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Why are aging and stress associated with dementia, cancer, and other diverse medical conditions? Role of pineal melatonin interactions with the HPA axis in mitochondrial regulation via BAG-1 为什么衰老和压力与痴呆、癌症和其他各种疾病有关?松果体褪黑素通过BAG-1与HPA轴相互作用在线粒体调控中的作用
Pub Date : 2023-09-30 DOI: 10.32794/mr112500158
George Anderson
Pineal melatonin and the cortisol awakening response (CAR) are integral aspects of the circadian rhythm. Pineal melatonin release during sleep is proposed to optimize mitochondrial function and dampen any residual oxidant and inflammatory activity. Little is known about CAR, which is generally thought to prepare the body for the coming day, primarily through the activation of the glucocorticoid receptor (GR). Melatonin, like the gut microbiome-derived butyrate, suppresses GR nuclear translocation, indicating that pineal melatonin and night-time butyrate may interact to modulate CAR effects via the GR, including CAR priming of immune and glia cells that underpin the pathogenesis of most medical conditions. Cutting edge research shows that the GR can be chaperoned by bcl2-associated athanogene (BAG)-1 to mitochondria, where GR can have significant and diverse impacts on mitochondrial function. A number of lines of evidence indicate that melatonin indirectly increases BAG-1, including via epigenetic mechanisms, such as derepressing miR-138 inhibition of BAG-1. The dramatic decrease in pineal melatonin production over aging will therefore have significant impacts on GR nuclear translocation, but also possibly the levels of BAG-1 mediated mitochondrial translocation of the GR. This may have dramatic consequences for how CAR ‘prepares the body for the coming day’, via the differential consequence of GR location in the cytoplasm, nucleus or mitochondria, with differential effects in different cell types. The interactions of melatonin/butyrate/BAG-1/GR are especially important in the hypothalamus, where a maintained heightened melatonin concentration occurs over the night due to the direct release of pineal melatonin, via the pineal recess, into the third ventricle. The interaction of melatonin/butyrate/BAG-1/GR will have differential effects in different cell types, thereby altering the intercellular homeostatic interactions in a given microenvironment that will contribute to the pathogenesis of many aging-associated conditions, including neurodegenerative conditions and cancer. This reframes the nature of the circadian rhythm as well as how stress-associated hypothalamus-pituitary-adrenal (HPA) axis may modulate both the pathogenesis and course of diverse medical presentations. This has a number of research and treatment implications across a host of current medical conditions.
松果体褪黑素和皮质醇唤醒反应(CAR)是昼夜节律的组成部分。睡眠期间松果体褪黑素的释放被认为可以优化线粒体功能,抑制任何残留的氧化和炎症活动。人们对CAR知之甚少,通常认为它主要通过激活糖皮质激素受体(GR)来为身体准备迎接新的一天。褪黑激素,如肠道微生物群衍生的丁酸盐,抑制GR核易位,表明松果体褪黑激素和夜间丁酸盐可能相互作用,通过GR调节CAR效应,包括支持大多数疾病发病机制的免疫和神经胶质细胞的CAR启动。最新研究表明,GR可以通过bcl2相关的无thanogene (BAG)-1陪同到达线粒体,在线粒体中,GR可以对线粒体功能产生显著而多样的影响。许多证据表明,褪黑激素间接增加BAG-1,包括通过表观遗传机制,如去抑制miR-138对BAG-1的抑制。因此,随着年龄的增长,松果体褪黑素分泌的急剧减少将对GR核易位产生重大影响,但也可能对BAG-1介导的GR线粒体易位水平产生重大影响。这可能对CAR如何“为未来的一天做好准备”产生重大影响,通过GR在细胞质、细胞核或线粒体中的位置的不同结果,在不同的细胞类型中产生不同的影响。褪黑素/丁酸盐/BAG-1/GR的相互作用在下丘脑中尤为重要,由于松果体褪黑素通过松果体隐窝直接释放到第三脑室,因此夜间褪黑素浓度持续升高。褪黑素/丁酸盐/BAG-1/GR的相互作用将对不同的细胞类型产生不同的影响,从而改变特定微环境中细胞间的稳态相互作用,这将有助于许多衰老相关疾病的发病机制,包括神经退行性疾病和癌症。这重新定义了昼夜节律的本质,以及与压力相关的下丘脑-垂体-肾上腺(HPA)轴如何调节各种医学表现的发病机制和过程。这对当前许多医疗状况的研究和治疗有许多启示。
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引用次数: 1
The preventive and protective role of melatonin in SARS-CoV-2 infection: a retrospective study 褪黑素在SARS-CoV-2感染中的预防和保护作用:回顾性研究
Pub Date : 2023-09-30 DOI: 10.32794/mr112500159
Antonio Molina-Carballo, Antonio Emilio Jerez-Calero, Luisa Fernández-López, María del Carmen Augustin-Morales, Antonio Muñoz-Hoyos, Ahmad Agil
This study has investigated the protective role of melatonin against SARS-CoV-2 infection. For this purpose, 62 adults were recruited who were in daily relatively high doses of melatonin intaking, with the particularity that they started taking it before the beginning of the COVID-19 pandemic and continued to present. A continuous validation process has been carried out with a series of questionnaires to identify the risk factors, whether they were contacts, were infected, if yes, the level of disease severity, need for treatment, hospitalization, etc. According to the dose of melatonin the individuals took/are taking, they were divided into two groups: a) those taking 20 mg (n = 27) and, b) those taking ≥ 40 mg (n = 32). For statistical analysis, the shi2 test and Fisher&#39;s exact test were used. The number of infected subjects with positive PCR was 7 (11.9%). Only one required medication, the rest had a very favorable clinical evolution, mild in three cases and asymptomatic in three others. While in their environment this percentage is 22.05% (chi2 = 2.928; p < 0.087). Melatonin offers a good safety profile, is well tolerated and can play an important role in the different levels of COVID-19 prevention.
本研究探讨了褪黑素对SARS-CoV-2感染的保护作用。为此,研究人员招募了62名成年人,他们每天摄入相对高剂量的褪黑激素,特别之处在于,他们在COVID-19大流行开始之前开始服用褪黑激素,并持续存在。通过一系列问卷进行了持续的验证过程,以确定风险因素,他们是否接触过,是否被感染,如果是,疾病严重程度,需要治疗,住院治疗等。根据个体服用/正在服用褪黑素的剂量,将他们分为两组:a)服用20 mg (n = 27)和b)服用≥40 mg (n = 32)。统计分析采用shi2检验和fisher精确检验。PCR阳性感染者7例(11.9%)。只有一名患者需要药物治疗,其余患者的临床进展非常良好,其中三例病情轻微,另外三例无症状。而在他们的环境中,这一比例为22.05% (chi2 = 2.928;p & lt;0.087)。褪黑素具有良好的安全性,耐受性良好,在不同程度的COVID-19预防中发挥重要作用。
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引用次数: 0
An insight into the importance of B vitamins and melatonin in the prevention of diabetes through modulation of the brain energy metabolism- a comprehensive review B族维生素和褪黑素通过调节大脑能量代谢在预防糖尿病中的重要性——一项全面的综述
Pub Date : 2023-09-30 DOI: 10.32794/mr112500160
Manisha Mukhopadhyay, Priyanka Ghosh, Aindrila Chattopadhyay, Debasish Bandyopadhyay
Energy metabolism is the biochemical pathway of converting macronutrients (carbohydrates, protein, and fat) to cellular energy for the maintenance of cell homeostasis. The brain is an organ that consumes unproportional energy compared to its size. Glucose (glycogen, in storage form of glucose) is the principal source of brain energy. Impairment in brain energy metabolism results in neuronal loss and subsequent neurodegenerative diseases including AD, PD, amyotrophic lateral sclerosis, Huntington’s disease, etc. However, metabolic disorders such as chronic hyperglycemia, and insulin resistance are also linked with neuronal activity. Dysregulation in neuronal transmission is associated with oxidative stress and brain insulin resistance. Diabetes mellitus jeopardizes brain function through various mechanisms including glucose toxicity, BBB damage, neuroinflammation, and gliosis. B vitamins as antioxidants and neuroprotective agents, can improve brain glucose metabolism. Melatonin is a potent free radical scavenger and it can also modulate cellular cytokine levels and prevent insulin resistance. The neuroprotective and antihyperglycemic effects of melatonin improve the brain&#39;s antioxidant defense system, decrease brain NOS activity, and prevent glucose toxicity. Hence this review suggests a therapeutic use of a combination of melatonin and B vitamins to improve brain functioning disrupted by diabetes.
能量代谢是将大量营养物质(碳水化合物、蛋白质和脂肪)转化为细胞能量以维持细胞稳态的生化途径。大脑是一个消耗与其体积不成比例的能量的器官。葡萄糖(以葡萄糖的储存形式存在的糖原)是大脑能量的主要来源。脑能代谢的损害导致神经元的丧失和随后的神经退行性疾病,包括AD、PD、肌萎缩性侧索硬化症、亨廷顿病等。然而,代谢紊乱,如慢性高血糖症和胰岛素抵抗也与神经元活动有关。神经元传递失调与氧化应激和脑胰岛素抵抗有关。糖尿病通过葡萄糖毒性、血脑屏障损伤、神经炎症和神经胶质瘤等多种机制损害脑功能。B族维生素作为抗氧化剂和神经保护剂,可以改善大脑葡萄糖代谢。褪黑素是一种有效的自由基清除剂,它还可以调节细胞细胞因子水平,防止胰岛素抵抗。褪黑素的神经保护和降糖作用改善大脑的抗氧化防御系统,降低大脑NOS活性,防止葡萄糖毒性。因此,这篇综述建议使用褪黑素和B族维生素的组合来改善被糖尿病破坏的大脑功能。
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引用次数: 0
Melatonin modulates the in vitro angiogenesis of granulosa cells collected from women with marital infertility for IVF 褪黑素调节体外血管生成颗粒细胞收集从妇女的婚姻不孕试管婴儿
Pub Date : 2023-09-30 DOI: 10.32794/mr112500156
Carla C Maganhin, Maria Candida P Baracat, Camilla M Luquetti, Daniella Buonfiglio, Manoel João Girão, José Cipolla-Neto, Manuel J Simoes, Ricardo S Simoes, Edson Lo Turco, Pedro Montelione, Edmund C Baracat, José Maria Soares-Jr
Melatonin concentration is several folds higher in the follicular fluid than that in blood suggesting an important role of this molecule on follicular physiology. However, the actions of melatonin on angiogenesis in granulosa cells are currently unknown. In this study, we have specifically investigated the potential effects of melatonin on the angiogenesis in granulosa cells from female individuals with marital infertility. Sixty patients who were submitted to the in vitrofertilization were included. The granulosa-luteal cells of these females were collected for cell culture. The cells were divided into four groups: a) vehicle (control); b) 0.1 µM melatonin; c) 1 µM melatonin; d) 10 µM melatonin treated groups, respectively. After a period of 10 days of culture, expression of genes involved in the angiogenesis signaling pathway were analyzed by Real-Time PCR and Western Blot assays. The results showed that the expressions of FGF1(fibroblast growth factor 1), IL1B (interleukin 1-beta), VEGFR-2(type 2 vascular-endothelial growth factor receptor), and TGFB1 (tumor growth factor 1- beta) were significantly upregulated in melatonin treated groups compared to the control. In contrast, the expressions of HIF-1A(hypoxia-inducing factor 1-alpha), FGF2 (fibroblastic growth factor 2), IGF-1(insulin-like growth factor 1), and VEGFA (vascular endothelial growth factor alpha) were significantly downregulated by melatonin compared to the control. The results suggest that melatonin modulates angiogenesis of granulosa cells from women with marital infertility. The underlining mechanism may relate to melatonin maintaining the homeostasis of VEGF, especially at a low dose of melatonin.
褪黑素浓度为 在卵泡液中比在血液中高几倍,提示an 该分子在卵泡生理中的重要作用。然而,行动 褪黑素对颗粒细胞血管生成的影响目前尚不清楚。在这个# x0D;研究中,我们专门研究了褪黑素对[#x0D;已婚女性个体颗粒细胞血管生成;不孕。纳入60例接受体外受精的患者。这些雌性的颗粒黄体细胞为 收集用于细胞培养。将细胞分为四组:a) vehicle (控制);b) 0.1µM褪黑素;c)褪黑素1µM;d) 10µM褪黑素处理 组,分别。培养10天后,基因 的表达;通过Real-Time pcr分析参与血管生成信号通路的基因;和Western Blot检测。结果显示,FGF1(成纤维细胞生长因子1)、IL1B(白细胞介素1- β)、VEGFR-2(2型血管内皮生长因子受体)和TGFB1(肿瘤 生长因子1- β)在褪黑素治疗组显著上调 与对照组比较。相比之下,HIF-1A(缺氧诱导因子1- α)、FGF2(成纤维细胞生长因子2)、IGF-1(胰岛素样生长因子1)和VEGFA(血管内皮生长因子 因子α)被褪黑素显著下调,与 控制。结果表明,褪黑激素调节颗粒血管生成 来自已婚不孕妇女的细胞。强调机制可能与 褪黑素维持VEGF的内稳态,特别是在低剂量的 褪黑激素。
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引用次数: 0
Tryptophan decarboxylase (TDC) in sweet pepper (Capsicum annuum L.): Gene expression analysis during fruit ripening and after nitric oxide exposure 甜椒(Capsicum annuum L.)色氨酸脱羧酶(TDC):果实成熟和一氧化氮暴露后的基因表达分析
Pub Date : 2023-08-31 DOI: 10.32794/mr112500155
Jorge Taboada, Salvador González-Gordo, José M Palma, Francisco J Corpas
Tryptophan decarboxylase (TDC) catalyzes the conversion of L-tryptophan (Trp) to tryptamine, a first step in the biosynthesis of serotonin and melatonin in plants. Pepper (Capsicum annuum L.) fruit, a globally popular horticultural product has great nutritional and economic values. In addition to that pepper fruit undergoes phenotypical changes during ripening, many other alterations also occur at the transcriptomic, proteomic, biochemical, and metabolic levels. However, little information is known on how many genes encoding for TDC in pepper plants and their expression levels during the ripening of sweet pepper fruit. In the current study, based on a data-mining approach on the pepper genome and transcriptome (RNA-seq), five putative CaTDC genes were identified. They are designated as 1 to 5 based on their localizations in chromosomes and also their previous biochemical data. Among them, CaTDC3 and CaTDC4 encode proteins with tryptophan decarboxylase activity; however, CaTDC1, CaTDC2 and CaTDC5 encode either tyrosine decarboxylase (TYDC) or aromatic aldehyde synthase (AAS), although CaTDC5 shares some degree TDC homology. Therefore, they are considered as the putative CaTDCs until their activity is corroborated. The CaTDC4 and putative CaTDC5 are expressed in pepper fruit. The time-course analysis of these genes during fruit ripening (green immature, breaking point, and red ripe) showed that they were differentially expressed, i.e., CaTDC4 was upregulated, and putative CaTDC5 was downregulated. CaTDC4 was positively modulated by two light-responsive elements, Box4 and TCT-motif, while CaTDC5 was influenced by GT1-motif and G-Box. The protein sequence analysis also allowed identifying the Trp-substrate-binding pocket which is a characteristic of the TDC proteins. Exogenous NO (a signaling molecule) treatment triggered the downregulation of CaTDC4 but not putative CaTDC5. These data provide a novel insight on the potential functions involved in the secondary metabolism of TDCs in fleshy fruits. In the identified three new CaTDC genes, two (CaTDC4 and CaTDC5) expressed in pepper fruits are modulated by exogenous NO treatment during ripening.
色氨酸脱羧酶(TDC)催化l -色氨酸(Trp)转化为色胺,是植物生物合成血清素和褪黑素的第一步。辣椒(Capsicum annuum L.)果实是一种全球流行的园艺产品,具有很高的营养价值和经济价值。除了辣椒果实在成熟过程中发生表型变化外,许多其他变化也发生在转录组学、蛋白质组学、生化和代谢水平上。然而,目前对甜椒植株中编码TDC的基因数量及其在甜椒果实成熟过程中的表达水平知之甚少。本研究基于辣椒基因组和转录组(RNA-seq)的数据挖掘方法,鉴定了5个可能的CaTDC基因。根据它们在染色体中的位置和它们之前的生化数据,它们被指定为1到5。其中,CaTDC3和CaTDC4编码具有色氨酸脱羧酶活性的蛋白;然而,CaTDC1、CaTDC2和CaTDC5编码酪氨酸脱羧酶(TYDC)或芳香醛合成酶(AAS),尽管CaTDC5具有一定程度的TDC同源性。因此,在它们的活性得到证实之前,它们被认为是假定的catdc。CaTDC4和推测的CaTDC5在辣椒果实中表达。对这些基因在果实成熟过程(绿未成熟、断裂点和红成熟)中的时间过程分析表明,它们是差异表达的,即CaTDC4上调,而CaTDC5可能下调。CaTDC4受两个光响应元件Box4和TCT-motif的正向调节,而CaTDC5受GT1-motif和G-Box的正向调节。蛋白质序列分析还允许鉴定trp底物结合袋,这是TDC蛋白的特征。外源性NO(一种信号分子)处理触发了CaTDC4的下调,但没有引发CaTDC5的下调。这些数据为肉质水果中tdc次生代谢的潜在功能提供了新的见解。在发现的3个新的CaTDC基因中,有2个CaTDC4和CaTDC5基因在辣椒果实成熟过程中受到外源NO处理的调控。
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引用次数: 0
Effects of melatonin on the circadian functions of sleep-wake cycle, metabolism, hormonal regulation and immune activity: A recent review 褪黑素对睡眠-觉醒周期、代谢、激素调节和免疫活性的影响:最新综述
Pub Date : 2023-08-31 DOI: 10.32794/mr112500154
Bugra Sarisozen, Feyza Sule Aslan, Enes Akyuz
Rhythms following a period of approximately 24 hours are called circadian (from Latin circa diem, approximately one day) rhythms. These rhythms are observed in the activities of various vital body functions. Melatonin is considered as an important molecule participating in the formation of circadian rhythms of virtually all organisms. As a molecular regulator of the circadian clock, melatonin has various regulatory functions in both physiological and pathological conditions. Sleep-wake cycle depends on CSF melatonin levels, and melatonin also has a protective effect on the disrupted sleep-wake cycle in various pathological conditions. Melatonin ensures the proper function of vital metabolic pathways; therefore, it improves metabolism-related systems and protects them from damage. A bidirectional relationship between hormonal activity and melatonin ensures it having a healing effect on various reproductive disorders. Finally, melatonin can target inflammation pathways and various elements of immune system by changing their behavior and structure. In summary, melatonin has important effects on vital body functions mediated by its receptors, signaling pathways and clock genes, and has the capacity to protect and improve these functions under pathological conditions.
周期约为24小时的节律称为昼夜节律(源自拉丁语circa diem,约为一天)。这些节律在人体各种重要功能的活动中都可以观察到。褪黑素被认为是几乎所有生物参与昼夜节律形成的重要分子。褪黑素作为生物钟的分子调节剂,在生理和病理条件下都具有多种调节功能。睡眠-觉醒周期取决于脑脊液褪黑激素水平,褪黑激素对各种病理状态下被打乱的睡眠-觉醒周期也有保护作用。褪黑素确保重要代谢途径的正常功能;因此,它改善代谢相关系统,保护它们免受损害。荷尔蒙活动和褪黑素之间的双向关系确保它对各种生殖疾病有治疗作用。最后,褪黑素可以通过改变免疫系统的行为和结构来靶向炎症途径和各种免疫系统元素。综上所述,褪黑激素通过其受体、信号通路和生物钟基因介导对机体重要功能有重要作用,并在病理条件下具有保护和改善这些功能的能力。
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引用次数: 0
Effect of iron on rat serum melatonin levels under different light/dark cycle patterns 不同光照/暗循环模式下铁对大鼠血清褪黑素水平的影响
Pub Date : 2023-06-30 DOI: 10.32794/mr112500146
Joaquín Xavier Cogo Pagella, M. Hernando, C. Cervino
Exposure to constant light or darkness for long periods has diverse effects on circadian physiology. Iron (Fe) overloading promotes oxidative stress and causes alterations in cellular structure and function in animals and humans. The aim of this study is to evaluate the interactions among serum melatonin (ML), photoperiod manipulation, and Fe overloading in rats. The results showed that constant darkness exposure for 15 days significantly increased serum ML levels (up to 22%) while the constant light exposure failed to reduce the serum ML level compared to the normal light/dark cycle treated rats. The lost serum ML level usually from the pineal gland under the long term of constant light exposure may be compensated by ML generated by other organs which adapted to the situation. Also, Fe overloading decreased ML production due to this molecule being consumed to scavenge the free radicals induced by the Fe overloading. In addition, we observed interactions among constant light or darkness exposure, Fe overloading and serum ML level. Overall, our results support the hypothesis of ML as scavenging molecule; it may be an effective therapeutic tool in iron-induced oxidative stress.
长时间暴露在恒定的光照或黑暗中对昼夜生理有不同的影响。铁(Fe)超载促进氧化应激,导致动物和人类细胞结构和功能的改变。本研究的目的是评估血清褪黑素(ML),光周期操作和铁超载大鼠之间的相互作用。结果表明,持续黑暗暴露15天显著提高血清ML水平(高达22%),而与正常光/暗循环处理的大鼠相比,持续光照暴露未能降低血清ML水平。在长期持续光照下,通常由松果体产生的血清ML水平下降,可由适应这种情况的其他器官产生的ML来补偿。此外,铁超载减少了ML的产生,这是由于这种分子被消耗以清除由铁超载引起的自由基。此外,我们观察到持续光照或黑暗暴露、铁超载和血清ML水平之间的相互作用。总之,我们的结果支持ML作为清除分子的假设;它可能是铁诱导氧化应激的有效治疗工具。
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引用次数: 0
Research in Plant Melatonin: Original and Current Studies 植物褪黑素的研究:原始研究和最新研究
Pub Date : 2023-06-30 DOI: 10.32794/mr112500151
M. B. Arnao, A. Cano, J. Hernández-Ruiz
Melatonin from plants, also known as phytomelatonin, was discovered in 1995, and since then, affecting many areas of research related to plants. Thus, the number of publications on phytomelatonin has grown exponentially in recent years, especially in Plant Physiology and Plant Molecular studies. In this paper, we try to expose the great incidence that the detection of this neurohormone in plants is having, and its relevance in areas such as agronomy, genetics, human nutrition and food chemistry/technology, animal nutrition and other more specific fields of interest such as cosmetics and nutraceuticals.
从植物中提取的褪黑素,也被称为植物褪黑素,于1995年被发现,从那时起,影响了许多与植物相关的研究领域。因此,近年来,关于褪黑素的出版物数量呈指数级增长,特别是在植物生理学和植物分子研究方面。在本文中,我们试图揭示这种神经激素在植物中检测的巨大发生率,以及它在农学、遗传学、人类营养和食品化学/技术、动物营养和其他更具体的领域(如化妆品和营养保健品)的相关性。
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引用次数: 1
Melatonin: Its expanding universe 褪黑素:它的宇宙在不断膨胀
Pub Date : 2023-06-30 DOI: 10.32794/mr112500152
V. M. Martín Giménez, Rama Sharma, W. Manucha
Dr. Russel J. Reiter was awarded his fifth honorary title by the National University of Cuyo, Argentina, for his exemplary contributions towards unraveling the mysteries of the pineal gland and, importantly, its major secretory product, melatonin. This commentary provides a glimpse of his accomplishments and a summary of his speech during the ceremony.
Russel J. Reiter博士被阿根廷库约国立大学授予第五个荣誉称号,以表彰他在解开松果体之谜方面做出的杰出贡献,更重要的是,解开了松果体的主要分泌产物褪黑素。这篇评论提供了他的成就的一瞥,并总结了他在典礼上的讲话。
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引用次数: 0
The dual-actions of melatonin as a potential oncostatic agent and a protector against chemotherapy-induced toxicity 褪黑素作为一种潜在的抑癌剂和抗化疗引起的毒性的保护剂的双重作用
Pub Date : 2023-06-30 DOI: 10.32794/mr112500149
Souradipta Chakraborty, Swaimanti Sarkar, A. Chattopadhyay, D. Bandyopadhyay
Cancer is one of the most complicated and arduous diseases, causing immense physical and emotional tribulations in the life of patients. Carcinogens can lead to genetic mutations and cancer progression either by directly binding to DNA covalently, forming cross-links, or indirectly via the generation of oxidative stress and/or by other recondite mechanisms. Despite being the most widely used treatment, chemotherapy has several adverse consequences, including acute and/or chronic toxicities. Numerous studies have demonstrated melatonin being a potential anticancer molecule with multiple activities including prevention of the initiation, promotion, and progression of cancer. In addition to its role as a potent antioxidant, melatonin exhibits its cytostatic effects by arresting the mutated cell in the G0/G1 phase, preventing epithelial-to-mesenchymal transition and inciting the immune battle against tumours, possibly by dampening MMP activities. Melatonin inhibits the MAP-K/ERK and p38 pathways and regulates NF-ĸB-mediated inflammatory responses. Melatonin exerts its anti-angiogenic activity by curbing VEGF levels, while its anti-estrogenic activity by inhibiting the cellular uptake of linoleic acid (LA). In addition, melatonin reduces the toxicities of the chemotherapy while improving its effectiveness in cancer treatment. The purpose of this review is to assemble the knowledge available on melatonin’s oncostatic role and its protective effects against chemotherapy-induced toxicities. Further studies are needed to investigate the adjunctive role of melatonin with chemotherapy in the clinical setting and to corroborate its effectiveness in cancer cure.
癌症是最复杂、最折磨人的疾病之一,给患者的生活带来巨大的身体和情感上的痛苦。致癌物可通过直接与DNA共价结合,形成交联,或通过产生氧化应激和/或通过其他未知机制间接导致基因突变和癌症进展。尽管化疗是最广泛使用的治疗方法,但它也有一些不良后果,包括急性和/或慢性毒性。大量研究表明,褪黑素是一种潜在的抗癌分子,具有多种活性,包括预防癌症的发生、促进和进展。除了作为一种有效的抗氧化剂的作用,褪黑素还表现出细胞抑制作用,通过在G0/G1期阻止突变细胞,阻止上皮细胞向间充质细胞的转变,并可能通过抑制MMP活性来激发对抗肿瘤的免疫战斗。褪黑素抑制MAP-K/ERK和p38通路,调节NF-ĸB-mediated炎症反应。褪黑素通过抑制VEGF水平发挥其抗血管生成活性,而其抗雌激素活性通过抑制亚油酸(LA)的细胞摄取发挥其抗雌激素活性。此外,褪黑素降低了化疗的毒性,同时提高了其在癌症治疗中的有效性。本综述的目的是收集有关褪黑素的抑瘤作用及其对化疗引起的毒性的保护作用的现有知识。褪黑素在化疗中的辅助作用需要进一步的研究,以证实其在癌症治疗中的有效性。
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引用次数: 0
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Melatonin Research
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