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1.
Eur J Pharmacol ; 917: 174755, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35016885

RESUMO

Aesculin, a coumarin compound, is one of the major active ingredients of traditional Chinese herbal medicine Qinpi (Cortex Fraxini), which has been reported to exhibit antioxidative, anti-inflammatory and neuroprotective properties against oxidative stress and cellular apoptosis. However, the regulatory mechanisms remain poorly characterized in vivo. This research was performed to explore the underlying molecular mechanisms behind aesculin response conferring oxidative stress resistance, and the protective effects on amyloid-ß (Aß)-mediated neurotoxicity in Caenorhabditis elegans. Study indicated that aesculin plays the protective roles for C. elegans against oxidative stress and Aß-mediated neurotoxicity and reduces the elevated ROS and MDA contents through enhancement of antioxidant defenses. The KEGG pathway analysis suggested that the differentially expressed genes are mainly involved in longevity regulating pathway, and the nuclear translocation of DAF-16 and the RNAi of daf-16 and hsf-1 indicated that DAF-16 and HSF-1 play critical roles in integrating upstream signals and inducing the expressions of stress resistance-related genes. Furthermore, the up-regulated expressions of their target genes such as sod-3 and hsp-16.2 were confirmed in transgenic GFP reporter strains CF1553 and CL2070, respectively. These results indicated that the regulators DAF-16 and HSF-1 elevate the stress resistance of C. elegans by modulating stress-responsive genes. Further experiments revealed that aesculin is capable of suppressing Aß-induced oxidative stress and apoptosis and improves chemosensory behavior dysfunction in Aß-transgenic nematodes. In summary, this study suggested that aesculin offers increased resistance against oxidative stress and protective effects against Aß-induced neurotoxicity through activation of stress regulators DAF-16 and HSF-1 in nematodes.


Assuntos
Caenorhabditis elegans , Animais
2.
Mar Drugs ; 18(10)2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32993031

RESUMO

The hydrolysate of golden cuttlefish (Sepia esculenta) was prepared by using papain, and then, it was further separated by ultrafiltration, gel filtration chromatography, and reverse-phase high-performance liquid chromatography (RP-HPLC). The peptide components of the active fraction were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then two novel peptides, SeP2 (DVEDLEAGLAK, 1159.27 Da) and SeP5 (EITSLAPSTM, 1049.22 Da), were obtained and displayed significant alleviation effects on oxidative stress in Caenorhabditis elegans. Studies indicated that S. esculenta antioxidant peptides (SePs) increase superoxide dismutase (SOD) activity but reduce reactive oxygen species (ROS) and malondialdehyde (MDA) levelsin oxidation-damaged nematodes. Using transgenic CF1553 nematodes, the sod-3p::GFP expression in the worms treated with SePs was significantly higher than that of the control nematodes. Real-time PCR also demonstrated that the expression of stress-related genes such as sod-3 is up-regulated by SePs. Furthermore, studies showed that SePs could obviously decrease fat accumulation as well as reduce the elevated ROS and MDA levels in high-fat nematodes. Taken together, these results indicated that SePs are capable of the activation of antioxidant defense and the inhibition of free radicals and lipid peroxidation, play important roles in attenuating oxidative stress and fat accumulation in C. elegans, and might have the potential to be used in nutraceutical and functional foods.


Assuntos
Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/farmacologia , Sepia/metabolismo , Tecido Adiposo/efeitos dos fármacos , Animais , Animais Geneticamente Modificados , Antioxidantes/isolamento & purificação , Caenorhabditis elegans/metabolismo , Cromatografia Líquida , Peroxidação de Lipídeos/efeitos dos fármacos , Peptídeos/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Espectrometria de Massas em Tandem
3.
Sci Rep ; 9(1): 9437, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263155

RESUMO

Accumulation of iron has been associated with the pathobiology of various disorders of the central nervous system. Our previous work has shown that hephaestin (Heph) and ceruloplasmin (Cp) double knockout (KO) mice induced iron accumulation in multiple brain regions and that this was paralleled by increased oxidative damage and deficits in cognition and memory. In this study, we enriched astrocytes and oligodendrocytes from the cerebral cortex of neonatal wild-type (WT), Heph KO and Cp KO mice. We demonstrated that Heph is highly expressed in oligodendrocytes, while Cp is mainly expressed in astrocytes. Iron efflux was impaired in Cp KO astrocytes and Heph KO oligodendrocytes and was associated with increased oxidative stress. The expression of Heph, Cp, and other iron-related genes was examined in astrocytes and oligodendrocytes both with and without iron treatment. Interestingly, we found that the expression of the mRNA encoding ferroportin 1, a transmembrane protein that cooperates with CP and HEPH to export iron from cells, was positively correlated with Cp expression in astrocytes, and with Heph expression in oligodendrocytes. Our findings collectively demonstrate that HEPH and CP are important for the prevention of glial iron accumulation and thus may be protective against oxidative damage.


Assuntos
Ceruloplasmina/genética , Ferro/metabolismo , Proteínas de Membrana/genética , Estresse Oxidativo , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Ceruloplasmina/deficiência , Proteínas de Membrana/deficiência , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oligodendroglia/citologia , Oligodendroglia/metabolismo , Estresse Oxidativo/genética
4.
Angew Chem Int Ed Engl ; 57(19): 5454-5458, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29543370

RESUMO

The herein reported visible-light-activated catalytic asymmetric [3+2] photocycloadditions between cyclopropanes and alkenes or alkynes provide access to chiral cyclopentanes and cyclopentenes, respectively, in 63-99 % yields and with excellent enantioselectivities of up to >99 % ee. The reactions are catalyzed by a single bis-cyclometalated chiral-at-metal rhodium complex (2-8 mol %) which after coordination to the cyclopropane generates the visible-light-absorbing complex, lowers the reduction potential of the cyclopropane, and provides the asymmetric induction and overall stereocontrol. Enabled by a mild single-electron-transfer reduction of directly photoexcited catalyst/substrate complexes, the presented transformations expand the scope of catalytic asymmetric photocycloadditions to simple mono-acceptor-substituted cyclopropanes affording previously inaccessible chiral cyclopentane and cyclopentene derivatives.

5.
Phys Rev Lett ; 113(12): 128302, 2014 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-25279647

RESUMO

We develop a theoretical description for mechanically stable frictional packings in terms of the difference between the total number of contacts required for isostatic packings of frictionless disks and the number of contacts in frictional packings, m=Nc0 - Nc. The saddle order m represents the number of unconstrained degrees of freedom that a static packing would possess if friction were removed. Using a novel numerical method that allows us to enumerate disk packings for each m, we show that the probability to obtain a packing with saddle order m at a given static friction coefficient µ, Pm(µ), can be expressed as a power series in µ. Using this form for Pm(µ), we quantitatively describe the dependence of the average contact number on the friction coefficient for static disk packings obtained from direct simulations of the Cundall-Strack model for all µ and N.

6.
Phys Rev E Stat Nonlin Soft Matter Phys ; 86(4 Pt 1): 041303, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23214576

RESUMO

We perform extensive molecular dynamics simulations of dense liquids composed of bidisperse dimer- and ellipse-shaped particles in two dimensions that interact via purely repulsive contact forces. We measure the structural relaxation times obtained from the long-time α decay of the self part of the intermediate scattering function for the translational and rotational degrees of freedom (DOF) as a function of packing fraction φ, temperature T, and aspect ratio α. We are able to collapse the packing-fraction and temperature-dependent structural relaxation times for disks, and dimers and ellipses over a wide range of α, onto a universal scaling function F(±)(|φ-φ(0)|,T,α), which is similar to that employed in previous studies of dense liquids composed of purely repulsive spherical particles in three dimensions. F(±) for both the translational and rotational DOF are characterized by the α-dependent scaling exponents µ and δ and packing fraction φ(0)(α) that signals the crossover in the scaling form F(±) from hard-particle dynamics to super-Arrhenius behavior for each aspect ratio. We find that the fragility of structural relaxation at φ(0), m(φ(0)), decreases monotonically with increasing aspect ratio for both ellipses and dimers. For α>α(p), where α(p) is the location of the peak in the packing fraction φ(J) at jamming onset, the rotational DOF are strongly coupled to the translational DOF, and the dynamic scaling exponents and φ(0) are similar for the rotational and translational DOF. For 1<α<α(p), the translational DOF become frozen at higher temperatures than the rotational DOF, and φ(0) for the rotational degrees of freedom increases above φ(J). Moreover, the results for the slow dynamics of dense liquids composed of dimer- and ellipse-shaped particles are qualitatively the same, despite the fact that zero-temperature static packings of dimers are isostatic, while static packings of ellipses are hypostatic. Thus, zero-temperature contact counting arguments do not apply to structural relaxation of dense liquids of anisotropic particles near the glass transition.

7.
Phys Rev E Stat Nonlin Soft Matter Phys ; 85(1 Pt 1): 011308, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22400566

RESUMO

Typical quasistatic compression algorithms for generating jammed packings of purely repulsive, frictionless particles begin with dilute configurations and then apply successive compressions with the relaxation of the elastic energy allowed between each compression step. It is well known that during isotropic compression these systems undergo a first-order-like jamming transition at packing fraction φ(J) from an unjammed state with zero pressure and no force-bearing contacts to a jammed, rigid state with nonzero pressure, a percolating network of force-bearing contacts, and contact number z=2d, where d is the spatial dimension. Using computer simulations of two-dimensional systems with monodisperse and bidisperse particle size distributions, we investigate the second-order-like contact percolation transition, which precedes the jamming transition with φ(P)<φ(J) and signals the formation of a system-spanning cluster of non-force-bearing contacts between particles. By measuring the number of nonfloppy modes of the dynamical matrix, the displacement field between successive compression steps, and the overlap between the adjacency matrix, which represents the network of contacting grains, at φ and φ(J), we find that the contact percolation transition also signals the onset of a nontrivial mechanical response to applied stress. Our results show that cooperative particle motion occurs in unjammed systems significantly below the jamming transition for φ(P)<φ<φ(J), not only for jammed systems with φ>φ(J).


Assuntos
Coloides/química , Modelos Químicos , Modelos Moleculares , Transição de Fase , Simulação por Computador , Temperatura Alta , Propriedades de Superfície
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