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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
2.
基于分形几何理论,考虑微凸体因应变硬化而造成弹塑性变形阶段硬度随变形量变化而变化,建立结合面第一、第二弹塑性变形阶段单次加载刚度分形模型。推导出在计入硬度变化的情况下,单个微凸体在弹塑性变形阶段法向接触刚度与接触面积之间的关系式,进而得出结合面在弹塑性变形阶段法向接触刚度与接触面积、接触载荷之间量纲为一的关系式,并通过仿真分析得出相关参数对结合面法向接触刚度的影响。仿真结果显示:考虑硬度变化时,结合面量纲一法向接触刚度的值与法向实际接触载荷、实际接触面积之间存在关系;结合面法向接触刚度随着分形维数D的增大而增大;分形维数一定时,结合面法向接触刚度随表面长度尺度参数G值增大而增大。 相似文献
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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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结合全球倡导的营养导向型农业和功能性食品的内容,首次提出“功能性小麦品种”的概念,将其定义为“含有对人体健康有益的活性成分,可调节人体有益代谢,能给人体健康带来某种益处或满足特定人群的特殊需求,同时可以作为日常食物的口感正常、无毒副作用的小麦品种类型”;结合疫情警示和我国进入后工业时代后,人们需求必将由“吃得饱”、“吃得好”向“吃得健康”转变,因而提出继高产品种、优质品种之后培育“功能性小麦品种”的育种目标。根据多年关于小麦淀粉、蛋白、酯类和其他成分的功能研究结果,介绍新育成的“麦黄酮”、“高色素”、“高抗性淀粉”、“富锌”、“低醇溶蛋白”和“低植酸”等功能性小麦新品种(系)的营养特性和农艺产量状况;根据“健康中国2030”规划等国家战略,进行“功能性品种培育是解决我国功能性食品‘卡脖子’的关键基础,一种功能性品种可以形成一类功能性食品,多种功能性品种可以形成我国功能性面制品产业,推动我国整个食品工业的发展”的前景展望;根据功能性品种及其食品的稳定性和可靠性是产品和市场的“生命线”,从对消费者负责的高度,提出关于“功能性农作物品种审定导向和组建功能性成分检测机构;编制有关功能性品种和食品的国家或行业标准,设立功能性食品和功能性农作物品种的商业标志,保证我国功能性农作物品种及其食品健康发展”等方面的具体建议。 相似文献
9.
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
10.
为延长带鱼鱼丸保质期,以带鱼鱼丸为原料,分别在250、300、350 MPa压力下处理5 min,以冷藏期间鱼丸菌落总数、总挥发性盐基氮(total volatile base nitrogen,TVB-N)含量、pH值为指标,并结合感官评价、色值、凝胶强度及质地剖面分析,探究超高压处理对冷藏带鱼鱼丸保鲜效果的影响。结果表明:超高压处理可显著降低贮藏期内鱼丸菌落总数、TVB-N含量,延缓pH值的增加;超高压处理对鱼丸色泽无负面影响,同时能较好保持鱼丸冷藏期间感官特性、色值、凝胶强度、硬度及弹性。对照组和超高压组鱼丸的菌落总数分别在冷藏的第21天和第56天超出105 CFU/g;随冷藏时间延长,对照组鱼丸感官评分明显下降,贮藏14 d后产生异味,第21天时感官已不可接受;超高压组鱼丸感官评分在贮藏35 d内均无明显变化,其中300 MPa处理5 min组在冷藏49 d后感官评分仍在5 分以上,但第56天时感官不可接受。综合考虑,对带鱼鱼丸进行300 MPa超高压处理5 min,可延长其冷藏货架期约35 d。该结果可以为超高压技术在鱼糜制品保鲜中的应用提供依据。 相似文献