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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]

Background: The present study aimed at assessing the validity of self-reported drug use in people aged 35 and older in a pilot phase of a population-based cohort study. Methods: A total of 1038 adults over 35 years old in Khamene city in East Azarbaijan province were recruited for the pilot phase of Azar cohort; a province-level of a nationwide PERSIAN cohort study completing a questionnaire and providing biological samples from October to December 2014. Information about the history and duration of smoking tobacco, using drug and medication were obtained by the physician. The validity of the drug use was assessed through comparing the questionnaire response with three urine strip tests for the detection of morphine, amphetamine and methamphetamine among 259 randomly selected subjects. Results: The prevalence of drug use according to self-report was 2.6% (95% CI: 1.7%-3.8%). One-step drug test as the gold standard for the use of drug self-reported demonstrated a sensitivity (95% CI) and specificity 15% (10-22) and 99.7% (98.9%-99.9%) respectively. All participants with positive self-report were male; however, in the urine analysis drug test, it was positive for 7 out of 68 randomly selected women. Conclusion: The validity of self-reported drug use in this population was low; therefore, the selfreported use of the drug should be used with caution in this population. It is recommended to use alternative techniques to improve the validity of data using the self-report procedure. [ABSTRACT FROM AUTHOR]

Introduction: The interactions between biomacromolecules such as serum albumin (SA) and various drugs have attracted increasing research attention in recent years. However, the study of SA with those drugs that have relatively high hydrophilicity and a lower affinity for SA could be a challenging issue. At the present study, the interaction of bovine SA (BSA) with neomycin as a hydrophilic drug has been investigated using surface plasmon resonance (SPR) and molecular docking methods. Methods: BSA was immobilized on the carboxymethyl dextran hydrogel sensor chip after activation of carboxylic groups through NHS/EDC and, then, the neomycin interaction with BSA at different concentrations (1-128 µM) was investigated. Results: Dose-response sensorgrams of BSA upon increasing concentration of neomycin has been shown through SPR analysis. The small KD value (4.96 e-7 at 40°C) demonstrated high affinity of neomycin to BSA. Thermodynamic parameters were calculated through van't Hoff equation at 4 different temperatures. The results showed that neomycin interacts with BSA via Van der Waals interactions and hydrogen bonds and increase of KD with temperature rising indicated that the binding process was entropy driven. Molecular docking study confirmed that hydrogen bond was the major intermolecular force stabilizing neomycin-BSA complex. Conclusion: The attained results showed that neomycin molecules can efficiently distribute within the body after interaction with BSA in spite of having hydrophilic properties. Besides, SPR can be considered as a useful instrument for study of the interaction of hydrophilic drugs with SA. [ABSTRACT FROM AUTHOR]

Purpose: Median septum of Juglans regia L. (Juglandaceae) with anti-diabetic effects has been used in Iranian traditional medicine. The present study estimates both oral acute and subchronic toxicities. Methods: In the oral acute toxicity study, female Wistar rats were treated with doses of 10, 100, 1000, 1600, 2900 and 5000 mg/ kg of the Juglans regia septum of methanol extract (JRSME), and were monitored for 14 days. In subchronic study, JRSME was administered by gavage at dose of 1000 mg/kg daily in Wistar rats for 28 days. Antioxidant status and biochemical examinations were fulfilled, and the vital organs were subjected to pathological analyses. Results: The extract did not produce any toxic signs or deaths; the medium lethal dose must be higher than 5000 mg/kg. In subchronic study, No significant morphological and histopathological changes were observed in the studied tissues. There was a significant increase in serum malondialdehyde (MDA) level in treated group compared to control after 4 weeks of JRSME intake. The treatment of rats resulted in a significant reduction of serum urea level (p<0.05), kidney's xanthine dehydrogenase (XDH) activity (p<0.001) and elevation of aldehyde oxidase (AO) activity (p<0.05) in kidney. In the treated group, the mean diameter of glomerulus and proximal urine tube epithelium stature was slightly greater than control group. A significant increase in serum MDA level is subject for further studies. Conclusion: This study showed that the extract has no acute or subacute adverse effects with dose of 1000 mg/kg. The administration of JRSME may improve kidney structure and function and help in treatment of some chronic diseases. [ABSTRACT FROM AUTHOR]

Introduction: Growing demands for ultrasensitive biosensing have led to the development of numerous signal amplification strategies. In this report, a novel electrochemiluminescence (ECL) method was developed for the detection and determination of caspase-3 activity based on reduced graphene oxide sheets decorated by gold nanoparticles as signal amplification element and horseradish peroxidase enzyme (HRP) as ECL intensity enhancing agent. Methods: The ECL intensity of the luminol was improved by using the streptavidin coated magnetic beads and HRP in the presence of hydrogen peroxide. The cleavage behavior of caspase-3 was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques using biotinylated peptide (DEVD containing peptide) which was coated on reduced graphene oxide decorated with gold nanoparticle. The surface modification of graphene oxide was successfully confirmed by FTIR, UV-vis and x-ray spectroscopy. Results: ECL based biosensor showed that the linear dynamic range (LDR) and the lower limit of quantification (LLOQ) were 0.5-100 and 0.5 femtomolar (fM), respectively. Finally, the performance of the engineered peptide based biosensor was validated in the A549 cell line as real samples. Conclusion: The prepared peptide based biosensor could be considered as an excellent candidate for early detection of apoptosis, cell turnover, and cancer related diseases. [ABSTRACT FROM AUTHOR]

Introduction: Quality assessment of conferences and congresses and their performance seems inevitable due to the status and problems of holding them. Therefore, the aim of this study was the situational analysisof conferences and congresses held in Tabriz University of Medical Sciences during the years 2005-2010. Methods: In this descriptive study, five checklists were designed through literature review and panel meetings of experts to assess the quality and performance of conferences and congresses held in the University during the years 2005-2010. There were a total of 40 questions in the checklists extracted from the interviews of the responsible bodies. The data were analyzed using SPSS 19. Results: There were no statutory duties assigned to any of the committees. No indicator was used for selecting committee members. None of the conferences had been recalled at least a year prior. The university priorities had no role in organizing the conferences. Evaluation results were not available, and the conferences had very poor performance. Conclusion: Regarding the results of this study and the importance and costs of the scientific meetings, it is necessary to revise planning, poll-making and regular evaluation of these meetings to overcome weaknesses and improve the quality of the conferences and congress in the Tabriz University of Medical Sciences. [ABSTRACT FROM AUTHOR]

Backgrounds and Objectives: Recently, the activity of paraoxonase-3 enzyme has been reported in follicular fluid, where the concentration of this enzyme in follicular fluid is three times higher than serum. However, the rule of this enzyme in the ovarian function is yet unknown. In the present study , the activity of this enzyme and the ratio of antioxidant/peroxidation activity within the follicular fluid of infertile and fertile who underwent reproductive cycles stimulatory will be evaluated and compared and their variation are correspond with to the oocyte number. Materials and Methods: The follicular fluid obtained from 50 infertile couples who underwent assisted reproductive techniques, follicular fluid paraoxonase-3 enzyme activity was determined by High Performance Liquid Chromatography, high-density lipoprotein was measured by sedimentary, total antioxidant capacity was by ELISA method and levels of malondialdehyde by tiobarbituric acid assay. Results: From 50 women that present in this study, 20 women were infertile and 30 subjects were fertile. The paraoxnase-3 activity rate in follicular fluid of infertile women were significantly lower in compared with fertile women (p<0.05). The average ratio of paraoxonase-3/ malondialdehyde in follicular fluid of infertile women were obtained lower than fertiles. Malondialdehyde concentration in follicular fluid of infertile women were significantly high (p<0.05). The level of high-density lipoprotein and total antioxidant capacity in follicular fluid were not significantly. Conclusion: The result of present study showed that paraoxonase-3 activity and paraoxonase-3/ malondialdehyde rato in follicular fluid of infertile women are lower and while malondialdehyde levels conversly was higher. [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]

Purpose: To achieve simultaneous imaging and therapy potentials, targeted fluoromagnetic nanoparticles were synthesized and examined in human breast cancer MCF-7 cells. Methods: Fe3O4 nanoparticles (NPs) were synthesized through thermal decomposition of Fe(acac)3. Then, magnetic nanoparticles (MNPs) modified by dopamine-poly ethylene glycol (PEG)-NH2; finally, half equivalent fluorescein isothiocyanate (FITC) and half equivalent folic acid were conjugated to one equivalent of it. The presence of Fe3O4-DPA-PEG-FA/FITC in the folate receptor (FR) positive MCF-7 cells was determined via fluorescent microscopy to monitor the cellular interaction of MNPs. Results: FT-IR spectra of final compound confirmed existence of fluorescein on folic acid grafted MNPs. The Fe3O4-DPA-PEG-FA/FITC NPs, which displayed a size rang about 30-35 nm using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), were able to actively recognize the FR-positive MCF-7 cells, but not the FR-negative A549 cells. Conclusion: The uniform nano-sized Fe3O4-DPA-PEG-FA/FITC NPs displayed great potential as theranostics and can be used for targeted imaging of various tumors that overexpress FR. [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]

Purpose: To achieve simultaneous imaging and therapy potentials, targeted fluoromagnetic nanoparticles were synthesized and examined in human breast cancer MCF-7 cells., Methods: Fe3O4 nanoparticles (NPs) were synthesized through thermal decomposition of Fe(acac)3. Then, magnetic nanoparticles (MNPs) modified by dopamine-poly ethylene glycol (PEG)-NH2; finally, half equivalent fluorescein isothiocyanate (FITC) and half equivalent folic acid were conjugated to one equivalent of it. The presence of Fe3O4-DPA-PEG-FA/FITC in the folate receptor (FR) positive MCF-7 cells was determined via fluorescent microscopy to monitor the cellular interaction of MNPs., Results: FT-IR spectra of final compound confirmed existence of fluorescein on folic acid grafted MNPs. The Fe3O4-DPA-PEG-FA/FITC NPs, which displayed a size rang about 30-35 nm using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), were able to actively recognize the FR-positive MCF-7 cells, but not the FR-negative A549 cells., Conclusion: The uniform nano-sized Fe3O4-DPA-PEG-FA/FITC NPs displayed great potential as theranostics and can be used for targeted imaging of various tumors that overexpress FR.

Introduction: We have already shown the protective effects of soy protein on rheumatoid arthritis in rats. In this study, the effects of genistein and daidzein, two isoflavones from soy on rheumatoid arthritis prognosis and prevention in rats have been investigated., Methods: Rheumatoid arthritis was induced in female Sprague-Dawley rats using collagen type II plus adjuvant. Rats were then treated with soy protein (7 g/kg), dexamethasone (1 mg/kg), genistein (20 mg/kg genistein), daidzein (20 mg/kg genistein) and casein (in control groups) by daily gavage feedings for 50 days. Scores of arthritis were recorded every day for each paw of animal. Serum concentrations of TNF-α, IL-6, adiponectin and leptin were characterized. Tibiotarsal tissue was used for histopathologic analyses., Results: Treatment with genistein and daidzein resulted in not only a reduction in disease symptoms but also a delay in the onset of symptoms. Results from delayed-type hypersensitivity test demonstrated that the ear thickness in treated rats was significantly lower than that in the control group (p<0.05). There was a reduction in TNF-α, IL-6, adiponectin and leptin serum concentrations after treatment with genistein and daidzein. Dexamethasone reduced the serum concentrations of TNF-α, IL-6 and adiponectin but increased leptin serum level. Prevention of the tissue damage and joint inflammation was also observed following treatment with two soy isoflavones., Conclusion: soy isoflavones, daidzein and especially genistein, could significantly improve rheumatoid arthritis symptoms in rats. The structural similarity of isoflavones to estrogen could be the possible underlying mechanism involved in the function.

Introduction: The aim of the present study was to assess the effects of vitamin E and selenium supplementation on serum paraoxonase (PON1) activity, lipid peroxidation and antioxidant defense in streptozotocin-induced diabetic rats., Methods: Thirty two female Sprague Dawley rats were divided into 3 groups: the control group (n=8) received a standard diet; streptozotocin (STZ)-induced diabetic rats (n=12), received corn oil and physiological solution; and vitamin E and selenium supplemented diabetic rats (n=12) were treated with oral administration of vitamin E (300 mg/kg) and sodium selenite (0.5 mg/kg) once a day for 4 weeks., Results: Significantly lower total antioxidant status (TAS), PON1and erythrocyte SOD activities and a higher fasting plasma glucose level were observed in the diabetic rats compared to the control. A significant increase in SOD and GPX activities in vitamin E and selenium supplemented diabetic group was observed after 5 weeks of the experiment. Compared to the normal rats, malondialdehyde (MDA) and oxidized LDL (Ox-LDL) levels were higher in the diabetic animals; however, these values reduced significantly following vitamin E and selenium supplementation., Conclusion: Vitamin E and selenium supplementation in diabetic rats has hypolipidemic, hypoglycemic and antioxidative effects and may slow down the progression of diabetic complications through its protective effect on PON1 activity and lipoproteins oxidation.

Integration of in vitro and in vivo investigations has brought the body of new emerging life sciences about. This inspirational domain needs a scientific platform to cover the relevant publications. BioImpacts (BI), as a peer-reviewed multidisciplinary international open access journal, intends to deal with all aspects of biological and biomedical researches at dimensions of molecular, cellular, functional and translational dimensions.