Sharif Digital Repository

A simple platform based on a hairpin oligonucleotide switch and multi-walled carbon nanotubes (MWCNTs) for the ultrasensitive detection of specific DNA sequences has been developed. In this approach, the π-stacking interaction of single-strand DNA-MWCNT was employed to construct an electrochemical DNA biosensor. Changes to the surface conductivity, based on the MWCNT replacement, were monitored by using the electrochemical species [Fe(CN)6]3-/4- as a redox probe. Morphological and voltammetric characterizations of the electrode surface were performed using atomic force microscopy (AFM), energy dispersive spectroscopy (EDS), cyclic voltammetry (CV), differential pulse voltammetry (DPV) and... 

Tissue transglutaminase (TG2) is a unique multifunctional enzyme. The enzyme possesses enzymatic activities such as transamidation/crosslinking and non-enzymatic functions such as cell migration and signal transduction. TG2 has been shown to be involved in molecular mechanisms of cancers and several neurodegenerative diseases such as Alzheimer's disease. The present study aimed at cloning and expression of full length human TG2 in Bac-to-Bac baculovirus expression system and evaluation of its activity. Methods: pFastBac HTA donor vector containing coding sequence of human TG2 was constructed. The construct was transformed to DH10Bac for generating recombinant bacmid. The verified bacmid was... 

In recent years, applications of dielectrophoresis-based platforms have been recognized as effective and dependable approach to separate cells and bioparticles, suspended in different carrier fluids, based on particle size and electrical properties. In this study, a microfluidic device was fabricated by an unprecedented electrode pattern, and several experiments were performed to enrich samples including either of yeast, Escherichia coli, or latex particles. A chemical deposition-based method was employed for fabrication of microelectrodes, inducing nonuniform electric field required for dielectrophoresis-based separation. One major advantage of our employed method is low fabrication cost,... 

A number of human diseases, including Alzheimer's and Parkinson's have been linked to amyloid formation. To search for an anti-amyloidogenic product, alkaloid enriched extract from borage leaves was examined for anti-amyloidogenic activity using Hen Egg White Lysozyme (HEWL) as a model protein. After isolation of the plant extract using rHPLC, only one fraction indicated a significant bioactivity. TEM analysis confirmed a remarkable reduction of amyloid fibrils in the presence of the bioactive fraction. To identify the effective substance in the fraction, mass spectrometry, FTIR, and NMR were performed. Our analyses determined that the bioactive compound as... 

Hepcidin is a peptide hormone that plays an important role in iron metabolism. We have produced a recombinant mouse hepcidin-1 by using baculovirus expression system. Its expression yield was 25 μg/ml when cell culture media were supplemented with a protease inhibitor cocktail. The recombinant mouse hepcidin-1 and synthetic human hepcidin-25 had similar effects on reducing ferroportin expression in J774A cell line and in peritoneal macrophages. However, synthetic human hepcidin-25 was more efficient than recombinant mouse hepcidin-1 in reducing iron concentration in blood circulation (p < 0.01)  

Xanthene dyes, such as fluorescein and rhodamine, have played crucial rules in biological sciences especially covalent attachment of these organic compounds to biomolecules. 3-O-methylfluorescein and 3,6-O-dimethylfluorescein were synthesized and purified using a facile procedure. 3,6-O-dimethylfluorescein, which lacks fluorescence, was treated with sodium hydroxide and sulfuric acid solutions, giving rise to yellow and green fluorescent compounds, respectively. In both basic and acidic conditions, donor-acceptor structures were formed. The reaction of 3,6-O-dimethylfluorescein with acids, in a reversible manner, emitted green fluorescence, whereas its reaction with hydroxide ion,... 

A number of conformational diseases in humans have been associated with protein/peptide fibrillation known as amyloid. Although extensive studies have been conducted in understanding the molecular basis of amyloid formation, a detailed mechanism is still missing. Experimentally, HEWL (hen egg white lysozyme) has been exploited ubiquitously as a model protein for amyloid fibrillation and drug inhibition. However, computational studies investigating fibril formation of HEWL have been a difficult task to perform mainly due to high stability of lysozymes and the absence of crystal structures of HEWL fibril oligomers. In this study, we have examined various conditions of HEWL amyloid formation... 

Surface functionality of nanoparticles has been pivotal in defining interactions of nanoparticles and biomolecules. To explore various functionalities on the surface of nanoparticle through a facile procedure, various carbon-based nanoparticles, modified with a specific natural amino acid, were synthesized; the amino acids were chosen in order that almost all classes of amino acids were included. After characterizations of the nanoparticles using several spectroscopic methods, the effects of surface modification of nanoparticles were examined against amyloid formation, exploiting insulin as a model amyloidogenic polypeptide. Although most amino acids afforded carbon nanoparticles, only... 

The release of anticoagulant drugs such as warfarin from human serum albumin (HSA) has been important not only mechanistically but also clinically for patients who take multiple drugs simultaneously. In this study, the role of some commonly used drugs, including s-ibuprofen, ascorbic acid, and salicylic acid, was investigated in the release of warfarin bound to HSA in silico. The effects of the aforementioned drugs on the HSA-warfarin complex were investigated with molecular dynamics (MD) simulations using two approaches; in the first perspective, molecular docking was used to model the interaction of each drug with the HSA-warfarin complex, and in the second approach, drugs were positioned... 

in recent decades, DEP due to its high efficiency has been exploited widely in separation and manipulation of bioparticles. In the present work a simple, low-cost, and efficient procedure for fabrication of microfluidic chips applied in medicine and biochemistry has been presented. In this method, electrodes are not in direct contact with biological samples which results in elimination of conventional systems' cons. Efficacy of the designed system has been evaluated by injecting samples containing yeast and Ecoli cells into the system and analyzing their trajectory. Experimental results demonstrate that precise adjustment of voltage and frequency can lead to the desired separation in this... 

Conformational diseases have been investigated extensively in recent years; as a result, a number of drug candidates have been introduced as amyloid inhibitors; however, no effective therapies have been put forward. RS-0406 with pyridazine as its core chemical structure has so far shown promising results in inhibiting amyloid formation. In the present work, using molecular dynamics, we undertook the investigation of RS-0406 interactions with U-shaped Aβ1−42 and Aβ1−40 pentamers, Aβ1−42 monomers, and double-horseshoe-like Aβ1−42. To set better parameters for the small molecule, experimental and computational log P values were obtained. In addition, an analogue of RS-0406 was also simulated... 

Conformational diseases, constituting a large number of diseases, have been connected with protein misfolding, leading to aggregation known as amyloid fibrils. Mainly due to the lack of detailed molecular mechanisms, there has not been an effective drug to combat amyloid-associated diseases. Recently, a small organic pyridazine-based molecule (RS-0406) has shown significant reductions in amyloid fibrils in both in vitro and in vivo animal studies. However, no information on molecular details of inhibition for the small molecule has been reported. In this work, we have decided to explore structure-activity relationship of pyridazine-based compounds to investigate structural parameters for... 

Hen egg white lysozyme (HEWL) was exploited for the synthesis of β-amino carbonyl compounds through a direct and three-component Mannich reaction in aqueous, confirming high chemoselectivity toward imine. In order to further extend the applications of the enzyme, HEWL was encapsulated using a metal-organic framework (MOF). The reactivity, stereoselectivity, and reusability of the encapsulated enzyme were investigated. The reaction was significantly enhanced as compared to the non-encapsulated enzyme. A mutated version of the enzyme, containing Asp52Ala (D52A), lacking important catalytical residue, has lost the bacterial site activity against Micrococcus luteus (M. luteus) while the D52A... 

In this review, effects of initial microstructure before intercritical annealing and processing routes of dual phase (DP) high strength steels are discussed. Prior-applied deformation processes as cold rolling and severe plastic deformation (SPD) including their impacts on mechanical properties of DP steels are described. Influences of heating rate, recrystallization of ferrite, nucleation and grain growth of austenite on the microstructure evolution are also presented. The intercritical annealing and thermomechanical processes of DP steels are comparatively outlined. Furthermore, post-intercritical annealing treatments, i.e., tempering, bake hardening, strain and quench aging are argued.... 

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... 

Designing drug delivery systems for therapeutic compounds whose receptors are located in the cytosol of cells is challenging as a bilayer cell membrane is negatively charged. The newly designed drug delivery systems should assist the mentioned drugs in passing the membrane barriers and achieving their targets. This study concentrated on developing novel ionic liquids (ILs) that interact effectively with cell membranes. These ILs are based on glucose-containing choline and are expected to be non-toxic. The binding energies of the known pharmaceutically active ionic liquids were calculated at the B3LYP/6-311++G(d,p) level in the gas phase and compared with those of our newly designed... 

DNA polymerase η (polη) is of significant value for designing new families of anticancer drugs. This protein takes a role in many stages of the cell cycle, including DNA replication, translesion DNA synthesis, and the repairing process of DNA. According to many studies, a high level of expression of polη in most cases has been associated with low rates of patients' survival, regardless of considering the stage of tumor cells. Thus, the design of new drugs with fewer side effects to inhibit polη in cancerous cells has attracted attention in recent years. This project aims to design and explore the alternative inhibitors for polη, which are based on carbohydrates and amino acids. In terms of... 

PIM-1 is a serine-threonine kinase mainly expressed in tissues like the Thymus, spleen, bone marrow, and liver. Overexpression of PIM kinases occurs in various types of human tumours, such as lymphomas, prostate cancer, and oral cancer. As a result, the design of drugs to inhibit PIM-1 in cancerous cells has attracted much attention in recent years. This study aimed to design the alternative inhibitors for PIM-1 kinase, which are based on carbohydrates and amino acids and are expected to be non-toxic with the same chemotherapeutic effects as the traditional known anticancer drugs. The combinatorial use of quantum mechanics (QM) and molecular dynamic simulation (MD) has enabled us to...