Sulforaphane Rescues Ethanol-Suppressed Angiogenesis through Oxidative and Endoplasmic Reticulum Stress in Chick Embryos

Our previous study showed that ethanol exposure inhibited embryonic angiogenesis mainly due to the excessive stimulation of reactive oxygen species (ROS) production. In this study, we investigated whether sulforaphane (SFN), a known dietary bioactive compound, could ameliorate ethanol-suppressed angiogenesis using chick embryo angiogenesis models. Using chick yolk sac membrane (YSM) and chorioallantoic membrane (CAM) models, we demonstrated that administration of low concentrations of SFN (2.5–10 μM) alone increased angiogenesis, but high concentrations of SFN (20–40 μM) inhibited angiogenesis. SFN administration alleviated ethanol-suppressed angiogenesis and angiogenesis-related gene expression in both angiogenesis models. Ethanol exposure caused cell apoptosis in chick CAM, and the cell apoptosis could be remitted by administration of SFN. Subsequently, we demonstrated that the ethanol-induced increase in production of ROS and reduction of antioxidant enzymes’ activity were partially rescued by SFN. Similar results were obtained in endoplasmic reticulum (ER) stress determination, indicated by ATF6 and GRP78 expression or thapsigargin-induced ER stress in the presence or absence of SFN. Taken together, our experiments show that SFN administration can ameliorate ethanol-suppressed embryonic angiogenesis, and this is mainly achieved by alleviating excessive ROS production and ER stress. This study suggests that SFN, in appropriate concentrations, could be a potential candidate compound for preventing the negative impact of alcohol on angiogenesis

Sulforaphane Rescues Ethanol-Suppressed Angiogenesis through Oxidative and Endoplasmic Reticulum Stress in Chick Embryos

Our previous study showed that ethanol exposure inhibited embryonic angiogenesis mainly due to the excessive stimulation of reactive oxygen species (ROS) production. In this study, we investigated whether sulforaphane (SFN), a known dietary bioactive compound, could ameliorate ethanol-suppressed angiogenesis using chick embryo angiogenesis models. Using chick yolk sac membrane (YSM) and chorioallantoic membrane (CAM) models, we demonstrated that administration of low concentrations of SFN (2.5–10 μM) alone increased angiogenesis, but high concentrations of SFN (20–40 μM) inhibited angiogenesis. SFN administration alleviated ethanol-suppressed angiogenesis and angiogenesis-related gene expression in both angiogenesis models. Ethanol exposure caused cell apoptosis in chick CAM, and the cell apoptosis could be remitted by administration of SFN. Subsequently, we demonstrated that the ethanol-induced increase in production of ROS and reduction of antioxidant enzymes’ activity were partially rescued by SFN. Similar results were obtained in endoplasmic reticulum (ER) stress determination, indicated by ATF6 and GRP78 expression or thapsigargin-induced ER stress in the presence or absence of SFN. Taken together, our experiments show that SFN administration can ameliorate ethanol-suppressed embryonic angiogenesis, and this is mainly achieved by alleviating excessive ROS production and ER stress. This study suggests that SFN, in appropriate concentrations, could be a potential candidate compound for preventing the negative impact of alcohol on angiogenesis

Differential effects of sulforaphane in regulation of angiogenesis in a co-culture model of endothelial cells and pericytes

Aberrant neovascularization supports nutrients and the oxygen microenvironment in tumour growth, invasion and metastasis. Recapitulation of functional microvascular structures in vitro could provide a platform for the study of vascular conditions. Sulforaphane (SFN), an isothiocyanate, has been reported to possess chemopreventive properties. In the present study, the effects of SFN on cell proliferation and tubular formation have been investigated using endothelial cells (ECs) and pericytes in coculture. SFN showed a dose-dependent inhibition on the growth of ECs and pericytes with IC50 values 46.7 and 32.4 µM, respectively. SFN (5-20 µM) inhibited tube formation in a 3D coculture although a lower dose (1.25 µM) promoted 30% more endothelial tube formation than control. Moreover, SFN affected intercellular communication between ECs and pericytes via inhibition of angiogenic factor such as vascular endothelial growth factor (VEGF) expression in pericytes. However, the expression of its receptor (VEGFR-2) was found significantly increased in ECs. These effects were associated with down-regulation of prolyl hydroxylase domain-containing protein 1 and 2 (PHD1/2) and activation of hypoxia-inducible factor-1 (HIF) pathway by SFN. Furthermore, thioredoxin reductase-1 was also up-regulated by SFN treatment, suggesting that anti-oxidant and redox regulation are involved in angiogenesis. Taken together, the results of this study suggest that SFN differentially regulates endothelial cells and pericytes, and disrupting their interplay through the VEGF-VEGFR signalling pathway. Anti-angiogenesis property of SFN indicates it has potential role as anticancer agent

Measuring Shapes of Galaxy Images I: Ellipticity and Orientation

We suggest a set of morphological measures that we believe can help in quantifying the shapes of two-dimensional cosmological images such as galaxies, clusters, and superclusters of galaxies. The method employs non-parametric morphological descriptors known as the Minkowski functionals in combination with geometric moments widely used in the image analysis. For the purpose of visualization of the morphological properties of image contour lines we introduce three auxiliary ellipses representing the vector and tensor Minkowski functionals. We study the discreteness, seeing, and noise effects on elliptic contours as well as their morphological characteristics such as the ellipticity and orientation. In order to reduce the effect of noise we employ a technique of contour smoothing. We test the method by studying simulated elliptic profiles of toy spheroidal galaxies ranging in ellipticity from E0 to E7. We then apply the method to real galaxies, including eight spheroidals, three disk spirals and one peculiar galaxy, as imaged in the near-infrared $K_s$-band (2.2 microns) with the Two Micron All Sky Survey (2MASS). The method is numerically very efficient and can be used in the study of hundreds of thousands images obtained in modern surveys.Comment: Accepted for publication in MNRAS. Revised version contains 20 pages, 17 PostScript figures. Results unchanged; high-resolution figures # 1,6,7,11,13,16 can be obtained from author

Antioxidant effects of sulforaphane in human HepG2 cells and immortalised hepatocytes

Sulforaphane (SFN) has shown anti-cancer effects in cellular and animal studies but its effectiveness has been limited in human studies. Here, the effects of SFN were measured in both human hepatocyte (HHL5) and hepatoma (HepG2) cells. Results showed that SFN inhibited cell viability and induced DNA strand breaks at high doses (≥ 20 µM). It also activated the nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and increased intracellular glutathione (GSH) levels at 24 hours. Pre-treatment with a low dose SFN (≤5 µM) protected against hydrogen peroxide (H2O2)-induced cell damage. High doses of SFN were more toxic towards HHL5 compared to HepG2 cells; the difference is likely due to the disparity in the responses of Nrf2-driven enzymes and -GSH levels between the two cell lines. In addition, HepG2 cells hijacked the cytoprotective effect of SFN over a wider dose range (1.25 - 20 µM) compared to HHL5. Manipulation of levels of GSH and Nrf2 in HepG2 cells confirmed that both molecules mediate the protective effects of SFN against H2O2. The non-specific nature of SFN in the regulation of cell death and survival could present undesirable risks, i.e. be more toxic to normal cells, and cause chemo-resistance in tumor cells. These issues should be addressed in the context for cancer prevention and treatment before large scale clinical trials are undertaken

Изменение психических состояний педагогов в процессе профессиональной деятельности с учетом стажа деятельности

It is relatively unknown how different dietary components, in partnership, regulate gene expression linked to colon pathology. It has been suggested that the combination of various bioactive components present in a plant-based diet is crucial for their potential anticancer activities. This study employed a combinatorial chemopreventive strategy to investigate the impact of selenium and/or isothiocyanates on DNA methylation processes in colorectal carcinoma cell lines

The potential for dietary factors to prevent or treat osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease for which there are no disease-modifying drugs. It is a leading cause of disability in the UK. Increasing age and obesity are both major risk factors for OA and the health and economic burden of this disease will increase in the future. Focusing on compounds from the habitual diet that may prevent the onset or slow the progression of OA is a strategy that has been under-investigated to date. An approach that relies on dietary modification is clearly attractive in terms of risk/benefit and more likely to be implementable at the population level. However, before undertaking a full clinical trial to examine potential efficacy, detailed molecular studies are required in order to optimise the design. This review focuses on potential dietary factors that may reduce the risk or progression of OA, including micronutrients, fatty acids, flavonoids and other phytochemicals. It therefore ignores data coming from classical inflammatory arthritides and nutraceuticals such as glucosamine and chondroitin. In conclusion, diet offers a route by which the health of the joint can be protected and OA incidence or progression decreased. In a chronic disease, with risk factors increasing in the population and with no pharmaceutical cure, an understanding of this will be crucial

Flavonoid intake and the risk of age-related cataract in China’s Heilongjiang Province

Background/Objectives: Epidemiological evidence suggests that diets rich in flavonoids may reduce the risk of developing age-related cataract (ARC). Flavonoids are widely distributed in foods of plant origin and the objective of this study was to evaluate retrospectively the association between the intakes of the five flavonoid subclasses and the risk of ARC.  Subjects/Methods: A population-based case-control study (249 cases and 66 controls) was carried out in Heilongjiang province, which is located in the Northeast of China, and where intakes and availability of fresh vegetables and fruits can be limited. Dietary data gathered by food-frequency questionnaire (FFQ) were used to calculate flavonoid intake. Adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression.  Results: No linear associations between risk of developing ARC and intakes of total dietary flavonoids, anthocyanidins, flavon-3-ol, flavanone, total flavones or total flavonols were found, but quercetin and isorhamnetin intake was inversely associated with ARC risk (OR 11.78, 95% CI: 1.62-85.84, P<0.05, and OR 6.99, 95% CI:1.12-43.44, P<0.05, quartile 4 vs quartile 1, respectively).  Conclusion: As quercetin is contained in many plant foods and isorhamnetin is only contained in very few foods, we concluded that higher quercetin intake may be an important dietary factor in the reduction of risk of age-related cataract

Universal factorial Schur P,QP,Q-functions and their duals

We define universal factorial Schur $P,Q$-functions and their duals, which specialize to generalized (co)-homology "Schubert basis" for loop spaces of the classical groups. We also investigate some of their properties.Comment: 10 pages, old paper written in 2012.1