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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.
Kavitej Samra Mathun Kuganesan William Smith Anna Kleyman Robert Tidswell Nishkantha Arulkumaran Mervyn Singer Alex Dyson 《International journal of molecular sciences》2021,22(6)
Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe−/H2Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O2 consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H2O2), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed. 相似文献
3.
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
7.
Ming Zhang Xuefeng Jiang Qicheng Zhang Tao Zheng Mohsen Mohammadniaei Wentao Wang Jian Shen Yi Sun 《Advanced functional materials》2021,31(38):2102274
Immunotherapy is an efficient approach to clinical oncology. However, the immune privilege of the central nervous system (CNS) limits the application of immunotherapeutic strategies for brain cancers, especially glioblastoma (GBM). Tumor resistance to immune checkpoint inhibitors is a further challenge in immunotherapies. To overcome the immunological tolerance of brain tumors, a novel multifunctional nanoparticle (NP) for highly efficient synergetic immunotherapy is reported. The NP contains an anti-PDL1 antibody (aPDL1), upconverting NPs, and the photosensitizer 5-ALA; the surface of the NP is conjugated with the B1R kinin ligand to facilitate transport across the blood-tumor-barrier. Upon irradiation with a 980 nm laser, 5-ALA is transformed into protoporphyrin IX, generating reactive oxygen species. Photodynamic therapy (PDT) further promotes intratumoral infiltration of cytotoxic T lymphocytes and sensitizes tumors to PDL1 blockade therapy. It is demonstrated that combining PDT and aPDL1 can effectively suppress GBM growth in mouse models. The proposed NPs provide a novel and effective strategy for boosting anti-GBM photoimmunotherapy. 相似文献
8.
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.
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
10.
以玉米淀粉为原料,用流变分析、食品物性分析、差示扫描量热分析、低场核磁共振成像分析等研究冷藏过程中不同含量(相对玉米淀粉干基质量的1%、3%、5%和7%)皂荚糖胶对玉米淀粉老化特性的影响。动态流变时间扫描结果表明:随着老化时间的延长,玉米淀粉的弹性模量增加,皂荚糖胶的加入使复配体系弹性模量的变化率减小,一定程度上抑制玉米淀粉的短期老化;凝胶强度实验表明:随着冷藏时间的延长,玉米淀粉凝胶体系的硬度值增加,皂荚糖胶的加入使玉米淀粉形成质地更柔软的凝胶,硬度值明显降低;差示扫描量热测定结果表明:随着皂荚糖胶含量的增加,复配体系的老化率逐渐减小。用低场核磁水分运动性实验方法,通过5%皂荚糖胶加入前后淀粉凝胶中自由水、结合水和不易流动水含量的对比证实该胶对凝胶的水分分布有较大的影响;该研究能进一步丰富植物胶体对淀粉老化性能影响的理论。 相似文献