Journal of Arak University of Medical Sciences

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Showing 7 results for Bioinformatic

Bioinformatic Evaluation of the MiR-124 Effect on Transcription Factors Involved in Neorogenesis Process

Mahdieh Mondanizadeh, Ghasem Mosayebi, Ehsan Arefian, Massoud Saidijam, Behzad Khansarinejad,
Volume 17, Issue 2 (5-2014)

Abstract

Background: Although miR-124 molecule has been known as an inducer of neurogenesis, few researches have been done on the targets of this molecule and its functional mechanisms in differentiation toward neurons and maintaining neuronal state. The microarray technique has been established as the reference method for studying the genes under the control of miRNAs. However, the high cost of this method has hampered its use in most research centers. On the other hand, the improvement of bioinformatical algorithms and computer modeling systems has led to the development of the bioinformatical softwares that can predict mRNA targets for miRNAs. Therefore, the aim of this theoretical study was to bioinformatically evaluate the effect of miR-124 on transcription factors that can be involved in neurogenesis and neuronal cell amplification, by using various specific softwares. Materials and Methods: Using different algorithms in TargetScan, DIANA and miRWalk databases, the potential transcription factors targets of miR-124 were identified. Then, a score table was prepared from the candidate genes, based on the affinity of the seed region of miR-124 and the number of targets in the 3`-UTR region of transcription factors. Finally, transcription factors with higher scores were chosen as candidates for practical analysis.

Results: The results of bioinformaical analysis showed that the LAMC1, ITGB1, PTBP1, SOX9, SP1, and EFNB1 molecules are the most potential factors that might be affected by miR-124 during neurogenesis.

Conclusion: It seems that transcription factor SP1 is under the control of the miR-124 and plays a crucial role in neurogenesis process. Therefore, this protein can be considered as a suitable new candidate for experimental evaluation.

Molecular Docking Study of HIV-1 Protease with Triterpenoides Compounds from Plants and Mushroom

Mokhtar Nosrati, Mandana Behbahani,
Volume 18, Issue 3 (6-2015)

Abstract

Background: Because of the reported high ability of virulence and medicinal resistance of HIV-1 virus during the last decades, many investigations have been performed concerning discovery and the introduction of anti-HIV-1 drugs. The results of numerous researches have shown that drugs and protease inhibitory compounds mainly containing plant derivatives specially terpenoids may control HIV-1 infection very effectively. The aim of this research is the bioinformatical study of HIV-1 protease inhibition by standard drugs and triterpenoides from plant and mushroom.

Materials and Methods: This is a descriptive-analytic study. In the present study , the structure of drugs, triterpene comounds, and HIV-1 protease enzyme was received from the databases such as Chem Spider, PubChem, Human Metabolome Database (HMDB), and Protein Data Bank (PDB). After that, molecular docking was performed by iGRMDOCK 2.1 software

Results: The results confirmed that the interactions of the triterpene compounds like the standard drugs were in three safeguarded and catalytic areas including central domain, flap and carboxylic terminal domain specially amino acids Asp25, Asp27, Ala28, Asp29 and Asp30 in active sites of HIV-1 protease. Also, The study of the interactions of these areas showed that there is a direct correlation between the strength of the interactions and IC50 values of these compounds.

Conclusion: Finally, with due attention to the high effectiveness and the proprietary function of triterpenoids, we can conclude that these compounds may be considered as effectire HIV-1 antiprotease drugs.

Bioinformatic Prediction of miRNAs Targeting NOTCH1 and HBx Genes in Chronic Hepatitis B-Induced Hepatocellular Carcinoma

Niloofar Moradi, Mehdi Paryan, Behzad Khansarinejad, Mohammad Rafiei, Mahdieh Mondanizadeh,
Volume 19, Issue 12 (3-2017)

Abstract

Abstract

Background: Hepatocellular carcinoma (HCC) is the third major cause of cancer death worldwide. Hepatitis B virus (HBV) and HBx gene play an important role in the development of HCC by influencing signaling pathways. Since there is no detectable symptom in the early phase of HCC, there is need to find new HCC-specific markers with high sensitivity for early detection and diagnosis of HCC. On the other hand, by the advent and development of bioinformatic sciences, it is now possible to predict miRNAs as biomarkers, and their targets. Therefore, in the present study, based on the results of the bioinformatic software applications with different algorithm, we selected the miRNA targeting HBx and NOTCH1 mRNAs according to higher score, suitable connection with target gene and confirming them in more softwares.

Materials and Methods: First, the sequences of NOTCH1 and HBx genes were retrieved from NCBI. Afterwards, several software applications such as TargetScan, mirWalk, miRBase, Miranda, PicTar, miRVir, and DIANA were applied to predict miRNAs.

Results: Based on the high scoring by bioinformatics softwares and suitable targeting, miR-34a were selected to target NOTCH1 and miR-6510, miR-5193 and miR-214 were chosen to targetHBX gene.

Conclusion: Because of tumor suppression roles of miR-214 and miR-34a, they probably could be used as therapeutic strategy in cancer researches. It is also seems that the miR-5193 could act as a specific marker in Hepatocellular carcinoma.

Bioinformatic prediction and introducing of some targeting microRNAs of Sirt1 and Bcl2 genes in model of Parkinson's disease

Mahsa Rostamian Delavar, Masoud Baghi, Elahe Yadegari, Kamran Ghaedi ,
Volume 20, Issue 8 (11-2017)

Abstract

Abstract
Background: Oxidative Stress and mitochondrial dysfunction leading to apoptotic death of neurons play key role in the pathogenesis of the Parkinson's disease. On the other hand، misregulation of microRNAs can cause several neurodegenerative diseases. Sirt1 and Bcl2 as two key genes, regulate pathogenic processes in neurodegenerative diseases such as mitochondrial dyfunction, oxidative stress and apoptosis.
Materials and Methods: To investigate the role of microRNAs in model of Parkinson's disease, miRWalk 2.0 and TargetScan (v7) databases were served to predict microRNA-target interactions.
Results: Possible targeting effects of different microRNAs on Bcl2 and Sirt1 genes in Rat organism were analyzed. Merging data from databases has shown that rno-miR-449a, rno-miR-182, rno-miR-211, rno-miR-34b, rno-miR-34c, rno-miR-448, rno-miR-466b and rno-miR-96 with strong possibility can inhibit expression of Bcl2 gene. Also, rno-miR-181, rno-miR-211, rno-miR-27a, rno-miR-449a, rno-miR-34c, rno-miR-30, rno-miR-200a and rno-miR-448can inhibit Sirt1 gene with high possibility.
Conclusion: According to the findings, it can be predicted that regarding to high interaction scores of rno-miR-211, rno-miR-34c and rno-miR-448 and 449awith Bcl2 and Sirt1 genes in above-mentioned databases, these microRNAs probably can have critical role in disease process. Thus, these microRNAs can be introduced as appropriate candidates for investigations in in vitro model of Parkinson's disease.

Bioinformatic Screening of Human Papillomavirus (HPV) E1 and E2 Inhibitor(S) from Phyllanthus Emblica and Ficus Religiosa

Komeil Amini, Kamran Mansouri,
Volume 21, Issue 5 (10-2018)

Abstract

Background and Aim: Human papillomavirus (HPV) infection is a prevalent, life-threatening disease and cause of cancer among women. Therefore, in recent years, developing novel anti-HPV agents is highly regarded. The study was planned to bioinformatic screening for E1 and E2 potential inhibitors of HPV serotypes including 16,18,31,33 and 45 types from medicinal plants.
Materials and Methods: This is a descriptive-analytic study. In the first step, three-dimension structure of phytochemicals were retrieved from PubChem database and then the cell cytotoxicity and mutagenesis potential of them were evaluated. In the next step, the amino acid sequences of two key proteins of mentioned types of HPV including E1 and E2 were obtained from Uniprot database. Furthermore, the conserved and variable regions of the protein sequences were predicted using multiple sequence alignment method. Finally, the three-dimension structure of mentioned proteins was determined by homology modeling method and potential interactions of the phytochemicals with the proteins were investigated using molecular docking method through Autodock 4.2.6 software.
Findings: The results demonstrated that ursolic acid has no cytotoxicity and mutagenesis potential with appropriate physicochemical properties. Results also showed that mentioned compound had strong interaction with both E1 and E2 of all studied serotypes. Furthermore, the evaluation of ursolic acid and E1 and E2 interactions showed that amino acid is involved in conserved regions of mentioned serotypes.
Conclusion: Based on the obtained results of present study ursolic acid could be good candidate for more in vitro and in vivo studies of its anti HPV activity.

Bioinformatic Prediction of miRNAs Targeting APRIL and BAFF Genes in Chronic Lymphocytic Leukemia

Mahdieh Mondanizadeh, Niloofar Moradi, Razieh Amini, Behzad Khansarinejad, Ghasem Mosayebi,
Volume 22, Issue 5 (11-2019)

Abstract

Background and Aim Chronic Lymphocytic Leukemia (CLL) is the most commonly occurring leukemia in adults, accounting for about 30-25% of total leukemia. One of the important etiological causes of this leukemia is the disruption of the Nuclear Factor Kappa B (NF-kB) signaling pathway. The two proteins of Apoptosis-Inducing Ligand (APRIL) and B-Cell Activating Factor (BAFF) play a role in the pathogenesis of this leukemia by affecting the NF-kB signaling pathway. In this study, due to the effect of miRNAs in regulating many cellular processes, the prediction of the prominent miRNAs targeting APRIL and BAFF transcripts in B-cell CLL patients was evaluated using specific and different bioinformatics programs.
Methods & Materials Afterwards retrieving the sequences of APRIL and BAFF proteins from the NCBI website, by using several programs including miRanda, TargetScan, miRWalk, DIANA and miRDB with different algorithms, the prediction of miRNAs targeting these genes was investigated.
Ethical Considerations This study was approved by the Research Ethics Committee of Arak University of Medical Sciences.
Results Based on the scoring system of bioinformatics programs, “hsa-miR-145-5p” and “hsa-miR-185-5p” were identified as miRNAs targeting APRIL gene, while “hsa-miR-424” and “hsa-miR-497”were miRNAs targeting BAFF gene. They were suggested for the practical studies in future.
Conclusion Based on the important role of APRIL and BAFF genes in the normal process of cell death and B-cell evolution, it seems that the mi-RNAs predicted by bioinformatics programs using different algorithms can be used as a diagnostic molecular biomarker to identify B-cell CLL patients.

Bioinformatics Prediction of miRNAs Targeting E6 and E7 Genes in Human Papillomavirus Types 16 and 18 in Cervical Cancer

Tahere Azimi, Malihe Bagheri, Mahdi Pariyan, Behzad Khansarinejad, Ashraf Zamani, Mahdieh Mondanizadeh,
Volume 23, Issue 3 (8-2020)

Abstract

Background and Aim: Cervical Cancer (CC) is the third most common malignancy in the women, the main cause of which is human papillomavirus (HPV). Both E6 and E7 oncogenes of the virus play an important role in its tumorigenesis. Today, methods available for screening CC are not capable of detecting the disease at an early stage. Therefore, it is important to identify new biomarkers for early detection of this cancer. For this purpose, in the present study, miRNAs targeting the two oncogenes E6 and E7 of human papillomavirus (types 16 and 18) were studied in CC by bioinformatics.
Methods & Materials: First, using the NCBI database, the E6 and E7 gene sequences were obtained for both human papillomavirus types 16 and 18. Then, using the miRBase and RNA22 bioinformatics databases, the most appropriate targeting miRNAs for these genes were selected.
Ethical Considerations: This study was approved by Ethics Committee of Arak University of Medical Sciences.
Results: Based on the P obtained from bioinformatics databases, miRNA including miR-92a-5p (P=7.51e-2), miR-195-3p (P=2.24e-1), miR-34a-5p (P=2.73e-1) and miR-155-5p (P=4.95e-2) were introduced for the two genes E6 and E7.
Conclusion: Results from bioinformatics studies revealed that of the four miRNAs identified, miR-155-5p and miR-92a-5p are probably the targeting miRNAs specific for the E6 and E7 genes, respectively. Therefore, it seems that these miRNAs can be a suitable candidate for in vitro studies in CC patients.

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