| 1. |
- Casado-Bedmar, Maite, et al.
(författare)
-
Elevated F-EDN correlates with mucosal eosinophil degranulation in patients with IBS : A possible association with microbiota?
- 2022
-
Ingår i: Journal of Leukocyte Biology. - : Alan R. Liss Inc.. - 0741-5400 .- 1938-3673. ; 111:3, s. 655-665
-
Tidskriftsartikel (refereegranskat)abstract
- Eosinophils have been linked to functional dyspepsia; however, less is known about their role in irritable bowel syndrome (IBS). This study tested the hypothesis of alterations in levels of fecal eosinophil-derived neurotoxin (F-EDN) and eosinophil density and degranulation within the colonic mucosa of IBS patients compared with healthy controls (HC). Colonic biopsies were collected from 37 IBS patients and 20 HC and analyzed for eosinophil numbers and local degranulation of eosinophil cationic protein (ECP) by histologic procedures. Fecal samples were collected for F-EDN and microbiota analysis. Differentiated 15HL-60 cells were used in vitro to investigate the direct effect of live bacteria on eosinophil activation measured by a colorimetric assay with o-phenylenediamine (OPD) substrate. We observed a higher number of eosinophils and increased extracellular ECP in the mucosa of IBS patients compared with HC. Moreover, F-EDN levels in IBS samples were elevated compared with HC and positively correlated to extracellular ECP. Metagenomic analysis showed significant correlations between bacterial composition and eosinophil measurements in both HC and IBS patients. In vitro experiments revealed an increased degranulation of 15HL-60 after stimulation with Salmonella typhimurium, Salmonella enterica, and Yersinia enterocolitica. To conclude, we could demonstrate alterations related to eosinophils in IBS, and, for the first time, a positive correlation between F-EDN levels and degranulated eosinophils in the colonic mucosa of IBS patients. Together our results suggest that eosinophils play a role in the pathophysiology of IBS and the mechanisms might be linked to an altered microbiota.
|
|
| 2. |
- Ling Lundström, Maria, et al.
(författare)
-
Faecal biomarkers for diagnosis and prediction of disease course in treatment-naïve patients with IBD.
- 2024
-
Ingår i: Alimentary Pharmacology and Therapeutics. - 0269-2813 .- 1365-2036.
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Faecal biomarkers can be used to assess inflammatory bowel disease (IBD).AIM: To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD.METHODS: We included 65 patients with treatment-naïve, new-onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil-derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression.RESULTS: All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79-0.89) and MPO (AUC 0.85, 95% CI: 0.80-0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006).CONCLUSIONS: This study provides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers.
|
|
| 3. |
- Ling Lundström, Maria, et al.
(författare)
-
Faecal biomarkers for diagnosis and prediction of disease course in treatment-naïve patients with IBD
- 2024
-
Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Faecal biomarkers can be used to assess inflammatory bowel disease (IBD).Aim: To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD.Methods: We included 65 patients with treatment-na & iuml;ve, new-onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil-derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression.Results: All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79-0.89) and MPO (AUC 0.85, 95% CI: 0.80-0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006).Conclusions: This study provides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers.
|
|
| 4. |
- Ling Lundström, Maria, et al.
(författare)
-
Fecal Biomarkers of Neutrophil and Eosinophil Origin Reflect the Response to Biological Therapy and Corticosteroids in Patients With Inflammatory Bowel Disease
- 2023
-
Ingår i: Clinical and Translational Gastroenterology. - : Nature Publishing Group. - 2155-384X. ; 14:8
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Fecal calprotectin (FC) is anoninvasive tool for examining response to biologics in inflammatory boweldisease (IBD), but its performance in relation to other novel fecal markers of various cellular origins is unknown.Methods: We performed a prospective multicenter cohort study and included patients with active IBD who provided a fecal sample at initiation of biological therapy. Levels of FC, myeloperoxidase (MPO), human neutrophil lipocalin (HNL), and eosinophil-derived neurotoxin (EDN) were analyzed 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 and 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.Discussion: Fecal MPO, HNL, and EDN are all promising biomarkers for assessing the treatment outcome of biologics in patients with IBD. Fecal levels of EDN and HNL are significantly affected by corticosteroids indicating a greater sensitivity to the effects of corticosteroids compared with levels of FC and MPO.
|
|
| 5. |
- Peterson, Lauri, 1989-
(författare)
-
Investigating the Determinants of International, National and Local Climate Policies
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Climate change is a global threat that requires policy action on all levels of governance. The 2015 Paris Agreement opened a new era of governance, entailing a shift away from the top-down approach embodied by the 1997 Kyoto Protocol. It relies instead mainly on voluntary climate pledges, which are meant to be ratcheted up through a process of assessment and review. This allows international organizations and country and local governments much more flexibility in deciding their own level of climate ambition, as well as their own methods for achieving it. I identify some significant variations in policy-making that are not explained by the “usual suspects” of material capacities and organizational capabilities. In keeping with the multi-level nature of modern climate governance, I examine the determinants of climate policies on the international, national, and local levels. I do so with the help of quantitative methods applied to survey results from high-income and middle-income countries, and to data on political institutions and physical vulnerability. With this dissertation, I contribute to the literature by identifying a number of key determinants of climate mitigation policy on different levels of climate governance. First, in a study of international climate finance, I ascertain that different organizational arrangements in the bureaucratic area determine the selection of developing countries, as well as the amount of funding allocated to them by developed countries. Second, in a comparison of domestic and international climate policies, I establish that countries which have adopted more ambitious climate policies domestically are also more likely to furnish greater amounts of international climate finance. Third, in a review of national climate policies, I show that extreme weather events do not impel governments to increase climate action in countries without strong democratic institutions. Fourth, in an examination of local climate policies, I find that it is public awareness of human-caused climate change – not partisanship – that matters most for the adoption of comprehensive climate plans among frontrunner cities. These results shed light on the multi-level challenge of climate change by identifying distinct determinants of climate policy on each level of governance. This dissertation adds nuance to our understanding of the determinants of policies for climate change mitigation by stressing the importance of domestic actors and institutions for effective climate action.
|
|
| 6. |
- Venge, Per, et al.
(författare)
-
Estimation of numbers of mature and immature neutrophils in blood by a novel, rapid and simple technology
- 2021
-
Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 81:4, s. 307-311
-
Tidskriftsartikel (refereegranskat)abstract
- Counting numbers of blood neutrophils is one of the most common laboratory tests in modern clinical medicine. In this report, we have tested the idea that immunoassay of major constituents of mature neutrophils might serve as proxy of cell counting and allow the development of rapid and simple point-of-care tests. The procedure may also allow for the estimate of the state of maturity of the circulating blood cells. Immunoassays for myeloperoxidase (MPO) and lactoferrin (LF) were used to measure the respective protein in whole blood extracts of 275 unselected hospitalized patient and in 51 healthy controls and leukemia patients of which eight were followed before, during and after remission treatment. MPO was correlated to neutrophil counts in the unselected hospitalized population (r = 0.95, p <.0001). Huge variations were seen in whole blood extracts of patients with AML with very high MPO/LF ratios in half of the AML patients and in all three patients with APL. In extracts from patients with ALL no difference was found in the ratio as compared to healthy persons. The monitoring of AML patients during remission treatment showed intriguing patterns one of which suggested the possibility to monitor the myelopoietic activity in the bone marrow during the recovery phase. We show a novel and easy technology to count mature neutrophils in blood and also to monitor myeloid cell maturity in the blood as well as myelopoietic activity in the bone marrow. The technology lends itself to the development of a rapid and simple point-of-care test.
|
|
| 7. |
- Venge, Per, et al.
(författare)
-
Plasma Biomarkers Associated to Outcome in Patients with Sars-Cov-2 Infection
- 2024
-
Ingår i: Journal of Clinical and Laboratory Medicine. - : Sci Forschen, Inc.. - 2572-9578. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A serious consequence of respiratory infections with SARS-CoV-2 is Acute Kidney Injury (AKI). The aim of this study was to evaluate some novel biomarkers measured in plasma for their associations with the outcome of this infection as to AKI and mortality. Methods: Four different HNL (Human Neutrophil Lipocalin) assays were constructed using different antibody configurations, reflecting both neutrophil and epithelial cell activities. TK-1 (Thymidine kinase-1) was measured as a sign of cell destruction and proliferation. For comparison the plasma concentrations of NGAL (Neutrophil Gelatinase Associated Lipocalin), the cytokines IL-6, IL-8 and IFN-γ and of cystatin C, and procalcitonin were also measured. One hundred and three patients with severe respiratory failure admitted to the ICU were sampled for blood at admittance and at day three (n=67) after admittance. Results: Sixty-five percent of the patients developed AKI. The performance of the HNL assay 763/8F was most closely associated to outcome as to AKI and mortality with Area Under the Receiver Operating Characteristics Curve (AUC) of 0.87 and a sensitivity of 80% and a specificity of 88% in COVID-19 patients with and without severe AKI (p<0.0001). TK-1 was significantly related to the development of AKI (p=0.01) and the three cytokines were related to mortality (p=0.004-p<0.001). Conclusion: The HNL variant 763/8F and TK-1 are novel biomarkers that might become useful and novel tools in the management of COVID-19 patients, but likely also in other patients affected by AKI.
|
|
| 8. |
- Wang, Guangxia, et al.
(författare)
-
Specific fibroblast subpopulations and neuronal structures provide local sources of Vegfc-processing components during zebrafish lymphangiogenesis
- 2020
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Proteolytical processing of the growth factor VEGFC through the concerted activity of CCBE1 and ADAMTS3 is required for lymphatic development to occur. How these factors act together in time and space, and which cell types produce these factors is not understood. Here we assess the function of Adamts3 and the related protease Adamts14 during zebrafish lymphangiogenesis and show both proteins to be able to process Vegfc. Only the simultaneous loss of both protein functions results in lymphatic defects identical to vegfc loss-of-function situations. Cell transplantation experiments demonstrate neuronal structures and/or fibroblasts to constitute cellular sources not only for both proteases but also for Ccbe1 and Vegfc. We further show that this locally restricted Vegfc maturation is needed to trigger normal lymphatic sprouting and directional migration. Our data provide a single-cell resolution model for establishing secretion and processing hubs for Vegfc during developmental lymphangiogenesis.
|
|
