Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor | Department of Health Technology and Informatics | en_US |
dc.contributor.advisor | Law, K. W. Helen (HTI) | en_US |
dc.creator | Li, Yue | - |
dc.identifier.uri | https://theses.lib.polyu.edu.hk/handle/200/13133 | - |
dc.language | English | en_US |
dc.publisher | Hong Kong Polytechnic University | en_US |
dc.rights | All rights reserved | en_US |
dc.title | Unveiling the function of trehalose in autophagy, macrophage polarization and microbiota regulation in inflammatory bowel disease | en_US |
dcterms.abstract | Inflammatory bowel disease (IBD) is a chronic, incurable, and debilitating condition characterized by non-specific inflammation that recurrently affects the mucosal lining of the gastrointestinal (GI) tract. It is widely accepted that IBD arises from a combination of factors including dysregulation of mucosal immunity, gut microbiome dysbiosis, and gut barrier defects, all influenced by genetic susceptibility and environmental triggers. Despite the identification of these contributing factors, the precise mechanisms underlying IBD remain elusive. | en_US |
dcterms.abstract | Given the complex pathogenesis of IBD, current therapies are primarily focused on symptom management. However, these treatments often fail or result in adverse effects over long-term use. Therefore, the development of new drugs and therapies for IBD remains a top priority. Trehalose (TRE), a non-reducing disaccharide, has gained significant attention due to its cytoprotective, protein-stabilizing, and autophagy-inducing properties in various cells, tissues, and organs. Emerging evidence suggests that TRE may serve as a therapeutic agent for a range of diseases. | en_US |
dcterms.abstract | In this study, we utilized the Dextran Sulfate Sodium (DSS)-induced IBD model to investigate the therapeutic effects of TRE on autophagy and inflammation in mice. We monitored weight, stool consistency, diarrhea, and blood in the stools daily to calculate the disease activity index (DAI). At the end of the experiment, colons were measured, opened longitudinally, washed, and collected. Colonic histological sections were used to assess pathological changes under the microscope. Tissue samples were collected for RNA, protein extraction, histology, and macrophage isolation. Autophagy analysis was conducted using Western Blot, while macrophage subtype and apoptosis analysis were performed using flow cytometry. Real-time quantitative Polymerase Chain Reaction (PCR) assay was used to examine cytokine expression, and stool samples were collected for 16S sequencing. | en_US |
dcterms.abstract | Our initial investigation revealed that TRE-treated mice experienced an earlier cessation of diarrhea and anal bleeding, resulting in a more rapid decrease in DAI scores compared to other groups. Correspondingly, the colons of TRE-treated mice showed less shortening than those of saline-treated controls, suggesting recovery from DSS-induced colitis. TRE appears to alleviate DSS-induced colitis in mice and shorten the inflammatory period. | en_US |
dcterms.abstract | We then evaluated the expression of monocyte-macrophage in mice with colitis after TRE treatment. Our results showed an increase in the percentage of CD206⁺ macrophages in CD11b⁺F4/80⁺ macrophages in the TRE groups compared to the NS group in the peritoneal lavage. Additionally, the expression of anti-inflammatory cytokines interleukin (IL)-10 decreased in colonic tissue and peritoneal lavage cells. | en_US |
dcterms.abstract | To explore the potential relationship between TRE and microbiota, we analyzed changes in gut microbiota following TRE treatment. Our findings suggest that TRE can increase the α diversity of gut microbiota and alter the β diversity compared to healthy mice. We observed significant increases in the relative abundance of Allobaculum, Paraprevotella, Ruminocococus, Turicibacter, and Alistipes, and significant decreases in Prevotella in the CON-TRE group compared with the CON group. Bacteroides significantly increased, and Lactobacillus significantly decreased in the DSS-NS group. In the DSS-TRE group, we found an enrichment of Allobaculum, Lactobacillus, and a significant reduction of Prevotella compared to the DSS-NS group. | en_US |
dcterms.abstract | In conclusion, TRE appears to attenuate DSS-induced mouse colitis by influencing autophagy, macrophage polarization, and microbiota. These effects of TRE in IBD suggest potential for the translation of these findings into drug development and treatment strategies to improve long-term therapy for IBD. | en_US |
dcterms.extent | xiv, 185 pages : color illustrations | en_US |
dcterms.isPartOf | PolyU Electronic Theses | en_US |
dcterms.issued | 2024 | en_US |
dcterms.educationalLevel | Ph.D. | en_US |
dcterms.educationalLevel | All Doctorate | en_US |
dcterms.LCSH | Inflammatory bowel diseases -- Treatment | en_US |
dcterms.LCSH | Trehalose -- Therapeutic use | en_US |
dcterms.LCSH | Hong Kong Polytechnic University -- Dissertations | en_US |
dcterms.accessRights | open access | en_US |
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