alpha-amylase

α - 淀粉酶
  • 文章类型: English Abstract
    这项研究的目的是确定咖啡消费对年轻人唾液皮质醇(sCort)和α淀粉酶(sAA)的影响。
    60名健康的大学生,习惯性的咖啡消费者,参加了这项描述性观察研究。参与者分为三组:G1低消费量(每天≤2杯咖啡,n=20),G2适度消费(每天2-5杯咖啡,n=20),和G3高消费(每天>5杯咖啡,n=20)。唾液自我收集是在早上(6:30-7:30AM)和晚上(08:00-09:00PM)。通过动力学方法使用化学发光和sAA活性分析sCort。使用Studentt检验和方差分析对数据进行统计学分析。
    样本由30名女性和30名男性组成,年龄在20至35岁之间。在所有组中,上午sCort值较高(AM0,29±0,19vs.PM0,09±0,05µg/dl,p<0.0001)。相比之下,夜间sAA水平较高(PM160,16±60,42vs.AM32,79±12,98U/ml,p<0.0001)。没有检测到显著差异,在Corts和AAs的内容中,群体之间。
    :咖啡消费,在非压力条件下,没有改变年轻人的索尔特和sAA的水平和模式。
    UNASSIGNED: The purpose of this study was to determine the effects of coffee consumption on salivary cortisol (sCort) and alpha amylase (sAA) in young adults.
    UNASSIGNED: Sixty healthy university students, habitual coffee consumers, participated in this descriptive observational study. Participants were divided into three groups: G1 low consumption (≤ 2 cups of coffee per day, n = 20), G2 moderate consumption (2-5 cups of coffee per day, n = 20), and G3 high consumption (>5 cups of coffee per day, n = 20). Saliva self-collection was in the morning (6:30-7:30 AM) and at night (08:00-09:00 PM). sCort was analyzed using chemiluminescence and sAA activity by kinetic method. Statistical analysis of the data was performed using Student\'s t-test and analysis of variance.
    UNASSIGNED: The sample consisted of 30 women and 30 men, aged between 20 and 35 years. In all groups, sCort values were higher in the morning (AM 0,29 ± 0,19 vs. PM 0,09 ± 0,05 µg/dl, p < 0.0001). In contrast, sAA levels were higher in the night (PM 160,16 ± 60,42 vs. AM 32,79 ± 12,98 U/ml, p < 0.0001). No significant differences were detected, in the contents of Corts and AAs, between the groups.
    UNASSIGNED: : Coffee consumption, in non-stressful conditions, did not alter levels and patterns of sCort and sAA in young adults.
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  • 文章类型: Journal Article
    八个化合物,包括一个蒽醌,两个双苄基,一个菲,三个二氢菲,和一种类黄酮,从多花石斛壁的根中分离出来。前Lindl.其中,研究了六个化合物对α-葡萄糖苷酶的抑制活性,α-淀粉酶,和糖基化终产物(AGEs)的生产。此外,进行分子对接以分析测试化合物与α-葡萄糖苷酶的相互作用。摩司他汀,唯一分离的菲,显示最强的抗α-葡萄糖苷酶活性,IC50为32.45±1.04μM,大约比阿卡波糖小10倍。此外,moscatilin最强烈地抑制α-淀粉酶和AGEs的产生,IC50值为256.94±9.87和67.89±9.42μM,分别。分子对接分析显示所有物质与α-葡萄糖苷酶的有效结合具有比阿卡波糖更小的最低结合能值。选择莫司他进行动力学研究,它被鉴定为非竞争性抑制剂,其抑制能力比阿卡波糖高约9倍。这项研究代表了有关源自D.polyanthumWall根的化合物的植物化学成分和抗糖尿病潜力的第一份报告。前Lindl.
    Eight compounds, including one anthraquinone, two bibenzyls, one phenanthrene, three dihydrophenanthrenes, and one flavonoid, were isolated from the roots of Dendrobium polyanthum Wall. ex Lindl. Among these, six compounds were investigated for inhibitory activities against alpha-glucosidase, alpha-amylase, and advanced glycation end products (AGEs) production. Additionally, molecular docking was conducted to analyze the interactions of the test compounds with alpha-glucosidase. Moscatin, the only isolated phenanthrene, displayed the strongest anti-alpha-glucosidase activity with an IC50 of 32.45 ± 1.04 μM, approximately 10-fold smaller than that of acarbose. Furthermore, moscatilin most strongly inhibited alpha-amylase and AGEs production with IC50 values of 256.94 ± 9.87 and 67.89 ± 9.42 μM, respectively. Molecular docking analysis revealed the effective binding of all substances to alpha-glucosidase with smaller lowest binding energy values than acarbose. Moscatin was selected for kinetics studies, and it was identified as a non-competitive inhibitor with approximately 9-fold greater inhibitory capability than acarbose. This study represents the first report on the phytochemical constituents and antidiabetic potential of compounds derived from the roots of D. polyanthum Wall. ex Lindl.
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  • 文章类型: Journal Article
    一般的围产期和产后特征可以作为将产前或早期产后事件与后期健康结局联系起来的标志。这反过来又与改变的压力和免疫系统活动有关。我们的探索性研究调查了A)常见的围产期测量“出生体重”和“出生模式”以及B)产后特征“母乳喂养”和“疫苗接种状态”是否与健康年轻人的应激系统-下丘脑-垂体-肾上腺(HPA)轴和自主神经系统(ANS)和炎症(n=68,女性:70.6%,平均年龄:24.21岁,SD=4.38)暴露于心理社会挑战,“特里尔社会压力测试”(TSST)。唾液皮质醇,α-淀粉酶(sAA)和血浆白细胞介素-6(IL-6)进行评估前,在TSST期间和之后。参与者提供了有关出生前后特征的信息。进行线性回归以确定出生前/出生后变量是否预测基础和应激反应相关的生物标志物水平。控制性别和性激素的使用作为相关的混杂因素,我们发现出生体重与皮质醇恢复之间存在显着关联(p=0.032),较高的出生体重预测较高的皮质醇恢复值。预测变量和结果变量之间没有其他显著关联。我们的研究结果表明,在混合性别的健康年轻人中,正常范围的出生体重与皮质醇对心理社会压力的反应有关,表明该围产期标志物与HPA轴功能的长期关联。相比之下,出生体重与成年期ANS应激反应或炎症标志物无关.我们的结果进一步表明,测量出生模式,母乳喂养的持续时间,4月龄时的疫苗接种状况与成年期炎症和应激系统的标志物无关。
    General peri- and postnatal characteristics may serve as markers linking pre- or early postnatal events to later health outcomes, which in turn are associated with altered stress- and immune system activity. Our exploratory study investigated whether A) the common perinatal measures \"birth weight\" and \"birth mode\" and B) the postnatal characteristics \"breastfeeding\" and \"vaccination status\" are associated with markers of stress systems - the hypothalamic-pituitary-adrenal (HPA) axis and autonomous nervous system (ANS) - and inflammation in healthy young adults (n = 68, females: 70.6 %, mean age: 24.21 years, SD = 4.38) exposed to psychosocial challenge, the \'Trier Social Stress Test\' (TSST). Salivary cortisol, alpha-amylase (sAA) and plasma interleukin-6 (IL-6) were assessed before, during and after the TSST. Participants provided information on peri- and postnatal characteristics. Linear regressions were performed to determine whether peri-/postnatal variables predict basal and stress-response-related biomarker levels. Controlling for sex and sex hormone use as relevant confounders, we found a significant association between birth weight and cortisol recovery (p = 0.032), with higher birth weight predicting higher cortisol recovery values. There were no other significant associations between predictor and outcome variables. Our results show that, in healthy young adults of mixed gender, normal-ranged birth weight is related to the cortisol response to psychosocial stress, indicating a long-term association of this perinatal marker with HPA axis function. In contrast, birth weight was not associated with markers of the ANS stress response or inflammation in adulthood. Our results further suggest that the measures birth mode, duration of breastfeeding, and vaccination status at 4 months of age do not relate to markers of the inflammatory and stress systems in adulthood.
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  • 文章类型: Journal Article
    α-淀粉酶(AMY)在调节植物生长中起着重要作用,发展,和植物采后品质的形成。然而,关于全基因组特征知之甚少,表达模式,亚细胞定位,和AMY基因(MaAMYs)在普通淀粉香蕉(Musaacuminata)中的功能调节。来自香蕉基因组数据库的12种MaAMY蛋白被分为两组,并包含一个保守的催化结构域。这些MaAMYs与玉米和水稻的AMYs形成共线对。在MaAMYs中发现了三个串联基因对,表明了推定的基因复制事件。发现MaAMY启动子的顺式作用元件与植物激素有关,发展,和应激反应。此外,MaAMY02、08、09和11在果实发育和成熟过程中活跃表达。具体来说,MaAMY11在香蕉成熟的中后期显示出最高的表达水平。亚细胞定位显示MaAMY02和11主要存在于叶绿体中,而MaAMY08和09主要位于细胞质中。值得注意的是,MaAMY11表达的瞬时衰减导致香蕉果实淀粉含量明显增加,而通过MaAMY11的瞬时过表达证实了淀粉含量的显着降低。一起,这些结果揭示了对结构的新见解,进化,和MaAmy家族的表达模式,肯定了MaAMY11在香蕉果实淀粉降解中的功能作用。
    Alpha-amylase (AMY) plays a significant role in regulating the growth, development, and postharvest quality formation in plants. Nevertheless, little is known about the genome-wide features, expression patterns, subcellular localization, and functional regulation of AMY genes (MaAMYs) in the common starchy banana (Musa acuminata). Twelve MaAMY proteins from the banana genome database were clustered into two groups and contained a conserved catalytic domain. These MaAMYs formed collinear pairs with the AMYs of maize and rice. Three tandem gene pairs were found within the MaAMYs and are indicative of putative gene duplication events. Cis-acting elements of the MaAMY promoters were found to be involved in phytohormone, development, and stress responses. Furthermore, MaAMY02, 08, 09, and 11 were actively expressed during fruit development and ripening. Specifically, MaAMY11 showed the highest expression level at the middle and later stages of banana ripening. Subcellular localization showed that MaAMY02 and 11 were predominately found in the chloroplast, whereas MaAMY08 and 09 were primarily localized in the cytoplasm. Notably, transient attenuation of MaAMY11 expression resulted in an obvious increase in the starch content of banana fruit, while a significant decrease in starch content was confirmed through the transient overexpression of MaAMY11. Together, these results reveal new insights into the structure, evolution, and expression patterns of the MaAMY family, affirming the functional role of MaAMY11 in the starch degradation of banana fruit.
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  • 文章类型: Journal Article
    糖尿病是一种持续的高血糖状况。泰国菜和药物包含香料:肉豆蔻,Mace,丁香芽,豆蔻,肉桂,还有香菜.这些香料在体外抗糖尿病的影响,抗氧化剂,抗炎,和总酚类和类黄酮含量进行了评估。
    进行α-淀粉酶和α-葡糖苷酶抑制测定。通过DPPH和ABTS测定测量抗氧化潜能。通过抑制RAW264.7细胞中的一氧化氮生成来测定抗炎活性。使用FolinCiocalteu方法定量总酚含量,总黄酮含量通过氯化铝比色法估算。
    香料混合物的乙醇和水提取物(暹罗豆蔻,肉豆蔻,Mace,和丁香芽),表示为4-GlurE和4-GlurA,显示α-葡萄糖苷酶的浓度依赖性抑制,IC50值为0.373和0.435mg/mL,分别。4-GlurE和4-GlurA表现出抗氧化活性,通过ABTS·+自由基和DPPH清除能力。4-GlurE通过减少一氧化氮产生(IC50:43.95±2.47μg/mL)显示抗炎潜力。4-GlurE和4-GlurA的总酚含量(TPC)为122.47±1.12和148.72±0.14mgGAE/g,分别。与水提取物相比,4-GlurE表现出更高的总类黄酮含量(TFC)(340.33±4.77和94.17±3.36mgQE/g)。肉桂和丁香水提物在抑制α-葡萄糖苷酶方面比阿卡波糖更有效,具有最高的抗氧化活性。多酚水平(TPC和TFC)与抗氧化能力具有很强的相关性。
    研究结果与4-Glur的传统使用一致,肉桂,用于糖尿病的预防和治疗。
    UNASSIGNED: Diabetes mellitus is a persistent hyperglycemic condition. Thai cuisine and medicine incorporate spices: nutmeg, mace, clove buds, cardamom, cinnamon, and coriander. The in vitro impacts of these spices on anti-diabetic, antioxidant, anti-inflammatory, and total phenolic and flavonoid content were assessed.
    UNASSIGNED: Alpha-amylase and alpha-glucosidase inhibition assays were conducted. Antioxidant potential was measured through DPPH and ABTS assays. Anti-inflammatory activity was determined by inhibiting nitric oxide generation in RAW 264.7 cells. Total phenolic content was quantified using the Folin Ciocalteu method, while total flavonoid content was estimated via the aluminum chloride colorimetric method.
    UNASSIGNED: Ethanolic and aqueous extracts of a blend of spices (Siam cardamom, nutmeg, mace, and clove buds), denoted as 4-GlurE and 4-GlurA, displayed concentration-dependent inhibition of alpha-glucosidase, with IC50 values of 0.373 and 0.435 mg/mL, respectively. 4-GlurE and 4-GlurA exhibited antioxidant activity, by ABTS·+ radical and DPPH scavenging capabilities. 4-GlurE demonstrated anti-inflammatory potential by reducing nitric oxide generation (IC50: 43.95 ± 2.47 μg/mL). 4-GlurE and 4-GlurA possessed total phenolic content (TPC) of 122.47 ± 1.12 and 148.72 ± 0.14 mg GAE/g, respectively. 4-GlurE exhibited a higher total flavonoid content (TFC) compared to the aqueous extract (340.33 ± 4.77 and 94.17 ± 3.36 mg QE/g). Cinnamon and clove aqueous extracts were more potent than acarbose in alpha-glucosidase inhibition with the highest antioxidant activity. Polyphenol levels (TPC and TFC) exhibited strong correlations with antioxidant capacity.
    UNASSIGNED: Findings are consistent with the traditional use of 4-Glur, with cinnamon, for diabetes prevention and treatment.
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  • 文章类型: Journal Article
    II型糖尿病是由葡萄糖水平波动导致的慢性病症,其导致高血糖症,在世界范围内具有增加的严重副作用。α-淀粉酶是参与葡萄糖形成机制的关键酶,因此α-淀粉酶抑制剂已成为开发新线索的治疗靶标,因为它们具有抑制葡萄糖水平的潜力。靶向α-淀粉酶的现有药物突出了导致几个胃肠问题的低吸收率方面的主要缺点。所以,这项研究的目的是开发新的抑制剂与α-淀粉酶的活性位点相互作用,使用基于结构的筛选,结合模式分析,分子动力学模拟。因此,寻找潜在的线索,我们分析了通过Lipinski过滤器筛选的133种伐他立胺衍生物和535种脱氧野立霉素衍生物,这些衍生物具有药物样特性.虚拟筛选,然后结合相互作用分析,我们确定了十种化合物,与标准药物伏格列波糖和米格列醇相比,它们表现出更好的结合能得分,在我们的研究中使用。对接分析,ADMET和代谢位点预测估计了具有良好药物谱的最佳前两种化合物。Further,使用BioviaDiscovery研究将顶级化合物VG9和VG15提升到模拟研究中,以100ns的时间间隔获得稳定性。MD模拟结果表明,与标准药物伏格列波糖相比,我们的化合物VG9在复合物中对α-淀粉酶靶蛋白的活性位点残基具有更好的构象稳定性。因此,我们的研究表明,化合物VG9还表现出最佳的药代动力学和结合亲和力结果,并且可以作为靶向α-淀粉酶治疗II型糖尿病的潜在先导化合物。
    Type-II diabetes mellitus is a chronic disorder that results from fluctuations in the glucose level leading to hyperglycemia with severe adverse effects increasing worldwide. Alpha-Amylase is the key enzyme involved in the mechanism of glucose formation therefore Alpha-Amylase inhibitors have become a therapeutic target in the development of new leads as they have the potential to suppress glucose levels. Existing drugs targeting Alpha-Amylase highlight major drawbacks in terms of poor absorption rate that causes several gastrointestinal issues. So, this research is aimed to develop novel inhibitors interacting with Alpha-Amylase\'s active site using structural-based screening, binding pattern analysis, and molecular dynamic simulation. Hence, to search for a potential lead, we analyzed a total of 133 valiolamine derivatives and 535 desoxynojirimycin derivatives that exhibited drug-like properties screened through Lipinski filters. Virtual screening followed by binding interaction analysis we identified ten compounds that exhibited better binding energy scores compared to the standard drugs voglibose and miglitol, used in our study. The docking analysis, ADMET and metabolic site prediction estimated the best top two compounds with good drug profiles. Further, top compounds VG9 and VG15 were promoted to simulation study using the Biovia Discovery study to access the stability at a time interval of 100 ns. MD simulation results revealed that our compound VG9 possesses better conformational stability in the complex to the active site residues of Alpha-Amylase target protein than standard drug voglibose. Thus, our investigation revealed that compound VG9 also exhibits the best pharmacokinetic as well as binding affinity results and could act as a potential lead compound targeting Alpha-Amylase for Type II diabetes.
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  • 文章类型: Journal Article
    背景:糖尿病(DM),由胰腺β细胞功能障碍和α-淀粉酶分泌中断引起,表现为高血糖。α淀粉酶的合成抑制剂,如阿卡波糖管理葡萄糖,但造成不利影响,促使人们对富含抗氧化剂和抗炎特性的植物性替代品产生兴趣。
    目的:当前的综述研究了基于植物的α-淀粉酶抑制剂,探索他们在DM管理中的潜在治疗作用。专注于他们通过调节α-淀粉酶分泌来调节餐后高血糖的能力,它评估它们的功效,健康益处,以及对糖尿病治疗的影响。
    方法:这篇综述研究了植物来源的α-淀粉酶抑制剂作为使用PubMed的前瞻性糖尿病治疗,谷歌学者,和Scopus数据。
    结果:植物衍生抑制剂,包括A.deliciosa,B.埃及,和N.Nucifera,表现出抗炎和抗氧化特性,有效降低糖尿病患者的α-淀粉酶水平。这样的α-淀粉酶抑制剂在控制糖尿病方面显示有希望的替代治疗,具有降低的副作用。
    结论:目前的文献得出结论,植物来源的α-淀粉酶抑制剂通过调节炎症来调节α-淀粉酶分泌,为糖尿病管理提供了可行的治疗途径。氧化应激,和凋亡机制参与糖尿病的发病机制。对其配方和临床疗效的进一步研究可能揭示其更全面的糖尿病治疗意义。强调它们对葡萄糖调节和整体健康的潜在影响。

    BACKGROUND: Diabetes mellitus (DM), arising from pancreatic β-cell dysfunction and disrupted alpha-amylase secretion, manifests as hyperglycemia. Synthetic inhibitors of alphaamylase like acarbose manage glucose but pose adverse effects, prompting interest in plantderived alternatives rich in antioxidants and anti-inflammatory properties.
    OBJECTIVE: The current review investigates plant-based alpha-amylase inhibitors, exploring their potential therapeutic roles in managing DM. Focusing on their ability to modulate postprandial hyperglycemia by regulating alpha-amylase secretion, it assesses their efficacy, health benefits, and implications for diabetes treatment.
    METHODS: This review examines plant-derived alpha-amylase inhibitors as prospective diabetic mellitus treatments using PubMed, Google Scholar, and Scopus data.
    RESULTS: Plant-derived inhibitors, including A. deliciosa, B. egyptiaca, and N. nucifera, exhibit anti-inflammatory and antioxidant properties, effectively reducing alpha-amylase levels in diabetic conditions. Such alpha-amylase inhibitors showed promising alternative treatment in managing diabetes with reduced adverse effects.
    CONCLUSIONS: The current literature concludes that plant-derived alpha-amylase inhibitors present viable therapeutic avenues for diabetes management by modulating alpha-amylase secretion by regulating inflammatory, oxidative stress, and apoptotic mechanisms involved in the pathogenesis of diabetes. Further investigation into their formulations and clinical efficacy may reveal their more comprehensive diabetes therapeutic significance, emphasizing their potential impact on glucose regulation and overall health.

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  • 文章类型: Journal Article
    糖尿病是一种持续的代谢病症,其特征在于由于胰岛素分泌或功能受损而导致的血糖水平升高。天然抗糖尿病药物的寻找由于其潜在的有效性和安全性而受到关注。SessuviumPortulacastrum,沿海植物,传统上用于各种医疗目的。本研究通过分析其对参与碳水化合物代谢的关键酶的抑制作用,并探索其与关键靶蛋白的分子相互作用,研究了马齿轮轴水提物的抗糖尿病潜力。制备了SessuviumMosulacastrum的水提物并用于体外分析。提取物对α-淀粉酶和α-葡萄糖苷酶的活性降低,对葡萄糖吸收和餐后高血糖至关重要,被评估。分子对接技术用于探索提取物中活性化合物与糖尿病相关蛋白之间的潜在相互作用。包括BAX,GSK3β,和CADH。该研究表明,SessuviumMouracastrum水提物对α-淀粉酶和α-葡萄糖苷酶均具有显着的抑制作用,表明其降低葡萄糖吸收和餐后高血糖的潜力。此外,分子对接分析显示提取物中的活性化合物与参与糖尿病相关途径的关键蛋白之间的强结合相互作用,即凋亡途径,糖原合成,和细胞粘附。这项研究的发现强调了Sessuvium马齿轮轴水提取物的有前途的抗糖尿病潜力。即将进行的研究应该注意从天然来源中分离和表征对这些抗糖尿病疗法产生影响的活性化合物。
    Diabetes mellitus is a persistent metabolic condition marked by elevated blood glucose levels due to compromised insulin secretion or functionality. The search for natural antidiabetic agents has gained attention due to their potential effectiveness and safety profiles. Sessuvium portulacastrum, a coastal plant, has been traditionally used for various medicinal purposes. This study investigates the antidiabetic potential of Sessuvium portulacastrum aqueous extract by analyzing its inhibitory effects on key enzymes involved in carbohydrate metabolism and exploring its molecular interactions with critical target proteins. The aqueous extract of Sessuvium portulacastrum was prepared and used for in vitro analysis. The reduced activity of the extract against α-amylase and α-glucosidase enzymes, crucial in glucose absorption and postprandial hyperglycemia, was assessed. Molecular docking techniques were employed to explore the potential interactions between active compounds in the extract and diabetes-related proteins, including BAX, GSK3β, and CADH. The study revealed significant inhibition of both alpha-amylase and alpha-glucosidase enzymes by Sessuvium portulacastrum aqueous extract, indicating its potential to reduce glucose absorption and postprandial hyperglycemia. Moreover, the molecular docking analysis demonstrated strong binding interactions between active compounds in the extract and key proteins involved in diabetes-related pathways, namely apoptotic pathways, glycogen synthesis, and cell adhesion. The findings of this study highlight the promising antidiabetic potential of Sessuvium portulacastrum aqueous extract. Upcoming research should get an attention on isolating and characterizing the active compounds responsible for these effects on antidiabetic therapies from natural sources.
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  • 文章类型: Journal Article
    芳族化合物是已知的抗淀粉样蛋白聚集体。它们对蛋白质的无定形聚集体的影响是,然而,研究较少。我们选择了芳香氨基酸Trp,Tyr,而Phe,以及另一种已知的稳定剂(即Arg),作为在解淀粉芽孢杆菌α-淀粉酶(BAA)上测试的潜在相容溶剂。在这些添加剂中,Phe是唯一对BAA的热灭活和无定形聚集有效的方法,同时保持其内在的活动。使用50mMPhe的浓度来测试其在体内抵消BAA无定形聚集体的有害作用的潜力。每天皮下注射天然酶给小鼠21天后,BAA的无定形聚集体,以及在50mMPhe存在下产生的聚集体,对注射部位的组织进行了组织学研究。无定形聚集体引起巨噬细胞和脂滴的增加。IL6和TNF-α的血清水平也相应地升高并指示炎症状态。聚集体还导致葡萄糖水平增加,甘油三酯和胆固醇,以及肝酶SGOT和SGPT。另一方面,Phe的存在阻止了这种加剧的炎症状态和随后的生化参数损害.总之,Phe是用于稳定蛋白质和抵消无定形聚集体的病理效应的令人感兴趣的化合物。
    Aromatic compounds are known anti-amyloid aggregates. Their effect on amorphous aggregates of proteins is, however, less studied. We chose aromatic amino acids Trp, Tyr, and Phe, as well as another known stabilizer (i.e. Arg), as potential compatible solvents to be tested on Bacillus amyloliquefaciens alpha-amylase (BAA). Among these additives, Phe was the only one to be effective on the thermal inactivation and amorphous aggregation of BAA, while preserving its intrinsic activity. A concentration of 50 mM Phe was used to test its potential in counteracting the deleterious effect of BAA amorphous aggregates in vivo. After 21 days of daily subcutaneous injections of the native enzyme to mice, amorphous aggregates of BAA, as well as aggregates produced in presence of 50 mM Phe, the tissues located at the site of injection were studied histologically. Amorphous aggregates caused an increase in macrophages and lipid droplets. Serum levels of IL6 and TNF-α were also accordingly elevated and indicative of an inflammation state. Aggregates also resulted into increased levels of glucose, triglycerides and cholesterol, as well as liver enzymes SGOT and SGPT. On the other hand, the presence of Phe prevented this exacerbated inflammatory state and the subsequent impairment of biochemical parameters. In conclusion, Phe is an interesting compound for both stabilizing proteins and counteracting the pathological effect of amorphous aggregates.
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  • 文章类型: Journal Article
    阿卡波糖是一种2型糖尿病药物,通过抑制宿主淀粉酶和葡萄糖苷酶来抑制饮食淀粉分解为葡萄糖。拟杆菌属中的许多肠道物种在阿卡波糖治疗的个体中酶促分解淀粉并改变肠道微生物组中的相对丰度。为了机械地解释这一观察,我们使用了两种淀粉降解拟杆菌模型,卵形拟杆菌(Bo)和类拟杆菌(Bt)。阿卡波糖严重损害了Bt生长,而Bo生长则没有。拟杆菌使用淀粉利用系统(Sus)在淀粉上生长。我们假设Bo和BtSus酶被阿卡波糖差异抑制。相反,我们发现,尽管阿卡波糖主要针对两种生物体中的Sus周质GH97酶,该药物在多个其他点影响淀粉加工。阿卡波糖竞争通过Susβ-桶蛋白的转运并与Sus转录调节因子结合。Further,当在具有阿卡波糖的淀粉中生长时,Bo表达非SusGH97(BoGH97D)。Bt同系物,BtGH97H,不是在相同的条件下表达的,在阿卡波糖存在下,过表达BoGH97D也不能补充Bt生长抑制。这项工作使我们了解拟杆菌中Sus功能和调节的意外复杂性,包括相关物种之间的变异。Further,这表明肠道微生物组可能是阿卡波糖治疗糖尿病不同反应的来源.
    阿卡波糖是一种2型糖尿病药物,主要通过阻止小肠中的淀粉分解为葡萄糖起作用。这是通过抑制宿主酶来实现的,通过降低从饮食淀粉中获得葡萄糖的能力,从而更好地控制血糖。药物和未消化的淀粉传播到大肠,在那里阿卡波糖干扰了一些细菌在淀粉上生长的能力。然而,人们对肠道细菌如何与阿卡波糖相互作用知之甚少,包括可以使用淀粉作为碳源的微生物。这里,我们展示了两种肠道物种,卵形拟杆菌(Bo)和类拟杆菌(Bt),对阿卡波糖的反应不同:阿卡波糖抑制Bt生长,而Bo生长不受抑制。我们揭示了一系列复杂的机制,涉及不同Bo和Bt响应背后的淀粉导入和感知差异。这表明肠道微生物组可能是通过常见肠道微生物中的复杂机制对阿卡波糖治疗糖尿病的可变反应的来源。
    Acarbose is a type-2 diabetes medicine that inhibits dietary starch breakdown into glucose by inhibiting host amylase and glucosidase enzymes. Numerous gut species in the Bacteroides genus enzymatically break down starch and change in relative abundance within the gut microbiome in acarbose-treated individuals. To mechanistically explain this observation, we used two model starch-degrading Bacteroides, Bacteroides ovatus (Bo) and Bacteroides thetaiotaomicron (Bt). Bt growth is severely impaired by acarbose whereas Bo growth is not. The Bacteroides use a starch utilization system (Sus) to grow on starch. We hypothesized that Bo and Bt Sus enzymes are differentially inhibited by acarbose. Instead, we discovered that although acarbose primarily targets the Sus periplasmic GH97 enzymes in both organisms, the drug affects starch processing at multiple other points. Acarbose competes for transport through the Sus beta-barrel proteins and binds to the Sus transcriptional regulators. Further, Bo expresses a non-Sus GH97 (BoGH97D) when grown in starch with acarbose. The Bt homolog, BtGH97H, is not expressed in the same conditions, nor can overexpression of BoGH97D complement the Bt growth inhibition in the presence of acarbose. This work informs us about unexpected complexities of Sus function and regulation in Bacteroides, including variation between related species. Further, this indicates that the gut microbiome may be a source of variable response to acarbose treatment for diabetes.
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