Hypoxanthine

次黄嘌呤
  • 文章类型: Journal Article
    (1)背景:用于评估氢代谢机制的血液生物标志物的多样性限制了对其改善运动表现的影响的全面理解。本研究使用代谢组学方法评估了富氢气体(HRG)对短跑间歇运动后代谢物的影响,旨在阐明其潜在的作用机制。(2)方法:10名健康成年男性在HRG或安慰剂(空气)吸入60分钟后参加了WingateSprint间隔测试(SIT)。在气体吸入之前和之后以及完成SIT之后,收集静脉血液样品用于代谢组学分析。(3)结果:与安慰剂相比,HRG吸入显著提高平均功率,疲劳指数,以及第四次冲刺的峰值时间,并显着降低了峰值功率的衰减值,平均力量,以及在第一和第四之间达到峰值的时间。代谢组学分析强调了乙酰肉碱的显着上调,丙酰基-L-肉碱,次黄嘌呤,和黄嘌呤吸入HRG,富集途径分析表明,HRG可能通过增强辅酶A合成促进脂肪动员,促进甘油磷脂代谢,抑制胰岛素水平。(4)结论:在SIT之前吸入HRG可增强终末期无氧冲刺能力并减轻疲劳。代谢组学分析表明,HRG可能通过加速脂肪氧化来增强间歇阶段的ATP恢复,为后期冲刺提供更多的能量补充。
    (1) Background: The diversity of blood biomarkers used to assess the metabolic mechanisms of hydrogen limits a comprehensive understanding of its effects on improving exercise performance. This study evaluated the impact of hydrogen-rich gas (HRG) on metabolites following sprint-interval exercise using metabolomics approaches, aiming to elucidate its underlying mechanisms of action. (2) Methods: Ten healthy adult males participated in the Wingate Sprint-interval test (SIT) following 60 min of HRG or placebo (air) inhalation. Venous blood samples were collected for metabolomic analysis both before and after gas inhalation and subsequent to completing the SIT. (3) Results: Compared with the placebo, HRG inhalation significantly improved mean power, fatigue index, and time to peak for the fourth sprint and significantly reduced the attenuation values of peak power, mean power, and time to peak between the first and fourth. Metabolomic analysis highlighted the significant upregulation of acetylcarnitine, propionyl-L-carnitine, hypoxanthine, and xanthine upon HRG inhalation, with enrichment pathway analysis suggesting that HRG may foster fat mobilization by enhancing coenzyme A synthesis, promoting glycerophospholipid metabolism, and suppressing insulin levels. (4) Conclusions: Inhaling HRG before an SIT enhances end-stage anaerobic sprint capabilities and mitigates fatigue. Metabolomic analysis suggests that HRG may enhance ATP recovery during interval stages by accelerating fat oxidation, providing increased energy replenishment for late-stage sprints.
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  • 文章类型: Journal Article
    非靶向代谢组学为肌少症的发病机制提供了新的见解。在这项研究中,我们在一项基于LC-MS的非靶向代谢组学的队列研究中探讨了与肌肉减少症风险增加相关的血浆代谢特征.
    在这项来自成人体质与健康队列研究(APFHCS)的嵌套病例对照研究中,我们收集了30例新发肌少症患者(平均年龄73.2±5.6岁)和30例健康对照(平均年龄74.2±4.6岁)的血浆样本,性别,BMI,生活方式,和合并症。采用非靶向代谢组学方法来辨别新诊断的肌肉减少症个体中存在的代谢组学改变。
    将新发肌少症患者与正常对照组进行比较,使用液相色谱-质谱(LC-MS)进行的综合分析确定了总共62种代谢物,主要包含脂质,类脂分子,有机酸,和衍生品。受试者工作特征(ROC)曲线分析表明,3种代谢产物次黄嘌呤(AUC=0.819,95%CI=0.711-0.927),L-2-氨基-3-氧代丁酸(AUC=0.733,95%CI=0.598-0.868)和PC(14:0/20:2(11Z,14Z))(AUC=0.717,95%CI=0.587-0.846)的曲线下面积最高。然后,这些显著的代谢物被观察到显著富集在四个不同的代谢途径,即,“嘌呤代谢”;“甲状旁腺激素合成,分泌和作用“;”癌症中的胆碱代谢“;”和“结核病”。
    当前的研究阐明了在诊断为肌少症的个体中观察到的代谢扰动。鉴定的代谢物有望成为潜在的生物标志物,为探索与肌少症相关的潜在病理机制提供了途径。
    UNASSIGNED: Untargeted metabonomics has provided new insight into the pathogenesis of sarcopenia. In this study, we explored plasma metabolic signatures linked to a heightened risk of sarcopenia in a cohort study by LC-MS-based untargeted metabonomics.
    UNASSIGNED: In this nested case-control study from the Adult Physical Fitness and Health Cohort Study (APFHCS), we collected blood plasma samples from 30 new-onset sarcopenia subjects (mean age 73.2 ± 5.6 years) and 30 healthy controls (mean age 74.2 ± 4.6 years) matched by age, sex, BMI, lifestyle, and comorbidities. An untargeted metabolomics methodology was employed to discern the metabolomic profile alterations present in individuals exhibiting newly diagnosed sarcopenia.
    UNASSIGNED: In comparing individuals with new-onset sarcopenia to normal controls, a comprehensive analysis using liquid chromatography-mass spectrometry (LC-MS) identified a total of 62 metabolites, predominantly comprising lipids, lipid-like molecules, organic acids, and derivatives. Receiver operating characteristic (ROC) curve analysis indicated that the three metabolites hypoxanthine (AUC=0.819, 95% CI=0.711-0.927), L-2-amino-3-oxobutanoic acid (AUC=0.733, 95% CI=0.598-0.868) and PC(14:0/20:2(11Z,14Z)) (AUC= 0.717, 95% CI=0.587-0.846) had the highest areas under the curve. Then, these significant metabolites were observed to be notably enriched in four distinct metabolic pathways, namely, \"purine metabolism\"; \"parathyroid hormone synthesis, secretion and action\"; \"choline metabolism in cancer\"; and \"tuberculosis\".
    UNASSIGNED: The current investigation elucidates the metabolic perturbations observed in individuals diagnosed with sarcopenia. The identified metabolites hold promise as potential biomarkers, offering avenues for exploring the underlying pathological mechanisms associated with sarcopenia.
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  • 文章类型: Journal Article
    碱基的脱氨基是DNA损伤的一种形式,通过活细胞的水解和亚硝化自发发生,从腺嘌呤产生次黄嘌呤。大肠杆菌核酸内切酶V(eEndoV)切割含有次黄嘌呤的双链DNA,而人类核酸内切酶V(hEndoV)切割含有次黄嘌呤的RNA;然而,hEndoV在体内的功能尚不清楚。迄今为止,hEndoV仅使用次黄嘌呤进行了检查,因为它与位于切割位点的碱基紧密结合。这里,我们检查了hEndoV是否切割其他病变(例如,AP站点,6-甲基腺嘌呤,黄嘌呤)以揭示其功能以及2'-核苷修饰是否会影响其切割活性。我们观察到hEndoV是次黄嘌呤特异性的;其活性最高,核糖中的2'-OH修饰。基于其碱基序列比较hEndoV的切割活性。我们观察到它对位于次黄嘌呤裂解位点3'末端的腺嘌呤具有特异性,乳沟之前和之后。这些数据表明hEndoV识别并切割在polyA尾巴上产生的肌苷以维持RNA质量。我们的结果提供了对hEndoV在体内作用的机制见解。
    Deamination of bases is a form of DNA damage that occurs spontaneously via the hydrolysis and nitrosation of living cells, generating hypoxanthine from adenine. E. coli endonuclease V (eEndoV) cleaves hypoxanthine-containing double-stranded DNA, whereas human endonuclease V (hEndoV) cleaves hypoxanthine-containing RNA; however, hEndoV in vivo function remains unclear. To date, hEndoV has only been examined using hypoxanthine, because it binds closely to the base located at the cleavage site. Here, we examined whether hEndoV cleaves other lesions (e.g., AP site, 6-methyladenine, xanthine) to reveal its function and whether 2\'-nucleoside modification affects its cleavage activity. We observed that hEndoV is hypoxanthine-specific; its activity was the highest with 2\'-OH modification in ribose. The cleavage activity of hEndoV was compared based on its base sequence. We observed that it has specificity for adenine located on the 3\'-end of hypoxanthine at the cleavage site, both before and after cleavage. These data suggest that hEndoV recognizes and cleaves the inosine generated on the poly A tail to maintain RNA quality. Our results provide mechanistic insight into the role of hEndoV in vivo.
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  • 文章类型: Journal Article
    通过原位合成GQDs获得TiO2/石墨烯量子点复合材料(TiO2/GQDs),源自咖啡渣,并以过氧钛配合物作为电极修饰剂同时电化学测定尿酸和次黄嘌呤。通过光致发光对TiO2/GQDs材料进行了表征,X射线衍射,拉曼光谱,高分辨率透射电子显微镜,和能量色散X射线测绘。在差分脉冲伏安法(DPV)测量中,TiO2/GQDs-GCE对尿酸和次黄嘌呤的电化学活性优于GQDs/GCE或TiO2/GCE。在优化条件下,尿酸和次黄嘌呤的校准曲线在1.00~15.26μM范围内呈线性关系.该方法对尿酸和次黄嘌呤的检出限分别为0.58和0.68μM,分别。提出的DPV方法用于测定尿液样品中的尿酸和次黄嘌呤,回收率可接受。
    A TiO2/graphene quantum dots composite (TiO2/GQDs) obtained by in situ synthesis of GQDs, derived from coffee grounds, and peroxo titanium complexes was used as electrode modifier in the simultaneous electrochemical determination of uric acid and hypoxanthine. The TiO2/GQDs material was characterized by photoluminescence, X-ray diffraction, Raman spectroscopy, high-resolution transmission electron microscopy, and energy-dispersive X-ray mapping. The TiO2/GQDs-GCE exhibits better electrochemical activity for uric acid and hypoxanthine than GQDs/GCE or TiO2/GCE in differential pulse voltammetry (DPV) measurements. Under optimized conditions, the calibration plots were linear in the range from 1.00 to 15.26 μM for both uric acid and hypoxanthine. The limits of detection of this method were 0.58 and 0.68 μM for uric acid and hypoxanthine, respectively. The proposed DPV method was employed to determine uric acid and hypoxanthine in urine samples with acceptable recovery rates.
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  • 文章类型: Journal Article
    嘌呤核苷酸对于RNA和DNA合成至关重要,信令,新陈代谢,和能量稳态。要合成嘌呤,细胞使用两种主要途径:从头途径和救助途径。传统上,据认为,增殖细胞主要依赖于从头合成,而分化的组织倾向于挽救途径。出乎意料的是,我们发现腺嘌呤和肌苷是向组织和肿瘤提供嘌呤核苷酸的最有效的循环前体,而次黄嘌呤在体内快速分解代谢且回收不良。定量代谢分析证明了从头合成和补救途径在维持肿瘤中嘌呤核苷酸库方面的比较贡献。值得注意的是,喂食小鼠核苷酸加速肿瘤生长,而抑制嘌呤挽救减缓肿瘤进展,揭示了挽救途径在肿瘤代谢中的关键作用。这些发现为正常组织和肿瘤如何维持嘌呤核苷酸提供了基本见解,并强调了嘌呤补救在癌症中的重要性。
    Purine nucleotides are vital for RNA and DNA synthesis, signaling, metabolism, and energy homeostasis. To synthesize purines, cells use two principal routes: the de novo and salvage pathways. Traditionally, it is believed that proliferating cells predominantly rely on de novo synthesis, whereas differentiated tissues favor the salvage pathway. Unexpectedly, we find that adenine and inosine are the most effective circulating precursors for supplying purine nucleotides to tissues and tumors, while hypoxanthine is rapidly catabolized and poorly salvaged in vivo. Quantitative metabolic analysis demonstrates comparative contribution from de novo synthesis and salvage pathways in maintaining purine nucleotide pools in tumors. Notably, feeding mice nucleotides accelerates tumor growth, while inhibiting purine salvage slows down tumor progression, revealing a crucial role of the salvage pathway in tumor metabolism. These findings provide fundamental insights into how normal tissues and tumors maintain purine nucleotides and highlight the significance of purine salvage in cancer.
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  • 文章类型: Journal Article
    次黄嘌呤是评价各种水产品新鲜度的一个有前途的指标。结合含有上转换纳米粒子(UCNPs)的水凝胶,Co3O4NP,和N-乙基-N-(3-磺丙基)-3-甲基苯胺钠盐/4-氨基安替比林(TOPS/4-AAP)与智能手机,为了方便起见,开发了便携式传感器,次黄嘌呤的灵敏检测。利用黄嘌呤氧化酶(XOD)催化的H2O2催化的次黄嘌呤反应,由具有过氧化物酶活性的Co3O4NP催化的TOPS/4-AAP氧化产生的紫色产物有效地猝灭了UCNPs的荧光,其中颜色变化可以转化为数字信号,用于定量次黄嘌呤。荧光图像的RGB分析中的绿色值与次黄嘌呤浓度在2.5-20mg/L范围内呈负相关,检出限为0.69mg/L,定量限为2.30mg/L。最后,该传感器用于实际水产品中的次黄嘌呤检测,对水产品新鲜度评价具有潜在的应用价值。
    Hypoxanthine is a promising index for evaluating the freshness of various aquatic products. Combined the hydrogels containing upconversion nanoparticles (UCNPs), Co3O4 NPs, and N-ethyl-N-(3-sulfopropyl)-3-methylaniline sodium salt/4-amino-antipyrine (TOPS/4-AAP) with a smartphone, a portable sensor was developed for the convenient, sensitive detection of hypoxanthine. With the H2O2 from xanthine oxidase (XOD)-catalyzed reactions of hypoxanthine, the fluorescence of UCNPs was effectively quenched by the purple product produced from the oxidization of TOPS/4-AAP catalyzed by Co3O4 NPs exhibiting peroxidase activity, among which the color change could be transformed into digital signals for quantification of hypoxanthine. The Green value in the RGB analysis of the fluorescence image was negatively proportional to hypoxanthine concentration in the range of 2.5-20 mg/L with a detection limit of 0.69 mg/L and a quantitation limit of 2.30 mg/L. Finally, this sensor was applied for hypoxanthine detection in real aquatic products, showing potential application for freshness evaluation of aquatic products.
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  • 文章类型: Journal Article
    使用量子力学/波动电荷(QM/FQ)多尺度方法结合通过原子分子动力学(MD)模拟对构型进行采样,研究了溶剂化嘌呤衍生物次黄嘌呤(HYX)的UV-Vis光谱。Keto1H7H和1H9H互变异构形式的HYX在水溶液中最稳定,并与周围的水分子形成不同的稳定复合物,最终影响电子吸收光谱。由互变异构体的各个光谱的组合产生的最终模拟光谱与测量光谱中的大多数特征非常吻合。考虑溶质互变异构体的影响的重要性,并行,在模拟光谱性质时,溶质周围不同溶剂排列的贡献,突出显示。此外,计算光谱的高质量导致提出了一种从组合的计算/实验光谱中获取互变异构种群的替代方法。
    The UV-Vis spectrum of the solvated purine derivative Hypoxanthine (HYX) is investigated using the Quantum Mechanics/Fluctuating Charges (QM/FQ) multiscale approach combined with a sampling of configurations through atomistic Molecular Dynamics (MD) simulations. Keto 1H7H and 1H9H tautomeric forms of HYX are the most stable in aqueous solution and form different stable complexes with the surrounding water molecules, ultimately affecting the electronic absorption spectra. The final simulated spectrum resulting from the combination of the individual spectra of tautomers agrees very well with most of the characteristics in the measured spectrum. The importance of considering the effect of the solute tautomers and, in parallel, the contribution of the different solvent arrangements around the solute when modeling spectral properties, is highlighted. In addition, the high quality of the computed spectra leads to suggesting an alternative way for acquiring tautomeric populations from combined computational/experimental spectra.
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  • 文章类型: Journal Article
    建立快速、准确的水产品新鲜度监测方法具有重要意义。次黄嘌呤被认为是水产品新鲜度的重要指标。这里,建立了一种新型的智能手机比色/电感耦合等离子体质谱(ICP-MS)/光热三模式传感策略,用于监测次黄嘌呤。黄嘌呤氧化酶可以催化次黄嘌呤生成H2O2和尿酸,可以同时将MnO2纳米片(NSs)降解为Mn2。过滤辅助分离后,通过监测膜的颜色和滤液中的Mn2+来进行智能手机和ICP-MS。此外,MnO2NSs可以促进多巴胺氧化形成聚多巴胺纳米颗粒,表现出很强的光热效率。该方法通过便携式温度计和具有低检测限(LODs)的智能手机,成功地监测了各种储存条件下水产品的变质,为水产品新鲜度的原位评价提供了潜在的应用。
    Establishing a rapid and accurate method for monitoring the freshness of aquatic products is of great importance. Hypoxanthine has been considered an essential indicator of aquatic products\' freshness. Here, a novel smartphone colorimetric / inductively coupled plasma mass spectrometry (ICP-MS) / photothermal three-mode sensing strategy was established for monitoring hypoxanthine. Hypoxanthine can be catalyzed by xanthine oxidase to H2O2 and uric acid, which can simultaneously degrade MnO2 nanosheets (NSs) to Mn2+. After filter-assisted separation, the smartphone and ICP-MS were performed by monitoring the color of the membrane and the Mn2+ in the filtrate. Additionally, MnO2 NSs can facilitate the oxidation of dopamine to form polydopamine nanoparticles, which exhibit strong photothermal efficiency. The approach successfully monitored the deterioration of aquatic products under various storage conditions through portable thermometers and smartphones with low limits of detection (LODs), providing a potential application for in-situ evaluation of the freshness of aquatic products.
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  • 文章类型: Journal Article
    轻快的发展,低成本可靠,肉类产品中生物活性成分次黄嘌呤(Hx)的精确现场检测对保障食品安全和公众健康具有重要意义。在这里,我们提出了一种智能手机辅助的聚集诱导发射(AIE)四苯基乙烯(TPE)掺入的无定形Fe掺杂磷钨酸盐(Fe-Phos@TPE)纳米酶的比率荧光比色双模式生物传感器,用于实现现场视觉检测Hx。当Hx存在时,黄嘌呤氧化酶(XOD)将Hx催化成H2O2,在pH=6.5时,Fe-Phos@TPE的突出过氧化物酶活性进一步催化成•OH,导致非荧光邻苯二胺的氧化(OPD,裸眼无色)为黄色荧光发射2,3-二氨基吩嗪(DAP,在550nm处的裸眼深黄色)以及在440nm处的Fe-Phos@TPE的固有蓝色荧光将通过内部滤光片效应(IFE)作用降低,从而实现了在接近中性pH下的多酶级联催化反应,克服了传统的酸度依赖性引起的耗时和低灵敏度的麻烦。
    The development of facile, low-cost reliable, and precise onsite assays for the bioactive component hypoxanthine (Hx) in meat products is significant for safeguarding food safety and public health. Herein, we proposed a smartphone-assissted aggregation-induced emission (AIE) fluorogen tetraphenylethene (TPE)-incorporated amorphous Fe-doped phosphotungstates (Fe-Phos@TPE) nanozyme-based ratiometric fluorescence-colorimetric dual-mode biosensor for achieving the onsite visual detection of Hx. When the Hx existed, xanthine oxidase (XOD) catalyzed Hx into H2O2 to be further catalyzed into •OH by the prominent peroxidase activity of Fe-Phos@TPE at pH = 6.5, resulting in the oxidization of nonfluorescent o-phenylenediamine (OPD, naked-eye colorless) to be yellow fluorescent emissive 2,3-diaminophenazine (DAP, naked-eye dark yellow) at 550 nm as well as the intrinsic blue fluorescence of Fe-Phos@TPE at 440 nm to be decreased via inner-filter effect (IFE) action, thereby realizing a multi-enzyme cascade catalytic reaction at near-neutral pH to overcome the traditional acidity dependence-induced time-consuming and low sensitivity troublesome.
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  • 文章类型: Journal Article
    次黄嘌呤(Hx),三磷酸腺苷(ATP)代谢产生,是确定肉制品质量和降解状态的有价值指标,也是痛风等某些疾病的重要生化指标。纸质酶生物传感器的迅速出现已经彻底改变了其现场测定。但它仍然受到复杂的图案和制造的限制,不稳定的酶和不均匀的着色。本工作旨在开发一种生态友好的方法来构建工程纸微流控,其寻求在没有任何图案化程序的情况下产生反应区和非反应区。壳寡糖(COS),源自虾壳,用于修饰硝酸纤维素膜,固定黄嘌呤氧化酶(XOD)和氯化硝基蓝四唑(NBT)的显色剂。修改后,微流体可以会聚到改性区域,并且可以通过XOD催化的转化检测到Hx。由于COS的带正电的阳离子基本特性,通过COS和XOD与甲产品之间的静电吸引,可以大大增强酶的储存稳定性和颜色均匀性。检出限(LOD)为2.30μM;线性范围为0.05-0.35mM;完整的测试时间可短至5分钟。基于COS的生物传感器具有很高的特异性,可直接用于鱼虾样品等复杂样品中的Hx,和不同的肉汤。这个生物传感器是环保的,非技术性的,经济,因此是一个令人信服的平台,用于现场或基于家庭的食品新鲜度检测。
    Hypoxanthine (Hx), produced by adenosine triphosphate (ATP) metabolism, is a valuable indicator that determines the quality and degradation status of meat products and is also an important biochemical marker to certain diseases such as gout. The rapid emergence of paper-based enzyme biosensors has already revolutionized its on-site determination. But it is still limited by the complex patterning and fabrication, unstable enzyme and uneven coloration. This work aims to develop an eco-friendly method to construct engineered paper microfluidic, which seeks to produce reaction and non-reaction zones without any patterning procedure. Chito-oligosaccharide (COS), derived from shrimp shells, was used to modify nitrocellulose membranes and immobilize xanthine oxidase (XOD) and chromogenic agent of nitro blue tetrazolium chloride (NBT). After modification, micro fluids could converge into the modification area and Hx could be detected by XOD-catalyzed conversion. Due to the positively charged cationic basic properties of COS, the enzyme storage stability and the color homogeneity could be greatly strengthened through the electrostatic attraction between COS and XOD and formazan product. The detection limit (LOD) is 2.30 μM; the linear range is 0.05-0.35 mM; the complete test time can be as short as 5 min. The COS-based biosensor shows high specificity and can be used directly for Hx in complex samples such as fish and shrimp samples, and different broths. This biosensor is eco-friendly, nontechnical, economical and therefore a compelling platform for on-site or home-based detection of food freshness.
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