Identification of potential biomarkers for pathogenesis of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is an extremely complicated neurodegenerative disorder, which accounts for almost 80 % of all dementia diagnoses. Due to the limited treatment efficacy, it is imperative for AD patients to take reliable prevention and diagnosis measures. This study aimed to explore potential biomarkers for AD. METHODS: GSE63060 and GSE140829 datasets were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEG) between AD and control groups in GSE63060 were analyzed using the limma software package. The mRNA expression data in GSE140829 was analyzed using weighted gene co-expression network analysis (WGCNA) function package. Protein functional connections and interactions were analyzed using STRING and key genes were screened based on the degree and Maximal Clique Centrality (MCC) algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the key genes. RESULTS: There were 65 DEGs in GSE63060 dataset between AD patients and healthy controls. In GSE140829 dataset, the turquoise module was related to the pathogenesis of AD, among which, 42 genes were also differentially expressed in GSE63060 dataset. Then 8 genes, RPS17, RPL26, RPS3A, RPS25, EEF1B2, COX7C, HINT1 and SNRPG, were finally screened. Additionally, these 42 genes were significantly enriched in 12 KEGG pathways and 119 GO terms. CONCLUSIONS: In conclusion, RPS17, RPL26, RPS3A, RPS25, EEF1B2, COX7C, HINT1 and SNRPG, were potential biomarkers for pathogenesis of AD, which should be further explored in AD in the future.

A 2 miRNAs-based signature for the diagnosis of atherosclerosis.

BACKGROUND: Atherosclerosis (AS) is a leading cause of vascular disease worldwide. MicroRNAs (miRNAs) play an essential role in the development of AS. However, the miRNAs-based biomarkers for the diagnosis of AS are still limited. Here, we aimed to identify the miRNAs significantly related to AS and construct the predicting model based on these miRNAs for distinguishing the AS patients from healthy cases. METHODS: The miRNA and mRNA expression microarray data of blood samples from patients with AS and healthy cases were obtained from the GSE59421 and GSE20129 of Gene Expression Omnibus (GEO) database, respectively. Weighted Gene Co-expression Network Analysis (WGCNA) was performed to evaluate the correlation of the miRNAs and mRNAs with AS and identify the miRNAs and mRNAs significantly associated with AS. The potentially critical miRNAs were further optimized by functional enrichment analysis. The logistic regression models were constructed based on these optimized miRNAs and validated by threefold cross-validation method. RESULTS: WGCNA revealed 42 miRNAs and 532 genes significantly correlated with AS. Functional enrichment analysis identified 12 crucial miRNAs in patients with AS. Moreover, 6 miRNAs among the identified 12 miRNAs, were selected using a stepwise regression model, in which four miRNAs, including hsa-miR-654-5p, hsa-miR-409-3p, hsa-miR-485-5p and hsa-miR-654-3p, were further identified through multivariate regression analysis. The threefold cross-validation method showed that the AUC of logistic regression model based on the four miRNAs was 0.7308, 0.8258, and 0.7483, respectively, with an average AUC of 0.7683. CONCLUSION: We identified a total of four miRNAs, including hsa-miR-654-5p and hsa-miR-409-3p, are identified as the potentially critical biomarkers for AS. The logistic regression model based on the identified 2 miRNAs could reliably distinguish the patients with AS from normal cases.

iTRAQ-based quantitative proteomics and target-fishing strategies reveal molecular signatures on vasodilation of Compound Danshen Dripping Pills.

Angina pectoris can be used as an early warning for coronary artery disease. Vasodilation is an important mechanism of angina pectoris. Traditional Chinese medicine - Compound Danshen Dripping Pill (CDDP) is widely used to improve the symptoms of cardiovascular diseases (CVDs). To investigate the influence of vasodilation effect and underlying mechanisms of CDDP, we determined the vasodilation effect of thoracic aorta ring on rat induced by norepinephrine (NE). Then targets-fishing method was used to predict the potential mechanism of CDDP on vasodilation, based on the structures of the main components. Then, iTRAQ-based quantitative proteomics analysis was used for verification of the candidate target proteins and pathways to illustrate the underlying mechanisms. Furthermore, the differentially expressed proteins in the enriched pathways were validated by western blotting. In this study, we found that CDDP could significantly inhibit NE induced aortic contraction tension, and the mechanism may be related to platelet activation, cGMP - PKG signaling pathway and vascular smooth muscle contraction. The method provides a new way to uncover the vasodilation mechanism of CDDP, as well as other multi-component herbal medicines.

miR-29b in regulating blood pressure and cardiac function in the rat model of hypertension.

The possibility of micro ribonucleic acid-29b (miR-29b) regulating blood pressure and cardiac function in the rat model of hypertension was investigated. Sixty rat models of hypertension were established and randomly divided into the lentivirus group (n=20), the negative lentivirus group (n=20) and the control group (n=20). Rats in the lentivirus group were injected with the recombinant lentivirus, and those in the negative lentivirus and control groups were injected with the negative control virus and infection enhancement solution, respectively. The systolic pressure of rats was monitored using the tail-cuff method, and changes in the cardiac function of rats were evaluated via high-frequency ultrasound. At 3 weeks after virus infection, rats were weighed and sacrificed, the heart was taken and the left ventricular mass index was calculated. Moreover, the expression of miR-29b in myocardial tissues was detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The systolic pressure in the lentivirus group was significantly decreased compared with those in the negative lentivirus and control groups (P<0.05). In the lentivirus group, the systolic pressure was significantly reduced after virus transfection (P<0.05), and there were also statistically significant differences in ultrasonic measurement indexes (LVPWT, IVST, LVEDD and LVESD) (P<0.05). LVPWT was remarkably decreased at 5 weeks and 6 weeks compared with that in the previous week, and it was lower than those in the other two groups (all P<0.05). After virus transfection, IVST in the lentivirus group showed a decreasing trend, which was obviously lower than those in the other two groups (P<0.05). After virus transfection, LVEDD in the lentivirus group increased gradually, and was higher than that in the other two groups. The expression of miR-29b was upregulated in the lentivirus group compared with those in the other two groups (P<0.05). The overexpression of miR-29b can reduce the blood pressure and significantly improve the cardiac function of hypertension rats.

Impact of bone marrow mononuclear cells therapy on left ventricular function in patients with ST-elevated myocardial infarction: A meta-analysis.

BACKGROUND: Bone marrow mononuclear cell (BMMNC) therapy has been used as an adjunctive treatment in patients with ST-elevated myocardial infarction (STEMI). However, the therapeutic efficacy of this approach remains controversial. The present meta-analysis is aimed to evaluate the impact of cell therapy on left ventricular function after STEMI. METHODS: We searched through PubMed and EMBASE databases till 2017 for all relevant publications using certain search terms. Randomized controlled trials investigating the effect of BMMNC therapy in patients with STEMI who underwent percutaneous coronary intervention were selected. Wall motion score index (WMSI), infarct size, wall thickening, and myocardial perfusion were our endpoints. RESULTS: A total of 24 trials with 1536 patients were included in our study. Overall, as observed in our data, cell therapy reduced infarct size by -2.32 (95% confidence interval [CI] -4.03, -0.62; P = .007; I = 24%) and improved myocardial perfusion by -3.04 (95% CI -3.94, -2.15; P < .001; I = 0%). However, there was no significant difference between treatment group and control group in WMSI or wall thickening. CONCLUSION: Intracoronary BMMNC infusion is safe for patients with STEMI. It is also associated with improvement of infarct size and myocardial perfusion. Further multicenter randomized trials should be conducted to validate the therapeutic efficacy of this treatment.