Screening of active components in Astragalus mongholicus Bunge and Panax notoginseng formula for anti-fibrosis in CKD: nobiletin inhibits Lgals1/PI3K/AKT signaling to improve renal fibrosis.

The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) has been clinically shown to effectively slow down the progression of chronic kidney disease (CKD) and has demonstrated significant anti-fibrosis effects in experimental CKD model. However, the specific active ingredients and underlying mechanism are still unclear. The active ingredients of A&P were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-HR-MS). A mouse model of CKD was constructed by 5/6 nephrectomy. Renal function was assessed by creatinine and urea nitrogen. Real-time PCR and Western Blot were performed to detect the mRNA and protein changes in kidney and cells. An in vitro fibrotic cell model was constructed by TGF-ß induction in TCMK-1 cells. The results showed that thirteen active ingredients of A&P were identified by UPLC-HR-MS, nine of which were identified by analysis with standards, among which the relative percentage of NOB was high. We found that NOB treatment significantly improved renal function, pathological damage and reduced the expression level of fibrotic factors in CKD mice. The results also demonstrated that Lgals1 was overexpressed in the interstitial kidney of CKD mice, and NOB treatment significantly reduced its expression level, while inhibiting PI3K and AKT phosphorylation. Interestingly, overexpression of Lgals1 significantly increased fibrosis in TCMK1 cells and upregulated the activity of PI3K and AKT, which were strongly inhibited by NOB treatment. NOB is one of the main active components of A&P. The molecular mechanism by which NOB ameliorates renal fibrosis in CKD may be through the inhibition of Lgals1/PI3K/AKT signaling pathway.

Astragalus mongholicus bunge and panax notoginseng formula (A&P) improves renal fibrosis in UUO mice via inhibiting the long non-coding RNA A330074K22Rik and downregulating ferroptosis signaling.

BACKGROUND: Chronic kidney disease (CKD) and its associated end-stage renal disease (ESRD) are significant health problems that pose a threat to human well-being. Renal fibrosis is a common feature and ultimate pathological outcome of various CKD leading to ESRD. The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) is a refined compound formulated by our research group, which has been clinically administered for over a decade and has demonstrated the ability to improve the inflammatory state of various acute or chronic kidney diseases. However, the underlying mechanism by which A&P ameliorates renal fibrosis remains unclear. METHODS: We established a mouse model by surgically ligating the unilateral ureter to induce renal injury in vivo. And we utilized renal in situ electroporation of a plasmid with low LncRNA A33 expression to establish the unilateral ureteral obstruction(UUO)mouse model. In vitro, we stimulated primary tubular epithelial cells(pTEC) injury using TGF-ß1, siRNA-A33, and pcDNA3.1-A33 plasmids were transfected into pTECs to respectively knockdown and overexpress LncRNA A33, and both in vitro and in vivo models were intervened with A&P. RESULTS: The results demonstrated that A&P effectively alleviated renal fibrosis in mice. Subsequent findings indicated high expression of LncRNA A33 in the kidneys of UUO mice and TGF-ß1-induced renal tubular cells. In situ, renal electroporation of a plasmid with reduced LncRNA A33 expression revealed that inhibiting LncRNA A33 significantly improved renal fibrosis in UUO mice. Moreover, A&P effectively suppressed LncRNA A33 expression both in vitro and in vivo. Subsequent downregulation of LncRNA A33 in renal tubular epithelial cells resulted in the downregulation of numerous fibrotic markers, a significant inhibition of LncRNA A33, and a notable reduction in downstream ferroptosis signaling. Cell experiments demonstrated that A&P improved renal fibrosis in UUO mice by inhibiting LncRNA A33 and downregulating ferroptosis signaling. CONCLUSION: Through the inhibition of LncRNA A33 and subsequent downregulation of ferroptosis signaling, A&P showed potential as a therapeutic approach for improving renal fibrosis in UUO mice, providing a potential treatment avenue for CKD.

Case report and literature review: Acute rhabdomyolysis caused by overheating of electric blanket complicated with Guillain-Barré syndrome.

Rhabdomyolysis (RM) induced by electric blankets is exceedingly rare, with only three cases identified in our literature review. Both RM and Guillain-Barré syndrome (GBS) present with similar clinical manifestations of myalgia and muscle weakness, posing a potential challenge for accurate diagnosis in clinical settings. This report presents the case of a 22-year-old man who developed RM subsequent to the use of an electric blanket. Despite undergoing plasma exchange and renal replacement therapy, the patient continued to exhibit poor muscle strength in both lower limbs. Subsequent comprehensive evaluation revealed the presence of concurrent GBS. Following a 5-day course of intravenous gamma globulin treatment, the patient experienced rapid recovery of muscle strength and was discharged. Additionally, we reviewed seven cases from the literature of coexistent RM and GBS. This indicated that investigation of the timing of onset of muscle strength decline in RM patients could help to identify potential concurrent neurological or muscular disorders. In cases in which concurrent GBS and RM cannot be definitively ascertained during early hospitalization, prioritizing plasma exchange treatment may lead to improved patient outcomes.

Pretreated MSCs with IronQ Transplantation Attenuate Microglia Neuroinflammation via the cGAS-STING Signaling Pathway.

Background: Intracerebral hemorrhage (ICH), a devastating form of stroke, is characterized by elevated morbidity and mortality rates. Neuroinflammation is a common occurrence following ICH. Mesenchymal stem cells (MSCs) have exhibited potential in treating brain diseases due to their anti-inflammatory properties. However, the therapeutic efficacy of MSCs is limited by the intense inflammatory response at the transplantation site in ICH. Hence, enhancing the function of transplanted MSCs holds considerable promise as a therapeutic strategy for ICH. Notably, the iron-quercetin complex (IronQ), a metal-quercetin complex synthesized through coordination chemistry, has garnered significant attention for its biomedical applications. In our previous studies, we have observed that IronQ exerts stimulatory effects on cell growth, notably enhancing the survival and viability of peripheral blood mononuclear cells (PBMCs) and MSCs. This study aimed to evaluate the effects of pretreated MSCs with IronQ on neuroinflammation and elucidate its underlying mechanisms. Methods: The ICH mice were induced by injecting the collagenase I solution into the right brain caudate nucleus. After 24 hours, the ICH mice were randomly divided into four subgroups, the model group (Model), quercetin group (Quercetin), MSCs group (MSCs), and pretreated MSCs with IronQ group (MSCs+IronQ). Neurological deficits were re-evaluated on day 3, and brain samples were collected for further analysis. TUNEL staining was performed to assess cell DNA damage, and the protein expression levels of inflammatory factors and the cGAS-STING signaling pathway were investigated and analyzed. Results: Pretreated MSCs with IronQ effectively mitigate neurological deficits and reduce neuronal inflammation by modulating the microglial polarization. Moreover, the pretreated MSCs with IronQ suppress the protein expression levels of the cGAS-STING signaling pathway. Conclusion: These findings suggest that pretreated MSCs with IronQ demonstrate a synergistic effect in alleviating neuroinflammation, thereby improving neurological function, which is achieved through the inhibition of the cGAS-STING signaling pathway.

Development and validation of a nomogram for predicting the risk of poor prognosis in patients with cerebral infarction.

Objective: To identify factors related to poor prognosis in patients with cerebral infarction (CI) and to construct and validate a personalized prediction model based on these factors. Methods: A retrospective analysis was conducted on the clinical and follow-up data of 857 patients with CI who were diagnosed in the neurology department of a tertiary A hospital in Anhui Province, China from April 2020 to March 2022. Based on follow-up data and the Modified Rankin Scale (mRS) score one year after discharge, patients were divided into a good prognosis group (793 cases, mRS ≤2) and a poor prognosis group (64 cases, mRS >2). Multivariate logistic regression analysis was used to identify independent risk factors, which were then used to establish a nomogram model. The predictive performance of the model was evaluated using the area under the receiver operating characteristic curve (ROC, AUC), and the calibration curve was used to evaluate the calibration of the nomogram. Results: There was a statistically significant difference in the distribution of eight variables between the groups, including post-discharge use of biguanide hypoglycemic drugs, insulin, systolic blood pressure, exercise status, alcohol consumption, smoking status, age, and gender (P < 0.05). Multivariate logistic regression analysis suggested that gender, smoking after discharge, alcohol consumption, lack of exercise, and oral administration of biguanide hypoglycemic drugs are independent risk factors for poor prognosis in patients with CI (P < 0.05). The personalized poor prognosis nomogram constructed based on these five predictive factors showed good discriminative ability and predictive stability, with AUCs of 0.768 (95 % CI: 0.712-0.825) and 0.775 (95 % CI: 0.725-0.836) before and after internal validation, respectively. The calibration curve confirmed the accuracy and consistency of the nomogram (P = 0.956). Conclusion: Female gender, smoking, alcohol consumption, lack of exercise, and post-discharge use of biguanide hypoglycemic drugs are independent risk factors for poor prognosis in patients with CI. The constructed nomogram shows good predictive efficiency for post-discharge prognosis and can help in clinical decision-making.

Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (MSCs) show podocyte-protective effects in chronic kidney disease. Calycosin (CA), a phytoestrogen, is isolated from Astragalus membranaceus with a kidney-tonifying effect. CA preconditioning enhances the protective effect of MSCs against renal fibrosis in mice with unilateral ureteral occlusion. However, the protective effect and underlying mechanism of CA-pretreated MSCs (MSCsCA) on podocytes in adriamycin (ADR)-induced focal segmental glomerulosclerosis (FSGS) mice remain unclear. AIM: To investigate whether CA enhances the role of MSCs in protecting against podocyte injury induced by ADR and the possible mechanism involved. METHODS: ADR was used to induce FSGS in mice, and MSCs, CA, or MSCsCA were administered to mice. Their protective effect and possible mechanism of action on podocytes were observed by Western blot, immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction. In vitro, ADR was used to stimulate mouse podocytes (MPC5) to induce injury, and the supernatants from MSC-, CA-, or MSCsCA-treated cells were collected to observe their protective effects on podocytes. Subsequently, the apoptosis of podocytes was detected in vivo and in vitro by Western blot, TUNEL assay, and immunofluorescence. Overexpression of Smad3, which is involved in apoptosis, was then induced to evaluate whether the MSCsCA-mediated podocyte protective effect is associated with Smad3 inhibition in MPC5 cells. RESULTS: CA-pretreated MSCs enhanced the protective effect of MSCs against podocyte injury and the ability to inhibit podocyte apoptosis in ADR-induced FSGS mice and MPC5 cells. Expression of p-Smad3 was upregulated in mice with ADR-induced FSGS and MPC5 cells, which was reversed by MSCCA treatment more significantly than by MSCs or CA alone. When Smad3 was overexpressed in MPC5 cells, MSCsCA could not fulfill their potential to inhibit podocyte apoptosis. CONCLUSION: MSCsCA enhance the protection of MSCs against ADR-induced podocyte apoptosis. The underlying mechanism may be related to MSCsCA-targeted inhibition of p-Smad3 in podocytes.

Calycosin pretreatment enhanced the therapeutic efficacy of mesenchymal stem cells to alleviate unilateral ureteral obstruction-induced renal fibrosis by inhibiting necroptosis.

Bone marrow-derived mesenchymal stem cells (MSCs) show antifibrotic activity in various chronic kidney diseases. Here, we aimed to investigate whether Calycosin (CA), a phytoestrogen, could enhance the antifibrotic activity of MSCs in primary tubular epithelial cells (PTECs) induced by TGF-ß1 and in a mouse model of unilateral ureteral obstruction (UUO). We found that MSCs treatment significantly inhibited fibrosis, and CA pretreatment enhanced the effects of MSCs on fibrosis in vitro. Consistent with the in vitro studies, MSCs alleviated tubular injury and renal fibrosis in mice after UUO, and CA-pretreated MSCs resulted in more significant improvements in tubular injury and renal fibrosis than MSCs after UUO. Moreover, MSCs treatment significantly inhibited necroptosis by repressing the elevation of MLKL, RIPK1, and RIPK3 in PTECs treated by TGF-ß1and in mice after UUO, and CA-pretreated MSCs were superior to MSCs in alleviating necroptosis. MSCs significantly reduced TNF-α and TNFR1 expression induced by TGF-ß1 in PTECs and inhibited TGF-ß1, TNF-α, and TNFR1 expression induced by UUO in mice. These effects of MSCs were significantly enhanced after CA pretreatment. Therefore, our results suggest that CA pretreatment enhances the antifibrotic activity of MSCs by inhibiting TGF-ß1/TNF-α/TNFR1 signaling-induced necroptosis.

The hepatoprotective effects of plant-based foods based on the "gut-liver axis": a prospective review.

The importance of the "gut-liver axis" in the pathogenesis of liver diseases has been revealed recently; which promotes the process of developing preventive and therapeutic strategies. However, considering that there are still many challenges in the medical treatment of liver diseases, potential preventive dietary intervention may be a good alternative choice. Plant-based foods have received much attention due to their reported health-promoting effects in targeting multiple pathways involved in the pathogenesis of liver diseases as well as the relative safety for general use. Based on the PubMed and Web of Science databases, this review emphatically summarizes the plant-based foods and their chemical constituents with reported effects to impact the LPS/TLR4 signaling pathway of gut-liver axis of various liver diseases, reflecting their health benefits in preventing/alleviating liver diseases. Moreover, some plant-based foods with potential gut-liver effects are specifically analyzed from the reported studies and conclusions. This review intends to provide readers an overview of the current progress in the field of this research topic. We expect to see more hepatoprotective measures for alleviating the current prevalence of liver diseases.

The Smad3-dependent microRNA let-7i-5p promoted renal fibrosis in mice with unilateral ureteral obstruction.

Renal fibrosis is a common feature of all types of chronic kidney disease (CKD) and is tightly regulated by the TGF-ß/Smad3 pathway. Let-7i-5p belongs to the let-7 microRNA family with diverse biological functions. It has been reported that let-7i-5p suppresses fibrotic disease in the heart, lungs, and blood vessels, while the role of let-7i-5p in renal fibrosis remains limited. In this study, we aimed to investigate the role of let-7i-5p in renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) and TGF-ß1-stimulated renal tubular cell line TCMK1. The RNA-targeting CRISPR/Cas13d system was used to knock down let-7i-5p. Renal injury and fibrosis were determined by histological analysis, RT-PCR, Western blot, and immunostaining. Our results have shown that in the kidneys after UUO, the expression of let-7i-5p was significantly increased along with notable tubular injury and interstitial fibrosis. Electroporation of let-7i-targeting Cas13d plasmid efficiently knocked down let-7i-5p in kidneys after UUO with reduced tubular injury, fibrotic area, and expression of fibrotic marker genes α-SMA, fibronectin, and Col1a1. In TGF-ß1-stimulated TCMK1 cells, knockdown of let-7i-5p by Cas13d plasmid transfection also blunted the expression of fibrotic marker genes. Most importantly, the genomic locus of let-7i showed enriched binding of Smad3 as revealed by chromatin immunoprecipitation. In TCMK1 cells, the overexpression of Smad3 can directly induce the expression of let-7i-5p. However, the deletion of Smad3 abolished TGF-ß1-stimulated let-7i-5p expression. Collectively, these findings suggest that let-7i-5p is a Smad3-dependent microRNA that plays a pathogenic role in renal fibrosis. Let-7i-5p could be a promising target for the treatment of CKD-associated renal fibrosis.

Surgery and antibiotics for the treatment of lupus nephritis with cerebral abscesses: A case report.

BACKGROUND: Systemic lupus erythematosus (SLE) patients are extremely susceptible to opportunistic infections due to glucocorticoid and immunosuppressive treatments, which often occur in the respiratory system, the urinary system and the skin. However, multiple cerebral infections are rarely reported and their treatment is not standardized, especially when induced by a rare pathogen. CASE SUMMARY: A 46-year-old woman was treated with glucocorticoid and immunosuppressant for SLE involving the hematologic system and kidneys (class IV-G lupus nephritis) for more than one year. She was admitted to hospital due to headache and fever, and was diagnosed with multiple cerebral abscesses. Brain enhanced magnetic resonance imaging showed multiple nodular abnormal signals in both frontal lobes, left parietal and temporal lobes, left masseteric space (left temporalis and masseter region). The initial surgical plan was only to remove the large abscesses in the left parietal lobe and right frontal lobe. After surgery, based on the drug susceptibility test results (a rare pathogen Nocardia asteroides was found) and taking into consideration the patient's renal dysfunction, a multi-antibiotic regimen was selected for the treatment. The immunosuppressant mycophenolate mofetil was discontinued on admission and the dose of prednisone was reduced from 20 mg/d to 10 mg/d. Re-examination at 3 mo post-surgery showed that the intracranial lesions were reduced, the edema around the lesions was absorbed and dissipated, and her neurological symptoms had disappeared. The patient had no headaches or other neurological symptoms and lupus nephritis was stable during the 2-year follow-up period. CONCLUSION: In this report, we provide reasonable indications for immunosuppression, anti-infective therapy and individualized surgery for an SLE patient complicated with multiple cerebral abscesses caused by a rare pathogen, which may help improve the diagnosis and treatment of similar cases.

Tectorigenin protects against unilateral ureteral obstruction by inhibiting Smad3-mediated ferroptosis and fibrosis.

Renal tubular epithelial cell (TEC) injury and fibrosis are the key factors of the pathogenesis of chronic kidney disease. Here, we reported that tectorigenin is effectively protected against obstructive nephropathy established by unilateral ureteral obstruction (UUO). In vivo, tectorigenin administration significantly alleviated the deteriorations of renal functions including blood urea nitrogen and creatinine. Meanwhile, results from the histology suggested that renal injury characterized by tubular cell damage and fibrosis lesions of kidneys in UUO group were markedly attenuated following tectorigenin treatment. Mechanistically, we found that tectorigenin treatment greatly inhibited Smad3 phosphorylation, and the transcription and protein level of Nox4, a newly identified direct downstream molecule of Smad3 and a modulator of ferroptosis, while it indirectly restored the expression of glutathione peroxidase 4, a negative regulator of ferroptosis. Consistent with in vivo studies, treatment with tectorigenin also suppressed the ferroptosis induced by erastin/RSL3 and fibrosis stimulated by transforming growth factor ß1 (TGF-ß1) in primary renal TECs. What is more, treatment with ferroptosis inhibitor, ferrostatin-1, also impeded TGF-ß1 stimulated the profibrotic effects in TECs, indicating that tectorigenin may relieve fibrosis by inhibiting ferroptosis in TECs. In addition, tectorigenin treatment exhibited a similar tendency, which inhibited Smad3 activation, and the docking analysis revealed that tectorigenin docked well into the Smad3 binding cavity with strong binding affinity (-7.9 kcal/mol). Thus, this study deciphers the protective effect of tectorigenin against obstructive nephropathy through inhibiting Smad3-mediated ferroptosis and fibrosis.

Identification of Complex Pneumonia during the Outbreak of COVID-19: Bacterial Pneumonia Combined with Acute Eosinophilic Pneumonia in Patients with Maintenance Hemodialysis.

It is of crucial importance to diagnose patients in a timely and clear manner during the outbreak of COVID-19. Different causes of pneumonia makes it difficult to differentiate COVID-19 from others. Hemodialysis patients are a special group of people in this outbreak. We present a successfully treated case of a patient with maintenance hemodialysis from acute eosinophilic pneumonia for using meropenem when treating bacterial pneumonia, avoiding possible panic and waste of quarantine materials in dialysis centers.

Intestinal flora alterations in patients with early chronic kidney disease: a case-control study among the Han population in southwestern China.

OBJECTIVE: In this case-control study, we retrospectively analyzed the intestinal flora compositions of patients with early-stage chronic kidney disease (CKD). METHODS: Forty-seven patients with early CKD who were treated at the Traditional Chinese Medicine Hospital between March and October 2018 were enrolled, and 150 healthy volunteers were enrolled in the healthy control group. Fresh stool samples were collected. The V3-V4 region of the bacterial 16S rRNA was amplified via PCR. Biterminal sequencing was performed using the Illumina MiSeq platform. The flora compositions were compared between the two groups. RESULTS: The Chao1 and Shannon indices showed significantly lower intestinal flora diversity and abundances in the CKD group than in the healthy controls. Beta diversity analysis revealed notable differences in the intestinal flora compositions between the groups. At the phylum level, Actinobacteria and Proteobacteria abundances were significantly higher in the CKD group. Thirty-one species differed significantly between both groups, among which, differences in Ruminococcus and Roseburia displayed the highest diagnostic values for distinguishing CKD patients from healthy controls. CONCLUSIONS: Intestinal flora compositions are altered in early-stage CKD patients among the Han population in southwestern China.

Blood metabolism study on protection of residual renal function of hemodialysis patients by traditional Chinese medicine Kidney Flaccidity Compound.

In recent years, metabolomics using high-performance liquid chromatography (UPLC) has been used to study the metabolic profiles in plasma, urine, stool and tissue in animal model of chronic kidney disease (CKD). In the previous work, we found that traditional Chinese medicine (TCM) "Kidney Flaccidity Compound" (KFC) based on "kidney flaccidity theory" can improve renal function and quality of life of patients with kidney disease. This study aimed to investigate the metabolic profiles in peripheral blood of hemodialysis patients administrated by KFC for 1.5 and 3 months and explore the potential metabolic mechanism using UPLC. Results showed that 121 metabolites were different between KFC 3-months group and untreated control, of which 75 were significantly upregulated and 46 were significantly downregulated. In the 1.5-months treatment group, there were 365 metabolites, of which 164 were significantly upregulated and 192 downregulated. There were 6 metabolites and 15 metabolites upregulated 3-fold in 3-months and 1.5-months KFC treatment group, respectively. In addition, more than 60 new metabolites were identified in the peripheral blood in KFC treated patients, including two potential diagnostic markers MGDG 30:8 and 2-(hydroxymethyl)-6-[[(1R,4S) -2,2,4-trimethyl-3-oxabicyclo[2.2.2]octan-5-yl]oxy]oxane-3,4,5-triol. The pathway enrichment analysis showed thce differential metabolites mainly enriched in Arginine and proline metabolism, Urea cycle, Tyrosine metabolism, Methionine metabolism, Tricarboxylic acid cycle, and Androgen and estrogen metabolism. The findings are helpful to reveal the mechanism of KFC protects CKD, and to provide a new strategy for recovery renal function in hemodialysis patients.

Detection of epitopes in systemic lupus erythematosus using peptide microarray.

Systemic lupus erythematosus (SLE) is a common autoimmune disease, which features the secretion of antibodies directed against autoantigens in vivo. In the present study, a peptide microarray was developed to detect the epitopes recognized by autoantibodies in patients with SLE for an effective method of diagnosis. SLE­associated epitopes in 14 autoantigens were predicted using the antigenic epitope prediction software DNA star. Peptides were synthesized based on the predicted antigenic epitopes and immobilized on a slide surface and developed into a peptide microarray. Using this peptide microarray the autoantibodies in 120 patients with SLE and 110 healthy subjects were detected. A total of 73 potential antigenic epitopes in 14 autoantigens were predicted and screened. The peptide microarray based on the 73 epitopes was used to detect the autoantibodies in patients with SLE. A total of 14 epitopes with potential diagnostic values were screened out. The sensitivity and specificity of the 14 epitopes for the diagnosis of SLE were 71.6 and 85.8%, respectively. An optimal set of epitopes for SLE diagnosis was obtained. As individual patients had a specific autoantibody spectrum it was possible to detect autoantibodies in SLE and perform the diagnosis of SLE using the peptide microarray.

Ginsenoside Rg1 protects mouse podocytes from aldosterone-induced injury in vitro.

AIM: Aldosterone is elevated in many diseases such as hypertension, diabetic nephropathy and chronic kidney disease, etc. The aim of this study was to investigate the effects of aldosterone on intracellular ROS production and autophagy in podocytes in vitro, and to explore the possibility of ginsenoside Rg1 (Rg1) being used for protecting podocytes from aldosterone-induced injury. METHODS: MPC5 mouse podocyte cells were tested. Autophagosome and autophagic vacuole formation were examined under confocal microscopy with MDC and acridine orange staining, respectively. ROS were detected with flow cytometry. Malondialdehyde content and superoxide dismutase (T-SOD) activity were measured using commercial kits. The expression of LC3-II, beclin-1, SOD2 and catalase was measured by Western blotting. RESULTS: Treatment with aldosterone (10 nmol/L) significantly increased ROS generation and the expression of SOD2 and catalase in MPC5 cells. Furthermore, treatment with aldosterone significantly increased the conversion of LC3-I to LC3-II, beclin-1 expression and autophagosome formation. Co-treatment with rapamycin (1 ng/mL) or chloroquine (10 µmol/L) further increased aldosterone-induced autophagosome formation. Co-treatment with Rg1 (80 ng/mL) effectively relieved oxidative stress and increased T-SOD activity at the early stage and subsequently decreased autophagy in aldosterone-treated podocytes. Co-treatment with 3-MA (4 mmol/L) or NAC (50 mmol/L) exerted similar effects against aldosterone-induced autophagy in podocytes. CONCLUSION: Aldosterone enhances ROS generation and promotes autophagy in podocytes in vitro. Ginsenoside-Rg1 effectively relieves aldosterone-induced oxidative stress, thereby indirectly inhibiting aldosterone-induced podocyte autophagy.

[The study on the beclin1 expression and change in diabetic rats].

OBJECTIVE: To study the expression of beclin1 in renal tissue of diabetic rats, and its role in diabetic nephropathy (DN). METHODS: Diabetic rat model was produced by intraperitoneal injection of streptozotocin (50 mg/kg), it was considered to be diabetic nephropathy that 72 h blood glucose after modeling was higher than 16 mmol/L. The positive urine protein was detected by paper method at the end of 1 week. 24 h urine albumin excretion (ALb) and urinary albumin and urinary creatinine ratio (ACR) were examined by immunoturbidimetry, Beclin1 expression was also studied by immunohistochemistry with envision method. The electron microscopy was used to detect the form of autophagic vesicles and lysosome. RESULTS: (1) Compared with control group, the 24-hour urinary albumin excretion rate and ACR in diabetic rats were significantly higher. (2) The electron microscopy showed there were autophagic vesicles in renal tissue in both groups; (3) Immunohistochemistry showed beclin1 expression in normal rat kidney cells partly, while no expression in glomeruli. The expression of beclin1 in DN renal tissue was stronger than that in normal rats (P < 0.05). CONCLUSION: beclin1 may be involved in the pathogenesis of diabetic nephropathy with the mechanism related to the process of programmed cell death.