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Publications (10 of 45) 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
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
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
Scherbak, N. N., Kruse, R., Nyström, T. & Jendle, J. (2023). Glimepiride Compared to Liraglutide Increases Plasma Levels of miR-206, miR-182-5p, and miR-766-3p in Type 2 Diabetes Mellitus: A Randomized Controlled Trial. Diabetes & metabolism journal, 47(5), 668-681
Open this publication in new window or tab >>Glimepiride Compared to Liraglutide Increases Plasma Levels of miR-206, miR-182-5p, and miR-766-3p in Type 2 Diabetes Mellitus: A Randomized Controlled Trial
2023 (English)In: Diabetes & metabolism journal, ISSN 2233-6079, E-ISSN 2233-6087, Vol. 47, no 5, p. 668-681Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Diabetes is a chronic disease with several long-term complications. Several glucose-lowering drugs are used to treat type 2 diabetes mellitus (T2DM), e.g., glimepiride and liraglutide, in which both having different modes of action. Circulating microRNAs (miRNAs) are suggested as potential biomarkers that are associated with the disease development and the effects of the treatment. In the current study we evaluated the effect of glimepiride, liraglutide on the expression of the circulating miRNAs.

METHODS: The present study is a post hoc trial from a previously randomized control trial comparing liraglutide versus glimepiride both in combination with metformin in subjects with T2DM, and subclinical heart failure. miRNAs were determined in the subjects' serum samples with next generation sequencing. Expression patterns of the circulating miRNAs were analyzed using bioinformatic univariate and multivariate analyses (clinical trial registration: NCT01425580).

RESULTS: Univariate analyses show that treatment with glimepiride altered expression of three miRNAs in patient serum, miR-206, miR-182-5p, and miR-766-3p. Both miR-182-5p and miR-766-3p were also picked up among the top contributing miRNAs with penalized regularised logistic regressions (Lasso). The highest-ranked miRNAs with respect to Lasso coefficients were miR-3960, miR-31-5p, miR-3613-3p, and miR-378a-3p. Liraglutide treatment did not significantly influence levels of circulating miRNAs.

CONCLUSION: Present study indicates that glucose-lowering drugs differently affect the expression of circulating miRNAs in serum in individuals with T2DM. More studies are required to investigate possible mechanisms by which glimepiride is affecting the expression of circulating miRNAs.

Place, publisher, year, edition, pages
Korean Diabetes Association, 2023
Keywords
Circulating microRNA, Diabetes mellitus, type 2, Glimepiride, Liraglutide
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:oru:diva-106587 (URN)10.4093/dmj.2022.0342 (DOI)001151423000006 ()37349083 (PubMedID)2-s2.0-85174408868 (Scopus ID)
Funder
Novo Nordisk
Available from: 2023-06-27 Created: 2023-06-27 Last updated: 2024-02-14Bibliographically approved
Scherbak, N., Kruse, R., Nyström, T. & Jendle, J. (2023). Glimepiride Compared to Liraglutide Increases Plasma Levels of miR-206, miR-182-5p, and miR-766-3p in Type 2 Diabetes Mellitus: A Randomized Controlled Trial (Diabetes Metab J 2023;47:668-81) [Letter to the editor]. Diabetes & metabolism journal, 47(6), 882-883
Open this publication in new window or tab >>Glimepiride Compared to Liraglutide Increases Plasma Levels of miR-206, miR-182-5p, and miR-766-3p in Type 2 Diabetes Mellitus: A Randomized Controlled Trial (Diabetes Metab J 2023;47:668-81)
2023 (English)In: Diabetes & metabolism journal, ISSN 2233-6079, E-ISSN 2233-6087, Vol. 47, no 6, p. 882-883Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Korean Diabetes Association, 2023
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:oru:diva-110010 (URN)10.4093/dmj.2023.0355 (DOI)38043784 (PubMedID)2-s2.0-85178650647 (Scopus ID)
Available from: 2023-12-04 Created: 2023-12-04 Last updated: 2024-02-06Bibliographically 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
Tuerxun, K., Eklund, D., Wallgren, U., Dannenberg, K., Repsilber, D., Kruse, R., . . . Kurland, L. (2023). Predicting sepsis using a combination of clinical information and molecular immune markers sampled in the ambulance. Scientific Reports, 13(1), Article ID 14917.
Open this publication in new window or tab >>Predicting sepsis using a combination of clinical information and molecular immune markers sampled in the ambulance
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2023 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 14917Article in journal (Refereed) Published
Abstract [en]

Sepsis is a time dependent condition. Screening tools based on clinical parameters have been shown to increase the identification of sepsis. The aim of current study was to evaluate the additional predictive value of immunological molecular markers to our previously developed prehospital screening tools. This is a prospective cohort study of 551 adult patients with suspected infection in the ambulance setting of Stockholm, Sweden between 2017 and 2018. Initially, 74 molecules and 15 genes related to inflammation were evaluated in a screening cohort of 46 patients with outcome sepsis and 50 patients with outcome infection no sepsis. Next, 12 selected molecules, as potentially synergistic predictors, were evaluated in combination with our previously developed screening tools based on clinical parameters in a prediction cohort (n = 455). Seven different algorithms with nested cross-validation were used in the machine learning of the prediction models. Model performances were compared using posterior distributions of average area under the receiver operating characteristic (ROC) curve (AUC) and difference in AUCs. Model variable importance was assessed by permutation of variable values, scoring loss of classification as metric and with model-specific weights when applicable. When comparing the screening tools with and without added molecular variables, and their interactions, the molecules per se did not increase the predictive values. Prediction models based on the molecular variables alone showed a performance in terms of AUCs between 0.65 and 0.70. Among the molecular variables, IL-1Ra, IL-17A, CCL19, CX3CL1 and TNF were significantly higher in septic patients compared to the infection non-sepsis group. Combing immunological molecular markers with clinical parameters did not increase the predictive values of the screening tools, most likely due to the high multicollinearity of temperature and some of the markers. A group of sepsis patients was consistently miss-classified in our prediction models, due to milder symptoms as well as lower expression levels of the investigated immune mediators. This indicates a need of stratifying septic patients with a priori knowledge of certain clinical and molecular parameters in order to improve prediction for early sepsis diagnosis.Trial registration: NCT03249597. Registered 15 August 2017.

Place, publisher, year, edition, pages
Nature Portfolio, 2023
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-108188 (URN)10.1038/s41598-023-42081-6 (DOI)001066443900002 ()37691028 (PubMedID)2-s2.0-85170487168 (Scopus ID)
Funder
Örebro UniversityNyckelfondenLaerdal Foundation for Acute MedicineKnowledge Foundation, 20160044 20200017
Note

This study was supported by grants from Nyckelfonden, Laerdal, Falck Foundation, Knowledge Foundation (20160044, 20200017), the Emergency Department of Södersjukhuset, Stockholm, and Örebro University.

Available from: 2023-09-11 Created: 2023-09-11 Last updated: 2024-01-16Bibliographically approved
Chelslín, F., Lodefalk, M. & Kruse, R. (2023). Smoking during pregnancy is associated with the placental proteome. Reproductive Toxicology, 119, Article ID 108409.
Open this publication in new window or tab >>Smoking during pregnancy is associated with the placental proteome
2023 (English)In: Reproductive Toxicology, ISSN 0890-6238, E-ISSN 1873-1708, Vol. 119, article id 108409Article in journal (Refereed) Published
Abstract [en]

Maternal smoking during pregnancy (MSDP) is a significant risk factor for the development of foetal, neonatal, and childhood morbidities. We hypothesized that infants exposed to MSDP have a distinct proteomic expression in their term placentas compared to infants without such an exposure. A total of 39 infants exposed (cord blood cotinine levels of >1ng/ml) and 44 infants not exposed to MSDP were included in the study. Women with chronic disease, body mass index of >30, or a history of uterine surgery were excluded. Total proteome abundance was analysed with quantitative mass spectrometry. For univariate analysis of differences in placental protein levels between groups, ANOVA with multiple testing corrections by the Benjamini-Hochberg method was used. For multivariate analysis, we used principal component analysis, partial least squares, lasso, random forest, and neural networks. The univariate analyses showed four differentially abundant proteins (PXDN, CYP1A1, GPR183, and KRT81) when heavy and moderate smoking groups were compared to non-smokers. With the help of machine learning, we found that an additional six proteins (SEPTIN3, CRAT, NAAA, CD248, CADM3, and ZNF648) were discriminants of MSDP. The placental abundance of these ten proteins together explained 74.1% of the variation in cord blood cotinine levels (p = 0.002). Infants exposed to MSDP showed differential abundance of proteins in term placentas. We report differential placental abundance of several proteins for the first time in the setting of MSDP. We believe that these findings supplement the current understanding of how MSDP affects the placental proteome.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
CYP1A1, PXDN, Placenta, infant, newborn, protein, proteome, smoking
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-105985 (URN)10.1016/j.reprotox.2023.108409 (DOI)001008803600001 ()37209868 (PubMedID)2-s2.0-85161640987 (Scopus ID)
Funder
Nyckelfonden, OLL-886631Region Örebro County, OLL-766591 OLL-878121 OLL-840481
Available from: 2023-05-22 Created: 2023-05-22 Last updated: 2023-07-27Bibliographically approved
Tuerxun, K., Midtbö, K., Särndahl, E., Vorontsov, E., Karlsson, R., Persson, A., . . . Eklund, D. (2022). Cytokine responses to LPS in reprogrammed monocytes are associated with the transcription factor PU.1. Journal of Leukocyte Biology, 112(4), 679-692
Open this publication in new window or tab >>Cytokine responses to LPS in reprogrammed monocytes are associated with the transcription factor PU.1
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2022 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 112, no 4, p. 679-692Article in journal (Refereed) Published
Abstract [en]

Myeloid-derived suppressor cells (MDSCs) are functionally immunosuppressive cellsthat arise and expand during extensive inflammatory conditions by increasedhematopoietic output or reprogramming of immune cells. In sepsis, an increase of circulatingMDSCs is associated with adverse outcomes, but unique traits that can beused to identify increased activity of MDSCs are lacking. By using endotoxin toleranceas a model of sepsis-induced monocytic MDSCs (M-MDSC-like cells), this studyaims to identify the mediator and transcriptional regulator profile associated with MMDSCactivity. After analyzing 180 inflammation-associated proteins, a profile of differentiallyexpressed cytokines was found in M-MDSC-like cells versus normal monocytesstimulated with LPS. These cytokines were associated with 5 candidate transcriptionfactors,where particularly PU.1 showed differential expression on both transcriptionaland protein levels in M-MDSC-like cells. Furthermore, inhibition of PU.1led to increased production of CXCL5 and CCL8 in M-MDSC-like cells indicating itsrole in regulating the ability ofM-MDSC-like cells to recruit other immune cells. Takentogether, the study identifies a unique profile in the pattern of immune mediatorsdefining M-MDSC activity upon LPS stimulation, which offers a functional link to theircontribution to immunosuppression.

Place, publisher, year, edition, pages
Alan R. Liss Inc., 2022
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:oru:diva-102632 (URN)10.1002/jlb.3a0421-216r (DOI)000771127800001 ()35285058 (PubMedID)2-s2.0-85126116287 (Scopus ID)
Funder
Magnus Bergvall FoundationBertil and Ebon Norlin Foundation for Medical Research
Note

Funding Agency:

General Electric

Available from: 2022-12-09 Created: 2022-12-09 Last updated: 2022-12-12
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