A human embryonic stem cell reporter line for monitoring chemical-induced cardiotoxicity.

AIMS: Human embryonic stem cells (hESCs) can be used to generate scalable numbers of cardiomyocytes (CMs) for studying cardiac biology, disease modelling, drug screens, and potentially for regenerative therapies. A fluorescence-based reporter line will significantly enhance our capacities to visualize the derivation, survival, and function of hESC-derived CMs. Our goal was to develop a reporter cell line for real-time monitoring of live hESC-derived CMs. METHODS AND RESULTS: We used CRISPR/Cas9 to knock a mCherry reporter gene into the MYH6 locus of hESC lines, H1 and H9, enabling real-time monitoring of the generation of CMs. MYH6:mCherry+ cells express atrial or ventricular markers and display a range of cardiomyocyte action potential morphologies. At 20 days of differentiation, MYH6:mCherry+ cells show features characteristic of human CMs and can be used successfully to monitor drug-induced cardiotoxicity and oleic acid-induced cardiac arrhythmia. CONCLUSION: We created two MYH6:mCherry hESC reporter lines and documented the application of these lines for disease modelling relevant to cardiomyocyte biology.

Assessment of autonomic dysfunction in patients with type 2 diabetes using reactive hyperemia.

It is known that aging and type 2 diabetes mellitus contribute to atherosclerosis and autonomic dysfunction. By using the air pressure sensing system (APSS), peak-peak intervals (PPIs) of wrist arterial waveforms from baseline and reactive hyperemia (RH) were obtained. Through frequency domain analysis of heart rate variability (HRV) and nonlinear Poincaré method, the HRV of healthy young individuals (Group 1, n=25), healthy upper middle-aged individuals (Group 2, n=22), and patients with type 2 diabetes (Group 3, n=28) were assessed. By using the standard deviation (SD) of the instantaneous PPI variability (SD1)/the SD of the long PPI variability (SD2) ratio (SSR), PPIs of the same individuals before and after RH induction were compared. Reduced SSR1₋10 was noted only in patients with diabetes. Moreover, a significient correlation between SSR1₋10 and endothelial function was observed in all subjects (r=0.290, p=0.033) after RH. However, no correlation with low-frequency to high-frequency power ratio (LHR) was noted before and after RH. In conclusion, according to our results, campared to the baseline, there were more significant changes of SSR1₋10 after RH in patients with diabetes; and, a significient correlation between SSR1₋10 and endothelial function at the moment of RH was noted.

Multiscale entropy analysis of pulse wave velocity for assessing atherosclerosis in the aged and diabetic.

This study proposed a dynamic pulse wave velocity (PWV)-based biomedical parameter in assessing the degree of atherosclerosis for the aged and diabetic populations. Totally, 91 subjects were recruited from a single medical institution between July 2009 and October 2010. The subjects were divided into four groups: young healthy adults (Group 1, n = 22), healthy upper middle-aged adults (Group 2, n = 28), type 2 diabetics with satisfactory blood sugar control (Group 3, n = 21), and unsatisfactory blood sugar control (Group 4, n = 20). A self-developed six-channel electrocardiography (ECG)-PWV-based equipment was used to acquire 1000 successive recordings of PWV(foot) values within 30 min. The data, thus, obtained were analyzed with multiscale entropy (MSE). Large-scale MSE index (MEI(LS)) was chosen as the assessment parameter. Not only did MEI(LS) successfully differentiate between subjects in Groups 1 and 2, but it also showed a significant difference between Groups 3 and 4. Compared with the conventional parameter of PWV(foot) and MEI on R-R interval [i.e., MEI(RRI)] in evaluating the degree of atherosclerotic change, the dynamic parameter, MEI(LS) (PWV), could better reflect the impact of age and blood sugar control on the progression of atherosclerosis.

[Analysis on urban spatial expansion process in Shenyang City in 1979-2006].

Based on the 1979, 1992, 2001 and 2006 satellite images, the spatial expansion information of Shenyang City was extracted by human-computer interactive method, and the temporal and spatial expansion characteristics of Shenyang City as well as their driving forces were analyzed from the aspects of growth intensity, center coordinates, compact index, fractal index, and elasticity coefficient, with the help of the statistic and analytic functions of GIS for the spatial data. The results showed that in 1979-2006, both the urban build-up area and its expansion rate in Shenyang were increased continuously, and reached the maximum in 2001-2006. The urban expansion showed obvious spatial heterogeneity, with the gravity shifted to the southwest. In the meantime, the compact index was decreasing while the fractal index was increasing, implying that the urban spatial configuration in Shenyang became more and more complex. Natural environmental factors, economic development, population growth, traffic infrastructure construction, and government policy and planning were the main driving forces of the urban expansion.