scholarly journals A Network Pharmacology-Based Approach to Investigating the Mechanisms of Fushen Granule Effects on Intestinal Barrier Injury in Chronic Renal Failure

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Miaoru Han ◽  
Hangxing Yu ◽  
Kang Yang ◽  
Panying Liu ◽  
Haifeng Yan ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Signaling Pathway ◽  
Intestinal Barrier ◽  
Enrichment Analysis ◽  
Control Group ◽  
T84 Cells ◽  
Protein Expressions ◽  
Group Protein ◽  
Cox 2

Purpose. Fushen Granule (FSG) is a Chinese medicine prepared by doctors for treating patients with chronic renal failure, which is usually accompanied by gastrointestinal dysfunction. Here, we explore the protective effect of FSG on intestinal barrier injury in chronic renal failure through bioinformatic analysis and experimental verification. Methods. In this study, information on the components and targets of FSG related to CRF is collected to construct and visualize protein-protein interaction networks and drug-compound-target networks using network pharmacological methods. DAVID is used to conduct gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Then, it is validated by in vitro experiments. In this study, the human intestinal epithelial (T84) cells are used and divided into four groups: control group, model group, FSG low-dose group, and FSG high-dose group. After the experiment, the activity of T84 cells is detected by a MTT assay, and the expressions of tight junction protein ZO-1, claudin-1, nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), malondialdehyde (MDA), and cyclooxygenase-2 (COX-2) are examined by immunofluorescence and/or western blotting. Results. Eighty-six potential chronic renal failure-related targets are identified by FSG; among them, nine core genes are screened. Furthermore, GO enrichment analysis shows that the cancer-related signaling pathway, the PI3K-Akt signaling pathway, the HIF1 signaling pathway, and the TNF signaling pathway may play key roles in the treatment of CRF by FSG. The MTT method showed that FSG is not cytotoxic to uremic toxin-induced injured T84 cells. The results of immunofluorescence and WB indicate that compared with the control group, protein expressions level of ZO-1, claudin-1, and Nrf2 in T84 cells is decreased and protein expressions level of HO-1, MDA, and COX-2 is increased after urinary toxin treatment. Instead, compared with the model group, protein expressions level of ZO-1, claudin-1, and Nrf2 in T84 cells is increased and protein expressions level of HO-1, MDA, and COX-2 is decreased after FSG treatment. Conclusion. FSG had a protective effect on urinary toxin-induced intestinal epithelial barrier injury in chronic renal failure, and its mechanism may be related to the upregulation of Nrf2/HO-1 signal transduction and the inhibition of tissue oxidative stress and inflammatory responses. Screening CRF targets and identifying the corresponding FSG components by network pharmacological methods is a practical strategy to explain the mechanism of FSG in improving gastrointestinal dysfunction in CRF.

scholarly journals Based on HIF-1α/Wnt/β-Catenin Pathway to Explore the Effect of Qingshen Granules on Chronic Renal Failure Patients: A Randomized Controlled Trial

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Yiping Wang ◽  
Lei Zhang ◽  
Hua Jin ◽  
Dong Wang
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Treatment Group ◽  
Signaling Pathway ◽  
Clinical Symptoms ◽  
Controlled Trial ◽  
Serum Levels ◽  
Control Group ◽  
And Control ◽  
E Cadherin

Objectives. This study investigates the effect of Qingshen Granules (QSG) on chronic renal failure patients and the HIF-1α/Wnt/β-catenin signaling pathway. Methods. Subjects were randomly divided into treatment and control groups, with 42 patients in each group. Participants in the treatment group received 10 g oral doses of QSG 3 times a day, for 12 weeks, whereas subjects in the control group were given a placebo. The effective rates of traditional Chinese medicine (TCM) symptom, serum creatinine (Scr), and estimate glomerular filtration rate (eGFR) as well as the serum levels of HIF-1α, Wnt1, β-catenin, α-SMA, and E-cadherin were evaluated. Results. Eighty patients completed the treatment program and two dropped out. After 12 weeks, the effective rates of TCM symptom and eGFR were found to be higher in the treatment group than in the control group, with statistically significant differences (P = 0.024 and 0.019, respectively). Meanwhile, lower levels of HIF-1α, Wnt1, β-catenin, α-SMA, and E-cadherin were detected in the treatment group, and the differences were statistically significant (P ≤ 0.001, P = 0.001, P ≤ 0.001, P ≤ 0.001, and P = 0.039). No adverse events occurred during the study. Conclusions. QSG can alleviate the clinical symptoms of chronic renal failure (CRF) and protect renal function in patients by influencing the HIF-1α/Wnt/β-catenin signaling pathway. The treatment exhibits no adverse effects and is thus safe to be used by humans.

Effect of Proportional Reduction of Sodium Intake on the Adaptive Increase in Glomerular Filtration Rate/Nephron and Potassium and Phosphate Excretion in Chronic Renal Failure in the Rat

1975 ◽  
Vol 49 (3) ◽  
pp. 193-200 ◽  
Author(s):  
C. H. Espinel
Keyword(s):  
Renal Failure ◽  
Glomerular Filtration Rate ◽  
Chronic Renal Failure ◽  
Glomerular Filtration ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Sodium Intake ◽  
Dietary Sodium ◽  
Control Group ◽  
Phosphate Excretion

1. The influence of dietary sodium intake on the glomerular filtration rate (GFR/nephron) and potassium and phosphate excretion was examined at three stages of progressive chronic renal failure produced in rats by sequential partial nephrectomies. 2. The adaptive increased sodium excretion per nephron in the control group receiving a constant sodium intake did not occur in the experimental group that had a gradual reduction of dietary sodium in direct proportion to the fall in GFR. 3. Despite the difference in sodium excretion, the increase in GFR/nephron, the daily variation in the amount of potassium and phosphate excreted, the increase in potassium and phosphate excretion per unit nephron, and the plasma potassium and phosphate concentrations were the same in the two groups. 4. The concept of ‘autonomous adaptation’ in chronic renal failure is presented.

scholarly journals MicroRNA expression profiling involved in Borax-induced anti-tumor effect using gene-chip analysis

2020 ◽  
Author(s):  
Lun Wu ◽  
Ying Wei ◽  
Wen-Bo Zhou ◽  
Jiao Zhou ◽  
Li-Hua Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Enrichment Analysis ◽  
Gene Chip ◽  
Differentially Expressed ◽  
Control Group ◽  
Pathway Enrichment Analysis ◽  
Ras Signaling ◽  
Therapeutic Benefits ◽  
Differentially Expressed Mirnas

Abstract Background Borax, a boron compound, which is becoming widely recognized for its biological effects, including antioxidant activity, cytotoxicity, and potential therapeutic benefits. However, the specific molecular mechanisms underlying borax-induced anti-tumor effect still remain to be to further elucidated. MicroRNAs (miRNAs) may play key roles in cellular processes including tumor progression, cell apoptosis and cytotoxicity. Thus, this study aimed to investigate, whether miRNAs were involved in the borax-mediated anti-tumor effect using miRNA profiling of a human liver cancer cell line (HepG2) using gene-chip analysis.Methods Total RNA was extracted and purified from HepG2 cells that were treated with 4 mM borax for either 2 or 24 h. The samples underwent microarray analysis using an Agilent Human miRNA Array. Differentially expressed miRNAs were analysed by volcano plot and heatmap, and were validated using real-time fluorescent quantitative PCR (qPCR).ResultsAmong this, 2- or 24-h exposure to borax significantly altered the expression level of miRNAs in HepG2 cells, 4 or 14 were upregulated and 3 were downregulated compared with the control group, respectively (≥2-fold; P<0.05). GO enrichment analysis and KEGG pathway enrichment analysis revealed that target genes of differentially expressed miRNAs in HepG2 cells predominantly participated in MAPK signaling pathway, TGF-beta signaling pathway, NF-kappa B signaling pathway, etc; in 2-h borax treatment group, while Ras signaling pathway, FoxO signaling pathway, Cellular senescence, etc; involved in 24-h treatment group.Conclusions Result indicates that borax-induced anti-tumor effect may be associated with alterations in miRNAs.

scholarly journals ROLE OF CARDIAC MARKERS IN CHRONIC RENAL FAILURE PATIENTS.

2020 ◽  
pp. 81-82
Author(s):  
Ramesh Chandra Thanna ◽  
B K Agarwal ◽  
Rakesh Romday ◽  
Neha Sharma
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Positive Association ◽  
Morbidity And Mortality ◽  
Control Group ◽  
High Morbidity ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Hs Crp

Introduction: Cardiovascular diseases (CVD) are known as important reasons of the increased morbidity and mortality observed in patients with chronic renal failure (CRF). The association of serum Interlukin-6 , homocysteine as well as other cardiovascular risk factors in relation to existence and cause of CVD were investigated. Method: In this study 200 CRF patients were recruited and further stratified into group with Male and Female as case groups. Those without renal failure were assigned as control group (n=200). Results: The patients with CRF showed a significant increase in plasma levels of Cpk-MB homocysteine and C-reactive protein (CRP) compared to control. The positive association were observed between homocysteine, Urea and Hs-CRP, IL_6 . It shows a significant Association of parameters in CRF . Conclusion: The results demonstrated elevation in plasma values IL-6 , homocysteine and HS-CRP in patients with CRF . However, these modifications may be lead to atherosclerosis and consequence CVD event. These parameters may be important with respect to the high morbidity and mortality of CVD found in patients with CRF.

scholarly journals Effect of chronic renal failure on the hepatic, intestinal, and renal expression of bile acid transporters

2014 ◽  
Vol 306 (1) ◽  
pp. F130-F137 ◽  
Author(s):  
Zhibo Gai ◽  
Lei Chu ◽  
Christian Hiller ◽  
Denis Arsenijevic ◽  
Carlos A. Penno ◽  
...  
Keyword(s):  
Renal Failure ◽  
Bile Acid ◽  
Chronic Renal Failure ◽  
Plasma Cholesterol ◽  
Experimental Studies ◽  
Control Group ◽  
Early Event ◽  
Minor Role ◽  
Serum Bile Acid ◽  
Protein Levels

Although the kidney is believed to play a minor role in bile acid (BA) excretion, chronic renal failure (CRF) has been reported to be associated with increased serum bile acid levels and alterations in BA homeostasis. The mechanisms for elevated BA levels are poorly understood in both clinical and experimental studies. This study was designed to examine the effects of naturally progressing CRF of longer duration on the hepatic and renal mRNA and protein levels of the BA-synthesizing enzyme Cyp7a1 and the BA transporters Ntcp, Bsep, Mrp3, Ost-α, and Ost-β. Sprague-Dawley rats were randomized to the CRF group (⅚ nephrectomy) or to the sham-operated control group and were analyzed 8 wk after surgery. Results obtained in the CRF rats were compared with those obtained in rats that had undergone uninephrectomy (UNX). The CRF group exhibited significantly increased plasma cholesterol and BA concentrations. Hepatic Cyp7a1 mRNA and protein levels were almost identical in the two groups. Hepatic Mrp3, Ost-α, and Ost-β expression was increased, suggesting increased basolateral efflux of bile acids into the blood. However, no such changes in BA transporter expression were observed in the remnant kidney. In UNX rats, similar changes in plasma BA levels and in the expression of BA transporters were found. We hypothesize that the increase in plasma BA is an early event in the progression of CRF and is caused by increased efflux across the basolateral hepatocyte membrane.

scholarly journals Protein-to-creatinine urinary in the early diagnosis of renal injury in canine pyometra

2019 ◽  
Vol 39 (3) ◽  
pp. 186-191
Author(s):  
Marcos C. Sant’Anna ◽  
Guilherme F. Martins ◽  
Karina K.M.C. Flaiban ◽  
Luiz G.C. Trautwein ◽  
Maria I.M. Martins
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Renal Injury ◽  
Renal Damage ◽  
Systemic Disease ◽  
The Other ◽  
Control Group ◽  
Creatinine Ratio ◽  
Renal Lesions ◽  
Tubular Cells

ABSTRACT: Kidney disease that affects bitches with pyometra may lead patients to develop chronic renal failure even after pyometra treatment. Therefore, several studies have sought to clarify the gaps in the understanding of the pathogenesis of renal injury in pyometra. Identification of early detection markers for renal damage, which can predict and identify the prognosis of the disease, is very important. Proteinuria analysis can diagnose kidney damage, since proteins such as albumin are not filtered through the glomerulus and those that undergo glomerular filtration are almost completely reabsorbed by tubular cells. The objective of this study was to evaluate whether the urinary protein-to-creatinine ratio (UPC) can detect renal injury in bitches with pyometra before development of azotemia. For this, 44 bitches with pyometra were divided into two groups: bitches with azotemic piometra (A, n=15, creatinine >1.7) and bitches with non-azotemic pyometra (NA, n=29). The two groups were compared to the control group (CG, n=12), which had no signs of systemic disease. All animals underwent blood and urine tests. Leukocytosis was more evident in bitches in the A group than in the other groups. This shows that the inflammatory response may be associated with the pathogenesis of renal injury. The median UPC in bitches with pyometra was significantly higher than in the CG, with a median above the reference values. In conclusion, the UPC can be used in bitches with pyometra to detect renal damage before the development of azotemia. It has been suggested that the UPC of bitches with pyometra should be followed through during the postoperative period so that permanent renal lesions secondary to pyometra can be diagnosed and treated properly before the development of azotemia.

scholarly journals iTRAQ-Based Proteomics of Chronic Renal Failure Rats after FuShengong Decoction Treatment Reveals Haptoglobin and Alpha-1-Antitrypsin as Potential Biomarkers

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yu Yang ◽  
Junmeng Wei ◽  
Xuekuan Huang ◽  
Mingjun Wu ◽  
Zhenbing Lv ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Differentially Expressed ◽  
Coagulation Cascade ◽  
Control Group ◽  
Differentially Expressed Proteins ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Alpha 1 Antitrypsin ◽  
Global Health Problem

Background. Chronic renal failure (CRF) has become a global health problem and bears a huge economic burden. FuShengong Decoction (FSGD) as traditional Chinese medicine has multiple pharmacological effects. Objectives. To understand the underlying molecular mechanism and signaling pathway involved in the FSGD treatment of CRF and screen differentially expressed proteins in rats with CRF treated with FSGD. Methods. Thirty-three male Sprague-Dawley rats were randomly divided into control group, CRF group, and FSGD group. Differentially expressed proteins were screened by iTRAQ coupled with nanoLC-MS/MS, and these identified proteins were later analyzed by GO, KEGG, and STRING. Additionally, haptoglobin (HP) and alpha-1-antitrypsin (AAT) were finally verified by ELISA, Western blot, and real time PCR. Results. A total of 417 proteins were identified. Nineteen differentially expressed proteins were identified in the FSGD group compared with the model group, of which 3 proteins were upregulated and 16 proteins were downregulated. Cluster analysis indicated that inflammatory response was associated with these proteins and complement and coagulation cascade pathways were predominantly involved. The validation methods further confirmed that the levels of HP and AAT were significantly increased. Conclusions. HP and AAT may be the important biomarkers in the pathogenesis of CRF and FSGD therapy.

Allantoin as a marker of oxidative stress in human erythrocytes

2008 ◽  
Vol 46 (9) ◽  
Author(s):  
Roman Kand'ár ◽  
Pavla Žáková
Keyword(s):  
Oxidative Stress ◽  
Renal Failure ◽  
Uric Acid ◽  
Chronic Renal Failure ◽  
Gradient Elution ◽  
Reversed Phase ◽  
Control Group ◽  
Uric Acid Concentration ◽  
Reversed Phase Hplc

Abstract: Uric acid is the final product of purine metabolism in humans. It was determined that this compound has important antioxidative properties and it may be oxidized to allantoin by various reactive oxygen species. Therefore, the measurement of allantoin may be useful for the determination of oxidative stress in humans.: We measured allantoin and uric acid in human plasma and erythrocytes obtained from patients with chronic renal failure before hemodialysis (n=30) and blood donors (n=30). We used a method based on selective isolation of allantoin from deproteinized plasma and erythrocyte lysate samples on AG 1-X8 resin and its derivatization to glyoxylate-2, 4-dinitrophenylhydrazone. Separation of glyoxylate-2, 4-dinitrophenylhydrazone from interfering substances was achieved on reversed phase HPLC with gradient elution and UV/VIS detection at 360 nm. Uric acid was determined by reversed phase HPLC with UV/VIS detection at 292 nm.: We found significant differences in allantoin and uric acid concentration between the patients with chronic renal failure and the control group both in plasma (20.5±6.5 μmol/L and 323.9±62.9 μmol/L vs. 2.1±1.1 μmol/L and 270.1±62.3 μmol/L, p<0.05) and erythrocytes [82.8±39.1 nmol/g hemoglobin (Hb) and 110.7±28.8 nmol/g Hb vs. 20.1±6.1 nmol/g Hb and 82.1±23.7 nmol/g Hb, p<0.05].: Significant higher levels of allantoin in both plasma and erythrocytes of patients with chronic renal failure indicate that allantoin may be used as a good marker of oxidative stress.Clin Chem Lab Med 2008;46:1270–4.

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