gasotransmitter

气体发射器
  • 文章类型: Journal Article
    硫化氢(H2S)作为一种重要的气体发射器的重要性已经在植物中得到了广泛的证明,当植物对许多发育和环境线索作出反应时,通常会调节内源性H2S以激活H2S信号。因此,阐明植物的H2S生理浓度和H2S生成强度是理解H2S信号激活机制的关键,引起了越来越多的关注。目前,已经报道了用于体内和体外监测H2S浓度的多种基于反应的方法。在这次审查中,我们总结并详细描述了几种植物系统中内源性H2S的定量和生物成像方法,主要采用分光光度计依赖的亚甲基蓝(MB)法和荧光探针法,包括反应机理,设计策略,响应原则,和应用细节。此外,我们还总结了这些方法的优缺点以及适用的研究场景。我们希望这篇综述将为H2S传感方法的选择以及对植物中H2S信号的全面研究提供一些指导。
    The significance of hydrogen sulfide (H2S) as a crucial gasotransmitter has been shown extensively in plants, and endogenous H2S is often modulated to activate H2S signaling when plants respond to numerous developmental and environmental cues. Consequently, elucidating the H2S physiological concentrations and the H2S generation intensity of plants is key to understanding the activation mechanism of H2S signaling, which has attracted increasing attention. Currently, a variety of reaction-based methods have been reported for monitoring H2S concentration in vivo and in vitro. In this review, we summarize and describe in detail several methods for quantifying and bioimaging endogenous H2S in plants systems, mainly the spectrophotometer-dependent methylene blue (MB) method and fluorescence probes, including the reaction mechanisms, design strategies, response principles, and application details. Moreover, we also summarize the advantages and disadvantages of these methods as well as the research scenarios in which they are applicable. We expect that this review will provide some guidelines on the selection of methods for H2S sensing and the comprehensive investigations into H2S signaling in plants.
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  • 文章类型: Journal Article
    气体对于与人类健康相关的各种应用至关重要,包括在医学上,生物医学成像,和药物合成。然而,与液体和固体相比,气体的安全处理更具挑战性。在这里,我们回顾了多孔材料的使用,如金属有机骨架(MOFs),沸石,还有硅胶,吸附医疗相关气体,并促进其作为固体处理。具体主题包括使用MOFs和沸石输送H2S用于治疗应用,129Xe用于磁共振成像,O2用于治疗癌症和缺氧,和用于有机合成的各种气体。这个观点旨在汇集有机的,无机,药用,和材料化学界,以激发下一代多孔材料的设计,用于储存和输送医疗相关气体。
    Gases are essential for various applications relevant to human health, including in medicine, biomedical imaging, and pharmaceutical synthesis. However, gases are significantly more challenging to safely handle than liquids and solids. Herein, we review the use of porous materials, such as metal-organic frameworks (MOFs), zeolites, and silicas, to adsorb medicinally relevant gases and facilitate their handling as solids. Specific topics include the use of MOFs and zeolites to deliver H2S for therapeutic applications, 129Xe for magnetic resonance imaging, O2 for the treatment of cancer and hypoxia, and various gases for use in organic synthesis. This Perspective aims to bring together the organic, inorganic, medicinal, and materials chemistry communities to inspire the design of next-generation porous materials for the storage and delivery of medicinally relevant gases.
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  • 文章类型: Journal Article
    Irisin是一种在身体活动和暴露于低温的影响下通过其前体的裂解通过不同的外源刺激分泌的肌动蛋白,含纤连蛋白III型结构域的蛋白5(FNDC5)。它主要以维持代谢稳态而闻名,促进白色脂肪组织的褐变,产热过程,和葡萄糖稳态。越来越多的实验证据表明,irisin在调节心脏代谢病理生理过程中可能具有重要作用。在另一边,硫化氢(H2S)被公认为是一种多效性气体发射器,可调节多种稳态平衡和生理功能,并参与心脏代谢疾病的发病机理。通过半胱氨酸蛋白残基的S-过硫化,H2S能够与关键的信号通路相互作用,在调节葡萄糖和脂质稳态方面也发挥有益作用。H2S和irisin似乎交织在一起;事实上,最近,发现H2S通过激活过氧化物酶体增殖物激活受体γ辅激活因子1-α(PGC-1α)/FNDC5/irisin信号通路来调节irisin的分泌,他们有几个共同的行动机制。通过在肥胖和糖尿病受试者中检测到它们的较低循环水平来证实它们参与代谢疾病。随着代谢紊乱的重要性,这些调节剂对心血管疾病发挥有利作用,预防高血压事件,动脉粥样硬化,心力衰竭,心肌梗塞,和缺血再灌注损伤。这次审查,第一次,目的探讨H2S和irisin及其可能的串扰在心血管疾病中的作用,指出通过所涉及的常见分子途径发挥的主要作用。
    Irisin is a myokine secreted under the influence of physical activity and exposure to low temperatures and through different exogenous stimuli by the cleavage of its precursor, fibronectin type III domain-containing protein 5 (FNDC5). It is mainly known for maintaining of metabolic homeostasis, promoting the browning of white adipose tissue, the thermogenesis process, and glucose homeostasis. Growing experimental evidence suggests the possible central role of irisin in the regulation of cardiometabolic pathophysiological processes. On the other side, hydrogen sulfide (H2S) is well recognized as a pleiotropic gasotransmitter that regulates several homeostatic balances and physiological functions and takes part in the pathogenesis of cardiometabolic diseases. Through the S-persulfidation of cysteine protein residues, H2S is capable of interacting with crucial signaling pathways, exerting beneficial effects in regulating glucose and lipid homeostasis as well. H2S and irisin seem to be intertwined; indeed, recently, H2S was found to regulate irisin secretion by activating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/FNDC5/irisin signaling pathway, and they share several mechanisms of action. Their involvement in metabolic diseases is confirmed by the detection of their lower circulating levels in obese and diabetic subjects. Along with the importance of metabolic disorders, these modulators exert favorable effects against cardiovascular diseases, preventing incidents of hypertension, atherosclerosis, heart failure, myocardial infarction, and ischemia-reperfusion injury. This review, for the first time, aims to explore the role of H2S and irisin and their possible crosstalk in cardiovascular diseases, pointing out the main effects exerted through the common molecular pathways involved.
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  • 文章类型: Journal Article
    硫化物释放化合物通过减少线粒体衍生的活性氧的产生来减少再灌注损伤。我们以前表征了四硫钼酸铵(ATTM),临床上使用的铜螯合剂,作为啮齿动物的硫化物供体。在这里,我们在临床试验之前评估了对大型哺乳动物的翻译。在健康的猪中,静脉内ATTM剂量递增揭示了具有最小不良临床或生化事件的可再现的药代动力学/药效学(PK/PD)关系。在心肌梗死(左冠状动脉前降支闭塞1小时)再灌注模型中,就在再灌注前开始静脉ATTM或生理盐水.ATTM以药物暴露依赖性方式保护心脏(24小时组织学检查)(r2=0.58,p<0.05)。在ATTM处理的动物中,血肌钙蛋白T水平显着降低(p<0.05),而心肌谷胱甘肽过氧化物酶活性,抗氧化剂硒蛋白,升高(p<0.05)。总的来说,我们的研究代表了硫化物作为治疗剂的开发的重大进展,并强调了ATTM作为再灌注损伤的新型辅助疗法的潜力。机械上,我们的研究表明,调节硒蛋白活性可能代表了硫化物释放药物的另一种作用方式。
    Sulfide-releasing compounds reduce reperfusion injury by decreasing mitochondria-derived reactive oxygen species production. We previously characterised ammonium tetrathiomolybdate (ATTM), a clinically used copper chelator, as a sulfide donor in rodents. Here we assessed translation to large mammals prior to clinical testing. In healthy pigs an intravenous ATTM dose escalation revealed a reproducible pharmacokinetic/pharmacodynamic (PK/PD) relationship with minimal adverse clinical or biochemical events. In a myocardial infarction (1-h occlusion of the left anterior descending coronary artery)-reperfusion model, intravenous ATTM or saline was commenced just prior to reperfusion. ATTM protected the heart (24-h histological examination) in a drug-exposure-dependent manner (r2 = 0.58, p < 0.05). Blood troponin T levels were significantly (p < 0.05) lower in ATTM-treated animals while myocardial glutathione peroxidase activity, an antioxidant selenoprotein, was elevated (p < 0.05). Overall, our study represents a significant advance in the development of sulfides as therapeutics and underlines the potential of ATTM as a novel adjunct therapy for reperfusion injury. Mechanistically, our study suggests that modulating selenoprotein activity could represent an additional mode of action of sulfide-releasing drugs.
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  • 文章类型: Journal Article
    背景:躁狂抑郁性精神病(MDP)或双相情感障碍,在全球和印度人口中普遍存在的精神疾病,已被归因于各种病理机制。硫化氢(H2S),气体发射器家族的一员,可能与双相情感障碍的发展有关,因为它在维持适当的神经元功能方面起着至关重要的作用,可塑性,和稳态函数。在MDP中,关于气体传送器H2S的作用的数据很少,诊断能力,和严重程度预测,这导致我们在西孟加拉邦亚喜马拉雅地区的MDP患者中进行这项研究。
    方法:这是一项在生物化学系进行的观察性病例对照研究,北孟加拉医学院和医院,Siliguri,西孟加拉邦,印度,从2022年1月到2022年12月。研究了50名诊断为MDP的患者和50名符合纳入和排除标准的健康年龄和性别匹配的对照受试者。使用标准化的分光光度亚甲蓝方法测定血液中的H2S水平。采用汉密尔顿抑郁量表(HAM-D)评分评估抑郁的严重程度。
    结果:在50例MDP患者中,45人(90%)处于抑郁期,五个(10%)处于躁狂期。在45名抑郁症患者中,8人(17.8%)患有轻度抑郁症,12人(26.7%)有中度抑郁,19人(42.2%)患有严重抑郁症,6人(13.3%)有非常严重的抑郁症。MDP患者的平均H2S水平(41.98±18.88μmol/l)显着(P<0.05)低于对照组(99.20±15.20μmol/l)。还观察到MDP患者中的平均H2S水平随着疾病的持续时间而降低,但没有统计学意义。发现不同抑郁严重程度组的平均H2S水平存在显着差异(P<0.001)。受试者工作特征(ROC)曲线分析显示H2S的截止值<78.5μmol/l与MDP有关,灵敏度为96%,特异性为88%,H2S的临界值<53μmol/l可预测抑郁症的严重程度,敏感性为89.3%,特异性为76.5%。
    结论:MDP患者中气体传输型H2S的显著相关性及其作为诊断和严重程度预测指标的作用可以帮助我们采取适当的措施来更好地管理MDP并改善生活质量。
    BACKGROUND: Manic depressive psychosis (MDP) or bipolar disorder, a prevalent psychiatric condition globally and in the Indian population, has been attributed to various pathological mechanisms. Hydrogen sulphide (H2S), a member of the gasotransmitter family, may be linked to the development of bipolar disorder because it plays a crucial role in maintaining proper neuronal function in terms of excitability, plasticity, and homeostatic functions. There is very little data regarding the role of the gasotransmitter H2S in MDP in terms of its association, diagnostic ability, and severity prediction, which led us to conduct this study among MDP patients in the Sub-Himalayan region of West Bengal.
    METHODS: This was an observational case-control study performed in the Department of Biochemistry, North Bengal Medical College and Hospital, Siliguri, West Bengal, India, from January 2022 to December 2022. Fifty diagnosed MDP patients and 50 healthy age- and sex-matched control subjects satisfying the inclusion and exclusion criteria were studied. The H2S level in the blood was assayed using the standardised spectrophotometric methylene blue method. The severity of depression was assessed by Hamilton Depression Rating Scale (HAM-D) scoring.
    RESULTS: Of the 50 MDP patients, 45 (90%) were in the depressive phase, and five (10%) were in the manic phase. Of the 45 depressive patients, eight (17.8%) had mild depression, 12 (26.7%) had moderate depression, 19 (42.2%) had severe depression, and six (13.3%) had very severe depression. The mean H2S level in MDP patients (41.98±18.88 μmol/l) was significantly (P<0.05) lower than that in control subjects (99.20± 15.20 μmol/l). It was also observed that the mean H2S level in MDP patients decreased with the duration of the disease but was not statistically significant. The mean H2S levels in the different depression severity groups were found to be significantly different (P<0.001). Receiver operating characteristic (ROC) curve analysis revealed that a cut-off value of H2S <78.5 μmol/l was associated with MDP, with a sensitivity of 96% and a specificity of 88%, and a cut-off value of H2S < 53 μmol/l predicted the severity of depression with a sensitivity of 89.3% and a specificity of 76.5%.
    CONCLUSIONS: The significant association of the gasotransmitter H2S in MDP patients and its role as a diagnostic and severity predictive marker can help us to employ proper measures for better management of MDP and improving quality of life.
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  • 文章类型: Journal Article
    一氧化氮(NO)是控制植物发育和胁迫条件的多种机制所需的气体传递剂。然而,关于这种信号分子在种子脂质储存过程中的具体作用知之甚少。这里,我们表明,NO在发育中的胚胎中积累,并通过稳定碱性/亮氨酸拉链转录因子bZIP67调节脂肪酸谱。NO和硝基亚麻酸靶向并积累bZIP67诱导FAD3去饱和酶的下游表达,在非亚硝基版本的蛋白质中被错误调节。此外,bZIP67的翻译后修饰可通过过氧化物氧化还原蛋白IIE的反硝化活性而逆转,并定义了bZIP67氧化还原调节的反馈机制.这些发现为控制由NO引起的种子脂肪酸谱提供了分子框架,以及硝基脂肪酸在植物发育信号传导过程中体内功能的证据。
    Nitric oxide (NO) is a gasotransmitter required in a broad range of mechanisms controlling plant development and stress conditions. However, little is known about the specific role of this signaling molecule during lipid storage in the seeds. Here, we show that NO is accumulated in developing embryos and regulates the fatty acid profile through the stabilization of the basic/leucine zipper transcription factor bZIP67. NO and nitro-linolenic acid target and accumulate bZIP67 to induce the downstream expression of FAD3 desaturase, which is misregulated in a non-nitrosylable version of the protein. Moreover, the post-translational modification of bZIP67 is reversible by the trans-denitrosylation activity of peroxiredoxin IIE and defines a feedback mechanism for bZIP67 redox regulation. These findings provide a molecular framework to control the seed fatty acid profile caused by NO, and evidence of the in vivo functionality of nitro-fatty acids during plant developmental signaling.
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  • 文章类型: Journal Article
    许多生物使用外源和/或内源气体来获得进化益处。我们对人体的主要气藏之一进行了综合评估,即,肠,提供广泛的数据,可作为未来研究的参考。我们评估健康人的肠道气体,包括它们的体积,composition,近端和远端肠道的来源和局部分布。我们分析了每一种最丰富的肠道气体,包括氮气,氧气,一氧化氮,二氧化碳,甲烷,氢气,硫化氢,二氧化硫和氰化物.对于每一种气体,我们描述了扩散模式,主动跨屏障传输动力学,化学性质,由胞内介导的肠内/肠外代谢作用,细胞外,旁分泌和远处的动作。Further,我们强调了气体发射器的局部和系统作用,即,可以通过肠细胞膜自由扩散的信号气态分子。然而,我们提供了有关某些肠道气体对肌间和粘膜下神经元仍未知影响的可测试假设。
    Many living beings use exogenous and/or endogenous gases to attain evolutionary benefits. We make a comprehensive assessment of one of the major gaseous reservoirs in the human body, i.e., the bowel, providing extensive data that may serve as reference for future studies. We assess the intestinal gases in healthy humans, including their volume, composition, source and local distribution in proximal as well as distal gut. We analyse each one of the most abundant intestinal gases including nitrogen, oxygen, nitric oxide, carbon dioxide, methane, hydrogen, hydrogen sulfide, sulfur dioxide and cyanide. For every gas, we describe diffusive patterns, active trans-barrier transport dynamics, chemical properties, intra-/extra-intestinal metabolic effects mediated by intracellular, extracellular, paracrine and distant actions. Further, we highlight the local and systemic roles of gasotransmitters, i.e., signalling gaseous molecules that can freely diffuse through the intestinal cellular membranes. Yet, we provide testable hypotheses concerning the still unknown effects of some intestinal gases on the myenteric and submucosal neurons.
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  • 文章类型: Journal Article
    一氧化氮(NO),生物系统中重要的气体发射器,在神经系统疾病和癌症中起着至关重要的作用。目前,目前缺乏快速、灵敏地鉴定NO并阐明其与神经系统疾病的关系的有效方法。新型二氨基环金属铱磷光探针,Ir-CDA和Ir-BDA,已被设计用于可视化阿尔茨海默病(AD)和胶质母细胞瘤(GBM)中的气体发射器NO。Ir-CDA和Ir-BDA利用铱(III)作为中心离子并引入二氨基作为配体。二氨基结构与NO之间的相互作用导致形成三氮五元环结构,打开磷光。这两种探针可以选择性地结合NO并提供低检测限。此外,Ir-BDA/Ir-CDA可以在脑癌细胞模型中成像NO,神经炎症模型,和AD细胞模型。此外,AD小鼠的新鲜脑切片中的NO含量明显高于野生型(WT)小鼠。因此,似乎有可能的是,在承载较大Aβ沉积物的细胞周围产生大量的NO,逐渐扩散到整个大脑区域。此外,我们认为,与WT小鼠相比,这种现象是导致AD小鼠脑NO含量较高的关键因素。这一发现为AD的诊断和治疗提供了新的见解。
    Nitric Oxide (NO), a significant gasotransmitter in biological systems, plays a crucial role in neurological diseases and cancer. Currently, there is a lack of effective methods for rapidly and sensitively identifying NO and elucidating its relationship with neurological diseases. Novel diamino-cyclic-metalloiridium phosphorescence probes, Ir-CDA and Ir-BDA, have been designed to visualize the gasotransmitter NO in Alzheimer\'s disease (AD) and glioblastoma (GBM). Ir-CDA and Ir-BDA utilize iridium (III) as the central ion and incorporate a diamino group as a ligand. The interaction between the diamino structure and NO leads to the formation of a three-nitrogen five-membered ring structure, which opens up phosphorescence. The two probes can selectively bind to NO and offer low detection limits. Additionally, Ir-BDA/Ir-CDA can image NO in brain cancer cell models, neuroinflammatory models, and AD cell models. Furthermore, the NO content in fresh brain sections from AD mice was considerably higher than that in wild-type (WT) mice. Consequently, it is plausible that NO is generated in significant quantities around cells hosting larger Aβ deposits, gradually diffusing throughout the entire brain region. Furthermore, we posit that this phenomenon is a key factor contributing to the higher brain NO content in AD mice compared to that in WT mice. This discovery offers novel insights into the diagnosis and treatment of AD.
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  • 文章类型: Journal Article
    硫化氢(H2S)被认为是一种气体信号分子,类似于一氧化氮(-NO)和一氧化碳(CO)。这篇综述的目的是概述人体内硫化氢(H2S)的形成。H2S是通过涉及半胱氨酸和几种酶的酶促过程合成的,包括胱硫醚-β-合酶(CBS),胱硫醚-γ-裂解酶(CSE),半胱氨酸氨基转移酶(CAT),3-巯基丙酮酸硫转移酶(3MST)和D-氨基酸氧化酶(DAO)。硫化氢(H2S)对人体各种系统的生理和病理影响导致了广泛的研究努力,以开发在模拟生理环境并响应各种刺激的条件下递送H2S的适当方法。这些函数的范围很广,从对内分泌系统和细胞寿命的影响到保护肝肾功能。目前还没有很好地了解人体内硫化氢(H2S)的确切生理和危险阈值,需要深入研究。本文就H2S在人体内的生理意义作一综述。它强调了不同情况下H2S产生的各种来源,并研究了检测这种气体的现有技术。
    Hydrogen sulfide (H2S) was recognized as a gaseous signaling molecule, similar to nitric oxide (-NO) and carbon monoxide (CO). The aim of this review is to provide an overview of the formation of hydrogen sulfide (H2S) in the human body. H2S is synthesized by enzymatic processes involving cysteine and several enzymes, including cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), cysteine aminotransferase (CAT), 3-mercaptopyruvate sulfurtransferase (3MST) and D-amino acid oxidase (DAO). The physiological and pathological effects of hydrogen sulfide (H2S) on various systems in the human body have led to extensive research efforts to develop appropriate methods to deliver H2S under conditions that mimic physiological settings and respond to various stimuli. These functions span a wide spectrum, ranging from effects on the endocrine system and cellular lifespan to protection of liver and kidney function. The exact physiological and hazardous thresholds of hydrogen sulfide (H2S) in the human body are currently not well understood and need to be researched in depth. This article provides an overview of the physiological significance of H2S in the human body. It highlights the various sources of H2S production in different situations and examines existing techniques for detecting this gas.
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  • 文章类型: Journal Article
    背景:硫化氢(H2S),内源性气体发射器,在多种条件下都有潜在的应用。然而,由于其气体性质和其他物理化学性质,其在模拟生理溶液中的定量是一个重大挑战。目的:本研究旨在比较四种常用的水溶液中H2S的检测和定量方法。方法:四种技术的比较是一种比色法,一种色谱法和两种电化学方法。结果:比色法和色谱法在毫摩尔和微摩尔范围内定量H2S,分别。电化学方法在纳摩尔和皮摩尔范围内定量了H2S,并且耗时较少。结论:H2S定量方法的选择应根据研究项目在灵敏度方面的具体要求,响应时间和成本效益。
    Background: Hydrogen sulfide (H2S), an endogenous gasotransmitter, has potential applications in several conditions. However, its quantification in simulated physiological solutions is a major challenge due to its gaseous nature and other physicochemical properties. Aim: This study was designed to compare four commonly used H2S detection and quantification methods in aqueous solutions. Methods: The four techniques compared were one colorimetric, one chromatographic and two electrochemical methods. Results: Colorimetric and chromatographic methods quantified H2S in millimolar and micromole ranges, respectively. The electrochemical methods quantified H2S in the nanomole and picomole ranges and were less time-consuming. Conclusion: The H2S quantification method should be selected based on the specific requirements of a research project in terms of sensitivity, response time and cost-effectiveness.
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