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Yan-Ling Z.,University of Sichuan | Chang-Quan H.,Third Hospital of Mianyang | Li Y.,Center for Perinatal Biology | Bi-Rong D.,University of Sichuan
Age | Year: 2014

In this study, we examined the association of fasting serum insulin (FSI) and fasting serum glucose (FSG) with cognitive impairment in the very elderly using a sample of Chinese nonagenarians/centenarians. This study used data from a survey that was conducted in 2005 on all residents aged 90 years or more in a district with 2,311,709 inhabitants. FSG, FSI, and cognitive function were analyzed. The sample included 661 unrelated Chinese individuals (aged 90-108 years; mean, 93.52±3.37 years; 67.17% women; FSI, 6.27± 2.27 mU/mL; FSG levels, 4.46±1.45 mmol/L). The prevalence of cognitive impairment was 61.81% and that of hypoinsulinemia was 31.92%. Individuals with hypoinsulinemia showed lower cognitive function scores (14.81±5.79 vs. 15.78±5.24, t=2.160, P =0.031). No differences in cognitive function score between different FSI and FSG groups were significant, and no differences in FSI and FSG between individuals with and without cognitive impairment were statistically significant. Unadjusted multiple logistic regressions showed that hypoinsulinemia, impaired fasting glucose, or diabetes did not change the risk of cognitive impairment significantly. In summary, we found that in elderly subjects, cognitive function appeared associated with FSI, and higher FSI may be associated with enhanced cognitive function. © The Author(s) 2013. Source


Paradis A.N.,Center for Perinatal Biology | Gay M.S.,Center for Perinatal Biology | Wilson C.G.,Center for Perinatal Biology | Wilson C.G.,Loma Linda University | Zhang L.,Center for Perinatal Biology
PLoS ONE | Year: 2015

In the developing heart, cardiomyocytes undergo terminal differentiation during a critical window around birth. Hypoxia is a major stress to preterm infants, yet its effect on the development and maturation of the heart remains unknown. We tested the hypothesis in a rat model that newborn anoxia accelerates cardiomyocyte terminal differentiation and results in reduced cardiomyocyte endowment in the developing heart via an endothelin-1-dependent mechanism. Newborn rats were exposed to anoxia twice daily from postnatal day 1 to 3, and hearts were isolated and studied at postnatal day 4(P4), 7(P7), and 14 (P14). Anoxia significantly increased HIF-1α protein expression and pre-proET-1 mRNA abundance in P4 neonatal hearts. Cardiomyocyte proliferation was significantly decreased by anoxia in P4 and P7, resulting in a significant reduction of cardiomyocyte number per heart weight in the P14 neonates. Furthermore, the expression of cyclin D2 was significantly decreased due to anoxia, while p27 expression was increased. Anoxia has no significant effect on cardiomyocyte binucleation or myocyte size. Consistently, prenatal hypoxia significantly decreased cardiomyocyte proliferation but had no effect on binucleation in the fetal heart. Newborn administration of PD156707, an ETA-receptor antagonist, significantly increased cardiomyocyte proliferation at P4 and cell size at P7, resulting in an increase in the heart to body weight ratio in P7 neonates. In addition, PD156707 abrogated the anoxia-mediated effects. The results suggest that hypoxia and anoxia via activation of endothelin-1 at the critical window of heart development inhibits cardiomyocyte proliferation and decreases myocyte endowment in the developing heart, which may negatively impact cardiac function later in life. © 2015 Paradis et al. Source


Hu X.-Q.,Center for Perinatal Biology | Xiao D.,Center for Perinatal Biology | Zhu R.,Center for Perinatal Biology | Huang X.,Center for Perinatal Biology | And 3 more authors.
Hypertension | Year: 2012

Our previous study demonstrated that increased Ca-activated K+ (BKCa) channel activity played a key role in the normal adaptation of reduced myogenic tone of uterine arteries in pregnancy. The present study tested the hypothesis that chronic hypoxia during gestation inhibits pregnancy-induced upregulation of BKCa channel function in uterine arteries. Resistance-sized uterine arteries were isolated from nonpregnant and near-term pregnant sheep maintained at sea level (≈300 m) or exposed to high-altitude (3801 m) hypoxia for 110 days. Hypoxia during gestation significantly inhibited pregnancy-induced upregulation of BKCa channel activity and suppressed BKCa channel current density in pregnant uterine arteries. This was mediated by a selective downregulation of BKCa channel β1 subunit in the uterine arteries. In accordance, hypoxia abrogated the role of the BKCa channel in regulating pressure-induced myogenic tone of uterine arteries that was significantly elevated in pregnant animals acclimatized to chronic hypoxia. In addition, hypoxia abolished the steroid hormone-mediated increase in the β1 subunit and BKCa channel current density observed in nonpregnant uterine arteries. Although the activation of protein kinase C inhibited BKCa channel current density in pregnant uterine arteries of normoxic sheep, this effect was ablated in the hypoxic animals. The results demonstrate that selectively targeting BKCa channel β1 subunit plays a critical role in the maladaption of uteroplacental circulation caused by chronic hypoxia, which contributes to the increased incidence of preeclampsia and fetal intrauterine growth restriction associated with gestational hypoxia. © 2012 American Heart Association, Inc. Source


Dubicke A.,Karolinska University Hospital | Ekman-Ordeberg G.,Karolinska University Hospital | Mazurek P.,Center for Perinatal Biology | Miller L.,Center for Perinatal Biology | And 2 more authors.
Reproductive Sciences | Year: 2015

Remodeling of the cervix occurs in advance of labor both at term and at preterm birth. Morphological characteristics associated with remodeling in rodents were assessed in cervix biopsies from women at term (39 weeks' gestation) and preterm (<33 weeks' gestation). Collagen I and III messenger RNA and hydroxyproline concentrations declined in cervix biopsies from women in labor at term and preterm compared to that in the cervix from nonlaboring women. Extracellular collagen was more degraded in sections of cervix from women at term, based on optical density of picrosirius red stain, versus that in biopsies from nonpregnant women. However, collagen structure was unchanged in the cervix from women at preterm labor versus the nonpregnant group. As an indication of inflammation, cell nuclei density was decreased in cervix biopsies from pregnant women irrespective of labor compared to the nonpregnant group. Moreover, CD68-stained macrophages increased to an equivalent extent in cervix subepithelium and stroma from groups in labor, both at term and preterm, as well as in women not in labor at term. Evidence for a similar inflammatory process in the remodeled cervix of women at term and preterm birth parallels results in rodent models. Thus, a conserved final common mechanism involving macrophages and inflammation may characterize the transition to a ripe cervix before birth at term and in advance of premature birth. © The Author(s) 2015. Source


Gay M.S.,Center for Perinatal Biology | Li Y.,Center for Perinatal Biology | Xiong F.,Center for Perinatal Biology | Lin T.,Loma Linda University | Zhang L.,Center for Perinatal Biology
PLoS ONE | Year: 2015

The potential adverse effect of synthetic glucocorticoid, dexamethasone therapy on the developing heart remains unknown. The present study investigated the effects of dexamethasone on cardiomyocyte proliferation and binucleation in the developing heart of newborn rats and evaluated DNA methylation as a potential mechanism. Dexamethasone was administered intraperitoneally in a three day tapered dose on postnatal day 1 (P1), 2 and 3 to rat pups in the absence or presence of a glucocorticoid receptor antagonist Ru486, given 30 minutes prior to dexamethasone. Cardiomyocytes from P4, P7 or P14 animals were analyzed for proliferation, binucleation and cell number. Dexamethasone treatment significantly increased the percentage of binucleated cardiomyocytes in the hearts of P4 pups, decreased myocyte proliferation in P4 and P7 pups, reduced cardiomyocyte number and increased the heart to body weight ratio in P14 pups. Ru486 abrogated the effects of dexamethasone. In addition, 5-aza-2′-deoxycytidine (5-AZA) blocked the effects of dexamethasone on binucleation in P4 animals and proliferation at P7, leading to recovered cardiomyocyte number in P14 hearts. 5-AZA alone promoted cardiomyocyte proliferation at P7 and resulted in a higher number of cardiomyocytes in P14 hearts. Dexamethasone significantly decreased cyclin D2, but not p27 expression in P4 hearts. 5-AZA inhibited global DNA methylation and blocked dexamethasone-mediated down-regulation of cyclin D2 in the heart of P4 pups. The findings suggest that dexamethasone acting on glucocorticoid receptors inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via increased DNA methylation in a gene specific manner. © 2015 Gay et al. Source

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