@article{TsuprykovChenHocheretal.2018,
  author    = {Tsuprykov, Oleg and Chen, Xin and Hocher, Carl-Friedrich and Skoblo, Roman and Yin, Lianghong and Hocher, Berthold},
  title     = {Why should we measure free 25(OH) vitamin D?},
  series = {The Journal of Steroid Biochemistry and Molecular Biology},
  volume    = {180},
  journal   = {The Journal of Steroid Biochemistry and Molecular Biology},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0960-0760},
  doi       = {10.1016/j.jsbmb.2017.11.014},
  pages     = {87 -- 104},
  year      = {2018},
  abstract  = {Vitamin D, either in its D-2 or D-3 form, is essential for normal human development during intrauterine life, kidney function and bone health. Vitamin D deficiency has also been linked to cancer development and some auto immune diseases. Given this huge impact of vitamin Don human health, it is important for daily clinical practice and clinical research to have reliable tools to judge on the vitamin D status. The major circulating form of vitamin D is 25-hydroxyvitamin D (25(OH)D), although it is not the most active metabolite, the concentrations of total 25-hydroxyvitamin D in the serum are currently routinely used in clinical practice to assess vitamin D status. In the circulation, vitamin D - like other steroid hormones - is bound tightly to a special carrier - vitamin D-binding protein (DBP). Smaller amounts are bound to blood proteins - albumin and lipoproteins. Only very tiny amounts of the total vitamin D are free and potentially biologically active. Currently used vitamin D assays do not distinguish between the three forms of vitamin D - DBP-bound vitamin D, albumin-bound vitamin D and free, biologically active vitamin D. Diseases or conditions that affect the synthesis of DBP or albumin thus have a huge impact on the amount of circulating total vitamin D. DBP and albumin are synthesized in the liver, hence all patients with an impairment of liver function have alterations in their total vitamin D blood concentrations, while free vitamin D levels remain mostly constant. Sex steroids, in particular estrogens, stimulate the synthesis of DBP. This explains why total vitamin D concentrations are higher during pregnancy as compared to nonpregnant women, while the concentrations of free vitamin D remain similar in both groups of women. The vitamin D-DBP as well as vitamin D-albumin complexes are filtered through the glomeruli and re-uptaken by megalin in the proximal tubule. Therefore, all acute and chronic kidney diseases that are characterized by a tubular damage, are associated with a loss of vitamin D-DBP complexes in the urine. Finally, the gene encoding DBP protein is highly polymorphic in different human racial groups. In the current review, we will discuss how liver function, estrogens, kidney function and the genetic background might influence total circulating vitamin D levels and will discuss what vitamin D metabolite is more appropriate to measure under these conditions: free vitamin D or total vitamin D.},
  language  = {en}
}
@article{LuoChenZengetal.2018,
  author    = {Luo, Ting and Chen, Xiaoyi and Zeng, Shufei and Guan, Baozhang and Hu, Bo and Meng, Yu and Liu, Fanna and Wong, Taksui and Lu, Yongpin and Yun, Chen and Hocher, Berthold and Yin, Lianghong},
  title     = {Bioinformatic identification of key genes and analysis of prognostic values in clear cell renal cell carcinoma},
  series = {Oncology Letters},
  volume    = {16},
  journal   = {Oncology Letters},
  number    = {2},
  publisher = {Spandidos publ LTD},
  address   = {Athens},
  issn      = {1792-1074},
  doi       = {10.3892/ol.2018.8842},
  pages     = {1747 -- 1757},
  year      = {2018},
  abstract  = {The present study aimed to identify new key genes as potential biomarkers for the diagnosis, prognosis or targeted therapy of clear cell renal cell carcinoma (ccRCC). Three expression profiles (GSE36895, GSE46699 and GSE71963) were collected from Gene Expression Omnibus. GEO2R was used to identify differentially expressed genes (DEGs) in ccRCC tissues and normal samples. The Database for Annotation, Visualization and Integrated Discovery was utilized for functional and pathway enrichment analysis. STRING v10.5 and Molecular Complex Detection were used for protein-protein interaction (PPI) network construction and module analysis, respectively. Regulation network analyses were performed with the WebGestal tool. UALCAN web-portal was used for expression validation and survival analysis of hub genes in ccRCC patients from The Cancer Genome Atlas (TCGA). A total of 65 up- and 164 downregulated genes were identified as DEGs. DEGs were enriched with functional terms and pathways compactly related to ccRCC pathogenesis. Seventeen hub genes and one significant module were filtered out and selected from the PPI network. The differential expression of hub genes was verified in TCGA patients. Kaplan-Meier plot showed that high mRNA expression of enolase 2 (ENO2) was associated with short overall survival in ccRCC patients (P=0.023). High mRNA expression of cyclin D1 (CCND1) (P<0.001), fms related tyrosine kinase 1 (FLT1) (P=0.004), plasminogen (PLG) (P<0.001) and von Willebrand factor (VWF) (P=0.008) appeared to serve as favorable factors in survival. These findings indicate that the DEGs may be key genes in ccRCC pathogenesis and five genes, including ENO2, CCND1, PLT1, PLG and VWF, may serve as potential prognostic biomarkers in ccRCC.},
  language  = {en}
}
@article{LuReichetzederPrehnetal.2018,
  author    = {Lu, Yong-Ping and Reichetzeder, Christoph and Prehn, Cornelia and von Websky, Karoline and Slowinski, Torsten and Chen, You-Peng and Yin, Liang-Hong and Kleuser, Burkhard and Yang, Xue-Song and Adamski, Jerzy and Hocher, Berthold},
  title     = {Fetal serum metabolites are independently associated with Gestational diabetes mellitus},
  series = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology},
  volume    = {45},
  journal   = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology},
  number    = {2},
  publisher = {Karger},
  address   = {Basel},
  issn      = {1015-8987},
  doi       = {10.1159/000487119},
  pages     = {625 -- 638},
  year      = {2018},
  abstract  = {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},
  language  = {en}
}
@misc{HocherYin2017,
  author    = {Hocher, Berthold and Yin, Lianghong},
  title     = {Why Current PTH Assays Mislead Clinical Decision Making in Patients with Secondary Hyperparathyroidism},
  series = {Nephron},
  volume    = {136},
  journal   = {Nephron},
  number    = {2},
  publisher = {Karger},
  address   = {Basel},
  issn      = {1660-8151},
  doi       = {10.1159/000455289},
  pages     = {137 -- 142},
  year      = {2017},
  abstract  = {Preclinical studies in cell culture systems as well as in whole animal chronic kidney disease (CKD) models showed that parathyroid hormone (PTH), oxidized at the 2 methionine residues (positions 8 and 18), caused a loss of function. This was so far not considered in the development of PTH assays used in current clinical practice. Patients with advanced CKD are subject to oxidative stress, and plasma proteins (including PTH) are targets for oxidants. In patients with CKD, a considerable but variable fraction (about 70 to 90\%) of measured PTH appears to be oxidized. Oxidized PTH (oxPTH) does not interact with the PTH receptor resulting in loss of biological activity. Currently used intact PTH (iPTH) assays detect both oxidized and non-oxPTH (n-oxPTH). Clinical studies demonstrated that bioactive, n-oxPTH, but not iPTH nor oxPTH, is associated with mortality in CKD patients.},
  language  = {en}
}
@misc{LuReichetzederPrehnetal.2018,
  author    = {Lu, Yong-Ping and Reichetzeder, Christoph and Prehn, Cornelia and von Websky, Karoline and Slowinski, Torsten and Chen, You-Peng and Yin, Liang-Hong and Kleuser, Burkhard and Yang, Xue-Song and Adamski, Jerzy and Hocher, Berthold},
  title     = {Fetal serum metabolites are independently associated with Gestational diabetes mellitus},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {637},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-42458},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-424585},
  pages     = {14},
  year      = {2018},
  abstract  = {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},
  language  = {en}
}
@misc{LuReichetzederPrehnetal.2018,
  author    = {Lu, Yong-Ping and Reichetzeder, Christoph and Prehn, Cornelia and Yin, Liang-Hong and Yun, Chen and Zeng, Shufei and Chu, Chang and Adamski, Jerzy and Hocher, Berthold},
  title     = {Cord blood Lysophosphatidylcholine 16:1 is positively associated with birth weight},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {631},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-42456},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-424566},
  pages     = {11},
  year      = {2018},
  abstract  = {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},
  language  = {en}
}
@article{LuReichetzederPrehnetal.2018,
  author    = {Lu, Yong-Ping and Reichetzeder, Christoph and Prehn, Cornelia and Yin, Liang-Hong and Yun, Chen and Zeng, Shufei and Chu, Chang and Adamski, Jerzy and Hocher, Berthold},
  title     = {Cord blood Lysophosphatidylcholine 16:1 is positively associated with birth weight},
  series = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology},
  volume    = {45},
  journal   = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology},
  number    = {2},
  publisher = {Karger},
  address   = {Basel},
  issn      = {1015-8987},
  doi       = {10.1159/000487118},
  pages     = {614 -- 624},
  year      = {2018},
  abstract  = {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},
  language  = {en}
}