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Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and the accumulation of beta-amyloid plaques and tau tangles in the brain. Current therapies have limited efficacy, prompting the search for novel treatments. Selenium nanoparticles (SeNPs) have emerged as promising candidates for AD therapy due to their unique physicochemical properties and potential therapeutic effects. This review provides an overview of SeNPs and their potential application in AD treatment, as well as the main bioanalytical techniques applied in this field. SeNPs possess antioxidant and anti-inflammatory properties, making them potential candidates to combat the oxidative stress and neuroinflammation associated with AD. Moreover, SeNPs have shown the ability to cross the blood-brain barrier (BBB), allowing them to target brain regions affected by AD pathology. Various methods for synthesizing SeNPs are explored, including chemical, physical and biological synthesis approaches. Based on the employment of algae, yeast, fungi, and plants, green methods offer a promising and biocompatible alternative for SeNPs production. In vitro studies have demonstrated the potential of SeNPs in reducing beta-amyloid aggregation and inhibiting tau hyperphosphorylation, providing evidence of their neuroprotective effects on neuronal cells. In vivo studies using transgenic mouse models and AD-induced symptoms have shown promising results, with SeNPs treatment leading to cognitive improvements and reduced amyloid plaque burden in the hippocampus. Looking ahead, future trends in SeNPs research involve developing innovative brain delivery strategies to enhance their therapeutic potential, exploring alternative animal models to complement traditional mouse studies, and investigating multi-targeted SeNPs formulations to address multiple aspects of AD pathology. Overall, SeNPs represent a promising avenue for AD treatment, and further research in this field may pave the way for effective and much-needed therapeutic interventions for individuals affected by this debilitating disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Selenium nanoparticles (SeNPs) are a unique type of nano-sized elemental selenium that have recently found wide application in biomedicine. It has been shown that the properties of SeNPs can be varied by different fabrication methods. Moreover, SeNPs have various therapeutic effects in medical applications due to their excellent biological and adaptable physical properties. At the same time, SeNPs can be used as a carrier medium for various therapeutic substances, which can bring out the full curative effects of the drugs. In this review, the differences in bioactivity properties of SeNPs prepared from different substances were reviewed; the therapeutic effects and mechanisms of SeNPs in cancer, inflammation, neurodegenerative diseases, diabetes, reproductive diseases, cardiovascular diseases, and other diseases were discussed; and the importance of the development of SeNPs was further emphasized., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jing Han reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2023. Published by Elsevier B.V.)

Selenium has good antitumor effects in vitro, but the hypoxic microenvironment in solid tumors makes its clinical efficacy unsatisfactory. We hypothesized that the combination with oxygen therapy might improve the treatment efficacy of selenium in hypoxic tumors through the changes of redox environment. In this work, two selenium compounds, Na 2 SeO 3 and CysSeSeCys, were selected to interrogate their therapeutic effects on hepatocellular carcinoma (HCC) under different oxygen levels. In tumor-bearing mice, both selenium compounds significantly inhibited the tumor growth, and combined with oxygen therapy further reduced the tumor volume about 50 %. In vitro HepG2 cell experiments, selenium induced autophagy and delayed apoptosis under hypoxia (1 % O 2 ), while inhibited autophagy and accelerated apoptosis under hyperoxia (60 % O 2 ). We found that, in contrast to hypoxia, the hyperoxic environment facilitated the H 2 Se, produced by the selenium metabolism in cells, to be rapidly oxidized to generate H 2 O 2 , leading to inhibit the expression level of Nrf2 and to increase that of phosphorylation of p38 and MKK4, resulting in inhibiting autophagy and accelerating apoptosis. Once the Nrf2 gene was knocked down, selenium compounds combined with hyperoxia treatment would further activate the MAPK signaling pathway and further increase apoptosis. These findings highlight oxygen can significantly enhance the anti-HCC effect of selenium compounds through regulating the Nrf2 and MAPK signaling pathways, thus providing novel therapeutic strategy for the hypoxic tumors and pave the way for the application of selenium in clinical treatment., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The ability to develop novel medications based on nanoscale complexes has greatly enhanced the capabilities of current pharmaceuticals and has made multidimensional research of these complexes extremely relevant in recent years. Selenium nanoparticles (SeNPs) constitute one such example which in general, could be created by biological, chemical, and physical techniques. Biogenic SeNPs show improved compatibility with human organs and tissues. While sufficient levels of selenium (Se) are crucial for triggering immunity, they also play a role in controlling exaggerated immunological responses and persistent inflammation. More significantly, SeNPs can activate the immune systems, both innate and adaptive, in the tumor microenvironment, which results in an immunological response that fights various diseases caused by chronic inflammation. In this article, we discuss the functions of Se and SeNPs in controlling inflammation with particular emphasis given to their role in combating inflammation in different diseases. Finally, even though Se status exhibits considerable promise as a reliable indicator of autoimmune and inflammatory diseases, novel functionalized SeNPs may likely offer a more effective and reliable tool in both disease prevention and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The purpose of this study was to construct Phragmites rhizoma polysaccharide-based nano-drug delivery systems (PRP2-SeNPs-H/Aza-Lips) for synergistically alleviating ulcerative colitis and to investigate the important roles of Phragmites rhizoma polysaccharide-based nanocarriers in PRP2-SeNPs-H/Aza-Lips. Phragmites rhizoma polysaccharide (PRP2) was isolated and used for the preparation of Phragmites rhizoma polysaccharide selenium nanoparticles with low selenium content (PRP2-SeNPs-L) and high selenium content (PRP2-SeNPs-H). Based on the electrostatic attraction between PRP2-SeNPs-H and azathioprine liposomes (Aza-Lips), PRP2-SeNPs-H/Aza-Lips were constructed for precise delivery of the model drug azathioprine (Aza) to colon lesions. Results showed that PRP2 significantly alleviated the clinical symptoms and colon tissue damage and down-regulated the levels of inflammatory factors in serum and colon, demonstrating beneficial effects on mice with ulcerative colitis. PRP2-SeNPs-L had better relieving effects on ulcerative colitis. Phragmites rhizoma polysaccharide-based nanocarriers may protect azathioprine liposomes against gastrointestinal digestion, enhance the therapeutic effects on ulcerative colitis, and significantly reduce liver damage from azathioprine, which helps to improve the efficacy and toxicity of clinical drugs., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Selenium is an indispensable trace element for all living organisms. It is an essential structural component of several selenium-dependent enzymes, which support the human body's defense mechanism. Recently, the significance of selenium in preventing/treating COVID-19 has been documented in the literature. This review highlights the clinical studies, compositions, and patent literature on selenium to prevent/treat COVID-19. Selenium exerts its anti-COVID-19 action by reducing oxidative stress, declining the expression of the ACE-2 receptor, lowering the discharge of pro-inflammatory substances, and inhibiting the 3CL Pro (main protease) and PL pro enzyme of SARS-CoV-2. The data of clinical studies, inventive compositions, and patent literature revealed that selenium monotherapy and its compositions with other nutritional supplements/drugs (vitamin, iron, zinc, copper, ferulic acid, resveratrol, spirulina, N-acetylcysteine, fish oil, many herbs, doxycycline, azithromycin, curcumin, quercetin, etc.,) might be practical to prevent/treat COVID-19. The studies have also suggested a correlation between COVID-19 and selenium deficiency. This indicates that adequate selenium supplementation may provide promising treatment outcomes in COVID-19 patients. The authors foresee the development and commercialization of Selenium-based compositions and dosage forms (spray, inhalers, control release dosage forms, etc.) to battle COVID-19. We also trust that numerous selenium-based compositions are yet to be explored. Accordingly, there is good scope for scientists to work on developing novel and inventive selenium-based compositions to fight against COVID-19. However, there is also a need to consider the narrow therapeutic window and chemical interaction of selenium before developing selenium-based compositions., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Current treatment for Chagas disease is based on only two drugs: benznidazole and nifurtimox. Compounds containing sulfur (S) in their structure have shown promising results in vitro and in vivo against Trypanosoma cruzi, the parasite causing Chagas disease. Notably, some reports show that the isosteric replacement of S by selenium (Se) could be an interesting strategy for the development of new compounds for the treatment of Chagas disease. To date, the activity against T. cruzi of three Se- containing groups has been compared with their S counterparts: selenosemicarbazones, selenoquinones, and selenocyanates. More studies are needed to confirm the positive results of Se compounds. Therefore, we have investigated S compounds described in the literature tested against T. cruzi. We focused on those tested in vivo that allowed isosteric replacement to propose their Se counterparts as promising compounds for the future development of new drugs against Chagas disease., (Copyright © 2022. Published by Elsevier B.V.)

Nanotechnology is used in a wide range of applications, including medical therapies that precisely target disease prevention and treatment. The current study aimed firstly, to synthesize selenium nanoparticles (SeNPs) in an eco-friendly manner using Moringa oleifera leaf extract (MOLE). Secondly, to compare the protective effects of green-synthesized MOLE-SeNPs conjugate and MOLE ethanolic extract as remedies for melamine (MEL) induced nephrotoxicity in male rats. One hundred and five male Sprague Dawley rats were divided into seven groups (n = 15), including 1 st control, 2 nd MOLE (800 mg/kg BW), 3 rd SeNPs (0.5 mg/kg BW), 4 th MOLE-SeNPs (200 μg/kg BW), 5 th MEL (700 mg/kg BW), 6 th MEL+MOLE, and 7 th MEL+MOLE SeNPs. All groups were orally gavaged day after day for 28 days. SeNPs and the colloidal SeNPs were characterized by TEM, SEM, and DLS particle size. SeNPs showed an absorption peak at a wavelength of 530 nm, spherical shape, and an average size between 3.2 and 20 nm. Colloidal SeNPs absorption spectra were recorded between 400 and 700 nm with an average size of 3.3-17 nm. MEL-induced nephropathic alterations represented by a significant increase in serum creatinine, urea, blood urea nitrogen (BUN), renal TNFα, oxidative stress-related indices, and altered the relative mRNA expression of apoptosis-related genes Bax, Caspase-3, Bcl2, Fas, and FasL. MEL-induced array of nephrotoxic morphological changes, and up-regulated immune-expression of proliferating cell nuclear antigen (PCNA) and proliferation-associated nuclear antigen Ki-67. Administration of MOLE or MOLE-SeNPs significantly reversed MEL-induced renal function impairments, oxidative stress, histological alterations, modulation in the relative mRNA expression of apoptosis-related genes, and the immune-expression of renal PCNA and Ki-67. Conclusively, the green-synthesized MOLE-SeNPs and MOLE display nephron-protective properties against MEL-induced murine nephropathy. This study is the first to report these effects which were more pronounced in the MOLE group than the green biosynthesized MOLE-SeNPs conjugate group., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Cadmium (Cd) is a toxic heavy metal that accumulates in the brain and causes a series of histopathological changes. Selenium (Se) exerts a crucial function in protecting damage caused by toxic heavy metals, but its potential mechanism is rarely studied. The main purpose of this study is to explore the protective effects of Se on Cd-induced oxidative stress and autophagy in rabbit cerebrum. Forty rabbits were randomly divided into four groups and treated as follows: Control group, Cd (1 mg/kg⋅BW) group, Se (0.5 mg/kg⋅BW) group and Cd (1 mg/kg⋅BW)+Se (0.5 mg/kg⋅BW) group, with 30 days feeding management. Our results suggested that Se treatment significantly suppressed the Cd-induced degenerative changes including cell necrosis, vacuolization, and atrophic neurons. In addition, Se decreased the contents of MDA and H 2 O 2 and increased the activities of CAT, SOD, GST, GSH and GSH-Px, alleviating the imbalance of the redox system induced by Cd. Furthermore, Cd caused the up-regulation of the mRNA levels of autophagy-related genes (ATG3, ATG5, ATG7, ATG12 and p62), AMPK (Prkaa1, Prkaa2, Prkab1, Prkab2, Prkag2, Prkag3) and Nrf2 (Nrf2, HO-1 and NQO1) signaling pathway, and the expression levels of LC3II/LC3I, p-AMPK/AMPK, Beclin-1, Nrf2 and HO-1 proteins, which were alleviated by Se, indicated that Se inhibited Cd-induced autophagy and Nrf2 signaling pathway activation. In conclusion, our study found that Se antagonized Cd-induced oxidative stress and autophagy in the brain by generating crosstalk between AMPK and Nrf2 signaling pathway., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Increased accumulation of reactive oxygen species (ROS) in the process of oogenesis is one of the most well known causes of ovarian insufficiency and decreased ovarian reserve. Selenium and vitamin E as cofactors of glutathione peroxidase plays an important role in the removal of ROS in the ovary. We evaluated the effects of selenium and vitamin E supplementation on anti-Mullerian hormone (AMH) index and antral follicle count (AFC) (primary outcomes) and mean ovarian volume (MOV) and side effects of these supplements (secondary outcome) in infertile women with occult premature ovarian insufficiency (OPOI)., Methods: 70 patients were allocated into the control and treatment groups through block randomization method. 35 women in the treatment group received 200 ng selenium and 400IU vitamin E and 35 women in the control group received placebo for a total of 90 days. AMH index, AFC and mean ovarian volume (MOV) were investigated in both groups after 12 months of study., Result: There was no significant difference between groups before intervention in AMH (Mean difference: -0.08; 95% CI: -0.20 to.08; p=0.33), AFC (-0.71; 95%CI: -1.44 to -0.01; p=0.05) and MOV (-0.55; 95% CI: -0.85 to -0.24; p=0.001). There was a significant increase in AMH (mean difference: 0.59; 95% CI: 0.48 to 0.71; p<0.001), AFC (5.08; 95% CI: 4.36 to 5.08; p<0.001) and MOV (2.17; 95% CI: 1.87 to 2.47; p<0.001) in selenium + vitamin E group compared to placebo group 12 months after intervention. These supplements had no side effects., Conclusion: Supplementation with selenium and vitamin E can increase AMH, AFC and MOV in women with OPOI., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In this study, the effect of chondroitin sulphate nano-selenium (CS@Se) on Alzheimer's disease (AD) in mice was investigated. CS@Se alleviated anxiety and improved the spatial learning and memory impairment in AD mice. CS@Se significantly reduced cell oedema and pyknosis, protected the mitochondria, and improved abnormal changes in the ultrastructure of hippocampal neuron synapses of AD mice. Moreover, CS@Se significantly increased the levels of superoxide dismutase(SOD), glutathione peroxidase (GSH-Px), Na + /K + -ATPase assay (Na + /K + -ATPase) and acetyltransferase (ChAT), and decreased the levels of malondialdehyde (MDA) and acetylcholinesterase (ChAE) in AD mice. Western blot results showed that CS@Se can attenuate excessive phosphorylation of tau (Ser396/Ser404) by regulating the expression of glycogen synthase kinase-3 beta (GSK-3β). In addition, CS@Se can activate the extracellular signal-regulated kinase 1/2 (ERK 1/2) and p38 mitogen-activated protein kinase (p38 MAPK) signalling pathways to inhibit nuclear transcription factor kappa B (NF-κB) nuclear translocation, thereby regulating the expression of pro-inflammatory cytokines. In summary, CS@Se can reduce oxidative stress damage, inhibit excessive tau phosphorylation, reduce inflammation to delay AD development, and increase the learning and memory capacities of AD mice., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cypermethrin (CYP), a class II synthetic pyrethroid, is used to control household insects. CYP can cross the blood-brain barrier to exert neurotoxicity through changes in sodium ion channels. Selenium is an essential component of glutathione peroxidise enzyme; in addition, it shows a potential anti-inflammatory property. The present study aimed to investigate the neuroprotective role of Nano-Se on CYP-induced neurotoxicity. Twenty-four adult male Wister rats were randomly divided into three groups: a) control, b) CYP (1mg/kg) administered orally for 21 days, c) CYP (1mg/kg) administered orally for 21 days and Nano-Se (2.5 mg/kg) given once a day three times a week for three weeks). Locomotor activity was assessed using open field test then rats were sacrificed under anaesthesia, and their brains were dissected out and processed for biochemical and histopathological studies. Histological examination of CYP-treated rats demonstrated some degenerative changes; besides, CYP affected rat locomotor activity. CYP-treated rats showed increased levels of malondialdehyde (MDA), TNF-α and IL-1β in addition to the reduction of glutathione (GSH) levels and gamma-Aminobutyric acid (GABA). Nano-Se restored normal behavioural function and significantly attenuated CYP-evoked degenerative changes. Nano-Se increased levels of GABA and glutathione; on the other hand, it significantly prevented the rise in the levels of MDA, TNF-α and IL-1β. Therefore, Nano-Se demonstrated both anti-oxidant and anti-inflammatory potential. Nano-Se may be suggested to be a prospective candidate to ameliorate CYP-induced neurotoxicity., Competing Interests: Declaration of competing interest The authors declared that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aims: Combined probiotic and selenium supplementation may improve Alzheimer's disease (AD) by correcting metabolic abnormalities, and attenuating inflammation and oxidative stress. This study aimed to determine the effects of probiotic and selenium co-supplementation on cognitive function and metabolic status among patients with AD., Methods: This randomized, double-blind, controlled clinical trial was conducted among 79 patients with AD. Patients were randomly assigned to receive either selenium (200 μg/day) plus probiotic containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium longum (2 × 10 9  CFU/day each) (n = 27), selenium (200 μg/day) (n = 26) or placebo (n = 26) for 12 weeks., Results: Selenium supplementation, compared with the placebo, significantly reduced serum high sensitivity C-reactive protein (hs-CRP) (P < 0.001), insulin (P = 0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (P = 0.002), LDL-cholesterol (P = 0.04) and total-/HDL-cholesterol ratio (P = 0.004), and significantly increased total glutathione (GSH) (P = 0.001) and the quantitative insulin sensitivity check index (QUICKI) (P = 0.01). Compared with only selenium and placebo, probiotic and selenium co-supplementation resulted in a significant increase in mini-mental state examination score (+1.5 ± 1.3 vs. +0.5 ± 1.2 and -0.2 ± 1.1, respectively, P < 0.001). Probiotic plus selenium intake resulted in a significant reduction in hs-CRP (-1.6 ± 1.4 vs. -0.8 ± 1.0 and +0.1 ± 0.5 mg/L, respectively, P < 0.001), and a significant increase in total antioxidant capacity (+89.4 ± 129.6 vs. +20.0 ± 62.5 and -0.7 ± 27.2 mmol/L, respectively, P = 0.001) and GSH (+122.8 ± 136.5 vs. +102.2 ± 135.2 and +1.5 ± 53.2 μmol/L, respectively, P = 0.001) compared with only selenium and placebo. In addition, subjects who received probiotic plus selenium supplements had significantly lower insulin levels (-2.1 ± 2.5 vs. -1.0 ± 1.3 and +0.7 ± 2.0 μIU/mL, respectively, P < 0.001), HOMA-IR (-0.5 ± 0.6 vs. -0.2 ± 0.3 and +0.1 ± 0.4, respectively, P < 0.001), and higher QUICKI (+0.01 ± 0.01 vs. +0.005 ± 0.007 and -0.002 ± 0.01, respectively, P < 0.006) compared with only selenium and placebo. Additionally, probiotic and selenium co-supplementation resulted in a significant reduction in serum triglycerides (-17.9 ± 26.1 vs. -3.5 ± 33.9 and +0.3 ± 9.3 mg/dL, respectively, P = 0.02), VLDL- (-3.6 ± 5.2 vs. -0.7 ± 6.8 and +0.05 ± 1.8 mg/dL, respectively, P = 0.02), LDL- (-8.8 ± 17.8 vs. -8.1 ± 19.2 and +2.7 ± 19.0 mg/dL, respectively, P = 0.04) and total-/HDL-cholesterol (-0.3 ± 0.7 vs. -0.4 ± 0.9 and +0.3 ± 0.6, respectively, P = 0.005) compared with only selenium and placebo., Conclusions: Overall, we found that probiotic and selenium co-supplementation for 12 weeks to patients with AD improved cognitive function and some metabolic profiles. This study was registered in the Iranian website (www.irct.ir) for registration of clinical trials (http://www.irct.ir: IRCT20170612034497N5)., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Selenium, at high-dose levels approaching its toxicity, protects tissues from dose-limiting toxicities of many cancer chemotherapeutics without compromising their therapeutic effects on tumors, there by allowing the delivery of higher chemotherapeutic doses to achieve increased cure rate. In this regard, selenium nanoparticles (SeNPs), which show the lowest toxicity among extensively investigated selenium compounds including methylselenocysteine and selenomethionine, are more promising for application. The key issue remains to be resolved is whether low-toxicity SeNPs possess a selective protective mechanism. p53 or p53-regulated thrombospondin-1 has each been confirmed to be an appropriate target for therapeutic suppression to reduce side effects of anticancer therapy. The present study demonstrated that SeNPs transiently suppressed the expression of many intestinal p53-associated genes in healthy mice. SeNPs did not interfere with tumor-suppressive effect of nedaplatin, a cisplatin analogue; however, effectively reduced nedaplatin-evoked diarrhea. Nedaplatin-induced diarrhea was associated with activation of intestinal p53 and high expression of intestinal thrombospondin-1. The preventive effect of SeNPs on nedaplatin-induced diarrhea was correlated with a powerful concomitant suppression of p53 and thrombospondin-1. Moreover, the high-dose SeNPs used in the present study did not suppress growth nor caused liver and kidney injuries as well as alterations of hematological parameters in healthy mice. Overall, the present study reveals that chemotherapeutic selectivity conferred by SeNPs involves a dual suppression of two well-documented targets, the p53 and thrombospondin-1, providing mechanistic and pharmacologic insights on low-toxicity SeNPs as a potential chemoprotectant for mitigating chemotherapy-induced diarrhea., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This meta-analysis and systematic review investigated evidence of the effect of oral micronutrient supplementation on male fertility. Following searches of PubMed, Ovid/Ovid Medline(r) and Embase, 18 randomized, double-blind, placebo-controlled trials were included in the meta-analysis (seven studies) and/or the systematic review (12 studies). The meta-analysis showed significant improvement in semen parameters for selenium (200µg/day and 100µg/day) (standard mean difference [SMD] 0.64 for oligozoospermia, 1.39 for asthenozoospermia), L-carnitine (2 g/day) and acetyl-L-carnitine (LAC; 1 g/day) combined (SMD 0.57 for asthenozoospermia), and co-enzyme Q10 (200 and 300 mg/day) (SMD 0.95 for oligozoospermia, 1.48 for asthenozoospermia, 0.63 for teratozoospermia). The systematic review identified promising data for supplementation with 66 mg/day zinc combined with folic acid (5 mg/day), and the polyunsaturated fatty acids eicosapentaenoic acid (EPA; 1.12 g/day) and docosahexaenoic acid (DHA; 0.72 g/day). Pregnancy rate was evaluated in a limited number of trials (four in the meta-analysis, three in the systematic review). This analysis suggests supplementation with selenium (alone or combined with N-acetylcysteine), co-enzyme Q10 and the combinations L-carnitine + acetyl-L-carnitine, folic acid + zinc and EPA + DHA is beneficial in the treatment of male infertility. Because of the small number of available studies and low number of participants, further well-designed clinical studies are needed to obtain a better overview of efficient methods of treating male infertility., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: The objective of this investigation was to assess the effects of probiotic and selenium co-supplementation on indicators of mental health and metabolic profiles in diabetic people with coronary heart disease (CHD)., Methods: This randomized, double-blind, placebo-controlled trial was conducted among 54 diabetic people with CHD. Patients were randomly allocated into two groups to receive either 200 μg/day selenium plus 8 × 10 9  CFU/day probiotic (n = 27) or placebo (n = 27) for 12 weeks., Results: Probiotic and selenium co-supplementation significantly decreased Beck Depression Inventory index (β -1.46; 95% CI, -2.61, -0.31; P = 0.01) and Beck Anxiety Inventory index (β -1.23; 95% CI, -2.33, -0.12; P = 0.02) compared with the placebo. Consuming probiotic plus selenium lowered fasting plasma glucose (β -10.80 mg/dL; 95% CI, -17.68, -3.92; P = 0.003), serum insulin levels (β -3.42 μIU/mL; 95% CI, -4.93, -1.90; P < 0.001), insulin resistance (β -0.96; 95% CI, -1.45, -0.47; P < 0.001), and enhanced insulin sensitivity (β 0.01; 95% CI, 0.007, 0.01; P < 0.001) compared with the placebo. Additionally, co-supplementation reduced triglycerides (β -34.45 mg/dL; 95% CI, -56.18, -12.72; P = 0.003), VLDL- (β -6.89 mg/dL; 95% CI, -11.23, -2.54; P = 0.003), total cholesterol (β -18.13 mg/dL; 95% CI, -23.42, -2.83; P = 0.02) and high sensitivity C-reactive protein (β -1043.28 ng/mL; 95% CI, -1929.67, -156.89; P = 0.02), and increased nitric oxide (β 7.86 μmol/L; 95% CI, 5.63, 10.09; P < 0.001), total antioxidant capacity (β 119.30 mmol/L; 95% CI, 63.04, 175.57; P < 0.001) and total glutathione (β 154.16 μmol/L; 95% CI, 82.57, 225.74; P < 0.001) compared with the placebo., Conclusions: Probiotic and selenium co-supplementation to diabetic people with CHD improved indicators of mental health and metabolic profiles. Registered under Clinical Trials.gov Identifier no. http://www.irct.ir: IRCT20170513033941N28., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Cancer is a disease that effects cell metabolism causing an imbalance in the health of the patient. On the other hand, malnutrition, presented by oncological patients, is caused by both the disease and its treatment. Some serum biochemical parameters cannot be determined by the traditional method of laboratory blood analysis (spectrophotometry). Among the various techniques that could be used for blood biochemical analysis, we opted for the Z-scan technique, due to its sensitivity to the reading of blood components. Our objective in this work was to compare the data obtained by the Z-scan technique and the spectrophotometry of the serological samples of children with solid tumors and leukemia under treatment, receiving or not selenium supplementation in a randomized, double-blind clinical trial. The biochemical parameters were read based on blood. These blood sampling made at different stages of chemotherapy and selenium supplementation. At each of these stages, the cholesterol, glucose and triglycerides parameters were read using the Z-scan and spectrophotometry techniques. We observed that selenium helps in balancing the health of these patients, and corroborates with our hypothesis that the Z-scan technique may be an alternative for the determination of biochemical parameters., (Copyright © 2019 Elsevier B.V. All rights reserved.)

L-carnitine (LC) and selenium (Se) have significant protective and antioxidant effects on several tissues. Cadmium (Cd), widely used in some industries and emitted from fossil fuels, is a heavy metal having a number of side effects, including hepatotoxicity. This study aims to assess the ameliorative function of both LC and SeCl 4 on cadmium chloride (CdCl 2 )-induced liver toxicity. In total, 70 male mice included in this study were allocated to seven groups: control, CdCl 2 , LC, SeCl 4 , CdCl 2 plus SeCl 4 , CdCl 2 plus LC, CdCl 2 plus SeCl 4 and LC groups. Hepatic aminotransferase (aspartate aminotransferase [AST] and alanine transaminase [ALT]) activity and tumor necrosis factor-alpha [TNF-α] levels, as well as the antioxidant biomarkers (superoxide dismutase [SOD], glutathione reductase [GRx], glutathione-S-transferase [GST] and catalase [CAT], were examined. Histological and transmission electron microscopic [TEM] variations in the liver were used as indicators of liver damage after the administration of CdCl 2 -alone or CdCl 2 with LC, SeCl 4 , or both. Genotoxic effects of CdCl 2 were also evaluated and the possible roles of SeCl 4 and/or LC on the expression of the antioxidant enzymes were studied. Results showed that administration of LC and SeCl 4 decreased CdCl 2 -induced increase in ALT and AST levels and reduced oxidative stress to normal levels. In addition, LC combined with SeCl 4 had a highly synergistic effect and elevated significantly the enzymatic antioxidants and decreased lipid peroxidation levels compared with those in the CdCl 2 -treated group. It is clear from the data that both LC and SeCl 4 inhibit liver injury and improve the redox state in mice., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Selenite (Se 4+ ) has been found to counteract the neurotoxicity of methylmercury (MeHg) in MeHg-poisoned rats. However, Se 4+ has narrow range between its toxic and beneficial effects. Nanoelemental selenium (SeNPs) was found to be less toxic than other forms of Se such as Se 4+ . In this study, the effects of SeNPs on the load of mercury (Hg) in rats were investigated. Hyphenated technique based on size-exclusion chromatography coupled with UV and inductively coupled plasma mass spectrometry (SEC-ICP-MS) detection and synchrotron radiation X-ray fluorescence spectroscopy (SR-XRF) were used to analyze the Hg-Se-containing proteins in the serum from MeHg-poisoned rats. The Hg-Se-containing fractions monitored by UV and ICP-MS were further characterized by MALDI-TOF-MS. Elevated serum Hg and Se levels were found in MeHg-poisoned rats after SeNPs treatment. Three main Hg-containing bands with molecular weights (MWs) of 25, 62 and 140 kDa were detected in the control samples. Treatment with SeNPs increased the Hg content in proteins at 62 and 170 kDa and decreased the Hg content at 25 kDa. The fraction with 25 kDa was assigned to metallothioneins (MTs), and fractions with 40 and 75 kDa were assigned to albumin. This study showed that the low-toxicity SeNPs could reduce the Hg load in the tissues and promote the formation of high molecular weight Hg- and Se-containing proteins in MeHg-poisoned rats., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Selenium, an essential trace element, has been investigated as a potential cancer prevention agent. However, several studies have indicated that selenium supplementation may be associated with an increased risk of type 2 diabetes (T2D), although an equivocal relation of this nature requires confirmation., Objective: We examined the association between baseline plasma concentrations of selenium and the prevalence of T2D, as well as whether participant characteristics or intake of other antioxidant nutrients modified this relation., Methods: We conducted cross-sectional analyses of 1727 participants from the Selenium Trial, a randomized clinical trial of selenium supplementation for colorectal adenoma chemoprevention that had data for baseline selenium plasma concentrations, T2D status, and dietary intake. Logistic regression modeling was used to evaluate the associations between plasma selenium concentrations and prevalent T2D, adjusting for confounding factors. Heterogeneity of effect by participant characteristics was evaluated utilizing likelihood-ratio tests., Results: Mean ± SD plasma selenium concentrations for those with T2D compared with those without T2D were 143.6 ± 28.9 and 138.7 ± 27.2 ng/mL, respectively. After adjustment for confounding, higher plasma selenium concentrations were associated with a higher prevalence of T2D, with ORs (95% CIs) of 1.25 (0.80, 1.95) and 1.77 (1.16, 2.71) for the second and third tertiles of plasma selenium, respectively, compared with the lowest tertile (P-trend = 0.007). No significant effect modification was observed for age, sex, body mass index, smoking, or ethnicity. Increased odds of T2D were seen among those who were in the highest tertile of plasma selenium and the highest category of intake of β-cryptoxanthin (P-trend = 0.03) and lycopene (P-trend = 0.008); however, interaction terms were not significant., Conclusions: These findings show that higher plasma concentrations of selenium were significantly associated with prevalent T2D among participants in a selenium supplementation trial. Future work is needed to elucidate whether there are individual characteristics, such as blood concentrations of other antioxidants, which may influence this relation.

Previous study revealed that Se-GP11 could exhibited its antitumor activity by improving the immune functions. 5-Fu, as a chemotherapeutic drugs, can kill many immune cells in addition to tumor cells. Accordingly, the enhanced antitumor and reduced toxicity of Se-GP11 on 5-Fu were estimated in this study. The results demonstrated that Se-GP11 could evidently increase the antitumor activity of 5-Fu. Furthermore, Se-GP11 could enhance the immune functions during the tumor inhibition process of 5-Fu for increasing the cytokines secretion (IL-2 and TNF-α) and immune organs weights. In addition, Se-GP11 could reduce the toxicity of 5-Fu on liver by improving the hematological and biochemical parameters and up-regulating the SOD activities and down-regulating the MDA levels. Taken together, the results indicated that Se-GP11 may develop as an auxiliary preparation to chemical antitumor drugs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Traumatic brain injury (TBI) is a major cause of death and debility following trauma. The initial brain tissue insult is worsened by secondary reactive responses including oxidative stress reactions, inflammatory changes and subsequent permanent neurologic deficits. Effective agents to improve functional outcome and survival following TBI are scarce. Selenium is an antioxidant which has shown to reduce oxidative stress. This study examines the effect of intravenous selenium (Selenase ® ) treatment in patients with severe TBI on functional outcome and survival in a prospective study design., Methods: Patients sustaining TBI were prospectively identified during a 12-month period at an academic urban trauma center. Study inclusion criteria applied were: age ≥18 years, blunt injury mechanism and admission to neurosurgical intensive care unit (NICU). Early deaths (≤48h) and patients suffering extracranial injuries requiring invasive interventions or surgery were excluded. All consecutive admissions during a six-month period were administered intravenous Selenase ® for a maximum 10-day period and constituted cases. Patient demographics and outcomes up to six-months post-discharge were collected for analysis., Results: A total of 307 patients met inclusion criteria of which 125 were administered Selenase ® . Stepwise Poisson regression analysis identified five common predictors of poor functional outcome and in-hospital mortality: GCS ≤8, age ≥55 years, hypotension at admission, high Rotterdam score and invasive neurosurgical intervention. Selenase ® significantly reduced the risk of unfavourable functional outcomes, defined as GOS-E ≤4, at both discharge (adjusted RR 0.69, 95% CI 0.51-0.92, p=0.012) and at six months follow-up (adjusted RR 0.61, 95% CI 0.44-0.83, p=0.002). Following adjustment for significant group differences similar results were seen for functional outcome. Selenase ® did not improve survival (adjusted RR 1.12, 95% CI 0.62-2.02, p=0.709)., Conclusion: Intravenous Selenase ® treatment demonstrates a significant improvement in functional neurologic outcome. This effect is sustained at six months following discharge., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Sepsis is one of the main causes of death among critically ill patients. Sepsis pathogenesis includes infection by gram-negative and gram-positive bacteria, fungi, or both; exacerbated inflammatory response; hypotension, with potential to cause vasodilatory shock; and lesser delivery of oxygen to tissues due to impairment of oxygen utilization by cells. The participation of reactive species and/or free radicals such as nitric oxide (NO), peroxynitrite (ONOO - ), superoxide (O 2 - ), hydrogen peroxide (H 2 O 2 ), and hydroxyl radical (OH) has been reported to underlie these effects. Mitochondrial dysfunction is related to loss of inner membrane potential and inhibition of the mitochondrial electron transfer chain and FoF1-adenosine triphosphate-synthase, resulting in cellular energetic failure. In addition, overproduction of NO due to inducible nitric oxide synthase (iNOS) activity has been associated with harmful effects such as general vasodilatation and hypo-responsiveness to therapeutic vasoconstrictor agents. Considering that iNOS expression is regulated by nuclear factor-κB, which may be activated by ROS, antioxidants could inhibit the overexpression of iNOS in sepsis. In line with this, several antioxidants such as vitamins C and E, polyphenols, melatonin, β-glucan, N-acetylcysteine, mitochondrion-targeted antioxidants (MitoQ, MitoE, and peptides associated with dimethyltyrosine), selenium salts, and organoselenium compounds were effective in ameliorating oxidative stress in animal models of sepsis and in a number of clinical trials with septic patients., (Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.)

Supplementation with nontoxic doses of micronutrient selenium has been shown to alleviate chronic myelogenous leukemia (CML) via the elimination of leukemia stem cells (LSCs) in mice. This treatment provides a new and novel method for eliminating the LSCs that are otherwise not targeted by existing therapies. The antileukemic effect of selenium was dependent on the production of endogenous cyclopentenone prostaglandins (CyPGs), Δ-12 prostaglandin J 2 (Δ 12 -PGJ 2 ), and 15-deoxy-Δ12,14-prostaglandin J 2 (15d-PGJ 2 ). Here, we show that these endogenous CyPGs, produced by mice maintained on selenium-supplemented diets, alleviate the symptoms of CML through their ability to activate the nuclear hormone receptor, peroxisome proliferator activated receptor γ (PPARγ). GW9662, a potent PPARγ antagonist, blocked the antileukemic effect of selenium supplementation by significantly reducing CyPGs. This effect was mediated by an increase in 15-prostaglandin dehydrogenase (15-Pgdh) activity, which oxidizes and inactivates Δ 12 -PGJ 2 and 15d-PGJ 2 In contrast, treatment with the PPARγ agonist pioglitazone mimicked selenium supplementation. This treatment led to decreased 15-Pgdh activity and increased CyPG levels, which inhibited CML progression. Selenium-dependent activation of PPARγ mediated by endogenous CyPGs decreased Stat5 expression leading to the downregulation of Cited2, a master regulator of LSC quiescence. These studies suggest a potential role for selenium supplementation as an adjuvant therapy in CML., (© 2017 by The American Society of Hematology.)

Selenium (Se) is an essential micronutrient that functions as "redox gatekeeper" and homeostasis factor of normal and cancer cells. Epidemiology and experimental studies, in the last years suggested that both inorganic and organic forms of Se may have favorable health effects. In this regard, a protective action of Se on cellular systems that may help preventing cancer cell differentiation has been demonstrated, while the hypothesis that Se compounds may cure cancer and its metastatic diffusion appears speculative and is still a matter of investigation. Indeed, the overall actions of Se compounds in carcinogenesis are controversial. The recognition that cancer is a stem cell disease instigated major paradigm shifts in our basic understanding of cancer and attracted a great deal of interest. Although current treatment approaches in cancer are grounded in the need to kill the majority of cancer cells, targeting cancer stem cells (CSCs) may hold great potential in improving cancer treatment. In this respect, Se compounds have been demonstrated modulating numerous signaling pathways involved in CSC biology and these findings are now stimulating further research on optimal Se concentrations, most effective and cancer-specific Se compounds, and inherent pathways involved in redox and metabolic regulation of CSCs. In this review, we summarize the current knowledge about the effects of Se compounds on CSCs, by focusing on redox-dependent pathways and main gene regulation checkpoints that affect self-renewal, differentiation, and migration responses in this subpopulation of cancer cells., (© 2017 Elsevier Inc. All rights reserved.)

Chemopreventive activity of selenium (Se) may influence epigenome. In this review, we have discussed two aspects of Se and epigenetics in cancer, related to (1) the association between Se and epigenetic regulation in cancer development and prevention; (2) epigenetic modification of selenoprotein-encoding genes in different cancers. In both issues, we focused on DNA methylation as the most investigated epigenetic mechanism. The existing evidence from experimental data in human cancer cell lines, rodents, and human studies in cancer-free subjects indicates that: high Se exposure leads to the inhibition of DNA methyltransferase expression/activity; the association between Se and global methylation remains unclear and requires further investigation with respect to the underlying mechanisms and possible nonlinear character of this relationship; Se affects methylation of specific tumor suppressor genes, possibly in a sex-dependent manner; and cancer phenotype is often characterized by altered methylation of selenoprotein-encoding genes, mainly glutathione peroxidase 3., (© 2017 Elsevier Inc. All rights reserved.)

Background: Low selenium status in pregnancy has been associated with a number of adverse conditions. In nonpregnant populations, the selenium status or response to supplementation has been associated with polymorphisms in dimethylglycine dehydrogenase (DMGDH), selenoprotein P (SEPP1) and the glutathione peroxidases [cytosolic glutathione peroxidase (GPx1) and phospholipid glutathione peroxidase (GPx4)]., Objective: We hypothesized that, in pregnant women, these candidate polymorphisms would be associated with selenium status in early pregnancy, its longitudinal change, and the interindividual response to selenium supplementation at 60 μg/d., Design: With the use of stored samples and data from the United Kingdom Selenium in Pregnancy Intervention (SPRINT) study in 227 pregnant women, we carried out genetic-association studies, testing for associations between selenium status, its longitudinal change, and response to supplementation and common genetic variation in DMGDH (rs921943), SEPP1 (rs3877899 and rs7579), GPx1 (rs1050450) and GPx4 (rs713041). Selenium status was represented by the concentration of whole-blood selenium at 12 and 35 wk of gestation, the concentration of toenail selenium at 16 wk of gestation, and plasma glutathione peroxidase (GPx3) activity at 12 and 35 wk of gestation., Results: Our results showed that DMGDH rs921943 was significantly associated with the whole-blood selenium concentration at 12 wk of gestation (P = 0.032), which explained ≤2.0% of the variance. This association was replicated with the use of toenail selenium (P = 0.043). In unsupplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in whole-blood selenium from 12 to 35 wk of gestation (P = 0.005), which explained 8% of the variance. In supplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in GPx3 activity from 12 to 35 wk of gestation (P = 0.01), which explained 5.3% of the variance. Selenium status was not associated with GPx1, GPx4, or SEPP1 rs7579., Conclusions: In agreement with previous studies, we show that the genetic variant rs921943 in DMGDH is significantly associated with selenium status in United Kingdom pregnant women. Notably, our study shows that women who carry the SEPP1 rs3877899 A allele are better able to maintain selenium status during pregnancy, and their GPx3 activity increases more with supplementation, which suggests better protection from low selenium status. The SPRINT study was registered at www.isrctn.com as ISRCTN37927591.

Background: Selenomethionine, which is the principal dietary form of selenium, is metabolized by the liver to selenide, which is the form of the element required for the synthesis of selenoproteins. The liver synthesizes selenium-rich selenoprotein P (SEPP1) and secretes it into the plasma to supply extrahepatic tissues with selenium., Objectives: We conducted a randomized controlled trial to determine whether cirrhosis is associated with functional selenium deficiency (the lack of selenium for the process of selenoprotein synthesis even though selenium intake is not limited) and, if it is, whether the deficiency is associated with impairment of selenomethionine metabolism., Design: Patients with Child-Pugh (C-P) classes A, B, and C (mild, moderate, and severe, respectively) cirrhosis were supplemented with a placebo or supranutritional amounts of selenium as selenate (200 or 400 μg/d) or as selenomethionine (200 μg/d) for 4 wk. Plasma SEPP1 concentration and glutathione peroxidase (GPX) activity, the latter due largely to the selenoprotein GPX3 secreted by the kidneys, were measured before and after supplementation., Results: GPX activity was increased more by both doses of selenate than by the placebo in C-P class B patients. The activity was not increased more by selenomethionine supplementation than by the placebo in C-P class B patients. Plasma selenium was increased more by 400 μg Se as selenate than by the placebo in C-P class C patients. Within the groups who responded to selenate, there was a considerable variation in responses., Conclusion: These results indicate that severe cirrhosis causes mild functional selenium deficiency in some patients that is associated with impaired metabolism of selenomethionine. This trial was registered at clinicaltrials.gov as NCT00271245., (© 2015 American Society for Nutrition.)

Carboxylic group-induced synthesis of selenium nanoparticles (SeNPs) was achieved using sodium selenosulphate as a precursor. The particles were stabilized and capped with 0.01% polyvinyl alcohol under ambient conditions. This is a simple and easy method of producing SeNPs in a size range from 35 to 105 nm. The synthesized SeNPs were purified by centrifugation at 11,500 × g for 20 min and characterized by UV-visible spectroscopy, FTIR spectroscopy, XRD, DSC and TEM. It was observed that the synthesized SeNPs showed differences in their absorption spectra, phase composition and crystal structure, thermodynamic behaviour, size and shape. Further, to confirm anti-tumour potential of the synthesized SeNPs induced by the carboxylic group of acetic acid, pyruvic acid and benzoic acid, cell viability assay, nuclear morphology testing and DNA fragmentation assay were carried out using Dalton's lymphoma (DL) cells. DL cells treated with the SeNPs showed reduced cell viability, altered nuclear morphology, typical apoptotic DNA ladder and apoptosis. Therefore, these SeNPs may have therapeutic relevance to treat this type of cancer., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Viral and bacterial infections are often associated with deficiencies in macronutrients and micronutrients, including the essential trace element selenium. In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains. Dietary supplementation to provide adequate or supranutritional selenium supply has been proposed to confer health benefits for patients suffering from some viral diseases, most notably with respect to HIV and influenza A virus (IAV) infections. In addition, selenium-containing multimicronutrient supplements improved several clinical and lifestyle variables in patients coinfected with HIV and Mycobacterium tuberculosis. Selenium status may affect the function of cells of both adaptive and innate immunity. Supranutritional selenium promotes proliferation and favors differentiation of naive CD4-positive T lymphocytes toward T helper 1 cells, thus supporting the acute cellular immune response, whereas excessive activation of the immune system and ensuing host tissue damage are counteracted through directing macrophages toward the M2 phenotype. This review provides an up-to-date overview on selenium in infectious diseases caused by viruses (e.g., HIV, IAV, hepatitis C virus, poliovirus, West Nile virus) and bacteria (e.g., M. tuberculosis, Helicobacter pylori). Data from epidemiologic studies and intervention trials, with selenium alone or in combination with other micronutrients, and animal experiments are discussed against the background of dietary selenium requirements to alter immune functions., (© 2015 American Society for Nutrition.)

Background: Selenium is found in soils and is essential for human antioxidant defense and immune function. In Malawi, low soil selenium and dietary intakes coupled with low plasma selenium concentrations in HIV infection could have negative consequences for the health of HIV-infected mothers and their exclusively breastfed infants., Objective: We tested the effects of lipid-based nutrient supplements (LNS) that contained 1.3 times the Recommended Dietary Allowance of sodium selenite and antiretroviral drugs (ARV) on maternal plasma and breast-milk selenium concentrations., Design: HIV-infected Malawian mothers in the Breastfeeding, Antiretrovirals, and Nutrition study were randomly assigned at delivery to receive: LNS, ARV, LNS and ARV, or a control. In a subsample of 526 mothers and their uninfected infants, we measured plasma and breast-milk selenium concentrations at 2 or 6 (depending on the availability of infant samples) and 24 wk postpartum., Results: Overall, mean (± SD) maternal (range: 81.2 ± 20.4 to 86.2 ± 19.9 μg/L) and infant (55.6 ± 16.3 to 61.0 ± 15.4 μg/L) plasma selenium concentrations increased, whereas breast-milk selenium concentrations declined (14.3 ± 11.5 to 9.8 ± 7.3 μg/L) from 2 or 6 to 24 wk postpartum (all P < 0.001). Compared with the highest baseline selenium tertile, low and middle tertiles were positively associated with a change in maternal plasma or breast-milk selenium from 2 or 6 to 24 wk postpartum (both P < 0.001). With the use of linear regression, we showed that LNS that contained selenium and ARV were not associated with changes in maternal plasma and breast-milk selenium, but maternal selenium concentrations were positively associated with infant plasma selenium at 2 or 6 and 24 wk postpartum (P < 0.001) regardless of the study arm., Conclusions: Selenite supplementation of HIV-infected Malawian women was not associated with a change in their plasma or breast-milk selenium concentrations. Future research should examine effects of more readily incorporated forms of selenium (ie, selenomethionine) in HIV-infected breastfeeding women.

Oxidative stress and low-grade systemic inflammation may contribute to the pathogenesis of obesity-induced comorbidities, including nonalcoholic fatty liver disease. Increasing intake of dietary antioxidants might be beneficial, but there are few data in obese children. To examine the effect of antioxidant supplementation on biomarkers of oxidative stress, inflammation, and liver function, we randomly assigned overweight or obese children and adolescents (n = 44; mean ± SD age: 12.7 ± 1.5 y) participating in a lifestyle modification program to a 4-mo intervention with daily antioxidants (vitamin E, 400 IU; vitamin C, 500 mg; selenium, 50 μg) or placebo. We measured anthropometrics, antioxidant status, oxidative stress (F(2)-isoprostanes, F(2)-isoprostane metabolites), inflammation, liver enzymes, fasting insulin and glucose, and lipid profile at baseline and endpoint. There was a significant treatment effect of antioxidant supplementation on antioxidant status [α-tocopherol, β = 23.2 (95% CI: 18.0, 28.4); ascorbic acid, β = 70.6 (95% CI: 51.7, 89.4); selenium, β = 0.07 (95% CI: 0.01, 0.12)] and oxidative stress [8-iso-prostaglandin F2α, β = -0.11 (95% CI: -0.19, -0.02)] but not on any of the inflammatory markers measured. There was a significant treatment effect on alanine aminotransferase [β = -0.13 (95% CI: -0.23, -0.03)], a trend toward a significant effect on aspartate aminotransferase [β = -0.04 (95% CI: -0.09, 0.01)], and no significant effect on γ-glutamyltransferase [β = -0.03 (95% CI: -0.11, 0.06)]. In summary, antioxidant supplementation for 4 mo improved antioxidant-oxidant balance and modestly improved liver function tests; however, it did not reduce markers of systemic inflammation despite significant baseline correlations between oxidative stress and inflammation. The study was registered at clinicaltrials.gov as NCT01316081.

Selenium is incorporated as the unique amino acid selenocysteine into selenoproteins, which regulate important biologic processes such as redox balance. The results of epidemiologic and clinical investigations are inconclusive regarding the relation of the plasma selenium level to cardiometabolic parameters and does not support the routine use of selenium supplements to prevent cancer or cardiovascular disease. Variability in the selenium status of the populations studied and lack of standardization of measures of selenium status may account for part of the confusion regarding selenium and cardiometabolic health. Another possibility is that differences in the effects of selenoproteins, as opposed to those of low-molecular-weight selenium compounds derived from in vivo metabolism of selenium, may explain the unusual phenomenon of a similar phenotype induced by both selenium deficiency and excess in experimental models and offer a plausible explanation for the lack of consistency in clinical studies. The epidemiologic, clinical, and experimental evidence, although inconclusive in terms of the precise relation of selenium to cardiometabolic health, is however very intriguing in terms of the urgent need for further mechanistic research to enable the clinical use of this potent micronutrient.

In 2010, in France, 8,790 men died from prostate cancer despite a low and decreasing mortality rate. The individual risk/benefit ratio of prostate cancer screening is the focus of controversy and currently not in favor of a systematic screening program. Therefore, only prevention could reduce incidence, side effects of treatment and related mortality. Interestingly, prostate cancer prevention is also a field of controversy mainly about 5-alpha-reductase inhibitors. However, it could be expected that pharmaco- or diet-based prevention will be a huge tool for cancer control, even more for prostate cancer burden. This review comprehensively analyses which molecules or compounds could be used in preventive trials. With regard to pharmaco-prevention, three different kinds of drugs could be identified. First drugs, which aim at mainly or even solely reduce prostate cancer risk such as 5-alpha-reductase inhibitors and selective estrogen receptor modulators. Drugs, which aim at wider preventive impact such as: nonsteroidal anti-inflammatory drugs or difluoromethylornithine. Lastly, drugs for which reducing prostate cancer incidence is merely a side effect such as statins, metformin or histones desacetylase inhibitors. With regard to diet-based prevention, two main approaches could be identified: aliments and nutriments, on one hand, and vitamin and minerals, on the other. Interestingly if compounds reach experimental plausibility, natural foods or even global diet seem to have a higher impact. Lastly, besides assessment of efficacy, effectiveness required the critical step of compliance, which might actually be the weakest link of the prevention chain.

Oxidative stress is a key feature in the pathogenesis of pre-eclampsia and antioxidants have been proposed as a potential therapy in the treatment of this important complication of pregnancy. In this report selenium supplementation was used to up-regulate the antioxidant enzymes glutathione peroxidase and thioredoxin reductase and the protective effect that this had on cellular metabolism during oxidative stress was examined. Bewo and Jeg-3 trophoblast cells were supplemented with organic and inorganic forms of selenium and 3 forms of peroxide in a range of doses were utilised to generate oxidative stress. Thioredoxin reductase and glutathione peroxidase activity were maximally expressed after supplementation with 100 nM NaSe and 500 nM SeMethionine. Application of H₂O₂ in the range of 200-400 μM for 24h resulted in significant (p<0.001) inhibition of cellular activity, an effect negated by Se supplementation. Tert-butyl H₂O₂ and cumene H₂O₂ concentrations between 30 and 50 uM similarly inhibited cellular activity and this could be significantly (p<0.001) reversed by Se supplementation. Auranofin, a specific inhibitor of thioredoxin reductase and glutathione peroxidase was used to prove that the protective effect generated by Se supplementation was due to up regulation of these enzymes. These studies provide direct evidence that selenium supplementation can up-regulate endogenous antioxidant systems and protects trophoblast cells from oxidative stress. This may inform the development of future therapies for pre-eclampsia and emphasises the importance of selenium adequacy during pregnancy., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

Background: A genetic variant at codon 200 (Pro200Leu) of the gene encoding for glutathione peroxidase 1 (GPx1), a selenium-dependent enzyme, is associated with lower enzyme activity; however, the evidence is limited to in vitro and observational studies., Objective: The objective was to determine whether the GPx1 Pro200Leu genetic variants modify the response of whole-blood glutathione peroxidase (GPx) activity to selenium supplementation in patients with coronary artery disease in New Zealand., Design: The results from 2 parallel-design, double-blind trials were combined. Participants were randomly assigned to receive a daily supplement of 100 μg Se as l-selenomethionine (n = 129) or placebo (n = 126) for 12 wk. Plasma selenium and whole-blood GPx activity were measured at baseline and at week 12. Participants were genotyped for the GPx1 Pro200Leu polymorphism., Results: Selenium supplementation increased whole-blood GPx activity by 5 (95% CI: 4, 7) U/g hemoglobin (P < 0.001); however, the magnitude of the increase did not differ by genotype (P = 0.165 for treatment-by-genotype interaction). In an exploratory analysis, a significant nutrient-gene interaction was apparent when baseline plasma selenium concentrations were included in the regression model (P = 0.006 for treatment-by-genotype × baseline selenium concentration interaction). Increases in GPx activity were 2-fold higher in Pro homozygotes than in participants carrying a Leu allele when baseline selenium concentrations were ≤1.15 μmol/L (P < 0.05)., Conclusions: These results indicate that GPx1 Pro200Leu variants do not substantially modify the response of whole-blood GPx to selenium supplementation in individuals with relatively high plasma selenium concentrations. A nutrient-gene interaction was observed when the baseline selenium concentration was low, but this requires independent confirmation. This trial was registered at www.actr.org.au as ACTRN12605000412639 and ACTRN12606000197538.

The present study focuses on the synthesis of stable selenium nanoparticles (SeNPs) and the elucidation of their mechanism of action in preventing the growth of mammary tumors. Selenious acid and reduced glutathione in the presence of sodium alginate were used as precursors for synthesis of SeNPs. Cell viability and expression of apoptotic markers (pp38, Bax, and cytochrome c) were assessed in MCF-7 and MDA-MB-231 breast cancer cells treated with SeNPs. Reduction in tumor volume was measured in rats with dimethylbenz[a]anthracene-induced mammary tumors. Synthesized SeNPs ranged in size from 40 to 90 nm and were stable up to 3 months of storage. We report that SeNP-induced cell death and expression of pp38, Bax, and cytochrome c were significantly higher in estrogen receptor-α (ERα)-positive cells (MCF-7) but not in ERα-negative cells (MDA-MB-231). Interestingly, animals showing significant decrease in tumor volume (small tumors) had lower levels of ERα as compared with animals showing a nonsignificant decrease in tumor volume (large tumor). This is the first report in our knowledge suggesting that the anticancer activity of SeNPs correlates with the level of ERα in breast cancer cells both in vivo and in vitro., From the Clinical Editor: This study focuses on the synthesis of selenium nanoparticles (SeNPs) with the goal of preventing the growth of breast cancer cells, suggesting that the anticancer activity of SeNPs correlates with the level of ERα in breast cancer cells both in vivo and in vitro., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives and Methods: Alterations in redox biology are established in depression; however, there are no prospective epidemiological data on redox-active selenium in depression. We aimed to determine if low levels of dietary selenium are associated with an increased risk for de novo major depressive disorder (MDD). In this nested case-control study, women aged 20 years or more were identified from a randomly selected cohort being followed prospectively for the Geelong Osteoporosis Study. Cases were individuals with incident MDD, identified using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP); controls had no such history. Dietary selenium intake was measured using a food frequency questionnaire at baseline, together with anthropometric and lifestyle measures., Results: Eighteen women who developed de novo MDD were classified as cases; there were 298 controls. Low dietary selenium intakes increased the likelihood of developing MDD; OR 2.74 (95%CI 0.95-7.89). After adjusting for age and SES, compared with a high selenium intake, a low intake (<8.9 μg/MJ/day) was associated with an approximate trebling of the likelihood for developing de novo MDD; OR 2.95 (95%CI 1.00-8.72). Smoking, alcohol consumption and physical activity did not confound the association., Conclusion: These data suggest that lower dietary selenium intakes are associated with an increased risk of subsequent de novo MDD. We propose that selenium's function as an antioxidant, and as a constituent of selenoproteins that are important in redox homeostasis, warrants further investigation as a risk factor for depression, and suggest a potentially novel modifiable factor in the primary prevention and management of depression., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Antioxidants such as selenium, vitamin E and C and carotenoids have been hypothesized as chemopreventive agents for several cancers. In the current review, we evaluate the results of epidemiological and interventional studies and summarize current knowledge of the prevention potential of the antioxidants, specific to gastrointestinal cancers. While early studies based on animal models and cell lines showed promise for antioxidants as chemopreventive agents for several gastrointestinal cancers, results from epidemiological studies and randomized trials do not support this promise. One large randomized trial, conducted in a region with widespread nutritional deficiency, showed that antioxidant use may confer protection against gastrointestinal cancers. However, this result has not been replicated in other epidemiological studies or the 10 other randomized trials conducted in developed Western countries. Overall, currently there is no evidence that antioxidants are protective against gastrointestinal cancers in populations whose members are replete in antioxidant intake., (Copyright © 2011. Published by Elsevier Ltd.)

The past two decades of research into Xeroderma pigmentosum (XP), an autosomal recessive disease, has been marked by significant progress in understanding the molecular basis of this rare disease. More importantly, especially from the perspective of the affected families, is that this knowledge has been applied to diagnose the condition both in utero as well as in the very early days of life. The eight known XP genes and their different phenotypes present a number of challenges that the XP Workshop sponsored by the NIH in 2010 has highlighted. There is little current treatment specifically designed for any of the XP types other than standard dermatological and neurological evaluations and care. The Xeroderma Pigmentosum Family Support Group (XPFSG) is dedicated to serving families with children and adults with all forms of XP and to help them better understand the condition, to identify practical measures which can be taken by the XP patients and their families to mitigate the effects of the disease, and to serve as patient advocates to help families discuss issues with their physicians. We summarize our efforts in terms of outreach within the US and abroad to affected families and discuss XPFSG-sponsored clinical initiatives that include molecular diagnoses, treatment, and initial proof-of-concept studies that can, if successful, improve the lives of XP patients in the near term., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Acute exposure to pesticides can cause hepatotoxicity. Our study pertains to the potential ability of selenium and/or vitamin E, used as nutritional supplements, to alleviate oxidative stress induced by dimethoate. Female Wistar rats were randomly divided into seven groups of six each: group I served as controls; group II received in their drinking water dimethoate (2 g L(-1)); group III received both dimethoate and selenium (0.5 mg/kg of diet); group IV was treated with dimethoate and vitamin E (100 mg/kg of diet); group V received dimethoate+selenium+vitamin E and groups VI and VII received either selenium or vitamin E. The exposure of rats to dimethoate for 30 days promoted oxidative stress with an increase in malondialdehyde and a decrease in glutathione and non-protein thiol levels. A decrease in glutathione peroxidase, superoxide dismutase and catalase activities was also observed. While, plasma transaminases, lactate dehydrogenase activities and bilirubin levels increased. Co-administration of selenium and/or vitamin E through diet improved the biochemical parameters cited above. Liver histological studies confirmed biochemical parameters and the beneficial roles of selenium and vitamin E., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: This study compares the efficacies of vitamin E and selenium, both individually and in combination, for the prevention of postoperative intra-abdominal adhesions in rats., Methods: Forty-seven female rats were divided into five groups. The sham animals (S group, n = 7) were given only laparotomies and intraperitoneally received 0.9% NaCl (2 ml). In the 40 other rats, abrasions of the left uterine horn were performed, followed by intraperitoneal administration of either 2 ml 0.9% NaCl (C group), 10 mg vitamin E (vitamin E group), 0.2 mg/kg selenium (Se group) or 10 mg vitamin E with 0.2 mg/kg selenium (vitamin E + Se group), with 10 animals in each treatment group., Results: Adhesion formation was significantly reduced in animals in the Se and vitamin E + Se groups (p<0.05). Tissue catalase and glutathione peroxidase activities did not significantly differ between the groups. However, catalase and glutathione peroxidase activities and reduced glutathione levels were slightly increased in the vitamin E, Se and vitamin E + Se groups. In the vitamin E group, malondialdehyde concentrations were significantly lower than in the C group (p<0.05), but no significant differences were present among the S, C, Se and vitamin E + Se groups. Levels of nitric oxide were significantly higher in the C group than in the other groups (p<0.01)., Conclusion: Intraperitoneal administration of selenium or combined vitamin E and selenium appears to be effective in preventing intra-abdominal adhesion formation in rat models through the reduction of lipid peroxidation products.

Nutritional supplementation may provide a viable treatment alternative in patients with psoriasis. Randomized, controlled trials have shown the effectiveness of topical vitamin A and D derivatives, intravenous ω-3 fatty acids, oral inositol, and various combined therapies. Dual therapies of ultraviolet B phototherapy and fish oil, retinoids and thiazolidinediones, and cyclosporine and a low-calorie diet were effective in the treatment of psoriasis in randomized, controlled trials. This contribution also reviews the potential negative effect of alcohol and the potential positive effects of vitamin B(12), selenium, retinoic acid metabolism-blocking agents, and a gluten-free diet in the treatment of psoriasis., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: Recent studies have reported that antioxidant status, including serum selenium concentrations, is altered in women who develop preeclampsia. We wished to examine the effects of selenium supplementation in the prevention of preeclampsia in high-risk pregnant women., Design: We carried out a randomized, double-blind, placebo-controlled pilot trial. A total of 166 primigravid pregnant women, who were in the first trimester of pregnancy, were randomized to receive 100 microg of selenium (n = 83; dropouts, n = 22) or a placebo (n = 83; dropouts, n = 19) per day until delivery. The incidence of preeclampsia, serum selenium concentrations, lipid profile and high-sensitivity C-reactive protein status were evaluated at baseline and at the end of the study., Results: Supplementation with selenium was not associated with any reported major side effects and was associated with a significant increase in mean serum selenium concentrations at term (p < 0.001). In contrast, mean serum selenium concentrations remained unchanged in the control group (p = 0.63). The incidence of preeclampsia was lower in the selenium group (n = 0) than in the control group (n = 3), although this was not statistically significant (p > 0.05). After treatment, systolic and diastolic blood pressure, serum total cholesterol, triglycerides, low-density and high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein were significantly increased in both groups compared with pretreatment levels (p < 0.05)., Conclusion: Our findings indicate that selenium supplementation in pregnant women may be associated with a lower frequency of preeclampsia., (Copyright 2010 Taiwan Association of Obstetrics and Gynecology. Published by Elsevier B.V. All rights reserved.)

Information on selenium bioavailability is required to derive dietary recommendations and to evaluate and improve the quality of food products. The need for robust data is particularly important in light of recent suggestions of potential health benefits associated with different intakes of selenium. The issue is not straightforward, however, because of large variations in the selenium content of foods (determined by a combination of geologic/environmental factors and selenium supplementation of fertilizers and animal feedstuffs) and the chemical forms of the element, which are absorbed and metabolized differently. Although most dietary selenium is absorbed efficiently, the retention of organic forms is higher than that of inorganic forms. There are also complications in the assessment and quantification of selenium species within foodstuffs. Often, extraction is only partial, and the process can alter the form or forms present in the food. Efforts to improve, standardize, and make more widely available techniques for species quantification are required. Similarly, reliable and sensitive functional biomarkers of selenium status are required, together with improvements in current biomarker methods. This requirement is particularly important for the assessment of bioavailability, because some functional biomarkers respond differently to the various selenium species. The effect of genotype adds a potential further dimension to the process of deriving bioavailability estimates and underlines the need for further research to facilitate the process of deriving dietary recommendations in the future.

Inadequate supply of the essential trace element selenium (Se) has been associated with predisposition for, or manifestation of, various human diseases such as Keshan and Kashin-Beck disease, cancer, impaired immune function, neurodegenerative and age-related disorders and disturbances of the thyroid hormone axis. Se deficiency in combination with inadequate iodine contributes to the pathogenesis of myxedematous cretinism. The recent identification of various distinct selenocysteine-containing proteins, encoded by 25 human genes, provides information on the molecular and biochemical basis of beneficial and possible adverse effects of this trace element. The thyroid gland is among the human tissues with the highest Se content per mass unit similar to other endocrine organs and the brain. Selenoproteins involved in cellular antioxidative defence systems and redox control, such as the glutathione peroxidase (GPx) and the thioredoxin reductase (TxnRd) family, are involved in protection of the thyroid gland from excess hydrogen peroxide and reactive oxygen species produced by the follicles for biosynthesis of thyroid hormones. In addition, the three key enzymes involved in activation and inactivation of thyroid hormones, the iodothyronine deiodinases (DIO1,2,3), are selenoproteins with development, cell- and pathology-related expression patterns. While nutritional Se supply is normally sufficient for adequate expression of functional Dio enzymes with exception of long-term parenteral nutrition and certain diseases impairing gastrointestinal absorption of Se compounds, the nutritional Se supply for the protection of the thyroid gland and synthesis of some more abundant selenoproteins of the GPx and the TrxR family might be limiting their proper expression under (patho-)physiological conditions.