| 1. |
- Barman, Malin, 1983, et al.
(author)
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Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE): a prospective birth cohort in northern Sweden
- 2018
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In: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 8:10
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Journal article (peer-reviewed)abstract
- © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: Prenatal and neonatal environmental factors, such as nutrition, microbes and toxicants, may affect health throughout life. Many diseases, such as allergy and impaired child development, may be programmed already in utero or during early infancy. Birth cohorts are important tools to study associations between early life exposure and disease risk. Here, we describe the study protocol of the prospective birth cohort, 'Nutritional impact on Immunological maturation during Childhood in relation to the Environment' (NICE). The primary aim of the NICE cohort is to clarify the effect of key environmental exposures-diet, microbes and environmental toxicants-during pregnancy and early childhood, on the maturation of the infant's immune system, including initiation of sensitisation and allergy as well as some secondary outcomes: infant growth, obesity, neurological development and oral health.METHODS AND ANALYSIS: The NICE cohort will recruit about 650 families during mid-pregnancy. The principal inclusion criterion will be planned birth at the Sunderby Hospital in the north of Sweden, during 2015-2018. Questionnaires data and biological samples will be collected at 10 time-points, from pregnancy until the children reach 4 years of age. Samples will be collected primarily from mothers and children, and from fathers. Biological samples include blood, urine, placenta, breast milk, meconium, faeces, saliva and hair. Information regarding allergic heredity, diet, socioeconomic status, lifestyle including smoking, siblings, pet ownership, etc will be collected using questionnaires. Sensitisation to common allergens will be assessed by skin prick testing and allergic disease will be diagnosed by a paediatrician at 1 and 4 years of age. At 4 years of age, the children will also be examined regarding growth, neurobehavioural and neurophysiological status and oral health.ETHICS AND DISSEMINATION: The NICE cohort has been approved by the Regional Ethical Review Board in Umeå, Sweden (2013/18-31M). Results will be disseminated through peer-reviewed journals and communicated on scientific conferences.
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| 2. |
- Svensson, Mattias, 1982, et al.
(author)
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Fms-like tyrosine kinase 3 ligand controls formation of regulatory T cells in autoimmune arthritis.
- 2013
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
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Journal article (peer-reviewed)abstract
- Fms-like tyrosine kinase 3 ligand (Flt3L) is known as the primary differentiation and survival factor for dendritic cells (DCs). Furthermore, Flt3L is involved in the homeostatic feedback loop between DCs and regulatory T cell (Treg). We have previously shown that Flt3L accumulates in the synovial fluid in rheumatoid arthritis (RA) and that local exposure to Flt3L aggravates arthritis in mice, suggesting a possible involvement in RA pathogenesis. In the present study we investigated the role of Flt3L on DC populations, Tregs as well as inflammatory responses in experimental antigen-induced arthritis. Arthritis was induced in mBSA-immunized mice by local knee injection of mBSA and Flt3L was provided by daily intraperitoneal injections. Flow cytometry analysis of spleen and lymph nodes revealed an increased formation of DCs and subsequently Tregs in mice treated with Flt3L. Flt3L-treatment was also associated with a reduced production of mBSA specific antibodies and reduced levels of the pro-inflammatory cytokines IL-6 and TNF-α. Morphological evaluation of mBSA injected joints revealed reduced joint destruction in Flt3L treated mice. The role of DCs in mBSA arthritis was further challenged in an adoptive transfer experiment. Transfer of DCs in combination with T-cells from mBSA immunized mice, predisposed naïve recipients for arthritis and production of mBSA specific antibodies. We provide experimental evidence that Flt3L has potent immunoregulatory properties. Flt3L facilitates formation of Treg cells and by this mechanism reduces severity of antigen-induced arthritis in mice. We suggest that high systemic levels of Flt3L have potential to modulate autoreactivity and autoimmunity.
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| 3. |
- Andersson, Karin, 1972, et al.
(author)
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Down-regulation of survivin alleviates experimental arthritis.
- 2015
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In: Journal of leukocyte biology. - 1938-3673. ; 97:1, s. 135-45
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Journal article (peer-reviewed)abstract
- Survivin is a proto-oncogene that regulates cell division and apoptosis. It is a molecular marker of cancer. Recently, survivin has emerged as a feature of RA, associated with severe joint damage and poor treatment response. The present study examined if inhibition of survivin affects experimental arthritis, which was induced in mBSA-immunized mice by an injection of mBSA in the knee joint or developed spontaneously in collagen type II-immunized mice. The inhibition of survivin transcription by a lentivirus shRNA construct alleviated joint inflammation and reduced bone damage. The inhibition of survivin reduced the levels of metalloproteinases, β-catenin, and vimentin, limiting the invasive capacity of synovia, while no inhibition of osteoclastogenesis could be found. The inhibition of survivin led to a p53-independent reduction of T cell proliferation and favored the transcription and activity of Blimp-1, which limited IL-2 production and facilitated formation of regulatory Foxp3(+)CD4(+) and effector CD8(+) T cells. The study shows that the inhibition of survivin is sufficient to reduce joint inflammation and bone damage in preclinical models of arthritis. Antiarthritic effects of survivin inhibition are related to p53-independent control of lymphocyte proliferation.
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| 4. |
- Barman, Malin, 1983, et al.
(author)
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Exposure to a farm environment during pregnancy increases the proportion of arachidonic acid in the cord sera of offspring
- 2019
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 11:2
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Journal article (peer-reviewed)abstract
- Growing up in a farm environment is protective against allergy development. Various explanations have been put forward to explain this association. Fatty acids are regulators of immune function and the composition of fatty acids in the circulation system may affect immune development. Here, we investigate whether the fatty acid composition of cord serum differs for infants born to Farm (n = 26) or non-Farm mothers (n =29) in the FARMFLORA birth-cohort. For comparison, the levels of fatty acids in the maternal diet, serum and breast milk around 1 month post-partum were recorded. The fatty acids in the cord sera from infants born to Farm mothers had higher proportions of arachidonic acid (20:4 n-6) and adrenic acid (22:4 n-6) than those from infants born to non-Farm mothers. No differences were found for either arachidonic acid or adrenic acid in the diet, samples of the serum, or breast milk from Farm and non-Farm mothers obtained around 1 month post-partum. The arachidonic and adrenic acid levels in the cord blood were unrelated to allergy outcome for the infants. The results suggest that a farm environment may be associated with the fatty acid composition to which the fetus is exposed during pregnancy. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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| 5. |
- Barman, Malin, 1983, et al.
(author)
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No association between allergy and current 25-hydroxy vitamin D in serum or vitamin D intake
- 2015
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In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 104:4, s. 405-413
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Journal article (peer-reviewed)abstract
- Aim Vitamin D may be involved in allergy development, but there is conflicting evidence. We investigated if dietary intake of vitamin D and levels of 25OHD in serum differed between allergic and nonallergic adolescents and if serum 25OHD correlated with dietary intake of vitamin D or season of blood sampling. Methods Serum 25-hydroxy vitamin D (25OHD) levels were analysed in 13-year-old subjects with atopic eczema (n = 55), respiratory allergy (n = 55) or no allergy (n = 55). Intake of fat-containing foods was assessed by food-frequency questionnaires, and total daily vitamin D intake was calculated. Logistic regression was used to adjust for gender, parental allergy and time of blood sampling. Results Subjects with atopic eczema or respiratory allergy did not differ from nonallergic controls regarding serum 25OHD levels or calculated vitamin D intake. Subjects sampled in the autumn had significantly higher levels of serum 25OHD than subjects sampled in the winter or spring. Serum 25OHD levels correlated to consumption of vitamin D-fortified lean milk (p = 0.001). Conclusion The findings suggest no association between allergy and 25OHD levels in serum or vitamin D intake in adolescents. Serum 25OHD levels correlated to intake of vitamin D-fortified lean milk.
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| 6. |
- Barman, Malin, 1983, et al.
(author)
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Serum fatty acid profile does not reflect seafood intake in adolescents with atopic eczema.
- 2014
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In: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 103:9, s. 968-976
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Journal article (peer-reviewed)abstract
- AIM:Long-chain polyunsaturated fatty acids (LCPUFAs) are immunomodulatory, but their role in allergy development is controversial. We investigated whether proportions of LCPUFAs in serum phospholipids were related to allergic diagnosis, seafood intake and LCPUFA proportions in cord blood.METHODS:Serum was obtained from 148 birth cohort children at 13 years of age. Forty had atopic eczema, 53 had respiratory allergy, and 55 were nonallergic. Proportions of LCPUFAs were determined in serum phospholipids; cord blood from 128 of the individuals was previously analysed. Seafood intake was estimated using questionnaires.RESULTS:Allergic and nonallergic individuals did not differ significantly regarding individual LCPUFAs. However, arachidonic acid over docosahexaenoic acid (DHA) ratio was higher in allergic, compared with nonallergic, adolescents. In nonallergic individuals, LCPUFA proportions in cord serum and adolescent serum correlated weakly. In individuals with atopic eczema and respiratory allergy, these correlations were weak or absent. A moderate correlation between seafood intake and serum DHA was seen in nonallergic individuals and those with respiratory allergy, but not in those with atopic eczema.CONCLUSION:Serum LCPUFA pattern was similar in allergic and nonallergic adolescents. Fatty acid metabolism may be altered in atopic eczema subjects, suggested by poor correlations between fatty acid intake and serum levels.
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| 7. |
- Boström, Elisabeth Almer, 1983, et al.
(author)
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Resistin and insulin/insulin-like growth factor signaling in rheumatoid arthritis.
- 2011
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In: Arthritis and rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 63:10, s. 2894-904
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Journal article (peer-reviewed)abstract
- Human resistin has proinflammatory properties that activate NF-κB-dependent pathways, whereas its murine counterpart is associated with insulin resistance. The aim of this study was to examine potential cross-talk between resistin and insulin/insulin-like growth factor (IGF) signaling in rheumatoid arthritis (RA).
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| 8. |
- Brisslert, Mikael, 1974, et al.
(author)
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S100A4 regulates the Src-tyrosine kinase dependent differentiation of Th17 cells in rheumatoid arthritis
- 2014
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In: Biochimica Et Biophysica Acta-Molecular Basis of Disease. - : Elsevier BV. - 0925-4439. ; 1842:11, s. 2049-2059
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Journal article (peer-reviewed)abstract
- Objectives: To evaluate the role of S100A4, a calcium-binding regulator of nonmuscle myosin assembly, for T-cell responses in rheumatoid arthritis. Methods: Arthritis was induced in the methylated bovine serum albumin (mBSA)-immunized mice lacking the entire S100A4 protein (S100A4KO) and in wild-type counterparts treated with short hairpin ribonucleic acid (shRNA)-lentiviral constructs targeting S100A4 (S100A4-shRNA). The severity of arthritis was evaluated morphologically. T-cell subsets were characterized by the expression of master transcription factors, and functionally by proliferation activity and cytokine production. The activity of the Scr-kinases Fyn and Lck was assessed by the autophosphorylation of C-terminal thyrosine and by the phosphorylation of the CD5 cytodomain. The interaction between S100A4 and the CD5 cytodomain was analysed by nuclear magnetic resonance spectrophotometry. Results: S100A4-deficient mice (S100A4KO and S100A4-shRNA) had significantly alleviated morphological signs of arthritis and joint damage. Leukocyte infiltrates in the arthritic joints of S100A4-deficient mice accumulated Foxp3(+) Treg cells, while the number of ROR gamma t(+) and (pTyr705)STAT3(+) cells was reduced. S100A4-deficient mice had a limited formation of Th17-cells with low retinoic acid orphan receptor gamma t (ROR gamma t) mRNA and IL17 production in T-cell cultures. S100A4-deficient mice had a low expression and activity of T-cell receptor (TCR) inhibitor CD5 and low (pTyr705)STAT3 (signal transducer and activator of transcription 3), which led to increased (pTyr352)ZAP-70 (theta-chain associated protein kinase of 70 kDa), lymphocyte proliferation and production of IL2. In vitro experiments showed that S100A4 directly binds Lck and Fyn and reciprocally regulates their kinase activity towards the CD5 cytodomain. Spectrometry demonstrates an interaction between the CD5 cytodomain and EF2-binding sites of S100A4. Conclusion: The present. study demonstrates that S100A4 plays an important part in the pathogenesis of arthritis. It controls CD5-dependent differentiation of Th17 cells by regulating the activity of the Src-family kinases Lck and Fyn. (C) 2014 Elsevier B.V. All rights reserved.
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| 9. |
- Calvén, Anna, et al.
(author)
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Adolescents' attitudes, preferences and perceived behaviours regarding healthy eating and whole grains from a gender and health interest perspective
- 2023
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In: Food & Nutrition Research. - 1654-6628 .- 1654-661X. ; 67:8988, s. 1-15
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Journal article (peer-reviewed)abstract
- Background: A healthy diet is important not only for the growth and development of the human body but also for the prevention of chronic diseases. However, most Swedish adolescents do not follow dietary recommendations, especially the intake of whole grain is very low. To create targeted conditions for healthy food choices amongst adolescents, comprehensive knowledge of factors related to adolescents' unhealthy and healthy eating is needed. Objective: To investigate adolescents' attitudes, preferences and perceived behaviours regarding healthy eating, with a specific focus on whole grains and to evaluate differences between genders and between adolescents with higher versus lower health interest. Design: A total of 1,178 Swedish adolescents responded to a questionnaire about their attitudes, preferences and perceived behabviours towards healthy eating and whole grains, and their general interest in nutrition and health.Results of girls and boys were compared, as well as adolescents with a higher versus lower health interest. Results: Displays information about healthy eating among adolescents and a comprehensive set of factors that may affect their ability to eat healthier. Overall, adolescents had a positive attitude towards food and health, but less than half felt that they managed to eat healthy. The consumption of different whole grain products was low, although the willingness to eat healthier and more whole grain was high. The most reported barrier to healthy eating, as well as increasing whole grain intake, was the unavailability of tasty healthy products, taste being even more important for adolescents with a low health interest than those with a high interest. Whole grain consumption and factors increasing the willingness of whole grain consumption were most prominent not only in adolescents with high health interest but also in girls compared with boys. Conclusion: The results show good potential to improve dietary habits amongst adolescents. Taste and availability of healthy products were rated the most important, whilst knowledge about the products' healthiness was rated the least important, especially amongst those with low health interest. By focusing on the attitudes and preferences of adolescents, the effectiveness may increase of initiatives to improve their dietary habits.
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| 10. |
- Erlandsson, Malin, 1972, et al.
(author)
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Expression of metastasin S100A4 is essential for bone resorption and regulates osteoclast function.
- 2013
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In: Biochimica et biophysica acta. - : Elsevier BV. - 0006-3002. ; 1833:12, s. 2653-2663
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Journal article (peer-reviewed)abstract
- S100A4 is a Ca-binding protein that regulates cell growth, survival, and motility. The abundant expression of S100A4 in rheumatiod arthritis contributes to the invasive growth of joint tissue and to bone damage. In the present study, we analysed the role of S100A4 in bone homeostasis.
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