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      Effects of molecular weight on intestinal anti-inflammatory activities of β-D-glucan from Ganoderma lucidum

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          Abstract

          To investigate the influence of molecular weight ( M w) on the anti-inflammatory activity of β-D-glucan from Ganoderma lucidum, ultrasonic irradiation was applied to treat the β-D-glucan (GLP, 2.42 × 10 6 g/mol) solution to obtain two degraded fractions with molecular weight of 6.53 × 10 5 g/mol (GLPC) and 3.49 × 10 4 g/mol (GLPN). Structural analysis proved that the degraded fractions possessed similar repeated units with the original β-D-glucan. The in vitro anti-inflammatory activity studies showed that all fractions could significantly inhibit LPS-induced expression of cytokines including TNF-α, IL-8, MIF and MCP-1 in Caco-2 cells at certain concentrations. Moreover, GLPC and GLPN exhibited better anti-inflammatory activity than GLPC. The intestinal anti-inflammatory activity evaluated by dextran sulfate sodium (DSS)—induced colitis mice model showed that intragastric administration of GLPN (lower M w fraction) could significantly recover inflamed tissues of mice. Compared with GLP and GLPC, GLPN exhibited stronger ability to inhibit the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). The results revealed that M w of β-D-glucan influenced its anti-inflammatory activity and decreasing of M w would improve the activity, which provided evidence for the potential use of β-D-glucan from G. lucidum as anti-colitis ingredients.

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          Most cited references46

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          Unravelling the pathogenesis of inflammatory bowel disease.

          Recently, substantial advances in the understanding of the molecular pathogenesis of inflammatory bowel disease (IBD) have been made owing to three related lines of investigation. First, IBD has been found to be the most tractable of complex disorders for discovering susceptibility genes, and these have shown the importance of epithelial barrier function, and innate and adaptive immunity in disease pathogenesis. Second, efforts directed towards the identification of environmental factors implicate commensal bacteria (or their products), rather than conventional pathogens, as drivers of dysregulated immunity and IBD. Third, murine models, which exhibit many of the features of ulcerative colitis and seem to be bacteria-driven, have helped unravel the pathogenesis/mucosal immunopathology of IBD.
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            Inflammatory bowel disease: cause and immunobiology.

            Crohn's disease and ulcerative colitis are idiopathic inflammatory bowel disorders. In this paper, we discuss how environmental factors (eg, geography, cigarette smoking, sanitation and hygiene), infectious microbes, ethnic origin, genetic susceptibility, and a dysregulated immune system can result in mucosal inflammation. After describing the symbiotic interaction of the commensal microbiota with the host, oral tolerance, epithelial barrier function, antigen recognition, and immunoregulation by the innate and adaptive immune system, we examine the initiating and perpetuating events of mucosal inflammation. We pay special attention to pattern-recognition receptors, such as toll-like receptors and nucleotide-binding-oligomerisation-domains (NOD), NOD-like receptors and their mutual interaction on epithelial cells and antigen-presenting cells. We also discuss the important role of dendritic cells in directing tolerance and immunity by modulation of subpopulations of effector T cells, regulatory T cells, Th17 cells, natural killer T cells, natural killer cells, and monocyte-macrophages in mucosal inflammation. Implications for novel therapies, which are discussed in detail in the second paper in this Series, are covered briefly.
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              Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis.

              The inflammatory bowel disease ulcerative colitis (UC) frequently progresses to colon cancer. To understand the mechanisms by which UC patients develop colon carcinomas, we used a mouse model of the disease whereby administration of azoxymethane (AOM) followed by repeated dextran sulfate sodium (DSS) ingestion causes severe colonic inflammation and the subsequent development of multiple tumors. We found that treating WT mice with AOM and DSS increased TNF-alpha expression and the number of infiltrating leukocytes expressing its major receptor, p55 (TNF-Rp55), in the lamina propria and submucosal regions of the colon. This was followed by the development of multiple colonic tumors. Mice lacking TNF-Rp55 and treated with AOM and DSS showed reduced mucosal damage, reduced infiltration of macrophages and neutrophils, and attenuated subsequent tumor formation. WT mice transplanted with TNF-Rp55-deficient bone marrow also developed significantly fewer tumors after AOM and DSS treatment than either WT mice or TNF-Rp55-deficient mice transplanted with WT bone marrow. Furthermore, administration of etanercept, a specific antagonist of TNF-alpha, to WT mice after treatment with AOM and DSS markedly reduced the number and size of tumors and reduced colonic infiltration by neutrophils and macrophages. These observations identify TNF-alpha as a crucial mediator of the initiation and progression of colitis-associated colon carcinogenesis and suggest that targeting TNF-alpha may be useful in treating colon cancer in individuals with UC.
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                Author and article information

                Contributors
                Journal
                Front Nutr
                Front Nutr
                Front. Nutr.
                Frontiers in Nutrition
                Frontiers Media S.A.
                2296-861X
                29 September 2022
                2022
                : 9
                : 1028727
                Affiliations
                [1] 1Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, Ministry of Agriculture , Shanghai, China
                [2] 2Key Laboratory of Edible Fungi Resources and Utilization (South), Ministry of Agriculture , Shanghai, China
                [3] 3National Engineering Research Center of Edible Fungi , Shanghai, China
                [4] 4Shanghai Baixin Bio-Tech Co., Ltd. , Shanghai, China
                Author notes

                Edited by: Xin Wang, Northwest A&F University, China

                Reviewed by: Huihuang Ding, University of Guelph, Canada; Hui Zhang, University of Shanghai for Science and Technology, China; Yan Wu, Shanghai Jiao Tong University, China

                *Correspondence: Jingsong Zhang syja16@ 123456saas.sh.cn

                This article was submitted to Food Chemistry, a section of the journal Frontiers in Nutrition

                Article
                10.3389/fnut.2022.1028727
                9557179
                a8b878f6-c847-41d3-a62f-3f7833c5aabf
                Copyright © 2022 Liu, Tang, Feng, Liu, Tang, Yan, Zhou, Liu, Zhou and Zhang.

                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) and the copyright owner(s) 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.

                History
                : 26 August 2022
                : 14 September 2022
                Page count
                Figures: 7, Tables: 2, Equations: 0, References: 46, Pages: 14, Words: 7607
                Categories
                Nutrition
                Original Research

                ganoderma lucidum,β-(1 → 3,1 → 6)-d-glucan,molecular weight,inflamed caco-2 cells,dss-induced colitis,inflammatory cytokines

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