| 1. |
- Fridén, Michael, et al.
(author)
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Effects of a low-carbohydrate high polyunsaturated fat diet or a healthy Nordic diet versus usual care on liver fat content and cardiometabolic risk factors in people with type 2 diabetes and prediabetes: a randomized controlled trial (NAFLDiet)
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Other publication (other academic/artistic)abstract
- Background: Previous trials have shown that plant-derived polyunsaturated fatty acids (PUFA) in place of saturated fat reduces liver fat, a prerequisite for non-alcoholic fatty liver disease (NAFLD). The effect on liver fat from a novel “anti-lipogenic diet” replacing carbohydrates with PUFA or a healthy Nordic diet (HND) higher in whole-grains but lower in saturated fat has not yet been examined. Objectives: To investigate the effects on changes in liver fat (primary outcome) and other cardiometabolic risk factors after 12 months of follow-up in individuals with prediabetes or T2D from three different diet comparisons: a low carbohydrate high PUFA (LCPUFA) diet versus a HND, a LCPUFA diet versus usual care (UC) and a HND versus UC. Methods: A three-arm parallel ad libitum randomized trial was conducted. Adult men and women (n=148) were randomized to one of the three diet groups. Participants in all groups received key food items on a monthly/bimonthly basis. Liver fat and cardiometabolic risk factors were assessed at baseline and after 12 months. Dietary adherence was assessed using weighed food diaries and objective biomarkers. General linear models were employed to estimate the intention-to-treat (ITT) effect. Results: Dietary adherence was high for all diet groups. Liver fat was reduced to a similar extent in the LCPUFA and the HND group compared to UC (-1.46% (95% CI: -2.42, -0.51)) and -1.76 % (95% CI: -2.96, -0.57), respectively. No difference in liver fat between LCPUFA and HND was observed. Body weight and HbA1c decreased more in the HND compared to the other diet groups whereas no differences were observed between LCPUFA and UC. Similar reductions in LDL-cholesterol were observed for the HND and the LCPUFA group compared to UC, but only the HND reduced triglycerides and C-reactive protein (CRP) compared with UC. No differences were observed for any other secondary outcomes.Conclusions: A LCPUFA diet and a HND both reduced liver fat as compared with UC. Given the sustained weight loss after the HND compared to the other groups, together with improvements in other cardiometabolic markers, the HND in particular seems to be useful for the treatment of T2D and NAFLD.
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| 2. |
- Shi, Lin, et al.
(author)
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Variable selection and validation in multivariate modelling
- 2019
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In: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 35:6, s. 972-980
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Journal article (peer-reviewed)abstract
- Motivation Validation of variable selection and predictive performance is crucial in construction of robust multivariate models that generalize well, minimize overfitting and facilitate interpretation of results. Inappropriate variable selection leads instead to selection bias, thereby increasing the risk of model overfitting and false positive discoveries. Although several algorithms exist to identify a minimal set of most informative variables (i.e. the minimal-optimal problem), few can select all variables related to the research question (i.e. the all-relevant problem). Robust algorithms combining identification of both minimal-optimal and all-relevant variables with proper cross-validation are urgently needed. Results We developed the MUVR algorithm to improve predictive performance and minimize overfitting and false positives in multivariate analysis. In the MUVR algorithm, minimal variable selection is achieved by performing recursive variable elimination in a repeated double cross-validation (rdCV) procedure. The algorithm supports partial least squares and random forest modelling, and simultaneously identifies minimal-optimal and all-relevant variable sets for regression, classification and multilevel analyses. Using three authentic omics datasets, MUVR yielded parsimonious models with minimal overfitting and improved model performance compared with state-of-the-art rdCV. Moreover, MUVR showed advantages over other variable selection algorithms, i.e. Boruta and VSURF, including simultaneous variable selection and validation scheme and wider applicability.
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| 3. |
- Ahlin, Rebecca, 1989, et al.
(author)
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Effects on Serum Hormone Concentrations after a Dietary Phytoestrogen Intervention in Patients with Prostate Cancer: A Randomized Controlled Trial
- 2023
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In: Nutrients. - : MDPI. - 2072-6643 .- 2072-6643. ; 15:7
-
Journal article (peer-reviewed)abstract
- Phytoestrogens have been suggested to have an anti-proliferative role in prostate cancer, potentially by acting through estrogen receptor beta (ERβ) and modulating several hormones. We primarily aimed to investigate the effect of a phytoestrogen intervention on hormone concentrations in blood depending on the ERβ genotype. Patients with low and intermediate-risk prostate cancer, scheduled for radical prostatectomy, were randomized to an intervention group provided with soybeans and flaxseeds (∼200 mg phytoestrogens/d) added to their diet until their surgery, or a control group that was not provided with any food items. Both groups received official dietary recommendations. Blood samples were collected at baseline and endpoint and blood concentrations of different hormones and phytoestrogens were analyzed. The phytoestrogen-rich diet did not affect serum concentrations of testosterone, insulin-like growth factor 1, or sex hormone-binding globulin (SHBG). However, we found a trend of decreased risk of increased serum concentration of estradiol in the intervention group compared to the control group but only in a specific genotype of ERβ (p = 0.058). In conclusion, a high daily intake of phytoestrogen-rich foods has no major effect on hormone concentrations but may lower the concentration of estradiol in patients with prostate cancer with a specific genetic upset of ERβ.
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| 4. |
- Almquist, Martin, et al.
(author)
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Serum calcium and tumour aggressiveness in breast cancer: a prospective study of 7847 women.
- 2009
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In: European Journal of Cancer Prevention. - 1473-5709. ; 18, s. 354-360
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Journal article (peer-reviewed)abstract
- Experimental, epidemiological and clinical studies suggest that calcium and/or its regulating hormones affect breast cancer risk. There has been no prospective cohort study investigating serum calcium levels and breast cancer aggressiveness, as determined by tumour histology and stage. Dichotomized prediagnostic serum calcium levels were investigated in relation to breast cancer aggressiveness as determined by grade (mitotic frequency, tubule formation, nuclear atypia) and stage (tumour size and axillary lymph node status). Cox's proportional hazards analysis and heterogeneity analysis were used to investigate the associations between low/high calcium and grade/stage in a prospective cohort study of 7847 women, out of whom 462 women were diagnosed with incident breast cancer during a mean follow-up of 17.2 years. All analyses were stratified for body mass index and menopausal status. Prediagnostic serum calcium levels in premenopausal women were positively associated with increased tumour aggressiveness as determined by a higher risk of nodal metastasis; relative risk (RR) for calcium above median as compared with calcium below median was 1.88 with a 95% confidence interval (CI) of 1.04-3.38. In overweight women, prediagnostic serum calcium levels were also associated with tumour aggressiveness, as determined by both a higher risk of nodal metastasis [RR (95% CI) 1.69 (0.95-3.02)] and severe nuclear atypia [RR (95% CI) 2.06 (1.10-3.86)]. Results also indicate that, in overweight women, calcium is positively associated with worse grade as determined by tubule formation and mitotic frequency. In conclusion, prediagnostic serum calcium levels are positively associated with increased tumour aggressiveness in premenopausal and/or overweight women.
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| 5. |
- Arapovic, Lidija, et al.
(author)
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Age Rather Than Supplementation with Oat β-Glucan Influences Development of the Intestinal Microbiota and SCFA Concentrations in Suckling Piglets
- 2023
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In: Animals. - 2076-2615. ; 13:8
-
Journal article (peer-reviewed)abstract
- The effects of early supplementation with oat β-glucan during the suckling period on piglet gut microbiota composition, concentrations of short-chain fatty acids, and gut physiological markers were assessed. Fifty piglets from five litters, balanced for sex and birth weight, were divided within litters into two treatment groups: β-glucan and control. Piglets in the β-glucan group received the supplement three times/week from day 7 of age until weaning. Rectal swab samples were collected from 10 piglets per treatment group (balanced across litters) from week 1 to week 4, and plasma samples were collected at 1, 3, and 4 weeks of age. Additional samples of intestinal tissues and jugular and portal vein plasma were collected from 10 animals at weaning (one per treatment group and litter). The concentrations of short-chain fatty acids in plasma and the microbiota composition in rectal swabs were mainly influenced by piglet age, rather than the supplement. There were significant differences in microbiota composition between litters and several correlations between concentrations of short-chain fatty acids in plasma and specific microbial taxa in rectal swabs. Overall, β-glucan supplementation did not have any clear impact on the gut environment in suckling piglets, whereas a clear age-related pattern emerged.
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| 6. |
- Askmyr, Maria, et al.
(author)
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Modeling chronic myeloid leukemia in immunodeficient mice reveals expansion of aberrant mast cells and accumulation of pre-B cells.
- 2014
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In: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 4
-
Journal article (peer-reviewed)abstract
- Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that, if not treated, will progress into blast crisis (BC) of either myeloid or B lymphoid phenotype. The BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase, is thought to be sufficient to cause chronic phase (CP) CML, whereas additional genetic lesions are needed for progression into CML BC. To generate a humanized CML model, we retrovirally expressed BCR-ABL1 in the cord blood CD34(+) cells and transplanted these into NOD-SCID (non-obese diabetic/severe-combined immunodeficient) interleukin-2-receptor γ-deficient mice. In primary mice, BCR-ABL1 expression induced an inflammatory-like state in the bone marrow and spleen, and mast cells were the only myeloid lineage specifically expanded by BCR-ABL1. Upon secondary transplantation, the pronounced inflammatory phenotype was lost and mainly human mast cells and macrophages were found in the bone marrow. Moreover, a striking block at the pre-B-cell stage was observed in primary mice, resulting in an accumulation of pre-B cells. A similar block in B-cell differentiation could be confirmed in primary cells from CML patients. Hence, this humanized mouse model of CML reveals previously unexplored features of CP CML and should be useful for further studies to understand the disease pathogenesis of CML.
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| 7. |
- Bergh, Cecilia, 1972-, et al.
(author)
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Effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI): study protocol for a randomized, double-blind, placebo-controlled trial
- 2021
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In: Trials. - : Springer Science and Business Media LLC. - 1745-6215 .- 1745-6215. ; 22:1
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Journal article (peer-reviewed)abstract
- Background: Bilberries from Sweden, rich in polyphenols, have shown cholesterol-lowering effects in small studies, and the cholesterol-lowering properties of oats, with abundant beta-glucans and potentially bioactive phytochemicals, are well established. Both may provide cardiometabolic benefits following acute myocardial infarction (AMI), but large studies of adequate statistical power and appropriate duration are needed to confirm clinically relevant treatment effects. No previous study has evaluated the potential additive or synergistic effects of bilberry combined with oats on cardiometabolic risk factors. Our primary objective is to assess cardioprotective effects of diet supplementation with dried bilberry or with bioprocessed oat bran, with a secondary explorative objective of assessing their combination, compared with a neutral isocaloric reference supplement, initiated within 5 days following percutaneous coronary intervention (PCI) for AMI. Methods: The effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI) trial is a double-blind, randomized, placebo-controlled clinical trial. A total of 900 patients will be randomized post-PCI to one of four dietary intervention arms. After randomization, subjects will receive beverages with bilberry powder (active), beverages with high-fiber bioprocessed oat bran (active), beverages with bilberry and oats combined (active), or reference beverages containing no active bilberry or active oats, for consumption twice daily during a 3-month intervention. The primary endpoint is the difference in LDL cholesterol change between the intervention groups after 3 months. The major secondary endpoint is exercise capacity at 3 months. Other secondary endpoints include plasma concentrations of biochemical markers of inflammation, metabolomics, and gut microbiota composition after 3 months. Discussion: Controlling hyperlipidemia and inflammation is critical to preventing new cardiovascular events, but novel pharmacological treatments for these conditions are expensive and associated with negative side effects. If bilberry and/or oat, in addition to standard medical therapy, can lower LDL cholesterol and inflammation more than standard therapy alone, this could be a cost-effective and safe dietary strategy for secondary prevention after AMI. Trial registration: ClinicalTrials.gov NCT03620266. Registered on August 8, 2018.
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| 8. |
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| 9. |
- de Mello, Vanessa D., et al.
(author)
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Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study
- 2017
-
In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
-
Journal article (peer-reviewed)abstract
- Wide-scale profiling technologies including metabolomics broaden the possibility of novel discoveries related to the pathogenesis of type 2 diabetes (T2D). By applying non-targeted metabolomics approach, we investigated here whether serum metabolite profile predicts T2D in a well-characterized study population with impaired glucose tolerance by examining two groups of individuals who took part in the Finnish Diabetes Prevention Study (DPS); those who either early developed T2D (n = 96) or did not convert to T2D within the 15-year follow-up (n = 104). Several novel metabolites were associated with lower likelihood of developing T2D, including indole and lipid related metabolites. Higher indolepropionic acid was associated with reduced likelihood of T2D in the DPS. Interestingly, in those who remained free of T2D, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively. Furthermore, these metabolites were negatively correlated with low-grade inflammation. We replicated the association between indolepropionic acid and T2D risk in one Finnish and one Swedish population. We suggest that indolepropionic acid, a gut microbiota-produced metabolite, is a potential biomarker for the development of T2D that may mediate its protective effect by preservation of alpha-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity.
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| 10. |
- Ekberg, Jenny, et al.
(author)
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Expression of cyclin A1 and cell cycle proteins in hematopoietic cells and acute myeloid leukemia and links to patient outcome
- 2005
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In: European Journal of Haematology. - : Wiley-Blackwell Publishing Inc.. - 0902-4441 .- 1600-0609. ; 75:2, s. 106-115
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Journal article (peer-reviewed)abstract
- Abnormal expression of several key regulators essential for G1/S transitions has been implicated in tumorigenesis. A critical role of cyclin A1 in the development of acute myeloid leukemia (AML) has previously been demonstrated in transgenic mice. Our present study focused on the expression and prognostic significance of cyclin A1 and a panel of cell cycle regulatory proteins including cyclin A2, cyclin B1, cyclin E, CDK1, CDK2, p21 and p27 in bone marrow samples from 40 patients with AML. Freshly isolated CD34+ hematopoietic cells and bone marrow samples from 10 healthy donors were also assessed for cell type- and subcellular-specific expression of the cell cycle regulatory proteins. The level of cyclin A1 expression was the only factor that showed a significant correlation with patient outcome. In log-rank test stratified by levels of cyclin A1 expression, patients with high levels of cyclin A1 had significantly worse overall survival (OS) (P = 0.012) compared to those with low levels. Further, patients with high levels of cyclin A1 had significantly lower disease-free survival (DFS) (P = 0.028). Multivariate analysis indicated that cyclin A1 protein expression was an independent prognostic factor for predicting DFS (P = 0.035) and OS (P = 0.045). No correlation between cyclin A1 expression and age was found. However, expression of cyclin A2, cyclin B1, cyclin E, CDK1, CDK2, p21 and p27 did not show prognostic significance in these AML patients.
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| 11. |
- Ekberg, Jenny, et al.
(author)
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Regulation of the cyclin A1 protein is associated with its differential subcellular localization in hematopoietic and leukemic cells
- 2004
-
In: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 23:56, s. 9082-9089
-
Journal article (peer-reviewed)abstract
- An important role of the cell cycle regulatory protein cyclin A1 in the development of acute myeloid leukemia (AML) was previously demonstrated in a transgenic mouse model. We have now turned our attention to study specific aspects of the activity and subcellular distribution of cyclin A1 using bone marrow samples from normal donors and patients with AML, as well as leukemic cell lines. We show that the localization of cyclin A1 in normal hematopoietic cells is nuclear, whereas in leukemic cells from AML patients and cell lines, it is predominantly cytoplasmic. In leukemic cell lines treated with all-trans retinoic acid (ATRA), cyclin A1 localized to the nucleus. Further, there was a direct interaction between cyclin A1 and cyclin-dependent kinase 1, as well as a major ATRA receptor, RARalpha, in ATRA-treated cells but not in untreated leukemic cells. Our results indicate that the altered intracellular distribution of cyclin A1 in leukemic cells correlates with the status of the leukemic phenotype.
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| 12. |
- Eriksen, Anne Kirstine, et al.
(author)
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Effects of whole-grain wheat, rye, and lignan supplementation on cardiometabolic risk factors in men with metabolic syndrome: A randomized crossover trial
- 2020
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In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 111:4, s. 864-876
-
Journal article (peer-reviewed)abstract
- A whole-grain (WG)-rich diet has shown to have potential for both prevention and treatment of the metabolic syndrome (MetS), which is a cluster of risk factors that increase the risk of type 2 diabetes and cardiovascular disease. Different WGs may have different health effects. WG rye, in particular, may improve glucose homeostasis and blood lipids, possibly mediated through fermentable dietary fiber and lignans. Recent studies have also suggested a crucial role of the gut microbiota in response to WG. Objectives: The aim was to investigate WG rye, alone and with lignan supplements [secoisolariciresinol diglucoside (SDG)], and WG wheat diets on glucose tolerance [oral-glucose-tolerance test (OGTT)], other cardiometabolic outcomes, enterolignans, and microbiota composition. Moreover, we exploratively evaluated the role of gut microbiota enterotypes in response to intervention diets. Methods: Forty men with MetS risk profile were randomly assigned to WG diets in an 8-wk crossover study. The rye diet was supplemented with 280 mg SDG at weeks 4-8. Effects of treatment were evaluated by mixed-effects modeling, and effects on microbiota composition and the role of gut microbiota as a predictor of response to treatment were analyzed by random forest plots. Results: The WG rye diet (± SDG supplements) did not affect the OGTT compared with WG wheat. Total and LDL cholesterol were lowered (-0.06 and -0.09 mmol/L, respectively; P < 0.05) after WG rye compared with WG wheat after 4 wk but not after 8 wk. WG rye resulted in higher abundance of Bifidobacterium [fold-change (FC) = 2.58, P < 0.001] compared with baseline and lower abundance of Clostridium genus compared with WG wheat (FC = 0.54, P = 0.02). The explorative analyses suggest that baseline enterotype is associated with total and LDL-cholesterol response to diet. Conclusions: WG rye, alone or with SDG supplementation, compared with WG wheat did not affect glucose metabolism but caused transient LDL-cholesterol reduction. The effect of WG diets appeared to differ according to enterotype. This trial was registered at www.clinicaltrials.gov as NCT02987595.
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| 13. |
- Iversen, Kia Noehr, 1987, et al.
(author)
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The Effects of High Fiber Rye, Compared to Refined Wheat, on Gut Microbiota Composition, Plasma Short Chain Fatty Acids, and Implications for Weight Loss and Metabolic Risk Factors (the RyeWeight Study)
- 2022
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In: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 14:8
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Journal article (peer-reviewed)abstract
- Consumption of whole grain and cereal fiber have been inversely associated with body weight and obesity measures in observational studies but data from large, long-term randomized interventions are scarce. Among the cereals, rye has the highest fiber content and high rye consumption has been linked to increased production of gut fermentation products, as well as reduced risks of obesity and metabolic disease. The effects on body weight and metabolic risk factors may partly be mediated through gut microbiota and/or their fermentation products. We used data from a randomized controlled weight loss trial where participants were randomized to a hypocaloric diet rich in either high fiber rye foods or refined wheat foods for 12 weeks to investigate the effects of the intervention on gut microbiota composition and plasma short chain fatty acids, as well as the potential association with weight loss and metabolic risk markers. Rye, compared to wheat, induced some changes in gut microbiota composition, including increased abundance of the butyrate producing Agathobacter and reduced abundance of [Ruminococcus] torques group, which may be related to reductions in low grade inflammation caused by the intervention. Plasma butyrate increased in the rye group. In conclusion, intervention with high fiber rye foods induced some changes in gut microbiota composition and plasma short chain fatty acid concentration, which were associated with improvements in metabolic risk markers as a result of the intervention.
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| 14. |
- Jernbro, Carolina, 1976-, et al.
(author)
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Det är mitt liv! : om sambandet mellan barnmisshandel och att inte få välja sin framtida partner
- 2018
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Reports (other academic/artistic)abstract
- Alltför många tonåringar växer upp i hem där de känner att deras möjligheter att välja och styra sina egna liv begränsas. Det är vanligare att elever som har en eller båda föräldrar födda utanför Norden inte får välja själva, men även barn med svenskfödda föräldrar kan begränsas i sina val. Det kan handla om att inte själv få välja vem en ska gifta sig eller bo tillsammans med som vuxen (eller om en överhuvudtaget vill gifta sig). Det kan också handla om att inte få välja hur en ska se ut eller vad en ska ha på sig, att inte få välja kompisar eller vad en ska göra med kompisarna och/eller att inte få välja fritidsaktiviteter, utbildning, religion eller politisk uppfattning.I den här rapporten beskriver vi närmare de samband som finns vad gäller att inte få bestämma över sitt eget liv och sin framtida partner och utsatthet för barnmisshandel. De elever som inte får välja sin partner är betydligt oftare än andra utsatta för olika former av barnmisshandel. Det handlar om fysisk misshandel, psykisk misshandel, att bevittna våld mot en förälder, sexuella övergrepp och försummelse.De siffror vi redovisar säger ingenting om orsakssamband, men oavsett hur dessa ser ut är tonåringar som inte får välja sin framtida partner en särskilt utsatt grupp som behöver uppmärksammas.Uppgifterna är hämtade från en nationellt representativ elevenkätsundersökning som Stiftelsen Allmänna Barnhuset låtit Carolina Jernbro och Staffan Janson genomföra inom ramen för ett regeringsuppdrag.
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| 15. |
- Jernbro, Carolina, et al.
(author)
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Multiutsatta barn : om barn som utsatts för flera typer av barnmisshandel
- 2020
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Reports (other academic/artistic)abstract
- Vad är multiutsatthet? Hur vanligt är det att barn är utsatta för flera typer av våld? Hur mår de elever som utsätts och vilken hjälp har de fått? Vilka faktorer ökar risken för multiutsatthet?Varje barn har rätt att växa upp utan våld, och målet är att allt våld mot barn ska upphöra. Dit är det en bra bit kvar, i Sverige såväl som i resten av världen. Det är viktigt att försöka ta reda på hur vanligt våld mot barn är. Det ger förutsättningar för att förebygga, skydda och stötta.Den här rapporten fördjupar resultaten från den nationella studien Våld mot barn 2016 – En nationell kartläggning som forskarna Carolina Jernbro och Staffan Janson tidigare genomfört för Stiftelsen Allmänna Barnhuset på uppdrag av regeringen. Fokus i rapporten ligger på de barn som har utsatts för flera typer av barnmisshandel. Nya beräkningar om de multiutsatta barnen ger underlag för att förebygga våld. I studien har barn och unga själva svara på frågor anonymt. Det ger våldsutsatta barn, även de som inte kommit i kontakt med myndigheter, en möjlighet att komma till tals. Svaren ger en mer rättvisande bild av läget än vad antalet anmälningar gör. Man kan därmed börja ana vidden av det våld som barn utsätts för.En elev i studien uttrycker det så här: Jag tycker att ingen borde vara med om misshandel överhuvudtaget. Jag själv var med om det under åren och det förstör ens självtroende psykiskt och fysiskt. Än idag blir jag rädd om jag skulle göra samma fel och gifta mig med en människa som misshandlar mig och mina barn.
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| 16. |
- Jönsson, Christina, et al.
(author)
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Biocatalysis in the Recycling Landscape for Synthetic Polymers and Plastics towards Circular Textiles
- 2021
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In: ChemSusChem. - : Wiley. - 1864-5631 .- 1864-564X. ; 14:19, s. 4028-4040
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Journal article (peer-reviewed)abstract
- Although recovery of fibers from used textiles with retained material quality is desired, separation of individual components from polymer blends used in today's complex textile materials is currently not available at viable scale. Biotechnology could provide a solution to this pressing problem by enabling selective depolymerization of recyclable fibers of natural and synthetic origin, to isolate constituents or even recover monomers. We compiled experimental data for biocatalytic polymer degradation with a focus on synthetic polymers with hydrolysable links and calculated conversion rates to explore this path The analysis emphasizes that we urgently need major research efforts: beyond cellulose-based fibers, biotechnological-assisted depolymerization of plastics so far only works for polyethylene terephthalate, with degradation of a few other relevant synthetic polymer chains being reported. In contrast, by analyzing market data and emerging trends for synthetic fibers in the textile industry, in combination with numbers from used garment collection and sorting plants, it was shown that the use of difficult-to-recycle blended materials is rapidly growing. If the lack of recycling technology and production trend for fiber blends remains, a volume of more than 3400 Mt of waste will have been accumulated by 2030. This work highlights the urgent need to transform the textile industry from a biocatalytic perspective.
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| 17. |
- Landberg, Niklas, et al.
(author)
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CD36 defines primitive chronic myeloid leukemia cells less responsive to imatinib but vulnerable to antibody-based therapeutic targeting
- 2018
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 103:3, s. 447-455
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Journal article (peer-reviewed)abstract
- Tyrosine kinase inhibitors (TKIs) are highly effective for the treatment of chronic myeloid leukemia (CML), but very few patients are cured. The major drawbacks regarding TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Herein, we performed ribonucleic acid sequencing of flow-sorted primitive (CD34+CD38low) and progenitor (CD34+CD38+) chronic phase CML cells, and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells. Focusing on novel markers with increased expression on primitive CML cells, we confirmed upregulation of the scavenger receptor CD36 and the leptin receptor by flow cytometry. We also delineate a subpopulation of primitive CML cells expressing CD36 that is less sensitive to imatinib treatment. Using CD36 targeting antibodies, we show that the CD36 positive cells can be targeted and killed by antibody-dependent cellular cytotoxicity. In summary, CD36 defines a subpopulation of primitive CML cells with decreased imatinib sensitivity that can be effectively targeted and killed using an anti-CD36 antibody.
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| 18. |
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| 19. |
- Landberg, Åsa, 1963-, et al.
(author)
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En del av verkligheten : om barn, sexuella övergrepp och nätet
- 2017
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Reports (other academic/artistic)abstract
- I den här rapporten sammanfattar vi resultat från olika forskningsstudier. Mycket av materialet är hämtat från en nationell studie som har genomförts av forskare vid Linköpings och Lunds universitet inom ramen för uppdrag som Stiftelsen Allmänna Barnhuset fått av regeringen. Syftet med sammanfattningen är att sprida de mest angelägna forskningsresultaten från studien till en bredare publik.För barn och unga i Sverige idag är nätet en del av verkligheten. De spelar spel, ser filmklipp, lyssnar på musik, tar reda på fakta, läser nyheter, köper och säljer saker, umgås, lära känna nya människor, flirtar, skickar meddelanden, delar foton och filmer…Precis som livet i övrigt rymmer livet på nätet både bra och dåliga fenomen. Och precis som i livet utanför kan barn bli utsatta för sexuella övergrepp på nätet, såväl av andra barn och unga som av vuxna. Det är angeläget att alla som arbetar med barn lär sig mer om nätrelaterade övergrepp. Kunskap behövs för att förebygga och för att ge de barn som ändå utsätts det skydd och den rehabilitering de har rätt till. Sexuella övergrepp kan och ska förebyggas, och arbetet med att förebygga behöver bygga på kunskaper och fakta.Åsa Landberg är legitimerad psykolog, legitimerad psykoterapeut och arbetar för Stiftelsen Allmänna Barnhuset. Linda Jonsson är socionom och lektor i barn- och ungdomspsykiatri vid Barnafrid, Linköpings universitet. Bägge har lång erfarenhet av att möta barn som utsatts för sexuella övergrepp på nätet.
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| 20. |
- Lindahl, Thomas, et al.
(author)
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Overexpression of cyclin E protein is associated with specific mutation types in the p53 gene and poor survival in human breast cancer.
- 2004
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In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 25:3, s. 375-80
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Journal article (peer-reviewed)abstract
- Cyclin E is one of the key regulators of the G(1)/S transition in the cell cycle. Overexpression of cyclin E has been observed in several malignancies and is associated with high proliferation, aberrant expression of other cell cycle regulators and chromosomal instability in vitro. To explore potential associations between cyclin E deregulation and inactivation of the p53 tumor suppressor gene in human breast cancer, we investigated the immunohistochemical expression of cyclin E in paraffin embedded breast cancers from 270 women with known p53 status by cDNA based sequencing of the p53 gene. The breast cancers were divided into three subgroups according to the percentage of cyclin E-positive cells. One hundred and seventy-one patients (63%) had low cyclin E, 72 (27%) medium and 27 (10%) had high cyclin E content. Fifty-six percent (15/27) of the breast cancers with high cyclin E had p53 gene mutations, compared with 14% (24/171) of those with low cyclin E content (P < 0.0001). In p53 mutated breast cancers high cyclin E content was associated with insertions, deletions and nonsense point mutations in the p53 tumor suppressor gene, whereas low cyclin E was linked to p53 missense point mutations. We also observed statistically significant associations between a high cyclin E content and aneuploidy, high S phase, larger tumor size, estrogen receptor negativity, presence of axillary node metastases and high tumor grade. High cyclin E content was associated with poor overall survival in univariate and multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.3-4.5). In summary, our findings demonstrate that overexpression of cyclin E is associated with an aggressive tumor phenotype and specific types of p53 mutations.
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| 21. |
- Mhd Omar, Nor Adila, et al.
(author)
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Effect of a diet rich in galactose or fructose, with or without fructooligosaccharides, on gut microbiota composition in rats
- 2022
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In: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 9
-
Journal article (peer-reviewed)abstract
- Recent studies suggest that a diet rich in sugars significantly affects the gut microbiota. Adverse metabolic effects of sugars may partly be mediated by alterations of gut microbiota and gut health parameters, but experimental evidence is lacking. Therefore, we investigated the effects of high intake of fructose or galactose, with/without fructooligosaccharides (FOS), on gut microbiota composition in rats and explored the association between gut microbiota and low-grade systemic inflammation. Sprague-Dawley rats (n = 6/group) were fed the following isocaloric diets for 12 weeks (% of the dry weight of the sugars or FOS): (1) starch (control), (2) fructose (50%), (3) galactose (50%), (4) starch+FOS (15%) (FOS control), (5) fructose (50%)+FOS (15%), (6) galactose (50%)+FOS (15%), and (7) starch+olive (negative control). Microbiota composition in the large intestinal content was determined by sequencing amplicons from the 16S rRNA gene; 341F and 805R primers were used to generate amplicons from the V3 and V4 regions. Actinobacteria, Verrucomicrobia, Tenericutes, and Cyanobacteria composition differed between diets. Bifidobacterium was significantly higher in all diet groups where FOS was included. Modest associations between gut microbiota and metabolic factors as well as with gut permeability markers were observed, but no associations between gut microbiota and inflammation markers were observed. We found no coherent effect of galactose or fructose on gut microbiota composition. Added FOS increased Bifidobacterium but did not mitigate potential adverse metabolic effects induced by the sugars. However, gut microbiota composition was associated with several metabolic factors and gut permeability markers which warrant further investigations.
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| 22. |
- Nordin, Elise, 1985, et al.
(author)
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Effects of FODMAPs and Gluten on Gut Microbiota and Their Association with the Metabolome in Irritable Bowel Syndrome: A Double-Blind, Randomized, Cross-Over Intervention Study
- 2023
-
In: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 15:13
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Journal article (peer-reviewed)abstract
- Background: A mechanistic understanding of the effects of dietary treatment in irritable bowel syndrome (IBS) is lacking. Our aim was therefore to investigate how fermentable oligo- di-, monosaccharides, and polyols (FODMAPs) and gluten affected gut microbiota and circulating metabolite profiles, as well as to investigate potential links between gut microbiota, metabolites, and IBS symptoms. Methods: We used data from a double-blind, randomized, crossover study with week-long provocations of FODMAPs, gluten, and placebo in participants with IBS. To study the effects of the provocations on fecal microbiota, fecal and plasma short-chain fatty acids, the untargeted plasma metabolome, and IBS symptoms, we used Random Forest, linear mixed model and Spearman correlation analysis. Results: FODMAPs increased fecal saccharolytic bacteria, plasma phenolic-derived metabolites, 3-indolepropionate, and decreased isobutyrate and bile acids. Gluten decreased fecal isovalerate and altered carnitine derivatives, CoA, and fatty acids in plasma. For FODMAPs, modest correlations were observed between microbiota and phenolic-derived metabolites and 3-indolepropionate, previously associated with improved metabolic health, and reduced inflammation. Correlations between molecular data and IBS symptoms were weak. Conclusions: FODMAPs, but not gluten, altered microbiota composition and correlated with phenolic-derived metabolites and 3-indolepropionate, with only weak associations with IBS symptoms. Thus, the minor effect of FODMAPs on IBS symptoms must be weighed against the effect on microbiota and metabolites related to positive health factors.
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| 23. |
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| 24. |
- Palmnäs, Marie, 1988, et al.
(author)
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Characterization of the Bacterial Composition of 47 Fermented Foods in Sweden
- 2023
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In: Foods. - : MDPI. - 2304-8158. ; 12:20
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Journal article (peer-reviewed)abstract
- Fermentation has long been utilized to preserve and enhance the flavor and nutritional value of foods. Recently, fermented foods have gained popularity, reaching new consumer groups due to perceived health benefits. However, the microbial composition of many fermented foods re-mains unknown. Here, we characterized the bacterial composition, diversity, and richness of 47 fermented foods available in Sweden, including kombucha, water kefir, milk kefir, yogurt, plant-based yogurt alternatives, kimchi, sauerkraut, and fermented vegetables. Via 16S rRNA gene sequencing, we identified 2497 bacteria (amplicon sequence variants). The bacterial composition was strongly associated with the type of fermented food, and lactic acid bacteria and/or acetic acid bacteria dominated most samples. However, each fermented food had a unique composition, with kombucha and water kefir having the highest diversity across and within samples. Few bacteria were abundant in multiple foods and food groups. These were Streptococcus thermophilus in yogurts and plant-based yoghurts; Lactococcus lactis in milk kefirs and one water kefir; and Lactiplantibacillus plantarum in kimchi, sauerkraut, and fermented cucumber. The broad range of fermented foods included in this study and their diverse bacterial communities warrant further investigation into the implications of microbial compositions for product traits and potential impact on human health.
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| 25. |
- Palmnäs, Marie, 1988, et al.
(author)
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The human gut microbiota and glucose metabolism: a scoping review of key bacteria and the potential role of SCFAs
- 2022
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In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 116:4, s. 862-874
-
Journal article (peer-reviewed)abstract
- The gut microbiota plays a fundamental role in human nutrition and metabolism and may have direct implications for type 2 diabetes and associated preconditions. An improved understanding of relations between human gut microbiota and glucose metabolism could lead to novel opportunities for type 2 diabetes prevention, but human observational studies reporting on such findings have not been extensively reviewed. Here, we review the literature on associations between gut microbiota and markers and stages of glucose dysregulation and insulin resistance in healthy adults and in adults with metabolic disease and risk factors. We present the current evidence for identified key bacteria and their potential roles in glucose metabolism independent of overweight, obesity, and metabolic drugs. We provide support for SCFAs mediating such effects and discuss the role of diet, as well as metabolites derived from diet and gut microbiota interactions. From 5983 initially identified PubMed records, 45 original studies were eligible and reviewed. alpha Diversity and 45 bacterial taxa were associated with selected outcomes. Six taxa were most frequently associated with glucose metabolism: Akkermansia muciniphila, Bifidobacterium longum, Clostridium leptum group, Faecalibacterium prausnitzii, and Faecalibacterium (inversely associated) and Dorea (directly associated). For Dorea and A. muciniphila, associations were independent of metabolic drugs and body measures. For A. muciniphila and F. prausnitzii, limited evidence supported SCFA mediation of potential effects on glucose metabolism. We conclude that observational studies applying metagenomics sequencing to identify species-level relations are warranted, as are studies accounting for confounding factors and investigating SCFA and postprandial glucose metabolism. Such advances in the field will, together with mechanistic and prospective studies and investigations into diet-gut microbiota interactions, have the potential to bring critical insight into roles of gut microbiota and microbial metabolites in human glucose metabolism and to contribute toward the development of novel prevention strategies for type 2 diabetes, including precision nutrition.
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| 26. |
- Rizzardi, Kristina
(author)
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Epigenetic Regulation of Light and Hormonal Signaling in Arabidopsis thaliana
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Plants are stationary and need to adapt to the environment they live in. Integration of environmental cues, such as changes in light and temperature, can occur either directly or through the action of hormones. Hormone and light signaling leads to rapid changes in gene expression, and eventually changes in protein levels. In this thesis I have studied how the epigenetic regulator TERMINAL FLOWER2 (TFL2) is involved in light and hormonal signaling in the model organism Arabidopsis thaliana (thale cress). TFL2 is the only Arabidopsis homologue of HETEROCHROMATIN PROTEIN1 (HP1). HP1 proteins have been shown to be involved in repressing gene expression by maintaining the tight structure of heterochromatin or by forming a heterochromatin like structure in euchromatic regions. Unlike metazoan HP1 which can be localized both to eu- and heterochromatin, TFL2 is uniquely localized to euchromatin. tfl2 mutants have reduced levels of free auxin and a reduced rate of auxin biosynthesis. TFL2 binds to and promotes spatial and temporal expression of the genes belonging to the YUCCA gene family, which are believed to regulate a rate limiting step in the auxin biosynthesis pathway. Further, TFL2 binds to a subset of Aux/IAA proteins to repress auxin regulated genes involved in ovule and carpel development. In a similar way, TFL2 is also involved in repressing two jasmonate responsive genes, VEGETATIVE STORAGE PROTEIN1 and 2. This TFL2 regulated repression might occur through the interaction with the jasmonate responsive protein JAZ6. In light signaling TFL2 is involved in repressing both phytochrome A and B signaling as the response to red and far red light is enhanced in tfl2 mutants. The shade avoidance response and chloroplast biogenesis are also regulated by TFL2 as the hypocotyls of tfl2 are not able to elongate as wt in shade conditions and greening is delayed upon de-etiolation of tfl2 seedlings. This work shows that TFL2 has a repressive function in auxin, jasmonate and light signaling and for the first time we show that TFL2 is directly involved in promoting gene expression.
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| 27. |
- Rostgaard-Hansen, Agnetha, 1986, et al.
(author)
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Temporal gut microbiota variability and association with dietary patterns : from the one-year observational Diet, cancer, and health - Next generations MAX study
- 2024
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In: American Journal of Clinical Nutrition. - : Elsevier. - 0002-9165 .- 1938-3207. ; 119:4, s. 1015-1026
-
Journal article (peer-reviewed)abstract
- Background: Knowledge about the variability of gut microbiota within an individual over time is important to allow meaningful investigations of the gut microbiota in relation to diet and health outcomes in observational studies. Plant-based dietary patterns have been associated with a lower risk of morbidity and mortality and may alter gut microbiota in a favorable direction.Objectives: To assess the gut microbiota variability during one year and investigate the association between adherence to diet indexes and the gut microbiota in a Danish population.Methods: Four hundred forty-four participants were included in the Diet, Cancer, and Health - Next Generations MAX study (DCH-NG MAX). Stool samples collected up to three times during a year were analyzed by 16S ribosomal ribonucleic acid gene sequencing. Diet was obtained by 24-hour dietary recalls. Intraclass correlation coefficient (ICC) was calculated to assess temporal microbial variability based on 214 individuals. Diet indexes (Nordic, Mediterranean, and plant-based diets) and food groups thereof were associated with gut microbiota using linear regression analyses.Results: We found that 91 out of 234 genera had an ICC >0.5. We identified three subgroups dominated by Bacteroides, Prevotella 9, and Ruminococcaceae and adherence to diet indexes differed between subgroups. Higher adherence to diet indexes was associated with the relative abundance of 22 genera. Across diet indexes, higher intakes of fruit, vegetables, whole grains/cereals, and nuts were most frequently associated with these genera.Conclusions: In the DCH-NG MAX study, 39% of the genera had an ICC >0.5 over one year, suggesting that these genera could be studied with health outcomes in prospective analyses with acceptable precision. Adherence to the Nordic, Mediterranean, and plant-based diets differed between bacterial subgroups and was associated with a higher abundance of genera with fiber-degrading properties. Fruits, vegetables, whole grains/cereals, and nuts were frequently associated with these genera.
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| 28. |
- Rouhi, Mohammad, et al.
(author)
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Assessing models for the prediction of mechanical properties for the recycled short fibre composites
- 2019
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In: Journal of reinforced plastics and composites (Print). - : SAGE Publications. - 0731-6844 .- 1530-7964. ; 38:10, s. 454-466
-
Journal article (peer-reviewed)abstract
- Processing of polymer fibre composites has a remarkable influence on their mechanical performance. These mechanical properties are even more influenced when using recycled reinforcement. Therefore, we place particular attention on the evaluation of micromechanical models to estimate the mechanical properties and compare them against the experimental results of the manufactured composites from recycled carbon fibre material. For the manufacturing process, an epoxy matrix and carbon fibre production cut-offs as reinforcing material are incorporated using a vacuum infusion process. In addition, continuous textile reinforcement in combination with the epoxy matrix is used as reference material to evaluate the degradation of mechanical performance of the recycled composite. The experimental results show higher degradation of the composite strength compared to the stiffness properties. Observations from the modelling also show the same trend as the deviation between the theoretical and experimental results is lower for stiffness comparisons than the strength calculations. Yet still, good mechanical performance for specific applications can be expected from these materials.
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| 29. |
- Rouhi, Mohammad Sadegh, 1983, et al.
(author)
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Large Scale Additive Manufacturing of Recycled Polymer Composites
- 2023
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In: Proceedings of the American Society for Composites - 38th Technical Conference, ASC 2023. - : DEStech Publications. ; , s. 2405-2411
-
Conference paper (peer-reviewed)abstract
- The production of large-scale products is currently undergoing a considerable shift in the manufacturing sector in favor of additive manufacturing (AM). Complex structures and elaborate designs that were previously impossible to produce using conventional manufacturing techniques are now possible thanks to the usage of additive printing technology. At the same time, using recycled materials in the production process has also risen to the top of the industry's priority list as a result of a growing focus on sustainability. In this context, the use of recycled polymer composites in large-scale additive manufacturing (LSAM) is beginning to attract attention from both industry and research. Indeed, recycled polymer composites offer several benefits, including not only lower costs but also significantly reduced environmental impact and improved mechanical properties compared to virgin polymer materials. However, several challenges are still associated with using recycled materials in AM, including issues with material properties and compatibility with the AM process. Perhaps the most difficult polymer for AM is nylon where different grades pose different printing properties and challenges, thus printing large-scale objects in recycled nylon is a challenge that few have taken on. One objective of our project is to improve the properties of recycled polymers for LSAM by investigating how different additives, such as mineral wastes and/or recycled short fibers, influence the LSAM process and the properties of the resulting printed object. One way to achieve this objective is by simulating the AM process where we use ABAQUS AM capabilities that enable us to optimize the process and material parameters. Thermal and mechanical analyses using the element activation technique in ABAQUS AM allow us to implement multi-scale multi-physical models for material and process simulation and ensure that the final product meets the desired mechanical and structural properties. To truly reach a circular economy, a systems-level transformation of manufacturing must be achieved [1]. Our vision is to digitally transform manufacturing by turning recycled polymers and other industrial wastes into secondary raw materials and composites for LSAM of final products. However, further research on different industrial use cases and applications is needed to address the remaining challenges associated with this approach and to fully realize its potential in the manufacturing industry.
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| 30. |
- Skantze, Viktor, 1992, et al.
(author)
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Differential Responders to a Mixed Meal Tolerance Test Associated with Type 2 Diabetes Risk Factors and Gut Microbiota—Data from the MEDGI-Carb Randomized Controlled Trial
- 2023
-
In: Nutrients. - : MDPI. - 2072-6643 .- 2072-6643. ; 15:20
-
Journal article (peer-reviewed)abstract
- The global prevalence of type 2 diabetes mellitus (T2DM) has surged in recent decades, and the identification of differential glycemic responders can aid tailored treatment for the prevention of prediabetes and T2DM. A mixed meal tolerance test (MMTT) based on regular foods offers the potential to uncover differential responders in dynamical postprandial events. We aimed to fit a simple mathematical model on dynamic postprandial glucose data from repeated MMTTs among participants with elevated T2DM risk to identify response clusters and investigate their association with T2DM risk factors and gut microbiota. Data were used from a 12-week multi-center dietary intervention trial involving high-risk T2DM adults, comparing high- versus low-glycemic index foods within a Mediterranean diet context (MEDGICarb). Model-based analysis of MMTTs from 155 participants (81 females and 74 males) revealed two distinct plasma glucose response clusters that were associated with baseline gut microbiota. Cluster A, inversely associated with HbA1c and waist circumference and directly with insulin sensitivity, exhibited a contrasting profile to cluster B. Findings imply that a standardized breakfast MMTT using regular foods could effectively distinguish non-diabetic individuals at varying risk levels for T2DM using a simple mechanistic model.
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| 31. |
- Stenemo, Markus
(author)
-
Molecular Epidemiology of Cardiovascular Disease
- 2019
-
Doctoral thesis (other academic/artistic)abstract
- Cardiovascular disease is a major cause of morbidity and mortality, with increasing prevalence worldwide.Identification of risk markers may enable improved prevention by targeting high-risk individuals, earlier disease diagnosis and treatment, as well as stratification of disease subtypes with different treatment options, thereby minimizing side effects while increasing success rates.The overall aim of this thesis was to investigate associations between proteomic and metabolomic biomarkers, and the development of heart failure and ischemic stroke. Specific objectives were to examine potential causal pathways, and the added value in risk prediction of the identified risk markers.In Studies I–II, we performed proximity extension assay based proteomic profiling of ≥80 circulating proteins in the Swedish cohorts Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS n=901, median age 70), and the Uppsala Longitudinal Study of Adult Men (ULSAM, n=685, median age 77). In Study I, we identified nine proteins involved in apoptosis, inflammation, matrix remodeling, and fibrinolysis associated with incident heart failure, including growth differentiation factor-15 (GDF-15). In Study II, we identified several proteins associated with incident ischemic stroke, including GDF-15. Both studies revealed potential to improve disease risk prediction by using proteomic data.In Study III, we performed mass spectrometry-based metabolomic profiling in plasma or serum samples from PIVUS, ULSAM, and TwinGene (total n=3,924). The metabolites urobilin and sphingomyelin (30:1) were associated with incident heart failure.In Study IV, we followed up on the results of Studies I–II, performing Mendelian randomization analyses (a framework for causal analysis using genetic variants) in 1,053,527 individuals, with 88,448 coronary artery disease cases, 70,305 ischemic stroke cases, and 1,420 heart failure cases. This study supports a causal role of genetically elevated GDF-15 levels in heart failure development, but not in coronary artery disease or ischemic stroke.In conclusion, we identified multiple biomarkers associated with incident heart failure and ischemic stroke, potentially involved in early disease development. We also saw potential to improve disease risk prediction for incident heart failure and ischemic stroke using proteomics data.Our findings encourage further large-scale proteomic, metabolomic, and genetic studies to give new insights into heart failure and stroke pathogenesis.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Verbeek, Else, et al.
(author)
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The gut microbiota and microbial metabolites are associated with tail biting in pigs
- 2021
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11
-
Journal article (peer-reviewed)abstract
- Tail biting is an abnormal behaviour that causes stress, injury and pain. Given the critical role of the gut-microbiota in the development of behavioural problems in humans and animals, the aim of this study was to determine whether pigs that are biters, victims of tail biting or controls (nine matched sets of pigs) have a different microbiota composition, diversity and microbial metabolite profile. We collected faecal and blood samples from each individual for analysis. The gut microbiota composition was most different between the biter and the control pigs, with a higher relative abundance of Firmicutes in tail biter pigs than the controls. Furthermore, we detected differences in faecal and plasma short chain fatty acids (SCFA) profiles between the biter and victim pigs, suggesting physiological differences even though they are kept in the same pen. Thus, in addition to supporting an association between the gut microbiota and tail biting in pigs, this study also provides the first evidence of an association between tail biting and SCFA. Therefore, further research is needed to confirm these associations, to determine causality and to study how the SCFA profiles of an individual play a role in the development of tail biting behaviour.
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| 36. |
- von Palffy, Sofia, et al.
(author)
-
A high-content cytokine screen identifies myostatin propeptide as a positive regulator of primitive chronic myeloid leukemia cells
- 2020
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 105:8, s. 2095-2104
-
Journal article (peer-reviewed)abstract
- Aberrantly expressed cytokines in the bone marrow (BM) niche are increasingly recognized as critical mediators of survival and expansion of leukemic stem cells. To identify regulators of primitive chronic myeloid leukemia (CML) cells, we performed a high-content cytokine screen using primary CD34+ CD38low chronic phase CML cells. Out of the 313 unique human cytokines evaluated, 11 were found to expand cell numbers ≥2-fold in a 7-day culture. Focusing on novel positive regulators of primitive CML cells, the myostatin antagonist myostatin propeptide gave the largest increase in cell expansion and was chosen for further studies. Herein, we demonstrate that myostatin propeptide expands primitive CML and normal BM cells, as shown by increased colony-forming capacity. For primary CML samples, retention of CD34-expression was also seen after culture. Furthermore, we show expression of MSTN by CML mesenchymal stromal cells, and that myostatin propeptide has a direct and instant effect on CML cells, independent of myostatin, by demonstrating binding of myostatin propeptide to the cell surface and increased phosphorylation of STAT5 and SMAD2/3. In summary, we identify myostatin propeptide as a novel positive regulator of primitive CML cells and corresponding normal hematopoietic cells.
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| 37. |
- Ågerstam, Helena, et al.
(author)
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IL1RAP antibodies block IL-1-induced expansion of candidate CML stem cells and mediate cell killing in xenograft models.
- 2016
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 128:23, s. 2683-2693
-
Journal article (peer-reviewed)abstract
- Chronic myeloid leukemia (CML) is currently treated with tyrosine kinase inhibitors, but these do not effectively eliminate the CML stem cells. As a consequence, CML stem cells persist and cause relapse in most patients upon drug discontinuation. Furthermore, no effective therapy exists for the advanced stages of the disease. Interleukin-1 receptor accessory protein (IL1RAP; IL1R3) is a coreceptor of interleukin-1 receptor type 1 and has been found upregulated on CML stem cells. Here, we show that primitive (CD34(+)CD38(-)) CML cells, in contrast to corresponding normal cells, express a functional interleukin-1 (IL-1) receptor complex and respond with NF-κB activation and marked proliferation in response to IL-1. IL1RAP antibodies that inhibit IL-1 signaling could block these effects. In vivo administration of IL1RAP antibodies in mice transplanted with chronic and blast phase CML cells resulted in therapeutic effects mediated by murine effector cells. These results provide novel insights into the role of IL1RAP in CML and a strong rationale for the development of an IL1RAP antibody therapy to target residual CML stem cells.
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