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    ABSTRACT: Considerable evidence implies that an enteroviral infection may accelerate or precipitate type 1 diabetes (T1D) in some individuals. However, causality is not proven. We present and critically assess evidence suggesting that islet β cells can become infected with enterovirus, and argue that this may result in one of several consequences. Occasionally, a fully lytic infection may arise and this culminates in fulminant diabetes. Alternatively, an atypical persistent infection develops which can be either benign or promote islet autoimmunity. We propose a model in which the ‘strength’ of the β cell response to the establishment of a persistent enteroviral infection determines the final disease outcome.
    No preview · Article · Dec 2014 · Trends in Endocrinology and Metabolism
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    ABSTRACT: Human ageing is a complex and integrated gradual deterioration of cellular processes. There are nine major hallmarks of ageing, that include changes in DNA repair and DNA damage response, telomere shortening, changes in control over the expression and regulation of genes brought about by epigenetic and mRNA processing changes, loss of protein homeostasis, altered nutrient signaling, mitochondrial dysfunction, stem cell exhaustion, premature cellular senescence and altered intracellular communication. Like practically all other cellular processes, genes associated in features of ageing are regulated by miRNAs. In this review, I will outline each of the features of ageing, together with examples of specific miRNAs that have been demonstrated to be involved in each one. This will demonstrate the interconnected nature of the regulation of transcripts involved in human ageing, and the role of miRNAs in this process. Definition of the factors involved in degeneration of organismal, tissue and cellular homeostasis may provide biomarkers for healthy ageing and increase understanding of the processes that underpin the ageing process itself.
    Full-text · Article · Sep 2014 · Genes
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    ABSTRACT: Background: In this substudy of the effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes, we report the development of a novel nitrate depleted beetroot juice for use clinical trials and determine if dietary nitrate supplementation improved cognitive function in patients with type 2 diabetes mellitus. Methods: Beetroot juice was treated with the anion exchange resin Purolite A520e. UV-vis-spectrophotometry, and a blind taste test were performed along with determination of sugar content, measurement of ascorbate and dehydroascorbate, the ionic composition of juice and Proton NMR. Subsequently, 27 patients, age 67.2±4.9 years, (18 male) were recruited for a double blind, randomised, placebo-controlled crossover trial. Participants were randomised to begin in either order beetroot juice (nitrate content 7.5 mmol per 250 ml) or placebo (nitrate depleted beetroot juice nitrate content 0.002 mmol per 250 ml). At the end of each 2 week supplementation period cognitive function was assessed using E-prime, E-Studio software with 5 separate tests being performed. The tests utilised in the present study have been adapted from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Results: The differences in the UV-vis spectra were comparable to the natural variation found in differing cultivars. There were no discernable differences in taste, sugar content, or Proton NMR. Ascorbate and dehydroascorbate were undetectable in either juice. After 2 weeks of beetroot juice simple reaction time was significantly quicker in the active arm at 327±40 ms versus 341.8±52.7 ms in the placebo arm, mean difference 13.9±25.6 ms (95% CI 3.8-24.0 ms), p=0.009. No other measures of cognitive function differed between treatment arms. Conclusion: We have developed an effective placebo beetroot juice for use in trials of supplementation of dietary nitrate. Two weeks supplementation of the diet with 7.5 mmol of nitrate per day caused a significant improvement in simple reaction time in individuals with T2DM.
    No preview · Article · May 2014 · Nitric Oxide
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