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Multiple sclerosis (MS) is a chronic myelin destructive disease which affects central nerves system. CD4+ T cells are a group of adaptive immune system cells that have Pivotal role in immune response against the foreign agents. Th17 (T helper 17) cells are one of the subsets of CD4+ T cells which increased in multiple sclerosis patients. MicroRNAs are single stranded non-coding RNAs that regulate protein expression by targeting their mRNA. The aim of this work was to determine miRNAs which probably have effect on theTh17 differentiation pathway by means of bioinformatics methods to suppress this pathway and decrease MS symptoms. by using miRWalk and miRTarBase databases, the probable and validated interactions between some miRNAs and Th17 differentiation pathway proteins were investigated .Disregulated expression of this miRNAs clinically have been shown previously in MS patients. Results showed that miR-9 probably could induce Th17 differentiation from naïve T cells by suppressing negative regulator of Th17 differentiation pathway. In contrast, miR-17and miR-106a/b probably could inhibit Th17 differentiation pathway by suppressing positive regulator of this pathway. Thus, this miRNAs can be considered as potential therapeutic targets for suppression or symptom reduction and also diagnostic markers in MS patients.

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Neurotrophins are a family of secretive growth factors that do their functions via binding to their specific receptors (Trks) or their common receptor (p75ntr). p75ntr has important roles in survival, differentiation and proliferation of several types of cells. MicroRNAs are non-coding small RNAs that regulate post-transcriptional mRNA expression. Recently, a MiRNA named hsa-miR-6165 has been discovered in forth intron of p75ntr. Bioinformatics analysis has revealed that this MiRNA has important roles on regulation of several cellular signaling pathways and signaling pathway involve in differentiation. Therefore, in the present study, the expression of hsa-miR-6165 in neuronal differentiation of NT2 human embryonic carcinoma stem cell line and non-nervous and nervous human cell lines was analyzed. Our results indicated that hsa-miR-6165 not only has been expressed in differentiation process of NT2 cells and neural cell lines but although significantly expressed in several human non-neural cell lines such as hFSF and Hela. In addition, the expression of this miRNA, unlike its host gene, upregulated at the end of the differentiation. These results indicate the probable presence of independent promoter for this MiRNA and revealed that hsa-mir-6165 maybe has roles in cellular differentiation which needs more investigation.

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Objectives: Tissue homeostasis is the result of strict regulatory mechanisms, which control self-renewal, differentiation, prevention of premature senescence and apoptosis of stem cells. Bmi-1, a Polycomb group repressor protein, represses genes that induce cellular senescence and cell death, and can contribute to cancer when improperly expressed. Material and methods: Bladder tumoral and nontumoral samples were collected from Labbafi-Nejad hospital. RNA was extracted from each sample, reverse transcribed and amplified by RT-PCR technique, using specific primers for Bmi-1 and β2-microglobolin, as an internal control. The production and distribution of Bmi-1 protein was also examined by western blotting and immunohistochemistry technique. Results: To clarify the role of Bmi-1 in bladder tumors, we examined the expression of Bmi-1 in tumoral and nontumoral samples. RT-PCR generated a 683 bp product, corresponding to the expected size of the Bmi-1 amplified region. The identity of the amplified fragment was then confirmed by direct DNA sequencing. The mean of expression of the Bmi-1 detected in tumoral tissues was significantly higher than the non-tumoral tissues and there is also a significant correlation between the mean of gene expression with stage of malignancy (p < 0.05). The expression of Bmi-1 at protein level was further confirmed by western blotting and immunohistochemistry. Conclusion: The tumor suppressor locus Cdkn2a (Ink4a/Arf locus) codes for two proteins, p16ink4a and p14arf. Ink4a and Arf are playing important roles in the retinoblastoma (pRB) and p53 pathways, respectively. Bmi-1 is a potent repressor of both pathways and hence elucidating its role in tumorigenisis is very important. Here, for the first time we are reporting the expression of Bmi-1 and its correlation with malignancy in bladder tumors.

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Objective: Inhibition of apoptosis may favor the onset and progression of cancer. Survivin is an inhibitor of apoptosis that has been considered as a potential marker for diagnostic and/or prognostic of bladder cancer. The survivin protein regulates both cell division and cell death and is overexpressed in the vast majority of human cancers. In this study, the expression pattern and potential prognostic value of survivin was assessed in Formalin-Fixed Paraffin-Embedded (FFPE) samples of bladder tumor. Materials and Methods:FFPE samples, from patients with a well-known five-year survival record, were assessed by semi-quantitative RT-PCR technique. 51 samples from 30 patients were analyzed on the basis of Survivin expression. Tissue distribution and subcellular localization of survivin protein in tumor tissues was also examined by immunohistochemistry (IHC). Results: The expression of survivin was detected in 66.6% of the samples, with an increase of expression in higher grades of tumor. Furthermore, survivin was overexpressed in 2nd and 3rd recurrences of the same patients. Also, with the increased malignancy and accordingly increased expression of surviving, the overall 5-year survival rate of patients was significantly declined (P=0.036). IHC results also localized a nuclear localization for Survivin protein in tumor tissues. Conclusion: In conclusion, we were able to detect the expression of survivin in FFPE samples of bladder tissues, at the level of mRNA and protein and find a correlation between the level of Survivin expression and the degree of malignancy of the tumors. Our findings introduce Survivin as a suitable prognostic marker for predicting the bladder tumors.

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Objective: Because of the necessity of more effective treatments for the nervous system injuries and considering the role of survivin in cellular proliferation and apoptotic cell death, we have monitored survivin gene expression changes during the course of regeneration in injured sciatic nerves and also L4-L6 segments of spinal cord. Materials and Methods: We used adult male NMRI mice as a model. After anesthetizing the animals, the right sciatic nerve was transected and at the indicated times (3, 6, 12, 24, 48, 96 and 144 hours) the animals were sacrificed and both distal and proximal segments of the transected sciatic nerve, intact left sciatic nerve and L4-L6 segments of spinal cord were dissected. The total RNA was extracted from each sample and semi-quantitative RT-PCR with specific primers for survivin and also 2-microglobulin genes, as an internal control, was performed. To determine cellular distribution of survivin protein, 6 days (144 hours) after the axotomy, survivin protein expression was evaluated using immunohistochemistry technique. Results: Our results demonstrated the expression of both survivin140 and survivin40 in distal and proximal segments of sciatic nerve with different intensity, where the expression of survivin140 was higher than survivin40. In spinal cord segments, only survivin140 expression was detected. In Immunohistochemistry analysis of spinal cord segments, both the nuclear and cytoplasmic distribution of survivin protein was observed. In contrast, survivin protein has not been detected in either distal or proximal segments of sciatic nerve. Conclusion: Our data suggest that survivin is differentially expressed and spliced during the course of regeneration in damaged nerve and spinal cord. It seems that manipulation of expression and/or splicing of survivin could potentially affect the process of regeneration in nerve and/or spinal cord injuries.

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Objective: Nucleostemin (NS) is a recently identified gene that is expressed mainly in the nucleoli of neuronal, embryonic and mesenchymal stem cells which plays a role in their self renewal. Over expression of this gene has been reported in several cancer cell lines tumoral tissues including gastric, hepatic and prostate cancer. In this study, we investigated the effects of suppression of this gene by RNAi technique in a human bladder cancer cell line. Materials and Methods: After confirmation of expression of nucleostemin in the bladder cancer cell line 5637, 21-mer oligoes against NS were transfected into cells and suppression of NS was confirmed by RT-PCR, immunocytochemistry (ICC) and western blotting. Proliferation assays were done by counting the cell numbers. Changes in cell cycle and apoptosis induction were assessed by staining cells with Propidium Iodide and Annexin V-FITC respectively. Results: Our results revealed that nucleostemin is highly expressed in 5637 carcinoma cells. Expression of NS, by semi-quantitative RT-PCR, after treatment with specific oligoes against it, decreased around 85% in comparison to control groups. In addition, ICC and western blotting further confirmed the suppression of nucleostemin at the protein levels. Analysis of cell proliferation assays showed a considerable decline in the number of cells, specially, 72 h after treatment of cells with oligoes against NS. Cell cycle analysis after NS suppression showed increase of sub-diploid events, characteristic of apoptotic cells that were confirmed by staining cells with Annexin V-FITC dye. Conclusion: It seems that nucleostemin expression plays an important role in the induction of cell proliferation as well as inhibition of apoptosis occurrence in 5637 cells. Further studies focusing on suppression of this gene in vivo, may help to find potential therapeutic strategies to cure bladder cancer.

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Clinical application of embryonic stem (ES) cells faces difficulties regarding tissue rejection as well as ethical limitations. One solution for these issues is to reprogram somatic cells by the injection of their nucleus into an enucleated oocyte or zygote. However, technical complications and ethical considerations have impeded the therapeutic implications of this technology. An approach which is most recently developed is in vitro induction of reprogramming in adult cells. This was first achieved by using four transcription factors, including Oct4, Sox2, c-Myc and Klf4. Subsequently, many ongoing efforts were performed for enhancing this method, also for making it compatible with clinical applications. However, there is still a long road ahead. In this paper we review strategies to reprogram somatic cells to embryonic state and discuss about the recent strategy and the relevant developments.

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The development and function of mammalian cells, like other multicellular animals, requires cell to cell interactions, which are carried out directly via cellular junctions or indirectly by secretion of secretory molecules such as hormones. During the last two decades, exosomes have been introduced as the third mechanism for cellular interactions. Exosomes are small vesicles with membranes and 30 to 100 nm in size that exist in blood, urine, saliva, semen, and serum. Exosomes play an important role in a variety of biological processes such as immune response and inflammation, pregnancy, tissue generalization, blood coagulation, and angiogenesis. Exosomes are also involved in pathologic process such as neurological disorders, cancer, infectious diseases, and cardiovascular diseases. Because of their small size, exosomes are able to cross the cell membrane and protect the proteins from degradation. They also have the potential of transferring different compounds into the cell. Due to their receiver specificity, lack of inducing immune system, and more importantly having the capacity to be engineered as drug carriers, exosomes have been introduced as new agents for the transfer of genetic material and disease treatment.

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Objective: The environmental exposure to Magnetic Fields (MFs) may interact with biological systems. MFs are generated from various sources such as power lines, electric appliances at homes and offices, electrified transportation systems including urban railway systems and diagnostic devices such as Magnetic Resonance Imaging (MRI). There are some scientific evidences that imply the exposure to MFs are hazardous to our health and increases the rate of some cancers like leukemia. The biological consequences of exposure to MFs have been investigated from a variety of endpoints. However, most studies have been performed in vitro and have examined effects on cellular processes and its malfunction; such studies can be used as evidence of effects in vivo. Materials and Methods: In this study Bone Marrow Stem Cells were grown in the absence and in the presence of a 15 mT Static Magnetic Field for 5 hours in order to determine any changes in cell cycle progression using the count of cells in different phases. The count of cells in a special phase of cell cycle indicates the length of that phase. The Static Magnetic Field was performed using a locally designed MF generator. Results: A significant increase in the number of cells in G0/G1 was observed in comparison with the controls. Also the number of cells in G0/G1 in the cells treated with Hydrogen-Peroxide, as an oxidative agent, was significantly increased in Static MF. Conclusion: Genetic material damages or mal-function of related proteins may cause these halts. Mfs have not enough energy to affect the biological molecules directly but the mechanism of free radical mediators is probable. These kinds of damages (direct or indirect) can permanently bring the cell cycle to a halt.

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Objective: Lymnaea palustris was previously found in Mazandaran province but there was not any report about its parasitologic aspects. This study was conducted to finding ecological and Parasitological aspects of snail in Mazandaran province, North of Iran. Materials and Methods: In this descriptive study, more than 181 locations, were checked, in 36 locations, colonies of the snail were found and 490 snails were collected. After diagnosis of snails as Lymanea palustris, in laboratory, they were crushed and their probable cercaria was checked out by a dissecting microscope. Data were analyzed and processed by ArcGIS 9.2 and Microsoft Office 2003 for descriptive analysis. Results: from 490 snails, 6 cases (1.22%) were infected with trematode larval stage. These cercariae were classified as echinostomaercaria. Optimum temperature for the snails was 15-19 degrees of celsius and optimum dissolved salt (TDS) was 200-400 ppm. Population of colonies were raised in autumn and winter but infected snails were seen in summer. Conclusion: This study could show the ecological pattern, distribution, and population dynamic of the snail. Also the existence of echinostomaercaria which is cercaria, generally belong to the Echinostoma sp, indicates veterinary and parasitological importance of local snails. It is probable these parasite, infect man also. More studies on definitive host and exact species of parasite are proposed.

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To determine ancient seed species, 3250-3450 year-old charred seeds obtained from different Iranian archaeological sites were studied using Scanning Electron Microscopy (SEM) and molecular analysis. SEM analysis of ancient seeds revealed that the surface of the seeds was damaged. Therefore, we could not accurately identify their species. Molecular analysis on ancient specimens was done on different samples obtained from Masjede Kabood (Tabriz), Tepe Rahmat Abad (Pasargad) and Tepe Sagz Abad (Qazvin plain). The specific primer pairs were designed based on a part of the promoter region of the High Molecular Weight (HMW) glutenin gene and a short fragment of the vrs1 gene were verified on samples of modern wheat and barley varieties, respectively. The designated primers failed to amplify ancient DNAs (aDNAs) obtained from Masjede Kabood and Tepe Rahmat Abad, but successfully amplified the aDNA obtained from Tepe Sagz Abad. This finding was expected since the latter seeds had a better morphological preservation in comparison to the former ones. The accuracy of the amplified products was further proved by cloning and sequencing.

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Objective: The current methods for bladder cancer diagnosis suffer from low sensitivity and specificity. Therefore, finding a novel tumor markers with high specificity and sensitivity is of great interest. MicroRNAs (miRNA, miR) are small endogenously-produced, non-coding RNAs with an important role in regulating gene expression. Recent studies show that miRNAs expression profiles represent significant tumor-specific changes that are unique for most cancers. The aim of this study was to optimize miRNA containing total RNA extraction from urine and use it as a reliable and repeatable technique for miRNA detection in urine of patients with bladder cancer. Materials and Methods: Total RNA was extracted from the urine of patients with bladder cancer and normal individuals using RNX and Trizol solutions with and without modifications of original protocols. Real-time quantitative RT-PCR was then used to detect miRNAs with a potential link to bladder tumorigenesis. Results: RNX and the modified Trizol are practical methods for RNA extraction from urine samples. The mir-21 amplification of the extracted RNAs using modified Trizol method was more efficient than that of RNX method. It is noteworthy that, the levels of miRNAs expression were much higher in the frozen urines compared to the fresh ones. Conclusion: We have succeeded to set-up a protocol to easily amplify miRNAs in urine samples. Based on the data, microRNAs seem to be good biomarkers for early detection and screening of bladder cancer.

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Drying characteristics of green pea (Pisum satium) with an initial moisture content of 76% (db) was studied in a fluidized bed dryer assisted by microwave heating. Four drying air temperatures (30, 40, 50 and 60ºC) and five microwave powers (180, 360, 540, 720 and 900W) were adopted. Several experiments were conducted to obtain data for sample moisture content versus drying time. The results showed that increasing the drying air temperature resulted in up to 5% decrease in drying time while in the microwave-assisted fluidized bed system, the drying time decreased dramatically up to 78.8%. As a result, addition of microwave energy to the fluidized bed drying is recommended to enhance the drying rate of green pea. Furthermore, in this study, the application of Artificial Neural Network (ANN) for predicting the drying time (output parameter) was investigated. Microwave power, drying air temperature, and green pea moisture content were considered as input parameters for the model. An ANN model with 50 neurons was selected for studying the influence of transfer functions and training algorithms. The results revealed that a network with the logsig (Log sigmoid) transfer function and trainrp (Resilient back propagation; Rprop) back propagation algorithm made the most accurate predictions for the green pea drying system. In order to test the ANN model, the root mean square error (RMSE), mean absolute error (MAE), and standard error (SE) were calculated and showed that the random errors were within and acceptable range of ±5% with a coefficient of determination (R2) of 98%.

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Boom and recession cycles in different countries relate to the U.S. business cycles. The study of severe recession in the U.S. can predict a contemporaneous global recession and provide policies to reduce the negative effects. This paper analyzes the business cycles of the U.S. using three stylized facts and reasons. The consequences of U.S. business cycles, as a developed country, have been compared to those of Iranian business cycle in the final section of each part. The period covers quarterly data for U.S during 1960-2010. This paper analyzes the data using VAR model. Our findings show the severe economic recessions have been started in the U.S. during 1980 and 2008.in addition, The U.S. economy has experienced the longest period of economic boom during 1980s and 1990s. Comparing business cycle features of the U.S. and Iran suggests that the severity and extent of boom and recession cycles is much higher in Iran than America. According to the stylized facts on business cycles, some common features of the variables have been confirmed in both countries. On the other variables, the Iranian model is the same of developing countries and the American model is consistent with the developed countries. In terms of the causes of business cycles, the private residential investment has been major cause of business cycles in American economy in the recent years, while exogenous oil price shocks on the Iranian economy has been the most important factor.

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Objective: In an attempt to develop safer and more effective gene therapy approaches as a realistic treatment for various forms of cancer, researchers are increasingly using tumor-specific promoters (TSP) to drive the expression of the gene of interest and eradicate cancer cells. In this study, for the first time we introduce the Oct-4 promoter as a cancer-specific promoter with a high efficacy. Methods: We cloned Oct-4 promoter and enhancers into a pGl3 control reporter vector and analyzed the expression of luciferase as a reporter gene in an AGS gastric cell line. Next, we used a suicide-inducing vector that included an Oct-4 promoter and the TK gene in the presence of the non-toxic prodrug, ganciclovir, to eradicate cancer cells. Cells were treated with PI and connexin V. FACS analysis was conducted to assess the effect of the system on cell cycle and apoptosis induction. Results: Under the activity of the Oct-4 promoter, luciferase expression was three-fold higher than the SV40 promoter. The HSV/TK/GCV system activated by the Oct-4 promoter and enhancers induced apoptosis (86.17%) in the AGS cell line. We verified that this system induced S-phase/G2-phase cell cycle arrest in the AGS cell line. Conclusion: These data indicate that the Oct-4 promoter is active in the AGS cell line. Oct-4 gene is expressed in a wide variety of tumors but not in normal cells. Thus, Oct-4 appears to be a promising tumor-specific promoter for numerous tumors.

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Objective: The anti-cancer properties of curcumin, a poliphenol extract from the rhizome of curry, has been confirmed by many investigators. However, low levels of uptake, tissue distribution and rapid metabolism has limited its application as an anti-cancer drug. This study is aimed at increasing curcumin's water solubility due to a biodegradable, neutral and non-toxic micellar nano-carrier called dendrosome. This study intends to evaluate the role of dendrosomal-curcumin (DNC) in bladder cancer cell growth. Methods: We performed the MTT assay, flow cytometry and Annexin V-FLUOS (as an apoptosis detection kit) to evaluate cell death. The genetic mechanism of DNC-induced apoptosis was accomplished by a study of the relative expressions of OCT4A, OCT4B1, SOX-2 and Nanog using real-time PCR. Results: DNC-induced cell death complied with a time and dose-dependent paradigm in the 5637 cell line. Cell cycle analysis revealed that the number of cells increased in pre-G1 and gradually decreased in G1 and S phases. This showed the inhibitory property of dendrosomal-curcumin on DNA synthesis. Data from real-time PCR determined that expressions of OCT4A, OCT4B1, SOX-2 and Nanog could be related to 5637 cancer cell growth. Dendrosomal-curcumin significantly suppressed mRNA expression of the above mentioned genes (pConclusion: The data showed that DNC induced apoptosis by suppression of pluripotency genes in 5637 bladder cancer cells, which confirmed the useful characteristic of nano-drug in bladder cancer therapy