Effect of inulin type fructans on protein fermentation by gut bacteria: in vitro and in vivo studies

In Europe and Northern America, protein intake is high, whilst fibre intake is relatively low. With large amounts of protein entering the colon, bacterial proteolysis may have some negative effects through potentially toxic end-products. Prebiotics could have the potential to reverse negative consequences of gut bacterial protein fermentation. Single stage, pH controlled, anaerobic, stirred batch culture systems simulating the distal colon were applied first with faecal inoculum from both omnivore and vegetarian volunteers. Fermentation of different protein sources with and without supplementation of inulin type fructans (ITF) were tested. A significant increase of bifidobacteria was observed with the addition of the ITF together with lower concentrations of protein fermentation metabolites (BCFA and ammonia). Three-stage continuous colonic model systems simulating the whole colon were then studied with both omnivore and vegetarian volunteers. Casein, with and without two different doses of ITF were assessed. A significantly higher number of bifidobacteria and reduction of bacteroides and Desulfovibrio spp. were found with ITF addition. Furthermore, production of metabolites from protein fermentation (BCFA and ammonia) was significantly lowered with ITF. To confirm the health benefit of ITF on high protein population in vivo, 43 volunteers were recruited to complete a randomised, double blind, cross over trial. A significant increase in bifidobacteria and a decrease in Desulfovibrio spp. was confirmed with the addition of prebiotic treatment. Stool frequency was significantly higher with ITF as compared to the placebo group, with a trend towards softness as based on the Bristol scale. Total bacteria and bifidobacteria changes during interventions were significantly correlated with stool frequency. In conclusion, all three phases of the project found favourable bacterial and metabolic changes with ITF supplementation. ITF had inhibitory effects on colonic microbial proteolysis, and could exert health benefit for high protein consumers, especially those who also consume low fibre diet

Association of Bacteroides acidifaciens relative abundance with high-fibre diet-associated radiosensitisation

Funding Information: This work was funded by Cancer Research UK Programme grant C5255/ A23755 and Wellcome Trust Investigator Award 209397/Z/17/Z. The funding body had no role in the design of the study; in the collection, analysis, and interpretation of data; or in the writing of the manuscript. Acknowledgements We thank Professor Simon Kroll and Dr. Anderson Ryan for their very helpful comments. We thank Dr. Jia-Yu Ke at Research Diets, Inc. for formulation of the mouse diets, Dr. Lisa Folkes for assistance with the faecal butyrate quantification, and Omega Bioservices (Georgia, USA) for the 16S rRNA gene sequencing on a MiSeq platform.Peer reviewedPublisher PD

Transcriptional activation of microRNA-34a by NF-kappa B in human esophageal cancer cells

<p>Abstract</p> <p>Background</p> <p>miR-34a functions as an important tumor suppressor during the process of carcinogenesis. However, the mechanism of miR-34a dysregulation in human malignancies has not been well elucidated. Our study aimed to further investigate the regulation mechanism of miR-34a.</p> <p>Results</p> <p>We found that overexpression of NF-kappa B p65 subunit could increase miR-34a levels in EC109, an esophageal squamous cancer cell line, while ectopic expression of DN IkappaB leaded to a significant reduction of miR-34a expression. Bioinformatics analysis suggested three putative KB sites in promoter region of miR-34a gene. Mutation two of these KB sites impaired p65 induced miR-34a transcriptional activity. Chromatin immunoprecipitation and electrophoretic mobility shift assays both showed that NF-kappaB could specifically bind to the third KB site located in miR-34a promoter. In addition, we found that overexpression of NF-kappaB p65 could not successfully induce miR-34a expression in esophageal cancer cell lines with mutant p53 or decreased p53. Reporter assay further showed that NF-kappaB-induced miR-34a transcriptional activity was reduced by p53 impairment. Nevertheless, CHIP analysis suggested binding of NF-kappaB to miR-34a promoter was not affected in cells with mutant p53.</p> <p>Conclusions</p> <p>Our work indicates a novel mechanism of miR-34a regulation that NF-kappaB could elevate miR-34a expression levels through directly binding to its promoter. And wildtype p53 is responsible for NF-kappaB-mediated miR-34a transcriptional activity but not for NF-kappaB binding. These findings might be helpful in understanding miR-34a abnormality in human malignancies and open new perspectives for the roles of miR-34a and NF-kappaB in tumor progression.</p

Prebiotic supplementation of In Vitro fecal fermentations inhibits proteolysis by gut bacteria, and host diet shapes gut bacterial metabolism and response to intervention

Metabolism of protein by gut bacteria is potentially detrimental due to the production of toxic metabolites, such as ammonia, amines, p-cresol, and indole. The consumption of prebiotic carbohydrates results in specific changes in the composition and/or activity of the microbiota that may confer benefits to host well-being and health. Here, we have studied the impact of prebiotics on proteolysis within the gut in vitro. Anaerobic stirred batch cultures were inoculated with feces from omnivores (n = 3) and vegetarians (n = 3) and four protein sources (casein, meat, mycoprotein, and soy protein) with and without supplementation by an oligofructose-enriched inulin. Bacterial counts and concentrations of short-chain fatty acids (SCFA), ammonia, phenol, indole, and p-cresol were monitored during fermentation. Addition of the fructan prebiotic Synergy1 increased levels of bifidobacteria (P = 0.000019 and 0.000013 for omnivores and vegetarians, respectively). Branched-chain fatty acids (BCFA) were significantly lower in fermenters with vegetarians’ feces (P = 0.004), reduced further by prebiotic treatment. Ammonia production was lower with Synergy1. Bacterial adaptation to different dietary protein sources was observed through different patterns of ammonia production between vegetarians and omnivores. In volunteer samples with high baseline levels of phenol, indole, p-cresol, and skatole, Synergy1 fermentation led to a reduction of these compounds

Empowering Students’ Learning Achievement Through Project-Based Learning As Perceived By Electrical Instructors And Students

Purposes of this research were to find out factors empowering electrical students‘ learning achievement through Project-Based Learning (PBL) as perceived by instructors‘ and students‘ opinions. The sample chosen for this study were 247 electrical power instructors at vocational education institutes and 161 electrical students in the 3 rd and 4th year who were studying in the 1st semester of academic year 2006 at Electrical Education Department, Faculty of Industrial Education and Technology, King Mongkut‘s University of Technology Thonburi by using simple random sampling. The instrument used for data collection was 7 rating scales questionnaire. The reliability of the instrument calculated by Cronbach Alpha Coefficient was 0.8185 and 0.9839, respectively. The data were analysed by using mean ( ), Standard Deviation (S.D.) and Analysis of Factors by Principal Component Analysis technique: PCA, orthogonal rotation axis by Varimax Method. The results of the study on factors empowering electrical students‘ learning achievement through Project-Based Learning (PBL) were as follows: both instructors and students agreed on Interesting/Attention(0.799 and 0.885, respectively) while other factors such as Planning(0.722), Sharing Ideas(0.582), Thinking(0.576), Facilitating (0.547), Constructionism (0.540), Scientific Process (0.525), Multiple Intelligence (0.479), and Goal Setting(0.453) were perceived by instructors, and students‘ opinions were on Advising/Guiding(0.863), Thinking(0.661), Goal Setting (0.634), Multiple Intelligence(0.553), Scientific Process(0.528), Assisting(0.524), and Sharing Ideas (0.492), if not more so

The Synthesis and Initial Evaluation of MerTK Targeted PET Agents

MerTK (Mer tyrosine kinase), a receptor tyrosine kinase, is ectopically or aberrantly expressed in numerous human hematologic and solid malignancies. Although a variety of MerTK targeting therapies are being developed to enhance outcomes for patients with various cancers, the sensitivity of tumors to MerTK suppression may not be uniform due to the heterogeneity of solid tumors and different tumor stages. In this report, we develop a series of radiolabeled agents as potential MerTK PET (positron emission tomography) agents. In our initial in vivo evaluation, [18F]-MerTK-6 showed prominent uptake rate (4.79 ± 0.24%ID/g) in B16F10 tumor-bearing mice. The tumor to muscle ratio reached 1.86 and 3.09 at 0.5 and 2 h post-injection, respectively. In summary, [18F]-MerTK-6 is a promising PET agent for MerTK imaging and is worth further evaluation in future studies

Tuberous Sclerosis Complex With Multiple Organ Tumors: Case Report and Literature Review

Pancreatic neuroendocrine neoplasms (PNEN) are tumors that originate from neuroendocrine cells. Only about 1% patients are related to mutation of tuberous sclerosis complex gene. Here, we reported a rare case with involvement of multiple organs and space-occupying lesions. Initially, the patient was thought to have metastasis of a pancreatic tumor. However, the patient was diagnosed as pancreatic neuroendocrine tumors, liver perivascular epithelioid tumors, splenic hamartoma, and renal angiomyolipoma by pathological examination after surgery. We performed genetic mutation detection to identify that tuberous sclerosis complex 2 gene presented with a heterozygous variant. Tuberous sclerosis often presents with widespread tumors, but it is less common to present with pancreatic neuroendocrine tumors and liver perivascular tumors as highlighted in the case. So we analyzed the relationship between TSC gene mutations and related tumors. And we also reviewed the current molecular mechanisms and treatments for tuberous sclerosis complex

Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity.

Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy

Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity

Acknowledgements We thank Professor William Kim (University of North Carolina, Chapel Hill) for his generous gift of the UPPL1591 cell line. We thank Dr. Mark Hill (Department of Oncology, University of Oxford) for assistance with irradiation procedures, and Dr. Jia-Yu Ke and Dr. Vijay Indukuri (Research Diets, Inc.) for formulation of the mouse diets. We thank Dr. Graham Horgan (James Hutton Research Institute, Aberdeen) for statistical advice. We thank Grampian Biorepository at Aberdeen Royal Infirmary for providing the faecal samples from cancer patients.Peer reviewe