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1.
Peter K. Windsor Stephen P. Plassmeyer Dominic S. Mattock Jonathan C. Bradfield Erika Y. Choi Bill R. Miller III Byung Hee Han 《International journal of molecular sciences》2021,22(6)
Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC50 values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease. 相似文献
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为研究在常温(21±1)℃条件下不同搅拌方式对于厌氧氨氧化污泥复壮及运行影响,采用3组反应器(R1、R2、R3)搅拌方式分别为连续搅拌、间歇搅拌、间歇搅拌方式(R2、R3转速不同),对系统复壮及运行过程的脱氮性能、颗粒污泥性能等进行分析.结果表明,R1、R2、R3分别用10,2,2 d的时间氨氮、亚硝酸盐氮去除率接近100%,R2、R3的厌氧氨氧化速率更高,更适合厌氧氨氧化菌生长;周期实验结果可知,间歇搅拌方式形成的水流流化状态较弱,使反应器呈较低溶解氧的时间较长,更易抑制AOB活性,从而提高厌氧氨氧化菌活性;R1系统提供剪切力大,且持续与基质溶液接触,产生EPS多,稳定运行时期末,R1、R2、R3的颗粒污泥平均粒径为723,675,649μm. 相似文献
4.
Eugene Metakovsky Laura Pascual Patrizia Vaccino Viktor Melnik Marta Rodriguez-Quijano Yulia Popovych Sabina Chebotar William John Rogers 《International journal of molecular sciences》2021,22(4)
The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat. 相似文献
5.
Md Saifur Rahman Md Badrul Alam Young Kyun Kim Mst Hur Madina Ismail Fliss Sang Han Lee Jin Cheol Yoo 《International journal of molecular sciences》2021,22(10)
In this study, we investigate the immunomodulatory effects of a novel antimicrobial peptide, YD1, isolated from Kimchi, in both in vitro and in vivo models. We establish that YD1 exerts its anti-inflammatory effects via up-regulation of the Nrf2 pathway, resulting in the production of HO-1, which suppresses activation of the NF-κB pathway, including the subsequent proinflammatory cytokines IL-1β, IL-6, and TNF-α. We also found that YD1 robustly suppresses nitric oxide (NO) and prostaglandin E2 (PGE2) production by down-regulating the expression of the upstream genes, iNOS and COX-2, acting as a strong antioxidant. Collectively, YD1 exhibits vigorous anti-inflammatory and antioxidant activity, presenting it as an interesting potential therapeutic agent. 相似文献
6.
Kyunghee Kim Jisue Kim Hyoungseob Kim Gun Yong Sung 《International journal of molecular sciences》2021,22(4)
Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models. 相似文献
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凝胶是一种性质介于固体和液体之间的特殊分散体系,魔芋葡甘聚糖(KGM)凝胶稳定性差、强度低,物理共混能方便、快捷地改善其凝胶性质。主要综述KGM复合凝胶的网络结构变化,并介绍不同复合凝胶在食品、医药、材料工程等领域的应用。分析表明,KGM复合凝胶网络能通过氢键、席夫碱反应、形成多重网络结构和填充的方式改善其凝胶特性。 相似文献
9.
以玉米粉作为主要原料,利用蛹虫草固态发酵同时生产多糖和纤溶酶。以多糖含量和纤溶酶活力为指标,通过单因素和正交试验优化了蛹虫草固态发酵培养基和培养条件。结果表明:培养基由玉米粉和麸皮构成,比例为18:2(g/g),料水比例1:1(m/V),接入6%(V/m)蛹虫草液体菌种,23℃发酵时间3 d。在优化条件下获得浸提液中的胞外多糖含量为3.23 mg/mL,纤溶酶在血纤维蛋白平板上形成的溶圈面积为169.34 mm2。研究结果为生产蛹虫草功能食品基料提供了基础。 相似文献
10.
为了探讨远志多糖的体内、外活性,采用力竭运动动物模型,给予受试动物低、中、高剂量(0.10、0.20、0.40 mg/g·d)远志多糖后,分别测定各组动物负重游泳时间、肝糖原、肌糖原、乳酸、尿素氮含量及乳酸脱氢酶的活力和体外抗氧化活性。结果表明,与空白对照组相较,低、中、高剂量的远志多糖分别延长小鼠的负重游泳时间96.6 s (P<0.05)、254.4 s (P<0.01)和421.8 s (P<0.01),肝糖原含量分别提高13.1%(P<0.05)、37.4%(P<0.01)和56.4%(P<0.01),肌糖原含量分别提高10.8%(P<0.05)、31.2%(P<0.01)和42.0%(P<0.01),运动后乳酸含量分别下降4.6%(P<0.05)、8.6%(P<0.01)和14.5%(P<0.01),尿素氮含量分别降低1.5%(P<0.05)、3.9%(P<0.01)和7.5%(P<0.01),乳酸脱氢酶活力分别提高10.4%(P<0.01)、14.0%(P<0.01)和19.9%(P<0.01)。当远志多糖浓度为4 mg/mL时,对羟基自由基清除率和DPPH自由基的清除率分别为61.3%和79.5%,表明远志多糖有助于缓解机体疲劳,且体外抗氧化性较好。 相似文献