The primary objective of this study investigated the role of microRNA-320 (miR-320) on left ventricular remodeling in the rat model of myocardial ischemia-reperfusion (I/R) injury, and we intended to explore the myocardial mechanism of miR-320-mediated myocardium protection. We collected 120 male Wistar rats (240–280 g) in this study and then randomly divided them into three groups: (1) sham surgery group (sham group: n = 40); (2) ischemia-reperfusion model group (I/R group: n = 40); and (3) I/R model with antagomir-320 group (I/R + antagomir-320 group: n = 40). Value changes of heart function in transesophageal echocardiography were recorded at various time points (day 1, day 3, day 7, day 15 and day 30) after surgery in each group. Myocardial sections were stained with hematoxylin and eosin (H&E) and examined with optical microscope. The degree of myocardial fibrosis was assessed by Sirius Red staining. Terminal dUTP nick end-labeling (TUNEL) and qRT-PCR methods were used to measure the apoptosis rate and to determine the miR-320 expression levels in myocardial tissues. Transesophageal echocardiography showed that the values of left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP) and ±dp/dtmax in the I/R group were obviously lower than those in the sham group, while the left ventricular end-diastolic pressure (LVEDP) value was higher than that in the sham group. The values of LVEF, LVFS, LVSP and ±dp/dtmax showed a gradual decrease in the I/R group, while the LVEDP value showed an up tendency along with the extension of reperfusion time. The H&E staining revealed that rat myocardial tissue in the I/R group presented extensive myocardial damage; for the I/R + antagomir-320 group, however, the degree of damage in myocardial cells was obviously better than that of the I/R group. The Sirius Red staining results showed that the degree of myocardial fibrosis in the I/R group was more severe along with the extension of the time of reperfusion. For the I/R + antagomir-320 group, the degree of myocardial fibrosis was less severe than that in the I/R group. Tissues samples in both the sham and I/R + antagomir-320 groups showed a lower apoptosis rate compared to I/R group. The qRT-PCR results indicated that miR-320 expression in the I/R group was significantly higher than that in both the sham and I/R + antagomir-320 groups. The expression level of miR-320 is significantly up-regulated in the rat model of myocardial I/R injury, and it may be implicated in the prevention of myocardial I/R injury-triggered left ventricular remodeling.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: This study aimed to explore the association of long non-coding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1) with exacerbation risk, lung function, and inflammatory cytokines in asthma. Methods:A total of 170 patients with asthma in exacerbation, 170 patients with asthma in remission, and 170 healthy controls (HCs) were enrolled, and their plasma samples were collected. The expressions of lncRNA NEAT1 and microRNA-124 (miRNA-124) in plasma were detected by real-time quantitative polymerase chain reaction; inflammatory cytokines in plasma were measured by the Enzyme-linked immunosorbent assay (ELISA); and pulmonary ventilation function was detected by examination of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC).Results: LncRNA NEAT1 expression was upregulated in asthma patients in exacerbation compared with HCs and asthma patients in remission, and receiver operating characteristic curve exhibited that it was of good value in distinguishing asthma patients in exacerbation from HCs (AUC: 0.869 (0.830-0.908)) and asthma patients in remission (AUC: 0.775 (0.724-0.825)). Furthermore, lncRNA NEAT1 was positively correlated with exacerbation severity, TNF-α, IL-1β, and IL-17, but negatively correlated with IL-10, FEV 1 /FVC and FEV 1 %predicted in asthma patients. Additionally, lncRNA NEAT1 was negatively correlated with miR-124, and miR-124 was negatively associated with exacerbation risk, exacerbation severity, and inflammation, but positively associated with lung function in asthma patients. Conclusion:Circulating lncRNA NEAT1 exhibits potential to be a new biomarker for elevated exacerbation risk and severity of asthma. K E Y W O R D S asthma, exacerbation, lncRNA NEAT1, miR-124 S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Li X, Ye S, Lu Y. Long non-coding RNA NEAT1 overexpression associates with increased exacerbation risk, severity, and inflammation, as well as decreased lung function through the interaction with microRNA-124 in asthma.

To investigate the correlation of miR-125a/b expression with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients and inflammatory cytokines.Eighty-seven AECOPD patients, 93 stable chronic obstructive pulmonary disease (COPD) patients and 100 health volunteers (HCs) were recruited. Plasma samples were collected from AECOPD patients at the day 1, day 7, day 14, and day 28 of admission and from stable COPD patients as well as HCs. Total RNA was extracted from plasma, and miR-125a/b relative expressions were determined by quantitative real time-polymerase chain reaction.MiR-125b had a great capacity for distinguishing AECOPD from stable COPD (AUC = 0.926, 95% CI: 0.884–0.967) and HCs (AUC = 0.923, 95% CI: 0.880–0.966), while miR-125a did not. There were associations between miR-125b expression with TNF-α, IL-8, and LTB-4 in AECOPD patients (P = .012, P = .032, and P = .047, respectively), while no correlation of miR-125a with inflammatory cytokines was found. MiR-125b expression gradually decreased at day 7, day 14, and day 28 compared with day 1 (all P < .05) on admission, while no difference in miR-125a was discovered between each visit compared to day 1. Besides, TNF-α, IL-1β, IL-8, and LTB-4 were elevated in AECOPD patients compared with stable COPD patients (all P < .01).MiR-125b, but not miR-125a, was positively associated with inflammatory cytokines and could be a novel biomarker for distincting AECOPD from stable COPD patients and HCs.

Metastasis-associated in colon cancer-1 (MACC1) promotes colorectal cancer progression and predicts prognosis. The aim of our study was to determine the diagnostic and prognostic value of preoperative serum MACC1 levels in breast cancer patients. Serum MACC1 levels were measured in 378 breast cancer patients, 120 patients with benign breast disease, and 40 healthy volunteers using an ELISA. Serum MACC1 levels were higher in breast cancer patients than patients with benign disease or healthy volunteers. Increased serum MACC1 was associated with breast cancer TNM stage (P < 0.001), tumor size (P < 0.001), lymph node metastasis (P < 0.001), and Ki-67 status (P = 0.014). Serum MACC1 measurement successfully discriminated breast cancer patients from normal and healthy controls (AUC = 0.785, 95% CI: 0.746–0.825) with an optimal cut-off value of 38.35 pg/ml (sensitivity = 0.725, specificity = 0.696). Moreover, serum MACC1 exhibited significant prognostic value in breast cancer (AUC = 0.757, 95% CI: 0.700–0.814), and high MACC1 was associated with poor disease-free survival (HR 5.63, 95% CI: 3.51–9.04; P < 0.001). Our findings demonstrated that circulating MACC1 could serve as a reliable diagnostic and prognostic biomarker for breast cancer.

Background : To investigate prognostic factors and recurrence patterns in T4 gastric cancer (GC) patients after curative resection. Methods : Between January 2004 and December 2014, 249 patients with T4 gastric cancer undergoing curative resection were recruited. Patient characteristics, survival, prognostic factors and recurrence patterns were analyzed. Results : Our results showed that the median survival time (MST) for T4 gastric cancer after curative resection was 55.47 months, with 59.47 months for T4a (tumor perforating serosa) and 25.90 months for T4b (tumor invasion of the adjacent structure). Multivariate analysis indicated that age (hazard ratio [HR], 1.86; P = 0.006), location of tumor (HR, 1.25, 0.90 - 5.64; P < 0.001) and intraoperative blood loss (HR, 1.85; P = 0.010) were independent prognostic factors for overall survival (OS). After a median follow-up of 25.87 months, a total of 109 (43.8%) patients suffered from recurrence, and 90 patients had been observed specific recurrence sites, among which peritoneal metastasis was the most common recurrence pattern, 59.0% for T4a and 88.3% for T4b, respectively. Conclusions : For T4 gastric cancer patients after curative resection, older age, gastric cancer of the entire stomach and more intraoperative blood loss were associated with poor OS. The recurrence rate after curative resection for T4 was high, and the most common recurrence pattern was peritoneal metastasis.

Pre-existing Ca2+ handling abnormalities constitute the arrhythmogenic substrate in patients developing postoperative atrial fibrillation (POAF), a common complication after cardiac surgery. Postoperative interleukin (IL)-6 levels are associated with atrial fibrosis in several animal models of POAF, contributing to atrial arrhythmias. Here, we hypothesize that IL-6-mediated-Ca2+ handling abnormalities contribute to atrial fibrillation (AF) in sterile pericarditis (SP) rats, an animal model of POAF. SP was induced in rats by dusting atria with sterile talcum powder. Anti-rat-IL-6 antibody (16.7 μg/kg) was administered intraperitoneally at 30 min after the recovery of anesthesia. In vivo electrophysiology, ex vivo optical mapping, western blots, and immunohistochemistry were performed to elucidate mechanisms of AF susceptibility. IL-6 neutralization ameliorated atrial inflammation and fibrosis, as well as AF susceptibility in vivo and the frequency of atrial ectopy and AF with a reentrant pattern in SP rats ex vivo. IL-6 neutralization reversed the prolongation and regional heterogeneity of Ca2+ transient duration, relieved alternans, reduced the incidence of discordant alternans, and prevented the reduction and regional heterogeneity of the recovery ratio of Ca2+ transient. In agreement, western blots showed that IL-6 neutralization reversed the reduction in the expression of ryanodine receptor 2 (RyR2) and phosphorylated phospholamban. Acute IL-6 administration to isolated rat hearts recapitulated partial Ca2+ handling phenotype in SP rats. In addition, intraperitoneal IL-6 administration to rats increased AF susceptibility, independent of fibrosis. Our results reveal that IL-6-mediated-Ca2+ handling abnormalities in SP rats, especially RyR2-dysfunction, independent of IL-6-induced-fibrosis, early contribute to the development of POAF by increasing propensity for arrhythmogenic alternans.

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The calcium (Ca2+) permeable transient receptor potential vanilloid 4 (TRPV4) cation channel is expressed in neutrophils and contributes to myocardial ischemia/reperfusion (I/R) injury. Here we tested the hypotheses that TRPV4 promotes neutrophil activation and subsequently aggregates myocardial I/R injury. TRPV4 protein was confirmed in neutrophils and its function was assessed by the current and intracellular Ca2+ concentration elevations evoked by TRPV4 agonists. Furthermore, TRPV4 agonists dose-repandly promoted migration toward fMLP, reactive oxygen species (ROS) production, and myeloperoxidase (MPO) release, which were prevented by pretreatment with a selective TRPV4 antagonist, in neutrophils from TRPV4 knock-out (KO) mice, Ca2+-free medium, or BAPTA-AM + Ca2+-free medium. Blockade of TRPV4 also inhibited the effects of commonly used neutrophil activators N-formyl-l-methionyl-leucyl-l-phenylalanine (fMLP) and Phorbol 12-myristate 13-acetate (PMA). Mechanically, TRPV4 regulated neutrophil activation, particularly ROS production, by affecting PKCα, P38, and AKT via Ca2+ signaling. In addition, isolated hearts infused with neutrophils from wild-type (WT) mice showed additional myocardial I/R injuries, but not those infused with TRPV4 KO. Our study reveals that TRPV4-mediated neutrophil activation enhances myocardial I/R injury, and it might be a novel therapeutic target for myocardial I/R injury and other neutrophil-mediated inflammatory diseases.