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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]

Vasculogenic mimicry (VM) is regarded as a process where very aggressive cancer cells generate vascular‐like patterns without the presence of endothelial cells. It is considered as the main mark of malignant cancer and has pivotal role in cancer metastasis and progression in various types of cancers. On the other hand, resistance to the antiangiogenesis therapies leads to the cancer recurrence. Therefore, development of novel chemotherapies and their combinations is urgently needed for abolition of VM structures and also for better tumor therapy. Hence, identifying compounds that target VM structures might be superior therapeutic factors for cancers treatment and controlling the recurrence and metastasis. In recent times, naturally occurring compounds, especially phytochemicals have obtained great attention due to their safe properties. Phytochemicals are also capable of targeting VM structure and also their main signaling pathways. Consequently, in this review article, we illustrated key signaling pathways in VM, and the phytochemicals that affect these structures including curcumin, genistein, lycorine, luteolin, columbamine, triptolide, Paris polyphylla, dehydroeffusol, jatrorrhizine hydrochloride, grape seed proanthocyanidins, resveratrol, isoxanthohumol, dehydrocurvularine, galiellalactone, oxacyclododecindione, brucine, honokiol, ginsenoside Rg3, and norcantharidin. The recognition of these phytochemicals and their safety profile may lead to new therapeutic agents' development for VM elimination in different types of tumors. [ABSTRACT FROM AUTHOR]

A novel electrochemical immunosensor was developed for ultrasensitive determination of the hormone insulin-like growth factor 1 (IGF-1) based on immobilization of a specific monoclonal antibody on the electrospun nanofibers of Polyacrylonitrile (PAN)/Zein-reduced graphene oxide (rGO) nanoparticle. The nanofibers deposited on glassy carbon electrode (GCE) showed good electrochemical behaviors with synergistic effects between PAN, Zein, and rGO. PAN/Zein nanofibers were used due to flexibility, high porosity, good mechanical strength, high specific surface area, and flexible structures, while rGO nanoparticles were used to improve the detection sensitivity and anti-IGF-1 immobilizing. Different characterization techniques were applied consisting of FE-SEM, FT-IR, and EDS for the investigation of morphological features and nanofiber size. The redox reactions of [Fe(CN) 6 ]4−/3− on the modified electrode surface were probed for studying the immobilization and determination processes, using differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Under optimal conditions, LOD (limit of detection) and LOQ (limit of quantification) were obtained as 55.72 fg/mL and 185.73 fg/mL respectively, and sensitivity was acquired 136.29 μA/cm2.dec. Moreover, a wide linear range was obtained ranging from 1 pg/mL to 10 ng/mL for IGF-1. Furthermore, the proposed method was applied for the analysis of IGF-1 in several human plasma samples with acceptable results, and it also exhibited high selectivity, stability, and reproducibility. [Display omitted] • An electrochemical immunosensor was developed for determination of the hormone IGF-1. • The immunosensor is based on Polyacrylonitrile/Zein-rGO electrospun nanofibers. • LOD (limit of detection) was obtained 55.72 fg/mL. • A wide linear range was obtained ranging from 1 pg/mL to 10 ng/mL for IGF-1. [ABSTRACT FROM AUTHOR]

Abstract Surface plasmon resonance (SPR), as an optical technique, has widely been used for the detection of biomarkers. Various investigations have been conducted to address the impacts of SPR on the kinetics of biological interactions between the ligand and its cognate bio-element. Up until now, different biofunctionalized metal nanoparticles (NPs) have been used for the ultrasensitive detection of biomarkers in the enhanced SPR. The enhancement of plasmonic properties and refractive index by means of metal NPs in SPR-based biosensors have significantly improved the diagnosis and monitoring of molecular markers in different disesaes including malignancies. In all the enhanced SPR systems utilized for the direct/sandwich assay, each NP is covalently modified with the analyte molecules like antibody (Ab) or a nucleic acid such as DNA/RNA aptamer (Ap) capable of interaction with the related biomarker(s). The increasing of density near the gold surface and plasmonic coupling of gold film and NPs can provide a large shift in the refractive index enhancing the plasmonic resonance because the SPR response unit is sensitive to alteration of the refractive index and the mass shifting onto the chip surface. In this study, we review the potential applications of two major NPs for enhancing the SPR signals for the detection of molecular biomarkers, including gold and magnetic NPs. Graphical abstract fx1 Highlights • Ultra-sensitive detections using metal nanoparticles in SPR-based biosensors was described. • The potential applications of gold NPs and magnetic NPs for intensifying the SPR signals are reviewed. • The impacts of metal nanoparticles-based enhanced SPR biosensors in the monitoring of biomarkers were discussed. [ABSTRACT FROM AUTHOR]

A great body of evidence unveiled the existence of different stem cell types in various tissues with efficient capability for self-renewal and differentiation. Characterization and enumeration of a specific stem cell population seem difficult because these cells consist of a small percentage of cells within different milieu. As such, due to lack of accuracy provided by convenient methods, biosensing techniques are at the center of attention to improve stem cells characterization with high rate of sensitivity and specificity. In line with this statement, bio-sensing, as a sensitive analytical method, opens novel avenues in biological aspects. Physicochemical signals produced by the interaction of analyte-ligands could be applicable for a wide range of scientific fields such as chemical, biochemical, pharmaceutical and immunological purposes. Noninvasive and label free monitoring methods without need to stain, fix, lyse, or fluorescent-tags are desirable in basic stem cell technology and therapeutic applications of cells. We, here, highlighted basic concepts and terms associated with label free biosensor technology for measuring cell entity, evaluating cell surface marker, and peculiarly in the field of stem cell biology. Furthermore, different aspects and methodologies concerning with bio-sensing techniques, including photonic-based detection systems like Surface Plasmon Resonance (SPR) assays, Impedance-based method , Quartz Crystal Microbalance (QCM) and paper based detection of lateral flow biosensor (LFB) were discussed. [ABSTRACT FROM AUTHOR]

An electrochemical immunosensing platform was developed for the detection of receptor tyrosine kinase-orphan receptor-2 (ROR2) at a glassy carbon electrode (GCE) modified with the electrospun nanofiber containing polyvinylpyrrolidone (PVP), soy, and Au nanoparticles (AuNPs). The PVP/soy/AuNP nanofiber exhibited good electrochemical behavior due to synergistic effects between PVP, soy, and AuNPs. The PVP/soy in the modified film provided good mechanical strength, high porosity, flexible structures, and high specific surface area. On the other hand, the presence of AuNPs effectively improved conductivity, as well as the immobilization of anti-ROR2 on the modified GCE, leading to enhanced sensitivity. Various characterization approaches such as FE-SEM, FTIR, and EDS were used for investigating the morphological and structural features, and the elemental composition. The designed immunosensor performance was investigated using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and differential pulse voltammetry (DPV). Under optimum conditions with a working potential range from −0.2 to 0.6 V (vs. SCE), sensitivity, linear range (LR), limit of detection (LOD), and correlation coefficient (R2) were acquired at 122.26 μA/cm2 dec, 0.01–1000 pg/mL, 3.39 fg/mL, and 0.9974, respectively. Furthermore, the determination of ROR2 in human plasma samples using the designed immunosensing platform was examined and exhibited satisfactory results including good selectivity against other proteins, reproducibility, and cyclic stability. [ABSTRACT FROM AUTHOR]

Background: Paraoxonase-3 (PON3), as a high density lipoprotein (HDL)-associated lactonase, is capable of preventing the oxidative modification of low density lipoprotein (LDL). PON3 activity in follicular fluid (FF) is three times more than its activity in serum. However, the detailed role of PON3 in women's fertility remains unknown. The aim of this study was to investigate the correlation between PON3 activity in the FF of women undergoing assisted reproductive technique (ART), in vitro fertilization (IVF), or intra-cytoplasmic sperm injection (ICSI). Materials and Methods: This cross-sectional study consisted of 50 women from couples with male factor infertility (MFI) or with female factor infertility (FFI). The FF samples were obtained during the ART intervention. PON3 activity, HDL cholesterol (HDL C), total antioxidant status (TAS) and the level of malondialdehyde (MDA) were determined. The morphology of the embryo was determined using embryo cell number (ECN) and embryo fragmentation score (EFS). In addition, fertilization rate (FR) was used an oocyte fertilization index. Results: Of 50 women, 20 women belonged to FFI group and the remaining 30 women belonged to MFI group. PON3 activity in FF of women in FFI group was significantly lower (p<0.05) in comparison with corresponding value in MFI group. The value of PON3 activity/MDA in the FFI group was lower than that in MFI group. Moreover, MDA level in the FF of FFI group was significantly higher (p<0.05) than its concentration in MFI group. Meanwhile, no significant difference was found in HDL-C concentration and TAS of both groups. No significant correlation was observed between the ECN and FF biochemical parameters. There was also a negative correlation between FR and MDA (r=-0.42, p=0.02), whereas a positive relation between FR with PON3 activity (r=0.59, p=0.004), HDL-C (r=0.35, p=0.04) and PON3/MDA (r=0.59, p=0.001). Conclusion: According to the results of this study, PON3 activity level as a key component of antioxidant system in FF may directly be associated with the success rate of ART and fertilization rate in women. [ABSTRACT FROM AUTHOR]

Silica inverse opal (IO) structures were fabricated by the self-assembly of silica precursors and mono-dispersed colloidal crystal template method. The morphological investigation of prepared IO films was done by SEM analyses and optical image was used for checking of all periodic microporous structure of IOs surface. For first time, in this study we introduced optical density of IO films for sensing different concentration of ethanol solutions and their optical images have been used for comparison of sensing properties. The intensity of the absorbance spectrum was decreased by increasing the ethanol concentration using silica IO structures as the sensing chip. There is a good linear relationship and very good correlation (R2 = 0.98) between the optical intensity of absorbance peak and the 2–100% ethanol concentration (v/v 0) in the silica IO sensors. The results show that by the area scan of optical density in IO materials, we are able to detect of ethanol concentration. According to which, the proposed optic based imaging method can find numerous applications in non-destructive of fluid detection in IO arrays. [Display omitted] • Silica inverse opal structures were fabricated by the self-assembly method. • Optical images were used for the checking of uniformity in developed IO arrays. • There was a perfect linear relationship between the optical intensity and the ethanol concentrations. • The proposed optic based imaging method can find numerous applications for non-destructive of fluid detection in IO arrays. [ABSTRACT FROM AUTHOR]

To evaluate preventive and therapeutic effects of soy protein on collagen-induced arthritis rats. Sprague-Dawley rats immunized with bovine type II collagen emulsified in adjuvant and treated with soy protein (7 g/kg), dexamethasone (1 mg/kg), and casein (in control groups) by daily gavages feedings for 30 days. Score of arthritis recorded every day for each paws of animal. Tumor necrosis factor-alpha, interleukin6, leptin, and adiponectin were measured in serums. Treatment with soy protein resulted in significant delay in time to onset of arthritis as well as significantly decreased arthritis incidence, clinical arthritis severity score, histopathological arthritis severity score, and in vivo cell-mediated immunity to collagen ( P < 0.05). Administration of soy protein significantly suppressed the progression of collagen II-induced arthritis and inhibited the production of tumor necrosis factor-alpha, interleukin6, leptin, and adiponectin. Soy protein appeared to be a potent immunomodulatory inhibitor of collagen II-induced arthritis in rats. It could delay onset of RA and reduced cartilage erosion and synovitis inflammation. Therefore, it may be a useful protein in the prevention and treatment of rheumatoid arthritis patient. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the effect of recombinant erythropoietin on serum oxidants and the viability of ischemic ovaries after detorsion. Study design: A non-randomized single-blind clinical trial was conducted from December 2009 to January 2011 in a University Teaching Hospital affiliated with the School of Medicine, Tabriz University of Medical Sciences. Surgery was carried out on 40 patients, aged 18–35 years, with signs and symptoms of ovarian torsion. The patients were divided into two equal groups: group 1 received recombinant erythropoietin 150IU/kg subcutaneously during the operation and 72h after detorsion, and group 2 received no medication. Blood samples were taken before and 72h after detorsion to determine the plasma levels of malondialdehyde, xanthine oxidase, glutathione, superoxide dismutase, nitric oxide, and total antioxidants. In both groups, the arterial and venous blood supply of the ovary and arterial blood flow resistance were evaluated before surgery and 72h after detorsion of the ovary. The main outcome measures were improving ovarian blood flow and reducing oxidative damage. SPSS 17.0 was used for statistical analyses. Results: The levels of malondialdehyde, glutathione, superoxide dismutase, nitric oxide, and total antioxidants 72h after detorsion were significantly different between the interventional and non-interventional groups (p <0.001). There was no significant difference in the levels of xanthine oxidase (p =0.13). The difference between groups in the blood flow of the ovary 72h after surgery was not statistically significant (p =0.61). Conclusion: Recombinant erythropoietin was effective in reducing the oxidative damage of ovarian torsion. [Copyright &y& Elsevier]

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]

Abstract: Although the term ‘evidence-based medicine’ (EBM) is of recent origin, its roots are generally agreed to lie in earlier times. Several writers have suggested that the 11th century CE physician and philosopher Avicenna (Ibn Sina) formulated an approach to EBM that broadly resembles modern-day principles and practice. The aim of this paper is to explore the origins and influence of Avicenna''s version of EBM. A survey of the literature suggests that two influences on Avicenna''s thought were crucial: the doctrine of Ijma; and Stoic logic, perhaps transmitted via the writings of Galen. In turn, Avicenna is known to have been a major influence on both medical practice and the development of logic in medieval Europe. Through this route, Avicennian logic (notably its inductive aspect) inspired the new style of thought associated with the scientific revolution, which later came to be reflected in ‘scientific medicine’, and may therefore have been an indirect source of EBM today. [Copyright &y& Elsevier]

Total of 500 samples from triceps, gluteal and diaphragm muscles, kidney, and liver, were obtained randomly from beef carcasses of a slaughterhouse in Tabriz. We measured oxytetracycline, tetracycline, and chlortetracycline (TCs) residues by high performance liquid chromatography (HPLC) method. Seventy four percent of samples (380 samples) had detectable TCs residues. The mean amounts of oxytetracycline, tetracycline, and chlortetracycline residues in all samples were 52.2, 33.8, and 125.2 μg/kg, respectively. The mean amounts of total residues of TCs in all meat samples, triceps, gluteal and diaphragm muscles, kidney, and liver were 131.0, 163.1, 63.4, 66.7, 408.1, and 254.9 μg/kg, respectively. Five percent of kidney and liver samples and 21.7% of all samples contained residues more than the maximum residue limits (MRLs) of the World Health Organization (WHO). This study indicates presence of different levels of tetracycline residues in the various edible tissues. Regulatory authorities should ensure proper withdrawal period before slaughtering of the animals. [ABSTRACT FROM AUTHOR]

Polyethylene glycol (PEG) derivatives of ibuprofen were prepared by esterification of PEG monosuccinate with hydroxy ethyl ester (HEE), hydroxy ethylamide (HEA), and hydroxy ethyl thioester (HET) of ibuprofen. Hydrolysis of HEE-PEG, HEA-PEG, and HET-PEG were studied in vitro with or without esterases to investigate the applicability of these PEGylated prodrugs. The polymeric prodrugs released major fraction of the parent drug (ibuprofen) and a small fraction of hydroxy ethyl derivatives after 48 hr. In HET-PEG, the amount of drug release was higher than HEE-PEG and HEA-PEG. The difference between acidic and alkali buffered solutions was considerable. In human plasma, 50% of drug was released after 150 hr incubation at 37°C from HET-PEG. [ABSTRACT FROM AUTHOR]

Abstract: Partial least-squares (PLS) calibration and principal component regression (PCR) methods were utilized for the simultaneous spectrofluorimetric and spectrophotometric determination of pyridoxine (PY) and melatonin (MT). Since emission and adsorption spectra of these drugs overlap, PY and MT cannot be directly determined by fluorimetric nor by spectrophotometric methods. Full-spectrum multivariate calibration PLS and PCR methods were developed for both fluorimetry and spectrophotometry. The conditions were optimized for fluorimetric as well as for spectrophotometric determination of both drugs. The simultaneous determination of PY and MT was carried out in mixtures by recording the emission fluorescence spectrum between 324 and 500 nm (λ ex 285 nm) for fluorimetry, and by recording the absorption spectrum between 250 and 350 nm for spectrophotometry (λ max(PY) 310 nm, λ max(MT) 278 nm). The experimental calibration matrixes were designed orthogonally. At the optimum conditions, dynamic ranges were 0.04–1.3 and 0.1–4 μg ml–1 for fluorimetry and 1–22 and 1–24 μg ml–1 for spectrophotometry for MT and PY, respectively. The calibration concentrations were prepared in the dynamic ranges. The parameters of the chemometrics procedure for the simultaneous determination of MT and PY were optimized, and the proposed methods were validated with prediction set. Finally the procedures were successfully applied to simultaneous spectrofluorimetric and spectrophotometric determination of PY and MT in synthetic mixtures and in a pharmaceutical formulation. [Copyright &y& Elsevier]

This research presents a selective and sensitive electrochemical biosensor for the detection of the mesenchymal–epithelial transition factor (c-MET). The biosensing is based on a modification of the SPCE (screen-printed carbon electrode) with the electrospun nanofiber containing eudragit (EU), hydroxypropyl methylcellulose (HPMC), and Zeolite imidazolate frameworks (ZIF-8) nanoparticles. EU/HPMC/ZIF-8 nanofibers have presented a high capability of electron transfer, and more active surface area than bare SPCE due to synergistic effects between EU, HPMC, and ZIF-8. On the other hand, EU/HPMC nanofibers provided high porosity, flexible structures, high specific surface area, and good mechanical strength. The presence of ZIF-8 nanoparticles improved the immobilization of anti-c-MET on the modified SPCE and also resulted in increasing the conductivity. By c-MET incubation on the modified SPCE, c-MET was connected to anti-c-MET, and consequently the electrochemical signal of [Fe(CN) 6 ]3-/4- as the anion redox probe was reduced. In order to investigate the structural and morphological characteristics and elemental composition of electrospun nanofibers, various characterization methods including FE-SEM, XRD, FTIR, and EDS were used. Under optimum conditions with a working potential range −0.3−0.6 V (vs. Ag/AgCl), linear range (LR), correlation coefficient (R2), sensitivity, and limit of detection (LOD) were acquired at 100 fg/mL-100 ng/mL, 0.9985, 53.28 μA/cm2.dec, and 1.28 fg/mL, respectively. Moreover, the mentioned biosensor was investigated in a human plasma sample to determine c-MET and showed ideal results including reproducibility, stability, and good selectivity against other proteins. [ABSTRACT FROM AUTHOR]

Photonic crystal (PC)-based inverse opal (IO) arrays are one of the substrates for label-free sensing mechanism. IO-based materials with their advanced and ordered three-dimensional microporous structures have recently found attractive optical sensor and biological applications in the detection of biomolecules like proteins, DNA, viruses, etc. The unique optical and structural properties of IO materials can simplify the improvements in non-destructive optical study capabilities for point of care testing (POCT) used within a wide variety of biosensor research. In this review, which is an interdisciplinary investigation among nanotechnology, biology, chemistry and medical sciences, the recent fabrication methodologies and the main challenges regarding the application of (inverse opals) IOs in terms of their bio-sensing capability are summarized. Image 1 • The recent main challenges regarding the application of inverse opals (IOs) in the detection of biomolecules are reviewed. • Sensing mechanisms of biomolecules including glucose, proteins, DNA, viruses were summarized. • IO materials with their ordered 3D microporous structures have found attractive optical biosensor applications. [ABSTRACT FROM AUTHOR]

The fast and precise diagnosis of acute myocardial infarction (AMI) is of great importance for the survival of patients. Here, we provide key insights into the recent progress in amperometry/voltammetry biosensors for the detection of AMI biomarkers. Voltammetry-based biosensors have been developed to simultaneously detect multiplexed biomarkers, which can also serve as beneficial point-of-care diagnostic devices, and provide fast and cost-efficient tools for monitoring of biomarkers involved in AMI such as cardiac troponin (cTnI, cTnT) isoforms. Various voltammetry labeled and label-free techniques are articulated, and enzymatic and non-enzymatic systems are delineated with emphasis on the structural details and figures of merits of these methods. Much more robust and sensitive voltammetric biosensors are prognosticated to be developed by the integration of nanoscale advanced materials and progress in engineering through merging microfluidics in voltammetric techniques. Altogether, it is envisioned that the voltammetric biosensors be translated into clinical practice soon. Image 1 • The fast diagnosis of acute myocardial infarction (AMI) is a vital step. • Survival of patients before the heart attack depends on the accuracy of the AMI diagnostic test. • Detection of biomarkers such as cardiac troponin (cTn) I and T play a key role in the diagnosis of cardiovascular disease. • Electrochemical biosensors can provide fast and cost-effective analytical platforms for the detection of cTn biomarkers. [ABSTRACT FROM AUTHOR]

Metastasis is one of the main issues in cancer treatment and it has been documented that angiogenesis plays an important role in this process. Studies showed that vascular endothelial growth factor (VEGF) and its receptor (VEGFR) have elevated expression in tumors and are involved in tumor progression and metastasis; suggesting their potential for being a therapeutic target. In this regard, Apatinib or YN968D1, a specific inhibitor of VEGFR-2 has been suggested as a promising therapeutic agent for cancer that can prevent tumor angiogenesis and metastasis. Furthermore, this drug can sensitize resistant tumor cells to chemotherapy drugs and increase the effectiveness of conventional chemotherapy drugs. Recent studies have shown that Apatinib has beneficial implications as a post-second and third-line therapy agent in a variety of cancers. Furthermore, Apatinib has the capacity to promote the overall survival and progression-free survival of cancer patients. This review discussed about, the molecular mechanisms and clinical relevance underlying the therapeutic potential of Apatinib in cancer treatment. Unlabelled Image [ABSTRACT FROM AUTHOR]

Biopolymer films have drawn growing demand for their application in the point of care domain owing to their biocompatibility, eco-friendly, and eligibility for in vivo analyses. However, their poor conductivity restricts their sensitivity in diagnostics. For high-quality electrochemical biosensor monitoring, two vital factors to be greatly paid attention are the effective merge of amplification modifiers with transducing surface and the superior linking across the recognition interface. Here, we introduce an enzyme-free electrochemical biosensor based on electrosynthesized biocompatible WO3/poly glutamic acid nano-biocomposites to address the hardships specific to the analysis of circulating proteins clinical samples. In addition to its green synthesis route, the poor tendency of both components of the prepared nano-biocomposite to amine groups makes it excellent working in untreated biological samples with high contents of proteins. Several electrochemical and morphological investigations (SEM, EDX, and dot mapping) were fulfilled to gain a reliable and trustful standpoint of the framework. By using this nanobiosensor, the concentration of HER-2 was detectable as low as 1 fg mL−1 with a wide linear response between 1 ng mL−1 and 1 fg mL−1. Meanwhile, the protocol depicted ideal specificity, stability, and reproducibility for the detection of HER-2 protein in untreated serum samples of breast cancer patients. [ABSTRACT FROM AUTHOR]

GO-Fc@Fe3O4 nanohybrid as a powerful and reusable nanocatalyst was synthesized. The graphene oxide (GO) sheets with meta-chloroperoxybenzoic acid (mCPBA) were treatment, afterward were chemically modified with 4-Fc derivative through the ring-opening reaction between GO nanosheets and 4-ferrocenylbutylamine. Then, the final nanocatalyst was obtained by synthesizing of Fe3O4 nanoparticles onto the modified GO surface. The structure and morphology of GO-Fc@Fe3O4 nanohybrid were characterized using different analysis, such as FT-IR, XRD, FE-SEM, EDX, and VSM techniques. Then, 2-amino-3-cyano-4H-pyran derivatives (4a–l) as a synthetic precursor were synthesized via multi-component reaction in the presence of GO-Fc@Fe3O4 nanohybrid as a novel heterogeneous nanocatalyst. Finally, according to the importance of finding a solution to treat Alzheimer's disease, 14-aryl-10,11,12,14-tetrahydro-9H-benzo[5,6]chromeno[2,3-b]-quinolin-13-amines (5a–l) as new tacrine-naphthopyran hybrid analogs were designed and prepared as acetylcholinesterase inhibitors. These compounds were synthesized via Friedländer reaction of 2-amino-3-cyano-4H-pyran derivatives (4a–l) with cyclohexanone. HAChE inhibition assay was carried out in vitro on the synthesized compounds 5a–l. Among them, compound 5f exhibited potent hAChE inhibitors with IC50 values of 0.16 µM. Also, the molecular docking and kinetic studies performed for a better understanding of compound 5f as a representative compound. [ABSTRACT FROM AUTHOR]

Background: In this label-free bioassay, an electrochemiluminescence (ECL) immunosensor was developed for the quantification of breast cancer using HER-2 protein as a metastatic biomarker. Method: For this purpose, the ECL emitter, [Ru(bpy)3]2+, was embedded into biocompatible chitosan (CS) polymer. The prepared bio-composite offered high ECL reading due to the depletion of human epidermal growth factor receptor 2 (HER-2) protein. Reduced graphene oxide (rGO) was used as substrate to increase signal stability and achieve greater sensitivity. For this, rGO was initially placed electrochemically on the glassy carbon electrode (GCE) surface by cyclic voltammetry (CV) technique. Next, the prepared CS/[Ru(bpy)3]2+ biopolymer solution was coated on a drop of the modified electrode such that the amine groups of CS and the carboxylic groups of rGO could covalently interact. Using EDC/NHS chemistry, monoclonal antibodies (Abs) of HER-2 were linked to CS/[Ru(bpy)3]2+/rGO/GCE via amide bonds between the carboxylic groups of Ab molecules and amine groups of CS. The electrochemical behavior of the electrode was studied using different electrochemical techniques such as electrochemical impedance spectroscopy (EIS), differential pulse voltammetry (DPV) and square wave voltammetry (SWV) and also ECL tests. Results: After passing all optimization steps, the lower limit of detection (LLOQ) and linear dynamic range (LDR) of HER-2 protein were practically obtained as 1 fM and 1 fM to 1 nM, individually. Importantly, the within and between laboratory precisions were performed and the suitable relative standard deviations (RSDs) were recorded as 3.1 and 3.5%, respectively. Conclusions: As a proof of concept, the designed immunosensor was desirably applied for the quantification of HER-2 protein in breast cancer suffering patients. As a result, the designed ECL-based immunosensor has the capability of being used as a conventional test method in biomedical laboratories for early detection of HER-2 protein in biological fluids. [ABSTRACT FROM AUTHOR]

[Display omitted] • Electrospinning, as a very powerful approach, produce highly complex nanofibers with tunable properties. • Electrospun nanofiber have showed considerable potential in various fields. • Nanofiber-based (bio)sensors offer several advantages over conventional approaches. • We explore advanced platforms based on electrospun natural and synthetic polymer-based (bio)sensors. • Enhanced responsiveness linear range, sensitivity, LOD, and cost-effectiveness are considerable in this regard. Electrospinning is a very powerful technique to produce highly complex nanofibers with tunable properties. This technique provides efficiency, versatility, and low cost to create nanofiber assemblies from a rich variety of natural and synthetic polymers combined with different types of nanoparticles. Electrospun nanofiber materials have demonstrated significant potential in various applications, such as sensors and biosensors, tissue engineering, drug delivery, energy conversion, and storage. This is mainly due to their unique characteristics including mechanical strength, large specific surface area, diverse polymer composition, and simple manufacturing process. Nanofiber-based biosensors offer several advantages over conventional biosensors, including enhanced responsiveness, wider linear range, higher sensitivity, lower limit of detection (LOD), and cost-effectiveness. Recently, there has been considerable interest in developing nanobiocomposites by integrating bioreceptors and conductive nanomaterials into carbon, metal oxide, or polymer electrospun nanofibers. In this comprehensive review, we explore advanced biosensors based on electrospinning technology, including biosensors modified with electrospun carbon, metal/metal oxide, as well as polymer-based and polymer-modified biosensors. After a general and short description of the electrospinning process and electrospinning conditions affecting the production of different nanofibers, the application of electrospun nanofibers for the design of electrochemical (bio)sensors is discussed. [ABSTRACT FROM AUTHOR]

Dipyrromethanes are useful mediator structures which can be used as a part of other molecules such as bis-porphyrins and their derivations. Various methods have been developed for their synthesis. This study presents the synthesis of a new bisdipyrromethane, 7,12-bis(4-(di(1H-pyrrol-2-yl)methyl)phenyl)benzo[k]fluoranthene, using the Lewis acid catalyzed reaction between a new dialdehyde and pyrrole at room temperature. The UV spectroscopic and fluorometric properties of the final product and precursors were determined. The newly synthesized product with desirable UV spectroscopic and fluorometric properties has the potential to be applied as a part of bis porphyrins or it can be used for other purposes in future studies. [ABSTRACT FROM AUTHOR]

Objective: Silibinin is an antioxidant agent and is shown to have anticancer effects in different cancers including lung, breast, colorectal, liver, prostate, and kidney. There are challenges in the clinical use of silibinin. The main limitation is low solubility, poor oral absorption, and extensive hepatic metabolism. We aim to develop a High-Performance Liquid Chromatography (HPLC) sensitive method for quantification of silibinin in aqueous samples to quantify its concentration in new formulations. A reverse-phase high-performance liquid chromatography (RP-HPLC) composed of C18 column as stationary phase and the mixture of methanol (90%) and water (10%) as mobile phase. The developed method was validated based on the established guidelines. Results: The retention time for silibinin was seen in 2.97 min after injection. The calibration curve was drawn and the established method demonstrated a linear ranged from 10 to 100 µg/ml, with a correlation coefficient of 0.996. The sensitivity of the developed method was 10 µg/ml. The accuracy calculated in the range of 88–105.9% and the precision (as relative standard deviation) was between 2.7 and 10.9%. These results demonstrate that the developed method can be a fast and accurate method for quantification of silibinin in aqueous samples. [ABSTRACT FROM AUTHOR]

Abstract Biosensors have been commonly used in biomedical diagnostic tools in recent years, because of a wide range of application, such as point-of-care monitoring of treatment and disease progression, drug discovery, commonly use food control, environmental monitoring and biomedical research. Additionally, development of DNA biosensors has been increased enormously over the past few years as confirmed by the large number of scientific publications in this field. A wide range of techniques can be used for the development of DNA biosensors, such as DNA nano-machines and various signal amplification strategies. This article selectively reviews the recent advances in DNA base biosensors with various signal amplification strategies for detection of cancer DNA and microRNA, infectious microorganisms, and toxic metal ions. Highlights • Biosensor technology solves some problems regarding to low sensitivity, time, and cost issues in clinical diagnosis. • Biosensors are employed in disease monitoring, drug discovery, detection of pollutants, disease-causing microorganisms and markers in bodily fluids. • The acid biosensors have been considered for genetic therapy, cancer screening, molecular diagnosis, and environmental monitoring. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive brain disorder characterized by the ongoing decline of brain functions. Studies have revealed the detrimental effects of hyperphosphorylated tau (p-tau) protein fibrils in AD pathogenesis, highlighting the importance of this factor in the early-stage detection of AD conditions. We designed an electrochemical immunosensor for quantitative detection of the cis conformation of the p-tau protein (cis-p-tau) employing platinum nanoparticles (Pt NPs) supported on zeolitic imidazolate frameworks (ZIF) for modifying the glassy carbon electrode (GCE) surface. Under optimum conditions, the immunosensor selectively and sensitively detected cis-p-tau within the broad linear range of 1 fg mL−1 to 10 ng mL−1 and the low limit of detection (LOD) of 1 fg mL−1 with desired reproducibility and stability. Furthermore, the fabricated immunosensor's performance was examined for the cis-p-tau analysis in the serum of AD patients, indicating its accuracy and feasibility for real-sample analysis. Notably, this is the first application of Pt@ZIF-8 nanocomposite in fabricating a valid immunosensor for selective cis-p-tau detection, even in the presence of trans-p-tau. It is worth mentioning that the enzyme-linked immunosorbent assay (ELISA) reference technique is not able to evaluate pico- or femtomolar concentrations of cis-p-tau, making the fabricated immunosensor superior for early-stage measurement and screening of AD. [ABSTRACT FROM AUTHOR]

[Display omitted] • Indium tin oxide coated polyethylene terephthalate film was used for the immobilization of aptamer. • An efficient disposal electro-device was developed for the recognition of Rivaroxaban. • An analytical method based on label-free aptasensing was developed for the monitoring of Rivaroxaban. • Linear range of Rivaroxaban concentration are from 10 to 600 nM in human real samples. A novel ultrasensitive electrochemical aptasensor was developed for the detection of rivaroxaban (RIV). For this purpose, poly toluidine blue (P(TB)), silver nanoparticles (AgNPs), aptamer conjugated with polyethylene glycol (PEG), and ITO-PET (indium tin oxide coated polyethylene terephthalate film) electrode was utilized. In order to fabrication of the low fouling aptasensor, the surface of ITO-PET was efficiently modified by P(TB-AgNPs) to provide a suitable substrate for the stable immobilization of aptamer sequence, 5′ SH-TAG GGA AGA GAA GGA CAT ATG ATG ACT CAC AAC TGG ACG AAC GTA CTT ATC CCC CCC AAT CAC TAG TGA ATT-3′). Using ITO PET-OH-P (TB-Ag)-PEG as substrate and aptamer as bioreceptor, RIV were measured in human plasma and exhaled breath condensate samples by chronoamperometry technique with limit of detections of 6.65 and 4.13 nM, respectively. Importantly, using PEG conjugated aptamer, a low fouling aptasensor was developed for the sensitive and selective determination of RIV in spiked samples. For the first time, a novel aptasensor for determination of RIV in human plasma and exhaled breath condensate (EBC) samples was developed which is able to use for therapeutic drug monitoring (TDM) studies. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells (CSCs) are of great diagnostic importance due to their involvement in tumorigenesis, therapeutic resistance, metastasis and relapse. Method: In this work, a sensitive electrochemical cytosensor was successfully established to detect HT-29 colorectal cancer stem cells based on a nanocomposite composed of mesoporous silica nanoparticles (MSNs) and platinum nanoparticles (PtNPs) using a simple and fast electrodeposition technique on a glassy carbon electrode (GCE). Results: According to SEM images, the PtNPs nanoparticles formed on the MSNs substrate are about 100 nm. As expected, high-rate porosity, increased surface-to-volume ratio, provides appropriate local electron transfer rate and suitable platform for the efficient formation of PtNPs. These features allow direct and stable binding of biotinylated monoclonal antibody of CD133 to streptavidin (Strep) and the subsequent availability of active sites for CSCs identification. Differential pulse voltammetry (DPV) results show that close interaction of CD133+ cells with monoclonal antibodies reduces charge transfer and electrical current, as confirmed by square wave voltammogram (SWV). Based on the recorded current versus number of CSCs, we noted that our developed system can sense CSCs from 5 to 20 cells/5 μL. Conclusions: As a proof of concept, the designed nanobiocomposite was able to specifically detect CD133+ cells compared to whole HT-29 cells before magnetic activated cell sorting (MACS) process. [ABSTRACT FROM AUTHOR]

Background: Developing high-performance sensing frameworks for diagnosing anaplastic changes is the subject of debate. The lack of on-time diagnosis in patients with suspicious cancers can affect the prognosis and survival rate. As a correlate, the emergence of de novo strategies for developing transducing frameworks has an inevitable role in advanced biosensing. The combination of green chemistry procedures with eco-friendly and biocompatible materials is of high desirability in this context. The synthesis of new biocompatible and cost-effective nanomaterials to meet the emerging needs of rising demands appeals to new synthetic methodologies. Methods: Here, we applied the electrochemical synthesis method to the fabrication of biocompatible and subtly governed Molybdenum trioxide/poly taurine nano-bio films to monitor human epidermal growth factor receptor-2 (HER-2) in sera from breast cancer patients. Morphological and elemental assessments were performed using a scanning electron microscope, energy-dispersive X-Ray spectroscopy, and dot mapping analyses. In addition, HER-2 immunohistochemistry (IHC) staining was performed on tissue samples, and data were compared to the values obtained by Molybdenum trioxide/poly taurine nano-bio films. Results: We also noted our platform is eligible for feasible, rapid, and specific determination of HER-2 factor in human samples. The method had a lower limit of quantification of 0.000001 ng/mL and a linear dynamic range between 0.1 ng/mL and 0.000001 ng/mL. IHC imaging showed that the degree of anaplastic changes in breast samples (intensity of HER-2 factor) was closely associated with the intensity of signals obtained by our developed immunosensor. Conclusions: According to the obtained desirable coordination with pathological studies, the designed biosensor has excellent capability to use as a reliable diagnostic tool in clinical laboratories. [ABSTRACT FROM AUTHOR]

Due to a lack of sufficient blood supply and unique physicochemical properties, the treatment of injured cartilage is laborious and needs an efficient strategy. Unfortunately, most of the current therapeutic approaches are, but not completely, unable to restore the function of injured cartilage. Tissue engineering-based modalities are an alternative option to reconstruct the injured tissue. Considering the unique structure and consistency of cartilage tissue (osteochondral junction), it is mandatory to apply distinct biomaterials with unique properties slightly different from scaffolds used for soft tissues. PCL is extensively used for the fabrication of fine therapeutic scaffolds to accelerate the restorative process. Thermosensitive PCL hydrogels with distinct chemical compositions have paved the way for sophisticated cartilage regeneration. This review aimed to collect recent findings regarding the application of PCL in hydrogels blended with natural, synthetic materials in the context of cartilage healing. [ABSTRACT FROM AUTHOR]

Delivery of small interfering RNAs (siRNAs) into cells still remains a challenge in gene delivery studies. Here, we investigated the ability of synthesized Fe 3 O 4 -PEG-LAC-chitosan-PEI nanoparticles for siRNA delivery of survivin as the model gene into cells. The cellular uptake of survivin siRNA carried by synthesized nanoparticles into MCF-7 breast cancer cell line was evaluated by florescent microscopy and flowcytometry, both proving the efficacy of nanoparticles in delivery of up to 64.7% in comparison with lipofectamine 2000. Furthermore, the delivery of survivin siRNA by the nanoparticles (nanoplex) induced apoptosis that was assessed through DAPI staining and Annexin V/PI assays. In addition, we evaluated the efficacy of treatment with nanoplexes in the presence of mitoxantrone, as a chemotherapeutic agent. Our data indicated that inhibition of survivin expression increased the cell sensitivity to mitoxantrone. Real-time PCR and western blotting analysis revealed a significant reduction in mRNA and protein levels of survivin upon delivery of siRNA. Molecular docking studies showed that nanoparticles can bind to centeral BIR domain of survivin, exactly above zinc ion location with high affinity (ΔG: −10.3 Kcal/mol). Also, thermodynamic studies proved the experimental results theoretically, revealing that the siRNA-loaded nanoparticles have a suppressing effect on survivin mRNA. Therefore, delivery of survivin siRNA into MCF-7 cells using Fe 3 O 4 -PEG-LAC-chitosan-PEI nanoparticles as a carrier enhances the cell death. [ABSTRACT FROM AUTHOR]

As a gene delivery method in breast cancer therapy, knocking down the undesired genes in the cancerous cells would be promising. Inhibitors of Apoptosis Protein (IAP) family genes are some of the genes whose responsibility is inhibition of apoptosis in cells. Silencing these genes seems to be helpful directing the tumor cells to death. siRNA sequence designed against survivin anti-apoptotic gene can play this role if carried to the cytoplasm. Here we prepared a positive charged biocompatible nano-sized particle made up of a Fe 3 O 4 core covered respectively by polyacrylate (PA) and polyethyleneimine (PEI) layer, which could successfully deliver the siRNA into the MCF-7 cells. The particle structure was checked and having less than 50 nm diameter in size, positive charge and, safety towards MCF-7 cells besides being able to form nanoplexes with the siRNA strand helps it entering into the biologic assays part. The siRNA delivery evaluated via flowcytometry. Apoptosis induction was determined by DAPI staining. The efficiency of survivin gene knockdown was evaluated in mRNA and protein levels using Real time PCR and western blotting methods. Overall, the Fe 3 O 4 -PA-PEI nanoparticles can deliver siRNA effectively into the cytoplasm of the MCF-7 breast cancer cells and induce apoptosis. [ABSTRACT FROM AUTHOR]

Propyl gallate (PG) and tert -butylhydroquinone (TBHQ) are examples of phenolic antioxidant agents, which have widespread uses in food industry. In this study, for the first time, we report on the interaction of PG and TBHQ with bovine serum albumin (BSA) using surface plasmon resonance (SPR). In order to modify Au slide with carboxyl functional group, 11-mercaptoundecanoic acid (MUA) was used. After activation of carboxylic groups, BSA was immobilized onto the MUA through both covalent amide bond and electrostatic binding formation. The SPR analysis showed dose-response sensograms of BSA upon increasing concentration of PG and TBHQ. At pH 4.5, the equilibrium dissociation constant or affinity unit (K D ) for PG and TBHQ were 1.89e −10 and 1.49e −10 and at pH 7.5 were 4.74e −10 and 1.83e −9 , respectively. The smaller amount of K D demonstrated high food additive molecules affinity to BSA. Based on these findings, it can be concluded that PG and TBHQ molecules can interact with BSA and effectively distributed within the body. Besides, SPR can be considered as useful automatic tool for quantification of PG and TBHQ interaction with serum albumin and it can deliver precise real-time kinetic data. [ABSTRACT FROM AUTHOR]

A green, environmentally friendly protocol was developed for ultrasensitive and highly specific recognition of prostate-specific antigen (PSA) based on the ECL effect of luminol supported by chitosan-silver nanoparticles (CS/AgNPs) nanocomposites. The transducing surface was fabricated through two consecutive electrodeposition steps of gold nanoparticles (AuNPs) and chitosan (CS)-AgNPs-luminol electrochemiluminophore onto the glassy carbon electrode. In addition to an appropriate desirable biocompatibility, the electrochemical synthesis presents low-cost preparation and ultrafast determination opportunity. AgNPs play a linking role to attach luminol, as an ECL agent to the CS support via donor-acceptor bonds between Ag atoms with NH groups of luminol and CS. Also, AgNPs can amplify the ECL intensity as a consequence of their excellent specific surface area and conductivity. To enhance the performance of the nanobiosensor, AuNPs were also used due to their high-specific surface area and excellent affinity toward amine groups of CS. Based on this high-performance analysis strategy, ultrasensitive screening of PSA was attained with a desirable limit of detection of 0.6 ng mL-1 and a broad linear range between 1 pg mL-1 and 10 ng⋅mL-1 (R2=0.994). Approximately, the same results were recorded for the analysis of the unprocessed serum samples of patients with prostate cancer at different stages. This research provided significant insight into electrografting methods to construct ECL transducers for clinical monitoring of PSA and other tumor biomarkers in the clinical setting. [ABSTRACT FROM AUTHOR]

Endothelial cell integrity and cell junction disruption are involved in many biological processes such as vascular permeability, progression of ischemic injury and cancer metastasis. In this study, the protective effect of crocin in endothelial cells integrity induced by vascular endothelial growth factor (VEGF) was monitored by surface plasmon resonance (SPR), an optical-based method. In addition, the expression of vascular endothelial (VE)-cadherins, the basic endothelial adhesion molecule, which plays a crucial role in the integrity of endothelial cells and cellular junctions, was assessed using flow cytometry (FC). Also, actin filaments which have main roles in alignment and maintaining the integrity of intracellular integrity were investigated by the fluorescence staining method. For the SPR test, the human umbilical vein endothelial cells (HUVECs) were immobilized on cysteamine-coated gold chips, and the effect of VEGF injection on crocin-treated endothelial cells was studied. The increase of the angle shift (∆Ө) with cells deposition near 0.8° indicated that cells were successfully immobilized on the gold chip surface. A linear relation (R2 = 0.95) was obtained between the amount of VEGF absorbed on the cell surface and the change in the response unit (RU) values. Our SPR curve results along with FC and imaging data suggest that the crocin has a protective effect on cellular integrity. [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]

In this study, stimuli-responsive nanofibers (NFs) were successfully prepared via electrospinning method. Poly(N-isopropylacrylamide-co-acrylamide-co-vinylpyrrolidone) P(NIPAAM-AAm-VP) was used as the material for preparing the electrospinning NFs. Doxorubicin (Dox)-loaded NFs were prepared and characterized by XRD, Scanning electron microscopy and FTIR. A response surface methodology was used to evaluate the effect of key parameters on the fiber diameter. The cytotoxicity of Dox-loaded NFs was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole assay on lung cancer A549 cell lines.In vitrocytotoxicity assay showed that the P(NIPAAM-AAm-VP) fibers themselves did not affect the growth of A549 cells. Antitumor activity of the Dox-loaded fibers against the cells was kept over the whole experimental process, while that of pristine Dox disappeared within 48 h. Drug release pattern from these systems is in zero order and drug release rate is not dependent on drug/polymer ratio in different implant formulations. These novel NFs were stable and preserved their morphology even after incubation in release medium (pH 7.4, 37 °C), while collapsed and dispersed quickly in aqueous solution of acidic medium at room. The reported incorporation of stimuli-responsive properties into NFs takes advantage of their extremely large surface area and porosity and is expected to provide a simple platform for smart drug delivery. [ABSTRACT FROM PUBLISHER]

Background: Recently, biosensors have become popular analytical tools for small analytes due to their high sensitivity and wide analytical range. In the present work, development of a novel biosensing method based on tungsten disulfide quantum dots (WS2 QDs)-Au for rapidly and selectively detecting c-Met protein is introduced. As a proof of concept, M13 bacteriophage-based biosensors were used for the electrochemical detection of c-Met protein as a colon cancer biomarker. Method: The M13 bacteriophage (virus), as the biorecognition element, was immobilized on glassy carbon electrodes which were modified by WS2 QDs-functionalized gold nanoparticles. The stepwise presence of the WS2 QDs, gold nanoparticles, and immobilized phage on glassy carbon electrodes were confirmed by scanning electron microscope (SEM) and square wave voltammetry (SWV) technique. Results: The designed biosensor was applied to measure the amount of c-Met protein in standard solutions, and consequently the desirable detection limit of 1 pg was obtained. Finally, as a proof of concept, the developed platform was used for the evaluation of c-Met protein in serum samples of colon cancer-suffering patients and the results were compared with the results of the common Elisa kit. Conclusions: As an interesting part of this study, some concentrations of the c-Met protein in colon cancer serum samples which could not be determined by Elisa, were easily analyzed by the developed bioassay system. The developed bioassay system has great potential to application in biomedical laboratories. [ABSTRACT FROM AUTHOR]

1. Flavonoids are a group of polyphenolic plant metabolites most commonly known for their antioxidant activities. They also show inhibitory activities on molybdo-flavoenzymes family of enzymes which are involved in biotransformation of some exogenous and endogenous chemicals. Most notably, aldehyde oxidase (AO), a member of this family, is responsible for metabolism of some therapeutic agents. On the other hand, there are some therapeutics which inhibit AO. As flavonoids are ubiquitous in human diet and have potential to interact with AO, it is important to investigate their effects at the molecular details. 2. The inhibitory effects of 15 flavonoids on the activity of rat liver AO were assessed. Quantitative structure-activity relationship studies were performed using genetic algorithm coupled partial least square and stepwise multiple linear regression methods to elucidate the important structural properties responsible for the observed inhibitory effects. To further understand the mode of interaction between these flavonoids and AO, a homology model of the enzyme was built and flavonoids were docked into its active site. The most important amino acids involved in the interactions were identified. 3. Quercetin, myricetin and genistein were the most potent inhibitors establishing favorable interactions with the enzyme. However, the glycosylated flavonoids showed relatively weaker inhibition which may be attributed to their hindered binding into the active site of AO by bulky sugar groups. [ABSTRACT FROM AUTHOR]

In the present study, rat liver xanthine oxidase activity and its thermostability in the presence of pyridine were investigated. The activity of the enzyme was determined by following the formation of uric acid spectrophotometrically. The thermal stability of the enzyme was studied in the presence of 0.0%-2.0% of pyridine in Sorenson's buffer. Thermal stability parameters (half-life, inactivation constant, and activation energies for enzyme inactivation), thermodynamic constants (ΔH*, ΔS*, and ΔG*) and the kinetic parameters (Km and Vmax), were determined in pyridine-free and pyridine-containing buffer solution. A dramatic reduction was observed in xanthine oxidase activity in the presence of pyridine. However, the pyridine-treated enzyme showed a marked enhancement in thermal stability compared with the native enzyme. The ΔG values for the enzyme activity in the presence of pyridine were found to be about 1.5-fold larger than that calculated for the native enzyme, indicating that the enzyme becomes kinetically more stable in the presence of pyridine. The Km value for xanthine oxidase in the presence of 0.5% pyridine increased by 4.8-fold compared with the enzyme in the pyridine-free buffer solution; however, there was 1.8-fold reduction in the Vmax value in the hydro-organic solution compared with the enzyme activity in the buffer solution. As the stability of enzymes is one of the most difficult problems in protein chemistry, this thermostability property of xanthine oxidase could be of great value in developing novel strategies to improve and expand its application in various areas. [ABSTRACT FROM AUTHOR]

The importance of aldehyde oxidase (AOX) in drug metabolism necessitates the development and application of the in silico rational drug design methods as an integral part of drug discovery projects for the early prediction and modulation of AOX-mediated metabolism. The current study represents an up-to-date and thorough review of in silico studies of AOX-mediated metabolism and modulation methods. In addition, the challenges and the knowledge gap that should be covered have been discussed. The importance of aldehyde oxidase (AOX) in drug metabolism is a hot topic in drug discovery. Different strategies are available for the modulation of the AOX-mediated metabolism of drugs. Application of the rational drug design methods as an integral part of drug discovery projects is necessary for the early prediction of AOX-mediated metabolism. The current study represents a comprehensive review of AOX molecular structure, AOX-mediated reactions, AOX substrates, AOX inhibition, approaches to modify AOX-mediated metabolism, prediction of AOX metabolism/substrates/inhibitors, and the AOX related structure-activity relationship (SAR) studies. Furthermore, an up-to-date and thorough review of in silico studies of AOX metabolism has been carried out. In addition, the challenges and the knowledge gap that should be covered in the scientific literature have been discussed in the current review. [Display omitted] • AOX mediated metabolism is as an integrated part of drug discovery projects. • Lack of reliable in vitro/in vivo and general in silico models are the main challenges. • SAR-based chemical modifications are the main approach of AOX-mediated metabolism modulation. • It is possible to achieve rational modulation of AOX-mediated metabolism by in silico models. [ABSTRACT FROM AUTHOR]

Biodegradable nanoparticles, as drug delivery paradigms, have been extensively used for delivery of a wide range of small molecules as well as macromolecules, such as peptides, proteins, and genes. The morphological modification may improve the physicochemical characteristics of the biodegradable polymers. In the current investigation, the synthesis and characterization of linear, poly(D,L-lactide-co-glycolide) (PLGA)-poly(ethylene glycol) (PEG-PLGA), star-branched (ß-cyclodextrin-PLGA (ß-CD-PLGA), and glucose-PLGA (Glu-PLGA) copolymers containing insulin as a model peptide drug have been reported. Linear and star-branched copolymers of PLGA were synthesized by bulk melt polymerization of the lactones (lactide and glycolide) in the presence of PEG, glucose, or n-CD using Sn-octoate as catalyst. Nanoparticles were prepared by a modified (w1/o/w2) double emulsion method. Bovine insulin was successfully encapsulated into the linear and star-branched PLGA nanoparticles with retention of insulin stability and the nanoparticles preparation process was optimized to reduce the burst effect and provide in vitro sustained release. The average particle size of samples was 120(–355 nm. The cumulative amount of 65(–84% insulin was released from the samples after 24 days. The yield of encapsulation of insulin was superior to 95%. Based on these findings, it is suggested that the novel PLGA nanoparticles can be used as a carrier for prolonged delivery of protein-peptide drugs. [ABSTRACT FROM AUTHOR]

Amyloid-β 1–42 (Aβ1–42) aggregation is considered as an important process in the pathology of Alzheimer's disease (AD). Astaxanthin (ATX), a xanthophyll carotenoid, has a broad range of biological activities such as neuroprotective one. The present study aimed to elucidate the interaction of ATX with Aβ1–42, as well as its effect on Aβ1–42 aggregates under different conditions. Based on the surface plasmon resonance (SPR) results, ATX possessed a high affinity towards Aβ1–42 and the binding process was spontaneous, endothermic, and entropy-driven. Additionally, the binding affinity of ATX to Aβ1–42 was glucose and insulin concentration-dependent. Hydrophobic interactions may play an important role in the interaction between ATX and Aβ1–42. The results of SPR, thioflavin T (ThT), and transmission electron microscopy (TEM) analyses represented the dependency of the anti-amyloid activity of ATX on glucose, insulin, and ATX concentrations. Further, molecular docking results indicated the presence of some same binding sites on Aβ1–42 for ATX and glucose, as well as ATX and insulin, which suggests the possible competition between the molecules for Aβ1–42 binding. Furthermore, the MTT results confirmed that ATX effect on the viability of Aβ1–42-treated PC12 cells was dependent on glucose, insulin, and ATX concentrations. In general, the results provided further insights into the interaction between Aβ1–42 and ATX, as well as the effect of ATX on Aβ1–42 aggregates under various conditions. [Display omitted] • The interaction of astaxanthin (ATX) with Aβ1–42 was exothermic and enthalpy-driven. • ATX-binding affinity to Aβ1–42 was temperature- and glucose-concentration dependent. • ATX interacts with Aβ1–42 through hydrophobic and hydrogen bonds. • Anti-amyloid activity of ATX was dependent on glucose, insulin, and ATX concentration. • The same or overlapping binding sites were predicted for glucose and ATX on Aβ1–42. [ABSTRACT FROM AUTHOR]

Recently, using antibiotic-free nanofibrous mats in wound healing has significant attention for infection cure after tissue injuries as a result of no drug resistance. Honey is a natural wound-healing agent that has been reintroduced to clinical wound treatment because of its good antioxidant and antibacterial properties. In this work, honey in various blending ratios was incorporated into the ethylcellulose (EC)/gum tragacanth (GT) electrospun nanofibrous (EGH NF) mat to develop an effective wound covering biomaterial. The physicochemical and biological characteristics of fabricated EGH NFs were evaluated by several methods. The effect of honey and the honey concentration enhancement (from 5 wt% to 20 wt%) was studied on the various properties of the NFs. The obtained results presented suitable antibacterial properties, enhanced antioxidant activity, improved degradation ability, increased mechanical features, proper cell growth, attachment, and proliferation against NIH-3 T3 fibroblast cells. The cytotoxicity assay showed the biocompatibility and non-cytotoxicity of the developed NF mats. Therefore, these achieved results suggested that the developed EGH NFs can be a promising candidate for wound dressing applications. [Display omitted] [ABSTRACT FROM AUTHOR]

In the present article, we developed a highly sensitive label-free electrochemical immunosensor based on NiFe-layered double hydroxides (LDH)/reduced graphene oxide (rGO)/gold nanoparticles modified glassy carbon electrode for the determination of receptor tyrosine kinase-like orphan receptor (ROR)-1. In this electrochemical immunoassay platform, NiFe-LDH/rGO was used due to great electron mobility, high specific surface area and flexible structures, while Au nanoparticles were prepared and coated on the modified electrodes to improve the detection sensitivity and ROR1 antibody immobilizing (ROR1Ab). The modification procedure was approved by using cyclic voltammetry and differential pulse voltammetry based on the response of peak current to the step by step modifications. Under optimum conditions, the experimental results showed that the immunosensor revealed a sensitive response to ROR1 in the range of 0.01–1 pg mL−1, and with a lower limit of quantification of 10 attogram/mL (10 ag mL−1). Furthermore, the designed immunosensor was applied for the analysis of ROR1 in several serum samples of chronic lymphocytic leukemia suffering patients with acceptable results, and it also exhibited good selectivity, reproducibility and stability. [ABSTRACT FROM AUTHOR]

• A new, simple, cost-effective, and rapid way was introduced for the synthesis monodispersed CdS QDs. • A novel immunosandwich biosensor was engineered to serve as a promissing tool for the detection of cardiac troponin marker. • The biosensor revealed a LOD of 2 ng L−1 and a LDR of 5–1000 ng L−1 compare to existing cut-off (13–20 ng L−1). Here, we report on a reproducible one-pot synthesis of high-quality and monodispersed CdS semiconducting nanocrystals (NCs) by mixing precursors cadmium acetate and elemental sulfur into the new solvent system of dibenzyl ether and oleylamine without using any extra reagent or precursor activator. The NCs (5 nm) exhibited a dominant band-edge emission with a good photoluminescence quantum yield of 13.76% without trap emission. The CdS NCs were characterized using UV–Vis and photoluminescence spectroscopy, electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The practical efficiency of the synthesized NCs was proved by applying the synthesized CdS NCs as the tracer in the engineering of an immunosandwich biosensor to evaluate the cardiac troponin (cTn) marker for the diagnosis and monitoring of myocardial infarction (MI). The biosensor revealed significant analytical efficiency with the limit of detection of 2 ng L−1 and the linear dynamic range of 5–1000 ng L−1, which is lower than the existing cutoff values (13–20 ng L−1). Having capitalized on the anodic stripping voltammetry method, the screen-printed biosensor could efficiently detect the cTn markers. Therefore, the biosensor is proposed to be used in clinical settings for fast, sensitive, and accurate monitoring of cTn markers. [ABSTRACT FROM AUTHOR]

Background: The goal of the present study was to create a new biodegradable hybrid PCL-P (HEMA-NIPAAm) thermosensitive hydrogel scaffold by grafting PNIPAAm-based copolymers with biodegradable polyesters to promote the chondrogenic differentiation of human progenitor cells (adipose-derived stem cells-hASCs) in the presence of the platelet-derived growth factor (PDGF-BB). Different mixture ratios including 50 mmol ε-caprolactone and 10 mmol HEMA (S-1), 30 mmol ε-caprolactone and 10 mmol HEMA (S-2), 10 mmol ε-caprolactone and 30 mmol HEMA (S-3) were copolymerized followed by the addition of NIPAAm. Results: A mild to moderate swelling and wettability rates were found in S-2 group copmpared to the S-1 ans S-3 samples. After 7 weeks, S-2 degradation rate reached ~ 43.78%. According to the LCST values, S-2, reaching 37 °C, was selected for different in vitro assays. SEM imaging showed nanoparticulate structure of the scaffold with particle size dimensions of about 62–85 nm. Compressive strength, Young's modulus, and compressive strain (%) of S-2 were 44.8 MPa, 0.7 MPa, and 75.5%. An evaluation of total proteins showed that the scaffold had the potential to gradually release PDGF-BB. When hASCs were cultured on PCL-P (HEMA-NIPAAm) in the presence of PDGF-BB, the cells effectively attached and flattened on the scaffold surface for a period of at least 14 days, the longest time point evaluated, with increased cell viability rates as measured by performing an MTT assay (p < 0.05). Finally, a real-time RT-PCR analysis demonstrated that the combination of PCL-P (HEMA-NIPAAm) and PDGF-BB promoted the chondrogenesis of hASCs over a period of 14 days by up-regulating the expression of aggrecan, type-II collagen, SOX9, and integrin β1 compared with the non-treated control group (p < 0.05). Conclusion: These results demonstrate that the PCL-P(HEMA-NIPAAm) hydrogel scaffold carrying PDGF-BB as a matrix for hASC cell seeding is a valuable system that may be used in the future as a three-dimensional construct for implantation in cartilage injuries. [ABSTRACT FROM AUTHOR]

• Yellow and blue emitting carbon were synthetized in totally green way. • A novel molecular imprinting ratiometric fluorescence sensor was developed. • Mesoporous structure was applied to reduce mass transfer resistance. • Point-of-care detection of penicillin G residues in milk. Instant detection of antibiotic residues in dairy products has been remained a challenge. Current methods require careful samples storage and handling, skilled personnel, and expensive instrumentations. Herein, we report the preparation of a ratiometric fluorescent sensor that contains different colored Carbon dots (CDs) as dual fluorophores, and a mesoporous structured molecularly imprinted polymer as a receptor (B/YCDs@mMIP) for penicillin-G (PNG) detection in milk. Upon PNG addition, only the fluorescence of yellow emissive CDs was quenched due to analyte blockage, while that of the blue emissive CDs stayed almost constant, which led to an obvious change in the fluorescence color from the yellow to blue. A linear response in the range of 1–32 nM with a detection limit of 0.34 nM and excellent recognition specificity for PNG over its analogs were also observed. Comparing our sensor with its counterparts, it exhibited a promising potential in the in-situ PNG detection in milk. [ABSTRACT FROM AUTHOR]