selenoproteins

硒蛋白
  • 文章类型: Journal Article
    硒已被证明可以影响多种生物学功能,显示为必需的微量营养素。功能研究证明了均衡硒饮食的好处,以及硒的缺乏与多种疾病的关系。尤其是癌症和病毒性疾病。硒是一种抗氧化剂,保护细胞免受损害,增强免疫系统的反应,预防心血管疾病,减少炎症。硒可以以无机和有机形式发现,其在细胞中的主要形式是掺入硒蛋白的硒代半胱氨酸。目前人类基因组中已知25种硒蛋白:谷胱甘肽过氧化物酶,碘甲状腺原氨酸脱碘酶,硫氧还蛋白还原酶,硒磷酸合成酶,和其他硒蛋白。这些蛋白质导致硒在组织中的运输,防止氧化损伤,有助于内质网的应激,控制炎症。由于这些功能,在过去的二十年中,人们对硒蛋白多态性的影响越来越感兴趣。硒蛋白基因多态性可能影响蛋白质结构和血浆硒浓度及其吸收,甚至影响某些疾病的发生和发展。这篇综述旨在阐明硒蛋白的作用,并了解其基因多态性如何影响生理条件的平衡。在这篇多态性综述中,我们专注于PubMed数据库,仅在2003年至2023年之间以英文发表的文章。使用的关键词是“硒蛋白”和“多态性”。不涉及主题的文章被排除在外。硒和硒蛋白在分子研究中还有很长的路要走,一些工作证明了它们的多态性作为某些疾病的风险生物标志物的重要性,尤其是心血管和甲状腺疾病,糖尿病,和癌症。
    Selenium has been proven to influence several biological functions, showing to be an essential micronutrient. The functional studies demonstrated the benefits of a balanced selenium diet and how its deficiency is associated with diverse diseases, especially cancer and viral diseases. Selenium is an antioxidant, protecting the cells from damage, enhancing the immune system response, preventing cardiovascular diseases, and decreasing inflammation. Selenium can be found in its inorganic and organic forms, and its main form in the cells is the selenocysteine incorporated into selenoproteins. Twenty-five selenoproteins are currently known in the human genome: glutathione peroxidases, iodothyronine deiodinases, thioredoxin reductases, selenophosphate synthetase, and other selenoproteins. These proteins lead to the transport of selenium in the tissues, protect against oxidative damage, contribute to the stress of the endoplasmic reticulum, and control inflammation. Due to these functions, there has been growing interest in the influence of polymorphisms in selenoproteins in the last two decades. Selenoproteins\' gene polymorphisms may influence protein structure and selenium concentration in plasma and its absorption and even impact the development and progression of certain diseases. This review aims to elucidate the role of selenoproteins and understand how their gene polymorphisms can influence the balance of physiological conditions. In this polymorphism review, we focused on the PubMed database, with only articles published in English between 2003 and 2023. The keywords used were \"selenoprotein\" and \"polymorphism\". Articles that did not approach the theme subject were excluded. Selenium and selenoproteins still have a long way to go in molecular studies, and several works demonstrated the importance of their polymorphisms as a risk biomarker for some diseases, especially cardiovascular and thyroid diseases, diabetes, and cancer.
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  • 文章类型: Journal Article
    硒(Se)是一种必需的微量营养素,在细胞和分子抗癌过程中具有多种功能。有证据表明,根据其化学形式和剂量使用,Se可以在某些抗癌机制中充当调节剂。然而,有机和无机形式的膳食硒的代谢集中在主要途径上。据报道,不同的硒化合物作为化学预防剂具有至关重要的作用,如抗氧化活性,激活凋亡途径,选择性细胞毒性,抗血管生成作用,和细胞周期调制。如今,人们对寻找可以增强不同硒源的抗肿瘤作用的疗法产生了极大的兴趣。在这里,据报道,不同的研究与组合疗法的效果有关,硒与蛋白质结合使用,多糖,化疗剂或纳米颗粒。另一个重要因素是与硒代谢或硒蛋白合成相关的基因中存在单核苷酸多态性,可以预防癌症。这些研究和机制在癌症治疗中显示出有希望的结果。这篇综述旨在汇编已证明硒在分子水平上的抗癌作用及其用作化学预防和癌症治疗的潜力的研究。
    Selenium (Se) is an essential micronutrient with several functions in cellular and molecular anticancer processes. There is evidence that Se depending on its chemical form and the dosage use could act as a modulator in some anticancer mechanisms. However, the metabolism of organic and inorganic forms of dietary selenium converges on the main pathways. Different selenocompounds have been reported to have crucial roles as chemopreventive agents, such as antioxidant activity, activation of apoptotic pathways, selective cytotoxicity, antiangiogenic effect, and cell cycle modulation. Nowadays, great interest has arisen to find therapies that could enhance the antitumor effects of different Se sources. Herein, different studies are reported related to the effects of combinatorial therapies, where Se is used in combination with proteins, polysaccharides, chemotherapeutic agents or as nanoparticles. Another important factor is the presence of single nucleotide polymorphisms in genes related to Se metabolism or selenoprotein synthesis which could prevent cancer. These studies and mechanisms show promising results in cancer therapies. This review aims to compile studies that have demonstrated the anticancer effects of Se at molecular levels and its potential to be used as chemopreventive and in cancer treatment.
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  • 文章类型: Meta-Analysis
    过度暴露于硒(Se)对葡萄糖代谢有害,主要是因为它的促氧化作用和硒蛋白的过表达。这项系统评价和荟萃分析前所未有地评估了补充硒对健康啮齿动物血糖控制的影响。该方法遵循系统审查和荟萃分析(PRISMA)的首选报告项目。我们在电子数据库中搜索了截至2022年5月发表的文章。使用实验动物实验系统审查中心(SYRCLE)和荟萃分析和实验研究动物数据审查协作方法(CAMARADES)评估偏倚风险和方法学质量。结果表示为整体(SMD)和95%置信限(CI)的荟萃分析估计。在检索到的2359条记录中,包括13项研究,其中11个使用亚硒酸钠,两个使用零价硒纳米颗粒(SeNP)作为补充。9项研究纳入荟萃分析。一般来说,偏倚风险较高,23.1%的研究质量较高.补充亚硒酸钠显着增加空腹血糖(FBG)[SMD=2.57(95%CI1.07-4.07),I2=93.5%(p=0.001)。亚组分析显示,持续21天至28天的干预措施效果更大[SMD=25.74(95%CI2.29-9.18),I²=96.1%(p=0.001)]和剂量为864.7μg/kg/天的亚硒酸钠[SMD=10.26(95%CI2.42-18.11),I²=97.1%(p=0.010)]。然而,它不影响谷胱甘肽过氧化物酶(GPX)活性[SMD=0.60(95%CI-0.71-1.91),I²=83.2%(p=0.37])。当前的分析表明,亚硒酸钠补充剂对健康啮齿动物的血糖控制有不利影响。
    Overexposure to Se is detrimental to glucose metabolism, mainly because of its pro-oxidant effects and the overexpression of selenoproteins. This systematic review evaluated the effects of Se supplementation on glycaemic control in healthy rodents. The methodology followed the PRISMA. We searched the databases for articles published up to May 2022. The risk of bias and the methodological quality were assessed using the SYRCLE and CAMARADES. The results are presented as meta-analytic estimates of the overall standardised mean difference (SMD) and 95 % CI. Of the 2359 records retrieved, thirteen studies were included, of which eleven used sodium selenite and two used zero-valent Se nanoparticles as supplement. Nine studies were included in the meta-analysis. Generally, the risk of bias was high, and 23·1 % of the studies were of high quality. Supplementation with sodium selenite significantly increased fasting blood glucose (SMD = 2·57 (95 % CI (1·07, 4·07)), I2 = 93·5 % (P = 0·001). Subgroup analyses showed effect size was larger for interventions lasting between 21 and 28 d (SMD = 25·74 (95 % CI (2·29, 9·18)), I2 = 96·1 % (P = 0·001)) and for a dose of 864·7 μg/kg/d of sodium selenite (SMD = 10·26 (95 % CI (2·42, 18·11), I2 = 97·1 % (P = 0·010)). However, it did not affect glutathione peroxidase activity (SMD = 0·60 (95 % CI (-0·71, 1·91)), I2 = 83·2 % (P = 0·37)). The current analysis demonstrated the adverse effects of sodium selenite supplementation on glycaemic control in healthy rodents.
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  • 文章类型: Journal Article
    硒(Se)是一种对人类和动物具有促健康作用的元素。然而,根据硒的化学形式,这种元素的缺乏和过量都可能对身体有害,补充的持续时间,以及人类的健康状况。许多数据表明,由于硒在土壤和食品中的含量低,人类和动物对硒的需求覆盖面不足。通过动物和人类饲料中有机活性矿物质的适当百分比,可以实现身体生理过程的平衡。硒是一种对人体非常重要的微量矿物质,维护各种过程所需的;主要是,硒维持免疫内分泌,新陈代谢,和细胞稳态。最近,这一因素已成为各种疾病最有希望的治疗选择.因此,近年来,基于Se的研究一直在增加。本审查旨在提供与硒及其不同形式及其对健康的影响有关的最新信息。
    Selenium (Se) is an element that has a pro-health effect on humans and animals. However, both the deficiency of this element and its excess may prove harmful to the body depending on the chemical form of the selenium, the duration of supplementation, and the human health condition. Many data indicate insufficient coverage of the demand for selenium in humans and animals due to its low content in soils and food products. A balance in the physiological process of the body can be achieved via the proper percentage of organically active minerals in the feed of animals as well as human beings. Selenium is a trace mineral of great importance to the body, required for the maintenance of a variety of its processes; primarily, selenium maintains immune endocrine, metabolic, and cellular homeostasis. Recently, this element has been emerging as a most promising treatment option for various disorders. Therefore, research based on Se has been increasing in recent times. The present review is designed to provide up-to-date information related to Se and its different forms as well as its effects on health.
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  • 文章类型: Journal Article
    Stroke is characterized by deleterious oxidative stress. Selenoprotein enzymes are essential endogenous antioxidants, and detailed insight into their role after stroke could define new therapeutic treatments. This systematic review aimed to elucidate how blood selenoprotein concentration and activity change in the acute phase of stroke.
    We searched PubMed, EMBASE, and Medline databases for studies measuring serial blood selenoprotein concentration or activity in acute stroke patients or in stroke patients compared to non-stroke controls. Meta-analyses of studies stratified by the type of stroke, blood compartment, and type of selenoprotein measurement were conducted.
    Eighteen studies and data from 941 stroke patients and 708 non-stroke controls were included in this review. Glutathione peroxidase (GPx) was the only identified selenoprotein, and its activity was most frequently measured. Results from 12 studies and 693 patients showed that compared to non-stroke controls in acute ischaemic stroke patients, the GPx activity increased in haemolysate (standardized mean difference [SMD]: 0.27, 95% CI: 0.07-0.47) but decreased in plasma (mean difference [MD]: -1.08 U/L, 95% CI: -1.94 to -0.22) and serum (SMD: -0.54, 95% CI: -0.91 to -0.17). From 4 identified studies in 106 acute haemorrhagic stroke patients, the GPx activity decreased in haemolysate (SMD: -0.40, 95% CI: -0.68 to -0.13) and remained unchanged in plasma (MD: -0.10 U/L, 95% CI: -0.81 to 0.61) and serum (MD: -5.00 U/mL, 95% CI: -36.17 to 26.17) compared to non-stroke controls. Results from studies assessing the GPx activity in the haemolysate compartment were inconsistent and characterized by high heterogeneity.
    Our results suggest a reduction of the blood GPx activity in acute ischaemic stroke patients, a lack of evidence regarding a role for GPx in haemorrhagic stroke patients, and insufficient evidence for other selenoproteins.
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  • 文章类型: Journal Article
    Over the last few decades, substantial progress has been made towards the understanding of cardiovascular diseases. In-depth mechanistic insights have also provided opportunities to explore novel therapeutic targets and to discover new treatment regimens. Therapeutic enzymes are examples of such opportunities. The enzymes protect against a variety of cardiovascular diseases, however, even minor malfunctioning of these enzymes may lead to deleterious outcomes. Owing to their great versatility, the inhibition and activation of these enzymes are key regulatory approaches to counter the onset and progression of several cardiovascular impairments. While cardiovascular remedies are already available in excess and are efficacious, a comprehensive description of novel therapeutic enzymes to combat cardiovascular diseases would still be of great benefit. In the light of this, the regulation of functional activities of these enzymes also opens a new avenue for the treatment approaches to be employed. This review describes the importance of non-conventional enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), phosphodiesterase (PDE), arginase, superoxide dismutase (SOD), thioredoxin reductase (TXNRD) and selenoprotein T (SELENOT), cytochrome b5 reductase 3 (CYB5R3), epoxide hydrolase (EHs), xanthine oxidoreductase (XOR), matrix metalloprotease (MMPs), and dopamine beta hydroxylase (DBH), as potential candidates in several cardiovascular disorders while highlighting some of the recently targeted therapeutic enzymes in cardiovascular diseases. We also discuss the role of intrinsic antioxidant defense system involved in cardioprotection followed by addressing some of the clinical investigations considering the use of antioxidant as a preferred therapy of cardiovascular complications.
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  • 文章类型: Journal Article
    硒(Se)是一种重要的微量元素,对人类健康和疾病具有许多积极作用。重要的是要指定硒的状态和消耗是针对特定社区的,因为硒的水平在不同人群和地区之间是极其不可预测的。我们现有的论文基于硒对人类健康和疾病的影响以及中东国家硒水平的数据。总的来说,这项全面审查的结果表明,中东国家的硒的消费量和水平不足。这样的发现,随着人们越来越意识到硒对整体健康的重要性,需要进一步的工作,主要是建立一个可接受的血硒浓度范围或其他措施,以确定最佳的硒消耗和,因此,确保低硒摄入高风险人群补充充足的硒。
    Selenium (Se) is an important microelement with numerous positive effects on human health and diseases. It is important to specify that the status and consumption of Se are for a specific community as the levels of Se are extremely unpredictable between different populations and regions. Our existing paper was based on the impacts of Se on human health and disease along with data on the Se levels in Middle Eastern countries. Overall, the findings of this comprehensive review show that the consumption and levels of Se are inadequate in Middle Eastern nations. Such findings, together with the growing awareness of the importance of Se to general health, require further work primarily on creating an acceptable range of blood Se concentration or other measures to determine optimal Se consumption and, consequently, to guarantee adequate Se supplementation in populations at high risk of low Se intake.
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  • 文章类型: Journal Article
    硒(Se)是一种重要的痕量矿物质,在动物和人类健康中在细胞和生物体水平上具有许多重要作用。硒的生物学效应主要由硒蛋白(在人类中由25个基因编码,在小鼠中由24个基因编码)进行。作为硒蛋白的重要组成部分,Se发挥结构和酶作用;在后一种情况下,它以其催化和抗氧化功能而闻名。涉及不同动物模型的研究为我们对硒和硒蛋白在哺乳动物生育和繁殖中的潜在影响的理解增加了巨大价值。在这次审查中,我们强调了硒蛋白在男性生育力和生殖中的意义,以及硒和硒蛋白与整体男性生殖功能相关的特征性生物学功能。从过去的研究(动物和人类)的观察中可以明显看出,硒是精子发生和男性生育能力所必需的。推测是由于其在调节抗氧化防御机制和其他必需的生物学途径以及氧化还原敏感转录因子中的重要作用。然而,铭记主流文学的证据,还建议进行更多的研究,重点是阐明特殊和规范的硒蛋白所扮演的其他角色,即,谷胱甘肽过氧化物酶4(GPX4)和硒蛋白P(SELENOP)在男性生殖中的作用。然而,寻找阐明可能由其他生物学相关硒蛋白调节的其他推定机制也应包括在未来的研究范围内.然而,至于硒对男性生育力和生殖的影响,尽管有一些临床试验探讨了硒补充剂对男性生育能力的影响,由于受试者招募的不一致和设计的异质性,这些研究的比较仍然很复杂,不太清楚。因此,我们期待进一步研究硒和硒蛋白的作用,以验证现有证据,并概述旨在提高男性生育力的任何治疗方案。因此,可以为男性生育力和硒补充主题增加新的维度。
    Selenium (Se) is an important trace mineral having many essential roles at the cellular and organismal levels in animal and human health. The biological effects of Se are mainly carried out by selenoproteins (encoded by 25 genes in humans and 24 in mice). As an essential component of selenoproteins, Se performs structural and enzymic roles; in the latter context it is well known for its catalytic and antioxidative functions. Studies involving different animal models have added great value to our understanding regarding the potential implications of Se and selenoproteins in mammalian fertility and reproduction. In this review, we highlight the implications of selenoproteins in male fertility and reproduction followed by the characteristic biological functions of Se and selenoproteins associated with overall male reproductive function. It is evident from observations of past studies (both animal and human) that Se is essentially required for spermatogenesis and male fertility, presumably because of its vital role in modulation of antioxidant defense mechanisms and other essential biological pathways and redox sensitive transcription factors. However, bearing in mind the evidences from mainstream literature, it is also advisable to perform more studies focusing on the elucidation of additional roles played by the peculiar and canonical selenoproteins i.e., glutathione peroxidase 4 (GPX4) and selenoprotein P (SELENOP) in the male reproductive functions. Nevertheless, search for the elucidation of additional putative mechanisms potentially modulated by other biologically relevant selenoproteins should also be included in the scope of future studies. However, as for the implication of Se in fertility and reproduction in men, though a few clinical trials explore the effects of Se supplementation on male fertility, due to inconsistencies in the recruitment of subjects and heterogeneity of designs, the comparison of such studies is still complicated and less clear. Therefore, further research focused on the roles of Se and selenoproteins is awaited for validating the evidences at hand and outlining any therapeutic schemes intended for improving male fertility. As such, new dimensions could be added to the subject of male fertility and Se supplementation.
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  • 文章类型: Journal Article
    Selenium (Se) is an essential micronutrient that has several important functions in animal and human health. The biological functions of Se are carried out by selenoproteins (encoded by twenty-five genes in human and twenty-four in mice), which are reportedly present in all three domains of life. As a component of selenoproteins, Se has structural and enzymatic functions; in the latter context it is best recognized for its catalytic and antioxidant activities. In this review, we highlight the biological functions of Se and selenoproteins followed by an elaborated review of the relationship between Se and female reproductive function. Data pertaining to Se status and female fertility and reproduction are sparse, with most such studies focusing on the role of Se in pregnancy. Only recently has some light been shed on its potential role in ovarian physiology. The exact underlying molecular and biochemical mechanisms through which Se or selenoproteins modulate female reproduction are largely unknown; their role in human pregnancy and related complications is not yet sufficiently understood. Properly powered, randomized, controlled trials (intervention vs. control) in populations of relatively low Se status will be essential to clarify their role. In the meantime, studies elucidating the potential effect of Se supplementation and selenoproteins (i.e., GPX1, SELENOP, and SELENOS) in ovarian function and overall female reproductive efficiency would be of great value.
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  • 文章类型: Journal Article
    Selenium (Se) is an essential trace element of significant importance in human health. Diet is the major source of Se, and intake of this element depends on its concentration in food sources as well as the amount of those sources consumed. Unfortunately, daily dietary intake of Se in most European countries is generally low, ∼30-40μg/day, compared with the recommended dietary allowance, ∼55 and 70μg/day for adult females and males, respectively. The importance of Se as an essential trace element is linked to its role as selenocysteine in a number of selenoproteins including antioxidant enzymes glutathione peroxidases (GSH-Pxs), thioredoxin reductases (TrxRs), and selenoprotein P (SePP). These enzymes protect tissues against the damaging effect of reactive oxygen species (ROS) and other endogenous products of cellular metabolism implicated in DNA damage and potentially leading to mutagenesis, cell death, and carcinogenesis. Reduced body Se and antioxidant enzyme activity during pregnancy results in oxidative stress within tissues contributing to premature birth, miscarriage, preeclampsia, and intrauterine growth retardation. Because placenta development is highly dependent on oxygen status, uncontrolled ROS formation is likely detrimental. Despite these findings, the role of Se and Se-dependent enzymes in pregnancy remains controversial. The objective of this review is to explore Se status in pregnancy with respect to adverse outcomes. Effects related to decreased antioxidant activity and increased oxidative stress will be highlighted.
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