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Sehested Hjorth posted an update 6 months ago
Alzheimer’s disease (AD) is the most common form of dementia that progressively disrupts neurocognitive function, which has neither cure nor effective treatment. Hypercholesterolemia might be involved in brain alterations that could evolve into AD. The present study aims to evaluate the potential of omega-3, Co-enzyme Q10 (Co-Q10), as well as their combination in ameliorating hypercholesterolemia-initiated AD-like disease. We adapted a hypercholesterolemic (HC) rat model, a model of oxidative stress-mediated neurodegeneration, to study AD-like pathology. Hypercholesterolemia resulted in increased lipid peroxidation coupled with declined nitric oxide production, reduced glutathione levels, and decreased antioxidant activities of glutathione-s-transferase (GST) and glutathione peroxidase (GSH-Px) in the brain. Moreover, hypercholesterolemia resulted in decreased acetylcholine (ACh) levels and increased acetylcholine-esterase (AChE) activity, along with an increment of tumor necrosis factor and amyloid-β 42. AZD9291 Behaviorally, HC-rats demonstrated depressive-like behavior and declined memory. Treatment of HC-rats with omega-3 and Co-Q10 (alone or in combination) alleviated the brain oxidative stress and inflammation, regulated cholinergic functioning, and enhanced the functional outcome. These findings were verified by the histopathological investigation of brain tissues. This neuroprotective potential of omega-3 and Co-Q10 was achieved through anti-oxidative, anti-inflammatory, anti-amyloidogenic, pro-cholinergic, and memory-enhancing activities against HC-induced AD-like disease; suggesting that they may be useful as prophylactic and therapeutic agents against the neurotoxic effects of hypercholesterolemia.In the present study, we used a serum-free culture media to propagate goat putative spermatogonial stem cells (SSCs) and evaluated the effect of crucial growth factors on relative expression of some SSC markers and self-renewal related genes. The enriched SSCs were cultured on a homologous Sertoli cell feeder layer in KO-DMEM supplemented with 10% KOSR. Putative SSC colonies emerged between day 6 and 10 which were then characterized by the expression of numerous spermatogonial and pluripotency related markers. After 15 days of subculture, the relative mRNA expression study revealed that 40 ng/mL concentration of Glial cell line-derived neurotrophic factor (GDNF) upregulated the expression of BCL6B, ID4, PLZF, and UCHL1. Moreover, the supplementation of GDNF + bFGF up-regulated the expression of PLZF and BCL6B. UCHL1 expression was higher after addition of GDNF + LIF while, THY1 overexpressed in response to the addition of GDNF + CSF1. These results demonstrated that the goat SSCs were efficiently propagated using a KOSR based serum-free media and the growth factor supplementation markedly influences their gene expression profile.ETHNOPHARMACOLOGICAL RELEVANCE β-Sitosterol is a plant derived compound similar to cholesterol structure and used in the treatment of hypercholesterolemia, prostate cancer, breast cancer and coronary artery disease. But no studies have been reported the effect of β-sitosterol on glucose homeostasis by sensitization of insulin resistance via enhanced protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and glucose transporter 4 (GLUT4) in insulin dependent tissues of high fat diet and streptozotocin-induced diabetic rats. MATERIALS AND METHODS Type 2 diabetes was induced in male albino Wistar rats by feeding them with high fat diet comprising of 84.3% standard laboratory chow, 5% lard, 10% yolk powder, 0.2% cholesterol and 0.5% bile salt for 2 weeks. After 2 weeks, the animals were kept in an overnight fast and injected with low dose of streptozotocin (35 mg/kg, dissolved in 0.1 M sodium citrate buffer, pH 4.5). Analysis of blood glucose, insulin, hemoglobin and glycated hemoglobin were done by commercially available diagnostic kits. The PPARγ and GLUT4 were analyzed by western blotting using respective primary and secondary antibodies. RESULTS Upon administration of β-sitosterol at a dose of 15 mg/kg body weight per day to high fat diet and streptozotocin induced diabetic rats for 30 days significantly decreased the levels of plasma glucose, homeostatic model assessment of insulin resistance and glycosylated hemoglobin and increased the levels of insulin, hemoglobin and protein expression of PPARγ and GLUT4 in insulin dependent tissues. Furthermore, β-sitosterol administration prevented the body weight loss and excessive intake of food and water. CONCLUSION These finding suggest that β-sitosterol can replace the commercial drugs which could lead to reduction in toxicity and side effect caused by the later as well as reduce the secondary complications.Stressful life changes may tax people’s adaptive capacity. We sought to determine if and when experiences of stressful life changes were associated with increased odds of adverse nutrition-related health outcomes among US Army soldiers relative to those who did not experience the same stressful life change. An additional aim was to determine which stressful life changes had the greatest association with these outcomes and if there were gender differences in the magnitude of the associations. Stressful life changes studied included changes in marital status, combat deployment or return from deployment, relocation, adding a child, change in rank, change in occupation, and development of a physical limitation to duty. Using longitudinal data from the Stanford Military Data Repository, which represents all active-duty soldiers aged 17-62 between 2011 and 2014 (n = 827,126), we employed an event history analysis to examine associations between stressful life changes and a subsequent diagnosis of hyperlipidemia, substantial weight gain, and weight-related separation from the Army. Marriage was associated with an increase in the odds of substantial weight gain 3 months later for both men and women. Developing a physical duty limitation was associated with an increase in the odds of a hyperlipidemia diagnosis 2 months later for both men and women, as was substantial weight gain 2 months later. Stressful life changes were also associated with increased odds of nutrition-related health outcomes, although we found gender differences in the magnitude of the associations. Findings could be used to mitigate the effects of stress on health by health professionals.
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