TY  - JOUR
A1  - Kuhn, Eugênia Carla
A1  - Tavares Jacques, Maurício
A1  - Teixeira, Daniela
A1  - Meyer, Sören
A1  - Gralha, Thiago
A1  - Roehrs, Rafael
A1  - Camargo, Sandro
A1  - Schwerdtle, Tanja
A1  - Bornhorst, Julia
A1  - Ávila, Daiana Silva
T1  - Ecotoxicological assessment of Uruguay River and affluents pre- and biomonitoring
JF  - Environmental science and pollution research : ESPR
N2  - Uruguay River is the most important river in western Rio Grande do Sul, separating Brazil from Argentina and Uruguay. However, its pollution is of great concern due to agricultural activities in the region and the extensive use of pesticides. In a long term, this practice leads to environmental pollution, especially to the aquatic system. The objective of this study was to analyze the physicochemical characteristics, metals and pesticides levels in water samples obtained before and after the planting and pesticides' application season from three sites: Uruguay River and two minor affluents, Mezomo Dam and Salso Stream. For biomonitoring, the free-living nematode Caenorhabditis elegans was used, which were exposed for 24 h. We did not find any significant alteration in physicochemical parameters. In the pre- and post-pesticides' samples we observed a residual presence of three pesticides (tebuconazole, imazethapyr, and clomazone) and metals which levels were above the recommended (As, Hg, Fe, and Mn). Exposure to both pre- and post-pesticides' samples impaired C. elegans reproduction and post-pesticides samples reduced worms' survival rate and lifespan. PCA analysis indicated that the presence of metals and pesticides are important variables that impacted C. elegans biological endpoints. Our data demonstrates that Uruguay River and two affluents are contaminated independent whether before or after pesticides' application season. In addition, it reinforces the usefulness of biological indicators, since simple physicochemical analyses are not sufficient to attest water quality and ecological safety.
KW  - Heavy metals
KW  - Pesticides
KW  - Contamination
KW  - Arsenic
KW  - Environmental
KW  - pollution
KW  - Uruguay River
Y1  - 2021
U6  - https://doi.org/10.1007/s11356-020-11986-4
SN  - 0944-1344
SN  - 1614-7499
VL  - 28
IS  - 17
SP  - 21730
EP  - 21741
PB  - Springer
CY  - Berlin ; Heidelberg
ER  - 
TY  - JOUR
A1  - Pan, Yuanwei
A1  - Ma, Xuehua
A1  - Liu, Chuang
A1  - Xing, Jie
A1  - Zhou, Suqiong
A1  - Parshad, Badri
A1  - Schwerdtle, Tanja
A1  - Li, Wenzhong
A1  - Wu, Aiguo
A1  - Haag, Rainer
T1  - Retinoic acid-loaded dendritic polyglycerol-conjugated gold nanostars for targeted photothermal therapy in breast cancer stem cells
JF  - ACS nano
N2  - The existence of cancer stem cells (CSCs) poses a major obstacle for the success of current cancer therapies, especially the fact that non-CSCs can spontaneously turn into CSCs, which lead to the failure of the treatment and tumor relapse. Therefore, it is very important to develop effective strategies for the eradication of the CSCs. In this work, we have developed a CSCs-specific targeted, retinoic acid (RA)-loaded gold nanostars-dendritic polyglycerol (GNSs-dPG) nanoplatform for the efficient eradication of CSCs. The nanocomposites possess good biocompatibility and exhibit effective CSCs-specific multivalent targeted capability due to hyaluronic acid (HA) decorated on the multiple attachment sites of the bioinert dendritic polyglycerol (dPG). With the help of CSCs differentiation induced by RA, the self-renewal of breast CSCs and tumor growth were suppressed by the high therapeutic efficacy of photothermal therapy (PTT) in a synergistic inhibitory manner. Moreover, the stemness gene expression and CSC-driven tumorsphere formation were significantly diminished. In addition, the in vivo tumor growth and CSCs were also effectively eliminated, which indicated superior anticancer activity, effective CSCs suppression, and prevention of relapse. Taken together, we developed a CSCs-specific targeted, RA-loaded GNSs-dPG nanoplatform for the targeted eradication of CSCs and for preventing the relapse.
KW  - cancer stem cells
KW  - dendritic polyglycerol
KW  - gold nanostars
KW  - retinoic acid
KW  - photothermal therapy
Y1  - 2021
U6  - https://doi.org/10.1021/acsnano.1c05452
SN  - 1936-0851
SN  - 1936-086X
VL  - 15
IS  - 9
SP  - 15069
EP  - 15084
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Sellem, Laury
A1  - Antoni, Rona
A1  - Koutsos, Athanasios
A1  - Ozen, Ezgi
A1  - Wong, Gloria
A1  - Ayyad, Hasnaa
A1  - Weech, Michelle
A1  - Schulze, Matthias Bernd
A1  - Wernitz, Andreas
A1  - Fielding, Barbara A.
A1  - Robertson, M. Denise
A1  - Jackson, Kim G.
A1  - Griffin, Bruce A.
A1  - Lovegrove, Julie A.
T1  - Impact of a food-based dietary fat exchange model for replacing dietary saturated with unsaturated fatty acids in healthy men on plasma phospholipids fatty acid profiles and dietary patterns
JF  - European journal of nutrition
N2  - Purpose UK guidelines recommend dietary saturated fatty acids (SFAs) should not exceed 10% total energy (%TE) for cardiovascular disease prevention, with benefits observed when SFAs are replaced with unsaturated fatty acids (UFAs). This study aimed to assess the efficacy of a dietary exchange model using commercially available foods to replace SFAs with UFAs. Methods Healthy men (n = 109, age 48, SD 11 year) recruited to the Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention-1 (RISSCI-1) study (ClinicalTrials.Gov n degrees NCT03270527) followed two sequential 4-week isoenergetic moderate-fat (34%TE) diets: high-SFA (18%TE SFAs, 16%TE UFAs) and low-SFA (10%TE SFAs, 24%TE UFAs). Dietary intakes were assessed using 4-day weighed diet diaries. Nutrient intakes were analysed using paired t-tests, fasting plasma phospholipid fatty acid (PL-FA) profiles and dietary patterns were analysed using orthogonal partial least square discriminant analyses. Results Participants exchanged 10.2%TE (SD 4.1) SFAs for 9.7%TE (SD 3.9) UFAs between the high and low-SFA diets, reaching target intakes with minimal effect on other nutrients or energy intakes. Analyses of dietary patterns confirmed successful incorporation of recommended foods from commercially available sources (e.g. dairy products, snacks, oils, and fats), without affecting participants' overall dietary intakes. Analyses of plasma PL-FAs indicated good compliance to the dietary intervention and foods of varying SFA content. Conclusions RISSCI-1 dietary exchange model successfully replaced dietary SFAs with UFAs in free-living healthy men using commercially available foods, and without altering their dietary patterns. Further intervention studies are required to confirm utility and feasibility of such food-based dietary fat replacement models at a population level.
KW  - Dietary fat composition
KW  - Food-exchange model
KW  - Dietary compliance
KW  - Dairy biomarkers
KW  - Dietary fat replacement
Y1  - 2022
U6  - https://doi.org/10.1007/s00394-022-02910-2
SN  - 1436-6207
SN  - 1436-6215
VL  - 61
IS  - 7
SP  - 3669
EP  - 3684
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Jannasch, Franziska
A1  - Nickel, Daniela
A1  - Schulze, Matthias B.
T1  - The reliability and relative validity of predefined dietary patterns were higher than that of exploratory dietary patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam population
JF  - British journal of nutrition : BJN : an international journal of nutritional science / published on behalf of The Nutrition Society
N2  - The aim of this study was to assess the ability of the FFQ to describe reliable and valid dietary pattern (DP) scores. In a total of 134 participants of the European Prospective Investigation into Cancer and Nutrition-Potsdam study aged 35-67 years, the FFQ was applied twice (baseline and after 1 year) to assess its reliability. Between November 1995 and March 1997, twelve 24-h dietary recalls (24HDR) as reference instrument were applied to assess the validity of the FFQ. Exploratory DP were derived by principal component analyses. Investigated predefined DP were the Alternative Healthy Eating Index (AHEI) and two Mediterranean diet indices. From dietary data of each FFQ, two exploratory DP were retained, but differed in highly loading food groups, resulting in moderate correlations (r 0 center dot 45-0 center dot 58). The predefined indices showed higher correlations between the FFQ (r(AHEI) 0 center dot 62, r(Mediterranean Diet Pyramid Index (MedPyr)) 0 center dot 62 and r(traditional Mediterranean Diet Score (tMDS)) 0 center dot 51). From 24HDR dietary data, one exploratory DP retained differed in composition to the first FFQ-based DP, but showed similarities to the second DP, reflected by a good correlation (r 0 center dot 70). The predefined DP correlated moderately (r 0 center dot 40-0 center dot 60). To conclude, long-term analyses on exploratory DP should be interpreted with caution, due to only moderate reliability. The validity differed extensively for the two exploratory DP. The investigated predefined DP showed a better reliability and a moderate validity, comparable to other studies. Within the two Mediterranean diet indices, the MedPyr performed better than the tMDs in this middle-aged, semi-urban German study population.
KW  - dietary patterns
KW  - reliability
KW  - validity
Y1  - 2020
U6  - https://doi.org/10.1017/S0007114520003517
SN  - 1475-2662
SN  - 0007-1145
VL  - 125
IS  - 11
SP  - 1270
EP  - 1280
PB  - Cambridge University Press
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Varão Moura, Alexandre
A1  - Aparecido Rosini Silva, Alex
A1  - Domingos Santo da Silva, José
A1  - Aleixo Leal Pedroza, Lucas
A1  - Bornhorst, Julia
A1  - Stiboller, Michael
A1  - Schwerdtle, Tanja
A1  - Gubert, Priscila
T1  - Determination of ions in Caenorhabditis elegans by ion chromatography
JF  - Journal of chromatography. B
N2  - The Caenorhabditis elegans (C. elegans) is a model organism that has been increasingly used in health and environmental toxicity assessments. The quantification of such elements in vivo can assist in studies that seek to relate the exposure concentration to possible biological effects. 
Therefore, this study is the first to propose a method of quantitative analysis of 21 ions by ion chromatography (IC), which can be applied in different toxicity studies in C. elegans. 
The developed method was validated for 12 anionic species (fluoride, acetate, chloride, nitrite, bromide, nitrate, sulfate, oxalate, molybdate, dichromate, phosphate, and perchlorate), and 9 cationic species (lithium, sodium, ammonium, thallium, potassium, magnesium, manganese, calcium, and barium). 
The method did not present the presence of interfering species, with R2 varying between 0.9991 and 0.9999, with a linear range from 1 to 100 mu g L-1. 
Limits of detection (LOD) and limits of quantification (LOQ) values ranged from 0.2319 mu g L-1 to 1.7160 mu g L-1 and 0.7028 mu g L-1 to 5.1999 mu g L-1, respectively. 
The intraday and interday precision tests showed an Relative Standard Deviation (RSD) below 10.0 % and recovery ranging from 71.0 % to 118.0 % with a maximum RSD of 5.5 %. 
The method was applied to real samples of C. elegans treated with 200 uM of thallium acetate solution, determining the uptake and bioaccumulated Tl+ content during acute exposure.
KW  - ion chromatography
KW  - C. elegans
KW  - method development
KW  - method validation
KW  - ion quantification
Y1  - 2022
U6  - https://doi.org/10.1016/j.jchromb.2022.123312
SN  - 1570-0232
SN  - 1873-376X
VL  - 1204
PB  - Elsevier
CY  - Amsterdam [u.a.]
ER  - 
TY  - JOUR
A1  - Schmiedeskamp, Amy
A1  - Schreiner, Monika
A1  - Baldermann, Susanne
T1  - Impact of cultivar selection and thermal processing by air drying, air frying, and deep frying on the carotenoid content and stability and antioxidant capacity in carrots (Daucus carota L.)
JF  - Journal of agricultural and food chemistry : a publication of the American Chemical Society
N2  - Epidemiological data suggest that consuming diets rich in carotenoids can reduce the risk of developing several non-communicable diseases. Thus, we investigated the extent to which carotenoid contents of foods can be increased by the choice of food matrices with naturally high carotenoid contents and thermal processing methods that maintain their stability. For this purpose, carotenoids of 15 carrot (Daucus carota L.) cultivars of different colors were assessed with UHPLC-DAD-ToF-MS. Additionally, the processing effects of air drying, air frying, and deep frying on carotenoid stability were applied. Cultivar selection accounted for up to 12.9-fold differences in total carotenoid content in differently colored carrots and a 2.2-fold difference between orange carrot cultivars. Air frying for 18 and 25 min and deep frying for 10 min led to a significant decrease in total carotenoid contents. TEAC assay of lipophilic extracts showed a correlation between carotenoid content and antioxidant capacity in untreated carrots.
KW  - air-dried
KW  - air-fried
KW  - deep-fried
KW  - domestic cooking
KW  - TEAC
KW  - color
KW  - Daucus
KW  - carota L
Y1  - 2022
U6  - https://doi.org/10.1021/acs.jafc.1c05718
SN  - 0021-8561
SN  - 1520-5118
VL  - 70
IS  - 5
SP  - 1629
EP  - 1639
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Jonas, Wenke
A1  - Kluth, Oliver
A1  - Helms, Anett
A1  - Voss, Sarah
A1  - Jahnert, Markus
A1  - Gottmann, Pascal
A1  - Speckmann, Thilo
A1  - Knebel, Birgit
A1  - Chadt, Alexandra
A1  - Al-Hasani, Hadi
A1  - Schürmann, Annette
A1  - Vogel, Heike
T1  - Identification of novel genes involved in hyperglycemia in mice
JF  - International journal of molecular sciences
N2  - Current attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options. 
Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls. 
Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis. 
Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified the calcium-binding protein S100z gene to affect islet cell proliferation as well as apoptosis when overexpressed in MINE cells. In summary, we define S100z as the most striking gene to be causal for the diabetes QTL Nidd13/NZO by affecting beta-cell proliferation and apoptosis. Thus, S100z is an entirely novel diabetes gene regulating islet cell function.
KW  - beta-cell
KW  - diabetes
KW  - proliferation
KW  - apoptosis
KW  - QTL
Y1  - 2022
U6  - https://doi.org/10.3390/ijms23063205
SN  - 1661-6596
SN  - 1422-0067
VL  - 23
IS  - 6
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Fitzner, Maria
A1  - Fricke, Anna
A1  - Schreiner, Monika
A1  - Baldermann, Susanne
T1  - Utilization of regional natural brines for the indoor cultivation of Salicornia europaea
JF  - Sustainability / Multidisciplinary Digital Publishing Institute (MDPI)
N2  - Scaling agriculture to the globally rising population demands new approaches for future crop production such as multilayer and multitrophic indoor farming. Moreover, there is a current trend towards sustainable local solutions for aquaculture and saline agriculture. In this context, halophytes are becoming increasingly important for research and the food industry. As Salicornia europaea is a highly salt-tolerant obligate halophyte that can be used as a food crop, indoor cultivation with saline water is of particular interest. Therefore, finding a sustainable alternative to the use of seawater in non-coastal regions is crucial. Our goal was to determine whether natural brines, which are widely distributed and often available in inland areas, provide an alternative water source for the cultivation of saline organisms. This case study investigated the potential use of natural brines for the production of S. europaea. In the control group, which reflects the optimal growth conditions, fresh weight was increased, but there was no significant difference between the treatment groups comparing natural brines with artificial sea water. A similar pattern was observed for carotenoids and chlorophylls. Individual components showed significant differences. However, within treatments, there were mostly no changes. In summary, we showed that the influence of the different chloride concentrations was higher than the salt composition. Moreover, nutrient-enriched natural brine was demonstrated to be a suitable alternative for cultivation of S. europaea in terms of yield and nutritional quality. Thus, the present study provides the first evidence for the future potential of natural brine waters for the further development of aquaculture systems and saline agriculture in inland regions.
KW  - carotenoids
KW  - glasswort
KW  - land-based aquaculture
KW  - seawater
KW  - phytochemicals
KW  - halophytes
KW  - salt composition
KW  - chlorophylls
KW  - artificial
KW  - salt
KW  - saline agriculture
Y1  - 2021
U6  - https://doi.org/10.3390/su132112105
SN  - 2071-1050
VL  - 13
IS  - 21
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Wigger, Dominik
A1  - Schumacher, Fabian
A1  - Schneider-Schaulies, Sibylle
A1  - Kleuser, Burkhard
T1  - Sphingosine 1-phosphate metabolism and insulin signaling
JF  - Cellular signalling
N2  - Insulin is the main anabolic hormone secreted by 13-cells of the pancreas stimulating the assimilation and storage of glucose in muscle and fat cells. It modulates the postprandial balance of carbohydrates, lipids and proteins via enhancing lipogenesis, glycogen and protein synthesis and suppressing glucose generation and its release from the liver. Resistance to insulin is a severe metabolic disorder related to a diminished response of peripheral tissues to the insulin action and signaling. This leads to a disturbed glucose homeostasis that precedes the onset of type 2 diabetes (T2D), a disease reaching epidemic proportions. A large number of studies reported an association between elevated circulating fatty acids and the development of insulin resistance. The increased fatty acid lipid flux results in the accumulation of lipid droplets in a variety of tissues. However, lipid intermediates such as diacylglycerols and ceramides are also formed in response to elevated fatty acid levels. These bioactive lipids have been associated with the pathogenesis of insulin resistance. More recently, sphingosine 1-phosphate (S1P), another bioactive sphingolipid derivative, has also been shown to increase in T2D and obesity. Although many studies propose a protective role of S1P metabolism on insulin signaling in peripheral tissues, other studies suggest a causal role of S1P on insulin resistance. In this review, we critically summarize the current state of knowledge of S1P metabolism and its modulating role on insulin resistance. A particular emphasis is placed on S1P and insulin signaling in hepatocytes, skeletal muscle cells, adipocytes and pancreatic 13-cells. In particular, modulation of receptors and enzymes that regulate S1P metabolism can be considered as a new therapeutic option for the treatment of insulin resistance and T2D.
KW  - Insulin resistance
KW  - Type 2 diabetes
KW  - Sphingolipids
KW  - Hepatocytes
KW  - Adipocytes
KW  - Skeletal muscle cells
Y1  - 2021
U6  - https://doi.org/10.1016/j.cellsig.2021.109959
SN  - 0898-6568
SN  - 1873-3913
VL  - 82
PB  - Elsevier Science
CY  - Amsterdam [u.a.]
ER  - 
TY  - JOUR
A1  - Dwi Putra, Sulistyo Emantoko
A1  - Reichetzeder, Christoph
A1  - Hasan, Ahmed Abdallah Abdalrahman Mohamed
A1  - Slowinski, Torsten
A1  - Chu, Chang
A1  - Krämer, Bernhard K.
A1  - Kleuser, Burkhard
A1  - Hocher, Berthold
T1  - Being born large for gestational age is associated with increased global placental DNA methylation
JF  - Scientific Reports
N2  - Being born small (SGA) or large for gestational age (LGA) is associated with adverse birth outcomes and metabolic diseases in later life of the offspring. It is known that aberrations in growth during gestation are related to altered placental function. Placental function is regulated by epigenetic mechanisms such as DNA methylation. Several studies in recent years have demonstrated associations between altered patterns of DNA methylation and adverse birth outcomes. However, larger studies that reliably investigated global DNA methylation are lacking. The aim of this study was to characterize global placental DNA methylation in relationship to size for gestational age. Global DNA methylation was assessed in 1023 placental samples by LC-MS/MS. LGA offspring displayed significantly higher global placental DNA methylation compared to appropriate for gestational age (AGA; p<0.001). ANCOVA analyses adjusted for known factors impacting on DNA methylation demonstrated an independent association between placental global DNA methylation and LGA births (p<0.001). Tertile stratification according to global placental DNA methylation levels revealed a significantly higher frequency of LGA births in the third tertile. Furthermore, a multiple logistic regression analysis corrected for known factors influencing birth weight highlighted an independent positive association between global placental DNA methylation and the frequency of LGA births (p=0.001).
KW  - fetal origins hypothesis
KW  - birth weight
KW  - repetitive elements
KW  - glucocorticoid receptor
KW  - nutrient transport
KW  - growth restriction
KW  - later health
KW  - pregnancy
KW  - genes
KW  - patterns
Y1  - 2020
U6  - https://doi.org/10.1038/s41598-020-57725-0
SN  - 2045-2322
VL  - 10
IS  - 1
SP  - 1
EP  - 10
PB  - Springer Nature
CY  - London
ER  - 
TY  - JOUR
A1  - Lang, Judith
A1  - Bohn, Patrick
A1  - Bhat, Hilal
A1  - Jastrow, Holger
A1  - Walkenfort, Bernd
A1  - Cansiz, Feyza
A1  - Fink, Julian
A1  - Bauer, Michael
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Lang, Karl S.
T1  - Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease
JF  - Nature Communications
N2  - Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1(-/-) mice results in replication of HSV-1 and Asah1(-/-) mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol.
KW  - immunology
KW  - infection
KW  - membrane fusion
KW  - phagocytosis
KW  - sphingolipids
Y1  - 2020
U6  - https://doi.org/10.1038/s41467-020-15072-8
SN  - 2041-1723
VL  - 11
IS  - 1
SP  - 1
EP  - 15
PB  - Nature Publishing Group UK
CY  - London
ER  - 
TY  - JOUR
A1  - Harms, Laura M.
A1  - Scalbert, Augustin
A1  - Zamora-Ros, Raul
A1  - Rinaldi, Sabina
A1  - Jenab, Mazda
A1  - Murphy, Neil
A1  - Achaintre, David
A1  - Tjønneland, Anne
A1  - Olsen, Anja
A1  - Overvad, Kim
A1  - Aleksandrova, Krasimira
T1  - Plasma polyphenols associated with lower high-sensitivity C-reactive protein concentrations
BT  - a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
JF  - British Journal of Nutrition
N2  - Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterise the association between plasma concentrations of thirty-five polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis, the OR and 95 % CI of elevated serum hsCRP (>3 mg/l) were calculated within quartiles and per standard deviation higher level of plasma polyphenol concentrations. In a multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per standard deviation) was associated with 29 (95 % CI 50, 1) % lower odds of elevated hsCRP. In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR 0 center dot 66, 95 % CI 0 center dot 46, 0 center dot 96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR 0 center dot 58, 95 % CI 0 center dot 39, 0 center dot 86), 3,4-dihydroxyphenylpropionic acid (OR 0 center dot 63, 95 % CI 0 center dot 46, 0 center dot 87), ferulic acid (OR 0 center dot 65, 95 % CI 0 center dot 44, 0 center dot 96) and caffeic acid (OR 0 center dot 69, 95 % CI 0 center dot 51, 0 center dot 93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR 0 center dot 67, 95 % CI 0 center dot 48, 0 center dot 93). The present study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies.
KW  - polyphenols
KW  - plasma measurements
KW  - C-reactive protein
KW  - inflammation
KW  - chronic diseases
Y1  - 2019
U6  - https://doi.org/10.1017/S0007114519002538
SN  - 0007-1145
SN  - 1475-2662
VL  - 123
IS  - 2
SP  - 198
EP  - 208
PB  - Cambridge University Press
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - McNulty, Margaret A.
A1  - Goupil, Brad A.
A1  - Albarado, Diana C.
A1  - Castaño-Martinez, Teresa
A1  - Ambrosi, Thomas H.
A1  - Puh, Spela
A1  - Schulz, Tim Julius
A1  - Schürmann, Annette
A1  - Morrison, Christopher D.
A1  - Laeger, Thomas
T1  - FGF21, not GCN2, influences bone morphology due to dietary protein restrictions
JF  - Bone Reports
N2  - Background: Dietary protein restriction is emerging as an alternative approach to treat obesity and glucose intolerance because it markedly increases plasma fibroblast growth factor 21 (FGF21) concentrations. Similarly, dietary restriction of methionine is known to mimic metabolic effects of energy and protein restriction with FGF21 as a required mechanism. However, dietary protein has been shown to be required for normal bone growth, though there is conflicting evidence as to the influence of dietary protein restriction on bone remodeling. The purpose of the current study was to evaluate the effect of dietary protein and methionine restriction on bone in lean and obese mice, and clarify whether FGF21 and general control nonderepressible 2 (GCN2) kinase, that are part of a novel endocrine pathway implicated in the detection of protein restriction, influence the effect of dietary protein restriction on bone.

Methods: Adult wild-type (WT) or Fgf21 KO mice were fed a normal protein (18 kcal%; CON) or low protein (4 kcal%; LP) diet for 2 or 27 weeks. In addition, adult WT or Gcn2 KO mice were fed a CON or LP diet for 27 weeks. Young New Zealand obese (NZO) mice were placed on high-fat diets that provided protein at control (16 kcal%; CON), low levels (4 kcal%) in a high-carbohydrate (LP/HC) or high-fat (LP/HF) regimen, or on high-fat diets (protein, 16 kcal%) that provided methionine at control (0.86%; CON-MR) or low levels (0.17%; MR) for up to 9 weeks. Long bones from the hind limbs of these mice were collected and evaluated with micro-computed tomography (mu CT) for changes in trabecular and cortical architecture and mass.

Results: In WT mice the 27-week LP diet significantly reduced cortical bone, and this effect was enhanced by deletion of Fgf21 but not Gcn2. This decrease in bone did not appear after 2 weeks on the LP diet. In addition, Fgf21 KO mice had significantly less bone than their WT counterparts. In obese NZO mice dietary protein and methionine restriction altered bone architecture. The changes were mediated by FGF21 due to methionine restriction in the presence of cystine, which did not increase plasma FGF21 levels and did not affect bone architecture.

Conclusions: This study provides direct evidence of a reduction in bone following long-term dietary protein restriction in a mouse model, effects that appear to be mediated by FGF21.
KW  - dietary restriction
KW  - protein restriction
KW  - FGF21
KW  - GCN2
KW  - microcomputed tomography
Y1  - 2020
U6  - https://doi.org/10.1016/j.bonr.2019.100241
SN  - 2352-1872
VL  - 12
SP  - 1
EP  - 10
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Naser, Eyad
A1  - Kadow, Stephanie
A1  - Schumacher, Fabian
A1  - Mohamed, Zainelabdeen H.
A1  - Kappe, Christian
A1  - Hessler, Gabriele
A1  - Pollmeier, Barbara
A1  - Kleuser, Burkhard
A1  - Arenz, Christoph
A1  - Becker, Katrin Anne
A1  - Gulbins, Erich
A1  - Carpinteiro, Alexander
T1  - Characterization of the small molecule ARC39
BT  - a direct and specific inhibitor of acid sphingomyelinase in vitro[S]
JF  - Journal of Lipid Research
N2  - Inhibition of acid sphingomyelinase (ASM), a lysosomal enzyme that catalyzes the hydrolysis of sphingomyelin into ceramide and phosphorylcholine, may serve as an investigational tool or a therapeutic intervention to control many diseases. Specific ASM inhibitors are currently not sufficiently characterized. Here, we found that 1-aminodecylidene bis-phosphonic acid (ARC39) specifically and efficiently (>90%) inhibits both lysosomal and secretory ASM in vitro. Results from investigating sphingomyelin phosphodiesterase 1 (SMPD1/Smpd1) mRNA and ASM protein levels suggested that ARC39 directly inhibits ASM's catalytic activity in cultured cells, a mechanism that differs from that of functional inhibitors of ASM. We further provide evidence that ARC39 dose- and time-dependently inhibits lysosomal ASM in intact cells, and we show that ARC39 also reduces platelet- and ASM-promoted adhesion of tumor cells. The observed toxicity of ARC39 is low at concentrations relevant for ASM inhibition in vitro, and it does not strongly alter the lysosomal compartment or induce phospholipidosis in vitro. When applied intraperitoneally in vivo, even subtoxic high doses administered short-term induced sphingomyelin accumulation only locally in the peritoneal lavage without significant accumulation in plasma, liver, spleen, or brain. These findings require further investigation with other possible chemical modifications. In conclusion, our results indicate that ARC39 potently and selectively inhibits ASM in vitro and highlight the need for developing compounds that can reach tissue concentrations sufficient for ASM inhibition in vivo.
KW  - sphingolipids
KW  - sphingomyelin
KW  - cerami-des
KW  - lipid metabolism
KW  - enzymology
KW  - lysosome
KW  - lysosomal hydrolases
KW  - acid ceramidase
KW  - bisphosphonates
KW  - functional inhibitors of acid sphin-gomyelinase
KW  - 1-aminodecylidene bis-phosphonic acid
Y1  - 2021
U6  - https://doi.org/10.1194/jlr.RA120000682
SN  - 1539-7262
SN  - 0022-2275
VL  - 61
IS  - 6
SP  - 896
EP  - 910
PB  - American Society for Biochemistry and Molecular Biology
CY  - Bethesda
ER  - 
TY  - JOUR
A1  - Weber, Daniela
A1  - Kochlik, Bastian
A1  - Demuth, Ilja
A1  - Steinhagen-Thiessen, Elisabeth
A1  - Grune, Tilman
A1  - Norman, Kristina
T1  - Plasma carotenoids, tocopherols and retinol
BT  - Association with age in the Berlin Aging Study II
JF  - Redox Biology
N2  - Regular consumption of fruits and vegetables, which is related to high plasma levels of lipid-soluble micro-nutrients such as carotenoids and tocopherols, is linked to lower incidences of various age-related diseases. Differences in lipid-soluble micronutrient blood concentrations seem to be associated with age. Our retrospective analysis included men and women aged 22-37 and 60-85 years from the Berlin Aging Study II. Participants with simultaneously available plasma samples and dietary data were included (n = 1973). Differences between young and old groups were found for plasma lycopene, alpha-carotene, alpha-tocopherol, beta-cryptoxanthin (only in women), and gamma-tocopherol (only in men). beta-Carotene, retinol and lutein/zeaxanthin did not differ between young and old participants regardless of the sex. We found significant associations for lycopene, alpha-carotene (both inverse), alpha-tocopherol, gamma-tocopherol, and beta-carotene (all positive) with age. Adjusting for BMI, smoking status, season, cholesterol and dietary intake confirmed these associations, except for beta-carotene. These micronutrients are important antioxidants and associated with lower incidence of age-related diseases, therefore it is important to understand the underlying mechanisms in order to implement dietary strategies for the prevention of age-related diseases. To explain the lower lycopene and alpha-carotene concentration in older subjects, bioavailability studies in older participants are necessary.
KW  - carotenoids
KW  - tocopherols
KW  - micronutrients
KW  - age
KW  - plasma
KW  - food frequency questionnaire
Y1  - 2020
U6  - https://doi.org/10.1016/j.redox.2020.101461
SN  - 2213-2317
VL  - 32
SP  - 1
EP  - 8
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Olayide, Priscilla
A1  - Large, Annabel
A1  - Stridh, Linnea
A1  - Rabbi, Ismail
A1  - Baldermann, Susanne
A1  - Stavolone, Livia
A1  - Alexandersson, Erik
T1  - Gene expression and metabolite profiling of thirteen Nigerian cassava landraces to elucidate starch and carotenoid composition
JF  - Agronomy
N2  - The prevalence of vitamin A deficiency in sub-Saharan Africa necessitates effective approaches to improve provitamin A content of major staple crops. Cassava holds much promise for food security in sub-Saharan Africa, but a negative correlation between beta-carotene, a provitamin A carotenoid, and dry matter content has been reported, which poses a challenge to cassava biofortification by conventional breeding. To identify suitable material for genetic transformation in tissue culture with the overall aim to increase beta-carotene and maintain starch content as well as better understand carotenoid composition, root and leaf tissues from thirteen field-grown cassava landraces were analyzed for agronomic traits, carotenoid, chlorophyll, and starch content. The expression of five genes related to carotenoid biosynthesis were determined in selected landraces. Analysis revealed a weak negative correlation between starch and beta-carotene content, whereas there was a strong positive correlation between root yield and many carotenoids including beta-carotene. Carotenoid synthesis genes were expressed in both white and yellow cassava roots, but phytoene synthase 2 (PSY2), lycopene-epsilon-cyclase (LCY epsilon), and beta-carotenoid hydroxylase (CHY beta) expression were generally higher in yellow roots. This study identified lines with reasonably high content of starch and beta-carotene that could be candidates for biofortification by further breeding or plant biotechnological means.
KW  - carotenoid biosynthesis
KW  - ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS)
KW  - provitamin A
KW  - biofortification
Y1  - 2020
U6  - https://doi.org/10.3390/agronomy10030424
SN  - 2073-4395
VL  - 10
IS  - 3
SP  - 1
EP  - 16
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Kessler, Katharina
A1  - Hornemann, Silke
A1  - Rudovich, Natalia
A1  - Weber, Daniela
A1  - Grune, Tilman
A1  - Kramer, Achim
A1  - Pfeiffer, Andreas F. H.
A1  - Pivovarova-Ramich, Olga
T1  - Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers
JF  - Nutrients
N2  - Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies.
KW  - meal timing
KW  - saliva
KW  - circadian clock
KW  - adiponectin
KW  - resistin
KW  - visfatin
KW  - insulin
KW  - melatonin
KW  - cortisol
KW  - cytokines
Y1  - 2020
U6  - https://doi.org/10.3390/nu12020340
SN  - 2072-6643
IS  - 2
SP  - 1
EP  - 12
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Fink, Julian
A1  - Schumacher, Fabian
A1  - Schlegel, Jan
A1  - Stenzel, Philipp
A1  - Wigger, Dominik
A1  - Sauer, Markus
A1  - Kleuser, Burkhard
A1  - Seibel, Jürgen
T1  - Azidosphinganine enables metabolic labeling and detection of sphingolipid de novo synthesis
JF  - Organic & biomolecular chemistry : an international journal of synthetic, physical and biomolecular organic chemistry
N2  - Here were report the combination of biocompatible click chemistry of omega-azidosphinganine with fluorescence microscopy and mass spectrometry as a powerful tool to elaborate the sphingolipid metabolism. The azide probe was efficiently synthesized over 13 steps starting from l-serine in an overall yield of 20% and was used for live-cell fluorescence imaging of the endoplasmic reticulum in living cells by bioorthogonal click reaction with a DBCO-labeled fluorophore revealing that the incorporated analogue is mainly localized in the endoplasmic membrane like the endogenous species. A LC-MS(/MS)-based microsomal in vitro assay confirmed that omega-azidosphinganine mimics the natural species enabling the identification and analysis of metabolic breakdown products of sphinganine as a key starting intermediate in the complex sphingolipid biosynthetic pathways. Furthermore, the sphinganine-fluorophore conjugate after click reaction was enzymatically tolerated to form its dihydroceramide and ceramide metabolites. Thus, omega-azidosphinganine represents a useful biofunctional tool for metabolic investigations both by in vivo fluorescence imaging of the sphingolipid subcellular localization in the ER and by in vitro high-resolution mass spectrometry analysis. This should reveal novel insights of the molecular mechanisms sphingolipids and their processing enzymes have e.g. in infection.
Y1  - 2021
U6  - https://doi.org/10.1039/d0ob02592e
SN  - 1477-0520
SN  - 1477-0539
VL  - 19
IS  - 10
SP  - 2203
EP  - 2212
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Bishop, Christopher Allen
A1  - Machate, Tina
A1  - Henning, Thorsten
A1  - Henkel-Oberländer, Janin
A1  - Püschel, Gerhard
A1  - Weber, Daniela
A1  - Grune, Tilman
A1  - Klaus, Susanne
A1  - Weitkunat, Karolin
T1  - Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle
JF  - Nutrition & Diabetes
N2  - Objective: 
Current data regarding the roles of branched-chain amino acids (BCAA) in metabolic health are rather conflicting, as positive and negative effects have been attributed to their intake. 

Methods:
To address this, individual effects of leucine and valine were elucidated in vivo (C57BL/6JRj mice) with a detailed phenotyping of these supplementations in high-fat (HF) diets and further characterization with in vitro approaches (C2C12 myocytes). 

Results:
 Here, we demonstrate that under HF conditions, leucine mediates beneficial effects on adiposity and insulin sensitivity, in part due to increasing energy expenditure-likely contributing partially to the beneficial effects of a higher milk protein intake. On the other hand, valine feeding leads to a worsening of HF-induced health impairments, specifically reducing glucose tolerance/ insulin sensitivity. These negative effects are driven by an accumulation of the valine-derived metabolite 3-hydroxyisobutyrate (3HIB). Higher plasma 3-HIB levels increase basal skeletal muscle glucose uptake which drives glucotoxicity and impairs myocyte insulin signaling. 

Conclusion:
These data demonstrate the detrimental role of valine in an HF context and elucidate additional targetable pathways in the etiology of BCAA-induced obesity and insulin resistance.
Y1  - 2022
U6  - https://doi.org/10.1038/s41387-022-00200-8
SN  - 2044-4052
VL  - 12
IS  - 1
PB  - Nature Publishing Group
CY  - London
ER  - 
TY  - JOUR
A1  - Nicolai, Merle Marie
A1  - Witt, Barbara
A1  - Friese, Sharleen
A1  - Michaelis, Vivien
A1  - Hölz-Armstrong, Lisa
A1  - Martin, Maximilian
A1  - Ebert, Franziska
A1  - Schwerdtle, Tanja
A1  - Bornhorst, Julia
T1  - Mechanistic studies on the adverse effects of manganese overexposure in differentiated LUHMES cells
JF  - Food and chemical toxicology
N2  - Manganese (Mn) is an essential trace element, but overexposure is associated with toxicity and neurological dysfunction. Accumulation of Mn can be observed in dopamine-rich regions of the brain in vivo and Mn-induced oxidative stress has been discussed extensively. Nevertheless, Mn-induced DNA damage, adverse effects of DNA repair, and possible resulting consequences for the neurite network are not yet characterized. For this, LUHMES cells were used, as they differentiate into dopaminergic-like neurons and form extensive neurite networks. Experiments were conducted to analyze Mn bioavailability and cytotoxicity of MnCl2, indicating a dose-dependent uptake and substantial cytotoxic effects. DNA damage, analyzed by means of 8-oxo-7,8-dihydro-2'-guanine (8oxodG) and single DNA strand break formation, showed significant dose- and time-dependent increase of DNA damage upon 48 h Mn exposure. Furthermore, the DNA damage response was increased which was assessed by analytical quantification of poly(ADP-ribosyl)ation (PARylation). Gene expression of the respective DNA repair genes was not significantly affected. Degradation of the neuronal network is significantly altered by 48 h Mn exposure. Altogether, this study contributes to the characterization of Mn-induced neurotoxicity, by analyzing the adverse effects of Mn on genome integrity in dopaminergic-like neurons and respective outcomes.
KW  - Manganese
KW  - Dopaminergic neurons
KW  - DNA integrity
KW  - DNA repair
KW  - Neurodegeneration
KW  - Oxidative stress
KW  - Genotoxicity
Y1  - 2022
U6  - https://doi.org/10.1016/j.fct.2022.112822
SN  - 0278-6915
SN  - 1873-6351
VL  - 161
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Klaus, Susanne
A1  - Igual Gil, Carla
A1  - Ost, Mario
T1  - Regulation of diurnal energy balance by mitokines
JF  - Cellular and molecular life sciences : CMLS
N2  - The mammalian system of energy balance regulation is intrinsically rhythmic with diurnal oscillations of behavioral and metabolic traits according to the 24 h day/night cycle, driven by cellular circadian clocks and synchronized by environmental or internal cues such as metabolites and hormones associated with feeding rhythms. Mitochondria are crucial organelles for cellular energy generation and their biology is largely under the control of the circadian system. Whether mitochondrial status might also feed-back on the circadian system, possibly via mitokines that are induced by mitochondrial stress as endocrine-acting molecules, remains poorly understood. Here, we describe our current understanding of the diurnal regulation of systemic energy balance, with focus on fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), two well-known endocrine-acting metabolic mediators. FGF21 shows a diurnal oscillation and directly affects the output of the brain master clock. Moreover, recent data demonstrated that mitochondrial stress-induced GDF15 promotes a day-time restricted anorexia and systemic metabolic remodeling as shown in UCP1-transgenic mice, where both FGF21 and GDF15 are induced as myomitokines. In this mouse model of slightly uncoupled skeletal muscle mitochondria GDF15 proved responsible for an increased metabolic flexibility and a number of beneficial metabolic adaptations. However, the molecular mechanisms underlying energy balance regulation by mitokines are just starting to emerge, and more data on diurnal patterns in mouse and man are required. This will open new perspectives into the diurnal nature of mitokines and action both in health and disease.
KW  - Mitochondria
KW  - FGF21
KW  - GDF15
KW  - Circadian rhythm
KW  - Hormones
KW  - Nutrition
Y1  - 2021
U6  - https://doi.org/10.1007/s00018-020-03748-9
SN  - 1420-682X
SN  - 1420-9071
VL  - 78
IS  - 7
SP  - 3369
EP  - 3384
PB  - Springer International Publishing AG
CY  - Cham (ZG)
ER  - 
TY  - JOUR
A1  - Schweigert, Florian J.
ED  - Kollodzeiski, Ulrike
ED  - Hafner, Johann Evangelist
T1  - Hässlich aber gut
BT  - Insekten als Nahrungsmittel – Warum wir uns ekeln
JF  - Du sollst nicht essen: Warum Menschen auf Nahrung verzichten – interdisziplinäre Zugänge
Y1  - 2024
SN  - 978-3-98740-007-0
SN  - 978-3-98740-008-7
U6  - https://doi.org/10.5771/9783987400087
SP  - 47
EP  - 59
PB  - Ergon Verlag
CY  - Baden-Baden
ER  - 
TY  - JOUR
A1  - Burkhardt, Wiebke
A1  - Rausch, Theresa
A1  - Klopfleisch, Robert
A1  - Blaut, Michael
A1  - Braune, Annett
T1  - Impact of dietary sulfolipid-derived sulfoquinovose on gut microbiota composition and inflammatory status of colitis-prone interleukin-10-deficient mice
JF  - International journal of medical microbiology : IJMM
N2  - The interplay between diet, intestinal microbiota and host is a major factor impacting health. A diet rich in unsaturated fatty acids has been reported to stimulate the growth of Bilophila wadsworthia by increasing the proportion of the sulfonated bile acid taurocholate (TC). The taurine-induced overgrowth of B. wadsworthia promoted the development of colitis in interleukin-10-deficient (IL-10(-/-)) mice. This study aimed to investigate whether intake of the sulfonates sulfoquinovosyl diacylglycerols (SQDG) with a dietary supplement or their degradation product sulfoquinovose (SQ), stimulate the growth of B. wadsworthia in a similar manner and, thereby, cause intestinal inflammation. Conventional IL-10(-/-) mice were fed a diet supplemented with the SQDG-rich cyanobacterium Arthrospira platensis (Spirulina). SQ or TC were orally applied to conventional IL-10(-/-) mice and gnotobiotic IL-10(-/-) mice harboring a simplified human intestinal microbiota with or without B. wadsworthia. Analyses of inflammatory parameters revealed that none of the sulfonates induced severe colitis, but both, Spirulina and TC, induced expression of pro-inflammatory cytokines in cecal mucosa. Cell numbers of B. wadsworthia decreased almost two orders of magnitude by Spirulina feeding but slightly increased in gnotobiotic SQ and conventional TC mice. Changes in microbiota composition were observed in feces as a result of Spirulina or TC feeding in conventional mice. In conclusion, the dietary sulfonates SQDG and their metabolite SQ did not elicit bacteria-induced intestinal inflammation in IL-10(-/-) mice and, thus, do not promote colitis.
KW  - Sulfonate
KW  - Sulfoquinovose
KW  - Spirulina
KW  - Inflammatory bowel disease
KW  - Bilophila wadsworthia
KW  - Taurocholate
Y1  - 2021
U6  - https://doi.org/10.1016/j.ijmm.2021.151494
SN  - 1618-0607
VL  - 311
IS  - 3
PB  - Elsevier
CY  - München
ER  - 
TY  - JOUR
A1  - Volk, Christin
A1  - Brandsch, Corinna
A1  - Schlegelmilch, Ulf
A1  - Wensch-Dorendorf, Monika
A1  - Hirche, Frank
A1  - Simm, Andreas
A1  - Gargum, Osama
A1  - Wiacek, Claudia
A1  - Braun, Peggy G.
A1  - Kopp, Johannes F.
A1  - Schwerdtle, Tanja
A1  - Treede, Hendrik
A1  - Stangl, Gabriele I.
T1  - Postprandial metabolic response to rapeseed protein in healthy subjects
JF  - Nutrients
N2  - Plant proteins have become increasingly important for ecological reasons. Rapeseed is a novel source of plant proteins with high biological value, but its metabolic impact in humans is largely unknown. A randomized, controlled intervention study including 20 healthy subjects was conducted in a crossover design. All participants received a test meal without additional protein or with 28 g of rapeseed protein isolate or soy protein isolate (control). Venous blood samples were collected over a 360-min period to analyze metabolites; satiety was assessed using a visual analog scale. Postprandial levels of lipids, urea, and amino acids increased following the intake of both protein isolates. The postprandial insulin response was lower after consumption of the rapeseed protein than after intake of the soy protein (p< 0.05), whereas the postmeal responses of glucose, lipids, interleukin-6, minerals, and urea were comparable between the two protein isolates. Interestingly, the rapeseed protein exerted stronger effects on postprandial satiety than the soy protein (p< 0.05). The postmeal metabolism following rapeseed protein intake is comparable with that of soy protein. The favorable effect of rapeseed protein on postprandial insulin and satiety makes it a valuable plant protein for human nutrition.
KW  - rapeseed protein
KW  - soy protein
KW  - postprandial study
KW  - metabolic response
KW  - healthy subjects
Y1  - 2020
U6  - https://doi.org/10.3390/nu12082270
SN  - 2072-6643
VL  - 12
IS  - 8
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Schulze, Matthias Bernd
T1  - Dietary linoleic acid: will modifying dietary fat quality reduce the risk of type 2 diabetes?
JF  - Diabetes care
Y1  - 2021
U6  - https://doi.org/10.2337/dci21-0031
SN  - 0149-5992
SN  - 1935-5548
VL  - 44
IS  - 9
SP  - 1913
EP  - 1915
PB  - American Diabetes Association
CY  - Alexandria
ER  - 
TY  - JOUR
A1  - Jannasch, Franziska
A1  - Nickel, Daniela V.
A1  - Bergmann, Manuela M.
A1  - Schulze, Matthias Bernd
T1  - A new evidence-based diet score to capture associations of food consumption and chronic disease risk
JF  - Nutrients / Molecular Diversity Preservation International (MDPI)
N2  - Previously, the attempt to compile German dietary guidelines into a diet score was predominantly not successful with regards to preventing chronic diseases in the EPIC-Potsdam study. Current guidelines were supplemented by the latest evidence from systematic reviews and expert papers published between 2010 and 2020 on the prevention potential of food groups on chronic diseases such as type 2 diabetes, cardiovascular diseases and cancer. A diet score was developed by scoring the food groups according to a recommended low, moderate or high intake. The relative validity and reliability of the diet score, assessed by a food frequency questionnaire, was investigated. The consideration of current evidence resulted in 10 key food groups being preventive of the chronic diseases of interest. They served as components in the diet score and were scored from 0 to 1 point, depending on their recommended intake, resulting in a maximum of 10 points. Both the reliability (r = 0.53) and relative validity (r = 0.43) were deemed sufficient to consider the diet score as a stable construct in future investigations. This new diet score can be a promising tool to investigate dietary intake in etiological research by concentrating on 10 key dietary determinants with evidence-based prevention potential for chronic diseases.
KW  - diet score
KW  - dietary guidelines
KW  - food groups
KW  - chronic disease
KW  - type 2
KW  - diabetes
KW  - cardiovascular disease
KW  - cancer
KW  - prevention
KW  - reliability;
KW  - validity
Y1  - 2022
U6  - https://doi.org/10.3390/nu14112359
SN  - 2072-6643
VL  - 14
IS  - 11
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Xiong, Chan
A1  - Stiboller, Michael
A1  - Glabonjat, Ronald A.
A1  - Rieger, Jaqueline
A1  - Paton, Lhiam
A1  - Francesconi, Kevin A.
T1  - Transport of arsenolipids to the milk of a nursing mother after consuming salmon fish
JF  - Journal of trace elements in medicine and biology
N2  - Objective: 
We address two questions relevant to infants' exposure to potentially toxic arsenolipids, namely, are the arsenolipids naturally present in fish transported intact to a mother's milk, and what is the efficiency of this transport.

Methods: 
We investigated the transport of arsenolipids and other arsenic species present in fish to mother's milk by analyzing the milk of a single nursing mother at 15 sampling times over a 3-day period after she had consumed a meal of salmon. Total arsenic values were obtained by elemental mass spectrometry, and arsenic species were measured by HPLC coupled to both elemental and molecular mass spectrometry.

Results: 
Total arsenic increased from background levels (0.1 mu g As kg(-1)) to a peak value of 1.72 lig As kg(-1) eight hours after the fish meal. The pattern for arsenolipids was similar to that of total arsenic, increasing from undetectable background levels (< 0.01 mu g As kg(-1)) to a peak after eight hours of 0.45 mu g As kg(-1). Most of the remaining total arsenic in the milk was accounted for by arsenobetaine. The major arsenolipids in the salmon were arsenic hydrocarbons (AsHCs; 55 % of total arsenolipids), and these compounds were also the dominant arsenolipids in the milk where they contributed over 90 % of the total arsenolipids. 

Conclusions:
Our study has shown that ca 2-3 % of arsenic hydrocarbons, natural constituents of fish, can be directly transferred unchanged to the milk of a nursing mother. In view of the potential neurotoxicity of AsHCs, the effects of these compounds on the brain developmental stage of infants need to be investigated.
KW  - human milk
KW  - arsenolipids
KW  - salmon fish
KW  - HPLC/ICPMS
KW  - HPLC/HR-ESMS
Y1  - 2020
U6  - https://doi.org/10.1016/j.jtemb.2020.126502
SN  - 0946-672X
VL  - 61
PB  - Elsevier
CY  - München
ER  - 
TY  - JOUR
A1  - Gellner, Anne-Kathrin
A1  - Sitter, Aileen
A1  - Rackiewicz, Michal
A1  - Sylvester, Marc
A1  - Philipsen, Alexandra
A1  - Zimmer, Andreas
A1  - Stein, Valentin
T1  - Stress vulnerability shapes disruption of motor cortical neuroplasticity
JF  - Translational Psychiatry
N2  - Chronic stress is a major cause of neuropsychiatric conditions such as depression. Stress vulnerability varies individually in mice and humans, measured by behavioral changes. In contrast to affective symptoms, motor retardation as a consequence of stress is not well understood. We repeatedly imaged dendritic spines of the motor cortex in Thy1-GFP M mice before and after chronic social defeat stress. Susceptible and resilient phenotypes were discriminated by symptom load and their motor learning abilities were assessed by a gross and fine motor task. Stress phenotypes presented individual short- and long-term changes in the hypothalamic-pituitary-adrenal axis as well as distinct patterns of altered motor learning. Importantly, stress was generally accompanied by a marked reduction of spine density in the motor cortex and spine dynamics depended on the stress phenotype. We found astrogliosis and altered microglia morphology along with increased microglia-neuron interaction in the motor cortex of susceptible mice. In cerebrospinal fluid, proteomic fingerprints link the behavioral changes and structural alterations in the brain to neurodegenerative disorders and dysregulated synaptic homeostasis. Our work emphasizes the importance of synaptic integrity and the risk of neurodegeneration within depression as a threat to brain health.
Y1  - 2022
U6  - https://doi.org/10.1038/s41398-022-01855-8
SN  - 2158-3188
VL  - 12
IS  - 1
PB  - Nature Publishing Group
CY  - London
ER  - 
TY  - JOUR
A1  - Stepanovska, Bisera
A1  - Zivkovic, Aleksandra
A1  - Enzmann, Gaby
A1  - Tietz, Silvia
A1  - Homann, Thomas
A1  - Kleuser, Burkhard
A1  - Engelhardt, Britta
A1  - Stark, Holger
A1  - Huwiler, Andrea
T1  - Morpholino analogues of fingolimod as novel and selective S1P1 ligands with in vivo efficacy in a mouse model of experimental antigen-induced encephalomyelitis
JF  - International journal of molecular sciences
N2  - Multiple sclerosis (MS) is a chronic, inflammatory, autoimmune disease of the central nervous system (CNS) which is associated with lower life expectancy and disability. The experimental antigen-induced encephalomyelitis (EAE) in mice is a useful animal model of MS, which allows exploring the etiopathogenetic mechanisms and testing novel potential therapeutic drugs. A new therapeutic paradigm for the treatment of MS was introduced in 2010 through the sphingosine 1-phosphate (S1P) analogue fingolimod (FTY720, Gilenya(R)), which acts as a functional S1P(1) antagonist on T lymphocytes to deplete these cells from the blood. In this study, we synthesized two novel structures, ST-1893 and ST-1894, which are derived from fingolimod and chemically feature a morpholine ring in the polar head group. These compounds showed a selective S1P(1) activation profile and a sustained S1P(1) internalization in cultures of S1P(1)-overexpressing Chinese hamster ovary (CHO)-K1 cells, consistent with a functional antagonism. In vivo, both compounds induced a profound lymphopenia in mice. Finally, these substances showed efficacy in the EAE model, where they reduced clinical symptoms of the disease, and, on the molecular level, they reduced the T-cell infiltration and several inflammatory mediators in the brain and spinal cord. In summary, these data suggest that S1P(1)-selective compounds may have an advantage over fingolimod and siponimod, not only in MS but also in other autoimmune diseases.
KW  - ST-1893
KW  - ST-1894
KW  - morpholino analogues of fingolimod
KW  - sphingosine
KW  - 1-phosphate
KW  - immunomodulator
KW  - lymphopenia
KW  - multiple sclerosis
KW  - experimental antigen-induced encephalomyelitis
Y1  - 2020
U6  - https://doi.org/10.3390/ijms21186463
SN  - 1422-0067
VL  - 21
IS  - 18
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Birukov, Anna
A1  - Cuadrat, Rafael R. C.
A1  - Polemiti, Elli
A1  - Eichelmann, Fabian
A1  - Schulze, Matthias Bernd
T1  - Advanced glycation end-products, measured as skin autofluorescence, associate with vascular stiffness in diabetic, pre-diabetic and normoglycemic individuals
BT  - a cross-sectional study
JF  - Cardiovascular diabetology
N2  - Background Advanced glycation end-products are proteins that become glycated after contact with sugars and are implicated in endothelial dysfunction and arterial stiffening. We aimed to investigate the relationships between advanced glycation end-products, measured as skin autofluorescence, and vascular stiffness in various glycemic strata. Methods We performed a cross-sectional analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, comprising n = 3535 participants (median age 67 years, 60% women). Advanced glycation end-products were measured as skin autofluorescence with AGE-Reader (TM), vascular stiffness was measured as pulse wave velocity, augmentation index and ankle-brachial index with Vascular Explorer (TM). A subset of 1348 participants underwent an oral glucose tolerance test. Participants were sub-phenotyped into normoglycemic, prediabetes and diabetes groups. Associations between skin autofluorescence and various indices of vascular stiffness were assessed by multivariable regression analyses and were adjusted for age, sex, measures of adiposity and lifestyle, blood pressure, prevalent conditions, medication use and blood biomarkers. Results Skin autofluorescence associated with pulse wave velocity, augmentation index and ankle-brachial index, adjusted beta coefficients (95% CI) per unit skin autofluorescence increase: 0.38 (0.21; 0.55) for carotid-femoral pulse wave velocity, 0.25 (0.14; 0.37) for aortic pulse wave velocity, 1.00 (0.29; 1.70) for aortic augmentation index, 4.12 (2.24; 6.00) for brachial augmentation index and - 0.04 (- 0.05; - 0.02) for ankle-brachial index. The associations were strongest in men, younger individuals and were consistent across all glycemic strata: for carotid-femoral pulse wave velocity 0.36 (0.12; 0.60) in normoglycemic, 0.33 (- 0.01; 0.67) in prediabetes and 0.45 (0.09; 0.80) in diabetes groups; with similar estimates for aortic pulse wave velocity. Augmentation index was associated with skin autofluorescence only in normoglycemic and diabetes groups. Ankle-brachial index inversely associated with skin autofluorescence across all sex, age and glycemic strata. Conclusions Our findings indicate that advanced glycation end-products measured as skin autofluorescence might be involved in vascular stiffening independent of age and other cardiometabolic risk factors not only in individuals with diabetes but also in normoglycemic and prediabetic conditions. Skin autofluorescence might prove as a rapid and non-invasive method for assessment of macrovascular disease progression across all glycemic strata.
KW  - Advanced glycation end-products
KW  - AGE
KW  - Ankle-brachial index
KW  - Augmentation
KW  - index
KW  - Prediabetes
KW  - Glycemia
KW  - Pulse wave velocity
KW  - Skin
KW  - autofluorescence
KW  - Vascular stiffness
Y1  - 2021
U6  - https://doi.org/10.1186/s12933-021-01296-5
SN  - 1475-2840
VL  - 20
IS  - 1
PB  - BioMed Central
CY  - London
ER  - 
TY  - JOUR
A1  - Pedro Ernesto, Pinho Tavares Leal
A1  - da Silva, Alexandre Alves
A1  - Rocha-Gomes, Arthur
A1  - Riul, Tania Regina
A1  - Cunha, Rennan Augusto
A1  - Reichetzeder, Christoph
A1  - Villela, Daniel Campos
T1  - High-salt diet in the pre- and postweaning periods leads to amygdala oxidative stress and changes in locomotion and anxiety-like behaviors of male wistar rats
JF  - Frontiers in behavioral neuroscience
N2  - High-salt (HS) diets have recently been linked to oxidative stress in the brain, a fact that may be a precursor to behavioral changes, such as those involving anxiety-like behavior. However, to the best of our knowledge, no study has evaluated the amygdala redox status after consuming a HS diet in the pre- or postweaning periods. This study aimed to evaluate the amygdala redox status and anxiety-like behaviors in adulthood, after inclusion of HS diet in two periods: preconception, gestation, and lactation (preweaning); and only after weaning (postweaning). Initially, 18 females and 9 male Wistar rats received a standard (n = 9 females and 4 males) or a HS diet (n = 9 females and 5 males) for 120 days. After mating, females continued to receive the aforementioned diets during gestation and lactation. Weaning occurred at 21-day-old Wistar rats and the male offspring were subdivided: control-control (C-C)-offspring of standard diet fed dams who received a standard diet after weaning (n = 9-11), control-HS (C-HS)-offspring of standard diet fed dams who received a HS diet after weaning (n = 9-11), HS-C-offspring of HS diet fed dams who received a standard diet after weaning (n = 9-11), and HS-HS-offspring of HS diet fed dams who received a HS diet after weaning (n = 9-11). At adulthood, the male offspring performed the elevated plus maze and open field tests. At 152-day-old Wistar rats, the offspring were euthanized and the amygdala was removed for redox state analysis. The HS-HS group showed higher locomotion and rearing frequency in the open field test. These results indicate that this group developed hyperactivity. The C-HS group had a higher ratio of entries and time spent in the open arms of the elevated plus maze test in addition to a higher head-dipping frequency. These results suggest less anxiety-like behaviors. In the analysis of the redox state, less activity of antioxidant enzymes and higher levels of the thiobarbituric acid reactive substances (TBARS) in the amygdala were shown in the amygdala of animals that received a high-salt diet regardless of the period (pre- or postweaning). In conclusion, the high-salt diet promoted hyperactivity when administered in the pre- and postweaning periods. In animals that received only in the postweaning period, the addition of salt induced a reduction in anxiety-like behaviors. Also, regardless of the period, salt provided amygdala oxidative stress, which may be linked to the observed behaviors.
KW  - high-sodium
KW  - open-field
KW  - elevated plus-maze
KW  - pre-natal
KW  - post-natal
KW  - redox state
Y1  - 2022
U6  - https://doi.org/10.3389/fnbeh.2021.779080
SN  - 1662-5153
VL  - 15
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Aga-Barfknecht, Heja
A1  - Soultoukis, George A.
A1  - Stadion, Mandy
A1  - Garcia-Carrizo, Francisco
A1  - Jähnert, Markus
A1  - Gottmann, Pascal
A1  - Vogel, Heike
A1  - Schulz, Tim Julius
A1  - Schürmann, Annette
T1  - Distinct adipogenic and fibrogenic differentiation capacities of mesenchymal stromal cells from pancreas and white adipose tissue
JF  - International journal of molecular sciences
N2  - Pancreatic steatosis associates with beta-cell failure and may participate in the development of type-2-diabetes. Our previous studies have shown that diabetes-susceptible mice accumulate more adipocytes in the pancreas than diabetes-resistant mice. In addition, we have demonstrated that the co-culture of pancreatic islets and adipocytes affect insulin secretion. The aim of this current study was to elucidate if and to what extent pancreas-resident mesenchymal stromal cells (MSCs) with adipogenic progenitor potential differ from the corresponding stromal-type cells of the inguinal white adipose tissue (iWAT). miRNA (miRNome) and mRNA expression (transcriptome) analyses of MSCs isolated by flow cytometry of both tissues revealed 121 differentially expressed miRNAs and 1227 differentially expressed genes (DEGs). Target prediction analysis estimated 510 DEGs to be regulated by 58 differentially expressed miRNAs. Pathway analyses of DEGs and miRNA target genes showed unique transcriptional and miRNA signatures in pancreas (pMSCs) and iWAT MSCs (iwatMSCs), for instance fibrogenic and adipogenic differentiation, respectively. Accordingly, iwatMSCs revealed a higher adipogenic lineage commitment, whereas pMSCs showed an elevated fibrogenesis. As a low degree of adipogenesis was also observed in pMSCs of diabetes-susceptible mice, we conclude that the development of pancreatic steatosis has to be induced by other factors not related to cell-autonomous transcriptomic changes and miRNA-based signals.
KW  - MSCs
KW  - fatty pancreas
KW  - WAT
KW  - lineage commitment
KW  - transcriptomics
KW  - miRNAs
Y1  - 2022
U6  - https://doi.org/10.3390/ijms23042108
SN  - 1422-0067
VL  - 23
IS  - 4
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  - 
TY  - JOUR
A1  - Knoche, Lisa
A1  - Lisec, Jan
A1  - Schwerdtle, Tanja
A1  - Koch, Matthias
T1  - LC-HRMS-Based identification of transformation products of the drug salinomycin generated by electrochemistry and liver microsome
JF  - Antibiotics
N2  - The drug salinomycin (SAL) is a polyether antibiotic and used in veterinary medicine as coccidiostat and growth promoter. Recently, SAL was suggested as a potential anticancer drug. However, transformation products (TPs) resulting from metabolic and environmental degradation of SAL are incompletely known and structural information is missing. In this study, we therefore systematically investigated the formation and identification of SAL derived TPs using electrochemistry (EC) in an electrochemical reactor and rat and human liver microsome incubation (RLM and HLM) as TP generating methods. Liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS) was applied to determine accurate masses in a suspected target analysis to identify TPs and to deduce occurring modification reactions of derived TPs. A total of 14 new, structurally different TPs were found (two EC-TPs, five RLM-TPs, and 11 HLM-TPs). The main modification reactions are decarbonylation for EC-TPs and oxidation (hydroxylation) for RLM/HLM-TPs. Of particular interest are potassium-based TPs identified after liver microsome incubation because these might have been overlooked or declared as oxidated sodium adducts in previous, non-HRMS-based studies due to the small mass difference between K and O + Na of 21 mDa. The MS fragmentation pattern of TPs was used to predict the position of identified modifications in the SAL molecule. The obtained knowledge regarding transformation reactions and novel TPs of SAL will contribute to elucidate SAL-metabolites with regards to structural prediction.
KW  - salinomycin
KW  - ionophore antibiotics
KW  - transformation product
KW  - electrochemistry
KW  - rat
KW  - human liver microsomes
KW  - HRMS
Y1  - 2022
U6  - https://doi.org/10.3390/antibiotics11020155
SN  - 2079-6382
VL  - 11
IS  - 2
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Schiborn, Catarina
A1  - Schulze, Matthias Bernd
T1  - Precision prognostics for the development of complications in diabetes
JF  - Diabetologia : journal of the European Association for the Study of Diabetes (EASD)
N2  - Individuals with diabetes face higher risks for macro- and microvascular complications than their non-diabetic counterparts. The concept of precision medicine in diabetes aims to optimise treatment decisions for individual patients to reduce the risk of major diabetic complications, including cardiovascular outcomes, retinopathy, nephropathy, neuropathy and overall mortality. In this context, prognostic models can be used to estimate an individual's risk for relevant complications based on individual risk profiles. This review aims to place the concept of prediction modelling into the context of precision prognostics. As opposed to identification of diabetes subsets, the development of prediction models, including the selection of predictors based on their longitudinal association with the outcome of interest and their discriminatory ability, allows estimation of an individual's absolute risk of complications. As a consequence, such models provide information about potential patient subgroups and their treatment needs. This review provides insight into the methodological issues specifically related to the development and validation of prediction models for diabetes complications. We summarise existing prediction models for macro- and microvascular complications, commonly included predictors, and examples of available validation studies. The review also discusses the potential of non-classical risk markers and omics-based predictors. Finally, it gives insight into the requirements and challenges related to the clinical applications and implementation of developed predictions models to optimise medical decision making.
KW  - Cardiovascular diseases
KW  - Complications in diabetes
KW  - Macrovascular
KW  - complications
KW  - Microvascular complications
KW  - Personalised medicine
KW  - Precision medicine
KW  - Precision prognostics
KW  - Review
KW  - Risk prediction
KW  - Risk
KW  - scores
Y1  - 2022
U6  - https://doi.org/10.1007/s00125-022-05731-4
SN  - 0012-186X
SN  - 1432-0428
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Solger, Franziska
A1  - Kunz, Tobias C.
A1  - Fink, Julian
A1  - Paprotka, Kerstin
A1  - Pfister, Pauline
A1  - Hagen, Franziska
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Seibel, Jürgen
A1  - Rudel, Thomas
T1  - A role of sphingosine in the intracellular survival of Neisseria gonorrhoeae
JF  - Frontiers in Cellular and Infection Microbiology
N2  - Obligate human pathogenic Neisseria gonorrhoeae are the second most frequent bacterial cause of sexually transmitted diseases. These bacteria invade different mucosal tissues and occasionally disseminate into the bloodstream. Invasion into epithelial cells requires the activation of host cell receptors by the formation of ceramide-rich platforms. Here, we investigated the role of sphingosine in the invasion and intracellular survival of gonococci. Sphingosine exhibited an anti-gonococcal activity in vitro. We used specific sphingosine analogs and click chemistry to visualize sphingosine in infected cells. Sphingosine localized to the membrane of intracellular gonococci. Inhibitor studies and the application of a sphingosine derivative indicated that increased sphingosine levels reduced the intracellular survival of gonococci. We demonstrate here, that sphingosine can target intracellular bacteria and may therefore exert a direct bactericidal effect inside cells.
KW  - Neisseria gonorrhoeae
KW  - sphingosine
KW  - sphingolipids
KW  - sphingosine kinases
KW  - invasion
KW  - survival
KW  - click chemistry
Y1  - 2020
U6  - https://doi.org/10.3389/fcimb.2020.00215
SN  - 2235-2988
VL  - 10
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Fechner, Carolin
A1  - Hackethal, Christin
A1  - Höpfner, Tobias
A1  - Dietrich, Jessica
A1  - Bloch, Dorit
A1  - Lindtner, Oliver
A1  - Sarvan, Irmela
T1  - Results of the BfR MEAL Study
BT  - in Germany, mercury is mostly contained in fish and seafood while cadmium, lead, and nickel are present in a broad spectrum of foods
JF  - Food chemistry: X
N2  - The BfR MEAL Study provides representative levels of substances in foods consumed in Germany. Mercury, cadmium, lead, and nickel are contaminants present in foods introduced by environmental and industrial processes. Levels of these elements were investigated in 356 foods. Foods were purchased representatively, prepared as consumed and pooled with similar foods before analysis. Highest mean levels of mercury were determined in fish and seafood, while high levels of cadmium, lead, and nickel were present in cocoa products and legumes, nuts, oilseeds, and spices. The sampling by region, season, and production type showed minor differences in element levels for specific foods, however no tendency over all foods or for some food groups was apparent. The data on mercury, cadmium, lead, and nickel provide a comprehensive basis for chronic dietary exposure assessment of the population in Germany. All levels found were below regulated maximum levels.
KW  - Total diet study
KW  - BfR MEAL Study
KW  - Metals
KW  - Contaminants
KW  - Unprepared and
KW  - prepared foods
KW  - Regionality
KW  - Seasonality
KW  - Organic and conventional type of production
Y1  - 2022
U6  - https://doi.org/10.1016/j.fochx.2022.100326
SN  - 2590-1575
VL  - 14
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Witt, Barbara
A1  - Stiboller, Michael
A1  - Raschke, Stefanie
A1  - Friese, Sharleen
A1  - Ebert, Franziska
A1  - Schwerdtle, Tanja
T1  - Characterizing effects of excess copper levels in a human astrocytic cell line with focus on oxidative stress markers
JF  - Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements, GMS
N2  - Background: Being an essential trace element, copper is involved in diverse physiological processes. However, excess levels might lead to adverse effects. Disrupted copper homeostasis, particularly in the brain, has been associated with human diseases including the neurodegenerative disorders Wilson and Alzheimer?s disease. In this context, astrocytes play an important role in the regulation of the copper homeostasis in the brain and likely in the prevention against neuronal toxicity, consequently pointing them out as a potential target for the neurotoxicity of copper. Major toxic mechanisms are discussed to be directed against mitochondria probably via oxidative stress. However, the toxic potential and mode of action of copper in astrocytes is poorly understood, so far. Methods: In this study, excess copper levels affecting human astrocytic cell model and their involvement in the neurotoxic mode of action of copper, as well as, effects on the homeostasis of other trace elements (Mn, Fe, Ca and Mg) were investigated. Results: Copper induced substantial cytotoxic effects in the human astrocytic cell line following 48 h incubation (EC30: 250 ?M) and affected mitochondrial function, as observed via reduction of mitochondrial membrane potential and increased ROS production, likely originating from mitochondria. Moreover, cellular GSH metabolism was altered as well. Interestingly, not only cellular copper levels were affected, but also the homeostasis of other elements (Ca, Fe and Mn) were disrupted. Conclusion: One potential toxic mode of action of copper seems to be effects on the mitochondria along with induction of oxidative stress in the human astrocytic cell model. Moreover, excess copper levels seem to interact with the homeostasis of other essential elements such as Ca, Fe and Mn. Disrupted element homeostasis might also contribute to the induction of oxidative stress, likely involved in the onset and progression of neurodegenerative disorders. These insights in the toxic mechanisms will help to develop ideas and approaches for therapeutic strategies against copper-mediated diseases.
KW  - Copper
KW  - Astrocytes
KW  - Toxicity
KW  - Mitochondria
KW  - ROS
KW  - Trace elements
Y1  - 2021
U6  - https://doi.org/10.1016/j.jtemb.2021.126711
SN  - 1878-3252
VL  - 65
PB  - Elsevier
CY  - München
ER  - 
TY  - JOUR
A1  - Schell, Mareike
A1  - Wardelmann, Kristina
A1  - Kleinridders, Andre
T1  - Untangling the effect of insulin action on brain mitochondria and metabolism
JF  - Journal of neuroendocrinology
N2  - The regulation of energy homeostasis is controlled by the brain and, besides requiring high amounts of energy, it relies on functional insulin/insulin-like growth factor (IGF)-1 signalling in the central nervous system. This energy is mainly provided by mitochondria in form of ATP. Thus, there is an intricate interplay between mitochondrial function and insulin/IGF-1 action to enable functional brain signalling and, accordingly, propagate a healthy metabolism. To adapt to different nutritional conditions, the brain is able to sense the current energy status via mitochondrial and insulin signalling-dependent pathways and exerts an appropriate metabolic response. However, regional, cell type and receptor-specific consequences of this interaction occur and are linked to diverse outcomes such as altered nutrient sensing, body weight regulation or even cognitive function. Impairments of this cross-talk can lead to obesity and glucose intolerance and are linked to neurodegenerative diseases, yet they also induce a self-sustainable, dysfunctional 'metabolic triangle' characterised by insulin resistance, mitochondrial dysfunction and inflammation in the brain. The identification of causal factors deteriorating insulin action, mitochondrial function and concomitantly a signature of metabolic stress in the brain is of utter importance to offer novel mechanistic insights into development of the continuously rising prevalence of non-communicable diseases such as type 2 diabetes and neurodegeneration. This review aims to determine the effect of insulin action on brain mitochondrial function and energy metabolism. It precisely outlines the interaction and differences between insulin action, insulin-like growth factor (IGF)-1 signalling and mitochondrial function; distinguishes between causality and association; and reveals its consequences for metabolism and cognition. We hypothesise that an improvement of at least one signalling pathway can overcome the vicious cycle of a self-perpetuating metabolic dysfunction in the brain present in metabolic and neurodegenerative diseases.
KW  - brain
KW  - energy homeostasis
KW  - inflammation
KW  - insulin signalling
KW  - metabolism
KW  - mitochondrial function
Y1  - 2021
U6  - https://doi.org/10.1111/jne.12932
SN  - 0953-8194
SN  - 1365-2826
VL  - 33
IS  - 4
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Hackethal, Christin
A1  - Kopp, Johannes Florian
A1  - Sarvan, Irmela
A1  - Schwerdtle, Tanja
A1  - Lindtner, Oliver
T1  - Total arsenic and water-soluble arsenic species in foods of the first German total diet study (BfR MEAL Study)
JF  - Food chemistry
N2  - Arsenic can occur in foods as inorganic and organic forms. Inorganic arsenic is more toxic than most watersoluble organic arsenic compounds such as arsenobetaine, which is presumed to be harmless for humans. Within the first German total diet study, total arsenic, inorganic arsenic, arsenobetaine, dimethylarsinic acid and monomethylarsonic acid were analyzed in various foods. Highest levels of total arsenic were found in fish, fish products and seafood (mean: 1.43 mg kg(-1); n = 39; min-max: 0.01-6.15 mg kg(-1)), with arsenobetaine confirmed as the predominant arsenic species (1.233 mg kg 1; n = 39; min-max: 0.01-6.23 mg kg (1)). In contrast, inorganic arsenic was determined as prevalent arsenic species in terrestrial foods (0.02 mg kg (1); n = 38; min-max: 0-0.11 mg kg (1)). However, the toxicity of arsenic species varies and measurements are necessary to gain information about the composition and changes of arsenic species in foods due to household processing of foods.
KW  - Occurrence data
KW  - Food
KW  - Total arsenic
KW  - Arsenic speciation
KW  - Inductively
KW  - coupled plasma mass spectrometry
Y1  - 2021
U6  - https://doi.org/10.1016/j.foodchem.2020.128913
SN  - 0308-8146
SN  - 1873-7072
VL  - 346
PB  - Elsevier
CY  - Amsterdam [u.a.]
ER  - 
TY  - JOUR
A1  - Raupbach, Jana
A1  - Ott, Christiane
A1  - König, Jeannette
A1  - Grune, Tilman
T1  - Proteasomal degradation of glycated proteins depends on substrate unfolding: Preferred degradation of moderately modified myoglobin
JF  - Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research
N2  - The Maillard reaction generates protein modifications which can accumulate during hyperglycemia or aging and may have inflammatory consequences. The proteasome is one of the major intracellular systems involved in the proteolytic degradation of modified proteins but its role in the degradation of glycated proteins is scarcely studied. In this study, chemical and structural changes of glycated myoglobin were analyzed and its degradation by 20S proteasome was studied. Myoglobin was incubated with physiological (5-10 mM), moderate (50-100 mM) and severe levels (300 mM) of glucose or methylglyoxal (MGO, 50 mM). Glycation increased myoglobin's fluorescence and surface hydrophobicity. Severe glycation generated crosslinked proteins as shown by gel electrophoresis. The concentration of advanced glycation endproducts (AGEs) N-epsilon-carboxymethyl lysine (CML), N-epsilon-carboxyethyl lysine (CEL), methylglyoxal-derived hydroimidazolone-1 (MG-H1), pentosidine and pyrraline was analyzed after enzymatic hydrolysis followed by UPLC-MS/MS. Higher concentrations of glucose increased all analyzed AGEs and incubation with MGO led to a pronounced increase of CEL and MG-H1. The binding of the heme group to apo-myoglobin was decreased with increasing glycation indicating the loss of tertiary protein structure. Proteasomal degradation of modified myoglobin compared to native myoglobin depends on the degree of glycation: physiological conditions decreased proteasomal degradation whereas moderate glycation increased degradation. Severe glycation again decreased proteolytic cleavage which might be due to crosslinking of protein monomers. The activity of the proteasomal subunit beta 5 is influenced by the presence of glycated myoglobin. In conclusion, the role of the proteasome in the degradation of glycated proteins is highly dependent on the level of glycation and consequent protein unfolding.
KW  - Glycation
KW  - Myoglobin
KW  - Heme
KW  - Advanced glycation endproducts
KW  - 20S
KW  - proteasome
Y1  - 2020
U6  - https://doi.org/10.1016/j.freeradbiomed.2019.11.024
SN  - 0891-5849
SN  - 1873-4596
VL  - 152
SP  - 516
EP  - 524
PB  - Elsevier
CY  - New York
ER  - 
TY  - JOUR
A1  - Gohlke, Sabrina
A1  - Mancini, Carola
A1  - Garcia-Carrizo, Francisco
A1  - Schulz, Tim J.
T1  - Loss of the ciliary gene Bbs4 results in defective thermogenesis due to metabolic inefficiency and impaired lipid metabolism
JF  - The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology
N2  - Adipose tissue is central to the regulation of energy balance. While white adipose tissue (WAT) is responsible for triglyceride storage, brown adipose tissue specializes in energy expenditure. Deterioration of brown adipocyte function contributes to the development of metabolic complications like obesity and diabetes. These disorders are also leading symptoms of the Bardet-Biedl syndrome (BBS), a hereditary disorder in humans which is caused by dysfunctions of the primary cilium and which therefore belongs to the group of ciliopathies. The cilium is a hair-like organelle involved in cellular signal transduction. The BBSome, a supercomplex of several Bbs gene products, localizes to the basal body of cilia and is thought to be involved in protein sorting to and from the ciliary membrane. The effects of a functional BBSome on energy metabolism and lipid mobilization in brown and white adipocytes were tested in whole-body Bbs4 knockout mice that were subjected to metabolic challenges. Chronic cold exposure reveals cold-intolerance of knockout mice but also ameliorates the markers of metabolic pathology detected in knockouts prior to cold. Hepatic triglyceride content is markedly reduced in knockout mice while circulating lipids are elevated, altogether suggesting that defective lipid metabolism in adipose tissue creates increased demand for systemic lipid mobilization to meet energetic demands of reduced body temperatures. These findings taken together suggest that Bbs4 is essential for the regulation of adipose tissue lipid metabolism, representing a potential target to treat metabolic disorders.
KW  - adipose tissue
KW  - Bbs4
KW  - BBsome
KW  - browning
KW  - cilium
KW  - lipid metabolism
Y1  - 2021
U6  - https://doi.org/10.1096/fj.202100772RR
SN  - 1530-6860
VL  - 35
IS  - 11
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Häseli, Steffen
A1  - Deubel, Stefanie
A1  - Jung, Tobias
A1  - Grune, Tilman
A1  - Ott, Christiane
T1  - Cardiomyocyte contractility and autophagy in a premature senescence model of cardiac aging
JF  - Oxidative medicine and cellular longevity
N2  - Globally, cardiovascular diseases are the leading cause of death in the aging population. While the clinical pathology of the aging heart is thoroughly characterized, underlying molecular mechanisms are still insufficiently clarified. The aim of the present study was to establish an in vitro model system of cardiomyocyte premature senescence, culturing heart muscle cells derived from neonatal C57Bl/6J mice for 21 days. Premature senescence of neonatal cardiac myocytes was induced by prolonged culture time in an oxygen-rich postnatal environment. Age-related changes in cellular function were determined by senescence-associated beta-galactosidase activity, increasing presence of cell cycle regulators, such as p16, p53, and p21, accumulation of protein aggregates, and restricted proteolysis in terms of decreasing (macro-)autophagy. Furthermore, the culture system was functionally characterized for alterations in cell morphology and contractility. An increase in cellular size associated with induced expression of atrial natriuretic peptides demonstrated a stress-induced hypertrophic phenotype in neonatal cardiomyocytes. Using the recently developed analytical software tool Myocyter, we were able to show a spatiotemporal constraint in spontaneous contraction behavior during cultivation. Within the present study, the 21-day culture of neonatal cardiomyocytes was defined as a functional model system of premature cardiac senescence to study age-related changes in cardiomyocyte contractility and autophagy.
Y1  - 2020
U6  - https://doi.org/10.1155/2020/8141307
SN  - 1942-0994
VL  - 2020
IS  - Special Issue
PB  - Landes Bioscience
CY  - Austin, Tex.
ER  - 
TY  - JOUR
A1  - Ost, Mario
A1  - Igual Gil, Carla
A1  - Coleman, Verena
A1  - Keipert, Susanne
A1  - Efstathiou, Sotirios
A1  - Vidic, Veronika
A1  - Weyers, Miriam
A1  - Klaus, Susanne
T1  - Muscle-derived GDF15 drives diurnal anorexia and systemic metabolic remodeling during mitochondrial stress
JF  - EMBO reports
N2  - Mitochondrial dysfunction promotes metabolic stress responses in a cell-autonomous as well as organismal manner. The wasting hormone growth differentiation factor 15 (GDF15) is recognized as a biomarker of mitochondrial disorders, but its pathophysiological function remains elusive. To test the hypothesis that GDF15 is fundamental to the metabolic stress response during mitochondrial dysfunction, we investigated transgenic mice (Ucp1-TG) with compromised muscle-specific mitochondrial OXPHOS capacity via respiratory uncoupling. Ucp1-TG mice show a skeletal muscle-specific induction and diurnal variation of GDF15 as a myokine. Remarkably, genetic loss of GDF15 in Ucp1-TG mice does not affect muscle wasting or transcriptional cell-autonomous stress response but promotes a progressive increase in body fat mass. Furthermore, muscle mitochondrial stress-induced systemic metabolic flexibility, insulin sensitivity, and white adipose tissue browning are fully abolished in the absence of GDF15. Mechanistically, we uncovered a GDF15-dependent daytime-restricted anorexia, whereas GDF15 is unable to suppress food intake at night. Altogether, our evidence suggests a novel diurnal action and key pathophysiological role of mitochondrial stress-induced GDF15 in the regulation of systemic energy metabolism.
KW  - anorexia
KW  - GDF15
KW  - integrated stress response
KW  - mitochondrial dysfunction
KW  - muscle wasting
Y1  - 2020
U6  - https://doi.org/10.15252/embr.201948804
SN  - 1469-221X
SN  - 1469-3178
VL  - 21
IS  - 3
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Kehm, Richard
A1  - Jähnert, Markus
A1  - Deubel, Stefanie
A1  - Flore, Tanina
A1  - König, Jeannette
A1  - Jung, Tobias
A1  - Stadion, Mandy
A1  - Jonas, Wenke
A1  - Schürmann, Annette
A1  - Grune, Tilman
A1  - Höhn, Annika
T1  - Redox homeostasis and cell cycle activation mediate beta-cell mass expansion in aged, diabetes-prone mice under metabolic stress conditions: role of thioredoxin-interacting protein (TXNIP)
JF  - Redox Biology
N2  - Overnutrition contributes to insulin resistance, obesity and metabolic stress, initiating a loss of functional beta-cells and diabetes development. Whether these damaging effects are amplified in advanced age is barely investigated. Therefore, New Zealand Obese (NZO) mice, a well-established model for the investigation of human obesity-associated type 2 diabetes, were fed a metabolically challenging diet with a high-fat, carbohydrate restricted period followed by a carbohydrate intervention in young as well as advanced age. Interestingly, while young NZO mice developed massive hyperglycemia in response to carbohydrate feeding, leading to beta-cell dysfunction and cell death, aged counterparts compensated the increased insulin demand by persistent beta-cell function and beta-cell mass expansion. Beta-cell loss in young NZO islets was linked to increased expression of thioredoxin-interacting protein (TXNIP), presumably initiating an apoptosis-signaling cascade via caspase-3 activation. In contrast, islets of aged NZOs exhibited a sustained redox balance without changes in TXNIP expression, associated with higher proliferative potential by cell cycle activation. These findings support the relevance of a maintained proliferative potential and redox homeostasis for preserving islet functionality under metabolic stress, with the peculiarity that this adaptive response emerged with advanced age in diabetesprone NZO mice.
KW  - aging
KW  - redox homeostasis
KW  - metabolic stress
KW  - beta-cells
KW  - cell cycle
KW  - thioredoxin-interacting protein
Y1  - 2020
U6  - https://doi.org/10.1016/j.redox.2020.101748
SN  - 2213-2317
VL  - 37
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Nicolai, Merle Marie
A1  - Baesler, Jessica
A1  - Aschner, Michael
A1  - Schwerdtle, Tanja
A1  - Bornhorst, Julia
T1  - Consequences of manganese overload in C. elegans
BT  - oxidative stress and DNA damage
JF  - Naunyn-Schmiedeberg's archives of pharmacology / ed. for the Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie
Y1  - 2020
U6  - https://doi.org/10.1007/s00210-020-01828-y
SN  - 0028-1298
SN  - 1432-1912
VL  - 393
IS  - SUPPL 1
SP  - 9
EP  - 9
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Borremans, An
A1  - Bußler, Sara
A1  - Sagu Tchewonpi, Sorel
A1  - Rawel, Harshadrai Manilal
A1  - Schlüter, Oliver K.
A1  - Leen, Van Campenhout
T1  - Effect of blanching plus fermentation on selected functional properties of mealworm (Tenebrio molitor) powders
JF  - Foods : open access journal
N2  - The aim of this study was to determine the effect of blanching followed by fermentation of mealworms (Tenebrio molitor) with commercial meat starter cultures on the functional properties of powders produced from the larvae. Full fat and defatted powder samples were prepared from non-fermented and fermented mealworm pastes. Then the crude protein, crude fat, and dry matter contents, pH, bulk density, colour, water and oil binding capacity, foaming capacity and stability, emulsion capacity and stability, protein solubility, quantity of free amino groups, and protein composition of the powders were evaluated. Regardless of the starter culture used, the blanching plus fermentation process reduced the crude and soluble protein contents of the full fat powders and in general impaired their water and oil binding, foaming, and emulsifying properties. Defatting of the powders improved most functional properties studied. The o-phthaldialdehyde assay revealed that the amount of free amino groups was higher in the fermented powders while sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that the soluble proteins of the fermented powders were composed of molecules of lower molecular mass compared to non-fermented powders. As molecular sizes of the soluble proteins decreased, it was clear that the protein structure was also modified by the fermentation process, which in turn led to changes in functional properties. In general, it was concluded that fermentation of mealworms with blanching as a pre-treatment does not contribute to the functional properties studied in this work. Nevertheless, the results confirmed that the properties of non-fermented powders are comparable to other food protein sources.
KW  - mealworm
KW  - fermentation
KW  - functional properties
KW  - insect proteins
KW  - SDS-PAGE
Y1  - 2020
U6  - https://doi.org/10.3390/foods9070917
SN  - 2304-8158
VL  - 9
IS  - 7
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Stadion, Mandy
A1  - Schürmann, Annette
T1  - Intermittierendes Fasten
BT  - was gibt es Neues aus der Wissenschaft?
BT  - what’s new from science?
JF  - Der Diabetologe
N2  - Obesity increases the risk of metabolic disorders and can lead to type 2 diabetes. Therefore, the treatment and prevention of obesity represent important medical challenges. Increased physical activity and a reduction in daily caloric intake of 25-30% are often recommended. Another possibility is intermittent fasting, by limiting dietary caloric content over certain times, i.e. one or more days a week or for more than 14 h a day. Animal and human studies provide evidence that intermittent fasting in obesity leads to a reduction in body fat mass as well as to improvements of metabolic parameters and insulin sensitivity. These positive effects are mediated not only by the decrease in body mass, but also by the activation of metabolic pathways and cellular processes that are specific for fasting conditions. In this article, we describe the current knowledge about the mechanisms induced by intermittent fasting and present results from randomized controlled human trials.
N2  - Übergewicht und Adipositas erhöhen die Risiken für Stoffwechselstörungen und können zu einem Typ-2-Diabetes führen. Deshalb stellen die Behandlung und Prävention von Fettleibigkeit eine große medizinische Herausforderung dar. Häufig werden eine erhöhte körperliche Aktivität und die Reduktion der täglichen Kalorienaufnahme um 25–30 % angeraten. Eine andere Möglichkeit bietet intermittierendes Fasten, also eine Kalorieneinschränkung über bestimmte Zeiten, d. h. an einem oder mehreren Tagen pro Woche oder über mehr als 14 h pro Tag. Tier- und Humanstudien lieferten Hinweise darauf, dass intermittierendes Fasten bei Adipositas zu einer Verringerung der Körperfettmasse sowie zu Verbesserungen der Stoffwechselparameter und der Insulinsensitivität führt. Diese positiven Effekte werden nicht nur allein durch die Abnahme der Körpermasse, sondern auch durch die Aktivierung von Stoffwechselwegen und zellulären Prozessen ausgelöst, die für Fastenbedingungen spezifisch sind. In diesem Artikel beschreiben wir die derzeit bekannten Mechanismen, die durch intermittierendes Fasten induziert werden, und stellen Ergebnisse aus randomisierten kontrollierten Studien am Menschen vor.
T2  - Intermittent fasting
KW  - Glucose metabolism disorders
KW  - Lipid metabolism
KW  - Insulin sensitivity
KW  - Energy metabolism
KW  - Circadian rhythm
KW  - Glukosestoffwechselstörungen
KW  - Fettstoffwechsel
KW  - Insulinsensitivität
KW  - Energiestoffwechsel
KW  - Zirkadianer Rhythmus
Y1  - 2020
U6  - https://doi.org/10.1007/s11428-020-00666-z
SN  - 1860-9716
SN  - 1860-9724
VL  - 16
IS  - 7
SP  - 641
EP  - 646
PB  - Springer Medizin
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Grune, Tilman
T1  - Oxidized protein aggregates
BT  - formation and biological effects
JF  - Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research
N2  - The study of protein aggregates has a long history. While in the first decades until the 80ies of the 20th century only the observation of the presence of such aggregates was reported, later the biochemistry of the formation and the biological effects of theses aggregates were described. 
This review focusses on the complexity of the biological effects of protein aggregates and its potential role in the aging process.
Y1  - 2020
U6  - https://doi.org/10.1016/j.freeradbiomed.2020.02.014
SN  - 0891-5849
SN  - 1873-4596
VL  - 150
SP  - 120
EP  - 124
PB  - Elsevier
CY  - New York
ER  - 
TY  - JOUR
A1  - Wright, Stephanie L.
A1  - Ulke, Jannis
A1  - Font, Anna
A1  - Chan, Ka Lung Andrew
A1  - Kelly, Frank J.
T1  - Atmospheric microplastic deposition in an urban environment and an evaluation of transport
JF  - Environment international
N2  - Microplastics are a global environmental issue contaminating aquatic and terrestrial environments. They have been reported in atmospheric deposition, and indoor and outdoor air, raising concern for public health due to the potential for exposure. Moreover, the atmosphere presents a new vehicle for microplastics to enter the wider environment, yet our knowledge of the quantities, characteristics and pathways of airborne microplastics is sparse. Here we show microplastics in atmospheric deposition in a major population centre, central London. Microplastics were found in all samples, with deposition rates ranging from 575 to 1008 microplastics/m(2)/d. They were found in various shapes, of which fibrous microplastics accounted for the great majority (92%). Across all samples, 15 different petrochemical-based polymers were identified. Bivariate polar plots indicated dependency on wind, with different source areas for fibrous and non-fibrous airborne microplastics. This is the first evidence of airborne microplastics in London and confirms the need to include airborne pathways when consolidating microplastic impacts on the wider environment and human health.
KW  - microplastics
KW  - atmospheric deposition
KW  - air pollution
KW  - urban
Y1  - 2020
U6  - https://doi.org/10.1016/j.envint.2019.105411
SN  - 0160-4120
SN  - 1873-6750
VL  - 136
PB  - Elsevier, Pergamon Press
CY  - New York, NY [u.a.]
ER  - 
TY  - JOUR
A1  - Weitkunat, Karolin
A1  - Bishop, Christopher Allen
A1  - Wittmüss, Maria
A1  - Machate, Tina
A1  - Schifelbein, Tina
A1  - Schulze, Matthias Bernd
A1  - Klaus, Susanne
T1  - Effect of microbial status on hepatic odd-chain fatty acids is diet-dependent
JF  - Nutrients / Molecular Diversity Preservation International (MDPI)
N2  - Odd-chain fatty acids (OCFA) are inversely associated with type-2-diabetes in epidemiological studies. They are considered as a biomarker for dairy intake because fermentation in ruminants yields high amounts of propionate, which is used as the primer for lipogenesis. Recently, we demonstrated endogenous OCFA synthesis from propionate in humans and mice, but how this is affected by microbial colonization is still unexplored. Here, we investigated the effect of increasing microbiota complexity on hepatic lipid metabolism and OCFA levels in different dietary settings. Germ-free (GF), gnotobiotic (SIH, simplified human microbiota) or conventional (CONV) C3H/HeOuJ-mice were fed a CHOW or high-fat diet with inulin (HFI) to induce microbial fermentation. We found that hepatic lipogenesis was increased with increasing microbiota complexity, independently of diet. In contrast, OCFA formation was affected by diet as well as microbiota. On CHOW, hepatic OCFA and intestinal gluconeogenesis decreased with increasing microbiota complexity (GF > SIH > CONV), while cecal propionate showed a negative correlation with hepatic OCFA. On HFI, OCFA levels were highest in SIH and positively correlated with cecal propionate. The propionate content in the CHOW diet was 10 times higher than that of HFI. We conclude that bacterial propionate production affects hepatic OCFA formation, unless this effect is masked by dietary propionate intake.
KW  - pentadecanoic acid (C15:0)
KW  - heptadecanoic acid (C17:0)
KW  - type-2-diabetes
KW  - fatty acid synthesis
KW  - acetate
KW  - propionate
KW  - probiotics
KW  - gut microbiota
KW  - prebiotics
KW  - inulin
Y1  - 2021
U6  - https://doi.org/10.3390/nu13051546
SN  - 2072-6643
VL  - 13
IS  - 5
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Wetzel, Alexandra Nicole
A1  - Scholtka, Bettina
A1  - Schumacher, Fabian
A1  - Rawel, Harshadrai Manilal
A1  - Geisendörfer, Birte
A1  - Kleuser, Burkhard
T1  - Epigenetic DNA methylation of EBI3 modulates human interleukin-35 formation via NFkB signaling
BT  - a promising therapeutic option in ulcerative colitis
JF  - International journal of molecular sciences
N2  - Ulcerative colitis (UC), a severe chronic disease with unclear etiology that is associated with increased risk for colorectal cancer, is accompanied by dysregulation of cytokines. Epstein-Barr virus-induced gene 3 (EBI3) encodes a subunit in the unique heterodimeric IL-12 cytokine family of either pro- or anti-inflammatory function. After having recently demonstrated that upregulation of EBI3 by histone acetylation alleviates disease symptoms in a dextran sulfate sodium (DSS)-treated mouse model of chronic colitis, we now aimed to examine a possible further epigenetic regulation of EBI3 by DNA methylation under inflammatory conditions. Treatment with the DNA methyltransferase inhibitor (DNMTi) decitabine (DAC) and TNF alpha led to synergistic upregulation of EBI3 in human colon epithelial cells (HCEC). Use of different signaling pathway inhibitors indicated NF kappa B signaling was necessary and proportional to the synergistic EBI3 induction. MALDI-TOF/MS and HPLC-ESIMS/MS analysis of DAC/TNF alpha-treated HCEC identified IL-12p35 as the most probable binding partner to form a functional protein. EBI3/IL-12p35 heterodimers (IL-35) induce their own gene upregulation, something that was indeed observed in HCEC cultured with media from previously DAC/TNF alpha-treated HCEC. These results suggest that under inflammatory and demethylating conditions the upregulation of EBI3 results in the formation of anti-inflammatory IL-35, which might be considered as a therapeutic target in colitis.
KW  - decitabine
KW  - DNMT inhibitor
KW  - EBI3
KW  - inhibitory cytokines
KW  - interleukin-35
KW  - TNF alpha
KW  - Ulcerative colitis
Y1  - 2021
U6  - https://doi.org/10.3390/ijms22105329
SN  - 1422-0067
VL  - 22
IS  - 10
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Gehre, Christian
A1  - Flechner, Marie
A1  - Kammerer, Sarah
A1  - Küpper, Jan-Heiner
A1  - Coleman, Charles Dominic
A1  - Püschel, Gerhard Paul
A1  - Uhlig, Katja
A1  - Duschl, Claus
T1  - Real time monitoring of oxygen uptake of hepatocytes in a microreactor using optical microsensors
JF  - Scientific reports
N2  - Most in vitro test systems for the assessment of toxicity are based on endpoint measurements and cannot contribute much to the establishment of mechanistic models, which are crucially important for further progress in this field. Hence, in recent years, much effort has been put into the development of methods that generate kinetic data. Real time measurements of the metabolic activity of cells based on the use of oxygen sensitive microsensor beads have been shown to provide access to the mode of action of compounds in hepatocytes. However, for fully exploiting this approach a detailed knowledge of the microenvironment of the cells is required. In this work, we investigate the cellular behaviour of three types of hepatocytes, HepG2 cells, HepG2-3A4 cells and primary mouse hepatocytes, towards their exposure to acetaminophen when the availability of oxygen for the cell is systematically varied. We show that the relative emergence of two modes of action, one NAPQI dependent and the other one transient and NAPQI independent, scale with expression level of CYP3A4. The transient cellular response associated to mitochondrial respiration is used to characterise the influence of the initial oxygen concentration in the wells before exposure to acetaminophen on the cell behaviour. A simple model is presented to describe the behaviour of the cells in this scenario. It demonstrates the level of control over the role of oxygen supply in these experiments. This is crucial for establishing this approach into a reliable and powerful method for the assessment of toxicity.
Y1  - 2020
U6  - https://doi.org/10.1038/s41598-020-70785-6
SN  - 2045-2322
VL  - 10
IS  - 1
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  - 
TY  - JOUR
A1  - Schiborn, Catarina
A1  - Schulze, Matthias B.
T1  - Diabetes risk scores
T1  - Diabetesrisikoscores
BT  - use in diabetes prevention
BT  - Einsatz in der Diabetesprävention
JF  - Der Diabetologe
N2  - Risk scores are used to identify high-risk individuals for type 2 diabetes (T2DM) who benefit from preventive measures. The DIfE-DEUTSCHER DIABETES-RISIKO-TEST (R) (DRT) is used to determine the absolute 5-year risk for T2DM. Since the calculation is based on non-clinical information, the test can be used independently of a doctor's visit. Data from prospective population-based long-term studies serve as the basis for the development of risk scores. As in the case of the DRT, the very good predictive quality of a score should be confirmed in independent populations. In addition to the use by doctors and for individual self-anamnesis, non-clinical risk scores can be used in the context of broader, population-based prevention concepts and information offers to reduce the risk of disease. Prevention services billable by health insurance companies should support the integration of health-promoting behavior into everyday life within the meaning of the German Prevention Act. Although obesity and diet are relevant lifestyle risk factors for T2DM, the proportion of preventive courses taken on this topic is only 3% of the courses billed. Appropriate recommendations in medical examinations could promote more extensive use. The use of risk scores as the basis for systematic and targeted recommendations for behavioral prevention could also support this, as is already established in guidelines for cardiovascular prevention. The further development of implementation research is also important for the efficient use of risk scores.
N2  - Risikoscores werden zur Identifizierung von Hochrisikopersonen für Typ-2-Diabetes (T2DM) eingesetzt, die von Präventionsmaßnahmen profitieren. Der DIfE – DEUTSCHER DIABETES-RISIKO-TEST® (DRT [DIfE: Deutsches Institut für Ernährungsforschung Potsdam‐Rehbrücke]) wird genutzt, um das absolute 5‑Jahres-Risiko für T2DM zu bestimmen. Da die Berechnung auf nichtklinischen Informationen basiert, kann der Test unabhängig von einem Arztbesuch genutzt werden. Als Grundlage für die Entwicklung von Risikoscores dienen Daten aus prospektiven populationsbezogenen Langzeitstudien. Die sehr gute Vorhersagegüte eines Scores sollte, wie im Fall des DRT, in unabhängigen Populationen bestätigt werden. Neben dem Einsatz durch Ärzte/‑innen und zur individuellen Selbstanamnese können nichtklinische Risikoscores im Kontext breiterer, bevölkerungsbezogener Präventionskonzepte und Informationsangebote zur Senkung des Erkrankungsrisikos Anwendung finden. Durch Krankenkassen abrechenbare Präventionsleistungen sollen im Sinne des deutschen Präventionsgesetzes die Integration von gesundheitsförderndem Verhalten in den Alltag unterstützen. Obwohl Übergewicht und Ernährung relevante Lebensstilrisikofaktoren für T2DM sind, beträgt der Anteil der in Anspruch genommenen Präventionskurse in diesem Bereich nur 3 % der abgerechneten Kurse. Entsprechende Empfehlungen in ärztlichen Untersuchungen könnten eine umfangreichere Inanspruchnahme fördern. Die Verwendung von Risikoscores als Grundlage für systematische und gezielte Handlungsempfehlungen hinsichtlich einer Verhaltensprävention könnte dies, wie es bereits in Richtlinien der kardiovaskulären Prävention etabliert ist, darüber hinaus unterstützen. Auch die Weiterentwicklung der Implementationsforschung ist für den effizienten Einsatz von Risikoscores von Bedeutung.
KW  - Type 2 diabetes
KW  - preventive measures
KW  - risk assessment
KW  - life style
KW  - behavior
KW  - screening
KW  - Typ-2-Diabetes
KW  - Prävention
KW  - Risikoeinschätzung
KW  - Lebensstil
KW  - Verhalten
Y1  - 2020
U6  - https://doi.org/10.1007/s11428-020-00592-0
SN  - 1860-9716
SN  - 1860-9724
VL  - 16
IS  - 3
SP  - 226
EP  - 233
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Dünkelberg, Sophie
A1  - Maywald, Martina
A1  - Schmitt, Anne Kristina
A1  - Schwerdtle, Tanja
A1  - Meyer, Sören
A1  - Rink, Lothar
T1  - The interaction of sodium and zinc in the priming of T cell subpopulations regarding Th17 and Treg cells
JF  - Molecular nutrition & food research : bioactivity, chemistry, immunology, microbiology, safety, technology
N2  - Scope:
Nutrition is a critical determinant of a functional immune system. The aim of this study is to investigate the molecular mechanisms by which immune cells are influenced by zinc and sodium.

Methods and Results:
 Mixed lymphocyte cultures and Jurkat cells are generated and incubated with zinc, sodium, or a combination of both for further tests. Zinc induces the number of regulatory T cells (Treg) and decreases T helper 17 cells (Th17), and sodium has the opposite effect. The transforming growth factor beta receptor signaling pathway is also enhanced by zinc and reduced by sodium as indicated by contrary phosphoSmad 2/3 induction. Antagonistic effects can also be seen on zinc transporter and metallothionein-1 (MT-1) mRNA expression: zinc declines Zip10 mRNA expression while sodium induces it, whereas MT-1 mRNA expression is induced by zinc while it is reduced by sodium. 

Conclusion:
This data indicate that zinc and sodium display opposite effects regarding Treg and Th17 induction in MLC, respectively, resulting in a contrary effect on the immune system. Additionally, it reveals a direct interaction of zinc and sodium in the priming of T cell subpopulations and shows that Zip10 and MT-1 play a significant role in those differentiation pathways.
KW  - Foxp3
KW  - regulatory T cells
KW  - sodium
KW  - T helper 17 cells
KW  - zinc
Y1  - 2020
U6  - https://doi.org/10.1002/mnfr.201900245
SN  - 1613-4133
VL  - 64
IS  - 2
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Kotthoff, Lisa
A1  - O'Callaghan, Sarah-Louise
A1  - Lisec, Jan
A1  - Schwerdtle, Tanja
A1  - Koch, Matthias
T1  - Structural annotation of electro- and photochemically generated transformation products of moxidectin using high-resolution mass spectrometry
JF  - Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica
N2  - Moxidectin (MOX) is a widely used anthelmintic drug for the treatment of internal and external parasites in food-producing and companion animals. Transformation products (TPs) of MOX, formed through metabolic degradation or acid hydrolysis, may pose a potential environmental risk, but only few were identified so far. In this study, we therefore systematically characterized electro- and photochemically generated MOX TPs using high-resolution mass spectrometry (HRMS). Oxidative electrochemical (EC) TPs were generated in an electrochemical reactor and photochemical (PC) TPs by irradiation with UV-C light. Subsequent HRMS measurements were performed to identify accurate masses and deduce occurring modification reactions of derived TPs in a suspected target analysis. In total, 26 EC TPs and 59 PC TPs were found. The main modification reactions were hydroxylation, (de-)hydration, and derivative formation with methanol for EC experiments and isomeric changes, (de-)hydration, and changes at the methoxime moiety for PC experiments. In addition, several combinations of different modification reactions were identified. For 17 TPs, we could predict chemical structures through interpretation of acquired MS/MS data. Most modifications could be linked to two specific regions of MOX. Some previously described metabolic reactions like hydroxylation or O-demethylation were confirmed in our EC and PC experiments as reaction type, but the corresponding TPs were not identical to known metabolites or degradation products. The obtained knowledge regarding novel TPs and reactions will aid to elucidate the degradation pathway of MOX which is currently unknown.
KW  - veterinary drug
KW  - moxidectin
KW  - transformation products
KW  - electrochemistry
KW  - photochemistry
KW  - LC
KW  - HRMS
Y1  - 2020
U6  - https://doi.org/10.1007/s00216-020-02572-1
SN  - 1618-2642
SN  - 1618-2650
VL  - 412
IS  - 13
SP  - 3141
EP  - 3152
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Ouni, Meriem
A1  - Schürmann, Annette
T1  - Epigenetic contribution to obesity
JF  - Mammalian genome
N2  - Obesity is a worldwide epidemic and contributes to global morbidity and mortality mediated via the development of nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), cardiovascular (CVD) and other diseases. It is a consequence of an elevated caloric intake, a sedentary lifestyle and a genetic as well as an epigenetic predisposition. This review summarizes changes in DNA methylation and microRNAs identified in blood cells and different tissues in obese human and rodent models. It includes information on epigenetic alterations which occur in response to fat-enriched diets, exercise and metabolic surgery and discusses the potential of interventions to reverse epigenetic modifications.
Y1  - 2020
U6  - https://doi.org/10.1007/s00335-020-09835-3
SN  - 0938-8990
SN  - 1432-1777
VL  - 31
IS  - 5-6
SP  - 134
EP  - 145
PB  - Springer
CY  - New York, NY ; Berlin ; Heidelberg [u.a.]
ER  - 
TY  - JOUR
A1  - Knoche, Lisa
A1  - Lisec, Jan
A1  - Koch, Matthias
T1  - Analysis of electrochemical and liver microsomal transformation products of lasalocid by LC/HRMS
JF  - Rapid communications in mass spectrometry : RCM
N2  - Rationale:
Lasalocid (LAS), an ionophore, is used in cattle and poultry farming as feed additive for its antibiotic and growth-promoting properties. Literature on transformation products (TP) resulting from LAS degradation is limited. So far, only hydroxylation is found to occur as the metabolic reaction during the LAS degradation. To investigate potential TPs of LAS, we used electrochemistry (EC) and liver microsome (LM) assays to synthesize TPs, which were identified using liquid chromatography high-resolution mass spectrometry (LC/HRMS). 

Methods:
Electrochemically produced TPs were analyzed online by direct coupling of the electrochemical cell to the electrospray ionization (ESI) source of a Sciex Triple-TOF high resolution mass spectrometer. Then, EC-treated LAS solution was collected and analyzed offline using LC/HRMS to confirm stable TPs and improve their annotation with a chemical structure due to informative MS/MS spectra. In a complementary approach, TPs formed by rat and human microsomal incubation were investigated using LC/HRMS. The resulting data were used to investigate LAS modification reactions and elucidate the chemical structure of obtained TPs.

Results:
The online measurements identified a broad variety of TPs, resulting from modification reactions like (de-)hydrogenation, hydration, methylation, oxidation as well as adduct formation with methanol. We consistently observed different ion complexations of LAS and LAS-TPs (Na+; 2Na(+) K+; NaNH4+; KNH4+). Two stable methylated EC-TPs were found, structurally annotated, and assigned to a likely modification reaction. Using LM incubation, seven TPs were formed, mostly by oxidation/hydroxylation. After the identification of LM-TPs as Na+-complexes, we identified LM-TPs as K+-complexes.

Conclusion:
We identified and characterized TPs of LAS using EC- and LM-based methods. Moreover, we found different ion complexes of LAS-based TPs. This knowledge, especially the different ion complexes, may help elucidate the metabolic and environmental degradation pathways of LAS.
Y1  - 2022
U6  - https://doi.org/10.1002/rcm.9349
SN  - 0951-4198
SN  - 1097-0231
VL  - 36
IS  - 18
PB  - Wiley
CY  - New York, NY
ER  - 
TY  - JOUR
A1  - Cencetti, Francesca
A1  - Bruno, Gennaro
A1  - Bernacchioni, Caterina
A1  - Japtok, Lukasz
A1  - Puliti, Elisa
A1  - Donati, Chiara
A1  - Bruni, Paola
T1  - Sphingosine 1-phosphate lyase blockade elicits myogenic differentiation of murine myoblasts acting via Spns2/S1P(2) receptor axis
JF  - Biochimica et biophysica acta : Molecular and cell biology of lipids
N2  - The bioactive sphingolipid sphingosine 1-phosphate (S1P) has emerged in the last three decades as main regulator of key cellular processes including cell proliferation, survival, migration and differentiation. A crucial role for this sphingolipid has been recognized in skeletal muscle cell biology both in vitro and in vivo. S1P lyase (SPL) is responsible for the irreversible degradation of S1P and together with sphingosine kinases, the S1P producing enzymes, regulates cellular S1P levels. In this study is clearly showed that the blockade of SPL by pharmacological or RNA interference approaches induces myogenic differentiation of C2C12 myoblasts. Moreover, down-regulation of the specific S1P transporter spinster homolog 2 (Spns2) abrogates myogenic differentiation brought about by SPL inhibition or down-regulation, pointing at a role of extracellular S1P in the pro-myogenic action induced by SPL blockade. Furthermore, also S1P(2) receptor down-regulation was found to abrogate the pro-myogenic effect of SPL blockade. These results provide further proof that inside-out S1P signaling is critically implicated in skeletal muscle biology and provide support to the concept that the specific targeting of SPL could represent an exploitable strategy to treat skeletal muscle disorders.
KW  - Sphingosine 1-phosphate
KW  - Myogenic differentiation
Y1  - 2020
U6  - https://doi.org/10.1016/j.bbalip.2020.158759
SN  - 1388-1981
SN  - 1879-2618
VL  - 1865
IS  - 9
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Bishop, Christopher Allen
A1  - Schulze, Matthias Bernd
A1  - Klaus, Susanne
A1  - Weitkunat, Karolin
T1  - The branched-chain amino acids valine and leucine have differential effects on hepatic lipid metabolism
JF  - The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology
N2  - Dairy intake, as a source of branched-chain amino acids (BCAA), has been linked to a lower incidence of type-2-diabetes and increased circulating odd-chain fatty acids (OCFA). To understand this connection, we aimed to investigate differences in BCAA metabolism of leucine and valine, a possible source of OCFA, and their role in hepatic metabolism. Male mice were fed a high-fat diet supplemented with leucine and valine for 1 week and phenotypically characterized with a focus on lipid metabolism. Mouse primary hepatocytes were treated with the BCAA or a Ppar alpha activator WY-14643 to systematically examine direct hepatic effects and their mechanisms. Here, we show that only valine supplementation was able to increase hepatic and circulating OCFA levels via two pathways; a PPAR alpha-dependent induction of alpha-oxidation and an increased supply of propionyl-CoA for de novo lipogenesis. Meanwhile, we were able to confirm leucine-mediated effects on the inhibition of food intake and transport of fatty acids, as well as induction of S6 ribosomal protein phosphorylation. Taken together, these data illustrate differential roles of the BCAA in lipid metabolism and provide preliminary evidence that exclusively valine contributes to the endogenous formation of OCFA which is important for a better understanding of these metabolites in metabolic health.
KW  - fatty acid metabolism
KW  - leucine
KW  - liver
KW  - OCFA
KW  - valine
Y1  - 2020
U6  - https://doi.org/10.1096/fj.202000195R
SN  - 0892-6638
SN  - 1530-6860
VL  - 34
IS  - 7
SP  - 9727
EP  - 9739
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Schedlbauer, Carola
A1  - Blaue, Dominique
A1  - Raila, Jens
A1  - Vervuert, Ingrid
T1  - Alterations of serum vitamin E and vitamin A concentrations of ponies and horses during experimentally induced obesity
JF  - Journal of animal physiology and animal nutrition
JF  - Zeitschrift für Tierphysiologie, Tierernährung und Futtermittelkunde
N2  - Vitamin A, vitamin E and retinol-binding protein 4 (RBP4) are a focus of current obesity research in humans. The impact of body weight (BW) gain on fat-soluble vitamins and its associated parameters in equines has not been previously reported. Ten Shetland ponies and 9 Warmblood horses, all adult geldings, non-obese and healthy, were fed an excessive energy diet for 20 months to induce BW gain. Serum alpha-tocopherol (vitamin E), retinol (vitamin A), retinol-binding protein 4 (RBP4) and retinol/RBP4 ratio were analysed before BW gain induction and at six timepoints during the BW gaining period. The mean (+/- SD) % BW gain achieved during two years of excess energy intake was 29.9 +/- 19.4% for ponies and 17 +/- 6.74% for horses. Serum alpha-tocopherol increased significantly in ponies and horses during excess energy intake and circulating alpha-tocopherol levels correlated positively with alpha-tocopherol intake (r = .6; p < .001). Serum retinol concentrations showed variations during the study but without relation to intake. Serum RBP4 decreased at the end of the study. The retinol/RBP4 ratio increased with BW gain without differences between ponies and horses. In comparison with human research, the increase in the retinol/RBP4 ratio was unexpected and needs further elucidation.
KW  - body weight gain
KW  - equine
KW  - laminitis
KW  - retinol-binding protein 4
KW  - alpha-tocopherol
Y1  - 2020
U6  - https://doi.org/10.1111/jpn.13385
SN  - 0931-2439
SN  - 1439-0396
VL  - 104
IS  - 5
SP  - 1501
EP  - 1508
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Wiedmer, Petra
A1  - Jung, Tobias
A1  - Castro, Jose Pedro
A1  - Pomatto, Laura C. D.
A1  - Sun, Patrick Y.
A1  - Davies, Kelvin J. A.
A1  - Grune, Tilman
T1  - Sarcopenia
BT  - molecular mechanisms and open questions
JF  - Ageing research reviews : ARR
N2  - Sarcopenia represents a muscle-wasting syndrome characterized by progressive and generalized degenerative loss of skeletal muscle mass, quality, and strength occurring during normal aging. Sarcopenia patients are mainly suffering from the loss in muscle strength and are faced with mobility disorders reducing their quality of life and are, therefore, at higher risk for morbidity (falls, bone fracture, metabolic diseases) and mortality. <br /> Several molecular mechanisms have been described as causes for sarcopenia that refer to very different levels of muscle physiology. These mechanisms cover e. g. function of hormones (e. g. IGF-1 and Insulin), muscle fiber composition and neuromuscular drive, myo-satellite cell potential to differentiate and proliferate, inflammatory pathways as well as intracellular mechanisms in the processes of proteostasis and mitochondrial function. <br /> In this review, we describe sarcopenia as a muscle-wasting syndrome distinct from other atrophic diseases and summarize the current view on molecular causes of sarcopenia development as well as open questions provoking further research efforts for establishing efficient lifestyle and therapeutic interventions.
KW  - molecular pathways
KW  - proteostasis
KW  - proteasome
KW  - autophagy
KW  - mitochondria,
KW  - muscle fibre composition
Y1  - 2020
U6  - https://doi.org/10.1016/j.arr.2020.101200
SN  - 1568-1637
SN  - 1872-9649
VL  - 65
PB  - Elsevier
CY  - Clare
ER  - 
TY  - JOUR
A1  - Rothwell, Joseph A.
A1  - Murphy, Neil
A1  - Aleksandrova, Krasimira
A1  - Schulze, Matthias B.
A1  - Bešević, Jelena
A1  - Kliemann, Nathalie
A1  - Jenab, Mazda
A1  - Ferrari, Pietro
A1  - Achaintre, David
A1  - Gicquiau, Audrey
A1  - Vozar, Béatrice
A1  - Scalbert, Augustin
A1  - Huybrechts, Inge
A1  - Freisling, Heinz
A1  - Prehn, Cornelia
A1  - Adamski, Jerzy
A1  - Cross, Amanda J.
A1  - Pala, Valeria Maria
A1  - Boutron-Ruault, Marie-Christine
A1  - Dahm, Christina C.
A1  - Overvad, Kim
A1  - Gram, Inger Torhild
A1  - Sandanger, Torkjel M.
A1  - Skeie, Guri
A1  - Jakszyn, Paula
A1  - Tsilidis, Kostas K.
A1  - Hughes, David J.
A1  - van Guelpen, Bethany
A1  - Bodén, Stina
A1  - Sánchez, Maria-José
A1  - Schmidt, Julie A.
A1  - Katzke, Verena
A1  - Kühn, Tilman
A1  - Colorado-Yohar, Sandra
A1  - Tumino, Rosario
A1  - Bueno-de-Mesquita, Bas
A1  - Vineis, Paolo
A1  - Masala, Giovanna
A1  - Panico, Salvatore
A1  - Eriksen, Anne Kirstine
A1  - Tjønneland, Anne
A1  - Aune, Dagfinn
A1  - Weiderpass, Elisabete
A1  - Severi, Gianluca
A1  - Chajès, Véronique
A1  - Gunter, Marc J.
T1  - Metabolic signatures of healthy lifestyle patterns and colorectal cancer risk in a European cohort
JF  - Clinical gastroenterology and hepatology
N2  - BACKGROUND & AIMS: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

METHODS: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression.

RESULTS: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29-0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50-0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86-1.00) overall. Signature associations were stronger in male compared with female participants.

CONCLUSIONS: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.
KW  - colorectal neoplasm
KW  - risk factors
KW  - World Cancer Research Fund/American Institute for Cancer Research Recommendations
KW  - targeted metabolomics
Y1  - 2020
U6  - https://doi.org/10.1016/j.cgh.2020.11.045
SN  - 1542-3565
SN  - 1542-7714
VL  - 20
SP  - E1061
EP  - E1082
PB  - Elsevier
CY  - New York, NY
ER  - 
TY  - JOUR
A1  - Bußler, Sara
A1  - Rawel, Harshadrai Manilal
A1  - Schlüter, Oliver K.
T1  - Impact of plasma processed air (PPA) on phenolic model systems
BT  - suggested mechanisms and relevance for food applications
JF  - Innovative food science & emerging technologies : the official journal of the European Federation of Food Science and Technology
N2  - Cold plasma is considered to be a novel, non-thermal, chemical-free and eco-friendly disinfection and surface modification technology. Plasma treatment of air to generate the so called plasma processed air (PPA) induces the formation of reactive oxygen (ROS) and nitrogen species (RNS). As a result, PPA has a different chemical composition compared to untreated air and suits therefore as an alternative method for microbial disinfection. However, depending on the product properties of the food matrix and its composition, a number of plasmainduced reactions also need to be taken into consideration. 
This necessitates also the elucidation and understanding of the basic interactions of plasma species with bioactive compounds. The intention here is to avoid the degradation of these valuable substances and to prevent other undesirable effects in future food related applications.
In the present study, the effects of PPA treatment on selected antioxidants such as pyrocatechol and derivatives of hydroxycinnimic acid were investigated in model systems to specify possible reactions induced. Antioxidant capacity, pH value, UV-Vis spectroscopy, RP-HPLC and LC-MS analysis were applied to identify reaction products providing information on possible changes induced in food matrices by PPA treatment. 
Exposure to PPA caused a perceptible color change towards yellow-brown accompanied by a strong reduction of the pH and the formation of insoluble sediments in the model solutions. The accumulation of nitrate, nitrite, but not of hydrogen peroxide was shown. LC-MS analysis demonstrated the formation of plasma-modified derivatives in all tested systems. The main reactions in liquid model solutions exposed to PPA were attributed to oxidation, nitration and polymerization of the phenolic compounds.
KW  - cold atmospheric pressure plasma
KW  - reactive oxygen and nitrogen species
KW  - food safety
KW  - antioxidative phenolic ingredients
KW  - phenol oxidation
KW  - phenol nitration
KW  - plasma process indicators
Y1  - 2020
U6  - https://doi.org/10.1016/j.ifset.2020.102432
SN  - 1466-8564
SN  - 1878-5522
VL  - 64
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Zhou, Suqiong
A1  - Pan, Yuanwei
A1  - Zhang, Jianguang
A1  - Li, Yan
A1  - Neumann, Falko
A1  - Schwerdtle, Tanja
A1  - Li, Wenzhong
A1  - Haag, Rainer
T1  - Dendritic polyglycerol-conjugated gold nanostars with different densities of functional groups to regulate osteogenesis in human mesenchymal stem cells
JF  - Nanoscale
N2  - Nanomaterials play an important role in mimicking the biochemical and biophysical cues of the extracellular matrix in human mesenchymal stem cells (MSCs). Increasing studies have demonstrated the crucial impact of functional groups on MSCs, while limited research is available on how the functional group's density on nanoparticles regulates MSC behavior. Herein, the effects of dendritic polyglycerol (dPG)-conjugated gold nanostars (GNSs) with different densities of functional groups on the osteogenesis of MSCs are systematically investigated. dPG@GNS nanocomposites have good biocompatibility and the uptake by MSCs is in a functional group density-dependent manner. The osteogenic differentiation of MSCs is promoted by all dPG@GNS nanocomposites, in terms of alkaline phosphatase activity, calcium deposition, and expression of osteogenic protein and genes. Interestingly, the dPGOH@GNSs exhibit a slight upregulation in the expression of osteogenic markers, while the different charged densities of sulfate and amino groups show more efficacy in the promotion of osteogenesis. Meanwhile, the sulfated nanostars dPGS20@GNSs show the highest enhancement. Furthermore, various dPG@GNS nanocomposites exerted their effects by regulating the activation of Yes-associated protein (YAP) to affect osteogenic differentiation. These results indicate that dPG@GNS nanocomposites have functional group density-dependent influence on the osteogenesis of MSCs, which may provide a new insight into regulating stem cell fate.
Y1  - 2020
U6  - https://doi.org/10.1039/d0nr06570f
SN  - 2040-3364
SN  - 2040-3372
VL  - 12
IS  - 47
SP  - 24006
EP  - 24019
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Jonas, Wenke
A1  - Schürmann, Annette
T1  - Genetic and epigenetic factors determining NAFLD risk
JF  - Molecular metabolism
N2  - Background: Hepatic steatosis is a common chronic liver disease that can progress into more severe stages of NAFLD or promote the development of life-threatening secondary diseases for some of those affected. These include the liver itself (nonalcoholic steatohepatitis or NASH; fibrosis and cirrhosis, and hepatocellular carcinoma) or other organs such as the vessels and the heart (cardiovascular disease) or the islets of Langerhans (type 2 diabetes). In addition to elevated caloric intake and a sedentary lifestyle, genetic and epigenetic predisposition contribute to the development of NAFLD and the secondary diseases. Scope of review: We present data from genome-wide association studies (GWAS) and functional studies in rodents which describe polymorphisms identified in genes relevant for the disease as well as changes caused by altered DNA methylation and gene regulation via specific miRNAs. The review also provides information on the current status of the use of genetic and epigenetic factors as risk markers. Major conclusion: With our overview we provide an insight into the genetic and epigenetic landscape of NAFLD and argue about the applicability of currently defined risk scores for risk stratification and conclude that further efforts are needed to make the scores more usable and meaningful.
KW  - NAFLD
KW  - genetic variants
KW  - epigenetics
KW  - risk score
Y1  - 2020
U6  - https://doi.org/10.1016/j.molmet.2020.101111
SN  - 2212-8778
VL  - 50
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Saberi Hosnijeh, Fatemeh
A1  - Casabonne, Delphine
A1  - Nieters, Alexandra
A1  - Solans, Marta
A1  - Naudin, Sabine
A1  - Ferrari, Pietro
A1  - Mckay, James D.
A1  - Benavente, Yolanda
A1  - Weiderpass, Elisabete
A1  - Freisling, Heinz
A1  - Severi, Gianluca
A1  - Boutron Ruault, Marie-Christine
A1  - Besson, Caroline
A1  - Agnoli, Claudia
A1  - Masala, Giovanna
A1  - Sacerdote, Carlotta
A1  - Tumino, Rosario
A1  - Huerta, Jose Maria
A1  - Amiano, Pilar
A1  - Rodriguez-Barranco, Miguel
A1  - Bonet, Catalina
A1  - Barricarte, Aurelio
A1  - Christakoudi, Sofia
A1  - Knuppel, Anika
A1  - Bueno-de-Mesquita, Bas
A1  - Schulze, Matthias B.
A1  - Kaaks, Rudolf
A1  - Canzian, Federico
A1  - Spath, Florentin
A1  - Jerkeman, Mats
A1  - Rylander, Charlotta
A1  - Tjonneland, Anne
A1  - Olsen, Anja
A1  - Borch, Kristin Benjaminsen
A1  - Vermeulen, Roel
T1  - Association between anthropometry and lifestyle factors and risk of B-cell lymphoma
BT  - an exposome-wide analysis
JF  - International journal of cancer
N2  - To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single-study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL.
KW  - exposome
KW  - exposome‐ wide association study
KW  - lifestyle
KW  - lymphoma
KW  - prospective study
Y1  - 2020
U6  - https://doi.org/10.1002/ijc.33369
SN  - 0020-7136
SN  - 1097-0215
VL  - 148
IS  - 9
SP  - 2115
EP  - 2128
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Samaha, Doaa
A1  - Hamdo, Housam H.
A1  - Cong, Xiaojing
A1  - Schumacher, Fabian
A1  - Banhart, Sebastian
A1  - Aglar, Öznur
A1  - Möller, Heiko Michael
A1  - Heuer, Dagmar
A1  - Kleuser, Burkhard
A1  - Saied, Essa M.
A1  - Arenz, Christoph
T1  - Liposomal FRET assay identifies potent drug-like inhibitors of the Ceramide Transport Protein (CERT)
JF  - Chemistry - a European journal
N2  - Ceramide transfer protein (CERT) mediates non-vesicular transfer of ceramide from endoplasmic reticulum to Golgi apparatus and thus catalyzes the rate-limiting step of sphingomyelin biosynthesis. Usually, CERT ligands are evaluated in tedious binding assays or non-homogenous transfer assays using radiolabeled ceramides. Herein, a facile and sensitive assay for CERT, based on Forster resonance energy transfer (FRET), is presented. To this end, we mixed donor and acceptor vesicles, each containing a different fluorescent ceramide species. By CERT-mediated transfer of fluorescent ceramide, a FRET system was established, which allows readout in 96-well plate format, despite the high hydrophobicity of the components. Screening of a 2 000 compound library resulted in two new potent CERT inhibitors. One is approved for use in humans and one is approved for use in animals. Evaluation of cellular activity by quantitative mass spectrometry and confocal microscopy showed inhibition of ceramide trafficking and sphingomyelin biosynthesis.
KW  - enzyme assays
KW  - Forster resonance energy transfer (FRET)
KW  - liposomes
KW  - sphingolipids
KW  - transport proteins
Y1  - 2020
U6  - https://doi.org/10.1002/chem.202003283
SN  - 0947-6539
SN  - 1521-3765
VL  - 26
IS  - 70
SP  - 16616
EP  - 16621
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Schäfer, Marjänn Helena
A1  - Kakularam, Kumar Reddy
A1  - Reisch, Florian
A1  - Rothe, Michael
A1  - Stehling, Sabine
A1  - Heydeck, Dagmar
A1  - Püschel, Gerhard Paul
A1  - Kuhn, Hartmut
T1  - Male Knock-in Mice Expressing an Arachidonic Acid Lipoxygenase 15B (Alox15B) with Humanized Reaction Specificity Are Prematurely Growth Arrested When Aging
JF  - Biomedicines
N2  - Mammalian arachidonic acid lipoxygenases (ALOXs) have been implicated in cell differentiation and in the pathogenesis of inflammation. The mouse genome involves seven functional Alox genes and the encoded enzymes share a high degree of amino acid conservation with their human orthologs. There are, however, functional differences between mouse and human ALOX orthologs. Human ALOX15B oxygenates arachidonic acid exclusively to its 15-hydroperoxy derivative (15S-HpETE), whereas 8S-HpETE is dominantly formed by mouse Alox15b. The structural basis for this functional difference has been explored and in vitro mutagenesis humanized the reaction specificity of the mouse enzyme. To explore whether this mutagenesis strategy may also humanize the reaction specificity of mouse Alox15b in vivo, we created Alox15b knock-in mice expressing the arachidonic acid 15-lipoxygenating Tyr603Asp+His604Val double mutant instead of the 8-lipoxygenating wildtype enzyme. These mice are fertile, display slightly modified plasma oxylipidomes and develop normally up to an age of 24 weeks. At later developmental stages, male Alox15b-KI mice gain significantly less body weight than outbred wildtype controls, but this effect was not observed for female individuals. To explore the possible reasons for the observed gender-specific growth arrest, we determined the basic hematological parameters and found that aged male Alox15b-KI mice exhibited significantly attenuated red blood cell parameters (erythrocyte counts, hematocrit, hemoglobin). Here again, these differences were not observed in female individuals. These data suggest that humanization of the reaction specificity of mouse Alox15b impairs the functionality of the hematopoietic system in males, which is paralleled by a premature growth arrest.
KW  - eicosanoids
KW  - lipid peroxidation
KW  - oxidative stress
KW  - polyenoic fatty acids
KW  - erythropoiesis
Y1  - 2022
U6  - https://doi.org/10.3390/biomedicines10061379
SN  - 2227-9059
VL  - 10
SP  - 1
EP  - 22
PB  - MDPI
CY  - Basel, Schweiz
ET  - 6
ER  - 
TY  - JOUR
A1  - Christakoudi, Sofia
A1  - Pagoni, Panagiota
A1  - Ferrari, Pietro
A1  - Cross, Amanda J.
A1  - Tzoulaki, Ioanna
A1  - Muller, David C.
A1  - Weiderpass, Elisabete
A1  - Freisling, Heinz
A1  - Murphy, Neil
A1  - Dossus, Laure
A1  - Turzanski Fortner, Renee
A1  - Agudo, Antonio
A1  - Overvad, Kim
A1  - Perez-Cornago, Aurora
A1  - Key, Timothy J.
A1  - Brennan, Paul
A1  - Johansson, Mattias
A1  - Tjonneland, Anne
A1  - Halkjaer, Jytte
A1  - Boutron-Ruault, Marie-Christine
A1  - Artaud, Fanny
A1  - Severi, Gianluca
A1  - Kaaks, Rudolf
A1  - Schulze, Matthias B.
A1  - Bergmann, Manuela M.
A1  - Masala, Giovanna
A1  - Grioni, Sara
A1  - Simeon, Vittorio
A1  - Tumino, Rosario
A1  - Sacerdote, Carlotta
A1  - Skeie, Guri
A1  - Rylander, Charlotta
A1  - Borch, Kristin Benjaminsen
A1  - Quiros, J. Ramon
A1  - Rodriguez-Barranco, Miguel
A1  - Chirlaque, Maria-Dolores
A1  - Ardanaz, Eva
A1  - Amiano, Pilar
A1  - Drake, Isabel
A1  - Stocks, Tanja
A1  - Häggström, Christel
A1  - Harlid, Sophia
A1  - Ellingjord-Dale, Merete
A1  - Riboli, Elio
A1  - Tsilidis, Konstantinos K.
T1  - Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
JF  - International journal of cancer
N2  - Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (+/- 0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.
KW  - BMI change
KW  - cancer
KW  - middle adulthood
KW  - weight gain
KW  - weight loss
Y1  - 2020
U6  - https://doi.org/10.1002/ijc.33339
SN  - 0020-7136
SN  - 1097-0215
VL  - 148
IS  - 7
SP  - 1637
EP  - 1651
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Reichetzeder, Christoph
T1  - Overweight and obesity in pregnancy
BT  - their impact on epigenetics
JF  - European journal of clinical nutrition
N2  - Over the last few decades, the prevalence of obesity has risen to epidemic proportions worldwide. Consequently, the number of obesity in pregnancy has risen drastically. Gestational overweight and obesity are associated with impaired outcomes for mother and child. Furthermore, studies show that maternal obesity can lead to long-term consequences in the offspring, increasing the risk for obesity and cardiometabolic disease in later life. In addition to genetic mechanisms, mounting evidence demonstrates the induction of epigenetic alterations by maternal obesity, which can affect the offspring's phenotype, thereby influencing the later risk of obesity and cardiometabolic disease. Clear evidence in this regard comes from various animal models of maternal obesity. Evidence derived from clinical studies remains limited. The current article gives an overview of pathophysiological changes associated with maternal obesity and their consequences on placental structure and function. Furthermore, a short excurse is given on epigenetic mechanisms and emerging data regarding a putative interaction between metabolism and epigenetics. Finally, a summary of important findings of animal and clinical studies investigating maternal obesity-related epigenetic effects is presented also addressing current limitations of clinical studies.
Y1  - 2021
U6  - https://doi.org/10.1038/s41430-021-00905-6
SN  - 0954-3007
SN  - 1476-5640
VL  - 75
IS  - 12
SP  - 1710
EP  - 1722
PB  - Springer Nature
CY  - London
ER  - 
TY  - JOUR
A1  - Shahid, Muhammad
A1  - Manchi, G.
A1  - Slunsky, Pavel
A1  - Naseer, O.
A1  - Fatima, A.
A1  - Leo, B.
A1  - Raila, Jens
T1  - A systemic review of existing serological possibilities to diagnose canine osteoarthritis with a particular focus on extracellular matrix proteoglycans and protein
JF  - Polish journal of veterinary sciences : PJVS : the journal of Committee of Veterinary Sciences of Polish Academy of Sciences and University of Warmia and Mazury in Olsztyn
N2  - Extra-cellular matrix (ECM) components are important and their stabilization is significant in maintaining normal healthy joint environment. In osteoarthritis (OA), ECM components are altered and indicate disease progression. The joint ECM is composed of proteoglycans (aggrecan, perlecan,inter α-trypsin inhibitor), glycoproteins (fibronectin, lubricin, COMP) and collagen types (most abundantly collagen type II) which represent structural and functional transformation during disease advancement. ECM investigation revealed significant biomarkers of OA that could be used as a diagnostic and therapeutic tool in different canine orthopedic diseases. This review deliberates our current findings of how the components of ECM change at the molecular level during disease progression in canine OA.
KW  - extra-cellular matrix
KW  - canine osteoarthritis
KW  - biomarker
KW  - synovial fluid
KW  - proteomix analysis
Y1  - 2017
U6  - https://doi.org/10.1515/pjvs-2017-0024
SN  - 1505-1773
SN  - 2300-2557
VL  - 20
IS  - 1
SP  - 189
EP  - 201
PB  - De Gruyter
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Püschel, Gerhard
A1  - Klauder, Julia
A1  - Henkel-Oberländer, Janin
T1  - Macrophages, low-grade inflammation, insulin resistance and hyperinsulinemia
BT  - A mutual ambiguous relationship in the development of metabolic diseases
JF  - Journal of Clinical Medicine : open access journal
N2  - Metabolic derangement with poor glycemic control accompanying overweight and obesity is associated with chronic low-grade inflammation and hyperinsulinemia. Macrophages, which present a very heterogeneous population of cells, play a key role in the maintenance of normal tissue homeostasis, but functional alterations in the resident macrophage pool as well as newly recruited monocyte-derived macrophages are important drivers in the development of low-grade inflammation. While metabolic dysfunction, insulin resistance and tissue damage may trigger or advance pro-inflammatory responses in macrophages, the inflammation itself contributes to the development of insulin resistance and the resulting hyperinsulinemia. Macrophages express insulin receptors whose downstream signaling networks share a number of knots with the signaling pathways of pattern recognition and cytokine receptors, which shape macrophage polarity. The shared knots allow insulin to enhance or attenuate both pro-inflammatory and anti-inflammatory macrophage responses. This supposedly physiological function may be impaired by hyperinsulinemia or insulin resistance in macrophages. This review discusses the mutual ambiguous relationship of low-grade inflammation, insulin resistance, hyperinsulinemia and the insulin-dependent modulation of macrophage activity with a focus on adipose tissue and liver.
KW  - NAFLD/MAFLD
KW  - type 2 diabetes
KW  - obesity
KW  - vicious cycle
KW  - TLR signaling
KW  - M1/M2 differentiation
KW  - Akt pathway
Y1  - 2022
U6  - https://doi.org/10.3390/jcm11154358
SN  - 2077-0383
VL  - 11
IS  - 15
SP  - 1
EP  - 30
PB  - MDPI
CY  - Basel, Schweiz
ER  - 
TY  - JOUR
A1  - Wilhelmi, Ilka
A1  - Grunwald, Stephan
A1  - Gimber, Niclas
A1  - Popp, Oliver
A1  - Dittmar, Gunnar
A1  - Arumughan, Anup
A1  - Wanker, Erich E.
A1  - Laeger, Thomas
A1  - Schmoranzer, Jan
A1  - Daumke, Oliver
A1  - Schürmann, Annette
T1  - The ARFRP1-dependent Golgi scaffolding protein GOPC is required for insulin secretion from pancreatic 13-cells
JF  - Molecular metabolism
N2  - Objective: Hormone secretion from metabolically active tissues, such as pancreatic islets, is governed by specific and highly regulated signaling pathways. Defects in insulin secretion are among the major causes of diabetes. The molecular mechanisms underlying regulated insulin secretion are, however, not yet completely understood. In this work, we studied the role of the GTPase ARFRP1 on insulin secretion from pancreatic 13-cells. <br /> Methods: A 13-cell-specific Arfrp1 knockout mouse was phenotypically characterized. Pulldown experiments and mass spectrometry analysis were employed to screen for new ARFRP1-interacting proteins. Co-immunoprecipitation assays as well as super-resolution microscopy were applied for validation. <br /> Results: The GTPase ARFRP1 interacts with the Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC). Both proteins are co localized at the trans-Golgi network and regulate the first and second phase of insulin secretion by controlling the plasma membrane localization of the SNARE protein SNAP25. Downregulation of both GOPC and ARFRP1 in Min6 cells interferes with the plasma membrane localization of SNAP25 and enhances its degradation, thereby impairing glucose-stimulated insulin release from 13-cells. In turn, overexpression of SNAP25 as well as GOPC restores insulin secretion in islets from 13-cell-specific Arfrp1 knockout mice. <br /> Conclusion: Our results identify a hitherto unrecognized pathway required for insulin secretion at the level of trans-Golgi sorting. (c) 2020 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
KW  - Insulin secretion
KW  - Endosomal sorting
KW  - SNARE proteins
KW  - trans-Golgi
KW  - network
Y1  - 2020
U6  - https://doi.org/10.1016/j.molmet.2020.101151
SN  - 2212-8778
VL  - 45
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Zheng, Ju-Sheng
A1  - Luan, Jian'an
A1  - Sofianopoulou, Eleni
A1  - Imamura, Fumiaki
A1  - Stewart, Isobel D.
A1  - Day, Felix R.
A1  - Pietzner, Maik
A1  - Wheeler, Eleanor
A1  - Lotta, Luca A.
A1  - Gundersen, Thomas E.
A1  - Amiano, Pilar
A1  - Ardanaz, Eva
A1  - Chirlaque, Maria-Dolores
A1  - Fagherazzi, Guy
A1  - Franks, Paul W.
A1  - Kaaks, Rudolf
A1  - Laouali, Nasser
A1  - Mancini, Francesca Romana
A1  - Nilsson, Peter M.
A1  - Onland-Moret, N. Charlotte
A1  - Olsen, Anja
A1  - Overvad, Kim
A1  - Panico, Salvatore
A1  - Palli, Domenico
A1  - Ricceri, Fulvio
A1  - Rolandsson, Olov
A1  - Spijkerman, Annemieke M. W.
A1  - Sanchez, Maria-Jose
A1  - Schulze, Matthias B.
A1  - Sala, Nuria
A1  - Sieri, Sabina
A1  - Tjonneland, Anne
A1  - Tumino, Rosario
A1  - van der Schouw, Yvonne T.
A1  - Weiderpass, Elisabete
A1  - Riboli, Elio
A1  - Danesh, John
A1  - Butterworth, Adam S.
A1  - Sharp, Stephen J.
A1  - Langenberg, Claudia
A1  - Forouhi, Nita G.
A1  - Wareham, Nicholas J.
T1  - Plasma vitamin C and type 2 diabetes
BT  - genome-wide association study and Mendelian randomization analysis in European populations
JF  - Diabetes care
N2  - OBJECTIVE: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.

RESEARCH DESIGN AND METHODS: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. 

RESULTS: We identified 11 genomic regions associated with plasma vitamin C (P < 5 x 10(-8)), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).

CONCLUSIONS: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
Y1  - 2020
U6  - https://doi.org/10.2337/dc20-1328
SN  - 0149-5992
SN  - 1935-5548
VL  - 44
IS  - 1
SP  - 98
EP  - 106
PB  - American Diabetes Association
CY  - Alexandria
ER  - 
TY  - JOUR
A1  - Herpich, Catrin
A1  - Haß, Ulrike
A1  - Kochlik, Bastian Max
A1  - Franz, Kristina
A1  - Laeger, Thomas
A1  - Klaus, Susanne
A1  - Bosy-Westphal, Anja
A1  - Norman, Kristina
T1  - Postprandial dynamics and response of fibroblast growth factor 21 in older adults
JF  - Clinical Nutrition
N2  - Background & aims: Fibroblast growth factor 21 (FGF21) plays a pivotal role in glucose and lipid metabolism and has been proposed as a longevity hormone. However, elevated plasma FGF21 concentrations are paradoxically associated with mortality in higher age and little is known about the postprandial regulation of FGF21 in older adults. In this parallel group study, we investigated postprandial FGF21 dynamics and response in older (65-85 years) compared to younger (18-35 years) adults following test meals with varying macronutrient composition.

Methods: Participants (n = 60 older; n = 60 younger) were randomized to one of four test meals: dextrose, high carbohydrate (HC), high fat (HF) or high protein (HP). Blood was drawn before and 15, 30, 60, 120, 240 min after meal ingestion. Postprandial dynamics were evaluated using repeated measures ANCOVA. FGF21 response was assessed by incremental area under the curve.

Results: Fasting FGF21 concentrations were significantly higher in older adults. FGF21 dynamics were affected by test meal (p < 0.001) and age (p = 0.013), when adjusted for BMI and fasting FGF21. Postprandial FGF21 concentrations steadily declined over 240 min in both age groups after HF and HP, but not after dextrose or HC ingestion. At 240 min, FGF21 concentrations were significantly higher in older than in younger adults following dextrose (133 pg/mL, 95%CI: 103, 172 versus 91.2 pg/mL, 95%CI: 70.4, 118; p = 0.044), HC (109 pg/mL, 95%CI: 85.1, 141 versus 70.3 pg/mL, 95%CI: 55.2, 89.6; p = 0.014) and HP ingestion (45.4 pg/mL, 95%CI: 34.4, 59.9 versus 27.9 pg/mL 95%CI: 20.9, 37.1; p = 0.018). FGF21 dynamics and response to HF were similar for both age groups.

Conclusions: The age-specific differences in postprandial FGF21 dynamics and response in healthy adults, potentially explain higher FGF21 concentrations in older age. Furthermore, there appears to be a significant impact of acute and recent protein intake on FGF21 secretion.
Y1  - 2021
U6  - https://doi.org/10.1016/j.clnu.2021.04.037
SN  - 0261-5614
SN  - 1532-1983
VL  - 40
IS  - 6
SP  - 3765
EP  - 3771
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Wei, Xiaoyan
A1  - Franke, Julia
A1  - Ost, Mario
A1  - Wardelmann, Kristina
A1  - Börno, Stefan
A1  - Timmermann, Bernd
A1  - Meierhofer, David
A1  - Kleinridders, Andre
A1  - Klaus, Susanne
A1  - Stricker, Sigmar
T1  - Cell autonomous requirement of neurofibromin (Nf1) for postnatal muscle hypertrophic growth and metabolic homeostasis
JF  - Journal of cachexia, sarcopenia and muscle
N2  - Background Neurofibromatosis type 1 (NF1) is a multi-organ disease caused by mutations in neurofibromin 1 (NF1). Amongst other features, NF1 patients frequently show reduced muscle mass and strength, impairing patients' mobility and increasing the risk of fall. The role of Nf1 in muscle and the cause for the NF1-associated myopathy are mostly unknown. Methods To dissect the function ofNf1in muscle, we created muscle-specific knockout mouse models for NF1, inactivatingNf1in the prenatal myogenic lineage either under the Lbx1 promoter or under the Myf5 promoter. Mice were analysed during prenatal and postnatal myogenesis and muscle growth. Results Nf1(Lbx1)and Nf1(Myf5)animals showed only mild defects in prenatal myogenesis. Nf1(Lbx1)animals were perinatally lethal, while Nf1(Myf5)animals survived only up to approximately 25 weeks. A comprehensive phenotypic characterization of Nf1(Myf5)animals showed decreased postnatal growth, reduced muscle size, and fast fibre atrophy. Proteome and transcriptome analyses of muscle tissue indicated decreased protein synthesis and increased proteasomal degradation, and decreased glycolytic and increased oxidative activity in muscle tissue. High-resolution respirometry confirmed enhanced oxidative metabolism in Nf1(Myf5)muscles, which was concomitant to a fibre type shift from type 2B to type 2A and type 1. Moreover, Nf1(Myf5)muscles showed hallmarks of decreased activation of mTORC1 and increased expression of atrogenes. Remarkably, loss of Nf1 promoted a robust activation of AMPK with a gene expression profile indicative of increased fatty acid catabolism. Additionally, we observed a strong induction of genes encoding catabolic cytokines in muscle Nf1(Myf5)animals, in line with a drastic reduction of white, but not brown adipose tissue. Conclusions Our results demonstrate a cell autonomous role for Nf1 in myogenic cells during postnatal muscle growth required for metabolic and proteostatic homeostasis. Furthermore, Nf1 deficiency in muscle drives cross-tissue communication and mobilization of lipid reserves.
KW  - neurofibromatosis
KW  - NF1
KW  - myopathy
KW  - muscle atrophy
KW  - muscle metabolism
KW  - muscle fibre type
KW  - AMPK
Y1  - 2020
U6  - https://doi.org/10.1002/jcsm.12632
SN  - 2190-5991
SN  - 2190-6009
VL  - 11
IS  - 6
SP  - 1758
EP  - 1778
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Aga-Barfknecht, Heja
A1  - Hallahan, Nicole
A1  - Gottmann, Pascal
A1  - Jähnert, Markus
A1  - Osburg, Sophie
A1  - Schulze, Gunnar
A1  - Kamitz, Anne
A1  - Arends, Danny
A1  - Brockmann, Gudrun
A1  - Schallschmidt, Tanja
A1  - Lebek, Sandra
A1  - Chadt, Alexandra
A1  - Al-Hasani, Hadi
A1  - Joost, Hans-Georg
A1  - Schürmann, Annette
A1  - Vogel, Heike
T1  - Identification of novel potential type 2 diabetes genes mediating beta-cell loss and hyperglycemia using positional cloning
JF  - Frontiers in genetics
N2  - Type 2 diabetes (T2D) is a complex metabolic disease regulated by an interaction of genetic predisposition and environmental factors. To understand the genetic contribution in the development of diabetes, mice varying in their disease susceptibility were crossed with the obese and diabetes-prone New Zealand obese (NZO) mouse. Subsequent whole-genome sequence scans revealed one major quantitative trait loci (QTL),Nidd/DBAon chromosome 4, linked to elevated blood glucose and reduced plasma insulin and low levels of pancreatic insulin. Phenotypical characterization of congenic mice carrying 13.6 Mbp of the critical fragment of DBA mice displayed severe hyperglycemia and impaired glucose clearance at week 10, decreased glucose response in week 13, and loss of beta-cells and pancreatic insulin in week 16. To identify the responsible gene variant(s), further congenic mice were generated and phenotyped, which resulted in a fragment of 3.3 Mbp that was sufficient to induce hyperglycemia. By combining transcriptome analysis and haplotype mapping, the number of putative responsible variant(s) was narrowed from initial 284 to 18 genes, including gene models and non-coding RNAs. Consideration of haplotype blocks reduced the number of candidate genes to four (Kti12,Osbpl9,Ttc39a, andCalr4) as potential T2D candidates as they display a differential expression in pancreatic islets and/or sequence variation. In conclusion, the integration of comparative analysis of multiple inbred populations such as haplotype mapping, transcriptomics, and sequence data substantially improved the mapping resolution of the diabetes QTLNidd/DBA. Future studies are necessary to understand the exact role of the different candidates in beta-cell function and their contribution in maintaining glycemic control.
KW  - type 2 diabetes
KW  - beta-cell loss
KW  - insulin
KW  - positional cloning
KW  - transcriptomics
KW  - haplotype
Y1  - 2020
U6  - https://doi.org/10.3389/fgene.2020.567191
SN  - 1664-8021
VL  - 11
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Perez-Cornago, Aurora
A1  - Crowe, Francesca L.
A1  - Appleby, Paul N.
A1  - Bradbury, Kathryn E.
A1  - Wood, Angela M.
A1  - Jakobsen, Marianne Uhre
A1  - Johnson, Laura
A1  - Sacerdote, Carlotta
A1  - Steur, Marinka
A1  - Weiderpass, Elisabete
A1  - Wurtz, Anne Mette L.
A1  - Kuhn, Tilman
A1  - Katzke, Verena
A1  - Trichopoulou, Antonia
A1  - Karakatsani, Anna
A1  - La Vecchia, Carlo
A1  - Masala, Giovanna
A1  - Tumino, Rosario
A1  - Panico, Salvatore
A1  - Sluijs, Ivonne
A1  - Skeie, Guri
A1  - Imaz, Liher
A1  - Petrova, Dafina
A1  - Quiros, J. Ramon
A1  - Yohar, Sandra Milena Colorado
A1  - Jakszyn, Paula
A1  - Melander, Olle
A1  - Sonestedt, Emily
A1  - Andersson, Jonas
A1  - Wennberg, Maria
A1  - Aune, Dagfinn
A1  - Riboli, Elio
A1  - Schulze, Matthias B.
A1  - di Angelantonio, Emanuele
A1  - Wareham, Nicholas J.
A1  - Danesh, John
A1  - Forouhi, Nita G.
A1  - Butterworth, Adam S.
A1  - Key, Timothy J.
T1  - Plant foods, dietary fibre and risk of ischaemic heart disease in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
JF  - International journal of epidemiology
N2  - Background:
Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC). 

Methods:
We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD. 

Results: 
There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95% confidence interval (CI): 0.90-0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95-1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82-0.98, Ptrend = 0.020), total fibre (per 10 g/day 0.91, 0.85-0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91-0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95-1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk. 

Conclusions:
In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear.
KW  - fruit
KW  - vegetables
KW  - legumes
KW  - nuts
KW  - seeds
KW  - coronary heart disease
Y1  - 2021
U6  - https://doi.org/10.1093/ije/dyaa155
SN  - 0300-5771
SN  - 1464-3685
VL  - 50
IS  - 1
SP  - 212
EP  - 222
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Schjeide, Brit-Maren
A1  - Schenke, Maren
A1  - Seeger, Bettina
A1  - Püschel, Gerhard
T1  - Validation of a novel double control quantitative copy number PCR method to quantify off-target transgene integration after CRISPR-induced DNA modification
JF  - Methods and protocols : M&Ps
N2  - In order to improve a recently established cell-based assay to assess the potency of botulinum neurotoxin, neuroblastoma-derived SiMa cells and induced pluripotent stem-cells (iPSC) were modified to incorporate the coding sequence of a reporter luciferase into a genetic safe harbor utilizing CRISPR/Cas9. A novel method, the double-control quantitative copy number PCR (dc-qcnPCR), was developed to detect off-target integrations of donor DNA. The donor DNA insertion success rate and targeted insertion success rate were analyzed in clones of each cell type. The dc-qcnPCR reliably quantified the copy number in both cell lines. The probability of incorrect donor DNA integration was significantly increased in SiMa cells in comparison to the iPSCs. This can possibly be explained by the lower bundled relative gene expression of a number of double-strand repair genes (BRCA1, DNA2, EXO1, MCPH1, MRE11, and RAD51) in SiMa clones than in iPSC clones. The dc-qcnPCR offers an efficient and cost-effective method to detect off-target CRISPR/Cas9-induced donor DNA integrations.
KW  - CRISPR editing validation
KW  - copy number analyses
KW  - homology-directed repair
KW  - homologous recombination deficiency
Y1  - 2022
U6  - https://doi.org/10.3390/mps5030043
SN  - 2409-9279
VL  - 5
IS  - 3
SP  - 1
EP  - 14
PB  - MDPI
CY  - Basel, Schweiz
ER  - 
TY  - JOUR
A1  - Hauffe, Robert
A1  - Rath, Michaela
A1  - Agyapong, Wilson
A1  - Jonas, Wenke
A1  - Vogel, Heike
A1  - Schulz, Tim Julius
A1  - Schwarz, Maria
A1  - Kipp, Anna Patricia
A1  - Blüher, Matthias
A1  - Kleinridders, André
T1  - Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling
JF  - Antioxidants
N2  - The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.
KW  - selenite
KW  - insulin
KW  - adipose tissue
KW  - obesity
KW  - insulin resistance
Y1  - 2022
U6  - https://doi.org/10.3390/antiox11050862
SN  - 2076-3921
VL  - 11
SP  - 1
EP  - 16
PB  - MDPI
CY  - Basel, Schweiz
ET  - 5
ER  - 
TY  - JOUR
A1  - Lu, Yong-Ping
A1  - Hasan, Ahmed A.
A1  - Zeng, Shufei
A1  - Hocher, Berthold
T1  - Plasma ET-1 concentrations are elevated in pregnant women with hypertension - meta-analysis of clinical studies
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie ; official organ of the Deutsche Liga zur Bekämpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft
N2  - Background/Aims:
The ET system might be involved in the pathogenesis of hypertensive disorders during pregnancy. The objective is to analyse the impact of ET-1 in hypertensive pregnant women by a strict meta-analysis of published human clinical studies. 
Methods:
Based on the principle of Cochrane systematic reviews, Cohort studies in PubMed (Medline), Google Scholar and China Biological Medicine Database (CBM-disc) designed to identify the role of endothelin-1 (ET-1) in the pathophysiology of gestational hypertension and preeclampsia were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects model.
Results:
Sixteen published cohort studies including 1739 hypertensive cases and 409 controls were used in the meta-analysis. ET-1 plasma concentrations were higher in hypertensive pregnant women as compared to the controls (mean difference between groups: 19.02 [15.60～22.44], P < 0.00001,). These finding were driven by severity of hypertension and/or degree of proteinuria.
Conclusion:
Plasma ET-1 concentrations are elevated in hypertensive disorders during human pregnancy. In particular women with preeclampsia (hypertensive pregnant women with proteinuria) have substantially elevated plasma ET-1 concentration as compared to pregnant women with normal blood pressure.
KW  - Et-1
KW  - Pregnancy
KW  - Hypertension
KW  - Meta-analysis
Y1  - 2017
U6  - https://doi.org/10.1159/000482004
SN  - 1420-4096
SN  - 1423-0143
VL  - 42
IS  - 4
SP  - 654
EP  - 663
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Fayyaz, Susann
A1  - Japtok, Lukasz
A1  - Schumacher, Fabian
A1  - Wigger, Dominik
A1  - Schulz, Tim Julius
A1  - Haubold, Kathrin
A1  - Gulbins, Erich
A1  - Völler, Heinz
A1  - Kleuser, Burkhard
T1  - Lysophosphatidic acid inhibits insulin signaling in primary rat hepatocytes via the LPA(3) receptor subtype and is increased in obesity
JF  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology
N2  - Background/Aims:
Obesity is a main risk factor for the development of hepatic insulin resistance and it is accompanied by adipocyte hypertrophy and an elevated expression of different adipokines such as autotaxin (ATX). ATX converts lysophosphatidylcholine to lysophosphatidic acid (LPA) and acts as the main producer of extracellular LPA. This bioactive lipid regulates a broad range of physiological and pathological responses by activation of LPA receptors (LPA1-6).
Methods:
The activation of phosphatidylinositide 3-kinases (PI3K) signaling (Akt and GSK-3ß) was analyzed via western blotting in primary rat hepatocytes. Incorporation of glucose into glycogen was measured by using radio labeled glucose. Real-time PCR analysis and pharmacological modulation of LPA receptors were performed. Human plasma LPA levels of obese (BMI > 30, n = 18) and normal weight individuals (BMI 18.5-25, n = 14) were analyzed by liquid chromatography tandem-mass spectrometry (LC-MS/MS).
Results:
Pretreatment of primary hepatocytes with LPA resulted in an inhibition of insulin-mediated Gck expression, PI3K activation and glycogen synthesis. Pharmacological approaches revealed that the LPA3-receptor subtype is responsible for the inhibitory effect of LPA on insulin signaling. Moreover, human plasma LPA concentrations (16: 0 LPA) of obese participants (BMI > 30) are significantly elevated in comparison to normal weight individuals (BMI 18.5-25).
Conclusion:
LPA is able to interrupt insulin signaling in primary rat hepatocytes via the LPA3 receptor subtype. Moreover, the bioactive lipid LPA (16: 0) is increased in obesity.
KW  - Lysophosphatidic acid
KW  - Insulin signaling
KW  - Adipose tissue
KW  - Autotaxin
KW  - Hepatic insulin resistance
KW  - LPA(3) receptor subtype
Y1  - 2017
U6  - https://doi.org/10.1159/000480470
SN  - 1015-8987
SN  - 1421-9778
VL  - 43
SP  - 445
EP  - 456
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Neuber, Corinna
A1  - Schumacher, Fabian
A1  - Gulbins, Erich
A1  - Kleuser, Burkhard
T1  - Mass Spectrometric Determination of Fatty Aldehydes Exemplified by Monitoring the Oxidative Degradation of (2E)-Hexadecenal in HepG2 Cell Lysates
JF  - Lipidomics
N2  - Within the last few decades, liquid chromatography-mass spectrometry (LC-MS) has become a preferred method for manifold issues in analytical biosciences, given its high selectivity and sensitivity. However, the analysis of fatty aldehydes, which are important components of cell metabolism, remains challenging. Usually, chemical derivatization prior to MS detection is required to enhance ionization efficiency. In this regard, the coupling of fatty aldehydes to hydrazines like 2,4-dinitrophenylhydrazine (DNPH) is a common approach. Additionally, hydrazones readily react with fatty aldehydes to form stable derivatives, which can be easily separated using high-performance liquid chromatography (HPLC) and subsequently detected by MS. Here, we exemplarily present the quantification of the long-chain fatty aldehyde (2E)-hexadecenal, a break-down product of the bioactive lipid sphingosine 1-phosphate (S1P), after derivatization with 2-diphenylacetyl-1,3-indandione-1-hydrazone (DAIH) via isotope-dilution HPLC-electrospray ionization-quadrupole/time-of-flight (ESI-QTOF) MS. Moreover, we show that the addition of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC hydrochloride) as a coupling agent allows for simultaneous determination of fatty aldehydes and fatty acids as DAIH derivatives. Taking advantage of this, we describe in detail how to monitor the degradation of (2E)-hexadecenal and the concurrent formation of its oxidation product (2E)-hexadecenoic acid in lysates of human hepatoblastoma (HepG2) cells within this chapter.
KW  - (2E)-hexadecenal
KW  - (2E)-hexadecenoic acid
KW  - Sphingosine 1-phosphate
KW  - Derivatization
KW  - DAIH
KW  - EDC
KW  - Isotope-dilution
KW  - HPLC-ESI-QTOF
Y1  - 2017
SN  - 978-1-4939-6946-3
SN  - 978-1-4939-6944-9
U6  - https://doi.org/10.1007/978-1-4939-6946-3_10
SN  - 0893-2336
SN  - 1940-6045
VL  - 125
SP  - 147
EP  - 158
PB  - Humana Press
CY  - Totowa
ER  - 
TY  - JOUR
A1  - Schwiebs, Anja
A1  - Thomas, Dominique Jeanette
A1  - Kleuser, Burkhard
A1  - Pfeilschifter, Josef
A1  - Radeke, Heinfried H.
T1  - Nuclear translocation of SGPP-1 and decrease of SGPL-1 activity contribute to sphingolipid rheostat regulation of inflammatory dendritic cells
JF  - Mediators of inflammation
N2  - A balanced sphingolipid rheostat is indispensable for dendritic cell function and survival and thus initiation of an immune response. Sphingolipid levels are dynamically maintained by the action of sphingolipid enzymes of which sphingosine kinases, S1P phosphatases (SGPP-1/2) and S1P lyase (SGPL-1), are pivotal in the balance of S1P and sphingosine levels. In this study, we present that SGPP-1 and SGPL-1 are regulated in inflammatory dendritic cells and contribute to S1P fate. TLR-dependent activation caused SGPL-1 protein downregulation with subsequent decrease of enzymatic activity by two-thirds. In parallel, confocal fluorescence microscopy revealed that endogenous SGPP-1 was expressed in nuclei of naive dendritic cells and was translocated into the cytoplasmatic compartment upon inflammatory stimulation resulting in dephosphorylation of S1P. Mass spectrometric determination showed that a part of the resulting sphingosine was released from the cell, increasing extracellular levels. Another route of diminishing intracellular S1P was possibly taken by its export via ATP-binding cassette transporter C1 which was upregulated in array analysis, while the S1P transporter, spinster homolog 2, was not relevant in dendritic cells. These investigations newly describe the sequential expression and localization of the endogenous S1P regulators SGPP-1 and SGPL-1 and highlight their contribution to the sphingolipid rheostat in inflammation.
Y1  - 2017
U6  - https://doi.org/10.1155/2017/5187368
SN  - 0962-9351
SN  - 1466-1861
PB  - Hindawi Publishing Corp.
CY  - London
ER  - 
TY  - JOUR
A1  - Hoehn, Richard S.
A1  - Jernigan, Peter L.
A1  - Japtok, Lukasz
A1  - Chang, Alex L.
A1  - Midura, Emily F.
A1  - Caldwell, Charles C.
A1  - Kleuser, Burkhard
A1  - Lentsch, Alex B.
A1  - Edwards, Michael J.
A1  - Gulbins, Erich
A1  - Pritts, Timothy A.
T1  - Acid sphingomyelinase inhibition in stored erythrocytes reduces transfusion-associated lung inflammation
JF  - Annals of surgery : a monthly review of surgical science and practice
N2  - Objective: We aimed to identify the role of the enzyme acid sphingomyelinase in the aging of stored units of packed red blood cells (pRBCs) and subsequent lung inflammation after transfusion.
Summary Background Data: Large volume pRBC transfusions are associated with multiple adverse clinical sequelae, including lung inflammation. Microparticles are formed in stored pRBCs over time and have been shown to contribute to lung inflammation after transfusion.
Methods: Human and murine pRBCs were stored with or without amitriptyline, a functional inhibitor of acid sphingomyelinase, or obtained from acid sphingomyelinase-deficient mice, and lung inflammation was studied in mice receiving transfusions of pRBCs and microparticles isolated from these units.
Results: Acid sphingomyelinase activity in pRBCs was associated with the formation of ceramide and the release of microparticles. Treatment of pRBCs with amitriptyline inhibited acid sphingomyelinase activity, ceramide accumulation, and microparticle production during pRBC storage. Transfusion of aged pRBCs or microparticles isolated from aged blood into mice caused lung inflammation. This was attenuated after transfusion of pRBCs treated with amitriptyline or from acid sphingomyelinase-deficient mice.
Conclusions: Acid sphingomyelinase inhibition in stored pRBCs offers a novel mechanism for improving the quality of stored blood.
KW  - acid sphingomyelinase
KW  - blood banking
KW  - ceramide
KW  - lung inflammation
KW  - microparticle
Y1  - 2017
U6  - https://doi.org/10.1097/SLA.0000000000001648
SN  - 0003-4932
SN  - 1528-1140
VL  - 265
IS  - 1
SP  - 218
EP  - 226
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  - 
TY  - JOUR
A1  - He, Jing
A1  - Liu, Zhi-Wei
A1  - Lu, Yong-Ping
A1  - Li, Tao-Yuan
A1  - Liang, Xu-Jing
A1  - Arck, Petra
A1  - Huang, Si-Min
A1  - Hocher, Berthold
A1  - Chen, You-Peng
T1  - A systematic review and meta-analysis of influenza a virus infection during pregnancy associated with an increased risk for stillbirth and low birth weight
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie ; official organ of the Deutsche Liga zur Bekämpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft
N2  - Background/Aims: Impaired pregnancy outcomes, such as low birth weight are associated with increased disease risk in later life, however little is known about the impact of common infectious diseases during pregnancy on birth weight. The study had two aims: a) to investigate risk factors of influenza virus infection during pregnancy, and b) to analyze the impact of influenza virus infection on pregnancy outcome, especially birth weight.
Methods: Prospective and retrospective observational studies found in PubMed, MEDLINE, Embase, Google Scholar, and WangFang database were included in this meta analysis. Data of included studies was extracted and analyzed by the RevMan software.
Results: Pregnant women with anemia (P=0.004, RR=1.46, 95% CI: 1.13-1.88), obesity (P<0.00001, RR=1.35, 95% CI: 1.25-1.46) and asthma (P<0.00001, RR=1.99, 95% CI: 1.67-2.37) had higher rates of influenza virus infection. Regarding birth outcomes, influenza A virus infection did not affect the likelihood for cesarean section. Mothers with influenza had a higher rate of stillbirth (P=0.04, RR=2.36, 95% CI: 1.05-5.31), and their offspring had low 5-minute APGR Scores (P=0.009, RR=1.39, 95% CI: 1.08-1.79). Furthermore, the rate for birth weight < 2500g (P=0.04, RR=1.71, 95% CI: 1.03-2.84) was increased.
Conclusion: Results of this study showed that anemia, asthma and obesity during pregnancy are risk factors influenza A virus infection during pregnancy. Moreover, gestational influenza A infection impairs pregnancy outcomes and increases the risk for low birth weight, a known risk factor for later life disease susceptibility.
KW  - Apgar score
KW  - Influenza virus
KW  - Offspring
KW  - Outcome
KW  - Pregnancy
KW  - Stillbirth
KW  - Birth weight
Y1  - 2017
U6  - https://doi.org/10.1159/000477221
SN  - 1420-4096
SN  - 1423-0143
VL  - 42
IS  - 2
SP  - 232
EP  - 243
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Reichetzeder, Christoph
A1  - Heunisch, Fabian
A1  - von Einem, Gina-Franziska
A1  - Tsuprykov, Oleg
A1  - Kellner, Karl-Heinz
A1  - Dschietzig, Thomas
A1  - Kretschmer, Axel
A1  - Hocher, Berthold
T1  - Pre-interventional kynurenine predicts medium-term outcome after contrast media exposure due to coronary angiography
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie ; official organ of the Deutsche Liga zur Bekämpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft
N2  - Background/Aims: Contrast induced acute kidney injury (CI-AKI) remains a serious complication of contrast media enhanced procedures like coronary angiography. There is still a lack of established biomarkers that help to identify patients at high risk for short and long-term complications. The aim of the current study was to evaluate plasma kynurenine as a predictive biomarker for CI-AKI and long-term complications, measured by the combined endpoint "major adverse kidney events" (MAKE) up to 120 days after CM application.
Methods: In this prospective cohort study 245 patients undergoing coronary angiography were analyzed. Blood samples were obtained at baseline, 24h and 48h after contrast media (CM) application to diagnose CI-AKI. Patients were followed for 120 days for adverse clinical events including death, the need for dialysis, and a doubling of plasma creatinine. Occurrence of any of these events was summarized in the combined endpoint MAKE.
Results: Preinterventional plasma kynurenine was not associated with CI-AKI. Patients who later developed MAKE displayed significantly increased preinterventional plasma kynurenine levels (p<0.0001). ROC analysis revealed that preinterventional kynurenine is highly predictive for MAKE (AUC=0.838; p<0.0001). The optimal cutoff was found at >= 3.5 mu mol/L. Using this cutoff, the Kaplan-Meier estimator demonstrated that concentrations of plasma kynurenine >= 3.5 mu mol/L were significantly associated with a higher prevalence of MAKE until follow up (p<0.0001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome.
Conclusion: Preinterventional plasma kynurenine might serve as a highly predictive biomarker for MAKE up to 120 days after coronary angiography.
KW  - Contrast induced acute kidney injury
KW  - Coronary angiography
KW  - Major adverse kidney event
KW  - Kynurenine
KW  - Preinterventional biomarker
Y1  - 2017
U6  - https://doi.org/10.1159/000477222
SN  - 1420-4096
SN  - 1423-0143
VL  - 42
IS  - 2
SP  - 244
EP  - 256
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Xu, Mei
A1  - Lu, Yong-Ping
A1  - Hasan, Ahmed A.
A1  - Hocher, Berthold
T1  - Plasma ET-1 concentrations are elevated in patients with hypertension meta-analysis of clinical studies
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie ; official organ of the Deutsche Liga zur Bekämpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft
N2  - Background/Aims: A recent study revealed that global overexpression of ET-1 causes a slight reduction in systemic blood pressure. Moreover, heterozygous ET-1 knockout mice are hypertensive. The role of ET-1 in human hypertension was so far not addressed by a strict meta-analysis of published human clinical studies.
Methods: We included studies published between January 1, 1990 and February 28, 2017. We included case control studies analyzing untreated essential hypertension or hypertensive patients where antihypertensive medication was discontinued for at least two weeks. Based on the principle of Cochrane systematic reviews, case control studies (CCSs) in PubMed (Medline) and Google Scholar designed to identify the role of endothelin-1 (ET-1) in the pathophysiological of hypertension were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects models.
Results: Eleven studies fulfilling our in-and exclusion criteria were eligible for this meta-analysis. These studies included 450 hypertensive patients and 328 controls. Our meta-analysis revealed that ET-1 plasma concentrations were higher in hypertensive patients as compared to the control patients [mean difference between groups 1.57 pg/mL, 95%Ci [0.47 similar to 2.68, P = 0.005]. These finding were driven by patients having systolic blood pressure higher than 160 mmHg and diastolic blood pressure higher than 100 mmHg.
Conclusions: This meta-analysis showed that hypertensive patients do have elevated plasma ET-1 concentrations. This finding is driven by those patients with high systolic/diastolic blood pressure. Given that the ET-1 gene did not appear in any of the whole genome association studies searching for hypertension associated gene loci, it is very likely that the elevated plasma ET-1 concentrations in hypertensive patients are secondary to hypertension and may reflect endothelial cell damage.
KW  - Hypertension
KW  - ET-1
KW  - Meta-analysis
Y1  - 2017
U6  - https://doi.org/10.1159/000477572
SN  - 1420-4096
SN  - 1423-0143
VL  - 42
IS  - 2
SP  - 304
EP  - 313
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Sagu Tchewonpi, Sorel
A1  - Huschek, Gerd
A1  - Waldbach Braga, Tess
A1  - Rackiewicz, Michal
A1  - Homann, Thomas
A1  - Rawel, Harshadrai Manilal
T1  - Design of Experiment (DoE) for Optimization of HPLC Conditions for the Simultaneous Fractionation of Seven α-Amylase/Trypsin Inhibitors from Wheat (Triticum aestivum L.)
JF  - Processes : open access journal
N2  - Wheat alpha-amylase/trypsin inhibitors remain a subject of interest considering the latest findings showing their implication in wheat-related non-celiac sensitivity (NCWS). Understanding their functions in such a disorder is still unclear and for further study, the need for pure ATI molecules is one of the limiting problems. In this work, a simplified approach based on the successive fractionation of ATI extracts by reverse phase and ion exchange chromatography was developed. ATIs were first extracted from wheat flour using a combination of Tris buffer and chloroform/methanol methods. The separation of the extracts on a C18 column generated two main fractions of interest F1 and F2. The response surface methodology with the Doehlert design allowed optimizing the operating parameters of the strong anion exchange chromatography. Finally, the seven major wheat ATIs namely P01083, P17314, P16850, P01085, P16851, P16159, and P83207 were recovered with purity levels (according to the targeted LC-MS/MS analysis) of 98.2 ± 0.7; 98.1 ± 0.8; 97.9 ± 0.5; 95.1 ± 0.8; 98.3 ± 0.4; 96.9 ± 0.5, and 96.2 ± 0.4%, respectively. MALDI-TOF-MS analysis revealed single peaks in each of the pure fractions and the mass analysis yielded deviations of 0.4, 1.9, 0.1, 0.2, 0.2, 0.9, and 0.1% between the theoretical and the determined masses of P01083, P17314, P16850, P01085, P16851, P16159, and P83207, respectively. Overall, the study allowed establishing an efficient purification process of the most important wheat ATIs. This paves the way for further in-depth investigation of the ATIs to gain more knowledge related to their involvement in NCWS disease and to allow the absolute quantification in wheat samples.
KW  - wheat
KW  - α-amylase/trypsin inhibitors
KW  - fractionation
KW  - purification
KW  - reversed-phase chromatography
KW  - ion-exchange chromatography
KW  - design of experiment
KW  - LC–MS/MS
KW  - MALDI-TOF-MS
Y1  - 2022
U6  - https://doi.org/10.3390/pr10020259
SN  - 2227-9717
VL  - 10
SP  - 1
EP  - 18
PB  - MDPI
CY  - Basel, Schweiz
ET  - 2
ER  - 
TY  - JOUR
A1  - Neuschäfer-Rube, Frank
A1  - Pathe-Neuschäfer-Rube, Andrea
A1  - Püschel, Gerhard Paul
T1  - Discrimination of the activity of low-affinity wild-type and high-affinity mutant recombinant BoNT/B by a SIMA cell-based reporter release assay
JF  - Toxins
N2  - Botulinum neurotoxin (BoNT) is used for the treatment of a number of ailments. The activity of the toxin that is isolated from bacterial cultures is frequently tested in the mouse lethality assay. Apart from the ethical concerns inherent to this assay, species-specific differences in the affinity for different BoNT serotypes give rise to activity results that differ from the activity in humans. Thus, BoNT/B is more active in mice than in humans. The current study shows that the stimulus-dependent release of a luciferase from a differentiated human neuroblastoma–based reporter cell line (SIMA-hPOMC1-26-Gluc) was inhibited by clostridial and recombinant BoNT/A to the same extent, whereas both clostridial and recombinant BoNT/B inhibited the release to a lesser extent and only at much higher concentrations, reflecting the low activity of BoNT/B in humans. By contrast, the genetically modified BoNT/B-MY, which has increased affinity for human synaptotagmin, and the BoNT/B protein receptor inhibited luciferase release effectively and with an EC50 comparable to recombinant BoNT/A. This was due to an enhanced uptake into the reporter cells of BoNT/B-MY in comparison to the recombinant wild-type toxin. Thus, the SIMA-hPOMC1-26-Gluc cell assay is a versatile tool to determine the activity of different BoNT serotypes providing human-relevant dose-response data.
KW  - cell-based assay
KW  - genetically modified BoNT
KW  - BoNT/B uptake
Y1  - 2022
U6  - https://doi.org/10.3390/toxins14010065
SN  - 2072-6651
VL  - 14
SP  - 1
EP  - 11
PB  - MDPI
CY  - Basel, Schweiz
ET  - 1
ER  - 
TY  - JOUR
A1  - Figueroa Campos, Gustavo Adolfo
A1  - G. K. T. Kruizenga, Johannes
A1  - Sagu Tchewonpi, Sorel
A1  - Schwarz, Steffen
A1  - Homann, Thomas
A1  - Taubert, Andreas
A1  - Rawel, Harshadrai Manilal
T1  - Effect of the post-harvest processing on protein modification in green coffee beans by phenolic compounds
JF  - Foods : open access journal
N2  - The protein fraction, important for coffee cup quality, is modified during post-harvest treatment prior to roasting. Proteins may interact with phenolic compounds, which constitute the major metabolites of coffee, where the processing affects these interactions. This allows the hypothesis that the proteins are denatured and modified via enzymatic and/or redox activation steps. The present study was initiated to encompass changes in the protein fraction. The investigations were limited to major storage protein of green coffee beans. Fourteen Coffea arabica samples from various processing methods and countries were used. Different extraction protocols were compared to maintain the status quo of the protein modification. The extracts contained about 4–8 µg of chlorogenic acid derivatives per mg of extracted protein. High-resolution chromatography with multiple reaction monitoring was used to detect lysine modifications in the coffee protein. Marker peptides were allocated for the storage protein of the coffee beans. Among these, the modified peptides K.FFLANGPQQGGK.E and R.LGGK.T of the α-chain and R.ITTVNSQK.I and K.VFDDEVK.Q of β-chain were detected. Results showed a significant increase (p < 0.05) of modified peptides from wet processed green beans as compared to the dry ones. The present study contributes to a better understanding of the influence of the different processing methods on protein quality and its role in the scope of coffee cup quality and aroma. View Full-Text
KW  - Arabica coffee
KW  - coffee processing
KW  - protein modification
KW  - bound phenolic compounds
KW  - peptide biomarkers
KW  - LC-MS/MS
Y1  - 2022
U6  - https://doi.org/10.3390/foods11020159
SN  - 2304-8158
VL  - 11
PB  - MDPI
CY  - Basel, Schweiz
ET  - 2
ER  - 
TY  - JOUR
A1  - de Pinho Tavares Leal, Pedro Ernesto
A1  - da Silva, Alexandre Alves
A1  - Rocha-Gomes, Arthur
A1  - Riul, Tania Regina
A1  - Cunha, Rennan Augusto
A1  - Reichetzeder, Christoph
A1  - Villela, Daniel Campos
T1  - High-Salt Diet in the Pre- and Postweaning Periods Leads to Amygdala Oxidative Stress and Changes in Locomotion and Anxiety-Like Behaviors of Male Wistar Rats
JF  - Frontiers in Behavioral Neuroscience
N2  - High-salt (HS) diets have recently been linked to oxidative stress in the brain, a fact that may be a precursor to behavioral changes, such as those involving anxiety-like behavior. However, to the best of our knowledge, no study has evaluated the amygdala redox status after consuming a HS diet in the pre- or postweaning periods. This study aimed to evaluate the amygdala redox status and anxiety-like behaviors in adulthood, after inclusion of HS diet in two periods: preconception, gestation, and lactation (preweaning); and only after weaning (postweaning). Initially, 18 females and 9 male Wistar rats received a standard (n = 9 females and 4 males) or a HS diet (n = 9 females and 5 males) for 120 days. After mating, females continued to receive the aforementioned diets during gestation and lactation. Weaning occurred at 21-day-old Wistar rats and the male offspring were subdivided: control-control (C-C)—offspring of standard diet fed dams who received a standard diet after weaning (n = 9–11), control-HS (C-HS)—offspring of standard diet fed dams who received a HS diet after weaning (n = 9–11), HS-C—offspring of HS diet fed dams who received a standard diet after weaning (n = 9–11), and HS-HS—offspring of HS diet fed dams who received a HS diet after weaning (n = 9–11). At adulthood, the male offspring performed the elevated plus maze and open field tests. At 152-day-old Wistar rats, the offspring were euthanized and the amygdala was removed for redox state analysis. The HS-HS group showed higher locomotion and rearing frequency in the open field test. These results indicate that this group developed hyperactivity. The C-HS group had a higher ratio of entries and time spent in the open arms of the elevated plus maze test in addition to a higher head-dipping frequency. These results suggest less anxiety-like behaviors. In the analysis of the redox state, less activity of antioxidant enzymes and higher levels of the thiobarbituric acid reactive substances (TBARS) in the amygdala were shown in the amygdala of animals that received a high-salt diet regardless of the period (pre- or postweaning). In conclusion, the high-salt diet promoted hyperactivity when administered in the pre- and postweaning periods. In animals that received only in the postweaning period, the addition of salt induced a reduction in anxiety-like behaviors. Also, regardless of the period, salt provided amygdala oxidative stress, which may be linked to the observed behaviors.
KW  - high-sodium
KW  - open-field
KW  - elevated plus-maze
KW  - pre-natal
KW  - post-natal
KW  - redox state
Y1  - 2022
U6  - https://doi.org/10.3389/fnbeh.2021.779080
SN  - 1662-5153
VL  - 15
SP  - 1
EP  - 12
PB  - Frontiers Research Foundation
CY  - Lausanne, Schweiz
ER  - 
TY  - JOUR
A1  - Gerecke, Christian
A1  - Edlich, Alexander
A1  - Giulbudagian, Michael
A1  - Schumacher, Fabian
A1  - Zhang, Nan
A1  - Said, Andre
A1  - Yealland, Guy
A1  - Lohan, Silke B.
A1  - Neumann, Falko
A1  - Meinke, Martina C.
A1  - Ma, Nan
A1  - Calderon, Marcelo
A1  - Hedtrich, Sarah
A1  - Schaefer-Korting, Monika
A1  - Kleuser, Burkhard
T1  - Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes
JF  - Nanotoxicology
N2  - Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery.
KW  - Drug delivery
KW  - nanoparticles
KW  - particle characterization
KW  - keratinocytes
KW  - nanotoxicology
Y1  - 2017
U6  - https://doi.org/10.1080/17435390.2017.1292371
SN  - 1743-5390
SN  - 1743-5404
VL  - 11
SP  - 267
EP  - 277
PB  - Routledge, Taylor & Francis Group
CY  - Abingdon
ER  - 
TY  - JOUR
A1  - Sahle, Fitsum Feleke
A1  - Gerecke, Christian
A1  - Kleuser, Burkhard
A1  - Bodmeier, Roland
T1  - Formulation and comparative in vitro evaluation of various dexamethasone-loaded pH-sensitive polymeric nanoparticles intended for dermal applications
JF  - International Journal of Pharmaceutics
N2  - pH-sensitive nanoparticles have a great potential for dermal and transfollicular drug delivery. In this study, pH-sensitive, dexamethasone-loaded Eudragit (R) L 100, Eudragit (R) L 100-55, Eudragit (R) S 100, HPMCP-50, HPMCP-55 and cellulose acetate phthalate nanoparticles were prepared by nanoprecipitation and characterized. The pH-dependent swelling, erosion, dissolution and drug release kinetics were investigated in vitro using dynamic light scattering and Franz diffusion cells, respectively. Their toxicity potential was assessed by the ROS and MTT assays. 100-700 nm nanoparticles with high drug loading and entrapment efficiency were obtained. The nanoparticles bear no toxicity potential. Cellulose phthalates nanoparticles were more sensitive to pH than acrylates nanoparticles. They dissolved in 10 mM pH 7.5 buffer and released > 80% of the drug within 7 h. The acrylate nanoparticles dissolved in 40 mM pH 7.5 buffer and released 65-70% of the drug within 7 h. The nanoparticles remained intact in 10 and 40 mM pH 6.0 buffers (HPMCP nanoparticles dissolved in 40 mM pH 6.0 buffer) and released slowly. The nanoparticles properties could be modulated by blending the different polymers. In conclusion, various pH-sensitive nanoparticles that could release differently on the skin surface and dissolve and release in the hair follicles were obtained.
KW  - Cellulose acetate phthalate
KW  - Dexamethasone
KW  - Eudragit (R)
KW  - HPMCP
KW  - pH-sensitive nanoparticle
KW  - Skin nanocarrier
Y1  - 2016
U6  - https://doi.org/10.1016/j.ijpharm.2016.11.029
SN  - 0378-5173
SN  - 1873-3476
VL  - 516
IS  - 1-2
SP  - 21
EP  - 31
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Heunisch, Fabian
A1  - Chaykovska, Lyubov
A1  - von Einem, Gina
A1  - Alter, Markus
A1  - Dschietzig, Thomas
A1  - Kretschmer, Axel
A1  - Kellner, Karl-Heinz
A1  - Hocher, Berthold
T1  - ADMA predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus undergoing coronary angiography
JF  - Medicine
N2  - Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of the nitric oxide (NO)-synthase and a biomarker of endothelial dysfunction (ED). ED plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of our study was to evaluate serum ADMA concentration as a biomarker of an acute renal damage during the follow-up of 90 days after contrast medium (CM) application. Blood samples were obtained from 330 consecutive patients with diabetes mellitus or mild renal impairment immediately before, 24 and 48 hours after the CM application for coronary angiography. The patients were followed for 90 days. The composite endpoints were major adverse renal events (MARE) defined as occurrence of death, initiation of dialysis, or a doubling of serum creatinine concentration. Overall, ADMA concentration in plasma increased after CM application, although, there was no differences between ADMA levels in patients with and without CIN. ADMA concentration 24 hours after the CM application was predictive for dialysis with a specificity of 0.889 and sensitivity of 0.653 at values higher than 0.71 mu mol/L (area under the curve: 0.854, 95% confidential interval: 0.767-0.941, P<0.001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome. 24 hours after the CM application, ADMA concentration in plasma was predictive for MARE with a specificity of 0.833 and sensitivity of 0.636 at a value of more than 0.70 mu mol/L (area under the curve: 0.750, 95% confidence interval: 0.602-0.897, P=0.004). Multivariate logistic regression analysis confirmed that ADMA and anemia were significant predictors of MARE. Further analysis revealed that increased ADMA concentration in plasma was highly significant predictor of MARE in patients with CIN. Moreover, patients with CIN and MARE had the highest plasma ADMA levels 24 hours after CM exposure in our study cohort. The impact of ADMA on MARE was independent of such known CIN risk factors as anemia, pre-existing renal failure, pre-existing heart failure, and diabetes. ADMA concentration in plasma is a promising novel biomarker of major contrast-induced nephropathy-associated events 90 days after contrast media exposure.
KW  - asymmetric dimethylarginine (ADMA)
KW  - biomarkers of renal failure
KW  - contrast-induced nephropathy
Y1  - 2017
U6  - https://doi.org/10.1097/MD.0000000000006065
SN  - 0025-7974
SN  - 1536-5964
VL  - 96
IS  - 6
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  - 
TY  - JOUR
A1  - Taylor, Vivien
A1  - Goodale, Britton
A1  - Raab, Andrea
A1  - Schwerdtle, Tanja
A1  - Reimer, Ken
A1  - Conklin, Sean
A1  - Karagas, Margaret R.
A1  - Francesconi, Kevin A.
T1  - Human exposure to organic arsenic species from seafood
JF  - The science of the total environment : an international journal for scientific research into the environment and its relationship with man
N2  - Seafood, including finfish, shellfish, and seaweed, is the largest contributor to arsenic (As) exposure in many human populations. In contrast to the predominance of inorganic As in water and many terrestrial foods, As in marine-derived foods is present primarily in the form of organic compounds. To date, human exposure and toxicological assessments have focused on inorganic As, while organic As has generally been considered to be nontoxic. However, the high concentrations of organic As in seafood, as well as the often complex As speciation, can lead to complications in assessing As exposure from diet. In this report, we evaluate the presence and distribution of organic As species in seafood, and combined with consumption data, address the current capabilities and needs for determining human exposure to these compounds. The analytical approaches and shortcomings for assessing these compounds are reviewed, with a focus on the best practices for characterization and quantitation. Metabolic pathways and toxicology of two important classes of organic arsenicals, arsenolipids and arsenosugars, are examined, as well as individual variability in absorption of these compounds. Although determining health outcomes or assessing a need for regulatory policies for organic As exposure is premature, the extensive consumption of seafood globally, along with the preliminary toxicological profiles of these compounds and their confounding effect on assessing exposure to inorganic As, suggests further investigations and process-level studies on organic As are needed to fill the current gaps in knowledge.
KW  - Organic arsenic
KW  - Seafood
KW  - Arsenosugar
KW  - Arsenolipid
Y1  - 2017
U6  - https://doi.org/10.1016/j.scitotenv.2016.12.113
SN  - 0048-9697
SN  - 1879-1026
VL  - 580
SP  - 266
EP  - 282
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Marschall, Talke Anu
A1  - Kroepfl, Nina
A1  - Jensen, Kenneth Bendix
A1  - Bornhorst, Julia
A1  - Meermann, B.
A1  - Kühnelt, Doris
A1  - Schwerdtle, Tanja
T1  - Tracing cytotoxic effects of small organic Se species in human liver cells back to total cellular Se and Se metabolites
JF  - Metallomics
N2  - Small selenium (Se) species play a major role in the metabolism, excretion and dietary supply of the essential trace element selenium. Human cells provide a valuable tool for investigating currently unresolved issues on the cellular mechanisms of Se toxicity and metabolism. In this study, we developed two isotope dilution inductively coupled plasma tandem-mass spectrometry based methods and applied them to human hepatoma cells (HepG2) in order to quantitatively elucidate total cellular Se concentrations and cellular Se species transformations in relation to the cytotoxic effects of four small organic Se species. Species-and incubation time-dependent results were obtained: the two major urinary excretion metabolites trimethylselenonium (TMSe) and methyl-2-acetamido-2-deoxy-1-seleno-beta- D-galactopyranoside (SeSugar 1) were taken up by the HepG2 cells in an unmodified manner and did not considerably contribute to the Se pool. In contrast, Se-methylselenocysteine (MeSeCys) and selenomethionine (SeMet) were taken up in higher amounts, they were largely incorporated by the cells (most likely into proteins) and metabolized to other small Se species. Two new metabolites of MeSeCys, namely gamma-glutamyl-Se-methylselenocysteine and Se-methylselenoglutathione, were identified by means of HPLC-electrospray-ionization-Orbitrap-MS. They are certainly involved in the (de-) toxification modes of Se metabolism and require further investigation.
Y1  - 2017
U6  - https://doi.org/10.1039/c6mt00300a
SN  - 1756-5901
SN  - 1756-591X
VL  - 9
SP  - 268
EP  - 277
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Bönick, Josephine
A1  - Huschek, Gerd
A1  - Rawel, Harshadrai Manilal
T1  - Determination of wheat, rye and spelt authenticity in bread by targeted peptide biomarkers
JF  - Journal of Food Composition and Analysis
N2  - Adulteration of food and mislabeled products in global market is a major financial and reputational risk for food manufacturers and trade companies. Consequently, there is a necessity to develop analytical methods to meet these issues. An analytical strategy to check the authenticity of wheat, spelt and rye addition in bread products was developed based on database research, in silico digestion confirming peptide specificity and finally quantification by liquid chromatography-tandem mass spectrometry analysis. Peptide markers for wheat (SQQQISQQPQQLPQQQQIPQQPQQF; QQHQIPQQPQQFPQQQQF and QPHQPQQPYPQQ), spelt (ASIVVGIGGQ; SQQPGQIIPQQPQQPSPL) and rye (LPQSHKQHVGQGAL; AQVQGIIQPQQL and QQFPQQPQQSFPQQPQQPVPQQPL) were identified, verified by protein Basic Local Alignment Search Tool and database research and used for quantification in bread. The specific use of multi-reaction monitoring transitions of selected peptides permitted the identification of closely related species wheat and spelt. Other cereal species (emmer, einkorn, barley, maize, rye and oat) were also checked. The target peptides were quantified at different levels using own reference baked products (bread) after in-solution chymotryptic digestion. Sensitivity of the identification was 0.5-1% using flour-based (0-25%) matrix calibration and the analytical recovery in bread was 80-125%. The analytical strategy described here supplies an emerging, independent and flexible tool in controlling the labeling of bread.
KW  - Food analysis
KW  - Food composition
KW  - Food safety
KW  - Plant authentication
KW  - Wheat
KW  - Spelt
KW  - Rye
KW  - LC-MS-MS
KW  - Quantification of peptides
KW  - Food labeling
Y1  - 2017
U6  - https://doi.org/10.1016/j.jfca.2017.01.019
SN  - 0889-1575
SN  - 1096-0481
VL  - 58
SP  - 82
EP  - 91
PB  - Elsevier
CY  - San Diego
ER  - 
TY  - JOUR
A1  - Balzus, Benjamin
A1  - Sahle, Fitsum Feleke
A1  - Hönzke, Stefan
A1  - Gerecke, Christian
A1  - Schumacher, Fabian
A1  - Hedtrich, Sarah
A1  - Kleuser, Burkhard
A1  - Bodmeier, Roland
T1  - Formulation and ex vivo evaluation of polymeric nanoparticles for controlled delivery of corticosteroids to the skin and the corneal epithelium
JF  - European journal of pharmaceutics and biopharmaceutics : EJPB ; official journal of the International Association for Pharmaceutical Technology
N2  - Controlled delivery of corticosteroids using nanoparticles to the skin and corneal epithelium may reduce their side effects and maximize treatment effectiveness. Dexamethasone-loaded ethyl cellulose, Eudragit® RS and ethyl cellulose/Eudragit® RS nanoparticles were prepared by the solvent evaporation method. Dexamethasone release from the polymeric nanoparticles was investigated in vitro using Franz diffusion cells. Drug penetration was also assessed ex vivo using excised human skin. Nanoparticle toxicity was determined by MTT and H2DCFDA assays. Eudragit® RS nanoparticles were smaller and positively charged but had a lower dexamethasone loading capacity (0.3–0.7%) than ethyl cellulose nanoparticles (1.4–2.2%). By blending the two polymers (1:1), small (105 nm), positively charged (+37 mV) nanoparticles with sufficient dexamethasone loading (1.3%) were obtained. Dexamethasone release and penetration significantly decreased with decreasing drug to polymer ratio and increased when Eudragit® RS was blended with ethyl cellulose. Ex vivo, drug release and penetration from the nanoparticles was slower than a conventional cream. The nanoparticles bear no toxicity potentials except ethyl cellulose nanoparticles had ROS generation potential at high concentration. In conclusion, the nanoparticles showed great potential to control the release and penetration of corticosteroids on the skin and mucus membrane and maximize treatment effectiveness.
KW  - Dermal delivery
KW  - Dexamethasone
KW  - Ethyl cellulose
KW  - Eudragit (R) RS
KW  - Ocular delivery
KW  - Polymeric nanoparticle
Y1  - 2017
U6  - https://doi.org/10.1016/j.ejpb.2017.02.001
SN  - 0939-6411
SN  - 1873-3441
VL  - 115
SP  - 122
EP  - 130
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - McVey, Mark J.
A1  - Kim, Michael
A1  - Tabuchi, Arata
A1  - Srbely, Victoria
A1  - Japtok, Lukasz
A1  - Arenz, Christoph
A1  - Rotstein, Ori
A1  - Kleuser, Burkhard
A1  - Semple, John W.
A1  - Kuebler, Wolfgang M.
T1  - Acid sphingomyelinase mediates murine acute lung injury following transfusion of aged platelets
JF  - American journal of physiology : Lung cellular and molecular physiology
N2  - Pulmonary complications from stored blood products are the leading cause of mortality related to transfusion. Transfusion-related acute lung injury is mediated by antibodies or bioactive mediators, yet underlying mechanisms are incompletely understood. Sphingolipids such as ceramide regulate lung injury, and their composition changes as a function of time in stored blood. Here, we tested the hypothesis that aged platelets may induce lung injury via a sphingolipid-mediated mechanism. To assess this hypothesis, a two-hit mouse model was devised. Recipient mice were treated with 2 mg/kg intraperitoneal lipopolysaccharide (priming) 2 h before transfusion of 10 ml/kg stored (1-5 days) platelets treated with or without addition of acid sphingomyelinase inhibitor ARC39 or platelets from acid sphingomyelinase-deficient mice, which both reduce ceramide formation. Transfused mice were examined for signs of pulmonary neutrophil accumulation, endothelial barrier dysfunction, and histological evidence of lung injury. Sphingolipid profiles in stored platelets were analyzed by mass spectrophotometry. Transfusion of aged platelets into primed mice induced characteristic features of lung injury, which increased in severity as a function of storage time. Ceramide accumulated in platelets during storage, but this was attenuated by ARC39 or in acid sphingomyelinase-deficient platelets. Compared with wild-type platelets, transfusion of ARC39-treated or acid sphingomyelinase-deficient aged platelets alleviated lung injury. Aged platelets elicit lung injury in primed recipient mice, which can be alleviated by pharmacological inhibition or genetic deletion of acid sphingomyelinase. Interventions targeting sphingolipid formation represent a promising strategy to increase the safety and longevity of stored blood products.
KW  - transfusion-related acute lung injury
KW  - ceramide
KW  - acid sphingomyelinase
KW  - platelets
KW  - storage
Y1  - 2017
U6  - https://doi.org/10.1152/ajplung.00317.2016
SN  - 1040-0605
SN  - 1522-1504
VL  - 312
IS  - 5
SP  - 625
EP  - 637
PB  - American Physiological Society
CY  - Bethesda
ER  -