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Dipti Sarma, Vikram Singh Chauhan, Kandarpa Kumar Saikia, Partha Sarma, Sukanta Nath
Aims: To investigate the association between Vitamin D receptor gene polymorphisms (BsmI, TaqI and FokI) and type 2 diabetes mellitus in patients in north eastern India. Settings and Design: This was a case control study with 40 cases of type 2 diabetes and 20 controls. Materials and Methods: Genomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism (SNPs) of BsmI [rs1544410], TaqI [rs731236] and FokI [rs2228570] by polymerase chain reaction and gene sequencing...
March 2018: Indian Journal of Endocrinology and Metabolism
Liangliang Chen, Junjun Wei, Shuwei Zhang, Zhongguan Lou, Xue Wang, Yu Ren, Honggang Qi, Zhenhua Xie, Yirun Chen, Feng Chen, Qihang Wu, Xiaoxiao Fan, Honglei Xu, Shuaishuai Huang, Guobin Weng
Background: The vitamin D receptor (VDR) plays a key role in vitamin-mediated signaling pathway. Emerging evidence has suggested that the VDR polymorphism may contribute to the risk of prostate cancer (PCa). However, the existing results are not conclusive in Asian population. Methods: We aim to evaluate the potential role of VDR polymorphisms on PCa of Asian population. PubMed, Scopus, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wang Fang Data, and VIP Periodical were retrieved, and eligible studies (case-control or cohort study) meeting the inclusion criteria were evaluated through an updated meta-analysis using Stata13...
2018: OncoTargets and Therapy
Wafaa M Abdel-Rehim, Rasha A El-Tahan, Mennatullah A El-Tarawy, Rowaida R Shehata, Maher A Kamel
Vitamin D3 deficiency was found to be tightly linked to many health problems including metabolic syndrome, cancer, cardiovascular diseases, and type 2 diabetes mellitus. In our study, we tested the possible antidiabetic effects of one of vitamin D3 analogs, alfacalcidol, solely or in a combination with metformin on type 2 diabetic rats. Type 2 diabetic model rats were induced by feeding high-fat diet for 4 weeks followed by intraperitoneal injection of streptozotocin. In addition to the control group, the diabetic rats were divided into four groups: untreated, metformin-treated, alfacalcidol-treated, and combination-treated group (metformin + alfacalcidol) for 4 weeks...
June 16, 2018: Molecular and Cellular Biochemistry
Lishen Shan, Xinyuan Kang, Fen Liu, Xuxu Cai, Xiaohua Han, Yunxiao Shang
Vitamin D receptors (VDRs) are associated with the occurrence and development of asthma. The aim of the present study was to analyze the secondary structure and B‑cell and T‑cell epitopes of VDR using online prediction software and aid in the future development of a highly efficient epitope‑based vaccine against asthma. Blood samples were collected from peripheral blood of asthmatic children. Reverse transcription quantitative‑polymerase chain reaction (RT‑qPCR) was performed to detect the expression of VDR in the peripheral blood...
June 13, 2018: Molecular Medicine Reports
Takao Susa, Masayoshi Iizuka, Hiroko Okinaga, Mimi Tamamori-Adachi, Tomoki Okazaki
Recently, the antiproliferative action of 1,25(OH)2 D3 (1,25D3), an active metabolite of vitamin D3 , in the management of prostate cancer has been argued rigorously. In this study, we found that at a physiological concentration, 25(OH)D3 (25D3), the precursor of 1,25D3 and an inactive form of vitamin D because of its much weaker binding activity to the vitamin D receptor (VDR) compared with 1,25D3, had a gene expression profile similar to that of 1,25D3 in prostate cancer LNCaP cells. By immunocytochemistry, western blotting, and CYP27B1 and/or VDR knockdown by small interfering RNAs, we found that 10-7  M 25D3, which is within its uppermost physiological concentration in the bloodstream, induced VDR nuclear import and robustly activated its target genes in the virtual absence of CYP27B1 expression...
June 13, 2018: Scientific Reports
Mila W Reginatto, Bartira M Pizarro, Roberto A Antunes, Ana C A Mancebo, Luísa Hoffmann, Pâmela Fernandes, Patrícia Areas, Maria I Chiamolera, Rosane Silva, Maria do Carmo Borges de Souza, Enrrico Bloise, Tânia M Ortiga-Carvalho
Purpose: Calcitriol, or 1,25-hydroxycholecalciferol, is the active form of vitamin D. It binds and activates vitamin D receptor (VDR). Infertility and defective folliculogenesis have been observed in female vdr- knockout mice; however, whether VDR polymorphisms affect human ovarian responses to controlled ovarian stimulation (COS) remains unclear. We hypothesized that VDR polymorphisms are associated with infertility and COS responses. Thus, we evaluated the association between the TaqI, BsmI , and FokI VDR polymorphisms and ovarian responses in women undergoing COS...
2018: Frontiers in Endocrinology
Debabrata Mahapatra, Jill A Franzosa, Kyle Roell, Melaine Agnes Kuenemann, Keith A Houck, David M Reif, Denis Fourches, Seth W Kullman
High throughput screening (HTS) programs have demonstrated that the Vitamin D receptor (VDR) is activated and/or antagonized by a wide range of structurally diverse chemicals. In this study, we examined the Tox21 qHTS data set generated against VDR for reproducibility and concordance and elucidated functional insights into VDR-xenobiotic interactions. Twenty-one potential VDR agonists and 19 VDR antagonists were identified from a subset of >400 compounds with putative VDR activity and examined for VDR functionality utilizing select orthogonal assays...
June 11, 2018: Scientific Reports
Maged Saleh, Christoph Welsch, Chengcong Cai, Claudia Döring, Jérôme Gouttenoire, Judith Friedrich, Katrin Haselow, Christoph Sarrazin, Klaus Badenhoop, Darius Moradpour, Stefan Zeuzem, Sabrina Rueschenbaum, Christian M Lange
BACKGROUND AND AIMS: Vitamin D signaling is involved in infectious and non-infectious liver diseases, yet the natural vitamin D metabolites are suboptimal therapeutic agents. In the present study, we therefore aimed to explore the potential and mechanism of selected calcitriol analogs to regulate the hepatocellular transcriptome and to inhibit hepatitis C virus (HCV) in comparison with calcitriol. METHODS: Human hepatoma cell lines and primary human macrophages were stimulated with calcitriol and selected calcitriol analogs...
June 7, 2018: Journal of Steroid Biochemistry and Molecular Biology
Evrett N Thompson, Vibhavari Sail, Daniel S Raccuia, M Kyle Hadden
Calcitriol, vitamin D3 (VD3), and structurally related VD3 analogues are inhibitors of Hh signaling in multiple contexts and are promising anti-cancer agents in Hh-dependent forms of cancer; however, the cellular mechanisms through which these compounds regulate Hh signal transmission are not clearly defined. Previous studies in this area have implicated both Smoothened, a key mediator of Hh signaling, and the vitamin D receptor (VDR) as potential mediators of Hh inhibition for this class of seco-steroids. We have performed a series of in vitro studies to more fully probe the cellular mechanisms that govern seco-steroid-mediated inhibition of Hh signaling...
June 6, 2018: Molecular and Cellular Biochemistry
Carsten Carlberg
The vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] is the exclusive high-affinity ligand of the vitamin D receptor (VDR), a transcription factor with direct effects on gene expression. Transcriptome- and epigenome-wide data obtained in THP-1 human monocytes are the basis of the chromatin model of vitamin D signaling. The model describes, how VDR's spatio-temporal binding profile provides key insight into the pleiotropic action of vitamin D. The transcription of some 300 primary target genes is significantly modulated through the action of genomic VDR binding sites in concert with the pioneer transcription factor PU...
2018: Frontiers in Endocrinology
Selvaraman Nagamani, Chandrasekhar Kesavan, Muthusamy Karthikeyan
Vitamin D3 (1, 25(OH) 2D3) is a biologically active metabolite and plays a wide variety of regulatory functions in human systems. Currently, several Vitamin D analogues have synthesized and tested against VDR (Vitamin D Receptor). Electrostatic potential methods are greatly influenced the structure based drug discovery. In this study, ab inito (DFT, HF, LMP2) and semi-empirical (RM1, AM1, PM3, MNDO, MNDO/d) charges were examined on the basis of their concert in predicting the docking pose using Induced Fit Docking (IFD) and binding free energy calculations against the VDR...
June 6, 2018: Combinatorial Chemistry & High Throughput Screening
Chiara Ricca, Alessia Aillon, Loredana Bergandi, Daniela Alotto, Carlotta Castagnoli, Francesca Silvagno
Vitamin D receptor (VDR) mediates many genomic and non-genomic effects of vitamin D. Recently, the mitochondrial effects of vitamin D have been characterized in many cell types. In this article, we investigated the importance of VDR not only in mitochondrial activity and integrity but also in cell health. The silencing of the receptor in different healthy, non-transformed, and cancer cells initially decreased cell growth and modulated the cell cycle. We demonstrated that, in silenced cells, the increased respiratory activity was associated with elevated reactive oxygen species (ROS) production...
June 5, 2018: International Journal of Molecular Sciences
Fu-Chen Huang, Shun-Chen Huang
Alternative therapies are needed to reduce the use of antibiotics and incidence of drug-resistant Salmonellosis . Previous studies have revealed important roles of statins in regulating innate immunity. Therefore, we investigated the effects of statins on innate immunity in Salmonella -infected intestinal epithelial cells (IECs), which are involved in mucosal innate immunity. SW480 cells and Akt siRNA- or vitamin D receptor (VDR) siRNA-transfected SW480 cells were infected by wild-type S. Typhimurium strain SL1344 in the presence or absence of statins...
June 2, 2018: International Journal of Molecular Sciences
Natalia Jorgelina Prado, Mariana Casarotto, Juan Pablo Calvo, Luciana Mazzei, Amira Zulma Ponce Zumino, Isabel Mercedes García, Fernando Darío Cuello-Carrión, Miguel Walter Fornés, León Ferder, Emiliano Raúl Diez, Walter Manucha
Lethal ventricular arrhythmias increase in patients with chronic kidney disease that suffer an acute coronary event. Chronic kidney disease induces myocardial remodeling, oxidative stress, and arrhythmogenesis. A manifestation of the relationship between kidney and heart is the concomitant reduction in vitamin D receptor (VDR) and the increase in angiotensin II receptor type 1 (AT1 ). Melatonin has renal and cardiac protective actions. One potential mechanism is the increase of the heat shock protein 70 (Hsp70) -an antioxidant factor-...
May 31, 2018: Journal of Pineal Research
Milica Velimirović, Gordana Jevtić Dožudić, Vesna Selaković, Tihomir Stojković, Nela Puškaš, Ivan Zaletel, Milica Živković, Vesna Dragutinović, Tatjana Nikolić, Ankica Jelenković, Djordje Djorović, Aleksandar Mirčić, Nataša D Petronijević
Decreased blood flow in the brain leads to a rapid increase in reactive oxygen species (ROS). NADPH oxidase (NOX) is an enzyme family that has the physiological function to produce ROS. NOX2 and NOX4 overexpression is associated with aggravated ischemic injury, while NOX2/4-deficient mice had reduced stroke size. Dysregulation of matrix metalloproteinases (MMPs) contributes to tissue damage. The active form of vitamin D3 expresses neuroprotective, immunomodulatory, and anti-inflammatory effects in the CNS. The present study examines the effects of the vitamin D3 pretreatment on the oxidative stress parameters and the expression of NOX subunits, MMP9, microglial marker Iba1, and vitamin D receptor (VDR), in the cortex and hippocampus of Mongolian gerbils subjected to ten minutes of global cerebral ischemia, followed by 24 hours of reperfusion...
2018: Oxidative Medicine and Cellular Longevity
Meijin Zhang, Liming Lin, Changsheng Xu, Dajun Chai, Feng Peng, Jinxiu Lin
Background and aim: Upregulation of prolyl isomerase-1 (Pin1) protein expression and activity was associated with the pathogenesis of diabetic vasculopathy through induction of endothelial oxidative stress and inflammation. Moreover, VDR agonist protects against high glucose-induced endothelial apoptosis through the inhibition of oxidative stress. We aimed to explore the effects of the VDR agonist on diabetes-associated endothelial dysfunction and the role of Pin1 in this process. Methods: Streptozocin-induced diabetic mice were randomly treated with vehicle, VDR agonist (10  μ g/kg/d, i...
2018: Oxidative Medicine and Cellular Longevity
Teija Raivisto, AnnaMaria Heikkinen, Leena Kovanen, Hellevi Ruokonen, Kaisa Kettunen, Taina Tervahartiala, Jari Haukka, Timo Sorsa
Background: Dental caries is the most common infection in the world and is influenced by genetic and environmental factors. Environmental factors are largely known, but the role of genetic factors is quite unknown. The aim was to investigate the genetic background of caries in Finnish adolescents. Materials and Methods: This study was carried out at the Kotka Health Center in Eastern Finland. 94 participants aged 15-17 years gave approval for the saliva and DNA analyses...
2018: International Journal of Dentistry
Jeffrey Barminko, Brad M Reinholt, Alexander Emmanuelli, Alannah N Lejeune, Margaret H Baron
The pathways that regulate the growth of erythroid progenitors are incompletely understood. In a computational analysis of gene expression changes during erythroid ontogeny, the vitamin D receptor ( Vdr ) nuclear hormone receptor transcription factor gene was identified in fetal and adult stages, but not at the embryonic stage of development. Vdr was expressed in definitive erythroid (EryD) progenitors and was downregulated during their maturation. Activation of Vdr signaling by the vitamin D3 agonist calcitriol increased the outgrowth of EryD colonies from fetal liver and adult bone marrow, maintained progenitor potential, and delayed erythroid maturation, as revealed by clonogenic assays, suspension culture, cell surface phenotype, and gene expression analyses...
June 12, 2018: Blood Advances
Vanessa Meyer, Liza Bornman
Caudal-type homeobox protein 2 (CDX-2) is an intestine-specific transcription factor (TF), with a polymorphic binding site (Cdx-2, rs11568820, A/G) in the vitamin D receptor gene (VDR). The molecular mechanism underlying Cdx-2 association with conditions like osteoporosis, which depends on intestinal VDR expression and calcium absorption, is believed to be due to higher affinity of CDX-2 for the ancestral A allele compared to the G allele. However, it is unclear why the polymorphism is associated with diseases like tuberculosis, which is dependent on VDR expression in immune cells that do not express CDX-2...
May 28, 2018: Immunogenetics
L Wang, X Chen, Z X Cheng, Z Lian, A D Sun
Objective: To investigate the gene expression and polymorphisms of vitamin D receptor (VDR) in nasopharyngeal carcinoma. Method: The expression of VDR mRNA was detected by fluorescent quantitative PCR in PBMC from 48 patients with nasopharyngeal carcinoma and 48 controls. The FokI and ApaI loci of all subjects were detected by TaqMan-MGB fluorescent probe PCR. Result: The VDR mRNA △Ct value was 9.32±0.91 and 7.31±1.04 in nasopharyngeal carcinoma patients and controls, respectively. Using multivariate Logistic regression analysis, the results showed that the distribution of FokI point Ff genotype in the case group was significantly higher than that in the control group (adjusted OR =1...
December 5, 2017: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
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