Search

Copyright of Turkish Journal of Obstetrics & Gynecology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Nonmedullary thyroid cancer (NMTC) comprises approximately 90% of all thyroid cancers, and about 3% to 9% of NMTC cases have a familial origin. Familial NMTC (FNMTC) in the absence of a documented familial cancer syndrome such as Cowden syndrome is characterized by the occurrence of thyroid cancer of follicular cell origin in 2 or more first-degree relatives. Methods Whole-exome sequencing (WES) was used to identify pathogenic genetic variants in 2 Persian families with FNMTC. The purpose of this work is to assess the pathogenic status of these variants as well as the cosegregation status of the variants observed in the examined families. Results By analyzing WES data in the first family, SRGAP1 : NM_020762: exon16: c.C1849T was identified as a pathogenic variant. This variant was confirmed by Sanger sequencing. In the second family, the variant FOXE1 : NM_004473: exon1: c.531_532insCGCGA was identified but was not confirmed by Sanger sequencing. Conclusion Based on the data, SRGAP1 can be a potential candidate gene for susceptibility to FNMTC in the first family. However, additional analyses like whole genome sequencing and copy number variations are required to ascertain the disease status in second family. [ABSTRACT FROM AUTHOR]

Background: Haemagglutinin–neuraminidase (HN) is one of the membrane proteins of Newcastle disease virus (NDV) that plays a significant role during host viral infection. Therefore, antibodies against HN are vital for the host's ability to protect itself against NDV infection due to their critical functions in viral infection. As a result, HN has been a candidate protein in vaccine development against the Newcastle disease virus. Methods: This report used the full‐length sequence of the HN protein of NDV isolated in Iran (VIId subgenotype). We characterize and identify amino acid substitutions in comparison to other more prevalent NDV genotypes, VII subgenotypes and vaccine strains. Furthermore, bioinformatics tools were applied to determine the three‐dimensional structure, molecular dynamics simulation and prediction of B‐cell antigenic epitopes. Results: The results showed that the antigenic regions of our isolate are quite comparable to the other VII subgenotypes of NDV isolated from different geographical places. Moreover, by employing the final 3D structure of our HN protein, the amino acid residues are proposed as a B‐cell epitope by epitope prediction servers, which leads to the introduction of linear and conformational antigenic sites. Conclusions: Immunoinformatic vaccine design principles currently exhibit tremendous potential for developing a new generation of candidate vaccines quickly and economically to eradicate infectious viruses, including the NDV. In order to accomplish this, focus is directed on residues that might be considered antigenic. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer, which is one of the most common cancers with high mortality in women, has always been the focus of researchers, and every day, scientists are trying to identify mechanisms, genes, and medicines related to this disease. Nowadays, bioinformatics methods are used to identify and repurpose drugs for the treatment of diseases, especially cancer. Material & Methods: In this study, bioinformatics and biological network analysis were used to identify candidate drugs for breast cancer treatment. In this regard, analysis of the protein interaction network and drug-gene network were employed. The needed data were collected from the GEO database with the access code GSE54002. For the selected data set, genes with significant expression changes between two groups of healthy people and people with breast cancer cases were selected and considered primary genes. Thereafter, the protein-protein interaction network was constructed using the STRING database, and a significant gene module was obtained from the network. Following that, gene ontology studies and biological pathways were conducted. Next, the drug-gene network was constructed to identify drugs that target module genes and were introduced as essential drugs for the treatment of breast cancer. Cytoscape software and STRING and OncoDB databases were used to reconstruct and analyze the networks. Results: After analyzing the protein-protein interaction network and the drug-gene network, three important drugs that target the genes of the modules were identified and introduced as candidate drugs for the treatment of breast cancer. These drugs were RG1530, R-406, and GW441756x. Discussion & Conclusion: The obtained results demonstrated that the introduced drugs (RG-1530, R-406, and GW441756x) can be effective in the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) is a small, non-enveloped DNA virus related to human cervical cancer. The genome is maintained within the basal epithelium where the primary infection is latent. During the late phase of infection, the capsid proteins (L1 and L2) are expressed to encapsidate the viral genome, generating the infectious virion particles required for HPV propagation. HPV genome encodes six proteins, namely E6 oncoprotein, E7 oncoprotein, E1 replication protein, E2 regulatory protein, L1 major capsid protein, and L2 minor capsid protein. L1 is the principal part of the current vaccines, and any changes in this region can decrease vaccine efficiency. The aim of this research was to conduct a comparative analysis among Iranian L1 protein sequences with reference sequences to determine the possible substation in this region and to find the physicochemical and structural properties of L1 by using bioinformatics tools to provide comprehensive comprehension of the HPV L1 protein. Methods: Thirteen Iranian PV sequences of the L1 protein and reference sequences were selected and obtained from the NCBI data bank. CLC Sequence Viewer software was used to translate the alignment. PrediSi and Phobius were employed to predict the signal peptide. The secondary and tertiary structures and structure validations of all sequences were analyzed by Qmean, (PS)2-v2, Phyre2server, Discovery Studio, and I-TASSER. Results: The findings showed that L1 is highly conserved, and only two mutations were found in this region. No signal peptide was described, and this region's main part included a random coil. The tertiary structure was mapped using different software, and five distinct loops were found. Conclusion: This study is the first report that investigated the changes in the L1 protein of Iranian patients and provided helpful comprehension of the L1 properties vital for cloning and producing the new generation of virus-like particle (VLP) vaccines. Furthermore, the structural analysis showed several loops that had an indispensable role in antibody binding and the prevention of HPV infections [ABSTRACT FROM AUTHOR]

Background: In recent decades, many long non-coding RNAs (lncRNAs) have been reported to play a prominent role in tumorigenesis and the progression of human cancers, including gastric cancer (GC), a leading cause of cancer death in Iranian men and women. Studies have demonstrated that thymopoietin antisense transcript 1 (TMPO-AS1) was upregulated indifferent cancers by acting as an oncogenic lncRNA. Objectives: This study aimed to evaluate the expression of lncRNA TMPO-AS1 in Iranian patients with GC. Methods: In order to conduct the present study, 40 gastric tumor samples and 40 marginal noncancerous counterparts were collected. The characteristics of patients' samples were recorded, and the TMPO-AS1 expression levels were evaluated by qRT-PCR analysis. The Cancer Genome Atlas (TCGA) data for TMPO-AS1 were used and analyzed through GEPIA and TANRIC online tools. Receiver operating characteristic (ROC) curve analysis was used to estimate the diagnostic value. Student t-test, one-way ANOVA, and chi-square test were accomplished via SPSS software. Results: Our data demonstrated that TMPO-AS1 was overexpressed in cancerous tissues compared to adjacent nonmalignant ones (P = 0.0076). None of the demographic and clinicopathological data were associated with TMPO-ASl expression levels. The TCGA data demonstrated that TMPO-AS1 was upregulated in GC tissues in comparison to adjacent nonmalignant ones (P = 0.001). ROC curve analysis suggested that TMPO-AS1 expression levels could discriminate GC tumor tissues from normal ones (AUC = 0.699, P = 0.001). Conclusions: Altogether, in our study, we demonstrated that lncRNA TMPO-AS1 maybe considered a biomarker in Iranian patients with GC. However, further investigations are required to confirm the potential application of this lncRNA in diagnosis, prognosis, and therapeutic applications of GC. [ABSTRACT FROM AUTHOR]

Background & Objective: Lung transplantation is a promising therapy for patients with end-stage lung disease. Pulmonary surfactant is a lipid and protein complex which has a key role in lung function. Molecular mechanisms mediating in rejection of lung transplantation related to surfactants are not still comprehensively understood. In this study, we applied bioinformatics approaches to identify genes and molecular mechanisms involved in surfactant function in rejection of lung transplantation. Materials & Methods: At first, transcriptomics data was extracted and analyzed to construct the protein-protein interaction network and gene regulatory network using Cytoscape. Then, networks analysis were performed to determine hubs, bottlenecks, clusters, and regulatory motifs to identify critical genes and molecular mechanisms involve in surfactant function in rejection of lung transplantation. Finally, critical genes selected for repuposing drugs. Results: Analyzing the constructed PPIN and GRN identified SCD, FN1, ICAM1, ITGB8, FOXC1, SIX1, FHL2, KRT5, TFAP2A, GAS5, MALAT1, and lnrCXCR4 as critical genes. Enrichment analysis showed the genes are enriched for pulmonary surfactant metabolism dysfunction, defective CSF2RB causes pulmonary surfactant metabolism dysfunction 4 and 5, Interleukin-4 and Interleukin-13 signaling may be the mechanisms for surfactant function in rejection of lung transplantation. We predicted some candidate drugs for preventing of lung transplantation rejection such as Sunitinib, Gemcitabine, Oxaliplatin, Hyaluronic acid. Conclusion: Following our model validation using the existing experimental data, our model suggested critical molecules and candidate medicines involve in surfactant function in rejection of lung transplantation for furtur investigations. [ABSTRACT FROM AUTHOR]

Purpose. ITP is the most prevalent autoimmune blood disorder. The lack of predictive biomarkers for therapeutic response is a major challenge for physicians caring of chronic ITP patients. This study is aimed at identifying predictive biomarkers for drug therapy responses. Methods. 2D gel electrophoresis (2-DE) was performed to find differentially expressed proteins. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS) analysis was performed to identify protein spots. The Cytoscape software was employed to visualize and analyze the protein-protein interaction (PPI) network. Then, enzyme-linked immunosorbent assays (ELISA) were used to confirm the results of the proteins detected in the blood. The DAVID online software was used to explore the Gene Ontology and pathways involved in the disease. Results. Three proteins, including APOA1, GC, and TF, were identified as hub-bottlenecks and confirmed by ELISA. Enrichment analysis results showed the importance of several biological processes and pathway, such as the PPAR signaling pathway, complement and coagulation cascades, platelet activation, vitamin digestion and absorption, fat digestion and absorption, cell adhesion molecule binding, and receptor binding. Conclusion and Clinical Relevance. Our results indicate that plasma proteins (APOA1, GC, and TF) can be suitable biomarkers for the prognosis of the response to drug therapy in ITP patients. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is a prevalent problem in worldwide healthcare related to several system disorders. Food fortification as a solution is associated with several challenges including insufficient coverage of the entire population, required degree of fortification, the vehicles used for fortification and potential toxicity. This study aimed to determine the optimal amount of vitamin D for fortification without surpassing the upper intake level (UL) of intake at the 95th percentile of the Iranian population and compare two methods of food fortification. Methods: This study is aimed to develop a model of two different fortifying approaches related to an available dataset called MASHAD cohort study. The dataset comprised demographic and nutritional data of 9704 Iranian individuals living in the Greater Mashhad region. The first approach was a computational method necessary to implement a range of eight foods and calculate the optimal approach. In the second case, we used the European formula method called ILSI. Results: To find the appropriate value for fortification, we calculated the consumption of 400 IU and 1000 IU supplements of vitamin D. Three micrograms per 100 g in each food was the optimal output. We also used Flynn and Rasmussen's formula on our data. Using these methods, we found that 2.1 micrograms per 100 kcal provides the best result. Hence, using the two different approaches, the results appear to be consistent and promising. Conclusion: One interesting finding was that supplement consumption did not greatly affect the impact of fortification. This observation may support the hypothesis to determine the amount of fortification, and we can ignore the study population's supplement consumption. [ABSTRACT FROM AUTHOR]

Background & Objective: Psoriasis is one of the most common skin disorders in humans and is believed to have genetic foundations. The aim of this study is to identify potential genetic biomarkers for psoriasis using penalized methods. Materials & Methods: The gene chip GSE55201, which included 74 individuals (34 patients with psoriasis and 30 healthy individuals), was obtained from GEO. Three penalized approaches were used in logistic regression, including Least Absolute Shrinkage Selection Operator, Minimax Concave Penalty, and Smoothing Clipped Absolute Deviation, to identify the most important genes associated with psoriasis. To validate the results, Random Forest was used to assess the predictive power of the selected genes in a validation dataset. Results: The analysis identified ADORA3 and C16orf72 as two genes that were commonly associated with psoriasis. The independent samples t-test revealed significantly higher expression of ADORA3 and C16orf72 among psoriasis cases (p<0.001). The area under the ROC curve for predicting psoriasis was 0.88 (95% CI: 0.80-0.96) for ADORA3 and 0.75 (95% CI: 0.75-0.94) for C16orf72. The Random Forest analysis showed that the model using these genes had a prediction probability of 0.68 (95% CI: 0.53-0.83). Conclusion: Among all the methods used, MCP outperformed other penalties, selecting a smaller subset with compatible performance. Two key genes, ADORA3 and C16orf72, were found to be associated with psoriasis and were identified for further study. These genes may serve as genetic biomarkers for predicting psoriasis. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) is the most common human solid tumor and the leading cause of cancer death. SCC of the breast is a very rare type of cancer that has not been well researched. Early identification of the genetic factors involved can lead to early diagnosis and targeted treatment. The present study was conducted in 2018 at Isfahan University of Medical Sciences (Isfahan, Iran). The proband was a 66-year-old woman with SCC of the breast and a positive family history of cancer. Blood DNA samples were used for whole-exome sequencing to identify germline pathogenic variants. Variant annotation and prioritization were done on variant call format files using bioinformatics software tools. The screened variants were confirmed using the Sanger sequencing method. Co-segregation analysis was performed on the blood DNA samples of the first- and second-degree relatives of the proband to assess the presence of the mutation. A novel germline pathogenic variant was identified in the RECQL4 gene of the family. RECQL4 is a known protein in DNA repair and replication. Considering its effect on other types of SCC, it may play an important role in SCC initiation and progression in the breast. [ABSTRACT FROM AUTHOR]

Purpose. As a scientific field, bioinformatics has drawn remarkable attention from various fields, such as information technology, mathematics, and modern biological sciences, in recent years. The topic models originating from the field of natural language processing have become the focus of attention with the rapid accumulation of biological datasets. Thus, this research is aimed at modeling the topic content of the bioinformatics literature presented by Iranian researchers in the Scopus Citation Database. Methodology. This research was a descriptive-exploratory study, and the studied population included 3899 papers indexed in the Scopus database, which had been indexed in this database until March 9, 2022. The topic modeling was then performed on the abstracts and titles of the papers. A combination of LDA and TF-IDF was utilized for topic modeling. Findings. The data analysis with topic modeling resulted in identifying seven main topics "Molecular Modeling," "Gene Expression," "Biomarker," "Coronavirus," "Immunoinformatics," "Cancer Bioinformatics," and "Systems Biology." Moreover, "Systems Biology" and "Coronavirus" had the largest and smallest clusters, respectively. Conclusion. The present investigation demonstrated an acceptable performance for the LDA algorithm in classifying the topics included in this field. The extracted topic clusters indicated excellent consistency and topic connection with each other. [ABSTRACT FROM AUTHOR]

Background & Aims: Chirgwin et al. (1979) were the first authors who proposed the ribonucleic acid (RNA) isolation technique. Without denaturation of the structure of nucleic acid, this method breaks the cell membrane using guanidinium thiocyanate and 2-mercaptoethanol (β-met). The extraction is carried out using ethanol or ultracentrifuge, and cesium chloride gradient. This method is time-consuming, inefficient, and involves toxic and incompatible compounds for the user. Thus, the quality and efficiency of the process of extraction were developed over time and through conducting more studies. Chomczynski and Sacchi (1987) improved the method suggested by Chirgwin et al. and proposed a single-step extraction process called the AGPC method, and it used acid guanidinium, phenol, and chloroform. The advantage of this method is its higher purity and efficiency, plus this process of isolation does not include RNA fragmentation. This method has been developed and using silica columns together with magnetic beads resulted in a revolution in the process of isolating nucleic acids. Extraction of viral nucleic acid includes high-purity DNA and RNA, determining sensitivity, and genome viral load within a short process is quite crucial for the majority of downstream molecular and medical studies such as sequencing, real-time PCR, PCR for research or diagnostic purposes. Efficient protocols for the extraction of nucleic acids are the prerequisite of these methods. As already mentioned the most available protocols are time-consuming and have limitations regarding some samples or disparate types of nucleic acids. An optimal protocol must provide a high sensitivity concerning the extraction of the viral genome from a broad spectrum of samples together with a shorter scientific time and lower price. The majority of methods up to the present time have been using precipitation steps to obtain pure nucleic acids from the extracts. New protocols use the binding capacity of the nucleic acid extract to the silica column. Vogelstein and Gillespie were the first scholars to describe the absorption of nucleic acid to the surface of silica in the presence of great concentrations of chaotropic salts. They used pieces of DNA recovered from agarose gel using silica powder. This technology is developed over time and now selective binding of DNA or RNA through silica gel surfaces is modified and binding and wash buffers have been optimized to provide the maximum separation and isolation capacity in nucleic acids. After the initial lysis of the sample, the respective nucleic acid bound to the membrane is regulated. Polysaccharides and proteins in the extract fail to function properly and lose their ability to bind to the membrane due to the destruction of the molecular structure. Finally, nucleic acid bounded to the column is desalinated by alcohol and washed, and then, separated from the column by elution buffer. One of the limitations of the process of extraction is separating various types of nucleic acids from different viral resources. For instance, Coronavirus contains an RNA genome and on the other hand, the samples are collected from the patient’s nose and throat, which requires an efficient and extremely sensitive procedure for extracting the genome of this virus. Given that, Tehran Cavosh Clon (former Sinaclon), a knowledge-based complex, proposed an optimal method for spearing viral RNA with high efficiency and free from toxic materials in accordance with conducted studies. The present research reported the results of the clinical studies on the basis of European Pharmacopoeia standards. Methods: Viral RNA was extracted from HCV, HIV, and COVID-19 samples. Sensitivity, specificity, verification, and stability tests were carried out according to the European pharmacopeia standard. Furthermore, Tehran Cavosh Clon’s viral extraction kit (SinaPure Viral) was compared with extraction kits of QIA Gen and GeneAll companies, as valid and the most common brands in the market. Finally, the results of PCR and Real-Time tests by these kits were compared. Serums infected with HCV, HIV, and COVID-19 swab nasopharyngeal were provided from Keyvan Laboratory. The reference viral genome extraction kits (QIA Gen:CAT:52904; GeneAll: CAT:128-150), and HCV, HIV, and COVID-19 diagnostic kits (GenproofHIV1/ISEX/050:HCVD/ISEX/050; CMV/ISEX/050; Sansure Biotech: S3104E) Were purchased from the respective agencies. Chemicals used in the kit structure were purchased from Sigma Company. Kit comprises lysis buffer, precipitation buffer, wash buffer I, wash buffer II, and elution buffer, carrier RNA, and binding columns. First, 400 μl lysis buffer together with 5-6 μl of carrier RNA were added to microtubes containing the samples and they were vortexed for 20 seconds. Then, 300 μl of the precipitation buffer was added to the above solution and vortexed for 5 seconds. The final solution was transferred to the column and centrifuged at 12,100 x g,13,000 rpm, for 1 minute. It must be noted that the transferred solution must be discarded. In the next step, 400 μl of wash buffer I was poured on the column, and centrifuged, at the aforesaid revolutions for 1 minute. The transferred solution was discarded. 400 μl of wash buffer II was transferred to the above column, and centrifuged, at the aforesaid revolutions for 1 minute. The transferred solution was discarded. Finally, without adding any solution, the collector column was centrifuged for 2 minutes. Then, it was transferred to 1.5 ml sterile microtubes and 50 μl elution buffer was added to it. It was placed at 55 degrees centigrade for 3 to 5 minutes. Upon the final centrifuge, the viral RNA was separated from the column with elution buffer. The extracted nucleic acid was collected. This product is used for diagnostic tests. The data were statistically analyzed using SPSS, 18. The diagrams were illustrated using Excel 2010. The One-way ANOVA test was carried out. The means were compared using Duncan's test with a significance level of P<0.05. Results: Table 1 shows the results of comparing the sensitivity test of SinaPure viral extraction kit with the QIA Gen and GeneAll regarding samples with HIV, HCV, and COVID-19. According to these results, the obtained Ct for LOD of HIV samples indicated no significant difference between GeneAll and SinaPure viral kits. While there was a significant difference between the QIA Gen and the aforesaid kits. The results of the sensitivity test of samples with HCV and COVID-19 manifested a similar pattern. The only significant difference between the QIA Gen and SinaPure viral with respect to the amount of LOD. Table 1 shows the results of the specificity of the SinaPure viral kit on different viral, bacterial, plant, and animal samples. Per the results, except for viruses with RNA such as HCV, HIV, and COVID-19, no positive response was observed in none of the viruses with DNA such as HSV, EPV, HPV, CMV, HBV, plus gram-negative bacteria, (Ecoli), gram-positive bacteria (Staphylococcus aureus), plant samples (wheat), and animal sample (CHO Cell). This confirms SinaPure Viral’s ability in extracting the genome of viruses with RNA. SinaPure Viral confirmation kit was compared to QIA Gen and GeneAll kits in high, medium, and law counts of HCV and HIV serums, plus Swab Nasopharyngeal for COVID-19. The results of disparate counts of HIV-positive samples using all three kits demonstrated no significant difference (Table 2). On the other hand, the same pattern was observed in HCV samples (Table 3). Table 4 shows the results for the COVID-19 samples. Even though kits manifested no significant difference in the high and medium counts, in lower counts of the virus, QIA Gen had a significant difference with SinaPure Viral and GeneAll. It can be due to the difference in the sensitivity of sampling since in the lower loads of virus there is a possibility of making mistakes by the sample collector. On the other hand, the lack of significant difference between the HIV and HCV samples in disparate counts confirms this. Tables 5, 6, and 7 show the results of investigating the stability of the SinaPure Viral kit in the time intervals of 6, 12, and 18 months. Per these results, SinaPure Viral kit manifested no significant difference with QIA Gen and GeneAll in the time intervals of 6 and 12 months. Even after after18 months, the SinaPure Viral kit manifested a significant difference with reference kits in low viral counts in all samples. These high count viruses did not demonstrate this reduction of efficiency. The possible cause of reduction of kit efficiency could be the location of storing carrier RNA after the first time they were used. Taking into account the considerable role of carrier RNA in the viral genome precipitation, after preparing the carriers RNA solution, its storage condition is extremely effective on the stability of RNA. Conclusion: In accordance with the results, the pharmacopoeia standard of the kit designed by Tehran Cavosh Clon corresponded to reference kits, i.e. QIA Gen and GeneAll. Given that, this kit is comparable to reference kits and it can be considered as a valid replacement for foreign kits in the market. [ABSTRACT FROM AUTHOR]

Background and Aim: One of the main reasons for the ongoing pandemic is the substitutions in the Receptor binding domain (RBD), which is involved in binding to the ACE2 receptor. Materials and Methods: Oro-nasopharyngeal swabs were collected from 41 confirmed patients between September 2020 and May 2021 to analyze the mutations of SARS-CoV-2 RBD in Khuzestan Province. Bi-Directional sequencing was used, and Mutation analysis was performed using multiple Bioinformatics tools. Results: A total of 35 Single nucleotide polymorphisms (SNPs) were observed in 26 samples. Nonsynonymous substitutions occurred only in the receptor-binding motif (RBM), which accounted for 97% of the detected mutations. 37.14% of observed mutations were N501Y. L452R, T478K, and S477N accounted for 22.86%, 20%, and 11.43% of detected substitutions, respectively. Subsequently, the S477G and Y449N were identified in only one sample. The only synonymous substitution of this study was observed in C432 of one sample. It was found that December 2020 and May 2021 could be the probable prevalence times of the Alpha and Delta variants in Khuzestan, respectively. Also, in a December 2020 sample, a mutation was detected that was only seen in Epsilon among the Variants of interest and Variants of concern. Conclusion: Our study showed the existence of some Omicron-related mutations before the emergence of this variant in Khuzestan Province, Iran. In addition, it strengthened the possibility of unconfirmed variants, such as Epsilon entering Iran. It also provided a reference for studies that need to be aware of the circulating variants in Iran. [ABSTRACT FROM AUTHOR]

Background: Coronary heart disease is the leading cause of death worldwide. Myocardial infarction (MI) is a fatal manifestation of coronary heart disease, which can present as sudden death. Although the molecular mechanisms of coronary heart disease are still unknown, global gene expression profiling is regarded as a useful approach for deciphering the pathophysiology of this disease and subsequent diseases. This study used a bioinformatics analysis approach to better understand the molecular mechanisms underlying coronary heart disease. Methods: This experimental study was conducted in the department of cardiology, Aja University of Medical Sciences (2021-2022), Tehran, Iran. To identify the key deregulated genes and pathways in coronary heart disease, an integrative approach was used by merging three gene expression datasets, including GSE19339, GSE66360, and GSE29111, into a single matrix. The t test was used for the statistical analysis, with a significance level of P<0.05. Results: The limma package in R was used to identify a total of 133 DEGs, consisting of 124 upregulated and nine downregulated genes. KDM5D, EIF1AY, and CCL20 are among the top upregulated genes. Moreover, the interleukin 17 (IL-17) signaling pathway and four other signaling pathways were identified as the potent underlying pathogenesis of both coronary artery disease (CAD) and MI using a systems biology approach. Accordingly, these findings can provide expression signatures and potential biomarkers in CAD and MI pathophysiology, which can contribute to both diagnosis and therapeutic purposes. Conclusion: Five signaling pathways were introduced in MI and CAD that were primarily involved in inflammation, including the IL-17 signaling pathway, TNF signaling pathway, toll-like receptor signaling pathway, C-type lectin receptor signaling pathway, and rheumatoid arthritis signaling pathway. [ABSTRACT FROM AUTHOR]

Background and Aim: Carbapenem-resistant Acinetobacter baumannii (CRAb) has the ability to develop and acquire resistance making it one of the most critical nosocomial pathogens globally. Whole genome sequencing (WGS) technology was employed to map genes associated with antimicrobial resistance (AMR), and virulence factors and to identify multilocus sequence types (MLST). In order to understand the resistance mechanism for A. baumannii species, this study set out to establish the genetic makeup of the species. Materials and Methods: Whole-genome sequencing (WGS) of A.b4, A.b49, and A.b75 was performed using Illumina MiSeq and the genomes were assembled with SPAdes. ARG-ANNOT, CARD-RGI, VFDB, PHAST, PlasmidFinder were used to analyze all genomes. Results: Genome analysis revealed that Ab4 belongs to ST944, represented singletons that could not be attributed to any, A.b49 belongs to ST1104, representing unique ST.While A.b75 belongs to ST195 which represented known international clones of high risk. Molecular characterization showed the presence 23 antibiotic-resistance genes in all strains of A. baumannii. 12 of them are shared by all 3 strains and 11 are common between A. baumannii 4(ST/944), 49 (ST/1104), and 75(ST/195). The common drug-resistance genes shared by all 3 strains include bla OXA-72 (resistance to carbapenems), ade genes, RND (adeFJK, adeLN & adeR), and SMR (abeS) encoding for efflux pumps. Conclusion: We present WGS analysis of three A. baumannii strains belonging to three different STs. The presence of strains harboring acquired AMR genes makes them more dangerous. Acquired resistance genes and chromosomal gene mutation are successful routes for disseminating AMR determinants among A. baumannii. Identification of chromosomal and plasmidencoded AMR in the genome of A. baumannii may help understand the mechanism behind the genetic mobilization and spread of AMR genes. [ABSTRACT FROM AUTHOR]

Background and Objectives: Bioactive secondary metabolites are the products of microbial communities adapting to environmental challenges, which have yet remained anonymous. As a result of demands in the pharmaceutical, agricultural, and food industries, microbial metabolites should be investigated. The most substantial sources of secondary metabolites are Streptomyces strains and are potential candidates for bioactive compound production. So, we used genome mining and bioinformatics to predict the isolates secondary metabolites, biosynthesis, and potential pharmaceuticals. Materials and Methods: This is a bioinformatics part of our previous experimental research. Here, we aimed to inspect the underlying secondary metabolite properties of 20 phylogenetically diverse Streptomyces species of saline soil by a rationalized computational workflow by several software tools. We examined the Metabolites' cytotoxicity and antibacterial effects using the MTT assay and plate count technique, respectively. Results: Among Streptomyces species, three were selected for genome mining and predicted novel secondary metabolites and potential drug abilities. All 11 metabolites were cytotoxic to A549, but ectoine (p≤0.5) and geosmin (p≤0.001) significantly operated as an anti-cancer drug. Metabolites of oxytetracycline and phosphinothricin (p≤0.001), 4Z-annimycin and geosmin (p≤0.01), and ectoine (p≤0.5) revealed significant antibacterial activity. Conclusion: Of all the 11 compounds investigated, annimycin, geosmin, phosphinothricin, and ectoine had antimicrobial properties, but geosmin also showed very significant anti-cancer properties. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the prevalent cancers in the world with a high recurrence rate. In recent years, different researches have focused on designing efficient multi-epitope peptide vaccines against HCC. In designing these vaccines, over-expressed antigens in HCC patients, such as α-fetoprotein (AFP) and glypican-3 (GPC-3), have been employed. In our previous study, a multi-epitope peptide vaccine for HCC was designed by in-silico methods. The designed vaccine construct included the AFP, GPC-3, and aspartyl-β-hydroxylase (ASPH) as CytoLoxic T cell Lymphocytes (CTL), one epitope from Tetanus Toxin Fragment C (TTFrC) as Helper T cell Lymphocytes (HTL), and a segment of microbial heat shock protein (HSP70) peptide407-426 as an adjuvant. All the mentioned parts were connected by appropriate linkers. The aim of this study is the production of the designed vaccine. Methods: This research is experimental and was carried out in Fasa, Iran, in 2017. The designed vaccine construct gene was transformed to the Escherchia coli BL21 (DE3) strain and expressed in different isopropyl β-D-1-thiogalactopyranoside (IPTG) concentrations (0.6 and 1 mM), times (4, 6, 8, 16 hours), and temperatures (25 and 37 °C). Then, the expressed protein was analyzed by Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and the Western blot methods. Results: The best conditions for protein expression were obtained in the Super Optimal Broth (SOB) medium at 37 °C after the induction of expression by 1 mM IPTG for six hour. Conclusion: The recombinant HCC vaccine was produced with a proper concentration. [ABSTRACT FROM AUTHOR]

Objective Maple syrup urine disease (MSUD; OMIM #248600) is an autosomal recessive metabolic disorder in the catabolism of branched-chain amino acids (leucine, isoleucine, and valine) and may be lethal if untreated in affected newborns. Methods Single-nucleotide polymorphism haplotyping and Sanger sequencing of BCKDHA , BCKDHB , and DBT genes were performed in a cohort of 10 MSUD patients. Results We identified a 16.6 Mb homozygous region harboring the DBT gene in an Iranian girl presenting with MSUD. Sanger sequencing revealed a pathogenic homozygous variant (NM_001918.3: c.1174A > C) in the DBT gene. We further found a controversial variant (rs12021720: c.1150 A > G) in the DBT gene. This substitution (p.Ser384Gly) is highly debated in literature. Bioinformatics and cosegregation analysis, along with identifying the real pathogenic variants (c.1174 A > C), lead to terminate these various interpretations of c.1150 A > G variant. Conclusion Our study introduced c.1150 A > G as a polymorphic variant, which is informative for variant databases and also helpful in molecular diagnosis. [ABSTRACT FROM AUTHOR]

Objective Solute carrier family 19 member 2 (SLC19A2 , OMIM *603941) encodes thiamine human transporter 1 (THTR-1), which contributes to bringing thiamine (vitamin B1) into cells. Mutations in SLC19A2 lead to a rare recessive genetic disorder termed thiamine-responsive megaloblastic anemia (TRMA) syndrome. Methods An Iranian family with TRMA was investigated by whole-exome sequencing (WES) to determine the genetic cause(s) of the disease. Accordingly, SLC19A2 genetic variants were gathered through literature analysis. Results WES recognized a known pathogenic variant, c.697C > T (p. Q233X), within exon 2 of SLC19A2 (NM_006996). Subsequently, the proband's parents and sister were confirmed as heterozygous carriers of the identified variant. Conclusion The diagnostic utility and affordability of WES were confirmed as the first approach for the genetic testing of TRMA to verify the diagnosis. This analysis can be used to guide future prenatal diagnoses and determine the consequences in the other family members. [ABSTRACT FROM AUTHOR]

Background: Hepatocyte growth factor (HGF) protein regulates cell growth, motility, and morphogenesis in a variety of cells and tissues by binding to the HGF receptor. The rs5745687 SNPs in the introns of the HGF gene could affect the splicing and expression of HGF mRNA. Objectives: In this study, the genotype frequency of rs5745687 in breast cancer (BC) and gastric cancer (GC) (positive helicobacter) patients has been investigated and compared with the healthy controls in the Isfahan population. Methods: Firstly, initial bioinformatics studies were done. Then, according to the results, bioinformatics High-Resolution Melt (HRM) and Real-Time PCR were recruited to determine genotypes rs5745678 for 432 participants in the case-control analysis (84 GC with 126 healthy control samples, as well as 111 BC cases with 111 normal controls). The conditional logistic regression model was used to measure odds ratios (OR) and 95% confidence intervals (CI) to produce these cancers based on genotype frequency. Results: The homozygote genotype of the mutant (G) allele of rs5745678 has a significant association with the lower risk of gastric cancer (P-value < 0.0001) and this allele can increase the risk of GC in a co-dominant model (OR: 5.541, P-value < 0.0001). Also, the rs5745678 SNP had a significant association with the clinicopathological features (age, smoking, H. Pylori infection) in GC patients. Conclusions: The presence of a single G allele in rs5745678 heterozygote (AG/AA) and co-dominant (AG/AA+GG) models could significantly impact GC pathogenicity in different ways. There was no significant correlation between the rs5745678 polymorphism and BC (P-value: 0.671) in the studied sample size. [ABSTRACT FROM AUTHOR]

Objective The most important tumor characteristic of Lynch syndrome (LS) is microsatellite instability (MSI). In the current study, BAT34c4 and BAT26 mononucleotide markers were evaluated as part of efforts to test a cost-effective panel for MSI testing in Iranian patients, comparing it with the Promega kit. Methods Amsterdam II clinical criteria were used to identify patients at risk for LS. The MSI status of these patients was determined using BAT34c4 and BAT26 markers, as well as the Promega kit. The results of both methods were compared, and the sensitivity and specificity of new short tandem repeat (STR) markers were estimated using statistical formulas. Results Of the 37 patients we studied who were at risk for LS, 27% showed MSI-high results, via the Promega kit. The same results were achieved for BAT34c4 and BAT26 separately. Conclusions The novel 2-marker kit for MSI testing has similar accuracy as the Promega kit at a lower cost, due to fewer markers and a more economical labeling method. [ABSTRACT FROM AUTHOR]

Background: NS5A and NS5B proteins of hepatitis C virus (HCV) are the main targets of compounds that directly inhibit HCV infections. However, the emergence of resistance-associated substitutions (RASs) may cause substantial reductions in susceptibility to inhibitors.Methods: Viral load and genotyping were determined in eighty-seven naïve HCV-infected patients, and the amplified NS5A and NS5B regions were sequenced by Sanger sequencing. In addition, physicochemical properties, structural features, immune epitopes, and inhibitors-protein interactions of sequences were analyzed using several bioinformatics tools.Results: Several amino acid residue changes were found in NS5A and NS5B proteins; however, we did not find any mutations related to resistance to the treatment in NS5B. Different phosphorylation and few glycosylation sites were assessed. Disulfide bonds were identified in both proteins that had a significant effect on the function and structure of HCV proteins. Applying reliable software to predict B-cell epitopes, 3 and 5 regions were found for NS5A and NS5B, respectively, representing a considerable potential to induce the humoral immune system. Docking analysis determined amino acids involved in the interaction of inhibitors and mentioned proteins may not decrease the drug efficiency.Conclusions: Strong interactions between inhibitors, NS5A and NS5B proteins and the lack of efficient drug resistance mutations in the analyzed sequences may confirm the remarkable ability of NS5A and NS5B inhibitors to control HCV infection amongst Iranian patients. The results of bioinformatics analysis could unveil all features of both proteins, which can be beneficial for further investigations on HCV drug resistance and designing novel vaccines. [ABSTRACT FROM AUTHOR]

Background: Ocriplasmin has been developed for the induction of posterior vitreous detachment in patients with vitreomacular adhesion. At physiological pH, ocriplasmin is susceptible to autolytic and proteolytic degradation, limiting its activity duration. These undesirable properties of ocriplasmin can be reduced by site-directed mutagenesis, so that its enzymatic activities can be augmented. This study aimed to design ocriplasmin variants with improved biological/physicochemical characteristics via bioinformatics tools. Methods: This study was performed in Tabriz University of Medical Sciences, Tabriz, Iran, 2019. Through site-directed mutagenesis, three ocriplasmin variants were designed. Structural analysis was performed on the wild-type variant and the mutant variants using the Protein Interactions Calculator (PIC) server. The interactions between the S-2403 substrate and the ocriplasmin variants were studied by molecular docking simulations, and binding capability was evaluated by the calculation of free binding energy. The conformational features of protein-substrate complex systems for all the variants were evaluated using molecular dynamic simulations at 100 nanoseconds. Results: The structural analysis of ocriplasmin revealed that the substitution of threonine for alanine 59 significantly reduced proteolytic activity, while the substitution of glutamic acid for lysine 156 influenced autolytic function. The molecular docking simulation results indicated the appropriate binding of the substrate to the ocriplasmin variants with high-to-low affinities. The binding affinity of the wild-type variant for the substrate was higher than that between the mutant variants and the substrate. Simulation analyses, consisting of the root-meansquare deviation, the root-mean-square fluctuation, and the center-of-mass average distance showed a higher affinity of the substrate for the wild type than for the mutant variants. Conclusion: The mutational analysis of ocriplasmin revealed that A59T and K156E mutagenesis could be used for the development of a new variant with higher therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Hypohidrotic ectodermal dysplasia (HED) is the most common type of ectodermal dysplasia that is the result of faulty ectodermal development leading to such ectodermal defects as hypotrichosis, anodontia or hypodontia, and hypohidrosis or anhidrosis. Xlinked HED is caused by mutations in ectodysplasin A (EDA) gene and accounts for 90% of all HED cases. Autosomal HED is caused by mutations in other involved genes, such as EDA-receptor (EDAR) gene. In this study, we included two distinct families with three HED patients. We collected 5 mL of peripheral blood from the probands, associated parents, and 120 matched unrelated controls (from related ethnicity) without any ectodermal disorder. DNA was extracted using the routine salting-out protocol from blood leukocytes. Polymerase chain reaction (PCR) purification and bidirectional Sanger sequencing of the PCR products were performed. We identified p.R156H (c.467 G > A) mutation in EDA gene in two affected brothers and their carrier mother (family 1) and a novel missense mutation c.1210G > A (p.A404T) in EDAR gene in a 4-year-old affected boy and his heterogeneous parents (family 2). Clinical evaluation, genetic findings, and bioinformatic analysis supported deleterious effects of both identified mutations on the EDA and EDAR gene products, which should be considered in genetic assessment of HED cases in Southwest of Iran. [ABSTRACT FROM AUTHOR]

Copyright of Medical Journal of Tabriz University of Medical Sciences is the property of Tabriz University of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective Tyrosine kinase inhibitors (TKIs) are considered standard first-line treatment in patients with chronic myeloid leukemia. Because ABL kinase domain mutations are the most common causes of treatment resistance, their prevalence and assessment during treatment may predict subsequent response to therapy. Methods The molecular response in Bcr-Abl1 IS was tested via quantitative real-time polymerase chain reaction. We used the direct sequencing technique to discover the mutations in the ABL kinase domain. The IRIS trial established a standard baseline for measurement – (100% BCR-ABL1 on the 'international scale') and a major molecular response (good response to therapy) was defined as a 3-log reduction in the amount of BCR-ABL1 – 0.1% BCR-ABL1 on the international scale. Results We observed 11 different mutations in 13 patients, including E255K, which had the highest mutation rate. A lack of hematologic response was found in 22 patients, who showed a significantly higher incidence of mutations. Conclusion Detection of kinase domain mutations is a reliable method for choosing the best treatment strategy based on patients' conditions, avoiding ineffective treatments, and running high-cost protocols in patients with acquired resistance to TKIs. [ABSTRACT FROM AUTHOR]

The aim of this study is to develop a computational prediction model for implantation outcome after an embryo transfer cycle. In this study, information of 500 patients and 1360 transferred embryos, including cleavage and blastocyst stages and fresh or frozen embryos, from April 2016 to February 2018, were collected. The dataset containing 82 attributes and a target label (indicating positive and negative implantation outcomes) was constructed. Six dominant machine learning approaches were examined based on their performance to predict embryo transfer outcomes. Also, feature selection procedures were used to identify effective predictive factors and recruited to determine the optimum number of features based on classifiers performance. The results revealed that random forest was the best classifier (accuracy = 90.40% and area under the curve = 93.74%) with optimum features based on a 10-fold cross-validation test. According to the Support Vector Machine-Feature Selection algorithm, the ideal numbers of features are 78. Follicle stimulating hormone/human menopausal gonadotropin dosage for ovarian stimulation was the most important predictive factor across all examined embryo transfer features. The proposed machine learning-based prediction model could predict embryo transfer outcome and implantation of embryos with high accuracy, before the start of an embryo transfer cycle. [ABSTRACT FROM AUTHOR]

Human Papilloma Virus (HPV) genome encodes several proteins, as L1is major capsid protein and L2 is minor capsid protein. Among all HPV types HPV-16 and HPV-18 are the most common high-risk HPV (HR-HPV) types globally and the majority of cases are infected with these types. HPV entry and the initial interaction with the host cell are mainly related to the L1 protein which is the main component of HPV vaccines. The aim of this research was comparison analysis among all Iranian L1 protein sequences submitted in NCBI GenBank to find the major substitutions as well as structural and immune properties of this protein. All sequences HPV L1 protein from Iranian isolates from 2014 to 2016 were selected and obtained from NCBI data bank. "CLC Genomics Workbench" was used to translate alignment. To predict B cell epitopes, we employed several programs. Modification sites such as phosphorylation, glycosylation, and disulfide bonds were determined. Secondary and tertiary structures of all sequences were analyzed. Several mutations were found and major mutations were in amino acid residues 102, 202, 207, 292, 379, and 502. The mentioned mutations showed the minor effect on B cell and physicochemical properties of the L1 protein. Six disulfide bonds were determined in L1 protein and also in several N-link glycosylation and phosphorylation sites. Five L1 loops were determined, which had great potential to be B cell epitopes with high antigenic properties. All in all, this research as the first report from Iran described the tremendous potential of two L1 loops (BC and FG) to induce immune system which can be used as the descent candidate to design a new vaccine against HPV in the Iranian population. In addition, some differences between the reference sequence and Iranian patients' sequences were determined. It is essential to consider these differences to monitor the effectiveness and efficacy of the vaccine for the Iranian population. Our results provide a vast understanding of L1 protein that can be useful for further studies on HPV infections and new vaccine generations. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) is an emerging zoonotic viral infection, which was started in Wuhan, China, in December 2019 and transmitted to other countries worldwide as a pandemic outbreak. Iran is one of the top ranked countries in the tables of COVID-19-infected and -mortality cases that make the Iranian patients as the potential targets for diversity of studies including epidemiology, biomedical, biodata, and viral proteins computational modelling studies. Results: In this study, we applied bioinformatic biodata mining methods to detect CDS and protein sequences of ORF1ab polyprotein of SARS-CoV-2 isolated from oronasopharynx of an Iranian patient. Then through the computational modelling and antigenicity prediction approaches, the identified polyprotein sequence was analyzed. The results revealed that the identified ORF1ab polyprotein belongs to a part of nonstructural protein 1 (nsp1) with the high antigenicity residues in a glycine-proline or hydrophobic amino acid rich domain. Conclusions: The results revealed that nsp1 as a virulence factor and crucial agent in spreading of the COVID-19 among the society can be a potential target for the future epidemiology, drug, and vaccine studies. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a serious global health problem and a cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Bioinformatics software has been an effective tool to study the HCV genome as well as core domains. Our research was based on employing several bioinformatics software applications to find important mutations in domain 1 of core protein in Iranian HCV infected samples from 2006 to 2017, and an investigation of general properties, B-cell and T-cell epitopes, modification sites, and structure of domain 1. Domain 1 sequences of 188 HCV samples isolated from 2006 to 2017, Iran, were retrieved from NCBI gene bank. Using several tools, all sequences were analyzed for determination of mutations, physicochemical analysis, B-cell epitopes prediction, T-cell and CTL epitopes prediction, post modification, secondary and tertiary structure prediction. Our analysis determined several mutations in some special positions (70, 90, 91, and 110) that are associated with HCC and hepatocarcinogenesis, efficacy of triple therapy and sustained virological response, and interaction between core and CCR6. Several B-cell, T-cell, and CTL epitopes were recognized. Secondary and tertiary structures were mapped fordomain1 and core proteins. Our study, as a first report, offered inclusive data about frequent mutation in HCV-core gene domain 1 in Iranian sequences that can provide helpful analysis on structure and function of domain 1 of the core gene. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is one of the most frequent cancers among men and women. Patients with gastric cancer are mostly diagnosed in advanced stages because of asymptomatic progression. Due to the heterogeneity and poor prognosis of this cancer, a comprehensive study at the transcriptome level gene expression is needed to find the various genes and mechanisms involved in gastric cancer. Differentially expressed genes (DEG) derived from high-throughput RNA-sequencing could lead to the achievement of new molecular biomarkers. Objectives: In this study, after transcriptome reanalysis, we focused on the genes involved in epithelial-mesenchymal transition (EMT) via extracellular matrix (ECM).We have aimed at findingmRNAlevel changes in new candidate genes among Iranian patients with gastric cancer. Methods: Six gastric cancer and two normal sequencing rawsample datasets were collected from the European Nucleotide Archive (ENA). The bioinformatic pipeline was used to reanalyze raw datasets and get DEGs, using the DESeq2 package. After analyzing, THBS2,OSMR,andCHI3L1 genes were selected for validationandverification in 25confirmedadenocarcinoma gastric cancer patients and non-malignant normal tissues from the Iranian population by real-time polymerase chain reaction (PCR). Results: The bioinformatic analysis of raw datasets revealed many upregulated and downregulated genes in gastric cancer tissues compared with normal samples. Then, real-time PCR verified the upregulation of THBS2, OSMR, and CHI3L1 genes in a group of Iranian patients with gastric cancer. Analyzing graphs showed a significant increase in the expression of targeted genes in patients with gastric cancer (P < 0.0001, P = 0.0016, and P = 0.0002, respectively). Conclusions: The results validated an obvious increase in the expression of THBS2, OSMR, and CHI3L1 genes in gastric cancer of Iranian patients. These genes are involved in EMT and may have a role in cancer invasion if tested further for their diagnostic and prognostic value in larger sample sizes. [ABSTRACT FROM AUTHOR]

Schematic Diagram Showing the Steps of Research. [Display omitted] • This is the first time that nucleotide changes in the THBD gene have been investigated by RPL in Iran. • Point mutations in the THBD gene may alter various coagulation pathways, inflammation, and cell/cell adhesion mechanisms. • These nucleotide changes in the THBD gene can be developed as new biomarkers for RPL risk assessment. • Val138Asp and Arg278His mutations caused significant changes in the local hydrophobic properties of the protein. • The results of In-silico assays predicted that these mutations may lead to functional disorders of the protein. Recurrent pregnancy loss (RPL) is a common but complex complication in fertility conditions, affecting about 15–20% of couples. Although several causes have been proposed for RPL, it occurs in about 35–60% of cases without a known explanation. A strong assumption is that genetic factors play a role in the etiology and pathophysiology of PRL. Therefore, several genes are proposed as candidates in the pathogenesis of RPL. The current study aimed to investigate the effects of nucleotide changes in the THBD (thrombomodulin) gene as an RPL-related candidate gene. This gene encodes a cell receptor for thrombin and is involved in reproductive loss in RPL cases. Its involvement in the natural anticoagulant system has been extensively studied. By genetic screening of the entire coding and noncoding regions of the THBD gene, we found twenty-seven heterozygous and homozygous nucleotide changes. Ten of them led to amino acid substitutions, seven variants were identified in the promoter region, and eight of them occurred in 3′UTR. Potentially, the pathogenicity effects of these variations on THBD protein were evaluated by several prediction tools. The numerous genomic variations prompted noticeable modifications of the protein's structural and functional properties. Furthermore, in-silico scores were consistent with deleterious effects for these mutations. The results of this study provide genetic information that will be useful in the future for clinicians, scientists, and students to understand the unknown causes of RPL better. It may also pave the way for developing diagnostic/prognostic approaches to help treat PRL patients. [ABSTRACT FROM AUTHOR]

Three populations of Xiphinema primum n. sp. and two populations of X. pachtaicum were recovered from natural forests and cultural regions of northern Iran. Both species belong to the X. americanum-group and were characterized by their morphological, morphometric and molecular data. The new species, which was recovered in three locations, belongs to the X. brevicolle-complex and is characterized by 2124–2981 μm long females with a widely rounded lip region separated from the rest of the body by a depression, 103–125 μm long odontostyle, two equally developed genital branches with endosymbiont bacteria inside the ovary, which are visible under light microscope (LM), vulva located at 51.8–58.0%, the tail is 26–37 μm long with a bluntly rounded end and four juvenile developmental stages. It was morphologically compared with nine similar species viz. X. brevicolle, X. diffusum, X. incognitum, X. himalayense, X. luci, X. parabrevicolle, X. paramonovi, X. parataylori and X. taylori. The second species, X. pachtaicum, was recovered in two geographically distant points close to city of Amol. Molecular phylogenetic studies of the new species were performed using partial sequences of the D2-D3 expansion segments of the large subunit ribosomal RNA gene (LSU rDNA D2-D3), the internal-transcribed spacer rDNA (ITS = ITS1+5.8S+ITS2), and the mitochondrial cytochrome c oxidase I gene (COI mtDNA) regions. The Iranian population of X. pachtaicum was also phylogenetically studied based upon its LSU rDNA D2-D3 sequences. Both species were also inspected for their putative endosymbiont bacteria. Candidatus Xiphinematobacter sp. was detected from two examined populations of the new species, whereas the second endosymbiont bacterium, detected from three examined isolates of X. pachtaicum, was related to the plant and fungal endosymbionts of the family Burkholderiaceae. The phylogenetic analyses of the two endosymbiont bacteria were performed using partial sequences of 16S rDNA. In cophylogenetic analyses, significant levels of cophylogenetic signal were observed using both LSU rDNA D2-D3 and COI mtDNA markers of the host nematodes and 16S rDNA marker of the endosymbiont bacteria. [ABSTRACT FROM AUTHOR]

Tumor cells in breast cancer are immunogenic and express proteins that can induce immune responses. One important antigen is human telomerase reverse transcriptase (hTERT). The main aim of this study was to use an epitope from hTERT accompanied by an epitope derived from influenza virus restricted to HLA-A2, a common Class I HLA in Iran, to induce T cells against tumoral cells. The epitopes were analyzed in IEDB and EpiMHC databases for the strength of binding to HLA-A2 and immunogenicity, respectively. Peripheral blood mononuclear cells (PBMCs) from 11 HLA-A2-positive breast cancer patients were isolated and then were harvested and co-cultured with MCF-7 cells that were previously trans-loaded with synthesized peptides. PBMC proliferation, interferon-γ (IFN-γ) secretion, and activated T cell cytotoxicity were analyzed by MTT, ELISA, and LDH cytotoxicity assays, respectively. Proliferation of PBMCs incubated with the tumoral peptide was significantly greater than that of controls (P < 0.001). In addition, the proliferation of PBMCs incubated with tumoral and viral peptides was greater than that of PBMCs incubated with tumoral peptide alone. The same was true of IFN-γ secretion and LDH release (P < 0.001 and P < 0.05 respectively). Tumoral peptide can induce PBMCs through a class I MHC pathway and this induction is intensified with viral peptides. [ABSTRACT FROM AUTHOR]

Background: Congenital Heart Disease (CHD) occurs in nearly 1% of newborns due to genetic and environmental factors. There are many genes involved in CHD. Variants of Gap Junction Protein Alpha 1 (GJA1), Zic Family Member 3 (ZIC3), Nodal Growth Differentiation Factor (NODAL), and Forkhead Box H1 (FOXH1) genes are common to develop CHD. Objectives: To date, no study has been published about CHD patients in Iran. Therefore, the present study aimed to evaluate the sequence variants of these genes in Iranian patients. Methods: This study was conducted on 73 patients with familial CHD and their family members. Genetic investigations were performed using Polymerase Chain Reaction (PCR) and direct DNA sequencing of the exons and flanking regions of the genes. The variants were evaluated using available online software tools. Mutation taster, PROVEAN, SIFT, PolyPhen-2, and CADD were used to predict the effects of the variants and I-TASSER was applied to evaluate the possible structural effects of the genetic variations. Results: c.612G > A, c.717G > A, and c.895C > T in GJA1 were found in the study participants. c.1248T > G in the ZIC3 was observed in a twin with CHD. Besides, c.193 + 12C > T, c.-109T > C, c.494A > G, c.417C > T, and c.357C > T variants were detected in the NODAL gene. Additionally, c.-314T > G, c.175-30C > T, and c.373A > T sequence changes were determined in the FOXH1 gene. Two novel heterozygous variants, namely c.1061C > G and c.-465C > A, were also found in the FOXH1 gene. Bioinformatics analysis indicated that the detected reported/novel variants might not have a damaging effect among Iranian CHD patients. Conclusion: The study results indicated the first variation screening of GJA1, ZIC3, NODAL, and FOXH1 genes in Iranian familial CHD patients. The results also suggested a minor role for GJA1, ZIC3, NODAL, and FOXH1 genes in familial CHD pathogenesis. However, their exact role in CHD causation entails further research. [ABSTRACT FROM AUTHOR]

Two ektaphelenchid nematodes representing one new and one known species are illustrated and characterized using morphological and molecular data. Ektaphelenchus kanzakii n. sp. is mainly characterized by its tripartite stylet having a well visible wide lumen, encompassing a sclerotized and acute anterior part (the conus), a short and slightly tapering middle part (the conophore) that is equally sclerotized but clearly separate from the conus, and a long posterior part that is cylindrical and only weakly sclerotized (the shaft) without basal knobs or swellings. It is further characterized by 863.5 (772–926) μm long females having 23.8 (21.2–27.0) μm long total stylet, distinctly annulated cuticle, three lines in lateral field, vulva at 76.6 (75.3–80.0)%, no rectum, vestigial anus in some individuals, conical posterior body end (tail) with narrow ventrally bent tip, common males in population with two pairs of caudal papillae (the single precloacal papilla and the third caudal pair lacking), spicules with dorsally bent tip and conical tail with sharp or blunt tip. The new species is morphologically compared with close species having conical posterior body end and stylet lacking basal knobs or swellings. Iranian population of Devibursaphelenchus teratospicularis, the second studied species, is characterized by 679.5 (620–709) μm long females having 18.6 (17.5–20.0) μm long total stylet with similar structure to the previous species, subcylindrical body end with widely rounded tip, and rare males with typical spicules of this species and a pair of precloacal and a pair of caudal papillae. Molecular phylogenetic studies of the two recovered species using small and large subunit ribosomal DNA (SSU and LSU rDNA) partial sequences revealed they have close phylogenetic affinities with Ektaphelenchus obtusus in both reconstructed trees. However, species of both genera Ektaphelenchus and Devibursaphelenchus don’t form monophyletic groups in SSU and LSU trees. New observations on stylet structure of the two presently studied and some other ektaphelenchid species having available light microphotographs (LM) yielded on definition of a new term “conophore” for the middle part of the ektaphelenchid-type tripartite stylet. [ABSTRACT FROM AUTHOR]

Objectives: Niemann-Pick diseases (NPD) is an autosomal recessive inherited lysosomal lipid storage disorder which occurs due to a defect in cellular cholesterol trafficking, leading to excess lipid accumulation in multiple organ systems such as the brain, lungs, spleen, and liver. SPMD1-associated disease includes classic infantile and visceral NPD type A and B respectively. Type C NPD is subacute or juvenile. Materials & Methods During 2012-2016, the patients who had the clinical and biochemical signs and symptoms of different types of NPD, underwent genetic analysis. All patients were collected from five provinces in Iran (Razavi Khorasan, South Khorasan, Khozaestan, Isfahan and Tehran province). Sanger sequencing of the candidate genes for NPD was performed followed by bioinformatics analysis to confirm the types of NPD and to identify novel mutations. All patients underwent full clinical assessment. Results: We present two cases with NPD type A, six cases with NPD type B, and 11 cases with type C with various enzymatic defects identified in these cases. Within these 19 patients, we present 9 previously reported mutations and 10 novel mutations causing NPD. Conclusion: This study is the largest Iranian study for NPD analysis ever. Our report demonstrates that NPD has a variable age of onset and can present early in life. We investigated the clinical and genetic manifestations of a large Iranian cohort. Understanding the variable presentation of NPD will allow for clinicians to have a high index of suspicion for the disease. [ABSTRACT FROM AUTHOR]

• In 2015–2016 flu season, A/H1N1/pdm09 was predominant all around the world and in our region. • Software including MEGA-X, MODELLER, UCSF ChimeraX, auto-dock 4.2, and other online tools were used to analyze the phylogenetic relationship, antiviral resistance and vaccine efficiency of selected NA proteins. • Iranian isolates were located in clade 6B similar to A/Michigan/45/2015 reference sequence. • The phylogenetic study showed that most Iranian NA sequences (between 2015 and 2016) were located in a single clade and following years were located in its subclade by 3 major mutations (G77R/K, V81A, and J188T). • Resistant mutations in drug targets of NA including I117M, D151E, I223V, and S247N were ascertained in 10 isolates during the 2015–2016 flu seasons. Influenza A viruses (H1N1) have been consistently one of the most evolving viruses that escape from vaccine-induced immunity. Although there has been a rapid rise in human influenza virus knowledge since the 2009 pandemic, the molecular information about Iranian strains is still inadequate. The aim of this study was to analyze the neuraminidase (NA) segment of the Iranian isolates in terms of phylogenetic, antiviral resistance, and vaccine efficiency. Ninety-three NA sequences collected among 1758 nasopharyngeal swab samples during the 2015–2016 influenza season were sequenced and submitted to NCBI. Moreover, all the submitted Iranian influenza H1N1 NA sequences since 2010 till 2019 were included in the study. Software including MEGA-X, MODELLER, UCSF ChimeraX, Auto-Dock 4.2, and other online tools were used to analyze the phylogenetic relationship, vaccine efficiency, and binding affinity to sialic acid of the selected NA proteins. Moreover, the information about antiviral drug resistance mutations of NA were gathered and compared to the Iranian NA segments to check the presence of antiviral drug-resistant strains. The phylogenetic study showed that most Iranian NA sequences (between 2015 and 2016) were located in a single clade and following years were located in its subclade by 3 major mutations (G77R/K, V81A, and J188T). Resistant mutations in drug targets of NA including I117M, D151E, I223V, and S247N were ascertained in 10 isolates during the 2015–2016 flu seasons. Investigation of vaccination effect revealed that Iranian isolates in 2017 and 2018 were best matched to A/Brisbane/02/2018 (H1N1), and in 2019 to A/Guangdong-Maonan/SWL1536/2019 (H1N1). Furthermore, we performed an in-silico analysis of NA enzymatic activity of all Iranian sequences by assessment of enzyme stability, ligand affinity, and active site availability. Overall, the enzyme activity of four Iranian strains (AUG84119, AUG84157, AUG84095, and AUG84100) was assumed as the maximum enzyme activity. This study highlighted the evolutionary trend of influenza A virus/H1N1 circulating in Iran, which provides a preliminary viewpoint for a better comprehension of new emerging strains' virulence and thus, more appropriate monitoring of influenza virus A/H1N1 during each outbreak season. [ABSTRACT FROM AUTHOR]

Objectives: Preeclampsia (PE) is a leading cause of maternal death worldwide and involves vascular endothelial dysfunction. The aim of this study was to investigate the association of the G894T polymorphism in the endothelial nitric oxide synthase (eNOS) gene and the risk of preeclampsia in a case-control design in an Iranian population, which was followed by a meta-analysis and an in silico approach., Methods: In the case-control study, 300 people including 135 pregnant women with preeclampsia and 165 healthy pregnant women were included. The genotype of G894T polymorphism was determined by the PCR-RFLP method. We searched authoritative scientific databases to find eligible studies for meta-analysis. The odds ratio with a 95% confidence interval was estimated to find the strength of the association of the mentioned polymorphism with the risk of preeclampsia. In addition, the effect of G894T transversion on eNOS gene function was evaluated by some bioinformatics tools., Results: Our case-control data showed that the G894T polymorphism is associated with an increased risk of preeclampsia. In the meta-analysis, 33 eligible studies were included, and the results showed that the G894T polymorphism is associated with an increased risk of preeclampsia in the overall analysis and some stratified analyses. In addition, the structural analysis showed that the G894T variant can affect the splicing process as well as the protein stability., Conclusions: Based on the results, the aforementioned polymorphism may be a risk factor for preeclampsia and could be considered a potential molecular biomarker for screening susceptible individuals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

One of the most important fungal agents of pistachio dieback disease belongs to the ascomycete genus Paecilomyces that has been identified as P. variotii. In 2012–2014, 700 plant samples from pistachio trees and 27 other plant species with dieback symptoms were collected from 10 provinces of Iran. Of the 567 pistachio samples, 277 Paecilomyces strains were obtained and from the 133 samples of other plants (except pistachio and including Pistacia mutica, Punica granatum, Prunus amygdalus, Caesalpinia gilliesii, Nerium oleander, Tamarix aphylla, Tamarix hispida and Haloxylon sp.), 23 fungal isolates were recovered and five isolates were obtained from the air of infected pistachio orchards. Based on morphology, all 305 isolates were identified as P. variotii. Physiological studies revealed that 299 isolates belong to P. formosus. Three isolates were assigned to P. variotii, while three isolates could not be assigned to any of the known species. Of the 305 isolates, 62 were selected for phylogenetic analysis based on DNA variation (ITS, β-tubulin and calmodulin). This analysis showed that all of our isolates form a clade with P. formosus. P. formosus consists of the three former species P. formosa, P. lecythidis and P. maximus. This study shows that our isolates form a strongly supported clade with strains of P. lecythidis. So, the causal agent of dieback disease of pistachio and other examined trees is P. formosus which is closely related to the former species P. lecythidis and has some differences with the former species P. formosa and P. maximus. Based on phylogenetic studies P. formosus thus seems to be a species complex that could be divided into three separate species. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Razi Institute is the property of Institut Razi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Viral hepatitis is considered as a worldwide health problem and hepatitis B virus (HBV) infection is one of the major health concerns which are annually responsible for more than one million deaths. HBV can be classified into at least eight genotypes, A–H and four major subtypes. Predominant HBV genotype in Mediterranean and Middle East countries is genotype D, but there is a few studies have been performed on the HBV genotype in Iran. The genotype characteristic and phylogenetic analyses were determined in chronic HBV patients in the northeast of Iran. First, seventy-eight patients with chronic HBV infection were enrolled. Demographic features were reviewed and sera samples were collected. HBV genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and results were confirmed by sequencing. Finally, a phylogenetic tree was obtained using Geneious software. Sixty-two (79.48%) of patients were males (mean age: 36.82 years). Twelve out of 78 patients (15.4%) were hepatitis B envelope antigen (HBeAg)-reactive. There were no significant differences between the clinical and HBeAg-positive serological data and HBeAb positive individuals. RFLP DNA sequencing and phylogenetic analysis showed that genotype D was the only genotype which observed in Mashhad, northeast of Iran. This is the first report of HBV genotyping in Mashhad. The results revealed that genotype D was the only genotype detected in this area which was consistence with previous studies in the Middle East, Mediterranean countries, southwest and center of Iran. [ABSTRACT FROM AUTHOR]

• The mean prevalence rate of CPV in Iran in 2018 was 24%. • There is a higher rate of prevalence and more intense symptoms of CPV-2 in dogs under 6 months. • The predominant variant of CPV in Iran is variant −2a. • The central part of Iran is the first infected region, specially Alborz province. • Original date of CPV proposed to be 1970. • The VP2 fragment of the CPV-2a variant in Iran is under positive selection pressure. Canine Parvo Virus 2 (CPV-2) culminated in lots of fatalities in domestic dogs since its emergence in 1978. Mainly, it is responsible for severe hemorrhagic diarrhea, vomiting, and dehydration. CPV-2 has three main variants known as 2a, 2b, and 2c. Due to the necessity of monitoring the evolutionary parameters of the virus, and also the lack of comprehensive study of CPV2 in Iran, this study is done for the first time in this country not only to characterize Iranian CPV genomes but also to study the evolutionary parameters and phylodynamics of CPV. The phylogenetic trees were constructed using the Maximum Likelihood (ML) method. By the use of the Bayesian Monte Carlo Markov Chain (BMCMC) method, evolutionary analysis and phylodynamics of the virus were investigated. Phylogenetic results showed that all Iranian isolates were classified in the CPV-2a variant. The central part of Iran was suggested to be the origin of the virus, especially the Alborz province. Before its prevalence throughout the country, the virus circulated in the central part, in Thran, Karaj, and Qom. Mutational analysis showed a positive selection pressure of CPV-2a. Investigating the evolutionary parameters of the virus proposed 1970 to be the date of birth of the virus, with a 95% credible interval between 1953 and 1987. The effective number of infections increased dramatically from 2012 to 2015, then faced a slightly decreasing trend from 2015 to 2019. A considerable up warding pattern was witnessed from the middle of 2019, which can be taken as a concern about the risk of vaccination failure. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to determine comprehensive maternal characteristics associated with birth weight using Bayesian modeling. Materials and Methods: A total of 526 participants were included in this prospective study. Nutritional status, supplement consumption during the pregnancy, demographic and socioeconomic characteristics, anthropometric measures, physical activity, and pregnancy outcomes were considered as effective variables on the birth weight. Bayesian approach of complex statistical models using Markov chain Monte Carlo approach was used for modeling the data considering the real distribution of the response variable. Results: There was strong positive correlation between infant birth weight and the maternal intake of Vitamin C, folic acid, Vitamin B3, Vitamin A, selenium, calcium, iron, phosphorus, potassium, magnesium as micronutrients, and fiber and protein as macronutrients based on the 95% high posterior density regions for parameters in the Bayesian model. None of the maternal characteristics had statistical association with birth weight. Conclusion: Higher maternal macro- and micro-nutrient intake during pregnancy was associated with a lower risk of delivering low birth weight infants. These findings support recommendations to expand intake of nutrients during pregnancy to high level. [ABSTRACT FROM AUTHOR]

Background: The 'a' determinant domain of hepatitis B surface antigen (HBsAg) (positions 124 to 147) is recognized by antibodies raised either naturally or induced by vaccine. Failure to protect against hepatitis B virus (HBV) infection may occur due to the conformational changes of 'a' determinant induced by mutations. Objectives: The present study analyzed the molecular and three-dimensional (3D) characteristics of the HBsAg 'a' determinant mutations among Iranian chronic hepatitis B (CHB) patients, who were vaccine and drug naive. Methods: Eighty patients with HBsAg positive test results were selected according to the data extracted from questionnaires. Serologic and molecular assays were performed using real-time Polymerase Chain Reaction (PCR) and subsequently surface nested PCR on CHB patients. Next, an extensive mutational analysis was applied following direct sequencing on HBsAg amplified genes. The potential impacts of altered antigenic and 3D properties of amino acid substitutions were carried out using bioinformatics approaches. Results: All patients were negative for HBeAg and positive for anti-HBe. Mutational analysis showed that 60 (75%) of 80 patients had at least one amino acid substitution. Several mutations were found in 'a' determinant (P127L, P127T, G130N, and S136Y). Bioinformatics investigations indicated that all mutations induced a conformational change in 'a' determinant region. P127L substitution led to a considerable decreased HBsAg antigenicity compared to other mutants. Conclusions: The current analyses revealed that the studied mutations induced a local change in the 'a' determinant conformation. These findings could be useful for the design of HBsAg detection assays, which may significantly improve the ability to detect particular HBsAg mutants. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]