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  1. Article ; Online: Quantitative Phase Imaging Using Digital Holographic Microscopy to Assess the Degree of Intestinal Inflammation in Patients with Ulcerative Colitis

    Arne Bokemeyer / Joost Buskermolen / Steffi Ketelhut / Phil-Robin Tepasse / Richard Vollenberg / Jonel Trebicka / Hartmut H. Schmidt / Michael Vieth / Dominik Bettenworth / Björn Kemper

    Journal of Clinical Medicine, Vol 12, Iss 4067, p

    2023  Volume 4067

    Abstract: Ulcerative colitis (UC) is characterized by chronic inflammation of the colorectum. Histological remission has emerged as a potential future treatment goal; however, the histopathological assessment of intestinal inflammation in UC remains challenging ... ...

    Abstract Ulcerative colitis (UC) is characterized by chronic inflammation of the colorectum. Histological remission has emerged as a potential future treatment goal; however, the histopathological assessment of intestinal inflammation in UC remains challenging with a multitude of available scoring systems and the need for a pathologist with expertise in inflammatory bowel disease (IBD). In previous studies, quantitative phase imaging (QPI) including digital holographic microscopy (DHM) was successfully applied as an objective method for stain-free quantification of the degree of inflammation in tissue sections. Here, we evaluated the application of DHM for the quantitative assessment of histopathological inflammation in patients with UC. In our study, endoscopically obtained colonic and rectal mucosal biopsy samples from 21 patients with UC were analyzed by capturing DHM-based QPI images that were subsequently evaluated using the subepithelial refractive index (RI). The retrieved RI data were correlated with established histological scoring systems including the Nancy index (NI) as well as with endoscopic and clinical findings. As a primary endpoint, we found a significant correlation between the DHM-based retrieved RI and the NI (R 2 = 0.251, p < 0.001). Furthermore, RI values correlated with the Mayo endoscopic subscore (MES; R 2 = 0.176, p < 0.001). An area under the receiver operating characteristics (ROC) curve of 0.820 confirms the subepithelial RI as a reliable parameter to distinguish biopsies with histologically active UC from biopsies without evidence of active disease as determined by conventional histopathological examination. An RI higher than 1.3488 was found to be the most sensitive and specific cut-off value to identify histologically active UC (sensitivity of 84% and specificity of 72%). In conclusion, our data demonstrate DHM to be a reliable tool for the quantitative assessment of mucosal inflammation in patients with UC.
    Keywords quantitative phase imaging ; digital holographic microscopy ; inflammatory bowel disease ; ulcerative colitis ; inflammation ; refractive index ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The Influence of Capsaicin on the Integrity of Microvascular Endothelial Cell Monolayers

    Mathias Kaiser / Malgorzata Burek / Stefan Britz / Frauke Lankamp / Steffi Ketelhut / Björn Kemper / Carola Förster / Christian Gorzelanny / Francisco M. Goycoolea

    International Journal of Molecular Sciences, Vol 20, Iss 1, p

    2018  Volume 122

    Abstract: Microvascular endothelial cells are an essential part of many biological barriers, such as the blood–brain barrier (BBB) and the endothelium of the arteries and veins. A reversible opening strategy to increase the permeability of drugs across the BBB ... ...

    Abstract Microvascular endothelial cells are an essential part of many biological barriers, such as the blood–brain barrier (BBB) and the endothelium of the arteries and veins. A reversible opening strategy to increase the permeability of drugs across the BBB could lead to improved therapies due to enhanced drug bioavailability. Vanilloids, such as capsaicin, are known to reversibly open tight junctions of epithelial and endothelial cells. In this study, we used several in vitro assays with the murine endothelial capillary brain cells (line cEND) as a BBB model to characterize the interaction between capsaicin and endothelial tight junctions.
    Keywords tight junctions ; capsaicin ; endothelial cells ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2018-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Nanoencapsulated capsaicin changes migration behavior and morphology of madin darby canine kidney cell monolayers.

    Mathias Kaiser / Luisa Pohl / Steffi Ketelhut / Lena Kastl / Christian Gorzelanny / Martin Götte / Jürgen Schnekenburger / Francisco M Goycoolea / Björn Kemper

    PLoS ONE, Vol 12, Iss 11, p e

    2017  Volume 0187497

    Abstract: We have developed a drug delivery nanosystem based on chitosan and capsaicin. Both substances have a wide range of biological activities. We investigated the nanosystem's influence on migration and morphology of Madin Darby canine kidney (MDCK-C7) ... ...

    Abstract We have developed a drug delivery nanosystem based on chitosan and capsaicin. Both substances have a wide range of biological activities. We investigated the nanosystem's influence on migration and morphology of Madin Darby canine kidney (MDCK-C7) epithelial cells in comparison to the capsaicin-free nanoformulation, free capsaicin, and control cells. For minimally-invasive quantification of cell migration, we applied label-free digital holographic microscopy (DHM) and single-cell tracking. Moreover, quantitative DHM phase images were used as novel stain-free assay to quantify the temporal course of global cellular morphology changes in confluent cell layers. Cytoskeleton alterations and tight junction protein redistributions were complementary analyzed by fluorescence microscopy. Calcium influx measurements were conducted to characterize the influence of the nanoformulations and capsaicin on ion channel activities. We found that both, capsaicin-loaded and unloaded chitosan nanocapsules, and also free capsaicin, have a significant impact on directed cell migration and cellular motility. Increase of velocity and directionality of cell migration correlates with changes in the cell layer surface roughness, tight junction integrity and cytoskeleton alterations. Calcium influx into cells occurred only after nanoformulation treatment but not upon addition of free capsaicin. Our results pave the way for further studies on the biological significance of these findings and potential biomedical applications, e.g. as drug and gene carriers.
    Keywords Medicine ; R ; Science ; Q
    Subject code 500
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Quantitative stain-free and continuous multimodal monitoring of wound healing in vitro with digital holographic microscopy.

    Dominik Bettenworth / Philipp Lenz / Philipp Krausewitz / Markus Brückner / Steffi Ketelhut / Dirk Domagk / Björn Kemper

    PLoS ONE, Vol 9, Iss 9, p e

    2014  Volume 107317

    Abstract: Impaired epithelial wound healing has significant pathophysiological implications in several conditions including gastrointestinal ulcers, anastomotic leakage and venous or diabetic skin ulcers. Promising drug candidates for accelerating wound closure ... ...

    Abstract Impaired epithelial wound healing has significant pathophysiological implications in several conditions including gastrointestinal ulcers, anastomotic leakage and venous or diabetic skin ulcers. Promising drug candidates for accelerating wound closure are commonly evaluated in in vitro wound assays. However, staining procedures and discontinuous monitoring are major drawbacks hampering accurate assessment of wound assays. We therefore investigated digital holographic microscopy (DHM) to appropriately monitor wound healing in vitro and secondly, to provide multimodal quantitative information on morphological and functional cell alterations as well as on motility changes upon cytokine stimulation. Wound closure as reflected by proliferation and migration of Caco-2 cells in wound healing assays was studied and assessed in time-lapse series for 40 h in the presence of stimulating epidermal growth factor (EGF) and inhibiting mitomycin c. Therefore, digital holograms were recorded continuously every thirty minutes. Morphological changes including cell thickness, dry mass and tissue density were analyzed by data from quantitative digital holographic phase microscopy. Stimulation of Caco-2 cells with EGF or mitomycin c resulted in significant morphological changes during wound healing compared to control cells. In conclusion, DHM allows accurate, stain-free and continuous multimodal quantitative monitoring of wound healing in vitro and could be a promising new technique for assessment of wound healing.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: A multifunctional organosilica cross-linker for the bio-conjugation of gold nanorods

    Lai, Sarah / Bjӧrn Kemper / Claudia Borri / Filippo Micheletti / Francesca Rossi / Fulvio Ratto / Leonardo Gonnelli / Lucia Cavigli / Roberto Pini / Sonia Centi / Stefano Colagrande / Steffi Ketelhut / Tatiana Kozyreva

    Colloids and surfaces. 2017 Sept. 01, v. 157

    2017  

    Abstract: We report on the use of organosilica shells to couple gold nanorods to functional peptides and modulate their physiochemical and biological profiles. In particular, we focus on the case of cell penetrating peptides, which are used to load tumor-tropic ... ...

    Abstract We report on the use of organosilica shells to couple gold nanorods to functional peptides and modulate their physiochemical and biological profiles. In particular, we focus on the case of cell penetrating peptides, which are used to load tumor-tropic macrophages and implement an innovative drug delivery system for photothermal and photoacoustic applications. The presence of organosilica exerts subtle effects on multiple parameters of the particles, including their size, shape, electrokinetic potential, photostability, kinetics of endocytic uptake and cytotoxicity, which are investigated by the interplay of colorimetric methods and digital holographic microscopy. As a rule of thumb, as the thickness of organosilica increases from none to ∼30nm, we find an improvement of the photophysical performances at the expense of a deterioration of the biological parameters. Therefore, detailed engineering of the particles for a certain application will require a careful trade-off between photophysical and biological specifications.
    Keywords colloids ; colorimetry ; cytotoxicity ; drug delivery systems ; engineering ; gold ; macrophages ; microscopy ; nanorods ; peptides ; photostability ; zeta potential
    Language English
    Dates of publication 2017-0901
    Size p. 174-181.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 1500523-9
    ISSN 1873-4367 ; 0927-7765
    ISSN (online) 1873-4367
    ISSN 0927-7765
    DOI 10.1016/j.colsurfb.2017.05.068
    Database NAL-Catalogue (AGRICOLA)

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