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Publications (10 of 145) Show all publications
Mathisen, C.-W. B., Nyström, N., Bazov, I., Andersen, S., Olbjørn, C., Perminow, G., . . . Halfvarson, J. (2023). A novel diagnostic serum protein signature for paediatric Inflammatory Bowel Disease: A discovery and validation study in two independent inception cohorts. Paper presented at 8th Congress of ECCO Copenhagen, Denmark, March 1-4, 2023. Journal of Crohn's & Colitis, 17(Suppl. 1), I71-I73, Article ID DOP11.
Open this publication in new window or tab >>A novel diagnostic serum protein signature for paediatric Inflammatory Bowel Disease: A discovery and validation study in two independent inception cohorts
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2023 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no Suppl. 1, p. I71-I73, article id DOP11Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2023
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-107213 (URN)000960367600052 ()
Conference
8th Congress of ECCO Copenhagen, Denmark, March 1-4, 2023
Available from: 2023-07-31 Created: 2023-07-31 Last updated: 2023-07-31Bibliographically approved
Alijagic, A., Scherbak, N., Kotlyar, O., Karlsson, P., Wang, X., Odnevall, I., . . . Engwall, M. (2023). A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles. Cells, 12(2), Article ID 281.
Open this publication in new window or tab >>A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles
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2023 (English)In: Cells, E-ISSN 2073-4409, Vol. 12, no 2, article id 281Article in journal (Refereed) Published
Abstract [en]

Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.

Place, publisher, year, edition, pages
MDPI, 2023
Keywords
Additive manufacturing, high-content screening (HCS), inflammation, multivariate analysis, nanoparticle emissions, new approach methodologies (NAMs), targeted metabolomics
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:oru:diva-103319 (URN)10.3390/cells12020281 (DOI)000916977400001 ()36672217 (PubMedID)2-s2.0-85146736511 (Scopus ID)
Note

Funding agency:

General Electric 20190107 20160019

Available from: 2023-01-23 Created: 2023-01-23 Last updated: 2023-02-14Bibliographically approved
Bazov, I., Kruse, R., Bergemalm, D., Eriksson, C., Hedin, C. R., Carlson, M., . . . Halfvarson, J. (2023). A novel serum protein signature as biomarker for Inflammatory Bowel Disease: A diagnostic performance and prediction modelling study using data from two independent inception cohorts. Paper presented at 18th Congress of ECCO Copenhagen, Denmark, March 1-4, 2023. Journal of Crohn's & Colitis, 17(Suppl. 1), I314-I315, Article ID P154.
Open this publication in new window or tab >>A novel serum protein signature as biomarker for Inflammatory Bowel Disease: A diagnostic performance and prediction modelling study using data from two independent inception cohorts
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2023 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no Suppl. 1, p. I314-I315, article id P154Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2023
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-107219 (URN)000960367600284 ()
Conference
18th Congress of ECCO Copenhagen, Denmark, March 1-4, 2023
Available from: 2023-07-31 Created: 2023-07-31 Last updated: 2024-01-02Bibliographically approved
Zhang, X., Li, M., Ye, S., Shen, K., Yuan, H., Bakhtyar, S., . . . Sun, X.-F. (2023). CBD2: A functional biomarker database for colorectal cancer. iMeta
Open this publication in new window or tab >>CBD2: A functional biomarker database for colorectal cancer
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2023 (English)In: iMeta, ISSN 2770-5986Article in journal (Refereed) Epub ahead of print
Abstract [en]

The rapidly evolving landscape of biomarkers for colorectal cancer (CRC) necessitates an integrative, updated repository. In response, we constructed the Colorectal Cancer Biomarker Database (CBD), which collected and displayed the curated biomedicine information for 870 CRC biomarkers in the previous study. Building on CBD, we have now developed CBD2, which includes information on 1569 newly reported biomarkers derived from different biological sources (DNA, RNA, protein, and others) and clinical applications (diagnosis, treatment, and prognosis). CBD2 also incorporates information on nonbiomarkers that have been identified as unsuitable for use as biomarkers in CRC. A key new feature of CBD2 is its network analysis function, by which users can investigate the visible and topological network between biomarkers and identify their relevant pathways. CBD2 also allows users to query a series of chemicals, drug combinations, or multiple targets, to enable multidrug, multitarget, multipathway analyses, toward facilitating the design of polypharmacological treatments for CRC. CBD2 is freely available at http://www.eyeseeworld.com/cbd.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
biomarker, colorectal cancer, database, network analysis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-110211 (URN)10.1002/imt2.155 (DOI)001112778000001 ()2-s2.0-85178410575 (Scopus ID)
Note

This work was supported by the National Natural Science Foundation of China (Grant numbers: 32200545 and 32271292), and the GDPH Supporting Fund for Talent Program (Grant numbers: KJ012020633 and KJ012019530) from Guangdong Provincial People's Hospital. This work was also supported by the Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (Grant number: 2022B121 2010011).

Available from: 2023-12-13 Created: 2023-12-13 Last updated: 2024-01-10Bibliographically approved
Lundström, M. L., Peterson, C., Lampinen, M., Hedin, C. R. H., Keita, Å. V., Kruse, R., . . . Carlson, M. (2023). Faecal biomarkers of neutrophil and eosinophil origin reflect the response to biological therapy and corticosteroids in patients with IBD. Clinical and Translational Gastroenterology, 14(8), Article ID e00605.
Open this publication in new window or tab >>Faecal biomarkers of neutrophil and eosinophil origin reflect the response to biological therapy and corticosteroids in patients with IBD
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2023 (English)In: Clinical and Translational Gastroenterology, E-ISSN 2155-384X, Vol. 14, no 8, article id e00605Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Faecal calprotectin (FC) is a non-invasive tool for examining response to biologics in inflammatory bowel disease (IBD), but its performance in relation to other novel faecal markers of various cellular origins is unknown.

METHODS: We performed a prospective multicentre cohort study and included patients with active IBD who provided a faecal sample at initiation of biological therapy. Levels of FC, myeloperoxidase (MPO), human neutrophil lipocalin (HNL), and eosinophil-derived neurotoxin (EDN) were analysed and related to clinical remission status at 3 months. Changes in levels of markers at 3 months were calculated and the impact of concomitant use of corticosteroids at baseline was estimated.

RESULTS: In patients achieving clinical remission (n=27), a decrease in levels of FC (p=0.005), MPO (p<0.001), HNL (p<0.001) and EDN (p<0.001) was observed, whereas no significant decrease was seen in patients not achieving remission (n=39). There was a significant difference in the change in the level of MPO (p=0.01) and HNL (p=0.02) between patients achieving clinical remission compared with those who did not, but changes in FC and EDN could not differentiate between these groups. Patients with concomitant systemic corticosteroids at inclusion had lower levels of HNL (p=0.01) and EDN (p<0.001) at baseline, compared with patients without corticosteroids.

CONCLUSION: Faecal MPO, HNL, and EDN are all promising biomarkers for assessing the treatment outcome of biologics in patients with IBD. Faecal levels of EDN and HNL are significantly affected by corticosteroids indicating a greater sensitivity to the effects of corticosteroids compared with FC and MPO.

Place, publisher, year, edition, pages
Nature Publishing Group, 2023
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-106121 (URN)10.14309/ctg.0000000000000605 (DOI)37256716 (PubMedID)2-s2.0-85169188411 (Scopus ID)
Available from: 2023-06-01 Created: 2023-06-01 Last updated: 2023-09-06Bibliographically approved
Salihovic, S., Nyström, N., Mathisen, C.-W. B., Andersen, S., Olbjørn, C., Perminow, G., . . . Halfvarson, J. (2023). Identification and validation of a lipidomic signature as a novel diagnostic biomarker of paediatric Inflammatory Bowel Disease. Journal of Crohn's & Colitis, 17(Suppl. 1), I76-I77, Article ID DOP14.
Open this publication in new window or tab >>Identification and validation of a lipidomic signature as a novel diagnostic biomarker of paediatric Inflammatory Bowel Disease
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2023 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no Suppl. 1, p. I76-I77, article id DOP14Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2023
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-107222 (URN)000960367600055 ()
Available from: 2023-07-31 Created: 2023-07-31 Last updated: 2023-07-31Bibliographically approved
Nikaein, N., Tuerxun, K., Cedersund, G., Eklund, D., Kruse, R., Särndahl, E., . . . Nyman, E. (2023). Mathematical models disentangle the role of IL-10 feedbacks in human monocytes upon proinflammatory activation. Journal of Biological Chemistry, 299(10), Article ID 105205.
Open this publication in new window or tab >>Mathematical models disentangle the role of IL-10 feedbacks in human monocytes upon proinflammatory activation
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2023 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 299, no 10, article id 105205Article in journal (Refereed) Published
Abstract [en]

Inflammation is one of the vital mechanisms through which the immune system responds to harmful stimuli. During inflammation, pro and anti-inflammatory cytokines interplay to orchestrate fine-tuned, dynamic immune responses. The cytokine interplay governs switches in the inflammatory response and dictates the propagation and development of the inflammatory response. Molecular pathways underlying the interplay are complex, and time-resolved monitoring of mediators and cytokines is necessary as a basis to study them in detail. Our understanding can be advanced by mathematical models which enable to analyze the system of interactions and their dynamical interplay in detail. We, therefore, used a mathematical modeling approach to study the interplay between prominent pro and anti-inflammatory cytokines with a focus on tumor necrosis factor (TNF) and interleukin 10 (IL-10) in lipopolysaccharide (LPS)-primed primary human monocytes. Relevant time-resolved data were generated by experimentally adding or blocking IL-10 at different time points. The model was successfully trained and could predict independent validation data and was further used to perform simulations to disentangle the role of IL-10 feedbacks during an acute inflammatory event. We used the insight to obtain a reduced predictive model including only the necessary IL-10-mediated feedbacks. Finally, the validated reduced model was used to predict early IL-10 - TNF switches in the inflammatory response. Overall, we gained detailed insights into fine-tuning of inflammatory responses in human monocytes and present a model for further use in studying the complex and dynamic process of cytokine-regulated acute inflammation.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
NF‐kappa B (NF‐κB), computational biology, computer modeling, cytokine, endotoxin, human monocytes, inflammation, interleukin 10 (IL-10), lipopolysaccharide (LPS), mathematical modeling, ordinary differential equations (ODE), signal transduction, systems biology, tumor necrosis factor (TNF)
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:oru:diva-108034 (URN)10.1016/j.jbc.2023.105205 (DOI)37660912 (PubMedID)2-s2.0-85172191670 (Scopus ID)
Available from: 2023-09-04 Created: 2023-09-04 Last updated: 2023-10-26Bibliographically approved
Bachmann, R., Van Hul, M., Baldin, P., Léonard, D., Delzenne, N. M., Belzer, C., . . . Cani, P. D. (2022). Akkermansia muciniphila Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism. Cells, 11(17), Article ID 2666.
Open this publication in new window or tab >>Akkermansia muciniphila Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism
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2022 (English)In: Cells, E-ISSN 2073-4409, Vol. 11, no 17, article id 2666Article in journal (Refereed) Published
Abstract [en]

Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. Akkermansia muciniphila has shown beneficial effects on the gut barrier function. Whether A. muciniphila reduces peritonitis and mortality during colonic leakage is unknown. Whether A. muciniphila can directly modulate the expression of genes in the colonic mucosa in humans has never been studied. We investigated the effects of a pretreatment (14 days) with live A. muciniphila prior to surgical colonic perforation on peritonitis, mortality, and wound healing. We used mice with an inducible intestinal-epithelial-cell-specific deletion of MyD88 (IEC-MyD88 KO) to investigate the role of the innate immune system in this context. In a proof-of-concept pilot study, healthy humans were exposed to A. muciniphila for 2 h and colonic biopsies taken before and after colonic instillation for transcriptomic analysis. Seven days after colonic perforation, A.-muciniphila-treated mice had significantly lower mortality and severity of peritonitis. This effect was associated with significant improvements of wound histological healing scores, higher production of IL22, but no changes in the mucus layer thickness or genes involved in cell renewal, proliferation, or differentiation. All these effects were abolished in IEC-MyD88 KO mice. Finally, human subjects exposed to A. muciniphila exhibited an increased level of the bacterium at the mucus level 2 h after instillation and significant changes in the expression of different genes involved in the regulation of cell cycling, gene transcription, immunity, and inflammation in their colonic mucosa. A. muciniphila improves wound healing during transmural colonic wall defect through mechanisms possibly involving IL22 signaling and requiring MyD88 in the intestinal cells. In healthy humans, colonic administration of A. muciniphila is well tolerated and changes the expression of genes involved in the immune pathways.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
Akkermansia muciniphila, Myd88, colonic leakage, peritonitis, wound healing
National Category
Immunology
Identifiers
urn:nbn:se:oru:diva-101170 (URN)10.3390/cells11172666 (DOI)000851017500001 ()36078075 (PubMedID)2-s2.0-85137845423 (Scopus ID)
Note

Funding agencies:

Fonds de la Recherche Scientifique - FNRS FNRS T.0030.21 J.0027.22 WELBIO-CR-2022A-02 WELBIO-CR-2019C-02R 30770923 40007505  

Netherlands Organization for Scientific Research (NWO) 024.002.002

Available from: 2022-09-12 Created: 2022-09-12 Last updated: 2023-12-08Bibliographically approved
Moraes Holst, L., Halfvarson, J., Carlson, M., Hedin, C., Kruse, R., Lindqvist, C. M., . . . Öhman, L. (2022). Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis. Clinical and Experimental Gastroenterology, 15, 129-144
Open this publication in new window or tab >>Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis
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2022 (English)In: Clinical and Experimental Gastroenterology, E-ISSN 1178-7023, Vol. 15, p. 129-144Article in journal (Refereed) Published
Abstract [en]

Background: Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohn's disease (CD active).

Methods: Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways.

Results: The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed.

Conclusion: This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares.

Keywords
Gene expression, homeostasis, host response, inflammatory bowel diseases, mucosal transcriptome
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-100605 (URN)10.2147/CEG.S368040 (DOI)000834352200001 ()35928254 (PubMedID)2-s2.0-85134839391 (Scopus ID)
Funder
Swedish Foundation for Strategic ResearchWilhelm och Martina Lundgrens Vetenskapsfond
Note

Funding Agencies:

Julins Foundation

Bengt Ihre Fellowship

Magtarmfonden

Available from: 2022-08-18 Created: 2022-08-18 Last updated: 2024-01-09Bibliographically approved
Parodis, I., Lindblom, J., Toro-Dominguez, D., Borghi, M. O., Enman, Y., Repsilber, D., . . . Barturen, G. (2022). DRUG REPURPOSING FOR TREATING LUPUS NEPHRITIS BASED ON TRANSCRIPTOME PROFILING AND AUTOIMMUNITY-RELATED SEROLOGICAL MARKERS. Paper presented at European Congress of Rheumatology (EULAR 2022), Copenhagen, Denmark, June 1-4, 2022. Annals of the Rheumatic Diseases, 81(Suppl. 1), 326-326, Article ID POS0187.
Open this publication in new window or tab >>DRUG REPURPOSING FOR TREATING LUPUS NEPHRITIS BASED ON TRANSCRIPTOME PROFILING AND AUTOIMMUNITY-RELATED SEROLOGICAL MARKERS
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2022 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 81, no Suppl. 1, p. 326-326, article id POS0187Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
HighWire Press, 2022
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:oru:diva-102034 (URN)10.1136/annrheumdis-2022-eular.5348 (DOI)000850279001126 ()
Conference
European Congress of Rheumatology (EULAR 2022), Copenhagen, Denmark, June 1-4, 2022
Available from: 2022-11-08 Created: 2022-11-08 Last updated: 2022-11-08Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-7173-5579

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