The LncRNA MIAT is identified as a regulator of stemness-associated transcript in glioma.

BACKGROUND: Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA) with altered expression in different diseases and malignancies. In this study, the potential expression and function of lncRNA MIAT in intuition and progression of brain cancer was investigated. METHODS AND RESULTS: At first, TCGA data analysis demonstrated that lncRNA MIAT is significantly upregulated in various malignancies, especially its expression is dramatically elevated in brain tumors. In line with the data, we further evaluated the expression of MIAT in a series of brain tumor tissue, and our results revealed that the expression of MIAT was noticeably overexpressed in glioblastoma (p = < 0.0001). We further found that the expression of MIAT was markedly upregulated in low-grade brain tumors rather than high-grade ones. To further investigate the biological function of MIAT in brain cancer cells, its expression was suppressed by si-RNA-mediated knocking down. Inhibition of MIAT resulted in reduced proliferation of brain tumor cells followed by cell cycle arrest at the G1 phase, and significant induction of apoptosis, and senescence, but limited the migration ability and epithelial-mesenchymal-transition (EMT). Moreover, knocking-down of MIAT reduced the expression of stemness factors, followed by upregulation of their downstream miRNAs (micro RNAs), let-7a-5p, and miR-29b-3p. CONCLUSIONS: Altogether, our data demonstrated that lncRNA MIAT could control proliferation, migration, and metastasis of brain cancer cells via regulating the Nanog/ Sox2 / let-7a-5p / miR-29b-3p axis. This data could introduce lncRNA MIAT as a novel oncogene in brain cancer pathogenesis.

Green synthesis of silver nanoparticles (AgNPs) by Pistacia terebinthus extract: Comprehensive evaluation of antimicrobial, antioxidant and anticancer effects.

In recent years, because of the various functions associated with silver nanoparticles (AgNPs) in manufacturing, different ways for their synthesis have been established. The antioxidant and antibacterial effects of terebinth (Pistacia terebinthus) have been proven. In this study, for the first time, using the extract of terebinth, we have synthesized AgNPs using a green method. Ultraviolet-visible spectrophotometry, X-ray diffraction (XRD), Infrared spectroscopy (FTIR), and the field emission scanning electron microscopy (FE-SEM) spectroscopy analyses were applied to evaluate and verify the formation of NPs, and the antioxidant, antibacterial and anticancer activity of synthesized AgNPs was also studied. The highest absorption was obtained 24 h following the synthesis at 420 nm because of the Ag + to Ag0 reduction. The functional groups stabilizing activity was obtained by FTIR. Moreover, size and surface morphology were assessed by FE-SEM. The present research showed the AgNPs had spherical shape and had a 32 nm diameter. The face-centered cubic construction of AgNPs was evaluated through XRD method with peaks at 2θ = 37°, 49°, 63°, and 76° (related to the planes of silver 111, 200, 220, 311), respectively. Antimicrobial assessment revealed that the biosynthesized AgNPs had a great antimicrobial activity in response to Gram-positive and Gram-negative strains. Suppression of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was determined to be associated with dosage. In addition, a high anticancer activity, against MCF-7 cell line, was observed for the 25 µg/mL concentration of the AgNPs. Altogether, these results show that biogenic AgNPs can be functioned as beneficial medicinal compounds.

MiR-182-5p, MiR-192-5p, and MiR-493-5p Constitute a Regulatory Network with CRISP3 in Seminal Plasma Fluid of Teratozoospermia Patients.

Numerous evidences suggested that microRNAs (miRs) could play an active and significant role during spermatogenesis. Cysteine-rich secretory protein (CRISP3) has a role in inflammatory response and is extremely over-expressed in adolescents with varicocele seminal plasma and modified semen analysis. Nowadays, the miRs expression's association with their target genes is well recognized. The aim of this study was evaluating the association of CRISP3 and four candidate miRs among teratozoospermia (TZ) infertile men. First, we have selected four miRs, miR-182-5p, miR-192-5p, miR-204-5p, and miR-493-5p bioinformatically. After that, RNA was extracted from semen samples of 21 TZ patients and 20 normozoospermia (Norm). Then, their expression levels were assessed using real-time polymerase chain reaction method. In the next step, we quantified the expression of two CRISP3 protein isoforms, targeted by these miRs, using western blotting. According to our results, up-regulation of miR-182-5p, miR-192-5p, and miR-493-5p was observed. MiR-182-5p, miR-192-5p, and miR-493-5p showed good AUC values which can be introduced as possible biomarkers of TZ. In addition, the expression level of the CRISP3 glycosylated (31 kDa) isoform was significantly lower in TZ patients than Norm ones. Notably, in TZ patients, there was a possibly positive correlation of glycosylated CRISP3 expression with normal sperm morphology. According to our results, CRISP3 protein can play a significant role in male infertility especially in maturation formation of spermatozoa. Also, deregulation of the studied miRs, miR-182-5p, miR-92-5p, and miR-493-5p, can suggest a regulatory network between these miRs and CRISP3 isoforms and suggest their regulatory roles in male infertility.

Approaches for the integration of big data in translational medicine: single-cell and computational methods.

Translational medicine describes a bench-to-bedside approach that eventually converts findings from basic scientific studies into real-world clinical research. It encompasses new treatments, advanced equipment, medical procedures, preventive and diagnostic approaches creating a bridge between basic studies and clinical research. Despite considerable investment in basic science, improvements in technology, and increased knowledge of the biology of human disease, translation of laboratory findings into substantial therapeutic progress has been slower than expected, and the return on investment has been limited in terms of clinical efficacy. In this review, we provide a fresh perspective on some experimental and computational approaches for translational medicine. We cover the analysis, visualization, and modeling of high-dimensional data, with a focus on single-cell technologies, sequence, and structure analysis. Current challenges, limitations, and future directions, with examples from cancer and fibrotic disease, will be discussed.

Associations of BCL2 CA-Repeat Polymorphism and Breast Cancer Susceptibility in Isfahan Province of Iran.

BCL2 apoptosis regulator (BCL2) is a cause of tumorigenesis whose CA-repeat promoter polymorphisms has inconsistent association with various types of cancers. The association of BCL2 polymorphism with breast cancer was investigated in the Isfahan province of Iran. PCRamplification of the CA-repeat was followed by polyacrylamide gel electrophoresis and direct sequencing for 120 breast cancer women and an equal number of corresponding healthy control individuals. Seven different alleles, ranging from 11 to 17 CA-repeats were observed. Short alleles with 11 to 14 repeats were protective (OR 0.363, P = 0.001), but large alleles with 15 to 17 repeats were threatening against breast cancer development (OR 2.780, P = 0.001). Accordingly, genotypes with large alleles showed a higher risk of breast cancer development (OR 3.400, P = 0.004). ERS1\ERBB2 positive breast cancer patients, but not PGRpositive ones, showed protection against breast cancer (OR 0.405, OR 0.346 respectively). In conclusion, women with at least one large allele of BCL2 were 3.4 times at higher risk of breast cancer development in the Isfahan province of Iran.

CG/CA genotypes represent novel markers in the NPHS2 gene region associated with nephrotic syndrome.

Nephrotic syndrome (NS) is considered as a primary disease of the kidney that represents a heterogeneous group of glomerular disorders occurring mainly in children. It is generally divided into steroid-sensitive and steroid-resistant forms, depending upon the patient's response to steroid therapy. Among the genes involved, the NPHS2 gene has been reported as the causative gene in steroid resistant form of nephrotic syndrome. In the present study, heterozygosity rate, allelic frequency and linkage of rs2274625 and rs3829795 markers were investigated in the NPHS2 gene region. To determine the SNP alleles, tetra-primer ARMS PCR was used. After genotyping rs2274625 and rs3829795 polymorphic markers in 120 unrelated individuals and nine trios families, the data were analysed using various computer programs such as UCSC Genome Browser, dbSNP and SNPper. Based on the statistical analysis of the results, for rs2274625 marker, allele frequency for C and T alleles was 97% and 3%, respectively. For rs3829795 marker allele frequency for G and A alleles was 55% and 45%, respectively. The values of heterozygosity index for the examined markers were 5% for rs2274625 and 45/8% for rs3829795. Consequently, two informative haplotypes, CG/CA, were identified in the NPHS2 gene region through combination of these two markers. These haplotypes can serve as appropriate tools for the identification of heterozygous carriers and linkage analysis of nephrotic syndrome disease in the Iranian families with an affected child.

Assessment of changes in growth traits, oxidative stress parameters, and enzymatic and non-enzymatic antioxidant defense mechanisms in Lepidium draba plant under osmotic stress induced by polyethylene glycol.

Lepidium draba is a weed with the medicinal properties which few researches have been done on it. In this study, some traits, related to the osmotic stress, in 14-day-old L. draba sprouts that were grown 9 days in the presence of various doses of polyethylene glycol 6000 (PEG 6000) including 0, 3, 6, 9, and 12%, with different osmotic potentials (- 0.04, - 0.12, - 0.23, - 0.34, and - 0.48 MPa, respectively) were investigated. Based on our results, germination percentage besides stem and root lengths decreased with increasing the concentrations of PEG. The contents of electrolyte leakage, malondialdehyde, other aldehydes, total protein, free amino acids, total soluble carbohydrate as well as free proline increased with increasing the concentrations of PEG. Also, for the first time, our results have proven that under osmotic stress, there is an adverse relationship between hydrogen peroxide content and the activity of catalase, peroxidase, ascorbate peroxidase, and guaiacol peroxidase enzymes, such that hydrogen peroxide content decreased with induction of PEG up to 6% and after that increased, while the activity of catalase, peroxidase, ascorbate peroxidase, and guaiacol peroxidase enzymes increased up to 6% PEG and after that decreased. The expression levels of catalase, peroxidase, ascorbate peroxidase, and guaiacol peroxidase genes showed the same pattern as was seen for these enzyme activities. According to the results of this study, it can be deduced that decreasing H2O2 content cannot be the main reason for other oxidative stress parameters to decrease. In this study, P5CS and P5CR gene expression levels increased with increasing levels of PEG up to 12% which was completely similar to free proline content. Based on our results, L. draba can be considered as a semi-tolerant plant to osmotic stress.

Evaluating the expression level of Survivin gene in different groups of B-cell acute lymphoblastic leukemia patients of Iran.

Survivin is one of the major members of Inhibitory Apoptotic Proteins (IAP) family. The functional anti-apoptotic and regulatory role of Survivin in the cell cycle had made it as an interesting candidate for tumor studies. Acute lymphoblastic leukemia is one of the most common malignancies of children that accounts for 30% of all the childhood malignancies. The purpose of this study was to investigate the prognostic importance of Survivin level in B-cell acute lymphoblastic leukemia patients of Iran in four different steps of disease in order to follow up its impact on various treatment ways, the development of the disease, and the response to treatment in the patients. The expression level of Survivin was evaluated in 85 patients with B-cell acute lymphoblastic leukemia and 85 healthy controls using Quantitative Real-Time Polymerase Chain Reaction. Also, western blot analysis was done to confirm the results. Based on our findings, the expression of Survivin showed a significant up-regulation in patients compared to controls. Therefore, a correlation between Survivin expression and the development pattern of B-cell acute lymphoblastic leukemia with a strong diagnostic efficiency (AUC-ROC, 0.8562) was observed. Therefore, it can be introduced as a potential marker for prognosis B-cell Acute Lymphoblastic Leukemia in the future.

Selection and validation of reference genes for normalization of qRT-PCR gene expression in wheat (Triticum durum L.) under drought and salt stresses.

Eight candidate housekeeping genes were examined as internal controls for normalizing expression analysis of durum wheat (Triticum durum L.) under drought and salinity stress conditions. Quantitative real-time PCR was used to analyse gene expression of multiple stress levels, plant ages (24 and 50 days old), and plant tissues (leaf and root). The algorithms BestKeeper, NormFinder, GeNorm, the delta Ct method and the RefFinder were applied to determine the stability of candidate genes. Under drought stress, the most stable reference genes were glyceraldehyde-3 phosphate, ubiquitin and ß-tubulin2, whereas under salinity stress conditions, eukaryotic elongation factor 1-α, glyceraldehyde-3 phosphate and actin were identified as the most stable reference genes. Validation with stress-responsive genes NAC29 and NAC6 demonstrated that the expression level of target genes could be determined reliably with combinations of up to three of the reference genes. This is the first report on reference genes appropriate for quantification of target gene expression in T. durum under drought and salt stresses. Results of this investigation may be applicable to other Triticum species.

Association of T/A polymorphism in miR-1302 binding site in CGA gene with male infertility in Isfahan population.

Infertility occurs in 10-15% of couples worldwide and close to half of it is caused by male factors. One of the genes that can affect male infertility is CGA. Polymorphisms in CGA gene may affect gene expression, therefore affecting male infertility by disrupting the regulation of this gene. One of the polymorphisms is the substitution of T with A in the miR-1302 binding site in the 3' untranslated region of the CGA gene. In this study, we explored this polymorphism in Isfahan population. In this case-control study, by the use of Tetra primer-ARMS-PCR technique, rs6631 has been investigated in 224 infertile men and 196 controls. Infertile men were recruited from Isfahan Fertility and Infertility Center. Analysis of genotype and allele frequencies indicated that the differences between case and control populations were significant for rs6631 because P = 0.00 which is above the threshold. We found a significant relationship between this polymorphism and male infertility. This study which performed for the first time in Iran suggests that polymorphism in CGA gene can affect male infertility. Also, this polymorphism has high heterozygosity, so it can be used for further studies in different populations.