ） for inducing type 2 diabetes. After successful modeling， they were randomized into the model group， low- （0.72 g·kg-1） and high-dose （1.44 g·kg-1） Danggui Buxuetang group， and irbesartan （0.017 g·kg-1） group and gavaged with the corresponding drugs， while those in the normal group and model group with an equal volume of normal saline， once per day， for 20 weeks. During the medication， the fasting blood glucose （FBG） and 24 h urine protein （24 h-UTP） were measured regularly. After administration， the pathological changes in renal tissues were observed by periodic acid-silver metheramine （PASM） staining， followed by the observation of ultrastructural changes in podocytes under the transmission electron microscope （TEM）. Serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were determined by enzyme-linked immunosorbent assay （ELISA）. The DNA damage in renal tissue cells of rats was detected by in situ nick end-labeling （TUNEL） assay. The protein expression levels of thioredoxin interacting protein （TXNIP）， cysteine-dependent aspartate-directed protease-1 （Caspase-1）， and gasdermin D （GSDMD） in renal tissues of rats were detected by immunohistochemistry （IHC）， the expression levels of nucleotide binding domain like receptor protein 3 （NLRP3） and Wilms tumor protein-1 （WT-1） in podocytes by immunofluorescent （IF） staining， and the expression levels of TXNIP/NLRP3/Caspase-1/GSDMD pathway proteins and Synaptopodin in renal podocytes by Western blot. ResultCompared with the normal group， the model group exhibited increased FBG and 24 h UTP， glomerular hypertrophy， mesangial hyperplasia， increased extracellular matrix， thickened basement membrane， K-W nodules， vacuolar degeneration in renal tubular epithelial cells， foot process fusion or loss， elevated serum IL-1β and IL-18 levels and TUNEL-positive cells in renal tissue， enhanced NLRP3 but diminished WT-1 expression in podocytes， down-regulated Synaptopodin protein expression， and up-regulated TXNIP/NLRP3/Caspase-1/GSDMD protein expression （P<0.01）. Compared with the model group， Danggui Buxuetang high-dose group remarkably lowered FBG， 24-h UTP， and TUNEL-positive cells in renal tissue， improved renal histopathology and podocyte injury and loss， down-regulated NLRP3 expression in podocytes and TXNIP/NLRP3/Caspase-1/GSDMD protein expression levels， and up-regulated WT-1 expression in podocytes and Synaptopodin protein expression （P<0.05， P<0.01）. ConclusionDanggui Buxuetang inhibits podocyte pyroptosis to reduce proteinuria and delays the development of DKD possibly by regulating the TXNIP/NLRP3/GSDMD signaling pathway.

Relationship Between Podocyte Autophagy and Diabetic Nephropathy and Regulation of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Diabetic nephropathy （DN） is one of the serious microvascular complications of diabetes mellitus （DM），and is the main cause of end-stage renal disease（ESRD） worldwide. Although lowering blood glucose and，lowering blood pressure and blocking the renin-angiotensin-aldosterone system（RAAS） can reduce blood glucose，blood pressure and urinary protein to a certain extent，it is still difficult to prevent the progression of DN sometimes. The curative effect of traditional Chinese medicine on DN has been confirmed，but its mechanism is has not been fully clarified. Autophagy is a highly conserved lysosomal degradation pathway in mammals that removes protein aggregates and damaged organelles to maintain cell homeostasis. Podocyte，also known as glomerular epithelial cells，is an important component in maintaining the homeostasis of glomerular filtration barrier，and podocyte injury is considered to be a central link in the occurrence and development of DN. As a highly differentiated cell，podocyte maintains a high level of autophagy to maintain its homeostasis under physiological conditions. In DN state，mammalian target of rapamycin （mTOR），AMP-activated protein kinase （AMPK），silent information regulator 1（SIRT1） and other nutritional signaling pathways as well as intracellular stress response signaling pathways such as oxidative stress，endoplasmic reticulum stress ，and hypoxia stress，etc.，affect podocyte autophagy of podocytes， and ultimately leading to podocyte injury and the progression of DN. In recent years，regulation of podocyte autophagy has become one of the hot spots in DN research，and has also received extensive attention in the field of Chinese medicine. A review and summary of the domestic and international literature in this field reveals that Chinese medicine can affect podocyte autophagy in multiple pathways and targets. Nevertheless， those studiesbut mainly focuses on two nutrient-sensing signaling pathways，mTOR and AMPK，and there lacks more comprehensive and in-depth mechanism studies. In addition，the current research mainly concentrates focuses on the field of Chinese medicine monomers and Chinese medicine compounds，and rarely studies multi-component Chinese medicinelacking research on Chinese medicine component drugs and single drugs，and the research still lacks there is a lack of hierarchy. The regulatory mechanism of Chinese medicine on podocyte autophagy of podocytes in DN state in Chinese medicine still needs to be further studied in depth and systematically.

Jiangzhi Tongluo Soft Capsules Regulate SIRT1/FoxO3 Pathway to Affect Cell Apoptosis in Rats with Membranous Nephropathy / 中国实验方剂学杂志

ObjectiveTo observe the effect of Jiangzhi Tongluo soft capsule on the protein levels of silent mating-type information regulation 2 homolog 1 （SIRT1） and forkhead transcription factor FoxO3 and podocyte apoptosis in the renal tissue of rats with membranous nephropathy and to reveal the underlying molecular mechanisms for the treatment of MN. MethodSixty male SD rats were randomly assigned into 6 groups with 10 rats each. The six groups included a normal group， a model group， benazepril hydrochloride group， and Jiangzhi Tongluo soft capsule groups of low， medium and high doses （25， 50， 100 mg·kg-1， respectively）. The model rats were established by injection with cationized bovine serum albumin into the tail vein. After modeling， the rats were administrated with corresponding agents by gavage for 4 weeks. At the end of the 4th week， an electron microscope was used to observe the pathological changes in the kidney. Western blot was employed to detect the protein levels of SIRT1 and FoxO3 protein in rat kidney， and immunohistochemistry to detect the expression of B lymphocytoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， Bcl-2-associated death promoter （Bad）， and podocyte split diaphragm proteins nephrin and podocin. ResultCompared with normal group， the expression of pro-apoptotic factors Bax， Bad， and FoxO3 in the kidney was up-regulated （P<0.05）， while that of anti-apoptotic factors Bcl-2， SIRT1， nephrin， and podocin was down-regulated （P<0.05） after modeling. Compared with the model group， the treatments down-regulated the expression of Bax， Bad， and FoxO3 （P<0.05） and up-regulated that of Bcl-2， SIRT1， nephrin， and podocin （P<0.05）. ConclusionJiangzhi Tongluo soft capsule may regulate the SIRT1/FoxO3 pathway to reduce podocyte apoptosis and maintain podocyte structure stability， thereby exerting the renal protection effect.

Clinical Effect of Jianpi Yangyin Guse Decoction on Podocin and Nephrin and Its Protection Against Podocyte Injury in Diabetic Nephropathy Patients with Qi and Yin Deficiency / 中国实验方剂学杂志

ObjectiveTo observe the clinical effect of Jianpi Yangyin Guse decoction on patients with diabetic nephropathy （DN），and to explore its protection against podocyte injury. MethodThe enrolled 120 DN patients at stages Ⅲ and Ⅳ and diagnosed with Qi and Yin deficiency from January 2017 to January 2020 were randomly divided into observation group and control group. During the same period，20 healthy volunteers were recruited as the normal group. In addition to the basic treatment in control group，patients in the observation group were given Jianpi Yangyin Guse decoction，and the course of treatment lasted for 3 months. The traditional Chinese medicine （TCM）syndrome score，24 h urine protein （24 h UP），urine albumin-to-creatinine ratio（UACR），liver and renal functions，D-dimer， hemoglobin A1c （HbA1c）， urine podocin and nephrin and α-smooth muscle actin （α-SMA） excretion of the two groups were observed before and after treatment，and the changes were statistically analyzed and compared with those in the normal group. ResultAfter treatment，the reduction of TCM syndrome score in the observation group was more significant than that in the control group（P<0.01）. The 24 h UP level，UACR and renal function in the observation group in the 2nd and 3rd months after treatment were lower than the conditions before treatment（P<0.05）， and those in the 3rd month after treatment were decreased compared with the conditions in the control group during the same period. The levels of podocin and nephrin in each month and the α-SMA excretion in the 3rd month after treatment in the observation group were down-regulated compared with the conditions before treatment and in the control group （P<0.05）， and the observation group had reduced α-SMA excretion in the 2nd month after treatment compared with before treatment. There were no marked changes in D-dimer and liver function of the two groups before and after treatment. The level of HbA1c in the observation group was higher than that in the control group after treatment（P<0.05）. ConclusionJianpi Yangyin Guse decoction has desirable clinical efficacy in DN patients，and its mechanism may be related to reducing podocin and nephrin and α-SMA excretion levels.

B7/CD28 costimulatory molecules involved in the immune mechanism of kidney disease / 国际儿科学杂志

The body′s specific immune response is a very complicated process involving a series of immune cells and molecules that regulate and restrict each other.At present, the pathogenesis of most kidney diseases is not clear.B7(CD80)is located on antigen-presenting cells that regulate CD4+ and CD8+ T cells and play a role in enhancing or amplifying immune responses by binding to the cellular glycoprotein CD28.It also binds to cytotoxic T lymphocyte-Antigen4(CTLA-4)to inhibit the immune response.In general, renal tissue has no or low expression of B7.However, some glomerular diseases are associated with increased B7, which reduces the ability of podocytes to attach to the glomerular basement membrane and increases inflammation and renal fibrosis.When the B7-CTLA-4 interaction occurs, the immune response is attenuated.The disease can be prevented by blocking CD28 or enhancing the CTLA-4 signal.This article reviewed the role of costimulatory molecule B7/CD28 in the pathogenesis of kidney diseases, such as pod-cell damage, primary glomerulonephritis, purpura nephritis, lupus nephritis.Furthermore, it discussed the feasibility of B7 blockers were used as targeted therapies for kidney diseases.