Signaling mechanisms

  • 文章类型: Journal Article
    在播种植物中,植物激素乙烯的生物合成,调节包括果实成熟和衰老在内的过程,由1-氨基环丙基-1-羧酸(ACC)氧化酶催化。植物病原体Savastanoi假单胞菌(以前分类为:丁香假单胞菌)采用不同类型的乙烯形成酶(psEFE),虽然来自与ACC氧化酶相同的结构超家族,以精氨酸依赖性方式催化2-酮戊二酸(2OG)形成乙烯。psEFE还催化更典型的精氨酸氧化生成L-Δ1-吡咯啉-5-羧酸酯(P5C),与产生琥珀酸酯和CO2的2OG的氧化脱羧偶联的反应。我们报道了C3和/或C4取代的2OG衍生物对psEFE反应模式的影响。1HNMR测定,包括使用纯移位方法,透露这一点,在我们的检测范围内,测试的2OG衍生物均未转化为烯烃;一些转化为相应的β-羟基丙酸酯或琥珀酸酯衍生物,只有后者与精氨酸氧化有关。NMR结果表明,2OG衍生化的性质可以影响分叉反应的结果,某些2OG衍生物仅有利于精氨酸氧化途径。鉴于一些测试的2OG衍生物是天然产物,结果具有潜在的生物学相关性。还存在通过使用20G衍生物治疗或生物催化调节由20G依赖性加氧酶催化的反应结果的机会。
    In seeding plants, biosynthesis of the phytohormone ethylene, which regulates processes including fruit ripening and senescence, is catalyzed by 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase. The plant pathogen Pseudomonas savastanoi (previously classified as: Pseudomonas syringae) employs a different type of ethylene-forming enzyme (psEFE), though from the same structural superfamily as ACC oxidase, to catalyze ethylene formation from 2-oxoglutarate (2OG) in an arginine dependent manner. psEFE also catalyzes the more typical oxidation of arginine to give L-Δ1-pyrroline-5-carboxylate (P5C), a reaction coupled to oxidative decarboxylation of 2OG giving succinate and CO2. We report on the effects of C3 and/or C4 substituted 2OG derivatives on the reaction modes of psEFE. 1H NMR assays, including using the pure shift method, reveal that, within our limits of detection, none of the tested 2OG derivatives is converted to an alkene; some are converted to the corresponding β-hydroxypropionate or succinate derivatives, with only the latter being coupled to arginine oxidation. The NMR results reveal that the nature of 2OG derivatization can affect the outcome of the bifurcating reaction, with some 2OG derivatives exclusively favoring the arginine oxidation pathway. Given that some of the tested 2OG derivatives are natural products, the results are of potential biological relevance. There are also opportunities for therapeutic or biocatalytic regulation of the outcomes of reactions catalyzed by 2OG-dependent oxygenases by the use of 2OG derivatives.
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  • 文章类型: Journal Article
    疲劳是影响人类正常活动的常见生理状态。长时间的疲劳会诱发多种疾病,严重影响人类健康,因此,必须发现没有副作用的营养膳食补充剂和治疗方法,其中天然抗疲劳多糖显示出巨大的潜力。多糖,由植物等多种生物产生的一类生物分子,动物,细菌和藻类,近年来由于其抗疲劳活性和较少的副作用而备受关注。这篇综述总结了分类,从不同天然来源获得的具有抗疲劳活性的多糖的剂量和实验模型。我们还回顾了这些多糖通过调节氧化损伤等机制缓解疲劳的作用,调节能量代谢,影响肠道菌群,以及分子量的影响,单糖组合物,多糖的结构特征和化学修饰对其抗疲劳活性的影响,支持其在功能性食品和药物中的潜在应用价值。在生物基功能材料的自然生产领域也提出了对未来天然多糖研究的新的有价值的见解,功能性食品和治疗剂。
    Fatigue is a common physiological state that affects normal human activities. Prolonged fatigue induces a variety of diseases and seriously affects human health, so it is imperative to discover nutritional dietary supplements and treatments without side effects, among which natural anti-fatigue polysaccharides have shown great potential. Polysaccharides, a class of biomolecules produced by a variety of organisms such as plants, animals, bacteria and algae, have attracted much attention in recent years due to their anti-fatigue activity and fewer side effects. This review summarizes the classification, dosage and experimental models of polysaccharides with anti-fatigue activity obtained from different natural sources. We also review the fatigue-relieving effects of these polysaccharides through mechanisms such as modulating oxidative damage, regulating energy metabolism and influencing intestinal flora, as well as the effects of molecular weights, monosaccharide compositions, structural features and chemical modifications of the polysaccharides on their anti-fatigue activities to support their potential application value in functional foods and pharmaceuticals. New valuable insights for future research on natural polysaccharides are also presented in the field of natural production of bio-based functional materials, functional foods and therapeutic agents.
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  • 文章类型: Journal Article
    非生物和生物胁迫条件导致产生作为脂质过氧化物衍生物的反应性羰基物质(RCS),并且特别是在高浓度下对植物细胞具有有害作用。有几种分子可以在RCS中分类;其中,4-羟基-(E)-2-壬烯醛(HNE)和丙烯醛因其毒性而被广泛认可和研究。RCS的毒性机制在动物中是众所周知的,但它们在植物系统中的作用,特别是在代谢中的信号方面需要解决。本章重点介绍植物中RCS的产生机制,以及植物如何清除和修改它们以防止细胞中不可逆的损害。我们旨在全面了解文献,以总结RCS在植物代谢中的信号作用及其与其他信号机制的相互作用,例如高度认可的活性氧(ROS)信号。气候变化会对植物产生更严重的非生物胁迫效应,从而降低田间产量。本章还收集了非生物胁迫条件对RCS代谢的影响,包括它们在非生物胁迫期间的信号作用。本章还介绍了测量植物RCS的不同方法,以引起人们对植物RCS代谢研究的更多关注。
    Abiotic and biotic stress conditions lead to production of reactive carbonyl species (RCS) which are lipid peroxide derivatives and have detrimental effects on plant cells especially at high concentrations. There are several molecules that can be classified in RCS; among them, 4-hydroxy-(E)-2-nonenal (HNE) and acrolein are widely recognized and studied because of their toxicity. The toxicity mechanisms of RCS are well known in animals but their roles in plant systems especially signaling aspects in metabolism need to be addressed. This chapter focuses on the production mechanisms of RCS in plants as well as how plants scavenge and modify them to prevent irreversible damage in the cell. We aimed to get a comprehensive look at the literature to summarize the signaling roles of RCS in plant metabolism and their interaction with other signaling mechanisms such as highly recognized reactive oxygen species (ROS) signaling. Changing climate promotes more severe abiotic stress effects on plants which also decrease yield on the field. The effects of abiotic stress conditions on RCS metabolism are also gathered in this chapter including their signaling roles during abiotic stresses. Different methods of measuring RCS in plants are also presented in this chapter to draw more attention to the study of RCS metabolism in plants.
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  • 文章类型: Journal Article
    农药已成为现代农业实践的一个组成部分,但是它们的广泛使用对人类健康构成了重大威胁。因此,迫切需要开发检测食品和环境样品中农药的有效方法。传统的色谱办法和普通的疾速检测办法不克不及知足精确性,便携性,储存时间长,和溶液的稳定性在同一时间。近年来,光电化学(PEC)传感技术作为一种有前途的检测各种农药的方法,由于其突出的优势而受到关注,包括高灵敏度,低成本,操作简单,快速反应,易于小型化,从而成为实时和现场监测农药水平的有竞争力的候选人。这篇综述概述了PEC农药检测方法的最新进展及其在确保食品和环境安全方面的应用。重点关注光敏材料的类别,从单个半导体到半导体-半导体异质结,和PEC传感平台的信号机制,包括农药的氧化,空间位阻,牺牲剂的产生/减少,和光敏材料的引入/释放。此外,这次审查将提供对未来前景和对抗的见解,从而为这个不断发展的领域贡献了新的观点。
    Pesticides have become an integral part of modern agricultural practices, but their widespread use poses a significant threat to human health. As such, there is a pressing need to develop effective methods for detecting pesticides in food and environmental samples. Traditional chromatography methods and common rapid detection methods cannot satisfy accuracy, portability, long storage time, and solution stability at the same time. In recent years, photoelectrochemical (PEC) sensing technology has gained attention as a promising approach for detecting various pesticides due to its salient advantages, including high sensitivity, low cost, simple operation, fast response, and easy miniaturization, thus becoming a competitive candidate for real-time and on-site monitoring of pesticide levels. This review provides an overview of the recent advancements in PEC methods for pesticide detection and their applications in ensuring food and environmental safety, with a focus on the categories of photoactive materials, from single semiconductor to semiconductor-semiconductor heterojunction, and signaling mechanisms of PEC sensing platforms, including oxidation of pesticides, steric hindrance, generation/decrease in sacrificial agents, and introduction/release of photoactive materials. Additionally, this review will offer insights into future prospects and confrontations, thereby contributing novel perspectives to this evolving domain.
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  • 背景:髓母细胞瘤(MDB)是恶性的,主要影响儿童的侵袭性脑肿瘤。14岁以下儿童的存活率约为72%,而对于15至39岁的人,这一比例约为78%。越来越多的证据表明,信号传导机制的失调和非编码RNA表观遗传学在这种疾病中起着关键作用。
    方法:本研究对PubMed和Google等网站上的文章进行了电子搜索。当前的评论还使用了计算机数据库搜索和生物信息学分析以及广泛的综合文献检索原始研究文章和评论文章以及临床试验中当前和未来药物的检索。
    结果:这项研究表明,比如SonicHedgehog,WNT/β-连环蛋白,未折叠蛋白反应介导的内质网应激,凹口,神经营养因子和TGF-β和ERK,MAPK,ERK在MDB的发病机制中起着至关重要的作用。基因和ncRNA/蛋白也作为轴长ncRNA参与海绵micro-RNAs,影响下游信号蛋白的表达和翻译影响疾病的病理生理,预后并提出药物再利用的潜在目标。目前的治疗方案包括手术,辐射,和化疗;不幸的是,这种疾病经常复发,存活率低于5%。因此,需要开发更有效的治疗方法来对抗复发并提高生存率。
    结论:这篇综述描述了各种MDB疾病的标志,包括病理生理学中涉及的信号机制,相关因果基因,表观遗传学,下游基因/表观基因,以及可能的致病基因/非蛋白质编码(nc)RNA/蛋白质轴。此外,讨论了与MDB治疗相关的挑战,以及如何使用纳米技术和纳米生物医学来解决这些问题,列出了可能的治疗方案和未来的潜在治疗方式。
    Medulloblastomas (MDB) are malignant, aggressive brain tumors that primarily affect children. The survival rate for children under 14 is approximately 72%, while for ages 15 to 39, it is around 78%. A growing body of evidence suggests that dysregulation of signaling mechanisms and noncoding RNA epigenetics play a pivotal role in this disease.
    This study conducted an electronic search of articles on websites like PubMed and Google. The current review also used an in silico databases search and bioinformatics analysis and an extensive comprehensive literature search for original research articles and review articles as well as retrieval of current and future medications in clinical trials.
    This study indicates that several signaling pathways, such as sonic hedgehog, WNT/β-catenin, unfolded protein response mediated ER stress, notch, neurotrophins and TGF-β and ERK, MAPK, and ERK play a crucial role in the pathogenesis of MDB. Gene and ncRNA/protein are also involved as an axis long ncRNA to sponge micro-RNAs that affect downstream signal proteins expression and translation affection disease pathophysiology, prognosis and present potential target hit for drug repurposing. Current treatment options include surgery, radiation, and chemotherapy; unfortunately, the disease often relapses, and the survival rate is less than 5%. Therefore, there is a need to develop more effective treatments to combat recurrence and improve survival rates.
    This review describes various MDB disease hallmarks, including the signaling mechanisms involved in pathophysiology, related-causal genes, epigenetics, downstream genes/epigenes, and possibly the causal disease genes/non-protein coding (nc)RNA/protein axis. Additionally, the challenges associated with MDB treatment are discussed, along with how they are being addressed using nano-technology and nano-biomedicine, with a listing of possible treatment options and future potential treatment modalities.
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  • 文章类型: Journal Article
    左心发育不良综合征(HLHS)是一种致命的先天性心脏病(CHD),影响全球每100,000名新生儿中8-25名。临床干预,主要是外科,多年来大幅改善了受影响受试者的预期寿命。然而,HLHS的病因学基础至今仍不清楚.基于现有的研究范式,HLHS表现出由复杂的遗传和信号级联过程介导的多因素病因模式。这篇综述提供了HLHS表型的详细概述,产前和产后风险,以及驱动HLHS发病机制的信号和分子机制。该综述讨论了为解决现有科学差距而可以进行的研究的潜在局限性和未来观点。解释HLHS病因的机制研究将有可能阐明新的可药物靶标,并在未来授权开发针对HLHS的治疗方案。
    Hypoplastic left heart syndrome (HLHS) is a lethal congenital heart disease (CHD) affecting 8-25 per 100,000 neonates globally. Clinical interventions, primarily surgical, have improved the life expectancy of the affected subjects substantially over the years. However, the etiological basis of HLHS remains fundamentally unclear to this day. Based upon the existing paradigm of studies, HLHS exhibits a multifactorial mode of etiology mediated by a complicated course of genetic and signaling cascade. This review presents a detailed outline of the HLHS phenotype, the prenatal and postnatal risks, and the signaling and molecular mechanisms driving HLHS pathogenesis. The review discusses the potential limitations and future perspectives of studies that can be undertaken to address the existing scientific gap. Mechanistic studies to explain HLHS etiology will potentially elucidate novel druggable targets and empower the development of therapeutic regimens against HLHS in the future.
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  • 文章类型: Journal Article
    放射状神经胶质(RG)的发育对于大脑皮层的生长和组织至关重要。在人类中,外放射状神经胶质(oRG)亚型扩展并产生不同的神经元和神经胶质。然而,调节ORG分化的机制尚不清楚。ORG细胞在神经发生过程中表达白血病抑制因子(LIF)受体,与干细胞自我更新的作用相一致,LIF扰动影响皮质组织和类器官中的oRG增殖。令人惊讶的是,LIF处理还增加皮质培养物中抑制性中间神经元(INs)的产生。比较转录组学分析确定,增强的IN群体类似于尾神经节隆起中产生的IN。为了评估IN是否可能来自ORG,我们分离了原代oRG细胞,并用LIF培养。我们观察到在LIF处理后从oRG细胞产生INs和IN丰度的增加。我们的观察表明,LIF信号调节oRG细胞产生INs的能力。
    Radial glial (RG) development is essential for cerebral cortex growth and organization. In humans, the outer radial glia (oRG) subtype is expanded and gives rise to diverse neurons and glia. However, the mechanisms regulating oRG differentiation are unclear. oRG cells express leukemia-inhibitory factor (LIF) receptors during neurogenesis, and consistent with a role in stem cell self-renewal, LIF perturbation impacts oRG proliferation in cortical tissue and organoids. Surprisingly, LIF treatment also increases the production of inhibitory interneurons (INs) in cortical cultures. Comparative transcriptomic analysis identifies that the enhanced IN population resembles INs produced in the caudal ganglionic eminence. To evaluate whether INs could arise from oRGs, we isolated primary oRG cells and cultured them with LIF. We observed the production of INs from oRG cells and an increase in IN abundance following LIF treatment. Our observations suggest that LIF signaling regulates the capacity of oRG cells to generate INs.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    衰老是指生物体在成年后逐渐发生的生理变化,导致衰老和生物功能下降,最终导致死亡。流行病学证据表明,衰老是各种疾病发展的驱动因素,包括心血管疾病,神经退行性疾病,免疫系统紊乱,癌症,和慢性低度炎症。天然植物多糖已成为延缓衰老过程的关键食品成分。因此,必须不断研究植物多糖作为衰老新药的潜在来源。现代药理研究表明,植物多糖通过清除自由基发挥抗衰老作用,增加端粒酶活性,调节细胞凋亡,增强免疫力,抑制糖基化,改善线粒体功能障碍调节基因表达,激活自噬,和调节肠道微生物群。此外,植物多糖的抗衰老活性由一个或多个信号通路介导,包括IIS,mTOR,Nrf2,NF-κB,Sirtuin,p53,MAPK,和UPR信号通路。本文综述了植物多糖的抗衰老特性以及参与多糖调节衰老过程的信号通路。最后,我们讨论了抗衰老多糖的构效关系。
    Aging refers to the gradual physiological changes that occur in an organism after reaching adulthood, resulting in senescence and a decline in biological functions, ultimately leading to death. Epidemiological evidence shows that aging is a driving factor in the developing of various diseases, including cardiovascular diseases, neurodegenerative diseases, immune system disorders, cancer, and chronic low-grade inflammation. Natural plant polysaccharides have emerged as crucial food components in delaying the aging process. Therefore, it is essential to continuously investigate plant polysaccharides as potential sources of new pharmaceuticals for aging. Modern pharmacological research indicates that plant polysaccharides can exert antiaging effects by scavenging free radicals, increasing telomerase activity, regulating apoptosis, enhancing immunity, inhibiting glycosylation, improving mitochondrial dysfunction regulating gene expression, activating autophagy, and modulating gut microbiota. Moreover, the antiaging activity of plant polysaccharides is mediated by one or more signaling pathways, including IIS, mTOR, Nrf2, NF-κB, Sirtuin, p53, MAPK, and UPR signaling pathways. This review summarizes the antiaging properties of plant polysaccharides and signaling pathways participating in the polysaccharide-regulating aging process. Finally, we discuss the structure-activity relationships of antiaging polysaccharides.
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  • 文章类型: Journal Article
    心肌梗死等心脏损伤导致心肌细胞丢失,纤维化组织沉积,和疤痕的形成。这些变化会降低心脏收缩力,导致心力衰竭,这造成了巨大的公共卫生负担。军事人员,与平民相比,承受更大的压力,心脏病的危险因素,使心血管健康管理和治疗创新成为军事医学的重要课题。到目前为止,医学干预可以减缓心血管疾病的进展,但还不能诱导心脏再生.在过去的几十年里,研究集中在心脏再生能力的潜在机制和逆转心脏损伤的适用方法。从动物模型和早期临床试验的研究中已经出现了见解。临床干预显示出减少瘢痕形成和增强心肌细胞增殖的潜力,从而抵消心脏病的发病机理。在这次审查中,我们讨论了控制心脏组织再生的信号事件,并总结了当前促进损伤后心脏再生的治疗方法。
    Heart injury such as myocardial infarction leads to cardiomyocyte loss, fibrotic tissue deposition, and scar formation. These changes reduce cardiac contractility, resulting in heart failure, which causes a huge public health burden. Military personnel, compared with civilians, is exposed to more stress, a risk factor for heart diseases, making cardiovascular health management and treatment innovation an important topic for military medicine. So far, medical intervention can slow down cardiovascular disease progression, but not yet induce heart regeneration. In the past decades, studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury. Insights have emerged from studies in animal models and early clinical trials. Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease. In this review, we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.
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