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Bassem Refaat, Jawwad Ahmad, Shakir Idris, Fadi Fayez Kamfar, Ahmed Mohamed Ashshi, Sarah Abdullah Batwa, Faizah Ahmed Malibary
This is a prospective observational study that measures the expression of vitamin D (VD) metabolising and signalling molecules and Ca(2+) sensing receptor (CaSR) in human Fallopian tube (FT) during the menstrual cycle and ectopic pregnancy (EP). Fresh FTs were obtained during total abdominal hysterectomy at the follicular (n = 16) and midluteal (n = 16) phases. Specimens from remote and implantation sites as well as trophoblastic tissues were also freshly collected from each FT with EP (n = 10)...
October 22, 2016: Cell and Tissue Research
Hiroko Mataki, Naohiko Seki, Keiko Mizuno, Nijiro Nohata, Kazuto Kamikawaji, Tomohiro Kumamoto, Keiichi Koshizuka, Yusuke Goto, Hiromasa Inoue
Patients with lung adenocarcinoma may benefit from recently developed molecular targeted therapies. However, analogous advanced treatments are not available for patients with lung squamous cell carcinoma (lung SCC). The survival rate of patients with the advanced stage of lung SCC remains poor. Exploration of novel lung SCC oncogenic pathways might lead to new treatment protocols for the disease. Based on this concept, we have identified microRNA- (miRNA) mediated oncogenic pathways in lung SCC. It is well known that miR-145-5p (the guide strand) functions as a tumor suppressor in several types of cancer...
September 27, 2016: Oncotarget
Xin Gu, Bingjie Gu, Xianhui Lv, Zhenzhen Yu, Rong Wang, Xiaoli Zhou, Wanxin Qiao, Zhiyuan Mao, Guoping Zuo, Qing Li, Dengshun Miao, Jianliang Jin
Impaired apoptosis of fibroblast-like synoviocytes (FLSs) causes synovial hyperplasia, facilitating destruction of cartilage and bone in rheumatoid arthritis (RA). Tumor necrosis factor (TNF)-α, a dominant inflammatory mediator in RA pathogenesis, promotes progression of RA symptoms. Prevalence of 1, 25-dihydroxy-vitamin D3 (hereafter termed VD) deficiency is 30-63% in patients with RA. Whether VD leads to apoptosis or enhances TNF-α-mediated apoptosis in FLSs to ameliorate RA is unclear. To determine this, 10-week-old CYP27B1-deficient (CYP27B1(-/-)) mice with collagen-induced arthritis (CIA) were intraperitoneally treated with 1 μg/kg VD every other day for 9 weeks...
October 20, 2016: Cell Death & Disease
Ma'an Abdullah Al-Barry, Alia M Albalawi, Mohammed Abu Sayf, Abdulrahman Badawi, Sibtain Afzal, Muhammad Latif, Mohammed I Samman, Sulman Basit
BACKGROUND: VKH is a rare autoimmune disease. Decreased level of vitamin D has recently been found to be involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. This study was designed to screen the vitamin D pathway genes for pathogenic mutations, if any, in VKH patients. METHODS: Genomic DNA was extracted from blood samples collected from patients with VKH disease and healthy controls. Entire coding region, exon-intron junctions of four genes were sequenced in DNA from 39 Saudi VKH patients and 50 ethnically matched healthy individuals...
October 4, 2016: BMC Ophthalmology
Mauricio Cortes, Michael J Chen, David L Stachura, Sarah Y Liu, Wanda Kwan, Francis Wright, Linda T Vo, Lindsay N Theodore, Virginie Esain, Isaura M Frost, Thorsten M Schlaeger, Wolfram Goessling, George Q Daley, Trista E North
Vitamin D insufficiency is a worldwide epidemic affecting billions of individuals, including pregnant women and children. Despite its high incidence, the impact of active vitamin D3 (1,25(OH)D3) on embryonic development beyond osteo-regulation remains largely undefined. Here, we demonstrate that 1,25(OH)D3 availability modulates zebrafish hematopoietic stem and progenitor cell (HSPC) production. Loss of Cyp27b1-mediated biosynthesis or vitamin D receptor (VDR) function by gene knockdown resulted in significantly reduced runx1 expression and Flk1(+)cMyb(+) HSPC numbers...
October 4, 2016: Cell Reports
Andrzej T Slominski, Tae-Kang Kim, Judith V Hobrath, Allen S W Oak, Edith K Y Tang, Elaine W Tieu, Wei Li, Robert C Tuckey, Anton M Jetten
The classical pathway of vitamin D activation follows the sequence D3→25(OH)D3→1,25(OH)2D3 with the final product acting on the receptor for vitamin D (VDR). An alternative pathway can be started by the action of CYP11A1 on the side chain of D3, primarily producing 20(OH)D3, 22(OH)D3, 20,23(OH)2D3, 20,22(OH)2D3 and 17,20,23(OH)3D3. Some of these metabolites are hydroxylated by CYP27B1 at C1α, by CYP24A1 at C24 and C25, and by CYP27A1 at C25 and C26. The products of these pathways are biologically active...
September 28, 2016: Journal of Steroid Biochemistry and Molecular Biology
E Gaffney-Stomberg, L J Lutz, A Shcherbina, D O Ricke, M Petrovick, T L Cropper, S J Cable, J P McClung
Initial military training (IMT) is associated with increased stress fracture risk. In prior studies, supplemental calcium (Ca) and vitamin D provided daily throughout IMT reduced stress fracture incidence, suppressed PTH, and improved measures of bone health compared to placebo. Data were analyzed from a randomized, double-blind, placebo-controlled trial to determine whether SNPs in Ca and vitamin D related genes were associated with circulating biomarkers of bone metabolism in young adults entering IMT, and whether responses to Ca and vitamin D supplementation were modulated by genotype...
September 28, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Xiayu Wu, Jiaoni Cheng, Kaiyun Yang
Epidemiological studies regarding the relationship between vitamin D, genetic polymorphisms in the vitamin D metabolism, cigarette smoke and non-small cell lung cancer (NSCLC) risk have not been investigated comprehensively. To search for additional evidence, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and radioimmunoassay method were utilized to evaluate 5 single-nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR), 6 SNPs in 24-hydroxylase (CYP24A1), 2 SNPs in 1α-hydroxylase (CYP27B1) and 2 SNPs in vitamin D-binding protein (group-specific component, GC) and plasma vitamin D levels in 426 NSCLC cases and 445 controls from China...
2016: International Journal of Molecular Sciences
Daniel D Bikle
The vitamin D receptor (VDR) is found in nearly all, if not all, cells in the body. The enzyme that produces the active metabolite of vitamin D and ligand for VDR, namely CYP27B1, likewise is widely expressed in many cells of the body. These observations indicate that the role of vitamin D is not limited to regulation of bone and mineral homeostasis, as important as that is. Rather, the study of its extraskeletal actions has become the major driving force behind the significant increase in research articles on vitamin D published over the past several decades...
July 2016: Annals of the New York Academy of Sciences
Janice García-Quiroz, Rocío García-Becerra, Galia Lara-Sotelo, Euclides Avila, Sofía López, Nancy Santos-Martínez, Ali Halhali, David Ordaz-Rosado, David Barrera, Andrea Olmos-Ortiz, María J Ibarra-Sánchez, José Esparza-López, Fernando Larrea, Lorenza Díaz
Factors affecting vitamin D metabolism may preclude anti-carcinogenic effects of its active metabolite calcitriol. Chronic ethanol consumption is an etiological factor for breast cancer that affects vitamin D metabolism; however, the mechanisms underlying this causal association have not been fully clarified. Using a murine model, we examined the effects of chronic moderate ethanol intake on tumoral and renal CYP27B1 and CYP24A1 gene expression, the enzymes involved in calcitriol synthesis and inactivation, respectively...
September 14, 2016: Journal of Steroid Biochemistry and Molecular Biology
Aiwu Shi, Juan Wen, Guangquan Liu, Heng Liu, Ziyi Fu, Jing Zhou, Yao Zhu, Yaoqiu Liu, Xirong Guo, Jianguo Xu
Vitamin D (VD) deficiency during pregnancy has been repeatedly linked to an increased gestational diabetes mellitus (GDM) risk. We sought to determine the influences of genetic variants in vitamin D signaling pathways on the risk of GDM. In this study, we genotyped 15 single nucleotide polymorphisms (SNPs) within 8 representative genes (CYP27A1, CYP27B1, CYP24A1, VDR, RXRA, RXRB, RXRG and GC) of the vitamin D signaling pathways in a case-control study with 964 GDM cases and 1,021 controls using the Sequenom MassARRAY iPLEX platform...
September 12, 2016: Oncotarget
Sara Azarpeykan, Keren E Dittmer, Jonathan C Marshall, Kalyani C Perera, Erica K Gee, Els Acke, Keith G Thompson
The aim of this study was to determine the relative abundance and relationship of vitamin D responsive and calcium transporting transcripts (TRPV5, TRPV6, calD9k, calD28k, PMCA, NCX1, CYP27B1, CYP24A1, and VDR) in ovine, canine and, equine kidney using quantitative real-time PCR (RT-qPCR), and then perform a comparison between the three species. Renal tissue samples were harvested post-mortem from 10 horses, 10 sheep, and five dogs. Primers were designed for each gene. For each sample total RNA was extracted, cDNA synthesised, and RT-qPCR was performed...
2016: PloS One
Jenna M Christensen, Jasmine Cheng, Peter Earls, Jenny Gunton, William Sewell, Raymond Sacks, Richard J Harvey
BACKGROUND: Vitamin D deficiency is associated with many inflammatory respiratory disease states. However, serum vitamin D concentrations may not reflect tissue-specific availability. In this study we sought to assess the local expression of genes essential in vitamin D regulation in chronic rhinosinusitis (CRS). METHODS: A cross-sectional study of adult patients undergoing endoscopic sinus surgery was performed. Patients were defined as having CRS with polyps (CRSwNP) or without polyps (CRSsNP), or normal sinus mucosa...
September 12, 2016: International Forum of Allergy & Rhinology
Peter J Tebben, Ravinder J Singh, Rajiv Kumar
Hypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D...
October 2016: Endocrine Reviews
Olivia B Yu, Leggy A Arnold
Calcitroic acid was isolated and characterized almost four decades ago, but little is known about this important vitamin D metabolite. Four reported synthetic strategies to generate calcitroic acid are presented that highlight the scientific progress in the field of chemistry directed to vitamin D analog synthesis. The most recent synthesis described the generation of calcitroic acid with an overall yield of 12.8% in 13 steps. The endogenous formation of calcitroic acid has been demonstrated in perfused rat kidney using 24,25,26,27-tetranor-1,23(OH)2D3...
October 21, 2016: ACS Chemical Biology
Susana Cubillos, Johannes Norgauer
Psoriasis is an inflammatory skin disease with or without joint involvement. In this disease, the thickened epidermis and impaired barrier are associated with altered calcium gradients. Calcium and vitamin D are known to play important roles in keratinocyte differentiation and bone metabolism. Intracellular calcium is regulated by calcium-sensing receptor (CASR), calcium release-activated calcium modulator (ORAI) and stromal interaction molecule (STIM). Other proteins modulated by vitamin D play important roles in calcium regulation e...
October 2016: International Journal of Molecular Medicine
Loan Nguyen-Yamamoto, Andrew C Karaplis, Rene St-Arnaud, David Goltzman
Circulating levels of fibroblast growth factor 23 (FGF23) increase during the early stages of kidney disease, but the underlying mechanism remains incompletely characterized. We investigated the role of vitamin D metabolites in regulating intact FGF23 production in genetically modified mice without and with adenine-induced uremia. Exogenous calcitriol (1,25-dihydroxyvitamin D) and high circulating levels of calcidiol (25-hydroxyvitamin D) each increased serum FGF23 levels in wild-type mice and in mice with global deficiency of the Cyp27b1 gene encoding 25-hydroxyvitamin D 1-α-hydroxylase, which produces 1,25-hydroxyvitamin D...
August 17, 2016: Journal of the American Society of Nephrology: JASN
Yovani Llamas Valle, Sami G Almalki, Devendra K Agrawal
BACKGROUND: Vitamin D, a hormone once thought to have a role limited to calcium homeostasis and bone mineralization, has pleiotropic effects on different types of cells. Vitamin D receptors are reported in vascular smooth muscle cells, endothelial cells, and cardiomyocytes. Adipose-derived MSCs (ADMSCs) are multipotent cells with the capacity to differentiate into cells of different lineages. To our knowledge, the presence of vitamin D machinery on porcine ADMSCs has not yet been examined...
2016: Stem Cell Research & Therapy
Kun-Chun Chiang, Chun-Nan Yeh, Cheng-Cheng Huang, Ta-Sen Yeh, Jong-Hwei S Pang, Jun-Te Hsu, Li-Wei Chen, Sheng-Fong Kuo, Atsushi Kittaka, Tai C Chen, Horng-Heng Juang
Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1α,25(OH)₂D₃, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1α,25(OH)₂D₃, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1α,25(OH)₂D₃ has been found in some cancer cells with CYP27B1 expression...
2016: International Journal of Molecular Sciences
Franz J J Rieder, Charlotte Gröschel, Marie-Theres Kastner, Karin Kosulin, Johannes Laengle, Rene Zadnikar, Rodrig Marculescu, Martina Schneider, Thomas Lion, Michael Bergmann, Enikö Kallay, Christoph Steininger
Vitamin D (VD) is essential for the human body and involved in a wide variety of critical physiological processes including bone, muscle, and cardiovascular health, as well as innate immunity and antimicrobial responses. Here, we elucidated the significance of the VD system in cytomegalovirus (CMV) infection, which is one of the most common opportunistic infections in immunocompromised or -suppressed patients. We found that expression of vitamin D receptor (VDR) was downregulated in CMV-infected cells within 12hours [hrs] post infection [p...
August 9, 2016: Journal of Steroid Biochemistry and Molecular Biology
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