Gastric carcinoma is one of the most lethal malignancy at present with leading cause of cancer-related deaths worldwide. Aquaporins (AQPs) are a family of small, integral membrane proteins, which have been evidenced to play a crucial role in cell migration and proliferation of different cancer cells including gastric cancers. However, the aberrant expression of specific AQPs and its correlation to detect predictive and prognostic significance in gastric cancer remains elusive. In the present study, we comprehensively explored immunohistochemistry based map of protein expression profiles in normal tissues, cancer and cell lines from publicly available Human Protein Atlas (HPA) database. Moreover, to improve our understanding of general gastric biology and guide to find novel predictive prognostic gastric cancer biomarker, we also retrieved ‘The Kaplan–Meier plotter’ (KM plotter) online database with specific AQPs mRNA to overall survival (OS) in different clinicopathological features. We revealed that ubiquitous expression of AQPs protein can be effective tools to generate gastric cancer biomarker. Furthermore, high level AQP3, AQP9, and AQP11 mRNA expression were correlated with better OS in all gastric patients, whereas AQP0, AQP1, AQP4, AQP5, AQP6, AQP8, and AQP10 mRNA expression were associated with poor OS. With regard to the clinicopathological features including Laurens classification, clinical stage, human epidermal growth factor receptor 2 (HER2) status, and different treatment strategy, we could illustrate significant role of individual AQP mRNA expression in the prognosis of gastric cancer patients. Thus, our results indicated that AQP’s protein and mRNA expression in gastric cancer patients provide effective role to predict prognosis and act as an essential agent to therapeutic strategy.
The present study was aimed at investigating the effect of amifostine on myocardial ischemia/reperfusion (I/R) injury of mice and H9c2 cells cultured with TBHP (tert-butyl hydroperoxide). The results showed that pretreatment with amifostine significantly attenuated cell apoptosis and death, accompanied by decreased reactive oxygen species (ROS) production and lower mitochondrial potential (ΔΨm). In vivo, amifostine pretreatment alleviated I/R injury and decreased myocardial apoptosis and infarct area, which was paralleled by increased superoxide dismutase (SOD) and reduced malondialdehyde (MDA) in myocardial tissues, increased Bcl2 expression, decreased Bax expression, lower cleaved caspase-3 level, fewer TUNEL positive cells, and fewer DHE-positive cells in heart. Our results indicate that amifostine pretreatment has a protective effect against myocardial I/R injury via scavenging ROS.
BackgroundLong-term recurrence (LR) is a tendency that re-occurs within 3 months after catheter ablation for atrial fibrillation (AF). Whether very early recurrence (VER) within 7 days of post ablation is a prognostic factor of LR or not is unclear. For this reason, present study sought to examine the relationship between VER and LR.MethodsIn this prospective analysis 378 consecutive patients underwent an initial catheter ablation for paroxysmal or persistent AF. The association between VER and LR was analyzed by univariate and multivariate Cox regression, as well as time-dependent receiver operator characteristic (ROC) analysis.ResultsAfter a mean follow-up of 14.71 ± 8.58 months, 81 (65.90%) patients with VER experienced LR and were associated with lower event of free survival from LR (Log rank test, P < 0.001). Multivariate Cox regression analysis revealed that VER (HR = 7.02, 95% CI = 4.78–10.31; P < 0.001), left atrial enlargement (HR = 2.92, 95% CI = 1.88–4.54; P < 0.001), tendency in advanced age (HR = 1.50, 95% CI = 0.99–2.28; P = 0.054), and tendency in male (HR = 0.71, 95% CI = 0.50–1.01; P = 0.060) were independent predictors of LR. According to time-dependent ROC analysis, it was found that VER was more sensitive than common risk factors in predicting LR (0.74 vs 0.66, P < 0.001) and combination model further improved the C statistic for predicting LR (0.82 vs 0.66, P < 0.001).ConclusionsAfter a single procedure of catheter ablation, patients with VER were strongly associated with LR and combination of VER and common risk factors could further improve prediction of patients who were at high risk for LR.
Autophagy is fundamental to myocardial ischemia/reperfusion (I/R) injury. Antithrombin III (AT) has been shown to protect cardiomyocytes against I/R injury; however, it is unknown whether it modulates autophagy. The objective of this study was to investigate whether AT regulates autophagy during I/R injury and, if so, to identify the potential mechanism involved. Our study showed that AT attenuated I/R injury in vivo and hypoxia/reoxygenation (H/R) injury in vitro . Autophagy was increased both in H9C2 cardiomyocytes during H/R injury and in mouse hearts following I/R injury. The stimulation of autophagy by rapamycin attenuated the protective effect of AT against H9C2 cell injury, indicating that autophagy is involved in the protective role of AT. Furthermore, the cardioprotective effects of AT were abolished by A6730, a specific Akt inhibitor. This study shows that AT exhibits cardioprotective effects by modulating autophagy during I/R injury in a phosphoinositide 3-kinase/Akt-dependent manner.
Abdominal aortic aneurysm (AAA) is an unpredictable but lethal disease that poses a therapeutic dilemma. Circular RNAs (circRNAs), whose functional roles as transcriptional regulators and microRNA (miRNA) sponges have been shown in former studies, are potential biomarkers for many diseases. AAA in male C57BL/6 J mice was induced by coadministration of angiotensin II (Ang II) and 3,4-benzopyrene (BaP). The circRNA expression profiling was performed using two samples from the control group and two samples from the AAA group.Quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm the reliability of the microarray results. Among the 14 236 detected circRNAs, 413 showed obvious expression changes (fold change ≥ 2; P < 0.05) between the BaP/Ang II-induced AAA group and control group. Of the 413 that showed significant changes, 271 were upregulated, while the other 142 were downregulated. The expression levels of 10 circRNAs were validated by qRT-PCR. The interactions of the differentially expressed circRNAs with miRNAs were predicted. Immunofluorescence showed prominent vascular smooth muscle cell apoptosis in abdominal aortic tissues in the BaP/Ang II group. Furthermore, a circRNA-miRNA coexpression network based on six apoptosisrelated circRNAs was built. The genes regulated by the network mapped to several pathways, including apoptosis, the IL-17 signaling pathway, and vascular endothelial growth factor signaling pathway, all of which are related to AAA formation. This study performed circRNA expression profiling in AAA and the results specifically predicted the regulatory role of circRNAs in AAA pathogenesis. K E Y W O R D Sabdominal aortic aneurysm, apoptosis, biomarkers, circular RNA, gene expression profiling
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