Encapsulation of vitamin E in yogurt-based beverage emulsions : Influence of bulk pasteurization and chilled storage on physicochemical stability and starter culture viability

This research was funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS). Author Contributions Conceptualization, V.R.; methodology, V.R., H.E.H., L.P.P. and S.G.; formal analysis, H.E.H.; data curation, H.E.H. and V.R.; writing—original draft preparation, V.R. and H.E.H.; supervision, V.R. and H.E.H.; funding acquisition, V.R. All authors have read and agreed to the published version of the manuscript.Peer reviewedPublisher PD

The effect of short-term kaempferol exposure on reactive oxygen levels and integrity of human (HL-60) leukaemic cells

AbstractFlavonoids may be a principal contributor to the cancer preventative activity of fruit- and vegetable-rich diets and there is interest in their use as dietary supplements. However, there is potential conflict between the cytoprotective and cytotoxic activities of flavonoids, and their efficacy as anti-cancer agents is unresolved. Here, the integrity and survival of HL-60 promyelocytic leukaemia cells following short-term (90 min) exposure to the dietary abundant flavonoid kaempferol (1–100 μM) is reported. Supplementation initially decreased reactive oxygen levels but, paradoxically, a dose-dependent increase in single-strand DNA breakage occurred. However, there was no increase in oxidised DNA purines or membrane damage. Following a 24-h recovery period in non-kaempferol supplemented media, DNA single-strand breakage had declined and kaempferol exposed and control cultures possessed similar reactive oxygen levels. A reduction in 3H-thymidine incorporation occurred with ≥10 μM kaempferol. One hundred micromolar kaempefrol increased the proportion of cells in G2-M phase, the proportion of cells with a sub-G1 DNA content and enhanced ‘active’ caspase-3 expression but only induced a loss of mitochondrial membrane potential within a minority of cells. The relevance of induced DNA damage within a non-overtly oxidatively stressed environment to the disease preventative and therapeutic use of kaempferol is discussed

Differential effects of nutritional folic acid deficiency and moderate hyperhomocysteinemia on aortic plaque formation and genome-wide DNA methylation in vascular tissue from ApoE-/- mice

Low folate intake is associated with vascular disease. Causality has been attributed to hyperhomocysteinemia. However, human intervention trials have failed to show the benefit of homocysteine-lowering therapies. Alternatively, low folate may promote vascular disease by deregulating DNA methylation. We investigated whether folate could alter DNA methylation and atherosclerosis in ApoE null mice. Mice were fed one of six diets (n = 20 per group) for 16 weeks. Basal diets were either control (C; 4% lard) or high fat (HF; 21% lard and cholesterol, 0.15%) with different B-vitamin compositions: (1) folic acid and B-vitamin replete, (2) folic acid deficient (−F), (3) folic acid, B6 and B12 deficient (−F−B). −F diets decreased plasma (up to 85%; P < 0.05), whole blood (up to 70%; P < 0.05), and liver folate (up to 65%; P < 0.05) and hepatic SAM/SAH (up to 80%; P < 0.05). −F−B diets reduced plasma (up to 76%; P < 0.05), whole blood (up to 72%; P < 0.05), and liver B12 (up to 39%; P < 0.05) and hepatic SAM/SAH (up to 90%; P < 0.05). −F increased homocysteine 2-fold, while −F−B increased homocysteine 3.6- and 6.8-fold in the C and HF groups (P < 0.05). Plaque formation was increased 2-fold (P < 0.0001) in mice fed a HF diet. Feeding a HF–F diet increased lesion formation by 17% (P < 0.05). There was no change in 5-methyldeoxycytidine in liver or vascular tissue (aorta, periadventitial tissue and heart). These data suggest that atherogenesis is not associated with genome-wide epigenetic changes in this animal model

Effect of increasing fruit and vegetable intake by dietary intervention on nutritional biomarkers and attitudes to dietary change : a randomised trial

This work was funded by The Scottish Government Rural and Environmental Science and Analytical Sciences Division (RESAS) and supported by the Rank Prize Funds.Peer reviewedPublisher PD

Nutritional B vitamin deficiency alters the expression of key proteins associated with vascular smooth muscle cell proliferation and migration in the aorta of atherosclerotic apolipoprotein E null mice.

Low B vitamin status is linked with human vascular disease. We employed a proteomic and biochemical approach to determine whether nutritional folate deficiency and/or hyperhomocysteinemia altered metabolic processes linked with atherosclerosis in ApoE null mice. Animals were fed either a control fat (C; 4 % w/w lard) or a high-fat [HF; 21 % w/w lard and cholesterol (0/15 % w/w)] diet with different B vitamin compositions for 16 weeks. Aorta tissue was prepared and global protein expression, B vitamin, homocysteine and lipoprotein status measured. Changes in the expression of aorta proteins were detected in response to multiple B vitamin deficiency combined with a high-fat diet (P < 0.05) and were strongly linked with lipoprotein concentrations measured directly in the aorta adventitia (P < 0.001). Pathway analysis revealed treatment effects in the aorta-related primarily to cytoskeletal organisation, smooth muscle cell adhesion and invasiveness (e.g., fibrinogen, moesin, transgelin, vimentin). Combined B vitamin deficiency induced striking quantitative changes in the expression of aorta proteins in atherosclerotic ApoE null mice. Deregulated expression of these proteins is associated with human atherosclerosis. Cellular pathways altered by B vitamin status included cytoskeletal organisation, cell differentiation and migration, oxidative stress and chronic inflammation. These findings provide new insight into the molecular mechanisms through which B vitamin deficiency may accelerate atherosclerosis

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Personal status law reform in Egypt: Women’s rights NGOs navigating between Islamic law and human rights

This thesis explores the ways in which Islamic law and human rights interact within the work of women’s rights non-governmental organizations (NGOs) that advocate the reform of the Egyptian Personal Status Law (PSL) in the period between 2006 and 2010. The thesis shows the relevance of the human rights framework as well as the flexibility of Islamic legal discourse in the work of the NGOs. Drawing on both Islamic law and human rights enabled NGOs to develop a more gender-sensitive religious discourse, which supported their PSL reform demands. However the interaction between these two frameworks was largely affected by several important factors, which sometimes led NGOs to dilute some of their demands. These factors included the implications of the change in the form of Shari‘a as codified law under the modern nation-state; the Egyptian political context both internally and externally; the common local perception that human rights are a Western production and an extension of Western colonialism; the dominant religious but patriarchal discourse governing the PSL; the implications of activism through the NGO structure; and the personal religiosity of individual activists. The thesis explores NGOs’ PSL reform demands in depth bearing in mind these factors. It investigates NGOs’ discourse and shows its strengths and weaknesses. It shows that the interaction between Islamic law and human rights within NGOs’ work in this particular Egyptian context produced reform demands that were innovative and practically appealing on one hand, but epistemologically problematic in some instances, on another.This thesis is not currently available on ORA

Folate deficiency promotes differentiation of vascular smooth muscle cells without affecting the methylation status of regulated genes.

Elevated serum homocysteine, an intermediate of cellular one-carbon metabolism, is an independent risk factor for cardiovascular disease (CVD). Folate deficiency increases serum homocysteine and may contribute to CVD progression. Vascular smooth muscle cells (VSMCs) regulate vascular contractility, but also contribute to repair processes in response to vascular injury. Nutritional deficiencies, like folate deficiency, are thought to impact on this phenotypic plasticity, possibly by epigenetic mechanisms. We have investigated the effect of folate deficiency on VSMCs in two cell culture systems representing early and late stages of smooth muscle cells differentiation. We find that folate deficiency promotes differentiation towards a more contractile phenotype as indicated by increased expression of respective marker genes. However, microarray analysis identified markers of striated muscle as the predominant gene expression change elicited by folate deficiency. These changes are not merely a reflection of cell cycle arrest, as foetal calf serum restriction or iron deficiency do not replicate the gene expression changes observed in response to folate deficiency. Folate deficiency only has a marginal effect on global DNA methylation. DNA methylation of CpG islands associated with genes regulated by folate deficiency remains unaffected. This supports our earlier findings in a mouse model system which also did not show any changes in global DNA methylation in response to folate and vitamin B6/B12 deficiency. These data suggest that folate deficiency enhances the expression of smooth muscle marker gene expression, promotes a shift towards a skeletal muscle phenotype, and does not regulate gene expression via DNA methylation