This study aimed to investigate the ameliorative effect of Xinyang Tablets on myocardial fibrosis in uremic cardiomyopathy(UCM) using single-cell sequencing technology. UCM mouse models were established by 5/6 nephrectomy(NPM) and randomly divided into the model group, Xinyang Tablets group, and sham-operated(sham) group as the control. The Xinyang Tablets group received postoperative interventions of Xinyang Tablets(0.34 g·kg~(-1)). After eight weeks, the hearts of the mice in each group were disassociated and subjected to 10×Genomics single-cell sequencing. The data were subjected to t-SNE dimensionality reduction, K-means clustering, and CellMarker annotation prior to analyzing differential expression and cell differentiation trajectories using the Seurat and Monocle3 tools. Additionally, the CellChat tool was used to parse intercellular signaling communication. The results showed that a total of nine types of cells including fibroblasts, endothelial cells, and immune cells were identified in this study. The single-cell expression results of fibroblasts and Gene Ontology(GO) enrichment analysis showed that Xinyang Tablets regulated myocardial fibrosis factors and related signals. Mimetic timing analysis identified three major differentiation trajectories of mouse cardiac fibroblasts and identified the expression of secreted phosphoprotein 1(Spp1) as consistent with the fibroblast differentiation trajectory. Cellular interaction network analysis showed that the communication signals between mouse cardiac fibroblasts and other cells were weakened in the Xinyang Tablets group compared with the model group. The results of ligand-receptor interaction analysis showed that the interaction between myeloid cell-derived osteopontin(OPN) and cardiac fibroblasts and between myeloid cell Spp1 ligand and cardiac fibroblast receptor of mice in the Xinyang Tablets group was weakened compared with the model group. In conclusion, Xinyang Tablets may improve myocardial fibrosis in UCM by inhibiting both endogenous and exogenous OPN at the single-cell level.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cardiomyopathies/pathology* ; Single-Cell Analysis ; Male ; Fibrosis/drug therapy* ; Myocardium/metabolism* ; Uremia/metabolism* ; Tablets ; Mice, Inbred C57BL ; Humans

Background: Hyperphosphatemia is a risk factor associated with mortality in patients on maintenance hemodialysis. Gut absorption of phosphate is the major source. Recent studies indicated that the intestinal flora of uremic patients changed a lot compared with the healthy population, and phosphorus is an essential element of bacterial survival and reproduction. The purpose of this study was to explore the role of intestinal microbiota in phosphorus metabolism. Methods: A prospective self-control study was performed from October 2015 to January 2016. Microbial DNA was isolated from the stools of 20 healthy controls and 21 maintenance hemodialysis patients. Fourteen out of the 21 patients were treated with lanthanum carbonate for 12 weeks. Thus, stools were also collected before and after the treatment. The bacterial composition was analyzed based on 16S ribosomal RNA pyrosequencing. Bioinformatics tools, including sequence alignment, abundance profiling, and taxonomic diversity, were used in microbiome data analyses. Correlations between genera and the serum phosphorus were detected with Pearson's correlation. For visualization of the internal interactions and further measurement of the microbial community, SparCC was used to calculate the Spearman correlation coefficient with the corresponding P value between each two genera. Results: Thirteen genera closely correlated with serum phosphorus and the correlation coefficient was above 0.4 (P < 0.05). We also found that 58 bacterial operational taxonomic units (OTUs) were significantly different and more decreased OTUs were identified and seven genera (P < 0.05) were obviously reduced after using the phosphate binder. Meanwhile, the microbial richness and diversity presented downward trend in hemodialysis patients compared with healthy controls and more downward trend after phosphorus reduction. The co-occurrence network of genera revealed that the network complexity of hemodialysis patients was significantly higher than that of controls, whereas treatment with lanthanum carbonate reduced the network complexity. Conclusions Gut flora related to phosphorus metabolism in hemodialysis patients, and improving intestinal microbiota may regulate the absorption of phosphate in the intestine. The use of phosphate binder lanthanum carbonate leads to a tendency of decreasing microbial diversity and lower network complexity.
Child ; Female ; Gastrointestinal Microbiome ; drug effects ; physiology ; Humans ; Lanthanum ; therapeutic use ; Male ; Middle Aged ; Phosphorus ; metabolism ; Prospective Studies ; Renal Dialysis ; Risk Factors ; Uremia ; drug therapy ; metabolism ; microbiology

Calcific uremic arteriopathy (CUA), termed calciphylaxis, is a rare but highly fatal clinical syndrome. There is no clearly laboratory diagnostic criteria for CUA. The medium and small arterial calcification and microthrombosis discovered by skin biopsy, radiologic imaging，bone scan and the evidence of activation of the bone morphogenetic protein signal (BMPs) transduction pathway are useful for early diagnosis of this disease. The common therapies (including intravenous sodium thiosulfate (STS) and bisphosphonates, hyperbaric oxygen therapy and other symptomatic supports) are used for the management of wounds, pain, nutrition, dialysis and so on. Controlling the chronic kidney disease-mineral and bone disorder (CKD-MBD) and some complications of dialysis and drugs (such as warfarin, active vitamin D) can prevent CUA. However, CUA patients still have poor prognosis and high mortality. Since some patients progress rapidly, it is of great importance to make early diagnosis and provide effective treatments with multidisciplinary management.
Calciphylaxis ; diagnosis ; prevention & control ; therapy ; Early Diagnosis ; Humans ; Renal Dialysis ; Uremia ; Warfarin

Chronic kidney disease (CKD) is a major disease that threatens human health. With the progression of CKD, the risk of cardiovascular death increases, which is associated with the elevated levels of uremic toxins (UTs). Representative toxins such as indoxyl sulfate and p-cresyl sulfate are involed in CKD progression and cardiovascular events inseparable from the key role of endothelial dysfunction. The therapeutic strategies of UTs are aimed at signaling pathways that target the levels and damage of toxins in modern medicine. There is a certain relevance between toxins and "turbid toxin" in the theory of Chinese medicine (CM). CM treatments have been demonstrated to reduce the damage of gut-derived toxins to the heart, kidney and blood vessels. Modern medicine still lacks evidence-based therapies, so it is necessary to explore the treatments of CM.
Humans ; Intestinal Mucosa ; metabolism ; Medicine, Chinese Traditional ; Renal Insufficiency, Chronic ; drug therapy ; Signal Transduction ; drug effects ; Toxins, Biological ; analysis ; metabolism ; Uremia ; metabolism

Aneurysm, False ; surgery ; Factor VIII ; therapeutic use ; Hemophilia A ; drug therapy ; Humans ; Uremia

OBJECTIVE: To investigate the serum levels of microRNA-155 (miR-155) and interleukin-6 (IL-6) in uremic dialysis patients and to evaluate the effect of alprostadil (A) on them.
 METHODS: A total of 81 chronic kidney disease (CKD) uremic patients were divided into 4 groups: the peritoneal dialysis group (PD group, n=20), the peritoneal dialysis plus alprostadil group (PD+A group, n=20), the hemodialysis group (HD group, n=21), the hemodialysis plus alprostadil group (HD+A group, n=20). Sixteen healthy people were taken as the normal control (NC) group. The peripheral blood of all objects were collected for serum preparation. The expression of miRNA-155 was determined by real-time qPCR and the serum level of IL-6 was measured by ELISA. Experimental and clinical data of all the objects were collected.
 RESULTS: Serum levels of miRNA-155 and IL-6 were increased in all dialysis patients groups compared with NC group (P<0.05); miRNA-155 expression in PD+A group was down-regulated compared with PD group or HD group (P<0.05); the levels of IL-6 in PD+A and HD+A group were significantly decreased compared with PD group or HD group (P<0.05). Correlation analysis showed that serum level of miR-155 was positively correlated with the level of IL-6 as well as high-sensitivity C-reactive protein (hs-CRP), while miR-155 was negatively correlated with HDL and albumin (P<0.01). Linear stepwise regression analysis indicated that serum miR-155 was independently associated with albumin and hs-CRP.
 CONCLUSION Serum miRNA-155 and IL-6 in uremic dialysis patients were remarkably increased compared to healthy objects. Serum miRNA-155 was positively correlated with the level of IL-6 as well as hs-CRP, while miR-155 was negatively correlated with HDL and albumin. Alprostadil could ameliorate the inflammatory conditions of uremic dialysis patients by inhibition of the IL-6 expression. Serum miRNA-155 may be a novel target for the treatment of uremic dialysis patients.
Alprostadil ; therapeutic use ; C-Reactive Protein ; metabolism ; Case-Control Studies ; Humans ; Interleukin-6 ; blood ; MicroRNAs ; blood ; Peritoneal Dialysis ; Regression Analysis ; Renal Dialysis ; Renal Insufficiency, Chronic ; therapy ; Uremia ; blood ; drug therapy

No abstract available.
Aged ; Anti-Bacterial Agents/*adverse effects ; Anticonvulsants/therapeutic use ; Cephalosporins/*adverse effects ; Consciousness Disorders/diagnosis/drug therapy/*etiology ; Diabetic Nephropathies/complications/*therapy ; Electroencephalography ; Female ; Humans ; Pneumonia, Bacterial/complications/*drug therapy ; *Renal Dialysis ; Status Epilepticus/diagnosis/drug therapy/*etiology ; Treatment Outcome ; Uremia/therapy

Relative deficiency in production of glycoprotein hormone erythropoietin (Epo) is a major cause of renal anemia. This study planned to investigate whether the hypoxia-regulated system of Epo expression, constructed by fusing Epo gene to the chimeric phosphoglycerate kinase (PGK) hypoxia response elements (HRE) in combination with cytomegalovirus immediate-early (CMV IE) basal gene promoter and delivered by plasmid intramuscular injection, might provide a long-term physiologically regulated Epo secretion expression to correct the anemia in adenine-induced uremic rats. Plasmid vectors (pHRE-Epo) were synthesized by fusing human Epo cDNA to the HRE/CMV promoter. Hypoxia-inducible activity of this promoter was evaluated first in vitro and then in vivo in healthy and uremic rats (n = 30 per group). The vectors (pCMV-Epo) in which Epo expression was directed by a constitutive CMV gene promoter served as control. ANOVA and Student's t-test were used to analyze between-group differences. A high-level expression of Epo was induced by hypoxia in vitro and in vivo. Though both pHRE-Epo and pCMV-Epo corrected anemia, the hematocrit of the pCMV-Epo-treated rats exceeded the normal (P < 0.05), but that of the pHRE-Epo-treated rats didn't. Hypoxia-regulated system of Epo gene expression constructed by fusing Epo to the HRE/CMV promoter and delivered by plasmid intramuscular injection may provide a long-term and stable Epo expression and secretion in vivo to correct the anemia in adenine-induced uremic rats.
Anemia/blood/*therapy ; Animals ; Base Sequence ; Blood Urea Nitrogen ; Cell Hypoxia ; Creatinine/blood ; Erythropoietin/biosynthesis/*genetics/secretion ; Gene Expression Regulation ; Genes, Reporter ; Genetic Therapy ; HeLa Cells ; Humans ; Injections, Intramuscular ; Kidney/pathology ; Luciferases, Firefly/biosynthesis/genetics ; Molecular Sequence Data ; Plasmids/*genetics ; Promoter Regions, Genetic ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/biosynthesis/genetics/secretion ; Response Elements ; Transcriptional Activation ; Uremia/blood/*therapy

Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; Hepatitis C ; complications ; drug therapy ; Humans ; Kidney Transplantation ; methods ; Male ; Premedication ; Renal Dialysis ; Uremia ; complications

Aged ; Aged, 80 and over ; Blood Platelets ; chemistry ; Humans ; Receptor, PAR-1 ; blood ; Receptors, Thrombin ; blood ; Renal Dialysis ; Uremia ; blood ; therapy