Methylglyoxal

甲基乙二醛
  • 文章类型: Journal Article
    电子烟的潜在危害和好处,或电子尼古丁输送系统(ENDS),已受到公共卫生和监管社区的极大关注。这样的产品可以为可燃香烟吸烟者提供降低的尼古丁递送风险的手段,同时不适当地吸引尼古丁幼稚的年轻人。许多作者已经检查了来自各种开放和封闭系统ENDS的气溶胶的化学复杂性。这里回顾了这一系列的文献,使用两种非致癌物(甲基乙二醛,丁醛)和致癌物N-亚硝基或尼古丁(NNN)的癌症风险分析。我们确定了96篇相关论文,包括17、13和5个甲基乙二醛的报告数据,丁醛,NNN,分别。使用低端(最小气溶胶浓度,低ENDS使用)和高端(最大气溶胶浓度,高端使用)假设,甲基乙二醛(1.78×10-3-135μg/kg-bw/day)和丁醛(1.9×10-4-66.54μg/kg-bw/day)的估计剂量分别对应于227-17,200,000和271-280,000,使用确定的出发点(PoD)。9.90×10-6-1.99×10-4μg/kg-bw/天NNN的剂量对应于每100,000个ENDS用户1.4-28个剩余癌症,相对于每100,000吸烟者7440的NNN归属盈余。结论是ENDS气溶胶中的甲基乙二醛和丁醛,虽然不是无害的,在ENDS用户中没有出现刺激性效应的显著风险。ENDS气溶胶中NNN的致癌风险降低,但没有消除,相对于可燃香烟烟雾中报告的浓度。
    The potential harms and benefits of e-cigarettes, or electronic nicotine delivery systems (ENDS), have received significant attention from public health and regulatory communities. Such products may provide a reduced risk means of nicotine delivery for combustible cigarette smokers while being inappropriately appealing to nicotine naive youth. Numerous authors have examined the chemical complexity of aerosols from various open- and closed-system ENDS. This body of literature is reviewed here, with the risks of ENDS aerosol exposure among users evaluated with a margin of exposure (MoE) approach for two non-carcinogens (methylglyoxal, butyraldehyde) and a cancer risk analysis for the carcinogen N-nitrosonornicotine (NNN). We identified 96 relevant papers, including 17, 13, and 5 reporting data for methylglyoxal, butyraldehyde, and NNN, respectively. Using low-end (minimum aerosol concentration, low ENDS use) and high-end (maximum aerosol concentration, high ENDS use) assumptions, estimated doses for methylglyoxal (1.78 × 10-3-135 μg/kg-bw/day) and butyraldehyde (1.9 × 10-4-66.54 μg/kg-bw/day) corresponded to MoEs of 227-17,200,000 and 271-280,000,000, respectively, using identified points of departure (PoDs). Doses of 9.90 × 10-6-1.99 × 10-4 μg/kg-bw/day NNN corresponded to 1.4-28 surplus cancers per 100,000 ENDS users, relative to a NNN-attributable surplus of 7440 per 100,000 cigarette smokers. It was concluded that methylglyoxal and butyraldehyde in ENDS aerosols, while not innocuous, did not present a significant risk of irritant effects among ENDS users. The carcinogenic risks of NNN in ENDS aerosols were reduced, but not eliminated, relative to concentrations reported in combustible cigarette smoke.
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  • 文章类型: Journal Article
    麦卢卡蜂蜜(MH)是一种非常珍贵的天然产品,来自Leptospermumscovarium花的花蜜。全球市场竞争的加剧推动了MH产品创新。这篇综述更新了比较和非比较研究,以强调营养,治疗性的,生物工程,和MH的化妆品值。MH是酚类和独特化合物的良好来源,如甲基乙二醛,二羟基丙酮,leptosperin乙二醛,甲基丁香酸盐和leptosin。根据体外的证据,体内和临床研究,MH的多功能生物活性化合物表现出抗氧化,抗炎,免疫调节,抗微生物,和抗癌活性。有一些与MH有关的有争议的话题,如MH分级,安全性/有效性,隐含的好处,以及相关污染物的最高水平。人工智能可以优化与化学分析相关的MH研究,毒性预测,多功能机制探索和产品创新。
    Manuka honey (MH) is a highly prized natural product from the nectar of Leptospermum scoparium flowers. Increased competition on the global market drives MH product innovations. This review updates comparative and non-comparative studies to highlight nutritional, therapeutic, bioengineering, and cosmetic values of MH. MH is a good source of phenolics and unique chemical compounds, such as methylglyoxal, dihydroxyacetone, leptosperin glyoxal, methylsyringate and leptosin. Based on the evidence from in vitro, in vivo and clinical studies, multifunctional bioactive compounds of MH have exhibited anti-oxidative, anti-inflammatory, immunomodulatory, anti-microbial, and anti-cancer activities. There are controversial topics related to MH, such as MH grading, safety/efficacy, implied benefits, and maximum levels of contaminants concerned. Artificial intelligence can optimize MH studies related to chemical analysis, toxicity prediction, multi-functional mechanism exploration and product innovation.
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  • 文章类型: Journal Article
    治疗性蛋白质是有效的,在治疗各种疾病中非常有效的速效药物。在过去的10年里,药用蛋白质的使用有所增加,随着我们更好地了解疾病的分子途径,它将进一步发展。然而,它与高加工成本有关,有限的稳定性,作为口服药物给药困难,以及大型蛋白质无法穿透组织并到达其目标位置。已经开发了许多方法来克服治疗性蛋白质的稳定性和伴侣活性的问题。viz.,添加外部试剂(通过使用稳定赋形剂改变周围溶剂的性质,例如,氨基酸,糖,糖多元醇)和内部试剂(影响其结构特性的化学修饰,例如,突变,糖基化)。然而,这些方法必须彻底清除蛋白质的不稳定性和伴侣问题。在精细调整伴侣蛋白质以增加其生物学功效和稳定性方面仍有许多工作要做。甲基乙二醛(MGO),一种有效的二羰基化合物,与蛋白质反应并形成共价交联。许多关于MGO清除剂的研究已经进行了,因为已知它们会改变蛋白质结构,这可能导致生物活性和稳定性的改变。MGO是在我们体内自然产生的,然而,它对伴侣和蛋白质稳定性的影响需要更好地理解,并且似乎因浓度而异。这篇综述强调了几个研究小组对MGO对各种蛋白质的影响的努力。它还解决了MGO对客户端蛋白质的影响,α-晶状体蛋白,了解蛋白质伴侣和稳定性问题的潜在解决方案。
    Therapeutic proteins are potent, fast-acting drugs that are highly effective in treating various conditions. Medicinal protein usage has increased in the past 10 years, and it will evolve further as we better understand disease molecular pathways. However, it is associated with high processing costs, limited stability, difficulty in being administered as an oral medication, and the inability of large proteins to penetrate tissue and reach their target locations. Many methods have been developed to overcome the problems with the stability and chaperone activity of therapeutic proteins, viz., the addition of external agents (changing the properties of the surrounding solvent by using stabilizing excipients, e.g., amino acids, sugars, polyols) and internal agents (chemical modifications that influence its structural properties, e.g., mutations, glycosylation). However, these methods must completely clear protein instability and chaperone issues. There is still much work to be done on finetuning chaperone proteins to increase their biological efficacy and stability. Methylglyoxal (MGO), a potent dicarbonyl compound, reacts with proteins and forms covalent cross-links. Much research on MGO scavengers has been conducted since they are known to alter protein structure, which may result in alterations in biological activity and stability. MGO is naturally produced within our body, however, its impact on chaperones and protein stability needs to be better understood and seems to vary based on concentration. This review highlights the efforts of several research groups on the effect of MGO on various proteins. It also addresses the impact of MGO on a client protein, α-crystallin, to understand the potential solutions to the protein\'s chaperone and stability problems.
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  • 文章类型: Journal Article
    内生真菌,生活在植物内部组织和器官中的微生物,已知会产生许多生物活性化合物,包括,有时,寄主植物的一些植物化学物质。出于这样的原因,内生菌被引用为发现生物活性化合物的潜在来源,特别是,医学兴趣。目前,许多非传染性疾病威胁着全球人类健康,值得注意的是:糖尿病,神经退行性疾病,癌症,和其他与慢性炎症和衰老有关的疾病。有趣的是,这些疾病的发病机制和发展与糖基化终产物(AGEs)的过度形成和积累有关。AGEs是一组异质的化合物,可以改变构象,函数,和蛋白质的寿命。因此,防止AGEs形成和随后积累的化合物(抗AGEs化合物)可能有助于延缓一些慢性疾病的进展,和/或不当AGEs积累的有害影响。尽管内生菌产生生物活性化合物的能力显著,文献中报道的大多数天然抗AGEs化合物来源于植物。因此,这项工作涵盖了26种植物抗AGEs化合物和一些被报道为内生代谢产物的衍生物,并讨论了重要性,可能的优势,以及使用内生菌作为抗AGEs化合物的潜在来源的挑战。
    Endophytes, microorganisms that live in the internal tissues and organs of the plants, are known to produce numerous bioactive compounds, including, at times, some phytochemicals of their host plant. For such reason, endophytes have been quoted as a potential source for discovering bioactive compounds, particularly, of medical interest. Currently, many non-communicable diseases are threatening global human health, noticeably: diabetes, neurodegenerative diseases, cancer, and other ailment related to chronic inflammation and ageing. Intriguingly, the pathogenesis and development of these diseases have been linked to an excessive formation and accumulation of advanced glycation end products (AGEs). AGEs are a heterogeneous group of compounds that can alter the conformation, function, and lifetime of proteins. Therefore, compounds that prevent the formation and consequent accumulation of AGEs (AntiAGEs compounds) could be useful to delay the progress of some chronic diseases, and/or harmful effects of undue AGEs accumulation. Despite the remarkable ability of endophytes to produce bioactive compounds, most of the natural antiAGEs compounds reported in the literature are derived from plants. Accordingly, this work covers 26 plant antiAGEs compounds and some derivatives that have been reported as endophytic metabolites, and discusses the importance, possible advantages, and challenges of using endophytes as a potential source of antiAGEs compounds.
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  • 文章类型: Journal Article
    麦卢卡蜂蜜(MH)从其他蜂蜜类型中脱颖而出,是一种独特的超级食品,具有临床证明的抗菌和伤口愈合活性。其独特的特性和广泛的应用(即食品,化妆品,保健品/天然保健品)的价格是其他蜂蜜类型的6到25倍。随着市场需求的增加,出现了更多的MH欺诈行为。这敦促使用分析工具进行MH的真实性和质量评估,并且在过去的几十年中一直是许多研究人员的重点。我们的主要重点是通过Scifinder(https://sinfinder。cas.org)和WebofScience(https://webofknowledge.com)研究引擎。我们使用了“manuka蜂蜜分析”,“麦卢卡蜂蜜质量控制”,和“manuka蜂蜜真实性”作为搜索词,应用布尔运算符“AND/OR”组合,在2017年1月从以下电子数据库进行表演。重点介绍了MH的最新分析方法和各自的化学标记。本研究利用了用于MH质量控制和分析的最新方法,以确保其真实性和掺假检测。MH的独特成分允许其通过各种分析平台成功进行区分,包括与合适的色谱分离(即GC-MS和LC-MS)耦合的质谱,核磁共振(NMR),和荧光分析。此外,化学计量学工具显示了MH辨别的潜力,尚未在MH质量控制分析中得到更多利用。
    Manuka honey (MH) stands out from other honey types as a unique super-food with clinically proven antimicrobial and wound healing activities. Its unique traits and the broad range of applications (i.e. food, cosmetics, nutraceuticals /natural health products) have marked up its price 6 to 25 times than other honey types. Concurrent to the increased market demand, more fraudulence of MH emerged. This urged for the employment of analytical tools for the authenticity and quality assessment of MH and has been the focus of many researchers during the last decades. Our main focus was to review the literature dealing with MH authenticity during the period from 2010 to mid-2021 comprehensively via the Scifinder (https://sinfinder.cas.org) and Web of Science (https://webofknowledge.com) research engines. We used \"manuka honey analysis\", \"manuka honey quality control\", and \"manuka honey authenticity\" as a search terms, applied Boolean operators \'AND/OR\' combination, performing in Jan 2017 from the following electronic databases. The state-of-the-art analytical approaches and respective chemical markers of MH are highlighted. The present study capitalizes on the most updated methodologies employed for the quality control and analysis of MH to ensure its authenticity and adulteration detection. The unique constituents of MH allowed for its successful discrimination through various analytical platforms, including mass spectrometry coupled to suitable chromatographic separation (i.e. GC-MS and LC-MS), nuclear magnetic resonance (NMR), and fluorescence analysis. Moreover, chemometric tools present potential for MH discrimination and has yet to be capitalized more upon for MH quality control analysis.
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  • 文章类型: Journal Article
    乙二醛酶系统是一个普遍存在的酶网络,在生物生命中起着重要作用。它由乙二醛酶1(GLO1)组成,乙二醛酶2(GLO2),和还原型谷胱甘肽(GSH),通过将甲基乙二醛(MG)和其他内源性有害代谢物解毒成无毒的d-乳酸,在细胞中发挥必需的代谢功能。MG和MG衍生的糖基化终产物(AGEs)与各种疾病有关,比如糖尿病,心血管疾病,神经退行性疾病和癌症,GLO1是抗糖基化防御中的关键限速酶。GLO1在各种疾病中的异常活性和表达使这种酶成为药物设计和开发的有希望的靶标。本文综述了GLO1在各种致病条件下的调控机制,并对GLO1调控因子的发现进行了深入的讨论。包括GLO1活化剂和抑制剂。不同的阶级,包括化学结构和构效关系。此外,本文还介绍了发现乙二醛酶系统小分子调节剂的方法。与基于分光光度计的测定法相比,基于微孔板的检测方法更简单,快速定量的高通量方法。这篇综述将有助于设计新颖且有效的GLO1调节剂,并希望为研究人员提供方便的参考。
    The glyoxalase system is a ubiquitous enzymatic network which plays important roles in biological life. It consists of glyoxalase 1 (GLO1), glyoxalase 2 (GLO2), and reduced glutathione (GSH), which perform an essential metabolic function in cells by detoxifying methylglyoxal (MG) and other endogenous harmful metabolites into non-toxic d-lactate. MG and MG-derived advanced glycation endproducts (AGEs) are associated with various diseases, such as diabetes, cardiovascular disease, neurodegenerative disorders and cancer, and GLO1 is a key rate-limiting enzyme in the anti-glycation defense. The abnormal activity and expression of GLO1 in various diseases make this enzyme a promising target for drug design and development. This review focuses on the regulatory mechanism of GLO1 in diverse pathogenic conditions with a thorough discussion of GLO1 regulators since their discovery, including GLO1 activators and inhibitors. The different classes, chemical structure and structure-activity relationship are embraced. Moreover, assays for the discovery of small molecule regulators of the glyoxalase system are also introduced in this article. Compared with spectrophotometer-based assay, microplate-based assay is a more simple, rapid and quantitative high-throughput method. This review will be useful to design novel and potent GLO1 regulators and hopefully provide a convenient reference for researchers.
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  • 文章类型: Journal Article
    晚期糖基化终产物(AGEs)是在非酶促反应中通过糖与DNA的氨基结合产生的一组异质分子,脂质和蛋白质。肌肽是一种天然存在的具有抗氧化活性的二肽,抑制蛋白质羰基化和糖基化。本系统综述搜索了截至2018年4月底的任何一年的所有已发表和未发表的英文原创研究的国际资料。PubMed的电子搜索,进行了Scopus和GoogleScholar。最初发现187篇文章,排除重复数据后选择133篇文章。评论文章,基于肌肽成分的研究和关于肌肽对AGEs诱导变化的影响的研究被排除.总的来说,36项研究符合纳入标准。这包括19项体外研究,15项动物研究和两项人体研究。除了两项研究外,所有研究都表明肌肽可以防止AGEs的形成。这篇综述的结果表明肌肽具有抗糖基化特性,并可能阻碍蛋白质羰基的形成和还原糖诱导的交联;然而,很少有人类研究。肌肽阻止AGEs形成的机制需要进一步研究。
    Advanced glycation end products (AGEs) are a cluster of heterogeneous molecules that are generated in a non-enzymatic reaction by the binding of sugars with amino groups of DNA, lipids and proteins. Carnosine is a naturally occurring dipeptide with antioxidant activity, which inhibits protein carbonylation and glycoxidation. This systematic review searched international sources for all published and unpublished original research in English from any year up to the end of April 2018. An electronic search of PubMed, Scopus and Google Scholar was conducted. 187 articles were initially found and 133 articles were selected after excluding duplicated data. Review articles, studies based on the components of carnosine and studies that were about the effects of carnosine on AGEs-induced changes were excluded. In total, 36 studies met the inclusion criteria. This included 19 in vitro studies, 15 animal studies and two human studies. All but two of the studies indicated that carnosine can prevent the formation of AGEs. The findings of this review indicating that carnosine has anti-glycating properties, and may hinder the formation of protein carbonyls and the cross-links induced by reduced sugars; however, there were few human studies. The mechanism by which carnosine prevents the formation of AGEs needs further investigation.
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