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71.
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
72.
James I. Mitchell-White Thomas Stockner Nicholas Holliday Stephen J. Briddon Ian D. Kerr 《International journal of molecular sciences》2021,22(6)
The five members of the mammalian G subfamily of ATP-binding cassette transporters differ greatly in their substrate specificity. Four members of the subfamily are important in lipid transport and the wide substrate specificity of one of the members, ABCG2, is of significance due to its role in multidrug resistance. To explore the origin of substrate selectivity in members 1, 2, 4, 5 and 8 of this subfamily, we have analysed the differences in conservation between members in a multiple sequence alignment of ABCG sequences from mammals. Mapping sets of residues with similar patterns of conservation onto the resolved 3D structure of ABCG2 reveals possible explanations for differences in function, via a connected network of residues from the cytoplasmic to transmembrane domains. In ABCG2, this network of residues may confer extra conformational flexibility, enabling it to transport a wider array of substrates. 相似文献
73.
Patricia A. Miguez Stephen A. Tuin Adam G. Robinson Joyce Belcher Prapaporn Jongwattanapisan Kimberly Perley Vinicius de Paiva Gon«alves Arash Hanifi Nancy Pleshko Elisabeth R. Barton 《International journal of molecular sciences》2021,22(6)
This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin’s influence in mineralized tissue formation and regeneration. Hesperidin was added to a culture of MC3T3-E1 cells at various concentrations. Cell proliferation, viability, osteogenic gene expression and deposited collagen matrix analyses were performed. Treatment with hesperidin showed significant upregulation of osteogenic markers, particularly with lower doses. Mature and compact collagen fibrils in hesperidin-treated cultures were observed by picrosirius red staining (PSR), although a thinner matrix layer was present for the higher dose of hesperidin compared to osteogenic media alone. Fourier-transform infrared spectroscopy indicated a better mineral-to-matrix ratio and matrix distribution in cultures exposed to hesperidin and confirmed less collagen deposited with the 100-µM dose of hesperidin. In vivo, hesperidin combined with a suboptimal dose of bone morphogenetic protein 2 (BMP2) (dose unable to promote healing of a rat mandible critical-sized bone defect) in a collagenous scaffold promoted a well-controlled (not ectopic) pattern of bone formation as compared to a large dose of BMP2 (previously defined as optimal in healing the critical-sized defect, although of ectopic nature). PSR staining of newly formed bone demonstrated that hesperidin can promote maturation of bone organic matrix. Our findings show, for the first time, that hesperidin has a modulatory role in mineralized tissue formation via not only osteoblast cell differentiation but also matrix organization and matrix-to-mineral ratio and could be a potential adjunct in regenerative bone therapies. 相似文献
74.
Surface preparation of various metals and alloys before plating and other finishing applications 总被引:1,自引:0,他引:1
Stephen F. Rudy 《Metal Finishing》2007,105(10):147-162
75.
76.
Gwan Hee Han Ilseon Hwang Hanbyoul Cho Kris Ylaya Jung-A Choi Hyunja Kwon Joon-Yong Chung Stephen M. Hewitt Jae-Hoon Kim 《International journal of molecular sciences》2021,22(11)
Hormone receptor expression patterns often correlate with infiltration of specific lymphocytes in tumors. Specifically, the presence of specific tumor-infiltrating lymphocytes (TILs) with particular hormone receptor expression is reportedly associated with breast cancer, however, this has not been revealed in epithelial ovarian cancer (EOC). Therefore, we investigated the association between hormone receptor expression and TILs in EOC. Here we found that ERα, AR, and GR expression increased in EOC, while PR was significantly reduced and ERβ expression showed a reduced trend compared to normal epithelium. Cluster analysis indicated poor disease-free survival (DFS) in AR+/GR+/PR+ subgroup (triple dominant group); while the Cox proportional-hazards model highlighted the triple dominant group as an independent prognostic factor for DFS. In addition, significant upregulation of FoxP3+ TILs, PD-1, and PD-L1 was observed in the triple dominant group compared to other groups. NanoString analyses further suggested that tumor necrosis factor (TNF) and/or NF-κB signaling pathways were activated with significant upregulation of RELA, MAP3K5, TNFAIP3, BCL2L1, RIPK1, TRAF2, PARP1, and AKT1 in the triple dominant EOC group. The triple dominant subgroup correlates with poor prognosis in EOC. Moreover, the TNF and/or NF-κB signaling pathways may be responsible for hormone-mediated inhibition of the immune microenvironment. 相似文献
77.
Determination of Binder Decomposition Kinetics for Specifying Heating Parameters in Binder Burnout Cycles 总被引:2,自引:0,他引:2
The decomposition kinetics of poly(vinyl butyral) binder from barium titanate multilayer ceramic capacitors with platinum metal electrodes were analyzed by thermogravimetric analysis as a function of the heating rate. The activation energy and pre-exponential factor for the decomposition kinetics were determined from two types of integral equations, from the Redhead method, and from the variation in heating rate method. The accuracy of the kinetic parameters determined from these methods was then evaluated for describing the observed rate of binder decomposition. Although the individual models yielded very different kinetic parameters, all were capable of describing the experimental data within ±15% accuracy. The kinetic parameters were then used in a coupled transport and kinetic model for describing the buildup of pressure within the ceramic green body as a function of the heating cycle. A methodology based on calculus of variations was also developed to predict the minimum duration for the binder burnout cycle. 相似文献
78.
Indentation-crack-length procedures were used to determine the critical fracture toughness (KIC ) and the sensitivity to environmentally enhanced crack growth in heavy-metal fluoride glasses of varying chemical composition. The data show that while KIC was more or less invariant with composition, some glasses were more susceptible to subcritical crack growth than others. The results are interpreted in terms of existing crack-growth models. A technique for predicting KIC from fundamental atomic bonding and crystal-structure data for these glasses is discussed. 相似文献
79.
A novel technique for the preparation of secondary fatty amides 总被引:1,自引:0,他引:1
Alexander Bilyk Raymond G. Bistline Jr. George J. Piazza Stephen H. Feairheller Michael J. Haas 《Journal of the American Oil Chemists' Society》1992,69(5):488-491
A technique for the synthesis of monosubstituted fatty amides at low temperature and ambient pressure was developed. This
method involved the condensation of an amine with a triacylglycerol. The primary amine (ethyl,n-butyl,n-hexyl andn-octyl were tested) acted as reagent and solvent for the fatty substrates. No additional organic solvent or catalyst was added.
Tallow, vegetable oils and fish oil all served well as substrates, as did pure tripalmitin. The rate of amidation was dependent
upon temperature and the ratio of fat to amine. In a series of experiments conducted with tallow andn-butylamine at a fat:amine molar ratio of 1:16, amidation could be carried out at 20°C, producingn-butyltallowamide in 83% yield in 24 hr. When the fat:amine molar ratio was reduced to 1:8, and the temperature raised to
45°C, the amide yield was 87.6% in 24 hr. When the reaction was carried out at the boiling point ofn-butylamine (78°C) and at a fat:amine ratio of 1:8, the amide yield was 93.2% in 4 hr. The reaction progressed more rapidly
with higher molecular weight amines. The identity and purity of the amides was assessed by thin-layer chromatography and confirmed
by elemental analyses and infrared and C13 nuclear magnetic resonance spectroscopy. 相似文献
80.
The aziridinyl group has been introduced as a terminal substituent into a series of monoazo disperse dyes; the dyes absorb hypsochromically in comparison with their counterparts containing larger terminal ring systems. When applied from aqueous dyebaths the dyes exhibit higher wash fastness on nylon 6.6 and diacetate fibres than conventional dispersedyes of similar structure and relative molecular mass. On polyester and triacetate fibresthe aziridinyl dyes display similar wash fastness to conventional dyes. Dye polymerisation and/or covalent fixation may account for the observed high fastness of the dyes on diacetate and nylon fibres. With the exception of nylon 6.6, the aziridinyl dyes display lower light fastness than conventional disperse dyes on the fibres studied, this being attributable to the greater susceptibility of the aziridinyl dyes to oxidative rather than reductive photodegradation. 相似文献