mohammad zaefizadeh

Natural compounds, such as Oleuropein, Quercetin, Coumarin, and Valproic acid, play a vital role in preventing the spread and progression of cancer. Oleuropein increases the expression of certain caspases, Quercetin reduces the activity of the PI3K/Akt/IKK-/NF-κB pathway, Coumarin inhibits aromatase, and Valproic acid acts as an inhibitor of histone deacetylases. This study aimed to produce a quadruple magnetic nanocomplex with high bioavailability and to examine whether this nanocomplex can induce apoptosis in MCF7 breast cancer cell lines.

A silicon bridge (Sio-N-) was built using nanomagnetic iron and methoxysilane to create a magnetic nanocomplex that incorporated the four natural substances. This quadruple nanocomplex was then analyzed using various spectroscopic techniques and measurements. The researchers assessed the inhibitory impact of the nanocomplex on apoptotic genes in the MCF7 breast cancer cell line using the MTT assay, Hoechst staining, flow cytometry, and real-time PCR analysis.

The magnetic nanocomplex exhibited a greater level of toxicity and reduced the number of cancer cells compared to any of the individual natural compounds or the quadruple combination without nanoparticles. The quadruple magnetic nanocomplex induced overexpression of the pro-apoptotic genes P53, Bim, and Bak, while reducing the expression of the anti-apoptotic gene Bcl2. Additionally, the nanocomplex treatment increased the expression level of genes involved in apoptosis by up to two-fold.

The combination of plant-derived natural compounds and magnetic nanoparticles can enhance the toxicity and concentration of the materials against breast cancer cells. This approach may provide synergistic effects through the modulation of various molecular pathways, leading to the inhibition of cancer cell proliferation and the induction of apoptosis.

Carotenoids play important role as antioxidant and induction of gene expression changes lead to plants acclimation to environmental stresses. Βetacyclocitral (BCC) derived from Galium mite Boiss. & Hohen. in the process of β-carotene oxidation has recently proved that has a new function in breast cancer treatment. In this project we used drug loaded delivery released system (DDRS) strategy, coupled with super paramagnetite nanoparticles (SNPs) based on graphene quantum dots (GQDs) synthesis to deliver drugs to tumor sites. The validation of synthesized SNPs was implemented with several techniques such as Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning electron microscope (SEM) and transmission electron microscope (TEM). MCF-7 cell lines were treated with GQD, β-cyclocitral and GQD@β-cyclocitral (each with concentration of 3.93, 7.87, 15.75, 31.25, 62.5, 125, 250, 500, and 1000 µg/ml) in MTT assay in 24 and 48 hours respectively. IC50% was calculated in 24 h.  Results indicated that β-cyclocitral had prominent effects in breast cancer cell lines controlling.

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.

Breast cancer (BC) is a malignant tumor that occurs in the epithelial tissue of the breast gland and has become the most common malignancy in women. Various studies have reported the effect of epigenetic changes, including DNA methylation and microRNAs, on breast carcinogenesis. microRNAs play an important role in the post-transcriptional regulation of genes and are important regulators of oncogenic pathways. Studying microRNAs in BC facilitates the development of targeted therapies and early detection of this cancer.

This study aimed to evaluate the expression level of miR-508-5p and miR-635 in BC tumor tissues compared to healthy marginal tissues.

In silico analysis confirmed microarray datasets (GSE40525, GSE44124 and GSE45666) downloaded from the GEO database. The analysis was defined using the Affy packages in R software to screen remarkably dysregulated miRNAs attended by utilized to predict the potential biological processes and molecular pathways of miR-508-5p and miR-635. Experimental statistical significance of differences in miRNA relative expression results was analyzed by pair-wise fixed reallocation randomization test as a statistical model included in the REST (relative expression software tool).

GEO microarray data set, similar to qPCR results, showed that miR-508-5p was downregulated in the sample group by a mean factor of 0.327 (S.E.M range is 0.031-2.000). Moreover, miR-635 was upregulated in the sample group by a mean factor of 2.361 (S.E.M range is 0.250-16.000).

miR-508-5p was downregulated, while miR-635 was upregulated in BC tissues. They may be proposed as diagnostic and therapeutic biomarkers for patients with BC.

 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.

Nanotechnology is a branch of science that that has opened new research horizons, particularly in the field of ofmedicine and cancer treatment.In the present paper, magnetite nanoparticles (Fe3O4) were produced by the co-precipitating of two and three valent iron chloride salts in an alkaline medium. The surface of the nanoparticles was functionalized with (3-Aminopropyl)-trimethoxysilane(APTS), and finally the cisplatinanticancer drug was loaded onto the modified nanoparticles. Properties, structure and morphology of the nanoparticles obtained were evaluated and analyzed by X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Vibrating Sample Magnetometer (VSM) for measuring magnetic properties. Results showed that cisplatinwas attached to the surface of the nanoparticles confirmed by FT-IR analysis. Magnetic properties using VSM results showed that the nanocomposite is the result of superparamagnetism. Findings showed that magnetic cisplatin magnetic nanocomposites are promising for targeted magnetic drug delivery and can be used as a targeted nanoparticle suitable for delivering anticancer drugs.

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.

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.

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.

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.