@article{AbebeHakiSchweigertetal.2019, author = {Abebe, Zeweter and Haki, Gulelat Desse and Schweigert, Florian J. and Henkel, Ina M. and Baye, Kaleab}, title = {Low breastmilk vitamin A concentration is prevalent in rural Ethiopia}, series = {European journal of clinical nutrition}, volume = {73}, journal = {European journal of clinical nutrition}, number = {8}, publisher = {Nature Publ. Group}, address = {London}, issn = {0954-3007}, doi = {10.1038/s41430-018-0334-4}, pages = {1110 -- 1116}, year = {2019}, abstract = {Background There is scant information on the breastmilk vitamin A (BMVA) concentration of lactating women in developing countries, partly due to lack of methods applicable in-field. Objective To assess BMVA concentrations of samples collected from lactating women of children aged 6-23 months, in Mecha district, Ethiopia. Subjects/methods Data on socio-demographic and anthropometric characteristics were collected from randomly selected lactating women (n = 104). Breast milk samples were collected and vitamin A concentrations were analyzed using HPLC and iCheck FLUORO then the two measurements were compared. Results The prevalence of underweight (BMI < 18.5 kg/m(2)) among lactating women was 17\%. Seventy six percent of the BMVA values were < 1.05 mu mol/l and 81\% were < 8 mu g/g fat. The mean BMVA concentration accounted to 41\% of the estimated average value for mothers in developing countries. The BMVA values from HPLC and iCheck were correlated (r = 0.59, p = < 0.001), but it was not strong. Conclusions The result indicates the low vitamin A status of the lactating women and their children. It further indicates that intake assessments should not use average BMVA composition. The possibility of using iCheck for monitoring interventions designed to improve vitamin A status of lactating women with low BMVA requires further investigation.}, language = {en} } @article{Abraham2003, author = {Abraham, Klaus}, title = {Minimal Inflammation, Acute Phase Response and Avoidance of Misclassification of Vitamin A and Iron Status in Infants-Importance of a High-Sensitivity C-Reactive Protein (CRP) Assay}, year = {2003}, language = {en} } @article{AgaBarfknechtHallahanGottmannetal.2020, author = {Aga-Barfknecht, Heja and Hallahan, Nicole and Gottmann, Pascal and J{\"a}hnert, Markus and Osburg, Sophie and Schulze, Gunnar and Kamitz, Anne and Arends, Danny and Brockmann, Gudrun and Schallschmidt, Tanja and Lebek, Sandra and Chadt, Alexandra and Al-Hasani, Hadi and Joost, Hans-Georg and Sch{\"u}rmann, Annette and Vogel, Heike}, title = {Identification of novel potential type 2 diabetes genes mediating beta-cell loss and hyperglycemia using positional cloning}, series = {Frontiers in genetics}, volume = {11}, journal = {Frontiers in genetics}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1664-8021}, doi = {10.3389/fgene.2020.567191}, pages = {11}, year = {2020}, abstract = {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.}, language = {en} } @article{AgaBarfknechtSoultoukisStadionetal.2022, author = {Aga-Barfknecht, Heja and Soultoukis, George A. and Stadion, Mandy and Garcia-Carrizo, Francisco and J{\"a}hnert, Markus and Gottmann, Pascal and Vogel, Heike and Schulz, Tim Julius and Sch{\"u}rmann, Annette}, title = {Distinct adipogenic and fibrogenic differentiation capacities of mesenchymal stromal cells from pancreas and white adipose tissue}, series = {International journal of molecular sciences}, volume = {23}, journal = {International journal of molecular sciences}, number = {4}, publisher = {Molecular Diversity Preservation International}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms23042108}, pages = {21}, year = {2022}, abstract = {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.}, language = {en} } @article{AhlbergRancanEppleetal.2016, author = {Ahlberg, Sebastian and Rancan, Fiorenza and Epple, Matthias and Loza, Kateryna and H{\"o}ppe, David and Lademann, J{\"u}rgen and Vogt, Annika and Kleuser, Burkhard and Gerecke, Christian and Meinke, Martina C.}, title = {Comparison of different methods to study effects of silver nanoparticles on the pro- and antioxidant status of human keratinocytes and fibroblasts}, series = {Methods : focusing on rapidly developing techniques}, volume = {109}, journal = {Methods : focusing on rapidly developing techniques}, publisher = {Elsevier}, address = {San Diego}, issn = {1046-2023}, doi = {10.1016/j.ymeth.2016.05.015}, pages = {55 -- 63}, year = {2016}, language = {en} } @article{AlFadelFayyazJaptoketal.2016, author = {Al Fadel, Frdoos and Fayyaz, Susann and Japtok, Lukasz and Kleuser, Burkhard}, title = {Involvement of Sphingosine 1-Phosphate in Palmitate-Induced Non-Alcoholic Fatty Liver Disease}, series = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology}, volume = {40}, journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology}, publisher = {Karger}, address = {Basel}, issn = {1015-8987}, doi = {10.1159/000453213}, pages = {1637 -- 1645}, year = {2016}, abstract = {Background/Aims: Ectopic lipid accumulation in hepatocytes has been identified as a risk factor for the progression of liver fibrosis and is strongly associated with obesity. In particular, the saturated fatty acid palmitate is involved in initiation of liver fibrosis via formation of secondary metabolites by hepatocytes that in turn activate hepatic stellate cells (HSCs) in a paracrine manner Methods: a-smooth muscle actin-expression (alpha-SMA) as a marker of liver fibrosis was investigated via western blot analysis and immunofluorescence microscopy in HSCs (LX-2). Sphingolipid metabolism and the generation of the bioactive secondary metabolite sphingosine I-phosphate (SIP) in response to palmitate were analyzed by LC-MS/MS in hepatocytes (HepG2). To identify the molecular mechanism involved in the progression of liver fibrosis real-time PCR analysis and pharmacological modulation of SIP receptors were performed. Results: Palmitate oversupply increased intra- and extracellular SIP-concentrations in hepatocytes. Conditioned medium from HepG2 cells initiated fibrosis by enhancing alpha-SMA-expression in LX-2 in a S1P-dependent manner In accordance, fibrotic response in the presence of SIP was also observed in HSCs. Pharmacological inhibition of SIP receptors demonstrated that S1P(3) is the crucial receptor subtype involved in this process. Conclusion: SIP is synthesized in hepatocytes in response to palmitate and released into the extracellular environment leading to an activation of HSCs via the S1P(3) receptor (C) 2016 The Author(s) Published by S. Karger AG, Basel}, language = {en} } @article{AlterKretschmerVonWebskyetal.2012, author = {Alter, Markus L. and Kretschmer, Axel and Von Websky, Karoline and Tsuprykov, Oleg and Reichetzeder, Christoph and Simon, Alexandra and Stasch, Johannes-Peter and Hocher, Berthold}, title = {Early urinary and plasma biomarkers for experimental diabetic Nephropathy}, series = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, volume = {58}, journal = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, number = {7-8}, publisher = {Clin Lab Publ., Verl. Klinisches Labor}, address = {Heidelberg}, issn = {1433-6510}, doi = {10.7754/Clin.Lab.2011.111010}, pages = {659 -- 671}, year = {2012}, abstract = {Background: As the prevalence of diabetes rises, its complications such as diabetic nephropathy affect an increaseing number of patients. Consequently, the need for biomarkers in rodent models which reflect the stage and course of diabetic nephropathy is high. This article focuses on Heart-type fatty acid binding protein (H-FABP), osteopontin (OPN), nephrin, and Neutrophil gelatinase-associated lipocalin (NGAL) in urine, and kidney injury molecule (KIM)-1, clusterin, and tissue inhibitior of metalloproteinases (TIMP) 1 in plasma in uni-nephrectomized rats with streptocotozin-induced type 1 diabetes mellitus, a common animal model to explore renal impairment in the setting of diabetes mellitus. Methods: 23 male Wistar rats were uni-nephrectomized and subsequently divided into two study groups. The diabetic group received streptozotocin (STZ) via tail-vein injection, the non-diabetic group received citrate buffer without STZ. Subsequently, blood glucose, body weight, and blood pressure were checked regularly. After 18 weeks, animals were placed in metabolic cages, blood and urine obtained and subsequently organs were harvested after sacrifice. Results: Blood glucose levels were highly increased in diabetic animals throughout the experiment, whereas systolic blood pressure did not differ between the study groups. At study end, classical biomarkers such as urinary albumin and protein and plasma cystatin c were only slightly but not significantly different between groups indicating a very early disease state. In contrast, urinary excretion of H-FABP, OPN, nephrin, and NGAL were highly increased in diabetic animals with a highly significant p-value (p<0.01 each) compared to non-diabetic animals. In plasma, differences were found for calbindin, KIM-1, clusterin, TIMP-1, and OPN. These findings were confirmed by means of the area under the receiver operating characteristic curve (ROC-AUC) analysis. Conclusions: In summary, our study revealed elevated levels of new plasma and urinary biomarkers (urinary osteopontin, urinary nephrin, urinary NGAL, urinary H-FABP, plasma KIM-1, plasma TIMP-1) in uni-nephrectomized diabetic rats, an established rat model of diabetic nephropathy. These biomarkers appeared even before the classical biomarkers of diabetic nephropathy such as albuminuria and urinary protein excretion. The new biomarkers might offer advantage to urinary albumin and plasma cystatin c with respect to early detection.}, language = {en} } @article{AlterOttvonWebskyetal.2012, author = {Alter, Markus L. and Ott, Ina M. and von Websky, Karoline and Tsuprykov, Oleg and Sharkovska, Yuliya and Krause-Relle, Katharina and Raila, Jens and Henze, Andrea and Klein, Thomas and Hocher, Berthold}, title = {DPP-4 Inhibition on top of angiotensin receptor blockade offers a new therapeutic approach for diabetic nephropathy}, series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, volume = {36}, journal = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, number = {1}, publisher = {Karger}, address = {Basel}, issn = {1420-4096}, doi = {10.1159/000341487}, pages = {119 -- 130}, year = {2012}, abstract = {Background: The need for an improved treatment for diabetic nephropathy is greatest in patients who do not adequately respond to angiotensin II receptor blockers (ARBs). This study investigated the effect of the novel dipeptidyl peptidase-4 inhibitor linagliptin alone and in combination with the ARB telmisartan on the progression of diabetic nephropathy in diabetic endothelial nitric oxide synthase (eNOS) knockout mice. Methods: Sixty male eNOS knockout C57BL/6J mice were divided into four groups after receiving intraperitoneal high-dose streptozotocin: telmisartan (1 mg/kg), linagliptin (3 mg/kg), linagliptin + telmisartan (3 mg/kg + 1 mg/kg) and vehicle. Fourteen mice were used as non-diabetic controls. Results: After 12 weeks, urine and blood were obtained and blood pressure measured. Glucose concentrations were increased and similar in all diabetic groups. Telmisartan alone reduced systolic blood pressure by 5.9 mmHg versus diabetic controls (111.2 +/- 2.3 mmHg vs 117.1 +/- 2.2 mmHg; mean +/- SEM; P = 0.071). Combined treatment significantly reduced albuminuria compared with diabetic controls (71.7 +/- 15.3 mu g/24 h vs 170.8 +/- 34.2 mu g/24 h; P = 0.017), whereas the effects of single treatment with either telmisartan (97.8 +/- 26.4 mu g/24 h) or linagliptin (120.8 +/- 37.7 mu g/24 h) were not statistically significant. DPP-4 inhibition, alone and in combination, led to significantly lower plasma osteopontin levels compared with telmisartan alone. Histological analysis revealed reduced glomerulosclerosis after Linagliptin alone and in combination with telmisartan in comparison to non treated diabetic animals (p < 0.01 and p < 0.05). Kidney malonaldehyde immune-reactivity, a marker of oxidative stress, was significantly lower in animals treated with linagliptin. Conclusions: DPP-4 inhibition on top of ARB treatment significantly reduced urinary albumin excretion and oxidative stress in diabetic eNOS knockout mice. Linagliptin on top of an angiotensin II receptor blocker may offer a new therapeutic approach for patients with diabetic nephropathy.}, language = {en} } @article{AndertSanchaisuriyaSanchaisuriyaetal.2006, author = {Andert, Christoph U. and Sanchaisuriya, Pattara and Sanchaisuriya, Kanokwan and Schelp, Frank P. and Schweigert, Florian J.}, title = {Nutritional status of pregnant women in Northeast Thailand}, issn = {0964-7058}, year = {2006}, abstract = {A comparative study on the nutritional status of primiparous and multiparous women in the first trimester of pregnancy was conducted in the northeastern province of Thailand, Khon Kaen, to investigate differences in protein- energy-mal nutrition, iron deficiency anaemia, vitamin A deficiency and carotenoid status between both parity groups. 94 subjects were recruited at first attendance of antenatal clinic. Data about weight, height, haemoglobin and haematocrit were obtained from hospital records. Anthropometric measurements of mid-upper arm circumference and triceps skinfold were done on a sub sample. Retinol, carotenoids and alpha-tocopherol were analysed using a reversed-phase high- performance liquid chromatography method. Ferritin, transthyretin and retinol-binding protein were determined by enzyme- linked immunosorbent assay. Primiparous women showed lower body mass index, mid-upper arm circumference, corrected arm muscle area (P <0.001) as well as lower retinol, cholesterol and triceps skinfold (P <0.05). After adjusting for age and socio-economical status the significant difference persisted for all parameters but triceps skinfold. No significant differences of alpha-tocopherol, serum proteins, carotenoids and iron indices could be observed, even though a tendency to higher values for ferritin, haemoglobin and haematocrit was shown in multiparous women. Prevalence of protein-energy- malnutrition (body mass index <18.5 kg/m(2)) in the primiparous group was significantly higher compared to the multiparous group (P<0.05). Prevalence of protein-energy-malnutrition, iron deficiency anaemia and vitamin A deficiency were 15.1\%, 6.3\% and 3.3\%, respectively, in the total study population. No differences between parity groups could be observed for prevalence of iron deficiency anaemia and vitamin A deficiency}, language = {en} } @article{AngerWalzelKahrmann1994, author = {Anger, Horst and Walzel, Erwin and Kahrmann, Bettina}, title = {About the absorption of oligogalacturonates from the caecum of rats}, year = {1994}, language = {en} } @article{AuyyuenyongHenzeUngruetal.2017, author = {Auyyuenyong, Ratchada and Henze, Andrea and Ungru, Julia and Schweigert, Florian Johannes and Raila, Jens and Vervuert, Ingrid}, title = {Determination of lipid profiles in serum of obese ponies before and after weight reduction by using multi-one-dimensional thin-layer chromatography}, series = {Research in veterinary science}, volume = {117}, journal = {Research in veterinary science}, publisher = {Elsevier}, address = {Oxford}, issn = {0034-5288}, doi = {10.1016/j.rvsc.2017.11.013}, pages = {111 -- 117}, year = {2017}, abstract = {Obesity is a key component of equine metabolic syndrome, which is highly associated with laminitis. Feed restriction and/or exercise are known to alleviate the detrimental effects of insulin resistance in obese ponies. However, little is known about changes in the serum lipid patterns due to weight reduction and its association with disease outcomes. Therefore, the lipid patterns in the serum of 14 mature ponies before and after a 14-week body weight reduction program (BWRP) were investigated by multi-one-dimensional thin-layer chromatography (MOD-TLC). Additionally, sensitivity to insulin (SI), body condition scores (BCS) and cresty neck scores (CNS) were measured. A BWRP resulted in a significant loss of body weight (P < 0.001), which was associated with beneficial decreases in BCS and CNS (both, P < 0.001). Serum lipid compositions revealed significantly increased free fatty acid (FFA), sphingomyelin (SM; both P < 0.001), total cholesterol (C) and cholesterol ester (CE) (both P < 0.01) and triacylglycerol (TG; P < 0.05) densities. Improvement of SI after the BWRP was associated with increases in neutral lipids (C, CE and TG, all P < 0.01), FFA and the phospholipid SM (both, P < 0.001). The results show that a BWRP in obese ponies was effective and associated with changes in the concentrations of neutral lipids and the phospholipid SM, indicating that SM may play a role in insulin signaling pathways and thus in the pathogenesis of insulin resistance and the progression of metabolic syndrome in obese ponies.}, language = {en} } @article{AvilaBenedettoAuetal.2016, author = {Avila, Daiana Silva and Benedetto, Alexandre and Au, Catherine and Bornhorst, Julia and Aschner, Michael A.}, title = {Involvement of heat shock proteins on Mn-induced toxicity in Caenorhabditis elegans}, series = {Plant Methods}, volume = {17}, journal = {Plant Methods}, publisher = {BioMed Central}, address = {London}, issn = {2050-6511}, doi = {10.1186/s40360-016-0097-2}, pages = {9}, year = {2016}, abstract = {Background: All living cells display a rapid molecular response to adverse environmental conditions, and the heat shock protein family reflects one such example. Hence, failing to activate heat shock proteins can impair the cellular response. In the present study, we evaluated whether the loss of different isoforms of heat shock protein (hsp) genes in Caenorhabditis elegans would affect their vulnerability to Manganese (Mn) toxicity. Conclusions: Taken together, our data suggest that Mn exposure modulates heat shock protein expression, particularly HSP-70, in C. elegans. Furthermore, loss of hsp-70 increases protein oxidation and dopaminergic neuronal degeneration following manganese exposure, which is associated with the inhibition of pink1 increased expression, thus potentially exacerbating the vulnerability to this metal.}, language = {en} } @article{BachmannHomeierArltetal.2009, author = {Bachmann, Lutz and Homeier, Timo and Arlt, Sebastian and Brueckner, Monika and Rawel, Harshadrai Manilal and Deiner, Carolin and Hartmann, Helmut}, title = {Influence of different oral rehydration solutions on abomasal conditions and the acid-base status of suckling calves}, issn = {0022-0302}, doi = {10.3168/jds.2008-1487}, year = {2009}, abstract = {The aim of the study was to investigate the influence of oral rehydration solutions (ORS) on milk clotting, abomasal pH, electrolyte concentrations, and osmolality, as well as on the acid-base status in blood of suckling calves, as treatment with ORS is the most common therapy of diarrhea in calves to correct dehydration and metabolic acidosis. Oral rehydration solutions are suspected to inhibit abomasal clotting of milk; however, it is recommended to continue feeding cow's milk or milk replacer (MR) to diarrheic calves to prevent body weight losses. Three calves with abomasal cannulas were fed MR, MR-ORS mixtures, or water-ORS mixtures, respectively. Samples of abomasal fluid were taken before and after feeding at various time points, and pH, electrolyte concentrations, and osmolality were measured. The interference of ORS with milk clotting was examined in vivo and in vitro. To evaluate the effects of ORS on systemic acid-base status, the Stewart variables strong ion difference ([SID]), acid total ([A(tot)]), and partial pressure of CO2 (pCO(2)) were quantified in venous blood samples drawn before and after feeding. Calves reached higher abomasal pH values when fed with MR-ORS mixtures than when fed MR. Preprandial pH values were re-established after 4 to 6 h. Oral rehydration solutions prepared in water increased the abomasal fluid pH only for 1 to 2 h. Oral rehydration solutions with high [SID3] ([Na+] + [K+] - [Cl-]) values produced significantly higher abomasal pH values and area under the curve data of the pH time course. Caseinomacropeptide, an indicator of successful enzymatic milk clotting, could be identified in every sample of abomasal fluid after feeding MR-ORS mixtures. The MR-ORS mixtures with [SID3] values >= 92 mmol/L increased serum [SID3] but did not change venous blood pH. Oral rehydration solutions do not interfere with milk clotting in the abomasum and can, therefore, be administered with milk. In this study, MR-ORS mixtures with high [SID3] values caused an increase of serum [SID3] in healthy suckling calves and may be an effective treatment for metabolic acidosis in calves suffering from diarrhea.}, language = {en} } @article{BaeslerKoppPohletal.2019, author = {Baesler, Jessica and Kopp, Johannes F. and Pohl, Gabriele and Aschner, Michael and Haase, Hajo and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Zn homeostasis in genetic models of Parkinson's disease in Caenorhabditis elegans}, series = {Journal of trace elements in medicine and biology}, volume = {55}, journal = {Journal of trace elements in medicine and biology}, publisher = {Elsevier GMBH}, address = {M{\"u}nchen}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2019.05.005}, pages = {44 -- 49}, year = {2019}, language = {en} } @article{BaeslerKoppPohletal.2019, author = {Baesler, Jessica and Kopp, Johannes Florian and Pohl, Gabriele and Aschner, Michael and Haase, Hajo and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Zn homeostasis in genetic models of Parkinson's disease in Caenorhabditis elegans}, series = {Journal of Trace Elements in Medicine and Biology}, volume = {55}, journal = {Journal of Trace Elements in Medicine and Biology}, publisher = {Elsevier}, address = {M{\"u}nchen}, doi = {10.1016/j.jtemb.2019.05.005}, pages = {44 -- 49}, year = {2019}, abstract = {While the underlying mechanisms of Parkinson's disease (PD) are still insufficiently studied, a complex interaction between genetic and environmental factors is emphasized. Nevertheless, the role of the essential trace element zinc (Zn) in this regard remains controversial. In this study we altered Zn balance within PD models of the versatile model organism Caenorhabditis elegans (C. elegans) in order to examine whether a genetic predisposition in selected genes with relevance for PD affects Zn homeostasis. Protein-bound and labile Zn species act in various areas, such as enzymatic catalysis, protein stabilization pathways and cell signaling. Therefore, total Zn and labile Zn were quantitatively determined in living nematodes as individual biomarkers of Zn uptake and bioavailability with inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) or a multi-well method using the fluorescent probe ZinPyr-1. Young and middle-aged deletion mutants of catp-6 and pdr-1, which are orthologues of mammalian ATP13A2 (PARK9) and parkin (PARK2), showed altered Zn homeostasis following Zn exposure compared to wildtype worms. Furthermore, age-specific differences in Zn uptake were observed in wildtype worms for total as well as labile Zn species. These data emphasize the importance of differentiation between Zn species as meaningful biomarkers of Zn uptake as well as the need for further studies investigating the role of dysregulated Zn homeostasis in the etiology of PD.}, language = {en} } @article{BaeslerMichaelisStibolleretal.2021, author = {Baesler, Jessica and Michaelis, Vivien and Stiboller, Michael and Haase, Hajo and Aschner, Michael and Schwerdtle, Tanja and Sturzenbaum, Stephen R. and Bornhorst, Julia}, title = {Nutritive manganese and zinc overdosing in aging c. elegans result in a metallothionein-mediated alteration in metal homeostasis}, series = {Molecular Nutrition and Food Research}, volume = {65}, journal = {Molecular Nutrition and Food Research}, number = {8}, publisher = {Wiley-VCH GmbH}, address = {Weinheim}, issn = {1613-4133}, doi = {10.1002/mnfr.202001176}, pages = {1 -- 11}, year = {2021}, abstract = {Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration.}, language = {en} } @article{BaierPurschkeSchmittetal.2015, author = {Baier, Daniel and Purschke, Benedict and Schmitt, Christophe and Rawel, Harshadrai Manilal and Knorr, Dietrich}, title = {Effect of high pressure - low temperature treatments on structural characteristics of whey proteins and micellar caseins}, series = {Food chemistry}, volume = {187}, journal = {Food chemistry}, publisher = {Elsevier}, address = {Oxford}, issn = {0308-8146}, doi = {10.1016/j.foodchem.2015.04.049}, pages = {354 -- 363}, year = {2015}, abstract = {In this study, structural changes in micellar caseins and whey proteins due to high pressure - low temperature treatments (HPLT) were investigated and compared to changes caused by high pressure treatments at room temperature. Whey protein isolate (WPI) solutions as well as micellar casein (MC) dispersions and mixtures were treated at 500 MPa (pH 7.0 and 5.8) at room temperature, -15 degrees C and -35 degrees C. Surface hydrophobicity and accessible thiol groups remained nearly unchanged after HPLT treatments whereas HP treatments at room temperature caused an unfolding of the WPI, resulting in an increase in surface hydrophobicity and exposure of the thiol groups. For HPLT treatments, distinct changes in the secondary structure (increase in the amount of beta-sheets) were observed while the tertiary structure remained unchanged. Large flocs, stabilized by hydrophobic interactions and hydrogen bonds, were formed in casein containing samples due to HPLT treatments. Depending on the pH and the applied HPLT treatment parameters, these interactions differed significantly from the interactions determined in native micelles. (C) 2015 Elsevier Ltd. All rights reserved.}, language = {en} } @article{BaldermannHomannNeugartetal.2018, author = {Baldermann, Susanne and Homann, Thomas and Neugart, Susanne and Chmielewski, Frank M. and G{\"o}tz, Klaus-Peter and G{\"o}deke, Kristin and Huschek, Gerd and Morlock, Gertrud E. and Rawel, Harshadrai Manilal}, title = {Selected Plant Metabolites Involved in Oxidation-Reduction Processes during Bud Dormancy and Ontogenetic Development in Sweet Cherry Buds (Prunus avium L.)}, series = {Molecules}, volume = {23}, journal = {Molecules}, number = {5}, publisher = {Molecular Diversity Preservation International}, address = {Basel}, issn = {1420-3049}, doi = {10.3390/molecules23051197}, pages = {1 -- 19}, year = {2018}, abstract = {Many biochemical processes are involved in regulating the consecutive transition of different phases of dormancy in sweet cherry buds. An evaluation based on a metabolic approach has, as yet, only been partly addressed. The aim of this work, therefore, was to determine which plant metabolites could serve as biomarkers for the different transitions in sweet cherry buds. The focus here was on those metabolites involved in oxidation-reduction processes during bud dormancy, as determined by targeted and untargeted mass spectrometry-based methods. The metabolites addressed included phenolic compounds, ascorbate/dehydroascorbate, reducing sugars, carotenoids and chlorophylls. The results demonstrate that the content of phenolic compounds decrease until the end of endodormancy. After a long period of constancy until the end of ecodormancy, a final phase of further decrease followed up to the phenophase open cluster. The main phenolic compounds were caffeoylquinic acids, coumaroylquinic acids and catechins, as well as quercetin and kaempferol derivatives. The data also support the protective role of ascorbate and glutathione in the para- and endodormancy phases. Consistent trends in the content of reducing sugars can be elucidated for the different phenophases of dormancy, too. The untargeted approach with principle component analysis (PCA) clearly differentiates the different timings of dormancy giving further valuable information.}, language = {en} } @article{BalzusSahleHoenzkeetal.2017, author = {Balzus, Benjamin and Sahle, Fitsum Feleke and H{\"o}nzke, Stefan and Gerecke, Christian and Schumacher, Fabian and Hedtrich, Sarah and Kleuser, Burkhard and Bodmeier, Roland}, title = {Formulation and ex vivo evaluation of polymeric nanoparticles for controlled delivery of corticosteroids to the skin and the corneal epithelium}, series = {European journal of pharmaceutics and biopharmaceutics : EJPB ; official journal of the International Association for Pharmaceutical Technology}, volume = {115}, journal = {European journal of pharmaceutics and biopharmaceutics : EJPB ; official journal of the International Association for Pharmaceutical Technology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0939-6411}, doi = {10.1016/j.ejpb.2017.02.001}, pages = {122 -- 130}, year = {2017}, abstract = {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.}, language = {en} } @article{BanningDeubelKluthetal.2005, author = {Banning, Anja and Deubel, S. and Kluth, Dirk and Zhou, Z. W. and Brigelius-Floh{\´e}, Regina}, title = {The GI-GPx gene is a target for Nrf2}, issn = {0270-7306}, year = {2005}, abstract = {The gastrointestinal glutathione peroxidase (GI-GPx, GPx2) is a selenoprotein that was suggested to act as barrier against hydroperoxide absorption but has also been implicated in the control of inflammation and malignant growth. In CaCo-2 cells, GI-GPx was induced by t-butyl hydroquinone (tBHQ) and sulforaphane (SFN), i.e., "antioxidants" known to activate the "antioxidant response element" (ARE) via electrophilic thiol modification of Keap1 in the Nrf2/ Keap1 system. The functional significance of a putative ARE in the GI-GPx promoter was validated by transcriptional activation of reporter gene constructs upon exposure to electrophiles (tBHQ, SFN, and curcumin) or overexpression of Nrf2 and by reversal of these effects by mutation of the ARE in the promoter and by overexpressed Keap1. Binding of Nrf2 to the ARE sequence in authentic gpx2 was corroborated by chromatin immunoprecipitation. Thus, the presumed natural antioxidants sulforaphane and curcumin may exert their anti-inflammatory and anticarcinogenic effects not only by induction of phase 2 enzymes but also by the up-regulation of the selenoprotein GI-GPx}, language = {en} } @article{BarceloCoblijnLauraMartindeAlmeidaetal.2011, author = {Barcelo-Coblijn, Gwendolyn and Laura Martin, Maria and de Almeida, Rodrigo F. M. and Antonia Noguera-Salva, Maria and Marcilla-Etxenike, Amaia and Guardiola-Serrano, Francisca and Lueth, Anja and Kleuser, Burkhard and Halver, John E. and Escriba, Pablo V.}, title = {Sphingomyelin and sphingomyelin synthase (SMS) in the malignant transformation of glioma cells and in 2-hydroxyoleic acid therapy}, series = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {108}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {49}, publisher = {National Acad. of Sciences}, address = {Washington}, issn = {0027-8424}, doi = {10.1073/pnas.1115484108}, pages = {19569 -- 19574}, year = {2011}, abstract = {The mechanism of action of 2-hydroxyoleic acid (2OHOA), a potent antitumor compound, has not yet been fully elucidated. Here, we show that human cancer cells have markedly lower levels of sphingomyelin (SM) than nontumor (MRC-5) cells. In this context, 2OHOA treatment strongly augments SM mass (4.6-fold), restoring the levels found in MRC-5 cells, while a loss of phosphatidylethanolamine and phosphatidylcholine is observed (57 and 30\%, respectively). The increased SM mass was due to a rapid and highly specific activation of SM synthases (SMS). This effect appeared to be specific against cancer cells as it did not affect nontumor MRC-5 cells. Therefore, low SM levels are associated with the tumorigenic transformation that produces cancer cells. SM accumulation occurred at the plasma membrane and caused an increase in membrane global order and lipid raft packing in model membranes. These modifications would account for the observed alteration by 2OHOA in the localization of proteins involved in cell apoptosis (Fas receptor) or differentiation (Ras). Importantly, SMS inhibition by D609 diminished 2OHOA effect on cell cycle. Therefore, we propose that the regulation of SMS activity in tumor cells is a critical upstream event in 2OHOA antitumor mechanism, which also explains its specificity for cancer cells, its potency, and the lack of undesired side effects. Finally, the specific activation of SMS explains the ability of this compound to trigger cell cycle arrest, cell differentiation, and autophagy or apoptosis in cancer cells.}, language = {en} } @article{BarlowGreigBridgesetal.2002, author = {Barlow, S. M. and Greig, J. B. and Bridges, J. W. and Carere, A. and Carpy, A. J. and Galli, Corrado L. and Kleiner, J. and Knudsen, I. and Koeter, H. B. and Levy, L. S. and Madsen, C. and Mayer, S. and Narbonne, J. F. and Pfannkuch, F. and Prodanchuk, M. G. and Smith, Mason R. and Steinberg, Pablo}, title = {Hazard identification by methods of animal-based toxicology}, year = {2002}, language = {en} } @article{Barth2009, author = {Barth, Christian A.}, title = {Nutritional value of rapeseed oil and its high oleic/low linolenic variety : a call for differentiation}, issn = {1438-7697}, doi = {10.1002/ejlt.200900019}, year = {2009}, abstract = {To offer the best choice of healthy and acceptable food to the consumer a coordination of plant breeding, food processing and nutrition science is required. Here the nutritional aspects of the high oleic/low linolenic (HOLLi) varieties of rapeseed with a low alpha-linolenic acid content of about 3\% are reviewed. The content of alpha-linolenic acid amounting to around 9\% is the hallmark of the positive nutritional value of the original (erucic acid free) 00 varieties of rapeseed oil ("canola" quality in North America). n-3 fatty acids are endowed with the property to protect the cardiovascular system from chronic disease and the consumption of food containing n-3 fatty acids is explicitly recommended by national and international nutritional and medical authorities. Although the use of HOLLi with a low n-3 fatty acid content can be unavoidable for specific purposes, because of technological and health considerations the continuous future consumption of the original rapeseed oil with around 9\% of alpha-linolenic acid by the consumer should have high priority from the standpoint of public health. To pursue this aim confusion of the consumer must be avoided by creating a new name and a new brand for HOLLi varieties.}, language = {en} } @article{BartschZschalerHaseloffetal.2003, author = {Bartsch, Ingrid and Zschaler, Ingrid and Haseloff, Monika and Steinberg, Pablo}, title = {Establishment of a long-term culture system for rat colon epithelial cells}, issn = {1071-2690}, doi = {10.1290/0404035.1}, year = {2003}, abstract = {The aim of this study was to establish a long-term culture. system for rat colon epithelia isolaled by incubating a 4-cm-long rat colon segment cut longitudinally with all ethylenediaminetetraacetic acid [disodium salt]- containing buffer, taken up in conditioned medium from the normal rat kidney fibroblast cell line NRK (i.e., the supernatant Of pure NRK cultures), directly plated on mitomycin C-treated NRK cells and subcultured with conditioned medium from NRK cells. Cells started to migrate out of the crypts shortly after plating them on NRK feeder layers. Some of the crypts fell apart during the isolation procedure. whereas the vast majority of them did it within I to 2 Ill after plating. The cells proliferated extremely slowly but continuously over a period of 4 mo and were epithelial because they expressed cytokeratin 19 and were stained by crystal violet at pH 2.8. In conclusion, the experimental system described ill this study allows to maintain rat colon epithelial cells for up to 4 mo in culture and can be used to Study the effects of a variety of tumor-modulating factors on growth and gene expression of normal colon epithelial cells in vitro}, language = {en} } @article{BasaranDuyduUstundagetal.2019, author = {Basaran, Nursen and Duydu, Yalcin and Ustundag, Aylin and Taner, Gokce and Aydin, Sevtap and Anlar, Hatice Gul and Yalcin, Can {\"O}zg{\"u}r and Bacanli, Merve and Aydos, Kaan and Atabekoglu, Cem Somer and Golka, Klaus and Ickstadt, Katja and Schwerdtle, Tanja and Werner, Matthias and Meyer, S{\"o}ren and Bolt, Hermann M.}, title = {Evaluation of the DNA damage in lymphocytes, sperm and buccal cells of workers under environmental and occupational boron exposure conditions}, series = {Mutation Research/Genetic Toxicology and Environmental Mutagenesis}, volume = {843}, journal = {Mutation Research/Genetic Toxicology and Environmental Mutagenesis}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1383-5718}, doi = {10.1016/j.mrgentox.2018.12.013}, pages = {33 -- 39}, year = {2019}, abstract = {Industrial production and use of boron compounds have increased during the last decades, especially for the manufacture of borosilicate glass, fiberglass, metal alloys and flame retardants. This study was conducted in two districts of Balikesir; Bandirma and Bigadic, which geographically belong to the Marmara Region of Turkey. Bandirma is the production and exportation zone for the produced boric acid and some borates and Bigadic has the largest B deposits in Turkey. 102 male workers who were occupationally exposed to boron from Bandirma and 110 workers who were occupationally and environmentally exposed to boron from Bigadic participated to our study. In this study the DNA damage in the sperm, blood and buccal cells of 212 males was evaluated by comet and micronucleus assays. No significant increase in the DNA damage in blood, sperm and buccal cells was observed in the residents exposed to boron both occupationally and environmentally (p = 0.861) for Comet test in the sperm samples, p = 0.116 for Comet test in the lymphocyte samples, p = 0.042 for micronucleus (MN) test, p = 0.955 for binucleated cells (BN), p = 1.486 for condensed chromatin (CC), p = 0.455 for karyorrhectic cells (KHC), p = 0.541 for karyolitic cells (KLY), p = 1.057 for pyknotic cells (PHC), p = 0.331 for nuclear bud (NBUD)). No correlations were seen between blood boron levels and tail intensity values of the sperm samples, lymphocyte samples, frequencies of MN, BN, KHC, KYL, PHC and NBUD. The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions.}, language = {en} } @article{BaşaranDuyduUestuendağetal.2019, author = {Ba{\c{s}}aran, Nur{\c{s}}en and Duydu, Yal{\c{c}}{\i}n and {\"U}st{\"u}ndağ, Aylin and Taner, G{\"o}k{\c{c}}e and Aydin Dilsiz, Sevtap and Anlar, Hatice G{\"u}l and Yal{\c{c}}in, Can {\"O}zg{\"u}r and Bacanli, Merve and Golka, Klaus and Schwerdtle, Tanja and Bolt, Hermann M.}, title = {Environmental boron exposure does not induce DNA damage in lymphocytes and buccal cells of females DNA damage in lymphocytes and buccal cells of boron exposed females}, series = {Journal of trace elements in medicine and biology}, volume = {53}, journal = {Journal of trace elements in medicine and biology}, publisher = {Elsevier B.V.}, address = {M{\"u}nchen}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2019.03.004}, pages = {150 -- 153}, year = {2019}, abstract = {Boron (B) compounds are essential for plants and animals and beneficial for humans in nutritional amounts. I animals and humans increasing evidence have shown beneficial effects on B compounds on nutrition and on antioxidant status. The genotoxic effects of environmental B exposure in women living in boron-rich and boronpoor areas was examined in this study. For this purpose, the DNA damage in the lymphocytes and buccal cells of females were assessed by Comet and micronucleus (MN) assays respectively. No significant difference was observed in the DNA damage of the lymphocytes of B exposed groups of female volunteers in Comet assay. Even buccal micronucleus (MN) frequency observed in the high exposure group was significantly lower than the low exposure group (p < 0.05). The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions.}, language = {en} } @article{BechirSchellingKraemeretal.2012, author = {Bechir, Mahamat and Schelling, E. and Kr{\"a}mer, K. and Schweigert, Florian J. and Bonfoh, Bassirou and Crump, L. and Tanner, M. and Zinsstag, J.}, title = {Retinol assessment among women and children in sahelian mobile pastoralists}, series = {EcoHealth : conservation medicine, human health, ecosystem sustainability}, volume = {9}, journal = {EcoHealth : conservation medicine, human health, ecosystem sustainability}, number = {2}, publisher = {Springer}, address = {New York}, issn = {1612-9202}, doi = {10.1007/s10393-012-0781-7}, pages = {113 -- 121}, year = {2012}, abstract = {Micronutrient deficiencies are widespread in developing countries, particularly in remote communities such as mobile pastoralists. The nutritional and vitamin A status of this population is not well-documented in Chad. This study assessed serum retinol levels among women and children under five-year-old in nomadic and semi-nomadic pastoralist and rural-settled communities, who are similarly exposed to risk factors such as gastrointestinal parasitic infection, anaemia and emaciation. The novel method of portable fluorometry was used for the first time to measure beta-carotene and retinol levels in a pastoral nomadic area. Moderate level blood retinol deficiency (< 0.7 mu mol/L) was observed in 5\% (CI 1-11) of nomadic, 29\% (CI 13-45) of semi-nomadic and 22\% (CI 8-35) of sedentary women. In children, 1\% (CI 0.1-4), 17\% (CI 9-25) and 28\% (CI 18-39), respectively, had moderate level blood retinol deficiency. In nomadic communities, women and children had blood retinol levels close to normal. Deficiency of retinol was strongly linked with lifestyle (nomadic, semi-nomadic and settled) among women and lifestyle and age among children. The results support an ecological linkage between human retinol levels and livestock milk retinol. This study shows the feasibility of portable retinol and beta-carotene measurement in human blood as well as human and animal milk under remote field conditions, but the approach requires further validation.}, language = {en} } @article{BeckmannSchumacherKleuseretal.2021, author = {Beckmann, Nadine and Schumacher, Fabian and Kleuser, Burkhard and Gulbins, Erich and Nomellini, Vanessa and Caldwell, Charles C.}, title = {Burn injury impairs neutrophil chemotaxis through increased ceramide}, series = {Shock : injury, inflammation, and sepsis, laboratory and clinical approaches}, volume = {56}, journal = {Shock : injury, inflammation, and sepsis, laboratory and clinical approaches}, number = {1}, publisher = {Lippincott Williams \& Wilkins}, address = {Hagerstown, Md.}, issn = {1073-2322}, doi = {10.1097/SHK.0000000000001693}, pages = {125 -- 132}, year = {2021}, abstract = {Infection is a common and often deadly complication after burn injury. A major underlying factor is burn-induced immune dysfunction, particularly with respect to neutrophils as the primary responders to infection. Temporally after murine scald injury, we demonstrate impaired bone marrow neutrophil chemotaxis toward CXCL1 ex vivo. Additionally, we observed a reduced recruitment of neutrophils to the peritoneal after elicitation 7 days after injury. We demonstrate that neutrophil ceramide levels increase after burn injury, and this is associated with decreased expression of CXCR2 and blunted chemotaxis. A major signaling event upon CXCR2 activation is Akt phosphorylation and this was reduced when ceramide was elevated. In contrast, PTEN levels were elevated and PTEN-inhibition elevated phospho-Akt levels and mitigated the burn-induced neutrophil chemotaxis defect. Altogether, this study identifies a newly described pathway of ceramide-mediated suppression of neutrophil chemotaxis after burn injury and introduces potential targets to mitigate this defect and reduce infection-related morbidity and mortality after burn.}, language = {en} } @article{BergerBaldermannRuppel2017, author = {Berger, Beatrice and Baldermann, Susanne and Ruppel, Silke}, title = {The plant growth-promoting bacterium Kosakonia radicincitans improves fruit yield and quality of Solanum lycopersicum}, series = {Journal of the Science of Food and Agriculture}, volume = {97}, journal = {Journal of the Science of Food and Agriculture}, publisher = {Wiley}, address = {Hoboken}, issn = {0022-5142}, doi = {10.1002/jsfa.8357}, pages = {4865 -- 4871}, year = {2017}, abstract = {BACKGROUNDProduction and the quality of tomato fruits have a strong economic relevance. Microorganisms such as the plant growth-promoting bacterium (PGPB) Kosakonia radicincitans (DSM 16656) have been demonstrated to improve shoot and root growth of young tomato plants, but data on yield increase and fruit quality by K. radicincitans are lacking. RESULTSThis study investigated how K. radicincitans affects tomato fruits. After inoculation of tomato seeds with K. radicincitans or a sodium chloride buffer control solution, stalk length, first flowering and the amount of ripened fruits produced by inoculated and non-inoculated plants were monitored over a period of 21 weeks. Inoculation of tomato seeds with K. radicincitans accelerated flowering and ripening of tomato fruits. Sugars, acidity, amino acids, volatile organic compounds and carotenoids in the fruits were also analyzed. CONCLUSIONIt was found that the PGPBK. radicincitans affected the amino acid, sugar and volatile composition of ripened fruits, contributing to a more pleasant-tasting fruit without forfeiting selected quality indicators. (c) 2017 Society of Chemical Industry}, language = {en} } @article{BernacchioniGhiniCencettietal.2017, author = {Bernacchioni, Caterina and Ghini, Veronica and Cencetti, Francesca and Japtok, Lukasz and Donati, Chiara and Bruni, Paola and Turano, Paola}, title = {NMR metabolomics highlights sphingosine kinase-1 as a new molecular switch in the orchestration of aberrant metabolic phenotype in cancer cells}, series = {Molecular oncology / Federation of European Biochemical Societies}, volume = {11}, journal = {Molecular oncology / Federation of European Biochemical Societies}, publisher = {Wiley}, address = {Hoboken}, issn = {1878-0261}, doi = {10.1002/1878-0261.12048}, pages = {517 -- 533}, year = {2017}, abstract = {Strong experimental evidence in animal and cellular models supports a pivotal role of sphingosine kinase-1 (SK1) in oncogenesis. In many human cancers, SK1 levels are upregulated and these increases are linked to poor prognosis in patients. Here, by employing untargeted NMR- based metabolomic profiling combined with functional validations, we report the crucial role of SK1 in the metabolic shift known as the Warburg effect in A2780 ovarian cancer cells. Indeed, expression of SK1 induced a high glycolytic rate, characterized by increased levels of lactate along with increased expression of the proton/monocarboxylate symporter MCT1, and decreased oxidative metabolism, associated with the accumulation of intermediates of the tricarboxylic acid cycle and reduction in CO2 production. Additionally, SK1-expressing cells displayed a significant increase in glucose uptake paralleled by GLUT3 transporter upregulation. The role of SK1 is not limited to the induction of aerobic glycolysis, affecting metabolic pathways that appear to support the biosynthesis of macromolecules. These findings highlight the role of SK1 signaling axis in cancer metabolic reprogramming, pointing out innovative strategies for cancer therapies.}, language = {en} } @article{BijleveldHuschekLiefbroer2016, author = {Bijleveld, Catrien and Huschek, Doreen and Liefbroer, Aart C.}, title = {Parental criminality and entry into parenthood among sons and daughters}, series = {Advances in life course research}, volume = {28}, journal = {Advances in life course research}, publisher = {Elsevier}, address = {Oxford}, issn = {1569-4909}, doi = {10.1016/j.alcr.2016.03.006}, pages = {81 -- 90}, year = {2016}, abstract = {In this article, we examined to what extent parental offending influences the timing of entry into parenthood of children. Based on a literature review, we hypothesized that children of delinquent parents would be more likely to enter into parenthood at a relatively young age, and that part of that association could be explained by differences between children of delinquent and non-delinquent parents in the timing of entry into marriage and in their own delinquent behaviour. Using data from a five-generation study of high risk families in the Netherlands, we found that parental delinquency increases the chance of early childbearing among daughters, but not among sons. Among sons, parental delinquency increased son's delinquency, suggesting that parental delinquency has different consequences for the life courses of their sons and daughters.}, language = {en} } @article{BirukovCuadratPolemitietal.2021, author = {Birukov, Anna and Cuadrat, Rafael R. C. and Polemiti, Elli and Eichelmann, Fabian and Schulze, Matthias Bernd}, title = {Advanced glycation end-products, measured as skin autofluorescence, associate with vascular stiffness in diabetic, pre-diabetic and normoglycemic individuals}, series = {Cardiovascular diabetology}, volume = {20}, journal = {Cardiovascular diabetology}, number = {1}, publisher = {BioMed Central}, address = {London}, issn = {1475-2840}, doi = {10.1186/s12933-021-01296-5}, pages = {11}, year = {2021}, abstract = {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.}, language = {en} } @article{BirukovPolemitiJaegeretal.2022, author = {Birukov, Anna and Polemiti, Elli and Jaeger, Susanne and Stefan, Norbert and Schulze, Matthias Bernd}, title = {Fetuin-A and risk of diabetes-related vascular complications}, series = {Cardiovascular diabetology}, volume = {21}, journal = {Cardiovascular diabetology}, number = {1}, publisher = {BMC}, address = {London}, issn = {1475-2840}, doi = {10.1186/s12933-021-01439-8}, pages = {11}, year = {2022}, abstract = {Background Fetuin-A is a hepatokine which has the capacity to prevent vascular calcification. Moreover, it is linked to the induction of metabolic dysfunction, insulin resistance and associated with increased risk of diabetes. It has not been clarified whether fetuin-A associates with risk of vascular, specifically microvascular, complications in patients with diabetes. We aimed to investigate whether pre-diagnostic plasma fetuin-A is associated with risk of complications once diabetes develops. Methods Participants with incident type 2 diabetes and free of micro- and macrovascular disease from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 587) were followed for microvascular and macrovascular complications (n = 203 and n = 60, respectively, median follow-up: 13 years). Plasma fetuin-A was measured approximately 4 years prior to diabetes diagnosis. Prospective associations between baseline fetuin-A and risk of complications were assessed with Cox regression. Results In multivariable models, fetuin-A was linearly inversely associated with incident total and microvascular complications, hazard ratio (HR, 95\% CI) per standard deviation (SD) increase: 0.86 (0.74; 0.99) for total, 0.84 (0.71; 0.98) for microvascular and 0.92 (0.68; 1.24) for macrovascular complications. After additional adjustment for cardiometabolic plasma biomarkers, including triglycerides and high-density lipoprotein, the associations were slightly attenuated: 0.88 (0.75; 1.02) for total, 0.85 (0.72; 1.01) for microvascular and 0.95 (0.67; 1.34) for macrovascular complications. No interaction by sex could be observed (p > 0.10 for all endpoints). Conclusions Our data show that lower plasma fetuin-A levels measured prior to the diagnosis of diabetes may be etiologically implicated in the development of diabetes-associated microvascular disease.}, language = {en} } @article{BishopMachateHenningetal.2022, author = {Bishop, Christopher Allen and Machate, Tina and Henning, Thorsten and Henkel-Oberl{\"a}nder, Janin and P{\"u}schel, Gerhard and Weber, Daniela and Grune, Tilman and Klaus, Susanne and Weitkunat, Karolin}, title = {Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle}, series = {Nutrition \& Diabetes}, volume = {12}, journal = {Nutrition \& Diabetes}, number = {1}, publisher = {Nature Publishing Group}, address = {London}, issn = {2044-4052}, doi = {10.1038/s41387-022-00200-8}, pages = {9}, year = {2022}, abstract = {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.}, language = {en} } @article{BishopSchulzeKlausetal.2020, author = {Bishop, Christopher Allen and Schulze, Matthias Bernd and Klaus, Susanne and Weitkunat, Karolin}, title = {The branched-chain amino acids valine and leucine have differential effects on hepatic lipid metabolism}, series = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology}, volume = {34}, journal = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology}, number = {7}, publisher = {Wiley}, address = {Hoboken}, issn = {0892-6638}, doi = {10.1096/fj.202000195R}, pages = {9727 -- 9739}, year = {2020}, abstract = {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.}, language = {en} } @article{BluvshteinGlassVolohonskyetal.1999, author = {Bluvshtein, Evgenia and Glass, George and Volohonsky, Gloria and Yaakubowitz, Margalit and Harness, Ella and Smorodinsky, Nechama and Seidel, Albrecht and Frank, Heinz and Stark, Avishay Abraham and Steinberg, Pablo}, title = {Inhibition of the hydrolytic and transpeptidatic activities of rat kidney gamma-glutamyltranspeptidase by specific monoclonal antibodies}, year = {1999}, language = {en} } @article{BobbertRailaSchwarzetal.2010, author = {Bobbert, Thomas and Raila, Jens and Schwarz, Franziska and Mai, Knut and Henze, Andrea and Pfeiffer, Andreas F. H. and Schweigert, Florian J. and Spranger, Joachim}, title = {Relation between retinol, retinol-binding protein 4, transthyretin and carotid intima media thickness}, issn = {0021-9150}, doi = {10.1016/j.atherosclerosis.2010.07.063}, year = {2010}, abstract = {Objective: Retinol is transported in a complex with retinol-binding protein 4 (RBP4) and transthyretin (TTR) in the circulation. While retinol is associated with various cardiovascular risk factors, the relation between retinol, RBP4, TTR and carotid intima media thickness (IMT) has not been analysed yet. Methods: Retinol, RBP4 and TTR were measured in 96 individuals and their relation to mean and maximal IMT was determined. Results: Mean IMT correlated with RBP4 (r = 0.335, p < 0.001), retinol (r = -0.241, p = 0.043), RBP/TTR ratio (r = 0.254, p = 0.025) and retinol/RBP4 ratio (r = -0.549, p < 0.001). Adjustment for age, sex, BMI, blood pressure, HDL/total cholesterol ratio, triglyceride, diabetes and smoking revealed that the retinol/RBP4 ratio was strongly and independently associated with mean IMT. Similar results were found for maximal IMT, which included the measurement of plaques. Conclusion: The data support that the transport complex of vitamin A is associated with the IMT, an established parameter of atherosclerosis. Changes in RBP4 saturation with retinol may link renal dysfunction and insulin resistance to atherosclerosis.}, language = {en} } @article{BoekstegersMarcelainBarahonaPonceetal.2020, author = {Boekstegers, Felix and Marcelain, Katherine and Barahona Ponce, Carol and Baez Benavides, Pablo F. and M{\"u}ller, Bettina and de Toro, Gonzalo and Retamales, Javier and Barajas, Olga and Ahumada, Monica and Aleksandrova, Krasimira and Bermejo, Justo Lorenzo}, title = {ABCB1/4 gallbladder cancer risk variants identified in India also show strong effects in Chileans}, series = {Cancer Epidemiology}, volume = {65}, journal = {Cancer Epidemiology}, publisher = {Elsevier}, address = {Amsterdam}, pages = {5}, year = {2020}, abstract = {Background: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence. Methods: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication. Results: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low. Conclusion: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.}, language = {en} } @article{BornhorstEbertMeyeretal.2020, author = {Bornhorst, Julia and Ebert, Franziska and Meyer, S{\"o}ren and Ziemann, Vanessa and Xiong, Chan and Guttenberger, Nikolaus and Raab, Andrea and Baesler, Jessica and Aschner, Michael and Feldmann, J{\"o}rg and Francesconi, Kevin and Raber, Georg and Schwerdtle, Tanja}, title = {Toxicity of three types of arsenolipids}, series = {Metallomics}, volume = {12}, journal = {Metallomics}, number = {5}, publisher = {Oxford University Press}, address = {Cambridge}, issn = {1756-591X}, doi = {https://doi.org/10.1039/d0mt00039f}, pages = {794 -- 798}, year = {2020}, abstract = {Although fish and seafood are well known for their nutritional benefits, they contain contaminants that might affect human health. Organic lipid-soluble arsenic species, so called arsenolipids, belong to the emerging contaminants in these food items; their toxicity has yet to be systematically studied. Here, we apply the in vivo model Caenorhabditis elegans to assess the effects of two arsenic-containing hydrocarbons (AsHC), a saturated arsenic-containing fatty acid (AsFA), and an arsenic-containing triacylglyceride (AsTAG) in a whole organism. Although all arsenolipids were highly bioavailable in Caenorhabditis elegans, only the AsHCs were substantially metabolized to thioxylated or shortened metabolic products and induced significant toxicity, affecting both survival and development. Furthermore, the AsHCs were several fold more potent as compared to the toxic reference arsenite. This study clearly indicates the need for a full hazard identification of subclasses of arsenolipids to assess whether they pose a risk to human health.}, language = {en} } @article{BornhorstNustedeFudickar2019, author = {Bornhorst, Julia and Nustede, Eike Jannik and Fudickar, Sebastian}, title = {Mass Surveilance of C. elegans-Smartphone-Based DIY Microscope and Machine-Learning-Based Approach for Worm Detection}, series = {Sensors}, volume = {19}, journal = {Sensors}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {1424-8220}, doi = {10.3390/s19061468}, pages = {14}, year = {2019}, abstract = {The nematode Caenorhabditis elegans (C. elegans) is often used as an alternative animal model due to several advantages such as morphological changes that can be seen directly under a microscope. Limitations of the model include the usage of expensive and cumbersome microscopes, and restrictions of the comprehensive use of C. elegans for toxicological trials. With the general applicability of the detection of C. elegans from microscope images via machine learning, as well as of smartphone-based microscopes, this article investigates the suitability of smartphone-based microscopy to detect C. elegans in a complete Petri dish. Thereby, the article introduces a smartphone-based microscope (including optics, lighting, and housing) for monitoring C. elegans and the corresponding classification via a trained Histogram of Oriented Gradients (HOG) feature-based Support Vector Machine for the automatic detection of C. elegans. Evaluation showed classification sensitivity of 0.90 and specificity of 0.85, and thereby confirms the general practicability of the chosen approach.}, language = {en} } @article{BorremansBusslerSaguTchewonpietal.2020, author = {Borremans, An and Bußler, Sara and Sagu Tchewonpi, Sorel and Rawel, Harshadrai Manilal and Schl{\"u}ter, Oliver K. and Leen, Van Campenhout}, title = {Effect of blanching plus fermentation on selected functional properties of mealworm (Tenebrio molitor) powders}, series = {Foods : open access journal}, volume = {9}, journal = {Foods : open access journal}, number = {7}, publisher = {MDPI}, address = {Basel}, issn = {2304-8158}, doi = {10.3390/foods9070917}, pages = {17}, year = {2020}, abstract = {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.}, language = {en} } @article{BrauneMaulSchebbetal.2010, author = {Braune, Annett and Maul, Ronald and Schebb, Nils Helge and Kulling, Sabine E. and Blaut, Michael}, title = {The red clover isoflavone irilone is largely resistant to degradation by the human gut microbiota}, issn = {1613-4125}, doi = {10.1002/mnfr.200900233}, year = {2010}, abstract = {Intestinal bacteria may influence bioavailability and physiological activity of dietary isoflavones. We therefore investigated the ability of human intestinal microbiota to convert irilone and genistein in vitro. In contrast to genistein, irilone was largely resistant to transformation by fecal slurries of ten human subjects. The fecal microbiota converted genistein to dihydrogenistein, 6'-hydroxy-O-desmethylangolensin, and 2-(4-hydroxyphenyl)- propionic acid. However, considerable interindividual differences in the rate of genistein degradation and the pattern of metabolites formed from genistein were observed. Only one metabolite, namely dihydroirilone, was formed from irilone in minor amounts. In further experiments, Eubacterium ramulus, a prevalent flavonoid-degrading species of the human gut, was tested for transformation of irilone. In contrast to genistein, irilone was not converted by E. ramulus. Irilone only differs from genistein by a methylenedioxy group attached to the A-ring of the isoflavone skeleton. This substitution obviously restricts the degradability of irilone by human intestinal bacteria.}, language = {en} } @article{BrentenMorrisSaltetal.2014, author = {Brenten, Thomas and Morris, Penelope J. and Salt, Carina and Raila, Jens and Kohn, Barbara and Brunnberg, Leo and Schweigert, Florian J. and Zentek, Juergen}, title = {Energy intake, growth rate and body composition of young Labrador Retrievers and Miniature Schnauzers fed different dietary levels of vitamin A}, series = {The British journal of nutrition : an international journal devoted to the science of human and animal nutrition}, volume = {111}, journal = {The British journal of nutrition : an international journal devoted to the science of human and animal nutrition}, number = {12}, publisher = {Cambridge Univ. Press}, address = {Cambridge}, issn = {0007-1145}, doi = {10.1017/S0007114514000543}, pages = {2104 -- 2111}, year = {2014}, abstract = {Research in rodents has shown that dietary vitamin A reduces body fat by enhancing fat mobilisation and energy utilisation; however, their effects in growing dogs remain unclear. In the present study, we evaluated the development of body weight and body composition and compared observed energy intake with predicted energy intake in forty-nine puppies from two breeds (twenty-four Labrador Retriever (LAB) and twenty-five Miniature Schnauzer (MS)). A total of four different diets with increasing vitamin A content between 5.24 and 104.80 mu mol retinol (5000-100 000 IU vitamin A)/4184 kJ (1000 kcal) metabolisable energy were fed from the age of 8 weeks up to 52 (MS) and 78 weeks (LAB). The daily energy intake was recorded throughout the experimental period. The body condition score was evaluated weekly using a seven-category system, and food allowances were adjusted to maintain optimal body condition. Body composition was assessed at the age of 26 and 52 weeks for both breeds and at the age of 78 weeks for the LAB breed only using dual-energy X-ray absorptiometry. The growth curves of the dogs followed a breed-specific pattern. However, data on energy intake showed considerable variability between the two breeds as well as when compared with predicted energy intake. In conclusion, the data show that energy intakes of puppies particularly during early growth are highly variable; however, the growth pattern and body composition of the LAB and MS breeds are not affected by the intake of vitamin A at levels up to 104.80 mu mol retinol (100 000 IU vitamin A)/4184 kJ (1000 kcal).}, language = {en} } @article{BrigeliusFloheBanningKnyetal.2004, author = {Brigelius-Floh{\´e}, Regina and Banning, Anja and Kny, M. and B{\"o}l, Gaby Fleur}, title = {Redox events in interleukin-1 signaling}, issn = {0003-9861}, year = {2004}, abstract = {There is increasing evidence that reactive oxygen species (ROS) are mediators in growth factor and cytokine signaling pathways. Mechanisms by which ROS can interfere with signaling cascades may include regulation of protein activities by the modification of essential cysteines. Modification can be performed chemically or enzyme-catalyzed. Enzymes catalyzing a reversible thiol modification within proteins are to be able to react with both, ROS and protein thiols. If hydroperoxides are involved, promising candidates are peroxiredoxins and glutathione peroxidases (GPx), especially the phospholipid hydroperoxide GPx. Interleukin-1, one of the key players in inflammatory response, stimulates the production of ROS itself, but its signaling cascade can also be influenced by ROS and by thiol modifying agents. Targets are located in early, intermediate, and late events in the signaling cascade. We here summarize what is known about the effects of thiol modifying agents, selenium and glutathione peroxidases, on the assembly of the IL-1 receptor signaling complex as an early event, on the activation of NF-kappaB as an intermediate event, and on the expression of cell adhesion molecules as a late event in IL-1 signaling. (C) 2003 Elsevier Inc. All rights reserved}, language = {en} } @article{BrunoCencettiPerticietal.2015, author = {Bruno, Gennaro and Cencetti, Francesca and Pertici, Irene and Japtok, Lukasz and Bernacchioni, Caterina and Donati, Chiara and Bruni, Paola}, title = {CTGF/CCN2 exerts profibrotic action in myoblasts via the up-regulation of sphingosine kinase-1/S1P(3) signaling axis: Implications in the action mechanism of TGF beta}, series = {Biochimica et biophysica acta : Molecular and cell biology of lipids}, volume = {1851}, journal = {Biochimica et biophysica acta : Molecular and cell biology of lipids}, number = {2}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1388-1981}, doi = {10.1016/j.bbalip.2014.11.011}, pages = {194 -- 202}, year = {2015}, abstract = {The matricellular protein connective tissue growth factor (CTGF/CCN2) is recognized as key player in the onset of fibrosis in various tissues, including skeletal muscle. In many circumstances, CTGF has been shown to be induced by transforming growth factor beta (TGF beta) and accounting, at least in part, for its biological action. In this study it was verified that in cultured myoblasts CTGF/CCN2 causes their transdifferentiation into myofibroblasts by up-regulating the expression of fibrosis marker proteins alpha-smooth muscle actin and transgelin. Interestingly, it was also found that the profibrotic effect exerted by CTGF/CCN2 was mediated by the sphingosine kinase (SK)-1/S1P(3) signaling axis specifically induced by the treatment with the profibrotic cue. Following CTGF/CCN2-induced up-regulation, S1P(3) became the SIP receptor subtype expressed at the highest degree, at least at mRNA level, and was thus capable of readdressing the sphingosine 1-phosphate signaling towards fibrosis rather than myogenic differentiation. Another interesting finding is that CTGF/CCN2 silencing prevented the TGF beta-dependent up-regulation of SKI/S1P(3) signaling axis and strongly reduced the profibrotic effect exerted by TGF beta, pointing at a crucial role of endogenous CTGF/CCN2 generated following TGF beta challenge in the transmission of at least part of its profibrotic effect These results provide new insights into the molecular mechanism by which CTGF/CCN2 drives its biological action and strengthen the concept that SK1/S1P(3) axis plays a critical role in the onset of fibrotic cell phenotype. (C) 2014 Elsevier B.V. All rights reserved.}, language = {en} } @article{BurkhardtRauschKlopfleischetal.2021, author = {Burkhardt, Wiebke and Rausch, Theresa and Klopfleisch, Robert and Blaut, Michael and Braune, Annett}, title = {Impact of dietary sulfolipid-derived sulfoquinovose on gut microbiota composition and inflammatory status of colitis-prone interleukin-10-deficient mice}, series = {International journal of medical microbiology : IJMM}, volume = {311}, journal = {International journal of medical microbiology : IJMM}, number = {3}, publisher = {Elsevier}, address = {M{\"u}nchen}, issn = {1618-0607}, doi = {10.1016/j.ijmm.2021.151494}, pages = {11}, year = {2021}, abstract = {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.}, language = {en} } @article{BusslerRawelSchlueter2020, author = {Bußler, Sara and Rawel, Harshadrai Manilal and Schl{\"u}ter, Oliver K.}, title = {Impact of plasma processed air (PPA) on phenolic model systems}, series = {Innovative food science \& emerging technologies : the official journal of the European Federation of Food Science and Technology}, volume = {64}, journal = {Innovative food science \& emerging technologies : the official journal of the European Federation of Food Science and Technology}, publisher = {Elsevier}, address = {Oxford}, issn = {1466-8564}, doi = {10.1016/j.ifset.2020.102432}, pages = {11}, year = {2020}, abstract = {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.}, language = {en} } @article{BusslerRumpoldFroehlingetal.2016, author = {Bußler, Sara and Rumpold, Birgit A. and Fr{\"o}hling, Antje and Jander, Elisabeth and Rawel, Harshadrai Manilal and Schl{\"u}ter, Oliver K.}, title = {Cold atmospheric pressure plasma processing of insect flour from Tenebrio molitor: Impact on microbial load and quality attributes in comparison to dry heat treatment}, series = {Meteoritics \& planetary science : journal of the Meteoritical Society}, volume = {36}, journal = {Meteoritics \& planetary science : journal of the Meteoritical Society}, publisher = {Elsevier}, address = {Oxford}, issn = {1466-8564}, doi = {10.1016/j.ifset.2016.07.002}, pages = {277 -- 286}, year = {2016}, abstract = {In this study, the applicability of semi-direct cold atmospheric pressure plasma (CAPP) during postharvest processing of Tenebrio molitor flour is investigated. Besides analyzing the decontamination efficacy, plasma induced impact on techno-functionality, protein solubility, composition and structure was determined and compared to heat induced effects. Following CAPP treatment, the total microbial load of the Tenebrio flour of 7.72 log(10) cfu/g was reduced to 7.10 (1 min), 6.72 (2.5 min), 5.79 (5 min), 5.19 (7.5 min), 521 (10 min) and 4.73 (15 min) log(10) cfu/g. With increasing exposure to CAPP, protein solubility at pH 4 almost linearly decreased to a minimum of 54\%. Water binding capacity decreased from 0.79 to 0.64 gwatedg whereas oil binding capacity increased from 0.59 to 0.66 g(oil)/g. Gel electrophoresis revealed a decrease of all protein fractions at pH 4 whereas at pH 10 the band pattern significantly shifted to protein fractions with higher molecular weights. Industrial relevance: Edible insects are rich in valuable protein, fat, fibre, minerals and micronutrients. Although a wide range of species represent a valuable alternative protein source that could contribute to food and feed security, they are industrially hardly exploited. The tailored application of proper processing technologies could lead to novel insect-based high-protein food and feed products with unique functional properties supporting the increase in acceptability among potential consumers. Current research concentrates on developing processing chains including innovative nonthermal approaches. Cold atmospheric pressure plasma (CAPP) has gained attention as an effective technology for the decontamination and modification of fresh and dry agricultural products. In the postharvest chain of edible insects, the application of CAPP could contribute to the development of safe and high-quality insect-based products in the food and feed sector. (C) 2016 Published by Elsevier Ltd.}, language = {en} } @article{BzymekHorsthemkeIsfortetal.2016, author = {Bzymek, Robert and Horsthemke, Markus and Isfort, Katrin and Mohr, Simon and Tjaden, Kerstin and Mueller-Tidow, Carsten and Thomann, Marlies and Schwerdtle, Tanja and Baehler, Martin and Schwab, Albrecht and Hanley, Peter J.}, title = {Real-time two- and three-dimensional imaging of monocyte motility and navigation on planar surfaces and in collagen matrices: roles of Rho}, series = {Scientific reports}, volume = {6}, journal = {Scientific reports}, publisher = {Nature Publ. Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/srep25016}, pages = {15}, year = {2016}, abstract = {We recently found that macrophages from RhoA/RhoB double knockout mice had increased motility of the cell body, but severely impaired retraction of the tail and membrane extensions, whereas RhoA-or RhoB-deficient cells exhibited mild phenotypes. Here we extended this work and investigated the roles of Rho signaling in primary human blood monocytes migrating in chemotactic gradients and in various settings. Monocyte velocity, but not chemotactic navigation, was modestly dependent on Rho-ROCK-myosin II signaling on a 2D substrate or in a loose collagen type I matrix. Viewed by time-lapse epi-fluorescence microscopy, monocytes appeared to flutter rather than crawl, such that the 3D surface topology of individual cells was difficult to predict. Spinning disk confocal microscopy and 3D reconstruction revealed that cells move on planar surfaces and in a loose collagen matrix using prominent, curved planar protrusions, which are rapidly remodeled and reoriented, as well as resorbed. In a dense collagen type I matrix, there is insufficient space for this mode and cells adopt a highly Rho-dependent, lobular mode of motility. Thus, in addition to its role in tail retraction on 2D surfaces, Rho is critical for movement in confined spaces, but is largely redundant for motility and chemotaxis in loose matrices.}, language = {en} } @article{BoeerFennekohlPueschel2003, author = {B{\"o}er, Ulrike and Fennekohl, Alexandra and P{\"u}schel, Gerhard Paul}, title = {Sensitization by interleukin-6 of rat hepatocytes to tumor necrosis factor alpha-induced apoptosis}, year = {2003}, abstract = {BACKGROUND/AIMS: Tumor necrosis factor (TNF) elicits hepatocyte apoptosis in toxic liver injury and is also central in hepatocyte proliferation after partial hepatectomy. In both circumstances interleukin (IL)-6 levels are also elevated. In mouse liver IL-6 attenuated Fas receptor-mediated apoptosis indicating its interference with pro-apoptotic signal chains. It was, therefore, the aim to examine the modulation by IL-6 of TNFalpha-induced apoptosis in rat hepatocytes. METHODS: Primary rat hepatocytes were treated with IL-6 prior to induction of apoptosis with TNFalpha/ actinomycin D or anti-Fas antibody M-20. Apoptosis was detected by determination of caspase-3 activation and bisbenzimide staining of condensed nuclei. Expression of TNFalpha receptors was analyzed by semi-quantitative polymerase chain reaction and ligand binding studies with [125I]-TNFalpha. RESULTS: IL-6 treatment doubled TNFalpha/actinomycin D- induced caspase-3 activity and significantly enhanced chromatin condensation. By contrast IL-6 inhibited Fas-induced increase in caspase-3 activity by 45\% and significantly reduced chromatin condensation. IL-6 increased the mRNA level of TNF-R1 1.35-fold and augmented cell surface binding of [125I]-TNFalpha 3-fold. The latter and TNFalpha-mediated caspase activation was attenuated by prostaglandin E(2). CONCLUSIONS: IL-6 - in contrast to its anti-apoptotic modulation of the Fas-induced pathway - exerted a pro-apoptotic effect on the TNFalpha/actinomycin D-induced apoptosis by increasing the number of TNF-R on hepatocytes.}, language = {en} } @article{BoeerNeuschaeferRubeMoelleretal.2000, author = {B{\"o}er, Ulrike and Neusch{\"a}fer-Rube, Frank and M{\"o}ller, Ulrike and P{\"u}schel, Gerhard Paul}, title = {Requirement of N-glycosylation of the prostaglandin E2 receptor EP3beta for correct sorting to the plasma membrane but not for correct folding}, year = {2000}, abstract = {Eight heptahelical receptors have been characterized for prostaglandin (PG) D(2), PGE(2), PGF(2alpha), prostacyclin and thromboxane A(2). They share a sequence identity of 40\%. All of them have potential N-glycosylation sites. The current study analysed the role of the two N-glycosylation sites in the rat EP3beta-subtype PGE(2) receptor for protein folding and sorting. The N-glycosylation consensus sequences were eliminated by site-directed mutagenesis and receptors expressed in HEK-293 cells. Both potential N-glycosylation sites were used. Their joint elimination resulted in the synthesis of a receptor protein with full binding competence, biological activity and no reduction of affinity; however, the half-life of the non-glycosylated receptor was slightly reduced. Ligand binding to intact stably transfected cells and confocal laser microscopic immunocytochemistry showed that the glycosylated receptor was correctly inserted into the plasma membrane to a much larger extent than the non-glycosylated receptor, which tended to accumulate in the perinuclear zone of the endoplasmic reticulum. Inhibition of N-glycosylation with tunicamycin resulted in a similar perinuclear distribution of the wild-type receptor. Therefore, glycosylation of the EP3beta receptor seems not to be necessary for correct folding of the receptor protein but for the efficient transport of the receptor protein to the plasma membrane. This contrasts with a previous finding which described a reduction of the affinity for PGE(2) of the EP3alpha receptor by elimination of the distal glycosylation site when the receptor protein was expressed in insect cells.}, language = {en} } @article{BoehmFloesserErmleretal.2013, author = {B{\"o}hm, Andreas and Fl{\"o}ßer, Anja and Ermler, Swen and Fender, Anke C. and L{\"u}th, Anja and Kleuser, Burkhard and Schr{\"o}r, Karsten and Rauch, Bernhard H.}, title = {Factor-Xa-induced mitogenesis and migration require sphingosine kinase activity and S1P formation in human vascular smooth muscle cells}, series = {Cardiovascular research}, volume = {99}, journal = {Cardiovascular research}, number = {3}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0008-6363}, doi = {10.1093/cvr/cvt112}, pages = {505 -- 513}, year = {2013}, abstract = {Sphingosine-1-phosphate (S1P) is a cellular signalling lipid generated by sphingosine kinase-1 (SPHK1). The aim of the study was to investigate whether the activated coagulation factor-X (FXa) regulates SPHK1 transcription and the formation of S1P and subsequent mitogenesis and migration of human vascular smooth muscle cells (SMC). FXa induced a time- (36 h) and concentration-dependent (330 nmol/L) increase of SPHK1 mRNA and protein expression in human aortic SMC, resulting in an increased synthesis of S1P. FXa-stimulated transcription of SPHK1 was mediated by the protease-activated receptor-1 (PAR-1) and PAR-2. In human carotid artery plaques, expression of SPHK1 was observed at SMC-rich sites and was co-localized with intraplaque FX/FXa content. FXa-induced SPHK1 transcription was attenuated by inhibitors of Rho kinase (Y27632) and by protein kinase C (PKC) isoforms (GF109203X). In addition, FXa rapidly induced the activation of the small GTPase Rho A. Inhibition of signalling pathways which regulate SPHK1 expression, inhibition of its activity or siRNA-mediated SPHK1 knockdown attenuated the mitogenic and chemotactic response of human SMC to FXa. These data suggest that FXa induces SPHK1 expression and increases S1P formation independent of thrombin and that this involves the activation of Rho A and PKC signalling. In addition to its key function in coagulation, this direct effect of FXa on human SMC may increase cell proliferation and migration at sites of vessel injury and thereby contribute to the progression of vascular lesions.}, language = {en} } @article{BoenickHuschekRawel2017, author = {B{\"o}nick, Josephine and Huschek, Gerd and Rawel, Harshadrai Manilal}, title = {Determination of wheat, rye and spelt authenticity in bread by targeted peptide biomarkers}, series = {Journal of Food Composition and Analysis}, volume = {58}, journal = {Journal of Food Composition and Analysis}, publisher = {Elsevier}, address = {San Diego}, issn = {0889-1575}, doi = {10.1016/j.jfca.2017.01.019}, pages = {82 -- 91}, year = {2017}, abstract = {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.}, language = {en} } @article{CarlsohnRohnMayeretal.2010, author = {Carlsohn, Anja and Rohn, Sascha and Mayer, Frank and Schweigert, Florian J.}, title = {Physical activity, antioxidant status, and protein modification in adolescent athletes}, issn = {0195-9131}, doi = {10.1249/Mss.0b013e3181c74f7b}, year = {2010}, abstract = {Exercise may increase reactive oxygen species production, which might impair cell integrity and contractile function of muscle cells. However, little is known about the effect of regular exercise on the antioxidant status of adolescents. Purpose: This study aimed to evaluate the impact of exercise on the antioxidant status and protein modifications in adolescent athletes. Methods: In 90 athletes and 18 controls (16 +/- 2 yr), exercise-related energy expenditure was calculated on the basis of a 7-d activity protocol. Antioxidant intake and plasma concentrations of alpha-tocopherol, carotenoids, and uric acid were analyzed. Plasma antioxidant activity was determined by Trolox equivalent (TE) antioxidant capacity and electron spin resonance spectrometry. Protein modifications were assessed with structural changes of transthyretin using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Data were analyzed by two-way ANOVA and post hoc by the Tukey-Kramer test (alpha = 0.05). Results: Antioxidant intake correlated with energy intake and was within the recommended daily allowance for vitamins C and E and beta-carotene. Plasma levels of neither nutritional antioxidants nor uric acid differed between the groups. TE antioxidant capacity was higher in athletes (men = 1.47 perpendicular to 0.2 mmol TE per liter, women = 1.45 perpendicular to 0.2 mmol TE per liter) compared with controls (men = 1.17 +/- 0.04 mmol TE per liter, women = 1.14 +/- 0.04 mmol TE per liter) and increased with exercise-related energy expenditure (P = 0.007). Transthyretin cysteinylation rate differed between the groups, with the highest rate of protein modifications in moderately active subjects (P = 0.007). Conclusions: Results suggest that if the nutritional choice of athletes is well balanced, enough antioxidants are provided to meet recommended amounts. Moreover, regular exercise increases blood antioxidant capacity in young athletes, whereas chronic exercise was not shown to promote protein modifications. Thus, in young athletes who are sufficiently supplied with antioxidants, beneficial effects of exercise on antioxidant status rather than on oxidative stress may be anticipated.}, language = {en} } @article{CarlsohnScharhagRosenbergerCasseletal.2011, author = {Carlsohn, Anja and Scharhag-Rosenberger, Friederike and Cassel, Michael and Mayer, Frank}, title = {Resting metabolic rate in elite rowers and canoeists difference between indirect calorimetry and prediction}, series = {Annals of nutrition \& metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS)}, volume = {58}, journal = {Annals of nutrition \& metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS)}, number = {3}, publisher = {Karger}, address = {Basel}, issn = {0250-6807}, doi = {10.1159/000330119}, pages = {239 -- 244}, year = {2011}, abstract = {Background: Athletes may differ in their resting metabolic rate (RMR) from the general population. However, to estimate the RMR in athletes, prediction equations that have not been validated in athletes are often used. The purpose of this study was therefore to verify the applicability of commonly used RMR predictions for use in athletes. Methods: The RMR was measured by indirect calorimetry in 17 highly trained rowers and canoeists of the German national teams (BMI 24 +/- 2 kg/m(2), fat-free mass 69 +/- 15 kg). In addition, the RMR was predicted using Cunningham (CUN) and Harris-Benedict (HB) equations. A two-way repeated measures ANOVA was calculated to test for differences between predicted and measured RMR (alpha = 0.05). The root mean square percentage error (RMSPE) was calculated and the Bland-Altman procedure was used to quantify the bias for each prediction. Results: Prediction equations significantly underestimated the RMR in males (p < 0.001). The RMSPE was calculated to be 18.4\% (CUN) and 20.9\% (HB) in the entire group. The bias was 133 kcal/24 h for CUN and 202 kcal/24 h for HB. Conclusions: Predictions significantly underestimate the RMR in male heavyweight endurance athletes but not in females. In athletes with a high fat-free mass, prediction equations might therefore not be applicable to estimate energy requirements. Instead, measurement of the resting energy expenditure or specific prediction equations might be needed for the individual heavyweight athlete.}, language = {en} } @article{CarpinteiroBeckerJaptoketal.2015, author = {Carpinteiro, Alexander and Becker, Katrin Anne and Japtok, Lukasz and Hessler, Gabriele and Keitsch, Simone and Pozgajova, Miroslava and Schmid, Kurt W. and Adams, Constantin and M{\"u}ller, Stefan and Kleuser, Burkhard and Edwards, Michael J. and Grassme, Heike and Helfrich, Iris and Gulbins, Erich}, title = {Regulation of hematogenous tumor metastasis by acid sphingomyelinase}, series = {EMBO molecular medicine}, volume = {7}, journal = {EMBO molecular medicine}, number = {6}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1757-4676}, pages = {714 -- 734}, year = {2015}, abstract = {Metastatic dissemination of cancer cells is the ultimate hallmark of malignancy and accounts for approximately 90\% of human cancer deaths. We investigated the role of acid sphingomyelinase (Asm) in the hematogenous metastasis of melanoma cells. Intravenous injection of B16F10 melanoma cells into wild-type mice resulted in multiple lung metastases, while Asm-deficient mice (Smpd1(-/-) mice) were protected from pulmonary tumor spread. Transplanting wild-type platelets into Asm-deficient mice reinstated tumor metastasis. Likewise, Asm-deficient mice were protected from hematogenous MT/ret melanoma metastasis to the spleen in a mouse model of spontaneous tumor metastasis. Human and mouse melanoma cells triggered activation and release of platelet secretory Asm, in turn leading to ceramide formation, clustering, and activation of 51 integrins on melanoma cells finally leading to adhesion of the tumor cells. Clustering of integrins by applying purified Asm or C-16 ceramide to B16F10 melanoma cells before intravenous injection restored trapping of tumor cells in the lung in Asm-deficient mice. This effect was revertable by arginine-glycine-aspartic acid peptides, which are known inhibitors of integrins, and by antibodies neutralizing 1 integrins. These findings indicate that melanoma cells employ platelet-derived Asm for adhesion and metastasis.}, language = {en} } @article{CastroFernandoReegetal.2019, author = {Castro, Jose Pedro and Fernando, Raquel and Reeg, Sandra and Meinl, Walter and Almeida, Henrique and Grune, Tilman}, title = {Non-enzymatic cleavage of Hsp90 by oxidative stress leads to actin aggregate formation}, series = {Redox Biology}, volume = {21}, journal = {Redox Biology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2213-2317}, doi = {10.1016/j.redox.2019.101108}, pages = {10}, year = {2019}, abstract = {Aging is accompanied by the accumulation of oxidized proteins. To remove them, cells employ the proteasomal and autophagy-lysosomal systems; however, if the clearance rate is inferior to its formation, protein aggregates form as a hallmark of proteostasis loss. In cells, during stress conditions, actin aggregates accumulate leading to impaired proliferation and reduced proteasomal activity, as observed in cellular senescence. The heat shock protein 90 (Hsp90) is a molecular chaperone that binds and protects the proteasome from oxidative inactivation. We hypothesized that in oxidative stress conditions a malfunction of Hsp90 occurs resulting in the aforementioned protein aggregates. Here, we demonstrate that upon oxidative stress Hsp90 loses its function in a highly specific non-enzymatic iron-catalyzed oxidation event and its breakdown product, a cleaved form of Hsp90 (Hsp90cl), acquires a new function in mediating the accumulation of actin aggregates. Moreover, the prevention of Hsp90 cleavage reduces oxidized actin accumulation, whereas transfection of the cleaved form of Hsp90 leads to an enhanced accumulation of oxidized actin. This indicates a clear role of the Hsp90cl in the aggregation of oxidized proteins.}, language = {en} } @article{CastroWardelmannGruneetal.2018, author = {Castro, Jose Pedro and Wardelmann, Kristina and Grune, Tilman and Kleinridders, Andre}, title = {Mitochondrial Chaperones in the Brain}, series = {Frontiers in Endocrinology}, volume = {9}, journal = {Frontiers in Endocrinology}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-2392}, doi = {10.3389/fendo.2018.00196}, pages = {13}, year = {2018}, abstract = {The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As a consequence of high rate metabolism, mitochondria in the brain accumulate errors over time, such as mitochondrial DNA (mtDNA) mutations, reactive oxygen species, and misfolded and aggregated proteins. Thus, mitochondria need to employ specific mechanisms to avoid or ameliorate the rise of damaged proteins that contribute to aberrant mitochondrial function and oxidative stress. To maintain mitochondria homeostasis (mitostasis), cells evolved molecular chaperones that shuttle, refold, or in coordination with proteolytic systems, help to maintain a low steady-state level of misfolded/aggregated proteins. Their importance is exemplified by the occurrence of various brain diseases which exhibit reduced action of chaperones. Chaperone loss (expression and/or function) has been observed during aging, metabolic diseases such as type 2 diabetes and in neurode-generative diseases such as Alzheimer's (AD), Parkinson's (PD) or even Huntington's (HD) diseases, where the accumulation of damage proteins is evidenced. Within this perspective, we propose that proper brain function is maintained by the joint action of mitochondrial chaperones to ensure and maintain mitostasis contributing to brain health, and that upon failure, alter brain function which can cause metabolic diseases.}, language = {en} } @article{CencettiBrunoBernacchionietal.2020, author = {Cencetti, Francesca and Bruno, Gennaro and Bernacchioni, Caterina and Japtok, Lukasz and Puliti, Elisa and Donati, Chiara and Bruni, Paola}, title = {Sphingosine 1-phosphate lyase blockade elicits myogenic differentiation of murine myoblasts acting via Spns2/S1P(2) receptor axis}, series = {Biochimica et biophysica acta : Molecular and cell biology of lipids}, volume = {1865}, journal = {Biochimica et biophysica acta : Molecular and cell biology of lipids}, number = {9}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1388-1981}, doi = {10.1016/j.bbalip.2020.158759}, pages = {9}, year = {2020}, abstract = {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.}, language = {en} } @article{ChakrabortyChenBornhorstetal.2015, author = {Chakraborty, Sudipta and Chen, Pan and Bornhorst, Julia and Schwerdtle, Tanja and Schumacher, Fabian and Kleuser, Burkhard and Bowman, Aaron B. and Aschner, Michael A.}, title = {Loss of pdr-1/parkin influences Mn homeostasis through altered ferroportin expression in C-elegans}, series = {Metallomics : integrated biometal science}, volume = {7}, journal = {Metallomics : integrated biometal science}, number = {5}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/c5mt00052a}, pages = {847 -- 856}, year = {2015}, language = {en} } @article{ChaykovskaAltervonWebskyetal.2013, author = {Chaykovska, Lyubov and Alter, Markus L. and von Websky, Karoline and Hohmann, Margarete and Tsuprykov, Oleg and Reichetzeder, Christoph and Kutil, Barbara and Kraft, Robin and Klein, Thomas and Hocher, Berthold}, title = {Effects of telmisartan and linagliptin when used in combination on blood pressure and oxidative stress in rats with 2-kidney-1-clip hypertension}, series = {Journal of hypertension}, volume = {31}, journal = {Journal of hypertension}, number = {11}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0263-6352}, doi = {10.1097/HJH.0b013e3283649b4d}, pages = {2290 -- 2299}, year = {2013}, abstract = {Objective:To investigate the effects of linagliptin alone and in combination with the angiotensin II receptor blocker (ARB), telmisartan on blood pressure (BP), kidney function, heart morphology and oxidative stress in rats with renovascular hypertension.Methods:Fifty-seven male Wistar rats underwent unilateral surgical stenosis of the renal artery [2-kidney-1-clip (2k1c) method]. Animals were randomly divided into four treatment groups (n=14-18 per group) receiving: telmisartan (10mg/kg per day in drinking water), linagliptin (89ppm in chow), combination (linagliptin 89ppm+telmisartan 10mg/kg per day) or placebo. An additional group of 12 rats underwent sham surgery. BP was measured one week after surgery. Hypertensive animals entered a 16-week dosing period. BP was measured 2, 4, 8, 12 and 16 weeks after the initiation of treatment. Blood and urine were tested for assessment of kidney function and oxidative stress 6, 10, 14 and 18 weeks after surgery. Blood and urine sampling and organ harvesting were finally performed.Results:Renal stenosis caused an increase in meanSD systolic BP as compared with the sham group (157.7 +/- 29.3 vs. 106.2 +/- 20.5mmHg, respectively; P<0.001). Telmisartan alone and in combination with linagliptin, normalized SBP (111.1 +/- 24.3mmHg and 100.4 +/- 13.9mmHg, respectively; P<0.001 vs. placebo). Telmisartan alone and in combination with linagliptin significantly prevented cardiac hypertrophy, measured by heart weight and myocyte diameter. Renal function measured by cystatin C was not affected by 2k1c surgery. Telmisartan significantly increased plasma concentration of cystatin C. 2k1c surgery initiated fibrosis in both kidneys. Telmisartan promoted further fibrotic changes in the clipped kidney, as measured by protein expression of Col1a1 and histology for interstitial fibrosis and glomerulosclerosis. In non-clipped kidneys, telmisartan demonstrated antifibrotic properties, reducing Col1a1 protein expression. Plasma levels of oxidized low-density lipoprotein were higher in the placebo-treated 2k1c rats as compared to sham-operated animals. The increase was abolished by linagliptin alone (P=0.03 vs. placebo) and in combination with telmisartan (P=0.02 vs. placebo). Combination therapy also significantly reduced plasma concentration of carbonyl proteins (P=0.04 vs. placebo).Conclusion:Inhibition of type 4 dipeptidyl peptidase with linagliptin did not counter BP-lowering effects of ARB in 2k1c rats. Linagliptin reduced lipid and protein oxidation in 2k1c rats, and this effect was BP-independent.}, language = {en} } @article{ChaykovskaHeunischvonEinemetal.2016, author = {Chaykovska, Lyubov and Heunisch, Fabian and von Einem, Gina and Alter, Markus L. and Hocher, Carl-Friedrich and Tsuprykov, Oleg and Dschietzig, Thomas and Kretschmer, Axel and Hocher, Berthold}, title = {Urinary Vitamin D Binding Protein and KIM-1 Are Potent New Biomarkers of Major Adverse Renal Events in Patients Undergoing Coronary Angiography}, series = {PLoS one}, volume = {11}, journal = {PLoS one}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0145723}, pages = {11}, year = {2016}, abstract = {Background Vitamin-D-binding protein (VDBP) is a low molecular weight protein that is filtered through the glomerulus as a 25-(OH) vitamin D 3/VDBP complex. In the normal kidney VDBP is reabsorbed and catabolized by proximal tubule epithelial cells reducing the urinary excretion to trace amounts. Acute tubular injury is expected to result in urinary VDBP loss. The purpose of our study was to explore the potential role of urinary VDBP as a biomarker of an acute renal damage. Method We included 314 patients with diabetes mellitus or mild renal impairment undergoing coronary angiography and collected blood and urine before and 24 hours after the CM application. Patients were followed for 90 days for the composite endpoint major adverse renal events (MARE: need for dialysis, doubling of serum creatinine after 90 days, unplanned emergency rehospitalization or death). Results Increased urine VDBP concentration 24 hours after contrast media exposure was predictive for dialysis need (no dialysis: 113.06 +/- 299.61ng/ml, n = 303; need for dialysis: 613.07 +/- 700.45 ng/ml, n = 11, Mean +/- SD, p < 0.001), death (no death during follow-up: 121.41 +/- 324.45 ng/ml, n = 306; death during follow-up: 522.01 +/- 521.86 ng/ml, n = 8; Mean +/- SD, p < 0.003) and MARE (no MARE: 112.08 +/- 302.00ng/ml, n = 298; MARE: 506.16 +/- 624.61 ng/ml, n = 16, Mean +/- SD, p < 0.001) during the follow-up of 90 days after contrast media exposure. Correction of urine VDBP concentrations for creatinine excretion confirmed its predictive value and was consistent with increased levels of urinary Kidney Injury Molecule1 (KIM-1) and baseline plasma creatinine in patients with above mentioned complications. The impact of urinary VDBP and KIM-1 on MARE was independent of known CIN risk factors such as anemia, preexisting renal failure, preexisting heart failure, and diabetes. Conclusions Urinary VDBP is a promising novel biomarker of major contrast induced nephropathy-associated events 90 days after contrast media exposure.}, language = {en} } @article{ChaykovskaHeunischvonEinemetal.2018, author = {Chaykovska, Lyubov and Heunisch, Fabian and von Einem, Gina and Hocher, Carl-Friedrich and Tsuprykov, Oleg and Pavkovic, Mira and Sandner, Peter and Kretschmer, Axel and Chu, Chang and Elitok, Saban and Stasch, Johannes-Peter and Hocher, Berthold}, title = {Urinary cGMP predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus before exposure to contrast medium}, series = {PLoS one}, volume = {13}, journal = {PLoS one}, number = {4}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0195828}, pages = {13}, year = {2018}, abstract = {Background The use of iodine-based contrast agents entails the risk of contrast induced nephropathy (CIN). Radiocontrast agents elicit the third most common cause of nephropathy among hospitalized patients, accounting for 11-12\% of cases. CIN is connected with clinically significant consequences, including increased morbidity, prolonged hospitalization, increased risk of complications, potential need for dialysis, and increased mortality rate. The number of in hospital examinations using iodine-based contrast media has been significantly increasing over the last decade. In order to protect patients from possible complications of such examinations, new biomarkers are needed that are able to predict a risk of contrast-induced nephropathy. Urinary and plasma cyclic guanosine monophosphate (cGMP) concentrations are influenced by renal function. Urinary cGMP is primarily of renal cellular origin. Therefore, we assessed if urinary cGMP concentration may predict major adverse renal events (MARE) after contrast media exposure during coronary angiography. Methods Urine samples were prospectively collected from non-randomized consecutive patients with either diabetes or preexisting impaired kidney function receiving intra-arterial contrast medium (CM) for emergent or elective coronary angiography at the Charite Campus Mitte, University Hospital Berlin. Urinary cGMP concentration in spot urine was analyzed 24 hours after CM exposure. Patients were followed up over 90 days for occurrence of death, initiation of dialysis, doubling of plasma creatinine concentration or MARE. Results In total, 289 consecutive patients were included into the study. Urine cGMP/creatinine ratio 24 hours before CM exposure expressed as mean +/- SD was predictive for the need of dialysis (no dialysis: 89.77 +/- 92.85 mu M/mM, n = 277; need for dialysis: 140.3 +/- 82.90 mu M/mM, n = 12, p = 0.008), death (no death during follow-up: 90.60 +/- 92.50 mu M/mM, n = 280; death during follow-up: 169.88 +/- 81.52 mu M/mM, n = 9; p = 0.002), and the composite endpoint MARE (no MARE: 86.02 +/- 93.17 mu M/mM, n = 271; MARE: 146.64 +/- 74.68 mu M/mM, n = 18, p<0.001) during the follow-up of 90 days after contrast media application. cGMP/creatinine ratio stayed significantly increased at values exceeding 120 pM/mM in patients who developed MARE, required dialysis or died. Conclusions Urinary cGMP/creatinine ratio >= 120 mu M/mM before CM exposure is a promising biomarker for the need of dialysis and all-cause mortality 90 days after CM exposure in patients with preexisting renal impairment or diabetes.}, language = {en} } @article{ChaykovskavonWebskyRahnenfuehreretal.2011, author = {Chaykovska, Lyubov and von Websky, Karoline and Rahnenf{\"u}hrer, Jan and Alter, Markus L. and Heiden, Susi and Fuchs, Holger and Runge, Frank and Klein, Thomas and Hocher, Berthold}, title = {Effects of DPP-4 Inhibitors on the Heart in a Rat Model of Uremic Cardiomyopathy}, series = {PLoS one}, volume = {6}, journal = {PLoS one}, number = {11}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0027861}, pages = {9}, year = {2011}, abstract = {Background: Uremic cardiomyopathy contributes substantially to mortality in chronic kidney disease (CKD) patients. Glucagon-like peptide-1 (GLP-1) may improve cardiac function, but is mainly degraded by dipeptidyl peptidase-4 (DPP-4). Methodology/Principal Findings: In a rat model of chronic renal failure, 5/6-nephrectomized [5/6N] rats were treated orally with DPP-4 inhibitors (linagliptin, sitagliptin, alogliptin) or placebo once daily for 4 days from 8 weeks after surgery, to identify the most appropriate treatment for cardiac dysfunction associated with CKD. Linagliptin showed no significant change in blood level AUC(0-infinity) in 5/6N rats, but sitagliptin and alogliptin had significantly higher AUC(0-infinity) values; 41\% and 28\% (p=0.0001 and p=0.0324), respectively. No correlation of markers of renal tubular and glomerular function with AUC was observed for linagliptin, which required no dose adjustment in uremic rats. Linagliptin 7 mu mol/kg caused a 2-fold increase in GLP-1 (AUC 201.0 ng/l*h) in 5/6N rats compared with sham-treated rats (AUC 108.6 ng/l*h) (p=0.01). The mRNA levels of heart tissue fibrosis markers were all significantly increased in 5/6N vs control rats and reduced/normalized by linagliptin. Conclusions/Significance: DPP-4 inhibition increases plasma GLP-1 levels, particularly in uremia, and reduces expression of cardiac mRNA levels of matrix proteins and B-type natriuretic peptides (BNP). Linagliptin may offer a unique approach for treating uremic cardiomyopathy in CKD patients, with no need for dose-adjustment.}, language = {en} } @article{ChaykovskaZientaraReseretal.2014, author = {Chaykovska, Lyubov and Zientara, Alicja and Reser, Diana and Weise, Alexander and Reichert, Wolfgang and Hocher, Berthold}, title = {Development and validation of a macroarray system - MutaCHIP (R) ARTERO - for the detection of genetic variants involved in the pathogenesis of atherosclerosis}, series = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, volume = {60}, journal = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, number = {5}, publisher = {Clin Lab Publ., Verl. Klinisches Labor}, address = {Heidelberg}, issn = {1433-6510}, doi = {10.7754/Clin.Lab.2014.140104}, pages = {873 -- 878}, year = {2014}, abstract = {Background: Cardiovascular diseases are the leading cause of death in developed countries. The underlying mechanism is often atherosclerotic remodeling of blood vessels in organs such as heart, kidney, brain, and large arteries in case of peripheral arterial disease. Beside environmental and behavioral factors such as smoking or lack of physical activity, genetic variants in genes involved in lipid metabolism, blood pressure regulation, oxidative stress, and coagulation play a prominent role in the pathogenesis of atherosclerosis. Methods: Thus, we developed and validated for clinical use and research a macroarray system for the simultaneous detection of key genetic variants in genes involved in lipid metabolism, blood pressure regulation, oxidative stress, and coagulation. Results: When compared with standard PCR technologies to determine all these genetic variants in parallel, the macroarray system (MutaCHIP (R) ARTERO) was as accurate but faster, cheaper, and easier to handle compared to classical real time PCR based technologies. Conclusions: MutaCHIP (R) ARTERO is a gene chip for diagnostics of a complex genetic panel involved in the pathogenesis of atherosclerosis. This method is as sensitive and precise as real time PCR and is able to replicate real time PCR data previously validated in evaluation studies.}, language = {en} } @article{ChenDeWittBornhorstetal.2015, author = {Chen, Pan and DeWitt, Margaret R. and Bornhorst, Julia and Soares, Felix A. and Mukhopadhyay, Somshuvra and Bowman, Aaron B. and Aschner, Michael A.}, title = {Age- and manganese-dependent modulation of dopaminergic phenotypes in a}, series = {Metallomics : integrated biometal science}, volume = {7}, journal = {Metallomics : integrated biometal science}, number = {2}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/c4mt00292j}, pages = {289 -- 298}, year = {2015}, language = {en} } @article{ChenBaldermannCaoetal.2015, author = {Chen, Xiaomin and Baldermann, Susanne and Cao, Shuyan and Lu, Yao and Liu, Caixia and Hirata, Hiroshi and Watanabe, Naoharu}, title = {Developmental patterns of emission of scent compounds and related gene expression in roses of the cultivar Rosa x hybrida cv. 'Yves Piaget'}, series = {Plant physiology and biochemistry : an official journal of the Federation of European Societies of Plant Physiology}, volume = {87}, journal = {Plant physiology and biochemistry : an official journal of the Federation of European Societies of Plant Physiology}, publisher = {Elsevier}, address = {Paris}, issn = {0981-9428}, doi = {10.1016/j.plaphy.2014.12.016}, pages = {109 -- 114}, year = {2015}, abstract = {2-Phenylethanol (2PE) and 3,5-dimethoxytoluene (DMT) are characteristic scent compounds in specific roses such as Rosa x hybrida cv. 'Yves Piaget'. We analyzed the endogenous concentrations and emission of 2PE and DMT during the unfurling process in different floral organs, as well as changes in transcript levels of the two key genes, PAR and OOMT2. The emission of both 2PE and DMT increased during floral development to reach peaks at the fully unfurled stage. The relative transcripts of PAR and OOMT2 also increased during floral development. Whereas the maximum for OOMT2 was found at the fully unfurled stage (stage 4), similar expression levels of PAR were detected at stage 4 and the senescence stage (stage 6). The results demonstrate a positive correlation between the expression levels of PAR and OOMT2 and the emission of 2PE and DMT. In addition, endogenous volatiles and relative transcripts showed tissue- and development-specific patterns. (C) 2014 Elsevier Masson SAS. All rights reserved.}, language = {en} } @article{ChenHanschenNeugartetal.2019, author = {Chen, Xiaomin and Hanschen, Franziska S. and Neugart, Susanne and Schreiner, Monika and Vargas, Sara A. and Gutschmann, Bj{\"o}rn and Baldermann, Susanne}, title = {Boiling and steaming induced changes in secondary metabolites in three different cultivars of pak choi (Brassica rapa subsp. chinensis)}, series = {Journal of Food Composition and Analysis}, volume = {82}, journal = {Journal of Food Composition and Analysis}, publisher = {Elsevier}, address = {San Diego}, issn = {0889-1575}, doi = {10.1016/j.jfca.2019.06.004}, pages = {9}, year = {2019}, abstract = {Pak choi (Brassica rapa subsp. chinensis) is a leafy vegetable that is widely available in Asia and consumed in rising quantities in Europe. Pak choi contains high levels of secondary plant metabolites, such as carotenoids, chlorophylls, glucosinolates, phenolic compounds, and vitamin K, which are beneficial for humans if consumed on a regular basis. The evaluation of the genotype-induced variation of secondary plant metabolites revealed that the cultivar 'Amur' contained the highest concentration of secondary plant metabolites. Furthermore, steaming retained more chlorophylls, glucosinolates, phenolic acids and flavonoid compounds than boiling. In contrast, both domestic cooking methods - boiling, and steaming - reduced the formation of glucosinolate breakdown products, especially the undesired epithionitriles and nitriles but less of the health-beneficial isothiocyanates.}, language = {en} } @article{ChenLiWangetal.2012, author = {Chen, You-Peng and Li, Jian and Wang, Zi-Neng and Reichetzeder, Christoph and Xu, Hao and Gong, Jian and Chen, Guang-Ji and Pfab, Thiemo and Xiao, Xiao-Min and Hocher, Berthold}, title = {Renin angiotensin aldosterone system and glycemia in pregnancy}, series = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, volume = {58}, journal = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, number = {5-6}, publisher = {Clin Lab Publ., Verl. Klinisches Labor}, address = {Heidelberg}, issn = {1433-6510}, pages = {527 -- 533}, year = {2012}, abstract = {Background: The renin-angiotensin-aldosterone system (RAAS) is involved in the pathogenesis of insulin resistance and type 2 diabetes in the general population. The RAAS is activated during pregnancy. However, it is unknown whether the RAAS contributes to glycemia in pregnant women. Methods: Plasma renin activity (PRA) and plasma aldosterone levels were quantified at delivery in 689 Chinese mothers. An oral glucose tolerance test in fasted women was performed in the second trimester of pregnancy. The diagnosis of gestational diabetes mellitus (GDM) and impaired glucose tolerance during pregnancy were made according to the guidelines of the Chinese Society of Obstetrics. Results: Plasma aldosterone was significantly higher in pregnant women with GDM as compared to those without impairment of glycemic control (normal pregnancies: 0.27 +/- 0.21 ng/mL, GDM: 0.36 +/- 0.30 ng/mL; p<0.05). Regression analyses revealed that PRA was negatively correlated with fasting blood glucose (FBG) (R-2 = 0.03, p = 0.007), whereas plasma aldosterone and aldosterone/PRA ratio were positively correlated with FBG (R-2 = 0.05, p<0.001 and R-2 = 0.03, p = 0.007, respectively). Multivariable regression analysis models considering relevant confounding factors confirmed these findings. Conclusions: This study demonstrated that fasting blood glucose in pregnant women is inversely correlated with the PRA, whereas plasma aldosterone showed a highly significant positive correlation with fasting blood glucose during pregnancy. Moreover, plasma aldosterone is significantly higher in pregnant women with GDM as compared to those women with normal glucose tolerance during pregnancy. Although causality cannot be proven in association studies, these data may indicate that the RAAS during pregnancy contributes to the pathogenesis of insulin resistance/new onset of diabetes during pregnancy.}, language = {en} } @article{ChenLuLietal.2014, author = {Chen, You-Peng and Lu, Yong-Ping and Li, Jian and Liu, Zhi-Wei and Chen, Wen-Jing and Liang, Xu-Jing and Chen, Xin and Wen, Wang-Rong and Xiao, Xiao-Min and Reichetzeder, Christoph and Hocher, Berthold}, title = {Fetal and maternal angiotensin (1-7) are associated with preterm birth}, series = {Journal of hypertension}, volume = {32}, journal = {Journal of hypertension}, number = {9}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0263-6352}, doi = {10.1097/HJH.0000000000000251}, pages = {1833 -- 1841}, year = {2014}, abstract = {Background: Recent studies show that preterm birth is associated with hypertension in later life. The renin-angiotensin system (RAS) during pregnancy influences fetal growth and development. In the current study, we investigated the impact of fetal as well as maternal angiotensin (1-7) [Ang (1-7)] and angiotensin II (Ang II) plasma concentrations on the risk of preterm birth. Methods: Three hundred and nine pregnant women were prospectively included into the study. The pregnant women were divided into two groups, for example, preterm birth of lower than 37 gestational weeks (n = 17) and full-term birth of 37 gestational weeks or more (n = 292). Maternal and neonatal plasma Ang (1-7) and Ang II concentrations were analyzed at birth from maternal venous blood and umbilical cord blood, respectively. Risk factors for premature birth were determined by multiple logistic regression analysis. Results: Fetal and maternal plasma Ang (1-7) concentrations in the preterm group were lower than those of the term group fetal Ang (1-7) preterm birth: 486.15 +/- 337.34 ng/l and fetal Ang (1-7) term birth: 833.84 +/- 698.12 ng/l and maternal Ang (1-7) preterm birth: 399.86 +/- 218.93 ng/l; maternal Ang (1-7) term birth: 710.34 +/- 598.22 ng/l. Multiple logistic regression analysis considering confounding factors revealed that preeclampsia (P < 0.001), premature rupture of membranes (P = 0.001), lower concentration of maternal Ang (1-7) (P = 0.013) and fetal plasma Ang (1-7) (P = 0.032) were independently associated with preterm birth. We could furthermore demonstrate that the maternal Ang (1-7)/Ang II ratio is independently associated with gestational hypertension or preeclampsia, factors causing preterm birth. Conclusions: Lower concentrations of maternal and fetal Ang (1-7) are independently associated with preterm birth - a risk factor of hypertension in later life.}, language = {en} } @article{ChenXiaoLietal.2012, author = {Chen, You-Peng and Xiao, Xiao-Min and Li, Jian and Reichetzeder, Christoph and Wang, Zi-Neng and Hocher, Berthold}, title = {Paternal body mass index (BMI) is associated with offspring intrauterine growth in a gender dependent manner}, series = {PLoS one}, volume = {7}, journal = {PLoS one}, number = {5}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0036329}, pages = {9}, year = {2012}, abstract = {Background: Environmental alternations leading to fetal programming of cardiovascular diseases in later life have been attributed to maternal factors. However, animal studies showed that paternal obesity may program cardio-metabolic diseases in the offspring. In the current study we tested the hypothesis that paternal BMI may be associated with fetal growth. Methods and Results: We analyzed the relationship between paternal body mass index (BMI) and birth weight, ultrasound parameters describing the newborn's body shape as well as parameters describing the newborns endocrine system such as cortisol, aldosterone, renin activity and fetal glycated serum protein in a birth cohort of 899 father/mother/child triplets. Since fetal programming is an offspring sex specific process, male and female offspring were analyzed separately. Multivariable regression analyses considering maternal BMI, paternal and maternal age, hypertension during pregnancy, maternal total glycated serum protein, parity and either gestational age (for birth weight) or time of ultrasound investigation (for ultrasound parameters) as confounding showed that paternal BMI is associated with growth of the male but not female offspring. Paternal BMI correlated with birth parameters of male offspring only: birth weight; biparietal diameter, head circumference; abdominal diameter, abdominal circumference; and pectoral diameter. Cortisol was likewise significantly correlated with paternal BMI in male newborns only. Conclusions: Paternal BMI affects growth of the male but not female offspring. Paternal BMI may thus represent a risk factor for cardiovascular diseases of male offspring in later life. It remains to be demonstrated whether this is linked to an offspring sex specific paternal programming of cortisol secretion.}, language = {en} } @article{ChmielewskiGoetzHomannetal.2017, author = {Chmielewski, Frank M. and G{\"o}tz, Klaus-Peter and Homann, Thomas and Rawel, Harshadrai Manilal}, title = {Identification of Endodormancy Release for Cherries (Prunus Avium L.) by Abscisic Acid and Sugars}, series = {Journal of Horticulture}, volume = {4}, journal = {Journal of Horticulture}, number = {3}, issn = {2376-0354}, doi = {10.4172/2376-0354.1000210}, pages = {9}, year = {2017}, abstract = {In order to develop reliable and physiologically sound models for the plant development in spring, the date of endodormancy release is always a crucial and mostly unknown model parameter. Until present, classical approaches - such as climate chamber experiments - are used to derive this unknown parameter. In these experiments, progressive plant development or significant changes in bud's fresh weight or water content are measurable markers for dormancy release. This study presents an alternative approach, which is based on four well-known metabolites. For 5 seasons (2011/12-2015/16), the content of abscisic acid (ABA) and sugars such as fructose, sucrose and glucose in sweet cherry flower buds (cultivar 'Summit') were weekly analysed between beginning of October and April. These data allow comparing the annual course of these metabolites with the date of endodormancy release, derived from a classical climate chamber experiment, published in a previous study. Results showed that ABA and sucrose are two important metabolites which can help to identify the date of endodormancy release of sweet cherries. On average, ABA content reached a plateau of 5.65 μg g-1 DW-1 during endodormancy, which was maintained for 3-6 weeks. The significant reduction of the ABA content after this period to 4.41 μg g-1 DW-1 on average during ecodormancy was nearly in agreement with the date of endodormancy release of 'Summit' on 28 November (332 DOY). The annual cycle of sucrose, which has a cryoprotective effect during winter, is well comprehensible and showed a close relationship to the annual course of minimum air temperature after leaf fall(r=-0.90). The nearly constant level of sucrose during ecodormancy (21.0 mg g-1 DW-1, 5 yr. mean) did not only allow deriving the date of endodormancy release but can also be helpful to define the beginning of ontogenetic development.}, language = {en} } @article{ChristakoudiTsilidisMulleretal.2020, author = {Christakoudi, Sofa and Tsilidis, Konstantinos K. and Muller, David C. and Freisling, Heinz and Weiderpass, Elisabete and Overvad, Kim and S{\"o}derberg, Stefan and H{\"a}ggstr{\"o}m, Christel and Pischon, Tobias and Dahm, Christina C. and Zhang, Jie and Tj{\o}nneland, Anne and Schulze, Matthias Bernd}, title = {A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, number = {1}, publisher = {Springer Nature}, address = {Berlin}, pages = {15}, year = {2020}, abstract = {Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39\% of the individuals within each BMI category, which had 22-55\% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.}, language = {en} } @article{ChristakoudiPagoniFerrarietal.2020, author = {Christakoudi, Sofia and Pagoni, Panagiota and Ferrari, Pietro and Cross, Amanda J. and Tzoulaki, Ioanna and Muller, David C. and Weiderpass, Elisabete and Freisling, Heinz and Murphy, Neil and Dossus, Laure and Turzanski Fortner, Renee and Agudo, Antonio and Overvad, Kim and Perez-Cornago, Aurora and Key, Timothy J. and Brennan, Paul and Johansson, Mattias and Tjonneland, Anne and Halkjaer, Jytte and Boutron-Ruault, Marie-Christine and Artaud, Fanny and Severi, Gianluca and Kaaks, Rudolf and Schulze, Matthias Bernd and Bergmann, Manuela M. and Masala, Giovanna and Grioni, Sara and Simeon, Vittorio and Tumino, Rosario and Sacerdote, Carlotta and Skeie, Guri and Rylander, Charlotta and Borch, Kristin Benjaminsen and Quiros, J. Ramon and Rodriguez-Barranco, Miguel and Chirlaque, Maria-Dolores and Ardanaz, Eva and Amiano, Pilar and Drake, Isabel and Stocks, Tanja and H{\"a}ggstr{\"o}m, Christel and Harlid, Sophia and Ellingjord-Dale, Merete and Riboli, Elio and Tsilidis, Konstantinos K.}, title = {Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort}, series = {International journal of cancer}, volume = {148}, journal = {International journal of cancer}, number = {7}, publisher = {Wiley}, address = {Hoboken}, issn = {0020-7136}, doi = {10.1002/ijc.33339}, pages = {1637 -- 1651}, year = {2020}, abstract = {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.}, language = {en} } @article{ChupeerachHarnroongrojPhonratetal.2011, author = {Chupeerach, Chaowanee and Harnroongroj, Talabporn and Phonrat, Benjaluck and Tungtrongchitr, Anchalee and Schweigert, Florian J. and Tungtrongchitr, Rungsunn and Preutthipan, Sangchai}, title = {Decreased retinol transport proteins in thai post-menopausal women with Osteporosis}, series = {The Southeast Asian journal of tropical medicine and public health : official publication of the SEAMEO Regional Tropical Medicine and Public Health Project (TROPMED)}, volume = {42}, journal = {The Southeast Asian journal of tropical medicine and public health : official publication of the SEAMEO Regional Tropical Medicine and Public Health Project (TROPMED)}, number = {6}, publisher = {SEAMEO}, address = {Bangkok}, issn = {0125-1562}, pages = {1515 -- 1520}, year = {2011}, abstract = {High vitamin A ingestion or high serum retinol have been postulated to increase the risk of fractures and osteoporosis by reduced bone mineral density (BMD). Retinol is carried and transported to the tissues bound to retinol binding protein 4 (RBP4) and transthyretin (TTR). The relationships between retinol, retinol transport protein, retinol binding protein 4 (RBP4) and transthyretin (TTR) and BMD and osteoporosis are unclear. To examine the association between retinol and RBP4 and TTR and osteoporosis, 73 osteoporotic and 71 normal Thai postmenopausal women were studied. RBP4 and retinol levels did not differ between the groups. Serum TTR was significantly higher in control than osteoporotic subjects (89.47 and 144.53 mu g/ml, respectively, p=0.003, Mann-Whitney U test). TTR was positively correlated with BMD at several sites, such as the total radius bone (r=0.172, p=0.008, Spearman rank test). Osteoporosis risk was analyzed with binary logistic regression. Lean elderly Thais with lower TTR levels had a higher risk of osteoporosis. RBP4 and retinol levels had no relationship with disease status among Thai post-menopausal women. These results suggest calcium, minerals, vitamins and the retinol transport protein, transthyretin may be involved in the pathogenesis of osteoporosis.}, language = {en} } @article{ChupeerachTungtrongchitrPhonratetal.2012, author = {Chupeerach, Chaowanee and Tungtrongchitr, Anchalee and Phonrat, Benjaluck and Schweigert, Florian J. and Tungtrongchitr, Rungsunn and Preutthipan, Sangchai}, title = {Association of Thr420Lys polymorphism in DBP gene with fat-soluble vitamins and low radial bone mineral density in postmenopausal Thai women}, series = {Biomarkers in medicine}, volume = {6}, journal = {Biomarkers in medicine}, number = {1}, publisher = {Future Medicine}, address = {London}, issn = {1752-0363}, doi = {10.2217/BMM.11.88}, pages = {103 -- 108}, year = {2012}, abstract = {Aims: To investigate the genetic markers for osteoporosis bone mineral density by the genotyping of rs7041, rs4588 and rs1352845 in the DBP gene with either bone mineral density or serum 25-hydroxycholecalciferol, retinol and alpha-tocopherol, among 365 postmenopausal Thai women. Materials \& methods: The DBP genotypes were analyzed by a PCR restriction fragment-length polymorphism method. Serum 25-hydroxycholecalciferol was assessed using a commercial chemiluminescent immunoassay. Serum retinol and alpha-tocopherol were measured by reverse-phase high-performance liquid chromatography. Results: After adjustment for age >50 years, elder Thai subjects with low BMI (<= 25 kg/m(2)) and carrying the rs4588 CC genotype had a higher risk of radial bone mineral density osteoporosis (odds ratio: 6.29; p = 0.048). The rs1352845 genotype also had a statistical association with total hip bone mineral density; however, it disappeared after adjustment for age and BMI. No association was found in fat-soluble vitamins with bone mineral density. Conclusion: DBP genotypes may influence the osteoporosis bone mineral density in postmenopausal Thai women.}, language = {en} } @article{CollenburgWalterBurgertetal.2016, author = {Collenburg, Lena and Walter, Tim and Burgert, Anne and Mueller, Nora and Seibel, Juergen and Japtok, Lukasz and Kleuser, Burkhard and Sauer, Markus and Schneider-Schaulies, Sibylle}, title = {A Functionalized Sphingolipid Analogue for Studying Redistribution during Activation in Living T Cells}, series = {The journal of immunology}, volume = {196}, journal = {The journal of immunology}, publisher = {American Assoc. of Immunologists}, address = {Bethesda}, issn = {0022-1767}, doi = {10.4049/jimmunol.1502447}, pages = {3951 -- 3962}, year = {2016}, abstract = {Sphingolipids are major components of the plasma membrane. In particular, ceramide serves as an essential building hub for complex sphingolipids, but also as an organizer of membrane domains segregating receptors and signalosomes. Sphingomyelin breakdown as a result of sphingomyelinase activation after ligation of a variety of receptors is the predominant source of ceramides released at the plasma membrane. This especially applies to T lymphocytes where formation of ceramide-enriched membrane microdomains modulates TCR signaling. Because ceramide release and redistribution occur very rapidly in response to receptor ligation, novel tools to further study these processes in living T cells are urgently needed. To meet this demand, we synthesized nontoxic, azido-functionalized ceramides allowing for bio-orthogonal click-reactions to fluorescently label incorporated ceramides, and thus investigate formation of ceramide-enriched domains. Azido-functionalized C-6-ceramides were incorporated into and localized within plasma membrane microdomains and proximal vesicles in T cells. They segregated into clusters after TCR, and especially CD28 ligation, indicating efficient sorting into plasma membrane domains associated with T cell activation; this was abolished upon sphingomyelinase inhibition. Importantly, T cell activation was not abrogated upon incorporation of the compound, which was efficiently excluded from the immune synapse center as has previously been seen in Ab-based studies using fixed cells. Therefore, the functionalized ceramides are novel, highly potent tools to study the subcellular redistribution of ceramides in the course of T cell activation. Moreover, they will certainly also be generally applicable to studies addressing rapid stimulation-mediated ceramide release in living cells.}, language = {en} } @article{CosmeFrankenMewisetal.2014, author = {Cosme, Marco and Franken, Philipp and Mewis, Inga and Baldermann, Susanne and Wurst, Susanne}, title = {Arbuscular mycorrhizal fungi affect glucosinolate and mineral element composition in leaves of Moringa oleifera}, series = {Mycorrhiza}, volume = {24}, journal = {Mycorrhiza}, number = {7}, publisher = {Springer}, address = {New York}, issn = {0940-6360}, doi = {10.1007/s00572-014-0574-7}, pages = {565 -- 570}, year = {2014}, abstract = {Moringa is a mycorrhizal crop cultivated in the tropics and subtropics and appreciated for its nutritive and health-promoting value. As well as improving plant mineral nutrition, arbuscular mycorrhizal fungi (AMF) can affect plant synthesis of compounds bioactive against chronic diseases in humans. Rhizophagus intraradices and Funneliformis mosseae were used in a full factorial experiment to investigate the impact of AMF on the accumulation of glucosinolates, flavonoids, phenolic acids, carotenoids, and mineral elements in moringa leaves. Levels of glucosinolates were enhanced, flavonoids and phenolic acids were not affected, levels of carotenoids (including provitamin A) were species-specifically reduced, and mineral elements were affected differently, with only Cu and Zn being increased by the AMF. This study presents novel results on AMF effects on glucosinolates in leaves and supports conclusions that the impacts of these fungi on microelement concentrations in edible plants are species dependent. The nonspecific positive effects on glucosinolates and the species-specific negative effects on carotenoids encourage research on other AMF species to achieve general benefits on bioactive compounds in moringa.}, language = {en} } @article{CramerTackeBornhorstetal.2014, author = {Cramer, Sandra and Tacke, Sebastian and Bornhorst, Julia and Klingauf, J{\"u}rgen and Schwerdtle, Tanja and Galla, Hans-Joachim}, title = {The Influence of Silver Nanoparticles on the Blood-Brain and the Blood-Cerebrospinal Fluid Barrier in vitro}, series = {Journal of Nanomedicine \& Nanotechnology}, volume = {5}, journal = {Journal of Nanomedicine \& Nanotechnology}, number = {5}, issn = {2157-7439}, doi = {10.4172/2157-7439.1000225}, pages = {12}, year = {2014}, abstract = {The use of silver nanoparticles in medical and consumer products such as wound dressings, clothing and cosmetic has increased significantly in recent years. Still, the influence of these particles on our health and especially on our brain, has not been examined adequately up to now. We studied the influence of AgEO- (Ethylene Oxide) and AgCitrate-Nanoparticles (NPs) on the protective barriers of the brain, namely the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (blood-CSF) barrier in vitro. The NPs toxicity was evaluated by examining changes in membrane integrity, cell morphology, barrier properties, oxidative stress and inflammatory reactions. AgNPs decreased cell viability, disturbed barrier integrity and tight junctions and triggered oxidative stress and DNA strand breaks. However, all mentioned effects were, at least partly, suppressed by a Citrate-coating and were most pronounced in the cells of the BBB as compared to the epithelial cells representing the blood-CSF barrier. AgEO- but not AgCitrate-NPs also triggered an inflammatory reaction in porcine brain capillary endothelial cells (PBCEC), which represent the BBB. Our data indicate that AgNPs may cause adverse effects within the barriers of the brain, but their toxicity can be reduced by choosing an appropriate coating material.}, language = {en} } @article{CroneAschnerSchwerdtleetal.2015, author = {Crone, Barbara and Aschner, Michael A. and Schwerdtle, Tanja and Karst, Uwe and Bornhorst, Julia}, title = {Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS}, series = {Metallomics : integrated biometal science}, volume = {7}, journal = {Metallomics : integrated biometal science}, number = {7}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/c5mt00096c}, pages = {1189 -- 1195}, year = {2015}, abstract = {cis-Diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 mm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose) metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable.}, language = {en} } @article{DanquahDobruckyFranketal.2015, author = {Danquah, Ina and Dobrucky, C. Lydia and Frank, Laura K. and Henze, Andrea and Amoako, Yaw A. and Bedu-Addo, George and Raila, Jens and Schulze, Matthias Bernd and Mockenhaupt, Frank P. and Schweigert, Florian J.}, title = {Vitamin A: potential misclassification of vitamin A status among patients with type 2 diabetes and hypertension in urban Ghana}, series = {The American journal of clinical nutrition : a publication of the American Society for Nutrition, Inc.}, volume = {102}, journal = {The American journal of clinical nutrition : a publication of the American Society for Nutrition, Inc.}, number = {1}, publisher = {American Society for Nutrition, Inc.}, address = {Bethesda}, issn = {0002-9165}, doi = {10.3945/ajcn.114.101345}, pages = {207 -- 214}, year = {2015}, abstract = {Background: Sub-Saharan Africa is facing a double burden of malnutrition: vitamin A deficiency (VAD) prevails, whereas the nutrition-related chronic conditions type 2 diabetes (T2D) and hypertension are emerging. Serum retinol a VAD marker increases in kidney disease and decreases in inflammation, which can partly be attributed to alterations in the vitamin A transport proteins retinol-binding protein 4 (RBP4) and prealbumin. Kidney dysfunction and inflammation commonly accompany T2D and hypertension. Objective: Among urban Ghanaians, we investigated the associations of T2D and hypertension with serum retinol as well as the importance of kidney function and inflammation in this regard. Design: A hospital-based, case-control study in individuals for risk factors of T2D, hypertension, or both was conducted in Kumasi, Ghana (328 controls, 197 with T2D, 354 with hypertension, and 340 with T2D plus hypertension). In 1219 blood samples, serum retinol, RBP4, and prealbumin were measured. Urinary albumin and estimated glomerular filtration rate (eGFR) defined kidney function. C-reactive protein (CRP) >5 mg/L indicated inflammation. We identified associations of T2D and hypertension with retinol by linear regression and calculated the contribution of RBP4, prealbumin, urinary albumin, eGFR, and CRP to these associations as the percentages of the explained variance of retinol. Results: VAD (retinol <1.05 mu mol/L) was present in 10\% of this predominantly female, middle-aged, overweight, and deprived population. Hypertension, but not T2D, was positively associated with retinol (beta: 0.12; 95\% CI: 0.08, 0,17), adjusted for age, sex, socioeconomic factors, anthropometric measurements, and lifestyle. In addition to RBP4 (72\%) and prealbumin (22\%), the effect of increased retinol on individuals with hypertension was mainly attributed to impaired kidney function (eGFR: 30\%; urinary albumin: 5\%) but not to inflammation. Conclusions: In patients with hypertension, VAD might be underestimated because of increased serum retinol in the context of kidney dysfunction. Thus, the interpretation of serum retinol in sub-Saharan Africa should account for hypertension status.}, language = {en} } @article{dePinhoTavaresLealdaSilvaRochaGomesetal.2021, author = {de Pinho Tavares Leal, Pedro Ernesto and da Silva, Alexandre Alves and Rocha-Gomes, Arthur and Riul, Tania Regina and Cunha, Rennan Augusto and Reichetzeder, Christoph and Villela, Daniel Campos}, title = {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}, series = {Frontiers in Behavioral Neuroscience}, volume = {15}, journal = {Frontiers in Behavioral Neuroscience}, publisher = {Frontiers Research Foundation}, address = {Lausanne, Schweiz}, issn = {1662-5153}, doi = {10.3389/fnbeh.2021.779080}, pages = {1 -- 12}, year = {2021}, abstract = {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.}, language = {en} } @article{DelperoArendsSprechertetal.2022, author = {Delpero, Manuel and Arends, Danny and Sprechert, Maximilian and Krause, Florian and Kluth, Oliver and Sch{\"u}rmann, Annette and Brockmann, Gudrun A. and Hesse, Deike}, title = {Identification of four novel QTL linked to the metabolic syndrome in the Berlin Fat Mouse}, series = {International journal of obesity / North American Association for the Study of Obesity}, volume = {46}, journal = {International journal of obesity / North American Association for the Study of Obesity}, number = {2}, publisher = {Nature Publ. Group}, address = {Avenel, NJ}, issn = {0307-0565}, doi = {10.1038/s41366-021-00991-3}, pages = {307 -- 315}, year = {2022}, abstract = {Background The Berlin Fat Mouse Inbred line (BFMI) is a model for obesity and the metabolic syndrome. This study aimed to identify genetic variants associated with impaired glucose metabolism using the obese lines BFMI861-S1 and BFMI861-S2, which are genetically closely related, but differ in several traits. BFMI861-S1 is insulin resistant and stores ectopic fat in the liver, whereas BFMI861-S2 is insulin sensitive. Methods In generation 10, 397 males of an advanced intercross line (AIL) BFMI861-S1 x BFMI861-S2 were challenged with a high-fat, high-carbohydrate diet and phenotyped over 25 weeks. QTL-analysis was performed after selective genotyping of 200 mice using the GigaMUGA Genotyping Array. Additional 197 males were genotyped for 7 top SNPs in QTL regions. For the prioritization of positional candidate genes whole genome sequencing and gene expression data of the parental lines were used. Results Overlapping QTL for gonadal adipose tissue weight and blood glucose concentration were detected on chromosome (Chr) 3 (95.8-100.1 Mb), and for gonadal adipose tissue weight, liver weight, and blood glucose concentration on Chr 17 (9.5-26.1 Mb). Causal modeling suggested for Chr 3-QTL direct effects on adipose tissue weight, but indirect effects on blood glucose concentration. Direct effects on adipose tissue weight, liver weight, and blood glucose concentration were suggested for Chr 17-QTL. Prioritized positional candidate genes for the identified QTL were Notch2 and Fmo5 (Chr 3) and Plg and Acat2 (Chr 17). Two additional QTL were detected for gonadal adipose tissue weight on Chr 15 (67.9-74.6 Mb) and for body weight on Chr 16 (3.9-21.4 Mb). Conclusions QTL mapping together with a detailed prioritization approach allowed us to identify candidate genes associated with traits of the metabolic syndrome. In addition, we provided evidence for direct and indirect genetic effects on blood glucose concentration in the insulin-resistant mouse line BFMI861-S1.}, language = {en} } @article{DerakhshaniKurzJaptoketal.2019, author = {Derakhshani, Shaghayegh and Kurz, Andreas and Japtok, Lukasz and Schumacher, Fabian and Pilgram, Lisa and Steinke, Maria and Kleuser, Burkhard and Sauer, Markus and Schneider-Schaulies, Sibylle and Avota, Elita}, title = {Measles Virus Infection Fosters Dendritic Cell Motility in a 3D Environment to Enhance Transmission to Target Cells in the Respiratory Epithelium}, series = {Frontiers in immunology}, volume = {10}, journal = {Frontiers in immunology}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-3224}, doi = {10.3389/fimmu.2019.01294}, pages = {14}, year = {2019}, abstract = {Transmission of measles virus (MV) from dendritic to airway epithelial cells is considered as crucial to viral spread late in infection. Therefore, pathways and effectors governing this process are promising targets for intervention. To identify these, we established a 3D respiratory tract model where MV transmission by infected dendritic cells (DCs) relied on the presence of nectin-4 on H358 lung epithelial cells. Access to recipient cells is an important prerequisite for transmission, and we therefore analyzed migration of MV-exposed DC cultures within the model. Surprisingly, enhanced motility toward the epithelial layer was observed for MV-infected DCs as compared to their uninfected siblings. This occurred independently of factors released from H358 cells indicating that MV infection triggered cytoskeletal remodeling associated with DC polarization enforced velocity. Accordingly, the latter was also observed for MV-infected DCs in collagen matrices and was particularly sensitive to ROCK inhibition indicating infected DCs preferentially employed the amoeboid migration mode. This was also implicated by loss of podosomes and reduced filopodial activity both of which were retained in MV-exposed uninfected DCs. Evidently, sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as produced in response to virus-infection in DCs contributed to enhanced velocity because this was abrogated upon inhibition of sphingosine kinase activity. These findings indicate that MV infection promotes a push-and-squeeze fast amoeboid migration mode via the SphK/S1P system characterized by loss of filopodia and podosome dissolution. Consequently, this enables rapid trafficking of virus toward epithelial cells during viral exit.}, language = {en} } @article{DorenkampBonaventuraSohnsetal.2012, author = {Dorenkamp, Marc and Bonaventura, Klaus and Sohns, Christian and Becker, Christoph R. and Leber, Alexander W.}, title = {Direct costs and cost-effectiveness of dual-source computed tomography and invasive coronary angiography in patients with an intermediate pretest likelihood for coronary artery disease}, series = {Heart}, volume = {98}, journal = {Heart}, number = {6}, publisher = {BMJ Publ. Group}, address = {London}, issn = {1355-6037}, doi = {10.1136/heartjnl-2011-300149}, pages = {460 -- 467}, year = {2012}, abstract = {Aims The study aims to determine the direct costs and comparative cost-effectiveness of latest-generation dual-source computed tomography (DSCT) and invasive coronary angiography for diagnosing coronary artery disease (CAD) in patients suspected of having this disease. Methods The study was based on a previously elaborated cohort with an intermediate pretest likelihood for CAD and on complementary clinical data. Cost calculations were based on a detailed analysis of direct costs, and generally accepted accounting principles were applied. Based on Bayes' theorem, a mathematical model was used to compare the cost-effectiveness of both diagnostic approaches. Total costs included direct costs, induced costs and costs of complications. Effectiveness was defined as the ability of a diagnostic test to accurately identify a patient with CAD. Results Direct costs amounted to (sic)98.60 for DSCT and to (sic)317.75 for invasive coronary angiography. Analysis of model calculations indicated that cost-effectiveness grew hyperbolically with increasing prevalence of CAD. Given the prevalence of CAD in the study cohort (24\%), DSCT was found to be more cost-effective than invasive coronary angiography ((sic)970 vs (sic)1354 for one patient correctly diagnosed as having CAD). At a disease prevalence of 49\%, DSCT and invasive angiography were equally effective with costs of (sic)633. Above a threshold value of disease prevalence of 55\%, proceeding directly to invasive coronary angiography was more cost-effective than DSCT. Conclusions With proper patient selection and consideration of disease prevalence, DSCT coronary angiography is cost-effective for diagnosing CAD in patients with an intermediate pretest likelihood for it. However, the range of eligible patients may be smaller than previously reported.}, language = {en} } @article{DraudePelsterKoersgenetal.2014, author = {Draude, F. and Pelster, A. and Koersgen, M. and Kassenboehmer, R. and Schwerdtle, Tanja and Muething, J. and Arlinghaus, H. F.}, title = {ToF-SIMS imaging of plasma membrane lipids with sub-micrometer resolution}, series = {Surface and interface analysis : an international journal devoted to the development and application of techniques for the analysis surfaces, interfaces and thin films}, volume = {46}, journal = {Surface and interface analysis : an international journal devoted to the development and application of techniques for the analysis surfaces, interfaces and thin films}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0142-2421}, doi = {10.1002/sia.5576}, pages = {127 -- 130}, year = {2014}, abstract = {Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used for label-free analyses of the molecular lateral distribution of two different epithelial cell membranes (PANC-1 and UROtsa). The goal of the research was to enhance the ion yield of specific membrane molecules for improving the membrane imaging capability of ToF-SIMS on the nanoscale lateral dimension. For this task, a special silicon wafer sandwich preparation technique was optimized using different wafer materials, spacers, and washing procedures. Under optimized preparation conditions, the yield could be significantly enhanced, allowing imaging of the inhomogeneous distribution of phosphocholine (common head group for phosphatidylcholine and sphingomyelin) of a PANC-1 cell membrane's outer lipid layer with a lateral resolution of less than 200nm. Copyright (c) 2014 John Wiley \& Sons, Ltd.}, language = {en} } @article{DraudeKoersgenPelsteretal.2015, author = {Draude, Felix and K{\"o}rsgen, Martin and Pelster, Andreas and Schwerdtle, Tanja and M{\"u}thing, Johannes and Arlinghaus, Heinrich F.}, title = {Characterization of freeze-fractured epithelial plasma membranes on nanometer scale with ToF-SIMS}, series = {Analytical \& bioanalytical chemistry}, volume = {407}, journal = {Analytical \& bioanalytical chemistry}, number = {8}, publisher = {Springer}, address = {Heidelberg}, issn = {1618-2642}, doi = {10.1007/s00216-014-8334-2}, pages = {2203 -- 2211}, year = {2015}, abstract = {Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to characterize the freeze-fracturing process of human epithelial PANC-1 and UROtsa cells. For this purpose, phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, and phosphatidylserine standard samples were investigated to find specific signals with both high specificity and signal intensity. The results were used to investigate single cells of subconfluent cell layers prepared with a special silicon wafer sandwich preparation technique. This freeze-fracturing technique strips cell membranes off the cells, isolating them on opposing silicon wafer substrates. Criteria were found for defining regions with stripped off cell membranes and, on the opposing wafer, complementary regions with the remaining cells. Measured ethanolamine/choline and serine/choline ratios in these regions clearly showed that in the freeze-fracturing process, the lipid bilayer of the plasma membrane is split along its central zone. Accordingly, only the outer lipid monolayer is stripped off the cell, while the inner lipid monolayer remains attached to the cell on the opposing wafer, thus allowing detailed analysis of a single lipid monolayer. Furthermore, it could be shown that using different washing procedures did not influence the transmembrane lipid distribution. Under optimized preparation conditions, it became feasible to detect lipids with a lateral resolution of approximately 100 nm. The data indicate that ToF-SIMS would be a very useful technique to study with very high lateral resolution changes in lipid composition caused, for example, by lipid storage diseases or pharmaceuticals that interfere with the lipid metabolism.}, language = {en} } @article{DrobyshevKybarskayaDagaevetal.2019, author = {Drobyshev, Evgenii J. and Kybarskaya, Larisa and Dagaev, Sergey and Solovyev, Nikolay}, title = {New insight in beryllium toxicity excluding exposure to beryllium-containing dust}, series = {Archives of toxicology : official journal of EUROTOX}, volume = {93}, journal = {Archives of toxicology : official journal of EUROTOX}, number = {4}, publisher = {Springer}, address = {Heidelberg}, issn = {0340-5761}, doi = {10.1007/s00204-019-02432-7}, pages = {859 -- 869}, year = {2019}, abstract = {There is much contradiction between different experimental studies on beryllium (Be) toxicity. The majority of studies focus on occupational pathologies, caused by the exposure to Be dust. However, Be pollution may affect wide population groups through other exposure routes. The discrepancies between experimental studies may be attributed to the lack of adequate Be toxicity model since conventional administration routes are hampered by high acidity and low solubility of Be compounds. This study was aimed to develop a novel way to implement Be toxicity avoiding side effects, related to high acidity or low solubility of Be salts. Intraperitoneal injection of Be-glycine composition (containing BeSO4, glycine, purified water, pH adjusted to 5.5 with NaOH) was tested in the dose range 238-7622 mu molBekg(-1) (body weight, b/w) in full-grown Wistar male rats. The model provided reliable uptake of Be from the peritoneum into general circulation for at least 48h. LD50 was found to be 687 mu molBekg(-1) (b/w). The established LD50 value differed from previous data on gastrointestinal, intramuscular or intravenous administration of Be compounds. The liver was found to act as a primary elimination route for Be and related to the highest Be content in the animal. However, it had no signs of morphological damage, which was observed only in the testes (deterioration of germinal epithelium). At the same time, the lungs, stated as a primary target tissue for Be in the models of chronic beryllium disease, did not show strong Be accumulation nor morphological changes. Survived animals showed behavioral changes, including increased motor activity and aggressive reactions in some cases, and complete spasticity in other. The obtained data show the applicability of the established modeling protocol and testified for the independence of chronic beryllium disease on Be2+ ion toxicity per se.}, language = {en} } @article{DraegerMuschiolikRawel1995, author = {Dr{\"a}ger, Silke and Muschiolik, Gerald and Rawel, Harshadrai Manilal}, title = {Behaviour of whey protein stabilised emulsions}, year = {1995}, language = {en} } @article{DraegerMuschiolikRawel1995, author = {Dr{\"a}ger, Silke and Muschiolik, Gerald and Rawel, Harshadrai Manilal}, title = {Molecular and emulsifying behaviour of pea proteins}, year = {1995}, language = {en} } @article{DschietzigKrauseRelleHennequinetal.2015, author = {Dschietzig, Thomas Bernd and Krause-Relle, Katharina and Hennequin, Maud and von Websky, Karoline and Rahnenfuhrer, Jan and Ruppert, Jana and Groena, Hans Juergen and Armbruster, Franz Paul and Bathgate, Ross A. D. and Aschenbach, Joerg R. and Forssmann, Wolf-Georg and Hocher, Berthold}, title = {Relaxin-2 does not Ameliorate Nephropathy in an experimental model of Type-1 Diabetes}, series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, volume = {40}, journal = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, number = {1}, publisher = {Karger}, address = {Basel}, issn = {1420-4096}, doi = {10.1159/000368484}, pages = {77 -- 88}, year = {2015}, abstract = {Background/Aims: In diabetic nephropathy (DN), the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC), there is no specific remedy available. Relaxin-2 (Rlx) - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide - is a candidate drug for both. Methods: Low-dose (32 mu g/kg/day) and high-dose (320 mu g/kg/day) Rlx were tested against vehicle (n = 20 each) and non-diabetic controls (n = 14) for 12 weeks in a model of type-1 diabetes induced in endothelial nitric oxide synthase knock-out (eNOS-KO) mice by intraperitoneal injection of streptozotocin. Results: Diabetic animals showed normal plasma creatinine, markedly increased albuminuria and urinary malonyldialdehyde, elevated relative kidney weight, glomerulosclerosis, and increased glomerular size, but no relevant interstitial fibrosis. Neither dose of Rlx affected these changes although the drug was active and targeted plasma levels were achieved. Of note, we found no activation of the renal TGF-beta pathway in this model. In the hearts of diabetic animals, no fibrotic alterations indicative of DC could be determined which precluded testing of the initial hypothesis. Conclusions: We investigated a model showing early DN without overt tubulo-interstitial fibrosis and activation of the TGF-beta-Smad-2/3 pathway. In this model, Rlx proved ineffective; however, the same may not apply to other models and types of diabetes.}, language = {en} } @article{DuyduBasaranYalcinetal.2019, author = {Duydu, Yalcin and Basaran, Nursen and Yalcin, Can {\"O}zg{\"u}r and Ustundag, Aylin and Aydin, Sevtap and Anlar, Hatice Gul and Bacanli, Merve and Aydos, Kaan and Atabekoglu, Cem Somer and Golka, Klaus and Ickstadt, Katja and Schwerdtle, Tanja and Werner, Matthias and Bolt, Hermann M.}, title = {Boron-exposed male workers in Turkey}, series = {Archives of toxicology : official journal of EUROTOX}, volume = {93}, journal = {Archives of toxicology : official journal of EUROTOX}, number = {3}, publisher = {Springer}, address = {Heidelberg}, issn = {0340-5761}, doi = {10.1007/s00204-019-02391-z}, pages = {743 -- 751}, year = {2019}, abstract = {Boron-associated shifts in sex ratios at birth were suggested earlier and attributed to a decrease in Y- vs. X-bearing sperm cells. As the matter is pivotal in the discussion of reproductive toxicity of boron/borates, re-investigation in a highly borate-exposed population was required. In the present study, 304 male workers in Bandirma and Bigadic (Turkey) with different degrees of occupational and environmental exposure to boron were investigated. Boron was quantified in blood, urine and semen, and the persons were allocated to exposure groups along B blood levels. In the highest ("extreme") exposure group (n = 69), calculated mean daily boron exposures, semen boron and blood boron concentrations were 44.91 +/- 18.32 mg B/day, 1643.23 +/- 965.44 ng B/g semen and 553.83 +/- 149.52 ng B/g blood, respectively. Overall, an association between boron exposure and Y:X sperm ratios in semen was not statistically significant (p > 0.05). Also, the mean Y:X sperm ratios in semen samples of workers allocated to the different exposure groups were statistically not different in pairwise comparisons (p > 0.05). Additionally, a boron-associated shift in sex ratio at birth towards female offspring was not visible. In essence, the present results do not support an association between boron exposure and decreased Y:X sperm ratio in males, even under extreme boron exposure conditions.}, language = {en} } @article{DwiPutraReichetzederHasanetal.2020, author = {Dwi Putra, Sulistyo Emantoko and Reichetzeder, Christoph and Hasan, Ahmed Abdallah Abdalrahman Mohamed and Slowinski, Torsten and Chu, Chang and Kr{\"a}mer, Bernhard K. and Kleuser, Burkhard and Hocher, Berthold}, title = {Being born large for gestational age is associated with increased global placental DNA methylation}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, number = {1}, publisher = {Springer Nature}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-020-57725-0}, pages = {1 -- 10}, year = {2020}, abstract = {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).}, language = {en} } @article{DybingDoeGrotenetal.2002, author = {Dybing, E. and Doe, J. and Groten, J. and Kleiner, J. and O'Brien, J. and Renwick, A. G. and Schlatter, J. and Steinberg, Pablo and Tritschler, A. and Walker, R. and Younes, M.}, title = {Hazard characterisation of chemicals in food and diet : dose response, mechanisms and extrapolation issues}, year = {2002}, language = {en} } @article{DoegeHoenzkeSchumacheretal.2016, author = {D{\"o}ge, Nadine and H{\"o}nzke, Stefan and Schumacher, Fabian and Balzus, Benjamin and Colombo, Miriam and Hadam, Sabrina and Rancan, Fiorenza and Blume-Peytavi, Ulrike and Sch{\"a}fer-Korting, Monika and Schindler, Anke and R{\"u}hl, Eckart and Skov, Per Stahl and Church, Martin K. and Hedtrich, Sarah and Kleuser, Burkhard and Bodmeier, Roland and Vogt, Annika}, title = {Ethyl cellulose nanocarriers and nanocrystals differentially deliver dexamethasone into intact, tape-stripped or sodium lauryl sulfate-exposed ex vivo human skin - assessment by intradermal microdialysis and extraction from the different skin layers}, series = {Journal of controlled release}, volume = {242}, journal = {Journal of controlled release}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0168-3659}, doi = {10.1016/j.jconrel.2016.07.009}, pages = {25 -- 34}, year = {2016}, abstract = {Understanding penetration not only in intact, but also in lesional skin with impaired skin barrier function is important, in order to explore the surplus value of nanoparticle-based drug delivery for anti-inflammatory dermatotherapy. Herein, short-termex vivo cultures of (i) intact human skin, (ii) skin pretreated with tape-strippings and (iii) skin pre-exposed to sodium lauryl sulfate (SLS) were used to assess the penetration of dexamethasone (Dex). Intradermal microdialysis was utilized for up to 24 h after drug application as commercial cream, nanocrystals or ethyl cellulose nanocarriers applied at the therapeutic concentration of 0.05\%, respectively. In addition, Dex was assessed in culture media and extracts from stratum corneum, epidermis and dermis after 24 h, and the results were compared to those in heat-separated split skin from studies in Franz diffusion cells. Providing fast drug release, nanocrystals significantly accelerated the penetration of Dex. In contrast to the application of cream and ethyl cellulose nanocarriers, Dex was already detectable in eluates after 6 h when applying nanocrystals on intact skin. Disruption of the skin barrier further accelerated and enhanced the penetration. Encapsulation in ethyl cellulose nanocarriers delayed Dex penetration. Interestingly, for all formulations highly increased concentrations in the dialysate were observed in tape-stripped skin, whereas the extent of enhancement was less in SLS-exposed skin. The results were confirmed in tissue extracts and were in line with the predictions made by in vitro release studies and ex vivo Franz diffusion cell experiments. The use of 45 kDa probes further enabled the collection of inflammatory cytokines. However, the estimation of glucocorticoid efficacy by Interleukin (IL)-6 and IL-8 analysis was limited due to the trauma induced by the probe insertion. Ex vivo intradermal microdialysis combined with culture media analysis provides an effective, skin-sparing method for preclinical assessment of novel drug delivery systems at therapeutic doses in models of diseased skin. (C) 2016 Elsevier B.V. All rights reserved.}, language = {en} } @article{DoellDjalaliFarahaniKofoetZrenneretal.2021, author = {D{\"o}ll, Stefanie and Djalali Farahani-Kofoet, Roxana and Zrenner, Rita and Henze, Andrea and Witzel, Katja}, title = {Tissue-specific signatures of metabolites and proteins in asparagus roots and exudates}, series = {Horticulture research}, volume = {8}, journal = {Horticulture research}, number = {1}, publisher = {Nanjing Agricultural Univ.}, address = {Nanjing}, issn = {2052-7276}, doi = {10.1038/s41438-021-00510-5}, pages = {14}, year = {2021}, abstract = {Comprehensive untargeted and targeted analysis of root exudate composition has advanced our understanding of rhizosphere processes. However, little is known about exudate spatial distribution and regulation. We studied the specific metabolite signatures of asparagus root exudates, root outer (epidermis and exodermis), and root inner tissues (cortex and vasculature). The greatest differences were found between exudates and root tissues. In total, 263 non-redundant metabolites were identified as significantly differentially abundant between the three root fractions, with the majority being enriched in the root exudate and/or outer tissue and annotated as 'lipids and lipid-like molecules' or 'phenylpropanoids and polyketides'. Spatial distribution was verified for three selected compounds using MALDI-TOF mass spectrometry imaging. Tissue-specific proteome analysis related root tissue-specific metabolite distributions and rhizodeposition with underlying biosynthetic pathways and transport mechanisms. The proteomes of root outer and inner tissues were spatially very distinct, in agreement with the fundamental differences between their functions and structures. According to KEGG pathway analysis, the outer tissue proteome was characterized by a high abundance of proteins related to 'lipid metabolism', 'biosynthesis of other secondary metabolites' and 'transport and catabolism', reflecting its main functions of providing a hydrophobic barrier, secreting secondary metabolites, and mediating water and nutrient uptake. Proteins more abundant in the inner tissue related to 'transcription', 'translation' and 'folding, sorting and degradation', in accord with the high activity of cortical and vasculature cell layers in growth- and development-related processes. In summary, asparagus root fractions accumulate specific metabolites. This expands our knowledge of tissue-specific plant cell function.}, language = {en} } @article{DuenkelbergMaywaldSchmittetal.2020, author = {D{\"u}nkelberg, Sophie and Maywald, Martina and Schmitt, Anne Kristina and Schwerdtle, Tanja and Meyer, S{\"o}ren and Rink, Lothar}, title = {The interaction of sodium and zinc in the priming of T cell subpopulations regarding Th17 and Treg cells}, series = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology}, volume = {64}, journal = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology}, number = {2}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1613-4133}, doi = {10.1002/mnfr.201900245}, pages = {10}, year = {2020}, abstract = {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.}, language = {en} } @article{EbertMeyerLeffersetal.2016, author = {Ebert, Franziska and Meyer, S{\"o}ren and Leffers, Larissa and Raber, Georg and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {Toxicological characterisation of a thio-arsenosugar-glycerol in human cells}, series = {Journal of trace elements in medicine and biology}, volume = {38}, journal = {Journal of trace elements in medicine and biology}, publisher = {Springer Publishing Company}, address = {Jena}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2016.04.013}, pages = {150 -- 156}, year = {2016}, abstract = {Arsenosugars are water-soluble arsenic species predominant in marine algae and other seafood including mussels and oysters. They typically occur at levels ranging from 2 to 50 mg arsenic/kg dry weight. Most of the arsenosugars contain arsenic as a dimethylarsinoyl group (Me2As(O)-), commonly referred to as the oxo forms, but thio analogues have also been identified in marine organisms and as metabolic products of oxo-arsenosugars. So far, no data regarding toxicity and toxicokinetics of thio-arsenosugars are available. This in vitro-based study indicates that thio-dimethylarsenosugar-glycerol exerts neither pronounced cytotoxicity nor genotoxicity even though this arsenical was bioavailable to human hepatic (HepG2) and urothelial (UROtsa) cells. Experiments with the Caco-2 intestinal barrier model mimicking human absorption indicate for the thio-arsenosugar-glycerol higher intestinal bioavailability as compared to the oxo-arsenosugars. Nevertheless, absorption estimates were much lower in comparison to other arsenicals including arsenite and arsenic-containing hydrocarbons. Arsenic speciation in cell lysates revealed that HepG2 cells are able to metabolise the thio-arsenosugar-glycerol to some extent to dimethylarsinic acid (DMA). These first in vitro data cannot fully exclude risks to human health related to the presence of thio-arsenosugars in food. (C) 2016 Elsevier GmbH. All rights reserved.}, language = {en} } @article{EbertThomannWittetal.2016, author = {Ebert, Franziska and Thomann, Marlies and Witt, Barbara and M{\"u}ller, Sandra Marie and Meyer, S{\"o}ren and Weber, Till and Christmann, Markus and Schwerdtle, Tanja}, title = {Evaluating long-term cellular effects of the arsenic species thio-DMA(V): qPCR-based gene expression as screening tool}, series = {Journal of trace elements in medicine and biology}, volume = {37}, journal = {Journal of trace elements in medicine and biology}, publisher = {Yokohama Publishers}, address = {Jena}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2016.06.004}, pages = {78 -- 84}, year = {2016}, abstract = {Thio-dimethylarsinic acid (thio-DMA(V)) is a human urinary metabolite of the class 1 human carcinogen inorganic arsenic as well as of arsenosugars. Thio-DMA(V) exerts strong cellular toxicity, whereas its toxic modes of action are not fully understood. For the first time, this study characterises the impact of a long-term (21 days) in vitro incubation of thio-DMA(V) on the expression of selected genes related to cell death, stress response, epigenetics and DNA repair. The observed upregulation of DNMT1 might be a cellular compensation to counterregulate the in a very recent study observed massive global DNA hypomethylation after chronic thio-DMAv incubation. Moreover, our data suggest that chronic exposure towards subcytotoxic, pico- to nanomolar concentrations of thio-DMA(V) causes a stress response in human urothelial cells. The upregulation of genes encoding for proteins of DNA repair (Apex1,Lig1, XRCC1,DDB2, XPG, ATR) as well as damage response (GADD45A, GADD45G, Trp53) indicate a potential genotoxic risk emanating from thio-DMA(V) after long-term incubation. (C) 2016 Elsevier GmbH. All rights reserved.}, language = {en} } @article{EckelLiKuxhausetal.2018, author = {Eckel, Nathalie and Li, Yanping and Kuxhaus, Olga and Stefan, Norbert and Hu, Frank B. and Schulze, Matthias Bernd}, title = {Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses' Health Study)}, series = {The lancet diabetes \& endocrinology}, volume = {6}, journal = {The lancet diabetes \& endocrinology}, number = {9}, publisher = {Elsevier}, address = {New York}, issn = {2213-8587}, doi = {10.1016/S2213-8587(18)30137-2}, pages = {714 -- 724}, year = {2018}, abstract = {Background Cardiovascular disease risk among individuals across different categories of BMI might depend on their metabolic health. It remains unclear to what extent metabolic health status changes over time and whether this affects cardiovascular disease risk. In this study, we aimed to examine the association between metabolic health and its change over time and cardiovascular disease risk across BMI categories. Findings During 2 127 391 person-years of follow-up with a median follow-up of 24 years, we documented 6306 cases of cardiovascular disease including 3304 myocardial infarction cases and 3080 strokes. Cardiovascular disease risk of women with metabolically healthy obesity was increased compared with women with metabolically healthy normal weight (HR 1.39, 95\% CI 1.15-1.68), but risk was considerably higher in women with metabolically unhealthy normal weight (2.43, 2.19-2.68), overweight (2.61, 2.36-2.89) and obesity (3.15, 2.83-3.50). The majority of metabolically healthy women converted to unhealthy phenotypes (2555 [84\%] of 3027 women with obesity, 22 215 [68\%] of 32 882 women with normal-weight after 20 years). Women who maintained metabolically healthy obesity during follow-up were still at a higher cardiovascular disease risk compared with women with stable healthy normal weight (HR 1.57, 1.03-2.38), yet this risk was lower than for initially metabolically healthy women who converted to an unhealthy phenotype (normal-weight 1.90, 1.66-2.17 vs obesity 2.74, 2.30-3.27). Particularly incident diabetes and hypertension increased the risk among women with initial metabolic health. Interpretation Even when metabolic health is maintained during long periods of time, obesity remains a risk factor for cardiovascular disease. However, risks are highest for metabolically unhealthy women across all BMI categories. A large proportion of metabolically healthy women converted to an unhealthy phenotype over time across all BMI categories, which is associated with an increased cardiovascular disease risk. Copyright (C) 2018 Elsevier Ltd. All rights reserved.}, language = {en} }