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A Protective Role for Arachidonic Acid Metabolites against Advanced Colorectal Adenoma in a Phase III Trial of Selenium.
Martinez, JA, Skiba, MB, Chow, HS, Chew, WM, Saboda, K, Lance, P, Ellis, NA, Jacobs, ET
Nutrients. 2021;(11)
Abstract
Oxylipins derived from arachidonic acid (ARA) have been implicated in the development of colorectal adenomas and colorectal cancer. The primary purpose of this work was to determine the relationship between plasma levels of oxylipins and colorectal adenoma characteristics at study entry, as well as with the development of a new adenoma during follow-up within a Phase III adenoma prevention clinical trial with selenium (Sel). Secondarily, we sought to determine whether the selenium intervention influenced plasma oxylipin levels. Four oxylipins were quantified in stored plasma samples from a subset of Sel study subjects (n = 256) at baseline and at 12-months. There were significantly lower odds of an advanced adenoma at baseline with higher prostaglandin E2 (PGE2), with an OR (95% CI) of 0.55 (0.33-0.92), and with 5-hydroxyeicosatetraenoic acid (5-HETE) ((0.53 (0.33-0.94)); and of a large adenoma with higher PGE2 ((0.52 (0.31-0.87)). In contrast, no associations were observed between any oxylipin and the development of a new adenoma during follow-up. Selenium supplementation was associated with a significantly smaller increase in 5-HETE after 12 months compared to the placebo, though no other results were statistically significant. The ARA-derived oxylipins may have a role in the progression of non-advanced adenoma to advanced, but not with the development of a new adenoma.
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Network Analysis of Se-and Zn-related Proteins in the Serum Proteomics Expression Profile of the Endemic Dilated Cardiomyopathy Keshan Disease.
Wang, S, Lv, Y, Wang, Y, Du, P, Tan, W, Lammi, MJ, Guo, X
Biological trace element research. 2018;(1):40-48
Abstract
Keshan disease (KD) is an endemic cardiomyopathy with high mortality. Selenium (Se) and zinc (Zn) deficiencies are closely related to KD. The molecular mechanism of KD pathogenesis is still unclear. There are only few studies on the interaction of trace elements and proteins associated with the pathogenesis of KD. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS) technique analysis was used to analyze the differential expression of proteins from serum samples. Comparative Toxicogenomics Database (CTD) was used to screen Se- and Zn-associated proteins. Then, pathway and network analyses of Se- and Zn-associated proteins were constituted by Cytoscape ClueGO and GeneMANIA plugins. One hundred and five differentially expressed proteins were obtained by 2DLC-MS/MS, among them 19 Se- and 3 Zn-associated proteins. Fifty-two pathways were identified from ClueGO and 1 network from GeneMANIA analyses. The results showed that Se-associated proteins STAT3 and MAPK1 and Zn-associated proteins HIF1A and PARP1, the proteins involved in HIF-1 signaling pathway and apoptosis pathway, may play significant roles in the pathogenesis of KD. The approach of this study would be also beneficial for further dissecting molecular mechanism of other trace element-associated disease.
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Concentration of selenium, zinc, copper, Cu/Zn ratio, total antioxidant status and c-reactive protein in the serum of patients with psoriasis treated by narrow-band ultraviolet B phototherapy: A case-control study.
Wacewicz, M, Socha, K, Soroczyńska, J, Niczyporuk, M, Aleksiejczuk, P, Ostrowska, J, Borawska, MH
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2017;:109-114
Abstract
BACKGROUND Psoriasis is a common, an inflammatory skin disease. Trace elements may play an active role in the pathogenesis of psoriasis. OBJECTIVE The aim of this study was to estimate the concentration of selenium (Se), zinc (Zn), copper (Cu) and Cu/Zn ratio as well as total antioxidant status (TAS) and c-reactive protein (CRP) in the serum of patients with psoriasis. METHODS In this case-control study sixty patients with psoriasis and fifty-eight healthy people were examined. Serum levels of Se, Zn and Cu were determined by atomic absorption spectrometry. Cu/Zn ratio was calculated. TAS was measured spectrophotometrically. CRP was analyzed by immunoturbidimetric method. Clinical activity of psoriasis was evaluated using Psoriasis Area and Severity Index (PASI). RESULTS Serum concentration of Se in patients with psoriasis (71.89±16.90μg/L) was lower as compared to the control group (79.42±18.97μg/L) and after NB-UVB. Cu level of patients was higher (1.151±0.320mg/L) as compared to controls (1.038±0.336mg/L), but Zn level did not differ. We observed higher Cu/Zn ratio (p<0.05) in examined patients than in the control group and after NB-UVB. We found decrease TAS before and after NB-UVB. CRP levels was found to be normal range. A significant correlation coefficient between CRP and Cu/Zn was observed. CONCLUSIONS The study showed some disturbances in the serum levels of trace elements and TAS in psoriatic patients.
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4.
Myo-inositol and selenium reduce the risk of developing overt hypothyroidism in patients with autoimmune thyroiditis.
Ferrari, SM, Fallahi, P, Di Bari, F, Vita, R, Benvenga, S, Antonelli, A
European review for medical and pharmacological sciences. 2017;(2 Suppl):36-42
Abstract
OBJECTIVE The beneficial effects obtained by myo-inositol in association with seleno-methionine in patients affected by subclinical hypothyroidism have been recently demonstrated. Here, we evaluate the immune-modulating effect of myo-inositol in association with seleno-methionine in patients with euthyroid autoimmune thyroiditis (AT). PATIENTS AND METHODS Twenty-one consecutive Caucasian patients with newly diagnosed euthyroid chronic AT were evaluated. All subjects were treated with myo-inositol in association with selenium (600 mg/83 mg) tablets, twice per day, for six months. A complete thyroid assessment was done before the treatment, and after six months. RESULTS After the treatment thyroid-stimulating hormone (TSH) levels significantly declined with respect to basal values, overall in patients with an initial TSH value in the high normal range (2.1 CONCLUSIONS We first show an immune-modulatory effect of myo-inositol in association with seleno-methionine in patients with euthyroid AT. Further studies are needed to extend the observations in a large population, to evaluate the effect on the quality of life, and to study the mechanism of the effect on chemokines.
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5.
Selenium Status Is Positively Associated with Bone Mineral Density in Healthy Aging European Men.
Beukhof, CM, Medici, M, van den Beld, AW, Hollenbach, B, Hoeg, A, Visser, WE, de Herder, WW, Visser, TJ, Schomburg, L, Peeters, RP
PloS one. 2016;(4):e0152748
Abstract
OBJECTIVE It is still a matter of debate if subtle changes in selenium (Se) status affect thyroid function tests (TFTs) and bone mineral density (BMD). This is particularly relevant for the elderly, whose nutritional status is more vulnerable. DESIGN AND METHODS We investigated Se status in a cohort of 387 healthy elderly men (median age 77 yrs; inter quartile range 75-80 yrs) in relation to TFTs and BMD. Se status was determined by measuring both plasma selenoprotein P (SePP) and Se. RESULTS The overall Se status in our population was low normal with only 0.5% (2/387) of subjects meeting the criteria for Se deficiency. SePP and Se levels were not associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3) or reverse triiodothyronine (rT3) levels. The T3/T4 and T3/rT3 ratios, reflecting peripheral metabolism of thyroid hormone, were not associated with Se status either. SePP and Se were positively associated with total BMD and femoral trochanter BMD. Se, but not SePP, was positively associated with femoral neck and ward's BMD. Multivariate linear analyses showed that these associations remain statistically significant in a model including TSH, FT4, body mass index, physical performance score, age, smoking, diabetes mellitus and number of medication use. CONCLUSION Our study demonstrates that Se status, within the normal European marginally supplied range, is positively associated with BMD in healthy aging men, independent of thyroid function. Thyroid function tests appear unaffected by Se status in this population.
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6.
Selenium, Zinc, Copper, and Total Antioxidant Status in the Serum of Patients with Chronic Tonsillitis.
Michalska-Mosiej, M, Socha, K, Soroczyńska, J, Karpińska, E, Łazarczyk, B, Borawska, MH
Biological trace element research. 2016;(1):30-4
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Abstract
Antioxidants can play a significant role in chronic inflammatory process. The aim of this study was to evaluate the content of selenium (Se), zinc (Zn), copper (Cu), and total antioxidant status (TAS) of patients with chronic tonsillitis (CT). The study group consisted of 84 patients with CT from 18 to 62 years old and the control group of 67 healthy people aged 19-65 years. Se, Zn, and Cu concentration in serum samples were determined by atomic absorption spectrometry. Serum TAS was measured spectrophotometrically, using the test by Randox Laboratories-Us Ltd. The mean content of Se and Zn in the serum of patients with CT (61.122 ± 12.73 μg/L, 0.887 ± 0.26 mg/L, respectively) was lower compared to the control group (77.969 ± 12.73 μg/L, 0.993 ± 0.32 mg/L, respectively). The mean serum concentration of Cu in patients with CT (1.219 ± 0.35 mg/L) was higher compared to its serum concentration in healthy people (1.033 ± 0.37 mg/L). Serum TAS of patients with CT (1.171 ± 0.33 mmol/L) was lower in comparison with healthy volunteers (1.333 ± 0.42 mmol/L). The serum concentration of Se, Zn, and TAS in patients with CT was lower, whereas the concentration of Cu was higher compared to healthy volunteers. Smoking has an influence on reducing the concentration of Se and TAS of patients with CT.
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Phase III randomised chemoprevention study with selenium on the recurrence of non-invasive urothelial carcinoma. The SELEnium and BLAdder cancer Trial.
Goossens, ME, Zeegers, MP, van Poppel, H, Joniau, S, Ackaert, K, Ameye, F, Billiet, I, Braeckman, J, Breugelmans, A, Darras, J, et al
European journal of cancer (Oxford, England : 1990). 2016;:9-18
Abstract
BACKGROUND In Belgium, bladder cancer (BC) is the fifth most common cancer in men. The per-patient lifetime cost is high. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of BC. We therefore hypothesised that selenium may be suitable for chemoprevention of recurrence of BC. METHOD The Selenium and Bladder Cancer Trial (SELEBLAT) was an academic phase III placebo-controlled, double-blind, randomised clinical trial designed to determine the effect of selenium on recurrence of non-invasive urothelial carcinoma conducted in 14 Belgian hospitals. Patients were randomly assigned by a computer program to oral selenium yeast 200 μg once a day or placebo for three years, in addition to standard care. All study personnel and participants were blinded to treatment assignment for the duration of the study. All randomised patients were included in the intention to treat (ITT) and safety analyses. Per protocol analyses (PPAs) included all patients in the study three months after start date. RESULTS Between September 18, 2009 and April 18, 2013, 151 and 141 patients were randomised in the selenium and placebo group. Patients were followed until December 31, 2015. The ITT analysis resulted in 43 (28%; 95% CI, 0.21-0.35) and 45 (32%; 95% CI, 0.24-0.40) recurrences in the selenium and placebo group. The hazard ratio (HR) was 0.85 (95% CI, 0.56-1.29; p = 0.44) while the HR for the PPA resulted in 42 and 39 (28%; 95% CI, 0.20-0.35) recurrences in the selenium and placebo group (HR = 0.96 [95% CI, 0.62-1.48]; p = 0.93). CONCLUSION Selenium supplementation does not lower the probability of recurrence in BC patients.
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Serum Selenium Levels in Euthyroid Nodular Thyroid Diseases.
Sakız, D, Kaya, A, Kulaksizoglu, M
Biological trace element research. 2016;(1):21-26
Abstract
The thyroid gland is susceptible to nodulation. The mechanism responsible for the growth of only some follicular cells, which results in nodule formation, is not yet clear. Selenium deficiency may be a risk factor in the development of thyroid nodules. The aim of this study was to investigate the relationship between selenium levels in patients with euthyroid nodular thyroid disease. Seventy patients with a solitary euthyroid thyroid nodule, 70 patients with more than one euthyroid nodule, and 60 healthy patients without thyroid nodules were included in the study. Venous serum samples were stored at -80°C and analyzed the same day using spectrometry. The selenium levels of patients with multiple thyroid nodules, solitary nodules, and patients without nodules were 57.3 ± 14.8 μg/L; 58.8 ± 15.1 μg/L; and 57.6 ± 13.3 μg/L, respectively. The mean serum selenium level of all patients included in the study was 57.9 ± 14.4 μg/L. Although serum selenium levels were slightly higher in men, a statistically significant difference was not observed. In our study, a significant relationship between serum selenium levels and nodular thyroid disease was not seen. Our study was undertaken in an iodine sufficient region. Mean serum selenium levels were lower compared with many other studies, which may be associated with the low selenium content of the soil. Nodular thyroid disease shows multifactorial features. When our study is considered together with previous studies, serum selenium levels may considered to be effective on structural thyroid diseases if combined with additional factors such as severe iodine deficiency. Further studies are required to assess the role of selenium in thyroid nodule formation.
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Plasma Selenium Levels in First Trimester Pregnant Women with Hyperthyroidism and the Relationship with Thyroid Hormone Status.
Arikan, TA
Biological trace element research. 2015;(2):194-9
Abstract
The thyroid gland has the highest selenium (Se) concentration per unit weight among all tissues. The aims of the present study were to evaluate the Se levels in the plasma of hyperthyroidic pregnant women and to investigate the association between maternal plasma Se concentrations and thyroid hormone levels. The study population consisted of 107 pregnant women, 70 healthy pregnant women (group 1) and 37 pregnant women with hyperthyroidism (group 2). The plasma free triiodothyronine (fT3) and free thyroxine (fT4) levels were significantly higher, and the plasma thyroid-stimulating hormone (TSH) and Se levels were significantly lower in group 2 than in group 1 (p < 0.05). A correlation analysis showed a positive correlation between Se and fT4 in group 1 and with TSH in group 2 (p < 0.05). Decreased maternal serum antioxidant trace element Se in hyperthyroidic pregnant women compared with normal pregnant women supported the hypothesis that hyperthyroidism was associated with decreased antioxidant response.
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A randomized controlled trial of vitamin E and selenium on rate of decline in lung function.
Cassano, PA, Guertin, KA, Kristal, AR, Ritchie, KE, Bertoia, ML, Arnold, KB, Crowley, JJ, Hartline, J, Goodman, PJ, Tangen, CM, et al
Respiratory research. 2015;(1):35
Abstract
BACKGROUND The intake of nutrients with antioxidant properties is hypothesized to augment antioxidant defenses, decrease oxidant damage to tissues, and attenuate age-related rate of decline in lung function. The objective was to determine whether long-term intervention with selenium and/or vitamin E supplements attenuates the annual rate of decline in lung function, particularly in cigarette smokers. METHODS The Respiratory Ancillary Study (RAS) tested the single and joint effects of selenium (200 μg/d L-selenomethionine) and vitamin E (400 IU/day all rac-α-tocopheryl acetate) in a randomized double-blind placebo-controlled trial. At the end of the intervention, 1,641 men had repeated pulmonary function tests separated by an average of 3 years. Linear mixed-effects regression models estimated the effect of intervention on annual rate of decline in lung function. RESULTS Compared to placebo, intervention had no main effect on either forced expiratory volume in the first second (FEV1) or forced expiratory flow (FEF25-75). There was no evidence for a smoking by treatment interaction for FEV1, but selenium attenuated rate of decline in FEF25-75 in current smokers (P = 0.0219). For current smokers randomized to selenium, annual rate of decline in FEF25-75 was similar to the annual decline experienced by never smokers randomized to placebo, with consistent effects for selenium alone and combined with vitamin E. CONCLUSIONS Among all men, there was no effect of selenium and/or vitamin E supplementation on rate of lung function decline. However, current smokers randomized to selenium had an attenuated rate of decline in FEF25-75, a marker of airflow. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT00241865 .