TY  - JOUR
A1  - Christakoudi, Sofa
A1  - Tsilidis, Konstantinos K.
A1  - Muller, David C.
A1  - Freisling, Heinz
A1  - Weiderpass, Elisabete
A1  - Overvad, Kim
A1  - Söderberg, Stefan
A1  - Häggström, Christel
A1  - Pischon, Tobias
A1  - Dahm, Christina C.
A1  - Zhang, Jie
A1  - Tjønneland, Anne
A1  - Schulze, Matthias Bernd
T1  - A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort
JF  - Scientific Reports
N2  - Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
KW  - all-cause mortality
KW  - anthropometric measures
KW  - mass index
KW  - overweight
KW  - cancer
KW  - prediction
KW  - adiposity
KW  - size
Y1  - 2020
VL  - 10
IS  - 1
PB  - Springer Nature
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Winkelbeiner, Nicola Lisa
A1  - Wandt, Viktoria Klara Veronika
A1  - Ebert, Franziska
A1  - Lossow, Kristina
A1  - Bankoglu, Ezgi E.
A1  - Martin, Maximilian
A1  - Mangerich, Aswin
A1  - Stopper, Helga
A1  - Bornhorst, Julia
A1  - Kipp, Anna Patricia
A1  - Schwerdtle, Tanja
T1  - A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice
BT  - Impact of Sex and Age
JF  - International Journal of Molecular Sciences
N2  - Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.
KW  - maintenance of genomic integrity
KW  - ageing
KW  - sex
KW  - DNA damage
KW  - base excision repair (incision activity)
KW  - DNA damage response
KW  - poly(ADP-ribosyl)ation
KW  - liver
Y1  - 2020
U6  - https://doi.org/10.3390/ijms21186600
SN  - 1422-0067
VL  - 21
IS  - 18
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  - 
TY  - JOUR
A1  - Jannasch, Franziska
A1  - Nickel, Daniela V.
A1  - Bergmann, Manuela M.
A1  - Schulze, Matthias Bernd
T1  - A new evidence-based diet score to capture associations of food consumption and chronic disease risk
JF  - Nutrients / Molecular Diversity Preservation International (MDPI)
N2  - Previously, the attempt to compile German dietary guidelines into a diet score was predominantly not successful with regards to preventing chronic diseases in the EPIC-Potsdam study. Current guidelines were supplemented by the latest evidence from systematic reviews and expert papers published between 2010 and 2020 on the prevention potential of food groups on chronic diseases such as type 2 diabetes, cardiovascular diseases and cancer. A diet score was developed by scoring the food groups according to a recommended low, moderate or high intake. The relative validity and reliability of the diet score, assessed by a food frequency questionnaire, was investigated. The consideration of current evidence resulted in 10 key food groups being preventive of the chronic diseases of interest. They served as components in the diet score and were scored from 0 to 1 point, depending on their recommended intake, resulting in a maximum of 10 points. Both the reliability (r = 0.53) and relative validity (r = 0.43) were deemed sufficient to consider the diet score as a stable construct in future investigations. This new diet score can be a promising tool to investigate dietary intake in etiological research by concentrating on 10 key dietary determinants with evidence-based prevention potential for chronic diseases.
KW  - diet score
KW  - dietary guidelines
KW  - food groups
KW  - chronic disease
KW  - type 2
KW  - diabetes
KW  - cardiovascular disease
KW  - cancer
KW  - prevention
KW  - reliability;
KW  - validity
Y1  - 2022
U6  - https://doi.org/10.3390/nu14112359
SN  - 2072-6643
VL  - 14
IS  - 11
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Solger, Franziska
A1  - Kunz, Tobias C.
A1  - Fink, Julian
A1  - Paprotka, Kerstin
A1  - Pfister, Pauline
A1  - Hagen, Franziska
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Seibel, Jürgen
A1  - Rudel, Thomas
T1  - A role of sphingosine in the intracellular survival of Neisseria gonorrhoeae
JF  - Frontiers in Cellular and Infection Microbiology
N2  - Obligate human pathogenic Neisseria gonorrhoeae are the second most frequent bacterial cause of sexually transmitted diseases. These bacteria invade different mucosal tissues and occasionally disseminate into the bloodstream. Invasion into epithelial cells requires the activation of host cell receptors by the formation of ceramide-rich platforms. Here, we investigated the role of sphingosine in the invasion and intracellular survival of gonococci. Sphingosine exhibited an anti-gonococcal activity in vitro. We used specific sphingosine analogs and click chemistry to visualize sphingosine in infected cells. Sphingosine localized to the membrane of intracellular gonococci. Inhibitor studies and the application of a sphingosine derivative indicated that increased sphingosine levels reduced the intracellular survival of gonococci. We demonstrate here, that sphingosine can target intracellular bacteria and may therefore exert a direct bactericidal effect inside cells.
KW  - Neisseria gonorrhoeae
KW  - sphingosine
KW  - sphingolipids
KW  - sphingosine kinases
KW  - invasion
KW  - survival
KW  - click chemistry
Y1  - 2020
U6  - https://doi.org/10.3389/fcimb.2020.00215
SN  - 2235-2988
VL  - 10
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Boekstegers, Felix
A1  - Marcelain, Katherine
A1  - Barahona Ponce, Carol
A1  - Baez Benavides, Pablo F.
A1  - Müller, Bettina
A1  - de Toro, Gonzalo
A1  - Retamales, Javier
A1  - Barajas, Olga
A1  - Ahumada, Monica
A1  - Aleksandrova, Krasimira
A1  - Bermejo, Justo Lorenzo
T1  - ABCB1/4 gallbladder cancer risk variants identified in India also show strong effects in Chileans
JF  - Cancer Epidemiology
N2  - Background: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence.
Methods: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication.
Results: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low.
Conclusion: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.
KW  - cancer epidemiology
KW  - gallbladder cancer
KW  - native American ancestry
KW  - population-specific risk marker
Y1  - 2020
VL  - 65
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Lang, Judith
A1  - Bohn, Patrick
A1  - Bhat, Hilal
A1  - Jastrow, Holger
A1  - Walkenfort, Bernd
A1  - Cansiz, Feyza
A1  - Fink, Julian
A1  - Bauer, Michael
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Lang, Karl S.
T1  - Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease
JF  - Nature Communications
N2  - Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1(-/-) mice results in replication of HSV-1 and Asah1(-/-) mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol.
KW  - immunology
KW  - infection
KW  - membrane fusion
KW  - phagocytosis
KW  - sphingolipids
Y1  - 2020
U6  - https://doi.org/10.1038/s41467-020-15072-8
SN  - 2041-1723
VL  - 11
IS  - 1
SP  - 1
EP  - 15
PB  - Nature Publishing Group UK
CY  - London
ER  - 
TY  - JOUR
A1  - Birukov, Anna
A1  - Cuadrat, Rafael R. C.
A1  - Polemiti, Elli
A1  - Eichelmann, Fabian
A1  - Schulze, Matthias Bernd
T1  - Advanced glycation end-products, measured as skin autofluorescence, associate with vascular stiffness in diabetic, pre-diabetic and normoglycemic individuals
BT  - a cross-sectional study
JF  - Cardiovascular diabetology
N2  - Background Advanced glycation end-products are proteins that become glycated after contact with sugars and are implicated in endothelial dysfunction and arterial stiffening. We aimed to investigate the relationships between advanced glycation end-products, measured as skin autofluorescence, and vascular stiffness in various glycemic strata. Methods We performed a cross-sectional analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, comprising n = 3535 participants (median age 67 years, 60% women). Advanced glycation end-products were measured as skin autofluorescence with AGE-Reader (TM), vascular stiffness was measured as pulse wave velocity, augmentation index and ankle-brachial index with Vascular Explorer (TM). A subset of 1348 participants underwent an oral glucose tolerance test. Participants were sub-phenotyped into normoglycemic, prediabetes and diabetes groups. Associations between skin autofluorescence and various indices of vascular stiffness were assessed by multivariable regression analyses and were adjusted for age, sex, measures of adiposity and lifestyle, blood pressure, prevalent conditions, medication use and blood biomarkers. Results Skin autofluorescence associated with pulse wave velocity, augmentation index and ankle-brachial index, adjusted beta coefficients (95% CI) per unit skin autofluorescence increase: 0.38 (0.21; 0.55) for carotid-femoral pulse wave velocity, 0.25 (0.14; 0.37) for aortic pulse wave velocity, 1.00 (0.29; 1.70) for aortic augmentation index, 4.12 (2.24; 6.00) for brachial augmentation index and - 0.04 (- 0.05; - 0.02) for ankle-brachial index. The associations were strongest in men, younger individuals and were consistent across all glycemic strata: for carotid-femoral pulse wave velocity 0.36 (0.12; 0.60) in normoglycemic, 0.33 (- 0.01; 0.67) in prediabetes and 0.45 (0.09; 0.80) in diabetes groups; with similar estimates for aortic pulse wave velocity. Augmentation index was associated with skin autofluorescence only in normoglycemic and diabetes groups. Ankle-brachial index inversely associated with skin autofluorescence across all sex, age and glycemic strata. Conclusions Our findings indicate that advanced glycation end-products measured as skin autofluorescence might be involved in vascular stiffening independent of age and other cardiometabolic risk factors not only in individuals with diabetes but also in normoglycemic and prediabetic conditions. Skin autofluorescence might prove as a rapid and non-invasive method for assessment of macrovascular disease progression across all glycemic strata.
KW  - Advanced glycation end-products
KW  - AGE
KW  - Ankle-brachial index
KW  - Augmentation
KW  - index
KW  - Prediabetes
KW  - Glycemia
KW  - Pulse wave velocity
KW  - Skin
KW  - autofluorescence
KW  - Vascular stiffness
Y1  - 2021
U6  - https://doi.org/10.1186/s12933-021-01296-5
SN  - 1475-2840
VL  - 20
IS  - 1
PB  - BioMed Central
CY  - London
ER  - 
TY  - JOUR
A1  - Odongo, Grace Akinyi
A1  - Schlotz, Nina
A1  - Baldermann, Susanne
A1  - Neugart, Susanne
A1  - Huyskens-Keil, Susanne
A1  - Ngwene, Benard
A1  - Trierweiler, Bernhard
A1  - Schreiner, Monika
A1  - Lamy, Evelyn
T1  - African Nightshade (Solanum scabrum Mill.)
BT  - Impact of Cultivation and Plant Processing on Its Health Promoting Potential as Determined in a Human Liver Cell Model
JF  - Nutrients
N2  - 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.
KW  - aflatoxin B1
KW  - African indigenous vegetables
KW  - anti-genotoxicity
KW  - anti-oxidant activity
KW  - cancer chemoprevention
KW  - Solanaceae
Y1  - 2018
U6  - https://doi.org/10.3390/nu10101532
SN  - 2072-6643
VL  - 10
IS  - 10
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Schröter, David
A1  - Neugart, Susanne
A1  - Schreiner, Monika
A1  - Grune, Tilman
A1  - Rohn, Sascha
A1  - Ott, Christiane
T1  - Amaranth’s 2-Caffeoylisocitric Acid—An Anti-Inflammatory Caffeic Acid Derivative That Impairs NF-κB Signaling in LPS-Challenged RAW 264.7 Macrophages
JF  - Nutrients
N2  - For centuries, Amaranthus sp. were used as food, ornamentals, and medication. Molecular mechanisms, explaining the health beneficial properties of amaranth, are not yet understood, but have been attributed to secondary metabolites, such as phenolic compounds. One of the most abundant phenolic compounds in amaranth leaves is 2-caffeoylisocitric acid (C-IA) and regarding food occurrence, C-IA is exclusively found in various amaranth species. In the present study, the anti-inflammatory activity of C-IA, chlorogenic acid, and caffeic acid in LPS-challenged macrophages (RAW 264.7) has been investigated and cellular contents of the caffeic acid derivatives (CADs) were quantified in the cells and media. The CADs were quantified in the cell lysates in nanomolar concentrations, indicating a cellular uptake. Treatment of LPS-challenged RAW 264.7 cells with 10 µM of CADs counteracted the LPS effects and led to significantly lower mRNA and protein levels of inducible nitric oxide synthase, tumor necrosis factor alpha, and interleukin 6, by directly decreasing the translocation of the nuclear factor κB/Rel-like containing protein 65 into the nucleus. This work provides new insights into the molecular mechanisms that attribute to amaranth’s anti-inflammatory properties and highlights C-IA’s potential as a health-beneficial compound for future research.
KW  - inflammation
KW  - caffeic acid derivatives
KW  - RAW 264
KW  - 7 macrophages
KW  - NF-kappa B
KW  - amaranth
Y1  - 2019
U6  - https://doi.org/10.3390/nu11030571
SN  - 2072-6643
VL  - 11
IS  - 3
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Hoffmann, Holger
A1  - Ott, Christiane
A1  - Raupbach, Jana
A1  - Andernach, Lars
A1  - Renz, Matthias
A1  - Grune, Tilman
A1  - Hanschen, Franziska S.
T1  - Assessing bioavailability and bioactivity of 4-Hydroxythiazolidine-2-Thiones, newly discovered glucosinolate degradation products formed during domestic boiling of cabbage
JF  - Frontiers in nutrition
N2  - Glucosinolates are plant secondary metabolites found in cruciferous vegetables (Brassicaceae) that are valued for their potential health benefits. Frequently consumed representatives of these vegetables, for example, are white or red cabbage, which are typically boiled before consumption. Recently, 3-alk(en)yl-4-hydroxythiazolidine-2-thiones were identified as a class of thermal glucosinolate degradation products that are formed during the boiling of cabbage. Since these newly discovered compounds are frequently consumed, this raises questions about their potential uptake and their possible bioactive functions. Therefore, 3-allyl-4-hydroxythiazolidine-2-thione (allyl HTT) and 4-hydroxy-3-(4-(methylsulfinyl) butyl)thiazolidine-2-thione (4-MSOB HTT) as degradation products of the respective glucosinolates sinigrin and glucoraphanin were investigated. After consumption of boiled red cabbage broth, recoveries of consumed amounts of the degradation products in urine collected for 24 h were 18 +/- 5% for allyl HTT and 21 +/- 4% for 4-MSOB HTT (mean +/- SD, n = 3). To investigate the stability of the degradation products during uptake and to elucidate the uptake mechanism, both an in vitro stomach and an in vitro intestinal model were applied. The results indicate that the uptake of allyl HTT and 4-MSOB HTT occurs by passive diffusion. Both compounds show no acute cell toxicity, no antioxidant potential, and no change in NAD(P)H dehydrogenase quinone 1 (NQO1) activity up to 100 mu M. However, inhibition of glycogen synthase kinases-3 (GSK-3) in the range of 20% for allyl HTT for the isoform GSK-3 beta and 29% for 4-MSOB HTT for the isoform GSK-3 alpha at a concentration of 100 mu M was found. Neither health-promoting nor toxic effects of 3-alk(en)yl-4-hydroxythiazolidine-2-thiones were found in the four tested assays carried out in this study, which contrasts with the properties of other glucosinolate degradation products, such as isothiocyanates.
KW  - stomach model
KW  - glycogen synthase kinase-3
KW  - cytotoxicity
KW  - antioxidant potential
KW  - intestinal model
KW  - cellular uptake
KW  - isothiocyanate
Y1  - 2022
U6  - https://doi.org/10.3389/fnut.2022.941286
SN  - 2296-861X
VL  - 9
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Eichelmann, Fabian
A1  - Schulze, Matthias Bernd
A1  - Wittenbecher, Clemens
A1  - Menzel, Juliane
A1  - Weikert, Cornelia
A1  - di Giuseppe, Romina
A1  - Biemann, Ronald
A1  - Isermann, Berend
A1  - Fritsche, Andreas
A1  - Boeing, Heiner
A1  - Aleksandrova, Krasimira
T1  - Association of Chemerin Plasma Concentration With Risk of Colorectal Cancer
JF  - JAMA network open
N2  - IMPORTANCE Inflammatory processes have been suggested to have an important role in colorectal cancer (CRC) etiology. Chemerin is a recently discovered inflammatory biomarker thought to exert chemotactic, adipogenic, and angiogenic functions. However, its potential link with CRC has not been sufficiently explored. OBJECTIVE To evaluate the prospective association of circulating plasma chemerin concentrations with incident CRC. DESIGN, SETTING, AND PARTICIPANTS Prospective case-cohort study based on 27 548 initially healthy participants from the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam cohort who were followed for up to 16 years. Baseline study information and samples were collected between August 23, 1994, and September 25, 1998. Recruitment was according to random registry sampling from the geographical area of Potsdam, Germany, and surrounding municipalities. The last date of study follow-up was May 10, 2010. Statistical analysis was conducted in 2018. MAIN OUTCOMES AND MEASURES Incident CRC, colon cancer, and rectal cancer. Baseline chemerin plasma concentrations were measured by enzyme-linked immunosorbent assay. CONCLUSIONS AND RELEVANCE This study found that the association between chemerin concentration and the risk of incident CRC was linear and independent of established CRC risk factors. Further studies are warranted to evaluate chemerin as a novel immune-inflammatory agent in colorectal carcinogenesis.
Y1  - 2019
U6  - https://doi.org/10.1001/jamanetworkopen.2019.0896
SN  - 2574-3805
VL  - 2
IS  - 3
PB  - American Veterinary Medical Association
CY  - Chicago
ER  - 
TY  - JOUR
A1  - Wright, Stephanie L.
A1  - Ulke, Jannis
A1  - Font, Anna
A1  - Chan, Ka Lung Andrew
A1  - Kelly, Frank J.
T1  - Atmospheric microplastic deposition in an urban environment and an evaluation of transport
JF  - Environment international
N2  - Microplastics are a global environmental issue contaminating aquatic and terrestrial environments. They have been reported in atmospheric deposition, and indoor and outdoor air, raising concern for public health due to the potential for exposure. Moreover, the atmosphere presents a new vehicle for microplastics to enter the wider environment, yet our knowledge of the quantities, characteristics and pathways of airborne microplastics is sparse. Here we show microplastics in atmospheric deposition in a major population centre, central London. Microplastics were found in all samples, with deposition rates ranging from 575 to 1008 microplastics/m(2)/d. They were found in various shapes, of which fibrous microplastics accounted for the great majority (92%). Across all samples, 15 different petrochemical-based polymers were identified. Bivariate polar plots indicated dependency on wind, with different source areas for fibrous and non-fibrous airborne microplastics. This is the first evidence of airborne microplastics in London and confirms the need to include airborne pathways when consolidating microplastic impacts on the wider environment and human health.
KW  - microplastics
KW  - atmospheric deposition
KW  - air pollution
KW  - urban
Y1  - 2020
U6  - https://doi.org/10.1016/j.envint.2019.105411
SN  - 0160-4120
SN  - 1873-6750
VL  - 136
PB  - Elsevier, Pergamon Press
CY  - New York, NY [u.a.]
ER  - 
TY  - JOUR
A1  - Dwi Putra, Sulistyo Emantoko
A1  - Reichetzeder, Christoph
A1  - Hasan, Ahmed Abdallah Abdalrahman Mohamed
A1  - Slowinski, Torsten
A1  - Chu, Chang
A1  - Krämer, Bernhard K.
A1  - Kleuser, Burkhard
A1  - Hocher, Berthold
T1  - Being born large for gestational age is associated with increased global placental DNA methylation
JF  - Scientific Reports
N2  - Being born small (SGA) or large for gestational age (LGA) is associated with adverse birth outcomes and metabolic diseases in later life of the offspring. It is known that aberrations in growth during gestation are related to altered placental function. Placental function is regulated by epigenetic mechanisms such as DNA methylation. Several studies in recent years have demonstrated associations between altered patterns of DNA methylation and adverse birth outcomes. However, larger studies that reliably investigated global DNA methylation are lacking. The aim of this study was to characterize global placental DNA methylation in relationship to size for gestational age. Global DNA methylation was assessed in 1023 placental samples by LC-MS/MS. LGA offspring displayed significantly higher global placental DNA methylation compared to appropriate for gestational age (AGA; p<0.001). ANCOVA analyses adjusted for known factors impacting on DNA methylation demonstrated an independent association between placental global DNA methylation and LGA births (p<0.001). Tertile stratification according to global placental DNA methylation levels revealed a significantly higher frequency of LGA births in the third tertile. Furthermore, a multiple logistic regression analysis corrected for known factors influencing birth weight highlighted an independent positive association between global placental DNA methylation and the frequency of LGA births (p=0.001).
KW  - fetal origins hypothesis
KW  - birth weight
KW  - repetitive elements
KW  - glucocorticoid receptor
KW  - nutrient transport
KW  - growth restriction
KW  - later health
KW  - pregnancy
KW  - genes
KW  - patterns
Y1  - 2020
U6  - https://doi.org/10.1038/s41598-020-57725-0
SN  - 2045-2322
VL  - 10
IS  - 1
SP  - 1
EP  - 10
PB  - Springer Nature
CY  - London
ER  - 
TY  - JOUR
A1  - Häseli, Steffen
A1  - Deubel, Stefanie
A1  - Jung, Tobias
A1  - Grune, Tilman
A1  - Ott, Christiane
T1  - Cardiomyocyte contractility and autophagy in a premature senescence model of cardiac aging
JF  - Oxidative medicine and cellular longevity
N2  - Globally, cardiovascular diseases are the leading cause of death in the aging population. While the clinical pathology of the aging heart is thoroughly characterized, underlying molecular mechanisms are still insufficiently clarified. The aim of the present study was to establish an in vitro model system of cardiomyocyte premature senescence, culturing heart muscle cells derived from neonatal C57Bl/6J mice for 21 days. Premature senescence of neonatal cardiac myocytes was induced by prolonged culture time in an oxygen-rich postnatal environment. Age-related changes in cellular function were determined by senescence-associated beta-galactosidase activity, increasing presence of cell cycle regulators, such as p16, p53, and p21, accumulation of protein aggregates, and restricted proteolysis in terms of decreasing (macro-)autophagy. Furthermore, the culture system was functionally characterized for alterations in cell morphology and contractility. An increase in cellular size associated with induced expression of atrial natriuretic peptides demonstrated a stress-induced hypertrophic phenotype in neonatal cardiomyocytes. Using the recently developed analytical software tool Myocyter, we were able to show a spatiotemporal constraint in spontaneous contraction behavior during cultivation. Within the present study, the 21-day culture of neonatal cardiomyocytes was defined as a functional model system of premature cardiac senescence to study age-related changes in cardiomyocyte contractility and autophagy.
Y1  - 2020
U6  - https://doi.org/10.1155/2020/8141307
SN  - 1942-0994
VL  - 2020
IS  - Special Issue
PB  - Landes Bioscience
CY  - Austin, Tex.
ER  - 
TY  - JOUR
A1  - Barcena, Maria Luisa
A1  - Aslam, Muhammad
A1  - Pozdniakova, Sofya
A1  - Norman, Kristina
A1  - Ladilov, Yury
T1  - Cardiovascular inflammaging: mechanisms and translational aspects
JF  - Cells
N2  - Aging is one of the major non-reversible risk factors for several chronic diseases, including cancer, type 2 diabetes, dementia, and cardiovascular diseases (CVD), and it is a key cause of multimorbidity, disability, and frailty (decreased physical activity, fatigue, and weight loss). The underlying cellular mechanisms are complex and consist of multifactorial processes, such as telomere shortening, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, accumulation of senescent cells, and reduced autophagy. In this review, we focused on the molecular mechanisms and translational aspects of cardiovascular aging-related inflammation, i.e., inflammaging.
KW  - cardiac inflammaging
KW  - vascular senescence
KW  - mitochondrial homeostasis
KW  - microbiome
Y1  - 2022
U6  - https://doi.org/10.3390/cells11061010
SN  - 2073-4409
VL  - 11
IS  - 6
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Wei, Xiaoyan
A1  - Franke, Julia
A1  - Ost, Mario
A1  - Wardelmann, Kristina
A1  - Börno, Stefan
A1  - Timmermann, Bernd
A1  - Meierhofer, David
A1  - Kleinridders, Andre
A1  - Klaus, Susanne
A1  - Stricker, Sigmar
T1  - Cell autonomous requirement of neurofibromin (Nf1) for postnatal muscle hypertrophic growth and metabolic homeostasis
JF  - Journal of cachexia, sarcopenia and muscle
N2  - Background Neurofibromatosis type 1 (NF1) is a multi-organ disease caused by mutations in neurofibromin 1 (NF1). Amongst other features, NF1 patients frequently show reduced muscle mass and strength, impairing patients' mobility and increasing the risk of fall. The role of Nf1 in muscle and the cause for the NF1-associated myopathy are mostly unknown. Methods To dissect the function ofNf1in muscle, we created muscle-specific knockout mouse models for NF1, inactivatingNf1in the prenatal myogenic lineage either under the Lbx1 promoter or under the Myf5 promoter. Mice were analysed during prenatal and postnatal myogenesis and muscle growth. Results Nf1(Lbx1)and Nf1(Myf5)animals showed only mild defects in prenatal myogenesis. Nf1(Lbx1)animals were perinatally lethal, while Nf1(Myf5)animals survived only up to approximately 25 weeks. A comprehensive phenotypic characterization of Nf1(Myf5)animals showed decreased postnatal growth, reduced muscle size, and fast fibre atrophy. Proteome and transcriptome analyses of muscle tissue indicated decreased protein synthesis and increased proteasomal degradation, and decreased glycolytic and increased oxidative activity in muscle tissue. High-resolution respirometry confirmed enhanced oxidative metabolism in Nf1(Myf5)muscles, which was concomitant to a fibre type shift from type 2B to type 2A and type 1. Moreover, Nf1(Myf5)muscles showed hallmarks of decreased activation of mTORC1 and increased expression of atrogenes. Remarkably, loss of Nf1 promoted a robust activation of AMPK with a gene expression profile indicative of increased fatty acid catabolism. Additionally, we observed a strong induction of genes encoding catabolic cytokines in muscle Nf1(Myf5)animals, in line with a drastic reduction of white, but not brown adipose tissue. Conclusions Our results demonstrate a cell autonomous role for Nf1 in myogenic cells during postnatal muscle growth required for metabolic and proteostatic homeostasis. Furthermore, Nf1 deficiency in muscle drives cross-tissue communication and mobilization of lipid reserves.
KW  - neurofibromatosis
KW  - NF1
KW  - myopathy
KW  - muscle atrophy
KW  - muscle metabolism
KW  - muscle fibre type
KW  - AMPK
Y1  - 2020
U6  - https://doi.org/10.1002/jcsm.12632
SN  - 2190-5991
SN  - 2190-6009
VL  - 11
IS  - 6
SP  - 1758
EP  - 1778
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Pathe-Neuschäfer-Rube, Andrea
A1  - Neuschäfer-Rube, Frank
A1  - Püschel, Gerhard Paul
T1  - Cell-based reporter release assay to determine the activity of calcium-dependent neurotoxins and neuroactive pharmaceuticals
JF  - Toxins / Molecular Diversity Preservation International (MDPI)
N2  - The suitability of a newly developed cell-based functional assay was tested for the detection of the activity of a range of neurotoxins and neuroactive pharmaceuticals which act by stimulation or inhibition of calcium-dependent neurotransmitter release. In this functional assay, a reporter enzyme is released concomitantly with the neurotransmitter from neurosecretory vesicles. The current study showed that the release of a luciferase from a differentiated human neuroblastoma-based reporter cell line (SIMA-hPOMC1-26-GLuc cells) can be stimulated by a carbachol-mediated activation of the Gq-coupled muscarinic-acetylcholine receptor and by the Ca2+-channel forming spider toxin α-latrotoxin. Carbachol-stimulated luciferase release was completely inhibited by the muscarinic acetylcholine receptor antagonist atropine and α-latrotoxin-mediated release by the Ca2+-chelator EGTA, demonstrating the specificity of luciferase-release stimulation. SIMA-hPOMC1-26-GLuc cells express mainly L- and N-type and to a lesser extent T-type VGCC on the mRNA and protein level. In accordance with the expression profile a depolarization-stimulated luciferase release by a high K+-buffer was effectively and dose-dependently inhibited by L-type VGCC inhibitors and to a lesser extent by N-type and T-type inhibitors. P/Q- and R-type inhibitors did not affect the K+-stimulated luciferase release. In summary, the newly established cell-based assay may represent a versatile tool to analyze the biological efficiency of a range of neurotoxins and neuroactive pharmaceuticals which mediate their activity by the modulation of calcium-dependent neurotransmitter release.
KW  - cell-based assay
KW  - neurotoxins
KW  - muscarinic acetylcholine receptor
KW  - voltage-dependent calcium channels
KW  - VGCC
Y1  - 2021
U6  - https://doi.org/10.3390/toxins13040247
SN  - 2072-6651
VL  - 13
IS  - 4
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Wardelmann, Kristina
A1  - Rath, Michaela
A1  - Castro, José Pedro
A1  - Blümel, Sabine
A1  - Schell, Mareike
A1  - Hauffe, Robert
A1  - Schumacher, Fabian
A1  - Flore, Tanina
A1  - Ritter, Katrin
A1  - Wernitz, Andreas
A1  - Hosoi, Toru
A1  - Ozawa, Koichiro
A1  - Kleuser, Burkhard
A1  - Weiß, Jürgen
A1  - Schürmann, Annette
A1  - Kleinridders, André
T1  - Central acting Hsp10 regulates mitochondrial function, fatty acid metabolism and insulin sensitivity in the hypothalamus
JF  - Antioxidants
N2  - Mitochondria are critical for hypothalamic function and regulators of metabolism. Hypothalamic mitochondrial dysfunction with decreased mitochondrial chaperone expression is present in type 2 diabetes (T2D). Recently, we demonstrated that a dysregulated mitochondrial stress response (MSR) with reduced chaperone expression in the hypothalamus is an early event in obesity development due to insufficient insulin signaling. Although insulin activates this response and improves metabolism, the metabolic impact of one of its members, the mitochondrial chaperone heat shock protein 10 (Hsp10), is unknown. Thus, we hypothesized that a reduction of Hsp10 in hypothalamic neurons will impair mitochondrial function and impact brain insulin action. Therefore, we investigated the role of chaperone Hsp10 by introducing a lentiviral-mediated Hsp10 knockdown (KD) in the hypothalamic cell line CLU-183 and in the arcuate nucleus (ARC) of C57BL/6N male mice. We analyzed mitochondrial function and insulin signaling utilizing qPCR, Western blot, XF96 Analyzer, immunohistochemistry, and microscopy techniques. We show that Hsp10 expression is reduced in T2D mice brains and regulated by leptin in vitro. Hsp10 KD in hypothalamic cells induced mitochondrial dysfunction with altered fatty acid metabolism and increased mitochondria-specific oxidative stress resulting in neuronal insulin resistance. Consequently, the reduction of Hsp10 in the ARC of C57BL/6N mice caused hypothalamic insulin resistance with acute liver insulin resistance.
KW  - brain insulin signaling
KW  - mitochondria
KW  - oxidative stress
KW  - fatty acid metabolism
Y1  - 2021
U6  - https://doi.org/10.3390/antiox10050711
SN  - 2076-3921
VL  - 10
IS  - 5
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Naser, Eyad
A1  - Kadow, Stephanie
A1  - Schumacher, Fabian
A1  - Mohamed, Zainelabdeen H.
A1  - Kappe, Christian
A1  - Hessler, Gabriele
A1  - Pollmeier, Barbara
A1  - Kleuser, Burkhard
A1  - Arenz, Christoph
A1  - Becker, Katrin Anne
A1  - Gulbins, Erich
A1  - Carpinteiro, Alexander
T1  - Characterization of the small molecule ARC39
BT  - a direct and specific inhibitor of acid sphingomyelinase in vitro[S]
JF  - Journal of Lipid Research
N2  - Inhibition of acid sphingomyelinase (ASM), a lysosomal enzyme that catalyzes the hydrolysis of sphingomyelin into ceramide and phosphorylcholine, may serve as an investigational tool or a therapeutic intervention to control many diseases. Specific ASM inhibitors are currently not sufficiently characterized. Here, we found that 1-aminodecylidene bis-phosphonic acid (ARC39) specifically and efficiently (>90%) inhibits both lysosomal and secretory ASM in vitro. Results from investigating sphingomyelin phosphodiesterase 1 (SMPD1/Smpd1) mRNA and ASM protein levels suggested that ARC39 directly inhibits ASM's catalytic activity in cultured cells, a mechanism that differs from that of functional inhibitors of ASM. We further provide evidence that ARC39 dose- and time-dependently inhibits lysosomal ASM in intact cells, and we show that ARC39 also reduces platelet- and ASM-promoted adhesion of tumor cells. The observed toxicity of ARC39 is low at concentrations relevant for ASM inhibition in vitro, and it does not strongly alter the lysosomal compartment or induce phospholipidosis in vitro. When applied intraperitoneally in vivo, even subtoxic high doses administered short-term induced sphingomyelin accumulation only locally in the peritoneal lavage without significant accumulation in plasma, liver, spleen, or brain. These findings require further investigation with other possible chemical modifications. In conclusion, our results indicate that ARC39 potently and selectively inhibits ASM in vitro and highlight the need for developing compounds that can reach tissue concentrations sufficient for ASM inhibition in vivo.
KW  - sphingolipids
KW  - sphingomyelin
KW  - cerami-des
KW  - lipid metabolism
KW  - enzymology
KW  - lysosome
KW  - lysosomal hydrolases
KW  - acid ceramidase
KW  - bisphosphonates
KW  - functional inhibitors of acid sphin-gomyelinase
KW  - 1-aminodecylidene bis-phosphonic acid
Y1  - 2021
U6  - https://doi.org/10.1194/jlr.RA120000682
SN  - 1539-7262
SN  - 0022-2275
VL  - 61
IS  - 6
SP  - 896
EP  - 910
PB  - American Society for Biochemistry and Molecular Biology
CY  - Bethesda
ER  - 
TY  - JOUR
A1  - Reichel, Martin
A1  - Rhein, Cosima
A1  - Hofmann, Lena M.
A1  - Monti, Juliana
A1  - Japtok, Lukasz
A1  - Langgartner, Dominik
A1  - Füchsl, Andrea M.
A1  - Kleuser, Burkhard
A1  - Gulbins, Erich
A1  - Hellerbrand, Claus
A1  - Reber, Stefan O.
A1  - Kornhuber, Johannes
T1  - Chronic Psychosocial Stress in Mice Is Associated With Increased Acid Sphingomyelinase Activity in Liver and Serum and With Hepatic C16:0-Ceramide Accumulation
JF  - Frontiers in Psychiatry
N2  - 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.
KW  - chronic psychosocial stress
KW  - acid sphingomyelinase
KW  - ceramide
KW  - sphingolipid metabolism
KW  - chronic subordinate colony housing (CSC)
KW  - liver metabolism
Y1  - 2018
U6  - https://doi.org/10.3389/fpsyt.2018.00496
SN  - 1664-0640
VL  - 9
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Rawel, Harshadrai Manilal
A1  - Huschek, Gerd
A1  - Sagu Tchewonpi, Sorel
A1  - Homann, Thomas
T1  - Cocoa Bean Proteins-Characterization, Changes and Modifications due to Ripening and Post-Harvest Processing
JF  - Nutrients
N2  - The protein fractions of cocoa have been implicated influencing both the bioactive potential and sensory properties of cocoa and cocoa products. The objective of the present review is to show the impact of different stages of cultivation and processing with regard to the changes induced in the protein fractions. Special focus has been laid on the major seed storage proteins throughout the different stages of processing. The study starts with classical introduction of the extraction and the characterization methods used, while addressing classification approaches of cocoa proteins evolved during the timeline. The changes in protein composition during ripening and maturation of cocoa seeds, together with the possible modifications during the post-harvest processing (fermentation, drying, and roasting), have been documented. Finally, the bioactive potential arising directly or indirectly from cocoa proteins has been elucidated. The state of the art suggests that exploration of other potentially bioactive components in cocoa needs to be undertaken, while considering the complexity of reaction products occurring during the roasting phase of the post-harvest processing. Finally, the utilization of partially processed cocoa beans (e.g., fermented, conciliatory thermal treatment) can be recommended, providing a large reservoir of bioactive potentials arising from the protein components that could be instrumented in functionalizing foods.
KW  - cocoa processing
KW  - cocoa proteins
KW  - classification
KW  - extraction and characterization methods
KW  - fermentation-related enzymes
KW  - bioactive peptides
KW  - heath potentials
KW  - protein-phenol interactions
Y1  - 2019
U6  - https://doi.org/10.3390/nu11020428
SN  - 2072-6643
VL  - 11
IS  - 2
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Figueroa Campos, Gustavo A.
A1  - Sagu Tchewonpi, Sorel
A1  - Saravia Celis, Pedro
A1  - Rawel, Harshadrai Manilal
T1  - Comparison of batch and continuous wet-processing of coffee
BT  - changes in the main compounds in beans, by-products and wastewater
JF  - Foods
N2  - Many technical challenges still need to be overcome to improve the quality of the green coffee beans. In this work, the wet Arabica coffee processing in batch and continuous modus were investigated. Coffee beans samples as well as by-products and wastewaters collected at different production steps were analyzed in terms of their content in total phenols, antioxidant capacity, caffeine content, organic acids, reducing sugars, free amino group and protein content. The results showed that 40% of caffeine was removed with pulp. Green coffee beans showed highest concentration of organic acids and sucrose (4.96 ± 0.25 and 5.07 ± 0.39 g/100 g DW for the batch and continuous processing). Batch green coffee beans contained higher amount of phenols. 5-caffeoylquinic Acid (5-CQA) was the main constituent (67.1 and 66.0% for the batch and continuous processing, respectively). Protein content was 15 and 13% in the green coffee bean in batch and continuous processing, respectively. A decrease of 50 to 64% for free amino groups during processing was observed resulting in final amounts of 0.8 to 1.4% in the processed beans. Finally, the batch processing still revealed by-products and wastewater with high nutrient content encouraging a better concept for valorization.
KW  - Arabica coffee beans
KW  - coffee by-products
KW  - batch process
KW  - continuous process
KW  - nutritional characteristics
Y1  - 2020
U6  - https://doi.org/10.3390/foods9081135
SN  - 2304-8158
VL  - 9
IS  - 8
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Sagu Tchewonpi, Sorel
A1  - Zimmermann, Lynn
A1  - Landgräber, Eva
A1  - Homann, Thomas
A1  - Huschek, Gerd
A1  - Özpinar, Haydar
A1  - Schweigert, Florian J.
A1  - Rawel, Harshadrai Manilal
T1  - Comprehensive Characterization and Relative Quantification of α-Amylase/Trypsin Inhibitors from Wheat Cultivars by Targeted HPLC-MS/MS
JF  - Foods
N2  - The α-amylase/trypsin inhibitors (ATIs) are discussed as being responsible for non-celiac wheat sensitivity (NCWS), besides being known as allergenic components for baker’s asthma. Different approaches for characterization and quantification including proteomics-based methods for wheat ATIs have been documented. In these studies generally the major ATIs have been addressed. The challenge of current study was then to develop a more comprehensive workflow encompassing all reviewed wheat-ATI entries in UniProt database. To substantially test proof of concept, 46 German and Turkish wheat samples were used. Two extractions systems based on chloroform/methanol mixture (CM) and under buffered denaturing conditions were evaluated. Three aspects were optimized, tryptic digestion, chromatographic separation, and targeted tandem mass spectrometric analysis (HPLC-MS/MS). Preliminary characterization with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) documented the purity of the extracted ATIs with CM mixture and the amylase (60–80%)/trypsin (10–20%) inhibition demonstrated the bifunctional activity of ATIs. Thirteen (individual/common) biomarkers were established. Major ATIs (7–34%) were differently represented in samples. Finally, to our knowledge, the proposed HPLC-MS/MS method allowed for the first time so far the analysis of all 14 reviewed wheat ATI entries reported.
KW  - α-amylase/trypsin inhibitors
KW  - wheat cultivars
KW  - SDS-PAGE
KW  - peptides markers
KW  - relative quantification
KW  - mass spectrometry
KW  - LC-MRM-MS
Y1  - 2020
U6  - https://doi.org/10.3390/foods9101448
SN  - 2304-8158
VL  - 9
IS  - 10
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Koelman, Liselot A.
A1  - Pivovarova-Ramich, Olga
A1  - Pfeiffer, Andreas F. H.
A1  - Grune, Tilman
A1  - Aleksandrova, Krasimira
T1  - Cytokines for evaluation of chronic inflammatory status in ageing research
BT  - reliability and phenotypic characterisation
JF  - Immunity & Ageing
N2  - Background: There is a growing interest in the role of inflammageing for chronic disease development. Cytokines are potent soluble immune mediators that can be used as target biomarkers of inflammageing; however, their measurement in human samples has been challenging. This study aimed to assess the reliability of a pro- and anti-inflammatory cytokine panel in a sample of healthy people measured with a novel electrochemiluminescent multiplex immunoassay platform (Meso Scale Discovery, MSD), and to characterize their associations with metabolic and inflammatory phenotypes.
KW  - Reliability
KW  - Cytokines
KW  - Multiplex platforms
KW  - Inflammaging
KW  - Biomarkers
KW  - Ageing
KW  - BMI
Y1  - 2019
U6  - https://doi.org/10.1186/s12979-019-0151-1
SN  - 1742-4933
VL  - 16
PB  - BMC
CY  - London
ER  - 
TY  - JOUR
A1  - Kluth, Oliver
A1  - Stadion, Mandy
A1  - Gottmann, Pascal
A1  - Aga-Barfknecht, Heja
A1  - Jähnert, Markus
A1  - Scherneck, Stephan
A1  - Vogel, Heike
A1  - Krus, Ulrika
A1  - Seelig, Anett
A1  - Ling, Charlotte
A1  - Gerdes, Jantje
A1  - Schürmann, Annette
T1  - Decreased expression of cilia genes in pancreatic islets as a risk factor for type 2 diabetes in mice and humans
JF  - Cell reports
N2  - An insufficient adaptive beta-cell compensation is a hallmark of type 2 diabetes (T2D). Primary cilia function as versatile sensory antennae regulating various cellular processes, but their role on compensatory beta-cell replication has not been examined. Here, we identify a significant enrichment of downregulated, cilia-annotated genes in pancreatic islets of diabetes-prone NZO mice as compared with diabetes-resistant B6-ob/ob mice. Among 327 differentially expressed mouse cilia genes, 81 human orthologs are also affected in islets of diabetic donors. Islets of nondiabetic mice and humans show a substantial overlap of upregulated cilia genes that are linked to cell-cycle progression. The shRNA-mediated suppression of KIF3A, essential for ciliogenesis, impairs division of MINE beta cells as well as in dispersed primary mouse and human islet cells, as shown by decreased BrdU incorporation. These findings demonstrate the substantial role of cilia-gene regulation on islet function and T2D risk.
Y1  - 2019
U6  - https://doi.org/10.1016/j.celrep.2019.02.056
SN  - 2211-1247
VL  - 26
IS  - 11
SP  - 3027
EP  - 3036
PB  - Cell Press
CY  - Maryland Heights
ER  - 
TY  - JOUR
A1  - Rancan, Fiorenza
A1  - Volkmann, Hildburg
A1  - Giulbudagian, Michael
A1  - Schumacher, Fabian
A1  - Stanko, Jessica Isolde
A1  - Kleuser, Burkhard
A1  - Blume-Peytavi, Ulrike
A1  - Calderon, Marcelo
A1  - Vogt, Annika
T1  - Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels
JF  - Pharmaceutics : Molecular Diversity Preservation International
N2  - Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions.
KW  - tacrolimus formulation
KW  - nanogels
KW  - skin penetration
KW  - drug delivery
KW  - human excised skin
KW  - Jurkat cells
Y1  - 2019
U6  - https://doi.org/10.3390/pharmaceutics11080394
SN  - 1999-4923
VL  - 11
IS  - 8
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Sagu Tchewonpi, Sorel
A1  - Huschek, Gerd
A1  - Waldbach Braga, Tess
A1  - Rackiewicz, Michal
A1  - Homann, Thomas
A1  - Rawel, Harshadrai Manilal
T1  - Design of Experiment (DoE) for Optimization of HPLC Conditions for the Simultaneous Fractionation of Seven α-Amylase/Trypsin Inhibitors from Wheat (Triticum aestivum L.)
JF  - Processes : open access journal
N2  - Wheat alpha-amylase/trypsin inhibitors remain a subject of interest considering the latest findings showing their implication in wheat-related non-celiac sensitivity (NCWS). Understanding their functions in such a disorder is still unclear and for further study, the need for pure ATI molecules is one of the limiting problems. In this work, a simplified approach based on the successive fractionation of ATI extracts by reverse phase and ion exchange chromatography was developed. ATIs were first extracted from wheat flour using a combination of Tris buffer and chloroform/methanol methods. The separation of the extracts on a C18 column generated two main fractions of interest F1 and F2. The response surface methodology with the Doehlert design allowed optimizing the operating parameters of the strong anion exchange chromatography. Finally, the seven major wheat ATIs namely P01083, P17314, P16850, P01085, P16851, P16159, and P83207 were recovered with purity levels (according to the targeted LC-MS/MS analysis) of 98.2 ± 0.7; 98.1 ± 0.8; 97.9 ± 0.5; 95.1 ± 0.8; 98.3 ± 0.4; 96.9 ± 0.5, and 96.2 ± 0.4%, respectively. MALDI-TOF-MS analysis revealed single peaks in each of the pure fractions and the mass analysis yielded deviations of 0.4, 1.9, 0.1, 0.2, 0.2, 0.9, and 0.1% between the theoretical and the determined masses of P01083, P17314, P16850, P01085, P16851, P16159, and P83207, respectively. Overall, the study allowed establishing an efficient purification process of the most important wheat ATIs. This paves the way for further in-depth investigation of the ATIs to gain more knowledge related to their involvement in NCWS disease and to allow the absolute quantification in wheat samples.
KW  - wheat
KW  - α-amylase/trypsin inhibitors
KW  - fractionation
KW  - purification
KW  - reversed-phase chromatography
KW  - ion-exchange chromatography
KW  - design of experiment
KW  - LC–MS/MS
KW  - MALDI-TOF-MS
Y1  - 2022
U6  - https://doi.org/10.3390/pr10020259
SN  - 2227-9717
VL  - 10
SP  - 1
EP  - 18
PB  - MDPI
CY  - Basel, Schweiz
ET  - 2
ER  - 
TY  - JOUR
A1  - Bishop, Christopher Allen
A1  - Machate, Tina
A1  - Henning, Thorsten
A1  - Henkel-Oberländer, Janin
A1  - Püschel, Gerhard
A1  - Weber, Daniela
A1  - Grune, Tilman
A1  - Klaus, Susanne
A1  - Weitkunat, Karolin
T1  - Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle
JF  - Nutrition & Diabetes
N2  - Objective: 
Current data regarding the roles of branched-chain amino acids (BCAA) in metabolic health are rather conflicting, as positive and negative effects have been attributed to their intake. 

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

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

Conclusion:
These data demonstrate the detrimental role of valine in an HF context and elucidate additional targetable pathways in the etiology of BCAA-induced obesity and insulin resistance.
Y1  - 2022
U6  - https://doi.org/10.1038/s41387-022-00200-8
SN  - 2044-4052
VL  - 12
IS  - 1
PB  - Nature Publishing Group
CY  - London
ER  - 
TY  - JOUR
A1  - Rausch, Ann-Kristin
A1  - Brockmeyer, Robert
A1  - Schwerdtle, Tanja
T1  - Development, validation, and application of a multi-method for the determination of mycotoxins, plant growth regulators, tropane alkaloids, and pesticides in cereals by two-dimensional liquid chromatography tandem mass spectrometry
JF  - Analytical & bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica
N2  - Mycotoxins and pesticides regularly co-occur in agricultural products worldwide. Thus, humans can be exposed to both toxic contaminants and pesticides simultaneously, and multi-methods assessing the occurrence of various food contaminants and residues in a single method are necessary. A two-dimensional high performance liquid chromatography tandem mass spectrometry method for the analysis of 40 (modified) mycotoxins, two plant growth regulators, two tropane alkaloids, and 334 pesticides in cereals was developed. After an acetonitrile/water/formic acid (79:20:1, v/v/v) multi-analyte extraction procedure, extracts were injected into the two-dimensional setup, and an online clean-up was performed. The method was validated according to Commission Decision (EC) no. 657/2002 and document N° SANTE/12682/2019. Good linearity (R2 > 0.96), recovery data between 70-120%, repeatability and reproducibility values < 20%, and expanded measurement uncertainties < 50% were obtained for a wide range of analytes, including very polar substances like deoxynivalenol-3-glucoside and methamidophos. However, results for fumonisins, zearalenone-14,16-disulfate, acid-labile pesticides, and carbamates were unsatisfying. Limits of quantification meeting maximum (residue) limits were achieved for most analytes. Matrix effects varied highly (−85 to +1574%) and were mainly observed for analytes eluting in the first dimension and early-eluting analytes in the second dimension. The application of the method demonstrated the co-occurrence of different types of cereals with 28 toxins and pesticides. Overall, 86% of the samples showed positive findings with at least one mycotoxin, plant growth regulator, or pesticide.
KW  - 2D-LC-MS/MS
KW  - Multi-method
KW  - Mycotoxins
KW  - Modified mycotoxins
KW  - Pesticides
KW  - Cereals
Y1  - 2021
U6  - https://doi.org/10.1007/s00216-021-03239-1
SN  - 1618-2650
SN  - 1618-2642
VL  - 413
IS  - 11
SP  - 3041
EP  - 3054
PB  - Springer
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Menzel, Juliane
A1  - Longree, Alessa
A1  - Abraham, Klaus
A1  - Schulze, Matthias Bernd
A1  - Weikert, Cornelia
T1  - Dietary and plasma phospholipid profiles in vegans and omnivores-results from the RBVD study
JF  - Nutrients
N2  - Over the last few years, the vegan diet has become increasingly popular in Germany. It has been proposed that this diet is generally lower in fat, but less is known about the impact on fatty acid (FA) profiles. Therefore, the cross-sectional "Risks and Benefits of a Vegan Diet" (RBVD) study (n = 72) was used to investigate dietary FA intake as well as plasma phospholipid FA in vegans (n = 36) compared to omnivores (n = 36). Vegans had a significantly lower dietary intake of total fat (median 86 g/day, IQR 64-111) in comparison to omnivores (median 104 g/day, IQR 88-143, p = 0.004). Further, vegans had a lower intake of saturated fatty acids (SFA) (p < 0.0001) and monounsaturated fatty acids (MUFA) (p = 0.001) compared to omnivores. Vegans had a higher intake in total polyunsaturated fatty acids (PUFA), omega-3 and omega-6 PUFA compared to omnivores, but without statistical significance after Bonferroni correction. According to plasma phospholipid profiles, relatively lower proportions of SFA (p < 0.0001), total trans fatty acids (TFA) (p = 0.0004) and omega-3-FA (p < 0.0001), but higher proportions of omega-6-FA (p < 0.0001) were observed in vegans. With the exception of omega-3 PUFA, a vegan diet is associated with a more favorable dietary fat intake and more favorable plasma FA profiles and therefore may reduce cardiovascular risk.
KW  - SFA
KW  - TFA
KW  - MUFA
KW  - PUFA
KW  - n-3 fatty acid
KW  - n-6 fatty acid
KW  - fatty acids
KW  - vegan diet
Y1  - 2022
U6  - https://doi.org/10.3390/nu14142900
SN  - 2072-6643
VL  - 14
IS  - 14
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Koelman, Liselot A.
A1  - Huybrechts, Inge
A1  - Biesbroek, Sander
A1  - van 't Veer, Pieter
A1  - Schulze, Matthias Bernd
A1  - Aleksandrova, Krasimira
T1  - Dietary choices impact on greenhouse gas emissions
BT  - determinants and correlates in a sample of adults from Eastern Germany
JF  - Sustainability / Multidisciplinary Digital Publishing Institute (MDPI)
N2  - The present study estimated diet-related greenhouse gas emissions (GHGE) and land use (LU) in a sample of adults, examined main dietary contributors of GHGE, and evaluated socio demographic, lifestyle, and wellbeing factors as potential determinants of high environmental impact. A cross-sectional design based on data collected from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (2010-2012) was used. Usual diet was assessed using food frequency questionnaires. Diet-related GHGE and LU were calculated using a European-average lifecycle analyses-food-item database (SHARP-ID). Information on potential determinants were collected using self-administered questionnaires. Men (n = 404) and women (n = 401) at an average age of 66.0 +/- 8.4 years were included. Dietary-related energy-adjusted GHGE in men was 6.6 +/- 0.9 and in women was 7.0 +/- 1.1 kg CO2 eq per 2000 kcal. LU in men was 7.8 +/- 1.2 and in women was 7.7 +/- 1.2 m(2)/year per 2000 kcal. Food groups contributing to most GHGE included dairy, meat and non-alcoholic beverages. Among women, being single, having a job, being a smoker and having higher BMI were characteristics associated with higher GHGE, whereas for men these included being married, longer sleeping duration and higher BMI. Further studies are warranted to provide insights into population-specific determinants of sustainable dietary choices.
KW  - dietary choices
KW  - environmental impact
KW  - greenhouse gas emissions
KW  - land use
KW  - determinants
Y1  - 2022
U6  - https://doi.org/10.3390/su14073854
SN  - 2071-1050
VL  - 14
IS  - 7
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Neuschäfer-Rube, Frank
A1  - Pathe-Neuschäfer-Rube, Andrea
A1  - Püschel, Gerhard Paul
T1  - Discrimination of the activity of low-affinity wild-type and high-affinity mutant recombinant BoNT/B by a SIMA cell-based reporter release assay
JF  - Toxins
N2  - Botulinum neurotoxin (BoNT) is used for the treatment of a number of ailments. The activity of the toxin that is isolated from bacterial cultures is frequently tested in the mouse lethality assay. Apart from the ethical concerns inherent to this assay, species-specific differences in the affinity for different BoNT serotypes give rise to activity results that differ from the activity in humans. Thus, BoNT/B is more active in mice than in humans. The current study shows that the stimulus-dependent release of a luciferase from a differentiated human neuroblastoma–based reporter cell line (SIMA-hPOMC1-26-Gluc) was inhibited by clostridial and recombinant BoNT/A to the same extent, whereas both clostridial and recombinant BoNT/B inhibited the release to a lesser extent and only at much higher concentrations, reflecting the low activity of BoNT/B in humans. By contrast, the genetically modified BoNT/B-MY, which has increased affinity for human synaptotagmin, and the BoNT/B protein receptor inhibited luciferase release effectively and with an EC50 comparable to recombinant BoNT/A. This was due to an enhanced uptake into the reporter cells of BoNT/B-MY in comparison to the recombinant wild-type toxin. Thus, the SIMA-hPOMC1-26-Gluc cell assay is a versatile tool to determine the activity of different BoNT serotypes providing human-relevant dose-response data.
KW  - cell-based assay
KW  - genetically modified BoNT
KW  - BoNT/B uptake
Y1  - 2022
U6  - https://doi.org/10.3390/toxins14010065
SN  - 2072-6651
VL  - 14
SP  - 1
EP  - 11
PB  - MDPI
CY  - Basel, Schweiz
ET  - 1
ER  - 
TY  - JOUR
A1  - Aga-Barfknecht, Heja
A1  - Soultoukis, George A.
A1  - Stadion, Mandy
A1  - Garcia-Carrizo, Francisco
A1  - Jähnert, Markus
A1  - Gottmann, Pascal
A1  - Vogel, Heike
A1  - Schulz, Tim Julius
A1  - Schürmann, Annette
T1  - Distinct adipogenic and fibrogenic differentiation capacities of mesenchymal stromal cells from pancreas and white adipose tissue
JF  - International journal of molecular sciences
N2  - Pancreatic steatosis associates with beta-cell failure and may participate in the development of type-2-diabetes. Our previous studies have shown that diabetes-susceptible mice accumulate more adipocytes in the pancreas than diabetes-resistant mice. In addition, we have demonstrated that the co-culture of pancreatic islets and adipocytes affect insulin secretion. The aim of this current study was to elucidate if and to what extent pancreas-resident mesenchymal stromal cells (MSCs) with adipogenic progenitor potential differ from the corresponding stromal-type cells of the inguinal white adipose tissue (iWAT). miRNA (miRNome) and mRNA expression (transcriptome) analyses of MSCs isolated by flow cytometry of both tissues revealed 121 differentially expressed miRNAs and 1227 differentially expressed genes (DEGs). Target prediction analysis estimated 510 DEGs to be regulated by 58 differentially expressed miRNAs. Pathway analyses of DEGs and miRNA target genes showed unique transcriptional and miRNA signatures in pancreas (pMSCs) and iWAT MSCs (iwatMSCs), for instance fibrogenic and adipogenic differentiation, respectively. Accordingly, iwatMSCs revealed a higher adipogenic lineage commitment, whereas pMSCs showed an elevated fibrogenesis. As a low degree of adipogenesis was also observed in pMSCs of diabetes-susceptible mice, we conclude that the development of pancreatic steatosis has to be induced by other factors not related to cell-autonomous transcriptomic changes and miRNA-based signals.
KW  - MSCs
KW  - fatty pancreas
KW  - WAT
KW  - lineage commitment
KW  - transcriptomics
KW  - miRNAs
Y1  - 2022
U6  - https://doi.org/10.3390/ijms23042108
SN  - 1422-0067
VL  - 23
IS  - 4
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  - 
TY  - JOUR
A1  - Kleuser, Burkhard
T1  - Divergent role of sphingosine 1-phosphate in liver health and disease
JF  - International journal of molecular sciences
N2  - 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.
KW  - sphingolipids
KW  - sphingosine kinase
KW  - fibrosis
KW  - non-alcoholic fatty liver disease
KW  - insulin resistance
KW  - liver fibrosis
Y1  - 2018
U6  - https://doi.org/10.3390/ijms19030722
SN  - 1422-0067
VL  - 19
IS  - 3
PB  - MDPI
CY  - Basel
ER  - 
TY  - GEN
A1  - Reichetzeder, Christoph
A1  - Hocher, Berthold
T1  - DPP4 inhibition prevents AKI
T2  - Oncotarget
KW  - acute kidney injury
KW  - DPP-4 inhibitors
KW  - ischemia reperfusion injury
KW  - gliptins
KW  - Dipeptidyl peptidase IV
Y1  - 2017
U6  - https://doi.org/10.18632/oncotarget.20212
SN  - 1949-2553
VL  - 8
SP  - 64655
EP  - 64656
PB  - Impact Journals LLC
CY  - Orchard Park
ER  - 
TY  - BOOK
A1  - Kollodzeiski, Ulrike
A1  - Hafner, Johann Evangelist
A1  - Lippert, Rachel N.
A1  - Bartelmeß, Tina
A1  - Schweigert, Florian J.
A1  - Bigalke, Bernadett
A1  - Krochmalnik, Daniel
A1  - Sancı, Kadir
A1  - Kardas, Arhan
A1  - Dietzel, Irene
A1  - Yilmaz, Rümeysa
A1  - Olhoeft, Netanel
A1  - Struß, Lukas
ED  - Kollodzeiski, Ulrike
ED  - Hafner, Johann Evangelist
T1  - Du sollst nicht essen
BT  - Warum Menschen auf Nahrung verzichten – interdisziplinäre Zugänge
N2  - Zwar sind Menschen biologisch gesehen Allesesser, dennoch gibt es keine Gemeinschaft, die alle ihr zur Verfügung stehenden Nahrungsmittel voll ausschöpft. Immer wird etwas nicht gegessen. Warum wir nicht essen, was wir nicht essen – das beleuchtet dieser Sammelband aus neuro-, ernährungs-, gesellschafts- und religionswissenschaftlicher Perspektive. Ein „religiöser Nutriscore“ gibt Auskunft über die wichtigsten Verzichtsregeln in Judentum, Christentum und Islam. Eine Fotostrecke veranschaulicht, wie bestimmte Speisen zu Festen und Feiertagen zu einem heiligen Essen werden. Nicht zuletzt werden Wege aufgezeigt, wie Menschen, die verschiedene Speiseregeln befolgen, dennoch zusammen essen können – inklusive Praxistest in der Unimensa.
KW  - Speisegebot
KW  - Ernährungsgewohnheit
KW  - Religiöses Leben
KW  - Judentum
KW  - Christentum
KW  - Islam
Y1  - 2024
SN  - 978-3-98740-007-0
SN  - 978-3-98740-008-7
U6  - https://doi.org/10.5771/9783987400087
EP  - 172
PB  - Ergon Verlag
CY  - Baden-Baden
ER  - 
TY  - JOUR
A1  - Borremans, An
A1  - Bußler, Sara
A1  - Sagu Tchewonpi, Sorel
A1  - Rawel, Harshadrai Manilal
A1  - Schlüter, Oliver K.
A1  - Leen, Van Campenhout
T1  - Effect of blanching plus fermentation on selected functional properties of mealworm (Tenebrio molitor) powders
JF  - Foods : open access journal
N2  - The aim of this study was to determine the effect of blanching followed by fermentation of mealworms (Tenebrio molitor) with commercial meat starter cultures on the functional properties of powders produced from the larvae. Full fat and defatted powder samples were prepared from non-fermented and fermented mealworm pastes. Then the crude protein, crude fat, and dry matter contents, pH, bulk density, colour, water and oil binding capacity, foaming capacity and stability, emulsion capacity and stability, protein solubility, quantity of free amino groups, and protein composition of the powders were evaluated. Regardless of the starter culture used, the blanching plus fermentation process reduced the crude and soluble protein contents of the full fat powders and in general impaired their water and oil binding, foaming, and emulsifying properties. Defatting of the powders improved most functional properties studied. The o-phthaldialdehyde assay revealed that the amount of free amino groups was higher in the fermented powders while sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that the soluble proteins of the fermented powders were composed of molecules of lower molecular mass compared to non-fermented powders. As molecular sizes of the soluble proteins decreased, it was clear that the protein structure was also modified by the fermentation process, which in turn led to changes in functional properties. In general, it was concluded that fermentation of mealworms with blanching as a pre-treatment does not contribute to the functional properties studied in this work. Nevertheless, the results confirmed that the properties of non-fermented powders are comparable to other food protein sources.
KW  - mealworm
KW  - fermentation
KW  - functional properties
KW  - insect proteins
KW  - SDS-PAGE
Y1  - 2020
U6  - https://doi.org/10.3390/foods9070917
SN  - 2304-8158
VL  - 9
IS  - 7
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Tchewonpi Sagu, Sorel
A1  - Landgräber, Eva
A1  - Henkel, Ina M.
A1  - Huschek, Gerd
A1  - Homann, Thomas
A1  - Bußler, Sara
A1  - Schlüter, Oliver K.
A1  - Rawel, Harshadrai Manilal
T1  - Effect of cereal α-amylase/trypsin inhibitors on developmental characteristics and abundance of digestive enzymes of mealworm larvae (Tenebrio molitor L.)
JF  - Insects
N2  - The objective of this work was to investigate the potential effect of cereal α-amylase/trypsin inhibitors (ATIs) on growth parameters and selective digestive enzymes of Tenebrio molitor L. larvae. The approach consisted of feeding the larvae with wheat, sorghum and rice meals containing different levels and composition of α-amylase/trypsin inhibitors. The developmental and biochemical characteristics of the larvae were assessed over feeding periods of 5 h, 5 days and 10 days, and the relative abundance of α-amylase and selected proteases in larvae were determined using liquid chromatography tandem mass spectrometry. Overall, weight gains ranged from 21% to 42% after five days of feeding. The larval death rate significantly increased in all groups after 10 days of feeding (p < 0.05), whereas the pupation rate was about 25% among larvae fed with rice (Oryza sativa L.) and Siyazan/Esperya wheat meals, and only 8% and 14% among those fed with Damougari and S35 sorghum meals. As determined using the Lowry method, the protein contents of the sodium phosphate extracts ranged from 7.80 ± 0.09 to 9.42 ± 0.19 mg/mL and those of the ammonium bicarbonate/urea reached 19.78 ± 0.16 to 37.47 ± 1.38 mg/mL. The total protein contents of the larvae according to the Kjeldahl method ranged from 44.0 and 49.9 g/100 g. The relative abundance of α-amylase, CLIP domain-containing serine protease, modular serine protease zymogen and C1 family cathepsin significantly decreased in the larvae, whereas dipeptidylpeptidase I and chymotrypsin increased within the first hours after feeding (p < 0.05). Trypsin content was found to be constant independently of time or feed material. Finally, based on the results we obtained, it was difficult to substantively draw conclusions on the likely effects of meal ATI composition on larval developmental characteristics, but their effects on the digestive enzyme expression remain relevant.
KW  - growth behavior
KW  - Tenebrio molitor larvae
KW  - feeding
KW  - cereal meals
KW  - α-amylase/trypsin inhibitors
KW  - digestive enzymes quantification
KW  - LC-MS/MS
Y1  - 2021
U6  - https://doi.org/10.3390/insects12050454
SN  - 2075-4450
VL  - 12
IS  - 5
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Weitkunat, Karolin
A1  - Bishop, Christopher Allen
A1  - Wittmüss, Maria
A1  - Machate, Tina
A1  - Schifelbein, Tina
A1  - Schulze, Matthias Bernd
A1  - Klaus, Susanne
T1  - Effect of microbial status on hepatic odd-chain fatty acids is diet-dependent
JF  - Nutrients / Molecular Diversity Preservation International (MDPI)
N2  - Odd-chain fatty acids (OCFA) are inversely associated with type-2-diabetes in epidemiological studies. They are considered as a biomarker for dairy intake because fermentation in ruminants yields high amounts of propionate, which is used as the primer for lipogenesis. Recently, we demonstrated endogenous OCFA synthesis from propionate in humans and mice, but how this is affected by microbial colonization is still unexplored. Here, we investigated the effect of increasing microbiota complexity on hepatic lipid metabolism and OCFA levels in different dietary settings. Germ-free (GF), gnotobiotic (SIH, simplified human microbiota) or conventional (CONV) C3H/HeOuJ-mice were fed a CHOW or high-fat diet with inulin (HFI) to induce microbial fermentation. We found that hepatic lipogenesis was increased with increasing microbiota complexity, independently of diet. In contrast, OCFA formation was affected by diet as well as microbiota. On CHOW, hepatic OCFA and intestinal gluconeogenesis decreased with increasing microbiota complexity (GF > SIH > CONV), while cecal propionate showed a negative correlation with hepatic OCFA. On HFI, OCFA levels were highest in SIH and positively correlated with cecal propionate. The propionate content in the CHOW diet was 10 times higher than that of HFI. We conclude that bacterial propionate production affects hepatic OCFA formation, unless this effect is masked by dietary propionate intake.
KW  - pentadecanoic acid (C15:0)
KW  - heptadecanoic acid (C17:0)
KW  - type-2-diabetes
KW  - fatty acid synthesis
KW  - acetate
KW  - propionate
KW  - probiotics
KW  - gut microbiota
KW  - prebiotics
KW  - inulin
Y1  - 2021
U6  - https://doi.org/10.3390/nu13051546
SN  - 2072-6643
VL  - 13
IS  - 5
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Sagu Tchewonpi, Sorel
A1  - Huschek, Gerd
A1  - Homann, Thomas
A1  - Rawel, Harshadrai Manilal
T1  - Effect of sample preparation on the detection and quantification of selected nuts allergenic proteins by LC-MS/MS
JF  - Molecules : a journal of synthetic chemistry and natural product chemistry / Molecular Diversity Preservation International
N2  - The detection and quantification of nut allergens remains a major challenge. The liquid chroma-tography tandem mass spectrometry (LC-MS/MS) is emerging as one of the most widely used methods, but sample preparation prior to the analysis is still a key issue. The objective of this work was to establish optimized protocols for extraction, tryptic digestion and LC-MS analysis of almond, cashew, hazelnut, peanut, pistachio and walnut samples. Ammonium bicar-bonate/urea extraction (Ambi/urea), SDS buffer extraction (SDS), polyvinylpolypyrroli-done (PVPP) extraction, trichloroacetic acid/acetone extraction (TCA/acetone) and chloro-form/methanol/sodium chloride precipitation (CM/NaCl) as well as the performances of con-ventional tryptic digestion and microwave-assisted breakdown were investigated. Overall, the protein extraction yields ranged from 14.9 ± 0.5 (almond extract from CM/NaCl) to 76.5 ± 1.3% (hazelnut extract from Ambi/urea). Electrophoretic profiling showed that the SDS extraction method clearly presented a high amount of extracted proteins in the range of 0–15 kDa, 15–35 kDa, 35–70 kDa and 70–250 kDa compared to the other methods. The linearity of the LC-MS methods in the range of 0 to 0.4 µg equivalent defatted nut flour was assessed and recovery of internal standards GWGG and DPLNV(d8)LKPR ranged from 80 to 120%. The identified bi-omarkers peptides were used to relatively quantifier selected allergenic protein form the inves-tigated nut samples. Considering the overall results, it can be concluded that SDS buffer allows a better protein extraction from almond, peanut and walnut samples while PVPP buffer is more appropriate for cashew, pistachio and hazelnut samples. It was also found that conventional overnight digestion is indicated for cashew, pistachio and hazelnut samples, while microwave assisted tryptic digestion is recommended for almond, hazelnut and peanut extracts.
KW  - nut allergenic proteins
KW  - protein extraction
KW  - sample preparation
KW  - tryptic digestion
KW  - microwave assisted digestion
KW  - SDS PAGE
KW  - LC-MS/MS
Y1  - 2021
U6  - https://doi.org/10.3390/molecules26154698
SN  - 1420-3049
VL  - 26
IS  - 15
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Figueroa Campos, Gustavo Adolfo
A1  - G. K. T. Kruizenga, Johannes
A1  - Sagu Tchewonpi, Sorel
A1  - Schwarz, Steffen
A1  - Homann, Thomas
A1  - Taubert, Andreas
A1  - Rawel, Harshadrai Manilal
T1  - Effect of the post-harvest processing on protein modification in green coffee beans by phenolic compounds
JF  - Foods : open access journal
N2  - The protein fraction, important for coffee cup quality, is modified during post-harvest treatment prior to roasting. Proteins may interact with phenolic compounds, which constitute the major metabolites of coffee, where the processing affects these interactions. This allows the hypothesis that the proteins are denatured and modified via enzymatic and/or redox activation steps. The present study was initiated to encompass changes in the protein fraction. The investigations were limited to major storage protein of green coffee beans. Fourteen Coffea arabica samples from various processing methods and countries were used. Different extraction protocols were compared to maintain the status quo of the protein modification. The extracts contained about 4–8 µg of chlorogenic acid derivatives per mg of extracted protein. High-resolution chromatography with multiple reaction monitoring was used to detect lysine modifications in the coffee protein. Marker peptides were allocated for the storage protein of the coffee beans. Among these, the modified peptides K.FFLANGPQQGGK.E and R.LGGK.T of the α-chain and R.ITTVNSQK.I and K.VFDDEVK.Q of β-chain were detected. Results showed a significant increase (p < 0.05) of modified peptides from wet processed green beans as compared to the dry ones. The present study contributes to a better understanding of the influence of the different processing methods on protein quality and its role in the scope of coffee cup quality and aroma. View Full-Text
KW  - Arabica coffee
KW  - coffee processing
KW  - protein modification
KW  - bound phenolic compounds
KW  - peptide biomarkers
KW  - LC-MS/MS
Y1  - 2022
U6  - https://doi.org/10.3390/foods11020159
SN  - 2304-8158
VL  - 11
PB  - MDPI
CY  - Basel, Schweiz
ET  - 2
ER  - 
TY  - JOUR
A1  - Starzonek, Janine
A1  - Roscher, Katja
A1  - Blither, Matthias
A1  - Blaue, Dominique
A1  - Schedlbauer, Carola
A1  - Hire, Manuela
A1  - Raila, Jens
A1  - Vervuert, Ingrid
T1  - Effects of a blend of green tea and curcuma extract supplementation on lipopolysaccharide-induced inflammation in horses and ponies
JF  - PeerJ
N2  - Background. In horses and ponies numerous medical conditions are known to be linked with inflammation in different tissues, especially in the liver. Besides affecting other metabolic pathways such as the expression of certain interleukins (IL), inflammation is associated with stress of the endoplasmic reticulum (ER). In particular, ER stress leads to adaptive stress response and can be measured by several markers of inflammatory and stress signalling pathways, like nuclear factor kappa B (NF-kB). Objectives. To investigate lipopolysaccharide (LPS)-induced inflammatory reactions and their modulation in horses and ponies by feeding a polyphenol-rich supplement consisting of green tea and curcuma. Methods. In a cross-over study, 11 animals were allocated to either a placebo or a supplement group and supplemented with 10 g of a blend of green tea and curcuma extract (GCE) or a placebo (calcium carbonate) once daily. After 21 days of supplementation, all animals underwent a LPS challenge to induce moderate systemic inflammation. Blood samples and liver biopsies were taken at standardized time points: 24 hours before and 12 hours after LPS challenge. Inflammatory blood parameters such as serum amyloid A (SAA), haptoglobin and retinol binding protein 4 (RBP4) were measured in serum. Hepatic mRNA levels of selected markers of inflammation such as haptoglobin, tumor necrosis factor alpha (TNF-alpha), IL-1 beta, IL-6, cluster of differentiation 68 (CD68), fibroblast growth factor 21 (FGF-21), NF-kappa B, activating transcription factor 4 (ATF4) were quantified by RT-qPCR. In addition, liver biopsies were examined histologically for inflammatory alterations. Results. Blood markers of acute inflammatory response increased after LPS challenge. In the liver, the proinflammatory cytokine IL-1 beta showed significantly lower mRNA levels after LPS challenge in the supplemented group (P = 0.04) compared to the placebo group. Levels of the hepatic CD68 mRNA increased significantly in the placebo group (P = 0.04). There were no significant differences between supplemented and placebo groups concerning other markers of inflammation and markers of ER stress within the liver. The number of hepatic macrophages were not different after LPS challenge in both feeding groups. Conclusion. LPS was able to induce inflammation but seemed less suitable to induce ER stress in the horses and ponies. The polyphenol-rich supplement showed some potential to reduce inflammatory responses. Nevertheless, the supplementation did not exert an overall anti-inflammatory effect in horses and ponies.
KW  - Curcumin
KW  - Catechin
KW  - Equines
KW  - ER-stress
KW  - Polyphenols
Y1  - 2019
U6  - https://doi.org/10.7717/peerj.8053
SN  - 2167-8359
VL  - 7
PB  - PeerJ Inc.
CY  - London
ER  - 
TY  - JOUR
A1  - Kehm, Richard
A1  - Rückriemen, Jana
A1  - Weber, Daniela
A1  - Deubel, Stefanie
A1  - Grune, Tilman
A1  - Höhn, Annika
T1  - Endogenous advanced glycation end products in pancreatic islets after short-term carbohydrate intervention in obese, diabetes-prone mice
JF  - Nutrition & Diabetes
N2  - Diet-induced hyperglycemia is described as one major contributor to the formation of advanced glycation end products (AGEs) under inflammatory conditions, crucial in type 2 diabetes progression. Previous studies have indicated high postprandial plasma AGE-levels in diabetic patients and after long-term carbohydrate feeding in animal models. Pancreatic islets play a key role in glucose metabolism; thus, their susceptibility to glycation reactions due to high amounts of dietary carbohydrates is of special interest. Therefore, diabetes-prone New Zealand Obese (NZO) mice received either a carbohydrate-free, high-fat diet (CFD) for 11 weeks or were additionally fed with a carbohydrate-rich diet (CRD) for 7 days. In the CRD group, hyperglycemia and hyperinsulinemia were induced accompanied by increasing plasma 3-nitrotyrosine (3-NT) levels, higher amounts of 3-NT and inducible nitric oxide synthase (iNOS) within pancreatic islets. Furthermore, N-epsilon-carboxymethyllysine (CML) was increased in the plasma of CRD-fed NZO mice and substantially higher amounts of arg-pyrimidine, pentosidine and the receptor for advanced glycation end products (RAGE) were observed in pancreatic islets. These findings indicate that a short-term intervention with carbohydrates is sufficient to form endogenous AGEs in plasma and pancreatic islets of NZO mice under hyperglycemic and inflammatory conditions.
Y1  - 2019
U6  - https://doi.org/10.1038/s41387-019-0077-x
SN  - 2044-4052
VL  - 9
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Henkel-Oberländer, Janin
A1  - Klauder, Julia
A1  - Statz, Meike
A1  - Wohlenberg, Anne-Sophie
A1  - Kuipers, Sonja
A1  - Vahrenbrink, Madita
A1  - Püschel, Gerhard
T1  - Enhanced Palmitate-Induced Interleukin-8 Formation in Human Macrophages by Insulin or Prostaglandin E₂
JF  - Biomedicines : open access journal
N2  - Macrophages in pathologically expanded dysfunctional white adipose tissue are exposed to a mix of potential modulators of inflammatory response, including fatty acids released from insulin-resistant adipocytes, increased levels of insulin produced to compensate insulin resistance, and prostaglandin E₂ (PGE₂) released from activated macrophages. The current study addressed the question of how palmitate might interact with insulin or PGE₂ to induce the formation of the chemotactic pro-inflammatory cytokine interleukin-8 (IL-8). Human THP-1 cells were differentiated into macrophages. In these macrophages, palmitate induced IL-8 formation. Insulin enhanced the induction of IL-8 formation by palmitate as well as the palmitate-dependent stimulation of PGE₂ synthesis. PGE₂ in turn elicited IL-8 formation on its own and enhanced the induction of IL-8 release by palmitate, most likely by activating the EP4 receptor. Since IL-8 causes insulin resistance and fosters inflammation, the increase in palmitate-induced IL-8 formation that is caused by hyperinsulinemia and locally produced PGE₂ in chronically inflamed adipose tissue might favor disease progression in a vicious feed-forward cycle.
KW  - macrophages
KW  - insulin
KW  - prostaglandin E2
KW  - interleukin-8
KW  - inflammation
Y1  - 2021
U6  - https://doi.org/10.3390/biomedicines9050449
SN  - 2227-9059
VL  - 9
IS  - 5
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Wetzel, Alexandra Nicole
A1  - Scholtka, Bettina
A1  - Schumacher, Fabian
A1  - Rawel, Harshadrai Manilal
A1  - Geisendörfer, Birte
A1  - Kleuser, Burkhard
T1  - Epigenetic DNA methylation of EBI3 modulates human interleukin-35 formation via NFkB signaling
BT  - a promising therapeutic option in ulcerative colitis
JF  - International journal of molecular sciences
N2  - Ulcerative colitis (UC), a severe chronic disease with unclear etiology that is associated with increased risk for colorectal cancer, is accompanied by dysregulation of cytokines. Epstein-Barr virus-induced gene 3 (EBI3) encodes a subunit in the unique heterodimeric IL-12 cytokine family of either pro- or anti-inflammatory function. After having recently demonstrated that upregulation of EBI3 by histone acetylation alleviates disease symptoms in a dextran sulfate sodium (DSS)-treated mouse model of chronic colitis, we now aimed to examine a possible further epigenetic regulation of EBI3 by DNA methylation under inflammatory conditions. Treatment with the DNA methyltransferase inhibitor (DNMTi) decitabine (DAC) and TNF alpha led to synergistic upregulation of EBI3 in human colon epithelial cells (HCEC). Use of different signaling pathway inhibitors indicated NF kappa B signaling was necessary and proportional to the synergistic EBI3 induction. MALDI-TOF/MS and HPLC-ESIMS/MS analysis of DAC/TNF alpha-treated HCEC identified IL-12p35 as the most probable binding partner to form a functional protein. EBI3/IL-12p35 heterodimers (IL-35) induce their own gene upregulation, something that was indeed observed in HCEC cultured with media from previously DAC/TNF alpha-treated HCEC. These results suggest that under inflammatory and demethylating conditions the upregulation of EBI3 results in the formation of anti-inflammatory IL-35, which might be considered as a therapeutic target in colitis.
KW  - decitabine
KW  - DNMT inhibitor
KW  - EBI3
KW  - inhibitory cytokines
KW  - interleukin-35
KW  - TNF alpha
KW  - Ulcerative colitis
Y1  - 2021
U6  - https://doi.org/10.3390/ijms22105329
SN  - 1422-0067
VL  - 22
IS  - 10
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Birukov, Anna
A1  - Polemiti, Elli
A1  - Jaeger, Susanne
A1  - Stefan, Norbert
A1  - Schulze, Matthias Bernd
T1  - Fetuin-A and risk of diabetes-related vascular complications
BT  - a prospective study
JF  - Cardiovascular diabetology
N2  - Background
Fetuin-A is a hepatokine which has the capacity to prevent vascular calcification. Moreover, it is linked to the induction of metabolic dysfunction, insulin resistance and associated with increased risk of diabetes.
It has not been clarified whether fetuin-A associates with risk of vascular, specifically microvascular, complications in patients with diabetes. 
We aimed to investigate whether pre-diagnostic plasma fetuin-A is associated with risk of complications once diabetes develops. 

Methods 
Participants with incident type 2 diabetes and free of micro- and macrovascular disease from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 587) were followed for microvascular and macrovascular complications (n = 203 and n = 60, respectively, median follow-up: 13 years).
Plasma fetuin-A was measured approximately 4 years prior to diabetes diagnosis. Prospective associations between baseline fetuin-A and risk of complications were assessed with Cox regression. 

Results 
In multivariable models, fetuin-A was linearly inversely associated with incident total and microvascular complications, hazard ratio (HR, 95% CI) per standard deviation (SD) increase: 0.86 (0.74; 0.99) for total, 0.84 (0.71; 0.98) for microvascular and 0.92 (0.68; 1.24) for macrovascular complications. After additional adjustment for cardiometabolic plasma biomarkers, including triglycerides and high-density lipoprotein, the associations were slightly attenuated: 0.88 (0.75; 1.02) for total, 0.85 (0.72; 1.01) for microvascular and 0.95 (0.67; 1.34) for macrovascular complications. No interaction by sex could be observed (p > 0.10 for all endpoints). 

Conclusions 
Our data show that lower plasma fetuin-A levels measured prior to the diagnosis of diabetes may be etiologically implicated in the development of diabetes-associated microvascular disease.
KW  - Fetuin-A
KW  - biomarkers
KW  - epidemiology
KW  - Type 2 diabetes
KW  - vascular disease;
KW  - vascular calcification
KW  - microvascular complications
Y1  - 2022
U6  - https://doi.org/10.1186/s12933-021-01439-8
SN  - 1475-2840
VL  - 21
IS  - 1
PB  - BMC
CY  - London
ER  - 
TY  - JOUR
A1  - McNulty, Margaret A.
A1  - Goupil, Brad A.
A1  - Albarado, Diana C.
A1  - Castaño-Martinez, Teresa
A1  - Ambrosi, Thomas H.
A1  - Puh, Spela
A1  - Schulz, Tim Julius
A1  - Schürmann, Annette
A1  - Morrison, Christopher D.
A1  - Laeger, Thomas
T1  - FGF21, not GCN2, influences bone morphology due to dietary protein restrictions
JF  - Bone Reports
N2  - Background: Dietary protein restriction is emerging as an alternative approach to treat obesity and glucose intolerance because it markedly increases plasma fibroblast growth factor 21 (FGF21) concentrations. Similarly, dietary restriction of methionine is known to mimic metabolic effects of energy and protein restriction with FGF21 as a required mechanism. However, dietary protein has been shown to be required for normal bone growth, though there is conflicting evidence as to the influence of dietary protein restriction on bone remodeling. The purpose of the current study was to evaluate the effect of dietary protein and methionine restriction on bone in lean and obese mice, and clarify whether FGF21 and general control nonderepressible 2 (GCN2) kinase, that are part of a novel endocrine pathway implicated in the detection of protein restriction, influence the effect of dietary protein restriction on bone.

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

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

Conclusions: This study provides direct evidence of a reduction in bone following long-term dietary protein restriction in a mouse model, effects that appear to be mediated by FGF21.
KW  - dietary restriction
KW  - protein restriction
KW  - FGF21
KW  - GCN2
KW  - microcomputed tomography
Y1  - 2020
U6  - https://doi.org/10.1016/j.bonr.2019.100241
SN  - 2352-1872
VL  - 12
SP  - 1
EP  - 10
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Olayide, Priscilla
A1  - Large, Annabel
A1  - Stridh, Linnea
A1  - Rabbi, Ismail
A1  - Baldermann, Susanne
A1  - Stavolone, Livia
A1  - Alexandersson, Erik
T1  - Gene expression and metabolite profiling of thirteen Nigerian cassava landraces to elucidate starch and carotenoid composition
JF  - Agronomy
N2  - The prevalence of vitamin A deficiency in sub-Saharan Africa necessitates effective approaches to improve provitamin A content of major staple crops. Cassava holds much promise for food security in sub-Saharan Africa, but a negative correlation between beta-carotene, a provitamin A carotenoid, and dry matter content has been reported, which poses a challenge to cassava biofortification by conventional breeding. To identify suitable material for genetic transformation in tissue culture with the overall aim to increase beta-carotene and maintain starch content as well as better understand carotenoid composition, root and leaf tissues from thirteen field-grown cassava landraces were analyzed for agronomic traits, carotenoid, chlorophyll, and starch content. The expression of five genes related to carotenoid biosynthesis were determined in selected landraces. Analysis revealed a weak negative correlation between starch and beta-carotene content, whereas there was a strong positive correlation between root yield and many carotenoids including beta-carotene. Carotenoid synthesis genes were expressed in both white and yellow cassava roots, but phytoene synthase 2 (PSY2), lycopene-epsilon-cyclase (LCY epsilon), and beta-carotenoid hydroxylase (CHY beta) expression were generally higher in yellow roots. This study identified lines with reasonably high content of starch and beta-carotene that could be candidates for biofortification by further breeding or plant biotechnological means.
KW  - carotenoid biosynthesis
KW  - ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS)
KW  - provitamin A
KW  - biofortification
Y1  - 2020
U6  - https://doi.org/10.3390/agronomy10030424
SN  - 2073-4395
VL  - 10
IS  - 3
SP  - 1
EP  - 16
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Li, Chen
A1  - Stoma, Svetlana
A1  - Lotta, Luca A.
A1  - Warner, Sophie
A1  - Albrecht, Eva
A1  - Allione, Alessandra
A1  - Arp, Pascal P.
A1  - Broer, Linda
A1  - Buxton, Jessica L.
A1  - Boeing, Heiner
A1  - Langenberg, Claudia
A1  - Codd, Veryan
T1  - Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length
JF  - American Journal of Human Genetics
N2  - Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
KW  - Mendelian randomization
KW  - risk
KW  - variants
KW  - disease
KW  - cancer
KW  - loci
KW  - database
KW  - genes
KW  - heart
KW  - gwas
Y1  - 2019
VL  - 106
IS  - 3
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - de Pinho Tavares Leal, Pedro Ernesto
A1  - da Silva, Alexandre Alves
A1  - Rocha-Gomes, Arthur
A1  - Riul, Tania Regina
A1  - Cunha, Rennan Augusto
A1  - Reichetzeder, Christoph
A1  - Villela, Daniel Campos
T1  - High-Salt Diet in the Pre- and Postweaning Periods Leads to Amygdala Oxidative Stress and Changes in Locomotion and Anxiety-Like Behaviors of Male Wistar Rats
JF  - Frontiers in Behavioral Neuroscience
N2  - High-salt (HS) diets have recently been linked to oxidative stress in the brain, a fact that may be a precursor to behavioral changes, such as those involving anxiety-like behavior. However, to the best of our knowledge, no study has evaluated the amygdala redox status after consuming a HS diet in the pre- or postweaning periods. This study aimed to evaluate the amygdala redox status and anxiety-like behaviors in adulthood, after inclusion of HS diet in two periods: preconception, gestation, and lactation (preweaning); and only after weaning (postweaning). Initially, 18 females and 9 male Wistar rats received a standard (n = 9 females and 4 males) or a HS diet (n = 9 females and 5 males) for 120 days. After mating, females continued to receive the aforementioned diets during gestation and lactation. Weaning occurred at 21-day-old Wistar rats and the male offspring were subdivided: control-control (C-C)—offspring of standard diet fed dams who received a standard diet after weaning (n = 9–11), control-HS (C-HS)—offspring of standard diet fed dams who received a HS diet after weaning (n = 9–11), HS-C—offspring of HS diet fed dams who received a standard diet after weaning (n = 9–11), and HS-HS—offspring of HS diet fed dams who received a HS diet after weaning (n = 9–11). At adulthood, the male offspring performed the elevated plus maze and open field tests. At 152-day-old Wistar rats, the offspring were euthanized and the amygdala was removed for redox state analysis. The HS-HS group showed higher locomotion and rearing frequency in the open field test. These results indicate that this group developed hyperactivity. The C-HS group had a higher ratio of entries and time spent in the open arms of the elevated plus maze test in addition to a higher head-dipping frequency. These results suggest less anxiety-like behaviors. In the analysis of the redox state, less activity of antioxidant enzymes and higher levels of the thiobarbituric acid reactive substances (TBARS) in the amygdala were shown in the amygdala of animals that received a high-salt diet regardless of the period (pre- or postweaning). In conclusion, the high-salt diet promoted hyperactivity when administered in the pre- and postweaning periods. In animals that received only in the postweaning period, the addition of salt induced a reduction in anxiety-like behaviors. Also, regardless of the period, salt provided amygdala oxidative stress, which may be linked to the observed behaviors.
KW  - high-sodium
KW  - open-field
KW  - elevated plus-maze
KW  - pre-natal
KW  - post-natal
KW  - redox state
Y1  - 2022
U6  - https://doi.org/10.3389/fnbeh.2021.779080
SN  - 1662-5153
VL  - 15
SP  - 1
EP  - 12
PB  - Frontiers Research Foundation
CY  - Lausanne, Schweiz
ER  - 
TY  - JOUR
A1  - Pedro Ernesto, Pinho Tavares Leal
A1  - da Silva, Alexandre Alves
A1  - Rocha-Gomes, Arthur
A1  - Riul, Tania Regina
A1  - Cunha, Rennan Augusto
A1  - Reichetzeder, Christoph
A1  - Villela, Daniel Campos
T1  - High-salt diet in the pre- and postweaning periods leads to amygdala oxidative stress and changes in locomotion and anxiety-like behaviors of male wistar rats
JF  - Frontiers in behavioral neuroscience
N2  - High-salt (HS) diets have recently been linked to oxidative stress in the brain, a fact that may be a precursor to behavioral changes, such as those involving anxiety-like behavior. However, to the best of our knowledge, no study has evaluated the amygdala redox status after consuming a HS diet in the pre- or postweaning periods. This study aimed to evaluate the amygdala redox status and anxiety-like behaviors in adulthood, after inclusion of HS diet in two periods: preconception, gestation, and lactation (preweaning); and only after weaning (postweaning). Initially, 18 females and 9 male Wistar rats received a standard (n = 9 females and 4 males) or a HS diet (n = 9 females and 5 males) for 120 days. After mating, females continued to receive the aforementioned diets during gestation and lactation. Weaning occurred at 21-day-old Wistar rats and the male offspring were subdivided: control-control (C-C)-offspring of standard diet fed dams who received a standard diet after weaning (n = 9-11), control-HS (C-HS)-offspring of standard diet fed dams who received a HS diet after weaning (n = 9-11), HS-C-offspring of HS diet fed dams who received a standard diet after weaning (n = 9-11), and HS-HS-offspring of HS diet fed dams who received a HS diet after weaning (n = 9-11). At adulthood, the male offspring performed the elevated plus maze and open field tests. At 152-day-old Wistar rats, the offspring were euthanized and the amygdala was removed for redox state analysis. The HS-HS group showed higher locomotion and rearing frequency in the open field test. These results indicate that this group developed hyperactivity. The C-HS group had a higher ratio of entries and time spent in the open arms of the elevated plus maze test in addition to a higher head-dipping frequency. These results suggest less anxiety-like behaviors. In the analysis of the redox state, less activity of antioxidant enzymes and higher levels of the thiobarbituric acid reactive substances (TBARS) in the amygdala were shown in the amygdala of animals that received a high-salt diet regardless of the period (pre- or postweaning). In conclusion, the high-salt diet promoted hyperactivity when administered in the pre- and postweaning periods. In animals that received only in the postweaning period, the addition of salt induced a reduction in anxiety-like behaviors. Also, regardless of the period, salt provided amygdala oxidative stress, which may be linked to the observed behaviors.
KW  - high-sodium
KW  - open-field
KW  - elevated plus-maze
KW  - pre-natal
KW  - post-natal
KW  - redox state
Y1  - 2022
U6  - https://doi.org/10.3389/fnbeh.2021.779080
SN  - 1662-5153
VL  - 15
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Hauffe, Robert
A1  - Rath, Michaela
A1  - Schell, Mareike
A1  - Ritter, Katrin
A1  - Kappert, Kai
A1  - Deubel, Stefanie
A1  - Ott, Christiane
A1  - Jähnert, Markus
A1  - Jonas, Wenke
A1  - Schürmann, Annette
A1  - Kleinridders, André
T1  - HSP60 reduction protects against diet-induced obesity by modulating energy metabolism in adipose tissue
JF  - Molecular Metabolism
N2  - Objective
Insulin regulates mitochondrial function, thereby propagating an efficient metabolism. Conversely, diabetes and insulin resistance are linked to mitochondrial dysfunction with a decreased expression of the mitochondrial chaperone HSP60. The aim of this investigation was to determine the effect of a reduced HSP60 expression on the development of obesity and insulin resistance.

Methods
Control and heterozygous whole-body HSP60 knockout (Hsp60+/−) mice were fed a high-fat diet (HFD, 60% calories from fat) for 16 weeks and subjected to extensive metabolic phenotyping. To understand the effect of HSP60 on white adipose tissue, microarray analysis of gonadal WAT was performed, ex vivo experiments were performed, and a lentiviral knockdown of HSP60 in 3T3-L1 cells was conducted to gain detailed insights into the effect of reduced HSP60 levels on adipocyte homeostasis.

Results
Male Hsp60+/− mice exhibited lower body weight with lower fat mass. These mice exhibited improved insulin sensitivity compared to control, as assessed by Matsuda Index and HOMA-IR. Accordingly, insulin levels were significantly reduced in Hsp60+/− mice in a glucose tolerance test. However, Hsp60+/− mice exhibited an altered adipose tissue metabolism with elevated insulin-independent glucose uptake, adipocyte hyperplasia in the presence of mitochondrial dysfunction, altered autophagy, and local insulin resistance.

Conclusions
We discovered that the reduction of HSP60 in mice predominantly affects adipose tissue homeostasis, leading to beneficial alterations in body weight, body composition, and adipocyte morphology, albeit exhibiting local insulin resistance.
KW  - Mitochondria
KW  - Stress response
KW  - Obesity
KW  - Glucose homeostasis
KW  - Insulin resistance
KW  - Adipose tissue
Y1  - 2021
U6  - https://doi.org/10.1016/j.molmet.2021.101276
SN  - 2212-8778
VL  - 53
SP  - 1
EP  - 14
PB  - Elsevier
CY  - Amsterdam, Niederlande
ER  - 
TY  - JOUR
A1  - Schweigert, Florian J.
ED  - Kollodzeiski, Ulrike
ED  - Hafner, Johann Evangelist
T1  - Hässlich aber gut
BT  - Insekten als Nahrungsmittel – Warum wir uns ekeln
JF  - Du sollst nicht essen: Warum Menschen auf Nahrung verzichten – interdisziplinäre Zugänge
Y1  - 2024
SN  - 978-3-98740-007-0
SN  - 978-3-98740-008-7
U6  - https://doi.org/10.5771/9783987400087
SP  - 47
EP  - 59
PB  - Ergon Verlag
CY  - Baden-Baden
ER  - 
TY  - JOUR
A1  - Gohlke, Sabrina
A1  - Zagoriy, Vyacheslav
A1  - Inostroza, Alvaro Cuadros
A1  - Meret, Michael
A1  - Mancini, Carola
A1  - Japtok, Lukasz
A1  - Schumacher, Fabian
A1  - Kuhlow, Doreen
A1  - Graja, Antonia
A1  - Stephanowitz, Heike
A1  - Jähnert, Markus
A1  - Krause, Eberhard
A1  - Wernitz, Andreas
A1  - Petzke, Klaus-Juergen
A1  - Schürmann, Annette
A1  - Kleuser, Burkhard
A1  - Schulz, Tim Julius
T1  - Identification of functional lipid metabolism biomarkers of brown adipose tissue aging
JF  - Molecular Metabolism
N2  - Objective: Aging is accompanied by loss of brown adipocytes and a decline in their thermogenic potential, which may exacerbate the development of adiposity and other metabolic disorders. Presently, only limited evidence exists describing the molecular alterations leading to impaired brown adipogenesis with aging and the contribution of these processes to changes of systemic energy metabolism.

Methods: Samples of young and aged murine brown and white adipose tissue were used to compare age-related changes of brown adipogenic gene expression and thermogenesis-related lipid mobilization. To identify potential markers of brown adipose tissue aging, non-targeted proteomic and metabolomic as well as targeted lipid analyses were conducted on young and aged tissue samples. Subsequently, the effects of several candidate lipid classes on brown adipocyte function were examined.

Results: Corroborating previous reports of reduced expression of uncoupling protein-1, we observe impaired signaling required for lipid mobilization in aged brown fat after adrenergic stimulation. Omics analyses additionally confirm the age-related impairment of lipid homeostasis and reveal the accumulation of specific lipid classes, including certain sphingolipids, ceramides, and dolichols in aged brown fat. While ceramides as well as enzymes of dolichol metabolism inhibit brown adipogenesis, inhibition of sphingosine 1-phosphate receptor 2 induces brown adipocyte differentiation. 

Conclusions: Our functional analyses show that changes in specific lipid species, as observed during aging, may contribute to reduced thermogenic potential. They thus uncover potential biomarkers of aging as well as molecular mechanisms that could contribute to the degradation of brown adipocytes, thereby providing potential treatment strategies of age-related metabolic conditions.
KW  - Brown adipose tissue
KW  - Aging
KW  - Ceramides
KW  - Sphingolipids
KW  - Dolichol lipids
Y1  - 2019
U6  - https://doi.org/10.1016/j.molmet.2019.03.011
SN  - 2212-8778
VL  - 24
SP  - 1
EP  - 17
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Jonas, Wenke
A1  - Kluth, Oliver
A1  - Helms, Anett
A1  - Voss, Sarah
A1  - Jahnert, Markus
A1  - Gottmann, Pascal
A1  - Speckmann, Thilo
A1  - Knebel, Birgit
A1  - Chadt, Alexandra
A1  - Al-Hasani, Hadi
A1  - Schürmann, Annette
A1  - Vogel, Heike
T1  - Identification of novel genes involved in hyperglycemia in mice
JF  - International journal of molecular sciences
N2  - Current attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options. 
Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls. 
Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis. 
Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified the calcium-binding protein S100z gene to affect islet cell proliferation as well as apoptosis when overexpressed in MINE cells. In summary, we define S100z as the most striking gene to be causal for the diabetes QTL Nidd13/NZO by affecting beta-cell proliferation and apoptosis. Thus, S100z is an entirely novel diabetes gene regulating islet cell function.
KW  - beta-cell
KW  - diabetes
KW  - proliferation
KW  - apoptosis
KW  - QTL
Y1  - 2022
U6  - https://doi.org/10.3390/ijms23063205
SN  - 1661-6596
SN  - 1422-0067
VL  - 23
IS  - 6
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Aga-Barfknecht, Heja
A1  - Hallahan, Nicole
A1  - Gottmann, Pascal
A1  - Jähnert, Markus
A1  - Osburg, Sophie
A1  - Schulze, Gunnar
A1  - Kamitz, Anne
A1  - Arends, Danny
A1  - Brockmann, Gudrun
A1  - Schallschmidt, Tanja
A1  - Lebek, Sandra
A1  - Chadt, Alexandra
A1  - Al-Hasani, Hadi
A1  - Joost, Hans-Georg
A1  - Schürmann, Annette
A1  - Vogel, Heike
T1  - Identification of novel potential type 2 diabetes genes mediating beta-cell loss and hyperglycemia using positional cloning
JF  - Frontiers in genetics
N2  - Type 2 diabetes (T2D) is a complex metabolic disease regulated by an interaction of genetic predisposition and environmental factors. To understand the genetic contribution in the development of diabetes, mice varying in their disease susceptibility were crossed with the obese and diabetes-prone New Zealand obese (NZO) mouse. Subsequent whole-genome sequence scans revealed one major quantitative trait loci (QTL),Nidd/DBAon chromosome 4, linked to elevated blood glucose and reduced plasma insulin and low levels of pancreatic insulin. Phenotypical characterization of congenic mice carrying 13.6 Mbp of the critical fragment of DBA mice displayed severe hyperglycemia and impaired glucose clearance at week 10, decreased glucose response in week 13, and loss of beta-cells and pancreatic insulin in week 16. To identify the responsible gene variant(s), further congenic mice were generated and phenotyped, which resulted in a fragment of 3.3 Mbp that was sufficient to induce hyperglycemia. By combining transcriptome analysis and haplotype mapping, the number of putative responsible variant(s) was narrowed from initial 284 to 18 genes, including gene models and non-coding RNAs. Consideration of haplotype blocks reduced the number of candidate genes to four (Kti12,Osbpl9,Ttc39a, andCalr4) as potential T2D candidates as they display a differential expression in pancreatic islets and/or sequence variation. In conclusion, the integration of comparative analysis of multiple inbred populations such as haplotype mapping, transcriptomics, and sequence data substantially improved the mapping resolution of the diabetes QTLNidd/DBA. Future studies are necessary to understand the exact role of the different candidates in beta-cell function and their contribution in maintaining glycemic control.
KW  - type 2 diabetes
KW  - beta-cell loss
KW  - insulin
KW  - positional cloning
KW  - transcriptomics
KW  - haplotype
Y1  - 2020
U6  - https://doi.org/10.3389/fgene.2020.567191
SN  - 1664-8021
VL  - 11
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Burkhardt, Wiebke
A1  - Rausch, Theresa
A1  - Klopfleisch, Robert
A1  - Blaut, Michael
A1  - Braune, Annett
T1  - Impact of dietary sulfolipid-derived sulfoquinovose on gut microbiota composition and inflammatory status of colitis-prone interleukin-10-deficient mice
JF  - International journal of medical microbiology : IJMM
N2  - The interplay between diet, intestinal microbiota and host is a major factor impacting health. A diet rich in unsaturated fatty acids has been reported to stimulate the growth of Bilophila wadsworthia by increasing the proportion of the sulfonated bile acid taurocholate (TC). The taurine-induced overgrowth of B. wadsworthia promoted the development of colitis in interleukin-10-deficient (IL-10(-/-)) mice. This study aimed to investigate whether intake of the sulfonates sulfoquinovosyl diacylglycerols (SQDG) with a dietary supplement or their degradation product sulfoquinovose (SQ), stimulate the growth of B. wadsworthia in a similar manner and, thereby, cause intestinal inflammation. Conventional IL-10(-/-) mice were fed a diet supplemented with the SQDG-rich cyanobacterium Arthrospira platensis (Spirulina). SQ or TC were orally applied to conventional IL-10(-/-) mice and gnotobiotic IL-10(-/-) mice harboring a simplified human intestinal microbiota with or without B. wadsworthia. Analyses of inflammatory parameters revealed that none of the sulfonates induced severe colitis, but both, Spirulina and TC, induced expression of pro-inflammatory cytokines in cecal mucosa. Cell numbers of B. wadsworthia decreased almost two orders of magnitude by Spirulina feeding but slightly increased in gnotobiotic SQ and conventional TC mice. Changes in microbiota composition were observed in feces as a result of Spirulina or TC feeding in conventional mice. In conclusion, the dietary sulfonates SQDG and their metabolite SQ did not elicit bacteria-induced intestinal inflammation in IL-10(-/-) mice and, thus, do not promote colitis.
KW  - Sulfonate
KW  - Sulfoquinovose
KW  - Spirulina
KW  - Inflammatory bowel disease
KW  - Bilophila wadsworthia
KW  - Taurocholate
Y1  - 2021
U6  - https://doi.org/10.1016/j.ijmm.2021.151494
SN  - 1618-0607
VL  - 311
IS  - 3
PB  - Elsevier
CY  - München
ER  - 
TY  - JOUR
A1  - Maharjan, Romi Singh
A1  - Singh, Ajay Vikram
A1  - Hanif, Javaria
A1  - Rosenkranz, Daniel
A1  - Haidar, Rashad
A1  - Shelar, Amruta
A1  - Singh, Shubham Pratap
A1  - Dey, Aditya
A1  - Patil, Rajendra
A1  - Zamboni, Paolo
A1  - Laux, Peter
A1  - Luch, Andreas
T1  - Investigation of the associations between a nanomaterial's microrheology and toxicology
JF  - ACS omega / American Chemical Society
N2  - With the advent of Nanotechnology, the use of nanomaterials in consumer products is increasing on a daily basis, due to which a deep understanding and proper investigation regarding their safety and risk assessment should be a major priority. To date, there is no investigation regarding the microrheological properties of nanomaterials (NMs) in biological media. 
In our study, we utilized in silico models to select the suitable NMs based on their physicochemical properties such as solubility and lipophilicity. Then, we established a new method based on dynamic light scattering (DLS) microrheology to get the mean square displacement (MSD) and viscoelastic property of two model NMs that are dendrimers and cerium dioxide nanoparticles in Dulbecco's Modified Eagle Medium (DMEM) complete media at three different concentrations for both NMs. Subsequently, we established the cytotoxicological profiling using water-soluble tetrazolium salt-1 (WST-1) and a reactive oxygen species (ROS) assay. 
To take one step forward, we further looked into the tight junction properties of the cells using immunostaining with Zonula occluden-1 (ZO-1) antibodies and found that the tight junction function or transepithelial resistance (TEER) was affected in response to the microrheology and cytotoxicity. The quantitative polymerase chain reaction (q-PCR) results in the gene expression of ZO-1 after the 24 h treatment with NPs further validates the findings of immunostaining results. 
This new method that we established will be a reference point for other NM studies which are used in our day-to-day consumer products.
Y1  - 2022
U6  - https://doi.org/10.1021/acsomega.2c00472
SN  - 2470-1343
VL  - 7
IS  - 16
SP  - 13985
EP  - 13997
PB  - ACS Publications
CY  - Washington, DC
ER  - 
TY  - JOUR
A1  - Knoche, Lisa
A1  - Lisec, Jan
A1  - Schwerdtle, Tanja
A1  - Koch, Matthias
T1  - LC-HRMS-Based identification of transformation products of the drug salinomycin generated by electrochemistry and liver microsome
JF  - Antibiotics
N2  - The drug salinomycin (SAL) is a polyether antibiotic and used in veterinary medicine as coccidiostat and growth promoter. Recently, SAL was suggested as a potential anticancer drug. However, transformation products (TPs) resulting from metabolic and environmental degradation of SAL are incompletely known and structural information is missing. In this study, we therefore systematically investigated the formation and identification of SAL derived TPs using electrochemistry (EC) in an electrochemical reactor and rat and human liver microsome incubation (RLM and HLM) as TP generating methods. Liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS) was applied to determine accurate masses in a suspected target analysis to identify TPs and to deduce occurring modification reactions of derived TPs. A total of 14 new, structurally different TPs were found (two EC-TPs, five RLM-TPs, and 11 HLM-TPs). The main modification reactions are decarbonylation for EC-TPs and oxidation (hydroxylation) for RLM/HLM-TPs. Of particular interest are potassium-based TPs identified after liver microsome incubation because these might have been overlooked or declared as oxidated sodium adducts in previous, non-HRMS-based studies due to the small mass difference between K and O + Na of 21 mDa. The MS fragmentation pattern of TPs was used to predict the position of identified modifications in the SAL molecule. The obtained knowledge regarding transformation reactions and novel TPs of SAL will contribute to elucidate SAL-metabolites with regards to structural prediction.
KW  - salinomycin
KW  - ionophore antibiotics
KW  - transformation product
KW  - electrochemistry
KW  - rat
KW  - human liver microsomes
KW  - HRMS
Y1  - 2022
U6  - https://doi.org/10.3390/antibiotics11020155
SN  - 2079-6382
VL  - 11
IS  - 2
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Islam, Khan M. S.
A1  - Khalil, Mahmoud Abd Elhamid
A1  - Maenner, Klaus
A1  - Raila, Jens
A1  - Rawel, Harshadrai Manilal
A1  - Zentek, Jürgen
A1  - Schweigert, Florian J.
T1  - Lutein Specific Relationships among Some Spectrophotometric and Colorimetric Parameters of Chicken Egg Yolk
JF  - The journal of poultry science
N2  - Lutein is an essential dietary carotenoid with health benefits and is inter alia responsible for the colouration of egg yolk. The relationship between lutein accumulation and egg yolk colouration was therefore studied in more detail. After feeding a low-luteine diet for 21 days, 14 birds (Lohmann brown hens aged 20 weeks) were fed a diet containing marigold (80 mg lutein/kg feed) and 14 other birds were fed a diet containing oleoresin (45 mg lutein/kg feed) for 21 days; for both groups of birds, this feeding period was followed by withdrawal for 21 days. The Roche Yolk Colour Fan (RYCF) score (0 to 15, where higher values denote greater colour intensity; R-2=0.87; P<0.01) and redness (R-2=0.89; P<0.01) increased with increasing lutein content of egg yolk. Total carotenoid content had a poor relationship with lightness (R-2=0.13; P>0.05) and yellowness (R-2=0.12; P>0.05) of the yolk. It may be concluded that increased lutein is potentially responsible for an increased RYCF score and redness (a*), but decreased yellowness (b*) and lightness (L*), of egg yolk.
KW  - carotenoid
KW  - HPLC
KW  - iCheck
KW  - lutein
KW  - spectrophotometry
KW  - yolk
Y1  - 2017
U6  - https://doi.org/10.2141/jpsa.0160065
SN  - 1346-7395
VL  - 54
SP  - 271
EP  - 277
PB  - Japan Poultry Science Association
CY  - Tsukuba
ER  - 
TY  - JOUR
A1  - Püschel, Gerhard
A1  - Klauder, Julia
A1  - Henkel-Oberländer, Janin
T1  - Macrophages, low-grade inflammation, insulin resistance and hyperinsulinemia
BT  - A mutual ambiguous relationship in the development of metabolic diseases
JF  - Journal of Clinical Medicine : open access journal
N2  - Metabolic derangement with poor glycemic control accompanying overweight and obesity is associated with chronic low-grade inflammation and hyperinsulinemia. Macrophages, which present a very heterogeneous population of cells, play a key role in the maintenance of normal tissue homeostasis, but functional alterations in the resident macrophage pool as well as newly recruited monocyte-derived macrophages are important drivers in the development of low-grade inflammation. While metabolic dysfunction, insulin resistance and tissue damage may trigger or advance pro-inflammatory responses in macrophages, the inflammation itself contributes to the development of insulin resistance and the resulting hyperinsulinemia. Macrophages express insulin receptors whose downstream signaling networks share a number of knots with the signaling pathways of pattern recognition and cytokine receptors, which shape macrophage polarity. The shared knots allow insulin to enhance or attenuate both pro-inflammatory and anti-inflammatory macrophage responses. This supposedly physiological function may be impaired by hyperinsulinemia or insulin resistance in macrophages. This review discusses the mutual ambiguous relationship of low-grade inflammation, insulin resistance, hyperinsulinemia and the insulin-dependent modulation of macrophage activity with a focus on adipose tissue and liver.
KW  - NAFLD/MAFLD
KW  - type 2 diabetes
KW  - obesity
KW  - vicious cycle
KW  - TLR signaling
KW  - M1/M2 differentiation
KW  - Akt pathway
Y1  - 2022
U6  - https://doi.org/10.3390/jcm11154358
SN  - 2077-0383
VL  - 11
IS  - 15
SP  - 1
EP  - 30
PB  - MDPI
CY  - Basel, Schweiz
ER  - 
TY  - JOUR
A1  - Schäfer, Marjänn Helena
A1  - Kakularam, Kumar Reddy
A1  - Reisch, Florian
A1  - Rothe, Michael
A1  - Stehling, Sabine
A1  - Heydeck, Dagmar
A1  - Püschel, Gerhard Paul
A1  - Kuhn, Hartmut
T1  - Male Knock-in Mice Expressing an Arachidonic Acid Lipoxygenase 15B (Alox15B) with Humanized Reaction Specificity Are Prematurely Growth Arrested When Aging
JF  - Biomedicines
N2  - Mammalian arachidonic acid lipoxygenases (ALOXs) have been implicated in cell differentiation and in the pathogenesis of inflammation. The mouse genome involves seven functional Alox genes and the encoded enzymes share a high degree of amino acid conservation with their human orthologs. There are, however, functional differences between mouse and human ALOX orthologs. Human ALOX15B oxygenates arachidonic acid exclusively to its 15-hydroperoxy derivative (15S-HpETE), whereas 8S-HpETE is dominantly formed by mouse Alox15b. The structural basis for this functional difference has been explored and in vitro mutagenesis humanized the reaction specificity of the mouse enzyme. To explore whether this mutagenesis strategy may also humanize the reaction specificity of mouse Alox15b in vivo, we created Alox15b knock-in mice expressing the arachidonic acid 15-lipoxygenating Tyr603Asp+His604Val double mutant instead of the 8-lipoxygenating wildtype enzyme. These mice are fertile, display slightly modified plasma oxylipidomes and develop normally up to an age of 24 weeks. At later developmental stages, male Alox15b-KI mice gain significantly less body weight than outbred wildtype controls, but this effect was not observed for female individuals. To explore the possible reasons for the observed gender-specific growth arrest, we determined the basic hematological parameters and found that aged male Alox15b-KI mice exhibited significantly attenuated red blood cell parameters (erythrocyte counts, hematocrit, hemoglobin). Here again, these differences were not observed in female individuals. These data suggest that humanization of the reaction specificity of mouse Alox15b impairs the functionality of the hematopoietic system in males, which is paralleled by a premature growth arrest.
KW  - eicosanoids
KW  - lipid peroxidation
KW  - oxidative stress
KW  - polyenoic fatty acids
KW  - erythropoiesis
Y1  - 2022
U6  - https://doi.org/10.3390/biomedicines10061379
SN  - 2227-9059
VL  - 10
SP  - 1
EP  - 22
PB  - MDPI
CY  - Basel, Schweiz
ET  - 6
ER  - 
TY  - JOUR
A1  - Volkert, Dorothee
A1  - Beck, Anne Marie
A1  - Cederholm, Tommy
A1  - Cereda, Emanuele
A1  - Cruz-Jentoft, Alfonso J.
A1  - Goisser, Sabine
A1  - de Groot, Lisette
A1  - Grosshauser, Franz
A1  - Kiesswetter, Eva
A1  - Norman, Kristina
A1  - Pourhassan, Maryam
A1  - Reinders, Ilse
A1  - Roberts, Helen C.
A1  - Rolland, Yves
A1  - Schneider, Stéphane M.
A1  - Sieber, Cornel
A1  - Thiem, Ulrich
A1  - Visser, Marjolein
A1  - Wijnhoven, Hanneke
A1  - Wirth, Rainer
T1  - Management of malnutrition in older patients
BT  - Current approaches, evidence and open questions
JF  - Journal of Clinical Medicine : open access journal
N2  - Malnutrition is widespread in older people and represents a major geriatric syndrome with multifactorial etiology and severe consequences for health outcomes and quality of life. The aim of the present paper is to describe current approaches and evidence regarding malnutrition treatment and to highlight relevant knowledge gaps that need to be addressed. Recently published guidelines of the European Society for Clinical Nutrition and Metabolism (ESPEN) provide a summary of the available evidence and highlight the wide range of different measures that can be taken—from the identification and elimination of potential causes to enteral and parenteral nutrition—depending on the patient’s abilities and needs. However, more than half of the recommendations therein are based on expert consensus because of a lack of evidence, and only three are concern patient-centred outcomes. Future research should further clarify the etiology of malnutrition and identify the most relevant causes in order to prevent malnutrition. Based on limited and partly conflicting evidence and the limitations of existing studies, it remains unclear which interventions are most effective in which patient groups, and if specific situations, diseases or etiologies of malnutrition require specific approaches. Patient-relevant outcomes such as functionality and quality of life need more attention, and research methodology should be harmonised to allow for the comparability of studies.
KW  - Geriatric patients
KW  - older persons
KW  - malnutrition
KW  - therapy
KW  - interventions
Y1  - 2019
U6  - https://doi.org/10.3390/jcm8070974
SN  - 2077-0383
VL  - 8
IS  - 7
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Bornhorst, Julia
A1  - Nustede, Eike Jannik
A1  - Fudickar, Sebastian
T1  - Mass Surveilance of C. elegans-Smartphone-Based DIY Microscope and Machine-Learning-Based Approach for Worm Detection
JF  - Sensors
N2  - The nematode Caenorhabditis elegans (C. elegans) is often used as an alternative animal model due to several advantages such as morphological changes that can be seen directly under a microscope. Limitations of the model include the usage of expensive and cumbersome microscopes, and restrictions of the comprehensive use of C. elegans for toxicological trials. With the general applicability of the detection of C. elegans from microscope images via machine learning, as well as of smartphone-based microscopes, this article investigates the suitability of smartphone-based microscopy to detect C. elegans in a complete Petri dish. Thereby, the article introduces a smartphone-based microscope (including optics, lighting, and housing) for monitoring C. elegans and the corresponding classification via a trained Histogram of Oriented Gradients (HOG) feature-based Support Vector Machine for the automatic detection of C. elegans. Evaluation showed classification sensitivity of 0.90 and specificity of 0.85, and thereby confirms the general practicability of the chosen approach.
KW  - Caenorhabditis elegans
KW  - machine learning
KW  - smartphone
KW  - microscope
KW  - SVM
KW  - HOG
Y1  - 2019
U6  - https://doi.org/10.3390/s19061468
SN  - 1424-8220
VL  - 19
IS  - 6
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Gisch, Ulrike Alexandra
A1  - Robert, Margaux
A1  - Berlin, Noemi
A1  - Nebout, Antoine
A1  - Etile, Fabrice
A1  - Teyssier, Sabrina
A1  - Andreeva, Valentina A.
A1  - Hercberg, Serge
A1  - Touvier, Mathilde
A1  - Peneau, Sandrine
T1  - Mastery is associated with weight status, food intake, snacking, and eating disorder symptoms in the NutriNet-Sante cohort study
JF  - Frontiers in Nutrition
N2  - Mastery is a psychological resource that is defined as the extent to which individuals perceive having control over important circumstances of their lives. Although mastery has been associated with various physical and psychological health outcomes, studies assessing its relationship with weight status and dietary behavior are lacking. The aim of this cross-sectional study was to assess the relationship between mastery and weight status, food intake, snacking, and eating disorder (ED) symptoms in the NutriNet-Sante cohort study. Mastery was measured with the Pearlin Mastery Scale (PMS) in 32,588 adults (77.45% female), the mean age was 50.04 (14.53) years. Height and weight were self-reported. Overall diet quality and food group consumption were evaluated with >= 3 self-reported 24-h dietary records (range: 3-27). Snacking was assessed with an ad-hoc question. ED symptoms were assessed with the Sick-Control-One-Fat-Food Questionnaire (SCOFF). Linear and logistic regression analyses were conducted to assess the relationship between mastery and weight status, food intake, snacking, and ED symptoms, controlling for sociodemographic and lifestyle characteristics. Females with a higher level of mastery were less likely to be underweight (OR: 0.88; 95%CI: 0.84, 0.93), overweight [OR: 0.94 (0.91, 0.97)], or obese [class I: OR: 0.86 (0.82, 0.90); class II: OR: 0.76 (0.71, 0.82); class III: OR: 0.77 (0.69, 0.86)]. Males with a higher level of mastery were less likely to be obese [class III: OR: 0.75 (0.57, 0.99)]. Mastery was associated with better diet quality overall, a higher consumption of fruit and vegetables, seafood, wholegrain foods, legumes, non-salted oleaginous fruits, and alcoholic beverages and with a lower consumption of meat and poultry, dairy products, sugary and fatty products, milk-based desserts, and sweetened beverages. Mastery was also associated with lower snacking frequency [OR: 0.89 (0.86, 0.91)] and less ED symptoms [OR: 0.73 (0.71, 0.75)]. As mastery was associated with favorable dietary behavior and weight status, targeting mastery might be a promising approach in promoting healthy behaviors.
KW  - mastery
KW  - locus of control
KW  - weight status
KW  - diet quality
KW  - food group consumption
KW  - snacking
KW  - eating disorder symptoms
KW  - large population
Y1  - 2022
U6  - https://doi.org/10.3389/fnut.2022.871669
SN  - 2296-861X
VL  - 9
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Derakhshani, Shaghayegh
A1  - Kurz, Andreas
A1  - Japtok, Lukasz
A1  - Schumacher, Fabian
A1  - Pilgram, Lisa
A1  - Steinke, Maria
A1  - Kleuser, Burkhard
A1  - Sauer, Markus
A1  - Schneider-Schaulies, Sibylle
A1  - Avota, Elita
T1  - Measles Virus Infection Fosters Dendritic Cell Motility in a 3D Environment to Enhance Transmission to Target Cells in the Respiratory Epithelium
JF  - Frontiers in immunology
N2  - Transmission of measles virus (MV) from dendritic to airway epithelial cells is considered as crucial to viral spread late in infection. Therefore, pathways and effectors governing this process are promising targets for intervention. To identify these, we established a 3D respiratory tract model where MV transmission by infected dendritic cells (DCs) relied on the presence of nectin-4 on H358 lung epithelial cells. Access to recipient cells is an important prerequisite for transmission, and we therefore analyzed migration of MV-exposed DC cultures within the model. Surprisingly, enhanced motility toward the epithelial layer was observed for MV-infected DCs as compared to their uninfected siblings. This occurred independently of factors released from H358 cells indicating that MV infection triggered cytoskeletal remodeling associated with DC polarization enforced velocity. Accordingly, the latter was also observed for MV-infected DCs in collagen matrices and was particularly sensitive to ROCK inhibition indicating infected DCs preferentially employed the amoeboid migration mode. This was also implicated by loss of podosomes and reduced filopodial activity both of which were retained in MV-exposed uninfected DCs. Evidently, sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as produced in response to virus-infection in DCs contributed to enhanced velocity because this was abrogated upon inhibition of sphingosine kinase activity. These findings indicate that MV infection promotes a push-and-squeeze fast amoeboid migration mode via the SphK/S1P system characterized by loss of filopodia and podosome dissolution. Consequently, this enables rapid trafficking of virus toward epithelial cells during viral exit.
KW  - dendritic cell
KW  - cell migration
KW  - measles virus
KW  - 3D tissue model
KW  - sphingosine-1-phosphate
Y1  - 2019
U6  - https://doi.org/10.3389/fimmu.2019.01294
SN  - 1664-3224
VL  - 10
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - GEN
A1  - Chen, Pan
A1  - Bornhorst, Julia
A1  - Neely, M. Diana
A1  - Avila, Daiana Silva
T1  - Mechanisms and Disease Pathogenesis Underlying Metal-Induced Oxidative Stress
T2  - Oxidative Medicine and Cellular Longevity
Y1  - 2018
U6  - https://doi.org/10.1155/2018/7612172
SN  - 1942-0900
SN  - 1942-0994
PB  - Hindawi
CY  - London
ER  - 
TY  - JOUR
A1  - Shi, Jiang
A1  - Xie, Dongchao
A1  - Qi, Dandan
A1  - Peng, Qunhua
A1  - Chen, Zongmao
A1  - Schreiner, Monika
A1  - Lin, Zhi
A1  - Baldermann, Susanne
T1  - Methyl jasmonate-induced changes of flavor profiles during the processing of Green, Oolong, and Black Tea
JF  - Frontiers in plant science
N2  - Tea aroma is one of the most important factors affecting the character and quality of tea. Here we describe the practical application of methyl jasmonate (MeJA) to improve the aroma quality of teas. The changes of selected metabolites during crucial tea processing steps, namely, withering, fixing and rolling, and fermentation, were analyzed. MeJA treatment of tea leaves (12, 24, 48, and 168 h) greatly promotes the aroma quality of green, oolong, and black tea products when comparing with untreated ones (0 h) and as confirmed by sensory evaluation. MeJA modulates the aroma profiles before, during, and after processing. Benzyl alcohol, benzaldehyde, 2-phenylethyl alcohol, phenylacetaldehyde, and trans-2-hexenal increased 1.07- to 3-fold in MeJA-treated fresh leaves and the first two maintained at a higher level in black tea and the last two in green tea. This correlates with a decrease in aromatic amino acids by more than twofold indicating a direct relation to tryptophan- and phenylalanine-derived volatiles. MeJA-treated oolong tea was characterized by a more pleasant aroma. Especially the terpenoids linalool and oxides, geraniol, and carvenol increased by more than twofold.
KW  - methyl jasmonate
KW  - aroma quality
KW  - volatile compounds
KW  - amino acids
KW  - tea processing
Y1  - 2019
U6  - https://doi.org/10.3389/fpls.2019.00781
SN  - 1664-462X
VL  - 10
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Stepanovska, Bisera
A1  - Zivkovic, Aleksandra
A1  - Enzmann, Gaby
A1  - Tietz, Silvia
A1  - Homann, Thomas
A1  - Kleuser, Burkhard
A1  - Engelhardt, Britta
A1  - Stark, Holger
A1  - Huwiler, Andrea
T1  - Morpholino analogues of fingolimod as novel and selective S1P1 ligands with in vivo efficacy in a mouse model of experimental antigen-induced encephalomyelitis
JF  - International journal of molecular sciences
N2  - Multiple sclerosis (MS) is a chronic, inflammatory, autoimmune disease of the central nervous system (CNS) which is associated with lower life expectancy and disability. The experimental antigen-induced encephalomyelitis (EAE) in mice is a useful animal model of MS, which allows exploring the etiopathogenetic mechanisms and testing novel potential therapeutic drugs. A new therapeutic paradigm for the treatment of MS was introduced in 2010 through the sphingosine 1-phosphate (S1P) analogue fingolimod (FTY720, Gilenya(R)), which acts as a functional S1P(1) antagonist on T lymphocytes to deplete these cells from the blood. In this study, we synthesized two novel structures, ST-1893 and ST-1894, which are derived from fingolimod and chemically feature a morpholine ring in the polar head group. These compounds showed a selective S1P(1) activation profile and a sustained S1P(1) internalization in cultures of S1P(1)-overexpressing Chinese hamster ovary (CHO)-K1 cells, consistent with a functional antagonism. In vivo, both compounds induced a profound lymphopenia in mice. Finally, these substances showed efficacy in the EAE model, where they reduced clinical symptoms of the disease, and, on the molecular level, they reduced the T-cell infiltration and several inflammatory mediators in the brain and spinal cord. In summary, these data suggest that S1P(1)-selective compounds may have an advantage over fingolimod and siponimod, not only in MS but also in other autoimmune diseases.
KW  - ST-1893
KW  - ST-1894
KW  - morpholino analogues of fingolimod
KW  - sphingosine
KW  - 1-phosphate
KW  - immunomodulator
KW  - lymphopenia
KW  - multiple sclerosis
KW  - experimental antigen-induced encephalomyelitis
Y1  - 2020
U6  - https://doi.org/10.3390/ijms21186463
SN  - 1422-0067
VL  - 21
IS  - 18
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Klopsch, Rebecca
A1  - Baldermann, Susanne
A1  - Voss, Alexander
A1  - Rohn, Sascha
A1  - Schreiner, Monika
A1  - Neugart, Susanne
T1  - Narrow-Banded UVB Affects the Stability of Secondary Plant Metabolites in Kale (Brassica oleracea var. sabellica) and Pea (Pisum sativum) Leaves Being Added to Lentil Flour Fortified Bread: A Novel Approach for Producing Functional Foods
JF  - Foods
N2  - Young kale and pea leaves are rich in secondary plant metabolites (SPMs) whose profile can be affected by ultraviolet B (UVB) radiation. Carotenoids and flavonoids in kale and pea exposed to narrow-banded UVB, produced by innovative light-emitting diodes (LEDs), and subsequently used for breadmaking were investigated for the first time, thus combining two important strategies to increase the SPMs intake. Breads were also fortified with protein-rich lentil flour. Antioxidant activity in the ‘vegetable breads’ indicated health-promoting effects. Lentil flour increased the antioxidant activity in all of the ‘vegetable breads’. While carotenoids and chlorophylls showed a minor response to UVB treatment, kaempferol glycosides decreased in favor of increasing quercetin glycosides, especially in kale. Additionally, breadmaking caused major decreases in carotenoids and a conversion of chlorophyll to bioactive degradation products. In ‘kale breads’ and ‘pea breads’, 20% and 84% of flavonoid glycosides were recovered. Thus, kale and pea leaves seem to be suitable natural ingredients for producing innovative Functional Foods.
KW  - narrow-banded UVB
KW  - thermal processing
KW  - antioxidant activity
KW  - kale
KW  - pea
KW  - flavonoids
KW  - carotenoids
Y1  - 2019
U6  - https://doi.org/10.3390/foods8100427
SN  - 2304-8158
VL  - 8
IS  - 10
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Bernacchioni, Caterina
A1  - Ghini, Veronica
A1  - Cencetti, Francesca
A1  - Japtok, Lukasz
A1  - Donati, Chiara
A1  - Bruni, Paola
A1  - Turano, Paola
T1  - NMR metabolomics highlights sphingosine kinase-1 as a new molecular switch in the orchestration of aberrant metabolic phenotype in cancer cells
JF  - Molecular oncology / Federation of European Biochemical Societies
N2  - Strong experimental evidence in animal and cellular models supports a pivotal role of sphingosine kinase-1 (SK1) in oncogenesis. In many human cancers, SK1 levels are upregulated and these increases are linked to poor prognosis in patients. Here, by employing untargeted NMR- based metabolomic profiling combined with functional validations, we report the crucial role of SK1 in the metabolic shift known as the Warburg effect in A2780 ovarian cancer cells. Indeed, expression of SK1 induced a high glycolytic rate, characterized by increased levels of lactate along with increased expression of the proton/monocarboxylate symporter MCT1, and decreased oxidative metabolism, associated with the accumulation of intermediates of the tricarboxylic acid cycle and reduction in CO2 production. Additionally, SK1-expressing cells displayed a significant increase in glucose uptake paralleled by GLUT3 transporter upregulation. The role of SK1 is not limited to the induction of aerobic glycolysis, affecting metabolic pathways that appear to support the biosynthesis of macromolecules. These findings highlight the role of SK1 signaling axis in cancer metabolic reprogramming, pointing out innovative strategies for cancer therapies.
KW  - NMR-based metabolomics
KW  - ovarian cancer
KW  - sphingosine kinase-1
KW  - Warburg effect
Y1  - 2017
U6  - https://doi.org/10.1002/1878-0261.12048
SN  - 1878-0261
VL  - 11
SP  - 517
EP  - 533
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Castro, Jose Pedro
A1  - Fernando, Raquel
A1  - Reeg, Sandra
A1  - Meinl, Walter
A1  - Almeida, Henrique
A1  - Grune, Tilman
T1  - Non-enzymatic cleavage of Hsp90 by oxidative stress leads to actin aggregate formation
BT  - A novel gain-of-function mechanism
JF  - Redox Biology
N2  - Aging is accompanied by the accumulation of oxidized proteins. To remove them, cells employ the proteasomal and autophagy-lysosomal systems; however, if the clearance rate is inferior to its formation, protein aggregates form as a hallmark of proteostasis loss. In cells, during stress conditions, actin aggregates accumulate leading to impaired proliferation and reduced proteasomal activity, as observed in cellular senescence. The heat shock protein 90 (Hsp90) is a molecular chaperone that binds and protects the proteasome from oxidative inactivation. We hypothesized that in oxidative stress conditions a malfunction of Hsp90 occurs resulting in the aforementioned protein aggregates. Here, we demonstrate that upon oxidative stress Hsp90 loses its function in a highly specific non-enzymatic iron-catalyzed oxidation event and its breakdown product, a cleaved form of Hsp90 (Hsp90cl), acquires a new function in mediating the accumulation of actin aggregates. Moreover, the prevention of Hsp90 cleavage reduces oxidized actin accumulation, whereas transfection of the cleaved form of Hsp90 leads to an enhanced accumulation of oxidized actin. This indicates a clear role of the Hsp90cl in the aggregation of oxidized proteins.
KW  - Oxidative stress
KW  - Protein oxidation
KW  - Heat shock protein 90
KW  - Proteasome
KW  - Protein aggregates
Y1  - 2019
U6  - https://doi.org/10.1016/j.redox.2019.101108
SN  - 2213-2317
VL  - 21
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Galbete, Cecilia
A1  - Kröger, Janine
A1  - Jannasch, Franziska
A1  - Iqbal, Khalid
A1  - Schwingshackl, Lukas
A1  - Schwedhelm, Carolina
A1  - Weikert, Cornelia
A1  - Boeing, Heiner
A1  - Schulze, Matthias Bernd
T1  - Nordic diet, Mediterranean diet, and the risk of chronic diseases
BT  - the EPIC-Potsdam study
JF  - BMC Medicine
N2  - 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.
KW  - Mediterranean diet
KW  - Nordic diet
KW  - regional diets
KW  - chronic diseases
KW  - diabetes
KW  - myocardial infarction
KW  - stroke
KW  - cancer
KW  - EPIC-Potsdam study
KW  - longitudinal analysis
Y1  - 2018
U6  - https://doi.org/10.1186/s12916-018-1082-y
SN  - 1741-7015
VL  - 16
PB  - BMC
CY  - London
ER  - 
TY  - JOUR
A1  - Hauffe, Robert
A1  - Rath, Michaela
A1  - Agyapong, Wilson
A1  - Jonas, Wenke
A1  - Vogel, Heike
A1  - Schulz, Tim Julius
A1  - Schwarz, Maria
A1  - Kipp, Anna Patricia
A1  - Blüher, Matthias
A1  - Kleinridders, André
T1  - Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling
JF  - Antioxidants
N2  - The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.
KW  - selenite
KW  - insulin
KW  - adipose tissue
KW  - obesity
KW  - insulin resistance
Y1  - 2022
U6  - https://doi.org/10.3390/antiox11050862
SN  - 2076-3921
VL  - 11
SP  - 1
EP  - 16
PB  - MDPI
CY  - Basel, Schweiz
ET  - 5
ER  - 
TY  - JOUR
A1  - Krstic, Jelena
A1  - Reinisch, Isabel
A1  - Schupp, Michael
A1  - Schulz, Tim Julius
A1  - Prokesch, Andreas
T1  - p53 functions in adipose tissue metabolism and homeostasis
JF  - International journal of molecular sciences
N2  - 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
KW  - p53
KW  - adipose tissue
KW  - metabolic syndrome
KW  - obesity
KW  - adipogenesis
KW  - insulin resistance
Y1  - 2018
U6  - https://doi.org/10.3390/ijms19092622
SN  - 1422-0067
VL  - 19
IS  - 9
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Weber, Daniela
A1  - Kochlik, Bastian Max
A1  - Demuth, Ilja
A1  - Steinhagen-Thiessen, Elisabeth
A1  - Grune, Tilman
A1  - Norman, Kristina
T1  - Plasma carotenoids, tocopherols and retinol
BT  - Association with age in the Berlin Aging Study II
JF  - Redox Biology
N2  - Regular consumption of fruits and vegetables, which is related to high plasma levels of lipid-soluble micro-nutrients such as carotenoids and tocopherols, is linked to lower incidences of various age-related diseases. Differences in lipid-soluble micronutrient blood concentrations seem to be associated with age. Our retrospective analysis included men and women aged 22-37 and 60-85 years from the Berlin Aging Study II. Participants with simultaneously available plasma samples and dietary data were included (n = 1973). Differences between young and old groups were found for plasma lycopene, alpha-carotene, alpha-tocopherol, beta-cryptoxanthin (only in women), and gamma-tocopherol (only in men). beta-Carotene, retinol and lutein/zeaxanthin did not differ between young and old participants regardless of the sex. We found significant associations for lycopene, alpha-carotene (both inverse), alpha-tocopherol, gamma-tocopherol, and beta-carotene (all positive) with age. Adjusting for BMI, smoking status, season, cholesterol and dietary intake confirmed these associations, except for beta-carotene. These micronutrients are important antioxidants and associated with lower incidence of age-related diseases, therefore it is important to understand the underlying mechanisms in order to implement dietary strategies for the prevention of age-related diseases. To explain the lower lycopene and alpha-carotene concentration in older subjects, bioavailability studies in older participants are necessary.
KW  - carotenoids
KW  - tocopherols
KW  - micronutrients
KW  - age
KW  - plasma
KW  - food frequency questionnaire
Y1  - 2020
U6  - https://doi.org/10.1016/j.redox.2020.101461
SN  - 2213-2317
VL  - 32
SP  - 1
EP  - 8
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Zheng, Ju-Sheng
A1  - Luan, Jian'an
A1  - Sofianopoulou, Eleni
A1  - Imamura, Fumiaki
A1  - Stewart, Isobel D.
A1  - Day, Felix R.
A1  - Pietzner, Maik
A1  - Wheeler, Eleanor
A1  - Lotta, Luca A.
A1  - Gundersen, Thomas E.
A1  - Amiano, Pilar
A1  - Ardanaz, Eva
A1  - Chirlaque, Maria-Dolores
A1  - Fagherazzi, Guy
A1  - Franks, Paul W.
A1  - Kaaks, Rudolf
A1  - Laouali, Nasser
A1  - Mancini, Francesca Romana
A1  - Nilsson, Peter M.
A1  - Onland-Moret, N. Charlotte
A1  - Olsen, Anja
A1  - Overvad, Kim
A1  - Panico, Salvatore
A1  - Palli, Domenico
A1  - Ricceri, Fulvio
A1  - Rolandsson, Olov
A1  - Spijkerman, Annemieke M. W.
A1  - Sanchez, Maria-Jose
A1  - Schulze, Matthias Bernd
A1  - Sala, Nuria
A1  - Sieri, Sabina
A1  - Tjonneland, Anne
A1  - Tumino, Rosario
A1  - van der Schouw, Yvonne T.
A1  - Weiderpass, Elisabete
A1  - Riboli, Elio
A1  - Danesh, John
A1  - Butterworth, Adam S.
A1  - Sharp, Stephen J.
A1  - Langenberg, Claudia
A1  - Forouhi, Nita G.
A1  - Wareham, Nicholas J.
T1  - Plasma vitamin C and type 2 diabetes
BT  - genome-wide association study and Mendelian randomization analysis in European populations
JF  - Diabetes care
N2  - OBJECTIVE: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.

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

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

CONCLUSIONS: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
Y1  - 2020
U6  - https://doi.org/10.2337/dc20-1328
SN  - 0149-5992
SN  - 1935-5548
VL  - 44
IS  - 1
SP  - 98
EP  - 106
PB  - American Diabetes Association
CY  - Alexandria
ER  - 
TY  - JOUR
A1  - Volk, Christin
A1  - Brandsch, Corinna
A1  - Schlegelmilch, Ulf
A1  - Wensch-Dorendorf, Monika
A1  - Hirche, Frank
A1  - Simm, Andreas
A1  - Gargum, Osama
A1  - Wiacek, Claudia
A1  - Braun, Peggy G.
A1  - Kopp, Johannes F.
A1  - Schwerdtle, Tanja
A1  - Treede, Hendrik
A1  - Stangl, Gabriele I.
T1  - Postprandial metabolic response to rapeseed protein in healthy subjects
JF  - Nutrients
N2  - Plant proteins have become increasingly important for ecological reasons. Rapeseed is a novel source of plant proteins with high biological value, but its metabolic impact in humans is largely unknown. A randomized, controlled intervention study including 20 healthy subjects was conducted in a crossover design. All participants received a test meal without additional protein or with 28 g of rapeseed protein isolate or soy protein isolate (control). Venous blood samples were collected over a 360-min period to analyze metabolites; satiety was assessed using a visual analog scale. Postprandial levels of lipids, urea, and amino acids increased following the intake of both protein isolates. The postprandial insulin response was lower after consumption of the rapeseed protein than after intake of the soy protein (p< 0.05), whereas the postmeal responses of glucose, lipids, interleukin-6, minerals, and urea were comparable between the two protein isolates. Interestingly, the rapeseed protein exerted stronger effects on postprandial satiety than the soy protein (p< 0.05). The postmeal metabolism following rapeseed protein intake is comparable with that of soy protein. The favorable effect of rapeseed protein on postprandial insulin and satiety makes it a valuable plant protein for human nutrition.
KW  - rapeseed protein
KW  - soy protein
KW  - postprandial study
KW  - metabolic response
KW  - healthy subjects
Y1  - 2020
U6  - https://doi.org/10.3390/nu12082270
SN  - 2072-6643
VL  - 12
IS  - 8
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Kotthoff, Lisa
A1  - Lisec, Jan
A1  - Schwerdtle, Tanja
A1  - Koch, Matthias
T1  - Prediction of transformation products of monensin by electrochemistry compared to microsomal assay and hydrolysis
JF  - Molecules
N2  - The knowledge of transformation pathways and identification of transformation products (TPs) of veterinary drugs is important for animal health, food, and environmental matters. The active agent Monensin (MON) belongs to the ionophore antibiotics and is widely used as a veterinary drug against coccidiosis in broiler farming. However, no electrochemically (EC) generated TPs of MON have been described so far. In this study, the online coupling of EC and mass spectrometry (MS) was used for the generation of oxidative TPs. EC-conditions were optimized with respect to working electrode material, solvent, modifier, and potential polarity. Subsequent LC/HRMS (liquid chromatography/high resolution mass spectrometry) and MS/MS experiments were performed to identify the structures of derived TPs by a suspected target analysis. The obtained EC-results were compared to TPs observed in metabolism tests with microsomes and hydrolysis experiments of MON. Five previously undescribed TPs of MON were identified in our EC/MS based study and one TP, which was already known from literature and found by a microsomal assay, could be confirmed. Two and three further TPs were found as products in microsomal tests and following hydrolysis, respectively. We found decarboxylation, O-demethylation and acid-catalyzed ring-opening reactions to be the major mechanisms of MON transformation.
KW  - transformation products
KW  - monensin
KW  - veterinary drugs
KW  - electrochemistry
KW  - hydrolysis
KW  - LC/HRMS
Y1  - 2019
U6  - https://doi.org/10.3390/molecules24152732
SN  - 1420-3049
VL  - 24
IS  - 15
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Figueroa Campos, Gustavo Adolfo
A1  - Perez, Jeffrey Paulo H.
A1  - Block, Inga
A1  - Sagu Tchewonpi, Sorel
A1  - Saravia Celis, Pedro
A1  - Taubert, Andreas
A1  - Rawel, Harshadrai Manilal
T1  - Preparation of activated carbons from spent coffee and coffee parchment and assessment of their adsorbent efficiency
JF  - Processes : open access journal
N2  - The valorization of coffee wastes through modification to activated carbon has been considered as a low-cost adsorbent with prospective to compete with commercial carbons. So far, very few studies have referred to the valorization of coffee parchment into activated carbon. Moreover, low-cost and efficient activation methods need to be more investigated. The aim of this work was to prepare activated carbon from spent coffee grounds and parchment, and to assess their adsorption performance. The co-calcination processing with calcium carbonate was used to prepare the activated carbons, and their adsorption capacity for organic acids, phenolic compounds and proteins was evaluated. Both spent coffee grounds and parchment showed yields after the calcination and washing treatments of around 9.0%. The adsorption of lactic acid was found to be optimal at pH 2. The maximum adsorption capacity of lactic acid with standard commercial granular activated carbon was 73.78 mg/g, while the values of 32.33 and 14.73 mg/g were registered for the parchment and spent coffee grounds activated carbons, respectively. The Langmuir isotherm showed that lactic acid was adsorbed as a monolayer and distributed homogeneously on the surface. Around 50% of total phenols and protein content from coffee wastewater were adsorbed after treatment with the prepared activated carbons, while 44, 43, and up to 84% of hydrophobic compounds were removed using parchment, spent coffee grounds and commercial activated carbon, respectively; the adsorption efficiencies of hydrophilic compounds ranged between 13 and 48%. Finally, these results illustrate the potential valorization of coffee by-products parchment and spent coffee grounds into activated carbon and their use as low-cost adsorbent for the removal of organic compounds from aqueous solutions.
KW  - coffee by-products
KW  - spent coffee grounds
KW  - parchment
KW  - valorization
KW  - calcination
KW  - activated carbon
KW  - organic compounds adsorption
Y1  - 2021
U6  - https://doi.org/10.3390/pr9081396
SN  - 2227-9717
VL  - 9
IS  - 8
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Gehre, Christian
A1  - Flechner, Marie
A1  - Kammerer, Sarah
A1  - Küpper, Jan-Heiner
A1  - Coleman, Charles Dominic
A1  - Püschel, Gerhard Paul
A1  - Uhlig, Katja
A1  - Duschl, Claus
T1  - Real time monitoring of oxygen uptake of hepatocytes in a microreactor using optical microsensors
JF  - Scientific reports
N2  - Most in vitro test systems for the assessment of toxicity are based on endpoint measurements and cannot contribute much to the establishment of mechanistic models, which are crucially important for further progress in this field. Hence, in recent years, much effort has been put into the development of methods that generate kinetic data. Real time measurements of the metabolic activity of cells based on the use of oxygen sensitive microsensor beads have been shown to provide access to the mode of action of compounds in hepatocytes. However, for fully exploiting this approach a detailed knowledge of the microenvironment of the cells is required. In this work, we investigate the cellular behaviour of three types of hepatocytes, HepG2 cells, HepG2-3A4 cells and primary mouse hepatocytes, towards their exposure to acetaminophen when the availability of oxygen for the cell is systematically varied. We show that the relative emergence of two modes of action, one NAPQI dependent and the other one transient and NAPQI independent, scale with expression level of CYP3A4. The transient cellular response associated to mitochondrial respiration is used to characterise the influence of the initial oxygen concentration in the wells before exposure to acetaminophen on the cell behaviour. A simple model is presented to describe the behaviour of the cells in this scenario. It demonstrates the level of control over the role of oxygen supply in these experiments. This is crucial for establishing this approach into a reliable and powerful method for the assessment of toxicity.
Y1  - 2020
U6  - https://doi.org/10.1038/s41598-020-70785-6
SN  - 2045-2322
VL  - 10
IS  - 1
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  - 
TY  - JOUR
A1  - Kehm, Richard
A1  - Jähnert, Markus
A1  - Deubel, Stefanie
A1  - Flore, Tanina
A1  - König, Jeannette
A1  - Jung, Tobias
A1  - Stadion, Mandy
A1  - Jonas, Wenke
A1  - Schürmann, Annette
A1  - Grune, Tilman
A1  - Höhn, Annika
T1  - Redox homeostasis and cell cycle activation mediate beta-cell mass expansion in aged, diabetes-prone mice under metabolic stress conditions: role of thioredoxin-interacting protein (TXNIP)
JF  - Redox Biology
N2  - Overnutrition contributes to insulin resistance, obesity and metabolic stress, initiating a loss of functional beta-cells and diabetes development. Whether these damaging effects are amplified in advanced age is barely investigated. Therefore, New Zealand Obese (NZO) mice, a well-established model for the investigation of human obesity-associated type 2 diabetes, were fed a metabolically challenging diet with a high-fat, carbohydrate restricted period followed by a carbohydrate intervention in young as well as advanced age. Interestingly, while young NZO mice developed massive hyperglycemia in response to carbohydrate feeding, leading to beta-cell dysfunction and cell death, aged counterparts compensated the increased insulin demand by persistent beta-cell function and beta-cell mass expansion. Beta-cell loss in young NZO islets was linked to increased expression of thioredoxin-interacting protein (TXNIP), presumably initiating an apoptosis-signaling cascade via caspase-3 activation. In contrast, islets of aged NZOs exhibited a sustained redox balance without changes in TXNIP expression, associated with higher proliferative potential by cell cycle activation. These findings support the relevance of a maintained proliferative potential and redox homeostasis for preserving islet functionality under metabolic stress, with the peculiarity that this adaptive response emerged with advanced age in diabetesprone NZO mice.
KW  - aging
KW  - redox homeostasis
KW  - metabolic stress
KW  - beta-cells
KW  - cell cycle
KW  - thioredoxin-interacting protein
Y1  - 2020
U6  - https://doi.org/10.1016/j.redox.2020.101748
SN  - 2213-2317
VL  - 37
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Xiong, Yingquan
A1  - Delic, Denis
A1  - Zeng, Shufei
A1  - Chen, Xin
A1  - Chu, Chang
A1  - Hasan, Ahmed A.
A1  - Krämer, Bernhard K.
A1  - Klein, Thomas
A1  - Yin, Lianghong
A1  - Hocher, Berthold
T1  - Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy-effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker
JF  - BMC nephrology
N2  - Background Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-blockers may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2. Methods We investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression of Ace2, Tmprss2, Ren, Agtr2 and Agt was assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham + normal diet (ND) + placebo (PBO); 5/6Nx + ND + PBO; 5/6Nx + high salt-diet (HSD) + PBO; 5/6Nx + HSD + telmisartan; 5/6Nx + HSD + linagliptin; 5/6Nx + HSD + empagliflozin. Results In the kidney, the expression of Ace2 was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) were not affected, whereas the cardiac level was significantly increased in 5/6Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin. Conclusions Our study indicated that there is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials.
KW  - SARS CoV-2 host factors
KW  - 5/6 nephrectomy
KW  - High-salt diet
KW  - ARB
KW  - DPP4 inhibitor
KW  - SGLT2 blocker
Y1  - 2022
U6  - https://doi.org/10.1186/s12882-022-02747-1
SN  - 1471-2369
VL  - 23
IS  - 1
PB  - Springer Nature
CY  - London
ER  - 
TY  - JOUR
A1  - Sagu Tchewonpi, Sorel
A1  - Landgräber, Eva
A1  - Rackiewicz, Michal
A1  - Huschek, Gerd
A1  - Rawel, Harshadrai Manilal
T1  - Relative Abundance of Alpha-Amylase/Trypsin Inhibitors in Selected Sorghum Cultivars
JF  - Molecules
N2  - Sorghum is of growing interest and considered as a safe food for wheat related disorders. Besides the gluten, α-amylase/trypsin-inhibitors (ATIs) have been identified as probable candidates for these disorders. Several studies focused on wheat-ATIs although there is still a lack of data referring to the relative abundance of sorghum-ATIs. The objective of this work was therefore to contribute to the characterization of sorghum ATI profiles by targeted proteomics tools. Fifteen sorghum cultivars from different regions were investigated with raw proteins ranging from 7.9 to 17.0 g/100 g. Ammonium bicarbonate buffer in combination with urea was applied for protein extraction, with concentration from 0.588 ± 0.047 to 4.140 ± 0.066 mg/mL. Corresponding electrophoresis data showed different protein profiles. UniProtKB data base research reveals two sorghum ATIs, P81367 and P81368; both reviewed and a targeted LC–MS/MS method was developed to analyze these. Quantifier peptides ELAAVPSR (P81367) and TYMVR (P81368) were identified and retained as biomarkers for relative quantification. Different reducing and alkylating agents were assessed and combination of tris (2 carboxyethyl) phosphine/iodoacetamide gave the best response. Linearity was demonstrated for the quantifier peptides with standard recovery between 92.2 and 107.6%. Nine sorghum cultivars presented up to 60 times lower ATI contents as compared to wheat samples. This data suggests that sorghum can effectively be considered as a good alternative to wheat.
KW  - sorghum
KW  - α-amylase/trypsin inhibitors
KW  - reducing agents
KW  - cysteine alkylation
KW  - SDS PAGE
KW  - targeted proteomics
KW  - LC–MS/MS
Y1  - 2020
U6  - https://doi.org/10.3390/molecules25245982
SN  - 1420-3049
VL  - 25
IS  - 24
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Fechner, Carolin
A1  - Hackethal, Christin
A1  - Höpfner, Tobias
A1  - Dietrich, Jessica
A1  - Bloch, Dorit
A1  - Lindtner, Oliver
A1  - Sarvan, Irmela
T1  - Results of the BfR MEAL Study
BT  - in Germany, mercury is mostly contained in fish and seafood while cadmium, lead, and nickel are present in a broad spectrum of foods
JF  - Food chemistry: X
N2  - The BfR MEAL Study provides representative levels of substances in foods consumed in Germany. Mercury, cadmium, lead, and nickel are contaminants present in foods introduced by environmental and industrial processes. Levels of these elements were investigated in 356 foods. Foods were purchased representatively, prepared as consumed and pooled with similar foods before analysis. Highest mean levels of mercury were determined in fish and seafood, while high levels of cadmium, lead, and nickel were present in cocoa products and legumes, nuts, oilseeds, and spices. The sampling by region, season, and production type showed minor differences in element levels for specific foods, however no tendency over all foods or for some food groups was apparent. The data on mercury, cadmium, lead, and nickel provide a comprehensive basis for chronic dietary exposure assessment of the population in Germany. All levels found were below regulated maximum levels.
KW  - Total diet study
KW  - BfR MEAL Study
KW  - Metals
KW  - Contaminants
KW  - Unprepared and
KW  - prepared foods
KW  - Regionality
KW  - Seasonality
KW  - Organic and conventional type of production
Y1  - 2022
U6  - https://doi.org/10.1016/j.fochx.2022.100326
SN  - 2590-1575
VL  - 14
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Shen, Jinhua
A1  - Zhang, Xiaoli
A1  - Peng, Yangqin
A1  - Zhang, Qin
A1  - Hu, Liang
A1  - Reichetzeder, Christoph
A1  - Zeng, Suimin
A1  - Li, Jing
A1  - Tian, Mei
A1  - Gong, Fei
A1  - Lin, Ge
A1  - Hocher, Berthold
T1  - Risk factors associated with preterm birth after IVF/ICSI
JF  - Scientific reports
N2  - In vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is associated with an increased risk of preterm (33rd-37th gestational week) and early preterm birth (20th-32nd gestational week). The underlying general and procedure related risk factors are not well understood so far. 4328 infertile women undergoing IVF/ICSI were entered into this study. The study population was divided into three groups: (a) early preterm birth group (n = 66), (b) preterm birth group (n = 675) and (c) full-term birth group (n = 3653). Odds for preterm birth were calculated by stepwise multivariate logistic regression analysis. We identified seven independent risk factors for preterm birth and four independent risk factors for early preterm birth. Older (> 39) or younger (< 25) maternal age (OR: 1.504, 95% CI 1.108-2.042, P = 0.009; OR: 2.125, 95% CI 1.049-4.304, P = 0.036, respectively), multiple pregnancy (OR: 9.780, 95% CI 8.014-11.935, P < 0.001; OR: 8.588, 95% CI 4.866-15.157, P < 0.001, respectively), placenta previa (OR: 14.954, 95% CI 8.053-27.767, P < 0.001; OR: 16.479, 95% CI 4.381-61.976, P < 0.001, respectively), and embryo reduction (OR: 3.547, 95% CI 1.736-7.249, P = 0.001; OR: 7.145, 95% CI 1.990-25.663, P = 0.003, respectively) were associated with preterm birth and early preterm birth, whereas gestational hypertension (OR: 2.494, 95% CI 1.770-3.514, P < 0.001), elevated triglycerides (OR: 1.120, 95% CI 1.011-1.240, P = 0.030) and shorter activated partial thromboplastin time (OR: 0.967, 95% CI 0.949-0.985, P < 0.001) were associated only with preterm birth. In conclusion, preterm and early preterm birth risk factors in patients undergoing assisted IVF/ICSI are in general similar to those in natural pregnancy. The lack of some associations in the early preterm group was most likely due to the lower number of early preterm birth cases. Only embryo reduction represents an IVF/ICSI specific risk factor.
Y1  - 2022
U6  - https://doi.org/10.1038/s41598-022-12149-w
SN  - 2045-2322
VL  - 12
IS  - 1
PB  - Nature Research
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Kessler, Katharina
A1  - Hornemann, Silke
A1  - Rudovich, Natalia
A1  - Weber, Daniela
A1  - Grune, Tilman
A1  - Kramer, Achim
A1  - Pfeiffer, Andreas F. H.
A1  - Pivovarova-Ramich, Olga
T1  - Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers
JF  - Nutrients
N2  - Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies.
KW  - meal timing
KW  - saliva
KW  - circadian clock
KW  - adiponectin
KW  - resistin
KW  - visfatin
KW  - insulin
KW  - melatonin
KW  - cortisol
KW  - cytokines
Y1  - 2020
U6  - https://doi.org/10.3390/nu12020340
SN  - 2072-6643
IS  - 2
SP  - 1
EP  - 12
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Solovyev, Nikolay
A1  - Drobyshev, Evgenii
A1  - Blume, Bastian
A1  - Michalke, Bernhard
T1  - Selenium at the neural barriers
BT  - a review
JF  - Frontiers in neuroscience / Frontiers Research Foundation
N2  - Selenium (Se) is known to contribute to several vital physiological functions in mammals: antioxidant defense, fertility, thyroid hormone metabolism, and immune response. Growing evidence indicates the crucial role of Se and Se-containing selenoproteins in the brain and brain function. As for the other essential trace elements, dietary Se needs to reach effective concentrations in the central nervous system (CNS) to exert its functions. To do so, Se-species have to cross the blood-brain barrier (BBB) and/or blood-cerebrospinal fluid barrier (BCB) of the choroid plexus. The main interface between the general circulation of the body and the CNS is the BBB. Endothelial cells of brain capillaries forming the so-called tight junctions are the primary anatomic units of the BBB, mainly responsible for barrier function. The current review focuses on Se transport to the brain, primarily including selenoprotein P/low-density lipoprotein receptor-related protein 8 (LRP8, also known as apolipoprotein E receptor-2) dependent pathway, and supplementary transport routes of Se into the brain via low molecular weight Se-species. Additionally, the potential role of Se and selenoproteins in the BBB, BCB, and neurovascular unit (NVU) is discussed. Finally, the perspectives regarding investigating the role of Se and selenoproteins in the gut-brain axis are outlined.
KW  - selenium
KW  - selenoprotein P
KW  - low molecular weight selenium species
KW  - blood– cerebrospinal fluid barrier
KW  - blood– brain barrier
KW  - selenium transport
KW  - brain-gut axis
KW  - LRP8
Y1  - 2021
U6  - https://doi.org/10.3389/fnins.2021.630016
SN  - 1662-453X
VL  - 15
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Franz, Kristina
A1  - Otten, Lindsey
A1  - Müller-Werdan, Ursula
A1  - Döhner, Wolfram
A1  - Norman, Kristina
T1  - Severe Weight Loss and Its Association with Fatigue in Old Patients at Discharge from a Geriatric Hospital
JF  - Nutrients
N2  - Although malnutrition is frequent in the old, little is known about its association with fatigue. We evaluated the relation of self-reported severe weight loss with fatigue and the predictors for fatigue in old patients at hospital discharge. Severe weight loss was defined according to involuntary weight loss >= 5% in the last three months. We determined fatigue with the validated Brief Fatigue Inventory questionnaire. The regression analyses were adjusted for age, sex, number of comorbidities, medications/day, and BMI. Of 424 patients aged between 61 and 98 y, 34.1% had severe weight loss. Fatigue was higher in patients with severe weight loss (3.7 +/- 2.3 vs. 3.2 +/- 2.3 points, p = 0.021). In a multinomial regression model, weight loss was independently associated with higher risk for moderate fatigue (OR:1.172, CI:1.026-1.338, p = 0.019) and with increased risk for severe fatigue (OR:1.209, CI:1.047-1.395, p = 0.010) together with the number of medications/day (OR:1.220, CI:1.023-1.455, p = 0.027). In a binary regression model, severe weight loss predicted moderate-to-severe fatigue in the study population (OR:1.651, CI:1.052-2.590, p = 0.029). In summary, patients with self-reported severe weight loss at hospital discharge exhibited higher fatigue levels and severe weight loss was an independent predictor of moderate and severe fatigue, placing these patients at risk for impaired outcome in the post-hospital period.
KW  - malnutrition
KW  - involuntary weight loss
KW  - post-hospital syndrome
KW  - fatigue
KW  - old adults
Y1  - 2019
U6  - https://doi.org/10.3390/nu11102415
SN  - 2072-6643
VL  - 11
IS  - 10
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - John, Cathleen
A1  - Grune, Jana
A1  - Ott, Christiane
A1  - Nowotny, Kerstin
A1  - Deubel, Stefanie
A1  - Kühne, Arne
A1  - Schubert, Carola
A1  - Kintscher, Ulrich
A1  - Regitz-Zagrosek, Vera
A1  - Grune, Tilman
T1  - Sex Differences in Cardiac Mitochondria in the New Zealand Obese Mouse
JF  - Frontiers in Endocrinology
N2  - Background: Obesity is a risk factor for diseases including type 2 diabetes mellitus (T2DM) and cardiovascular disorders. Diabetes itself contributes to cardiac damage. Thus, studying cardiovascular events and establishing therapeutic intervention in the period of type T2DM onset and manifestation are of highest importance. Mitochondrial dysfunction is one of the pathophysiological mechanisms leading to impaired cardiac function. Methods: An adequate animal model for studying pathophysiology of T2DM is the New Zealand Obese (NZO) mouse. These mice were maintained on a high-fat diet (HFD) without carbohydrates for 13 weeks followed by 4 week HFD with carbohydrates. NZO mice developed severe obesity and only male mice developed manifest T2DM. We determined cardiac phenotypes and mitochondrial function as well as cardiomyocyte signaling in this model. Results: The development of an obese phenotype and T2DM in male mice was accompanied by an impaired systolic function as judged by echocardiography and MyH6/7 expression. Moreover, the mitochondrial function only in male NZO hearts was significantly reduced and ERK1/2 and AMPK protein levels were altered. Conclusions: This is the first report demonstrating that the cardiac phenotype in male diabetic NZO mice is associated with impaired cardiac energy function and signaling events.
KW  - NZO
KW  - heart
KW  - obesity
KW  - mitochondrial function
KW  - echocardiography
KW  - systolic function
Y1  - 2018
U6  - https://doi.org/10.3389/fendo.2018.00732
SN  - 1664-2392
VL  - 9
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Gellner, Anne-Kathrin
A1  - Sitter, Aileen
A1  - Rackiewicz, Michal
A1  - Sylvester, Marc
A1  - Philipsen, Alexandra
A1  - Zimmer, Andreas
A1  - Stein, Valentin
T1  - Stress vulnerability shapes disruption of motor cortical neuroplasticity
JF  - Translational Psychiatry
N2  - Chronic stress is a major cause of neuropsychiatric conditions such as depression. Stress vulnerability varies individually in mice and humans, measured by behavioral changes. In contrast to affective symptoms, motor retardation as a consequence of stress is not well understood. We repeatedly imaged dendritic spines of the motor cortex in Thy1-GFP M mice before and after chronic social defeat stress. Susceptible and resilient phenotypes were discriminated by symptom load and their motor learning abilities were assessed by a gross and fine motor task. Stress phenotypes presented individual short- and long-term changes in the hypothalamic-pituitary-adrenal axis as well as distinct patterns of altered motor learning. Importantly, stress was generally accompanied by a marked reduction of spine density in the motor cortex and spine dynamics depended on the stress phenotype. We found astrogliosis and altered microglia morphology along with increased microglia-neuron interaction in the motor cortex of susceptible mice. In cerebrospinal fluid, proteomic fingerprints link the behavioral changes and structural alterations in the brain to neurodegenerative disorders and dysregulated synaptic homeostasis. Our work emphasizes the importance of synaptic integrity and the risk of neurodegeneration within depression as a threat to brain health.
Y1  - 2022
U6  - https://doi.org/10.1038/s41398-022-01855-8
SN  - 2158-3188
VL  - 12
IS  - 1
PB  - Nature Publishing Group
CY  - London
ER  - 
TY  - JOUR
A1  - Wilhelmi, Ilka
A1  - Grunwald, Stephan
A1  - Gimber, Niclas
A1  - Popp, Oliver
A1  - Dittmar, Gunnar
A1  - Arumughan, Anup
A1  - Wanker, Erich E.
A1  - Laeger, Thomas
A1  - Schmoranzer, Jan
A1  - Daumke, Oliver
A1  - Schürmann, Annette
T1  - The ARFRP1-dependent Golgi scaffolding protein GOPC is required for insulin secretion from pancreatic 13-cells
JF  - Molecular metabolism
N2  - Objective: Hormone secretion from metabolically active tissues, such as pancreatic islets, is governed by specific and highly regulated signaling pathways. Defects in insulin secretion are among the major causes of diabetes. The molecular mechanisms underlying regulated insulin secretion are, however, not yet completely understood. In this work, we studied the role of the GTPase ARFRP1 on insulin secretion from pancreatic 13-cells. <br /> Methods: A 13-cell-specific Arfrp1 knockout mouse was phenotypically characterized. Pulldown experiments and mass spectrometry analysis were employed to screen for new ARFRP1-interacting proteins. Co-immunoprecipitation assays as well as super-resolution microscopy were applied for validation. <br /> Results: The GTPase ARFRP1 interacts with the Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC). Both proteins are co localized at the trans-Golgi network and regulate the first and second phase of insulin secretion by controlling the plasma membrane localization of the SNARE protein SNAP25. Downregulation of both GOPC and ARFRP1 in Min6 cells interferes with the plasma membrane localization of SNAP25 and enhances its degradation, thereby impairing glucose-stimulated insulin release from 13-cells. In turn, overexpression of SNAP25 as well as GOPC restores insulin secretion in islets from 13-cell-specific Arfrp1 knockout mice. <br /> Conclusion: Our results identify a hitherto unrecognized pathway required for insulin secretion at the level of trans-Golgi sorting. (c) 2020 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
KW  - Insulin secretion
KW  - Endosomal sorting
KW  - SNARE proteins
KW  - trans-Golgi
KW  - network
Y1  - 2020
U6  - https://doi.org/10.1016/j.molmet.2020.101151
SN  - 2212-8778
VL  - 45
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - GEN
A1  - Kleuser, Burkhard
T1  - The enigma of sphingolipids in health and disease
T2  - International journal of molecular sciences
Y1  - 2018
U6  - https://doi.org/10.3390/ijms19103126
SN  - 1422-0067
VL  - 19
IS  - 10
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Zoicas, Iulia
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Reichel, Martin
A1  - Gulbins, Erich
A1  - Fejtova, Anna
A1  - Kornhuber, Johannes
A1  - Rhein, Cosima
T1  - The forebrain-specific overexpression of acid sphingomyelinase induces depressive-like symptoms in mice
JF  - Cells
N2  - Human and murine studies identified the lysosomal enzyme acid sphingomyelinase (ASM) as a target for antidepressant therapy and revealed its role in the pathophysiology of major depression. In this study, we generated a mouse model with overexpression of Asm (Asm-tg(fb)) that is restricted to the forebrain to rule out any systemic effects of Asm overexpression on depressive-like symptoms. The increase in Asm activity was higher in male Asm-tg(fb) mice than in female Asm-tg(fb) mice due to the breeding strategy, which allows for the generation of wild-type littermates as appropriate controls. Asm overexpression in the forebrain of male mice resulted in a depressive-like phenotype, whereas in female mice, Asm overexpression resulted in a social anxiogenic-like phenotype. Ceramides in male Asm-tg(fb) mice were elevated specifically in the dorsal hippocampus. mRNA expression analyses indicated that the increase in Asm activity affected other ceramide-generating pathways, which might help to balance ceramide levels in cortical brain regions. This forebrain-specific mouse model offers a novel tool for dissecting the molecular mechanisms that play a role in the pathophysiology of major depression.
KW  - Smpd1
KW  - acid sphingomyelinase
KW  - forebrain
KW  - depressive-like behavior
KW  - anxiety-like behavior
KW  - ceramide
Y1  - 2020
VL  - 9
IS  - 5
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Schwingshackl, Lukas
A1  - Ruzanska, Ulrike Alexandra
A1  - Anton, Verena
A1  - Wallroth, Raphael
A1  - Ohla, Kathrin
A1  - Knueppel, Sven
A1  - Schulze, Matthias Bernd
A1  - Pischon, Tobias
A1  - Deutschbein, Johannes
A1  - Schenk, Liane
A1  - Warschburger, Petra
A1  - Harttig, Ulrich
A1  - Boeing, Heiner
A1  - Bergmann, Manuela M.
T1  - The NutriAct Family Study: a web-based prospective study on the epidemiological, psychological and sociological basis of food choice
JF  - BMC public health
N2  - 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.
KW  - NutriAct family study
KW  - Study protocol
KW  - Food choice
KW  - Determinants
Y1  - 2018
U6  - https://doi.org/10.1186/s12889-018-5814-x
SN  - 1471-2458
VL  - 18
PB  - BMC
CY  - London
ER  - 
TY  - JOUR
A1  - Johann, Kornelia
A1  - Kleinert, Maximilian
A1  - Klaus, Susanne
T1  - The role of GDF15 as a myomitokine
JF  - Cells
N2  - Growth differentiation factor 15 (GDF15) is a cytokine best known for affecting systemic energy metabolism through its anorectic action. GDF15 expression and secretion from various organs and tissues is induced in different physiological and pathophysiological states, often linked to mitochondrial stress, leading to highly variable circulating GDF15 levels. 

In skeletal muscle and the heart, the basal expression of GDF15 is very low compared to other organs, but GDF15 expression and secretion can be induced in various stress conditions, such as intense exercise and acute myocardial infarction, respectively. GDF15 is thus considered as a myokine and cardiokine. GFRAL, the exclusive receptor for GDF15, is expressed in hindbrain neurons and activation of the GDF15-GFRAL pathway is linked to an increased sympathetic outflow and possibly an activation of the hypothalamic-pituitary-adrenal (HPA) stress axis. 

There is also evidence for peripheral, direct effects of GDF15 on adipose tissue lipolysis and possible autocrine cardiac effects. Metabolic and behavioral outcomes of GDF15 signaling can be beneficial or detrimental, likely depending on the magnitude and duration of the GDF15 signal. 
This is especially apparent for GDF15 production in muscle, which can be induced both by exercise and by muscle disease states such as sarcopenia and mitochondrial myopathy.
KW  - anorexia
KW  - appetite regulation
KW  - cardiokine
KW  - cytokine
KW  - exercise
KW  - mitochondria
KW  - muscle
KW  - myokine
KW  - myopathy
KW  - sarcopenia
Y1  - 2021
U6  - https://doi.org/10.3390/cells10112990
SN  - 2073-4409
VL  - 10
IS  - 11
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Döll, Stefanie
A1  - Djalali Farahani-Kofoet, Roxana
A1  - Zrenner, Rita
A1  - Henze, Andrea
A1  - Witzel, Katja
T1  - Tissue-specific signatures of metabolites and proteins in asparagus roots and exudates
JF  - Horticulture research
N2  - Comprehensive untargeted and targeted analysis of root exudate composition has advanced our understanding of rhizosphere processes. However, little is known about exudate spatial distribution and regulation. We studied the specific metabolite signatures of asparagus root exudates, root outer (epidermis and exodermis), and root inner tissues (cortex and vasculature). The greatest differences were found between exudates and root tissues. In total, 263 non-redundant metabolites were identified as significantly differentially abundant between the three root fractions, with the majority being enriched in the root exudate and/or outer tissue and annotated as 'lipids and lipid-like molecules' or 'phenylpropanoids and polyketides'. Spatial distribution was verified for three selected compounds using MALDI-TOF mass spectrometry imaging. Tissue-specific proteome analysis related root tissue-specific metabolite distributions and rhizodeposition with underlying biosynthetic pathways and transport mechanisms. The proteomes of root outer and inner tissues were spatially very distinct, in agreement with the fundamental differences between their functions and structures. According to KEGG pathway analysis, the outer tissue proteome was characterized by a high abundance of proteins related to 'lipid metabolism', 'biosynthesis of other secondary metabolites' and 'transport and catabolism', reflecting its main functions of providing a hydrophobic barrier, secreting secondary metabolites, and mediating water and nutrient uptake. Proteins more abundant in the inner tissue related to 'transcription', 'translation' and 'folding, sorting and degradation', in accord with the high activity of cortical and vasculature cell layers in growth- and development-related processes. In summary, asparagus root fractions accumulate specific metabolites. This expands our knowledge of tissue-specific plant cell function.
Y1  - 2021
U6  - https://doi.org/10.1038/s41438-021-00510-5
SN  - 2052-7276
SN  - 2662-6810
VL  - 8
IS  - 1
PB  - Nanjing Agricultural Univ.
CY  - Nanjing
ER  - 
TY  - JOUR
A1  - Chaykovska, Lyubov
A1  - Heunisch, Fabian
A1  - von Einem, Gina
A1  - Hocher, Carl-Friedrich
A1  - Tsuprykov, Oleg
A1  - Pavkovic, Mira
A1  - Sandner, Peter
A1  - Kretschmer, Axel
A1  - Chu, Chang
A1  - Elitok, Saban
A1  - Stasch, Johannes-Peter
A1  - Hocher, Berthold
T1  - Urinary cGMP predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus before exposure to contrast medium
JF  - PLoS one
N2  - 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.
Y1  - 2018
U6  - https://doi.org/10.1371/journal.pone.0195828
SN  - 1932-6203
VL  - 13
IS  - 4
PB  - PLoS
CY  - San Fransisco
ER  - 
TY  - JOUR
A1  - Fitzner, Maria
A1  - Fricke, Anna
A1  - Schreiner, Monika
A1  - Baldermann, Susanne
T1  - Utilization of regional natural brines for the indoor cultivation of Salicornia europaea
JF  - Sustainability / Multidisciplinary Digital Publishing Institute (MDPI)
N2  - Scaling agriculture to the globally rising population demands new approaches for future crop production such as multilayer and multitrophic indoor farming. Moreover, there is a current trend towards sustainable local solutions for aquaculture and saline agriculture. In this context, halophytes are becoming increasingly important for research and the food industry. As Salicornia europaea is a highly salt-tolerant obligate halophyte that can be used as a food crop, indoor cultivation with saline water is of particular interest. Therefore, finding a sustainable alternative to the use of seawater in non-coastal regions is crucial. Our goal was to determine whether natural brines, which are widely distributed and often available in inland areas, provide an alternative water source for the cultivation of saline organisms. This case study investigated the potential use of natural brines for the production of S. europaea. In the control group, which reflects the optimal growth conditions, fresh weight was increased, but there was no significant difference between the treatment groups comparing natural brines with artificial sea water. A similar pattern was observed for carotenoids and chlorophylls. Individual components showed significant differences. However, within treatments, there were mostly no changes. In summary, we showed that the influence of the different chloride concentrations was higher than the salt composition. Moreover, nutrient-enriched natural brine was demonstrated to be a suitable alternative for cultivation of S. europaea in terms of yield and nutritional quality. Thus, the present study provides the first evidence for the future potential of natural brine waters for the further development of aquaculture systems and saline agriculture in inland regions.
KW  - carotenoids
KW  - glasswort
KW  - land-based aquaculture
KW  - seawater
KW  - phytochemicals
KW  - halophytes
KW  - salt composition
KW  - chlorophylls
KW  - artificial
KW  - salt
KW  - saline agriculture
Y1  - 2021
U6  - https://doi.org/10.3390/su132112105
SN  - 2071-1050
VL  - 13
IS  - 21
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Schjeide, Brit-Maren
A1  - Schenke, Maren
A1  - Seeger, Bettina
A1  - Püschel, Gerhard
T1  - Validation of a novel double control quantitative copy number PCR method to quantify off-target transgene integration after CRISPR-induced DNA modification
JF  - Methods and protocols : M&Ps
N2  - In order to improve a recently established cell-based assay to assess the potency of botulinum neurotoxin, neuroblastoma-derived SiMa cells and induced pluripotent stem-cells (iPSC) were modified to incorporate the coding sequence of a reporter luciferase into a genetic safe harbor utilizing CRISPR/Cas9. A novel method, the double-control quantitative copy number PCR (dc-qcnPCR), was developed to detect off-target integrations of donor DNA. The donor DNA insertion success rate and targeted insertion success rate were analyzed in clones of each cell type. The dc-qcnPCR reliably quantified the copy number in both cell lines. The probability of incorrect donor DNA integration was significantly increased in SiMa cells in comparison to the iPSCs. This can possibly be explained by the lower bundled relative gene expression of a number of double-strand repair genes (BRCA1, DNA2, EXO1, MCPH1, MRE11, and RAD51) in SiMa clones than in iPSC clones. The dc-qcnPCR offers an efficient and cost-effective method to detect off-target CRISPR/Cas9-induced donor DNA integrations.
KW  - CRISPR editing validation
KW  - copy number analyses
KW  - homology-directed repair
KW  - homologous recombination deficiency
Y1  - 2022
U6  - https://doi.org/10.3390/mps5030043
SN  - 2409-9279
VL  - 5
IS  - 3
SP  - 1
EP  - 14
PB  - MDPI
CY  - Basel, Schweiz
ER  -