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      Characterization of Tapeworm Metabolites and Their Reported Biological Activities

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          Abstract

          Parasitic helminths infect billions of people, livestock, and companion animals worldwide. Recently, they have been explored as a novel therapeutic modality to treat autoimmune diseases due to their potent immunoregulatory properties. While feeding in the gut/organs/tissues, the parasitic helminths actively release excretory-secretory products (ESP) to modify their environment and promote their survival. The ESP proteins of helminths have been widely studied. However, there are only limited studies characterizing the non-protein small molecule (SM) components of helminth ESP. In this study, using GC-MS and LC-MS, we have investigated the SM ESP of tapeworm Dipylidium caninum (isolated from dogs) which accidentally infects humans via ingestion of infected cat and dog fleas that harbor the larval stage of the parasite. From this D. caninum ESP, we have identified a total of 49 SM (35 polar metabolites and 14 fatty acids) belonging to 12 different chemotaxonomic groups including amino acids, amino sugars, amino acid lactams, organic acids, sugars, sugar alcohols, sugar phosphates, glycerophosphates, phosphate esters, disaccharides, fatty acids, and fatty acid derivatives. Succinic acid was the major small molecule present in the D. caninum ESP. Based on the literature and databases searches, we found that of 49 metabolites identified, only 12 possessed known bioactivities.

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          MetaboAnalyst: a web server for metabolomic data analysis and interpretation

          Metabolomics is a newly emerging field of ‘omics’ research that is concerned with characterizing large numbers of metabolites using NMR, chromatography and mass spectrometry. It is frequently used in biomarker identification and the metabolic profiling of cells, tissues or organisms. The data processing challenges in metabolomics are quite unique and often require specialized (or expensive) data analysis software and a detailed knowledge of cheminformatics, bioinformatics and statistics. In an effort to simplify metabolomic data analysis while at the same time improving user accessibility, we have developed a freely accessible, easy-to-use web server for metabolomic data analysis called MetaboAnalyst. Fundamentally, MetaboAnalyst is a web-based metabolomic data processing tool not unlike many of today's web-based microarray analysis packages. It accepts a variety of input data (NMR peak lists, binned spectra, MS peak lists, compound/concentration data) in a wide variety of formats. It also offers a number of options for metabolomic data processing, data normalization, multivariate statistical analysis, graphing, metabolite identification and pathway mapping. In particular, MetaboAnalyst supports such techniques as: fold change analysis, t-tests, PCA, PLS-DA, hierarchical clustering and a number of more sophisticated statistical or machine learning methods. It also employs a large library of reference spectra to facilitate compound identification from most kinds of input spectra. MetaboAnalyst guides users through a step-by-step analysis pipeline using a variety of menus, information hyperlinks and check boxes. Upon completion, the server generates a detailed report describing each method used, embedded with graphical and tabular outputs. MetaboAnalyst is capable of handling most kinds of metabolomic data and was designed to perform most of the common kinds of metabolomic data analyses. MetaboAnalyst is accessible at http://www.metaboanalyst.ca
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            Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease.

            To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. The effect of SCFAs on cytokine release from human neutrophils was studied with ELISA. SCFA-dependent modulation of NF-kappaB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFalpha release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-kappaB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-kappaB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.
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              Review article: short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders

              Butyrate, propionate and acetate are short chain fatty acids (SCFA), important for maintaining a healthy colon and are considered as protective in colorectal carcinogenesis. However, they may also regulate immune responses and the composition of the intestinal microbiota. Consequently, their importance in a variety of chronic inflammatory diseases is emerging.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                15 April 2019
                April 2019
                : 24
                : 8
                : 1480
                Affiliations
                [1 ]Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia; matt.field@ 123456jcu.edu.au (M.F.); alex.loukas@ 123456jcu.edu.au (A.L.)
                [2 ]College of Public Health, Medical & Vet Sciences, James Cook University, Townsville, QLD 4811, Australia; constantin.constantinoiu@ 123456jcu.edu.au
                [3 ]Institute of Parasitology, Vetsuisse faculty, University of Zurich, Winterthurerstrasse 266a, CH-8057 Zurich, Switzerland; ramon.eichenberger@ 123456uzh.ch
                [4 ]John Curtin School of Medical Research, Austalian National University, Canberra, ACT 2600, Australia
                Author notes
                [* ]Correspondence: phurpa.wangchuk@ 123456jcu.edu.au ; Tel.: +61-7-42321249
                Author information
                https://orcid.org/0000-0002-9337-9616
                https://orcid.org/0000-0003-0788-6513
                Article
                molecules-24-01480
                10.3390/molecules24081480
                6514793
                30991712
                9b609371-65e0-4935-8115-7ba80c69aafb
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 March 2019
                : 12 April 2019
                Categories
                Article

                helminths,tapeworm,excretory-secretory products,small molecules,bioactivities

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