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1.
Arezou Ghahghaei S. Zahra Bathaie Hoda Kheirkhah Elmira Bahraminejad 《Cellular & molecular biology letters》2013,18(3):328-339
Aβ is the main constituent of the amyloid plaque found in the brains of patients with Alzheimer’s disease. There are two common isoforms of Aβ: the more common form, Aβ40, and the less common but more amyloidogenic form, Aβ42. Crocin is a carotenoid from the stigma of the saffron flower and it has many medicinal properties, including antioxidant effects. In this study, we examined the potential of crocin as a drug candidate against Aβ42 amyloid formation. The thioflavin T-binding assay and electron microscopy were used to examine the effects of crocin on the extension and disruption of Aβ42 amyloids. To further investigate the relationship between crocin and Aβ42 structure, we analyzed peptide conformation using the ANS-binding assay and circular dichroism (CD) spectroscopy. An increase in the thioflavin T fluorescence intensity upon incubation revealed amyloid formation in Aβ42. It was found that crocin has the ability to prevent amyloid formation by decreasing the fluorescence intensity. Electron microscopy data also indicated that crocin decreased the amyloid fibril content of Aβ. The ANS-binding assay showed that crocin decreased the hydrophobic area in incubated Aβ42. CD spectroscopy results also showed that the peptide undergoes a structural change to α-helical and β-turn. Our study shows that the anti-amyloidogenic effect of crocin may be exerted not only by the inhibition of Aβ amyloid formation but also by the disruption of amyloid aggregates. Therefore, crocin could be essential in the search for therapies inhibiting aggregation or disrupting aggregation. 相似文献
2.
Arezou Sayad Soudeh Ghafouri-Fard Bahareh Shams Shahram Arsang-Jang Leila Gholami Mohammad Taheri 《Journal of cellular physiology》2020,235(12):9568-9576
Periodontitis is a complex disorder that affects a large number of human beings from different ethnic groups. This condition has been associated with dysregulation of a number of genes, among them are long noncoding RNAs (lncRNAs). In the current study, we assessed the expression of four lncRNAs (BDNF-AS, MIAT, MIR137HG, and PNKY) as well as BDNF in the peripheral blood and gingival tissues obtained from patients with periodontitis and healthy subjects. The expression of BDNF was significantly lower in blood samples of male patients with periodontitis compared with male controls (posterior β of RE = −4.754, p = .048). However, there was no significant difference in the expression of BDNF in tissue samples from the cases and controls. The expression of BDNF-AS was significantly lower in the tissue samples of patients compared with control tissue samples (posterior β of RE = −2.151, p = .019). Such an expression difference was detected between male subgroups as well (posterior β of RE = −3.679, p = .009). However, expression of this lncRNA was not different in blood samples obtained from patients compared with healthy subjects. The expression of PNKY was significantly higher in tissue samples obtained from female patients compared with sex-matched controls (posterior β of RE = 6.23, p = .037). Blood levels of this lncRNA were not different between cases and controls. There was no significant difference either in the tissue expression or in blood expression of MIR137HG or MIAT between cases and controls. The current study indicates the putative role of BDNF, BDNF-AS, and PNKY in the pathophysiology of periodontitis and potentiates these genes as candidates for functional studies. 相似文献
3.
DNA functionalisation is a proven route to program an assembly of nanoparticles into a vast array of nanostructures. In this paper, we used coarse-grained molecular dynamics simulations to study DNA-functionalised nanoparticles and demonstrate the effect of grafted DNA strand composition, specifically the placement and number of contiguous G/C bases in the grafted DNA single strands, on the thermodynamics and structure of nanoparticle assembly at varying grafting densities and particle sizes. At a constant G/C content, nanoparticles assemble more readily when the G/C bases are placed on the outer or middle portions of the strands than on the inner portion. In addition, the number of neighbours within the assembled cluster decreases as the placement of the G/C bases goes from the outer to middle to inner sections of the strand. As the G/C content decreases, the cluster dissociation temperature, Td, decreases, as the enthalpic drive to assemble decreases. At a high G/C content (number of grafts and G/C placement are held constant), as particle size decreases, Td increases. This is because the smaller particles experience a lower entropic loss than do larger particles upon assembly. On the other hand, at a low G/C content, small changes in particle size lead to negligible changes in Td. 相似文献
4.
Masoud Bagherpour Zarchi Arezou Rezaei 《Journal of biomolecular structure & dynamics》2013,31(13):3479-3486
Erythropoietin (EPO) is a hematopoietic growth factor. This substance, as a strong cell protector, can increase cell maintenance during different damages of central nervous system. Since the brain-blood barrier prevents the entrance of large proteins similar to EPO into the brain, its systemic delivery gets limited. The aim of this study was to find an alternative approach for EPO delivery into the brain to skip the blood-brain barrier prevention. So, a new quaternary ammonium-based cationic Gemini surfactant has been used to study the interaction of the cationic Gemini surfactant (as a carrier) with EPO using various spectroscopic techniques of (fluorescence and circular dichroism (CD)) and thermal denaturation. Fluorescence spectroscopy studies show the formation of Gemini-EPO complex and also static quenching of protein upon this interaction. The binding parameters of number of binding sites, binding affinity, Gibbs free energy, enthalpy, and entropy were calculated according to fluorescence quenching studies. Also, CD results have further represented that the content of regular secondary structure of EPO did not show any significant alterations by increasing the Gemini concentration. Finally, thermal denaturation behavior of EPO results indicates decreasing the thermal stability of protein in the presence of Gemini. In conclusion, the obtained results proposed that Gemini as a cationic surfactant can bind to EPO without any significant diverse effects on the structure of this drug (EPO) which can be considered as a candidate for EPO delivery in future. 相似文献
5.
Arezou Ghahghaei Sima Shahraki 《International journal of peptide research and therapeutics》2016,22(1):23-29
Alzheimer’s disease is associated with the fibril formation of β-amyloid peptide in extracellular plaque. β-Casein is a milk protein that has shown a remarkable ability to stabilize proteins by inhibiting their protein aggregation and precipitation. The aim of this study was to test in vitro the ability of β-casein to bind the Aβ1–40, change the structure and inhibit the formation of amyloid fibrils in Aβ1–40. Results from the ThT binding assay indicated that incubation of Aβ1–40 with β-casein retarded amyloid fibril formation of Aβ1–40 in a concentration dependent manner such that at a ratio of 1:1 (w:w) led to a significant reduction in the amount of fluorescent intensity. The results from transmission electron microscopy (TEM) also showed that β-casein significantly reduced the number and size of the Aβ1–40 fibrils, suggesting that the chaperone bound to the Aβ1–40 fibrils and/or interacted with the fibrils in some way. ANS results also showed that β-casein significantly decreased the exposed hydrophobic surface in Aβ1–40. Following an ANS binding assay, CD spectroscopy results also showed that incubation of Aβ1–40 resulted in a structural transition to a β-sheet. In the presence of β-casein, however, α-helical conformation was observed which indicated stabilization of the protein. These results reveal the highly efficacious chaperone action of β-casein against amyloid fibril formation of Aβ1–40. These results suggest that in vitro, β-casein binds to the Aβ1–40 fibrils, alters the Aβ1–40 structure and prevents amyloid fibril formation. This approach may result in the identification of a chaperone mechanism for the treatment of neurological diseases. 相似文献
6.
Abdollahi M Bahreini-Moghadam A Emami B Fooladian F Zafari K 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2003,135(3):331-336
The effect of cadmium on induction of oxidative stress in rat submandibular saliva and protective role of increasing intracellular cAMP and cGMP by use of specific phosphodiesterase inhibitors, theophylline and sildenafil were investigated. Pure submandibular saliva was collected intraorally by micro polyethylene cannula from anaesthetized rats using pilocarpine as secretagogue. Acute administration of cadmium (10 mg/kg) caused significant oxidative stress by increasing lipid peroxidation by-products (thiobarbituric reactive substances, TBARS) and decreasing total thiols and total antioxidant power of the saliva. Concurrent therapy of rats by theophylline (25 mg/kg) and sildenafil (5 mg/kg) prevented cadmium-induced oxidative stress in saliva. Theophylline and sildenafil inhibited cadmium-induced increase in lipid peroxidation and decrease in total thiols and antioxidant power. It is concluded that cadmium administration results in oxidative stress in rat submandibular saliva, which can be protected by concurrent administration of specific cyclic nucleotide phosphodiesterase inhibitors. 相似文献
7.
Arezou Ghahghaei S. Zahra Bathaie Ali Shahraki Farzad Rahmany Asgarabad 《International journal of peptide research and therapeutics》2011,17(2):101-111
β-Casein is one of the major components of the milk micelles of most mammals and has been shown to exhibit in vitro chaperone-like
activity. Glycerol is a chemical chaperone belonging to the polyol family, which increases protein stability and inhibits
protein aggregation. These prompted us to compare the chaperone-like activity of β-casein and glycerol. In this study, the
effect of β-casein and glycerol on folding of the target proteins (ovotransferrin, insulin and α-lactalbumin) in the presence
of dextran, as a macromolecular crowding agent, is examined using visible absorption spectroscopy, intrinsic fluorescence
spectroscopy, 1-anilino-8-naphthalene sulfonic acid fluorescence binding and near CD spectroscopy. In the presence of dextran,
the rate and extent of aggregation of target proteins was enhanced and β-casein was less effective in preventing the aggregation
and precipitation of target proteins. These data support the hypothesis that β-casein interacts more effectively with slowly
aggregating rather than rapidly aggregating target proteins. It is proposed that dextran-induced changes to protein conformation
and the rate of intermolecular association are in a kinetic competition with the chaperoning action of β-casein; however our
results demonstrated the higher activity of glycerol, as a chemical chaperone, than β-casein on the folding of target proteins,
especially in the presence of dextran. This is likely due to the stabilizing effect of glycerol on protein structure and environment.
The implications for the in vivo functions of β-casein and glycerol, based on their exhibiting such in vitro chaperone-like
activities, are discussed. 相似文献
8.
9.
Zhu B Guleria I Khosroshahi A Chitnis T Imitola J Azuma M Yagita H Sayegh MH Khoury SJ 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(6):3480-3489
Programmed death-1 (PD-1) is a negative costimulatory molecule, and blocking the interaction of PD-1 with its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), enhances autoimmune disease in several animal models. We have studied the role of PD-1 ligands in disease susceptibility and chronic progression in experimental autoimmune encephalomyelitis (EAE). In BALB/c mice immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55, PD-L1 but not PD-L2 blockade significantly increased EAE incidence. In B10.S mice immunized with myelin proteolipid protein (PLP) peptide 139-151, both PD-L1 and PD-L2 blockade markedly enhanced EAE severity. In prediabetic NOD mice immunized with PLP48-70, PD-L2 blockade worsened EAE but did not induce diabetes, whereas PD-L1 blockade precipitated diabetes but did not worsen EAE, suggesting different regulatory roles of these two ligands in EAE and diabetes. B6 mice immunized with MOG35-55 developed chronic persistent EAE, and PD-L2 blockade in the chronic phase exacerbated EAE, whereas PD-L1 blockade did not. In contrast, SJL/J mice immunized with PLP139-151 developed chronic relapsing-remitting EAE, and only PD-L1 blockade during remission precipitated EAE relapse. The strain-specific effects of PD-1 ligand blockade did not correlate with the expression of PD-L1 and PD-L2 on dendritic cells and macrophages in lymphoid tissue, or on inflammatory cells in the CNS. However, EAE enhancement is correlated with less prominent Th2 cytokine induction after specific PD-1 ligand blockade. In conclusion, PD-L1 and PD-L2 differentially regulate the susceptibility and chronic progression of EAE in a strain-specific manner. 相似文献
10.
Anna Andersson Omid Rasool Margit Schmidt Rimantas Kodzius Sabine Flückiger Arezou Zargari Reto Crameri Annika Scheynius 《European journal of biochemistry》2004,271(10):1885-1894
Malassezia sympodialis is an opportunistic yeast that colonizes human skin and may induce IgE and T cell reactivity in patients with atopic eczema/dermatitis syndrome (AEDS). Previously, we have cloned and expressed six recombinant allergens (rMala s 1 and rMala s 5 to rMala s 9) from this yeast. By combining high throughput screening and phage surface display techniques, 27 complete and partial IgE-binding clones of M. sympodialis have been identified. Here we enlarged the panel of recombinant M. sympodialis allergens by RACE-PCR, cloning and nucleotide sequencing to obtain the coding sequences of two new IgE-binding clones. The coding sequences of one of the clones showed similarity to the heat shock protein (HSP) family and the other to manganese superoxide dismutase (MnSOD), and both had a high degree of homology to human counterparts. The coding sequences were expressed in Escherichia coli as six-histidine tagged recombinant proteins and generated products with molecular masses of 86.1 kDa for HSP and 22.4 kDa for MnSOD. Their IgE-binding frequencies were shown to be 69% and 75%, respectively, to 28 sera from AEDS patients with serum IgE to M. sympodialis extract, indicating that HSP and MnSOD are major M. sympodialis allergens. In inhibition immunoblotting, M. sympodialis extract could inhibit the binding of serum IgE from AEDS patients to rHSP and rMnSOD in a concentration-dependent manner. The high frequency of sera from AEDS patients, showing IgE binding to both HSP and MnSOD, indicates that these allergens, designated Mala s 10 and Mala s 11, could play a role in AEDS. 相似文献