Shenfu Administration Improves Cardiac Fibrosis in Rats With Myocardial Ischemia-Reperfusion Through Adenosine A2a Receptor Activation.

OBJECTIVE: Shenfu injection (SFI) is commonly used for cardiac dysfunction in China. Adenosine receptors have been reported to exert anti-fibrosis effects. The intent of this study was to evaluate that SFI attenuates cardiac fibrosis through activating of adenosine A2a receptor (A2aR) in rats with myocardial ischemia-reperfusion (MI/R). METHODS: Sprague Dawley male rats were randomly divided into five groups, nine rats in each group. Injections in all rat groups were carried out prior to reperfusion, and in the sham and MI/R groups, only vehicle was injected. Injections in the remaining group were as follows: 5 mL/kg in the SFI group; 15 mg/kg nicorandil in the A2R agonist group; and 5 mL/kg SFI plus 5 mg/kg MSX-3 in the SFI + A2aR antagonist group. Changes in cyclic adenosine monophosphate (cAMP) and the development of myocardial infarction and cardiac fibrosis were documented among the groups. Additionally, the levels of A2aR, collagen Ⅰ, collagen Ⅲ, fibronectin, and matrix metalloproteinase-9 (MMP-9) were measured. RESULTS: Following injection with SFI or nicorandil, the cAMP concentration, infarct area, and cardiac fibrosis induced by MI/R injury were significantly decreased (p < 0.05). Additionally, the levels of collagen Ⅰ, collagen Ⅲ, fibronectin, and MMP-9 were clearly suppressed by SFI or nicorandil when compared with the MI/R group (p<0.01). However, the protective effects of SFI were counteracted by MSX-3. A negative correlation between A2aR and collagen I and collagen III was found (p = 0.00). CONCLUSION: SFI activated the A2aR to reduce myocardial fibrosis caused by MI/R injury, which provided an underlying mechanism of action of SFI.

Effects of Shenfu injection on myocardial adenosine receptors in rats with myocardial ischemia-reperfusion postconditioning.

OBJECTIVE: Shenfu injection (SFI) has been reported to have a protection against myocardial ischemia-reperfusion (MI/R) injury. However, the changes of adenosine receptors in MI/R postconditioning when pretreated with SFI are unclear. METHODS: Forty-five rats were randomly divided into sham group (sham), MI/R postconditioning group (MI/R-post), low-dose SFI group (1 mL/kg), middle-dose SFI group (2.5 mL/kg), and high-dose SFI group (5 mL/kg). In SFI groups, SFI was intravenously injected before reperfusion, and rats were treated with ischemic postconditioning after ischemia for 30 min. After 24 h of reperfusion, the levels of Ca2+ and cAMP in blood platelets were analyzed. Myocardial infarct volume and myocardial pathology were observed. The levels of adenosine receptor subtypes A1, A2b, and A3 in myocardium were analyzed using immunohistochemistry and Western blot. The oxidative stress-related indicators were also observed. RESULTS: Compared with the MI/R-post group, SFI ameliorated the MI/R injury by decreasing the myocardial infarct area, oxidative stress, and concentration of Ca2+ and cAMP (p < 0.01). Pretreatment with SFI enhanced the expression of adenosine receptors A1 and A2b in a dose manner compared with the MI/R-post group. In contrast, the levels of adenosine receptor A3 were increased after MI/R postconditioning compared with the sham group, and its expression continued to increase with the increase of SFI. Furthermore, the oxidative stress reduced with the concentrations of SFI. CONCLUSION: These results demonstrated that pretreatment with SFI might regulate the expression of adenosine receptors to improve the MI/R postconditioning.

MiR-30b-5p functions as a tumor suppressor in cell proliferation, metastasis and epithelial-to-mesenchymal transition by targeting G-protein subunit α-13 in renal cell carcinoma.

Increasing evidence has demonstrated that aberrant microRNAs (miRNAs) play important roles in the pathogenesis of most human malignancies. The purpose of this study was to explore the role of miR-30b-5p in human RCC. In the current study, we firstly found that the expression levels of miR-30b-5p were lower in both RCC tissues and cell lines. Then, we found that enforced miR-30b-5p expression and knockdown of GNA13 significantly suppressed the proliferation, invasion, migration and EMT of RCC cell lines. In addition, miR-30b-5p directly targeted GNA13 and repressed its expression. Furthermore, re-expression of GNA13 (without the 3'-UTR) could partially abrogate the miR-30b-5p-induced cell proliferation and metastasis inhibition. Taken together, these findings indicated that miR-30b-5p acts as a novel tumor suppressor to regulate RCC cell proliferation, metastasis and EMT through downregulation of GNA13 expression. Therefore, miR-30b-5p may be considered a potential biomarker for the diagnosis of RCC.

Predicting novel salivary biomarkers for the detection of pancreatic cancer using biological feature-based classification.

AIM: The use of saliva as a diagnostic fluid enables non-invasive sampling and thus is a prospective sample for disease tests. This study fully utilized the information from the salivary transcriptome to characterize pancreatic cancer related genes and predict novel salivary biomarkers. METHODS: We calculated the enrichment scores of gene ontology (GO) and pathways annotated in Kyoto Encyclopedia of Genes and Genomes database (KEGG) for pancreatic cancer-related genes. Annotation of GO and KEGG pathway characterize the molecular features of genes. We employed Random Forest classification and incremental feature selection to identify the optimal features among them and predicted novel pancreatic cancer-related genes. RESULTS: A total of 2175 gene ontology and 79 KEGG pathway terms were identified as the optimal features to identify pancreatic cancer-related genes. A total of 516 novel genes were predicted using these features. We discovered 29 novel biomarkers based on the expression of these 516 genes in saliva. Using our new biomarkers, we achieved a higher accuracy (92%) for the detection of pancreatic cancer. Another independent expression dataset confirmed that these novel biomarkers performed better than the previously described markers alone. CONCLUSION: By analyzing the information of the salivary transcriptome, we predict pancreatic cancer-related genes and novel salivary gene markers for detection.

Influence of random urine albumin-creatinine ratio of pregnant women with hypertension during the gestation period on perinatal outcome.

The aim of the present study was to investigate the influence of the random urine albumin-creatinine ratio (ACR) of pregnant women with hypertension during the gestation period on perinatal outcome. A total of 6,758 pregnant women with pregnancy-induced hypertension and proteinuria were randomly selected between September, 2009 and June, 2015 for the study. Kidney function, blood pressure, history of gravidity and parity, embryo number and the birth weight of the participants was determined. Logistic regression and paired data correlation analyses were carried out with kidney function, blood pressure, history of gravidity and parity, embryo number, birth weight, maternal age, labor presentation and other risk factors as the independent variables and the newborn APGAR score as the dependent variable. The results showed that random urine ACR was increased and negatively correlated with the APGAR score (OR=-0.095, P=0.017). In conclusion, the increased random urine ACR can influence the postpartum outcome. Early intervention of women of childbearing age in early pregnancy or before pregnancy can minimize the adverse complications of infants and mothers such as pregnancy hypertension syndrome, and improve the outcome of the pregnancy.

Molecular regulation of cervical cancer growth and invasion by VEGFa.

Although antivascular endothelial growth factor a (VEGFa) treatment has been well applied in cervical cancer therapy, the underlying molecular basis has not been precisely identified. Here, we examined the levels of VEGFa on the tumor growth and invasion in four commonly used human cervical cancer cell lines. We found that overexpression of VEGFa in these lines increased the tumor growth and invasiveness, while inhibition of VEGFa decreased the tumor growth and invasiveness. To figure out the involved signaling pathways, we applied specific inhibitors for ERK/MAPK, JNK, and PI3K/Akt signaling pathways, respectively, to VEGFa-overexpressing cervical cancer lines and found that only inhibition of PI3K/Akt signal transduction abolished VEGFa-induced increases in cell growth and invasiveness. Inhibition of Akt downstream mTor signaling similarly inhibited cell growth and invasion in VEGFa-overexpressing cervical cancer cells, suggesting that VEGFa may activate PI3K/Akt, and subsequently its downstream mTor signaling pathway, to promote cervical cancer cell growth and invasion. Furthermore, the effects of VEGFa-induced activation of mTor signaling cascades appeared to promote cancer cell growth through cyclinD1 and CDK4 activation and promote cancer cell invasion through MMP2 and MMP3. Taken together, our data suggest that anti-VEGFa treatment in cervical cancer may inhibit both tumor cell growth and invasion through PI3k/Akt/mTor signaling pathway.