Personalized and Precision Medicine Journal

Abstract Nanotechnology involves the creation and manipulation of materials at nanoscale to create products that exhibit novel properties. Nano-TiO2, as one of the top five nanoparticles in annual production, is widely applied in industries ranging from healthcare to drug delivery. The properties of nanoTiO2 have raised concerns regarding toxicity. Annexin V-FITC/PI double staining and a flow cytometer were used to detect apoptosis. A significant increase in apoptosis was observed at concentrations of TiO2-NP of 50-100 µg/ml, varying between 25-40% apoptosis by 24 h. To further investigate the aptotic and toxic effects of these substances, it is recommended that this study be performed in the in vivo phase.

Abstract Lung cancer is still the most common cancer worldwide in terms of the number of newly diagnosed cases and mortality rate. The expression of miR-146a was reduced in mesenchymal-like lung cancer cell lines. The overexpression of miR-146a induced a marked reduction of the mesenchymal marker and increase in the epithelial marker in lung cancer cell lines. The current study investigated the association of miR-146a genotypes and lung susceptibility in a Tehran population to determine the visibility of using RFLP-PCR genotype. The results revealed a significantly higher frequency of miR-146a CG and CC genotypes (p =0.01 and p=0.008, respectively) in patients compared with the control group. Those with the miR-146a GC and CC genotypes had an increased risk for developing lung cancer (OR=1.9; 95% CI: 1.1-3.3 and OR=4.1; 95% CI: 1.5-12.3, respectively). Moreover, the frequency rates of miR-146a CC genotype and C allele were significantly higher in patients than in the controls (p =0.006 and p=0.000, respectively).

Abstract The majority of ncRNAs are known as long non-coding RNAs (lncRNAs) whose length exceeds 200 nucleotides. H19, a lncRNA, is the transcription product of the H19 gene, an oncogene in breast cancer, and is highly expressed in cancer tissues compared with normal tissues. The expression level of H19 is associated with the oncogenesis, proliferation, invasion, metastasis, and drug resistance of breast cancer. H19 expression levels were detected in breast cancer plasma using qRT-Real-Time PCR assay in 50 breast cancer samples and 50 healthy control samples. The results showed that the expression of this gene in both the tissue and the plasma of patients increased compared to that of healthy individuals.

Abstract Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is characterized by high blood sugar, insulin resistance, and relative lack of insulin.Diabetic retinopathy, a secondary microvascular complication of diabetes mellitus, is the leading cause of blindness. There is extensive evidence that the pathologic ocular angiogenesis in diabetic retinopathy is regulated by the vascular endothelial growth factor-A (VEGF-A).The single nucleotide polymorphism (SNP) C936T (rs3025039) of the VEGF gene has been investigated in relation to cancer, endometriosis, and age-related macular degeneration. The relationship between the rs3025039 VEGF gene polymorphism and the risk of type 2 diabetic retinopathy in 80 DT2 patients was examined. No significant association was found between polymorphism C936T and type 2 diabetes. It is recommended that this study be repeated on a larger population.

Abstract Because of their small size, unique physics, and chemical properties, metal nanoparticles can easily cross obstacles and reach their target cells, which makes them an ideal choice for therapeutic purposes in various cancers. In this study, the effects of iron oxide nanoparticles on MDA-MB-231 breast cancer cell line were examined, and biomarkers related to oxidative stress were evaluated. Fe2O3 nanoparticles were suspended in a cell culture medium and diluted to appropriate concentrations (0, 10, 30, 60, and 120 μg/ml) for 24 and 48 h. GSH, superoxide dismutase, catalase, and ROS generation were evaluated. The results showed that iron oxide nanoparticles induced intracellular ROS generation in a dose- and time-dependent manner. The results further showed that iron oxide nanoparticles increased ROS and activated oxidative stress in cells.

Abstract Spermatogenesis is a very complex process that can be affected by a number of factors which may lead to reduced fertility or infertility. Busulfan kills spermatogonia stem cells and disrupts the connections between Sertoli and spermatogonia cells at base layers. Moreover, vitamin D is very important in the reproductive system of men. In this study, the effect of vitamin D on biosulfur-induced azoospermia in mice was investigated. The results showed an increase in the quality of sperm parameters in the group treated with vitamin D.

Abstract Lung cancer is the deadliest cancer in Iran after gastric cancer. The vast majority (85%) of cases of lung cancer are due to long-term tobacco smoking. About 10–15% of cases occur in people who have never smoked. These cases are often caused by a combination of genetic and environmental factors. Many human cancers are the result of mutations in the RAS family, and lung cancer is no exception. In this study, mutations in codon 12 and 13 of exon two were performed in 50 lung tumors from the Iranian Institute of Oncology. The exon 2 of the gene was amplified by PCR and sequenced for detection of the point mutation in codon 12 and 13. Of the 50 samples, 13 had mutations in codon 12 and 13, of which only two patients had single mutations in codon 12. No significant relationship was not found between age (P = 0.43) and gender (P = 0.37) and mutations in this gene. No significant relationship was found between disease stage and mutation in this gene (P = 0.51). Identifying k-ras gene mutations as an oncogene and having an effect on the treatment process can help the physician to choose the appropriate treatment.

Abstract Numerous studies have been conducted to investigate the relationship between genetic factors and drug use tendency, many of which have shown a significant correlation between genetic factors and drug use, especially heroin and cocaine. The most important site of drug action is the brain, which contains a variety of nerve receptors. Dynorphins are opioid peptides derived from the prodynorphins precursor (PDYN). These opioid peptides are capable of binding to the three types of opioid receptors. Studies have shown that heroin and cocaine use is associated with increased PDYN gene expression in specific areas of the brain. In this study, we investigated the association between rs910080 polymorphism in the 3'UTR region and the number of VNTR sequences in the promoter region with the tendency of heroin use in 155heroin addicts and 150 control with RFLP method. Results showed a significant relationship between heroin abuse and CC genotype in rs910080 polymorphism (P = 0.001), but no significant relationship between VNTR promoter repeats and heroin abuse. Rs910080 polymorphism can be used as a distinguishing factor.

Abstract Epithelial to mesenchymal transition (EMT) is a process by which epithelial cells lose their epithelial characteristics such as cell polarity and cell–cell contact, and gain mesenchymal properties, such as increased motility. In colorectal cancer (CRC), EMT is associated with an invasive or metastatic phenotype. EMT induced by special transcription factors such as EMT-TF. The ZEB and Twist proteins were defined as EMT‐TFs. All of these factors are expressed in embryogenesis and are capable of regulating developmental programs. In the current study, we evaluated Zeb1 and Twist1 expression levels in 30 CRC patients and 30 adjacent tissue from same patient. Our findings revealed a significant association of Zeb1 and Twist1 expression levels with CRC incidence, suggesting their potential for targeted therapy of disease.

Abstract Methylenetetrahydrofolate reductase (MTHFR) has a critical role in spermatogenesis process and altered expression level of this gene may leads to male infertility. In the present study, the assocaitions of gene expression and promoter methylation of MTHFR with risk of oligozoospermia was assessed. Sperm DNA and RNA were extracted from 20 oligozoospermia men and 20 controls consisting of healthy fertile men. Following the modification of DNAs by sodium bisulfite treatment, the methylation status of the MTHFR gene promoter was quantified by methyl specific PCR. MTHFR expression evaluated by Quantitative PCR, or real-time PCR, (qPCR). Our data revealed a significant association of CpG island promoter methylation and MTHFR expression with risk of oligospermia (P = 0.031). The prevalence of methylation in promoter region of MTHFR can be a useful molecular biomarker to predict the predisposition of male infertility.

Abstract Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. Non-alcoholic fatty liver disease is a spectrum of simple steatosis that is benign to non-alcoholic steatohepatitis (NASH) associated with fibrosis and inflammation. Genetic factors play an important role in this disease. The PNPLA3 gene (C > G) rs738409 polymorphism has been defined to be associated with increased liver fat content and liver damage in metabolic disorders. In this study, the association of this polymorphism with non-alcoholic fatty liver disease was investigated in the Mazandaran province population. Our study population consisted of 85 patients and 85 controls. Blood samples were collected from patients and DNA were then extracted by boiling method. Genotypes of this polymorphism were determined by PCR-RFLP method. There was a significant relationship between CG genotype and risk of NAFLD (P = 0.012).

Abstract Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder. The etiology of MS is not clear but genetic and epigenetic factors are involved in MS development. Studies have shown that IL7R gene polymorphisms is capable of changing MS susceptibility. We investigated the association of MS with rs11567658, rs11567686 promoter polymorphisms of IL7R gene in western provinces of Iran. In the present study, 187 MS patients and 190 healthy control were evaluated. Polymorphic regions of IL7R promoter were amplified by appropriated primers and polymorphisms were then evaluated by RFLP method followed by validation via Sanger sequencing. Results shown rs11567685 and rs11567686 are significantly associationed with MS (P = 0.017 P = 0.046), significant association of these polymorphism with age was also found (P = 0.002). This study showed that IL7 receptor gene polymorphism has a key role in MS development and may be important opportunity for development of therapeutic and diagnostic strategies in context of personalized medicine.