Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Cell-specific immune-modulation of cadmium on murine macrophages and mast cell lines in vitro
García-Mendoza, Diego ; Han, Biyao ; Berg, Hans J.H.J. van den; Brink, Nico W. van den - \ 2019
Journal of Applied Toxicology 39 (2019)7. - ISSN 0260-437X - p. 992 - 1001.
cadmium - glutathione (GSH) - histamine - innate immunity - nitrite - oxidative stress - TNFα

Toxic trace metals are widespread contaminants that are potentially immunotoxic even at environmentally low exposure levels. They can modulate the immunity to infections, e.g., in wildlife species living in contaminated areas. The diverse immune cell types can be differentially affected by the exposure leading to the modulation of specific protective mechanisms. Macrophages and mast cells, part of the innate immune system, trigger immune responses and perform particular effector functions. The present study compared toxicological and functional effects of cadmium in two models of murine macrophages (RAW264.7 and NR8383 cell lines) and two models of murine mast cells (MC/9 and RBL-2H3 cell lines). Cadmium was selected as a model compound because its known potential to induce reactive oxygen species and its relevance as an environmental contaminant. Mechanisms of toxicity, such as redox imbalance and apoptosis induction were measured in stationary cells, while functional outcome effects were measured in activated cells. Cadmium-depleted glutathione antioxidant in all four cell lines tested although reactive oxygen species was not significantly increased. Mast cells had full dose-response depletion of glutathione below cytotoxic levels while in macrophages the depletion was not complete. Functional endpoints tumour necrosis factor-alpha and nitrite production in lipopolysaccharide-activated macrophages were increased by cadmium exposure. In contrast, mast cell lipopolysaccharide-induced tumour necrosis factor-alpha and IgE-mediated histamine release were reduced by cadmium. These data indicate potentially differential effects of cadmium among murine innate immune cell types, where mast cells would be more susceptible to oxidative stress and their function might be at a higher risk to be modulated compared to macrophages.

Decision tree models to classify nanomaterials according to the DF4nanoGrouping scheme
Gajewicz, Agnieszka ; Puzyn, Tomasz ; Odziomek, Katarzyna ; Urbaszek, Piotr ; Haase, Andrea ; Riebeling, Christian ; Luch, Andreas ; Irfan, Muhammad A. ; Landsiedel, Robert ; Zande, Meike van der; Bouwmeester, Hans - \ 2018
Nanotoxicology 12 (2018)1. - ISSN 1743-5390 - p. 1 - 17.
(Q)SAR - categorization - Computational toxicology - grouping - nanomaterials - oxidative stress
To keep pace with its rapid development an efficient approach for the risk assessment of nanomaterials is needed. Grouping concepts as developed for chemicals are now being explored for its applicability to nanomaterials. One of the recently proposed grouping systems is DF4nanoGrouping scheme. In this study, we have developed three structure-activity relationship classification tree models to be used for supporting this system by identifying structural features of nanomaterials mainly responsible for the surface activity. We used data from 19 nanomaterials that were synthesized and characterized extensively in previous studies. Subsets of these materials have been used in other studies (short-term inhalation, protein carbonylation, and intrinsic oxidative potential), resulting in a unique data set for modeling. Out of a large set of 285 possible descriptors, we have demonstrated that only three descriptors (size, specific surface area, and the quantum-mechanical calculated property ‘lowest unoccupied molecular orbital’) need to be used to predict the endpoints investigated. The maximum number of descriptors that were finally selected by the classification trees (CT) was very low– one for intrinsic oxidative potential, two for protein carbonylation, and three for NOAEC. This suggests that the models were well-constructed and not over-fitted. The outcome of various statistical measures and the applicability domains of our models further indicate their robustness. Therefore, we conclude that CT can be a useful tool within the DF4nanoGrouping scheme that has been proposed before.
Data from: Simulated moult reduces flight performance but overlap with breeding does not affect breeding success in a long-distance migrant
Mizumo Tomotani, Barbara ; Muijres, F.T. ; Koelman, Julia ; Casagrande, Stefania ; Visser, Marcel E. - \ 2017
trade-off - pied flycatcher - high-speed camera - parental care - PIT-TAG - oxidative stress - plumage - Ficedula hypoleuca
1. Long-distance migrants are time-constrained as they need to incorporate many annual cycle stages within a year. Migratory passerines moult in the short interval between breeding and migration. To widen this interval, moult may start while still breeding, but this results in flying with moulting wings when food provisioning. 2. We experimentally simulated wing gaps in breeding male pied flycatchers by plucking 2 primary feathers from both wings. We quantified the nest visitations of both parents, proportion of high-quality food brought to the nestlings and adults and nestlings condition. Differences in oxidative damage caused by a possible reduction in flight efficiency were measured in amounts of ROMs and OXY in the blood. We also measured how flight performance was affected with recordings of the male`s escape flight using high-speed cameras. Finally, we collected data on adult survival, clutch size and laying date in the following year. 3. “Plucked” males travelled a 5% shorter distance per wingbeat, showing that our treatment reduced flight performance. In line with this, “plucked” males visited their nests less often. Females of “plucked” males, however, visited the nest more often than controls, and fully compensated their partner’s reduced visitation rate. As a result, there were no differences between treatments in food quality brought to the nest, adult or chick mass or number of successfully fledged chicks. Males did not differ in their oxidative damage or local survival to the following year. In contrast, females paired with plucked males tended to return less often to breed in the next year in comparison to controls, but this difference was not significant. For the birds that did return there were no effects on breeding. 5. Our results reveal that wing gaps in male pied flycatchers reduce their flight performance, but when it occurs during breeding they prioritise their future reproduction by reducing parental care. As a result, there is no apparent detriment to their condition during breeding. Because non-moulting females are able to compensate their partner’s reduced care, there is also no immediate costs to the offspring, but females may pay the cost suffering from a reduced survival.
Sex-specific effects of natural and sexual selection on the evolution of life span and ageing in Drosophila simulans
Archer, C.R. ; Duffy, E. ; Hosken, D.J. ; Mokkonen, M. ; Okada, K. ; Oku, K. ; Sharma, M.D. ; Hunt, J. - \ 2015
Functional Ecology 29 (2015)4. - ISSN 0269-8463 - p. 562 - 569.
extrinsic mortality - oxidative stress - female fitness - history traits - male-sterility - seed beetle - senescence - melanogaster - age - populations
1. Variation in the strength of age-dependent natural selection shapes differences in ageing rates across species and populations. Likewise, sexual selection can promote divergent patterns of senescence across the sexes. However, the effects of these processes on the evolution of ageing have largely been considered independently, and interactions between them are poorly understood. 2. We use experimental evolution to investigate how natural and sexual selection affect life span and ageing in Drosophila simulans. 3. Replicate populations were evolved under lifetime monogamy (relaxed sexual selection) or lifetime polyandry (elevated sexual selection) and at one of two temperatures, 25 °C (relaxed natural selection) or 27 °C (enhanced natural selection), in a fully factorial design. We measured longevity in 150 individually housed flies taken from each of three replicate populations per selection regime. 4. We found that natural and sexual selection affected the evolution of life span via sex-specific effects on different ageing parameters (ageing rate vs. baseline mortality): natural selection reduced the rate of ageing in both sexes but increased male baseline mortality, while sexual selection elevated baseline mortality in both sexes but particularly in males. 5. This means that sexual and natural selection interacted to reduce male life span but acted on female life span by independently affecting particular ageing parameters. Sex-specific effects of sexual and natural selection may help explain the diverse patterns of ageing seen in nature but complicate predictions about how ageing and life span evolve across the sexes.
Prediction of fruit and vegatable intake from biomarkers using individual participant data of diet-controntrolled intervantion studies
Souverein, O.W. ; Vries, J.H.M. de; Freese, R. ; Waltz, B. ; Bub, A. ; Winkels, R.M. ; Voet, H. van der; Boshuizen, H.C. - \ 2015
The British journal of nutrition 113 (2015)9. - ISSN 0007-1145 - p. 1396 - 1409.
food-frequency questionnaire - beta-carotene - plasma carotenoids - homocysteine concentrations - fractional polynomials - lipid-peroxidation - healthy nonsmokers - serum carotenoids - oxidative stress - controlled-trial
Fruit and vegetable consumption produces changes in several biomarkers in blood. The present study aimed to examine the dose–response curve between fruit and vegetable consumption and carotenoid (a-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein and zeaxanthin), folate and vitamin C concentrations. Furthermore, a prediction model of fruit and vegetable intake based on these biomarkers and subject characteristics (i.e. age, sex, BMI and smoking status) was established. Data from twelve diet-controlled intervention studies were obtained to develop a prediction model for fruit and vegetable intake (including and excluding fruit and vegetable juices). The study population in the present individual participant data meta-analysis consisted of 526 men and women. Carotenoid, folate and vitamin C concentrations showed a positive relationship with fruit and vegetable intake. Measures of performance for the prediction model were calculated using cross-validation. For the prediction model of fruit, vegetable and juice intake, the root mean squared error (RMSE) was 258·0 g, the correlation between observed and predicted intake was 0·78 and the mean difference between observed and predicted intake was - 1·7 g (limits of agreement: - 466·3, 462·8 g). For the prediction of fruit and vegetable intake (excluding juices), the RMSE was 201·1 g, the correlation was 0·65 and the mean bias was 2·4 g (limits of agreement: - 368·2, 373·0 g). The prediction models which include the biomarkers and subject characteristics may be used to estimate average intake at the group level and to investigate the ranking of individuals with regard to their intake of fruit and vegetables when validating questionnaires that measure intake.
Sources of variation in innate immunity in great tit nestlings living along a metal pollution gradient: An individual-based approach
Vermeulen, A. ; Müller, W. ; Matson, K.D. ; Tieleman, B.I. ; Bervoets, L. ; Eens, M. - \ 2015
Science of the Total Environment 508 (2015). - ISSN 0048-9697 - p. 297 - 306.
storks ciconia-ciconia - acute-phase responses - parus-major - heavy-metals - tree swallows - insectivorous passerines - reproductive success - tachycineta-bicolor - population-growth - oxidative stress
Excessive deposition of metals in the environment is a well-known example of pollution worldwide. Chronic exposure of organisms to metals can have a detrimental effect on reproduction, behavior, health and survival, due to the negative effects on components of the immune system. However, little is known about the effects of chronic sublethal metal exposure on immunity, especially for wildlife. In our study, we examined the constitutive innate immunity of great tit (Parus major) nestlings (N = 234) living in four populations along a metal pollution gradient. For each nestling, we determined the individual metal concentrations (lead, cadmium, arsenic) present in the red blood cells and measured four different innate immune parameters (agglutination, lysis, haptoglobin concentrations and nitric oxide concentrations) to investigate the relationship between metal exposure and immunological condition. While we found significant differences in endogenous metal concentrations among populations with the highest concentrations closest to the pollution source, we did not observe corresponding patterns in our immune measures. However, when evaluating relationships between metal concentrations and immune parameters at the individual level, we found negative effects of lead and, to a lesser extent, arsenic and cadmium on lysis. In addition, high arsenic concentrations appear to elicit inflammation, as reflected by elevated haptoglobin concentrations. Thus despite the lack of a geographic association between pollution and immunity, this type of association was present at the individual level at a very early life stage. The high variation in metal concentrations and immune measures observed within populations indicates a high level of heterogeneity along an existing pollution gradient. Interestingly, we also found substantial within nest variation, for which the sources remain unclear, and which highlights the need of an individual-based approach.
Linking effects of anthropogenic debris to ecological impacts
Browne, M.A. ; Underwood, A.J. ; Chapman, M.G. ; Williams, R. ; Thompson, R.C. ; Franeker, J.A. van - \ 2015
Proceedings of the Royal Society. B: Biological Sciences 282 (2015)1807. - ISSN 0962-8452
mytilus-edulis l. - marine debris - southern california - plastic ingestion - oxidative stress - atlantic-ocean - oil-spills - seabirds - particles - pacific
Accelerated contamination of habitats with debris has caused increased effort to determine ecological impacts. Strikingly, most work on organisms focuses on sublethal responses to plastic debris. This is controversial because (i) researchers have ignored medical insights about the mechanisms that link effects of debris across lower levels of biological organization to disease and mortality, and (ii) debris is considered non-hazardous by policy-makers, possibly because individuals can be injured or removed from populations and assemblages without ecological impacts. We reviewed the mechanisms that link effects of debris across lower levels of biological organization to assemblages and populations. Using plastic, we show microplastics reduce the ‘health’, feeding, growth and survival of ecosystem engineers. Larger debris alters assemblages because fishing-gear and tyres kill animals and damage habitat-forming plants, and because floating bottles facilitate recruitment and survival of novel taxa. Where ecological linkages are not known, we show how to establish hypothetical links by synthesizing studies to assess the likelihood of impacts. We also consider how population models examine ecological linkages and guide management of ecological impacts. We show that by focusing on linkages to ecological impacts rather than the presence of debris and its sublethal impacts, we could reduce threats posed by debris.
Differences in food intake of tumour-bearing cachectic mice are associated with hypothalamic serotonin signalling
Dwarkasing, J.T. ; Boekschoten, M.V. ; Witkamp, R.F. ; Norren, K. van - \ 2015
Journal of cachexia, sarcopenia and muscle 6 (2015)1. - ISSN 2190-5991 - p. 84 - 94.
integrin-linked kinase - rat skeletal-muscle - oxidative stress - soleus muscle - ubiquitin-proteasome - myoblast differentiation - apoptotic pathways - connective-tissue - tibialis anterior - atrophy
Background. Anorexia is a common symptom among cancer patients and contributes to malnutrition and strongly impinges on quality of life. Cancer-induced anorexia is thought to be caused by an inability of food intake-regulating systems in the hypothalamus to respond adequately to negative energy balance during tumour growth. Here, we show that this impaired response of food-intake control is likely to be mediated by altered serotonin signalling and by failure in post-transcriptional neuropeptide Y (NPY) regulation.MethodsTwo tumour cachectic mouse models with different food intake behaviours were used: a C26-colon adenocarcinoma model with increased food intake and a Lewis lung carcinoma model with decreased food intake. This contrast in food intake behaviour between tumour-bearing (TB) mice in response to growth of the two different tumours was used to distinguish between processes involved in cachexia and mechanisms that might be important in food intake regulation. The hypothalamus was used for transcriptomics (affymetrix chips).ResultsIn both models, hypothalamic expression of orexigenic NPY was significantly higher compared with controls, suggesting that this change does not directly reflect food intake status but might be linked to negative energy balance in cachexia. Expression of genes involved in serotonin signalling showed to be different between C26-TB mice and Lewis lung carcinoma-TB mice and was inversely associated with food intake. In vitro, using hypothalamic cell lines, serotonin repressed neuronal hypothalamic NPY secretion while not affecting messenger NPY expression, suggesting that serotonin signalling can interfere with NPY synthesis, transport, or secretion.ConclusionsAltered serotonin signalling is associated with changes in food intake behaviour in cachectic TB mice. Serotonins' inhibitory effect on food intake under cancer cachectic conditions is probably via affecting the NPY system. Therefore, serotonin regulation might be a therapeutic target to prevent the development of cancer-induced eating disorders.
Authentication of Geographical Origin and Crop System of Grape Juices by Phenolic Compounds and Antioxidant Activity Using Chemometrics
Granato, D. ; Koot, A.H. ; Schnitzler, E. ; Ruth, S.M. van - \ 2015
Journal of Food Science 80 (2015)3. - ISSN 0022-1147 - p. C584 - C593.
in-vitro - red wines - oxidative stress - fruit juices - rats - capacity - vivo - mechanism - profile
The main goal of this work was to propose an authentication model based on the phenolic composition and antioxidant and metal chelating capacities of purple grape juices produced in Brazil and Europe in order to assess their typicality. For this purpose, organic, conventional, and biodynamic grape juices produced in Brazil (n = 65) and in Europe (n = 31) were analyzed and different multivariate class-modeling and classification statistical techniques were employed to differentiate juices based on the geographical origin and crop system. Overall, Brazilian juices, regardless of the crop system adopted, presented higher contents of total phenolic compounds and flavonoids, total monomeric anthocyanins, proanthocyanidins, flavonols, flavanols, cyanidin-3-glucoside, delphinidin-3-glucoside, and malvidin-3,5-glucoside. No differences were observed for trans-resveratrol, malvidin-3-glucoside, and pelargonidin-3-glucoside between countries and among crop systems. A total of 91% of Brazilian and 97% of European juices were adroitly classified using partial least squares discriminant analysis when the producing region was considered (92% efficiency), in which the free-radical scavenging activity toward 2,2-diphenyl-1-picrylhydrazyl, content of total phenolic compounds, gallic acid, and malvidin-3-glucoside were the variables responsible for the classification. Intraregional models based on soft independent modeling of class analogy were able to differentiate organic from conventional Brazilian juices as well as conventional and organic/biodynamic European juices.
Characterization of Conventional, Biodynamic, and Organic Purple Grape Juices by Chemical Markers, Antioxidant Capacity, and Instrumental Taste Profile
Granato, D. ; Margraf, T. ; Brotzakis, I. ; Capuano, E. ; Ruth, S.M. van - \ 2015
Journal of Food Science 80 (2015)1. - ISSN 0022-1147 - p. C55 - C65.
phenolic-compounds - agricultural practices - oxidative stress - fruit juices - geographical origin - polyphenol content - electronic tongue - tomato juices - red wines - chemometrics
The objectives of this study were to characterize organic, biodynamic, and conventional purple grape juices (n = 31) produced in Europe based on instrumental taste profile, antioxidant activity, and some chemical markers and to propose a multivariate statistical model to analyze their quality and try to classify the samples from the 3 different crop systems. Results were subjected to ANOVA, correlation, and regression analysis, principal component analysis (PCA), hierarchical cluster analysis (HCA), soft independent modeling of class analogy (SIMCA), and partial least-squares discriminant analysis (PLSDA). No statistical significant differences (P > 0.05) were observed among juices from the 3 crop systems. Using PCA and HCA, no clear separation among crop systems was observed, corroborating the ANOVA data. However, PCA showed that the producing region highly affects the chemical composition, electronic tongue parameters, and bioactivity of grape juices. In this sense, when organic and biodynamic were grouped as “nonconventional” juices, SIMCA model was able to discriminate 12 out of 13 organic/biodynamic juices and 17 out of 18 conventional juices, presenting an efficiency of 93.5%, while 11 out of 13 non-conventional and 100% conventional grape juices were correctly classified using PLSDA. The use of electronic tongue and the determination of antioxidant properties and major phenolic compounds have shown to be a quick and accurate analytical approach to assess the quality of grape juices.
Peripheral blood mononuclear cells as a source to detect markers of homeostatic alterations caused by the intake of diets with an unbalanced macronutrient composition
Diaz-Rua, R. ; Keijer, J. ; Caimari, A. ; Schothorst, E.M. van; Oliver, P. ; Palou, A. - \ 2015
Journal of Nutritional Biochemistry 26 (2015)4. - ISSN 0955-2863 - p. 398 - 407.
high-fat-diet - high-protein diet - gene-expression profiles - preadipocyte factor-i - beta-casein 1-28 - insulin-resistance - oxidative stress - adipose-tissue - antigen presentation - energy homeostasis
Peripheral blood mononuclear cells (PBMC) are accessible in humans and their gene expression pattern was shown to reflect overall physiological response of the body to a specific stimulus, such as diet. We aimed to study the impact of sustained intake (4 months) of diets with an unbalanced macronutrient proportion (rich in fat or protein) administered isocalorically to a balanced control diet, as physiological stressors on PBMC whole genome gene expression in rats, to better understand the effects of these diets on metabolism and health and to identify biomarkers of nutritional imbalance. Dietary macronutrient composition (mainly increased protein content) altered PBMC gene expression, with genes involved in immune response being the most affected. Intake of a high-fat (HF) diet decreased the expression of genes related to antigen recognition/presentation, whereas the high-protein (HP) diet increased the expression of these genes and of genes involved in cytokine signaling and immune system maturation/activation. Key energy homeostasis genes (mainly related to lipid metabolism) were also affected, reflecting an adaptive response to the diets. Moreover, HF diet feeding impaired expression of genes involved in redox balance regulation. Finally, we identified a common gene expression signature of 7 genes whose expression changed in the same direction in response to the intake of both diets. These genes, individually or together, constitute a potential risk marker of diet macronutrient imbalance. In conclusion, we newly show that gene expression analysis in PBMC allows detection of diet-induced physiological deviations that distinguish from a diet with a proper and equilibrated macronutrient composition.
Regenerative toxicology: the role of stem cells in the development of chronic toxicities
Canovas-Jorda, D. ; Louisse, J. ; Pistollato, F. ; Zagoura, D. ; Bremer, S. - \ 2014
Expert Opinion on Drug Metabolism and Toxicology 10 (2014)1. - ISSN 1742-5255 - p. 39 - 50.
hippocampal synaptic plasticity - hepatic progenitor cells - chronic liver-injury - adult neurogenesis - in-vitro - propofol anesthesia - alagille-syndrome - ductular reaction - adjuvant therapy - oxidative stress
Introduction: Human stem cell lines and their derivatives, as alternatives to the use of animal cells or cancer cell lines, have been widely discussed as cellular models in predictive toxicology. However, the role of stem cells in the development of long-term toxicities and carcinogenesis has not received great attention so far, despite growing evidence indicating the relationship of stem cell damage to adverse effects later in life. However, testing this in vitro is a scientific/technical challenge in particular due to the complex interplay of factors existing under physiological conditions. Current major research programs in stem cell toxicity are not aiming to demonstrate that stem cells can be targeted by toxicants. Therefore, this knowledge gap needs to be addressed in additional research activities developing technical solutions and defining appropriate experimental designs. Areas covered: The current review describes selected examples of the role of stem cells in the development of long-term toxicities in the brain, heart or liver and in the development of cancer. Expert opinion: The presented examples illustrate the need to analyze the contribution of stem cells to chronic toxicity in order to make a final conclusion whether stem cell toxicities are an underestimated risk in mechanism-based safety assessments. This requires the development of predictive in vitro models allowing the assessment of adverse effects to stem cells on chronic toxicity and carcinogenicity.
Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)
Aleksandrova, K. ; Jenab, M. ; Bueno-de-Mesquita, H.B. ; Fedirko, V. ; Kaaks, R. ; Lukanova, A. ; Duijnhoven, F.J.B. van - \ 2014
European Journal of Epidemiology 29 (2014)4. - ISSN 0393-2990 - p. 261 - 275.
soluble leptin receptor - density-lipoprotein cholesterol - c-reactive protein - insulin-resistance - oxidative stress - hdl-cholesterol - multiple imputation - plasma adiponectin - binding-proteins - adipose-tissue
A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development.
Plasma and dietary carotenoids and vitamines A,C and E and the risk of colon and rectal cancer in the European prospective investigation into cancer and nutrition
Leenders, M. ; Leufkens, A.M. ; Siersema, P.D. ; Duijnhoven, F.J.B. van; Vrieling, A. ; Hulshof, P.J.M. - \ 2014
International Journal of Cancer 135 (2014)12. - ISSN 0020-7136 - p. 2930 - 2939.
serum alpha-tocopherol - colorectal-cancer - oxidative stress - physical-activity - epic project - antioxidants - retinol - health - cohort - biomarkers
Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was examined in this case-control study, nested within the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of carotenoids (alpha- and beta-carotene, canthaxanthin, beta-cryptoxanthin, lutein, lycopene, zeaxanthin) and vitamins A (retinol), C and E (alpha-, beta- and gamma-and delta-tocopherol) and dietary consumption of beta-carotene and vitamins A, C and E were determined in 898 colon cancer cases, 501 rectal cancer cases and 1,399 matched controls. Multivariable conditional logistic regression models were performed to estimate incidence rate ratios (IRR) and corresponding 95% confidence intervals (CIs). An association was observed between higher prediagnostic plasma retinol concentration and a lower risk of colon cancer (IRR for highest quartile = 0.63, 95% CI: 0.46, 0.87, p for trend = 0.01), most notably proximal colon cancer (IRR for highest quartile = 0.46, 95% CI: 0.27, 0.77, p for trend = 0.01). Additionally, inverse associations for dietary beta-carotene and dietary vitamins C and E with (distal) colon cancer were observed. Although other associations were suggested, there seems little evidence for a role of these selected compounds in preventing CRC through their antioxidative properties.
Comparative effects of zinc oxide nanoparticles and dissolved zinc on zebrafish embryos and eleuthero-embryos: Importance of zinc ions
Brun, N.R. ; Lenz, M. ; Wehrli, B. ; Fent, K. - \ 2014
Science of the Total Environment 476-477 (2014). - ISSN 0048-9697 - p. 657 - 666.
in-vitro evaluation - zno nanoparticles - oxidative stress - fresh-water - aggregation kinetics - silver nanoparticles - cell-line - bulk zno - toxicity - nanomaterials
The increasing use of zinc oxide nanoparticles (nZnO) and their associated environmental occurrence make it necessary to assess their potential effects on aquatic organisms. Upon water contact, nZnO dissolve partially to zinc (Zn(II)). To date it is not yet completely understood, whether effects of nZnO are solely or partly due to dissolved Zn(II). Here we compare potential effects of 0.2, 1 and 5 mg/L nZnO and corresponding concentrations of released Zn(II) by water soluble ZnCl2 to two development stages of zebrafish, embryos and eleuthero-embryos, by analysing expressional changes by RT-qPCR. Another objective was to assess uptake and tissue distribution of Zn(II). Laser ablation-ICP-MS analysis demonstrated that uptake and tissue distribution of Zn(II) were identical for nZnO and ZnCl2 in eleuthero-embryos. Zn(II) was found particularly in the retina/pigment layer of eyes and brain. Both nZnO and dissolved Zn(II) derived from ZnCl2 had similar inhibiting effects on hatching, and they induced similar expressional changes of target genes. At 72 hours post fertilization (hpf), both nZnO and Zn(II) delayed hatching at all doses, and inhibited hatching at 1 and 5 mg/L at 96 hpf. Both nZnO and Zn(II) lead to induction of metallothionein (mt2) in both embryos and eleuthero-embryos at all concentrations. Transcripts of oxidative stress related genes cat and Cu/Zn sod were also altered. Moreover, we show for the first time that nZnO exposure results in transcriptional changes of pro-inflammatory cytokines IL-1ß and TNFa. Overall, transcriptional alterations were higher in embryos than eleuthero-embryos. The similarities of the effects lead to the conclusion that effects of nZnO are mainly related to the release of Zn(II).
Mechanisms involved in apoptosis of carp leukocytes upon in vitro and in vivo immunostimulation
Kepka, M. ; Verburg-van Kemenade, B.M.L. ; Homa, J. ; Chadzinska, M.K. - \ 2014
Fish and Shellfish Immunology 39 (2014)2. - ISSN 1050-4648 - p. 386 - 395.
cytochrome-c release - molecular-cloning - cyprinus-carpio - nitric-oxide - transgenic zebrafish - signal-transduction - ceramide generation - respiratory burst - human neutrophils - oxidative stress
During inflammation leukocyte activity must be carefully regulated, as high concentrations and/or prolonged action of pro-inflammatory mediators e.g. reactive oxygen species (ROS) can be detrimental not only for pathogens but also for host tissues. Programmed cell death – apoptosis is a most effective regulatory mechanism for down regulation of leukocyte activity, but little is known about this process in fish. We aimed to reveal the mechanisms of initiation and regulation of apoptosis in carp neutrophilic granulocytes and macrophages. During zymosan-induced peritonitis in carp, activated inflammatory neutrophilic granulocytes and monocytes/macrophages died by apoptosis. This correlated with a strong production of ROS, but pretreatment of the fish with NADPH oxidase inhibitor only slightly decreased late apoptosis. Interestingly in vitro incubation with zymosan or phorbol ester, but not lipopolisaccharide and poli I:C induced apoptosis of head kidney neutrophilic granulocytes. This coincided with loss of mitochondrial membrane potential. Moreover, in zymosan-stimulated neutrophilic granulocytes NADPH oxidase inhibitor not only reduced the production of ROS but also apoptosis. A similar effect was not observed in cells stimulated with phorbol ester, where DPI reduced ROS production, but not apoptosis. In PMA-stimulated neutrophilic granulocytes both the respiratory burst and apoptosis were reduced by protein kinase inhibitor. Furthermore, a short neutrophil stimulation either with PMA or with zymosan did induce caspase-independent apoptosis. These results show that in carp, apoptosis is an important regulatory process during in vitro and in vivo immunostimulation. In neutrophils, protein kinase, but not NADPH oxidase, is involved in PMA-induced apoptosis while apoptosis induced by zymosan is ROS-dependent.
Transcriptional coordination between leaf cell differentiation and chloroplast development established by TCP20 and theand chloroplast development established by TCP20 and theand chloroplast development established by TCP20 and the subgroup Ib bHLH transcription factors
Andriankaja, M.E. ; Danisman, S.D. ; Mignolet-Spruyt, L.F. ; Claeys, H. ; Kochanke, I. ; Vermeersch, M. ; Milde, L. De; Bodt, S. De; Storme, V. ; Skirycz, A. ; Maurer, F. ; Bauer, P. ; Mühlenbock, P. ; Breusegem, F. Van; Angenent, G.C. ; Immink, R.G.H. ; Inzé, D. - \ 2014
Plant Molecular Biology 85 (2014)3. - ISSN 0167-4412 - p. 233 - 245.
iron-deficiency responses - arabidopsis-thaliana - plant-growth - gene-expression - chromatin immunoprecipitation - metal transporter - oxidative stress - circadian clock - pale cress - in-vivo
The establishment of the photosynthetic apparatus during chloroplast development creates a high demand for iron as a redox metal. However, iron in too high quantities becomes toxic to the plant, thus plants have evolved a complex network of iron uptake and regulation mechanisms. Here, we examined whether four of the subgroup Ib basic helix-loop-helix transcription factors (bHLH38, bHLH39, bHLH100, bHLH101), previously implicated in iron homeostasis in roots, also play a role in regulating iron metabolism in developing leaves. These transcription factor genes were strongly up-regulated during the transition from cell proliferation to expansion, and thus sink-source transition, in young developing leaves of Arabidopsis thaliana. The four subgroup Ib bHLH genes also showed reduced expression levels in developing leaves of plants treated with norflurazon, indicating their expression was tightly linked to the onset of photosynthetic activity in young leaves. In addition, we provide evidence for a mechanism whereby the transcriptional regulators SAC51 and TCP20 antagonistically regulate the expression of these four subgroup Ib bHLH genes. A loss-offunction mutant analysis also revealed that single mutants of bHLH38, bHLH39, bHLH100, and bHLH101 developed smaller rosettes than wild-type plants in soil. When grown in agar plates with reduced iron concentration, triple bhlh39 bhlh100 bhlh101 mutant plants were smaller than wildtype plants. However, measurements of the iron content in single and multiple subgroup Ib bHLH genes, as well as transcript profiling of iron response genes during early leaf development, do not support a role for bHLH38, bHLH39, bHLH100, and bHLH101 in iron homeostasis during early leaf development.
Model Steatogenic Compounds (Amiodarone, Valproic Acid, and Tetracycline) Alter Lipid Metabolism by Different Mechanisms in Mouse Liver Slices
Szalowska, E. ; Burg, B. van der; Man, H.Y. ; Hendriksen, P.J.M. ; Peijnenburg, A.A.C.M. - \ 2014
PLoS ONE 9 (2014)1. - ISSN 1932-6203 - 15 p.
gene-expression - rat-liver - hepatic steatosis - heparg cells - mitochondrial dysfunction - therapeutic targets - induced cholestasis - oxidative stress - fatty-acids - drug
Although drug induced steatosis represents a mild type of hepatotoxicity it can progress into more severe non-alcoholic steatohepatitis. Current models used for safety assessment in drug development and chemical risk assessment do not accurately predict steatosis in humans. Therefore, new models need to be developed to screen compounds for steatogenic properties. We have studied the usefulness of mouse precision-cut liver slices (PCLS) as an alternative to animal testing to gain more insight into the mechanisms involved in the steatogenesis. To this end, PCLS were incubated 24 h with the model steatogenic compounds: amiodarone (AMI), valproic acid (VA), and tetracycline (TET). Transcriptome analysis using DNA microarrays was used to identify genes and processes affected by these compounds. AMI and VA upregulated lipid metabolism, whereas processes associated with extracellular matrix remodelling and inflammation were downregulated. TET downregulated mitochondrial functions, lipid metabolism, and fibrosis. Furthermore, on the basis of the transcriptomics data it was hypothesized that all three compounds affect peroxisome proliferator activated-receptor (PPAR) signaling. Application of PPAR reporter assays classified AMI and VA as PPAR¿ and triple PPARa/(ß/d)/¿ agonist, respectively, whereas TET had no effect on any of the PPARs. Some of the differentially expressed genes were considered as potential candidate biomarkers to identify PPAR agonists (i.e. AMI and VA) or compounds impairing mitochondrial functions (i.e. TET). Finally, comparison of our findings with publicly available transcriptomics data showed that a number of processes altered in the mouse PCLS was also affected in mouse livers and human primary hepatocytes exposed to known PPAR agonists. Thus mouse PCLS are a valuable model to identify early mechanisms of action of compounds altering lipid metabolism
Termination of a toxic Alexandrium bloom with hydrogen peroxide
Burson, A. ; Matthijs, H.C.P. ; Bruijne, W. de; Talens, R. ; Hoogenboom, L.A.P. ; Gerssen, A. ; Visser, P.M. ; Stomp, M. ; Steur, K. ; Scheppingen, Y. van; Huisman, J. - \ 2014
Harmful Algae 31 (2014). - ISSN 1568-9883 - p. 125 - 135.
harmful algal blooms - northern baltic sea - ostenfeldii dinophyceae - water temperature - oxidative stress - shellfish toxins - eutrophication - cyanobacteria - phytoplankton - coastal
The dinoflagellate Alexandrium ostenfeldii is a well-known harmful algal species that can potentially cause paralytic shellfish poisoning (PSP). Usually A. ostenfeldii occurs in low background concentrations only, but in August of 2012 an exceptionally dense bloom of more than 1 million cells L-1 occurred in the brackish Ouwerkerkse Kreek in The Netherlands. The A. ostenfeldii bloom produced both saxitoxins and spirolides, and is held responsible for the death of a dog with a high saxitoxin stomach content. The Ouwerkerkse Kreek routinely discharges its water into the adjacent Oosterschelde estuary, and an immediate reduction of the bloom was required to avoid contamination of extensive shellfish grounds. Previously, treatment of infected waters with hydrogen peroxide (H2O2) successfully suppressed cyanobacterial blooms in lakes. Therefore, we adapted this treatment to eradicate the Alexandrium bloom using a three-step approach. First, we investigated the required H2O2 dosage in laboratory experiments with A. ostenfeldii. Second, we tested the method in a small, isolated canal adjacent to the Ouwerkerkse Kreek. Finally, we brought 50 mg L-1 of H2O2 into the entire creek system with a special device, called a water harrow, for optimal dispersal of the added H2O2. Concentrations of both vegetative cells and pellicle cysts declined by 99.8% within 48 h, and PSP toxin concentrations in the water were reduced below local regulatory levels of 15 µg L-1. Zooplankton were strongly affected by the H2O2 treatment, but impacts on macroinvertebrates and fish were minimal. A key advantage of this method is that the added H2O2 decays to water and oxygen within a few days, which enables rapid recovery of the system after the treatment. This is the first successful field application of H2O2 to suppress a marine harmful algal bloom, although Alexandrium spp. reoccurred at lower concentrations in the following year. The results show that H2O2 treatment provides an effective emergency management option to mitigate toxic Alexandrium blooms, especially when immediate action is required.
Reliability of Selected Antioxidants and Compounds Involved in One-Carbon Metabolism in Two Dutch Cohorts
Leenders, M. ; Ros, M.M. ; Sluijs, I. van der; Boshuizen, H.C. ; Gils, C.H. van; Jansen, E.H.J.M. ; Bueno-de-Mesquita, H.B. - \ 2013
Nutrition and Cancer 65 (2013)1. - ISSN 0163-5581 - p. 17 - 24.
c-reactive protein - nutritional biomarkers - plasma homocysteine - oxidative stress - carotenoids - cancer - serum - tocopherol - retinol - design
Many epidemiological studies assess nutritional status based on single blood measurements, without verifying if these remain reliable over repeated measurements. This study assessed the reliability over a period of 2 to 5yr of plasma carotenoids, vitamin C, retinol, tocopherols, and serum compounds involved in 1-carbon metabolism in a subsample of Dutch participants of European Prospective Investigation into Cancer and Nutrition (EPIC). Blood samples from 38 men from MORGEN-EPIC and 35 women from Prospect-EPIC were collected between 1993 and 1997 and again after 2 to 5yr. The reliability of plasma carotenoids, retinol, vitamin C, and tocopherols, and of serum folate, homocysteine, and vitamins B6 and B12 was estimated using an intraclass correlation coefficient (ICC). Serum homocysteine and vitamin B12 were highly reliable biomarkers, with ICCs of 0.91 and 0.75, respectively. All other analyzed biomarkers had a slight or fair reliability over several years (ICCs ranged from 0.17 to 0.56). Most examined biomarkers showed reliability values that may lead to considerable attenuation of the risk estimate when used as exposure assessment in a risk model. If multiple measurements are not available, the risk estimates can be adjusted for the regression dilution using the ICC as adjustment coefficient.
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