Evaluating changes in the expression of BCL-2 gene, lncRNA SRA, and miR-361-3p in unexplained recurrent pregnancy loss.

Unexplained recurrent pregnancy loss (RPL) composed almost half of all diagnosed miscarriage cases. As the apoptosis pathway is involved in the pregnancy process the present investigation aimed to assess the differential expression of the BCL-2 gene, SRA lncRNA, miR-361-3p in unexplained RPL patients. In this study, RNA was isolated from 50 blood samples of people with a history of RPL, and 50 blood samples of people with healthy fertility. After cDNA synthesis from these samples, alterations in the expression levels of the above-mentioned genes were examined by Real-Time PCR. Our results showed that the expression of BCL-2 and lncRNA SRA was significantly higher in the blood samples of RPL patients than in controls, while the expression of miR-361-3p was significantly downregulated. Besides, there were significant correlations between the changes in the expression of lncRNA SRA and miR-361-3p with BCL-2, in positive and negative directions, respectively. Also, miR-361-3p presented as a good diagnostic marker with the highest AUC value to discriminate between RPL and the healthy control subjects. These results proposed that ncRNAs may have a significant role in the regulation of apoptosis relates genes expression in RPL.

Altered expression of EGFR and miR-34a derived from serum and tumoral tissue was associated with glioblastoma multiform.

OBJECTIVE: Glioblastoma multiform (GBM) is the most prevalent and invasive brain malignancy in adults. There are ongoing researches to introduce novel and non-invasive potential biomarkers for the early detection of GBM. METHODS: Here we compared the expression of EGFR, miR-34a, and miR-19a between tumoral and adjacent non-cancerous tissues (ANCTs) of 50 GBM patients and also compared their expression levels in serum samples of GBM patients with serum samples of 50 control subjects. RESULTS: The expression level of the EGFR gene was elevated in GBM tissues in comparison to the corresponding ANCTs (P < 0.0001) and also was higher in the serum sample of patients compared with control serum (P < 0.0001). The miR-34a was significantly downregulated in serum samples as well as tissues obtained from GBM patients compared with the corresponding controls (expression ratio = 0.57 and 0.4, P = 0.02 and 0.001 respectively). CONCLUSIONS: Dysregulation of the EGFR gene and miR-34a in serum samples of GBM patients compared with the control subjects promises the emergence of non-invasive biomarkers for early detection of GBM which need confirmative studies with a large sample size.

Aberrant expression of BAX, MEG3, and miR-214-3P genes in recurrent pregnancy loss.

AIMS: Recurrent pregnancy loss (RPL), with unknown causes, is one of the most common challenges facing pregnancy. Apoptotic signaling pathways are involved in the normal and abnormal pregnancy process. Despite the evidence pointing toward the aberrant expression of apoptotic and apoptotic-related genes in pregnancy complications, the involvement of these genes in RPL remains to be elucidated. This study aimed to investigate the expression levels of BAX, MEG3, and miR-214-3p (as a microRNA), and their associations in an Iranian population. MATERIALS AND METHODS: Following the extraction of RNA from blood samples of RPL patients and controls, quantitative expression levels of BAX, MEG3, and miR-214-3p genes were analyzed by real-time RT-PCR. RESULTS: The findings showed that the expression levels of BAX and miRNA-214-3p were significantly higher in the blood samples of RPL patients than in control samples. In contrast, the expression of MEG3 was significantly down-regulated in women RPL. Furthermore, altered expressions of MEG3 and miRNA-214-3p are associated with their target gene BAX, where the BAX expression is positively and negatively correlated with the expressions of has-miR-214-3P and MEG3, respectively. ROC curve evaluation demonstrated the highest specificity and diagnostic value for miR-214-3p expression in distinguishing RPL samples from the healthy controls. CONCLUSIONS: These data indicated that the aberrant expression of BAX, MEG3, miRNA-214-3p genes in RPL patients could provide new insights into the biological characteristics and related pathways of differentially expressed genes, which could help as potential diagnostic biomarkers and a better understanding of the molecular mechanisms of RPL.

Genetic variants of the phenylalanine hydroxylase gene in patients with phenylketonuria in the northeast of Iran.

Background Phenylketonuria (PKU) is a common metabolic disorder with great burden if left untreated or undiagnosed. Genetic variations in the phenylalanine hydroxylase (PAH) gene may be widely varied across different regions of a country. By knowing the most common mutations, diagnostic work-ups will be offered sooner and with lower costs for patients. The present study defines the most common genetic variations in the PAH gene in Khorasan province of Iran. Methods The present cross-sectional study took place in Khorasan province of Iran within a 6-year period starting from 2012 to 2018. Every patient who had been referred as suspicious PKU cases or referred for prenatal diagnosis was included in the present study. Results A total number of 122 individuals with a mean age of 26.22 years were enrolled in the present study. The most frequent genetic variations in the PAH gene were c.1066-11G > A and c.143 T > C. Exon 7 carried the most genetic variations compared to any single exon. Also, three patients had compound heterozygous status for c.727 C > T/c.1066-11 G > A in exon 7 and 11 of the PAH gene. Conclusions Mutations in the PAH gene are widely varied among different populations, and our results confirmed this fact. Determination of the most prevalent mutations and polymorphisms in each region will reduce the time and cost of diagnosing such preventable diseases and will therefore reduce the disease burden.

Mutation Screening of KCNQ1 and KCNE1 Genes in Iranian Patients With Jervell and Lange-Nielsen Syndrome.

Background: Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive genetic disease with deafness and QT prolongation. Mutations in KCNQ1 and KCNE1 genes are a cause of JLNS. Our objective was to perform mutational analysis of the KCNQ1 and KCNE1 genes to determine the frequency of mutations in the Iranian population. Material and methods: Fourteen patients and their families were investigated. Mutational screening of the KCNQ1 and KCNE1 genes was performed by a polymerase chain reaction (PCR) followed by direct Sanger sequencing. Results: We identified two frameshift mutations in the KCNQ1 gene, including a novel mutation, c.1356 1356delG, and a known mutation, c.1534_1534delG. A common single nucleotide polymorphism (SNP), c.112G > A, was also found in KCNE1 in seven probands. Conclusion: A novel mutation in the KCNQ1 gene is described. There may be less frequency of mutations in the KCNQ1 and of KCNE1 genes in Iranian JLNS patients compared with other populations.

Gap Junction Protein Beta 2 Gene Variants and Non-Syndromic Hearing Impairment among Couples Referred For Prenatal Diagnosis in the Northeast of Iran.

INTRODUCTION: Hearing impairment is a complex medical disorder which has genetic and non-genetic causes. Gap Junction Protein Beta 2 (GJB2) gene variant is a well-known disease-causing gene among patients with hearing impairment. The frequencies of genetic variants in the GJB2 gene are different in each population. This study aimed to discuss the GJB2 gene status in an Iranian population with hearing impairment who referred for prenatal testing. MATERIALS AND METHODS: This cross-sectional study was conducted in a genetic laboratory affiliated with Mashhad Jahad Daneshgahi, Mashhad, Iran. A total number of 21 bilateral hearing impaired patients were enrolled in this study. The exons for target GJB2 gene were amplified by polymerase chain reaction after the confirmation of the hearing impairment and the exclusion of the acquired causes of hearing loss. RESULTS: The c.35delG and c.79G>A variants were the first and second most common variants in the study population, respectively. The mean age of the patients was 27.5 (8.7) years and 12 cases were male. There was no significant association between hearing impairment degree and age and heterozygosity status (P=0.376 and P=.074 respectively). CONCLUSION: The c.35delG and c.79G>A variants were determined as the first and second most common variants in the GJB2 gene, respectively. The mean age of 26 years in this study population indicates the late referral for the evaluation of the hearing difficulty. Furthermore, it highlights the further need to encourage families with a history of hearing impairment to engage in genetic counseling.

Targeting cancer stem cells as therapeutic approach in the treatment of colorectal cancer.

Colorectal cancer is one of the most common cancers globally. A large portion of colorectal cancer patients who are treated with conventional chemotherapy eventually develop local recurrence or metastases. The failure of a complete cure in colorectal cancer patients may be related to the lack of complete eradication of cancer stem cells when using conventional therapy. Colorectal cancer stem cells comprise a small population of tumor cells that possess the properties of rapid proliferation and differentiation. The colorectal cancer stem cells are also phenotypically and molecularly distinct, and resistant to conventional chemo-radiotherapy. Therefore, it is important to identify approaches in combination with conventional therapy for targeting and eradicating cancer cells. The aim of this review was to summarize the main findings of recent studies on targeting colorectal cancer stem cells as a novel therapeutic approach in colorectal cancer treatment.