Abstract-Nitric oxide generated by endothelial nitric oxide synthase (eNOS) plays an important role in maintaining cardiovascular homeostasis. Under various pathological conditions, abnormal expression of eNOS contributes to endothelial dysfunction and the development of cardiovascular diseases. A variety of pathological stimuli has been reported to decrease eNOS expression mainly through decreasing eNOS mRNA stability by regulating the binding of several cytosolic proteins to the cis-acting sequences within eNOS mRNA 3′ untranslated regions. However, the detailed mechanisms remain elusive. Because microRNAs inhibit gene expression through binding to the 3′ untranslated regions of their target mRNAs, microRNAs may be the important posttranscriptional modulators of eNOS expression. Here, we provided evidence that eNOS is a direct target of miR-155. Overexpression of miR-155 decreased, whereas inhibition of miR-155 increased, eNOS expression and NO production in human umbilical vein endothelial cells and acetylcholineinduced endothelium-dependent vasorelaxation in human internal mammary arteries. Inflammatory cytokines including tumor necrosis factor-α increased miR-155 expression. Inhibition of miR-155 reversed tumor necrosis factor-α-induced downregulation of eNOS expression and impairment of endothelium-dependent vasorelaxation. Moreover, we observed that simvastatin attenuated tumor necrosis factor-α-induced upregulation of miR-155 and ameliorated the effects of tumor necrosis factor-α on eNOS expression and endothelium-dependent vasodilation. Simvastatin decreased miR-155 expression through interfering mevalonate-geranylgeranyl-pyrophosphate-RhoA signaling pathway. These findings indicated that miR-155 is an essential regulator of eNOS expression and endothelium-dependent vasorelaxation.Inhibition of miR-155 may be a new therapeutic approach to improve endothelial dysfunction during the development of cardiovascular diseases.
BackgroundPublished data on influenza in severe acute respiratory infection (SARI) patients are limited. We conducted SARI surveillance in central China and estimated hospitalization rates of SARI attributable to influenza by viral type/subtype.MethodsSurveillance was conducted at four hospitals in Jingzhou, China from 2010 to 2012. We enrolled hospitalized patients who had temperature ≥37·3°C and at least one of: cough, sore throat, tachypnea, difficulty breathing, abnormal breath sounds on auscultation, sputum production, hemoptysis, chest pain, or chest radiograph consistent with pneumonia. A nasopharyngeal swab was collected from each case-patient within 24 hours of admission for influenza testing by real-time reverse transcription PCR.ResultsOf 17 172 SARI patients enrolled, 90% were aged <15 years. The median duration of hospitalization was 5 days. Of 16 208 (94%) SARI cases tested, 2057 (13%) had confirmed influenza, including 1427 (69%) aged <5 years. Multiple peaks of influenza occurred during summer, winter, and spring months. Influenza was associated with an estimated 115 and 142 SARI hospitalizations per 100 000 during 2010–2011 and 2011–2012 [including A(H3N2): 55 and 44 SARI hospitalizations per 100 000; pandemic A(H1N1): 33 SARI hospitalizations per 100 000 during 2010–2011; influenza B: 26 and 98 hospitalizations per 100 000], with the highest rate among children aged 6–11 months (3603 and 3805 hospitalizations per 100 000 during 2010–2011 and 2011–2012, respectively).ConclusionsIn central China, influenza A and B caused a substantial number of hospitalizations during multiple periods each year. Our findings strongly suggest that young children should be the highest priority group for annual influenza vaccination in China.
Ferulic acid (FA) is a derivative of cinnamic acid. It is used in the treatment of heart head blood-vessel disease and exerts protective effects against hypoxia/ischemia-induced cell injury in the brain. This study investigated the potential neuroprotective effects of FA against ischemia/reperfusion (I/R)-induced brain injury in vivo and in vitro through hematoxylin and eosin (H&E) and Nissl staining assays, flow cytometry, Hoechst 33258 staining, quantitative PCR, western blot analysis and fluorescence microscopic analysis. In this study, models of cerebral I/R injury were established using rats and pheochromocytoma (PC-12) cells. The results revealed that treatment with FA significantly attenuated memory impairment, and reduced hippocampal neuronal apoptosis and oxidative stress in a dose-dependent manner. The results from in vitro experiments also indicated that FA protected the PC-12 cells against I/R-induced reactive oxygen species (ROS) generation and apoptosis by inhibiting apoptosis, Ca2+ influx, superoxide anion (O2−), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) production in a concentration-dependent manner. Moreover, FA inactivated the Toll-like receptor (TLR)/myeloid differentiation factor 88 (MyD88) pathway. MyD88 overexpression abolished the neuroprotective effects of FA. On the whole, we found that FA attenuated memory dysfunction and exerted protective effects against oxidative stress and apoptosis induced by I/R injury by inhibiting the TLR4/MyD88 signaling pathway. This study supports the view that FA may be a promising neuroprotective agent for use in the treatment of cerebral ischemia.
Soft drinks have many potential health problems. The inherent acids and sugars have both acidogenic and cariogenic potential, resulting in dental caries and potential enamel erosion. In this report we present a 25-year-old man complaining with the severe worn-out of the front teeth during the past 3 years. He had a history of drinking cola for more than 7 years and had a poor oral hygiene. Severe decays were present in the incisors and the canines, while less severe lesions were noted on the premolars and the molars. The review is to show the relationship between dental erosion and caries and soft drinks. Some efforts have been taken to reduce the harmful effect of soft drinks.
Objective
To examined whether the long-term resting heart rate (RHR) pattern can predict the risk of having arterial stiffness in a large ongoing cohort.
Approach and Results
This community-based cohort included 12,554 participants in the Kailun study, free of myocardial infraction, stroke, arrhythmia, and cancer. We used latent mixture modeling to identify RHR trajectories in 2006, 2008 and 2010. We used multivariate linear regression model to examine the association between RHR trajectory patterns and the risk of having arterial stiffness, which was assessed by brachial-ankle pulse wave velocity (baPWV) in 2010–2016. We adjusted for possible confounding factors, including social economic status, lifestyle factors, use of medications, co-morbidities, serum concentrations of lipids, glucose and high-sensitive C-reactive proteins. We identified five distinct RHR trajectory patterns based on their 2006 status and pattern of change during 2006–2010 (low-stable, moderate-stable, moderate-increasing, elevated-decreasing, and elevated-stable). We found that individuals with elevated-stable RHR trajectory pattern had the highest bpPWV value and individuals with the low-stable RHR trajectory pattern had the lowest value (adjusted mean difference = 157 cm/s, P<0.001). Adjusted odds ratio for risk of having arterial stiffness (bpPWV≥1400 cm/s) was 4.14 (95% confidence interval: 2.61–6.57) relative to these two extreme categories. Consistently, a higher average RHR, a higher annual RHR increase rate and a higher RHR variability were all associated with a higher risk of having arterial stiffness.
Conclusion
Long-term RHR pattern is a strong predictor of having arterial stiffness.
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