Sharif Digital Repository

Simulating signal transduction in cellular signaling networks provides predictions of network dynamics by quantifying the changes in concentration and activity-level of the individual proteins. Since numerical values of kinetic parameters might be difficult to obtain, it is imperative to develop non-parametric approaches that combine the connectivity of a network with the response of individual proteins to signals which travel through the network. The activity levels of signaling proteins computed through existing non-parametric modeling tools do not show significant correlations with the observed values in experimental results. In this work we developed a non-parametric computational... 

During the drug delivery process in chemotherapy, both of the cancer cells and normal healthy cells may be killed. In this paper, three mathematical cell-kill models including log-kill hypothesis, Norton-Simon hypothesis and Emax hypothesis are considered. Three control approaches including optimal linear regulation, nonlinear optimal control based on variation of extremals and H∞-robust control based on μ-synthesis are developed. An appropriate cost function is defined such that the amount of required drug is minimized while the tumor volume is reduced. For the first time, performance of the system is investigated and compared for three control strategies; applied on three nonlinear models... 

In the current study, two series of antimicrobial dressings conjugated with silver sulfadiazine (SSD) and silver nanoparticles (AgNPs) were developed and evaluated for chronic wound healing. Highly porous polycaprolactone (PCL)/polyvinyl alcohol (PVA) nanofibers were loaded with different concentrations of SSD or AgNPs and compared comprehensively in vitro and in vivo. SSD and AgNPs indicated a strong and equal antimicrobial activity against S. aureus. However, SSD had more toxicity against fibroblast cells over one week in vitro culture. An in vivo model of wound healing on male Wistar rats was developed with a full thickness wound. All the wound dressings indicated enough flexibility and... 

Conductive self -electrical stimuli bioactive scaffolds could be used the potential for peripheral nerve regeneration with the maximum efficiency. To produce such conductive self-electrical stimuli bioactive scaffolds, chopped spun piezoelectric nanofibers of polyvinylidene fluoride/mesoporous silica nanoparticle (PVDF/MCM41) are prepared and incorporated in gellan/polyaniline/graphene (gellan/PAG) nanocomposites which have been previously prepared by incorporation of polyaniline/graphene (PAG) nanoparticles in gellan gel at 80 °C. Highly conductive binary doped polyaniline/graphene nanoparticles are prepared by chemical oxidative polymerization of aniline monomer using in-suite... 

Background: Newcastle disease virus (NDV) has shown noticeable oncolytic properties, especially against cervical cancer. However, in order to improve the spread rate and oncotoxicity of the virus, employment of other therapeutic reagents would be helpful. It has been shown that some viral fusogenic membrane glycoproteins (FMGs) could facilitate viral propagation and increase the infection rate of tumor cells by oncolytic viruses. Additionally, immune checkpoint blockade has widely been investigated for its anti-tumor effects against several types of cancers. Here, we investigated for the first time whether the incorporation of influenza hemagglutinin-2 (HA2) FMG could improve the oncolytic... 

Arms bearing ureido-pyrimidinone functional groups with self-association capability (through quadruple hydrogen bonds) were successfully grafted onto hydroxyapatite nanoparticles. The supramolecularly modified nanoparticles (nHApUPy) exhibited enhanced colloidal stability compared to the original hydroxyapatite nanoparticles and were uniformly dispersed in supramolecular polycaprolactone in PCL(UPy)2/HApUPy nanocomposites at different filler loadings. The combined atomic force microscopy, mechanical, and rheological analyses confirmed a high degree of compatibility of HApUPy nanoparticles with the polymer matrix. The temperature dependence of the supramolecular structure in PCL(UPy)2/HApUPy... 

To efficiently enhance the contrast obtaining from magnetic resonance imaging (MRI), pharmaceutical grade colloidal dispersions of PEG coated iron-based nanoparticles were prepared and compared to conventional pure iron oxide contrast agent. In this study, we synthesized ∼14 nm iron nanoparticles via NaBH4 reduction of iron(III) chloride in an aqueous medium. The resulting nanoparticles were further oxidized by two different methods via (CH3)3NO oxygen transferring agent and exposure to oxygen flow. XRD and electron microscopy analyses confirmed the formation of a second layer on the surface of α-Fe core. As magnetic measurements and Mössbauer spectra of 4-months post prepared nanoparticles... 

Superparamganetic iron oxide-based contrast agents in magnetic resonance imaging (MRI) have offered new possibility for early detection of lymph nodes and their metastases. According to important role of nanoparticle size in biodistribution, magnetite nanoparticles coated with different polyethylene glycol (PEG) concentrations up to 10/1 PEG/iron oxide weight ratio in an ex situ manner. To predict the PEG-coated nanoparticle behavior in biological media, such as blood stream or tissue, colloidal stability evaluation was performed to estimate the coating endurance in different conditions. Accordingly, optical absorbance measurements were conducted in solutions with different values of pH and... 

Electrospinning of composite polymer solutions provides fantastic potential to prepare novel nanofibers for use in a variety of applications. The addition of graphene (G) and graphene oxide (GO) nanosheets to bioactive polymers was found to enhance their conductivity and biocompatibility. Composite conductive nanofibers of polyaniline (PANI) and polyacrylonitrile (PAN) with G and GO nanosheets were prepared by an electrospinning process. The fabricated membranes were investigated by physical and chemical examinations including scanning electron microscopy (SEM), Raman spectroscopy, x-ray diffraction (XRD) and tensile assay. The muscle satellite cells enriched by a pre-plating technique were... 

Superparamagnetic iron oxide nanoparticles (SPIONs) are increasingly used in medical applications, such as targeting delivery and imaging. In the future, patients are more likely to be exposed to pharmaceutical products containing such particles. The study of toxicity of SPIONs has become of great importance in recent years, although the published data in this arena is limited. The aim of the present work is to investigate the cytotoxicity of SPIONs and the effect of the particles on the cell medium components. For this purpose, uncoated and polyvinyl alcohol (PVA) coated SPIONs with narrow size distribution were synthesized via a well-known coprecipitation method. The mouse fibroblast cell... 

The performance of nanoparticles for biomedical applications is often assessed by their narrow size distribution, suitable magnetic saturation and low toxicity effects. In this work, superparamagnetic iron oxide nanoparticles (SPIONs) with different size, shape and saturation magnetization levels were synthesized via a co-precipitation technique using ferrous salts with a Fe3+/Fe2+ mole ratio equal to 2. A parametric study is conducted, based on a uniform design-of-experiments methodology and a critical polymer/iron mass ratio (r-ratio) for obtaining SPION with narrow size distribution, suitable magnetic saturation, and optimum biocompatibility is identified. Polyvinyl alcohol (PVA) has been... 

As the use of superparamagnetic iron oxide nanoparticles (SPION) in biomedical applications increases (e.g. for targeting drug delivery and imaging), patients are likely to be exposed to products containing SPION. Despite their high biomedical importance, toxicity data for SPION are limited to date. The aim of this study is to investigate the cytotoxicity of SPION and its ability to change cell medium components. Bare and poly(ethylene glycol)-co-fumarate (PEGF)-coated SPION with narrow size distributions were synthesized. The particles were prepared by co-precipitation using ferric and ferrous salts with a molar Fe3+/Fe2+ ratio of 2. Dulbecco's modified Eagle's medium (DMEM) and primary... 

Electrospinning of biopolymers has gained significant interest for the fabrication of fibrous mats for potential applications in tissue engineering, particularly for wound dressing and skin regeneration. In this study, for the first time, we report successful electrospinning of chitosan-based biopolymers containing bacterial cellulous (33 wt %) and medical grade nanodiamonds (MND) (3 nm; up to 3 wt %). Morphological studies by scanning electron microscopy showed that long and uniform fibers with controllable diameters from 80 to 170 nm were prepared. Introducing diamond nanoparticles facilitated the electrospinning process with a decrease in the size of fibers. Fourier transform infrared... 

Microfluidic devices are beneficial in miniaturizing and multiplexing various cellular assays in a single platform. Chondrogenesis is known to pertain to chemical, topographical, and mechanical cues in the microenvironment. Mechanical cues themselves have numerous parameters such as strain magnitude, frequency, and stimulation time. Effects of different strain magnitudes on the chondrogenic differentiation of adult stem cells have not been explored thoroughly. Here, a new multilayer microdevice is presented for the unidirectional compressive stimulation of cells in a three-dimensional cell culture. Numerical simulations were performed to evaluate and optimize the design. Results showed a... 

Background: Human papillomavirus (HPV)-associated malignancy remain a main cause of cancer in men and women. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. Here, we report Mesenchymal stem cells (MSCs) as a carrier for the delivery of oncolytic Newcastle disease virus (NDV) for the treatment of HPV-associated tumor. Methods: For this purpose, MSCs obtained from the bone marrow of C57BL mice, then cultured and characterized subsequently by the flow cytometry analysis for the presence of cell surface markers. In this study, we sought out to determine the impacts of MSCs loaded with oncolytic NDV on splenic T cell and cytokine immune... 

This study presents a bilayer structure as a skin scaffold comprised of an electrospun sheet layer made of polycaprolactone and polyvinil alcohol and a porous hydrogel layer made of chitosan and gelatin. The hydrogel layer was fabricated by employing the freeze-gelation technique. The bilayer structure was achieved by pouring the hydrogel solution on the electrospun sheet at the bottom of a mold followed by the freeze-gelation technique to obtain a porous structure in the hydrogel. The hydrogel and hydrogel-electrospun samples were characterized by scanning electron microscopy, swelling, tensile strength, in vitro and in vivo analyses. From a mechanical strength standpoint, the combination... 

Introduction: This report describes the synthesis of 2-Amino-2-deoxy(S- benzoylthioacetyl)-D-glucose (S-Bz-TA-DG), radiolabeled with [ 99mTc(CO)3(OH2)3]+ complex with a procedure including deprotection of the benzoyl group, characterization by HPLC using a C18 reverse phase column and preliminary biodistribution study in normal mice. Methods: [99mTc(CO) 3(H2O)3]+ complex was used to label TA-DG with 99mTc. This complex was prepared using up to 46 mCi of Na99mTcO4 in 1mL saline. The radiochemical purity (>95%) was determined by TLC in normal saline solution as the mobile phase. Radio-HPLC analysis of [99mTc]-(TA-DG) at pH=9.5-10, revealed that labeling with 99mTc resulted in the formation of... 

In this study, superparamagnetic iron oxide nanoparticles (SPION) embedded by folic acid (SPION-folate) were prepared by a modified co-precipitation method. The structure, size, morphology, magnetic property and relaxivity of the SPION-folate were characterized systematically by means of XRD, VSM, HRSEM and TEM and the interaction between folate and iron oxide (Fe3O 4) was characterized by FT-IR. The particle size was shown to be ≈5-10 nm. To ensure biocompatibility, the interaction of these SPION with mouse connective tissue cells (adhesive) was investigated using an MTT assay. Consequently, gallium-67 labeled nanoparticles ([67Ga]-SPION-folate) were prepared using 67Ga with a high labeling... 

Core-shell iron-gold (Fe@Au) nanoparticles were synthesized by a facile reverse micelle procedure and the effect of water to surfactant molar ratio (w) on the size, size distribution and magnetic properties of the nanoparticles was studied. MTT assay was utilized to evaluate the cell toxicity of the nanoparticles. To functionalize the particles for MRI imaging and targeted drug delivery, the particles were coated by polyglycerol through capping with thiol followed by polymerization of glycidol. The characteristics of the particles were examined by X-ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometere (VSM), UV-visible spectroscopy, and Fourier... 

Context: Elevated expression of the folate receptor (FR) occurs in many human malignancies. Thus, folate targeting is widely utilized in drug delivery purposes specially using nano-radioactive agents. Aims: In this work, we report production and biological evaluation of gallium-67 labeled superparamagnetic iron oxide nanoparticles, embedded by folic acid (67 Ga-SPION-folate) complex especially in tumor-bearing mice for tumor imaging studies. Settings and Design: The structure of SPION-folate was confirmed by X-ray diffraction (XRD), transmission electron microscopy (TEM) and foureir transform infrared spectroscopy (FT-IR) analyses. The radiolabeled SPION-folate formation was confirmed by...