Identification of Important Modules and Hub Gene in Chronic Kidney Disease Based on WGCNA.

Chronic kidney disease (CKD) is an ongoing deterioration of renal function that often progresses to end-stage renal disease. In this study, we aimed to screen and identify potential key genes for CKD using the weighted gene coexpression network (WGCNA) analysis tool. Gene expression data related to CKD were screened from GEO database, and expression datasets of GSE66494 and GSE62792 were obtained. After discrete analysis of samples, WGCNA analysis was performed to construct gene coexpression module, and the correlation between the module and disease was calculated. The modules with a significant correlation with the disease were selected for Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Then, the interaction network of related molecules was constructed, and the high score subnetwork was selected, and the candidate key molecules were identified. A total of 882 DEGs were identified in the screening datasets. A subnetwork containing 6 nodes was found with a high score of 12.08, including CEBPZ, IFI16, LYAR, BRIX1, BMS1, and DDX18. DEGs could significantly differentiate CKD and healthy individuals in principal component analysis. In addition, the MEturquiose, MEred, and MEblue in group were significantly correlated with disease in WGCNA. These 6 hub genes were found to significantly discriminate between CKD and healthy controls in the validation dataset, suggesting that they could use these molecules as candidate markers to distinguish CKD from healthy people. Overall, our study indicated that 6 hub genes may play key roles in the occurrence and development of CKD.

Association of Parenteral Anticoagulation Therapy With Outcomes in Non-ST-Segment Elevation Acute Coronary Syndrome Patients Without Invasive Therapy: Findings from the Improving Care for Cardiovascular Disease in China (CCC) project.

Our previous study showed that parenteral anticoagulation therapy (PACT) in the context of aggressive antiplatelet therapy failed to improve clinical outcomes in patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). However, the role of PACT in patients managed medically remains unknown. This observational cohort study enrolled patients with NSTE-ACS receiving medical therapy from November 2014 to June 2017 in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. Eligible patients were included in the PACT group and non-PACT group. The primary outcomes were in-hospital all-cause mortality and major bleeding. The secondary outcome included minor bleeding. Among 23,726 patients, 8,845 eligible patients who received medical therapy were enrolled. After adjusting the potential confounders, PACT was not associated with a lower risk of in-hospital all-cause mortality (adjusted odds ratio (OR), 1.25; 95% confidence interval (CI), 0.92-1.71; P = 0.151). Additionally, PACT did not increase the incidence of major bleeding or minor bleeding (major bleeding: adjusted OR, 1.04; 95% CI, 0.80-1.35; P = 0.763; minor bleeding: adjusted OR, 1.27; 95% CI, 0.91-1.75; P = 0.156). The propensity score analysis confirmed the primary analyses. In patients with NSTE-ACS receiving antiplatelet therapy, PACT was not associated with a lower risk of in-hospital all-cause mortality or a higher bleeding risk in patients with NSTE-ACS receiving non-invasive therapies and concurrent antiplatelet strategies. Randomized clinical trials are warranted to reevaluate the safety and efficacy of PACT in all patients with NSTE-ACS who receive noninvasive therapies and current antithrombotic strategies.

Rosuvastatin Treatment for Preventing Contrast-Induced Acute Kidney Injury After Cardiac Catheterization: A Meta-Analysis of Randomized Controlled Trials.

We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the protective effects of rosuvastatin on contrast-induced acute kidney injury (CI-AKI) and major adverse cardiovascular events (MACEs) in patients undergoing cardiac catherization.PubMed, MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central RCTs were searched for RCTs from inception to May 2015, to compare rosuvastatin for preventing CI-AKI with placebo treatment in patients undergoing cardiac catherization.Five RCTs with a total of 4045 patients involving 2020 patients pretreated with rosuvastatin and 2025 control patients were identified and analyzed. Patients treated with rosuvastatin had a 51% lower risk of CI-AKI compared with the control group based on a fixed-effect model (OR = 0.49, 95% CI = 0.37-0.66, P < 0.001), and showed a trend toward a reduced risk of MACEs (OR = 0.62, 95% CI = 0.36-1.07, P = 0.08). A subgroup analysis showed that studies with Jadad score ≥3 showed a significant reduction of CI-AKI (OR = 0.53, 95% CI, 0.38-0.73, P < 0.001). However, the risk of CI-AKI did not significantly differ in the studies with Jadad score <3 (OR = 0.54, 95% CI, 0.13-2.24, P = 0.40). In addition, the rosuvastatin treatment showed no effect for preventing CI-AKI in patients with chronic kidney disease (CKD) undergoing elective cardiac catherization (I = 0%, OR = 0.81, 95% CI = 0.41-1.61, P = 0.55).This updated meta-analysis demonstrated that preprocedural rosuvastatin treatment could significantly reduce the incidence of CI-AKI, with a trend toward a reduced risk of MACEs in patients undergoing cardiac catheterization. However, rosuvastatin treatment did not seem to be effective for preventing CI-AKI in CKD patients undergoing elective cardiac catheterization.

[Effect of hydrogen sulfide on H2O2-stimulated primary neonatal rat cardiomyocytes].

OBJECTIVE: To investigate the effects of hydrogen sulfide (H2S) on H2O2-stimulated primary neonatal rat cardiomyocytes and related mechanism. METHODS: Primary neonatal rat cardiomyocytes were treated with various concentrations of H2O2 (10, 100, 1000 µmol/L) for 24 h to establish the oxidative stress-induced cell injury model after 3 days' conventional culture. In addition, different concentrations of NaHS (1, 10, 100 µmol/L) were added to cardiomyocytes in the absence and presence of 100 µmol/L H2O2 for 24 h. The viability of cardiomyocytes was measured by MTT assay. The SOD vitality was measured by xanthine oxidase method and MDA content was determined by thiobarbituric acid colorimetric method. LDH activity was measured by chemical colorimetric method. The percentage of apoptotic cells was assessed by flow cytometry (FCM). The mitochondrial membrane potential (MMP) was analyzed by rhodamine 123 (Rh123) staining and photofluorography. The level of reactive oxygen species (ROS) in cardiomyocytes was measured by DCFH-DA staining and photofluorography. RESULTS: Cell viability and SOD vitality were significantly reduced while MDA content and LDH activity were significantly increased with increasing H2O2 concentrations. These effects could be partly reduced by cotreatment with H2O2 in a concentration-dependent manner (all P < 0.05). Compared with control group, the DCF fluorescence intensity significantly increased in the 100 µmol/L H2O2 group (P = 0.003), which could be attenuated by NaHS in a dose-dependent manner. Compared with control group, the MMP significantly decreased in the 100 µmol/L H2O2 group (P = 0.000), which could be partly reversed by cotreatment with NaHS in a dose-dependent manner. Moreover, H2O2 treatment also significantly reduced 100 µmol/L H2O2 induced apoptosis in a dose-dependent manner. CONCLUSION: H2S protects primary neonatal rat cardiomyocytes against H2O2-induced oxidative stress injury through inhibition of H2O2 induced overproduction of ROS, dissipation of MMP and apoptosis.

Bone marrow stromal cell transplantation combined with angiotensin-converting enzyme inhibitor treatment in rat with acute myocardial infarction and the role of insulin-like growth factor-1.

BACKGROUND AIMS: We investigated bone marrow stromal cell (BMSC) transplantation combined with angiotensin-converting enzyme inhibitor (ACEI) treatment in acute myocardial infarction (AMI) and the role of insulin-like growth factor-1 (IGF-1). METHODS: AMI models were established in Sprague-Dawley rats by ligation of the left anterior descending coronary artery and grouped into blank control (BC), ACEI treatment (ACEI), BMSC transplantation (BMSC) and BMSC transplantation plus ACEI (combined). Perindopril (2.5 mg/kg) was administered by gavage to ACEI and combined groups from the day after AMI. BMSC (2 × 10(8)) were injected into the border of the MI area a week later in the BMSC and combined groups. RESULTS: After 4 weeks, hemodynamics in the BMSC and combined groups were significantly improved (P < 0.05 versus BC), with the greatest improvement in the combined group (P < 0.05). In addition, an increased number of BMSC survived in the combined group (P < 0.05 versus BMSC). A proportion of BMSC was positive for troponin T, as detected by immunofluorescence. The number of apoptotic cardiomyocytes was decreased in the BMSC and ACEI groups, and even further in the combined group (P < 0.05). IGF-1 expression was up-regulated in the BMSC and combined groups (P < 0.05 versus BC), but not in the ACEI group. B cell lymphoma-2 (Bcl-2) expression was up-regulated in the ACEI, BMSC and combined groups, with the highest expression in the combined group (P < 0.05). CONCLUSIONS: Our results show that BMSC engrafted in AMI can survive well and secrete IGF-1 and preserve cardiac function significantly. These data suggest that BMSC transplantation inhibits apoptosis of cardiomyocytes by up-regulation of Bcl-2 expression in the myocardium, and this effect might be sensitized by ACEI.

Effects of insulin-like growth factor-1 on the properties of mesenchymal stem cells in vitro.

OBJECTIVE: To explore the effects of insulin-like growth factor-1 (IGF-1) on migration, proliferation and differentiation of mesenchymal stem cells (MSCs). METHODS: MSCs were obtained from Sprague-Dawley rats by a combination of gradient centrifugation and cell culture techniques and treated with IGF-1 at concentrations of 5-20 ng/ml. Proliferation of MSCs was determined as the mean doubling time. Expression of CXC chemokine receptor 4 (CXCR4) and migration property were determined by flow cytometry and transwell migration essay, respectively. mRNA expression of GATA-4 and collagen II was determined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The mean doubling time of MSC proliferation was decreased, and the expression of CXCR4 on MSCs and migration of MSCs were increased by IGF-1, all in a dose-dependent manner, while the optimal concentration of IGF-1 on proliferation and migration was different. IGF-1 did not affect the expression of GATA-4 or collagen II mRNA. CONCLUSIONS: IGF-1 dose-dependently stimulated the proliferation of MSCs, upregulated the expression of CXCR4, and accelerated migration. There was no apparent differentiation of MSCs to cardiomyocytes or chondrocytes after culturing with IGF-1 alone.

[Effects of simvastatin on homocysteine-induced endothelial dysfunction and inflammatory response].

OBJECTIVE: To investigate the effects of simvastatin (SIM) on homocysteine (HCY)-induced endothelial dysfunction and inflammatory response. METHODS: Human umbilical vein endothelial cells (HUVECs) were isolated from the umbilical cords from healthy lying-in women and cultured and added with HCY of the concentrations of 0.1, 0.25, 0.5, and 1 mmol/L respectively, or HCY 0.25 mmol/L + SIM of the concentrations of 1, 10 and 20 micromol/L respectively for 1 hour. ELISA was used to detect the cell viability with MTT method. Western blotting was used to examine the protein expression of the cell inflammatory factors, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, macrophage chemoattractant protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1, ELISA was used to detect the contents of the cell inflammatory factors. RESULTS: HCY of different doses inhibited the viability of HUVECs dose-dependently (all P < 0. 01). The survival rates of the HCY-induced HUVECs pretreatment by SIM of the concentrations of 1, 10 and 20 micromol/L for 1 hour were 1.72 +/- 0.03 times, 2.54 +/- 0.09 times, and 3.14 +/- 0.11 times respectively that of the control group (all P < 0. 01). HCY of different concentration of 0.25 mmol/L increased the protein expression of TNF-alpha, IL-6, MCP-1, and ICAM-1 significantly; however, the expression levels of TNF-alpha, IL-6, MCP-1, and ICAM-1 of the 0.25 mmol/L HCY-treated HUVECs that were pretreated by SIM of the concentration of 10 micromol/L for 1 hour were, 0.23 +/- 0.05, 0.14 +/- 0.03, 0.13 +/- 0.04, and 0.21 +/- 0.07 respectively, not significantly different from those at the time of 0 hour (all P > 0.05). CONCLUSION: Simvastatin inhibits the homocysteine-induced endothelial impairment and inflammatory response.