Cooperative roles of the suprachiasmatic nucleus central clock and the adrenal clock in controlling circadian glucocorticoid rhythm

The mammalian circadian timing system consists of the central clock in the hypothalamic suprachiasmatic nucleus (SCN) and subsidiary peripheral clocks in other tissues. Glucocorticoids (GCs) are adrenal steroid hormones with widespread physiological effects that undergo daily oscillations. We previously demonstrated that the adrenal peripheral clock plays a pivotal role in circadian GC rhythm by driving cyclic GC biosynthesis. Here, we show that the daily rhythm in circulating GC levels is controlled by bimodal actions of central and adrenal clockwork. When mice were subjected to daytime restricted feeding to uncouple central and peripheral rhythms, adrenal GC contents and steroidogenic acute regulatory protein expression peaked around zeitgeber time 00 (ZT00), consistent with shifted adrenal clock gene expression. However, restricted feeding produced two distinct peaks in plasma GC levels: one related to adrenal GC content and the other around ZT12, which required an intact SCN. Light pulse-evoked activation of the SCN increased circulating GC levels in both wild-type and adrenal clock-disrupted mutant mice without marked induction of GC biosynthesis. In conclusion, we demonstrate that adrenal clock-dependent steroidogenesis and a SCN-driven central mechanism regulating GC release cooperate to produce daily circulatory GC rhythm. © The Author(s) 2017.1

Real-Time Monitoring of Neural Differentiation of Human Mesenchymal Stem Cells by Electric Cell-Substrate Impedance Sensing

Stem cells are useful for cell replacement therapy. Stem cell differentiation must be monitored thoroughly and precisely prior to transplantation. In this study we evaluated the usefulness of electric cell-substrate impedance sensing (ECIS) for in vitro real-time monitoring of neural differentiation of human mesenchymal stem cells (hMSCs). We cultured hMSCs in neural differentiation media (NDM) for 6 days and examined the time-course of impedance changes with an ECIS array. We also monitored the expression of markers for neural differentiation, total cell count, and cell cycle profiles. Cellular expression of neuron and oligodendrocyte markers increased. The resistance value of cells cultured in NDM was automatically measured in real-time and found to increase much more slowly over time compared to cells cultured in non-differentiation media. The relatively slow resistance changes observed in differentiating MSCs were determined to be due to their lower growth capacity achieved by induction of cell cycle arrest in G0/G1. Overall results suggest that the relatively slow change in resistance values measured by ECIS method can be used as a parameter for slowly growing neural-differentiating cells. However, to enhance the competence of ECIS for in vitro real-time monitoring of neural differentiation of MSCs, more elaborate studies are needed

Alpha-tocopherol exerts protective function against the mucotoxicity of particulate matter in amphibian and human goblet cells

Exposure to particulate matter (PM) in ambient air is known to increase the risk of cardiovascular disorders and mortality. The cytotoxicity of PM is mainly due to the abnormal increase of reactive oxygen species (ROS), which damage cellular components such as DNA, RNA, and proteins. The correlation between PM exposure and human disorders, including mortality, is based on long-term exposure. In this study we have investigated acute responses of mucus-secreting goblet cells upon exposure to PM derived from a heavy diesel engine. To this end, we employed the mucociliary epithelium of amphibian embryos and human Calu-3 cells to examine PM mucotoxicity. Our data suggest that acute exposure to PM significantly impairs mucus secretion and results in the accumulation of mucus vesicles in the cytoplasm of goblet cells. RNA-seq analysis revealed that acute responses to PM exposure significantly altered gene expression patterns; however, known regulators of mucus production and the secretory pathway were not significantly altered. Interestingly, pretreatment with alpha-tocopherol nearly recovered the hyposecretion of mucus from both amphibian and human goblet cells. We believe this study demonstrates the mucotoxicity of PM and the protective function of alpha-tocopherol on mucotoxicity caused by acute PM exposure from heavy diesel engines

Association of epicardial fat with left ventricular diastolic function in subjects with metabolic syndrome: assessment using 2-dimensional echocardiography

Background Metabolic syndrome (MetS) is related with left ventricular diastolic dysfunction (LVDD) and poor cardiovascular outcome. Epicardial adipose tissue (EAT) thickness, measured by echocardiography, is increased in subjects with MetS. However, the association of EAT with LV diastolic function has not been evaluated in subjects with MetS. Methods In this retrospective study, EAT thickness was measured in 1,486 consecutive asymptomatic patients with no known heart disease who had transthoracic echocardiography during a self-referred healthcare exam. Subjects with a history of ischemic heart disease, cardiomyopathy or significant valvular heart disease were excluded. LVDD was defined as E/e ratio ≥ 15. Subjects were grouped into two groups, those with MetS and those without. Results MetS was present in 346 subjects. There was no difference in LV systolic function between the two groups. However compared to patients without MetS, patients with MetS had larger left atrium (LA) size and higher E/e ratio (38 ± 5 versus 35 ± 5 mm for LA and 10.0 ± 3.3 versus 8.7 ± 2.7 for E/e ratio in subjects with versus without MetS both p < 0.001). LVDD was found in 27 (7.8%) subjects with MetS, compared to 30 (2.6%) subjects without MetS (p < 0.001). In subjects with MetS, EAT was significantly correlated with LVDD, even after adjusting for other cardiometabolic risk factors such as age, systolic blood pressure, BMI, blood glucose and LDL cholesterol (OR 1.845, 95% CI 1.153-2.951, p = 0.011).This study was supported by Seoul National University Hospital (0420100700, 2010–1096).Peer Reviewe