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  1. Article ; Online: Neutrophil-mediated type IV collagen degradation is elevated in patients with mild endoscopic ulcerative colitis reflecting early mucosal destruction.

    Alexdottir, Marta S / Pehrsson, Martin / Domislovic, Viktor / Godskesen, Line E / Krag, Aleksander / Kjeldsen, Jens / Brinar, Marko / Barisic, Ana / Bay-Jensen, Anne-Christine / Karsdal, Morten A / Krznaric, Zeljko / Mortensen, Joachim H

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 1641

    Abstract: Neutrophils play a significant role in sustaining chronic inflammation in Inflammatory Bowel Disease. The intestinal basement membrane acts as a barrier for immunological homeostasis, where the α3 and α4 chains of type IV collagen are expressed on the ... ...

    Abstract Neutrophils play a significant role in sustaining chronic inflammation in Inflammatory Bowel Disease. The intestinal basement membrane acts as a barrier for immunological homeostasis, where the α3 and α4 chains of type IV collagen are expressed on the mucosal surface. We wanted to develop a biomarker reflecting early tissue injury, providing an opportunity for intervention. Two competitive enzyme-linked immunosorbent assays (ELISAs) quantifying human neutrophil elastase (HNE) degraded neo-epitopes of COL4A3 and COL4A4 were developed and investigated in two observational cohorts (n = 161, n = 100). A biomarker of MMP-mediated degradation of COL4A1 (C4M) was used for comparison. In Cohort 1, patients with mild endoscopic ulcerative colitis showed elevated levels of C4A3-HNE compared to those with severe disease. C4M had a strong positive correlation with disease activity. C4A3-HNE/C4M provided superior discrimination between mild and severe endoscopic disease and negatively correlated to disease activity. In Cohort 2, C4A4-HNE and C4A4-HNE/C4M showed similar trends. C4A3-HNE and C4A4-HNE possibly reflect early intestinal tissue injury. Combining the markers with a biomarker of another α-chain of the same collagen provides information on two distinct stages of mucosal damage. These biomarkers may be used to monitor disease flare-up in patients in remission, reducing the need for frequent endoscopic procedures.
    MeSH term(s) Humans ; Colitis, Ulcerative/metabolism ; Collagen Type IV/metabolism ; Neutrophils/metabolism ; Basement Membrane/metabolism ; Biomarkers/metabolism
    Chemical Substances Collagen Type IV ; Biomarkers
    Language English
    Publishing date 2024-01-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-52208-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Endotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD.

    Lindholm, Majken / Godskesen, Line E / Manon-Jensen, Tina / Kjeldsen, Jens / Krag, Aleksander / Karsdal, Morten A / Mortensen, Joachim H

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 14713

    Abstract: In inflammatory bowel disease (IBD), the chronic inflammation deeply affects the intestinal extracellular matrix. The aim of this study was to investigate if remodeling of the intestinal basement membrane type VI collagen was associated with ... ...

    Abstract In inflammatory bowel disease (IBD), the chronic inflammation deeply affects the intestinal extracellular matrix. The aim of this study was to investigate if remodeling of the intestinal basement membrane type VI collagen was associated with pathophysiological changes in Crohn's disease (CD) and ulcerative colitis (UC). Serum from IBD patients (CD: n = 65; UC: n = 107; irritable bowel syndrome: n = 18; healthy subjects: n = 20) was investigated in this study. The serological biomarkers C6Ma3 (a matrix metalloproteinase (MMP) generated fragment of the type VI collagen α3 chain) and PRO-C6, also called endotrophin (the C-terminus of the released C5 domain of the type VI collagen α3 chain) were measured by ELISAs. Serum C6Ma3 was increased in CD patients with moderate to severe and mild endoscopically active disease compared to endoscopic remission (p = 0.002, p = 0.0048), respectively, and could distinguish endoscopically active disease from remission with an AUC of 1.0 (sensitivity: 100%, specificity: 100%) (p < 0.0001), which was superior to CRP. C6Ma3 was increased in CD patients with moderate to severe clinical disease compared to mild and remission (p = 0.04; p = 0.009). Serum PRO-C6, endotrophin, was increased in CD patients in clinically remission compared to mild disease (p = 0.04) and moderate to severe disease (p = 0.065). In UC, fecal calprotectin was the only marker that alone could distinguish both clinical and endoscopic active and inactive disease. Type VI collagen degradation of the α3 chain mediated by MMPs was increased in CD patients with endoscopically active disease, measured by the serological biomarker C6Ma3, which was able to distinguish endoscopically active from inactive CD.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers/blood ; Case-Control Studies ; Collagen Type VI/analysis ; Collagen Type VI/blood ; Collagen Type VI/metabolism ; Denmark ; Disease Progression ; Endoscopy, Gastrointestinal ; Extracellular Matrix/metabolism ; Female ; Humans ; Inflammatory Bowel Diseases/diagnosis ; Inflammatory Bowel Diseases/metabolism ; Inflammatory Bowel Diseases/pathology ; Male ; Middle Aged ; Peptide Fragments/analysis ; Peptide Fragments/blood ; Prognosis ; Protein Processing, Post-Translational ; Young Adult
    Chemical Substances Biomarkers ; Collagen Type VI ; Peptide Fragments ; endotrophin
    Language English
    Publishing date 2021-07-19
    Publishing country England
    Document type Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-94321-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Remote ischemic conditioning in active ulcerative colitis: An explorative randomized clinical trial.

    Godskesen, Line E / Lassen, Thomas R / Jespersen, Nichlas R / Siersbæk, Majken / Yan, Yan / Nielsen, Michael M / Tjønnfjord, Sara K / Grøntved, Lars / Madsen, Gunvor / Kjems, Jørgen / Bøtker, Hans E / Schmidt, Michael R / Krag, Aleksander / Kjeldsen, Jens

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 9537

    Abstract: Remote ischemic conditioning (RIC) by repetitive brief periods of limb ischemia and reperfusion renders organs more resistant to ischemic injury. The protection is partly through down-regulation of the inflammatory response. Our aim was to investigate ... ...

    Abstract Remote ischemic conditioning (RIC) by repetitive brief periods of limb ischemia and reperfusion renders organs more resistant to ischemic injury. The protection is partly through down-regulation of the inflammatory response. Our aim was to investigate the clinical and anti-inflammatory effects of RIC in patients with active ulcerative colitis (UC). We included 22 patients with active UC in this explorative, randomized, sham-controlled clinical trial. The patients were randomly assigned 1:1 to RIC (induced in the arm through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff) or sham (incomplete inflation of the blood-pressure cuff) once daily for 10 days. Outcome variables were measured at baseline and on day 11. When compared with sham, RIC did not affect inflammation in the UC patients measured by fecal calprotectin, plasma C-reactive protein, Mayo Score, Mayo Endoscopic Subscore, Nancy Histological Index or inflammatory cytokines involved in UC and RIC. The mRNA and miRNA expression profiles in the UC patients were measured by RNA sequencing and multiplexed hybridization, respectively, but were not significantly affected by RIC. We used the Langendorff heart model to assess activation of the organ protective mechanism induced by RIC, but could not confirm activation of the organ protective mechanism in the UC patients.
    MeSH term(s) Adult ; Colitis, Ulcerative/metabolism ; Colitis, Ulcerative/physiopathology ; Colon/blood supply ; Female ; Humans ; Inflammation/metabolism ; Inflammation/physiopathology ; Ischemia/metabolism ; Ischemic Preconditioning ; Leukocyte L1 Antigen Complex/metabolism ; Male ; MicroRNAs/metabolism ; Middle Aged ; Single-Blind Method ; Treatment Outcome ; Young Adult
    Chemical Substances Leukocyte L1 Antigen Complex ; MicroRNAs
    Language English
    Publishing date 2020-06-12
    Publishing country England
    Document type Clinical Trial ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-65692-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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