@article{MaaresKeilKozaetal.2018, author = {Maares, Maria and Keil, Claudia and Koza, Jenny and Straubing, Sophia and Schwerdtle, Tanja and Haase, Hajo}, title = {In Vitro Studies on Zinc Binding and Buffering by Intestinal Mucins}, series = {International Journal of Molecular Sciences}, volume = {19}, journal = {International Journal of Molecular Sciences}, number = {9}, issn = {1422-0067}, doi = {10.3390/ijms19092662}, pages = {20}, year = {2018}, abstract = {The investigation of luminal factors influencing zinc availability and accessibility in the intestine is of great interest when analyzing parameters regulating intestinal zinc resorption. Of note, intestinal mucins were suggested to play a beneficial role in the luminal availability of zinc. Their exact zinc binding properties, however, remain unknown and the impact of these glycoproteins on human intestinal zinc resorption has not been investigated in detail. Thus, the aim of this study is to elucidate the impact of intestinal mucins on luminal uptake of zinc into enterocytes and its transfer into the blood. In the present study, in vitro zinc binding properties of mucins were analyzed using commercially available porcine mucins and secreted mucins of the goblet cell line HT-29-MTX. The molecular zinc binding capacity and average zinc binding affinity of these glycoproteins demonstrates that mucins contain multiple zinc-binding sites with biologically relevant affinity within one mucin molecule. Zinc uptake into the enterocyte cell line Caco-2 was impaired by zinc-depleted mucins. Yet this does not represent their form in the intestinal lumen in vivo under zinc adequate conditions. In fact, zinc-uptake studies into enterocytes in the presence of mucins with differing degree of zinc saturation revealed zinc buffering by these glycoproteins, indicating that mucin-bound zinc is still available for the cells. Finally, the impact of mucins on zinc resorption using three-dimensional cultures was studied comparing the zinc transfer of a Caco-2/HT-29-MTX co-culture and conventional Caco-2 monoculture. Here, the mucin secreting co-cultures yielded higher fractional zinc resorption and elevated zinc transport rates, suggesting that intestinal mucins facilitate the zinc uptake into enterocytes and act as a zinc delivery system for the intestinal epithelium.}, 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} } @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} } @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} } @article{NitezkiSchulzKraemer2018, author = {Nitezki, Tina and Schulz, Nadja and Kr{\"a}mer, Stephanie}, title = {Color matters}, series = {Laboratory animals : the international journal of laboratory animal science and welfare}, volume = {52}, journal = {Laboratory animals : the international journal of laboratory animal science and welfare}, number = {6}, publisher = {Sage Publ.}, address = {Thousand Oaks}, issn = {0023-6772}, doi = {10.1177/0023677218766370}, pages = {611 -- 620}, year = {2018}, abstract = {Concerning standardization of laboratory animal husbandry, only exiguous changes of habitat can potentially influence animal physiology or results of behavioral tests. Routinely, mice chow is dyed when different types of diets are dispensed. Given the fact that the dye itself has no effects on food odor or flavor, we wanted to test the hypothesis that the color of chow has an impact on food uptake in mice. Twelve-week-old male mice of different strains (C57BL/6J, DBA/2J, C3H/HeJ, BALB/cJ; n = 12/strain) were single-housed in PhenoMaster (R) cages. After acclimatization standard mice chow in different colors was administered. Food intake was monitored as a two-alternative choice test of different color combinations. All animals had an average food intake of 3 g/d and no preferences were observed when a combination of identically colored food was offered. Preference tests yielded significant aversion to blue food and significant attraction to yellow and green food in C57BL/6 and DBA/2J mice. In C3H/HeJ and BALB/cJ mice no color-related pattern occurred. Selected mice strains have known differences concerning functionality of their visual sense. C57BL/6 and DBA/2 mice are considered to be normal sighted at testing age, BALB/c is representative for albino strains and C3H mice carry mutations resulting in retinal alterations. Results suggesting that normal-sighted mice would be selective concerning food color when given the choice. Nevertheless, this does not influence overall quantity of food intake when animals were provided solely with food colored with a single dye. Moreover, visually impaired mice showed no color-related food preferences.}, 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} } @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{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} } @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{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} } @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{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} } @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} } @misc{GiulbudagianYeallandHoenzkeetal.2018, author = {Giulbudagian, Michael and Yealland, Guy and H{\"o}nzke, Stefan and Edlich, Alexander and Geisend{\"o}rfer, Birte and Kleuser, Burkhard and Hedtrich, Sarah and Calder{\´o}n, Marcelo}, title = {Breaking the barrier}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1030}, issn = {1866-8372}, doi = {10.25932/publishup-45930}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-459301}, pages = {450 -- 463}, year = {2018}, abstract = {Topical administration permits targeted, sustained delivery of therapeutics to human skin. Delivery to the skin, however, is typically limited to lipophilic molecules with molecular weight of < 500 Da, capable of crossing the stratum corneum. Nevertheless, there are indications protein delivery may be possible in barrier deficient skin, a condition found in several inflammatory skin diseases such as psoriasis, using novel nanocarrier systems. Methods: Water in water thermo-nanoprecipitation; dynamic light scattering; zeta potential measurement; nanoparticle tracking analysis; atomic force microscopy; cryogenic transmission electron microscopy; UV absorption; centrifugal separation membranes; bicinchoninic acid assay; circular dichroism; TNF alpha binding ELISA; inflammatory skin equivalent construction; human skin biopsies; immunohistochemistry; fluorescence microscopy; western blot; monocyte derived Langerhans cells; ELISA Results: Here, we report the novel synthesis of thermoresponsive nanogels (tNG) and the stable encapsulation of the anti-TNFa fusion protein etanercept (ETR) (similar to 150 kDa) without alteration to its structure, as well as temperature triggered release from the tNGs. Novel tNG synthesis without the use of organic solvents was conducted, permitting in situ encapsulation of protein during assembly, something that holds great promise for easy manufacture and storage. Topical application of ETR loaded tNGs to inflammatory skin equivalents or tape striped human skin resulted in efficient ETR delivery throughout the SC and into the viable epidermis that correlated with clear anti-inflammatory effects. Notably, effective ETR delivery depended on temperature triggered release following topical application. Conclusion: Together these results indicate tNGs hold promise as a biocompatible and easy to manufacture vehicle for stable protein encapsulation and topical delivery into barrier-deficient skin.}, 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 = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1047}, issn = {1866-8372}, doi = {10.25932/publishup-46906}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-469069}, 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} } @misc{MaaresKeilKozaetal.2018, author = {Maares, Maria and Keil, Claudia and Koza, Jenny and Straubing, Sophia and Schwerdtle, Tanja and Haase, Hajo}, title = {In Vitro Studies on Zinc Binding and Buffering by Intestinal Mucins}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1079}, issn = {1866-8372}, doi = {10.25932/publishup-46907}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-469078}, pages = {22}, year = {2018}, abstract = {The investigation of luminal factors influencing zinc availability and accessibility in the intestine is of great interest when analyzing parameters regulating intestinal zinc resorption. Of note, intestinal mucins were suggested to play a beneficial role in the luminal availability of zinc. Their exact zinc binding properties, however, remain unknown and the impact of these glycoproteins on human intestinal zinc resorption has not been investigated in detail. Thus, the aim of this study is to elucidate the impact of intestinal mucins on luminal uptake of zinc into enterocytes and its transfer into the blood. In the present study, in vitro zinc binding properties of mucins were analyzed using commercially available porcine mucins and secreted mucins of the goblet cell line HT-29-MTX. The molecular zinc binding capacity and average zinc binding affinity of these glycoproteins demonstrates that mucins contain multiple zinc-binding sites with biologically relevant affinity within one mucin molecule. Zinc uptake into the enterocyte cell line Caco-2 was impaired by zinc-depleted mucins. Yet this does not represent their form in the intestinal lumen in vivo under zinc adequate conditions. In fact, zinc-uptake studies into enterocytes in the presence of mucins with differing degree of zinc saturation revealed zinc buffering by these glycoproteins, indicating that mucin-bound zinc is still available for the cells. Finally, the impact of mucins on zinc resorption using three-dimensional cultures was studied comparing the zinc transfer of a Caco-2/HT-29-MTX co-culture and conventional Caco-2 monoculture. Here, the mucin secreting co-cultures yielded higher fractional zinc resorption and elevated zinc transport rates, suggesting that intestinal mucins facilitate the zinc uptake into enterocytes and act as a zinc delivery system for the intestinal epithelium.}, language = {en} } @misc{Kleuser2018, author = {Kleuser, Burkhard}, title = {Divergent role of sphingosine 1-phosphate in liver health and disease}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1051}, issn = {1866-8372}, doi = {10.25932/publishup-47439}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-474398}, pages = {20}, 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} } @misc{Kleuser2018, author = {Kleuser, Burkhard}, title = {The enigma of sphingolipids in health and disease}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1040}, issn = {1866-8372}, doi = {10.25932/publishup-47263}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-472637}, pages = {5}, year = {2018}, 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{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{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} } @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{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} } @article{FranzOstOttenetal.2018, author = {Franz, Kristina and Ost, Mario and Otten, Lindsey and Herpich, Catrin and Coleman, Verena and Endres, Anne-Sophie and Klaus, Susanne and M{\"u}ller-Werdan, Ursula and Norman, Kristina}, title = {Higher serum levels of fibroblast growth factor 21 in old patients with cachexia}, series = {Nutrition : the international journal of applied and basic nutritional sciences}, volume = {63-64}, journal = {Nutrition : the international journal of applied and basic nutritional sciences}, publisher = {Elsevier}, address = {New York}, issn = {0899-9007}, doi = {10.1016/j.nut.2018.11.004}, pages = {81 -- 86}, year = {2018}, abstract = {Objective: Fibroblast growth factor (FGF)21 is promptly induced by short fasting in animal models to regulate glucose and fat metabolism. Data on FGF21 in humans are inconsistent and FGF21 has not yet been investigated in old patients with cachexia, a complex syndrome characterized by inflammation and weight loss. The aim of this study was to explore the association of FGF21 with cachexia in old patients compared with their healthy counterparts. Methods: Serum FGF21 and its inactivating enzyme fibroblast activation protein (FAP)-cc were measured with enzyme-linked immunoassays. Cachexia was defined as >= 5\% weight loss in the previous 3 mo and concurrent anorexia (Council on Nutrition appetite questionnaire). Results: We included 103 patients with and without cachexia (76.9 +/- 5.2 y of age) and 56 healthy controls (72.9 +/- 5.9 y of age). Cachexia was present in 16.5\% of patients. These patients had significantly higher total FGF21 levels than controls (952.1 +/- 821.3 versus 525.2 +/- 560.3 pg/mL; P= 0.012) and the lowest FGF21 levels (293.3 +/- 150.9 pg/mL) were found in the control group (global P < 0.001). Although FAP-alpha did not differ between the three groups (global P = 0.082), bioactive FGF21 was significantly higher in patients with cachexia (global P = 0.002). Risk factor-adjusted regression analyses revealed a significant association between cachexia and total ((beta = 649.745 pg/mL; P < 0.001) and bioactive FGF21 (beta = 393.200 pg/mL; P <0.001), independent of sex, age, and body mass index. Conclusions: Patients with cachexia exhibited the highest FGF21 levels. Clarification is needed to determine whether this is an adaptive response to nutrient deprivation in disease-related cachexia or whether the increased FGF21 values contribute to the catabolic state. (C) 2018 Elsevier Inc. All rights reserved.}, language = {en} } @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{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{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{NitezkiKleuserKraemer2018, author = {Nitezki, Tina and Kleuser, Burkhard and Kr{\"a}mer, Stephanie}, title = {Fatal gastric distension in a gold thioglucose mouse model of obesity}, series = {Laboratory Animals}, volume = {53}, journal = {Laboratory Animals}, number = {1}, publisher = {Sage Publ.}, address = {Thousand Oaks}, issn = {0023-6772}, doi = {10.1177/0023677218803384}, pages = {89 -- 94}, year = {2018}, abstract = {This case report addresses the problem of underreporting negative results and adverse side effects in animal testing. We present our findings regarding a hyperphagic mouse model associated with unforeseen high mortality. The results outline the necessity of reporting detailed information in the literature to avoid duplication. Obese mouse models are essential in the study of obesity, metabolic syndrome and diabetes mellitus. An experimental model of obesity can be induced by the administration of gold thioglucose (GTG). After transcending the blood-brain barrier, the GTG molecule interacts with regions of the ventromedial hypothalamus, thereby primarily targeting glucose-sensitive neurons. When these neurons are impaired, mice become insensitive to the satiety effects of glucose and develop hyperphagia. In a pilot study for optimising dosage and body weight development, C57BL/6 mice were treated with GTG (0.5 mg/g body weight) or saline, respectively. Animals were provided a physiological amount of standard diet (5 g per animal) for the first 24 hours after treatment to prevent gastric dilatation. Within 24 hours after GTG injection, all GTG-treated animals died of gastric overload and subsequent circulatory shock. Animals developed severe attacks of hyperphagia, and as the amount of provided chow was restricted, mice exhibited unforeseen pica and ingested bedding material. These observations strongly suggest that restricted feeding is contraindicated concerning GTG application. Presumably, the impulse of excessive food intake was a strong driving force. Therefore, the actual degree of suffering in the GTG-induced model of hyperphagia should be revised from moderate to severe.}, 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} } @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} } @misc{PatheNeuschaeferRubeNeuschaeferRubeHaasetal.2018, author = {Pathe-Neusch{\"a}fer-Rube, Andrea and Neusch{\"a}fer-Rube, Frank and Haas, Gerald and Langoth-Fehringer, Nina and P{\"u}schel, Gerhard Paul}, title = {Cell-Based Reporter Release Assay to Determine the Potency of Proteolytic Bacterial Neurotoxins}, series = {Toxins}, journal = {Toxins}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-418141}, pages = {10}, year = {2018}, abstract = {Despite the implementation of cell-based replacement methods, the mouse lethality assay is still frequently used to determine the activity of botulinum toxin (BoNT) for medical use. One explanation is that due to the use of neoepitope-specific antibodies to detect the cleaved BoNT substrate, the currently devised assays can detect only one specific serotype of the toxin. Recently, we developed a cell-based functional assay, in which BoNT activity is determined by inhibiting the release of a reporter enzyme that is liberated concomitantly with the neurotransmitter from neurosecretory vesicles. In theory, this assay should be suitable to detect the activity of any BoNT serotype. Consistent with this assumption, the current study shows that the stimulus-dependent release of a luciferase from a differentiated human neuroblastoma-based reporter cell line (SIMA-hPOMC1-26-GLuc cells) was inhibited by BoNT-A and-C. Furthermore, this was also inhibited by BoNT-B and tetanus toxin to a lesser extent and at higher concentrations. In order to provide support for the suitability of this technique in practical applications, a dose-response curve obtained with a pharmaceutical preparation of BoNT-A closely mirrored the activity determined in the mouse lethality assay. In summary, the newly established cell-based assay may represent a versatile and specific alternative to the mouse lethality assay and other currently established cell-based assays.}, language = {en} } @article{PatheNeuschaeferRubeNeuschaeferRubeHaasetal.2018, author = {Pathe-Neusch{\"a}fer-Rube, Andrea and Neusch{\"a}fer-Rube, Frank and Haas, Gerald and Langoth-Fehringer, Nina and P{\"u}schel, Gerhard Paul}, title = {Cell-Based Reporter Release Assay to Determine the Potency of Proteolytic Bacterial Neurotoxins}, series = {Toxins}, volume = {10}, journal = {Toxins}, number = {9}, publisher = {Molecular Diversity Preservation International (MDPI)}, address = {Basel}, issn = {2072-6651}, doi = {10.3390/toxins10090360}, pages = {1 -- 10}, year = {2018}, abstract = {Despite the implementation of cell-based replacement methods, the mouse lethality assay is still frequently used to determine the activity of botulinum toxin (BoNT) for medical use. One explanation is that due to the use of neoepitope-specific antibodies to detect the cleaved BoNT substrate, the currently devised assays can detect only one specific serotype of the toxin. Recently, we developed a cell-based functional assay, in which BoNT activity is determined by inhibiting the release of a reporter enzyme that is liberated concomitantly with the neurotransmitter from neurosecretory vesicles. In theory, this assay should be suitable to detect the activity of any BoNT serotype. Consistent with this assumption, the current study shows that the stimulus-dependent release of a luciferase from a differentiated human neuroblastoma-based reporter cell line (SIMA-hPOMC1-26-GLuc cells) was inhibited by BoNT-A and-C. Furthermore, this was also inhibited by BoNT-B and tetanus toxin to a lesser extent and at higher concentrations. In order to provide support for the suitability of this technique in practical applications, a dose-response curve obtained with a pharmaceutical preparation of BoNT-A closely mirrored the activity determined in the mouse lethality assay. In summary, the newly established cell-based assay may represent a versatile and specific alternative to the mouse lethality assay and other currently established cell-based assays.}, language = {en} } @misc{HenkelColemanMacGregorofInneregnySchraplauetal.2018, author = {Henkel, Janin and Coleman Mac Gregor of Inneregny, Charles Dominic and Schraplau, Anne and J{\"o}hrens, Korinna and Weiss, Thomas Siegfried and Jonas, Wenke and Sch{\"u}rmann, Annette and P{\"u}schel, Gerhard Paul}, title = {Augmented liver inflammation in a microsomal prostaglandin E synthase 1 (mPGES-1)-deficient diet-induced mouse NASH model}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {483}, issn = {1866-8372}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-420879}, pages = {11}, year = {2018}, abstract = {In a subset of patients, non-alcoholic fatty liver disease (NAFLD) is complicated by cell death and inflammation resulting in non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and subsequent organ failure. Apart from cytokines, prostaglandins, in particular prostaglandin E-2 (PGE(2)), play a pivotal role during inflammatory processes. Expression of the key enzymes of PGE(2) synthesis, cyclooxygenase 2 and microsomal PGE synthase 1 (mPGES-1), was increased in human NASH livers in comparison to controls and correlated with the NASH activity score. Both enzymes were also induced in NASH-diet-fed wild-type mice, resulting in an increase in hepatic PGE(2) concentration that was completely abrogated in mPGES-1-deficient mice. PGE(2) is known to inhibit TNF-alpha synthesis in macrophages. A strong infiltration of monocyte-derived macrophages was observed in NASH-diet-fed mice, which was accompanied with an increase in hepatic TNF-alpha expression. Due to the impaired PGE(2) production, TNF-alpha expression increased much more in livers of mPGES-1-deficient mice or in the peritoneal macrophages of these mice. The increased levels of TNF-alpha resulted in an enhanced IL-1 beta production, primarily in hepatocytes, and augmented hepatocyte apoptosis. In conclusion, attenuation of PGE(2) production by mPGES-1 ablation enhanced the TNF-alpha-triggered inflammatory response and hepatocyte apoptosis in diet-induced NASH.}, language = {en} } @phdthesis{Radloff2018, author = {Radloff, Katrin}, title = {The role of the fatty acid profile and its modulation by cytokines in the systemic inflammation in cancer cachexia}, school = {Universit{\"a}t Potsdam}, pages = {156}, year = {2018}, abstract = {Systemic inflammation is a hallmark of cancer cachexia. Among tumor-host interactions, the white adipose tissue (WAT) is an important contributor to inflammation as it suffers morphological reorganization and lipolysis, releasing free fatty acids (FA), bioactive lipid mediators (LM) and pro-inflammatory cytokines, which accentuate the activation of pro-inflammatory signaling pathways and the recruitment of immune cells to the tissue. This project aimed to investigate which inflammatory factors are involved in the local adipose tissue inflammation and what is the influence of such factors upon enzymes involved in FA or LM metabolism in healthy individuals (Control), weight stable gastro-intestinal cancer patients (WSC) and cachectic cancer patients (CC). The results demonstrated that the inflammatory signature of systemic inflammation is different from local adipose tissue inflammation. The systemic inflammation of the cachectic cancer patients was characterized by higher levels of circulating saturated fatty acids (SFA), tumor-necrosis-factor-α (TNF-α), interleukins IL-6, IL-8 and CRP while levels of polyunsaturated fatty acids (PUFAs), especially n3-PUFAs, were lower in CC than in the other groups. In vitro and in adipose tissue explants, pro-inflammatory cytokines and SFAs were shown to increase the chemokines IL-8 and CXCL10 that were found to be augmented in adipose tissue inflammation in CC which was more profound in the visceral adipose tissue (VAT) than in subcutaneous adipose tissue (SAT). Systemic inflammation was negatively associated with the expression of PUFA synthesizing enzymes, though gene and protein expression did hardly differ between groups. The effects of inflammatory factors on enzymes in the whole tissue could have been masked by differentiated modulation of the diverse cell types in the same tissue. In vitro experiments showed that the expression of FA-modifying enzymes such as desaturases and elongases in adipocytes and macrophages was regulated into opposing directions by TNF-α, IL-6, LPS or palmitate. The higher plasma concentration of the pro-resolving LM resolvin D1 in CC cannot compensate the overall inflammatory status and the results indicate that inflammatory cytokines interfere with synthesis pathways of pro-resolving LM. In summary, the data revealed a complex inter-tissue and inter-cellular crosstalk mediated by pro-inflammatory cytokines and lipid compounds enhancing inflammation in cancer cachexia by feed-forward mechanisms.}, language = {en} } @article{HenkelColemanMacGregorofInneregnySchraplauetal.2018, author = {Henkel, Janin and Coleman Mac Gregor of Inneregny, Charles Dominic and Schraplau, Anne and J{\"o}hrens, Korinna and Weiss, Thomas Siegfried and Jonas, Wenke and Sch{\"u}rmann, Annette and P{\"u}schel, Gerhard Paul}, title = {Augmented liver inflammation in a microsomal prostaglandin E synthase 1 (mPGES-1)-deficient diet-induced mouse NASH model}, series = {Scientific Reports}, journal = {Scientific Reports}, number = {8}, publisher = {Nature Research}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-018-34633-y}, pages = {1 -- 11}, year = {2018}, abstract = {In a subset of patients, non-alcoholic fatty liver disease (NAFLD) is complicated by cell death and inflammation resulting in non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and subsequent organ failure. Apart from cytokines, prostaglandins, in particular prostaglandin E-2 (PGE(2)), play a pivotal role during inflammatory processes. Expression of the key enzymes of PGE(2) synthesis, cyclooxygenase 2 and microsomal PGE synthase 1 (mPGES-1), was increased in human NASH livers in comparison to controls and correlated with the NASH activity score. Both enzymes were also induced in NASH-diet-fed wild-type mice, resulting in an increase in hepatic PGE(2) concentration that was completely abrogated in mPGES-1-deficient mice. PGE(2) is known to inhibit TNF-alpha synthesis in macrophages. A strong infiltration of monocyte-derived macrophages was observed in NASH-diet-fed mice, which was accompanied with an increase in hepatic TNF-alpha expression. Due to the impaired PGE(2) production, TNF-alpha expression increased much more in livers of mPGES-1-deficient mice or in the peritoneal macrophages of these mice. The increased levels of TNF-alpha resulted in an enhanced IL-1 beta production, primarily in hepatocytes, and augmented hepatocyte apoptosis. In conclusion, attenuation of PGE(2) production by mPGES-1 ablation enhanced the TNF-alpha-triggered inflammatory response and hepatocyte apoptosis in diet-induced NASH.}, 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{NeuschaeferRubePatheNeuschaeferRubeHippenstieletal.2018, author = {Neusch{\"a}fer-Rube, Frank and Pathe-Neusch{\"a}fer-Rube, Andrea and Hippenstiel, Stefan and P{\"u}schel, Gerhard Paul}, title = {PGE(2) enhanced TNF alpha-mediated IL-8 induction in monocytic cell lines and PBMC}, series = {Cytokine}, volume = {113}, journal = {Cytokine}, publisher = {Elsevier}, address = {London}, issn = {1043-4666}, doi = {10.1016/j.cyto.2018.06.020}, pages = {105 -- 116}, year = {2018}, abstract = {Background \& purpose: Recent studies suggested a role of prostaglandin E-2 (PGE(2)) in the expression of the chemokine IL-8 by monocytes. The function of EP4 receptor for TNF alpha-induced IL-8 expression was studied in monocytic cell lines. Experimental approach: IL-8 mRNA and protein induction as well as IL-8 promoter activity and transcription factor activation were assessed in monocytic cell lines, primary blood mononuclear cells (PBMC) and transgenic HEK293 cells expressing the EP4 receptor. Key results: In monocytic cell lines THP-1, MonoMac and U937 PGE(2) had only a marginal impact on IL-8 induction but strongly enhanced TNFa-induced IL-8 mRNA and protein synthesis. Similarly, in PBMC IL-8 mRNA induction was larger by simultaneous stimulation with TNF alpha and PGE(2) than by either stimulus alone. The EP4 receptor subtype was the most abundant EP receptor in all three cell lines and in PBMC. Stimulation of THP-1 cells with an EP4 specific agonist enhanced TNF alpha-induced IL-8 mRNA and protein formation to the same extent as PGE(2). In HEK293 cells expressing EP4, but not in wild type HEK293 cells lacking EP4, PGE(2) enhanced TNFainduced IL-8 protein and mRNA synthesis. In THP-1 cells, the enhancement of TNF alpha-mediated IL-8 mRNA induction by PGE(2) was mimicked by a PICA-activator. Furthermore in these cells PGE(2) induced expression of transcription factor C/EBPS, enhanced NF-KB activation by TNFa and inhibited TNF alpha-mediated AP-1 activation. PGE(2) and TNF alpha synergistically activated transcription factor CREB, induced C/EBPS expression and enhanced the activity of an IL-8 promoter fragment containing-223 bp upstream of the transcription start site. Conclusions and implications: These findings suggest that a combined stimulation of TNF alpha and PGE(2)/EP4 signal chains in monocytic cells leads to maximal IL-8 promoter activity, as well as IL-8 mRNA and protein induction, by activating the PICA/CREB/C/EB1313 as well as NF-kappa B signal chains.}, 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} } @phdthesis{Hasan2018, author = {Hasan, Ahmed Abdallah Abdalrahman Mohamed}, title = {GLP-1 receptor-independent mechanisms of DPP-4 inhibition on renal disease progression}, school = {Universit{\"a}t Potsdam}, pages = {113}, year = {2018}, language = {en} } @phdthesis{Dambeck2018, author = {Dambeck, Ulrike}, title = {Kohlenhydratarme, n-6-reiche Di{\"a}t versus fettarme Di{\"a}t}, school = {Universit{\"a}t Potsdam}, pages = {187}, year = {2018}, language = {de} } @article{HenkelAlfineSainetal.2018, author = {Henkel, Janin and Alfine, Eugenia and Sa{\´i}n, Juliana and J{\"o}hrens, Korinna and Weber, Daniela and Castro, Jos{\´e} Pedro and K{\"o}nig, Jeannette and Stuhlmann, Christin and Vahrenbrink, Madita and Jonas, Wenke and Kleinridders, Andr{\´e} and P{\"u}schel, Gerhard Paul}, title = {Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol}, series = {Nutrients}, volume = {10}, journal = {Nutrients}, number = {9}, publisher = {Molecular Diversity Preservation International (MDPI)}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu10091326}, pages = {1 -- 17}, year = {2018}, abstract = {While the impact of dietary cholesterol on the progression of atherosclerosis has probably been overestimated, increasing evidence suggests that dietary cholesterol might favor the transition from blunt steatosis to non-alcoholic steatohepatitis (NASH), especially in combination with high fat diets. It is poorly understood how cholesterol alone or in combination with other dietary lipid components contributes to the development of lipotoxicity. The current study demonstrated that liver damage caused by dietary cholesterol in mice was strongly enhanced by a high fat diet containing soybean oil-derived ω6-poly-unsaturated fatty acids (ω6-PUFA), but not by a lard-based high fat diet containing mainly saturated fatty acids. In contrast to the lard-based diet the soybean oil-based diet augmented cholesterol accumulation in hepatocytes, presumably by impairing cholesterol-eliminating pathways. The soybean oil-based diet enhanced cholesterol-induced mitochondrial damage and amplified the ensuing oxidative stress, probably by peroxidation of poly-unsaturated fatty acids. This resulted in hepatocyte death, recruitment of inflammatory cells, and fibrosis, and caused a transition from steatosis to NASH, doubling the NASH activity score. Thus, the recommendation to reduce cholesterol intake, in particular in diets rich in ω6-PUFA, although not necessary to reduce the risk of atherosclerosis, might be sensible for patients suffering from non-alcoholic fatty liver disease.}, language = {en} } @misc{HenkelAlfineSainetal.2018, author = {Henkel, Janin and Alfine, Eugenia and Sa{\´i}n, Juliana and J{\"o}hrens, Korinna and Weber, Daniela and Castro, Jos{\´e} Pedro and K{\"o}nig, Jeannette and Stuhlmann, Christin and Vahrenbrink, Madita and Jonas, Wenke and Kleinridders, Andr{\´e} and P{\"u}schel, Gerhard Paul}, title = {Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol}, series = {Nutrients}, journal = {Nutrients}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-419773}, pages = {17}, year = {2018}, abstract = {While the impact of dietary cholesterol on the progression of atherosclerosis has probably been overestimated, increasing evidence suggests that dietary cholesterol might favor the transition from blunt steatosis to non-alcoholic steatohepatitis (NASH), especially in combination with high fat diets. It is poorly understood how cholesterol alone or in combination with other dietary lipid components contributes to the development of lipotoxicity. The current study demonstrated that liver damage caused by dietary cholesterol in mice was strongly enhanced by a high fat diet containing soybean oil-derived ω6-poly-unsaturated fatty acids (ω6-PUFA), but not by a lard-based high fat diet containing mainly saturated fatty acids. In contrast to the lard-based diet the soybean oil-based diet augmented cholesterol accumulation in hepatocytes, presumably by impairing cholesterol-eliminating pathways. The soybean oil-based diet enhanced cholesterol-induced mitochondrial damage and amplified the ensuing oxidative stress, probably by peroxidation of poly-unsaturated fatty acids. This resulted in hepatocyte death, recruitment of inflammatory cells, and fibrosis, and caused a transition from steatosis to NASH, doubling the NASH activity score. Thus, the recommendation to reduce cholesterol intake, in particular in diets rich in ω6-PUFA, although not necessary to reduce the risk of atherosclerosis, might be sensible for patients suffering from non-alcoholic fatty liver disease.}, language = {en} } @phdthesis{Mueller2018, author = {M{\"u}ller, Sandra Marie}, title = {Food-relevant arsenic species}, school = {Universit{\"a}t Potsdam}, pages = {163, Viii}, year = {2018}, language = {en} } @phdthesis{Ring2018, author = {Ring, Christiane}, title = {The role of the commensal gut bacterium Akkermansia muciniphila in acute and chronic intestinal inflammation}, year = {2018}, abstract = {Microbiota analyses of patients suffering from various diseases suggest a beneficial role of Akkermansia muciniphila in the maintenance of health, whereas several studies in animal models of intestinal inflammation report that this organism may aggravate inflammation. Therefore, it is important to clarify under which circumstances A. muciniphila exerts negative effects in the intestine of its host. The previously reported observation that A. muciniphila aggravates acute intestinal inflammation in the Salmonella enterica serovar Typhimurium infection mouse model colonized with a simplified human intestinal microbiota was investigated in this study. To unravel the underlying mechanism that led to the observed phenomenon, the time course of events following the infection was analyzed. In mice colonized with a simplified human intestinal microbiota, Salmonella infection induced clear signs of intestinal inflammation three days post infection. The inflammatory response was similar in mice colonized with A. muciniphila before Salmonella infection. These observations were independent of the time when colonization with the simplified human intestinal microbiota occurred, right after birth or only after weaning, and contradict the previous report. To find out whether A. muciniphila influences the development of chronic intestinal inflammation in a genetically predisposed host, mono-associated interleukin-10-deficient (Il10-/-) mice, Il10-/- mice dual-associated with A. muciniphila and colitogenic Escherichia coli NC101, as well as Il10-/- mice associated with A. muciniphila and a simplified human intestinal microbiota were compared to the respective mice without A. muciniphila. The data clearly show that in these gnotobiotic Il10-/- mice, A. muciniphila neither induces intestinal inflammation itself nor modulates it after induction by a colitogenic bacterium or by a simplified human intestinal microbiota. The experiments lead to the conclusion that the promotion of intestinal inflammation is not an intrinsic feature of this bacterium. The results of this study encourage the proposed use of A. muciniphila for the prevention or treatment of metabolic disorders.}, language = {en} } @phdthesis{Waizenegger2018, author = {Waizenegger, Julia}, title = {Untersuchung der molekularen Toxizit{\"a}t von Pyrrolizidinalkaloiden in der humanen Hepatomzelllinie HepaRG}, school = {Universit{\"a}t Potsdam}, pages = {129, XLI}, year = {2018}, language = {de} } @phdthesis{Kammel2018, author = {Kammel, Anne}, title = {Identifizierung fr{\"u}her epigenetischer Ver{\"a}nderungen, die zur Ausbildung einer Fettleber beitragen}, school = {Universit{\"a}t Potsdam}, pages = {130}, year = {2018}, language = {de} } @phdthesis{Weiss2018, author = {Weiß, Stefanie}, title = {Contribution of bacterially synthesized folate vitamers to folate status and impact on crohn's Disease}, school = {Universit{\"a}t Potsdam}, pages = {148}, year = {2018}, language = {en} } @phdthesis{Edlich2018, author = {Edlich, Alexander}, title = {Interaktionen zwischen Nanotransportern und antigenpr{\"a}sentierenden Zellen der Haut}, school = {Universit{\"a}t Potsdam}, pages = {181}, year = {2018}, language = {de} }