更新于：2024-09-19

NANS

更新于：2024-09-19

基本信息

别名

N-acetylneuraminate synthase、N-acetylneuraminate-9-phosphate synthase、N-acetylneuraminic acid phosphate synthase

+ [4]

简介

Produces N-acetylneuraminic acid (Neu5Ac) and 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN) (PubMed:10749855, PubMed:27213289). Can also use N-acetylmannosamine 6-phosphate and mannose 6-phosphate as substrates to generate phosphorylated forms of Neu5Ac and KDN, respectively (PubMed:10749855).

关联

100 项与 NANS 相关的临床结果

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100 项与 NANS 相关的转化医学

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0 项与 NANS 相关的专利（医药）

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380

项与 NANS 相关的文献（医药）

2024-11-01·Life Science Alliance

Neutrophil-avid nanocarrier uptake by STAT3 dominant-negative hyper-IgE syndrome patient neutrophils

Article

作者: Fazelinia, Hossein ; Brenner, Jacob S ; Lin, Susan M ; Krymskaya, Vera P ; Rubey, Kathryn M ; Freeman, Alexandra ; Roof, Jennifer ; Mukhitov, Alexander R ; Spruce, Lynn A ; Rue, Ryan ; Paris, Andrew J ; Heimall, Jennifer

Recurrent infections are a hallmark of STAT3 dominant-negative hyper-IgE syndrome (STAT3 HIES), a rare immunodeficiency syndrome previously known as Jobs syndrome, along with elevated IgE levels and impaired neutrophil function. We have been developing nanoparticles with neutrophil trophism that home to the sites of infection via these first-responder leukocytes, named neutrophil-avid nanocarriers (NANs). Here, we demonstrate that human neutrophils can phagocytose nanogels (NGs), a type of NAN, with enhanced uptake after particle serum opsonization, comparing neutrophils from healthy individuals to those with STAT3 HIES, where both groups exhibit NG uptake; however, the patient group showed reduced phagocytosis efficiency with serum-opsonized NANs. Proteomic analysis of NG protein corona revealed complement components, particularly C3, as predominant in both groups. Difference between groups includes STAT3 HIES samples with higher neutrophil protein and lower acute-phase protein expression. The study suggests that despite neutrophil dysfunction in STAT3 HIES, NANs have potential for directed delivery of cargo therapeutics to improve neutrophil infection clearance.

2024-10-01·Food Chemistry

Study on the fabrication and controlled release behavior of N-Acetylneuraminic acid-loaded hydrogels stabilized by gelatin/whey protein isolate

Article

作者: Pang, Min ; Xu, Lu ; Cao, Lili ; Chen, Xiangsong ; Wang, Yingge

Gelatin (GEL), pectin (PEC), carboxymethyl cellulose (CMC), and whey protein isolate (WPI) were employed to formulate hydrogels for stabilizing N-Acetylneuraminic Acid (NeuAc). GEL/WPI-NeuAc hydrogels, irrespective of the ratio, exhibited a flexible and smooth surface with a continuous three-dimensional network structure internally. Porosity of the three types of hydrogels increased from 3.69% to 86.92% (GEL/WPI), 41.67% (PEC/WPI), and 87.62% (CMC/WPI), rendering them suitable as carriers for NeuAc encapsulation. The dynamic swelling behavior of all hydrogels followed Schott's second-order kinetics model. The degradation performance of GEL, PEC, and CMC/WPI-NeuAc hydrogels was optimal at a 5: 5 ratio, with degradation rates of 80.39 ± 1.26%, 82.38 ± 1.96%, and 81.39 ± 1.57%, respectively. GEL, PEC, CMC/WPI-NeuAc hydrogels demonstrated decreased release rates of 44.56%, 31.04%, and 41.26%, respectively, compared to free NeuAc, post gastric digestion. The present investigation suggests the potential of GEL/WPI hydrogels as effective carriers for delivering NeuAc encapsulation.

2024-09-01·Synthetic and Systems Biotechnology

Facilitating stable gene integration expression and copy number amplification in Bacillus subtilis through a reversible homologous recombination switch

Article

作者: Du, Guocheng ; Wu, Yaokang ; Tian, Rongzhen ; Liu, Yanfeng ; Chen, Jian ; Lv, Xueqin ; Liu, Long ; Li, Jianghua ; Guo, Haoyu

Strengthening the expression level of integrated genes on the genome is crucial for consistently expressing key enzymes in microbial cell factories for efficient bioproduction in synthetic biology. In comparison to plasmid-based multi-copy expression, the utilization of chromosomal multi-copy genes offers increased stability of expression level, diminishes the metabolic burden on host cells, and enhances overall genetic stability. In this study, we developed the "BacAmp", a stabilized gene integration expression and copy number amplification system for high-level expression in Bacillus subtilis, which was achieved by employing a combination of repressor and non-natural amino acids (ncAA)-dependent expression system to create a reversible switch to control the key gene recA for homologous recombination. When the reversible switch is turned on, genome editing and gene amplification can be achieved. Subsequently, the reversible switch was turned off therefore stabilizing the gene copy number. The stabilized gene amplification system marked by green fluorescent protein, achieved a 3-fold increase in gene expression by gene amplification and maintained the average gene copy number at 10 after 110 generations. When we implemented the gene amplification system for the regulation of N-acetylneuraminic acid (NeuAc) synthesis, the copy number of the critical gene increased to an average of 7.7, which yielded a 1.3-fold NeuAc titer. Our research provides a new avenue for gene expression in synthetic biology and can be applied in metabolic engineering in B. subtilis.

项与 NANS 相关的新闻（医药）

2023-06-26

·生物谷

Science子刊：饶浪/陈小元/程功等团队开发抗新冠纳米吸入制剂

吸入式给药输送的nanoDEX显著抑制了肺部损伤，具有巨大潜力对于COVID-19相关的免疫失调和肺部损伤。由于SARS-CoV-2引起的2019冠状病毒病（COVID-19）大流行，对公共卫生和全球经济产生了严重的影响。为了消除病毒并抑制感染，身体对SARS-CoV-2感染作出免疫细胞激活和细胞因子分泌的反应。然而，被称为“细胞因子风暴”的细胞因子持续高水平分泌可能会加重炎症并导致免疫功能障碍。临床上，大多数COVID-19患者表现出轻度或中度症状，但约20％的患者会因细胞因子风暴而表现出严重肺炎，多器官衰竭甚至感染性休克。目前，仅有少数药物或治疗策略可用于治疗严重COVID-19患者。地塞米松（DEX）是首个显示在严重COVID-19患者中具有挽救生命功效的药物。在全球最大的涉及COVID-19的临床试验中，使用DEX可将COVID-19患者的死亡率降低。DEX预计将在COVID-19上产生重大影响，不仅因为DEX是首个显著提高患者生存率的药物，而且因为它广泛可得且非常便宜。然而，DEX是一种糖皮质激素，其受体广泛表达于大多数细胞类型，因此使用DEX可能会导致严重的副作用，例如骨质疏松和骨折、股骨缺血性坏死等，这些都限制了DEX广泛应用，特别是高剂量的长期治疗。尽管存在这些问题，DEX对抑制细胞因子可能是有益的，尤其是DEX可以被输送到肺组织和靶细胞，这些细胞在COVID-19治疗中起着关键作用。细胞外囊泡（EVs）是细胞分泌的脂质囊泡，参与生理和病理过程，因此在免疫治疗方面具有巨大潜力。此外，由于其良好的安全性和稳定性，EVs被视为下一代药物输送平台。然而，从生产方面来看，细胞分泌的EVs不足以用于免疫治疗和药物输送。因此，细胞源性纳米囊泡（NVs）已被用作EVs的替代品，可以通过超声波和细胞膜挤压制备。更重要的是，NVs还包含源细胞的特定脂质和蛋白质，因此继承了源细胞的独特性质。例如，最近证明，NVs可以作为诱饵来捕获病毒和广谱细胞因子，抑制病毒感染和肺部炎症。前期的工作研究提示，我们可以使用NVs装载DEX的靶向输送和细胞因子的协同中和来改善COVID-19的治疗。 2023年6月14日，深圳湾实验室饶浪研究员、新加坡国立大学陈小元教授、清华大学程功教授等团队合作，在 Science Advances 期刊发表了题为：Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and non-human primates 的研究论文。研究团队开发了一种基于胆固醇工程化改造中性粒细胞纳米囊泡的iSEND（inhaled， Self-immunoregulatory，Extracellular Nanovesicle-based Delivery）新型递送载体，用于吸入递送皮质激素地塞米松（DEX），提高新冠重症治疗效果，降低DEX毒副作用。相较于DEX裸药，新型地塞米松纳米吸入制剂nanoDEX的肺部富集率提高超过14倍。相较于静脉注射DEX，吸入给药1/10剂量的nanoDEX，对SARS-CoV-2感染的非人灵长类动物模型的肺部炎症和损伤产生了更好的治疗效果。该研究提供了一种安全可靠的新型雾化吸入递送载体，有望为新冠肺炎和其他呼吸疾病的临床救治提供参考。研究团队开发了一种可吸入的nanoDEX纳米制剂，包括负载DEX的中性粒细胞膜囊泡（N-NVs），以改善COVID-19治疗和并发症管理。通过利用吸入途径输送和N-NVs上丰富的趋化因子受体，nanoDEX在炎症肺部显示出增强的滞留能力和对激活的巨噬细胞和树突细胞的靶向能力。 nanoDEX通过两步策略保护免受COVID-19细胞因子风暴的影响：第一步是细胞因子下调，随后是细胞因子中和（图1A）。nanoDEX在肺部的增强滞留能力促进了DEX的细胞因子下调作用，从而抑制了SARS-CoV-2感染引起的炎症细胞浸润和肺损伤。除此之外，依靠N-NVs上丰富的细胞因子受体，nanoDEX结合并中和广谱细胞因子，提高了COVID-19治疗的功效。由于在炎症肺部的增强滞留能力，nanoDEX治疗显著减轻了由DEX引起的骨质疏松，进一步凸显了nanoDEX的重要性。图1：(A) 可吸入nanoDEX用于治疗COVID-19的示意图。（B）中性粒细胞和N-NVs的TEM图，以及N-NVs粒径大小。(C) R-NVs和N-NVs的结合力分析。（D）趋化因子和细胞因子受体的Western blot分析。（E）N-NVs的载药率和释药率。该研究介绍了制备DEX-N-NVs的三个步骤：分离中性粒细胞、获得N-NVs、将DEX加载到N-NVs中。N-NVs是通过超声和小型挤压器的细胞膜纳米孔连续制备的，平均尺寸为90nm（图1B）。N-NVs具有趋化因子和细胞因子受体，包括CCR2、CXCR2、CXCR4、IL-6R、IL-1βR和TNF-αR，依靠这些细胞因子受体可以高效地吸附炎症细胞因子（图1C,D）。DEX-N-NVs的最佳载药率约为9.71%，以及约71.16%的总DEX在48小时内从N-NVs中泄露出来，表明DEX-N-NVs具有持续释放的特点（图1E）。 nanoDEX通过两步策略对抗COVID-19细胞因子风暴：第一步是DEX的细胞因子下调，第二步是iSEND的细胞因子中和。在LPS诱导的急性肺炎小鼠模型中，nanoDEX显著降低了肺部的细胞因子水平，并有效抑制了免疫失调状态，并且可显著抑制LPS诱导的肺损伤。为了研究nanoDEX的安全性，研究团队在大鼠模型中观察到，nanoDEX治疗显著保护了大鼠免受DEX引起的副作用的影响，包括骨质疏松症的发生（图2A）。 K18-hACE2转基因小鼠表达人类SARS-CoV-2受体（ACE2），易感SARS-CoV-2感染，导致剂量依赖性的肺炎症状。研究通过吸入式给药途径将DEX或nanoDEX输送到小鼠肺部，发现nanoDEX可以有效地抑制SARS-CoV-2感染引起的肺部细胞因子/趋化因子上调，并减轻肺部损伤。此外，nanoDEX还能够抑制SARS-CoV-2感染引起的全身炎症反应，且使用nanoDEX的小鼠体重下降更缓，进一步证明了其生物安全性。研究使用恒河猴测试了可吸入nanoDEX的抗COVID-19疗效。在遗传水平上，与DEX治疗相比，nanoDEX治疗有效抑制了SARS-CoV-2感染引起的细胞因子/趋化因子上调（图2B）。此外，吸入式给药输送的nanoDEX显著抑制了肺部损伤（图2C）。nanoDEX治疗后，与炎症和损伤修复相关的基因表达上调，凋亡通路的基因表达下降（图2D）。这项研究为COVID-19的治疗提供了新的治疗思路。图2：(A) 经指示治疗后大鼠的骨灰重、干重和灰/干比分析和骨中Ca2+、P5+含量的变化。（B）恒河猴血清细胞因子基因表达qRT-PCR分析。（C）治疗后H&E染色气管和肺组织。（D）不同组之间肺部差异表达基因的火山图和与炎症损伤相关通路相关的基因的热图。总之，吸入式给药输送的nanoDEX显著抑制了肺部损伤，具有巨大潜力对于COVID-19相关的免疫失调和肺部损伤。该研究特别感谢国家自然科学基金委员会、广东省自然科学基金委员会、深圳市科技创新委员会、深圳湾实验室开放基金等经费支持。