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#29054422   2017/10/21 Save this To Up

Selenoproteins in Tumorigenesis and Cancer Progression.

Selenium is a micronutrient essential to human health and has long been associated with cancer prevention. Functionally, these effects are thought to be mediated by a class of selenium-containing proteins known as selenoproteins. Indeed, many selenoproteins have antioxidant activity which can attenuate cancer development by minimizing oxidative insult and resultant DNA damage. However, oxidative stress is increasingly being recognized for its "double-edged sword" effect in tumorigenesis, whereby it can mediate both negative and positive effects on tumor growth depending on the cellular context. In addition to their roles in redox homeostasis, recent work has also implicated selenoproteins in key oncogenic and tumor-suppressive pathways. Together, these data suggest that the overall contribution of selenoproteins to tumorigenesis is complicated and may be affected by a variety of factors. In this review, we discuss what is currently known about selenoproteins in tumorigenesis with a focus on their contextual roles in cancer development, growth, and progression.

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#29054419   2017/10/21 Save this To Up

Selenium and Epigenetics in Cancer: Focus on DNA Methylation.

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.

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#29054415   2017/10/21 Save this To Up

Selenium-Dependent Glutathione Peroxidases During Tumor Development.

Five out of eight human glutathione peroxidases (GPxes) are selenoproteins and thus their expression depends on the selenium (Se) supply. Most Se-dependent GPxes are downregulated in tumor cells, while only GPx2 is considerably upregulated. Whether expression profiles of GPxes predict tumor development and patient survival is controversially discussed. Also, results from in vitro and in vivo studies modulating the expression of GPx isoforms provide evidence for both anti- and procarcinogenic mechanisms. GPxes are able to reduce hydroperoxides, which otherwise would damage DNA, possibly resulting in DNA mutations, modulate redox-sensitive signaling pathways affecting proliferation, differentiation, and cellular metabolism or initiate cell death. Considering these different processes, the role and functions of individual Se-dependent GPx isoforms will be discussed herein in the context of tumorigenesis.

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#29054015   2017/10/20 Save this To Up

Synergistic effect of copper and arsenic upon oxidative stress, inflammation and autophagy alterations in brain tissues of Gallus gallus.

Arsenic or copper is one of the most highly toxic pollution that can cause dysfunction to brains, however, the exact mechanism remains unclear. The aim of the study is to investigate the mechanisms of arsenic or/and copper-induced oxidative stress, inflammation and autophagy in chicken brains and elucidate the interactions between arsenic and copper. A total of 72 1-day-old Hy-line chickens were divided into four groups (18 chickens per group) treated with 30mg/kg arsenic trioxide (As2O3) or/and 300mg/kg copper sulfate (CuSO4) for 12weeks. Histological signs of inflammation were found in the cerebrum, cerebellum and brainstem exposure to arsenic or/and copper. The malondialdehyde (MDA) content were up-regulation, whereas oxidative damage parameters total antioxidant capacity (T-AOC), glutathione (GSH), the inhibition ability of hydroxyl radical (OH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were significantly decreased (P<0.05). The mRNA levels and protein expressions of inflammation markers, such as nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and prostaglandin E synthase (PTGEs) were significantly increased (P<0.05). The mRNA levels and protein expressions of autophagy markers including phosphatidylinositol 3-kinase (PI3K), Akt, autophagy-related gene 5 (ATG5), microtubule-associated protein light chains 3 (LC3), ATG4B, and Becline1 in different regions of brains were up-regulation (P<0.05), except the mammalian target of rapamycin complex (mTORC). In conclusion, we speculated that arsenic or copper could induce oxidative stress, inflammation and autophagy in chicken brains, and there may have a synergistic effect between copper and arsenic.

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#29053995   2017/10/20 Save this To Up

Effects of a whey protein supplementation on oxidative stress, body composition and glucose metabolism among overweight people affected by diabetes mellitus or impaired fasting glucose: A pilot study.

Obesity and diabetes mellitus type 2 (DM2) are characterized by chronic inflammation and oxidative stress [Donath et al. 2013] and this leads to cardiovascular diseases [Hulsmans & Holvoet 2010]. Whey proteins (WP) have antioxidant [Chitapanarux et al. 2009], anti-inflammatory [Sugawara et al. 2012] and hypoglycemic activities [Mignone et al. 2015], while data on weight, body composition [Frestedt et al. 2008; Aldrich et al. 2011] and blood pressure are conflicting [Kawase et al. 2000; Lee et al. 2007]. WP have unpleasant taste and smell [Patel 2015], but a new WP isolate (ProLYOtin®) seems to be more palatable. 40 g/die of ProLYOtin® were supplemented to overweight people (n=31) with impaired fasting glucose/DM2 for 12 weeks. Markers of antioxidant status (total antioxidant status, glutathione peroxidase, glutathione reductase, uric acid), oxidative damage (thiobarbituric acid reactive substances, advanced oxidation protein products, 8-hydroxydeoxyguanosine), inflammation (interleukin-6, high sensitive reactive protein C) and glicemic status (fasting glucose, insulin, glycated hemoglobin), anthropometric data (weight, height, waist circumference), body composition (body cell mass, fat mass), blood pressure, hand grip strength and skin autofluorescence were measured before and at the end of supplementation. Isolate palatability was evaluated. An increase in glutathione peroxidase, a decrease in uric acid and no change in glutathione reductase, total antioxidant status, oxidative damage, inflammation and glucose markers were found. Significant improvements in anthropometric parameters and fat mass were detected. There wasn't any change in blood pressure, skin autofluorescence and physical performance. Two-thirds of subjects judged the supplement positively. ProLYOtin® seems suitable for treatment of OS and overweight.

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#29053632   2017/10/20 Save this To Up

Protective Effect of Flavonoids from Ziziphus jujuba cv. Jinsixiaozao against Acetaminophen-Induced Liver Injury by Inhibiting Oxidative Stress and Inflammation in Mice.

This study was aimed to investigate the chemical composition, antioxidant activities and hepatoprotective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao (ZJF). The composition of ZJF was analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography-mass spectrometry (LC-MS), and antioxidant properties were investigated by biological assays in vitro. The hepatoprotective activity of ZJF was evaluated in acetaminophen (APAP)-treated BALB/c mice. Results indicate that ZJF displayed significant antioxidant capacity. Pretreatment with ZJF significantly decreased APAP-elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TB). Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were enhanced with ZJF administration, while malondialdehyde (MDA) level and glutathione (GSH) depletion were reduced. Meanwhile, ZJF reversed the suppression of nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and up-regulated the protein expression of NAD(P)H: quinone oxidoreductase 1(NQO1) in liver damage mice. Furthermore, ZJF attenuated APAP-induced inflammatory mediator production, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β). Expression of p65 showed that ZJF dampened nuclear factor-κB (NF-κB) activation. The results strongly indicate that the hepatoprotective role of ZJF in APAP-induced hepatotoxicity might result from its induction of antioxidant defense via activation of Nrf2 and reduction of inflammation via inhibition of NF-κB.

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#29050423   2017/10/20 Save this To Up

Effect of sodium selenite and selenium yeast on performance, egg quality, antioxidant capacity, and selenium deposition of laying hens.

This study compared the effects of sodium selenite and selenium yeast and their combination on laying performance, egg quality, antioxidant capacity, and selenium (Se) contents in tissues and eggs. Two-hundred-eighty-eight Jing Hong layers that were similar in laying rate (87.5 ± 0.38%) and body weight (1.70 ± 0.02 kg) were randomly distributed into 4 treatments for 11 wk (from 203 d old to 279 d old) with 9 replicates of 8 hens per replicate. The diets (corn-soybean meal diet) were supplemented with 0 [blank control (BC)], 0.3 mg/kg Se from sodium selenite (SS), 0.15 mg/kg Se from sodium selenite and 0.15 mg/kg Se from Se yeast (SS+SY), or 0.3 mg/kg Se from Se yeast (SY). Results showed that the laying rate of the SS+SY group increased significantly (P < 0.05) compared to the BC and SY groups. There were no differences (P > 0.05) in egg quality between the Se-supplemented diets and the BC diet. The serum glutathione peroxidase (GSH-Px) activity was increased (P < 0.01) in hens fed Se-supplemented diets compared to the BC diet. The liver superoxide dismutase (SOD) activity of the SY group was increased significantly (P < 0.05) compared to the BC group. Significant increase (P < 0.01) due to SY supplementation was noted in the serum vitamin E content compared to BC and SS. Layers fed Se-supplemented diets had higher (P < 0.01) contents of Se in the serum, liver, and kidney compared to the BC diet. Compared to BC, Se content in eggs was significantly increased (P < 0.05) by feeding supplementary Se. In conclusion, the effects of SS and Se yeast were approximately equal in promoting antioxidant capacity of laying hens, while Se yeast is easier to deposit into eggs and tissues. The diet with added equal amounts of the 2 sources of Se was more cost effective and affordable than a comparable amount of Se yeast to obtain the promising production performance and nearly similar Se deposition.

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#29048364   2017/10/19 Save this To Up

Protective Effect of Argan and Olive Oils against LPS-Induced Oxidative Stress and Inflammation in Mice Livers.

Sepsis causes severe dysregulation of organ functions, via the development of oxidative stress and inflammation. These pathophysiological mechanisms are mimicked in mice injected with bacterial lipopolysaccharide (LPS). Here, protective properties of argan oil against LPS-induced oxidative stress and inflammation are explored in the murine model. Mice received standard chow, supplemented with argan oil (AO) or olive oil (OO) for 25 days, before septic shock was provoked with a single intraperitoneal injection of LPS, 16 hours prior to animal sacrifice. In addition to a rise in oxidative stress and inflammatory markers, injected LPS also caused hepatotoxicity, accompanied by hyperglycemia, hypercholesterolemia and hyperuremia. These LPS-associated toxic effects were blunted by AO pretreatment, as corroborated by normal plasma parameters and cell stress markers (glutathione: GSH) and antioxidant enzymology (catalase, CAT; superoxide dismutase, SOD and glutathione peroxidase, GPx). Hematoxylin-eosin staining revealed that AO can protect against acute liver injury, maintaining a normal status, which is pointed out by absent or reduced LPS-induced hepatic damage markers (i.e., alanine aminotransferase (ALT) and aspartate transaminase (AST)). Our work also indicated that AO displayed anti-inflammatory activity, due to down-regulations of genes encoding pro-inflammatory cytokines Interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) and in up-regulations of the expression of anti-inflammatory genes encoding Interleukin-4 (IL-4) and Interleukin-10 (IL-10). OO provided animals with similar, though less extensive, protective changes. Collectively our work adds compelling evidence to the protective mechanisms of AO against LPS-induced liver injury and hence therapeutic potentialities, in regard to the management of human sepsis. Activations of IL-4/Peroxisome Proliferator-Activated Receptors (IL-4/PPARs) signaling and, under LPS, an anti-inflammatory IL-10/Liver X Receptor (IL-10/LXR) route, obviously indicated the high potency and plasticity of the anti-inflammatory properties of argan oil.

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#29044452   2017/10/18 Save this To Up

Effects of alpha lipoic acid on motor function and antioxidant enzyme activity of nerve tissue after sciatic nerve crush injury in rats.

Background: Alpha lipoic acid (ALA) that is a strong antioxidant drug is tried for both protection and treatment of various diseases of central and peripheral nervous systems.

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#29043349   2017/10/18 Save this To Up

Comparative suppressing effects of black and green teas on the formation of advanced glycation end products (AGEs) and AGE-induced oxidative stress.

This study aimed at investigating and comparing the anti-diabetic potential of black and green teas. Biochemical analyses indicate higher antioxidant potency, significantly correlated with the phytochemicals present, in green teas compared to black teas. Both extracts afforded a similar level of protection to erythrocytes against peroxyl radical-induced lysis. Non-cytotoxic concentration of green and black tea extracts significantly reduced the reactive oxygen species (ROS) production (P < 0.01), lowered the oxidation of proteins (P < 0.05) and decreased the IL-6 secretion (P < 0.01) induced by AGEs or H2O2 in 3T3-L1 preadipocytes. Both teas also inhibited the decline in the enzymatic activities of superoxide dismutase, catalase and glutathione peroxidase induced by the pro-oxidants. The teas further suppressed the glycation of BSA mediated by glucose, ribose and MGO by reducing fluorescent AGE, fructosamine, protein carbonyl and AOPP levels. Black and green teas also inhibited the activities of α-amylase (AA50: 589.86 ± 39.51 and 947.80 ± 18.20 μg mL(-1), respectively) and α-glucosidase (AA50: 72.31 ± 4.23 and 100.23 ± 8.10 μg mL(-1), respectively). The teas afforded a comparable level of protection at the cellular level and against glycation while black tea exerted the highest carbohydrate hydrolysing enzymes inhibitory activity. Our results clearly show that black and green teas represent an important source of antioxidants with anti-diabetic potential.

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