Analysis of the anti-cancer effects of cincau extract (Premna oblongifolia merr) and other types of non- digestible fibre using faecal fermentation supernatants and Caco-2 cells as a model of the human colon

© 2017 by the authors. Green cincau (Premna oblongifolia Merr) is an Indonesian food plant with a high dietary fibre content. Research has shown that dietary fibre mixtures may be more beneficial for colorectal cancer prevention than a single dietary fibre type. The aim of this study was to investigate the effects of green cincau extract on short chain fatty acid (SCFA) production in anaerobic batch cultures inoculated with human faecal slurries and to compare these to results obtained using different dietary fibre types (pectin, inulin, and cellulose), singly and in combination. Furthermore, fermentation supernatants (FSs) were evaluated in Caco-2 cells for their effect on cell viability, differentiation, and apoptosis. Cincau increased total SCFA concentration by increasing acetate and propionate, but not butyrate concentration. FSs from all dietary fibre sources, including cincau, reduced Caco-2 cell viability. However, the effects of all FSs on cell viability, cell differentiation, and apoptosis were not simply explainable by their butyrate content. In conclusion, products of fermentation of cincau extracts induced cell death, but further work is required to understand the mechanism of action. This study demonstrates for the first time that this Indonesian traditional source of dietary fibre may be protective against colorectal cancer

Combination of selenium and green tea improves the efficacy of chemoprevention in a rat colorectal cancer model by modulating genetic and epigenetic biomarkers

Dietary supplementation of selenium and green tea holds promise in cancer prevention. In this study, we evaluated the efficacies of selenium and green tea administered individually and in combination against colorectal cancer in an azoxymethane (AOM)-induced rat colonic carcinogenesis model and determined the underlying mechanisms of the protection. Four-week old Sprague-Dawley male rats were fed with diets containing 0.5% green tea extract, 1 ppm selenium as selenium-enriched milk protein, or combination of 1 ppm selenium and 0.5% green tea extract. Animals received 2 AOM (15 mg/kg) treatments to induce colonic oncogenesis. Rats were killed 8 or 30 wk later after the last AOM to examine the effect of dietary intervention on aberrant crypt foci (ACF) formation or tumor development. On sacrifice, colons were examined for ACF and tumors, the mRNA levels of SFRP5 and Cyclin D1, and the proteins levels of ß-catenin, COX-2, Ki-67, DNMT1 and acetyl histone H3. The combination of selenium and green tea resulted in a significant additive inhibition of large ACF formation, this effect was greater than either selenium or green tea alone, P<0.01; the combination also had a significant additive inhibition effect on all tumor endpoints, the effect of the combination diet on tumor incidence, multiplicity and size was greater than selenium or green tea alone, P<0.01. Rats fed the combination diet showed marked reduction of DNMT1 expression and induction of histone H3 acetylation, which were accompanied by restoration of SFRP5 mRNA in normal-appearing colonic crypts. The combination diet also significantly reduced ß-catenin nuclear translocation, Cyclin D1 expression and cell proliferation. These data show, for the first time, that combination of selenium and green tea is more effective in suppressing colorectal oncogenesis than either agent alone. The preventive effect is associated with regulation of genetic and epigenetic biomarkers implicated in colonic carcinogenesis.Ying Hu, Graeme H. McIntosh, Richard K. Le Leu, Laura S. Nyskohus, Richard J. Woodman, Graeme P. Youn

The transformation of funeral space in the Modern Shanghai : focusing on the original funeral space

Abstract not availableLaura S. Nyskohus, Amanda J. Watson, Geoffrey P. Margison, Richard K. Le Leu, Susan W. Kim, Trevor J. Lockett, Richard J. Head, Graeme P. Young, Ying H

A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study

Background: A number of studies, notably EPIC, have shown a descrease in colorectal cancer risk associated with increased fibre consumption. Whilst the underlying mechanisms are likely to be multifactorial, production of the short-chain fatty-acid butyrate fro butyratye is frequently cited as a major potential contributor to the effect. Butyrate inhibits histone deacetylases, which work on a wide range of proteins over and above histones. We therefore hypothesized that alterations in the acetylated proteome may be associated with a cancer risk phenotype in the colorectal mucosa, and that such alterations are candidate biomarkers for effectiveness of fibre interventions in cancer prevention. Methods an design: There are two principal arms to this study: (i) a cross-sectional study (FACT OBS) of 90 subjects recruited from gastroenterology clinics and; (ii) an intervention trial in 40 subjects with an 8 week high fibre intervention. In both studies the principal goal is to investigate a link between fibre intake, SCFA production and global protein acetylation. The primary measure is level of faecal butyrate, which it is hoped will be elevated by moving subjects to a high fibre diet. Fibre intakes will be estimated in the cross-sectional group using the EPIC Food Frequency Questionnaire. Subsidiary measures of the effect of butyrate on colon mucosal function and precancerous phenotype will include measures of apoptosis, apoptotic regulators cell cycle and cell division. Discussion: This study will provide a new level of mechanistic data on alterations in the functional proteome in response to the colon microenvironment which may underwrite the observed cancer preventive effect of fibre. The study may yield novel candidate biomarkers of fibre fermentation and colon mucosal function

Dietary Manipulation of Oncogenic MicroRNA Expression in Human Rectal Mucosa: A Randomized Trial

Author version made available in accordance with the publisher's policy.High red meat intake is associated with increased colorectal cancer (CRC) risk, while resistant starch is probably protective. Resistant starch fermentation produces butyrate, which can alter microRNA (miRNA) levels in CRC cells in vitro; effects of red meat and resistant starch on miRNA expression in vivo were unknown. This study examined whether a high red meat (HRM) diet altered miRNA expression in rectal mucosa tissue of healthy volunteers, and if supplementation with butyrylated resistant starch (HRM+HAMSB) modified this response. In a randomised cross-over design, twenty-three volunteers undertook four 4-week dietary interventions; an HRM diet (300 g/day lean red meat) and an HRM+HAMSB diet (HRM with 40 g/day butyrylated high amylose maize starch), preceded by an entry diet and separated by a washout. Faecal butyrate increased with the HRM+HAMSB diet. Levels of oncogenic mature miRNAs, including miR-17-92 cluster miRNAs and miR-21, increased in the rectal mucosa with the HRM diet, while the HRM+HAMSB diet restored miR-17-92 miRNAs, but not miR-21, to baseline levels. Elevated miR-17-92 and miR-21 in the HRM diet corresponded with increased cell proliferation, and a decrease in miR-17-92 target gene transcript levels, including CDKN1A. The oncogenic miR-17-92 cluster is differentially regulated by dietary factors that increase or decrease risk for CRC, and this may explain, at least in part, the respective risk profiles of high red meat and resistant starch. These findings support increased resistant starch consumption as a means of reducing risk associated with an HRM diet

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P &lt; 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes

MNS1 Is Essential for Spermiogenesis and Motile Ciliary Functions in Mice

During spermiogenesis, haploid round spermatids undergo dramatic cell differentiation and morphogenesis to give rise to mature spermatozoa for fertilization, including nuclear elongation, chromatin remodeling, acrosome formation, and development of flagella. The molecular mechanisms underlining these fundamental processes remain poorly understood. Here, we report that MNS1, a coiled-coil protein of unknown function, is essential for spermiogenesis. We find that MNS1 is expressed in the germ cells in the testes and localizes to sperm flagella in a detergent-resistant manner, indicating that it is an integral component of flagella. MNS1–deficient males are sterile, as they exhibit a sharp reduction in sperm production and the remnant sperm are immotile with abnormal short tails. In MNS1–deficient sperm flagella, the characteristic arrangement of “9+2” microtubules and outer dense fibers are completely disrupted. In addition, MNS1–deficient mice display situs inversus and hydrocephalus. MNS1–deficient tracheal motile cilia lack some outer dynein arms in the axoneme. Moreover, MNS1 monomers interact with each other and are able to form polymers in cultured somatic cells. These results demonstrate that MNS1 is essential for spermiogenesis, the assembly of sperm flagella, and motile ciliary functions

Net primary productivity estimates and environmental variables in the Arctic Ocean: An assessment of coupled physical-biogeochemical models

The relative skill of 21 regional and global biogeochemical models was assessed in terms of how well the models reproduced observed net primary productivity (NPP) and environmental variables such as nitrate concentration (NO3), mixed layer depth (MLD), euphotic layer depth (Zeu), and sea ice concentration, by comparing results against a newly updated, quality-controlled in situ NPP database for the Arctic Ocean (1959-2011). The models broadly captured the spatial features of integrated NPP (iNPP) on a pan-Arctic scale. Most models underestimated iNPP by varying degrees in spite of overestimating surface NO3, MLD, and Zeu throughout the regions. Among the models, iNPP exhibited little difference over sea ice condition (ice-free vs. ice-influenced) and bottom depth (shelf vs. deep ocean). The models performed relatively well for the most recent decade and towards the end of Arctic summer. In the Barents and Greenland Seas, regional model skill of surface NO3 was best associated with how well MLD was reproduced. . Regionally, iNPP was relatively well simulated in the Beaufort Sea and the central Arctic Basin, where in situ NPP is low and nutrients are mostly depleted. Models performed less well at simulating iNPP in the Greenland and Chukchi Seas, despite the higher model skill in MLD and sea ice concentration, respectively. iNPP model skill was constrained by different factors in different Arctic Ocean regions. Our study suggests that better parameterization of biological and ecological microbial rates (phytoplankton growth and zooplankton grazing) are needed for improved Arctic Ocean biogeochemical modeling

Scaling Up Sustainable Land Management and Restoration of Degraded Land

With current rates of land degradation reaching ten to twelve million ha per year, there is an urgent need to scale up and out successful, profitable and resource-efficient sustainable land management practices to maintain the health and resilience of the land that humans depend on. As much as 500 million out of two billion ha of degraded land, mainly in developing countries, have restoration potential, offering an immediate target for restoration and rehabilitation initiatives.1 In the past, piecemeal approaches to achieving sustainable land management have had limited impact. To achieve the ambitious goals of alleviating poverty, securing food and water supplies, and protecting the natural resource base, we need to recognize the inter-connectedness of the factors driving land degradation, so that solutions can be taken to scale, transforming management practices for millions of land users. An analysis of the critical barriers and incentives to achieve scaling up suggests that the most appropriate options should be selected through the involvement of stakeholders at all levels, from local to national and international. New incentives for land managers as well as the public and private sectors are required to achieve a land degradation-neutral world