MJ Rasaee

Epitope mapping of epidermal growth factor receptor (EGFR) monoclonal antibody and induction of growth-inhibitory polyclonal antibodies by vaccination with EGFR mimotope. (2014)

One of the proposed approaches in cancer therapy is to induce and direct the patients own immune system against cancer cells. In this study, we determined the epitope mapping of the rat anti-human epi...dermal growth factor receptor (EGFR) monoclonal antibody ICR-62 using a phage display of random peptide library and identified a 12 amino acids peptide, which was recognized as a mimotope. The peptide was synthesized and conjugated to bovine serum albumin (BSA) as carrier protein (P-BSA). We have shown that ICR-62 can react specifically with P-BSA as well as native EGFR. Two rabbits were immunized either by BSA or P-BSA and the rabbits IgGs were purified and examined for binding to the antigens, mimotope and the EGFR protein purified from the EGFR overexpressing A431 cell line. We showed that the rabbit IgG generated against the mimotope is capable of inhibiting the growth of A431 cells by 15%, but does not have any effect on the growth of EGFR-negative MDA-MB-453 cell line in vitro. Our results support the need for further investigations on the potential of vaccination with either mimotope of the EGFR or epitope displayed on the surface of phage particles for use in active immunotherapy of cancer. Read more
Immunopharmacology and immunotoxicology

MJ Rasaee

Combined MUC1-specific nanobody-tagged PEG-polyethylenimine polyplex targeting and transcriptional targeting of tBid transgene for directed killing of MUC1 over-expressing tumour cells. (2011)

We provide evidence for combining a single domain antibody (nanobody)-based targeting approach with transcriptional targeting as a safe way to deliver lethal transgenes to MUC1 over-expressing cancer ...cells. From a nanobody immune library, we have isolated an anti-DF3/Mucin1 (MUC1) nanobody with high specificity for the MUC1 antigen, which is an aberrantly glycosylated glycoprotein over-expressed in tumours of epithelial origin. The anti-MUC1 nanobody was covalently linked to the distal end of poly(ethylene glycol)(3500) (PEG(3500)) in PEG(3500)-25kDa polyethylenimine (PEI) conjugates and the resultant macromolecular entity successfully condensed plasmids coding a transcriptionally targeted truncated-Bid (tBid) killer gene under the control of the cancer-specific MUC1 promoter. The engineered polyplexes exhibited favourable physicochemical characteristics for transfection and dramatically elevated the level of Bid/tBid expression in both MUC1 over-expressing caspase 3-deficient (MCF7 cells) and caspase 3-positive (T47D and SKBR3) tumour cell lines and, concomitantly, induced considerable cell death. Neither transgene expression nor cell death occurred when the MUC1 promoter was replaced with the CNS-specific synapsin I promoter. Since PEGylated PEI was only responsible for DNA compaction and played no significant role in direct transfection and cell killing, our attempts overcome previously reported PEI-mediated apoptotic and necrotic cell death, which is advantageous for future in vivo transcriptional targeting as this will minimize (or eliminate) non-targeted cell damage. Read more
Journal of controlled release : official journal of the Controlled Release Society

Mohammad Najafi

Human PON promoters: from similarity to prediction of polymorphic positions within transcription factor elements. (2010)

The human paraoxonases (PON) are a group of anti-oxidative enzymes that catalyze important reactions in body. Some polymorphic variations within the PON genes have been reported to relate with several... diseases. In this article, the polymorphisms of the PON upstream regions were evaluated to predict their positions within elements of transcription factors by similarity tools. However, taxonomy studies suggested the PON2 duplication on the chromosome 7 but pairwise alignments did not show vast similarity among the fragments of PON promoters. Multiple sequence alignment (MSA) tool showed the PON1 T-107C and PON3 C-31T positions are conserved within several transcription elements. Based on these tools, the review assumes that the PON upstream regions have no similarity and only two polymorphisms are considered to interact with several transcription factors. Read more
Mini reviews in medicinal chemistry

MJ Rasaee

Nanobody-based chimeric receptor gene integration in Jurkat cells mediated by φC31 integrase. (2011)

The crucial role of T lymphocytes in anti-tumor immunity has led to the development of novel strategies that can target and activate T cells against tumor cells. Recombinant DNA technology has been us...ed to generate non-MHC-restricted chimeric antigen receptors (CARs). Here, we constructed a panel of recombinant CAR that harbors the anti-MUC1 nanobody and the signaling and co-signaling moieties (CD3ζ/CD28) with different spacer regions derived from human IgG3 with one or two repeats of the hinge sequence or the hinge region of FcγRII. The PhiC31 integrase system was employed to investigate if the recombination efficiency could be recruited for high and stable expression of T cell chimeric receptor genes. The effect of nuclear localization signal (NLS) and two different promoters (CMV and CAG) on efficacy of PhiC31 integrase in human T cell lines was evaluated. The presence of integrase in combination with NLS, mediated up to 7.6 and 8.5 fold increases in CAR expression in ZCHN-attB and ZCHHN-attB cassette integrated T cells, respectively. Our results showed that highly efficient and stable transduction of the Jurkat cell line by PhiC31 integrase is a feasible modality for generating anti-cancer chimeric T cells for use in cancer immunotherapy. Read more
Experimental cell research

MJ Rasaee

Selection of DNA aptamers against Human Cardiac Troponin I for colorimetric sensor based dot blot application. (2015)

Troponin T and I are ideal markers which are highly sensitive and specific for myocardial injury and have shown better efficacy than earlier markers. Since aptamers are ssDNA or RNA that bind to a wid...e variety of target molecules, the purpose of this research was to select an aptamer from a 79bp single-stranded DNA (ssDNA) random library that was used to bind the Human Cardiac Troponin I from a synthetic nucleic acids library by systematic evolution of ligands exponential enrichment (Selex) based on several selection and amplification steps. Human Cardiac Troponin I protein was coated onto the surface of streptavidin magnetic beads to extract specific aptamer from a large and diverse random ssDNA initial oligonucleotide library. As a result, several aptamers were selected and further examined for binding affinity and specificity. Finally TnIApt 23 showed beast affinity in nanomolar range (2.69nM) toward the target protein. A simple and rapid colorimetric detection assay for Human Cardiac Troponin I using the novel and specific aptamer-AuNPs conjugates based on dot blot assay was developed. The detection limit for this protein using aptamer-AuNPs-based assay was found to be 5ng/ml. Read more
Journal of biotechnology

rahman hallaj

Simultaneous determination of ascorbic acid, uric acid and neurotransmitters with a carbon ceramic electrode prepared by sol-gel technique. (2006)

A sol-gel carbon composite electrode (CCE) has been prepared by mixing a sol-gel precursor (e.g. methyltrimethoxysilane) and carbon powder without adding any electron transfer mediator or specific rea...gents. It was demonstrated that this sensor can be used for simultaneous determination ascorbic acid, neurotransmitters (dopamine and adrenaline) and uric acid. Direct electrochemical oxidation of ascorbic acid, uric acid and catecholamines at a carbon composite electrode was investigated. The experimental results were compared with other common carbon based electrodes, specifically, boron doped diamond, glassy carbon, graphite and carbon paste electrodes. It was found that the CCE shows a significantly higher of reversibility for dopamine. In addition, in comparison to the other electrodes used, for CCE the oxidation peaks of uric acid, ascorbic acid and catecholamines in cyclic and square wave voltammetry were well resolved at the low positive potential with good sensitivity. The advantages of this sensor were high sensitivity, inherent stability and simplicity and ability for simultaneous determination of uric acid, catecholamines and ascorbic acid without using any chromatography or separation systems. The analytical performance of this sensor has been evaluated for detection of biological molecules in urine and serum as real samples. Read more
Talanta

Reza Salman Yazdi

Effect of Ramadan Fasting on Stress Neurohormones in Women with Polycystic Ovary Syndrome. (2015)

To determine the effects of Ramadan fasting on serum levels of stress neurohormones in Iranian women with polycystic ovary syndrome (PCOS). Read more
Journal of family & reproductive health

Vahid Asgary

Green synthesis and evaluation of silver nanoparticles as adjuvant in rabies veterinary vaccine. (2016)

Green synthesis of nanoparticles by plant extracts plays a significant role in different applications. Recently, several studies were conducted on the use of nanoparticles as adjuvant. The main aim of... this study was to evaluate green synthesized silver nanoparticles (AgNPs) as adjuvant in rabies veterinary vaccine and compare the results with the existing commercially available alum adjuvant. Read more
International journal of nanomedicine

Adnan Kisa

Sexual harassment and its consequences: a study within Turkish hospitals. (2002)

Sexual harassment remains a universal factor that can affect nursing performance and worker productivity in any type of health care facility. There are few studies in this area that have been conducte...d in developing countries. To measure the occurrence of sexual harassment, a questionnaire was given to 353 nurses in two different hospitals yielding a response rate of 61%. Overall, the majority of the respondents (n = 157 out of 251) reported that they had been subjected to sexual harassment in the workplace, and the harassment experience was strong enough to affect worker productivity. In addition, many nurses reported the belief that sexual harassment remains a disturbing problem in this developing country that should not be ignored. Based on these findings, implications for policy and further study are suggested. Read more
Journal of health & social policy

MJ Rasaee

The effect of exercise mode and intensity of sub-maximal physical activities on salivary testosterone to cortisol ratio and α-amylase in young active males.

We examined the effect of exercise intensity and mode on the acute responses of free testosterone to cortisol ratio and salivary α-amylase. We also evaluated the relationship between cortisol and sali...vary α-amylase. Ten healthy young active males participated voluntarily in this study in six single sessions. They exercised on a cycle ergo meter, treadmill, and elliptical instrument at intensities of 70% and 85% maximum heart rate for 25 minutes. Saliva samples were collected 5 minutes before and 5 minutes after each exercise session. No significant changes were observed for cortisol. Free testosterone to cortisol ratio increased during each exercise session (F5, 45=3.15, P=0.02). However, these changes are only significant after exercise on the treadmill at 70% maximum heart rate (t=2.94, P=0.02) and 85% maximum heart rate (t=0.53, P=0.03). Salivary α-amylase significantly varied among exercise sessions (F5, 45=3.97, P=0.005), and a significant decline was observed after exercise on the elliptical instrument (t=2.38, P=0.04) and treadmill (t=3.55, P=0.006) at 85% maximum heart rate. We found that the free testosterone to cortisol ratio is dependent on the exercise mode, while the salivary α-amylase response is dependent on the intensity of exercise. The increase of free testosterone to cortisol ratio in this study may indicate lower physiological stress in response to performing these exercises. Applying muscular strength with moderate intensity weight-bearing exercises possibly activates the anabolic pathways. Although the cortisol and salivary α-amylase responses were opposite in the majority of the exercise sessions, no significant inverse relationship was observed. Read more
International journal of exercise science

MJ Rasaee

[3D structure of DKK1 indicates its involvement in both canonical and non-canonical Wnt pathways].

Dikkoppf-1 (DKK1) is an antagonist of the canonical Wnt signaling pathway. The importance of DKK1 as a diagnostic and therapeutic agent in a wide range of diseases along with its significance in a var...iety of biological processes accentuate the necessity to decipher its 3D structure that would pave the way towards the development of relevant selective inhibitors. A DKK1 structure model predicted by the Robetta server with structural refinements including a 10 ns molecular dynamics run was subjected to functional and docking analyses. We hypothesize that the N-terminal region of the DKK1 molecule could be functionally important for both canonical and noncanonical Wnt pathways. Moreover, it seems that DKK1 could be involved in interactions with the Frizzled receptors, leading to the activation of the Planar Cell Polarity (PCP) pathway (activation of Jun N-terminal kinase (JNK) Pathway) and Wnt/Ca^(2+) pathway (activation of CamKII). Read more
Molekuliarnaia biologiia

MJ Rasaee

Production and characterization of a recombinant chimeric antigen consisting botulinum neurotoxin serotypes A, B and E binding subdomains. (2010)

Botulinum neurotoxins (BoNTs) are potent toxicant proteins composed of a heavy chain (100 kDa) and a light chain (50 kDa) of seven (A-G) serotypes that is responsible for botulism syndrome. In this st...udy, polypeptides from C-terminal heavy chain of BoNTs serotypes A, B and E to the length of 54, 45 and 48 amino acid respectively were selected, linked together using a hydrophobic linker and expressed in E. coli. The expression efficiency of the chimeric protein was found to be 51%. The chimeric protein was produced in the form of inclusion body (IB) both at two studied temperatures, 30 degrees C and 37 degrees C. This IB was extracted by ultracentrifugation and followed for chimeric protein solubilization and purification using of ultrafiltration and preparative electrophoresis. The purified chimeric protein was characterized using blotting and ELISA. To evaluate the protection ability of this chimeric antigen against their active toxins, it was injected to mice and the antibody titer as well as the extent of protectivity were determined. Mice given three injections (10 microg/mice) of the antigen were protected against an intra-peritoneal administration of 10 LD(50 )of serotypes A and E, but 100 LD(50) of serotype B. We conclude that a significant correlation exists between the antigenic characteristics and protection capability of the chimeric protein prepared in this study. Read more
The Journal of toxicological sciences

rahman hallaj

A highly sensitive prostate-specific antigen immunosensor based on gold nanoparticles/PAMAM dendrimer loaded on MWCNTS/chitosan/ionic liquid nanocomposite. (2014)

We have developed a sensitive electrochemical immunosensor for the detection of prostate-specific antigen (PSA), based on covalently immobilizing of anti-PSA and redox mediator (thionine) onto gold na...noparticles-incorporated polyamidoamine dendrimer (AuNPs-PAMAM) and multiwalled carbon nanotubes/ionic liquid/chitosan nanocomposite (MWCNTs/IL/Chit) as the support platform. The MWCNTs/IL/Chit nanocomposite and synthesized AuNPs were characterized using SEM and TEM microscopy techniques. Greatly amplified immunoassay was established by sandwiching the antigen between anti-PSA immobilized on the MWCNTs/IL/Chit/AuNPs-PAMAM interface and anti-PSA labeled with horseradish peroxidase (HRP-labeled anti-PSA) as secondary antibody. Phtaloyl chloride (Ph) was used as linking agent for the subsequent immobilization of AuNPs-PAMAM onto platform and anti-PSA antibody and thionine onto AuNPs-PAMAM dendrimer. The increased electrocatalytic reduction of H2O2 by HRP was monitored by differential pulse voltammetry technique. Under optimized condition the calibration curve for PSA concentration was linear up to 80 ng ml(-1) with detection limit (signal-to-noise ratio of 3) of 1 pg ml(-1). AuNPs-PAMAM dendrimer as platform not only increased the amount of thionine and PSA antibody but also the electron transfer process accelerated by encapsulated AuNPs. Moreover, the proposed PSA immunosensor exhibited excellent stability and reproducibility. Accurate detection of PSA in human serum samples was demonstrated by comparison to standard ELISA assays. In addition, impedance technique was used as simple, rapid, low cost label free analytical method for PSA measurement with detection limit of 0.5 ng ml(-1) at concentration range up to 25 ng ml(-1). The results indicate that the present protocol is quite promising in developing other electrochemical immunosensors. Read more
Biosensors & bioelectronics

rahman hallaj

Immobilization of [Cu(bpy)2]Br2 complex onto a glassy carbon electrode modified with alpha-SiMo12O40(4-) and single walled carbon nanotubes: application to nanomolar detection of hydrogen peroxide and bromate. (2009)

A simple procedure has been used for preparation of modified glassy carbon electrode with carbon nanotubes and copper complex. Copper complex [Cu(bpy)(2)]Br(2) was immobilized onto glassy carbon (GC) ...electrode modified with silicomolybdate, alpha-SiMo(12)O(40)(4-) and single walled carbon nanotubes (SWCNTs). Copper complex and silicomolybdate irreversibly and strongly adsorbed onto GC electrode modified with CNTs. Electrostatic interactions between polyoxometalates (POMs) anions and Cu-complex, cations mentioned as an effective method for fabrication of three-dimensional structures. The modified electrode shows three reversible redox couples for polyoxometalate and one redox couple for Cu-complex at wide range of pH values. The electrochemical behavior, stability and electron transfer kinetics of the adsorbed redox couples were investigated using cyclic voltammetry. Due to electrostatic interaction, copper complex immobilized onto GC/CNTs/alpha-SiMo(12)O(40)(4-) electrode shows more stable voltammetric response compared to GC/CNTs/Cu-complex modified electrode. In comparison to GC/CNTs/Cu-complex the GC/CNTs/alpha-SiMo(12)O(40)(4-) modified electrodes shows excellent electrocatalytic activity toward reduction H(2)O(2) and BrO(3)(-) at more reduced overpotential. The catalytic rate constants for catalytic reduction hydrogen peroxide and bromate were 4.5(+/-0.2)x10(3) M(-1) s(-1) and 3.0(+/-0.10)x10(3) M(-1) s(-1), respectively. The hydrodynamic amperommetry technique at 0.08 V was used for detection of nanomolar concentration of hydrogen peroxide and bromate. Detection limit, sensitivity and linear concentration range proposed sensor for bromate and hydrogen peroxide detection were 1.1 nM and 6.7 nA nM(-1), 10 nM-20 microM, 1 nM, 5.5 nA nM(-1) and 10 nM-18 microM, respectively. Read more
Analytica chimica acta

MJ Rasaee

Preparation and biological evaluation of (177)Lu conjugated PR81 for radioimmunotherapy of breast cancer. (2011)

PR81 is a monoclonal antibody that binds with high affinity to MUC1 antigen that is over expressed in 80% of breast cancers. In this study, we developed a method for indirect labeling of PR81 with lut...etium-177 and performed all preclinical qualifications in production of a biologic agent for radioimmunotherapy of breast cancer. Read more
Nuclear medicine and biology

Ammar Mohseni

Photoinactivation related dynamics of ctenophore photoproteins: Insights from molecular dynamics simulation under electric-field. (2017)

Photoinactivation is a common phenomenon in bioluminescence ctenophore photoproteins (e.g mnemiopsin, berovin and BfosPP) with still unknown mechanism. The activity of coelenterate photoproteins (e.g ...aequorin), which has high structural similarity with ctenophore photoproteins, is not affected by light. Recently, we have characterized the effects of light on ctenophore photoprotein mnemiopsin, in different conformations, which has demonstrated light induced structural changes, uniquely secondary structures, of both apo and holo mnemiopsin. This paper is further expansion of our previous work, by applying molecular dynamics simulations to investigate photoinactivation related dynamics of berovin at atomistic level, in comparison with aequorin, under the influence of electric component of electromagnetic field. The results have indicated that the intense electric filed could influence structure of both berovin and aequorin but in different manner, whereas moderate electric field only effects on berovins structure remarkably. In this case, increased helicity of residues E180-M193 and decreased helical contents of L38-D46 and L125-D138 segments are considerable in berovin as well as flexibility elevation of calcium binding loops. These changes cause structural expansion of berovin, especially at N-terminal domain, in direction of electric field. In conclusion, the induced structural changes of mentioned helical parts together with elevated fluctuation of their adjacent segments, N26-D46 and M193-Y206, indicate the influence of light on substrate stabilizing residues, Arg41 and Y204. This condition could presumably leads to inactivation of bioluminescence reaction due to separation of substrate from the cavity of the protein. Read more
Biochemical and biophysical research communications

MJ Rasaee

Anti-MUC1 nanobody can redirect T-body cytotoxic effector function. (2009)

Chimeric antigen T cell receptors provide a good approach for adoptive immunotherapy of cancer, especially in the context of cancerous cells that fail to express major histocompatibility complex antig...en and co-stimulatory molecules. Clinical applications of these receptors are limited, mostly due to the xenogenic origin of the antibodies, which cause immunogenic reactions. Nanobodies are the smallest fragments of antibodies that have great homology to human VH and low immunogenic potential. MUC1 is a highly attractive immunotherapeutic target owing to increased expression, altered glycosylation, and loss of polarity in more than 80% of human malignancies. We used anti-MUC1 nanobody as an antigen binding domain, CD28 and CD3zeta as signaling domains, and IgG3 as a spacer in a chimeric receptor construct. This construct was transfected to Jurkat cells. The transfected Jurkat cells were exposed to MUC1-positive MCF7 cells. Then we analyzed the secretion of IL2, proliferation of Jurkat cells, and death of MCF7 cells. These data revealed that the nanobody chimeric receptor can target tumor-associated antigen-positive cells. Regarding the efficient and specific function of nanobody chimeric receptor and non-immunogenic nature of nanobodies, these chimeric receptors might be used as promising candidates for clinical applications. Read more
Hybridoma (2005)

MJ Rasaee

Essential strategies to optimize asymmetric PCR conditions as a reliable method to generate large amount of ssDNA aptamers. (2016)

Asymmetric PCR, a simple method to generate single-stranded DNA (ssDNA) aptamers in systematic evaluation of ligand by exponential enrichments rounds, is coupled with limitations. We investigated the ...essential strategies for optimization of conditions to perform a high-quality asymmetric PCR. Final concentrations of primers and template, the number of PCR cycles, and annealing temperature were selected as optimizing variables. The qualities of visualized PCR products were analyzed by ImageJ software. The highest proportion of interested DNA than unwanted products was considered as optimum conditions. Results revealed that the best values for primers ratio, final template concentration, annealing temperature, and PCR cycles were, respectively, 30:1, 1 ng/μL, 55 °C, and 20 cycles for the first and 50:1, 2 ng/μL, 59 °C, and 20 cycles for other rounds. No significant difference was found between optimized asymmetric PCR results in the rounds of two to eight (P > 0.05). The ssDNA quality in round 10 was significantly better than other rounds (P < 0.05). Generally, the ssDNA product with less dimers, double-stranded DNA (dsDNA), and smear are preferable. The dsDNA contamination is the worst, because it can act as antidote and inhibits aptameric performance. Therefore, to choose the best conditions, the lower amount of dsDNA is more important than other unwanted products. Read more
Biotechnology and applied biochemistry

MJ Rasaee

Radioimmunotherapy of MCF7 breast cancer cell line with 131I-PR81 monoclonal antibody against MUC1: comparison of direct and indirect radioiodination methods. (2010)

PR81 is a monoclonal antibody that binds with high affinity to MUC1, which is over expressed on breast and other tumors. The objective of this study was to compare the two labeling methods (direct and... indirect radioiodination) for application of this antibody against MUC1 as a radioimmunotherapeutical agent.Monoclonal antibody (PR81) against the tandem repeat of the core protein (MUC1) was prepared, characterized, purified, and labeled with 131I using the direct (chloramin-T) and indirect (Fmoc-D-Tyr (tBu)-D-Tyr (tBu)-D-Lys (Boc)-OH (YYK) attached to N-hydroxysuccinimide as a linker between PR81 and 131I) methods. The immunoreactivity of 131I-PR81 and 131I-TP-PR81 complexes with MUC1 (the native protein), BSA-P20 (a 20 amino acid corresponding the tandem repeat of MUC1) and MCF7 cell line were performed by RIA. In vitro stability of 131I-PR81 and 131I-YYK-peptide-PR81 complexes in human serum was determined by thin layer chromatography (TLC). Cell toxicity and in vitro internalization studies were performed with the MCF7 cell line, and the tissue biodistribution of the 131I-PR81 and 131I- YYK-peptide -PR81 complexes was evaluated in normal BALB/c mice at 4, 24 and 48 hrs. The labeling efficiency was determined by measuring the percentage recovery of radioactivity in the final product relative to the initial activity in the shipment vial, was found to be 59.9% +/- 7.9% for direct and 50% +/- 3.2% for indirect methods. 131I-PR81 and 131I- YYK- peptide -PR81 complexes showed high immunoreactivity towards MUC1 protein, BSA-P20 and MCF7 cell line. In vitro stability of the labeled products in human serum which was measured by thin layer chromatography (TLC) was found to be more than 50% over 24 hr for 131I-PR81 and 70% for 131I- YYK-peptide -PR81 complexes. Cell toxicity and in vitro internalization studies showed that the 131I-PR81 and 131I- YYK-peptide -PR81 complexes inhibited 80% growth of the MCF7 cultured cell lines in vitro in a high concentration and up to 40% of the 131I-PR81 and 60% of the 131I- YYK-peptide -PR81 complexes internalized after 24 h. Biodistribution studies were performed in normal BALB/c mice at 4, 24 and 48 hrs post-injection. Thyroid and stomach levels from PR81 labeled with 131I- YYK-peptide were two- to three- fold less than those with directly labeled 131I-PR81, suggesting low recognition of its D-iodotyrosine residue by endogenous deiodinase. These results show that the indirect labeling was better than the indirect labeling and 131I- YYK-peptide -PR81 may be considered as a promising candidate for therapy of breast cancer. Read more
Human antibodies

Esmaeel Azadian

Human RNAi pathway: crosstalk with organelles and cells. (2014)

Understanding gene regulation mechanisms has been a serious challenge in biology. As a novel mechanism, small non-coding RNAs are an alternative means of gene regulation in a specific and efficient ma...nner. There are growing reports on regulatory roles of these RNAs including transcriptional gene silencing/activation and post-transcriptional gene silencing events. Also, there are several known small non-coding RNAs which all work through RNA interference pathway. Interestingly, these small RNAs are secreted from cells toward targeted cells presenting new communication approach in cell-cell or cell-organ signal transduction. In fact, understanding cellular and molecular basis of these pathways will strongly improve developing targeted therapies and potent and specific regulatory tools. This study will review some of the most recent findings in this subject and will introduce a super-pathway RNA interference-based small RNA silencing network. Read more
Functional & integrative genomics

Reza Salman Yazdi

Abdominal obesity can induce both systemic and follicular fluid oxidative stress independent from polycystic ovary syndrome. (2015)

The abdominal form of obesity is prevalent in women with polycystic ovary syndrome (PCOS). Visceral fat accumulation seems to play an important role in etiology of PCOS. In this cross-sectional study ...we evaluated the association of oxidative stress (OS) induced with PCOS and abdominal obesity in serum and follicular fluid (FF) of infertile women. Read more
European journal of obstetrics, gynecology, and reproductive biology

rahman hallaj

Amperometric and voltammetric detection of hydrazine using glassy carbon electrodes modified with carbon nanotubes and catechol derivatives. (2008)

A simple procedure was developed to prepare a glassy carbon (GC) electrode modified with carbon nanotubes (CNTs) and catechol compounds. First, 25 microL of DMSO-CNTs solutions (0.4 mg/mL) was cast on... the surface of GC electrode and dried in air to form a CNTs film. Then the GC/CNTs modified electrode immersed into a chlorogenic acid, catechine hydrate and caffeic acid solution (electroless deposition) for a short period of time (2-80s). The cyclic voltammogram of the modified electrode in aqueous solution shows a pair of well-defined, stable and nearly reversible redox couple (quinone/hydroquinone) with surface confined characteristics. The combination of unique electronic and electrocatalytic properties of CNTs and catechol compounds results in a remarkable synergistic augmentation on the response. The electrochemical reversibility and stability of modified electrode prepared with incorporation of catechol compound into CNTs film was evaluated and compared with usual methods for attachment of catechols to electrode surfaces. The transfer coefficient (alpha), heterogeneous electron transfer rate constants (k(s)) and surface concentrations (Gamma) for GC/CNTs/catechol compound modified electrodes were calculated through the cyclic voltammetry technique. The modified electrodes showed excellent catalytic activity, fast response time and high sensitivity toward oxidation of hydrazine in phosphate buffer solutions at pH range 4-8. The modified electrode retains its initial response for at least 2 months if stored in dry ambient condition. The properties of modified electrodes as an amperometric sensor for micromolar or lower concentration detection of hydrazine have been characterized. Read more
Talanta

Mohammad Najafi

The sdLDL reduces MRC1 expression level and secretion of histamine in differentiated M2-macrophages from patients with coronary artery stenosis. (2017)

The macrophage polarization is proposed to be involved in initial events and remodeling of atherosclerosis plaques. Mannose receptor, C type 1 (MRC1) is a trans-membrane glycoprotein participating in ...phagocytosis and, is highly expressed in the M2 macrophages. The aim of this study was to investigate the effects of sdLDL (small dense LDL) on the MRC1 gene expression level and secretion of histamine in the differentiated M2 macrophages from monocytes of patients with coronary artery stenosis and healthy subjects. The monocytes were isolated from healthy subjects (< 5% stenosis) and patients (>70% stenosis, SVD (Single Vessel Disease), 2VD (Two-Vessel Disease) and 3VD (Three-Vessel Disease)) by RosetteSep kit and, were differentiated into M2 macrophages by macrophage colony-stimulating factor (M-CSF). The sdLDL particles were obtained by PEG-combined precipitation method. The MRC1 gene expression and histamine levels were measured by RT-qPCR and ELISA techniques, respectively. The MRC1 gene expression level was significantly increased in M2 macrophages of healthy subjects (P=0.05) while it reduced in SVD (P=0.05), 2VD (P=0.01) and 3VD (P=0.9) patients after treatment with sdLDL. The histamine value secreted from M2 macrophages (7-day) was higher (>3-fold, P=0.02) in patients as compared to healthy controls. The results showed that the sdLDL particles reduce the MRC1 gene expression levels in the differentiated M2 macrophages from patients with coronary artery disease. Furthermore, they had high inflammatory capacity for the secretion of histamine. Read more
Cardiovascular & hematological disorders drug targets

MJ Rasaee

A caspase 8-based suicide switch induces apoptosis in nanobody-directed chimeric receptor expressing T cells. (2012)

In accordance with the two-step hypothesis of T cell activation and the observation that stimulation through the T cell receptor (TCR) alone may lead to anergy, we focused on the introduction of co-st...imulatory signaling to this type of receptors to achieve optimal activation. Enhanced mRNA and cell surface receptor expression via the co-stimulatory gene fragment (OX40) was confirmed by RT-PCR and flow cytometry. Inclusion of the OX40 co-stimulatory signaling region in series with the TCR led to enhanced antigen-induced IL-2 production after stimulation by MUC1-expressing cancer cell lines as compared to the chimeric receptor without OX40. Moreover, with the aim of maintaining high efficiency, while providing a means of controlling any possible unwanted proliferation in vivo, a regulation system was used. This controls the dimerization of a membrane-bound caspase 8 protein. Toward that goal, pFKC8 and CAR constructs were co-transfected into Jurkat cells, and the level of apoptosis was measured. 24 h after addition of the dimerizer, a 91% decrease in transfected cells was observed. Read more
International journal of hematology

MJ Rasaee

Selection of specific inhibitor peptides in enzyme-linked immunosorbent assay (ELISA) of cardiac troponin I using immuno-dominant epitopes as competitor. (2017)

Human cardiac troponin I (cTni) is the gold marker for early diagnosis of myocardial infarction. In this regard, four immune-dominant epitopes of cTni were predicted and their 3D structures were deter...mined. Thereafter, the competitive performance of the peptides was monitored with the developed polyclonal antibody-based indirect competitive ELISA; a half-maximal inhibitory concentration (IC50) of 0.49 (µg/mL) and detection limit of 0.037 (µg/mL) were achieved for recombinant cTni. The competitive ELISA determined sensitivity levels of 0.306, 0.141, 0.960, and 0.155 (µg/mL), respectively, for each peptide as competitor. We indicated that two of the selected epitopes have significant sensitivity scales and inhibition ability. Read more
Journal of immunoassay & immunochemistry

Reza Salman Yazdi

The association of different auto-antibodies against ovarian tissues and gonadotropins and poor ovarian response in intracytoplasmic sperm injection cycles. (2017)

This study aimed to assess the possible association between ovarian auto-antibodies and poor ovarian response to controlled ovarian hyperstimulation (COH) in patients undergoing intracytoplasmic sperm... injection (ICSI) cycles. In total, 42 poor responders and 43 male factor subjects were enrolled in the study and underwent either a standard long gonadotropin-releasing hormone (GnRH) agonist or antagonist protocol. Anti-ovarian, anti-oocyte, anti-zona pellucida (anti-ZP) and anti-gonadotropin antibodies in their sera and follicular fluid (FF) were measured by an enzyme-linked immunosorbent assay technique (ELISA). The mean follicular fluid anti-oocyte antibody [ratio of optical density (OD) sample/OD Control] was significantly higher in poor responders compared to the normal group (2.40 ± 1.55 versus 1.72 ± 0.71, p = 0.012). The linear regression analysis showed an inverse correlation between FF anti-oocyte antibody concentrations and the number of: (i) retrieved oocytes (B = -1.212, r = -0.235, p = 0.030); (ii) mature oocytes (B = -1.042, r = -0.234, p = 0.031); (iii) embryos available (B = -0.713, r = -0.228, p = 0.036); and (iv) good quality embryos (B = -0.369, r = -0.229, p = 0.035). However, there were no significant differences between two groups in terms of FF and serum anti-ovarian, anti-gonadotropins and anti-ZP antibodies. The Pearson correlation analysis on 85 infertile patients showed a positive correlation between age and the levels of FF anti-oocyte antibody (r = 0.276, p = 0.010). This study demonstrated that FF anti-oocyte antibody could be associated with poor response to COH in ICSI cycles. Read more
Human fertility (Cambridge, England)

Milad Bastami

In silico dissection of miRNA targetome polymorphisms and their role in regulating miRNA-mediated gene expression in esophageal cancer. (2016)

Esophageal cancer is the eighth most common cancer worldwide. Also middle-aged obese adults with higher body mass index during childhood have a greater risk to develop esophageal cancer. The contribut...ion of microRNAs to esophageal cancer has been extensively studied and it became clear that these noncoding RNAs may play crucial roles in pathogenesis, diagnosis and prognosis of the disease. Increasing evidences have suggested that polymorphisms perturbing microRNA targetome (i.e., the compendium of all microRNA target sites) are associated with cancers including esophageal cancer. However, the extent to which such variants contribute to esophageal cancer is still unclear. In this study, we applied an in silico approach to systematically identify polymorphisms perturbing microRNA targetome in esophageal cancer and performed various analyses to predict the functional consequences of the occurrence of these variants. The computational results were integrated to provide a prioritized list of the most potentially disrupting esophageal cancer-implicated microRNA targetome polymorphisms along with the in silico insight into the mechanisms with which such variations may modulate microRNA-mediated regulation. The results of this study will be valuable for future functional experiments aimed at dissecting the roles of microRNA targetome polymorphisms in the onset and progression of esophageal cancer. Read more
Cell biochemistry and biophysics

rahman hallaj

Highly sensitive electrochemical aptasensor for immunoglobulin E detection based on sandwich assay using enzyme-linked aptamer. (2014)

Here, we describe the fabrication of an electrochemical immunoglobulin E (IgE) aptasensor using enzyme-linked aptamer in the sandwich assay method and thionine as redox probe. In this protocol, 5-amin...e-terminated IgE aptamer and thionine were covalently attached on glassy carbon electrode modified with carbon nanotubes/ionic liquid/chitosan nanocomposite. Furthermore, another IgE aptamer was modified with biotin and enzyme horseradish peroxidase (HRP), which attached to the aptamer via biotin-streptavidin interaction. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry were performed at each stage of the chemical modification process to confirm the resulting surface changes. The presence of IgE induces the formation of a double aptamer sandwich structure on the electrode, and the electrocatalytic reduction current of thionine in the presence of hydrogen peroxide was measured as the sensor response. Under optimized conditions and using differential pulse voltammetry as the measuring technique, the proposed aptasensor showed a low detection limit (6 pM) and high sensitivity (1.88 μA nM(-1)). This aptasensor also exhibited good stability and high selectivity for IgE detection without an interfering effect of some other proteins such as bovine serum albumin (BSA) and lysozyme. The application of the aptasensor for IgE detection in human serum sample was also investigated. The proposed protocol is quite promising as an alternative sandwich approach for various protein assays. Read more
Analytical biochemistry

Adnan Kisa

Analysis of the pharmaceuticals market and its technological development in Turkey. (2006)

The objectives of this study were to analyze the current structure of the Turkish pharmaceuticals market to explain the latest developments and to offer some insight into the likely policy issues that... this sector will face. Read more
International journal of technology assessment in health care

amir mirzadi gohari

Molecular characterization and functional analyses of ZtWor1, a transcriptional regulator of the fungal wheat pathogen Zymoseptoria tritici. (2014)

Zymoseptoria tritici causes the major fungal wheat disease septoria tritici blotch, and is increasingly being used as a model for transmission and population genetics, as well as host-pathogen interac...tions. Here, we study the biological function of ZtWor1, the orthologue of Wor1 in the fungal human pathogen Candida albicans, as a representative of a superfamily of regulatory proteins involved in dimorphic switching. In Z. tritici, this gene is pivotal for pathogenesis, as ZtWor1 mutants were nonpathogenic and complementation restored the wild-type phenotypes. In planta expression analyses showed that ZtWor1 is up-regulated during the initiation of colonization and fructification, and regulates candidate effector genes, including one that was discovered after comparative proteome analysis of the Z. tritici wild-type strain and the ZtWor1 mutant, which was particularly expressed in planta. Cell fusion and anastomosis occur frequently in ZtWor1 mutants, reminiscent of mutants of MgGpb1, the β-subunit of the heterotrimeric G protein. Comparative expression of ZtWor1 in knock-out strains of MgGpb1 and MgTpk2, the catalytic subunit of protein kinase A, suggests that ZtWor1 is downstream of the cyclic adenosine monophosphate (cAMP) pathway that is crucial for pathogenesis in many fungal plant pathogens. Read more
Molecular plant pathology

Adnan Kisa

The pharmaceutical sales rep/physician relationship in Turkey: ethical issues in an international context. (2004)

In many developed countries, the physician/pharmaceutical sales representative relationship has increasingly become the focus of ethical questions. Given this context, the purpose of the present study... was to determine the ethical dilemmas faced by pharmaceutical sales representatives in Turkey in their relations with physicians, and to identify possible solutions. Through an investigator-designed questionnaire, the ethical problems perceived by 215 pharmaceutical sales representatives were quantitatively analyzed. Nearly all of the participants (96.7%) reported that they had faced ethical dilemmas in marketing drugs to physicians. The most commonly reported problems included paramedical requests (for free lab test kits, etc.) and the necessity of bargaining with physicians over the use of their firms drugs by offering gifts and sponsorships. The participants in the study felt that physicians were the primary source of ethical problems in the marketing of drugs, and the participants most highly ranked potential solution to these ethical problems was a better understanding, on the part of physicians, of the role of pharmaceutical sales representatives. At the end of this study, suggestions are given with a view to helping health policy makers understand and address the current controversies involving drug company representatives and physicians. Read more
Health marketing quarterly

Adnan Kisa

Sex workers and the issues surrounding registration in Turkey. (2003)

Awareness of the activities of commercial sex workers can be an important step toward understanding the transmission of sexually transmitted infections (STIs) in developing countries. This study discu...sses how sex workers are viewed in Turkey and the process of mandatory registration. To support the information provided and the conclusions drawn, a sample of 150 sex workers who made regular visits to a STI hospital was interviewed. Information on socio-demographic characteristics, family and support information and certain risk behaviors were solicited. Recommendations for increasing preventive education are made, with considerations for increased attention and support for this group of individuals. Read more
Journal of health & social policy

Reza Salman Yazdi

Urine macrophage migration inhibitory factor in pediatric systemic lupus erythematosus. (2007)

We reported a series of ten patients with lupus nephritis (five patients in the relapse phase and five in the remission phase) and measured the macrophage migration inhibitory factor (MIF), an importa...nt pro-inflammatory cytokine with probable role in the pathogenesis of many inflammatory diseases, in their urine samples. MIF/creatinine (Cr) ratio directly correlated with disease activity and it does not have any significant difference between inactive disease and normal ones. We found that the urine MIF/Cr ratio not only differentiates active disease from inactive disease and normal ones but also correlates with the activity indices of renal pathology. Read more
Clinical rheumatology

MJ Rasaee

Treatment of oral squamous cell carcinoma using anti-HER2 immunonanoshells. (2011)

Worldwide, oral squamous cell carcinoma (potentially mediated by HER2) is recognized as the most commonly occurring malignant neoplasm of the oral cavity. Anti-HER2 nanobodies conjugated to gold-silic...a nanoshells and used as photothermal treatment for oral squamous cell carcinoma may provide a novel therapeutic alternative to current treatment for this disease. Read more
International journal of nanomedicine

Reza Salman Yazdi

Association of Ureaplasma urealyticum infection with varicocele-related infertility. (2008)

The role of seminal colonization of Ureaplasma urealyticum in varicocele-related infertility was investigated. Read more
Journal of infection in developing countries

Adnan Kisa

Job dissatisfaction among public hospital physicians is a universal problem: evidence from Turkey.

Several recent reports show that many physicians feel discontented and unhappy with their work situation. This could be due in part to factors such as declining social status, loss of influence on hea...lth care organizations, and reduced income. The professional life of physicians is characterized by long working days and pressure for efficiency. This threatens the quality of patient care. In this study we investigated levels of job stress as well as job and life satisfaction among a sample of 168 physicians (80 women and 88 men) who work in a large government facility in Ankara, Turkey. A self-administered questionnaire was distributed to physicians to determine factors contributing to stress and job satisfaction. The most important results of the study show that the participants were unhappy with their salary, did not have enough time to follow developments in medicine, and had a limited social life due to heavy workloads. The results of the study show that physicians who work in public facilities have low motivation due to the nature of their organizations. Public hospital working conditions and staff salaries must be improved to promote health professionals and healthy society. Read more
The health care manager

Reza Salman Yazdi

The Relationship between Occupation and Semen Quality. (2011)

Infertility can be a major concern for couples trying to conceive, and occupational hazards may constitute a main cause of infertility in men. Studies conducted throughout the world indicate that phys...ical and chemical hazards in the workplace can have a negative impact on male fertility. The main objective of this study was to determine the frequency of occupational categories of men who attended an infertility clinic, and to evaluate the differences in the semen quality parameters among occupational categories. Read more
International journal of fertility & sterility

Adnan Kisa

Developments in patients rights in Turkey. (2002)

Today, the social, economic, cultural, ethical, and political climate has given rise to an international movement, that is re-evaluating the importance of patients rights. In Turkey, as competition co...ntinues to increase between public and private hospitals, the emphasis on presenting health care services in the most advantageous way has become a focal point of debate. As a result, patients rights issues are being actively discussed in both the private and public health care sectors in the country. In this study, the development of patients rights issues in Turkey is reviewed and the results of some selected descriptive studies are summarized. Suggestions are made toward policies for effective and efficient health care provision in terms of both broad and specific issues that have arisen in the field of patients rights. Read more
Medicine and law

Reza Salman Yazdi

Prevalence of Ureaplasma urealyticum and Ureaplasma parvum in semen of infertile and healthy men. (2009)

Ureaplasma urealyticum is a causative agent of non-gonococcal urethritis and is implicated in the pathogenesis of prostatitis, epididymitis and infertility. The organism is more common in partners of ...infertile than fertile marriages. U. urealyticum infections not only jeopardize fertility but also pose a risk for infertility treatment and resulting pregnancies. The aim of this study was to determine the prevalence of U. urealyticum and Ureaplasma parvum in semen of infertile and healthy men by polymerase chain reaction (PCR). Semen samples were obtained from infertile patients and healthy controls and were subjected to the routine andrological analysis and PCR. DNA was extracted by the Cadieux method, and analysed by PCR protocol with specific primers for urease and multiple-banded antigen genes. Ureaplasmas were detected significantly by PCR in 12 of 100 (12%) semen specimens from infertile patients and in three of 100 (3%) healthy men. The volume of semen fluid, concentration of sperm cells, and sperm cell with normal morphology were significantly decreased in infertile men. In the group of infertile patients with PCR positive for Ureaplasmas, the volume, count and morphology of semen samples were lower than in the infertile patients with PCR-negative results. U. urealyticum species in semen of infertile men was found to be high (9%) than in healthy controls (1%). Detection rate for U. parvum was 3% in the infertile group and 2% in healthy men. The results indicate that U. urealyticum species is more common in specimens of infertile men. The percentage of normal sperm cells, the volume of semen and the percentage of sperm cells with motility in the PCR positive for U. urealyticum species group were lower than in the PCR positive for U. parvum group. Read more
International journal of STD & AIDS

MJ Rasaee

Epitope mapping of PR81 anti-MUC1 monoclonal antibody following PEPSCAN and phage display techniques. (2007)

PR81 is an anti-MUC1 monoclonal antibody (MAb) which was generated against human MUC1 mucin that reacted with breast cancerous tissue, MUC1 positive cell line (MCF-7, BT-20, and T-4 7 D), and syntheti...c peptide, including the tandem repeat sequence of MUC1. Here we characterized the binding properties of PR81 against the tandem repeat of MUC1 by two different epitope mapping techniques, namely, PEPSCAN and phage display. Epitope mapping of PR81 MAb by PEPSCAN revealed a minimal consensus binding sequence, PDTRP, which is found on MUC1 peptide as the most important epitope. Using the phage display peptide library, we identified the motif PD(T/S/G)RP as an epitope and the motif AVGLSPDGSRGV as a mimotope recognized by PR81. Results of these two methods showed that the two residues, arginine and aspartic acid, have important roles in antibody binding and threonine can be substituted by either glycine or serine. These results may be of importance in tailor making antigens used in immunoassay. Read more
Hybridoma (2005)

Fertility Biocenter

Stimulation of natural killer cells by homoeopathic complexes: an in vitro and in vivo pilot study in advanced cancer patients. (2013)

The present study was designed in order to evaluate the effects of five homoeopathic complex preparations on functional activity natural killer cells (NKCs) in advanced cancer patients. We examined th...e effects of Coenzyme Compositum®, Ubichinon Compositum®, Glyoxal Compositum®, Katalysatoren® and Traumeel® on the functional activity of NKCs. Experimental procedures included in vitro and in vivo trials. The in vitro trials were performed in NKCs isolated from 12 healthy volunteers (aged 44 ± 4 years) and incubated with the five homoeopathic complex preparations. The in vivo trials were performed in 15 advanced cancer patients (aged 55 ± 12 years) supplemented for 3 months with the homoeopathic preparations. All five homoeopathic preparations significantly increased the cytotoxic activity of the NKCs at the lowest NKCs/target cell ratio 12:1 (p < 0·05). The order of activity was: Ubichinon Compositum® > Glyoxal Compositum® > Katalysatoren® > Traumeel® > Coenzyme Compositum®. In the advanced cancer patients, the homoeopathic preparation significantly increased NKCs cytotoxic activity (p < 0·05). The homoeopathic complex preparations tested in this study can be used as an adjuvant immunotherapy in advanced cancer patients. Read more
Cell biochemistry and function

Adnan Kisa

The need for time management training is universal: evidence from Turkey. (2005)

In many developing countries, healthcare administrators are currently facing challenges that are representative of those in the United States. Most healthcare administrators here are physicians with n...o formal training in healthcare administration, and this is perhaps most apparent in their difficulties with time management. The authors purpose in this study was to characterize the time management difficulties of administrators working in primary healthcare facilities of the Ministry of Healthcare. In the study, 67 healthcare administrators each completed a 31-item time management questionnaire. Of the participants, 79.1% reported that they have never attended time management courses or workshops. Although 76.1% said they were free to choose the priority of their daily tasks, only 44.8% felt they knew how much time they should allow for each activity in their daily life. These and other findings in the study suggest that the need for time management education is a well-defined target for intervention, both in university-based programs for future healthcare administrators and in workplace-based programs, such as in-service training for healthcare administrators who are already working. Read more
Hospital topics

MJ Rasaee

Production of recombinant scFv against p24 of human immunodeficiency virus type 1 by phage display technology. (2014)

Phage display has a fundamental role in protein isolation and engineering. Isolated proteins produced with this method can be modified for specific binding and affinity. P24 is the most produced prote...in during human immune deficiency virus (HIV) replication; especially in the early steps of HIV-1 infection, its evaluation may have diagnostic values. To test the HIV-1 infection, p24 antigen assay appears to be a very promising alternative to RNA assays. In this study, we have generated a recombinant mouse single chain antibody fragment against p24 of the HIV-1 with the use of phage display technology. After isolation of antibody variable-region (V) gene of B cells extracted from the spleen of an immunized mouse, a library of single chain Fv fragments (scFv) was constructed. The library was used in a series of bio-panning processes against recombinant p24 protein expressed from Escherichia coli. The isolated scFv antibody specifically recognizes the HIV-1 capsid protein p24. The affinity constant of the isolated scFv antibody (MF85) was found to be 2×10(-9) M. Our studies showed that the MF85 scFV antibody has similar properties as that of monoclonal antibodies produced by the hybridoma technology. Read more
Monoclonal antibodies in immunodiagnosis and immunotherapy

Vahid Asgary

Synthesis and characterization of a novel chemically designed (Globo)3-DTPA-KLH antigen. (2015)

In recent years, many experiments have been conducted for the production and evaluation of anticancer glycoconjugated vaccines in developed countries and many achievements have been accomplished with ...Globo H derivatives. In the current experiment, a new chemically designed triplicate version of (Globo H)3-diethylenetriamine pentaacetic acid (DTPA)-KLH antigen was synthesized and characterized. Immunization with (Globo H)3-DTPA-KLH, a hexasaccharide that is a member of a family of antigenic carbohydrates that are highly expressed in various types of cancers conjugated with DTPA and KLH protein, induced a high level of antibody titer along with an elevated level of IL-4 in mice. Treatment of tumors with the collected sera from immunized mice decreased the tumor size in nude mice as well. None of the immunized mice illustrated any sign of tumor growth after injection of MCF-7 cells compared to the control animals. These findings, based on the newly presented structure of the Globo H antigen, lend exciting and promising evidence for clinical advancement in the development of a therapeutic vaccine in the future. Read more
Drug design, development and therapy

MJ Rasaee

Preparation and characterization of monoclonal antibody against melatonin. (2008)

Anti-melatonin monoclonal antibodies (MAb) were prepared following coupling melatonin to bovine serum albumin (BSA) by Mannich reaction. Balb/c mice were immunized via injection of the melatonin-BSA i...ntraperitonally. The spleen cells producing high titer of antibody were fused with myeloma cells of SP2/0 origin. After two limiting dilutions, two stable clones (AS-H10 and AS-D26) exhibiting best properties were selected for further studies. The class and subclass of two MAbs were found to be IgG(1) and IgG(2a) with lambda and kappa light chains, respectively. Antibodies secreted by these two clones showed high affinity of about 10(9)M(1). Study of the specificity criteria showed that these clones had no cross reactivity with indolic, aromatic, and imidazole ring-containing compounds, and had high specificity towards melatonin. The calibration curve was constructed with a sensitivity range of 10 ng/mL to 10 microg/mL. In conclusion, these MAbs may be useful for immunoassay of melatonin. Read more
Hybridoma (2005)

MJ Rasaee

Eliciting an antibody response against a recombinant TSH containing fusion protein. (2016)

Designing novel antigens to rise specific antibodies for Thyroid Stimulating Hormone (TSH) detection is of great significance. A novel fusion protein consisting of the C termini sequence of TSH beta s...ubunit and a fusion sequence was designed and produced for rabbit immunization. Thereafter, the produced antibodies were purified and characterized for TSH detection. Our results indicate that the produced antibody is capable of sensitive and specific detection of TSH with low cross reactivity. This study underscores the applicability of designed fusion protein for specific and sensitive polyclonal antibody production and the importance of selecting an amenable region of the TSH for immunization. Read more
Journal of immunoassay & immunochemistry

Vahid Asgary

Computational and nonglycosylated systems: a simpler approach for development of nanosized PEGylated proteins. (2016)

Cysteine PEGylation includes several steps, and is difficult to manage in practice. In the current investigation, the cysteine PEGylation of erythropoietin analogs was examined using computational and... nonglycosylated systems to define a simpler approach for specific PEGylation. Two model analogs (E31C and E89C) were selected for PEGylation based on lowest structural deviation from the native form, accessibility, and nucleophilicity of the free thiol group. The selected analogs were cloned and the expression was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot using Coomassie blue staining and anti-His monoclonal antibody, respectively. PEGylation with 20 kDa mPEG-maleimide resulted in 79% and 82% conjugation yield for E31C and E89C nonglycosylated erythropoietin (ngEPO) analogs, respectively. The size distribution and charge analysis showed an increase in size and negative charge of the PEGylated forms compared with nonconjugated ones. Biological assay revealed that E31C and E89C mutations and subsequent PEGylation of ngEPO analogs have no deleterious effects on in vitro biological activity when compared to CHO-derived recombinant human erythropoietin. In addition, PEG-conjugated ngEPOs showed a significant increase in plasma half-lives after injection into rats when compared to nonconjugated ones. The development of the cysteine-PEGylated proteins using nonglycosylated expression system and in silico technique can be considered an efficient approach in terms of optimization of PEGylation parameters, time, and cost. Read more
Drug design, development and therapy

Adnan Kisa

Electronic Health Object: Transforming Health Care Systems From Static to Interactive and Extensible. (2015)

Electronic health records (EHRs) store health-related patient information in an electronic format, improving the quality of health care management and increasing efficiency of health care processes. H...owever, in existing information systems, health-related records are generated, managed, and controlled by health care organizations. Patients are perceived as recipients of care and normally cannot directly interact with the system that stores their health-related records; their participation in enriching this information is not possible. Many businesses now allow customers to participate in generating information for their systems, strengthening customer relationships. This trend is supported by Web 2.0, which enables interactivity through various means, including social networks. Health care systems should be able to take advantage of this development. This article proposes a novel framework in addressing the emerging need for interactivity while preserving and extending existing electronic medical data. The framework has 3 dimensions of patient health record: personal, social, and medical dimensions. The framework is designed to empower patients, changing their roles from static recipient of health care services to dynamic and active partners in health care processes. Read more
Inquiry : a journal of medical care organization, provision and financing

Milad Bastami

Bioinformatics prioritization of SNPs perturbing microRNA regulation of hematological malignancy-implicated genes. (2015)

The contribution of microRNAs (miRNAs) to cancer has been extensively investigated and it became obvious that a strict regulation of miRNA-mRNA regulatory network is crucial for safeguarding cell heal...th. Apart from the direct impact of miRNA dysregulation in cancer pathogenesis, genetic variations in miRNAs are likely to disrupt miRNA-target interaction. Indeed, many evidences suggested that SNPs within miRNA regulome are associated with the development of different hematological malignancies. However, a full catalog of SNPs within miRNAs target sites of genes relevant to hematopoiesis and hematological malignancies is still lacking. Accordingly, we aimed to systematically identify and characterize such SNPs and provide a prioritized list of most potentially disrupting SNPs. Although in the present study we did not address the functional significance of these potential disturbing variants, we believe that our compiled results will be valuable for researchers interested in determining the role of target-SNPs in the development of hematological malignancies. Read more
Genomics

Adnan Kisa

Benign prostatic hyperplasia: cost and effectiveness of three alternative surgical treatment methods used in a Turkish hospital. (2005)

The purpose of this study was to compare three alternative surgical therapies for Benign prostatic hyperplasia (BPH) in terms of their cost and effectiveness in a general hospital setting in Turkey. B...PH is an important potential burden on health care resources in developing countries like Turkey, not only because of the increasing incidence of the disease, but also because of the differences in cost and effectiveness that exist among the various available treatment technologies. In this study, three alternative surgical treatments for BPH, namely open prostatectomy, transurethral resection of the prostate (TURP), and laser prostatectomy were compared in terms of their cost and effectiveness. Effectiveness was measured through the use of the International Prostate Symptom Score (IPSS) before the operation and at 3 months after. Laser prostatectomy was found to be the most costly and least effective way of treating BPH. This conclusion was valid both in terms of cost per prostate symptom score and cost per improvement of quality of life index. This study shows how a rough estimate can be made of the potential burdens that alternative treatment methods would impose on a countrys health budget. Read more
Journal of medical systems