Sharif Digital Repository

The synthesis of a new drug delivery system based on hybrid nanomaterials containing a β-CD core and hyperbranched PG is described. Conjugating PG branches onto β-CD not only increases its water solubility but also affects its host/guest properties deeply. It can form molecular inclusion complexes with small hydrophobic guest molecules such as ferrocene or FITC with reasonable release. In addition, the achievable payloads are significantly higher as for carriers such as hyperbranched PGs. Short-term in vitro cytotoxicity and hemocompatibility tests on L929 cell lines show that the hybrid nanomaterial is highly biocompatible. Due to their outstanding properties, β-CD-g-PG hybrid nanomaterials... 

Coaxial electrospinning with the ability to use simultaneously two separate solvents provides a promising strategy for drug delivery. Nevertheless, controlled release of hydrophilic and sensitive therapeutics from slow biodegradable polymers is still challenging. To address this gap, we fabricated core-sheath fibers for dual delivery of lysozyme, as a model protein, and phenytoin sodium as a small therapeutic molecule. The sheath was processed by a gelatin solution while the core fibers were fabricated from an aqueous gelatin/PVA solution. Microstructural studies by transmission and scanning electron microscopy reveal the formation of homogeneous core-sheath nanofibers with an outer and... 

Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. A systems genetics approach across 100 in-bred strains of mice demonstrated that collagen V is a critical driver of postinjury heart function. We show that collagen V deficiency alters the mechanical properties of scar tissue, and altered reciprocal feedback between matrix and cells induces... 

A single step supercritical method was introduced for synthesis of “magnetite - reduced graphene oxide (M-rGO)” composite in supercritical methanol. Modified surface, smaller size, lesser cytotoxicity, and homogenous dispersion of Fe3O4 nanoparticles on the graphene surface were advantages of this new M-rGO composite in comparison to the materials synthesized by conventional wet chemical method (M-GO). Nanocomposites were injected in tissue equivalent phantoms of agarose gel in 10 mg/g dosage, and were irradiated by a 1600 mW laser beam at wavelength of 800–810 nm. The M-rGO and M-GO were found to be the most and the least efficient samples for increasing the temperature of the phantom. As... 

Controlling topographic features at all length scales is of great importance for the interaction of cells with tissue regenerative materials. We utilized an indirect three-dimensional printing method to fabricate polymeric scaffolds with pre-defined and controlled external and internal architecture that had an interconnected structure with macro- (400-500 μm) and micro- (∼25 μm) porosity. Polycaprolactone (PCL) was used as model system to study the kinetics of tissue growth within porous scaffolds. The surface of the scaffolds was decorated with TiO2 and bioactive glass (BG) nanoparticles to the better match to nanoarchitecture of extracellular matrix (ECM). Micrometric BG particles were... 

Cervical cancer is the second-most-common cause of malignancies in women worldwide, and the oncogenic activity of the human papilloma virus types (HPV) E7 protein has a crucial role in anogenital tumors. In this study, we have designed a therapeutic vaccine based on chitosan nanodelivery systems to deliver HPV-16 E7 DNA vaccine, considered as a tumor specific antigen for immunotherapy of HPV-associated cervical cancer. We have developed a Nano-chitosan (NCS) as a carrier system for intramuscular administration using a recombinant DNA vaccine expressing HPV-16 E7 (NCS-DNA E7 vaccine). NCS were characterized in vitro for their gene transfection ability. Results: The transfection of CS-pEGFP... 

Naïve pluripotency can be established in human pluripotent stem cells (hPSCs) by manipulation of transcription factors, signaling pathways, or a combination thereof. However, differences exist in the molecular and functional properties of naïve hPSCs generated by different protocols, which include varying similarities with pre-implantation human embryos, differentiation potential, and maintenance of genomic integrity. We show here that short treatment with two chemical agonists (2a) of nuclear receptors, liver receptor homologue-1 (LRH-1) and retinoic acid receptor gamma (RAR-γ), along with 2i/LIF (2a2iL) induces naïve-like pluripotency in human cells during reprogramming of fibroblasts,... 

Harnessing neural stem cells to repair neuronal damage is a promising potential treatment for neuronal diseases. To enable future therapeutic efficacy, the survival, proliferation, migration and differentiation of neural stem/progenitor cells (NPCs) should be accurately studied and optimized in in vitro platforms before transplanting these cells into the body for treatment purposes. Such studies can determine the appropriate quantities of the biochemical and biomechanical factors needed to control and optimize NPC behavior in vivo. In this study, NPCs were cultured within a microfluidic device while being encapsulated within the collagen matrix. The migration and differentiation of NPCs were... 

In this study, physically cross-linked hydrogels were developed by freezing-thawing method while different concentrations of honey were included into the hydrogels for accelerated wound healing. The hydrogel was composed of chitosan, polyvinyl alcohol (PVA), and gelatin with the ratio of 2:1:1 (v/v), respectively. Further, the effect of honey concentrations on antibacterial properties, and cell behavior was investigated. In vivo studies, including wound healing mechanism using rat model and histological analysis of section tissue samples were performed. The results illustrated that the incorporation of honey in hydrogels increased the ultimate strain of hydrogels approximately two times,... 

miR-29b2 and miR-29c play a suppressive role in breast cancer progression. C1orf132 (also named MIR29B2CHG) is the host gene for generating both microRNAs. However, the region also expresses longer transcripts with unknown functions. We employed bioinformatics and experimental approaches to decipher C1orf132 expression and function in breast cancer tissues. We also used the CRISPR/Cas9 technique to excise a predicted C1orf132 distal promoter and followed the behavior of the edited cells by real-time PCR, flow cytometry, migration assay, and RNA-seq techniques. We observed that C1orf132 long transcript is significantly downregulated in triple-negative breast cancer. We also identified a... 

Nanomedicine has seen a significant rise in the development of new research tools and clinically functional devices. In this regard, significant advances and new commercial applications are expected in the pharmaceutical and orthopedic industries. For advanced orthopedic implant technologies, appropriate nanoscale surface modifications are highly effective strategies and are widely studied in the literature for improving implant performance. It is well-established that implants with nanotubular surfaces show a drastic improvement in new bone creation and gene expression compared to implants without nanotopography. Nevertheless, the scientific and clinical understanding of mixed oxide... 

Nanomedicine has seen a significant rise in the development of new research tools and clinically functional devices. In this regard, significant advances and new commercial applications are expected in the pharmaceutical and orthopedic industries. For advanced orthopedic implant technologies, appropriate nanoscale surface modifications are highly effective strategies and are widely studied in the literature for improving implant performance. It is well-established that implants with nanotubular surfaces show a drastic improvement in new bone creation and gene expression compared to implants without nanotopography. Nevertheless, the scientific and clinical understanding of mixed oxide... 

Animal models and traditional cell cultures are essential tools for drug development. However, these platforms can show striking discrepancies in efficacy and side effects when compared to human trials. These differences can lengthen the drug development process and even lead to drug withdrawal from the market. The establishment of preclinical drug screening platforms that have higher relevancy to physiological conditions is desirable to facilitate drug development. Here, a heart-on-a-chip platform, incorporating microgrooves and electrical pulse stimulations to recapitulate the well-aligned structure and synchronous beating of cardiomyocytes (CMs) for drug screening, is reported. Each chip... 

An effect-directed analysis (EDA) of fresh and artificially weathered (evaporated, photooxidized) samples of North Sea crude oil and residual heavy fuel oil is presented. Aliphatic, aromatic, and polar oil fractions were tested for the presence of aryl hydrocarbon receptor (AhR) agonist and androgen receptor (AR) antagonist, demonstrating for the first time the AR antagonist effects in the aromatic and, to a lesser extent, polar fractions. An extension of the typical EDA strategy to include an N-way partial least-squares (N-PLS) model capable of relating the comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS) data set to the bioassay data... 

Novel types of highly swelling hydrogels (superabsorbent) were prepared by grafting crosslinked poly acrylic acid-co-2-hydroxyethylmetacrylate (PAA-co-HEMA) chains onto starch through a free radical polymerization method. The effect of grafting variables (i.e., concentration of methylenebisacrylamide (MBA), acrylic acid/2-hydroxy methymetacrylate (AA/HEMA) weight ratio, ammonium persulfate (APS), starch, neutralization percent, were systematically optimized to achieve a hydrogel with a maximum swelling capacity. The superabsorbent (SAP) formation was confirmed by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The controlled-release behavior of... 

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...