TY  - JOUR
A1  - Yang, Guang
A1  - Zheng, Wei
A1  - Tao, Guoqing
A1  - Wu, Libin
A1  - Zhou, Qi-Feng
A1  - Kochovski, Zdravko
A1  - Ji, Tan
A1  - Chen, Huaijun
A1  - Li, Xiaopeng
A1  - Lu, Yan
A1  - Ding, Hong-ming
A1  - Yang, Hai-Bo
A1  - Chen, Guosong
A1  - Jiang, Ming
T1  - Diversiform and Transformable Glyco-Nanostructures Constructed from Amphiphilic Supramolecular Metallocarbohydrates through Hierarchical Self-Assembly: The Balance between Metallacycles and Saccharides
JF  - ACS nano
N2  - During the past decade, self-assembly of saccharide-containing amphiphilic molecules toward bioinspired functional glycomaterials has attracted continuous attention due to their various applications in fundamental and practical areas. However, it still remains a great challenge to prepare hierarchical glycoassemblies with controllable and diversiform structures because of the complexity of saccharide structures and carbohydrate-carbohydrate interactions. Herein, through hierarchical self-assembly of modulated amphiphilic supramolecular metallocarbohydrates, we successfully prepared various well-defined glyco-nanostructures in aqueous solution, including vesicles, solid spheres, and opened vesicles depending on the molecular structures of metallocarbohydrates. More attractively, these glyco-nanostructures can further transform into other morphological structures in aqueous solutions such as worm-like micelles, tubules, and even tupanvirus-like vesicles (TVVs). It is worth mentioning that distinctive anisotropic structures including the opened vesicles (OVs) and TVVs were rarely reported in glycobased nano-objects. This intriguing diversity was mainly controlled by the subtle structural trade-off of the two major components of the amphiphiles, i.e., the saccharides and metallacycles. To further understand this precise structural control, molecular simulations provided deep physical insights on the morphology evolution and balancing of the contributions from saccharides and metallacycles. Moreover, the multivalency of glyco-nanostructures with different shapes and sizes was demonstrated by agglutination with a diversity of sugarbinding protein receptors such as the plant lectins Concanavalin A (ConA). This modular synthesis strategy provides access to systematic tuning of molecular structure and self-assembled architecture, which undoubtedly will broaden our horizons on the controllable fabrication of biomimetic glycomaterials such as biological membranes and supramolecular lectin inhibitors.
KW  - glycomaterials
KW  - diversiform structures
KW  - hierarchical self-assembly
KW  - metallocarbohydrates
KW  - anisotropic structures
Y1  - 2019
U6  - https://doi.org/10.1021/acsnano.9b07134
SN  - 1936-0851
SN  - 1936-086X
VL  - 13
IS  - 11
SP  - 13474
EP  - 13485
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Reichetzeder, Christoph
A1  - Chen, Hong
A1  - Foeller, Michael
A1  - Slowinski, Torsten
A1  - Li, Jian
A1  - Chen, You-Peng
A1  - Lang, Florian
A1  - Hocher, Berthold
T1  - Maternal vitamin D deficiency and fetal programming - lessons learned from humans and mice
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background/Aims: Cardiovascular disease partially originates from poor environmental and nutritional conditions in early life. Lack of micronutrients like 25 hydroxy vitamin D-3 (25OHD) during pregnancy may be an important treatable causal factor. The present study explored the effect of maternal 25OHD deficiency on the offspring. Methods: We performed a prospective observational study analyzing the association of maternal 25OHD deficiency during pregnancy with birth outcomes considering confounding. To show that vitamin D deficiency may be causally involved in the observed associations, mice were set on either 25OHD sufficient or insufficient diets before and during pregnancy. Growth, glucose tolerance and mortality was analyzed in the F1 generation. Results: The clinical study showed that severe 25OHD deficiency was associated with low birth weight and low gestational age. ANCOVA models indicated that established confounding factors such as offspring sex, smoking during pregnancy and maternal BMI did not influence the impact of 25OHD on birth weight. However, there was a significant interaction between 25OHD and gestational age. Maternal 25OHD deficiency was also independently associated with low APGAR scores 5 minutes postpartum. The offspring of 25OHD deficient mice grew slower after birth, had an impaired glucose tolerance shortly after birth and an increased mortality during follow-up. Conclusions: Our study demonstrates an association between maternal 25OHD and offspring birth weight. The effect of 25OHD on birth weight seems to be mediated by vitamin D controlling gestational age. Results from an animal experiment suggest that gestational 25OHD insufficiency is causally linked to adverse pregnancy outcomes. Since birth weight and prematurity are associated with an adverse cardiovascular outcome in later life, this study emphasizes the need for novel monitoring and treatment guidelines of vitamin D deficiency during pregnancy.
KW  - Vitamin D
KW  - Birth weight
KW  - Preterm delivery
KW  - Fetal programming
KW  - Glucose tolerance
KW  - Cardiovascular diseases
Y1  - 2014
U6  - https://doi.org/10.1159/000355809
SN  - 1420-4096
SN  - 1423-0143
VL  - 39
IS  - 4
SP  - 315
EP  - 329
PB  - Karger
CY  - Basel
ER  - 
TY  - CHAP
A1  - Chen, Hong
A1  - Reichetzeder, Christoph
A1  - Föller, Michael
A1  - Slowinski, Torsten
A1  - Li, Jian
A1  - Chen, You-Peng
A1  - Lang, Florian
A1  - Hocher, Berthold
T1  - Maternal vitamin D deficiency and fetal programming
T2  - Acta physiologica : official journal of the Federation of European Physiological Societies
Y1  - 2015
SN  - 1748-1708
SN  - 1748-1716
VL  - 213
SP  - 155
EP  - 156
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Yang, Guang
A1  - Ding, Hong-ming
A1  - Kochovski, Zdravko
A1  - Hu, Rongting
A1  - Lu, Yan
A1  - Ma, Yu-qiang
A1  - Chen, Guosong
A1  - Jiang, Ming
T1  - Highly Ordered Self-Assembly of Native Proteins into 1D, 2D, and 3D Structures Modulated by the Tether Length of Assembly-Inducing Ligands
JF  - Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition
N2  - In nature, proteins self-assemble into various structures with different dimensions. To construct these nanostructures in laboratories, normally proteins with different symmetries are selected. However, most of these approaches are engineering-intensive and highly dependent on the accuracy of the protein design. Herein, we report that a simple native protein LecA assembles into one-dimensional nanoribbons and nanowires, two-dimensional nanosheets, and three-dimensional layered structures controlled mainly by small-molecule assembly-inducing ligands RnG (n = 1, 2, 3, 4, 5) with varying numbers of ethylene oxide repeating units. To understand the formation mechanism of the different morphologies controlled by the small-molecule structure, molecular simulations were performed from microscopic and mesoscopic view, which presented a clear relationship between the molecular structure of the ligands and the assembled patterns. These results introduce an easy strategy to control the assembly structure and dimension, which could shed light on controlled protein assembly.
KW  - carbohydrate-protein interactions
KW  - dual non-covalent interactions
KW  - molecular simulations
KW  - protein self-assembly
Y1  - 2017
U6  - https://doi.org/10.1002/anie.201703052
SN  - 1433-7851
SN  - 1521-3773
VL  - 56
SP  - 10691
EP  - 10695
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Glosse, Philipp
A1  - Feger, Martina
A1  - Mutig, Kerim
A1  - Chen, Hong
A1  - Hirche, Frank
A1  - Hasan, Ahmed Abdallah Abdalrahman Mohamed
A1  - Gaballa, Mohamed Mahmoud Salem Ahmed
A1  - Hocher, Berthold
A1  - Lang, Florian
A1  - Föller, Michael
T1  - AMP-activated kinase is a regulator of fibroblast growth factor 23 production
JF  - Kidney international : official journal of the International Society of Nephrology
N2  - Fibroblast growth factor 23 (FGF23) is a proteohormone regulating renal phosphate transport and vitamin D metabolism as well as inducing left heart hypertrophy. FGF23-deficient mice suffer from severe tissue calcification, accelerated aging and a myriad of aging-associated diseases. Bone cells produce FGF23 upon store-operated calcium ion entry (SOCE) through the calcium selective ion channel Orai1. AMP-activated kinase (AMPK) is a powerful energy sensor helping cells survive states of energy deficiency, and AMPK down-regulates Orai1. Here we investigated the role of AMPK in FGF23 production. Fgf23 gene transcription was analyzed by qRT-PCR and SOCE by fluorescence optics in UMR106 osteoblast-like cells while the serum FGF23 concentration and phosphate metabolism were assessed in AMPKa1-knockout and wild-type mice. The AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) down-regulated, whereas the AMPK inhibitor, dorsomorphin dihydrochloride (compound C) and AMPK gene silencing induced Fgf23 transcription. AICAR decreased membrane abundance of Orai1 and SOCE. SOCE inhibitors lowered Fgf23 gene expression induced by AMPK inhibition. AMPKa1-knockout mice had a higher serum FGF23 concentration compared to wild-type mice. Thus, AMPK participates in the regulation of FGF23 production in vitro and in vivo. The inhibitory effect of AMPK on FGF23 production is at least in part mediated by Orai1-involving SOCE.
KW  - calcium
KW  - FGF23
KW  - Klotho
KW  - Orai1
KW  - phosphate
KW  - parathyroid hormone
Y1  - 2018
U6  - https://doi.org/10.1016/j.kint.2018.03.006
SN  - 0085-2538
SN  - 1523-1755
VL  - 94
IS  - 3
SP  - 491
EP  - 501
PB  - Elsevier
CY  - New York
ER  - 
TY  - JOUR
A1  - Lu, Yong-Ping
A1  - Reichetzeder, Christoph
A1  - Prehn, Cornelia
A1  - von Websky, Karoline
A1  - Slowinski, Torsten
A1  - Chen, You-Peng
A1  - Yin, Liang-Hong
A1  - Kleuser, Burkhard
A1  - Yang, Xue-Song
A1  - Adamski, Jerzy
A1  - Hocher, Berthold
T1  - Fetal serum metabolites are independently associated with Gestational diabetes mellitus
JF  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology
N2  - Background/Aims: Gestational diabetes (GDM) might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. Methods: At the time of birth, serum samples from mothers and newborns (cord blood samples) were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. Results: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH) procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32:1 and proline still showed an independent association with GDM. Conclusions: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal serum metabolites and maternal GDM. Our findings might suggest a potential effect of the fetal metabolome on maternal GDM. (c) 2018 The Author(s) Published by S. Karger AG, Basel
KW  - Gestational diabetes
KW  - Metabolomics
KW  - Phosphatidylcholine acyl-alkyl C 32:1
KW  - Proline
Y1  - 2018
U6  - https://doi.org/10.1159/000487119
SN  - 1015-8987
SN  - 1421-9778
VL  - 45
IS  - 2
SP  - 625
EP  - 638
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Chen, You-Peng
A1  - Dong, Yun-Peng
A1  - Yu, Cal-Hong
A1  - Lu, Yong-Ping
A1  - Xiao, Xiao-Min
A1  - Hocher, Berthold
T1  - The impact of umbilical blood flow regulation on fetal development differs in diabetic and non-diabetic pregnancy
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background/Aims: Diabetes is well-known to influence endothelial function. Endothelial function and blood flow regulation might be different in diabetic and non-diabetic pregnancy. However, the impact of umbilical blood flow regulation in gestational diabetes on fetal development is unknown so far. Methods: In a prospective birth cohort study, we analyzed the association of the umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) and fetal size measures (biparietal diameter, head circumference, abdominal circumference, femur length and birth weight) in 519 non-gestational diabetes mellitus pregnancies (controls) and 226 gestational diabetes mellitus pregnancies in middle (day 160.32 +/- 16.29 of gestation) and late (day 268.12 +/- 13.04 of gestation) pregnancy. Results: Multiple regression analysis considering confounding factors (gestational day of ultrasound examination, offspring sex, maternal body mess index before pregnancy, maternal age at delivery, maternal body weight at delivery and maternal hypertension) showed that umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) were associated with fetal head circumference and femur length in middle gestational diabetes mellitus pregnancy but not in non-gestational diabetes mellitus pregnancy. Head circumference, biparietal diameter, abdominal circumference and femur length in mid gestation were smaller in fetus of gestational diabetes mellitus pregnancy versus non-gestational diabetes mellitus pregnancy. In contrast to non-gestational diabetes mellitus pregnancy in late gestation, umbilical artery Doppler indices in gestational diabetes mellitus pregnancy were not associated with ultrasound measures of fetal growth. Birth weight was slightly increased in gestational diabetes mellitus pregnancy as compared to non-gestational diabetes mellitus pregnancy. Conclusions: The impact of umbilical blood flow on fetal growth is time dependent in human gestational diabetes mellitus and non-gestational diabetes mellitus pregnancy. In gestational diabetes mellitus pregnancy umbilical blood flow is critical for organ development in much earlier stages of pregnancy as compared to non-gestational diabetes mellitus pregnancy. The physiological and molecular pathways why there is a catch up growth in later times of gestational diabetes mellitus pregnancy resulting in larger gestational diabetes mellitus babies at birth needs to be addressed in further studies.
KW  - Umbilical artery Doppler
KW  - Blood flow resistance
KW  - Gestational diabetes mellitus
KW  - Fetal development
Y1  - 2014
U6  - https://doi.org/10.1159/000355815
SN  - 1420-4096
SN  - 1423-0143
VL  - 39
IS  - 4
SP  - 369
EP  - 377
PB  - Karger
CY  - Basel
ER  - 
TY  - GEN
A1  - Lu, Yong-Ping
A1  - Reichetzeder, Christoph
A1  - Prehn, Cornelia
A1  - von Websky, Karoline
A1  - Slowinski, Torsten
A1  - Chen, You-Peng
A1  - Yin, Liang-Hong
A1  - Kleuser, Burkhard
A1  - Yang, Xue-Song
A1  - Adamski, Jerzy
A1  - Hocher, Berthold
T1  - Fetal serum metabolites are independently associated with Gestational diabetes mellitus
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Background/Aims: Gestational diabetes (GDM) might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. Methods: At the time of birth, serum samples from mothers and newborns (cord blood samples) were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. Results: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH) procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32:1 and proline still showed an independent association with GDM. Conclusions: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal serum metabolites and maternal GDM. Our findings might suggest a potential effect of the fetal metabolome on maternal GDM. (c) 2018 The Author(s) Published by S. Karger AG, Basel
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 637 
KW  - Gestational diabetes
KW  - metabolomics
KW  - phosphatidylcholine acyl-alkyl C 32:1
KW  - proline
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-424585
SN  - 1866-8372
IS  - 637
ER  - 
TY  - GEN
A1  - Lu, Yong-Ping
A1  - Reichetzeder, Christoph
A1  - Prehn, Cornelia
A1  - Yin, Liang-Hong
A1  - Yun, Chen
A1  - Zeng, Shufei
A1  - Chu, Chang
A1  - Adamski, Jerzy
A1  - Hocher, Berthold
T1  - Cord blood Lysophosphatidylcholine 16:1 is positively associated with birth weight
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Background/Aims: Impaired birth outcomes, like low birth weight, have consistently been associated with increased disease susceptibility to hypertension in later life. Alterations in the maternal or fetal metabolism might impact on fetal growth and influence birth outcomes. Discerning associations between the maternal and fetal metabolome and surrogate parameters of fetal growth could give new insight into the complex relationship between intrauterine conditions, birth outcomes, and later life disease susceptibility. Methods: Using flow injection tandem mass spectrometry, targeted metabolomics was performed in serum samples obtained from 226 mother/child pairs at delivery. Associations between neonatal birth weight and concentrations of 163 maternal and fetal metabolites were analyzed. Results: After FDR adjustment using the Benjamini-Hochberg procedure lysophosphatidylcholines (LPC) 14:0, 16:1, and 18:1 were strongly positively correlated with birth weight. In a stepwise linear regression model corrected for established confounding factors of birth weight, LPC 16: 1 showed the strongest independent association with birth weight (CI: 93.63 - 168.94; P = 6.94x10(-11)). The association with birth weight was stronger than classical confounding factors such as offspring sex (CI: - 258.81- -61.32; P = 0.002) and maternal smoking during pregnancy (CI: -298.74 - -29.51; P = 0.017). Conclusions: After correction for multiple testing and adjustment for potential confounders, LPC 16:1 showed a very strong and independent association with birth weight. The underlying molecular mechanisms linking fetal LPCs with birth weight need to be addressed in future studies. (c) 2018 The Author(s) Published by S. Karger AG, Basel
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 631 
KW  - metabolomics
KW  - Lysophosphatidylcholine
KW  - birth weight
KW  - DOHaD
KW  - hypertension
KW  - Type 2 Diabetes
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-424566
SN  - 1866-8372
IS  - 631
ER  - 
TY  - JOUR
A1  - Lu, Yong-Ping
A1  - Reichetzeder, Christoph
A1  - Prehn, Cornelia
A1  - Yin, Liang-Hong
A1  - Yun, Chen
A1  - Zeng, Shufei
A1  - Chu, Chang
A1  - Adamski, Jerzy
A1  - Hocher, Berthold
T1  - Cord blood Lysophosphatidylcholine 16:1 is positively associated with birth weight
JF  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology
N2  - Background/Aims: Impaired birth outcomes, like low birth weight, have consistently been associated with increased disease susceptibility to hypertension in later life. Alterations in the maternal or fetal metabolism might impact on fetal growth and influence birth outcomes. Discerning associations between the maternal and fetal metabolome and surrogate parameters of fetal growth could give new insight into the complex relationship between intrauterine conditions, birth outcomes, and later life disease susceptibility. Methods: Using flow injection tandem mass spectrometry, targeted metabolomics was performed in serum samples obtained from 226 mother/child pairs at delivery. Associations between neonatal birth weight and concentrations of 163 maternal and fetal metabolites were analyzed. Results: After FDR adjustment using the Benjamini-Hochberg procedure lysophosphatidylcholines (LPC) 14:0, 16:1, and 18:1 were strongly positively correlated with birth weight. In a stepwise linear regression model corrected for established confounding factors of birth weight, LPC 16: 1 showed the strongest independent association with birth weight (CI: 93.63 - 168.94; P = 6.94x10(-11)). The association with birth weight was stronger than classical confounding factors such as offspring sex (CI: - 258.81- -61.32; P = 0.002) and maternal smoking during pregnancy (CI: -298.74 - -29.51; P = 0.017). Conclusions: After correction for multiple testing and adjustment for potential confounders, LPC 16:1 showed a very strong and independent association with birth weight. The underlying molecular mechanisms linking fetal LPCs with birth weight need to be addressed in future studies. (c) 2018 The Author(s) Published by S. Karger AG, Basel
KW  - Metabolomics
KW  - Lysophosphatidylcholine
KW  - Birth Weight
KW  - DOHaD
KW  - Hypertension
KW  - Type 2 Diabetes
Y1  - 2018
U6  - https://doi.org/10.1159/000487118
SN  - 1015-8987
SN  - 1421-9778
VL  - 45
IS  - 2
SP  - 614
EP  - 624
PB  - Karger
CY  - Basel
ER  -