@article{HuschekBoenickMerkeletal.2018, author = {Huschek, Gerd and B{\"o}nick, Josephine and Merkel, Dietrich and Huschek, Doreen and Rawel, Harshadrai Manilal}, title = {Authentication of leguminous-based products by targeted biomarkers using high resolution time of flight mass spectrometry}, series = {LWT - food science and technology : an official journal of the Swiss Society of Food Science and Technology (SGLWT/SOSSTA) and the International Union of Food Science and Technology (IUFoST)}, volume = {90}, journal = {LWT - food science and technology : an official journal of the Swiss Society of Food Science and Technology (SGLWT/SOSSTA) and the International Union of Food Science and Technology (IUFoST)}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0023-6438}, doi = {10.1016/j.lwt.2017.12.034}, pages = {164 -- 171}, year = {2018}, abstract = {A growing number of health-conscious individuals supplements their diet with protein-rich plant-based products to reduce their meat consumption. Analytical methods are needed to authenticate these new vegetarian products not only for the correct labelling of ingredients according to European legislation but also to discourage food fraud. This paper presents new biomarkers for a targeted proteomics LC-MS/MS work-flow that can simultaneously prove the presence/absence of garden pea, a protein-rich legume, meat and honey and quantify their content in processed vegan food. We show a novel rapid strategy to identify biomarkers for species authentication and the steps for the multi-parameter LC-MS/MS method validation and quantification. A high resolution triple time of flight mass spectrometer (HRMS) with SWATH Acquisition was used for the rapid discovery of all measurable trypsin-digested proteins in the individual ingredients. From these proteins, species-selective biomarkers were identified with BLAST and Skyline. Vicilin and convicilin (UniProt: D3VND9, Q9M3X6) allow pea authentication with regard to other legume species. Myostatin (UniProt: 018831) is a single biomarker for all meat types. For honey, we identified three selective proteins (UniProt: C6K481, C6K482, Q3L6329). The final LC-MS/MS method can identity and quantify these markers simultaneously. Quantification occurs via external matrix calibration.}, language = {en} } @article{MuellerEbertBornhorstetal.2018, author = {M{\"u}ller, Sandra Marie and Ebert, Franziska and Bornhorst, Julia and Galla, Hans-Joachim and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {Arsenic-containing hydrocarbons disrupt a model in vitro blood-cerebrospinal fluid barrier}, series = {Journal of trace elements in medicine and biology}, volume = {49}, journal = {Journal of trace elements in medicine and biology}, publisher = {Elsevier GMBH}, address = {M{\"u}nchen}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2018.01.020}, pages = {171 -- 177}, year = {2018}, abstract = {Lipid-soluble arsenicals, so-called arsenolipids, have gained a lot of attention in the last few years because of their presence in many seafoods and reports showing substantial cytotoxicity emanating from arsenic-containing hydrocarbons (AsHCs), a prominent subgroup of the arsenolipids. More recent in vivo and in vitro studies indicate that some arsenolipids might have adverse effects on brain health. In the present study, we focused on the effects of selected arsenolipids and three representative metabolites on the blood-cerebrospinal fluid barrier (B-CSF-B), a brain-regulating interface. For this purpose, we incubated an in vitro model of the B-CSF-B composed of porcine choroid plexus epithelial cells (PCPECs) with three AsHCs, two arsenic-containing fatty acids (AsFAs) and three representative arsenolipid metabolites (dimethylarsinic acid, thio/oxo-dimethylpropanoic acid) to examine their cytotoxic potential and impact on barrier integrity. The toxic arsenic species arsenite was also tested in this way and served as a reference substance. While AsFAs and the metabolites showed no cytotoxic effects in the conducted assays, AsHCs showed a strong cytotoxicity, being up to 1.5-fold more cytotoxic than arsenite. Analysis of the in vitro B-CSF-B integrity showed a concentration dependent disruption of the barrier within 72 h. The correlation with the decreased plasma membrane surface area (measured as capacitance) indicates cytotoxic effects. These findings suggest exposure to elevated levels of certain arsenolipids may have detrimental consequences for the central nervous system.}, language = {en} } @article{MeyerMarkovaPohletal.2018, author = {Meyer, S{\"o}ren and Markova, Mariya and Pohl, Gabriele and Marschall, Talke Anu and Pivovarova, Olga and Pfeiffer, Andreas F. H. and Schwerdtle, Tanja}, title = {Development, validation and application of an ICP-MS/MS method to quantify minerals and (ultra-)trace elements in human serum}, series = {Journal of trace elements in medicine and biology}, volume = {49}, journal = {Journal of trace elements in medicine and biology}, publisher = {Elsevier GMBH}, address = {M{\"u}nchen}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2018.05.012}, pages = {157 -- 163}, year = {2018}, abstract = {Multi-element determination in human samples is very challenging. Especially in human intervention studies sample volumes are often limited to a few microliters and due to the high number of samples a high-throughput is indispensable. Here, we present a state-of-the-art ICP-MS/MS-based method for the analysis of essential (trace) elements, namely Mg, Ca, Fe, Cu, Zn, Mo, Se and I, as well as food-relevant toxic elements such as As and Cd. The developed method was validated regarding linearity of the calibration curves, method LODs and LOQs, selectivity and trueness as well as precision. The established reliable method was applied to quantify the element serum concentrations of participants of a human intervention study (LeguAN). The participants received isocaloric diets, either rich in plant protein or in animal protein. While the serum concentrations of Mg and Mo increased in participants receiving the plant protein-based diet (above all legumes), the Se concentration in serum decreased. In contrast, the animal protein-based diet, rich in meat and dairy products, resulted in an increased Se concentration in serum.}, language = {en} } @misc{ChenBornhorstNeelyetal.2018, author = {Chen, Pan and Bornhorst, Julia and Neely, M. Diana and Avila, Daiana Silva}, title = {Mechanisms and Disease Pathogenesis Underlying Metal-Induced Oxidative Stress}, series = {Oxidative Medicine and Cellular Longevity}, journal = {Oxidative Medicine and Cellular Longevity}, publisher = {Hindawi}, address = {London}, issn = {1942-0900}, doi = {10.1155/2018/7612172}, pages = {3}, year = {2018}, language = {en} } @misc{Steinberg2018, author = {Steinberg, Pablo}, title = {Only one Component of a holistic Nutrition Policy}, series = {Fleischwirtschaft}, volume = {98}, journal = {Fleischwirtschaft}, number = {11}, publisher = {Deutscher Fachverlag GmbH}, address = {Frankfurt am Main}, issn = {0015-363X}, pages = {8 -- 9}, year = {2018}, language = {de} } @article{GiulbudagianHoenzkeBergueiroetal.2018, author = {Giulbudagian, Michael and H{\"o}nzke, Stefan and Bergueiro, Juli{\´a}n and I{\c{s}}{\i}k, Doğu{\c{s}} and Schumacher, Fabian and Saeidpour, Siavash and Lohan, Silke and Meinke, Martina and Teutloff, Christian and Sch{\"a}fer-Korting, Monika and Yealland, Guy and Kleuser, Burkhard and Hedtrich, Sarah and Calder{\´o}n, Marcelo}, title = {Enhanced topical delivery of dexamethasone by beta-cyclodextrin decorated thermoresponsive nanogels}, series = {Nanoscale}, volume = {10}, journal = {Nanoscale}, number = {1}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {2040-3364}, doi = {10.1039/c7nr04480a}, pages = {469 -- 479}, year = {2018}, abstract = {Highly hydrophilic, responsive nanogels are attractive as potential systems for the topical delivery of bioactives encapsulated in their three-dimensional polymeric scaffold. Yet, these drug carrier systems suffer from drawbacks for efficient delivery of hydrophobic drugs. Addressing this, β-cyclodextrin (βCD) could be successfully introduced into the drug carrier systems by exploiting its unique affinity toward dexamethasone (DXM) as well as its role as topical penetration enhancer. The properties of βCD could be combined with those of thermoresponsive nanogels (tNGs) based on dendritic polyglycerol (dPG) as a crosslinker and linear thermoresponsive polyglycerol (tPG) inducing responsiveness to temperature changes. Electron paramagnetic resonance (EPR) studies localized the drug within the hydrophobic cavity of βCD by differences in its mobility and environmental polarity. In fact, the fabricated carriers combining a particulate delivery system with a conventional penetration enhancer, resulted in an efficient delivery of DXM to the epidermis and the dermis of human skin ex vivo (enhancement compared to commercial DXM cream: ∼2.5 fold in epidermis, ∼30 fold in dermis). Furthermore, DXM encapsulated in βCD tNGs applied to skin equivalents downregulated the expression of proinflammatory thymic stromal lymphopoietin (TSLP) and outperformed a commercially available DXM cream.}, language = {en} } @misc{HocherZeng2018, author = {Hocher, Berthold and Zeng, Shufei}, title = {Need for better PTH assays for clinical research and patient treatment}, series = {Clinical chemistry and laboratory medicine : journal of the Forum of the European Societies of Clinical Chemistry - the European Branch of the International Federation of Clinical Chemistry and Laboratory Medicine}, volume = {56}, journal = {Clinical chemistry and laboratory medicine : journal of the Forum of the European Societies of Clinical Chemistry - the European Branch of the International Federation of Clinical Chemistry and Laboratory Medicine}, number = {2}, publisher = {De Gruyter}, address = {Berlin}, issn = {1434-6621}, doi = {10.1515/cclm-2017-0617}, pages = {183 -- 185}, year = {2018}, language = {en} } @article{MuellerEbertRaberetal.2018, author = {M{\"u}ller, Sandra Marie and Ebert, Franziska and Raber, Georg and Meyer, S{\"o}ren and Bornhorst, Julia and H{\"u}wel, Stephan and Galla, Hans-Joachim and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {Effects of arsenolipids on in vitro blood-brain barrier model}, series = {Archives of toxicology : official journal of EUROTOX}, volume = {92}, journal = {Archives of toxicology : official journal of EUROTOX}, number = {2}, publisher = {Springer}, address = {Heidelberg}, issn = {0340-5761}, pages = {823 -- 832}, year = {2018}, abstract = {Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids (AsLs) occurring in fish and edible algae, possess a substantial neurotoxic potential in fully differentiated human brain cells. Previous in vivo studies indicating that AsHCs cross the blood-brain barrier of the fruit fly Drosophila melanogaster raised the question whether AsLs could also cross the vertebrate blood-brain barrier (BBB). In the present study, we investigated the impact of several representatives of AsLs (AsHC 332, AsHC 360, AsHC 444, and two arsenic-containing fatty acids, AsFA 362 and AsFA 388) as well as of their metabolites (thio/oxo-dimethylpropionic acid, dimethylarsinic acid) on porcine brain capillary endothelial cells (PBCECs, in vitro model for the blood-brain barrier). AsHCs exerted the strongest cytotoxic effects of all investigated arsenicals as they were up to fivefold more potent than the toxic reference species arsenite (iAsIII). In our in vitro BBB-model, we observed a slight transfer of AsHC 332 across the BBB after 6 h at concentrations that do not affect the barrier integrity. Furthermore, incubation with AsHCs for 72 h led to a disruption of the barrier at sub-cytotoxic concentrations. The subsequent immunocytochemical staining of three tight junction proteins revealed a significant impact on the cell membrane. Because AsHCs enhance the permeability of the in vitro blood-brain barrier, a similar behavior in an in vivo system cannot be excluded. Consequently, AsHCs might facilitate the transfer of accompanying foodborne toxicants into the brain.}, language = {en} } @misc{HonnenWellenbergWeidesetal.2018, author = {Honnen, S. and Wellenberg, Anna and Weides, L. and Bornhorst, Julia and Crone, B. and Karst, U. and Fritz, G.}, title = {Identification of potent drug candidates for the prevention of cisplatin-induced neurotoxicity in the model organism C. elegans}, series = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {391}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, publisher = {Springer}, address = {New York}, issn = {0028-1298}, doi = {10.1007/s00210-018-1477-5}, pages = {S4 -- S4}, year = {2018}, language = {en} } @misc{KrsticGalhuberSchulzetal.2018, author = {Krstic, Jelena and Galhuber, Markus and Schulz, Tim Julius and Schupp, Michael and Prokesch, Andreas}, title = {p53 as a dichotomous regulator of liver disease}, series = {International journal of molecular sciences}, volume = {19}, journal = {International journal of molecular sciences}, number = {3}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms19030921}, pages = {23}, year = {2018}, abstract = {Lifestyle-related disorders, such as the metabolic syndrome, have become a primary risk factor for the development of liver pathologies that can progress from hepatic steatosis, hepatic insulin resistance, steatohepatitis, fibrosis and cirrhosis, to the most severe condition of hepatocellular carcinoma (HCC). While the prevalence of liver pathologies is steadily increasing in modern societies, there are currently no approved drugs other than chemotherapeutic intervention in late stage HCC. Hence, there is a pressing need to identify and investigate causative molecular pathways that can yield new therapeutic avenues. The transcription factor p53 is well established as a tumor suppressor and has recently been described as a central metabolic player both in physiological and pathological settings. Given that liver is a dynamic tissue with direct exposition to ingested nutrients, hepatic p53, by integrating cellular stress response, metabolism and cell cycle regulation, has emerged as an important regulator of liver homeostasis and dysfunction. The underlying evidence is reviewed herein, with a focus on clinical data and animal studies that highlight a direct influence of p53 activity on different stages of liver diseases. Based on current literature showing that activation of p53 signaling can either attenuate or fuel liver disease, we herein discuss the hypothesis that, while hyper-activation or loss of function can cause disease, moderate induction of hepatic p53 within physiological margins could be beneficial in the prevention and treatment of liver pathologies. Hence, stimuli that lead to a moderate and temporary p53 activation could present new therapeutic approaches through several entry points in the cascade from hepatic steatosis to HCC.}, language = {en} } @misc{Kleuser2018, author = {Kleuser, Burkhard}, title = {Divergent role of sphingosine 1-phosphate in liver health and disease}, series = {International journal of molecular sciences}, volume = {19}, journal = {International journal of molecular sciences}, number = {3}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms19030722}, pages = {18}, year = {2018}, abstract = {Two decades ago, sphingosine 1-phosphate (S1P) was discovered as a novel bioactive molecule that regulates a variety of cellular functions. The plethora of S1P-mediated effects is due to the fact that the sphingolipid not only modulates intracellular functions but also acts as a ligand of G protein-coupled receptors after secretion into the extracellular environment. In the plasma, S1P is found in high concentrations, modulating immune cell trafficking and vascular endothelial integrity. The liver is engaged in modulating the plasma S1P content, as it produces apolipoprotein M, which is a chaperone for the S1P transport. Moreover, the liver plays a substantial role in glucose and lipid homeostasis. A dysfunction of glucose and lipid metabolism is connected with the development of liver diseases such as hepatic insulin resistance, non-alcoholic fatty liver disease, or liver fibrosis. Recent studies indicate that S1P is involved in liver pathophysiology and contributes to the development of liver diseases. In this review, the current state of knowledge about S1P and its signaling in the liver is summarized with a specific focus on the dysregulation of S1P signaling in obesity-mediated liver diseases. Thus, the modulation of S1P signaling can be considered as a potential therapeutic target for the treatment of hepatic diseases.}, language = {en} } @article{PrommerMaurervonWebskyetal.2018, author = {Prommer, Hans-Ulrich and Maurer, Johannes and von Websky, Karoline and Freise, Christian and Sommer, Kerstin and Nasser, Hamoud and Samapati, Rudi and Reglin, Bettina and Guimaraes, Pedro and Pries, Axel Radlach and Querfeld, Uwe}, title = {Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis}, series = {Scientific reports}, volume = {8}, journal = {Scientific reports}, publisher = {Nature Publ. Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-018-23663-1}, pages = {14}, year = {2018}, abstract = {Chronic kidney disease (CKD) is associated with excessive mortality from cardiovascular disease (CVD). Endothelial dysfunction, an early manifestation of CVD, is consistently observed in CKD patients and might be linked to structural defects of the microcirculation including microvascular rarefaction. However, patterns of microvascular rarefaction in CKD and their relation to functional deficits in perfusion and oxygen delivery are currently unknown. In this in-vivo microscopy study of the cremaster muscle microcirculation in BALB/c mice with moderate to severe uremia, we show in two experimental models (adenine feeding or subtotal nephrectomy), that serum urea levels associate incrementally with a distinct microangiopathy. Structural changes were characterized by a heterogeneous pattern of focal microvascular rarefaction with loss of coherent microvascular networks resulting in large avascular areas. Corresponding microvascular dysfunction was evident by significantly diminished blood flow velocity, vascular tone, and oxygen uptake. Microvascular rarefaction in the cremaster muscle paralleled rarefaction in the myocardium, which was accompanied by a decrease in transcription levels not only of the transcriptional regulator HIF-1 alpha, but also of its target genes Angpt-2, TIE-1 and TIE-2, Flkt-1 and MMP-9, indicating an impaired hypoxia-driven angiogenesis. Thus, experimental uremia in mice associates with systemic microvascular disease with rarefaction, tissue hypoxia and dysfunctional angiogenesis.}, language = {en} } @article{EdlichVolzBrodwolfetal.2018, author = {Edlich, Alexander and Volz, Pierre and Brodwolf, Robert and Unbehauen, Michael and Mundhenk, Lars and Gruber, Achim D. and Hedtrich, Sarah and Haag, Rainer and Alexiev, Ulrike and Kleuser, Burkhard}, title = {Crosstalk between core-multishell nanocarriers for cutaneous drug delivery and antigen-presenting cells of the skin}, series = {Biomaterials : biomaterials reviews online}, volume = {162}, journal = {Biomaterials : biomaterials reviews online}, publisher = {Elsevier}, address = {Oxford}, issn = {0142-9612}, doi = {10.1016/j.biomaterials.2018.01.058}, pages = {60 -- 70}, year = {2018}, abstract = {Owing their unique chemical and physical properties core-multishell (CMS) nanocarriers are thought to underlie their exploitable biomedical use for a topical treatment of skin diseases. This highlights the need to consider not only the efficacy of CMS nanocarriers but also the potentially unpredictable and adverse consequences of their exposure thereto. As CMS nanocarriers are able to penetrate into viable layers of normal and stripped human skin ex vivo as well as in in vitro skin disease models the understanding of nanoparticle crosstalk with components of the immune system requires thorough investigation. Our studies highlight the biocompatible properties of CMS nanocarriers on Langerhans cells of the skin as they did neither induce cytotoxicity and genotoxicity nor cause reactive oxygen species (ROS) or an immunological response. Nevertheless, CMS nanocarriers were efficiently taken up by Langerhans cells via divergent endocytic pathways. Bioimaging of CMS nanocarriers by fluorescence lifetime imaging microscopy (FLIM) and flow cytometry indicated not only a localization within the lysosomes but also an energy-dependent exocytosis of unmodified CMS nanocarriers into the extracellular environment. (C) 2018 Elsevier Ltd. All rights reserved.}, language = {en} } @misc{HocherZeng2018, author = {Hocher, Berthold and Zeng, Shufei}, title = {Clear the fog around parathyroid hormone assays}, series = {Clinical journal of the American Society of Nephrology}, volume = {13}, journal = {Clinical journal of the American Society of Nephrology}, number = {4}, publisher = {American Society of Nephrology}, address = {Washington}, issn = {1555-9041}, doi = {10.2215/CJN.01730218}, pages = {524 -- 526}, year = {2018}, 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{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{KaruwanarintPhonratTungtrongchitretal.2018, author = {Karuwanarint, Piyaporn and Phonrat, Benjaluck and Tungtrongchitr, Anchalee and Suriyaprom, Kanjana and Chuengsamarn, Somlak and Schweigert, Florian J. and Tungtrongchitr, Rungsunn}, title = {Vitamin D-binding protein and its polymorphisms as a predictor for metabolic syndrome}, series = {Biomarkers in medicine}, volume = {12}, journal = {Biomarkers in medicine}, number = {5}, publisher = {Future Medicine}, address = {London}, issn = {1752-0363}, doi = {10.2217/bmm-2018-0029}, pages = {465 -- 473}, year = {2018}, abstract = {Aim: To investigate the relationship of vitamin D-binding protein (GC) and genetic variation of GC (rs4588, rs7041 and rs2282679) with metabolic syndrome (MetS) in the Thai population. Materials \& methods: GCglobulin concentrations were measured by quantitative western blot analysis in 401 adults. All participants were genotyped using TaqMan allelic discrimination assays. Results: GC-globulin levels were significatly lower in MetS subjects than in control subjects, in which significant negative correlations of GC-globulin levels with systolic blood pressure, glucose and age were found. Male participants who carried the GT genotype for rs4588 showed an increased risk of MetS compared with the GG wild-type (odds ratio: 3.25; p = 0.004). Conclusion: GC-globulin concentrations and variation in GC rs4588 were supported as a risk factor for MetS in Thais.}, language = {en} } @article{KnebelNeebZahnetal.2018, author = {Knebel, Constanze and Neeb, Jannika and Zahn, Elisabeth and Schmidt, Flavia and Carazo, Alejandro and Holas, Ondej and Pavek, Petr and P{\"u}schel, Gerhard Paul and Zanger, Ulrich M. and S{\"u}ssmuth, Roderich and Lampen, Alfonso and Marx-Stoelting, Philip and Braeuning, Albert}, title = {Unexpected Effects of Propiconazole, Tebuconazole, and Their Mixture on the Receptors CAR and PXR in Human Liver Cells}, series = {Toxicological sciences}, volume = {163}, journal = {Toxicological sciences}, number = {1}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1096-6080}, doi = {10.1093/toxsci/kfy026}, pages = {170 -- 181}, year = {2018}, abstract = {Analyzing mixture toxicity requires an in-depth understanding of the mechanisms of action of its individual components. Substances with the same target organ, same toxic effect and same mode of action (MoA) are believed to cause additive effects, whereas substances with different MoAs are assumed to act independently. Here, we tested 2 triazole fungicides, propiconazole, and tebuconazole (Te), for individual and combined effects on liver toxicity-related endpoints. Both triazoles are proposed to belong to the same cumulative assessment group and are therefore thought to display similar and additive behavior. Our data show that Te is an antagonist of the constitutive androstane receptor (CAR) in rats and humans, while propiconazole is an agonist of this receptor. Both substances activate the pregnane X-receptor (PXR) and further induce mRNA expression of CYP3A4. CYP3A4 enzyme activity, however, is inhibited by propiconazole. For common targets of PXR and CAR, the activation of PXR by Te overrides CAR inhibition. In summary, propiconazole and Te affect different hepatotoxicity-relevant cellular targets and, depending on the individual endpoint analyzed, act via similar or dissimilar mechanisms. The use of molecular data based on research in human cell systems extends the picture to refine cumulative assessment group grouping and substantially contributes to the understanding of mixture effects of chemicals in biological systems.}, language = {en} } @article{NowotnyCastroHugoetal.2018, author = {Nowotny, Kerstin and Castro, Jose Pedro and Hugo, Martin and Braune, Sabine and Weber, Daniela and Pignitter, Marc and Somoza, Veronika and Bornhorst, Julia and Schwerdtle, Tanja and Grune, Tilman}, title = {Oxidants produced by methylglyoxal-modified collagen trigger ER stress and apoptosis in skin fibroblasts}, series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research}, volume = {120}, journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research}, publisher = {Elsevier}, address = {New York}, issn = {0891-5849}, doi = {10.1016/j.freeradbiomed.2018.03.022}, pages = {102 -- 113}, year = {2018}, abstract = {Methylglyoxal (MG), a highly reactive dicarbonyl, interacts with proteins to form advanced glycation end products (AGEs). AGEs include a variety of compounds which were shown to have damaging potential and to accumulate in the course of different conditions such as diabetes mellitus and aging. After confirming collagen as a main target for MG modifications in vivo within the extracellular matrix, we show here that MG-collagen disrupts fibroblast redox homeostasis and induces endoplasmic reticulum (ER) stress and apoptosis. In particular, MG-collagen-induced apoptosis is associated with the activation of the PERK-eIF2 alpha pathway and caspase-12. MG-collagen contributes to altered redox homeostasis by directly generating hydrogen peroxide and oxygen-derived free radicals. The induction of ER stress in human fibroblasts was confirmed using collagen extracts isolated from old mice in which MG-derived AGEs were enriched. In conclusion, MG-derived AGEs represent one factor contributing to diminished fibroblast function during aging.}, language = {en} } @misc{FernandoDrescherDeubeletal.2018, author = {Fernando, Raquel and Drescher, Cathleen and Deubel, Stefanie and Grune, Tilman and Castro, Jose Pedro}, title = {Distinct proteasomal activity for fast and slow twitch skeletal muscle during aging}, series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research}, volume = {120}, journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research}, publisher = {Elsevier}, address = {New York}, issn = {0891-5849}, doi = {10.1016/j.freeradbiomed.2018.04.393}, pages = {S119 -- S119}, year = {2018}, abstract = {Skeletal muscle alterations during aging lead to dysfunctional metabolism, correlating with frailty and early mortality. The loss of proteostasis is a hallmark of aging. Whether proteostasis loss plays a role in muscle aging remains elusive. To address this question we collected muscles, Soleus (SOL, type I) and Extensor digitorum longus (EDL, type II), from young (4 months) and old (25 months) C57BL/6 mice and evaluated the proteasomal system. Initial work showed decreased 26 S activity in old SOL. EDL displayed lower proteasomal activity in both ages compared to any of the SOL ages. Moreover, in order to understand if during aging there is the so-called "fiber switch from fast-to-slow", we performed western blots against sMHC and fMHC (slow and fast myosin heavy chain, respectively). Preliminary results suggest that young SOL is composed by slow twitch fibers but also contains fast twitch fibers, while young EDL seems to be mostly composed by fast twitch fibers that level down during aging, suggesting the switch. As a conclusion, EDL seems to have less proteasomal activity, however, if this is a contributor or a consequence to the muscle fiber switch during aging still needs further investigation.}, language = {en} } @article{RohnMarschallKroepfletal.2018, author = {Rohn, Isabelle and Marschall, Talke Anu and Kr{\"o}pfl, Nina and Jensen, Kenneth Bendix and Aschner, Michael and Tuck, Simon and Kuehnelt, Doris and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Selenium species-dependent toxicity, bioavailability and metabolic transformations in Caenorhabditis elegans}, series = {Metallomics : integrated biometal science}, volume = {10}, journal = {Metallomics : integrated biometal science}, number = {6}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/c8mt00066b}, pages = {818 -- 827}, year = {2018}, abstract = {The essential micronutrient selenium (Se) is required for various systemic functions, but its beneficial range is narrow and overexposure may result in adverse health effects. Additionally, the chemical form of the ingested selenium contributes crucially to its health effects. While small Se species play a major role in Se metabolism, their toxicological effects, bioavailability and metabolic transformations following elevated uptake are poorly understood. Utilizing the tractable invertebrate Caenorhabditis elegans allowed for an alternative approach to study species-specific characteristics of organic and inorganic Se forms in vivo, revealing remarkable species-dependent differences in the toxicity and bioavailability of selenite, selenomethionine (SeMet) and Se-methylselenocysteine (MeSeCys). An inverse relationship was found between toxicity and bioavailability of the Se species, with the organic species displaying a higher bioavailability than the inorganic form, yet being less toxic. Quantitative Se speciation analysis with HPLC/mass spectrometry revealed a partial metabolism of SeMet and MeSeCys. In SeMet exposed worms, identified metabolites were Se-adenosylselenomethionine (AdoSeMet) and Se-adenosylselenohomocysteine (AdoSeHcy), while worms exposed to MeSeCys produced Se-methylselenoglutathione (MeSeGSH) and -glutamyl-MeSeCys (-Glu-MeSeCys). Moreover, the possible role of the sole selenoprotein in the nematode, thioredoxin reductase-1 (TrxR-1), was studied comparing wildtype and trxr-1 deletion mutants. Although a lower basal Se level was detected in trxr-1 mutants, Se toxicity and bioavailability following acute exposure was indistinguishable from wildtype worms. Altogether, the current study demonstrates the suitability of C. elegans as a model for Se species dependent toxicity and metabolism, while further research is needed to elucidate TrxR-1 function in the nematode.}, language = {en} } @article{vonWebskyHasanReichetzederetal.2018, author = {von Websky, Karoline and Hasan, Ahmed Abdallah Abdalrahman Mohamed and Reichetzeder, Christoph and Tsuprykov, Oleg and Hocher, Berthold}, title = {Impact of vitamin D on pregnancy-related disorders and on offspring outcome}, series = {The Journal of Steroid Biochemistry and Molecular Biology}, volume = {180}, journal = {The Journal of Steroid Biochemistry and Molecular Biology}, publisher = {Elsevier}, address = {Oxford}, issn = {0960-0760}, doi = {10.1016/j.jsbmb.2017.11.008}, pages = {51 -- 64}, year = {2018}, abstract = {Observational studies from all over the world continue to find high prevalence rates of vitamin D insufficiency and deficiency in many populations, including pregnant women. Beyond its classical function as a regulator of calcium and phosphate metabolism, vitamin D elicits numerous effects in the human body. Current evidence highlights a vital role of vitamin D in mammalian gestation. During pregnancy, adaptations in maternal vitamin D metabolism lead to a physiologic increase of vitamin D levels, mainly because of an increased renal production, although other potential sources like the placenta are being discussed. A sufficient supply of mother and child with calcium and vitamin D during pregnancy ensures a healthy bone development of the fetus, whereas lack of either of these nutrients can lead to the development of rickets in the child. Moreover, vitamin D insufficiency during pregnancy has consistently been associated with adverse maternal and neonatal pregnancy outcomes. In multitudinous studies, low maternal vitamin D status was associated with a higher risk for pre-eclampsia, gestational diabetes mellitus and other gestational diseases. Likewise, several negative consequences for the fetus have been reported, including fetal growth restriction, increased risk of preterm birth and a changed susceptibility for later-life diseases. However, study results are diverging and causality has not been proven so far. Meta-analyses on the relationship between maternal vitamin D status and pregnancy outcomes revealed a wide heterogeneity of studied populations and the applied methodology in vitamin D assessment. Until today, clinical guidelines for supplementation cannot be based on high-quality evidence and it is not clear if the required intake for pregnant women differs from non-pregnant women. Long-term safety data of vitamin D supplementation in pregnant women has not been established and overdosing of vitamin D might have unfavorable effects, especially in mothers and newborns with mutations of genes involved in vitamin D metabolism. Reliable data from large observational and interventional randomized control trials are urgently needed as a basis for any detailed and safe recommendations for supplementation in the general population and, most importantly, in pregnant women. This is of utmost importance, as ensuring a sufficient vitamin D-supply of mother and child implies a great potential for the prevention of birth complications and development of diseases.}, language = {en} } @article{LaegerCastanoMartinezWernoetal.2018, author = {Laeger, Thomas and Castano-Martinez, Teresa and Werno, Martin W. and Japtok, Lukasz and Baumeier, Christian and Jonas, Wenke and Kleuser, Burkhard and Sch{\"u}rmann, Annette}, title = {Dietary carbohydrates impair the protective effect of protein restriction against diabetes in NZO mice used as a model of type 2 diabetes}, series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, volume = {61}, journal = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, number = {6}, publisher = {Springer}, address = {New York}, issn = {0012-186X}, doi = {10.1007/s00125-018-4595-1}, pages = {1459 -- 1469}, year = {2018}, abstract = {Aims/hypothesis Low-protein diets are well known to improve glucose tolerance and increase energy expenditure. Increases in circulating fibroblast growth factor 21 (FGF21) have been implicated as a potential underlying mechanism. Methods We aimed to test whether low-protein diets in the context of a high-carbohydrate or high-fat regimen would also protect against type 2 diabetes in New Zealand Obese (NZO) mice used as a model of polygenetic obesity and type 2 diabetes. Mice were placed on high-fat diets that provided protein at control (16 kJ\%; CON) or low (4 kJ\%; low-protein/high-carbohydrate [LP/HC] or low-protein/high-fat [LP/HF]) levels. Results Protein restriction prevented the onset of hyperglycaemia and beta cell loss despite increased food intake and fat mass. The effect was seen only under conditions of a lower carbohydrate/fat ratio (LP/HF). When the carbohydrate/fat ratio was high (LP/HC), mice developed type 2 diabetes despite the robustly elevated hepatic FGF21 secretion and increased energy expenditure. Conclusion/interpretation Prevention of type 2 diabetes through protein restriction, without lowering food intake and body fat mass, is compromised by high dietary carbohydrates. Increased FGF21 levels and elevated energy expenditure do not protect against hyperglycaemia and type 2 diabetes per se.}, language = {en} } @misc{SchulzeMartinezGonzalezFungetal.2018, author = {Schulze, Matthias Bernd and Martinez-Gonzalez, Miguel A. and Fung, Teresa T. and Lichtenstein, Alice H. and Forouhi, Nita G.}, title = {Food based dietary patterns and chronic disease prevention}, series = {BMJ-British medical journal}, volume = {361}, journal = {BMJ-British medical journal}, publisher = {BMJ Publishing Group}, address = {London}, issn = {1756-1833}, doi = {10.1136/bmj.k2396}, pages = {6}, year = {2018}, abstract = {Matthias B Schulze and colleagues discuss current knowledge on the associations between dietary patterns and cancer, coronary heart disease, stroke, and type 2 diabetes, focusing on areas of uncertainty and future research directions.}, language = {en} } @article{GalbeteKroegerJannaschetal.2018, author = {Galbete, Cecilia and Kr{\"o}ger, Janine and Jannasch, Franziska and Iqbal, Khalid and Schwingshackl, Lukas and Schwedhelm, Carolina and Weikert, Cornelia and Boeing, Heiner and Schulze, Matthias Bernd}, title = {Nordic diet, Mediterranean diet, and the risk of chronic diseases}, series = {BMC Medicine}, volume = {16}, journal = {BMC Medicine}, publisher = {BMC}, address = {London}, issn = {1741-7015}, doi = {10.1186/s12916-018-1082-y}, pages = {13}, year = {2018}, abstract = {Background: The Mediterranean Diet (MedDiet) has been acknowledged as a healthy diet. However, its relation with risk of major chronic diseases in non-Mediterranean countries is inconclusive. The Nordic diet is proposed as an alternative across Northern Europe, although its associations with the risk of chronic diseases remain controversial. We aimed to investigate the association between the Nordic diet and the MedDiet with the risk of chronic disease (type 2 diabetes (T2D), myocardial infarction (MI), stroke, and cancer) in the EPIC-Potsdam cohort. Methods: The EPIC-Potsdam cohort recruited 27,548 participants between 1994 and 1998. After exclusion of prevalent cases, we evaluated baseline adherence to a score reflecting the Nordic diet and two MedDiet scores (tMDS, reflecting the traditional MedDiet score, and the MedPyr score, reflecting the MedDiet Pyramid). Cox regression models were applied to examine the association between the diet scores and the incidence of major chronic diseases. Results: During a follow-up of 10.6 years, 1376 cases of T2D, 312 of MI, 321 of stroke, and 1618 of cancer were identified. The Nordic diet showed a statistically non-significant inverse association with incidence of MI in the overall population and of stroke in men. Adherence to the MedDiet was associated with lower incidence of T2D (HR per 1 SD 0.93, 95\% CI 0.88-0.98 for the tMDS score and 0.92, 0.87-0.97 for the MedPyr score). In women, the MedPyr score was also inversely associated with MI. No association was observed for any of the scores with cancer. Conclusions: In the EPIC-Potsdam cohort, the Nordic diet showed a possible beneficial effect on MI in the overall population and for stroke in men, while both scores reflecting the MedDiet conferred lower risk of T2D in the overall population and of MI in women.}, language = {en} } @article{TsuprykovBuseSkobloetal.2018, author = {Tsuprykov, Oleg and Buse, Claudia and Skoblo, Roman and Haq, Afrozul and Hocher, Berthold}, title = {Reference intervals for measured and calculated free 25-hydroxyvitamin D in normal pregnancy}, series = {The Journal of Steroid Biochemistry and Molecular Biology}, volume = {181}, journal = {The Journal of Steroid Biochemistry and Molecular Biology}, publisher = {Elsevier}, address = {Oxford}, issn = {0960-0760}, doi = {10.1016/j.jsbmb.2018.03.005}, pages = {80 -- 87}, year = {2018}, abstract = {The determination of free 25-hydroxyvitamin D (25(OH)D) as compared to the analysis of total 25-hydroxyvitamin D might reflect better the vitamin D status during pregnancy, since vitamin D-binding protein (DBP) concentrations increase throughout pregnancy and the vast majority of 25(OH)D is tightly bound to DBP thus strongly influencing total 25(OH)D. The concentration of the biologically active free 25(OH)D - on the other hand - is much less dependent on the DBP concentrations. The study was conducted in May-June 2016 in 368 Caucasian pregnant healthy women - residents of Northeastern Germany. Free 25(OH)D was either measured directly by commercial ELISA kit or assessed by calculation via total 25(OH)D, DBP, and albumin serum concentrations. Regardless of the detection method, free 25(OH)D lowers in the 3rd trimester comparing to the 1st trimester (by 12\% and 21\%, p < 0.05 and p < 0.001, for measured and calculated free 25(OH)D, respectively), whereas total 25(OH)D was not decreased in late pregnancy. DBP rises with gestational age. Total 25(OH)D was not correlated with serum calcium (p = 0.251), whereas free 25(OH)D was significantly (p = 0.007 for measured free 25(OH)D and p < 0.001 for calculated free 25(OH)D) positively correlated with calcium. All 25(OH) D isoforms were significantly negatively correlated with bone-specific alkaline phosphatase (BSAP), however the correlation strength was the lowest with total 25(OH)D (rho = -0.108, p = 0.038), whereas both measured and calculated free 25(OH)D revealed better associations with BSAP (rho = -0.203 and rho = -0.211 for measured and calculated free 25(OH)D, respectively, p < 0.001 for both). We established pregnancy trimester specific reference intervals for free measured and calculated 25(OH)D and DBP. Both measured and calculated free 25(OH)D showed better correlations with parameters of the endocrine vitamin D system (calcium and BSAP). Both ways of measuring free 25(OH)D in pregnant women are suitable as novel laboratory parameter for vitamin D status monitoring during human pregnancy and might replace in the future the routine total 25(OH)D assessment.}, language = {en} } @article{MuellerEngelMuelleretal.2018, author = {Mueller, Steffen and Engel, Tilman and M{\"u}ller, Juliane and Stoll, Josefine and Baur, Heiner and Mayer, Frank}, title = {Sensorimotor exercises and enhanced trunk function}, series = {International journal of sports medicine}, volume = {39}, journal = {International journal of sports medicine}, number = {7}, publisher = {Thieme}, address = {Stuttgart}, issn = {0172-4622}, doi = {10.1055/a-0592-7286}, pages = {555 -- 563}, year = {2018}, abstract = {The aim of this study was to investigate the effect of a 6-week sensorimotor or resistance training on maximum trunk strength and response to sudden, high-intensity loading in athletes. Interventions showed no significant difference for maximum strength in concentric and eccentric testing (p>0.05). For perturbation compensation, higher peak torque response following SMT (Extension: +24Nm 95\%CI +/- 19Nm; Rotation: + 19Nm 95\%CI +/- 13Nm) and RT (Extension: +35Nm 95\%CI +/- 16Nm; Rotation: +5Nm 95\%CI +/- 4Nm) compared to CG (Extension: -4Nm 95\%CI +/- 16Nm; Rotation: -2Nm 95\%CI +/- 4Nm) was present (p<0.05).}, language = {en} } @misc{BornhorstKippHaaseetal.2018, author = {Bornhorst, Julia and Kipp, Anna P. and Haase, Hajo and Meyer, Soeren and Schwerdtle, Tanja}, title = {The crux of inept biomarkers for risks and benefits of trace elements}, series = {Trends in Analytical Chemistry}, volume = {104}, journal = {Trends in Analytical Chemistry}, publisher = {Elsevier}, address = {Oxford}, issn = {0165-9936}, doi = {10.1016/j.trac.2017.11.007}, pages = {183 -- 190}, year = {2018}, abstract = {Nowadays, the role of trace elements (TE) is of growing interest because dyshomeostasis of selenium (Se), manganese (Mn), zinc (Zn), and copper (Cu) is supposed to be a risk factor for several diseases. Thereby, research focuses on identifying new biomarkers for the TE status to allow for a more reliable description of the individual TE and health status. This review mirrors a lack of well-defined, sensitive, and selective biomarkers and summarizes technical limitations to measure them. Thus, the capacity to assess the relationship between dietary TE intake, homeostasis, and health is restricted, which would otherwise provide the basis to define adequate intake levels of single TE in both healthy and diseased humans. Besides that, our knowledge is even more limited with respect to the real life situation of combined TE intake and putative interactions between single TE.}, language = {en} } @article{MaaresDumanKeiletal.2018, author = {Maares, Maria and Duman, Ayse and Keil, Claudia and Schwerdtle, Tanja and Haase, Hajo}, title = {The impact of apical and basolateral albumin on intestinal zinc resorption in the Caco-2/HT-29-MTX co-culture model}, series = {Metallomics : integrated biometal science}, volume = {10}, journal = {Metallomics : integrated biometal science}, number = {7}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/c8mt00064f}, pages = {979 -- 991}, year = {2018}, abstract = {The molecular mechanisms of intestinal zinc resorption and its regulation are still topics of ongoing research. To this end, the application of suitable in vitro intestinal models, optimized with regard to their cellular composition and medium constituents, is of crucial importance. As one vital aspect, the impact of cell culture media or buffer compounds, respectively, on the speciation and cellular availability of zinc has to be considered when investigating zinc resorption. Thus, the present study aims to investigate the impact of serum, and in particular its main constituent serum albumin, on zinc uptake and toxicity in the intestinal cell line Caco-2. Furthermore, the impact of serum albumin on zinc resorption is analyzed using a co-culture of Caco-2 cells and the mucin-producing goblet cell line HT-29-MTX. Apically added albumin significantly impaired zinc uptake into enterocytes and buffered its cytotoxicity. Yet, undigested albumin does not occur in the intestinal lumen in vivo and impairment of zinc uptake was abrogated by digestion of albumin. Interestingly, zinc uptake, as well as gene expression studies of mt1a and selected intestinal zinc transporters after zinc incubation for 24 h, did not show significant differences between 0 and 10\% serum. Importantly, the basolateral application of serum in a transport study significantly enhanced fractional apical zinc resorption, suggesting that the occurrence of a zinc acceptor in the plasma considerably affects intestinal zinc resorption. This study demonstrates that the apical and basolateral medium composition is crucial when investigating zinc, particularly its intestinal resorption, using in vitro cell culture.}, language = {en} } @article{GubertPuntelLehmenetal.2018, author = {Gubert, Priscila and Puntel, Bruna and Lehmen, Tassia and Fessel, Joshua P. and Cheng, Pan and Bornhorst, Julia and Trindade, Lucas Siqueira and Avila, Daiana S. and Aschner, Michael and Soares, Felix A. A.}, title = {Metabolic effects of manganese in the nematode Caenorhabditis elegans through DAergic pathway and transcription factors activation}, series = {Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system}, volume = {67}, journal = {Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0161-813X}, doi = {10.1016/j.neuro.2018.04.008}, pages = {65 -- 72}, year = {2018}, abstract = {Manganese (Mn) is an essential trace element for physiological functions since it acts as an enzymatic co-factor. Nevertheless, overexposure to Mn has been associated with a pathologic condition called manganism. Furthermore, Mn has been reported to affect lipid metabolism by mechanisms which have yet to be established. Herein, we used the nematode Caenorhabditis elegans to examine Mn's effects on the dopaminergic (DAergic) system and determine which transcription factors that regulate with lipid metabolism are affected by it. Worms were exposed to Mn for four hours in the presence of bacteria and in a liquid medium (85 mM NaCl). Mn increased fat storage as evidenced both by Oil Red O accumulation and triglyceride levels. In addition, metabolic activity was reduced as a reflection of decreased oxygen consumption caused by Mn. Mn also affected feeding behavior as evidenced by decreased pharyngeal pumping rate. DAergic neurons viability were not altered by Mn, however the dopamine levels were significantly reduced following Mn exposure. Furthermore, the expression of sbp-1 transcription factor and let-363 protein kinase responsible for lipid accumulation control was increased and decreased, respectively, by Mn. Altogether, our data suggest that Mn increases the fat storage in C. elegans, secondary to DAergic system alterations, under the control of SBP-1 and LET-363 proteins.}, language = {en} } @article{SammoudNevillNegraetal.2018, author = {Sammoud, Senda and Nevill, Alan Michael and Negra, Yassine and Bouguezzi, Raja and Chaabene, Helmi and Hachana, Younes}, title = {100-m Breaststroke Swimming Performance in Youth Swimmers}, series = {Pediatric exercise science}, volume = {30}, journal = {Pediatric exercise science}, number = {3}, publisher = {Human Kinetics Publ.}, address = {Champaign}, issn = {0899-8493}, doi = {10.1123/pes.2017-0220}, pages = {393 -- 401}, year = {2018}, abstract = {This study aimed to estimate the optimal body size, limb segment length, and girth or breadth ratios of 100-m breaststroke performance in youth swimmers. In total, 59 swimmers [male: n= 39, age = 11.5 (1.3) y; female: n= 20, age = 12.0 (1.0) y] participated in this study. To identify size/shape characteristics associated with 100-m breaststroke swimming performance, we computed a multiplicative allometric log-linear regression model, which was refined using backward elimination. Results showed that the 100-m breaststroke performance revealed a significant negative association with fat mass and a significant positive association with the segment length ratio (arm ratio = hand length/forearm length) and limb girth ratio (girth ratio = forearm girth/wrist girth). In addition, leg length, biacromial breadth, and biiliocristal breadth revealed significant positive associations with the 100-m breaststroke performance. However, height and body mass did not contribute to the model, suggesting that the advantage of longer levers was limb-specific rather than a general whole-body advantage. In fact, it is only by adopting multiplicative allometric models that the previously mentioned ratios could have been derived. These results highlighted the importance of considering anthropometric characteristics of youth breaststroke swimmers for talent identification and/or athlete monitoring purposes. In addition, these findings may assist orienting swimmers to the appropriate stroke based on their anthropometric characteristics.}, language = {en} } @misc{BeckerRiethmuellerSeitzetal.2018, author = {Becker, Katrin Anne and Riethmueller, Joachim and Seitz, Aaron P. and Gardner, Aaron and Boudreau, Ryan and Kamler, Markus and Kleuser, Burkhard and Schuchman, Edward and Caldwell, Charles C. and Edwards, Michael J. and Grassme, Heike and Brodlie, Malcolm and Gulbins, Erich}, title = {Sphingolipids as targets for inhalation treatment of cystic fibrosis}, series = {Advanced drug delivery reviews}, volume = {133}, journal = {Advanced drug delivery reviews}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0169-409X}, doi = {10.1016/j.addr.2018.04.015}, pages = {66 -- 75}, year = {2018}, abstract = {Studies over the past several years have demonstrated the important role of sphingolipids in cystic fibrosis (CF), chronic obstructive pulmonary disease and acute lung injury. Ceramide is increased in airway epithelial cells and alveolar macrophages of CF mice and humans, while sphingosine is dramatically decreased. This increase in ceramide results in chronic inflammation, increased death of epithelial cells, release of DNA into the bronchial lumen and thereby an impairment of mucociliary clearance; while the lack of sphingosine in airway epithelial cells causes high infection susceptibility in CF mice and possibly patients. The increase in ceramide mediates an ectopic expression of beta 1-integrins in the luminal membrane of CF epithelial cells, which results, via an unknown mechanism, in a down-regulation of acid ceramidase. It is predominantly this down-regulation of acid ceramidase that results in the imbalance of ceramide and sphingosine in CF cells. Correction of ceramide and sphingosine levels can be achieved by inhalation of functional acid sphingomyelinase inhibitors, recombinant acid ceramidase or by normalization of beta 1-integrin expression and subsequent re-expression of endogenous acid ceramidase. These treatments correct pulmonary inflammation and prevent or treat, respectively, acute and chronic pulmonary infections in CF mice with Staphylococcus aureus and mucoid or non-mucoid Pseudomonas aeruginosa. Inhalation of sphingosine corrects sphingosine levels only and seems to mainly act against the infection. Many antidepressants are functional inhibitors of the acid sphingomyelinase and were designed for systemic treatment of major depression. These drugs could be repurposed to treat CF by inhalation.}, language = {en} } @article{SchwingshacklRuzanskaAntonetal.2018, author = {Schwingshackl, Lukas and Ruzanska, Ulrike Alexandra and Anton, Verena and Wallroth, Raphael and Ohla, Kathrin and Knueppel, Sven and Schulze, Matthias Bernd and Pischon, Tobias and Deutschbein, Johannes and Schenk, Liane and Warschburger, Petra and Harttig, Ulrich and Boeing, Heiner and Bergmann, Manuela M.}, title = {The NutriAct Family Study: a web-based prospective study on the epidemiological, psychological and sociological basis of food choice}, series = {BMC public health}, volume = {18}, journal = {BMC public health}, publisher = {BMC}, address = {London}, issn = {1471-2458}, doi = {10.1186/s12889-018-5814-x}, pages = {12}, year = {2018}, abstract = {Background: Most studies on food choice have been focussing on the individual level but familial aspects may also play an important role. This paper reports of a novel study that will focus on the familial aspects of the formation of food choice among men and women aged 50-70 years by recruiting spouses and siblings (NutriAct Family Study; NFS). Discussion: Until August 4th 2017, 4783 EPIC-Participants were contacted by mail of which 446 persons recruited 2 to 5 family members (including themselves) resulting in 1032 participants, of whom 82\% had started answering or already completed the questionnaires. Of the 4337 remaining EPIC-participants who had been contacted, 1040 (24\%) did not respond at all, and 3297 (76\%) responded but declined, in 51\% of the cases because of the request to recruit at least 2 family members in the respective age range. The developed recruitment procedures and web-based methods of data collection are capable to generate the required study population including the data on individual and inter-personal determinants which will be linkable to food choice. The information on familial links among the study participants will show the role of familial traits in midlife for the adoption of food choices supporting healthy aging.}, language = {en} } @article{GaoWangZhangetal.2018, author = {Gao, Lin-rui and Wang, Guang and Zhang, Jing and Li, Shuai and Chuai, Manli and Bao, Yongping and Hocher, Berthold and Yang, Xuesong}, title = {High salt-induced excess reactive oxygen species production resulted in heart tube malformation during gastrulation}, series = {Journal of Cellular Physiology}, volume = {233}, journal = {Journal of Cellular Physiology}, number = {9}, publisher = {Wiley}, address = {Hoboken}, issn = {0021-9541}, doi = {10.1002/jcp.26528}, pages = {7120 -- 7133}, year = {2018}, abstract = {An association has been proved between high salt consumption and cardiovascular mortality. In vertebrates, the heart is the first functional organ to be formed. However, it is not clear whether high-salt exposure has an adverse impact on cardiogenesis. Here we report high-salt exposure inhibited basement membrane breakdown by affecting RhoA, thus disturbing the expression of Slug/E-cadherin/N-cadherin/Laminin and interfering with mesoderm formation during the epithelial-mesenchymal transition(EMT). Furthermore, the DiI(+) cell migration trajectory in vivo and scratch wound assays in vitro indicated that high-salt exposure restricted cell migration of cardiac progenitors, which was caused by the weaker cytoskeleton structure and unaltered corresponding adhesion junctions at HH7. Besides, down-regulation of GATA4/5/6, Nkx2.5, TBX5, and Mef2c and up-regulation of Wnt3a/-catenin caused aberrant cardiomyocyte differentiation at HH7 and HH10. High-salt exposure also inhibited cell proliferation and promoted apoptosis. Most importantly, our study revealed that excessive reactive oxygen species(ROS)generated by high salt disturbed the expression of cardiac-related genes, detrimentally affecting the above process including EMT, cell migration, differentiation, cell proliferation and apoptosis, which is the major cause of malformation of heart tubes.}, language = {en} } @misc{JamnokSanchaisuriyaYamsrietal.2018, author = {Jamnok, Jutatip and Sanchaisuriya, Kanokwan and Yamsri, Supawadee and Fucharoen, Goonnapa and Fucharoen, Supan and Schweigert, Florian J. and Sanchaisuriya, Pattara}, title = {Application of a new portable nephelometer for screening thalassemia in countries with limited resources}, series = {International Journal of Laboratory Hematology}, volume = {40}, journal = {International Journal of Laboratory Hematology}, publisher = {Wiley}, address = {Hoboken}, issn = {1751-5521}, pages = {62 -- 62}, year = {2018}, language = {en} } @article{VogelKamitzHallahanetal.2018, author = {Vogel, Heike and Kamitz, Anne and Hallahan, Nicole and Lebek, Sandra and Schallschmidt, Tanja and Jonas, Wenke and J{\"a}hnert, Markus and Gottmann, Pascal and Zellner, Lisa and Kanzleiter, Timo and Damen, Mareike and Altenhofen, Delsi and Burkhardt, Ralph and Renner, Simone and Dahlhoff, Maik and Wolf, Eckhard and M{\"u}ller, Timo Dirk and Bl{\"u}her, Matthias and Joost, Hans-Georg and Chadt, Alexandra and Al-Hasani, Hadi and Sch{\"u}rmann, Annette}, title = {A collective diabetes cross in combination with a computational framework to dissect the genetics of human obesity and Type 2 diabetes}, series = {Human molecular genetics}, volume = {27}, journal = {Human molecular genetics}, number = {17}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0964-6906}, doi = {10.1093/hmg/ddy217}, pages = {3099 -- 3112}, year = {2018}, abstract = {To explore the genetic determinants of obesity and Type 2 diabetes (T2D), the German Center for Diabetes Research (DZD) conducted crossbreedings of the obese and diabetes-prone New Zealand Obese mouse strain with four different lean strains (B6, DBA, C3H, 129P2) that vary in their susceptibility to develop T2D. Genome-wide linkage analyses localized more than 290 quantitative trait loci (QTL) for obesity, 190 QTL for diabetes-related traits and 100 QTL for plasma metabolites in the out-cross populations. A computational framework was developed that allowed to refine critical regions and to nominate a small number of candidate genes by integrating reciprocal haplotype mapping and transcriptome data. The efficiency of the complex procedure was demonstrated for one obesity QTL. The genomic interval of 35 Mb with 502 annotated candidate genes was narrowed down to six candidates. Accordingly, congenic mice retained the obesity phenotype owing to an interval that contains three of the six candidate genes. Among these the phospholipase PLA2G4A exhibited an elevated expression in adipose tissue of obese human subjects and is therefore a critical regulator of the obesity locus. Together, our broad and complex approach demonstrates that combined- and comparative-cross analysis exhibits improved mapping resolution and represents a valid tool for the identification of disease genes.}, language = {en} } @misc{JamnokSanchaisuriyaYamsrietal.2018, author = {Jamnok, Jutatip and Sanchaisuriya, Kanokwan and Yamsri, Supawadee and Fucharoen, Goonnapa and Fucharoen, Supan and Schweigert, Florian J. and Sanchaisuriya, Pattara}, title = {Application of a new portable nephelometer for screening thalassemia in countries with limited resources}, series = {International journal of laboratory hematology}, volume = {40}, journal = {International journal of laboratory hematology}, publisher = {Wiley}, address = {Hoboken}, issn = {1751-5521}, pages = {62 -- 62}, year = {2018}, abstract = {One-tube osmotic fragility (OF) test is a rapid test used widely for screening thalassemia in countries with limited resources. The test has important limitation in that its accuracy relies on observers' experience. The iCheck Turbidity is a prototype of portable nephelometer developed by BioAnalyt (Bioanalyt GmbH, Germany). In this study, we assessed the applicability of the iCheck Turbidity, for checking turbidity of the OF-test}, language = {en} } @article{RuszkiewiczdeMacedoMirandaVizueteetal.2018, author = {Ruszkiewicz, Joanna A. and de Macedo, Gabriel Teixeira and Miranda-Vizuete, Antonio and Teixeira da Rocha, Joao B. and Bowman, Aaron B. and Bornhorst, Julia and Schwerdtle, Tanja and Aschner, Michael}, title = {The cytoplasmic thioredoxin system in Caenorhabditis elegans affords protection from methylmercury in an age-specific manner}, series = {Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system}, volume = {68}, journal = {Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0161-813X}, doi = {10.1016/j.neuro.2018.08.007}, pages = {189 -- 202}, year = {2018}, abstract = {Methylmercury (MeHg) is an environmental pollutant linked to many neurological defects, especially in developing individuals. The thioredoxin (TRX) system is a key redox regulator affected by MeHg toxicity, however the mechanisms and consequences of MeHg-induced dysfunction are not completely understood. This study evaluated the role of the TRX system in C. elegans susceptibility to MeHg during development. Worms lacking or overexpressing proteins from the TRX family were exposed to MeHg for 1 h at different developmental stage: L1, L4 and adult. Worms without cytoplasmic thioredoxin system exhibited age-specific susceptibility to MeHg when compared to wild-type (wt). This susceptibility corresponded partially to decreased total glutathione (GSH) levels and enhanced degeneration of dopaminergic neurons. In contrast, the overexpression of the cytoplasmic system TRX-1/TRXR-1 did not provide substantial protection against MeHg. Moreover, transgenic worms exhibited decreased protein expression for cytoplasmic thioredoxin reductase (TRXR-1). Both mitochondrial thioredoxin system TRX-2/TRXR-2, as well as other thioredoxin-like proteins: TRX-3, TRX-4, TRX-5 did not show significant role in C. elegans resistance to MeHg. Based on the current findings, the cytoplasmic thioredoxin system TRX-1/TRXR-1 emerges as an important age-sensitive protectant against MeHg toxicity in C. elegans.}, 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} } @misc{KrsticReinischSchuppetal.2018, author = {Krstic, Jelena and Reinisch, Isabel and Schupp, Michael and Schulz, Tim Julius and Prokesch, Andreas}, title = {p53 functions in adipose tissue metabolism and homeostasis}, series = {International journal of molecular sciences}, volume = {19}, journal = {International journal of molecular sciences}, number = {9}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms19092622}, pages = {21}, year = {2018}, abstract = {As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms to humans. A function not directly related to tumor suppression, such as the regulation of metabolism in nontransformed cells, could explain this selective pressure. While this role of p53 in cellular metabolism is gradually emerging, it is imperative to dissect the tissue-and cell-specific actions of p53 and its downstream signaling pathways. In this review, we focus on studies reporting p53's impact on adipocyte development, function, and maintenance, as well as the causes and consequences of altered p53 levels in white and brown adipose tissue (AT) with respect to systemic energy homeostasis. While whole body p53 knockout mice gain less weight and fat mass under a high-fat diet owing to increased energy expenditure, modifying p53 expression specifically in adipocytes yields more refined insights: (1) p53 is a negative regulator of in vitro adipogenesis; (2) p53 levels in white AT are increased in diet-induced and genetic obesity mouse models and in obese humans; (3) functionally, elevated p53 in white AT increases senescence and chronic inflammation, aggravating systemic insulin resistance; (4) p53 is not required for normal development of brown AT; and (5) when p53 is activated in brown AT in mice fed a high-fat diet, it increases brown AT temperature and brown AT marker gene expression, thereby contributing to reduced fat mass accumulation. In addition, p53 is increasingly being recognized as crucial player in nutrient sensing pathways. Hence, despite existence of contradictory findings and a varying density of evidence, several functions of p53 in adipocytes and ATs have been emerging, positioning p53 as an essential regulatory hub in ATs. Future studies need to make use of more sophisticated in vivo model systems and should identify an AT-specific set of p53 target genes and downstream pathways upon different (nutrient) challenges to identify novel therapeutic targets to curb metabolic diseases}, language = {en} } @article{PeresArantesMiahetal.2018, author = {Peres, Tanara Vieira and Arantes, Leticia P. and Miah, Mahfuzur R. and Bornhorst, Julia and Schwerdtle, Tanja and Bowman, Aaron B. and Leal, Rodrigo B. and Aschner, Michael}, title = {Role of Caenorhabditis elegans AKT-1/2 and SGK-1 in Manganese Toxicity}, series = {Neurotoxicity Research}, volume = {34}, journal = {Neurotoxicity Research}, number = {3}, publisher = {Springer}, address = {New York}, issn = {1029-8428}, doi = {10.1007/s12640-018-9915-1}, pages = {584 -- 596}, year = {2018}, abstract = {Excessive levels of the essential metal manganese (Mn) may cause a syndrome similar to Parkinson's disease. The model organism Caenorhabditis elegans mimics some of Mn effects in mammals, including dopaminergic neurodegeneration, oxidative stress, and increased levels of AKT. The evolutionarily conserved insulin/insulin-like growth factor-1 signaling pathway (IIS) modulates worm longevity, metabolism, and antioxidant responses by antagonizing the transcription factors DAF-16/FOXO and SKN-1/Nrf-2. AKT-1, AKT-2, and SGK-1 act upstream of these transcription factors. To study the role of these proteins in C. elegans response to Mn intoxication, wild-type N2 and loss-of-function mutants were exposed to Mn (2.5 to 100 mM) for 1 h at the L1 larval stage. Strains with loss-of-function in akt-1, akt-2, and sgk-1 had higher resistance to Mn compared to N2 in the survival test. All strains tested accumulated Mn similarly, as shown by ICP-MS. DAF-16 nuclear translocation was observed by fluorescence microscopy in WT and loss-of-function strains exposed to Mn. qRT-PCR data indicate increased expression of γ-glutamyl cysteine synthetase (GCS-1) antioxidant enzyme in akt-1 mutants. The expression of sod-3 (superoxide dismutase homologue) was increased in the akt-1 mutant worms, independent of Mn treatment. However, dopaminergic neurons degenerated even in the more resistant strains. Dopaminergic function was evaluated with the basal slowing response behavioral test and dopaminergic neuron integrity was evaluated using worms expressing green fluorescent protein (GFP) under the dopamine transporter (DAT-1) promoter. These results suggest that AKT-1/2 and SGK-1 play a role in C. elegans response to Mn intoxication. However, tissue-specific responses may occur in dopaminergic neurons, contributing to degeneration.}, language = {en} } @misc{GalbeteSchwingshacklSchwedhelmetal.2018, author = {Galbete, Cecilia and Schwingshackl, Lukas and Schwedhelm, Carolina and Boeing, Heiner and Schulze, Matthias Bernd}, title = {Evaluating Mediterranean diet and risk of chronic disease in cohort studies}, series = {European journal of epidemiology}, volume = {33}, journal = {European journal of epidemiology}, number = {10}, publisher = {Springer}, address = {Dordrecht}, issn = {0393-2990}, doi = {10.1007/s10654-018-0427-3}, pages = {909 -- 931}, year = {2018}, abstract = {Several meta-analyses have been published summarizing the associations of the Mediterranean diet (MedDiet) with chronic diseases. We evaluated the quality and credibility of evidence from these meta-analyses as well as characterized the different indices used to define MedDiet and re-calculated the associations with the different indices identified. We conducted an umbrella review of meta-analyses on cohort studies evaluating the association of the MedDiet with type 2 diabetes, cardiovascular disease, cancer and cognitive-related diseases. We used the AMSTAR (A MeaSurement Tool to Assess systematic Reviews) checklist to evaluate the methodological quality of the meta-analyses, and the NutriGrade scoring system to evaluate the credibility of evidence. We also identified different indices used to define MedDiet; tests for subgroup differences were performed to compare the associations with the different indices when at least 2 studies were available for different definitions. Fourteen publications were identified and within them 27 meta-analyses which were based on 70 primary studies. Almost all meta-analyses reported inverse associations between MedDiet and risk of chronic disease, but the credibility of evidence was rated low to moderate. Moreover, substantial heterogeneity was observed on the use of the indices assessing adherence to the MedDiet, but two indices were the most used ones [Trichopoulou MedDiet (tMedDiet) and alternative MedDiet (aMedDiet)]. Overall, we observed little difference in risk associations comparing different MedDiet indices in the subgroup meta-analyses. Future prospective cohort studies are advised to use more homogenous definitions of the MedDiet to improve the comparability across meta-analyses.}, language = {en} } @article{OdongoSchlotzBaldermannetal.2018, author = {Odongo, Grace Akinyi and Schlotz, Nina and Baldermann, Susanne and Neugart, Susanne and Huyskens-Keil, Susanne and Ngwene, Benard and Trierweiler, Bernhard and Schreiner, Monika and Lamy, Evelyn}, title = {African Nightshade (Solanum scabrum Mill.)}, series = {Nutrients}, volume = {10}, journal = {Nutrients}, number = {10}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu10101532}, pages = {20}, year = {2018}, abstract = {Plant cultivation and processing may impact nutrient and phytochemical content of vegetables. The present study aimed at determining the influence of cultivation and processing on the health promoting capacity of African nightshade (Solanum scabrum Mill.) leaves, an indigenous vegetable, rich in nutrients and phytochemicals. Anti-genotoxicity against the human liver carcinogen aflatoxin B1 (AFB(1)) as determined by the comet assay and radical oxygen species (ROS) scavenging capacity of ethanolic and aqueous extracts were investigated in human derived liver (HepG2) cells. ROS scavenging activity was assessed using electron paramagnetic spin resonance and quantification of ARE/Nrf2 mediated gene expression. The cultivation was done under different environmental conditions. The processing included fermentation and cooking; postharvest ultraviolet irradiation (UV-C) treatment was also investigated. Overall, S. scabrum extracts showed strong health promoting potential, the highest potential was observed with the fermented extract, which showed a 60\% reduction of AFB(1) induced DNA damage and a 38\% reduction in FeSO4 induced oxidative stress. The content of total polyphenols, carotenoids and chlorophylls was indeed affected by cultivation and processing. Based on the present in vitro findings consumption of S. scabrum leaves could be further encouraged, preferentially after cooking or fermentation of the plant.}, language = {en} } @misc{Kleuser2018, author = {Kleuser, Burkhard}, title = {The enigma of sphingolipids in health and disease}, series = {International journal of molecular sciences}, volume = {19}, journal = {International journal of molecular sciences}, number = {10}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms19103126}, pages = {3}, year = {2018}, language = {en} } @misc{Henze2018, author = {Henze, Andrea}, title = {Proteinoxidation als Indikator des Alterungsph{\"a}notyps und Target einer individualisierten Ern{\"a}hrungsintervention (ProAID)}, series = {Ern{\"a}hrungs-Umschau : Forschung \& Praxis}, volume = {65}, journal = {Ern{\"a}hrungs-Umschau : Forschung \& Praxis}, number = {10}, publisher = {Umschau-Zeitschriftenverl.}, address = {Frankfurt, Main}, issn = {0174-0008}, pages = {M566 -- M567}, year = {2018}, abstract = {Oxidative posttranslationale Modifikationen endogener Proteine werden v. a. durch reaktive Sauerstoff- und Stickstoffspezies (engl:. Reactive Oxygen Species, ROS, reactive nitrogen species, RNS) hervorgerufen und k{\"o}nnen sowohl reversibel (z. B. Disulfidbindungen) als auch irreversibel (z. B. Proteincarbonyle) erfolgen [1-3]. Lange wurde angenommen, dass oxidative posttranslationale Proteinmodifikationen (oxPTPM) nur von untergeordneter Bedeutung f{\"u}r den Metabolismus sind. Tats{\"a}chlich handelt es sich jedoch um einen physiologischen Prozess, der {\"u}ber die Modulation der Proteinstruktur auch die Proteinfunktion (z. B. Enzymaktivit{\"a}t, Stabilit{\"a}t) und somit zahlreiche Stoffwechselwege wie den Energiestoffwechsel, die Immunfunktion, die vaskul{\"a}re Funktion sowie Apoptose und Genexpression beeinflussen kann. Die Bildung von oxPTPM ist dabei hochreguliert und h{\"a}ngt u. a. von der Proteinstruktur, der Verf{\"u}gbarkeit von ROS und RNS sowie dem lokalen Mikromilieu der Zelle ab [2, 4].}, language = {de} } @article{ReichelRheinHofmannetal.2018, author = {Reichel, Martin and Rhein, Cosima and Hofmann, Lena M. and Monti, Juliana and Japtok, Lukasz and Langgartner, Dominik and F{\"u}chsl, Andrea M. and Kleuser, Burkhard and Gulbins, Erich and Hellerbrand, Claus and Reber, Stefan O. and Kornhuber, Johannes}, title = {Chronic Psychosocial Stress in Mice Is Associated With Increased Acid Sphingomyelinase Activity in Liver and Serum and With Hepatic C16:0-Ceramide Accumulation}, series = {Frontiers in Psychiatry}, volume = {9}, journal = {Frontiers in Psychiatry}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-0640}, doi = {10.3389/fpsyt.2018.00496}, pages = {8}, year = {2018}, abstract = {Chronic psychosocial stress adversely affects human morbidity and is a risk factor for inflammatory disorders, liver diseases, obesity, metabolic syndrome, and major depressive disorder (MDD). In recent studies, we found an association of MDD with an increase of acid sphingomyelinase (ASM) activity. Thus, we asked whether chronic psychosocial stress as a detrimental factor contributing to the emergence of MDD would also affect ASM activity and sphingolipid (SL) metabolism. To induce chronic psychosocial stress in male mice we employed the chronic subordinate colony housing (CSC) paradigm and compared them to non-stressed single housed control (SHC) mice. We determined Asm activity in liver and serum, hepatic SL concentrations as well as hepatic mRNA expression of genes involved in SL metabolism. We found that hepatic Asm activity was increased by 28\% (P = 0.006) and secretory Asm activity by 47\% (P = 0.002) in stressed mice. C16:0-Cer was increased by 40\% (P = 0.008). Gene expression analysis further revealed an increased expression of tumor necrosis factor (TNF)-alpha (P = 0.009) and of several genes involved in SL metabolism (Cers5, P = 0.028; Cers6, P = 0.045; Gba, P = 0.049; Gba2, P = 0.030; Ormdl2, P = 0.034; Smpdl3B; P = 0.013). Our data thus provides first evidence that chronic psychosocial stress, at least in mice, induces alterations in SL metabolism, which in turn might be involved in mediating the adverse health effects of chronic psychosocial stress and peripheral changes occurring in mood disorders.}, language = {en} } @misc{UhligGehreKammereretal.2018, author = {Uhlig, Katja and Gehre, Christian P. and Kammerer, Sarah and K{\"u}pper, Jan-Heiner and Coleman, Charles Dominic and P{\"u}schel, Gerhard Paul and Duschl, Claus}, title = {Real-time monitoring of oxygen consumption of hepatocytes in a microbioreactor}, series = {Toxicology letters}, volume = {295}, journal = {Toxicology letters}, publisher = {Elsevier}, address = {Clare}, issn = {0378-4274}, doi = {10.1016/j.toxlet.2018.06.652}, pages = {S115 -- S115}, year = {2018}, language = {en} } @article{PloehnEdelmannJaptoketal.2018, author = {Pl{\"o}hn, Svenja and Edelmann, B{\"a}rbel and Japtok, Lukasz and He, Xingxuan and Hose, Matthias and Hansen, Wiebke and Schuchman, Edward H. and Eckstein, Anja and Berchner-Pfannschmidt, Utta}, title = {CD40 enhances sphingolipids in orbital fibroblasts}, series = {Investigative ophthalmology \& visual science}, volume = {59}, journal = {Investigative ophthalmology \& visual science}, number = {13}, publisher = {Association for Research in Vision and Opthalmology}, address = {Rockville}, issn = {0146-0404}, doi = {10.1167/iovs.18-25466}, pages = {5391 -- 5397}, year = {2018}, abstract = {METHODS. OFs and T cells were derived from GO patients and healthy control (Ctl) persons. S1P abundance in orbital tissues was evaluated by immunofluorescence. OFs were stimulated with CD40 ligand and S1P levels were determined by ELISA. Further, activities of acid sphingomyelinase (ASM), acid ceramidase, and sphingosine kinase were measured by ultraperformance liquid chromatography. Sphingosine and ceramide contents were analyzed by mass spectrometry. Finally, the role for S1P in T-cell attraction was investigated by T-cell migration assays. RESULTS. GO orbital tissue showed elevated amounts of S1P as compared to control samples. Stimulation of CD40 induced S1P expression in GO-derived OFs, while Ctl-OFs remained unaffected. A significant increase of ASM and sphingosine kinase activities, as well as lipid formation, was observed in GO-derived OFs. Migration assay of T cells in the presence of SphK inhibitor revealed that S1P released by GO-OFs attracted T cells for migration. CONCLUSIONS. The results demonstrated that CD40 ligand stimulates GO fibroblast to produce S1P, which is a driving force for T-cell migration. The results support the use of S1P receptor signaling modulators in GO management.}, language = {en} } @article{WirschingGrassmannEichelmannetal.2018, author = {Wirsching, Jan and Grassmann, Sophie and Eichelmann, Fabian and Harms, Laura Malin and Schenk, Matthew and Barth, Eva and Berndzen, Alide and Olalekan, Moses and Sarmini, Leen and Zuberer, Hedwig and Aleksandrova, Krasimira}, title = {Development and reliability assessment of a new quality appraisal tool for cross-sectional studies using biomarker data (BIOCROSS)}, series = {BMC Medical Research Methodology}, volume = {18}, journal = {BMC Medical Research Methodology}, publisher = {BMC}, address = {London}, issn = {1471-2288}, doi = {10.1186/s12874-018-0583-x}, pages = {8}, year = {2018}, abstract = {Background Biomarker-based analyses are commonly reported in observational epidemiological studies; however currently there are no specific study quality assessment tools to assist evaluation of conducted research. Accounting for study design and biomarker measurement would be important for deriving valid conclusions when conducting systematic data evaluation. Methods We developed a study quality assessment tool designed specifically to assess biomarker-based cross-sectional studies (BIOCROSS) and evaluated its inter-rater reliability. The tool includes 10-items covering 5 domains: 'Study rational', 'Design/Methods', 'Data analysis', 'Data interpretation' and 'Biomarker measurement', aiming to assess different quality features of biomarker cross-sectional studies. To evaluate the inter-rater reliability, 30 studies were distributed among 5 raters and intraclass correlation coefficients (ICC-s) were derived from respective ratings. Results The estimated overall ICC between the 5 raters was 0.57 (95\% Confidence Interval (CI): 0.38-0.74) indicating a good inter-rater reliability. The ICC-s ranged from 0.11 (95\% CI: 0.01-0.27) for the domain 'Study rational' to 0.56 (95\% CI: 0.40-0.72) for the domain 'Data interpretation'. Conclusion BIOCROSS is a new study quality assessment tool suitable for evaluation of reporting quality from cross-sectional epidemiological studies employing biomarker data. The tool proved to be reliable for use by biomedical scientists with diverse backgrounds and could facilitate comprehensive review of biomarker studies in human research.}, language = {en} } @article{WernoWilhelmiKuropkaetal.2018, author = {Werno, Martin Witold and Wilhelmi, Ilka and Kuropka, Benno and Ebert, Franziska and Freund, Christian and Sch{\"u}rmann, Annette}, title = {The GTPase ARFRP1 affects lipid droplet protein composition and triglyceride release from intracellular storage of intestinal Caco-2 cells}, series = {Biochemical and biophysical research communications}, volume = {506}, journal = {Biochemical and biophysical research communications}, number = {1}, publisher = {Elsevier}, address = {San Diego}, issn = {0006-291X}, doi = {10.1016/j.bbrc.2018.10.092}, pages = {259 -- 265}, year = {2018}, abstract = {Intestinal release of dietary triglycerides via chylomicrons is the major contributor to elevated postprandial triglyceride levels. Dietary lipids can be transiently stored in cytosolic lipid droplets (LDs) located in intestinal enterocytes for later release. ADP ribosylation factor-related protein 1 (ARFRP1) participates in processes of LD growth in adipocytes and in lipidation of lipoproteins in liver and intestine. This study aims to explore the impact of ARFRP1 on LD organization and its interplay with chylomicron-mediated triglyceride release in intestinal-like Caco-2 cells. Suppression of Arfrp1 reduced release of intracellularly derived triglycerides (0.69-fold) and increased the abundance of transitional endoplasmic reticulum ATPase TERA/VCP, fatty acid synthase-associated factor 2 (FAF2) and perilipin 2 (Plin2) at the LD surface. Furthermore, TERA/VCP and FAF2 co-occurred more frequently with ATGL at LDs, suggesting a reduced adipocyte triglyceride lipase (ATGL)-mediated lipolysis. Accordingly, inhibition of lipolysis reduced lipid release from intracellular storage pools by the same magnitude as Arfrp1 depletion. Thus, the lack of Arfrp1 increases the abundance of lipolysis-modulating enzymes TERA/VCP, FAF2 and Plin2 at LDs, which might decrease lipolysis and reduce availability of fatty acids for triglyceride synthesis and their release via chylomicrons. (C) 2018 The Authors. Published by Elsevier Inc.}, language = {en} }