1,201 research outputs found

    The anti-proliferative Effects of enterolactone in prostate cancer cells: evidence for the role of DNA licencing genes, mi-R106b cluster expression, and PTEN dosage

    Get PDF
    The mammalian lignan, enterolactone, has been shown to reduce the proliferation of the earlier stages of prostate cancer at physiological concentrations in vitro. However, efficacy in the later stages of the disease occurs at concentrations difficult to achieve through dietary modification. We have therefore investigated what concentration(s) of enterolactone can restrict proliferation in multiple stages of prostate cancer using an in vitro model system of prostate disease. We determined that enterolactone at 20 μM significantly restricted the proliferation of mid and late stage models of prostate disease. These effects were strongly associated with changes in the expression of the DNA licencing genes (GMNN, CDT1, MCM2 and 7), in reduced expression of the miR-106b cluster (miR-106b, miR-93, and miR-25), and in increased expression of the PTEN tumour suppressor gene. We have shown anti-proliferative effects of enterolactone in earlier stages of prostate disease than previously reported and that these effects are mediated, in part, by microRNA-mediated regulation

    The Effects of Unfermented and Fermented Cow and Sheep Milk on the Gut Microbiota

    Get PDF
    A variety of fermented foods have been linked to improved human health, but their impacts on the gut microbiome have not been well characterized. Dairy products are one of the most popular fermented foods and are commonly consumed worldwide. One area we currently lack data on is how the process of fermentation changes the gut microbiota upon digestion. What is even less well characterized are the possible differences between cow and other mammals’ milks. Our aim was to compare the impact of unfermented skim milk and fermented skim milk products (milk/yogurt) originating from two species (cow/sheep) on the gut microbiome using a rat model. Male Sprague-Dawley rats were fed a dairy-free diet supplemented with one of four treatment dairy drinks (cow milk, cow yogurt, sheep milk, sheep yogurt) for 2 weeks. The viable starter culture bacteria in the yogurts were depleted in this study to reduce their potential influence on gut bacterial communities. At the end of the study, cecal samples were collected and the bacterial community profiles determined via 16S rRNA high-throughput sequencing. Fermentation status drove the composition of the bacterial communities to a greater extent than their animal origin. While overall community alpha diversity did not change among treatment groups, the abundance of a number of taxa differed. The cow milk supplemented treatment group was distinct, with a higher intragroup variability and a distinctive taxonomic composition. Collinsella aerofaciens was of particularly high abundance (9%) for this group. Taxa such as Firmicutes and Lactobacillus were found in higher abundance in communities of rats fed with milk, while Proteobacteria, Bacteroidetes, and Parabacteroides were higher in yogurt fed rats. Collinsella was also found to be of higher abundance in both milk (vs. yogurt) and cows (vs. sheep). This research provides new insight into the effects of unfermented vs. fermented milk (yogurt) and animal origin on gut microbial composition in a healthy host. A number of differences in taxonomic abundance between treatment groups were observed. Most were associated with the effects of fermentation, but others the origin species, or in the case of cow milk, unique to the treatment group. Future studies focusing on understanding microbial metabolism and interactions, should help unravel what drives these differences

    Pro-inflammatory adjuvant properties of pigment-grade titanium dioxide particles are augmented by a genotype that potentiates interleukin 1β processing.

    Get PDF
    Background. Pigment-grade titanium dioxide (TiO2) particles are an additive to some foods (E171 on ingredients lists), toothpastes, and pharma-/nutraceuticals and are absorbed, to some extent, in the human intestinal tract. TiO2 can act as a modest adjuvant in the secretion of the pro-inflammatory cytokine interleukin 1β (IL-1β) when triggered by common intestinal bacterial fragments, such as lipopolysaccharide (LPS) and/or peptidoglycan. Given the variance in human genotypes, which includes variance in genes related to IL-1β secretion, we investigated whether TiO2 particles might, in fact, be more potent pro-inflammatory adjuvants in cells that are genetically susceptible to IL-1β-related inflammation. Methods. We studied bone marrow-derived macrophages from mice with a mutation in the nucleotide-binding oligomerisation domain-containing 2 gene (Nod2m/m), which exhibit heightened secretion of IL-1β in response to the peptidoglycan fragment muramyl dipeptide (MDP). To ensure relevance to human exposure, TiO2 was food-grade anatase (119 ± 45 nm mean diameter ± standard deviation). We used a short ‘pulse and chase’ format: pulsing with LPS and chasing with TiO2 +/− MDP or peptidoglycan. Results. IL-1β secretion was not stimulated in LPS-pulsed bone marrow-derived macrophages, or by chasing with MDP, and only very modestly so by chasing with peptidoglycan. In all cases, however, IL-1β secretion was augmented by chasing with TiO2 in a dose-dependent fashion (5–100 µg/mL). When co-administered with MDP or peptidoglycan, IL-1β secretion was further enhanced for the Nod2m/m genotype. Tumour necrosis factor α was triggered by LPS priming, and more so for the Nod2m/m genotype. This was enhanced by chasing with TiO2, MDP, or peptidoglycan, but there was no additive effect between the bacterial fragments and TiO2

    Lactobacillus plantarum MB452 enhances the function of the intestinal barrier by increasing the expression levels of genes involved in tight junction formation

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Intestinal barrier function is important for preserving health, as a compromised barrier allows antigen entry and can induce inflammatory diseases. Probiotic bacteria can play a role in enhancing intestinal barrier function; however, the mechanisms are not fully understood. Existing studies have focused on the ability of probiotics to prevent alterations to tight junctions in disease models, and have been restricted to a few tight junction bridging proteins. No studies have previously investigated the effect of probiotic bacteria on healthy intestinal epithelial cell genes involved in the whole tight junction signalling pathway, including those encoding for bridging, plaque and dual location tight junction proteins. Alteration of tight junction signalling in healthy humans is a potential mechanism that could lead to the strengthening of the intestinal barrier, resulting in limiting the ability of antigens to enter the body and potentially triggering undesirable immune responses.</p> <p>Results</p> <p>The effect of <it>Lactobacillus plantarum </it>MB452 on tight junction integrity was determined by measuring trans-epithelial electrical resistance (TEER) across Caco-2 cell layers. <it>L. plantarum </it>MB452 caused a dose-dependent TEER increase across Caco-2 cell monolayers compared to control medium. Gene expression was compared in Caco-2 cells untreated or treated with <it>L. plantarum </it>MB452 for 10 hours. Caco-2 cell RNA was hybridised to human oligonucleotide arrays. Data was analysed using linear models and differently expressed genes were examined using pathway analysis tools. Nineteen tight junction-related genes had altered expression levels in response to <it>L. plantarum </it>MB452 (modified-P < 0.05, fold-change > 1.2), including those encoding occludin and its associated plaque proteins that anchor it to the cytoskeleton. <it>L. plantarum </it>MB452 also caused changes in tubulin and proteasome gene expression levels which may be linked to intestinal barrier function. Caco-2 tight junctions were visualised by fluorescent microscopy of immuno-stained occludin, zona occludens (ZO)-1, ZO-2 and cingulin. Caco-2 cells treated with <it>L. plantarum </it>MB452 had higher intensity fluorescence of each of the four tight junction proteins compared to untreated controls.</p> <p>Conclusions</p> <p>This research indicates that enhancing the expression of genes involved in tight junction signalling is a possible mechanism by which <it>L. plantarum </it>MB452 improves intestinal barrier function.</p

    The Classification and Evolution of Bacterial Cross-Feeding

    Get PDF
    Bacterial feeding has evolved toward specific evolutionary niches and the sources of energy differ between species and strains. Although bacteria fundamentally compete for nutrients, the excreted products from one strain may be the preferred energy source or a source of essential nutrients for another strain. The large variability in feeding preferences between bacterial strains often provides for complex cross-feeding relationships between bacteria, particularly in complex environments such as the human lower gut, which impacts on the host's digestion and nutrition. Although a large amount of information is available on cross-feeding between bacterial strains, it is important to consider the evolution of cross-feeding. Adaptation to environmental stimuli is a continuous process, thus understanding the evolution of microbial cross-feeding interactions allows us to determine the resilience of microbial populations to changes to this environment, such as changes in nutrient supply, and how new interactions might emerge in the future. In this review, we provide a framework of terminology dividing bacterial cross-feeding into four forms that can be used for the classification and analysis of cross-feeding dynamics. Under the proposed framework, we discuss the evolutionary origins for the four forms of cross-feeding and factors such as spatial structure that influence their emergence and subsequent persistence. This review draws from both the theoretical and experimental evolutionary literature to provide a cross-disciplinary perspective on the evolution of different types of cross-feeding

    Promotility Action of the Probiotic Bifidobacterium lactis HN019 Extract Compared with Prucalopride in Isolated Rat Large Intestine

    Get PDF
    Copyright © 2017 Dalziel, Anderson, Peters, Lynch, Spencer, Dekker and Roy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Attention is increasingly being focussed on probiotics as potential agents to restore or improve gastrointestinal (GI) transit. Determining mechanism of action would support robust health claims. The probiotic bacterium Bifidobacterium lactis HN019 reduces transit time, but its mechanisms of action and effects on motility patterns are poorly understood. The aim of this study was to investigate changes in GI motility induced by an extract of HN019 on distinct patterns of colonic motility in isolated rat large intestine, compared with a known promotility modulator, prucalopride. The large intestines from male Sprague Dawley rats (3–6 months) were perfused with Kreb's buffer at 37°C in an oxygenated tissue bath. Isometric force transducers recorded changes in circular muscle activity at four independent locations assessing contractile propagation between the proximal colon and the rectum. HN019 extract was perfused through the tissue bath and differences in tension and frequency quantified relative to pre-treatment controls. Prucalopride (1 μM) increased the frequency of propagating contractions (by 75 ± 26%) in the majority of preparations studied (10/12), concurrently decreasing the frequency of non-propagating contractions (by 50 ± 11%). HN019 extract had no effect on contractile activity during exposure (n = 8). However, following wash out, contraction amplitude of propagating contractions increased (by 55 ± 18%) in the distal colon, while the frequency of non-propagating proximal contractions decreased by 57 ± 7%. The prokinetic action of prucalopride increased the frequency of synchronous contractions along the length of colon, likely explaining increased colonic rate of transit in vivo. HN019 extract modified motility patterns in a different manner by promoting propagating contractile amplitude and inhibiting non-propagations, also demonstrating prokinetic activity consistent with the reduction of constipation by B. lactis HN019 in humans

    A Web-Based Study of the Relationship of Duration of Insulin Pump Infusion Set Use and Fasting Blood Glucose Level in Adults with Type 1 Diabetes

    Full text link
    Background: To evaluate the impact of infusion set use duration on glycemic control, we conducted an Internet-based study using the T1D Exchange's online patient community, Glu (myGlu.org). Subjects and Methods: For 14 days, 243 electronically consented adults with type 1 diabetes (T1D) entered online that day's fasting blood glucose (FBG) level, the prior day's total daily insulin (TDI) dose, and whether the infusion set was changed. Results: Mean duration of infusion set use was 3.0 days. Mean FBG level was higher with each successive day of infusion set use, increasing from 126?mg/dL on Day 1 to 133?mg/dL on Day 3 to 147?mg/dL on Day 5 (P<0.001). TDI dose did not vary with increased duration of infusion set use. Conclusions: Internet-based data collection was used to rapidly conduct the study at low cost. The results indicate that FBG levels increase with each additional day of insulin pump infusion set use.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140356/1/dia.2014.0336.pd
    corecore