محمد ضعیفی زاده

Breast cancer is the most common cancer in women, which is the main cause of cancer-related death in women. The use of herbal compounds as anti-tumor with less side effects than chemotherapy has been considered. But it seems that over time drug resistance will reach this type of material. This study has been conducted to determine the effect of plant extracts and exosomes extracted from their effects on MCF7 cancer cells.

  In this comparative study, MCF7 cells were cultured in medium and treated with different concentrations of oleuropein, quercetin, coumarin and Valproic acid for 24 hours. Then the cell viability was evaluated by MTT method and its IC50 values were calculated and exosome was extracted from the culture medium of the treatments and applied to MCF7 and their IC50 values were also calculated by MTT method.

The results of MTT confirmed the inhibitory properties of four natural substances and their combination on MCf7 cells. Coumarin and quercetin were the most effective treatments of the studied materials. But the exosome obtained by applying 50% of their concentration had an inhibitory role with higher concentrations and the exosomes obtained from their IC75 actions had played their role in lower inhibitory concentrations.

Inhibition of breast cancer cells by the exosomes obtained from the combination of the above-mentioned 4 substances occurred in a lower dose Because at this concentration, all cell death-inducing substances and their signals accumulate in the exosome, and by transferring into cancer cells, they induce cell death.

Breast cancer is the most common type of cancer among women, which occurs in the epithelial tissue of the mammary gland. Various environmental, genetic and epigenetic factors play a role in the occurrence of breast cancer. According to the previous studies, one of the most important epigenetic changes involved in the occurrence of breast cancer is the dysregulationof the expression level of microRNAs. Therefore, the aim of this study was to investigate the expression level of miR-509-3-5p and miR-596 in breast cancer tumor tissue.

In the bioinformatics analysis, the datasets related to miRNAs (GSE40525 and GSE45666) were prepared from the GEO database. Data analysis was performed using the Affy package in R software. Sampling was done from 100 women with breast cancer and 100 control. Tissue RNA was extracted using Trizol solution. Then, using the cDNA synthesis kit, DNA was synthesized from the extracted RNAs, and the expression level of miR-509-3-5p and miR-596 was investigated using Realtime PCR method.

According to the bioinformatics results, the expression level of miR-509-3-5p and miR-596 in breast cancer tissue reduced compared to healthy tissue. The expression level of miR-509-3-5p and miR-596 in tumor tissue was significantly lower than normal tissue (p<0.05).So these results confirmed the results of bioinformatics studies.

According to the results of the present study, which showed a decrease in the expression of miR-509-3-5p and miR-596 in breast cancer, it can be said that these miRNAs can be used as important diagnostic and therapeutic biomarkers in breast cancer.

 Gastric cancer is one of the most common gastrointestinal cancers in the world, Iran and Ardabil. The used of exosomes for drug packaging to inhibition of drug-resistant of cancer cells is a new method. This study aimed to evaluate of extraction exosome of the AGS cell line to inhibit of MKN45 cell line.

 Exosomes in concentration LC50 and LC75 nano coumarins were extracted from supernatants of cultured AGS cells using Exosome Isolation Kit and confirmed by DLS, and their effect was applied to drug-resistant MKN45 cells. Inhibition test (MTT) and expression of Caspase 8, Caspase 9, BCL2, Bax, and P53 genes were measured.

 The results showed that the extraction of exosome with concentration LC75 From AGS on MKN45 in addition to the concentration-dependent inhibitory role of impact on a significant change in gene expression Caspase 8, BCL,2, and P53.

 Increased expression of genes Caspase 8, BCL2, and P53 in exosome treatment at LC75 level indicate induction of apoptosis from the external pathway by exosomes in resistant cells, as evidenced by the decrease in the expression of miR-21 oncomir and the increase in miR-34a in the exosome contents.

Breast cancer (BC) is a complex genetic disease that has an average annual incidence of one million people and is the second leading cause of death among women in the world. Therefore, a better understanding of tumor biology and the determination of biomarkers for early diagnosis of disease is essential. MicroRNAs and long non-coding RNAs are novel gene regulators that play key roles in tumor initiation and progression. The current study was performed to assess the biomarker potential. This study performed a combination of in-silico and experimental investigations of altered miRNAs in BC to assess the use of miRNAs as novel biomarkers for early detection and prognosis prediction of patients with BC.

We searched the miRNA expression patterns of BC from three expression arrays (GSE58606, GSE38867, and GSE40525,) from the Gene Expression Omnibus (GEO) database to recognize differentially expressed miRNAs (DEMs) between BC tissues and normal adjacent samples. Using “Limma" package's Quantile Normalization function and INMEX bioinformatic tool, hub DEMs were identified. MiRNAs targeted genes were found and visualized via the miRWalk and miRTargetLink databases and their Enrichment analysis was performed for identified genes. Due to more validation of DEGs, GSE70951, an independent expression array dataset, was analyzed. By merging DEMs and DEGs, miRNA-mRNA network was constructed. After elucidation of hub miRNAs, the capacity of detected miRNAs to differentiate BC from adjacent controls was estimated by Kaplan-Meier analysis.  Furthermore, RT-qPCR on 100 BC samples and 100 adjacent non-tumor tissues was performed to validate the in-silico results.

According to our study, in BC samples, miR-662 was differentially downregulated in comparison with normal adjacent tissues.

Altogether, miR-662 can be considered as a viable target for BC diagnostics and treatment.

Major depression is the commonest psychiatric disorder and in the world has the greatest impact of all biomedical diseases on disability.The purpose of the present study is comparing the expression of dopaminergic DRD3 and DRD4 receptors in patients with major depression and healthy Individuals.

The population of this study was, all depressed patients admitted to the clinical psychologists. The method is causal-comparative study. The research sample includes of 62 depressed patients (28 male and 34 female), with the random sampling of depressed patients referred to the clinics, to be selected, and 60 healthy individuals(30 male and 30 female) as comparison group. After the informed consent .Evaluate the relative expression of gene DRD3 and DRD4, using measured by quantitative Real-Time RT-PCR and SYBER Green used. Research data was analyzed using the T-Test, SPSS and Excel software.

Results showed that DRD3 gene in patients compared to healthy subjects had greater relative expression(p value<0.001),but the D4 gene expression in the two groups showed no significant difference (p value>0.05).The finding suggest that DRD3 gene seem to be important variables in depression, but DRD4genedoes not play a role in depression.

The finding suggest that he DRD3 receptor gene seem to be an important variable in depression, which showed decreased expression of receptor DRD3,under the influence of this disease, which we can be used as a marker for to screen major depression disorder (MDD) correctly.

Gastric cancer is the fourth most common cancer and the second leading cause of cancer-associated fatality in the world. During the recent decade, nanoparticles have been used widely to reduce the severity and also the treatment of cancers. The current study was performed to transfer Oleuropein into AGS cancer cells using paramagnetic nano-particles and to evaluate their effects on the cancer cell line. 2)

  In this research, nine concentrations of magnetic nano-oleuropein (0, 0.15, ... 333.33 and 1000 µg/mL ) were applied against AGS cells in in-vitro condition with three replicates in the form of a completely randomized statistical design (CRD), and cell viability was investigated using MTT and Flow Cytometry assays. To determine the molecular mechanism of this effect, the relative expression of K-ras and cd82 genes were investigated using the Real-time PCR assay. 3)

Our results for inhibition of cancer cells by different concentrations of magnetic nano-oleuropein showed that the inhibition rate of AGS cancer cells was dependent on the concentration and exposure time of the drug. The relative expression of K-ras oncogene decreased at the concentrations higher than 4.12 μg/mL and increased at lower concentrations (p-value <0.01). Also, the expression of cd82 gene at the concentrations below IC50 (23.6 μg/mL) increased while at higher concentrations reduced significantly. 4)

Balancing the expression of K-ras and cd82 oncogenes through the p53 protein could be one of the molecular reasons for inhibiting the AGS cells by magnetic nano-oleuropein. Therefore, magnetic nano-oleuropein at IC50 concentration plays a key role in inhibiting gastric cancer cells by the creation of an expression balance between K-ras and cd82 genes.

Lactobacillus reuteri has broad-spectrum effects on both gram-positive and negative bacteria as well as fungi and protozoa. Also, Coumarins have high ability to control and treat cancer. Apoptosis is a planned cell death that plays an essential role in the development and homostasis of living creatures. Bax and Bcl2 genes are among key target genes of internal pathway; thus the present study aimed to determine the effect of L. reuteri and Coumarin on the expression of these two genes on AGS cell line.

After cultivation of gastric cancer cells, Coumarin and L. reuteri were affected in these concentrations at different concentrations and the inhibitory effect on cell proliferation was evaluated using the MTT method. Afterwards, the RNA content of cells was extracted using an RNA extraction kit. Then the cDNA was synthesized for Bax and Bcl2 genes and finally Real time PCR was run.

The results of the MTT assay on gastric cancer cells showed the inhibitory effect of Coumarin and L. reuteri. Also, the results of Real Time PCR showed that the expression of Bax and Bcl2 expression in comparison with the control group was significantly increased.

Considering the effects of Coumarin and L. reuteri on inhibiting proliferation of AGS cells and increasing the Bax and Bcl2 gene, it can be concluded that Coumarin and L. reuteri can induce apoptosis in cancerous cells by affecting the expression of genes involved in apoptosis.

Prostate cancer is the most common cancer in men. Identification of cancer nature, progress and the mechanism of its inhibition have been always scientific important issues. The aim of this study was to analyze the effect of olives Oleuropein particles on protein expression levels in prostate cancer cell line, LNcap.

Survival test (MTT) has been applied in 8 concentrations of Oleuropein: 19, 39, 78, 156, 312, 625, 1250, and 2500 in LNcap cell line, as well differential comparative proteomics analyses has been performed. Two dimensional electrophoresis results in relation to differential proteins have been identified by MS- MALDI-TOF-TOF approach, as their aligns have been recognized in Mascot Database.

Survival test demonstrates that olive Oleuropein controled LNCap cells growth and increased their roundness. LNCap cells have most been controlled in 625ppm concentration. GSTP1and DMNT1proteins have been identified as differential proteins in Oleuropein treated samples. Where comparing to controls, DMNT1 had been downregulated. On the other hand GSTP1 had been upregulated in 625 ppm Oleuropein treated samples.

Oleuropein may be effective for inhibition of prostate cancer cells in LNcap cell line, by affecting protein expression, antioxidant genes expression, some transcriptional factors expression in relation with cells leading toward apoptosis direction, and metastasis activity reduction.

Transcriptionally silencing is related to abnormal methylation of tumor suppressor gene promoters by the enzyme of DNA methylase (DNMT1) in an alternate way in prostate cancer development. Ghareghate (acciniumarctostaphylos) have polyphenols and anthocyanins which may be investigated as natural antioxidants in prostate cancer cells treating.

In this study human invasive prostate cancer cell lines (PC3) were treated with various concentrations (156, 312, 625, 1250, 2500 µg/ml) of Ghareghate fruit extractions. DNMT1 expression levels and inhibition rates were assessed after 24, 48 hours by Q-RT-PCR and MTT test respectively.

DNMT1 expression rates in pc3 cell line which treated with Ghareghate extractions, reduced significantly comparing to control cells (p<0.001). Moreover it has demonstrated that Ghareghate extractions can significantly increase inhibition of cancer cells grow (p<0.001). The highest relative decrease of gene expression observed in 625µg/ml.

Ghareghat extractions can be used as an antioxidant recourse for the purpose of cancer therapy and prevention.

To evaluate the drought tolerance of lentil by morpho-physiological traits, 10 lentil lines were planted in randomized complete design with 3 replications under non-stress and drought stress conditions in agricultural station of Islamic Azad University, Ardabil, Iran in 2016. Grain yield, plant height, number of pods and 1000 kernels weight, leaf relative water content, activity of superoxide dismutase and catalase enzymes and cell membrane stability were measured. Results showed that differences among genotypes were significant in all of traits except for relative water content and CAT activity (under non-stress). Under drought, ILL-10088, ILL-10053 and Bilesavar, with 1244, 1153 and 1107 kg/ha and under non stress condition, ILL-10088, with 1905 kg/ha had the highest yield. Considering the yield of cultivars in two environments, ILL-10088, BileSavar, ILL-10017 and ILL-468 were the most tolerant cultivars. Results showed that under drought, grain yield had significant correlations with catalase activity, relative water content and cell membrane stability. Under non-stress condition, yield had significant correlations with relative water content, cell membrane stability, 1000 kernels weight and number of fertile pods. In regression analysis, using stepwise method, under stress, relative content remained in model. However, under non-stress condition, relative water content and cell membrane stability remained in model. Principle component analysis could separate susceptible cultivars from tolerant cultivars better than cluster analysis. Regarding to the presence of genetic diversity, ease of use and strong relations with yield, relative water content and cell membrane stability were proposed as indirect criteria for selection of drought tolerance in lentil.

Breast cancer is one of the most important causes of cancer deaths especially in developing countries. However, some synthetic compounds such as thiosemicarbazone and its metal derivatives can play a very significant role in reducing the death rate from cancer. The aim of this study was to investigate alterations in the expression of BRCA1, p53 and Bcl-2 genes in breast cancer cell line.

In this study, the effect of pyrazole derivative of thiosemicarbazone (T) as well as T-bound iron oxide magnetite nanoparticles (T/ Fe3o4 np) were investigated on expression changes of Bcl-2, BRCA1 and p53 in MCF-7 cells. For this purpose, the toxicity of the compounds was first measured using the MTT reaction for 24 hr. Then, the mRNA expression levels were evaluated using real-time PCR reaction.

The results showed a high toxicity for the nano-pyrazole derivative of thiosemicarbazone magnetite so that; the fatality rate for treated thiosemicarbazone magnetite derivative cells was much higher than the compound without any nanoparticle. Also, real-time polymerase chain reaction analysis of gene expression indicated a high effect of the derivative on increasing the expression levels of BRCA1 and p53 genes and also decreasing the Bcl-2 gene expression of Bcl-2.

The use of anticancer compounds like thiosemicarbazone which bound to iron oxide nanoparticles would increase the toxicity of the anticancer compounds along with enhancment of delivery of them with high solubility to target tissue.

Prostate cancer is one of the most common cancers in the world, and its prevention is expected to increase in the future appreciably. Following the emergence of the new field of nutritional genetics and investigations about the effect of natural antioxidants on the hypermethylation of genes, this study was performed to measure the effect of Vaccinium arctostaphylos poly phenols and anthocyanins on PC-3 cell line as well as methylation and expression changes of GSTP1 gene.
In order to evaluate the survival potency of PC-3 cell line in a completely randomized design, MTT test was used and these cells were treated with different concentrations of Vaccinium arctostaphylos extract (4500, 2250, 1125, 562.5, 140.62, 70.31, 35.15, 17.57, 8.78, 4.39 µg/ml) for 24, 48 and 72 hours. Expression level of GSTP1 gene was analyzed by Q-RT-PCR method in 2500, 1250, 625, 312 and 156 µg/ml concentrations of Vaccinium.
Statistical results showed that Vaccinium arctostaphylos poly phenolic extract at 35-70 ppm concentration significantly reduced the survival rate of PC-3 cells. Moreover, compared to control cells, the expression level of GST gene significantly increased in PC-3 cells treated with 1250ppm extract.
Anthocyanin- polyphenolic extract from Vaccinium arctostaphylos can decrease the survival rate of cancerous cells and GST gene expression in human prostate cancer PC-3 cells. This may be explained by changes in cell carcinogenesis pathway or CpG demethylation process.

Fatty acids accumulation pattern and oil oxidizability during fruit ripening of two olive cultivars of high and low oleic acid, Shengeh and Mary,were studied respectively while the environmental conditions kept constant. Samplings were done at 90, 120, 150 and 180 days after flowering (DAF) and the fatty acid composition was determined by gas chromatography (GC) after seed oil extraction by n-hexane. Analysis of variance (ANOVA) showed that accumulation of stearic, oleic and linoleic acids were significantly influenced by genotype. Indeed, there was a significant correlation between time andboth oleic and linoleic acids. Overall measurements demonstrated higher palmitic and linoleic acids in Shengeh cv. and higher steraric and oleic acids in Mari cv. During four studied stages olive development . Also, there was a positive correlation between linoleate and calculated oxidizability value (COX). Increasing pattern of oleic acid content in both genotypes implies the inhibitory effect of oleic acid on the phospholipase activity of oleosins leading prevention in out-course germination It is worthy to note that genotype plays a crucial role in fatty acid content in development stages as seed oli acid content in mary cv. is higher then Shengeh.

In order to investigate the effects of nitrogen levels on grain yield، phyllochron and leaf emergence rate of maize cultivars، a split plot experiment based on randomized complete block design with three replications was conducted at the Research Farm of Islamic Azad University of Ardabil during 2007 cropping. Factors were: nitrogen levels in main plots (0، 80، 160 and 240 Kg N ha-1) and maize cultivars in three levels (SC-301، DC-370 and SC-404) in sub plots. The results showed that phyllochron، time between the appearance of successive leaves on a shoot، was significantly affected by corn، nitrogen levels and interaction of nitrogen levels × maize cultivars. With increased nitrogen levels، the phyllochron was decreased but rate of leaf appearance was increased. Response of maize cultivars was different to these characteristics. Leaf appearance rate in SC-301 was more than SC-404 and DC-370. The highest leaf appearance rate and the least of time for phyllochron was obtained in treatment compounds of SC-301 with application of 240 kg N/ha. Grain yield was significantly as affected by nitrogen levels، cultivar and interaction of cultivar × nitrogen levels. Maximum grain yield was in SC-404 cultivar and minimum of it was in SC-301 cultivar. Means comparisons showed that maximum grain yield was obtained in SC-404 with application of 240 kg N/ ha. However، no significant different was between application of 160 and 240 kg n/ha. Minimum grain yield belonged to SC-301 without application of nitrogen fertilizer. If growth period was limited، it seems that SC-301 with 240 kg N/ha was applied in order to increasing leaf appearance rate and decreasing of phyllochron. However، if growth period wasn’t limited، it would be better to use of SC-404 with application of 240 kg N/ha.

Iran is one of the world’s centers of diversity for wheat and this country has rich genetic resources for durum wheat، but these genetic resources are under sever genetic erosion and an urgent need is necessary for collecting and protecting them. Therefore 39 landraces of durum wheat were collected from different regions of Ardabil province in 2006 and an experiment was carried out using RCB design with 3 check cultivars. Thirty agronomic، phenologic، morphologic and quality characters were measured. According to the Dorofeev’s classification keys، the landraces were classified in following 11 varieties: melanopus، africanum، albiprovinciale، riechenbachii، leucurum، hordeiform، murcience، melaleucum، albobscurum، boefi and one unknown variety. The results of ANOVA indicated that there were significant differences among landraces in yield، harvest index، 100 kernel weight، plant height، number of seeds per spiklet، days to heading، SDS sedimentation value، awn length، peduncle length and flag leaf length. A MANOVA was performed among 11 varieties and results showed that varieties significantly differ in agronomic traits. Discriminant analysis properly classified varieties into distinct groups however cluster analysis could not do this.

In this study، the morphological and micromorphological characters in form-series of species Rosa canina were considered. In this species، it is difficult to find constant morphological features due to its wide distribution and high potential for hybridization with other species of this genus. Therefore، 30 morphological and 31 micromorphological characters were studied. Regarding high variable of features specially four characters indumentum leaflet، pedicle، glandular leaflet and pedicle، this species was classified into 8 groups. Anatomical، micromorphological and statistical studies with SPSS and NTsysb softwares showed that these characters were valuable to separate these form-series from each other.

To evaluate the effect of various levels of nitrogen fertilizer on nitrogen use efficiency and grain yield of canola cultivars, a split plot experiment based on randomized complete block design was conducted in 2007. Factors were: nitrogen fertilizer at four levels (zero, 50, 100 and 150 kg/ha) in the main plots and canola cultivars at three levels (‘Clover’, ‘Opera’ and ‘Okape’) in the sub plots. The results showed that the effects of cultivar and nitrogen levels were significant on grain yield, grain per plant, pod per plant, grain 1000 weight, harvest index and plant height. The interaction effects of cultivars in nitrogen levels were significant on grain yield, grain per plant, pod per plant and plant height. Means comparison showed that with increasing nitrogen levels, grain yield increasing. Response of canola cultivars was different to grain yield. The highest grain yield (1.18 ton/ha) was obtained in Opera cultivar and the least (0.78 ton/ha) of it was in Okape cultivar. Means comparison showed that the highest grain yield, grain per plant, pod per plant and plant height was obtained by the plots which applied 150 kg N/ha with Opera cultivar and the least of it was in Okape cultivar without nitrogen application. However, application of 100 and 150 kg N/ha had similar grain yield in Opera cultivar. Nitrogen use efficiency was significantly as affected by cultivar, nitrogen levels and cultivar × nitrogen levels. Means comparison showed that with increasing of nitrogen, decreased nitrogen use efficiency. Response of canola cultivars was different with nitrogen use efficiency. Maximum nitrogen use efficiency (5.26 kg/kg) was obtained in the plots which 100 kg nitrogen ha-1 with Opera cultivar was used and minimum (2.64 kg/kg) was obtained in the plots which 150 kg nitrogen ha-1 with okape cultivar was used.

In order to optimize embryogenic calli production in date palm, meristematic tissues were excised from 2-3 years old offshoots of Zahedi, Kabkab and Dayri genotypes and cultured on MS medium containing 100 mg/l 2,4-D, 3 g/l activated charcoal, 30 g/l sucrose supplemented with different concentrations of zeatin and TDZ as cytokinin resources. The samples were incubated at 25±2oC in the darkness. Initial calli were generated from explants cultured in various treatments which were able to produce embryogenic callus after 6-8 weeks of sub culturing in the same medium. The best callus production was observed in 0.5 and 3.0 mg/l of zeatin with respect to Zahedi and Kabkab cultivars and 0.1 mg/l of TDZ for Dayri. Meanwhile, the shortest callus generation time was correspondent to Kabkab, Zahedi and Dayri genotypes, respectively.

University is the center in all fields of scientific developments which heightens the knowledge in the society. Investigating the effective factors on the quality of research and education in the faculty of medicin from the students planning to increase the quality and quantity of research and education status. This was a descriptive-analytic study which was done during the period April 2005 –April 2006 in two faculties of medicine in the state and Azad University of Ardabil. The samples included all the medical students, faculty members and employees of faculties of Medicine at Ardabil University. Data were collected through a questionare. In total, 308 status, 44 faculty members filled out the queitionnaire. Data were analyzed by SPSS version 11. Education and Research, educational Status, educational facilities and educational spaces of both faculties were compared and with the desirable standard of 80%. There was a significant difference in is education and research in both faculties from thr instructors point of view. However, in students, view this defference was not significant. In comparing the research status in both faculties with the desirable standard of 80%, the faculty of Medicine in Ardabil state University of Medical Sciences showed a significant difference whith this difference in Azad University was not significant. In comparing the educational Apace. The faculties with the desirable standard of 80%, there was a significant differency in Azad University where as it was not significant in state University. In terms of Education the faculty of medicine in state Universy was more desirable and in terms of research. Azad University was more desirable.

To determinate the most proper N.P.K. fertilizer level for increasing the quality and quantity of polygerm seeds of sugar beet, an experiment was conducted in randomized complete block design with three replications in 1998-2000 at Research Farm of Faculty of Agriculture, Azad University of Ardabil (Hassan Barog). Fertilizer treatments were: N30P60K60, N90P90K90, N0P0K0, N90P150K150, N90P120K120, N90P90K120 and N60P60K60. The results showed that generally in all treatments, plant height and number of main stems significantly differed at 5 percent and seed yield and germination percentage differed at 1 percent level of probability. The highest seed yield was obtained from N90P90K90 and N90P90K120 treatments. In addition, the treatment N90P90K120 had the highest germination percentage.