المؤلفون: Nichlas Davidsen, Louise Ramhøj, Anne-Sofie Ravn Ballegaard, Anna Kjerstine Rosenmai, Cecillie Sofie Henriksen, Terje Svingen

المصدر: Current Research in Toxicology, Vol 6, Iss , Pp 100154- (2024)

مصطلحات موضوعية: PFAS, PFOS, Thyroid, Development, Ex vivo, Cadherin 16, Toxicology. Poisons, RA1190-1270

الوصف: Perfluorooctanesulfonic acid (PFOS) can disrupt the thyroid hormone (TH) system in rodents, potentially affecting perinatal growth and neurodevelopment. Some studies also suggest that gestational exposure to PFOS can lead to lower TH levels throughout life, indicating that PFOS may compromise thyroid gland development. To address this question, we utilized a rat thyroid gland ex vivo culture system to study direct effects of PFOS on the developing thyroid. No significant changes to follicular structure or size were observed with 1 µM or 10 µM PFOS exposure. However, the transcription factor Foxe1, together with Tpo and Lrp2, were upregulated, whereas the key transcription factor Pax8 and its downstream target gene Cdh16 were significantly downregulated at the transcript level, observed with both RT-qPCR and RNAscope. Notably, Cdh16 expression was not uniformly downregulated across Cdh16-postive cells, but instead displayed a patchy expression pattern across the thyroid gland. This is a significant change in expression pattern compared to control thyroids where Cdh16 is expressed relatively uniformly. The disrupted expression pattern was also seen at the protein level. This suggests that PFOS exposure can impact follicular growth and structure. Compromised follicle integrity, if irreversible, could help explain reduced TH synthesis postnatally. This view is supported by observed changes to Tpo and Lrp2 expression, two factors that play a role in TH synthesis.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2666027X24000070Test; https://doaj.org/toc/2666-027XTest

الوصول الحر: https://doaj.org/article/5711583a02a84757aa0eb4a772c0bd42Test

المؤلفون: Monica Kam Draskau, Anne-Sofie Ravn Ballegaard, Louise Ramhøj, Josephine Bowles, Terje Svingen, Cassy M. Spiller

المصدر: Current Research in Toxicology, Vol 3, Iss , Pp 100069- (2022)

مصطلحات موضوعية: Adverse Outcome Pathway, Key event relationship, Retinoic acid, Ovary, Meiosis, Germ cells, Toxicology. Poisons, RA1190-1270

الوصف: The Adverse Outcome Pathway (AOP) concept is an emerging tool in regulatory toxicology that uses simplified descriptions to show cause-effect relationships between stressors and toxicity outcomes in intact organisms. The AOP structure is a modular framework, with Key Event Relationships (KERs) representing the unit of causal relationship based on existing knowledge, describing the connection between two Key Events. Because KERs are the only unit to support inference it has been argued recently that KERs should be recognized as the core building blocks of knowledge assembly within the AOP-Knowledge Base. Herein, we present a first case to support this proposal and provide a full description of a KER linking decreased all-trans retinoic acid (atRA) levels in developing ovaries with disrupted meiotic entry of oogonia. We outline the evidence to support a role for atRA in inducing meiosis in oogonia across mammals; this is important because elements of the RA synthesis/degradation pathway are recognized targets for numerous environmental chemicals. The KER we describe will be used to support an intended AOP linking inhibition of the atRA producing ALDH1A enzymes with reduced fertility in women.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2666027X22000068Test; https://doaj.org/toc/2666-027XTest

الوصول الحر: https://doaj.org/article/968e377676784e779ff1eece966d0ab8Test

المؤلفون: Katrine Bækby Graversen, Martin Iain Bahl, Jeppe Madura Larsen, Anne-Sofie Ravn Ballegaard, Tine Rask Licht, Katrine Lindholm Bøgh

المصدر: Frontiers in Microbiology, Vol 11 (2020)

مصطلحات موضوعية: antibiotics, microbiome, host response, Treg, regulatory T cells, IgA, Microbiology, QR1-502

الوصف: The intestinal gut microbiota is essential for maintaining host health. Concerns have been raised about the possible connection between antibiotic use, causing microbiota disturbances, and the increase in allergic and autoimmune diseases observed during the last decades. To elucidate the putative connection between antibiotic use and immune regulation, we have assessed the effects of the antibiotic amoxicillin on immune regulation, protein uptake, and bacterial community structure in a Brown Norway rat model. Daily intra-gastric administration of amoxicillin resulted in an immediate and dramatic shift in fecal microbiota, characterized by a reduction of within sample (α) diversity, reduced variation between animals (β diversity), increased relative abundance of Bacteroidetes and Gammaproteobacteria, with concurrent reduction of Firmicutes, compared to a water control group. In the small intestine, amoxicillin also affected microbiota composition significantly, but in a different way than observed in feces. The small intestine of control animals was vastly dominated by Lactobacillus, but this genus was much less abundant in the amoxicillin group. Instead, multiple different genera expanded after amoxicillin administration, with high variation between individual animals, thus the small intestinal α and β diversity were higher in the amoxicillin group compared to controls. After 1 week of daily amoxicillin administration, total fecal IgA level, relative abundance of small intestinal regulatory T cells and goblet cell numbers were higher in the amoxicillin group compared to controls. Several bacterial genera, including Escherichia/Shigella, Klebsiella (Gammaproteobacteria), and Bifidobacterium, for which the relative abundance was higher in the small intestine in the amoxicillin group than in controls, were positively correlated with the fraction of small intestinal regulatory T cells. Despite of epidemiologic studies showing an association between early life antibiotic consumption and later prevalence of inflammatory bowel diseases and food allergies, our findings surprisingly indicated that amoxicillin-induced perturbation of the gut microbiota promotes acute immune regulation. We speculate that the observed increase in relative abundance of small intestinal regulatory T cells is partly mediated by immunomodulatory lipopolysaccharides derived from outgrowth of Gammaproteobacteria.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fmicb.2020.00496/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/3150ed24c5574cf88c06e81983355788Test

المؤلفون: Natalia Zofia Maryniak, Egon Bech Hansen, Anne-Sofie Ravn Ballegaard, Ana Isabel Sancho, Katrine Lindholm Bøgh

المصدر: Nutrients, Vol 10, Iss 12, p 1903 (2018)

مصطلحات موضوعية: food allergy, cow’s milk, camel milk, infant formula, animal models, Nutrition. Foods and food supply, TX341-641

الوصف: Background: When breastfeeding is impossible or insufficient, the use of cow’s milk-based hypoallergenic infant formulas is an option for infants suffering from or at risk of developing cow’s milk allergy. As the Camelidae family has a large evolutionary distance to the Bovidae family and as camel milk differs from cow’s milk protein composition, there is a growing interest in investigating the suitability of camel milk as an alternative to cow’s milk-based hypoallergenic infant formulas. Methods: The aim of the study was to compare the allergenicity and immunogenicity of camel and cow’s milk as well as investigating their cross-reactivity using a Brown Norway rat model. Rats were immunised intraperitoneally with one of four products: camel milk, cow’s milk, cow’s milk casein or cow’s milk whey fraction. Immunogenicity, sensitising capacity, antibody avidity and cross-reactivity were evaluated by means of different ELISAs. The eliciting capacity was evaluated by an ear swelling test. Results: Camel and cow’s milk showed similarity in their inherent immunogenicity, sensitising and eliciting capacity. Results show that there was a lower cross-reactivity between caseins than between whey proteins from camel and cow’s milk. Conclusions: The study showed that camel and cow’s milk have a low cross-reactivity, indicating a low protein similarity. Results demonstrate that camel milk could be a promising alternative to cow’s milk-based hypoallergenic infant formulas.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6643/10/12/1903Test; https://doaj.org/toc/2072-6643Test

الوصول الحر: https://doaj.org/article/be0ad6ef21f94a68b61b604fdb895d4bTest

المؤلفون: Jeppe Madura Larsen, Anne‐Sofie Ravn Ballegaard, Angela Serrano Dominguez, Nanna Jordahn Kristoffersen, Natalia Zofia Maryniak, Arielle Vallee Locke, Sahar Kazemi, Michelle Epstein, Charlotte Bernhard Madsen, Katrine Lindholm Bøgh

المصدر: Larsen, J M, Ballegaard, A-S R, Dominguez, A S, Kristoffersen, N J, Maryniak, N Z, Locke, A V, Kazemi, S, Epstein, M, Madsen, C B & Bøgh, K L 2023, ' The role of skin inflammation, barrier dysfunction, and oral tolerance in skin sensitization to gluten-derived hydrolysates in a rat model ', Contact Dermatitis, vol. 88, no. 2, pp. 109-119 . https://doi.org/10.1111/cod.14233Test

مصطلحات موضوعية: Food allergy, Wheat, Immunology and Allergy, Skin inflammation, Animal model, Dermatology, Oral tolerance, Skin barrier dysfunction, Skin sensitization, Gluten

الوصف: Background: Adverse reactions to wheat-containing skin care products have been linked to food allergy development.Objectives: To determine the role of skin barrier dysfunction and inflammation in sensitization to gluten-derived hydrolysates via the skin in Brown Norway rats with and without oral tolerance to wheat.Methods: Skin barrier defect was induced by mechanical disruption, and skin inflammation was induced by topical application of SLS or MC903. Unmodified, enzyme hydrolyzed, or acid hydrolyzed gluten products were applied to the skin 3 times per week for 5 weeks. Subsequently, rats were orally gavaged with unmodified gluten.Results: Wheat-naïve rats were readily sensitized to gluten hydrolysates via the skin. Skin barrier defect and skin inflammation had little effect on the skin sensitization and hydrolysate-specific IgE levels. Oral administration of unmodified gluten promoted the production of unmodified gluten-specific IgE in rats sensitized via the skin. Sensitization through intact skin, disrupted skin barrier, or inflamed skin was unable to break tolerance to unmodified gluten in rats on a wheat-containing diet.Conclusions: Mechanical skin barrier disruption and skin inflammation play a limited role in experimental skin sensitization to gluten-derived hydrolysates.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e42f81677a69e4e31c8357e1caf9d391Test
https://pubmed.ncbi.nlm.nih.gov/36221232Test

المؤلفون: Anne-Sofie Ravn Ballegaard, Katrine Lindholm Bøgh

المصدر: Ballegaard, A-S R & Bøgh, K L 2023, ' Intestinal protein uptake and IgE-mediated food allergy ', Food Research International, vol. 163, 112150 . https://doi.org/10.1016/j.foodres.2022.112150Test

مصطلحات موضوعية: Adult, Biological Transport, Allergens, Immunoglobulin E, Lifestyle impact, Environmental impact, Cell junctional complexes, Child, Preschool, Immune System, Food allergy, Humans, Dietary Proteins, Epithelial transport, Child, Gut permeability, Intestinal barrier, Food Hypersensitivity, Food Science

الوصف: Food allergy is affecting 5-8% of young children and 2-4% of adults and seems to be increasing in prevalence. The cause of the increase in food allergy is largely unknown but proposed to be influenced by both environmental and lifestyle factors. Changes in intestinal barrier functions and increased uptake of dietary proteins have been suggested to have a great impact on food allergy. In this review, we aim to give an overview of the gastrointestinal digestion and intestinal barrier function and provide a more detailed description of intestinal protein uptake, including the various routes of epithelial transport, how it may be affected by both intrinsic and extrinsic factors, and the relation to food allergy. Further, we give an overview of in vitro, ex vivo and in vivo techniques available for evaluation of intestinal protein uptake and gut permeability in general. Proteins are digested by gastric, pancreatic and integral brush border enzymes in order to allow for sufficient nutritional uptake. Absorption and transport of dietary proteins across the epithelial layer is known to be dependent on the physicochemical properties of the proteins and their digestion fragments themselves, such as size, solubility and aggregation status. It is believed, that the greater an amount of intact protein or larger peptide fragments that is transported through the epithelial layer, and thus encountered by the mucosal immune system in the gut, the greater is the risk of inducing an adverse allergic response. Proteins may be absorbed across the epithelial barrier by means of various mechanisms, and studies have shown that a transcellular facilitated transport route unique for food allergic individuals are at play for transport of allergens, and that upon mediator release from mast cells an enhanced allergen transport via the paracellular route occurs. This is in contrast to healthy individuals where transcytosis through the enterocytes is the main route of protein uptake. Thus, knowledge on factors affecting intestinal barrier functions and methods for the determination of their impact on protein uptake may be useful in future allergenicity assessments and for development of future preventive and treatment strategies.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5c313a1c138c2105cb03b7add6ad5defTest
https://doi.org/10.1016/j.foodres.2022.112150Test

المؤلفون: Natalia Zofia Maryniak, Mette Halkjær Stage, Anne‐Sofie Ravn Ballegaard, Ana Isabel Sancho, Egon Bech Hansen, Katrine Lindholm Bøgh

المصدر: Maryniak, N Z, Stage, M H, Ballegaard, AS R, Sancho, A I, Hansen, E B & Bøgh, K L 2023, ' Camel Milk cannot prevent the Development of Cow's Milk Allergy – A Study in Brown Norway Rats ', Molecular Nutrition and Food Research, vol. 67, no. 2, 2200359 . https://doi.org/10.1002/mnfr.202200359Test

مصطلحات موضوعية: Cow’s milk allergy, Food allergy, Camel milk, Infant formula, Allergy prevention, Animal model, Food Science, Biotechnology

الوصف: ScopeCurrently there are no specific recommendations for the use of any particular infant formula in the prevention of cow's milk allergy (CMA). Recently, there has been an increasing interest in alternative infant formulas based on milk proteins from other sources than the cow, including milk from other mammalians such as goat, sheep, donkey, horse and camel. Whereas these have been studied for their usability in CMA management, there are no studies of their CMA preventive capacity. Thus, the aim of this study was to evaluate whether camel milk could prevent CMA and vice versa.Methods & resultsThe capacity of camel milk in preventing CMA and vice versa were evaluated in a well-established prophylactic Brown Norway rat model. IgG1, IgE and IgA responses, allergy elicitation, intestinal and mLN gene expression and protein uptake were analysed. The study demonstrated that camel and cow's milk in general had an insignificant cross-preventive capacity. Yet, whereas cow's milk was shown to have a low transient capacity to prevent sensitisation and clinically active camel milk allergy, camel milk did not show this effect for CMA.ConclusionsThis study suggested that due to lack of cross-tolerance camel milk cannot be used for CMA prevention.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53bd62e99068778b942cf6ed672c211fTest
https://doi.org/10.1002/mnfr.202200359Test

المؤلفون: Terje Svingen, Camilla Lindgren Schwartz, Anna Kjerstine Rosenmai, Louise Ramhøj, Hanna Katarina Lilith Johansson, Ulla Hass, Monica Kam Draskau, Nichlas Davidsen, Sofie Christiansen, Anne-Sofie Ravn Ballegaard, Marta Axelstad

المصدر: Svingen, T, Schwartz, C L, Rosenmai, A K, Ramhøj, L, Johansson, H K L, Hass, U, Draskau, M K, Davidsen, N, Christiansen, S, Ballegaard, A-S R & Axelstad, M 2022, ' Using alternative test methods to predict endocrine disruption and reproductive adverse outcomes : do we have enough knowledge? ', Environmental Pollution, vol. 304, 119242 . https://doi.org/10.1016/j.envpol.2022.119242Test

مصطلحات موضوعية: Male, Reproductive toxicity, Reproduction, Health, Toxicology and Mutagenesis, Endocrine disruption, Male reproduction, Animals, Wild, Endocrine System, General Medicine, Endocrine Disruptors, Toxicology, Risk Assessment, Pollution, Mode of action, Animals, Alternative test methods, AOP, Risk assessment

الوصف: Endocrine disrupting chemicals (EDCs) are a matter of great concern. They are ubiquitous in the environment, are considered harmful to humans and wildlife, yet remain challenging to identify based on current international test guidelines and regulatory frameworks. For a compound to be identified as an EDC within the EU regulatory system, a plausible link between an endocrine mode-of-action and an adverse effect outcome in an intact organism must be established. This requires in-depth knowledge about molecular pathways regulating normal development and function in animals and humans in order to elucidate causes for disease. Although our knowledge about the role of the endocrine system in animal development and function is substantial, it remains challenging to predict endocrine-related disease outcomes in intact animals based on non-animal test data. A main reason for this is that our knowledge about mechanism-of-action are still lacking for essential causal components, coupled with the sizeable challenge of mimicking the complex multi-organ endocrine system by methodological reductionism. Herein, we highlight this challenge by drawing examples from male reproductive toxicity, which is an area that has been at the forefront of EDC research since its inception. We discuss the importance of increased focus on characterizing mechanism-of-action for EDC-induced adverse health effects. This is so we can design more robust and reliable testing strategies using non-animal test methods for predictive toxicology; both to improve chemical risk assessment in general, but also to allow for considerable reduction and replacement of animal experiments in chemicals testing of the 21st Century.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1bd6065b867b6232ab383b08d3c97921Test
https://orbit.dtu.dk/en/publications/91cbfd9b-f963-46bb-bdff-2e96bb7bd3ceTest

المؤلفون: Monica Kam Draskau, Anne-Sofie Ravn Ballegaard, Louise Ramhøj, Josephine Bowles, Terje Svingen, Cassy M. Spiller

المصدر: Draskau, M K, Ballegaard, A-S R, Ramhøj, L, Bowles, J, Svingen, T & Spiller, C M 2022, ' AOP Key Event Relationship report : Linking decreased retinoic acid levels with disrupted meiosis in developing oocytes ', Current Research in Toxicology, vol. 3, 100069 . https://doi.org/10.1016/j.crtox.2022.100069Test

مصطلحات موضوعية: Meiosis, Key event relationship, Health, Toxicology and Mutagenesis, Infertility, Ovary, Adverse Outcome Pathway, Retinoic acid, Germ cells, Toxicology, Applied Microbiology and Biotechnology

الوصف: The Adverse Outcome Pathway (AOP) concept is an emerging tool in regulatory toxicology that uses simplified descriptions to show cause-effect relationships between stressors and toxicity outcomes in intact organisms. The AOP structure is a modular framework, with Key Event Relationships (KERs) representing the unit of causal relationship based on existing knowledge, describing the connection between two Key Events. Because KERs are the only unit to support inference it has been argued recently that KERs should be recognized as the core building blocks of knowledge assembly within the AOP-Knowledge Base. Herein, we present a first case to support this proposal and provide a full description of a KER linking decreased all-trans retinoic acid (atRA) levels in developing ovaries with disrupted meiotic entry of oogonia. We outline the evidence to support a role for atRA in inducing meiosis in oogonia across mammals; this is important because elements of the RA synthesis/degradation pathway are recognized targets for numerous environmental chemicals. The KER we describe will be used to support an intended AOP linking inhibition of the atRA producing ALDH1A enzymes with reduced fertility in women.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::71f503ee4ad20e0dda98de2af86675fdTest
https://pubmed.ncbi.nlm.nih.gov/35345548Test

المؤلفون: Anne-Sofie Ravn Ballegaard, Eva Untersmayr, Kirsten Pilegaard, Katrine Lindholm Bøgh, Peter Rasmussen, Jeppe Madura Larsen

المصدر: Ballegaard, A-S R, Larsen, J M, Rasmussen, P H, Untersmayr, E, Pilegaard, K & Bøgh, K L 2021, ' Quinoa (Chenopodium quinoa Willd.) Seeds Increase Intestinal Protein Uptake ', Molecular Nutrition and Food Research, vol. 65, no. 13, e2100102 . https://doi.org/10.1002/mnfr.202100102Test

مصطلحات موضوعية: 0301 basic medicine, Male, Cholera Toxin, Inflammation, Biology, Pharmacology, medicine.disease_cause, Chenopodium quinoa, Permeability, 03 medical and health sciences, chemistry.chemical_compound, SDG 3 - Good Health and Well-being, In vivo, medicine, Animals, Humans, Barrier function, Lamina propria, 030109 nutrition & dietetics, Intestinal permeability, Cholera toxin, medicine.disease, Rats, Intestines, 030104 developmental biology, medicine.anatomical_structure, chemistry, Capsaicin, Seeds, Female, Dietary Proteins, Goblet Cells, medicine.symptom, Caco-2 Cells, Food Science, Biotechnology

الوصف: Scope Within the last decade, quinoa seeds have gained much popularity as a new food and have recently been proposed as an appropriate food for early introduction in infants. Quinoa contains high levels of saponins, which are known for their adjuvant activity and effect on the intestinal barrier function. The aim of this study is to investigate the impact of quinoa on intestinal permeability and inflammation in comparison with the positive controls; cholera toxin (CT), and capsaicin. Methods and results The effect of quinoa on intestinal barrier function and inflammation is investigated in vitro using a Caco-2 cell line and in vivo using a Brown Norway rat model. Effects in vivo are analyzed by protein uptake, histology, gene expression, antibody levels, and flow cytometry. Quinoa and the positive controls all increased the intestinal permeability, but distinct patterns of absorbed protein are observed in the epithelium, Peyer's patches, lamina propria, and serum. The quinoa-mediated effect on intestinal barrier function is found to be distinct from the effect of the two positive controls. Conclusion The findings demonstrate the ability of quinoa to increase intestinal permeability and to promote compartment-specific protein uptake via mechanisms that may differ from CT and capsaicin.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a1a210d65d368474e2f477491de8f4c6Test
https://orbit.dtu.dk/en/publications/f0042bf1-b702-49a7-bf3d-f649612f67b2Test