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Marissa Penna-Martinez, Natalie Filmann, Dimitra Bogdanou, Firouzeh Shoghi, Sabine Huenecke, Ralf Schubert, Eva Herrmann, Ulrike Koehl, Eystein S Husebye, Klaus Badenhoop
OBJECTIVES: On the basis of the immunomodulatory actions of vitamin D (VD), we investigated the effects of high-dose VD therapy over a 3 mo period on the immune response in patients with Addison's disease (AD). METHODS: This randomized, controlled, crossover trial included 13 patients with AD who received either cholecalciferol (4000 IU/d) for 3 mo followed by 3 mo placebo oil or the sequential alternative placebo followed by verum. Glucocorticoid replacement doses remained stable...
December 2, 2017: Nutrition
Zhanyi Gao, Kaining Liu, Huanxin Meng
BACKGROUND: The vitamin D pathway, from toll-like receptor activation to human cationic antimicrobial protein (hCAP-18/LL-37) generation, has been identified in monocytes and keratinocytes. This study aimed to investigate the vitamin D pathway in human gingival fibroblasts (hGFs) and periodontal ligament cells (hPDLCs) and to provide preliminary evidence of its role in periodontal immune defense. METHODS: Primary cultures of hGFs and hPDLCs were stimulated with 1,25-dihydroxy vitamin D3 and 25-hydroxy vitamin D3 , with or without Porphyromonas gingivalis lipopolysaccharide...
February 18, 2018: Journal of Periodontology
Liping Xiao, Collin Homer-Bouthiette, Marja M Hurley
Mice overexpressing high molecular weight FGF2 isoforms (HMWTg) in osteoblast lineage phenocopy human X-linked hypophosphatemic rickets (XLH) and Hyp murine model of XLH demonstrating increased FGF23/FGF receptor signaling and hypophosphatemic rickets/osteomalacia. Since HMWFGF2 was up-regulated in bones of Hyp mice and abnormal FGF23 signaling is important in XLH, HMWTg mice were used to examine the effect of the FGF23 neutralizing antibody (FGF23Ab). Eight-week-old female Vector control mice and HMWTg mice were treated with FGF23Ab or control IgG...
March 4, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Oussama Lahmar, Mariem Salhi, Wajih Kaabachi, Anissa Berraies, Jamel Ammar, Munawar Hussain Soomro, Martin Larsen, Isabella Annesi-Maesano, Kamel Hamzaoui, Agnes Hamzaoui
INTRODUCTION: Several studies have shown a strong correlation between the serum vitamin D level and asthma severity and deficits in lung function. OBJECTIVE: Study the relationship between vitamin D and the severity of asthma by targeting five SNPs of vitamin D metabolism gene pathway in a Tunisian adult asthmatics population. METHODS: Our case-control study includes 154 adult asthmatic patients and 154 healthy Tunisian subjects. We genotyped many variants in three human genes encoding key components of the vitamin D metabolism, CYP2R1, CYP27B1, GC...
March 3, 2018: Lung
Iveta Bartonkova, Enikoe Kallay, Zdenek Dvorak
The role of vitamin D receptor (VDR) in immune responses has been broadly studied and it has been shown that activated VDR alters the levels of some interleukins (ILs). In this study, we studied the opposite, i.e. whether 13 selected pro-inflammatory and anti-inflammatory ILs influence the transcriptional activity of human VDR. The experimental models of choice were two human stably transfected gene reporter cell lines IZ-VDRE and IZ-CYP24, which were designed to evaluate the transcriptional activity of VDR...
2018: PloS One
Holly P Quach, Tamara Dzekic, Paola Bukuroshi, K Sandy Pang
Vitamin D3 and the synthetic vitamin D analogs, 1α-hydroxyvitamin D3 [1α(OH)D3 ] and 1α-hydroxyvitamin D2 [1α(OH)D2 ], and 25-hydroxyvitamin D3 [25(OH)D3 ] were appraised for their vitamin D receptor (VDR) associated-potencies as cholesterol lowering agents in mice in vivo. These precursors require activation in vivo: 1α(OH)D3 and 1α(OH)D2 are activated by liver Cyp2r1 and Cyp27a1 to active VDR ligands, 1α,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] and 1α,25-dihydroxyvitamin D2 [1,25(OH)2 D2 ], respectively...
February 27, 2018: Biopharmaceutics & Drug Disposition
Sisi Cao, Xiao-Li Dong, Ming-Xian Ho, Wen-Xuan Yu, Ka-Chun Wong, Xin-Sheng Yao, Man-Sau Wong
Oleanolic acid (OA) is a triterpenoid with reported bone anti-resorption activities. The present study aimed to characterize its bone protective effects in vivo and to study its effects on vitamin D metabolism, both in vivo and in vitro. OA significantly increased bone mineral density, improved micro-architectural properties, reduced urinary Ca excretion, increased 1,25(OH)₂D₃ and renal CYP27B1 mRNA expression in mature C57BL/6 ovariectomised (OVX) mice. OA also improved bone properties, Ca balance, and exerted modulatory effects on renal CYP27B1 and CYP24A1 expressions in aged normal female Sprague-Dawley rats...
February 22, 2018: Nutrients
Chunying Gao, Michael Z Liao, Lyrialle W Han, Kenneth E Thummel, Qingcheng Mao
Vitamin D3 is an important prohormone critical for maintaining calcium and phosphate homeostasis in the body and regulating drug-metabolizing enzymes and transporters. 25OHD3 , the most abundant circulating metabolite of vitamin D3 , is further transformed to the biologically active metabolite 1α,25-(OH)2 D3 by CYP27B1 in the kidney and extra-renal tissues, and to non-active metabolites by other CYP enzymes. In addition, 25OHD3 undergoes sulfonation and glucuronidation in the liver, forming two major conjugative metabolites, 25OHD3 -3- O -sulfate (25OHD3 -S) and 25OHD3 -3- O -glucuronide (25OHD3 -G), both of which were detected in human blood and bile...
February 21, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Yingying Wu, Yongbin Zeng, Wennan Wu, Jinpiao Lin, Qishui Ou
BACKGROUND: Host single nucleotide polymorphisms were associated with antiviral therapy in CHB patients. The CYP27B1 gene, encoding 25(OH)D3 -1α hydroxylase, might activate 25(OH)D3 to 1,25(OH)2 D3 in kidney resulted in influencing the efficacy of interferon (IFN). The aim of the study was to investigate the association between CYP27B1 polymorphisms and the response to IFN in HBeAg-positive patients. METHODS: Eighty-seven HBeAg-positive CHB patients infected with HBV genotype B or C were included in the study...
February 18, 2018: Journal of Clinical Laboratory Analysis
Jessica Cusato, Amedeo De Nicolò, Lucio Boglione, Fabio Favata, Alessandra Ariaudo, Simone Mornese Pinna, Chiara Carcieri, Federica Guido, Valeria Avataneo, Giuseppe Cariti, Giovanni Di Perri, Antonio D'Avolio
Vitamin D levels and genetic variants were associated with drug outcome/toxicity and concentrations. The plasma exposure of GS-331007, the main sofosbuvir metabolite, has been related to SVR. We evaluated the impact of polymorphisms in genes (CYP27B1, CYP24A1, VDBP and VDR) related to vitamin D pathway on sofosbuvir and GS-331007 plasma levels in HCV mono-infected patients at one month of treatment. Polymorphisms were investigated through real-time PCR; drug plasma quantification was performed through a UHPLC-MS/MS method...
February 13, 2018: Infection, Genetics and Evolution
Katharyn M Baca, Manika Govil, Joseph M Zmuda, Hyagriv N Simhan, Mary L Marazita, Lisa M Bodnar
Allelic variants in vitamin D metabolism genes may increase the risk of preeclampsia, but few studies have systematically tested this hypothesis. Our objective was to evaluate the relationship between maternal allelic variants in three vitamin D metabolism genes and risk of preeclampsia. Samples were from two case-control studies of pregnant women who delivered in Pittsburgh, PA from 1999 to 2010 and twelve recruiting sites across the United States from 1959 to 1965. Single-nucleotide polymorphisms (SNPs) were genotyped 50 kilobases up- and down-stream in three genes (VDR, GC, and CYP27B1) in the samples from both studies, for a total of 744 preeclampsia cases and 2411 controls...
January 2018: Physiological Reports
Ryouhei Yoshikawa, Hironori Yamamoto, Otoki Nakahashi, Tomohiro Kagawa, Mari Tajiri, Mari Nakao, Shiori Fukuda, Hidekazu Arai, Masashi Masuda, Masayuki Iwano, Eiji Takeda, Yutaka Taketani
In this study, we investigated the relationship between age-related changes in renal α-Klotho gene expression, vitamin D metabolism and the responsiveness of dietary phosphate in 1, 2 and 13 month-old mice fed a high phosphate (phosphate 1.2%) diet or low phosphate (phosphate 0.02%) diet for 5 days. We found that 1,25-dihydroxyvitamin D levels in plasma were significantly lower in the high phosphate group than the low phosphate group for 1 and 2 month-old mice, but not 13 month-old mice. In addition, in the high phosphate group plasma 1,25-dihydroxyvitamin D levels were decreased in 2 month-old mice relative to 1 month-old mice, but 13 month-old mice had higher levels than 2 month-old mice...
January 2018: Journal of Clinical Biochemistry and Nutrition
Zongtao Lin, Srinivasa R Marepally, Emily S Y Goh, Chloe Y S Cheng, Zorica Janjetovic, Tae-Kang Kim, Duane D Miller, Arnold E Postlethwaite, Andrzej T Slominski, Robert C Tuckey, Carole Peluso-Iltis, Natacha Rochel, Wei Li
20S-hydroxyvitamin D3 [20S(OH)D3] is anti-inflammatory and not hypercalcemic, suggesting its potential as a lead compound. In this study, side chain modified 20S(OH)D3 analogs (4, 13, 23 and 33) together with their 1α-OH derivatives were synthesized and their metabolism and biological activities tested. 4, 13 and 23 are good substrates for CYP27B1, enabling enzymatic synthesis of their 1α-OH derivatives 5, 14 and 24. However, 33 could not be hydroxylated by CYP27B1 and acts as an inhibitor. All analogs were poorer substrates for CYP24A1 than calcitriol, indicating improved catabolic stability...
January 24, 2018: Scientific Reports
Jessica Cusato, Lucio Boglione, Amedeo De Nicolò, Fabio Favata, Alessandra Ariaudo, Simone Mornese Pinna, Federica Guido, Valeria Avataneo, Marco Cantù, Chiara Carcieri, Giuseppe Cariti, Giovanni Di Perri, Antonio D'Avolio
PURPOSE: Since HCV infection may lead to hepatocellular carcinoma (HCC) and vitamin D (deficiency) is related to cancer, we investigated if SNPs in genes involved in vitamin D pathway could predict HCV-related HCC presence in patients treated with new anti-HCV drugs. METHODS: Patients with chronic hepatitis C and treated with direct-acting antivirals were enrolled. SNPs in VDR, CYP27B1, CYP24A1 and GC genes were assessed through real-time PCR. 258 patients were analyzed...
January 22, 2018: Cancer Chemotherapy and Pharmacology
Jessica Lopes Nobre, Patricia Cristina Lisboa, Janaine Cavalcanti Carvalho, Mariana Renovato Martins, Simone Vargas, Cristina Barja-Fidalgo, Egberto Gaspar de Moura, Elaine de Oliveira
Recently, we demonstrated high serum leptin and 25(OH)D (calcidiol) in obese animals, with high C/EBPβ and PPARγ expression in adipose tissue. Since the role of vitamin D in adipogenesis remains controversial and hyperleptinemia is found in obesity, we asked if leptin could interfere in vitamin D action on adipocytes. Here, we studied the direct effect of these two hormones upon 3T3L1 preadipocytes incubated with or without 1,25(OH)2D (100 nM, 24 h) and with leptin (10-7M, 4 h later). RT-PCR (VDR and Cyp27b1/1α-hydroxylase), western blotting (VDR, Cyp27b1/1α-hydroxylase, ObR-b, C/EBPβ, PPARγ and Bax content), a cell proliferation assay and an Annexin V-FITC binding assay were performed...
January 12, 2018: General and Comparative Endocrinology
Xiaolei Yao, M A Ei-Samahy, Hua Yang, Xu Feng, Fengzhe Li, Fanxing Meng, Haitao Nie, Feng Wang
The cellular response to 1,25-dihydroxyvitamin D3 (Vit D3; biologically active form of Vitamin D) is complex and depends not only on Vitamin D receptor (VDR) expression but also on cellular uptake of circulating Vit D3 and the presence and activity of Vitamin D-metabolizing enzyme. This study evaluated the expression of VDR and Vitamin D-metabolizing enzymes in the ram reproductive tract at different developmental stages and in spermatozoa. Nearly all cell types in the testes and epithelial cells of the caput, corpus, and cauda expressed VDR, CYP27B1, and CYP24A1 proteins...
January 10, 2018: Animal Reproduction Science
Corwin D Nelson, Kathryn E Merriman, Michael B Poindexter, Mercedes F Kweh, Leslie P Blakely
The bovine innate immune system has a strong repertoire of antimicrobial defenses to rapidly attack infectious pathogens that evade physical barriers of the udder. Exploration of the intracrine vitamin D pathway of bovine macrophages has improved understanding of the signals that initiate antimicrobial defenses that protect the udder. In the intracrine vitamin D pathway, pathogen recognition receptors upregulate CYP27B1 mRNA that encodes for the enzyme that converts 25-hydroxyvitamin D [25(OH)D3] to the active vitamin D hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]...
December 28, 2017: Journal of Dairy Science
Nan Ge, Xiu-Mei Chu, Yun-Peng Xuan, Dun-Qiang Ren, Yongjie Wang, Kai Ma, Hui-Jiang Gao, Wen-Jie Jiao
Lung cancer is a type of malignant tumor derived from the respiratory system, which is the leading cause of cancer-associated mortality worldwide, of which ~80% of cases are attributable to non-small cell lung cancer (NSCLC). A previous study demonstrated that 1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3), derived from the vitamin D metabolic pathway contributes an antitumor effect. Aberrant expression of the essential enzyme encoding genes, Cytochrome P450 Family 27 Subfamily A Member 1 (CYP27A1), Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1), and Cytochrome P450 Family 24 Subfamily A Member 1 (CYP24A1) may be associated with lung cancer...
December 2017: Oncology Letters
Xiaowen Lu, Zhong Chen, Namratha Mylarapu, Mitchell A Watsky
This study investigated the effects of 1,25(OH)2 D3 and 24R,25(OH)2 D3 on corneal epithelial cell proliferation, migration, and on the vitamin D activating enzyme CYP27B1 (produces 1,25(OH)2 D3) and inactivating enzyme CYP24A1 (produces 24R,25(OH)2 D3). The role of the vitamin D receptor (VDR) was also examined. In VDR wildtype mouse corneal epithelial cells (WT), 1,25(OH)2 D3 increased CYP24A1 protein expression and decreased CYP27B1 expression. In VDR knockout mouse epithelial cells (KO), 1,25(OH)2 D3 increased CYP24A1 and CYP27B1 protein expression...
December 5, 2017: Scientific Reports
Martin D Berger, Sebastian Stintzing, Volker Heinemann, Shu Cao, Dongyun Yang, Yu Sunakawa, Satoshi Matsusaka, Yan Ning, Satoshi Okazaki, Yuji Miyamoto, Mitsukuni Suenaga, Marta Schirripa, Diana L Hanna, Shivani Soni, Alberto Puccini, Wu Zhang, Chiara Cremolini, Alfredo Falcone, Fotios Loupakis, Heinz-Josef Lenz
Purpose: Vitamin D exerts its inhibitory influence on colon cancer growth by inhibiting Wnt signaling and angiogenesis. We hypothesized that SNPs in genes involved in vitamin D transport, metabolism, and signaling are associated with outcome in metastatic colorectal cancer (mCRC) patients treated with first-line FOLFIRI and bevacizumab. Experimental Design: 522 mCRC patients enrolled in the FIRE-3 (discovery cohort) and TRIBE (validation set) trials treated with FOLFIRI/bevacizumab were included in this study...
February 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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