Maternal over-nutrition may predispose offspring to obesity, type 2 diabetes and other adult diseases. The present study investigated long-term impact of prenatal high sucrose (HS) diets on cognitive capabilities in aged rat offspring. The fasting plasma glucose concentration did not differ between the control and HS groups. However, the fasting plasma insulin and insulin resistance index values were significantly increased in HS offspring that showed abnormal glucose tolerance test. HS offspring exhibited increased escape latency and swimming path length to the platform, and reduced time in the target quadrant and the number of crossing the platform, as compared with the control group. The expression of Grin2b/NR2B, Wnt2, Wnt3a and active form of β-catenin protein were decreased, and Dickkopf-related protein 1 was increased in the HS group. In addition, the levels of lipid peroxidation biomarker thiobarbituricacid reactive substance, nicotinamide adenine dinucleotide phosphate oxidases 2 and superoxide dismutase 1 were significantly increased, and the activity of catalase was decreased in the hippocampus in the HS group. The results demonstrate that prenatal HS-induced metabolic changes cause cognitive deficits in aged rat offspring, probably due to altered N-methyl-D-aspartate receptors/Wnt signaling and oxidative stress in the hippocampus.

INTRODUCTIONHuman cardiovascular diseases continue to cause major health and economic burden worldwide [1,2]. Cardiomyocytes differentiated from human pluripotent stem cells (hPSC-CMs), including both embryonic stem cell-derived cardiomyocytes (hESC-CMs) and induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), provide an enormous potential for the development of tissue engineering, drug screening, and cardiac disease www.aging-us.com

BackgroundOne of the most terrible famines last century was Great Chinese Famine (GCF) in 1959~1961 when millions of people died from starving. Under-nutrition during famine between the Western and Eastern (Dutch Hungry vs. GCF) was similar, while cardiovascular consequences might not be the same. Addressing such questions may gain new insight into prevention of cardiovascular diseases.MethodsA retrospective cohort of 18,593 participants aged 43–49 years of old, was from Suzhou, China. Logistic regression model was used to calculate the relative risk (RR) of hypertension and corresponding 95% confidence interval (CI). The multivariate RRs were adjusted for age, plasma glucose, triglyceride, and cholesterol.ResultsThe multivariate RRs of systolic and diastolic pressure were not significantly elevated in the rural subgroups, but was higher in the urban population born in the famine (systolic pressure adjust RR 1.382, 95% CI 1.235–1.545, diastolic pressure adjust RR 1.569, 95% CI 1.415–1.740). The risks of hypertension were significantly higher among the urban subjects than that in the rural subgroups (systolic hypertension adjust RR 2.915, 95% CI 2.616–3.249, diastolic hypertension adjust RR 4.568, 95% CI 4.079–5.116). Percentile of optimal diastolic pressure at mid-age was significantly lower in the urban population prenatally exposed to the famine regardless of sexes. However, a similar reduction of percentage of optimal systolic pressure was only seen in the female, not the male population in the urban region.ConclusionThe data suggest Asian genetic basis was not able to block famine-programmed vascular diseases as that happened in Europe, and the programmed problems due to under-nutrition could be reversed after birth. Protective mechanisms may be related to diet habits before age of 30 years old, which is important contribution to early prevention of hypertension.

The endothelial nitric oxide (NO) system may be damaged in preeclampsia; however, the involved mechanisms are unclear. In this study, we used primary human umbilical vein endothelial cells (HUVECs) to evaluate the endothelial NO system in preeclampsia and to determine the underlying mechanisms that are involved. We isolated and cultured HUVECs from normal and preeclamptic pregnancies and evaluated endothelial NO synthase enzyme (eNOS) expression and NO production. Whole-cell K currents and oxidative stress were also determined in normal and preeclamptic HUVECs. Compared with normal HUVECs, eNOS expression, NO production and whole-cell K currents in preeclamptic HUVECs were markedly decreased, whereas oxidative stress was significantly increased. The decreased K currents were associated with damaged Ca-activated K (KCa) channels, especially the large (BKCa) and small (SKCa) conductance KCa channels, and were involved in the downregulated eNOS expression in preeclamptic HUVECs. Moreover, the increased oxidative stress detected in preeclamptic HUVECs was mediated by NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2)-dependent reactive oxygen species overproduction that could downregulate whole-cell K currents, eNOS expression and NO production. Taken together, our study indicated that the increased oxidative stress in preeclamptic HUVECs could downregulate the NO system by suppressing BKCa and SKCa channels. Because the damaged NO system was closely related to endothelial dysfunction, this study provides important information to further understand the pathological process of endothelial cell dysfunction in preeclampsia.

Overnutrition during pregnancy could increase risks of cardiovascular diseases in late life. This study investigated whether and how reactive oxygen species (ROS) may influence functions of large-conductance Ca2+-activated K+ channels (BKCa) in the offspring exposed to prenatal high sucrose (HS). We found that prenatal HS diets significantly increased phenylephrine (PE)-induced vessel contractions in mesenteric arteries of the adult offspring. Pretreatment with iberiotoxin (BKCa blocker, IBTX) significantly increased PE-mediated vascular contractions in the control, not in the HS group. Electrophysiological studies demonstrated that BKCa current density and single-channel current were reduced in the vascular smooth muscle cells (VSMCs) of the HS offspring. The expression of BKCa alpha, beta1 subunits in mesenteric arteries was decreased in the HS offspring, indicating that both activity and number of BKCa channels in HS offspring were reduced. Superoxide production and NADPH oxidase (NOX)4 of the HS offspring were elevated. Following inhibiting NOX by apocynin, vasoconstriction in the HS offspring was weakened and the reduced currents in the VSMCs were improved with altered protein kinase B (AKT) pathway. The results suggested that NOX4-derived ROS might inhibit the offspring vascular BKCa channel activity via AKT pathway.

Placental vascular dysfunction was suggested to be critical for placental ischemia-initiated hypertension in preeclampsia, although the contributions of endothelium involved are unclear. The present study found, unlike non-placental vessels, acetylcholine showed no vasodilatation effect on placental vessels, indicating that endothelial-derived nitric oxide (NO) was extremely weak in placental vessels. Placental vascular responses to exogenous NO from sodium nitroprusside (SNP) were significantly different from non-placental vessels. These results were further confirmed in sheep, and rat vessels. In preeclamptic placental vessels, acetylcholine also showed no vasodilatation effects, while vascular responses to SNP were suppressed, associated with impaired cGMP/sGC pathway in vascular smooth muscle cells (VSMCs). The current theory on placental ischemia-initiated hypertension in preeclampsia focused on changes in placental vascular functions, including endothelial dysfunction. This study found the placental endothelium contributed very poorly to vasodilatation, and altered vascular functions in preeclampsia mainly occurred in VSMCs instead of endothelial cells. The findings contribute importantly to understanding the special feature of placental vascular functions and its pathophysiological changes in the development of hypertension in preeclampsia.

Osteoporosis is one of common bone disorders, affecting millions of people worldwide. Treatments of osteoporosis consist of pharmacotherapy and non-pharmacological interventions, such as mineral supplementation, lifestyle changes, and exercise programs. Due to the minimum side effects and favorable cost-effective therapeutic effects, herbal medicine has been widely applied in clinical practices for more than 2,000 years in China. Of the many traditional formulas reported for treating bone diseases, 4 single herbs namely (1) Herba Epimedii, (2) Rhizoma Drynariae, (3) Fructus Psoraleae, and (4) Cortex Eucommiae, are considered as the featured "Kidney-Yang" tonics, and frequently and effectively applied for preventing and treating osteoporosis. With the accruing development of modern chemistry, hundreds of active compounds have been identified and isolated for their anti-osteoporotic effects. This review would first sketch the phytochemistry of these featured "Kidney- Yang" tonics and present the pharmacological characteristics of the most abundant and bioactive compounds derived from the herb Herba Epimedii and Rhizoma Drynariae, including icariin and naringin. Then, the cellular and molecular underpinnings under anti-osteoporotic effects of icariin and naringin are discussed. The concerned structure-function relationships of the featured active herbal compounds would also be reviewed so as to pave the way for future drug design in treating osteoporosis.

Background/Aims: Chronic hypoxia in utero could impair vascular functions in the offspring, underlying mechanisms are unclear. This study investigated functional alteration in large-conductance Ca²⁺-activated K⁺ (BK) channels in offspring mesenteric arteries following prenatal hypoxia. Methods: Pregnant rats were exposed to normoxic control (21% O₂, Con) or hypoxic (10.5% O₂, Hy) conditions from gestational day 5 to 21, their 7-month-old adult male offspring were tested for blood pressure, vascular BK channel functions and expression using patch clamp and wire myograh technique, western blotting, and qRT-PCR. Results: Prenatal hypoxia increased pressor responses and vasoconstrictions to phenylephrine in the offspring. Whole-cell currents density of BK channels and amplitude of spontaneous transient outward currents (STOCs), not the frequency, were significantly reduced in Hy vascular myocytes. The sensitivity of BK channels to voltage, Ca²⁺, and tamoxifen were reduced in Hy myocytes, whereas the number of channels per patch and the single-channel conductance were unchanged. Prenatal hypoxia impaired NS1102- and tamoxifen-mediated relaxation in mesenteric arteries precontracted with phenylephrine in the presence of N^ω-nitro-L-arginine methyl ester. The mRNA and protein expression of BK channel β1, not the α-subunit, was decreased in Hy mesenteric arteries. Conclusions: Impaired BK channel β1-subunits in vascular smooth muscle cells contributed to vascular dysfunction in the offspring exposed to prenatal hypoxia.