Deacetylation

脱乙酰化
  • 文章类型: Journal Article
    背景:由SARS-CoV-2引起的COVID-19的全球爆发已导致数百万人死亡。这种意想不到的紧急情况促使全球病毒学家更深入地研究宿主-病毒界面的复杂动态性,旨在识别抗病毒靶标并阐明严重疾病的宿主和病毒决定因素。
    目的:本研究旨在分析组蛋白去乙酰化酶6(HDAC6)在调节SARS-CoV-2感染中的作用。
    结果:在SARS-CoV-2感染后,在不同的SARS-CoV-2允许细胞系中观察到HDAC6表达逐渐增加。SARS-CoV-2核衣壳蛋白(N蛋白)被鉴定为负责上调HDAC6表达的主要病毒因子。使用shRNA或特异性抑制剂tubacin下调HDAC6导致病毒复制减少,表明其脱乙酰酶活性的前病毒作用。进一步的研究揭示了HDAC6与应激颗粒蛋白G3BP1和N蛋白在感染过程中的相互作用。发现HDAC6介导的SARS-CoV-2N蛋白的去乙酰化对其与G3BP1的关联至关重要。
    结论:这项研究为SARS-CoV-2感染过程中细胞质应激颗粒破坏的分子机制提供了有价值的见解,并强调了HDAC6在此过程中的重要性。
    BACKGROUND: The global outbreak of COVID-19 caused by the SARS-CoV-2 has led to millions of deaths. This unanticipated emergency has prompted virologists across the globe to delve deeper into the intricate dynamicity of the host-virus interface with an aim to identify antiviral targets and elucidate host and viral determinants of severe disease.
    OBJECTIVE: The present study was undertaken to analyse the role of histone deacetylase 6 (HDAC6) in regulating SARS-CoV-2 infection.
    RESULTS: Gradual increase in HDAC6 expression was observed in different SARS-CoV-2-permissive cell lines following SARS-CoV-2 infection. The SARS-CoV-2 nucleocapsid protein (N protein) was identified as the primary viral factor responsible for upregulating HDAC6 expression. Downregulation of HDAC6 using shRNA or a specific inhibitor tubacin resulted in reduced viral replication suggesting proviral role of its deacetylase activity. Further investigations uncovered the interaction of HDAC6 with stress granule protein G3BP1 and N protein during infection. HDAC6-mediated deacetylation of SARS-CoV-2 N protein was found to be crucial for its association with G3BP1.
    CONCLUSIONS: This study provides valuable insights into the molecular mechanisms underlying the disruption of cytoplasmic stress granules during SARS-CoV-2 infection and highlights the significance of HDAC6 in the process.
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  • 文章类型: Journal Article
    高迁移率族蛋白B1(HMGB1)作为致病性炎症反应,介导各种疾病,如癫痫,感染性休克,缺血,创伤性脑损伤,帕金森病,阿尔茨海默病和质谱。HMGB1在无菌和感染性损伤期间促进炎症,并在疾病发展中起关键作用。从细胞核动员到细胞质是活化免疫细胞释放HMGB1的第一步重要步骤。这里,我们证明了Sirtuin2(SIRT2)在43个赖氨酸残基的核定位信号位置与HMGB1物理相互作用并去乙酰化,加强其与HMGB1的相互作用并使HMGB1定位于细胞质中。这些发现是第一个揭示SIRT2核质穿梭的发现,影响HMGB1及其降解,因此揭示了神经炎症治疗的新治疗靶点和途径。
    High mobility group protein B1 (HMGB1) acts as a pathogenic inflammatory response to mediate ranges of conditions such as epilepsy, septic shock, ischemia, traumatic brain injury, Parkinson\'s disease, Alzheimer\'s disease and mass spectrometry. HMGB1 promotes inflammation during sterile and infectious damage and plays a crucial role in disease development. Mobilization from the nucleus to the cytoplasm is the first important step in the release of HMGB1 from activated immune cells. Here, we demonstrated that Sirtuin 2 (SIRT2) physically interacts with and deacetylates HMGB1 at 43 lysine residue at nuclear localization signal locations, strengthening its interaction with HMGB1 and causing HMGB1 to be localized in the cytoplasm. These discoveries are the first to shed light on the SIRT2 nucleoplasmic shuttle, which influences HMGB1 and its degradation, hence revealing novel therapeutic targets and avenues for neuroinflammation treatment.
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  • 文章类型: Journal Article
    多糖广泛用于改善基于植物的肉类似物(PMA)的质量。在这项研究中,制备了四种不同脱乙酰度(DD)的魔芋葡甘聚糖(KG),即KG1(原生KG,DD=0.00%),KG2(DD=41.40%),KG3(DD=80.01%)和KG4(DD=89.07%),研究了它们对PMA质量的影响。结果表明,KG3在不降低P21的情况下提高了PMA的硬度(从3017.16g提高到3307.16g)和蛋白质消化率(从49.65%提高到53.01%),KG2和KG4的效果不如KG3,而KG1导致PMA的硬度和蛋白质消化率显着下降。流变学性质和分子间力分析表明,部分脱乙酰KG更有利于提高加热过程中蛋白质体系的G\'和PMA中共价键的比例。这些发现表明,在PMA中,部分脱乙酰的KG比天然或高度脱乙酰的KG更有前途。此外,扫描电镜显示,KG的形态从细丝逐渐改变,粗丝,短丝和颗粒随DD增加。本研究为部分脱乙酰KG在PMA中的应用提供了理论依据。
    Polysaccharides are widely used to improve the quality of plant-based meat analogue (PMA). In this study, four kinds of konjac glucomannan (KG) with different deacetylation degrees (DD) were prepared, namely KG1 (native KG, DD = 0.00 %), KG2 (DD = 41.40 %), KG3 (DD = 80.01 %) and KG4 (DD = 89.07 %), and their effects on the quality of PMA were studied. Results manifested that KG3 improved the hardness (from 3017.16 g to 3307.16 g) and protein digestibility (from 49.65 % to 53.01 %) of PMA without reducing the P21, KG2 and KG4 were less effective than KG3, while KG1 led to a significant decline in the hardness and protein digestibility of PMA. The rheological properties and intermolecular force analysis showed that the partially deacetylated KG was more conducive to improving the G\' of the protein system during heating and the proportion of covalent bonds in PMA. These findings suggested that partially deacetylated KG was more promising than native or highly deacetylated KG in PMA. Furthermore, scanning electron microscopy revealed that the morphology of KG gradually changed from fine filaments, to coarse filaments, short filaments and granules as DD increased. This study provides a theoretical basis for the application of partially deacetylated KG in PMA.
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  • 文章类型: Journal Article
    与天然大豆皂甙及其在人体肠道中通过酶促水解形成的苷元不同,体内中间大豆皂甙代谢物很难制备。因此,体内中间大豆皂甙的药理活性仍未研究。在这里,通过制备型高效液相色谱法对天然大豆皂甙进行体外脱乙酰(碱处理)和脱葡糖基化(β-葡萄糖苷酶处理),制备纯度>90%的体内中间大豆皂甙。这些化合物在体外生物测定中表现出比天然大豆皂甙更高的抗炎和抗氧化活性,这表明中间大豆皂甙可以用作改进的生物活性食品补充剂。据我们所知,这是首次报道人体肠道中形成的体内大豆皂甙代谢产物的体外制备和生物分析。
    Unlike natural soyasaponins and their aglycones formed by enzymatic hydrolysis in the human intestine, in vivo intermediate soyasaponin metabolites are difficult to prepare. Therefore, the pharmacological activities of in vivo intermediate soyasaponins remain uninvestigated. Herein, in vivo intermediate soyasaponins with purities of >90% were prepared by in vitro deacetylation (alkaline treatment) and deglucosylation (β-glucosidase treatment) of natural soyasaponins using preparative high-performance liquid chromatography. These compounds exhibited higher anti-inflammatory and antioxidant activities than natural soyasaponins in in vitro bioassays, suggesting that the intermediate soyasaponins can be used as improved bioactive food supplements. To the best of our knowledge, this is the first study reporting the in vitro preparation and bioassays of in vivo intermediate soyasaponin metabolites formed in the human intestine.
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  • 文章类型: Journal Article
    由于其乳化和增稠性能,魔芋葡甘聚糖(KGM)广泛应用于食品中,医学,和材料工业。然而,其高粘度和显著的吸水性限制了其应用范围。因此,为了提高KGM的脱乙酰效率,进行了电子束辐照预处理,并对KGM的理化性质和凝胶性质进行了研究。结果表明,电子束辐照和脱乙酰作用降低了吸水率,溶解度,透明度,分子量,和KGM的粘度。相反,水分含量,热稳定性,和水结合能力增加。FTIR和X射线衍射分析表明,改性前后KGM的化学和晶体结构没有显着变化。然而,改性削弱了KGM水溶胶的分子间相互作用,这影响了它们的流变学。此外,脱乙酰提高了KGM凝胶的机械性能和保水能力。总的来说,电子束辐照预处理提供了一种提高KGM脱乙酰效率和改善KGM理化性能的方法,从而扩大其在食品和化学工业中的潜在应用,在其他人中。
    Due to its emulsifying and thickening properties, konjac glucomannan (KGM) is widely used in the food, medicine, and materials industries. Nevertheless, its high viscosity and significant water absorption limit its application range. Therefore, electron beam (e-beam) irradiation pretreatment was carried out to improve the deacetylation efficiency of KGM, and the physicochemical and gel properties of KGM were investigated. The results show that e-beam irradiation and deacetylation decrease the water absorption, solubility, transparency, molecular weight, and viscosity of KGM. Conversely, the moisture content, thermal stability, and water-binding capacity increase. FTIR and X-ray diffraction analysis revealed no significant changes in the chemical and crystalline structure of KGM before and after modification. However, modification weakens the intermolecular interaction of KGM hydrosols, which affects their rheology. Furthermore, deacetylation improves the mechanical properties and water retention capacity of KGM gels. Overall, the e-beam irradiation pretreatment provides a method to increase the efficiency of KGM deacetylation and improve the physical and chemical properties of KGM, thus expanding its potential applications in the food and chemical industries, among others.
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  • 文章类型: Journal Article
    酸性矿山排水(AMD)是与采矿活动有关的环境问题,导致矿区释放有毒水。聚醚砜(PES)膜用于AMD治疗,但是它们有限的亲水性阻碍了它们的性能。壳聚糖增强亲水性,解决这个问题。然而,有效性取决于壳聚糖的脱乙酰度(DD),在壳聚糖生产的脱乙酰过程中确定。本研究优化了甲壳素脱乙酰温度,碱性(NaOH)浓度,和反应时间,对于PES/壳聚糖膜应用,壳聚糖脱乙酰度(DD)最高。先前的研究表明,高DD壳聚糖增强膜的防污和亲水性,增加污染物截留率和渗透通量。根据温度(80、100、120°C)评估最佳脱乙酰条件,NaOH浓度(20、40、60wt。%),和时间(2,4,6小时)进行。在80°C下获得的最高壳聚糖DD为87.11%,40wt。%NaOH在4小时的甲壳素脱乙酰。与原始PES膜(72.83°接触角)相比,PES/0.75壳聚糖膜(87.11%DD)显示表面亲水性(63.62°接触角)增加。这表明了膜性能的改善。因此,推测在AMD治疗背景下导致高污染物排斥和渗透通量,对文学的假设。
    Acid mine drainage (AMD) is an environmental issue linked with mining activities, causing the release of toxic water from mining areas. Polyethersulphone (PES) membranes are explored for AMD treatment, but their limited hydrophilicity hinders their performance. Chitosan enhances hydrophilicity, addressing this issue. However, the effectiveness depends on chitosan\'s degree of deacetylation (DD), determined during the deacetylation process for chitosan production. This study optimized the chitin deacetylation temperature, alkaline (NaOH) concentration, and reaction time, yielding the highest chitosan degree of deacetylation (DD) for PES/chitosan membrane applications. Prior research has shown that high DD chitosan enhances membrane antifouling and hydrophilicity, increasing contaminant rejection and permeate flux. Evaluation of the best deacetylation conditions in terms of temperature (80, 100, 120 °C), NaOH concentration (20, 40, 60 wt.%), and time (2, 4, 6 h) was performed. The highest chitosan DD obtained was 87.11% at 80 °C, 40 wt. %NaOH at 4 h of chitin deacetylation. The PES/0.75 chitosan membrane (87.11%DD) showed an increase in surface hydrophilicity (63.62° contact angle) as compared to the pristine PES membrane (72.83° contact angle). This was an indicated improvement in membrane performance. Thus, presumably leading to high contaminant rejection and permeate flux in the AMD treatment context, postulate to literature.
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  • 文章类型: Journal Article
    Idebenone,一种用于治疗氧化损伤相关疾病的抗氧化剂,神经保护机制不清楚。氧化应激影响细胞和线粒体膜,改变Adp-核糖基环化酶(CD38)和沉默信息调节因子3(SIRT3)蛋白表达,并可能影响SIRT3去乙酰化肿瘤蛋白p53(P53)的能力。本研究探讨了用艾地苯醌处理的H2O2损伤的HT22细胞中CD38,SIRT3和P53之间的关系。在确定适当的H2O2和艾地苯醌浓度后,使用流式细胞术和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)染色检测细胞凋亡。在这项研究中,通过检测凋亡相关蛋白的表达,发现艾地苯醌可以减少H2O2损伤的HT22细胞的凋亡并降低P53和Caspase3的表达。通过生物信息学方法,CD38被确定为艾地苯醌的靶标,它进一步表明,艾地苯醌降低CD38的表达,增加SIRT3的水平。检测到NAD+/NADH比率增加,提示艾地苯醌通过减少凋亡相关蛋白诱导SIRT3表达并保护HT22细胞。敲除SIRT3下调乙酰化P53(P53Ac),表明SIRT3在P53脱乙酰中的重要性。这些结果支持使用CD38作为艾地苯醌的靶标来上调SIRT3以使活化的P53脱乙酰,从而保护HT22细胞免受氧化应激损伤。因此,艾地苯醌是一种在保护活性氧(ROS)引起的疾病如帕金森氏病方面可能显示出巨大潜力的药物。和老年痴呆症。它可能能够弥补与CD38相关疾病相关的一些缺陷。
    Idebenone, an antioxidant used in treating oxidative damage-related diseases, has unclear neuroprotective mechanisms. Oxidative stress affects cell and mitochondrial membranes, altering Adp-ribosyl cyclase (CD38) and Silent message regulator 3 (SIRT3) protein expression and possibly impacting SIRT3\'s ability to deacetylate Tumor protein p53 (P53). This study explores the relationship between CD38, SIRT3, and P53 in H2O2-injured HT22 cells treated with Idebenone. Apoptosis was detected using flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining after determining appropriate H2O2 and Idebenone concentrations.In this study, Idebenone was found to reduce apoptosis and decrease P53 and Caspase3 expression in H2O2-injured HT22 cells by detecting apoptosis-related protein expression. Through bioinformatics methods, CD38 was identified as the target of Idebenone, and it further demonstrated that Idebenone decreased the expression of CD38 and increased the level of SIRT3. An increased NAD+/NADH ratio was detected, suggesting Idebenone induces SIRT3 expression and protects HT22 cells by decreasing apoptosis-related proteins. Knocking down SIRT3 downregulated acetylated P53 (P53Ac), indicating SIRT3\'s importance in P53 deacetylation.These results supported that CD38 was used as a target of Idebenone to up-regulate SIRT3 to deacetylate activated P53, thereby protecting HT22 cells from oxidative stress injury. Thus, Idebenone is a drug that may show great potential in protecting against reactive oxygen species (ROS) induced diseases such as Parkinson\'s disease, and Alzheimer\'s disease. And it might be able to compensate for some of the defects associated with CD38-related diseases.
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  • 文章类型: Journal Article
    多囊卵巢综合征(PCOS)是育龄女性普遍存在的代谢和内分泌疾病。这项工作是为了发现Dickkopf1(DKK1)的潜在作用及其在PCOS中的推定调节机制。
    小鼠注射脱氢表雄酮(DHEA)建立体内PCOS模型。进行苏木精和伊红(H&E)染色用于组织学分析。RT-qPCR和Westernblotting用于检测基因和蛋白质表达。应用CCK-8和流式细胞术检测细胞活力和凋亡。应用免疫共沉淀(Co-IP)和免疫共沉淀(IP)来评估DKK1和SIRT2之间的关联。
    在这项工作中,DKK1在PCOS大鼠中下调。发现DKK1敲低诱导KGN细胞凋亡和抑制增殖,而DKK1过表达具有完全相反的作用。此外,DKK1使TGF-β1/SMad3信号通路失活,从而控制KGN细胞增殖和凋亡。此外,SIRT2抑制逆转了DKK1过表达对KGN细胞增殖和凋亡的影响。此外,SIRT2通过使KGN细胞中的DKK1脱乙酰而下调DKK1的表达。
    总之,我们得出的结论是SIRT2诱导的DKK1脱乙酰触发TGF-β1/Smad3过度激活,从而抑制KGN细胞的增殖并促进其凋亡。以上结果表明,DKK1可能是PCOS治疗的潜在靶标。
    UNASSIGNED: Polycystic ovarian syndrome (PCOS) is a prevalent metabolic and endocrine condition in females of reproductive age. This work was to discover the underlying role of Dickkopf 1 (DKK1) and its putative regulating mechanism in P COS.
    UNASSIGNED: Mice recieved dehydroepiandrosterone (DHEA) injection to establish the in vivo P COS model.Hematoxylin and eosin (H&E) staining was performed for histological analysis. RT-qP CR and Western blotting were used to detect gene and protein expression. CCK-8 and flow cytometry assays were applied to detect cell viability and apoptosis. Co-immunoprecipitation (Co-IP) and immunoprecipitation (IP) were applied to assess association between DKK1 and SIRT2.
    UNASSIGNED: In this work, DKK1 is downregulated in P COS rats. It was revealed that DKK1 knockdown induced apoptosis and suppressed proliferation in KGN cells, whereas DKK1 overexpression had exactly the opposite effects. In addition, DKK1 deactivates the T GF-β1/SMad3 signaling pathway, thereby controlling KGN cell proliferation and apoptosis. Besides, SIRT2 inhibition reversed the impact of DKK1 overexpression on KGN cell proliferation and apoptosis. Furthermore, SIRT2 downregulated DKK1 expression by deacetylating DKK1 in KGN cells.
    UNASSIGNED: Altogether, we concluded that SIRT2-induced deacetylation of DKK1 triggers T GF-β1/Smad3 hyperactivation, thereby inhibiting proliferation and promoting apoptosis of KGN cells. The above results indicated that DKK1 might function as a latent target for P COS treatment.
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  • 文章类型: Journal Article
    在这项研究中,通过脱乙酰和臭氧氧化的组合制备了具有不同氧化程度的氧化脱乙酰魔芋葡甘露聚糖。发现羧基被引入到改性的魔芋葡甘露聚糖中,而乙酰基被去除。骨干,支链,改性魔芋葡甘聚糖的晶体结构没有显著影响。改性后,白度提高到97-99%,热降解温度高达250°C。改性魔芋葡甘露聚糖(氧化60分钟)的溶解度显著提高到84.56%(p<0.05),而由于分子量(从106到104)和官能团的变化,其粘度和溶胀能力显着降低。流变学分析表明,氧化的脱乙酰魔芋葡甘露聚糖具有形成柔软质地的凝胶的能力,并具有开发吞咽困难食品的潜力。未来的研究应集中在氧化脱乙酰魔芋葡甘聚糖的凝胶化机理上。
    In this study, oxidized deacetylated konjac glucomannans with different degrees of oxidation were prepared by a combination of deacetylation and ozone oxidation. Carboxyl groups were found to be introduced into the modified konjac glucomannan while acetyl groups were removed. The backbone, branched chains, and crystal structure of modified konjac glucomannan were not significantly affected. The whiteness was enhanced to 97-99 % and the thermal degradation temperature was up to 250 °C after modification. The solubility of the modified konjac glucomannan (oxidized for 60 min) was significantly increased to 84.56 % (p < 0.05), while its viscosity and swelling power were notably decreased owing to the changes in molecular weight (from 106 to 104) and functional groups. Rheological analysis showed that oxidized deacetylated konjac glucomannan has the ability to form soft-textured gels and the potential to develop dysphagia foods. Future studies should focus on the gelation mechanisms of oxidized deacetylated konjac glucomannan.
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  • 文章类型: Journal Article
    生物可降解塑料是那些容易经历降解过程的塑料,其中它们可以通过微生物活性在环境中处置后分解。在当前的研究中,使用了30种仅基于壳聚糖膜的生物塑料膜制剂作为阳性对照,并将其与从本地获得的Aristus触角的几丁质废物中回收的壳聚糖膜一起用作阳性对照。此外,蓖麻油被用作增塑剂。壳聚糖的产率为18%,壳中的水分含量为7.65%,灰分为32.27%,分离的几丁质的脱乙酰度(DD)为86%。通过许多标准表征合成的生物塑料膜。首先,与作为合成塑料的聚丙烯相比,这些生物膜的溶胀能力记录了相对较高的百分比。值得注意的是,FTIR剖面,除了DSC,TGA,和XRD,证实了这些生物膜的可接受的特性。此外,他们的SEM显示了几带壳聚糖膜的均匀性和连续性,并显示了壳聚糖和蓖麻油的均匀混合物,分别为5%和20%。此外,数据检测了不同生物塑料配方对一些常见细菌病原体的抗菌活性(粪肠球菌,肺炎克雷伯菌,枯草芽孢杆菌,和铜绿假单胞菌)。令人惊讶的是,我们的生物塑料薄膜进行了有效的抗菌活性。所以,他们可能会朝着这个方向发展。Further,形成的生物塑料膜的生物降解功效在许多环境中经过数周的孵育得到了证明。然而,所有生物塑料薄膜的重量都减少了,颜色也改变了,而聚丙烯,是非常恒定的所有的时间。目前的研究结果表明,我们的生物膜可能有很多应用前景,特别是在食品包装保护食品领域,防止微生物污染,因此,它可能有助于延长产品的保质期。
    Biodegradable plastics are those subjected easily to a degradation process, in which they can be decomposed after disposal in the environment through microbial activity. 30 bioplastic film formulations based only on chitosan film were used in the current investigation as a positive control together with chitosan film recovered from chitin-waste of locally obtained Aristeus antennatus. Additionally, castor oil was used as a plasticizer. While the yield of chitosan was 18% with 7.65% moisture content and 32.27% ash in the shells, the isolated chitin had a degree of deacetylation (DD) of 86%. The synthesized bioplastic films were characterized via numerous criteria. Firstly, the swelling capacity of these biofilms recorded relatively high percentages compared to polypropylene as synthetic plastic. Noticeably, the FTIR profiles, besides DSC, TGA, and XRD, confirmed the acceptable characteristics of these biofilms. In addition, their SEM illustrated the homogeneity and continuity with a few straps of the chitosan film and showed the homogeneous mixes of chitosan and castor oil with 5 and 20%. Moreover, data detected the antibacterial activity of different bioplastic formulas against some common bacterial pathogens (Enterococcus feacalis, Kelbsiella pnumina, Bacillus subtilis, and Pseudomonas aeruginosa). Amazingly, our bioplastic films have conducted potent antimicrobial activities. So, they may be promising in such a direction. Further, the biodegradability efficacy of bioplastic films formed was proved in numerous environments for several weeks of incubation. However, all bioplastic films decreased in their weights and changed in their colors, while polypropylene, was very constant all the time. The current findings suggest that our biofilms may be promising for many applications, especially in the field of food package protecting the food, and preventing microbial contamination, consequently, it may help in extending the shelf life of products.
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