Search results for “corticoid

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3 articles

Evaluation of Serum Vitamin D Levels in Foster's Children Care Center

Jan 2019 DOI 10.14302/issn.2691-5014.jphn-18-2456
Mohamadreza AmiriCorresponding author

Vitamin D, the sunshine vitamin, is now recognized not only for its importance in promoting bone health in children and adults, but also for its other health benefits, including reducing the risk of chronic diseases such as autoimmune diseases, common cancer, and cardiovascular diseases. Ultraviolet radiation of the sun with wavelengths of 290-310 nm penetrates into the skin and converts 7-dehydrocholesterol to previtamin D3, which quickly transforms to vitamin D3. Vitamin D (D represents either D2 or D3) made in the skin or ingested through diet is biologically inert and requires two successive hydroxylations first in the liver on carbon 25 to form 25-hydroxyvitamin D 25(OH)D and then in the kidney for a hydroxylation on carbon 1 to form the biologically active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) 121419. The concentration of the produced 25-hydroxy vitamin D in blood circulation is 1,000 times more than 1,25-dihydroxy vitamin D 4, and it is regarded as a standard indicator of vitamin D status in humans 3. 25-hydroxy vitamin D half-life is about 2-3 weeks and it is regulated by calcium (Ca), phosphorus (P), and serum parathyroid hormone (PTH) to some extent. 25-hydroxy vitamin D content also reflects the amount of vitamin D produced in the skin after exposure to sunlight or received through food intake 56. Guidelines for vitamin D insufficiency/deficiency defined by serum 25(OH)D concentrations have been published from many countries and regions all over the world 7891011. Vitamin D deficiency is a pandemic problem. According to global estimations, more than one billion people around the world suffer from vitamin D deficiency. Among Iranian population, the incidence of vitamin D deficiency varies from 2.5 to 98.5% based on geographic area 1213. Various factors may give rise to vitamin D deficiency, including skin pigments, low levels of vitamin D in diet (insufficient fish oil and egg yolk intake), malnutrition, genetic factors, exclusive breast feeding, vitamin D deficiency of mother during pregnancy, prematurity, chronic use of drugs (e.g., anticonvulsants, aluminum-containing anti-acids, rifampcin, isoniazid, antifungal drugs, antiviral drugs, and glucocorticoids), winter and obesity 113. Cultural habits, the need for full body coverage during outdoor activities and the lack of sunlight programs are the risk factors for low vitamin D levels in women 151617. Children enter foster care due to early childhood adverse experiences such as poor prenatal and infant health care, food insecurity, chronic stress, and the effects of abuse and neglect. As a result, they are at higher risk for poor physical, psychological, neuroendocrine and neurocognitive outcomes compared to others. Foster children are at risk for growth and nutritional deficiencies due to their poor nutritional environment prior to placement in foster care. Insufficient caloric intake results in growth deficiencies. Evidence showed that the risk of stunting and underweight is high in this population 18. The risk of developing hypovitaminosis D was significantly higher in children living in foster homes. One reason is that they are at higher risk of child abuse, emotional deprivation and physical neglect than children living with their families. Moreover, these children most likely do not spend much time outdoors and they lack adequate sun exposure. Another reason is that as children grow up in institutional care, they shift from a diet of vitamin D–fortified formula milk to cooked food, which may not be fortified with vitamin D 1. Iranian government has made some efforts to apply efficient interventions to reduce the prevalence of vitamin D deficiency, and the country’s healthcare system should be managed through accurate planning. Yet, in this country, studies on vitamin D deficiency in children living in foster homes are very limited, and given that timely diagnosis and treatment of this deficiency is vital, this research is conducted in Ali Asghar foster home in Mashhad, Iran.

GR-RNF43 Regulation in Colorectal Cancer

Mar 2016 DOI 10.14302/issn.2326-0793.jpgr-16-941
Chan ChristinaCorresponding author Cell and Molecular Biology Program, Michigan State University, 567 Wilson Road, Rm 2240A, East Lansing, Michigan 48824, USA

In contrast to approaches that compare pair-wise control (i.e. normal) to treated (i.e. disease) samples, we compared colorectal cancer samples not only to a set of control samples but also against a wide range of samples and conditions to collect the differentially expressed genes and identify target genes. We identified specific genes for colorectal cancer and showed that they are significantly associated with colorectal cancer in the literature. Analysis of independent datasets revealed a significantly distinct expression pattern for glucocorticoid receptor (GR) and ring finger protein 43 (RNF43) in colorectal cancer samples. GR was downregulated whereas RNF43 was upregulated in colorectal cancer with respect to various conditions in different datasets. In HCT116 colorectal cancer cell line, knock-down of GR levels with siRNA resulted in increased RNF43 levels, suggesting that GR might be a negative regulator of RNF43. Our study suggests that the downregulation of GR might be involved in the upregulation of RNF43 in colorectal cancer.

Computational EPAS1 rSNP Analysis, Transcriptional Factor Binding Sites and High Altitude Sickness or Adaptation

Feb 2016 DOI 10.14302/issn.2326-0793.jpgr-15-889
E. Buroker NormanCorresponding author Department of Pediatrics, University of Washington, Seattle, WA 98195, USA

Purpose The endothetal Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) gene which encodes hypoxia-inducible-factor-2 alpha (HIF2a) is a transcription factor that is involved in the response to hypoxia. EPAS1 has been found to have four (rs56721780, rs6756667, rs7589621, rs1868092) simple nucleotide polymorphisms (SNPs) associated with human disease.These SNPs were computationally examined with respect to changes in potential transcriptional factor binding sites (TFBS) and these changes were discussed in relation to disease and alterations in high altitude adaptation in humans. Methods The JASPAR CORE and ConSite databases were instrumental in identifying the TFBS. The Vector NTI Advance 11.5 computer program was employed in locating all theTFBS in theEPAS1 gene from 1.6 kb upstream of the transcriptional start site to 539 bps past the 3’UTR. The JASPAR CORE database was also involved in computing each nucleotide occurrence (%) within the TFBS. Results The EPAS1 SNPs in the promoter, intron two and the 3’UTR regions have previously been found to be significantly associated with disease and different levels of high-altitude hypoxia among native Tibetans. The SNP alleles were found to alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in TFBS and thereby, alter which transcriptional factors potentially regulate the EPAS1 genesuch as for the glucocorticoid and mineralocorticoid nuclear receptor binding sites created by the rs7589621 rSNP EPAS1-G allele. These receptors regulate carbohydrate, protein and fat metabolism. Also the minor rs7589621 rSNP EPAS1-A creates a punitive TFBS for the FOXC TF which is an important regulator of cell viability and resistance to oxidative stress. These EPAS1 SNPs should be considered as regulatory (r) SNPs. Conclusion The alleles of each rSNP were found to generate unique TFBS resulting in potential changes in TF EPAS1 regulation. The punitive changes in TFBS created by the four rSNPs could very well influence the significant cline in allele frequencies seen in Tibetans with increasing altitude or the haplotype association with high altitude polycythemia in male Han Chinese. These regulatory changes were discussed with respect to changes in human health that result in disease and sickness.

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