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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
Amber A Bokhari, Laura R Lee, Dewayne Raboteau, Jane Turbov, Isabel V Rodriguez, J Wesley Pike, Chad A Hamilton, G Larry Maxwell, Gustavo C Rodriguez, Viqar Syed
Here, we evaluated the expression of CYP24A1, a protein that inactivates vitamin D in tissues. CYP24A1 expression was increased in advanced-stage endometrial tumors compared to normal tissues. Similarly, endometrial cancer cells expressed higher levels of CYP24A1 than immortalized endometrial epithelial cells. RT-PCR and Western blotting were used to examine CYP24A1 mRNA and protein levels in endometrial cancer cells after 8, 24, 72, and 120 h of exposure to progesterone, progestin derivatives and calcitriol, either alone or in combination...
October 18, 2016: Oncotarget
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
Ida Marie Boisen, Lasse Bøllehuus Hansen, Li Juel Mortensen, Beate Lanske, Anders Juul, Martin Blomberg Jensen
Vitamin D is a versatile signaling molecule with an established role in the regulation of calcium homeostasis and bone health. In recent years the spectrum of vitamin D target organs has expanded and a reproductive role is supported by the presence of the vitamin D receptor (VDR) and the vitamin D metabolizing enzymes in the gonads, reproductive tract, and human spermatozoa. Interestingly, expression levels of VDR and the vitamin D inactivating enzyme CYP24A1 in human spermatozoa serve as positive predictive markers of semen quality and are higher expressed in spermatozoa from normal than infertile men...
September 28, 2016: Journal of Steroid Biochemistry and Molecular Biology
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
Stuart M Sprague, Paul W Crawford, Joel Z Melnick, Stephen A Strugnell, Shaukat Ali, Roberto Mangoo-Karim, Sungchun Lee, P Martin Petkovich, Charles W Bishop
BACKGROUND/AIMS: Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23. METHODS: Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites...
September 28, 2016: American Journal of Nephrology
Rui Zhou, Juw Won Park, Rene F Chun, Thomas S Lisse, Alejandro J Garcia, Kathryn Zavala, Jessica L Sea, Zhi-Xiang Lu, Jianzhong Xu, Yi Xing, John S Adams, Martin Hewison
Traditionally recognized as an RNA splicing regulator, heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC1/C2) can also bind to double-stranded DNA and function in trans as a vitamin D response element (VDRE)-binding protein. As such, hnRNPC1/C2 may couple transcription induced by the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) with subsequent RNA splicing. In MG63 osteoblastic cells, increased expression of the 1,25(OH)2D target gene CYP24A1 involved immunoprecipitation of hnRNPC1/C2 with CYP24A1 chromatin and RNA...
September 26, 2016: Nucleic Acids 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
Pietro Manuel Ferraro, Angelo Minucci, Aniello Primiano, Elisa De Paolis, Jacopo Gervasoni, Silvia Persichilli, Alessandro Naticchia, Ettore Capoluongo, Giovanni Gambaro
Mutations of the CYP24A1 gene, encoding for the enzyme 25(OH)D-24-hydroxylase, can cause hypercalcemia, hypercalciuria, nephrolithiasis and nephrocalcinosis. We report the case of a 22-year-old male patient with recurrent nephrolithiasis, nephrocalcinosis, hypercalcemia with low parathyroid hormone levels, hypercalciuria and low bone mass. Gene sequencing showed that the patient had compound heterozygous mutations including a novel genotype of the CYP24A1 gene. Genetic CYP24A1 testing and biochemical analyses were offered to other family members; the father was heterozygous for the same novel genotype and was also affected with recurrent nephrolithiasis...
September 17, 2016: Urolithiasis
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
Shan-Shan Li, Li-Hong Gao, Xiao-Ya Zhang, Jin-We He, Wen-Zhen Fu, Yu-Juan Liu, Yun-Qiu Hu, Zhen-Lin Zhang
Low serum 25-hydroxyvitamin D (25OHD) is associated with osteoporosis and osteoporotic fracture, but it remains uncertain whether these associations are causal. We conducted a Mendelian randomization (MR) study of 1,824 postmenopausal Chinese women to examine whether the detected associations between serum 25OHD and bone mineral density (BMD) and bone metabolism markers were causal. In observational analyses, total serum 25OHD was positively associated with BMD at lumbar spine (P = 0.003), femoral neck (P = 0...
2016: Scientific Reports
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
Jia-Jun Ye, Tian-Biao Zhou, Yun-Fang Zhang, Qi Wang, Yan-Yan Su, Jia-Min Tang, Hong-Yan Li
OBJECTIVE: This study was performed to detect the expression of vitamin D receptor (VDR) and cytochrome P450, family 24, subfamily A, polypeptide 1 (CYP24A1) in 24 end stage renal disease (ESRD) patients and 24 healthy controls. METHOD: In this study, 24 ESRD patients and 24 healthy controls were included. RESULTS: In our study, the levels of VDR in patients with ESRD were reduced when compared with those from healthy controls (5.20±0.32 vs 8...
June 2016: African Health Sciences
Makoto Osanai, Gang-Hong Lee
Vitamin D plays a critical role in tissue homeostasis by regulating the expression of genes affecting cell proliferation, differentiation, and apoptosis. The vitamin D 24-hydroxylase CYP24A1 functions in vitamin D target tissues to degrade the hormonal form of vitamin D. Existing knowledge regarding dysregulated CYP24A1 expression supports its candidacy as a putative oncogene. Here, we found that the suppression of constitutive CYP24A1 expression conferred target cells with increased susceptibility to apoptosis and consequently inhibited anchorage-independent growth in breast carcinoma cells...
September 5, 2016: Oncology Reports
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
Heng Xiao, Rongliang Tong, Beng Yang, Zhen Lv, Chengli Du, Chuanhui Peng, Chaofeng Ding, Shaobing Cheng, Lin Zhou, Haiyang Xie, Jian Wu, Shusen Zheng
The transcriptional coactivator with PDZ binding motif (TAZ) is reported as one of the nuclear effectors of Hippo-related pathways. TAZ is found overexpressed in many primary tumors and could regulate many biological processes. However, little is known about the role of TAZ in Intrahepatic Cholangiocarcinoma (ICC). In this study, we found that TAZ is expressed more in ICC tissues than in peritumoral tissue, and a robust expression of TAZ is correlated with a lower overall survival rate of ICC patients after hepatectomy...
October 28, 2016: Cancer Letters
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