sulfated polysaccharide

硫酸多糖
  • 文章类型: Journal Article
    在这项研究中,我们研究了海带多糖(岩藻依聚糖)对脂质代谢的调节作用。采用高糖高脂饮食联合链脲佐菌素建立糖尿病(DM)大鼠模型。记录实验期间大鼠体重和血糖水平的变化。在实验结束之前,采用全自动生化分析仪检测空腹血糖(FBG),血清脂质含量,和胰岛素含量,并计算胰岛素抵抗指数。油红O染色用于检测肝脏中的脂质沉积。H&E染色,Masson染色,PASM染色观察肝脏病理结构改变。采用16sRNA测序和靶向代谢组学方法检测肠道菌群和胆汁酸含量。结果表明,岩藻依聚糖能够抑制DM大鼠的体重减轻,降低甘油三酯(TG)的含量,胆固醇(TC),和血清低密度脂蛋白(LDL-C)。油红O染色显示岩藻依聚糖处理后肝脏脂肪积累减少。16sRNA测序表明,岩藻依聚糖增加了拟杆菌的丰度,弯曲杆菌,梭菌,γ变形杆菌,否认,和Verrucomicrobi。岩藻依聚糖还增加了次级胆汁酸的分泌(Nor-DCA,TLCA,β-UDCA)和减轻脂质代谢紊乱。岩藻依聚糖抑制α-SMA的表达,而FXR和TGR5的表达被促进。岩藻聚糖通过调节FXR和TGR5的表达并作用于肠道菌群-胆汁酸轴,在调节脂质代谢方面表现出良好的活性。
    In this study, we examined the effect of Laminaria japonica polysaccharide (fucoidan) on the regulation of lipid metabolism. A rat model of diabetes mellitus (DM) was established by a high-sugar and high-fat diet combined with streptozotocin. Changes in the rats\' body weight and blood glucose level during the experiment were recorded. Before the end of the experiment, an automatic biochemical analyzer was used to detect the fasting blood glucose (FBG), lipid content in serum, and insulin content, and calculate the insulin resistance index. Oil red O staining was used to detect lipid deposition in the liver. H&E staining, Masson staining, and PASM staining were used to observe the pathological structural changes in the liver. 16 s RNA sequencing and targeted metabolomics were used to detect intestinal microbiota and bile acid content. The results showed that fucoidan was able to inhibit weight loss in the DM rats and reduce the content of triglycerides (TG), cholesterol (TC), and low-density lipoprotein (LDL-C) in serum. Oil red O staining showed a decrease in liver fat accumulation after fucoidan treatment. 16 s RNA sequencing demonstrated that fucoidan increased the abundance of Bacteroidia, Campylobacteria, Clostridia, Gammaproteobacteria, Negativicutes, and Verrucomicrobi. Fucoidan also increased the secretion of secondary bile acids (Nor-DCA, TLCA, β-UDCA) and alleviated lipid metabolism disorders. The expression of α-SMA was inhibited by fucoidan, whereas the expression of FXR and TGR5 was promoted. Fucoidan shows good activity in regulating lipid metabolism by regulating the expression of FXR and TGR5 and acting on the intestinal flora-bile acid axis.
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  • 文章类型: Journal Article
    目的:草酸钙晶体与肾小管上皮细胞粘附是肾结石形成的重要原因,抑制晶体粘附的药物和抑制机制还有待探索。方法:采用纳米COM晶体构建细胞损伤模型,和氧化应激水平的变化,内质网(ER)应激水平,下游p38MAPK蛋白表达,凋亡,粘附蛋白骨桥蛋白表达,在受保护和未保护的条件下,在Laminarin多糖(DLP)和硫酸化DLP(SDLP)的存在下检查细胞晶体粘附。结果:DLP和SDLP均能抑制nano-COM对人肾近端小管上皮细胞(HK-2)的损伤,增加细胞活力,ROS水平降低,减少线粒体膜通透性转换孔的开口,显著降低ERCa2+离子浓度和粘附分子OPN表达,下调ER应激特征蛋白的表达,包括CHOP,半胱天冬酶12和p38MAPK,降低细胞凋亡率。SDLP比DLP对细胞具有更好的保护作用。结论:SDLP通过降低氧化应激和内质网应激水平及其下游因子保护HK-2细胞免受纳米COM晶体诱导的凋亡,从而减少晶体-细胞粘附相互作用和肾结石形成的风险。
    Purpose: Adhesion between calcium oxalate crystals and renal tubular epithelial cells is a vital cause of renal stone formation; however, the drugs that inhibit crystal adhesion and the mechanism of inhibition have yet to be explored. Methods: The cell injury model was constructed using nano-COM crystals, and changes in oxidative stress levels, endoplasmic reticulum (ER) stress levels, downstream p38 MAPK protein expression, apoptosis, adhesion protein osteopontin expression, and cell-crystal adhesion were examined in the presence of Laminarin polysaccharide (DLP) and sulfated DLP (SDLP) under protected and unprotected conditions. Results: Both DLP and SDLP inhibited nano-COM damage to human kidney proximal tubular epithelial cell (HK-2), increased cell viability, decreased ROS levels, reduced the opening of mitochondrial membrane permeability transition pore, markedly reduced ER Ca2+ ion concentration and adhesion molecule OPN expression, down-regulated the expression of ER stress signature proteins including CHOP, Caspase 12, and p38 MAPK, and decreased the apoptosis rate of cells. SDLP has a better protective effect on cells than DLP. Conclusions: SDLP protects HK-2 cells from nano-COM crystal-induced apoptosis by reducing oxidative and ER stress levels and their downstream factors, thereby reducing crystal-cell adhesion interactions and the risks of kidney stone formation.
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  • 文章类型: Journal Article
    本研究证明了羊尾藻硫酸化多糖(SFSP)在模拟消化道环境中的消化行为和发酵特性。结果表明,通过模拟消解,SFSP中两种组分的分子量均未发生变化,并且没有产生游离的单糖。这表明大多数SFSP可以作为原型到达结肠。在与人肠道菌群体外发酵过程中,利用了SFSP的高分子量成分,总糖含量下降了16%,还原糖含量增加,单糖组成中的半乳糖含量相对下降。这表明SFSP可以被人类肠道菌群选择性利用。同时,SFSP也改变了肠道菌群的结构。与空白组相比,SFSP显着增加了拟杆菌的丰度,并降低了厚壁菌的丰度。在属一级,拟杆菌和巨单胞菌的丰度增加,虽然丰富的志贺氏菌,克雷伯菌属,科林斯拉减少了。此外,总短链脂肪酸(SCFA)的浓度,乙酸,与空白组相比,丙酸和正丁酸显着增加。SFSP可以下调三甲胺的含量,发酵液中的哌啶酮和次级胆汁酸。烟酸的含量,泛酸和其他有机酸增加。因此,SFSP显示出调节肠道微生物群和促进人类健康的巨大潜力。
    The present study demonstrated the digestion behavior and fermentation characteristics of a sulfated polysaccharide from Sargassum fusiforme (SFSP) in the simulated digestion tract environment. The results showed that the molecular weight of two components in SFSP could not be changed by simulated digestion, and no free monosaccharide was produced. This indicates that most of SFSP can reach the colon as prototypes. During the fermentation with human intestinal flora in vitro, the higher-molecular-weight component of SFSP was utilized, the total sugar content decreased by 16%, the reducing sugar content increased, and the galactose content in monosaccharide composition decreased relatively. This indicates that SFSP can be selectively utilized by human intestinal flora. At the same time, SFSP also changed the structure of intestinal flora. Compared with the blank group, SFSP significantly increased the abundance of Bacteroidetes and decreased the abundance of Firmicutes. At the genus level, the abundances of Bacteroides and Megamonas increased, while the abundances of Shigella, Klebsiella, and Collinsella decreased. Moreover, the concentrations of total short-chain fatty acids (SCFAs), acetic, propionic and n-butyric acids significantly increased compared to the blank group. SFSP could down-regulate the contents of trimethylamine, piperidone and secondary bile acid in fermentation broth. The contents of nicotinic acid, pantothenic acid and other organic acids were increased. Therefore, SFSP shows significant potential to regulate gut microbiota and promote human health.
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  • 文章类型: Journal Article
    重组人骨形态发生蛋白-2(rhBMP-2)是在骨科手术中有效诱导成骨分化的主要生长因子。然而,rhBMP-2的生物活性和稳定性与其序列内在相关,结构,和储存条件。在这项研究中,通过X射线晶体结构分析,我们成功地确定了由大肠杆菌表达系统表达的非糖基化rhBMP-2的氨基酸序列和蛋白质二级结构模型。此外,我们观察到酸性储存条件增强了rhBMP-2的增殖和骨诱导活性。尽管与糖基化rhBMP-2相比,非糖基化rhBMP-2的成骨活性相对较弱;然而,这种差异可以通过掺入外源伴侣分子来缓解。总的来说,这些信息对于合理设计稳定方法和增强rhBMP-2的生物活性至关重要,这也可能适用于其他生长因子。
    Recombinant human bone morphogenetic protein-2 (rhBMP-2) is the predominant growth factor that effectively induces osteogenic differentiation in orthopedic procedures. However, the bioactivity and stability of rhBMP-2 are intrinsically associated with its sequence, structure, and storage conditions. In this study, we successfully determined the amino acid sequence and protein secondary structure model of non-glycosylated rhBMP-2 expressed by an E. coli expression system through X-ray crystal structure analysis. Furthermore, we observed that acidic storage conditions enhanced the proliferative and osteoinductive activity of rhBMP-2. Although the osteogenic activity of non-glycosylated rhBMP-2 is relatively weaker compared to glycosylated rhBMP-2; however, this discrepancy can be mitigated by incorporating exogenous chaperone molecules. Overall, such information is crucial for rationalizing the design of stabilization methods and enhancing the bioactivity of rhBMP-2, which may also be applicable to other growth factors.
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  • 文章类型: Journal Article
    一种来自棕色藻类IshigeOkamurae的水溶性多糖,命名为IOP-0,通过制备型阴离子交换和尺寸排阻色谱法获得。化学和光谱研究表明,IOP-0是硫酸化岩藻依聚糖,其骨架主要由3-连接和4-连接的L-岩藻糖组成,在3-连接的L-岩藻糖的C-2/C-4处具有硫酸基团。在这项工作中评估了IOP-0对溃疡性结肠炎的保护作用。结果表明,IOP-0可以通过防止体重减轻来显著缓解溃疡性结肠炎的症状,保留肠组织的结构,改善炎性细胞因子(TNF-α,IL-6和IL-10)。同时,IOP-0通过促进紧密连接蛋白ZO-1和闭塞蛋白的表达来保护结肠粘膜屏障。此外,IOP-0能够通过调节肠道菌群及其代谢产物来维持肠道稳态和改善肠道功能。例如短链脂肪酸(SCFA)。这些结果表明,IOP-0可能是预防和治疗溃疡性结肠炎的潜在膳食补充剂。
    A water-soluble polysaccharide from the brown alga Ishige Okamurae, designated IOP-0, was obtained by preparative anion-exchange and size-exclusion chromatography. Chemical and spectroscopic investigations revealed that IOP-0 was a sulfated fucoidan with a backbone primarily composed of 3-linked and 4-linked-L-fucose with sulfate groups at C-2/C-4 of the 3-linked-L-fucose. The protective effect of IOP-0 on ulcerative colitis was evaluated in this work. The results showed that IOP-0 could significantly alleviate the symptoms of ulcerative colitis by preventing weight loss, preserving the structure of intestinal tissues, and ameliorating the dysregulation of inflammatory cytokines (TNF-α, IL-6, and IL-10). Meanwhile, IOP-0 protected the colonic mucosal barrier by promoting the tight junction protein ZO-1 and occludin expression. In addition, IOP-0 was able to maintain intestinal homeostasis and improve intestinal function by regulating the gut microbiota and their metabolites, such as short-chain fatty acids (SCFAs). These results suggest that IOP-0 might be a potential dietary supplement for the prevention and treatment of ulcerative colitis.
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  • 文章类型: Journal Article
    废水资源回收不仅可以提取增值产品,还可以抵消废水处理的运营成本,但它也有利于缓解由于能源和化学品输入以及相关排放而导致的不利环境问题。许多有吸引力的化合物,如藻酸盐样聚合物,鸟粪石,聚羟基链烷酸酯,和硫酸多糖,并从废水中成功获得,具有广泛的应用前景。这项工作的目的是全面审查从废水中回收这些流行产品的最新进展,以及它们的物理化学性质,主要来源,并对目前的恢复状况进行了总结。深入讨论了影响这些材料回收性能的各种因素。此外,强调了废水资源回收的研究需求和未来方向。这项研究可以为未来的研究工作提供有价值的见解,旨在通过回收高附加值产品来提高废水资源的回收率。
    Wastewater resource recovery not only allows the extraction of value-added products and offsets the operational costs of wastewater treatment, but it is also conducive to alleviating adverse environmental issues due to energy and chemical inputs and associated emissions. A number of attractive compounds such as alginate-like polymers, struvite, polyhydroxyalkanoates, and sulfated polysaccharides, were found and successfully obtained from wastewater and have a wide range of application prospects. The aim of this work is to provide a comprehensive review of recent advances in recovery of these popular products from wastewater, and their physicochemical properties, main sources, and current recovery status are summarized. Various factors influencing the recovery performance of these materials are thoroughly discussed. Moreover, the research needs and future directions towards wastewater resource recovery are highlighted. This study can provide valuable insights for future research endeavors aiming to improve wastewater resource recovery through the retrieval of high value-added products.
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  • 文章类型: Journal Article
    卵转铁蛋白(OVT)在60°C下展开和聚集的趋势严重限制了鸡蛋加工过程中的灭菌温度。寻找提高OVT热稳定性的有效策略对于提高蛋产品质量和加工适应性至关重要。这里,我们研究了硫酸多糖(硫酸葡聚糖,DS)对热诱导的OVT聚集的影响。我们发现DS可以有效地抑制加热后pH7.0的OVT的无定形聚集。引人注目的是,添加5µMDS完全抑制了0.5mg/mLOVT的不溶性聚集体形成。结构分析证实,DS在加热过程中保留了OVT的几乎整个二级和三级结构。由OVT和DS之间的强静电相互作用引起的空间位阻效应,加上OVT疏水性降低,是抑制蛋白质-蛋白质相互作用的潜在机制,从而提高热稳定性。这些发现表明DS可以作为蛋白质稳定剂和伴侣,增强热敏蛋白的热稳定性。
    The tendency of ovotransferrin (OVT) to unfold and aggregate under 60 °C severely restricted sterilization temperature during egg processing. Searching for efficient strategies to improve OVT thermal stability is essential for improving egg product quality and processing suitability. Here, we investigated the effect of sulfate polysaccharide (dextran sulfate, DS) on heat-induced aggregation of OVT. We found that DS can effectively suppress amorphous aggregation of OVT at pH 7.0 after heating. Strikingly, the addition of 5 µM DS fully suppressed insoluble aggregates formation of 0.5 mg/mL OVT. Structure analysis confirmed that DS preserves nearly the entire secondary and tertiary structure of OVT during heating. The steric hindrance effect arising from strong electrostatic interactions between OVT and DS, coupled with reduced OVT hydrophobicity, is the underlying mechanism in suppressing protein-protein interactions, thus enhancing thermal stability. These findings suggest DS could act as protein stabilizers and chaperones, enhancing the thermostability of heat-sensitive proteins.
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  • 文章类型: Journal Article
    在本研究中,通过消化马尾藻并使用三种食品级酶进行酶辅助提取制备来获得硫酸化多糖,和他们的抗阿尔茨海默氏症的活性进行了调查。结果表明,使用AMGSP提取的粗硫酸多糖,CSP和VSP剂量依赖性(25-100µg·mL-1)提高了小鼠Y迷宫实验中的自发交替方式(%),并减少了Morris迷宫实验中的逃避潜伏期。AMGSP,CSP和VSP也表现出良好的抗AChE和中等的抗BuChE活性。CSP对AChE表现出最佳的抑制功效。IC50值为9.77µM。And,CSP还表现出对AChE相对于BuChE的良好抑制选择性。接下来,最佳活性粗提物的CSP通过制备型高效液相分离得到硫酸化岩藻寡糖切片:SFcup(→3-α-L-fucp(2-SO3-)-1→4-α-L-fucp(2,3-SO3-)-1→切片),SFcup对AChE表现出最佳的抑制功效,IC50值为4.03μM。动力学研究表明,SFcup通过双结合位点抑制AChE。此外,SFcup在AChE活性位点的分子对接与获得的药理学结果一致。
    In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer\'s activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100 µg·mL- 1) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (→3-α-L-fucp(2-SO3-)-1→4-α-L-fucp(2,3-SO3-)-1→section), SFcup showed a best inhibitory efficacy against AChE with IC50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results.
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  • 文章类型: Journal Article
    从可食用的藻类肠morpha中纯化了水溶性多糖(EP)。凝胶渗透色谱(GPC),离子色谱(IC),通过傅里叶变换红外(FT-IR)对其结构进行表征。EP被定义为由鼠李糖组成的低分子量(6625Da),葡萄糖,葡萄糖醛酸,木糖,半乳糖,阿拉伯糖,和甘露。此外,它是硫酸化多糖,取代度(DS)为1.48。然后,建立了高脂饮食/链脲佐菌素(HFD/STZ)诱导的糖尿病小鼠模型,以支持新的降血糖机制的证据。结果显示,血糖(47.32%),肝脏指数(7.65%),附睾脂肪指数(16.86%),高剂量EP(HEP)组血清总胆固醇(26.78%)和甘油三酯(37.61%)显著低于HFD组。值得注意的是,HEP组肝糖原含量显著高于HFD组(62.62%),表明促进糖原合成。这些有益作用归因于显著增加的蛋白激酶B(AKT)磷酸化及其下游信号应答。进一步的研究表明,糖尿病小鼠表现出过度的O-GlcNAcylation水平和O-连接的β-D-N-乙酰氨基葡萄糖转移酶(OGT)的高表达,HEP组分别下降62.21和30.43%。这一结果表明,EP具有与OGT抑制剂相似的作用,恢复AKT磷酸化并预防血糖异常。这项工作揭示了EP的一种新的降血糖机制,为进一步研究其改善T2DM的药理特性提供理论依据。
    A water-soluble polysaccharide (EP) was purified from edible algae Enteromorpha prolifera. Gel permeation chromatography (GPC), ion chromatography (IC), and fourier transform infrared (FT-IR) were performed to characterize its structure. EP was defined as a low molecular weight (6625 Da) composed of rhamnose, glucose, glucuronic acid, xylose, galactose, arabinose, and mannose. Moreover, it was a sulfated polysaccharide with a degree of substitution (DS) of 1.48. Then, the high-fat diet/streptozotocin (HFD/STZ) induced diabetic mouse model was established to support evidence for a novel hypoglycemic mechanism. Results showed that blood glucose (47.32%), liver index (7.65%), epididymal fat index (16.86%), serum total cholesterol (26.78%) and triglyceride (37.61%) in the high-dose EP (HEP) group were significantly lower than those in the HFD group. Noticeably, the content of liver glycogen in the HEP group was significantly higher (62.62%) than that in the HFD group, indicating the promotion of glycogen synthesis. These beneficial effects were attributed to significantly increased protein kinase B (AKT) phosphorylation and its downstream signaling response. Further studies showed that diabetic mice exhibited excessive O-GlcNAcylation level and high expression of O-linked β-D-N-acetylglucosamine transferase (OGT), which were decreased by 62.21 and 30.43% in the HEP group. This result suggested that EP had a similar effect to OGT inhibitors, which restored AKT phosphorylation and prevented pathoglycemia. This work reveals a novel hypoglycemic mechanism of EP, providing a theoretical basis for further studies on its pharmacological properties in improvement of T2DM.
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  • 文章类型: Journal Article
    SARS-CoV-2的疾病在全球范围内引起了相当大的发病率和死亡率。SARS-CoV-2表面的刺突蛋白使其与人类细胞结合,导致感染。富勒烯及其衍生物是有前途的SARS-CoV-2抑制剂和药物递送载体。在这项研究中,利用高斯加速分子动力学模拟和马尔可夫状态模型研究了富勒烯-线性-聚甘油-b-胺硫酸盐(F-LGPS)对刺突蛋白的抑制机理。在研究期间,发现富勒烯衍生物可以在受体结合域(RBD)和N末端域(NTD)的界面上起作用,保持结构域向下构象。还观察到,与野生型变体相比,F-LGPS对XBB变体表现出优异的抑制作用。这项研究为针对SARS-CoV-2刺突蛋白的有效疗法的潜在开发提供了宝贵的见解。
    The disease of SARS-CoV-2 has caused considerable morbidity and mortality globally. Spike proteins on the surface of SARS-CoV-2 allow it to bind with human cells, leading to infection. Fullerenes and their derivatives are promising SARS-CoV-2 inhibitors and drug-delivery vehicles. In this study, Gaussian accelerated molecular dynamics simulations and the Markov state model were employed to delve into the inhibitory mechanism of Fullerene-linear-polyglycerol-b-amine sulfate (F-LGPS) on spike proteins. During the study, it was discovered that fullerene derivatives can operate at the interface of the receptor-binding domain (RBD) and the N-terminal domain (NTD), keeping structural domains in a downward conformation. It was also observed that F-LGPS demonstrated superior inhibitory effects on the XBB variant in comparison to the wild-type variant. This study yielded invaluable insights for the potential development of efficient therapeutics targeting the spike protein of SARS-CoV-2.
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