Carnosol Attenuates LPS-Induced Inflammation of Cardiomyoblasts by Inhibiting NF-κB: A Mechanistic in Vitro and in Silico Study

Carnosol possesses several beneficial pharmacological properties. However, its role in lipopolysaccharide (LPS) induced inflammation and cardiomyocyte cell line (H9C2) has never been investigated. Therefore, the effect of carnosol and an NF-kappa B inhibitor BAY 11-7082 was examined, and the underlying role of the NF-kappa B-dependent inflammatory pathway was analyzed as the target enzyme. Cell viability, inflammatory cytokines levels (tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, IL-6, and prostaglandin E-2 (PGE(2))), and related gene expression (TNF-alpha, IL-1 beta, IL-6, and cyclooxygenase-2 (COX-2)) were analyzed by ELISA and real-time PCR. In addition, docking studies analyzed carnosol's molecular interactions and binding modes to NF-kappa B and IKK. We report that LPS caused the reduction of cell viability while enhancing both cytokines protein and mRNA levels (P < 0.001, for all cases). However, the BAY 11-7082 pretreatment of the cells and carnosol increased cell viability and reduced cytokine protein and mRNA levels (P < 0.001 vs. LPS, for all cases). Furthermore, our in silico analyses also supported the modulation of NF-kappa B and IKK by carnosol. This evidence highlights the defensive effects of carnosol against sepsis-induced myocardial dysfunction and, contextually, paved the rationale for the next in vitro and in vivo studies aimed to precisely describe its mechanism(s) of action

Investigating the relationship between fetus heart rate in the first trimester screening with fetus sex

Objective There is a common belief that sex of the fetus is predictable by assessing fetal heart rate (FHR) in the early weeks of pregnancy. We aimed to assess the relationship between FHR in the first trimester screening with fetus sex. Methods This mixed prospective–retrospective cohort study is done on 374 fetus samples of pregnant women who referred to evaluate nuchal translucency (NT) in a hospital in Tehran, Iran between October 2013 and March 2015. Adjusted multivariable linear regression model, receiver operating characteristic (ROC) curve and Youden index were used in analysis. Results There were 52.9% male among fetuses. The median and interquartile range (IQR) of FHR in male and female fetus were 155.5 (152–160) and 155 (150–160) beats per minute (bpm), respectively (P = 0.213). The crude regression results showed that the average FHR of the male fetuses was 1.27 bpm higher than females but it was not statistically significant (P = 0.131). The adjusted regression results showed that fetus sex was not significantly associated with FHR in terms of similar age and mother’s gravid and parity. Area under the ROC curve was 0.54 (95% confidence interval: 0.48, 0.59) which shows very low FHR power to determine sex of the fetus in the first trimester of pregnancy. The best cut off point was equal to 152 pulse bpm, sensitivity and specificity were 82.81 and 30.11, respectively. Conclusion The results showed that FHR is not a good factor to determine sex of the fetus