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91.
Yousuf Sameena 《Journal of biomolecular structure & dynamics》2018,36(7):1908-1917
Flavones are biologically active compounds obtained mainly from plant sources. Pharmaceutically important compounds can be delivered to the physiological target by loading them in carriers like cyclodextrins and magnetic nanoparticles. Herein, the binding of 6-methoxyflavone to β-cyclodextrin and DNA is studied using UV–visible absorption and fluorescence spectroscopy. The loading of 6-methoxyflavone onto a magnetic nanoparticles is employed. β-cyclodextrin encapsulates the 6-methoxyflavone to form an inclusion complex. β-cyclodextrin also used to draw forth 6-methoxyflavone loaded onto a magnetic nanoparticles. The morphology, magnetic property and the crystallite size of the nanoparticles are studied using scanning electron microscopy, vibrating sample magnetometry and X-ray diffraction techniques, respectively. The binding of the drug-loaded magnetic nanoparticles to DNA shows that the compound is accessible to DNA and available mostly on the surface of the nanoparticles despite a modified dextan polymer supposedly encapsulates the flavone. 相似文献
92.
Ramachandran Prakasam Mitsuaki Fujimoto Ryosuke Takii Naoki Hayashida Eiichi Takaki Ke Tan Fangxu Wu Sachiye Inouye Akira Nakai 《FEBS letters》2013
The febrile response is elicited by pyrogenic cytokines including IL-6 in response to microorganism infections and diseases in vertebrates. Mammalian HSF1, which senses elevations in temperature, negatively regulates the response by suppressing pyrogenic cytokine expression. We here showed that HSF3, an avian ortholog of mammalian HSF1, directly binds to and activates IL-6 during heat shock in chicken cells. Other components of the febrile response mechanism, such as IL-1β and ATF3, were also differently regulated in mammalian and chicken cells. These results suggest that the febrile response is exacerbated by a feed-forward circuit composed of the HSF3-IL-6 pathway in birds. 相似文献
93.
Kevin Ni Amar Gill Danting Cao Kengo Koike Kelly S. Schweitzer Stavros Garantziotis Irina Petrache 《Biochemistry and Biophysics Reports》2019
During inflammation, the covalent linking of the ubiquitous extracellular polysaccharide hyaluronan (HA) with the heavy chains (HC) of the serum protein inter alpha inhibitor (IαI) is exclusively mediated by the enzyme tumor necrosis factor α (TNFα)-stimulated-gene-6 (TSG-6). While significant advances have been made regarding how HC-modified HA (HC-HA) is an important regulator of inflammation, it remains unclear why HC-HA plays a critical role in promoting survival in intraperitoneal lipopolysaccharide (LPS)-induced endotoxemia while exerting only a modest role in the outcomes following intratracheal exposure to LPS. To address this gap, the two models of intraperitoneal LPS-induced endotoxic shock and intratracheal LPS-induced acute lung injury were directly compared in TSG-6 knockout mice and littermate controls. HC-HA formation, endogenous TSG-6 activity, and inflammatory markers were assessed in plasma and lung tissue. TSG-6 knockout mice exhibited accelerated mortality during endotoxic shock. While both intraperitoneal and intratracheal LPS induced HC-HA formation in lung parenchyma, only systemically-induced endotoxemia increased plasma TSG-6 levels and intravascular HC-HA formation. Cultured human lung microvascular endothelial cells secreted TSG-6 in response to both TNFα and IL1β stimulation, indicating that, in addition to inflammatory cells, the endothelium may secrete TSG-6 into circulation during systemic inflammation. These data show for the first time that LPS-induced systemic inflammation is uniquely characterized by significant vascular induction of TSG-6 and HC-HA, which may contribute to improved outcomes of endotoxemia. 相似文献
94.
95.
Shizuo Narimatsu Rika Kato Toshiharu Horie Satoshi Ono Michio Tsutsui Yoshiyasu Yabusaki Shigeru Ohmori Mitsukazu Kitada Takao Ichioka Noriaki Shimada Ryuichi Kato Tsutomu Ishikawa 《Chirality》1999,11(1):1-9
The enantioselectivity of 4‐hydroxylation of bunitrolol (BTL), a β‐adrenoceptor blocking drug, was studied in microsomes from human liver, human hepatoma (Hep G2) cells expressing CYP2D6, and lymphoblastoid cells expressing CYP2D6. Kinetics in human liver microsomes showed that the Vmax value for (+)‐BTL was 2.1‐fold that of (−)‐BTL, and that the Km value for (+)‐BTL was lower than that for the (−)‐antipode, resulting in the intrinsic clearance (Vmax/Km) of (+)‐BTL being 2.1‐fold over its (−)‐antipode. CYP2D6 (CYP2D6‐met) expressed in Hep G2 cells had a methionine residue at position 373 of the amino acid sequence and a rat‐type N‐terminal peptide (MELLNGTGLWSM) instead of the human‐type (MGLEALVPLAVIV), and showed enantioselectivity of [(+)‐BTL < (−)‐BTL] for the rate of BTL 4‐hydroxylation. In contrast, enantioselectivity [(+)‐BTL > (−)‐BTL] for Hep G2‐CYP2D6 (CYP2D6‐val) with a human‐type N‐terminal peptide that had a valine residue at 374, which corresponds to the methionine of the CYP2D6‐met variant, was the same as that for human liver microsomes. We further confirmed that CYP2D6‐met and CYP2D6‐val expressed in human lymphoblastoid cells, both of which have methionine and valine, respectively, at position 374 and a human‐type N‐terminal peptide, exhibited the same enantioselectivities as those obtained from CYP2D6‐met and CYP2D6‐val expressed in the Hep G2 cell system. These results indicate that the amino acid at 374 of CYP2D6 is one of the key factors influencing the enantioselectivity of BTL 4‐hydroxylation. Chirality 11:1–9, 1999. © 1999 Wiley‐Liss, Inc. 相似文献
96.
Megf6, a member of MEGF (multiple EGF‐like domains) protein family, is a conserved high molecular weight protein with 30 EGF‐like domains. Although many members of the MEGF protein family are essential for embryonic development and homeostasis, the role of Megf6 in development and physiology is still unknown. Here, we generated Megf6‐deficient mice using CRISPR‐Cas9 technique and showed that Megf6 is dispensable for embryonic development. We also constructed the Megf6Cre allele to study Megf6‐expressing cell lineages. Our results showed that Megf6‐expressing cells contribute to the periotic mesenchyme and its derivatives, skin epidermis, certain cells in brain and ribs. Therefore, the Megf6Cre allele can be a useful tool for conditional deletion in these tissues, in particular for periotic mesenchyme deletion. 相似文献
97.
《Bioorganic & medicinal chemistry letters》2014,24(5):1352-1357
The design, synthesis and biological evaluation of novel triazolyl p38α MAPK inhibitors with improved water solubility for formulation in cationic liposomes (SAINT-O-Somes) targeted at diseased endothelial cells is described. Water-solubilizing groups were introduced via a ‘click’ reaction of functional azides with 2-alkynyl imidazoles and isosteric oxazoles to generate two small libraries of 1,4-disubstituted 1,2,3-triazolyl p38α MAPK inhibitors. Triazoles with low IC50 values and desired physicochemical properties were screened for in vitro downregulation of proinflammatory gene expression and were formulated in SAINT-O-Somes. Triazolyl p38α MAPK inhibitor 88 (IC50 = 0.096 μM) displayed the most promising in vitro activity. 相似文献
98.
99.
The phenotypic traits of 7 independently isolated dam mutants of Escherichia coli have been examined. The mutant strains differ from the wildtype in the following respects: (1) decreased DNA adenine methylase activity in vivo and in vitro; (2) a 14--85-fold increase in spontaneous mutability; (3) decreased survival after ultraviolet irradiation; (4) a 10--21-fold increase in spontaneous induction of lambda phage from lysogens; (5) a 3--17-fold increase in the level of recombination; and (6) inviability of double mutants containing dam- and recB- or recC-. Unmethylated fd phage chromosomes are able to replicate normally in dam- mutants. A mutant strain in which the dcm gene is deleted is viable, showing that the dcm gene product is dispensible for growth. 相似文献
100.
Laura ConteBernard L. Trumpower Vincenzo Zara 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2011,1813(1):91-101
The yeast cytochrome bc1 complex, a component of the mitochondrial respiratory chain, is composed of ten distinct protein subunits. In the assembly of the bc1 complex, some ancillary proteins, such as the chaperone Bcs1p, are actively involved. The deletion of the nuclear gene encoding this chaperone caused the arrest of the bc1 assembly and the formation of a functionally inactive bc1 core structure of about 500-kDa. This immature bc1 core structure could represent, on the one hand, a true assembly intermediate or, on the other hand, a degradation product and/or an incorrect product of assembly. The experiments here reported show that the gradual expression of Bcs1p in the yeast strain lacking this protein was progressively able to rescue the bc1 core structure leading to the formation of the functional homodimeric bc1 complex. Following Bcs1p expression, the mature bc1 complex was also progressively converted into two supercomplexes with the cytochrome c oxidase complex. The capability of restoring the bc1 complex and the supercomplexes was also possessed by the mutated yeast R81C Bcsp1. Notably, in the human ortholog BCS1L, the corresponding point mutation (R45C) was instead the cause of a severe bc1 complex deficiency. Differently from the yeast R81C Bcs1p, two other mutated Bcs1p's (K192P and F401I) were unable to recover the bc1 core structure in yeast. This study identifies for the first time a productive assembly intermediate of the yeast bc1 complex and gives new insights into the molecular mechanisms involved in the last steps of bc1 assembly. 相似文献