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Introduction: The inhibition of vascularization into tumor stroma as well as dynamic cell growth is the center of attention. Here, we aimed to examine the role of vandetanib on angiogenesis capacity of breast cancer stem cell (CSCs). Methods: MDA-MB-231 cells were exposed to different doses of vandetanib and survival rate was monitored. Stimulatory effects of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF) were evaluated in vandetanibtreated MDA-MB-231 cells. In vitro tubulogenesis capacity was studied on the Matrigel surface. The synergistic effects of vandetanib on cell survival were also assessed after PI3K and/or Wnt3a inhibition. Vascular endothelial (VE)-cadherin, matrix metalloproteinase-2 (MMP-2), -9, Wnt3a, and p-Akt/Akt ratio were measured using western blotting. Results: Vandetanib reduced survival rate in a dose-dependent manner (P < 0.05). Proliferative effects associated with VEGF, FGF, and EGF were blunted in these cells pre-exposed to vandetanib (P < 0.05). The microcirculation pattern's triple-negative breast cancer (TNBC) was suppressed by 1, 5 µM of vandetanib (P < 0.05). Hence 1, 5 µM of vandetanib potentially decreased the population of CD24-cells. 1 and 5 µM of vandetanib inhibited cell proliferation by blocking PI3K and Wnt3a pathways and decreased the p-Akt/Akt ratio, Wnta3 protein levels (P < 0.05). 1 and 5 µM vandetanib combined with PI3K inhibitor diminished metastatic markers including, MMP-2, and MMP-9. The concurrent treatment (PI3K, inhibitor+ 1, 5 µM vandetanib) also considerably reduced epithelial-mesenchymal transition (EMT) markers such as VE-cadherin (P < 0.05). Conclusion: Vandetanib suppressed vasculogenic mimicry (VM) networking through blunting stemness properties, coincided with suppression of VE-cadherin in CSCs. [ABSTRACT FROM AUTHOR]

Introduction: Beta-Boswellic acid (BBA) is a pentacyclic terpene which has been obtained from frankincense and its beneficial effects on neurodegenerative disorders such as Alzheimer's disease (AD) have been addressed. Methods: In the present study, thermodynamic and kinetic aspects of BBA interaction with Tau protein as one of the important proteins involved in AD in the absence and presence of glucose has been investigated using surface plasmon resonance (SPR) method. Tau protein was immobilized onto the carboxy methyl dextran chip and its binding interactions with BBA were studied at physiological pH at various temperatures. Glucose interference with these interactions was also investigated. Results: Results showed that BBA forms a stable complex with Tau (KD=8.45×10-7 M) at 298 K. Molecular modeling analysis showed a hydrophobic interaction between BBA and HVPGGG segment of R2 and R4 repeated domains of Tau. Conclusion: The binding affinity increased by temperature enhancement, while it decreased significantly in the presence of glucose. Both association and dissociation of the BBA-Tau complex were accompanied with an entropic activation barrier; however, positive enthalpy and entropy changes revealed that hydrophobic bonding is the main force involved in the interaction. [ABSTRACT FROM AUTHOR]

Introduction: The detection of micrometer-sized particles like cells is limited by surface plasmon resonance (SPR) biosensors because of having a depth of evanescent wave <500 nm. In this study, for the first time, we exhibited the use of streptavidin-functionalized gold nanorods (GNRs) as intensification labels for detection of cell surface markers in SPR-based biosensors. Methods: The GNRs (ʎ max: 735 nm) were modified with streptavidin using EDC/NHS coupling method and human umbilical vein endothelial cells (HUVECs) were selected as the cell model for detecting VE-cadherin on cell surface using real-time SPR device in the 785 nm wavelength of the laser source. Results: The investigations revealed that the plasmonic field extension produced from the gold layer and GNRs resulted in multiple enhancement of SPR signals when the wavelength of laser source in SPR instrument was matched with the wavelength of maximum absorbance in GNRs. Moreover, the results showed that the growth of ΔRU value in specific and non-specific bindings for various cell number injections were produced with increasing the cell number. Conclusion: The results displayed that cell detection can be performed in real-time form without any need to a time-consuming process used in conventional methods like immunocytochemistry, flow cytometry, and western blotting. [ABSTRACT FROM AUTHOR]

Introduction : Dopamine is one of the key neurotransmitters (NTs) in nature, which plays a crucial role in the mammalian central nervous system (CNS). Its selective determination in the biological fluids is an essential need in the field of biomedicine studies. Methods : In this work, an amperometric sensor was developed using Nafion-coated cadmium pentacyanonitrosylferrate (CdPCNF) modified glassy carbon (GC) electrode (Nafion|CdPCNF|GC electrode) as an electrocatalyst to detect dopamine (DA) in human serum samples. To develop this sensor, the surface of bare GC electrode was coated with the film of CdPCNF through an electropolymerization method and then the modified electrode was coated with Nafion to minimize interferences, especially those arising from the presence of anionic compounds. The electrocatalytic behavior of the modified electrodes was studied using the cyclic voltammetry and amperometry, and then the ability of the sensor for the determination of DA in synthetic and biological samples was investigated. Results : The modified electrode was showed a significant electrocatalytic activity for the oxidation of DA at pH 7.4. The limit of detection (LOD) was 0.7 µM and also no interference effects arose from ascorbic acid (AA), uric acid (UA) or the other biological NTs was observed in the DA detection using the modified Nafion|CdPCNF|GC electrode. Conclusion : In comparison with the bare electrode, the Nafion|CdPCNF|GC electrode could determine DA in the biological samples with adequate sensitivity and selectivity. Therefore, we propose that the modified electrode is utilizable as an amperometric DA sensor for the biological sample analysis. [ABSTRACT FROM AUTHOR]

Introduction: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Because of limited efficacy and adverse side effects, identifying novel therapeutic and protective agents is important. The aim of this study is to examine the correlations between expanded disability status scale (EDSS) and cytokines after intervention with co-supplemented hemp seed and evening primrose oils and hot-natured diet in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: We studied a group of 23 patients with clinically definite RRMS, with EDSS<6 who received co-supplemented hemp seed and evening primrose oils with advising hot-natured diet. Clinically EDSS and immunological factors (plasma cytokines of IL-4, IFN-? and IL-17) were assessed at baseline and after 6 months. Results: Mean follow-up was 180±2.9 days (N=23, 7 Male and 16 Females aged 25.0±7.5 years with disease duration 6.26±3.9 years). After 6 months, significant improvements in extended disability status score were found in the patients in agreement with decrease cytokines of IFN-? and IL-17 and increase cytokines of IL-4. Clinical and immunological parameters showed improvement in the patients after the intervention. Conclusion: Our study shows that co-supplemented hemp seed and evening primrose oils with hot-natured diet can have beneficial effects in improving clinical symptoms in relapsing remitting MS patients and significant correlation was found between EDSS and immunological findings. [ABSTRACT FROM AUTHOR]

Introduction: Polyamidoamine (PAMAM) dendrimers are a unique family of dendritic polymers with numerous pharmaceutical and biomedical applications. One major problem with these polymers is their cytotoxicity. The purpose of this study was to synthesize novel dendrimers with aldehyde terminal groups and compare their cytotoxicity with that of dendrimers containing amine-terminated groups. Methods: G1(first generation) and G2 (second generation) dendrimers with amine-terminated groups were synthesized by divergent method and then the amine-terminated groups were converted to the aldehyde groups using surface modification of the functional group inversion (FGI) method. The cytotoxicity of the novel G1 and G2 polyamidoaldehyde (PAMAL) dendrimers together with that of G1 and G2 PAMAM-NH2 dendrimers was investigated by MTT assay using MCF-7 cell line. Results: The results showed that cytotoxicity of dendrimers with aldehyde-terminated groups is much lower than that of G1 and G2 PAMAM-NH2 dendri-mers. Conclusion: Dendrimers with aldehyde-terminated groups could be used as novel and convenient carriers for drug delivery with low cytotoxic effect compared with the amine-terminated dendrimers. The results revealed that the same generations of the dendri-mers with aldehyde-terminated groups are far less toxic than the corresponding amine-terminated dendrimers. [ABSTRACT FROM AUTHOR]

Introduction: Hypouricemic, antioxidant and xanthine oxidase inhibitory effects of orange juice and hesperetin have been already indicated. The objective of this study was to investigate the effects of orange juice and hesperetin on paraoxonase and arylesterase activity and lipid profile of hyperuricemic rats. Methods: Forty eight male Wistar rats were divided into 8 equal groups of healthy control, healthy+orange juice, healthy+hesperetin, healthy+allopurinol, hyperuricemic control, hyperuricemic+orange juice, hyperuricemic+ hesperetin and hyperuricemic+allopurinol. Hyperuricemia was induced using potassium oxonate (250 mg/kg ip). The treatments were carried out by daily gavage of 5 ml/kg orange juice, 5 mg/kg hesperetin and 5 mg/kg allopurinol for 2 weeks. Paraoxonase activity in serum was measured spectrophotometrically using paraoxon and phenylacetate as substrates. Serum lipids levels were determined using enzymatic colorimetric methods. Results: Hyperuricemia-induced reduction of paraoxonase and arylesterase activity was restored after treatment with orange juice and hesperetin (p<0.05). The effect of both treatments on lipid profile was marginal and only orange juice could significantly increase the levels of HDL-C. Conclusion: Supplementation of orange juice and hesperetin could restore paraoxonase and arylesterase activity in hyperuricemic rats. Orange juice could also partially improve the lipid profile. These effects could have major implications with respect to the prevention of cardiovascular disease in hyperuricemic patients. However, more studies are needed in future investigations. [ABSTRACT FROM AUTHOR]