MohammadReza Alivand

Novel Epigenetic Controlling of Hypoxia Pathway Related to Overexpression and Promoter Hypomethylation of TET1 and TET2 in RPE Cells. (2017)

CpG methylation of DNA takes part in a specific epigenetic memory that plays crucial roles in the differentiation and abnormality of the cells. The methylation pattern aberration of genomes is affecte...d in three ways, namely DNA methyltransferase(DNMT), Ten-eleven translocation(TET), and methyl-binding Domain(MBD) proteins. Of these, TET enzymes have recently been demonstrated to be master modifier enzymes in the DNA methylation process. Additionally, recent studies emphasize that not only do epigenetic phenomena play a role in controlling hypoxia pathway, but the hypoxia condition also triggers hypomethylation of genomes that may help with the expression of hypoxia pathway genes. In this study, we suggested that TET1 and TET2 could play a role in the demethylation of genomes under chemical hypoxia conditions. Herein, the evaluating methylation status and mRNA expression of mentioned genes were utilized through real-time PCR and methylation-specific PCR (MSP), respectively. Our results showed that TET1 and TET2 genes were overexpressed (p< 0.05) under chemical hypoxia conditions in Retinal Pigment Epithelial(RPE)cells, whereas the promoter methylation status of them were hypomethylated in the same condition. Therefore, chemical hypoxia not only causes overexpression of TET1 and TET2 but also could gradually do promoter demethylation of same genes. This is the first study to show the relationship between epigenetics and the expression of mentioned genes related to hypoxia pathways. Furthermore, it seems that these associations in RPE cells are subjected to chemical hypoxia as a mechanism that could play a crucial role in methylation pattern changes of hypoxia-related diseases such as cancer and ischemia. This article is protected by copyright. All rights reserved. Read more
Journal of cellular biochemistry

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

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

Vahid Asgary

M2000 (β-D-Mannuronic Acid) as a Novel Antagonist for Blocking the TLR2 and TLR4 Downstream Signalling Pathway. (2017)

To date, selective blockade of Toll-like receptor (TLR) signalling has been developed as a new approach for treatment for many inflammatory diseases. As β-D-mannuronic acid (M2000) has been known as a...n anti-inflammatory molecule in several experimental models, we investigated the antagonistic effects of M2000 on TLR2 and TLR4 downstream signalling transduction pathway in human embryonic kidney (HEK) 293 cell lines overexpressing TLR2/CD14 and the TLR4/MD2/CD14 complex, respectively. M2000 effectively inhibited mRNA expression of MyD88 and p65, major subunit of nuclear factor-κB, in HEK293 cells stimulated by lipoteichoic acid (LTA, a TLR2 agonist) and lipopolysaccharide (LPS, a TLR4 agonist) with no evidence of cytotoxicity. In addition, M2000 also suppressed LTA and LPS-induced production of TNF-α and IL-6 inflammatory cytokines in these cells. Furthermore, the results revealed that M2000 had no significant effect on Tollip mRNA expression as a negative regulator of TLR signalling in aforesaid cells. Overall, these data point to M2000 inhibitory effect on Toll-like receptor (TLR) 2, 4 signalling in HEK293 cells. This information might provide new insights into the possible roles of this small drug in order to introduce it as a TLR signalling pathway inhibitor. However, more studies are needed to confirm β-D-mannuronic acid antagonistic effects including the effects of M2000 on peritoneal isolated macrophages and also on blood cells in patients with inflammatory diseases such as ankylosing spondylitis. Read more
Scandinavian journal of immunology

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

Radiosensitization effect of folate-conjugated gold nanoparticles on HeLa cancer cells under orthovoltage superficial radiotherapy techniques. (2014)

Due to the high atomic number of gold nanoparticles (GNPs), they are known as new radiosensitizer agents for enhancing the efficiency of superficial radiotherapy techniques by increasing the dose abso...rbed in tumor cells wherein they can be accumulated selectively. The aim of this study was to compare the effect of various common low energy levels of orthovoltage x-rays and megavoltage γ-rays (Co-60) on enhancing the therapeutic efficiency of HeLa cancer cells in the presence of conjugated folate and non-conjugated (pegylated) GNPs. To achieve this, GNPs with an average diameter of 52 nm were synthesized and conjugated to folic acid molecules. Pegylated GNPs with an average diameter of 47 nm were also synthesized and used as non-conjugated folate GNPs. Cytotoxicity assay of the synthesized folate-conjugated and pegylated GNPs was performed using different levels of nanoparticle concentration incubated with HeLa cells for 24 h. The radiosensitizing effect of both the conjugated and pegylated GNPs on the cells at a concentration of 50 µM was compared using MTT as well as clonogenic assays after exposing them to 2 Gy ionizing radiation produced by an orthovoltage x-ray machine at four different kVps and γ-rays of a Co-60 unit. Significant differences were noted among various irradiated groups with and without the folate conjugation, with an average dose enhancement factor (DEF) of 1.64 ± 0.05 and 1.35 ± 0.05 for the folate-conjugated and pegylated GNPs, respectively. The maximum DEF was obtained with the 180 kVp x-ray beam for both of the GNPs. Folate-conjugated GNPs can significantly enhance the cell killing potential of orthovoltage x-ray energies (especially at 180 kVp) in folate receptor-expressing cancer cells, such as HeLa, in superficial radiotherapy techniques. Read more
Physics in medicine and biology

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

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

Mohammad Najafi

Neonatal thyroid screening in a mild iodine deficiency endemic area in Iran. (2008)

Evaluated serum thyroid-stimulating hormone (TSH), as an early index for diagnosis of neonatal hypothyroidism, indicates insufficient supply of thyroid hormones. Read more
Indian journal of medical sciences

Milad Bastami

MAP3K1 May be a Promising Susceptibility Gene for Type 2 Diabetes Mellitus in an Iranian Population. (2016)

Considering that MAPK (mitogen- activated protein kinase) signaling pathway has an important role in the progression of inflammatory cytokine secretion in type 2 diabetes mellitus (T2DM), we have rece...ntly investigated the reported genetic polymorphism from genome wide association study in MAP3K1 (mitogen-activated protein kinase kinase kinase 1) in diabetes as an important member of MAPK signaling. This study aimed to investigate the possible association of rs10461617 at the upstream of MAP3K1 gene in an Iranian case-control study with the risk of T2DM. The study population was comprised of 342 unrelated Iranian individuals including 177 patients with T2DM and 165 unrelated healthy control subjects. Genotyping was performed using PCR-RFLP and confirmed with sequencing. In a logistic regression analysis, the rs10461617A allele was associated with a significantly higher risk of T2DM assuming the log- additive model (OR: 1.44, 95% CI: 1.01-2.05, P = 0.039). In conclusion, we provided the first evidence for the association of rs10461617 at the upstream of MAP3K1 with the risk of T2DM in an Iranian population. Read more
International journal of molecular and cellular medicine

Milad Bastami

A Bioinformatics Approach to Prioritize Single Nucleotide Polymorphisms in TLRs Signaling Pathway Genes. (2016)

It has been suggested that single nucleotide polymorphisms (SNPs) in genes involved in Toll-like receptors (TLRs) pathway may exhibit broad effects on function of this network and might contribute to ...a range of human diseases. However, the extent to which these variations affect TLR signaling is not well understood. In this study, we adopted a bioinformatics approach to predict the consequences of SNPs in TLRs network. The consequences of non-synonymous coding SNPs (nsSNPs) were predicted by SIFT, PolyPhen, PANTHER, SNPs&GO, I-Mutant, ConSurf and NetSurf tools. Structural visualization of wild type and mutant protein was performed using the project HOPE and Swiss PDB viewer. The influence of 5-UTR and 3- UTR SNPs were analyzed by appropriate computational approaches. Nineteen nsSNPs in TLRs pathway genes were found to have deleterious consequences as predicted by the combination of different algorithms. Moreover, our results suggested that SNPs located at UTRs of TLRs pathway genes may potentially influence binding of transcription factors or microRNAs. By applying a pathway-based bioinformatics analysis of genetic variations, we provided a prioritized list of potentially deleterious variants. These findings may facilitate the selection of proper variants for future functional and/or association studies. Read more
International journal of molecular and cellular medicine

Milad Bastami

The miRNA targetome of coronary artery disease is perturbed by functional polymorphisms identified and prioritized by in-depth bioinformatics analyses exploiting genome-wide association studies. (2016)

In recent years, genome-wide association studies (GWAS) have made great progress in elucidating the genetic influence on complex traits. An overwhelming number of GWAS signals resides in regulatory el...ements, therefore most post-GWAS studies focused only on transcriptional regulatory variants. However, recent findings have expanded the spectrum of trait/disease-associated regulatory variants beyond transcriptional level and highlighted the importance of post-transcriptional variants like those in miRNA targetome. The present work integrated genome-wide association data of coronary artery disease (CAD) with population-specific linkage disequilibrium structures from 1000 Genomes Project to map disease associations to miRNA targetome. Moreover, we performed a variety of functional prediction analyses to prioritize disease-associated variants (DAVs) influencing miRNA targetome and in-silico analyses to get insights into their functional significance. In conclusion, although the role of miRNA targetome variations in the development of CAD still has to be fully elucidated, we provided a systematic bioinformatics approach to the miRNA targetome variations in CAD. The results of this study will be valuable for researchers interested in the identification of CAD GWAS signals that may implicate polymorphic miRNA targeting. Read more

amir mirzadi gohari

Flexible gateway constructs for functional analyses of genes in plant pathogenic fungi. (2015)

Genetic manipulation of fungi requires quick, low-cost, efficient, high-throughput and molecular tools. In this paper, we report 22 entry constructs as new molecular tools based on the Gateway technol...ogy facilitating rapid construction of binary vectors that can be used for functional analysis of genes in fungi. The entry vectors for single, double or triple gene-deletion mutants were developed using hygromycin, geneticin and nourseothricin resistance genes as selection markers. Furthermore, entry vectors containing green fluorescent (GFP) or red fluorescent (RFP) in combination with hygromycin, geneticin or nourseothricin selection markers were generated. The latter vectors provide the possibility of gene deletion and simultaneous labelling of the fungal transformants with GFP or RFP reporter genes. The applicability of a number of entry vectors was validated in Zymoseptoria tritici, an important fungal wheat pathogen. Read more
Fungal genetics and biology : FG & B

Adnan Kisa

Conflict management in public university hospitals in Turkey: a pilot study.

By nature, hospitals are extremely complex organizations, combining many different professional groups within an intricate administrative structure. Conflicts therefore expectedly arise between indivi...duals, groups, and departments. It is in the interest of health care administrators to periodically assess the major factors giving rise to these conflicts. In this study, a questionnaire designed to measure sources of conflict in the workplace was completed by 204 staff members at Gazi University Hospital. Of the participants, 30.9% were physicians, and 12.5% were administrators at various levels; 61.5% were female, and 38.5% were male. In terms of work experience, 52.6% of participants had worked less than 5 years at the hospital. The results of the study show that educational differences among the hospital staff were a major barrier to good communication and information flow between groups. Professionals in the same specialties experienced fewer conflicts. Another source of conflict was that resource allocation was considered unfair across departments. Although the hospital management provided an ombudsman for staff concerns, staff rarely resorted to the ombudsman because of the stigma associated with complaining. A lack of opportunity for career advancement was mentioned by 52% of the participants as a source of conflict. At present, job performance and rewards are not closely related in public university hospitals in Turkey because promotions and pay raises are strictly limited by law. Bureaucracy was also perceived to be a source of conflict, with 48.4% of participants saying that their performance was less than optimal because of the presence of multiple supervisors. This pilot study suggests that in Turkey, legislative reform is needed to give public university hospitals more flexibility regarding work incentives, open-door policies at the administrative level, and social interactions to improve teamwork among hospital staff. Read more
The health care manager

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

Potential cost-effectiveness of pneumococcal conjugate vaccine (PCV) in Turkey.

Pneumococcal infection is an important and preventable cause of morbidity and mortality. The Turkish government introduced 7-valent pneumococcal conjugate vaccine (PCV) into the national immunization ...program in 2009. This suggests that replacing 7-valent PCV with a higher-valent version could at least maintain standard of care if not improve it, and that it could be affordable. Read more
Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research

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

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

amir mirzadi gohari

FPLC and liquid-chromatography mass spectrometry identify candidate necrosis-inducing proteins from culture filtrates of the fungal wheat pathogen Zymoseptoria tritici. (2015)

Culture filtrates (CFs) of the fungal wheat pathogen Zymoseptoria tritici were assayed for necrosis-inducing activity after infiltration in leaves of various wheat cultivars. Active fractions were par...tially purified and characterized. The necrosis-inducing factors in CFs are proteinaceous, heat stable and their necrosis-inducing activity is temperature and light dependent. The in planta activity of CFs was tested by a time series of proteinase K (PK) co-infiltrations, which was unable to affect activity 30min after CF infiltrations. This suggests that the necrosis inducing proteins (NIPs) are either absent from the apoplast and likely actively transported into mesophyll cells or protected from the protease by association with a receptor. Alternatively, plant cell death signaling pathways might be fully engaged during the first 30min and cannot be reversed even after PK treatment. Further fractionation of the CFs with the highest necrosis-inducing activity involved fast performance liquid chromatography, SDS-PAGE and mass spectrometry. This revealed that most of the proteins present in the fractions have not been described before. The two most prominent ZtNIP encoding candidates were heterologously expressed in Pichia pastoris and subsequent infiltration assays showed their differential activity in a range of wheat cultivars. Read more
Fungal genetics and biology : FG & B

MJ Rasaee

Opium induces apoptosis in jurkat cells.

The direct effect of some opioids on immune cells has been demonstrated. The aim of this study was to assess the apoptotic effect of opium on Jurkat T lymphocyte cells. Read more
Addiction & health

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

MJ Rasaee

Selection of a high-affinity and in vivo bioactive ssDNA aptamer against angiotensin II peptide. (2016)

Unique features of aptamers have attracted interests for a broad range of applications. Aptamers are able to specifically bind to targets and inhibit their functions. This study, aimed to isolate the ...high affinity ssDNA aptamers against bio-regulator peptide angiotensin II (Ang II) and investigate their bioactivity in cellular and animal models. To isolate ssDNA aptamers, 12 rounds of affinity chromatography SELEX (Systematic Evolution of Ligands by EXponential enrichment) procedure were carried out. The SPR (surface plasmon resonance) and ELONA (enzyme linked oligonucleotide assay) analysis were used to determine the affinity and specificity of aptamers. The ability of selected aptamers to inhibit the proliferative effect of Ang II on human aortic vascular smooth muscle cells (HA-VSMCs) and their performance on Wistar rat urinary system and serum electrolyte levels were investigated. Two full-length aptamers (FLC112 and FLC125) with high affinity of respectively 7.52±2.44E-10 and 5.87±1.3E-9M were isolated against Ang II. The core regions of these aptamers (CRC112 and CRC125) also showed affinity of 5.33±1.15E-9 and 4.11±1.09E-9M. In vitro analysis revealed that FLC112 and FLC125 can inhibit the proliferative effect of Ang II on HA-VSMCs (P<0.05). They also significantly reduced the serum sodium level and increased the urine volume (P<0.05). The core regions of aptamers did not show high inhibitory potential against Ang II. It can be a spotlight that ssDNA aptamers have high potential for blocking Ang II. In conclusion, it appears that the researches focusing on high affinity and bioactive aptamers may lead to excellent results in blocking Ang II activity. Read more

Milad Bastami

A Bioinformatics Approach to the Identification of Variants Associated with Type 1 and Type 2 Diabetes Mellitus that Reside in Functionally Validated miRNAs Binding Sites. (2016)

The present work is aimed at finding variants associated with Type 1 and Type 2 diabetes mellitus (DM) that reside in functionally validated miRNAs binding sites and that can have a functional role in... determining diabetes and related pathologies. Using bioinformatics analyses we obtained a database of validated polymorphic miRNA binding sites which has been intersected with genes related to DM or to variants associated and/or in linkage disequilibrium (LD) with it and is reported in genome-wide association studies (GWAS). The workflow we followed allowed us to find variants associated with DM that also reside in functional miRNA binding sites. These data have been demonstrated to have a functional role by impairing the functions of genes implicated in biological processes linked to DM. In conclusion, our work emphasized the importance of SNPs located in miRNA binding sites. The results discussed in this work may constitute the basis of further works aimed at finding functional candidates and variants affecting protein structure and function, transcription factor binding sites, and non-coding epigenetic variants, contributing to widen the knowledge about the pathogenesis of this important disease. Read more
Biochemical genetics

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)

Adnan Kisa

The role of public relations activities in hospital choice. (2007)

Public relations activities for all organizations can have an important effect on consumer decision-making when buying goods or services. This study examines the effect that public relations activitie...s can have regarding consumer decisions and choice. To explore exemplify this relationship a questionnaire was given to 971 patients within public, university and private hospitals in Ankara, Turkey. Study results show that public relations activities were a crucial factor in determining consumer hospital choice. The majority of respondents reported that the behaviors and attitude of personnel as public relations activities that support the hospitals reputation within the public were the primary variables in hospital choice. Health care managers can use these findings to further understand how patients make informed choices related to usage of a health care facility and to develop and/or improve public relations activities. Read more
Health marketing quarterly

Adnan Kisa

Appropriateness of admission and length of stay in a Turkish Military Hospital. (2004)

The purpose of this study was to determine the extent of inappropriate days of stay in a Turkish military hospital, and to explore the variables correlated with these. A review was made of the medical... records of surgery patients admitted to the hospital of Gülhane Military Medical Academy. To determine the appropriateness of lengths of hospitalization, a Turkish version of the Appropriateness Evaluation Protocol (AEP) was applied retrospectively. A total of 375 patientsfiles were reviewed; and 21.3% of the hospital admissions were evaluated as inappropriate. Multiple logistic regression analysis showed that inappropriate length of stay was significantly increased with relation to age, emergency status, military rank, and distance from the hospital to the patients home. The results of the study suggest that changes in physicians behavior and in the organization of hospital activities may be effective in improving the quality and efficiency of hospital care. Read more
Journal of medical systems

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

Reza Hassan Sajedi

Proposed ionic bond between Arg300 and Glu270 and Glu271 are not involved in inactivation of a mutant firefly luciferase (LRR). (2016)

The weakness of firefly luciferase is its rapid inactivation. Many studies have been done to develop thermostable luciferases. One of these modifications was LRR mutant in which the Leu300 was substit...uted with Arg in the E(354)RR(356)Lampyris turkestanicus luciferase as template. LRR was more thermostable than the wild type but with only 0.02% activity. In this study, site-directed mutagenesis was used to change the proposed ionic bond between the Arg and two neighboring residues (Glu270 and Glu271), to understand if the induced interactions were responsible for inactivation in LRR. Our results showed that substitution of Glu270 and 271 with Ala removed the interactions but the activity of enzyme did not return. The E270A mutant was more active than LRR but the E271A and E270A/E271A mutants were inactive. Fluorescence and CD measurements showed that these mutations were accompanied by conformational changes. Extrinsic fluorescence measurement and obtained quenching data by KI and acrylamide also confirmed that the mutants were less compact than the LRR enzyme. In conclusion, in LRR, the interactions between Arg300 and Glu270 and Glu271 were not responsible for the enzyme inactivation and it is proposed that the enzyme inactivation is due to conformational changes of LRR mutant of firefly luciferase. Read more
Enzyme and microbial technology

MJ Rasaee

Influence of different combinations of antibodies and penicillinase-labeled testosterone derivatives on sensitivity and specificity of immunoassays. (1992)

Three antisera raised against bovine serum albumin (BSA) conjugates of testosterone-3-(O-carboxy-methyl)-oxime (T-3-CMO), 11 beta-hydroxytestosterone-11-carboxymethyl ether (T-11 beta-O-CME) and 19-hy...droxytestosterone-19-carboxymethyl-ether (T-19-O-CME) were evaluated in enzyme immunoassays (EIAs) in combinations with penicillinase-labeled T-3-CMO, T-11 beta-O-CME, T-19-O-CME, and testosterone-17 beta-hemisuccinate (T-17 beta-HS) for their influence on the sensitivity and specificity of EIAs. Of the various combinations, anti-T-3-CMO antiserum along with T-11 beta-O-CME-penicillinase showed no cross-reaction with any of the closely related steroids, although the same antibody had 21.6% binding to 5 alpha-dihydrotestosterone (5 alpha-DHT) in radioimmunoassay. All the homologous combinations appeared to be less sensitive due to their low affinity for testosterone. It was also apparent that of all the heterologous systems tested, only two combinations, (a) anti-T-19-O-CME antiserum and T-3-CMO-penicillinase and (b) anti-T-3-CMO antiserum and T-11 beta-O-CME-penicillinase, were found to be more sensitive. The former was less specific; it showed 70% cross-reaction with 5 alpha-DHT. The ability of testosterone to displace the hapten-enzyme conjugate and the specificity of the assay appear to depend on the position of the enzyme label on the steroid molecule as well as on the availability of antigenic sites in particular combinations of antibody and hapten-enzyme conjugates. Read more

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

ali jomehri

Nurses computer literacy and attitudes towards the use of computers in health care. (2015)

This descriptive and cross-sectional study was designed to address nurses computer literacy and attitudes towards the use of computers in health care and to determine the correlation between these two... variables. This study was conducted with the participation of 688 nurses who worked at two university-affiliated hospitals. These nurses were chosen using a stratified random sampling method. The data were collected using the Multicomponent Assessment of Computer Literacy and the Pretest for Attitudes Towards Computers in Healthcare Assessment Scale v. 2. The nurses, in general, had positive attitudes towards computers, and their computer literacy was good. Computer literacy in general had significant positive correlations with individual elements of computer competency and with attitudes towards computers. If the computer is to be an effective and beneficial part of the health-care system, it is necessary to help nurses improve their computer competency. Read more
International journal of nursing practice

amir mirzadi gohari

Horizontal gene and chromosome transfer in plant pathogenic fungi affecting host range. (2011)

Plant pathogenic fungi adapt quickly to changing environments including overcoming plant disease resistance genes. This is usually achieved by mutations in single effector genes of the pathogens, enab...ling them to avoid recognition by the host plant. In addition, horizontal gene transfer (HGT) and horizontal chromosome transfer (HCT) provide a means for pathogens to broaden their host range. Recently, several reports have appeared in the literature on HGT, HCT and hybridization between plant pathogenic fungi that affect their host range, including species of Stagonospora/Pyrenophora, Fusarium and Alternaria. Evidence is given that HGT of the ToxA gene from Stagonospora nodorum to Pyrenophora tritici-repentis enabled the latter fungus to cause a serious disease in wheat. A nonpathogenic Fusarium species can become pathogenic on tomato by HCT of a pathogenicity chromosome from Fusarium oxysporum f.sp lycopersici, a well-known pathogen of tomato. Similarly, Alternaria species can broaden their host range by HCT of a single chromosome carrying a cluster of genes encoding host-specific toxins that enabled them to become pathogenic on new hosts such as apple, Japanese pear, strawberry and tomato, respectively. The mechanisms HGT and HCT and their impact on potential emergence of fungal plant pathogens adapted to new host plants will be discussed. Read more
FEMS microbiology reviews

MJ Rasaee

Retroviral transduction of fluonanobody and the variable domain of camelid heavy-chain antibodies to chicken embryonic cells. (2013)

Single domain antibodies from camel heavy chain antibodies (VHH or nanobody), are advantages due to higher solubility, stability, high homology with human antibody, lower immunogenicity and low molecu...lar weight. These criteria make them candidates for production of engineered antibody fragments particularly in transgenic animals. Read more
Iranian journal of immunology : IJI

MJ Rasaee

Production of recombinant gG-1 protein of herpes simplex virus type 1 in a prokaryotic system in order to develop a type-specific enzyme-linked immunosorbent assay kit. (2007)

The herpes simplex viruses are important causes of disease worldwide. Herpes simplex virus type 1 (HSV-1) is the primary cause of oral-facial and pharyngeal infections and may cause herpetic whitlow, ...eye infections as well as severe and sometimes dangerous infections of the eyes and brain. HSV-1 also accounts for 10-15% of all genital herpetic infections. Therefore, laboratory diagnosis of this virus and development of diagnostic serological techniques for HSV-1 is of particular importance. In the present study, pTrc His2A-gG1 plasmid, containing the full-length glycoprotein G (gG) protein, was produced in a prokaryotic system for the first time. Upon confirmation of a 37-kDa gG-1 protein production in a prokaryotic system based on western blotting and monoclonal antibodies, the protein was produced at a large scale and purified by ion-exchange chromatography using DEAE-sepharose. An HSV-1 type-specific diagnostic kit was designed and developed and the specificity and sensitivity of this kit were demonstrated to be 89.5% and 100%, respectively, as compared with a commercially available kit. A significant correlation was shown between the developed kit and the commercial kit. Read more
FEMS immunology and medical microbiology

ali jomehri

Pretreating wheat straw by the concentrated phosphoric acid plus hydrogen peroxide (PHP): Investigations on pretreatment conditions and structure changes. (2016)

Wheat straw was pretreated by PHP (the concentrated H3PO4 plus H2O2) to clarify effects of temperature, time and H3PO4 proportion on hemicellulose removal, delignification, cellulose recovery and enzy...matic digestibility. Overall, hemicellulose removal was intensified by PHP comparing to the concentrated H3PO4. Moreover, efficient delignification specially happened in PHP pretreatment. Hemicellulose removal and delignification by PHP positively responded to temperature and time. Increasing H3PO4 proportion in PHP can promote hemicellulose removal, however, decrease the delignification. Maximum hemicellulose removal and delignification were achieved at 100% and 83.7% by PHP. Enzymatic digestibility of PHP-pretreated wheat straw was greatly improved by increasing temperature, time and H3PO4 proportion, and complete hydrolysis can be achieved consequently. As temperature of 30-40°C, time of 2.0 h and H3PO4 proportion of 60% were employed, more than 92% cellulose was retained in the pretreated wheat straw, and 29.1-32.6g glucose can be harvested from 100g wheat straw. Read more
Bioresource technology

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

Adnan Kisa

The influence of financial officers on the decision-making process in health facilities: a study in Ankara.

Financial officers in health facilities currently face 2 main duties. The first is to help the management team in the decision-making process and the second is to ensure the integrity of financial rep...orts to outsiders and outside agencies. A roster of 191 private outpatient clinics in Ankara was drawn up. Fourteen private hospitals and 66 private clinics were included in the study via systematic sampling. Financial officers perceptions of involvement in 46 decisions (grouped as strategic decisions, accounting and assessment, and nonfinancial decisions) were gauged using a responsive scale ranging from 1 (no involvement) to 5 (greatly involved). Involvement was defined as the extent of participation in specific decision-making issues. High involvement is assumed to be tantamount to influence and can be visualized in the extent to which financial officers could challenge plans, recommend or disapprove, or take a very significant role in reaching decisions. The results of the study show that in the dynamic environment in which health facilities operate, the financial officers role is somewhat equivocal. The study suggests that the power and influence of financial officers should be defined in such a way so as to develop a clear role for these members of the management team. Read more
The health care manager

MJ Rasaee

Cancer immunotherapy by a recombinant phage vaccine displaying EGFR mimotope: an in vivo study. (2015)

To date, several small molecule inhibitors and monoclonal-antibodies (like ICR-62) have been used to treat tumors over-expressing epidermal growth factor receptor (EGFR). However, the limitations asso...ciated with these conventional applications accentuate the necessity of alternative approaches. Mimotopes as compelling molecular tools could rationally be employed to circumvent these drawbacks. In the present study, an M13 phage displaying ICR-62 binding peptide mimotope is exploited as a vaccine candidate. It exhibited high affinity towards ICR62 and polyclonal anti-P-BSA antibodies. Following the mice immunization, phage-based mimotope vaccine induced humoral immunity. Elicited anti-EGFR mimotope antibodies were detected using ELISA method. Moreover, the phage vaccine was tested on the Lewis lung carcinoma mice model to investigate the prophylactic and therapeutic effects. The tumor volume was measured and recorded in different animal groups to evaluate the anti-tumor effects of the vaccine. Our data indicate that the reported phage-based mimotope could potentially elicit specific antibodies resulting in low titers of EGFR-specific antibodies and reduced tumor growth. However, in vivo experiments of prophylactic or therapeutic vaccination showed no specific advantage. Furthermore, phage-mimotope vaccine might be a promising approach in the field of cancer immunotherapy. Read more
Immunopharmacology and immunotoxicology

MJ Rasaee

Expression and Purification of a Novel Computationally Designed Antigen for Simultaneously Detection of HTLV-1 and HBV Antibodies. (2015)

Computational tools are reliable alternatives to laborious work in chimeric protein design. In this study, a chimeric antigen was designed using computational techniques for simultaneous detection of ...anti-HTLV-I and anti-HBV in infected sera. Databases were searched for amino acid sequences of HBV/HLV-I diagnostic antigens. The immunodominant fragments were selected based on propensity scales. The diagnostic antigen was designed using these fragments. Secondary and tertiary structures were predicted and the B-cell epitopes were mapped on the surface of built model. The synthetic DNA coding antigen was sub-cloned into pGS21a expression vector. SDS-PAGE analysis showed that glutathione fused antigen was highly expressed in E. coli BL21 (DE3) cells. The recombinant antigen was purified by nickel affinity chromatography. ELISA results showed that soluble antigen could specifically react with the HTLV-I and HBV infected sera. This specific antigen could be used as suitable agent for antibody-antigen based screening tests and can help clinicians in order to perform quick and precise screening of the HBV and HTLV-I infections. Read more
Iranian journal of allergy, asthma, and immunology

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 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

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

Adnan Kisa

National health system steps in Turkey: concerns of family physician residents in Turkey regarding the proposed national family physician system.

Many countries are currently struggling with the public desire for improved health care and provision of basic services on the one hand, and the rising costs of health care on the other. Turkey is acu...tely experiencing this problem because of its relatively advanced level of economic development and its relatively low level of health status compared to Organization for Economic Cooperation and Development and European Union countries. Since 1990, there has been vigorous debate in the Turkish society regarding the best way to improve public health through improved primary health care. The current government is pursuing a proposal that has been mentioned before, but in a more serious effort than has been previously made. This is an approach to primary care based on systems such as those in the United Kingdom and in Germany, and the basic components are family physicians who have a particular list of patients whom they provide care for. Financing of the system is to be provided with a new general health insurance scheme. In this study, 38 family practice residents at the 3 major training hospitals for this specialty completed an investigator-designed questionnaire for the purpose of characterizing their concerns regarding this proposed system of primary health care delivery. The participants responses indicated that the new system, which is known as the Family Physician System, will contribute importantly toward raising the overall level of health in Turkey. Specific expected benefits include closer patient-physician relationships, increased job satisfaction on the part of family physicians, and an overall increase in income for the physicians working in the system. Read more
The health care manager

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

Milad Bastami

Single-Nucleotide Polymorphisms Within MicroRNAs Sequences and Their 3 UTR Target Sites May Regulate Gene Expression in Gastrointestinal Tract Cancers. (2014)

Esophageal, stomach, and colorectal cancers are commonly lethal gastrointestinal tract (GIT) neoplasms, causing almost two million deaths worldwide each year. some environmental risk factors are ackno...wledged; however, genetic defects can significantly contribute to predisposition to GIT cancers. Accordingly, recent works have shown that single-nucleotide polymorphisms (SNPs) within miRNAs coding sequence (miR-SNPs) and miRNA target sites (target-SNPs) may further contribute to increased risk of developing cancer. Read more
Iranian Red Crescent medical journal

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

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

Vahid Asgary

Novel imatinib-loaded silver nanoparticles for enhanced apoptosis of human breast cancer MCF-7 cells. (2016)

In the current study, in vitro biological feature of imatinib-loaded silver nanoparticles (IMAB-AgNPs) on human breast cancer cell line was investigated. The formation of synthesized silver nanopartic...les (AgNPs) was characterized by UV-Visible spectroscopy, EDS, TEM imaging, SEM, FTIR, DLS and Zeta potentiometer. The developed IMAB-AgNPs with maximum percentage of loading efficiency was demonstrated in the average of 130 nm and mostly spherical. Additionally, in vitro drug release study showed a slow and continuous release of imatinib over a period of 80 h. We demonstrated that the synthesized IMAB-AgNPs exhibited a dose-dependent cytotoxicity against MCF-7 cell line. Then, real-time PCR method was also applied for the investigation of Bax and Bcl-2 gene expression in the cells. Comparing IMAB-AgNPs to AgNPs and Imatinib revealed the ability of IMAB-AgNPs to up-regulating Bax/Bcl-2 ratio. An induction of apoptosis was evidenced by Annexin-V/PI detection assay. Based on the current obtained data, the IMAB-AgNPs can exhibit inhibitory effect on viability through up regulation of apoptosis in MCF-7 cancer cells, which provides influencing evidence for the green synthesized AgNPs as a promising sustained drug delivery system. Read more
Artificial cells, nanomedicine, and biotechnology

Mohammad Najafi

Expression levels of the BAK1 and BCL2 genes highlight the role of apoptosis in age-related hearing impairment. (2016)

Age-related hearing impairment (ARHI) is a progressive and a common sensory disorder in the elderly and will become an increasingly important clinical problem given the growing elderly population. Apo...ptosis of cochlear cells is an important factor in animal models of ARHI. As these cells cannot regenerate, their loss leads to irreversible hearing impairment. Identification of molecular mechanisms can facilitate disease prevention and effective treatment. In this study, we compared the expression of the genes BAK1 and BCL2 as two arms of the intrinsic apoptosis pathway between patients with ARHI and healthy subjects. ARHI and healthy subjects were selected after an ear nose throat examination, otoscopic investigation, and pure tone audiometry. RNA was extracted from peripheral blood samples, and relative gene expression levels were measured using quantitative real-time polymerase chain reaction. BAK1 and the BAK1/BCL2 ratio were statistically significantly upregulated in the ARHI subjects. The BAK1/BCL2 ratio was positively correlated with the results of the audiometric tests. Our results indicate that BAK-mediated apoptosis may be a core mechanism in the progression of ARHI in humans, similar to finding in animal models. Moreover, the gene expression changes in peripheral blood samples could be used as a rapid and simple biomarker for early detection of ARHI. Read more
Clinical interventions in aging

Zeinab Takalloo

Artemin protects cells and proteins against oxidative and salt stress. (2017)

Artemin is an abundant thermostable protein in Artemia encysted embryos under environmental stresses. It is confirmed that high regulatory expression of artemin is relevant to stress resistance in thi...s crustacean. Here, the protective role of artemin from Artemia urmiana has been investigated on survival of bacterial cells under salt and oxidative shocks. Also, for continuous monitoring of the effect of artemin in prevention of proteins aggregation/inactivation, co-expression of artemin and luciferase (as an intracellular reporter) in bacterial cells was performed. According to the results, residual activity of luciferase in artemin expressing E. coli cells exposing to different concentrations of H2O2 and NaCl was significantly higher than non-expressing cells. The luciferase activity was rapidly lost in control cells under salt treatments while in co-transformed cells, the activity was considerably retained at higher salt concentrations. Also, analysis from cell viability assays showed that artemin-expressing cells exhibited more resistance to both stress conditions. In the present study, we document for the first time that artemin can protect proteins and bacterial cells against oxidative and salt stress conditions. These results can declare the resistance property of this crustacean against harsh environmental conditions. Read more
International journal of biological macromolecules

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