Association of rs1570360 and rs2010963 in VEGF and rs2279744 in the MDM2 gene with Recurrent Implantation Failure in Iranian Women.

OBJECTIVE: The embryo implantation includes a complex sequence of signaling events, comprising numerous molecular mediators, such as ovarian hormones, cytokines, adhesion molecules and, growth factors. One of the critical factors in angiogenesis is the vascular endothelial growth factor (VEGF). The VEGF plays a pivotal role in embryonic development, decidua vascularization and placental angiogenesis. Furthermore, the P53 gene and its negative regulator, murine double minute 2 (MDM2), are major players in reproductive processes. This study aimed to assess the association of polymorphisms of the VEGF and the MDM2 genes with idiopathic recurrent implantation failure. METHODS: We genotyped 60 women with previous idiopathic recurrent implantation failures and 60 fertile women as controls. Restriction Fragment Length Polymorphism (RFLP) and Sanger sequencing were used for genotyping the rs2010963 and the rs1570360 polymorphisms in VEGF; and the rs2279744 in MDM2 genes. RESULTS: Results indicated a higher frequency of the VEGF rs1570360 AA genotype and A allele in patients with a history of idiopathic implantation failure [OR=6.4 (1.22 - 33.64), p-value=0.02)]. However, the frequency of VEGF +405 G/C and MDM2 SNP309 T/G [(OR=3 (0.5 - 16) p-value=0.2, OR=1.18 (0.3 - 3.7) p-value=0.7, respectively)] genotypes were not significantly different between cases and controls. CONCLUSIONS: The VEGF polymorphism may influence embryo implantation and the VEGF rs1570360 AA genotype may predispose to the risk of recurrent implantation failure after IVF.

KCNQ1 rs2237895 polymorphism is associated with the therapeutic response to sulfonylureas in Iranian type 2 diabetes mellitus patients.

Background and Aims: Sulfonylureas are the most secondary prescribed oral anti-diabetic drug. Understanding its genetic role in pharmacodynamics can elucidate a considerable knowledge about personalized treatment in type 2 diabetes patients. This study aimed to assess the impact of KCNQ1 variants on sulfonylureas response among type 2 diabetes Iranian patients. Methods and Results: 100 patients were recruited who were under sulfonylureas therapy for six months. 50 responder and 50 non-responder patients were selected. KCNQ1 variants were determined by the RFLP method, and their role in treatment response was assessed retrospectively. Patients with rs2237895 CC and AC genotypes demonstrated a significant decrement in FBS and HbA1c after treatment over patients with AA genotypes (All P < 0.001). Compared to the A allele, the odds ratio for treatment success between carriers with rs2237895 C allele was 4.22-fold (P < 0.001). Patients with rs2237892 CT heterozygous genotype exhibit a higher reduction rate in HbA1c and FBS than CC homozygotes (P=0.064 and P=0.079, respectively). The rs2237892 T allele carriers showed an odds ratio equals to 2.83-fold over C allele carriers in the responder group compared to the non-responder group (p=0.081). Conclusion: Findings suggest that the KCNQ1 rs2237895 polymorphism is associated with the sulfonylureas response on Iranian type 2 diabetes patients.

Construction a CO2 Incubator for Cell Culture with Capability of Transmitting Microwave Radiation.

Background: The objective of this study was to design and construct a CO2 incubator with nonmetallic walls and to investigate the viability of the cells and microwave irradiance inside this incubator. Methods: Because the walls of conventional incubators are made of metal, this causes scattering, reflection, and absorption of electromagnetic waves. We decided to build a nonmetallic wall incubator to examine cells under microwave radiation. Incubator walls were made using polyvinyl chloride and Plexiglas and then temperature, CO2 pressure, and humidity sensors were placed in it. Atmel® ATmega1284, a low-power CMOS 8-bit microcontroller, collects and analyzes the sensor information, and if the values are less or more than the specified limits, the command to cut off or connect the electric current to the heater or CO2 solenoid valve is sent. Using a fan inside the incubator chamber, temperature and CO2 are uniforms. The temperature of the points where the cell culture plates are placed was measured, and the temperature difference was compared. Ovarian cancer cells (A2780) were cultured in the hand-made and commercial incubators at different times, and cell viability was compared by the MTT method. Microwave radiation in the incubator was also investigated using a spectrum analyzer. The survival of cells after microwave irradiation in the incubator was measured and compared with control cells. Results: The data showed that there was no significant difference in temperature of different points in hand-made incubator and also there was no significant difference between the viability of cells cultured in the hand-made and commercial incubators. The survival of irradiated cells in the incubator was reduced compared to control cells, but this reduction was not significant. Conclusion: This incubator has the ability to maintain cells and study the effects of electromagnetic radiations on the desired cells, which becomes possible by using this device.

Long Noncoding RNAs in Colorectal Adenocarcinoma; an in silico Analysis.

Long noncoding RNAs (lncRNAs) are lengthy noncoding transcripts which are involved in critical signaling pathways including cell cycle and apoptosis so it is not surprising to see their altered expression in human tumors. Colorectal adenocarcinoma is one the most frequent malignancies worldwide. The role of lncRNAs in colorectal adenocarcinoma is not well understood. To study the significance of lncRNAs in colorectal adenocarcinoma, we retrieved 189 approved lncRNAs from HGNC. The genes were imported into the cBioPortal database for transcriptomic analyses. We queried all the samples from TCGA provisional colorectal adenocarcinoma with RNA-seq v2 data in our study and considered RNA dysregulation with Z-score: ±2. The lncRNA which was altered in most of the patients were considered as "significant lncRNA" for further analyses. We considered the association of candidate lncRNAs with clinicopathologic parameters of samples including tumor disease anatomic site, neoplasm histologic types, tumor stage and survival. We also compute the specificity of the significant lncRNAs expression in colorectal adenocarcinoma comparing with other human cancers in cancer portal. Our analysis showed that lncRNAs SNHG6, PVT1 and ZFAS1 allocated the maximum alteration among the colorectal cases. The expression of SNHG6 and ZFAS1 was more in rectal adenocarcinoma than the colon carcinoma while the PVT1 showed the same expression levels in both tissues. However, we found that upregulation of PVT1 has been reduced the overall survival in patients. Altogether these data showed SNHG6, PVT1 and ZFAS1, are promising candidates for experimental research on colorectal adenocarcinoma to discover novel biomarker for this prevalent cancer.

Regulation of MicroRNAs by Phytochemicals: A Promising Strategy for Cancer Chemoprevention.

A growing body of evidence suggests that phytochemicals are potentially able to affect a variety of cellular processes, including proliferation, apoptosis, cell-cycle control, angiogenesis, inflammation, and DNA repair. Phytochemicals may typically play pleiotropic regulatory roles in cancer cells. Chemoprevention, which can be achieved by using these natural agents, has emerged as a helpful strategy to manage a variety of malignancies. With regard to cancer-associated chemopreventive mechanisms, phytochemicals can act by modulating microRNAs (miRNAs) and their target genes. This review aims to present an overview of recent findings on the effects of some wellcharacterized bioactive phytochemicals on miRNA regulation in different cancer types. The potential use of these phytochemicals for the chemoprevention and treatment of cancer is also discussed.

Long Non-Coding RNA SNHG6 as a Potential Biomarker for Hepatocellular Carcinoma.

Long Non-coding RNAs (lncRNAs) refer to all non-protein coding transcripts longer than 200 nucleotides. Their critical roles in different biological pathways have been already well established. Altered expression of lncRNAs can be involved in the cancer initiation and/or progression. Since patients with hepatocellular carcinoma (HCC) are usually diagnosed in late stages, developing diagnostic methods seems to be essential. In this study, the expression levels of different lncRNAs were systematically analysed in different genomic and transcriptome datasets. The analyses showed that SNHG6 is among the lncRNAs with distinctive dysregulation of expression and copy number variation in HCC tumors compared with normal tissues. The results also suggest that the dysregulation of SNHG6 is highly cancer type specific. Through co-occurrence analyses, we found that SNHG6 and its related co-expressed genes on 8q are involved in the structural integrity of ribosome and translation. This comprehensive in silico analysis, provides a resource for investigating SNHG6 in hepatocellular carcinoma and lays the groundwork for design of next researches.

Tissue Specific Expression Levels of Apoptosis Involved Genes Have Correlations with Codon and Amino Acid Usage.

Different mechanisms, including transcriptional and post transcriptional processes, regulate tissue specific expression of genes. In this study, we report differences in gene/protein compositional features between apoptosis involved genes selectively expressed in human tissues. We found some correlations between codon/amino acid usage and tissue specific expression level of genes. The findings can be significant for understanding the translational selection on these features. The selection may play an important role in the differentiation of human tissues and can be considered for future studies in diagnosis of some diseases such as cancer.

Tetraspanin-enriched microdomains and hepatocellular carcinoma progression.

As in many tumors, heterogeneity within the cell population is one of the main features of hepatocellular carcinoma (HCC). Heterogeneity results from the ability of tumor to produce multiple subpopulations of cells with diverse genetic, biochemical and immunological characteristics. Little is known about how heterogeneity emerges and how it is maintained. Fluctuations in single cells can be masked or completely misrepresented when cell populations are analyzed. It has become exceedingly apparent that the utility of measurement based on the analysis of bulk specimens is limited by intra-tumor genetic and epigenetic heterogeneity, as characteristics of the most abundant cell type might not necessarily predict the properties of cell populations. Yet, such non-uniformities often unveil molecular patterns that can represent mechanisms of tumor progression. Interestingly, variability among single cells in a population may arise from different responses to intrinsic and extrinsic perturbations mainly mediated by the plasma membrane. The association of certain proteins, including tetraspanins, and lipids in specific location on the plasma membrane constitutes specialized structure called tetraspanin-enriched microdomains (TEMs). TEMs organization in cancer may reveal essential clues for understanding pathogenic mechanisms underlying cancer progression. Along these lines, TEMs and HCC progression represent a valuable paradigm for gaining a deeper understanding of such mechanisms.