Evaluation of Coenzyme Q10 (CoQ10) Deficiency and Therapy in Mouse Models of Cardiomyopathy.

ABSTRACT: Mitochondrial dysfunction plays a key role in the development of heart failure, but targeted therapeutic interventions remain elusive. Previous studies have shown coenzyme Q10 (CoQ10) insufficiency in patients with heart disease with undefined mechanism and modest effectiveness of CoQ10 supplement therapy. Using 2 transgenic mouse models of cardiomyopathy owing to cardiac overexpression of Mst1 (Mst1-TG) or ß 2 -adrenoceptor (ß 2 AR-TG), we studied changes in cardiac CoQ10 content and alterations in CoQ10 biosynthesis genes. We also studied in Mst1-TG mice effects of CoQ10, delivered by oral or injection regimens, on both cardiac CoQ10 content and cardiomyopathy phenotypes. High performance liquid chromatography and RNA sequencing revealed in both models significant reduction in cardiac content of CoQ10 and downregulation of most genes encoding CoQ10 biosynthesis enzymes. Mst1-TG mice with 70% reduction in cardiac CoQ10 were treated with CoQ10 either by oral gavage or i.p. injection for 4-8 weeks. Oral regimens failed in increasing cardiac CoQ10 content, whereas injection regimen effectively restored the cardiac CoQ10 level in a time-dependent manner. However, CoQ10 restoration in Mst1-TG mice did not correct mitochondrial dysfunction measured by energy metabolism, downregulated expression of marker proteins, and oxidative stress nor to preserve cardiac contractile function. In conclusion, mouse models of cardiomyopathy exhibited myocardial CoQ10 deficiency likely due to suppressed endogenous synthesis of CoQ10. In contrast to ineffectiveness of oral administration, CoQ10 administration by injection regimen in cardiomyopathy mice restored cardiac CoQ10 content, which, however, failed in achieving detectable efficacy at molecular and global functional levels.

Interfacial Engineering of Supported Liquid Membranes by Vapor Cross-Linking for Enhanced Separation of Carbon Dioxide.

Supported liquid membranes (SLMs) based on ionic liquids (ILs) with not only high gas permeability and selectivity, but also high stability under high pressure, are highly desired for gas separation applications. In this work, permeable and selective polyamide network (PN) layers are deposited on the surface of SLMs by utilizing the cross-linking reaction of trimesoyl chloride, which was pre-dispersed in the SLMs, and vapor of amine linkers. The vapor cross-linking method makes it easy to control the growth and aggregation of PN layers, owing to the significantly reduced reaction rate, and thereby ensuring the good distribution of PN layers on the surface of SLMs. With rational choice of amine linkers and optimization of vapor cross-linking conditions, the prepared sandwich-like PN@SLMs with ILs embedded homogeneously within polymeric matrices displayed much-improved CO2 permeability and CO2 /N2 selectivity in relation to the pristine SLMs. Moreover, those SLMs with ILs impregnated into porous supports physically displayed improved stability under high pressure after vapor cross-linking, because the PN layers formed on the surface of SLMs help prevent the ILs from being squeezed out. This interfacial engineering strategy represents a significant advance in the surface modification of SLMs to endow them with promising applications in CO2 capture.

[Exhaled nitric oxide levels in school children of Beijing].

OBJECTIVE: To learn the normal values of exhaled nitric oxide (eNO) in children. METHOD: School children in Beijing from 11 to 18 years of age were included in the study. All the students were assigned into two groups: normal group and abnormal group (with allergic disease) according to the International Study of Asthma and Allergy in Childhood questionnaires. eNO, peak expiratory flow rate and sensitization were measured. RESULT: Totally 395 students were screened out as normal subject (male: 177, female: 218). The eNO level was not significantly different between genders (P > 0.05), but was associated positively with age in both male and female group (P = 0.008 and P = 0.05 respectively) and associated with height in male students (P = 0.02). The geometric mean value of eNO was 11.22 ppb (parts per billion, ppb = 10(9)) in children aged from 11 to 14 years and 14.13 ppb in children aged from 14 to 18 years, with 95% confidence interval 4.17 - 30.20, 5.50 - 36.31 ppb. The eNO level was significantly increased in children who "ever had asthma or wheezing" (n = 68), and children who "ever had rhinitis" (n = 96) compared with normal subjects (P = 0.001 and P = 0.008). The geometric mean value of eNO was 16.98 ppb in children with positive skin prick test and was significantly increased as compared with children with negative skin prick test with eNO level at 11.75 ppb (P = 0.001). CONCLUSION: eNO level varied between 10.72 ppb and 13.80 ppb in normal children 11 - 18 years of age, and was positively associated with age and height, but not with gender. eNO level increased significantly in children with wheezing and atopy.