Doxorubicin (DOX) is used extensively in anticancer therapy, but its clinical application is limited due to its cardiotoxicity. Carnosic acid (CA) is a bioactive compound found in rosemary. It has been shown to reduce inflammation and reactive oxygen species. The purpose of this study was to investigate the potential cardioprotective effects of CA in response to DOX-induced cardiotoxicity. Here, C57BL/6 mice were administered an intraperitoneal injection of DOX (5 mg kg⁻¹, ip) once a week for three consecutive weeks and treated with CA (40 mg kg⁻¹, ig) for a three-week experimental period. For in vitro study, neonatal rat ventricular cardiomyocytes were used to validate the protective effects of CA (20 μM) in response to DOX-induced cardiotoxicity. CA markedly suppressed oxidative stress, apoptosis, and pyroptosis responses in the mouse hearts, eventually improving cardiac function. CA showed its antioxidant effect by activating nuclear factor erythroid 2-related factor (Nrf2) and its downstream heme oxygenase-1 (HO-1); CA also reduced oxidative stress by lowering the MDA and lipid ROS levels and raising the SOD and GSH-px levels. Additionally, CA treatment significantly increased Bcl-2 and inhibited Bax and Caspase-3 cleavage in DOX-induced cardiotoxicity. Moreover, CA suppressed the NOD-like receptor protein 3 (NLRP3) pathway to mitigate pyroptosis, as evidenced by lowered caspase1, interleukin-18, and interleukin-1β. Consistently, the transfection of Nrf2-siRNA eliminated the protective effects of CA on cardiomyocytes. Altogether, our findings demonstrated that CA inhibited NLRP3 inflammasomes via activating the Nrf2-related cytoprotective system and protected the heart from oxidative damage, apoptosis, and pyroptosis, implying that the use of CA could be a potential therapeutic strategy in the prevention of DOX-associated myocardiopathy.

Background: MicroRNAs (miRNAs) have been shown to commonly contribute to cardiac hypertrophy (CH). The aim of this study was to test the hypothesis that miR‐200c plays an important role in the progression of CH by targeting myosin light chain kinase (MLCK/MYLK).Methods and results: Cardiac hypertrophy was induced by aortic banding (AB) in rats. Cellular hypertrophy in neonatal rat cardiomyocytes (NCMs) was induced by AngII treatment. Echocardiography, histology and molecular measurements were used to assess the results of the experiments. The levels of apoptosis and reactive oxygen species (ROS) were also measured. Quantitative real‐time PCR (qRT‐PCR) and Western blotting were used to measure mRNA and protein levels respectively. The present results showed that miR‐200c expression was increased in response to CH both in vivo and in vitro. The down‐regulation of miRNA‐200c by a specific inhibitor markedly ameliorated CH resulting from AngII treatment, and the mRNA levels of atrial natriuretic peptide, brain natriuretic peptide and β‐myosin heavy chain were simultaneously decreased. Notably, minimal apoptosis and ROS accumulation were identified in AngII‐induced hypertrophic cardiomyocytes. Conversely, the up‐regulation of miR‐200c using specific mimics reversed these effects. Mechanistic investigations demonstrated that the MLCK gene is a direct target of miR‐200c; an increase in miR‐200c levels led to a decrease in the expression of MLCK and its downstream effector, p‐MLC2, while miR‐200c inhibition increased the expression of these proteins. Furthermore, inhibiting MLCK impaired the anti‐hypertrophic effects contributions produced by the knockdown of miR‐200c.Conclusion: Our studies suggest that miR‐200c may serve as a potential therapeutic target that could delay hypertrophy. We have also uncovered a relationship between miR‐200c and MLCK, identifying MLCK as a direct mediator of miR‐200c.

Adiponectin, an adipocyte-derived hormone with anti-inflammatory and antitumor activity, inhibits esophageal adenocarcinoma (EAC) cell proliferation and induces apoptosis. Chronic inflammation is a key process involved in initiation and progression of EAC, but the roles and mechanisms of adiponectin in inflammation have not been fully understood in EAC. We aimed to analyze the effects of two types of adiponectin, full-length adiponectin (f-Ad) and globular adiponectin (g-Ad), on inflammatory factors’ expression and explore the roles of ROS/NF-κB signaling pathway in adiponectin-regulated inflammation in EAC cells. It was found that f-Ad and g-Ad differently regulated both mRNA and protein levels of TNF-α, IL-8, and IL-6 in a dose-dependent manner in OE19 cells. g-Ad apparently induced TNF-α, IL-8, and IL-6 production, which was inhibited by PDTC or NAC, and increased intracellular ROS levels and NF-κB p65 activation, whereas f-Ad significantly suppressed production of inflammatory factors and NF-κB p65 activation and also decreased the intracellular ROS levels. In conclusion, the study demonstrated that g-Ad exerts a proinflammatory effect whereas f-Ad appears to induce an anti-inflammatory effect in a ROS/NF-κB-dependent manner in OE19 cells.

Background: Limited studies have explored the difference of fatty acid profile between women with and without gestational diabetes mellitus (GDM), and the results were inconsistent. Individual fatty acids tend to be interrelated because of the shared food sources and metabolic pathways. Thus, whether fatty acid patters during pregnancy were related to GDM odds needs further exploration.Objective: To identify plasma fatty acid patters during pregnancy and their associations with odds of GDM.Methods: A hospital-based case-control study including 217 GDM cases and 217 matched controls was carried out in urban Wuhan, China from August 2012 to April 2015. All the participants were enrolled at the time of GDM screening and provided fasting blood samples with informed consent. We measured plasma concentrations of fatty acids by gas chromatography–mass spectrometry, and derived potential fatty acid patterns (FAPs) through principal components analysis. Conditional logistic regression and restricted cubic spline model were used to evaluate the associations between individual fatty acids or FAPs and odds of GDM.Results: Twenty individual fatty acids with relative concentrations ≥0.05% were included in the analyses. Compared with control group, GDM group had significantly higher concentrations of total fatty acids, 24:1n-9, and relatively lower levels of 14:0, 15:0, 17:0, 18:0, 24:0, 16:1n-7, 20:1n-9,18:3n-6, 20:2n-6, 18:3n-3, 20:3n-3, 22:5n-3. Two novel patterns of fatty acids were identified to be associated with lower odds of GDM: (1) relatively higher odd-chain fatty acids, 14:0, 18:0, 18:3n-3, 20:2n-6, 20:3n-6 and lower 24:1n-9 and 18:2n-6 [adjusted odds ratio (OR) (95% confidence interval) (CI) for quartiles 4 vs. 1: 0.42 (0.23–0.76), P-trend = 0.002], (2) relatively higher n-3 polyunsaturated fatty acids, 24:0, 18:3n-6 and lower 16:0 and 20:4n-6 [adjusted OR (95% CI) for quartiles 4 vs. 1: 0.48 (0.26–0.90), P-trend = 0.018].Conclusion: Our findings suggested that two novel FAPs were inversely associated with GDM odds. The combination of circulating fatty acids could be a more significant marker of GDM development than individual fatty acids or their subgroups.

Background: Premature ventricular contractions (PVCs) are associated with an increased risk of implanting implantable cardioverter defibrillator (ICD). Therefore, our study aimed to predict the risk factors for implantable cardioverter defibrillator in patients with premature ventricular contractions. Methods: A total of 309 patients (male 57%, mean age 66.73±16.12) in Olmstate Countywho had premature ventricular contractions and received a 24-hour electrocardiography monitoring were included between January 1994 and September 2010 at Mayo Clinic, Rochester, Minnesota. All these patients were continuously followed o Jun 2015. Student’s t-test, Chi-square, univariate and multivariate Logistic regression models were used to estimate the relationship between the risk factors and the incidence of implanting implantable cardioverter defibrillator (ICD) in PVCs patients. Kaplan–Meier curve of survival in PVCs patients with ICD or free-ICD. Results: The average follow-up time was 9.3±3.9 years, in which 43 (13.9%) patients died and 24 (7.8%) patients had received ICD therapy. Sex, age, pulse pressure, early repolarization syndrome (ERS), heart rate, PVC coupling interval, QRS duration, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic dimension (LVESD), diabetes were significantly associated with the mortality and the incidence of implanting ICD. Using a multivariate logistic regression model adjusted for potential confounders, showed that LVEF (OR=0.916, 95% CI:0.881 to 0.953, p<0.001) and pulse pressure (OR=1.032, 95% CI:1.001-1.064, p=0.045) were independent factors for ICD implant in PVCs patients. Moreover, implantation of ICD may not reduce mortality in patients with ventricular premature. Conclusions: Increased pulse pressure was associated a higher incidence of ICD in PVCs patients, among many electrocardiographic and clinical variables studied. We also showed that PVs patients with ICD were at high risk of death, and the great pulse pressure was linked with higher morality in PVCs patients.