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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]

Acute gastroenteritis caused by Rotavirus remains the leading cause of child mortality worldwide. Rotavirus genotype G9 circulates in humans throughout the world. Antibodies against the outer glycoproteins VP7 and VP4 Rotavirus capsid are the main neutralization antibodies in the vaccine assessment. This study aimed to select an epitope to evoke T and B cells' response, as a favorable candidate for vaccine development using in Silico evaluation. In the present study, Rotavirus genotypes were determined in 100 stools specimens collected from children with acute diarrhea. The results showed predominant G genotype, G9 (38.5%) followed by G2 (22.9%), G1 (16.5%), G12 (11.4%), G4 (6.4%), and G3 (4.3%). The G9 was dominant in this study and other regions of Iran; thus, this study was conducted to select an epitope from Rotavirus genotype G9 as a promising epitope candidate for future vaccine development. For this reason, several works including a complete sequence of VP7 G9, phylogenetic analysis, Prediction of Protein Structure, Physicochemical Properties of Protein and Epitope prediction were carried out. The outcomes of this study revealed that the complete sequence of VP7 (G9) was comprised of 1062 nt with 326 amino acids (accession number MH824633). The selected epitope contained amino acid sequence of STLCLYYPTEASTQIGDTEWKN with the best score for T and B cells response. Based on data of computational biology, the selected epitope can optimistically have considered as an epitope candidate for Rotavirus vaccine development. [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.)

Background: Maize Iranian mosaic virus (MIMV, genus Nucleorhabdovirus, family Rhabdoviridae) causes an economically important disease in maize and other gramineous crops in Iran. MIMV negative-sense RNA genome sequence of 12,426 nucleotides has recently been completed. Maize Genetics and Genomics database shows that 39,498 coding genes and 4,976 non-coding genes of maize have been determined, but still some transcripts could not be annotated. The molecular host cell responses of maize to MIMV infection including differential gene expression have so far not been elucidated. Methodology/Principal findings: Complementary DNA libraries were prepared from total RNA of MIMV-infected and mock-inoculated maize leaves and sequenced using Illumina HiSeq 2500. Cleaned raw transcript reads from MIMV-infected maize were mapped to reads from uninfected maize and to a maize reference genome. Differentially expressed transcripts were characterized by gene ontology and biochemical pathway analyses. Transcriptome data for selected genes were validated by real-time quantitative PCR. Conclusion/Significance: Approximately 42 million clean reads for each treatment were obtained. In MIMV-infected maize compared to uninfected plants, 1689 transcripts were up-regulated and 213 transcripts were down-regulated. In response to MIMV infection, several pathways were activated in maize including immune receptor signaling, metabolic pathways, RNA silencing, hormone-mediated pathways, protein degradation, protein kinase and ATP binding activity, and fatty acid metabolism. Also, several transcripts including those encoding hydrophobic protein RCI2B, adenosylmethionine decarboxylase NAC transcription factor and nucleic acid binding, leucine-rich repeat, heat shock protein, 26S proteasome, oxidoreductases and endonuclease activity protein were up-regulated. These data will contribute to the identification of genes and pathways involved in plant-virus interactions that may serve as future targets for improved disease control. [ABSTRACT FROM AUTHOR]

Colorectal cancers are derived from intestinal polyps. Normally, alterations in cell adhesion genes expression cause deviation from the normal cell cycle, leading to cancer development, progression, and invasion. The present study aimed to investigate the elusive expression pattern of CDC42, TAGLN, and GSN genes in patients with high and low-risk polyp samples, and also colorectal cancer patients and their adjacent normal tissues. In upcoming study, 40 biopsy samples from Taleghani Hospital (Tehran, Iran) were collected, consisting of 20 colon polyps and 20 paired adjacent normal tissues. The expression of the nominated genes CDC42, TAGLN, and GSN was analyzed using quantitative polymerase chain reaction (Q-PCR) and relative quantification was determined using the 2 -ΔΔCt method. ROC curve analysis was performed to compare high-risk and low-risk polyps for the investigated genes. The expression of adhesion molecule genes was also evaluated using TCGA data and the correlation between adhesion molecule gene expression and immunophenotype was analyzed. The role of mi-RNAs and lncRNAs in overexpression of adhesion molecule genes was studied. Lastly, GO and KEGG were performed to identify pathways related to adhesion molecule genes expression in healthy, normal adjacent, and COAD tissues. The results showed that the expression patterns of these genes were significantly elevated in high-risk adenomas compared to low-risk polyps and normal tissues and were associated with various clinicopathological characteristics. The estimated AUC for CDC42, TAGLN, and GSN were 0.87, 0.77, and 0.80, respectively. The study also analyzed COAD cancer patient data and found that the selected gene expression in cancer patients was significantly reduced compared to high-risk polyps and healthy tissues. Survival analysis showed that while the expression level of the GSN gene had no significant relationship with survival rate, the expression of CDC42 and TAGLN genes did have a meaningful relationship, but with opposite effects, suggesting the potential use of these genes as diagnostic or prognostic markers for colorectal cancer. The present study's findings suggest that the expression pattern of CDC42, TAGLN, and GSN genes was significantly increased during the transformation of normal tissue to polyp lesions, indicating their potential as prognostic biomarkers for colorectal polyp development. Further results provide valuable insights into the potential use of these genes as diagnostic or prognostic markers for colorectal cancer. However, further studies are necessary to validate these findings in larger cohorts and to explore the underlying mechanisms of these genes in the development and progression of colorectal cancer., (© 2023. The Author(s).)

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., Competing Interests: None declared., (Copyright: © Iranian Journal of Medical Sciences.)

Background: Brucellosis, a zoonosis mainly transmitted by consumption of unpasteurized dairy products as well as direct contact with infected animals, is endemic in Kyrgyzstan. However, Brucella species in humans have not been investigated and the origin of the disease remains poorly known in wide parts of Сentral Asia. Thus, molecular characterization of the circulating strains is a critical first step in understanding Brucella diversity in the country., Methods: In this study, isolates were collected from patients with suspected brucellosis from different regions in Kyrgyzstan between 2019 and 2020. The detection and identification of Brucella was carried out by Bruce-ladder PCR. Next generation sequencing was used to sequence the 89 Brucella isolates, which were genotyped by cgSNP and cgMLST to identify epidemiological connection between Brucella isolates as well as placing them in the context of the global Brucella phylogeny., Results: The Brucella strains isolated from all regions of Kyrgyzstan were identified as B. melitensis. Based on cgSNP analysis, 18 sequence types were differentiated. The highest numbers of different sequence types were found in Batken (n = 8), Osh (n = 8) and Jalal-Abad (n = 6) oblasts. According to cgSNP and cgMLST analyses, different B. melitensis lineages circulate in Kyrgyzstan, all of them belonging to the Eastern Mediterranean group of the global Brucella phylogeny with the highest similarity to strains from Turkmenistan, Iran and Turkey., Conclusion: In the present study, B. melitensis was identified as a causative agent of human brucellosis in Kyrgyzstan and different lineages could be identified. Since this study focused on isolates of human origin, the identity of Brucella species and lineages circulating among animal populations remains elusive. Implementing culture techniques and use of most recent molecular, bioinformatic and epidemiological tools are needed to set up a One Health approach to combat brucellosis in Kyrgyzstan. Further, other Сentral Asian countries need to take part in this effort as brucellosis is a transboundary disease in these regions., (© 2022. The Author(s).)

Background: Cystic fibrosis (CF) is the most common heredity disease among the Caucasian population. More than 350 known pathogenic variations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (NM&#95;000492.4) cause CF. Herein, we report the outcome of our investigation in two unrelated Iranian families with CF patients., Methods: We conducted phenotypic examination, segregation, linkage analysis, and CFTR gene sequencing to define causative mutations., Results: We found two novel mutations in the present study. The first one was a deletion causing frameshift, c.299delT p.(Leu100Profs*7), and the second one was a missense mutation, c.1857G>T, at nucleotide binding domain 1 of the CFTR protein. Haplotype segregation data supported our new mutation findings., Conclusion: Findings of this study expand the spectrum of CFTR pathogenic variations and can improve prenatal diagnosis and genetic counseling for CF.

Congenital hypothyroidism (CH) occurs with a relatively alarming prevalence in infants, and if not diagnosed and treated in time, it can have devastating consequences for the development of the nervous system. CH is associated with genetic changes in several genes that encode transcription factors responsible for thyroid development, including mutations in the NK2 homeobox 1 (NKX2.1) gene, which encodes the thyroid transcription factor-1 (TTF-1). Although CH is frequently observed in pediatric populations, there is still a limited understanding of the genetic factors and molecular mechanisms contributing to this disease. The sequence of the NKX2.1 gene was investigated in 75 pediatric patients with CH by polymerase chain reaction (PCR), single-stranded conformation polymorphism (SSCP), and direct DNA sequencing. Four missense heterozygous variations were identified in exon 3 of the NKX2.1 gene, including three novel missense variations, namely c.708A>G, p.Gln202Arg; c.713T>G, p.Tyr204Asp; c.833T>G, p.Tyr244Asp, and a previously reported variant rs781133468 (c.772C>G, p.His223Gln). Importantly, these variations occur in highly conserved residues of the TTF-1 DNA-binding domain and were predicted by bioinformatics analysis to alter the protein structure, with a probable alteration in the protein function. These results indicate that nucleotide changes in the NKX2.1 gene may contribute to CH pathogenesis.

Single nucleotide polymorphisms within genes encoding microRNAs may alter the expression of microRNAs and their target genes, contributing to the etiology of psychiatric disorders. We aimed to investigate the link between rs4705342T/C and rs4705343T/C polymorphisms in the promoter region of miR-143 and the risk of schizophrenia (SCZ) in a sample of an Iranian population. In this experimental study, a total of 398 subjects were recruited. Genotyping carried out using allele-specific PCR (AS-PCR) method. Different bioinformatics databases and Cytoscape V3.4.0 software were used for the analysis of the gene-miRNA interaction network. The genotypic analysis of rs4705342C/T showed that CC genotype in the co-dominant model significantly decreased the risk of SCZ (p < 0.001). Also, a significantly reduced risk of SCZ was observed under allelic (p < 0.001), dominant (p = 0.007), and recessive (p = 0.001) models of this variant. As regards rs4705343T/C, significantly enhanced risk of SCZ was found under the co-dominant CC (p = 0.01) and recessive (p = 0.007) contrasted genetic models. For this variant, the C allele conferred an increased risk of SCZ by 1.41 fold. Haplotype analysis showed that the C rs4705342 T rs4705343 haplotype significantly diminished SCZ susceptibility. The result of the bioinformatics analysis showed that miR-143, as a critical miRNA, targets ERK5, ERBB3, HK2, and PKCε, the four major genes involved in SCZ development. Our findings suggest that these two polymorphisms might affect SCZ susceptibility. Elucidating the precise regulatory mechanisms of gene expression in the development of SCZ will help researchers discover a novel target for therapeutic interventions., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Niemann-Pick disease type C (NPC) is a rare lysosomal neurovisceral storage disease caused by mutations in the NPC 1 (95%) or NPC2 (5%) genes. The products of NPC1 and NPC2 genes play considerable roles in glycolipid and cholesterol trafficking, which could consequently lead to NPC disease with variable phenotypes displaying a broad spectrum of symptoms., Materials: In the present study 35 Iranian NPC unrelated patients were enrolled. These patients were first analysed by the Filipin Staining test of cholesterol deposits in cells for NPC diagnostics. Genomic DNA was extracted from the samples of peripheral blood leukocytes in EDTA following the manufacturer's protocol. All exon-intron boundaries and coding exons of the NPC1gene were amplified by polymerase chain reaction (PCR) using appropriate sets of primers. Thereafter, the products of PCR were sequenced and analysed using the NCBI database ( https://blast.ncbi.nlm.nih.gov/Blast.cgi ). The variants were reviewed by some databases including the Human Gene Mutation Database (HGMD) ( http://www.hgmd.cf.ac.uk/ac/index.php ) and ClinVar ( https://www.ncbi.nlm.nih.gov/clinvar (. Moreover, all the variants were manually classified in terms of the American College of Medical Genetics and Genomics (ACMG) guideline., Results: The sequence analysis revealed 20 different variations, 10 of which are new, including one nonsense mutation (c.406C > T); three small deletions, (c.3126delC, c.2920&#95;2923delCCTG, and c.2037delG); and six likely pathogenic missense mutations, (c.542C > A, c.1970G > A, c.1993C > G, c.2821 T > C, c.2872C > G, and c.3632 T > A). Finally, the pathogenicity of these new variants was determined using the ACMG guidelines., Conclusion: The present study aimed to facilitate the prenatal diagnosis of NPC patients in the future. In this regard, we identified 10 novel mutations, and verified that the majority of them occurred in six NPC1 exons (5, 8, 9, 13, 19, and 21), that should be considered with a high priority for Iranian patients' cost-effective evaluation., (© 2022. The Author(s).)

Background: Risk factors of coronary heart disease have been discussed in the literature; however, conventional statistical models are not appropriate when the outcome of interest is number of vessels with obstructive coronary artery disease. In this paper, a novel statistical model is discussed to investigate the risk factors of number of vessels with obstructive coronary artery disease., Methods: This cross-sectional study was conducted on 633 elderly cardiovascular patients at Ghaem Hospital, Mashhad, Iran from September 2011 to May 2013. Clinical outcome is number of vessels with obstructive coronary artery disease (=0, 1, 2, 3), and predictor variables are baseline demographics and clinical features. A right-truncated zero-inflated double Poisson regression model is performed which can accommodate both underdispersion and excess zeros in the outcome. The goodness-of-fit of the proposed model is compared with conventional regression models., Results: Out of 633 cardiovascular patients, 327 were male (51.7%). Mean age was ~65 ± 7 years (for individuals with zero, one ,and two coronary artery stenosis) and ~66 ± 7 years (for individuals with three coronary artery stenosis). BMI (0.04 ± 0.01, p = 0.011) and female gender (0.19 ± 0.09, p = 0.032) were significant associated with the count part of the model, and only BMI (-0.47 ± 0.2, p = 0.011) was significantly predictive of logit part of the model. The goodness-of-fit measurements indicate that the proposed model outperforms the conventional regression models., Conclusion: The proposal regression model shows a better fit compared to the standard regression analysis in modeling number of vessels with obstructive coronary artery disease. Hence, using truncated zero-inflated double Poisson regression model-as an alternative model-is advised to study the risk factors of number of involved vessels of coronary artery stenosis., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Arezoo Orooji et al.)

Objective: Several discriminating techniques have been proposed to discriminate between β -thalassemia trait ( β TT) and iron deficiency anemia (IDA). These discrimination techniques are essential clinically, but they are challenging and typically difficult. This study is the first application of the Bayesian tree-based method for differential diagnosis of β TT from IDA., Method: This cross-sectional study included 907 patients with ages over 18 years old and a mean (±SD) age of 25 ± 16.1 with either β TT or IDA. Hematological parameters were measured using a Sysmex KX-21 automated hematology analyzer. Bayesian Logit Treed (BLTREED) and Classification and Regression Trees (CART) were implemented to discriminate β TT from IDA based on the hematological parameters., Results: This study proposes an automatic detection model of beta-thalassemia carriers based on a Bayesian tree-based method. The BLTREED model and CART showed that mean corpuscular volume (MCV) was the main predictor in diagnostic discrimination. According to the test dataset, CART indicated higher sensitivity and negative predictive value than BLTREED for differential diagnosis of β TT from IDA. However, the CART algorithm had a high false-positive rate. Overall, the BLTREED model showed better performance concerning the area under the curve (AUC)., Conclusions: The BLTREED model showed excellent diagnostic accuracy for differentiating β TT from IDA. In addition, understanding tree-based methods are easy and do not need statistical experience. Thus, it can help physicians in making the right clinical decision. So, the proposed model could support medical decisions in the differential diagnosis of β TT from IDA to avoid much more expensive, time-consuming laboratory tests, especially in countries with limited recourses or poor health services., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Mina Jahangiri et al.)

Hashimoto thyroiditis (HT) is a common autoimmune disorder with a strong genetic background. Several genetic factors have been suggested, yet numerous genetic contributors remain to be fully understood in HT pathogenesis. MicroRNAs (miRs) are gene expression regulators critically involved in biological processes, of which polymorphisms can alter their function, leading to pathologic conditions, including autoimmune diseases. We examined whether miR-499 rs3746444 polymorphism is associated with susceptibility to HT in an Iranian subpopulation. Furthermore, we investigated the potential interacting regulatory network of the miR-499. This case-control study included 150 HT patients and 152 healthy subjects. Genotyping of rs3746444 was performed by the PCR-RFLP method. Also, target genomic sites of the polymorphism were predicted using bioinformatics. Our results showed that miR-499 rs3746444 was positively associated with HT risk in heterozygous (OR = 3.32, 95%CI = 2.00-5.53, p < 0.001, CT vs. TT), homozygous (OR = 2.81, 95%CI = 1.30-6.10, p = 0.014, CC vs. TT), dominant (OR = 3.22, 95%CI = 1.97-5.25, p < 0.001, CT + CC vs. TT), overdominant (OR = 2.57, 95%CI = 1.62-4.09, p < 0.001, CC + TT vs. CT), and allelic (OR = 1.92, 95%CI = 1.37-2.69, p < 0.001, C vs. T) models. Mapping predicted target genes of miR-499 on tissue-specific-, co-expression-, and miR-TF networks indicated that main hub-driver nodes are implicated in regulating immune system functions, including immunorecognition and complement activity. We demonstrated that miR-499 rs3746444 is linked to HT susceptibility in our population. However, predicted regulatory networks revealed that this polymorphism is contributing to the regulation of immune system pathways.

Background: Early exacerbation of cutaneous leishmaniasis is mainly affected by both the salivary and Leishmania parasite components. Little is known of the vaccine combination made by immunogenic proteins of sandfly saliva (SP15) with Leishmania parasites (LeIF) as a single prophylactic vaccine, namely SaLeish. Also, there are no data available to determine the species-specific sequence of SP15 isolated from the Iranian Phlebotomus papatasi., Methods: Integrated bioinformatics and genetic engineering methods were employed to design, optimize and obtain a vector-parasite-based vaccine formulation in a whole-length fusion form of LeIF-SP15 against leishmaniasis. Holistic gene optimization was initially performed to obtain a high yield of pure 'whole-SaLeish' expression using bioinformatics analyses. Genomic and salivary gland RNAs of wild-caught P. papatasi were extracted and their complementary DNA was amplified and cloned into pJET vector., Results: The new chimeric protein of whole-SaLeish and randomly selected transcripts of native PpIRSP15 (GenBank accession nos. MT025054 and MN938854, MN938855 and MN938856) were successfully expressed, purified and validated by immunoblotting assay. Furthermore, despite the single amino acid polymorphisms of PpIRSP15 found at positions Y23 and E73 within the population of wild Iranian sandflies, antigenicity and conservancy of PpIRSP15 epitopes remained constant to activate T cells., Conclusions: The SaLeish vaccine strategy takes advantage of a plethora of vector-parasite immunogenic proteins with potential protective efficacy to stimulate both the innate and specific cellular immune responses against Leishmania parasites., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

COVID-19 has led to a pandemic, affecting almost all countries in a few months. In this work, we applied selected deep learning models including multilayer perceptron, random forest, and different versions of long short-term memory (LSTM), using three data sources to train the models, including COVID-19 occurrences, basic information like coded country names, and detailed information like population, and area of different countries. The main goal is to forecast the outbreak in nine countries (Iran, Germany, Italy, Japan, Korea, Switzerland, Spain, China, and the USA). The performances of the models are measured using four metrics, including mean average percentage error (MAPE), root mean square error (RMSE), normalized RMSE (NRMSE), and R 2 . The best performance was found for a modified version of LSTM, called M-LSTM (winner model), to forecast the future trajectory of the pandemic in the mentioned countries. For this purpose, we collected the data from January 22 till July 30, 2020, for training, and from 1 August 2020 to 31 August 2020, for the testing phase. Through experimental results, the winner model achieved reasonably accurate predictions (MAPE, RMSE, NRMSE, and R 2 are 0.509, 458.12, 0.001624, and 0.99997, respectively). Furthermore, we stopped the training of the model on some dates related to main country actions to investigate the effect of country actions on predictions by the model., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Rahele Kafieh et al.)

The application of high-throughput genotyping or sequencing data helps us to understand the genomic response to natural and artificial selection. In this study, we scanned the genomes of five indigenous buffalo populations belong to three recognized breeds, adapted to different geographical and agro-ecological zones in Iran, to unravel the extent of genomic diversity and to localize genomic regions and genes underwent past selection. A total of 46 river buffalo whole genomes, from West and East Azerbaijan, Gilan, Mazandaran, and Khuzestan provinces, were resequenced. Our sequencing data reached to a coverage above 99% of the river buffalo reference genome and an average read depth around 9.2× per sample. We identified 20.55 million SNPs, including 63,097 missense, 707 stop-gain, and 159 stop-loss mutations that might have functional consequences. Genomic diversity analyses showed modest structuring among Iranian buffalo populations following frequent gene flow or admixture in the recent past. Evidence of positive selection was investigated using both differentiation (Fst) and fixation (Pi) metrics. Analysis of fixation revealed three genomic regions in all three breeds with aberrant polymorphism contents on BBU2, 20, and 21. Fixation signal on BBU2 overlapped with the OCA2-HERC2 genes, suggestive of adaptation to UV exposure through pigmentation mechanism. Further validation using resequencing data from other five bovine species as well as the Axiom Buffalo Genotyping Array 90K data of river and swamp buffaloes indicated that these fixation signals persisted across river and swamp buffaloes and extended to taurine cattle, implying an ancient evolutionary event occurred before the speciation of buffalo and taurine cattle. These results contributed to our understanding of major genetic switches that took place during the evolution of modern buffaloes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Antioxidant enzymes such as glutathione S-transferases (GSTs) and cytochromes P450 (CYPs) are involved in the metabolism and detoxification of cytotoxic compounds, as well as the elimination of reactive oxygen species (ROS). Therefore, alterations in the structure of these enzymes could result in prolonged production of ROS with subsequent risk of development of disorders such as presbycusis. This study aimed to investigate the association between CYP1A1 (rs4646903, rs1048943) and GSTs (GSTM1-deletion, GSTT1-deletion, GSTP1-rs1695) with presbycusis risk in an Iranian population which was followed by an in silico approach. In a case-control study, 280 subjects including 140 cases with presbycusis and 140 healthy controls were enrolled. Genotypes of single-nucleotide polymorphisms (SNPs) were detected by PCR-RFLP method and the genotype of the above mentioned deletions was determined by touchdown PCR. Some bioinformatics tools were employed to evaluate the impact of SNPs on the gene function. SNP analysis revealed that there are significant associations between rs1048943 (AG vs. AA: OR = 2.46, 95%CI = 1.30-4.65, p = 0.006; GG + AG vs. AA: OR = 2.53, 95%CI = 1.36-4.69, p = 0.003; G vs. A: OR = 2.36, 95%CI = 1.33-4.17, p = 0.003) and rs4646903 (C vs. T: OR = 1.45, 95%CI = 1.02-2.06, p = 0.040) variations and increased risk of presbycusis. However, there was no significant association between rs1695 and presbycusis risk. Also, significant associations were observed between GSTM1 (OR = 4.28, 95%CI = 1.18-15.52, p = 0.027) and GSTT1 (OR = 1.64, 95%CI = 1.02-2.65, p = 0.041) deletions and elevated risk of presbycusis. Moreover, the combination analysis revealed a significant association between GSTM1+/GSTT1- genotype and presbycusis susceptibility (OR = 1.63, 95%CI = 1.00-2.67, p = 0.049). In silico analysis revealed that the rs1048943 SNP could influence significantly on the RNA structure of CYP1A1 (distance: 0.1454; p value: 0.1799). Based on our findings, the rs4646903, rs1048943 SNPs as well as GSTM1 and GSTT1 deletions could be considered as genetic risk factors for the development and progression of presbycusis.

Gastric cancer (GC), one of the most common cancers around the world, is a multifactorial disease and there are many risk factors for this disease. Assessing the risk of GC is essential for choosing an appropriate healthcare strategy. There have been very few studies conducted on the development of risk assessment systems for GC. This study is aimed at providing a medical decision support system based on soft computing using fuzzy cognitive maps (FCMs) which will help healthcare professionals to decide on an appropriate individual healthcare strategy based on the risk level of the disease. FCMs are considered as one of the strongest artificial intelligence techniques for complex system modeling. In this system, an FCM based on Nonlinear Hebbian Learning (NHL) algorithm is used. The data used in this study are collected from the medical records of 560 patients referring to Imam Reza Hospital in Tabriz City. 27 effective features in gastric cancer were selected using the opinions of three experts. The prediction accuracy of the proposed method is 95.83%. The results show that the proposed method is more accurate than other decision-making algorithms, such as decision trees, Naïve Bayes, and ANN. From the perspective of healthcare professionals, the proposed medical decision support system is simple, comprehensive, and more effective than previous models for assessing the risk of GC and can help them to predict the risk factors for GC in the clinical setting., Competing Interests: The authors claim no conflicts of interest., (Copyright © 2020 Seyed Abbas Mahmoodi et al.)

Cryptosporidium species and microsporidia, which can cause zoonotic intestinal infections in humans, have become an emerging public health concern. It seems that the identification and genotyping of these parasites are necessary for the prevention, control, and establishment of appropriate treatment. This study aimed to evaluate the distribution and zoonotic transmission routes of Cryptosporidium species and microsporidia to humans referred to medical laboratories of Kurdistan Province, Iran. A total of 1,383 stool samples were collected and investigated. Cryptosporidium spp. and microsporidia were detected using microscopic methods (i.e., formol-ether concentration, Ziehl-Neelsen staining, and modified trichrome staining methods). DNA was extracted from positive samples, and specific fragments of the Cryptosporidium GP60 gene and microsporidia SSU rRNA gene were amplified. Furthermore, positive samples were sequenced for genotype identification and bioinformatics analysis. Based on the microscopic analysis of 1,383 stool samples, 5 (0.36%) and 6 (0.43%) samples were considered positive for Cryptosporidium oocysts and microsporidia spores, respectively. Molecular analysis of positive samples identified the isolates as Cryptosporidium parvum and Enterocytozoon bieneusi. According to comparative phylogenetics, cryptosporidiosis and microsporidiosis may occur via zoonotic transmission in this region. Therefore, proper control and health education are strongly recommended to prevent zoonotic diseases., (© American Society of Parasitologists 2020.)

Kashk is a typical dairy product of Iran, made from sour milk. It is traditionally produced from buttermilk in a dry, round-shaped form. Today, it is also produced at industrial level in a liquid form starting from fermented milk. We aimed to characterise the kashk proteome and peptidome comparing a traditional product with the industrial using a combination of proteomic approaches including advanced chromatographic and electrophoretic separation technique coupled to tandem mass spectrometry. We identified also phosphorylated casein-derived peptides (CPP) and investigated kashk protein digestibility using a static model of food protein digestion. The molecular characterization, coupled with bioinformatic in silico analysis, allowed the identification of potential bioactive peptides., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Wolfram syndrome (WS) is a rare genetic disorder described by a pattern of clinical manifestations such as diabetes mellitus, diabetes insipidus, optic nerve atrophy, sensorineural hearing loss, urinary tract abnormalities, and psychiatric disorders. WFS1 and WFS2 loci are the main genetic loci associated with this disorder., Methods: In the current study, we investigated associations between these loci and WS via STR markers and homozygosity mapping in 13 Iranian families with WS. All families were linked to WFS1 locus., Results: Mutation analysis revealed four novel mutations (Q215X, E89X, S168Del, and E391Sfs*51) in the assessed families. Bioinformatics tools confirmed the pathogenicity of the novel mutations. Other identified mutations were previously reported in other populations for their pathogenicity., Conclusions: The current study adds to the mutation repository of WS and shows a panel of mutations in Iranian population. Such panel would facilitate genetic counseling and prenatal diagnosis in families with WS cases.

Background: Breast cancer (BC) is the highest cause of mortality among female cancer patients. In some cases, BC is due to Poly [ADP-ribose] polymerase 1 (PARP1) gene dysregulation, which has been involved in various important cellular processes. Among Iranian women, the association between PARP1 polymorphisms and BC was never studied before so in this case-control study, the genetic association of three SNPs (rs1136410, rs907187 and rs4653734) was analyzed with susceptibility to BC., Methods: The study subjects were 386 Iranian females divided into 186 patients and 200 healthy controls. The genotypes of PARP1 variants were detected using ARMS and a combined ARMS-RFLP PCR method., Results: The results showed that Carriers of CG and GG genotypes of the variant rs4653734 were at higher risk of BC compared with wild-type carriers (CC) and this variant was statistically significant under a recessive model of inheritance. Moreover, rs907187 was related to increased BC risk in the CC and GG genotypes under dominant and recessive models of inheritance. The G allele frequency of rs4653734 and rs907187 was higher in breast cancer patients than in normal subjects. No association was detected between rs1136410 and susceptibility to BC among studied groups. Furthermore, A-G-C haplotype was linked to an increased BC risk, whereas A-C-C and A-C-G haplotypes were related to a decreased risk of BC. In Silico predictions suggested that rs907187 affects E2F and E2F-4 transcription factors binding site., Conclusions: The current study suggests that rs907187 and rs4653734 have remarkable associations with BC risk among Iranian women., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Systemic lupus erythematous (SLE) is a multisystem and autoimmune disorder leading to damage of multi-organ systems. The current study aimed to assess the possible association between ERα gene polymorphisms and SLE in a southeast Iranian population., Methods: The ERα PvuII and XbaI polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method in 170 SLE patients and 186 healthy subjects., Results: There was no association between ERα PvuII and XbaI polymorphisms and SLE susceptibility; however, the combination of the TC/AA and CC/GG genotypes of ESR α PvuII and XbaI polymorphisms were more frequent in SLE patients. The results indicated that TT haplotype of the ERα gene polymorphisms could increase the SLE risk almost 2.4-fold (odds ratio 2.4, 95% CI 1.3-4.3, P = 0.005). The in silico analysis revealed that the ERα PvuII and XbaI single nucleotide polymorphisms occurred in acceptor splicing sites, and these mutations can lead to the increase of Human Splicing Finder score of the mutant alleles., Conclusions: The ESR α PvuII and XbaI polymorphisms have no association with SLE; however, the combination of the TC/AA and CC/GG genotypes were associated with SLE susceptibility., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: The genetic basis of longevity is an important field of study because the majority of supercentenarian cases experience healthy aging and may only show age-related diseases in their last few years of life. It is clear that genetic factors play an important role in survival beyond 90 years of age, but the exact relationship of genetic variants to this phenomenon remains unknown., Objective: The aim of this project was to investigate different hypotheses that describe the relationship between genetic variants and human longevity in a living Iranian man by Whole Exome Sequencing., Methods: Initially, we conducted high quality DNA extraction on a peripheral blood sample. Then, whole exome sequencing was performed on the DNA and different bioinformatic software packages and databases were used to analyze the data. Tertiary analysis was performed on four genetic hypotheses for longevity., Results: Analysis showed that among 27 metabolic variants which are related to longevity, 18 variants encompassed the exceptional longevity allele. In comparison with the NHGRI GWAS catalog, the case had 58 trait-associated variants of which 11 were homozygous for the risk allele. We also discovered 25 novel variants within candidate genes for aging and longevity and we detected seven longevity-associated variants in the sample., Conclusion: This study was performed on just one sample and so the results cannot be interpreted as a generalized principle for other elderly societies, but this is the first step towards investigation of the genetic basis of longevity in Iran and provides an insight for further studies in the field of longevity.

Evidence of primate-specific genes and gene regulatory mechanisms linked to bipolar disorder (BD) lend support to evolutionary/adaptive processes in the pathogenesis of this disorder. Following a genome-scale analysis of the entire protein coding genes annotated in the GeneCards database, we have recently reported that cytohesin-4 (CYTH4) contains the longest tetra-nucleotide short tandem repeat (STR) identified in a human protein-coding gene core promoter, which may be of adaptive advantage to this species. In the current study, we analyzed the evolutionary trend of this STR across evolution. We also analyzed the functional implication and distribution of this STR in a group of patients with type 1 BD (n=233) and controls (n=262). We found that this STR is exceptionally expanded in primates (Fisher exact p<0.00003). Association was observed between type I BD and the 6-repeat allele of this STR, (GTTT)₆ (Yates corrected Χ(2)=12.68, p<0.0001, OR: 1.68). This allele is the shortest length of the GTTT-repeat identified in the human subjects studied. Consistent with that finding, excess homozygosity was observed for the shorter alleles, (GTTT)₆ and (GTTT)₇, vs. the longer alleles, (GTTT)₈ and (GTTT)₉ in the BD group (Yates corrected Χ(2)=5.18, p<0.01, 1 df, OR: 1.96). Using Dual Glo luciferase system in HEK-293 cells, a trend for gene expression repression was observed from the 6- to the 9-repeat allele (p<0.003), and the GTTT-repeat significantly down-regulated gene expression, per se (p<0.0006). This is the first evidence of a link between a primate-specific STR and a major psychiatric disorder in human. It may be speculated that the CYTH4 GTTT-repeat in primates may have conferred selective advantage to this order, reflected in neural function and neurophenotypes. The role of the CYTH4 gene in the pathogenesis of type I BD remains to be clarified in the future studies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The role of apolipoprotein E gene polymorphisms in the pathogenesis of recurrent pregnancy loss remains controversial. Therefore, our objective was to investigate the association between recurrent pregnancy loss and apolipoprotein E gene polymorphisms among northwest Iranian women, and also to predict the impact of these nonsynonymous single nucleotide polymorphisms on structure and function of apolipoprotein E protein. The subjects of our current study consisted of 100 women that have had two or more consecutive idiopathic first trimester miscarriages, and one hundred healthy women from the same geographical areas were used as a control group. After DNA extraction, we used a polymerase chain reaction-restriction fragment length polymorphism to genotype of the apolipoprotein E gene. In addition, we predicted the possible effects of amino acid substitutions at codons 112 and/or 158 on the structure and function of apolipoprotein E protein using Polymorphism Phenotyping online software v2. Our results showed that the rate of apolipoprotein E ε4 carriers and the frequency of the ε4 allele in the case group were statistically and significantly higher than those in the control group (P<0.05). Therefore, our data support the association of the Apo ε4 allele with RPL; however, in silico analysis predicted that the amino acid substitution at residue 112 (Apo ε4 allele) is a benign mutation. Accordingly, further studies are required to elucidate the mechanism(s) underlying the link between RPL pathogenesis and the Apo ε4 allele., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: The NOD2 gene is known to have a strong association with Crohn's disease, but different trends were reported in occurrence of NOD2 variants in distinct ethnicities. The aim of this study was to assess all exonic sequences of the NOD2 gene in Iranian Crohn's disease patients and healthy controls to identify any existing variation and evaluate their association with Crohn's disease., Methods: A total of 90 non-related Crohn's disease patients and 120 sex- and age-matched healthy controls of Iranian origin were enrolled in this study. The participants were referred to a tertiary center in a 2-year period (2006-2008). The exonic regions of the NOD2 gene were amplified by polymerase chain reaction and evaluated by direct sequencing., Results: A total of 21 sequence variations were identified among all exonic regions of the NOD2 gene, of which eight had an allele frequency of more than 5%. Eight new mutations (one in exon 2 and seven in exon 4) were observed. The three main variants (R702W, G908R, and 1007fs) showed allele frequencies of 13.3%, 2.2%, and 1.7%, respectively. Three new variations (P371T, A794P, and Q908H) and R702W mutation were significantly more frequent in Crohn's disease patients compared to controls., Conclusions: Eight novel mutations were identified in the NOD2 exons, but the pathophysiological importance of these variants remains unclear. Iranian patients with their different genetic reservoirs may demonstrate some novel characteristics for disease susceptibility.

Background/aims: Present-day Iran has long represented a natural hub for the expansion of human genes and cultures. That being so, the overlapping of prehistoric and more recent demographic events interacting at different time scales with geographical and cultural barriers has yielded a tangled patchwork of anthropological types within this narrow area. This study aims to comprehensively evaluate this ethnic mosaic by depicting a fine-grained picture of the Iranian mitochondrial landscape., Methods: mtDNA variability at both HVS-I and coding regions was surveyed in 718 unrelated individuals belonging to 14 Iranian ethnic groups characterized by different languages, religions and patterns of subsistence., Results: A discordant pattern of high ethno-linguistic and low mtDNA heterogeneity was observed for the whole examined Iranian sample. Geographical factors and cultural/linguistic differences actually represented barriers to matrilineal gene flow only for the Baloch, Lur from Yasouj, Zoroastrian and Jewish groups, for which unusual reduced levels of mtDNA variability and high inter-population distances were found., Conclusion: Deep rooting genealogies and endogamy in a few of the examined ethnic groups might have preserved ancestral lineages that can be representative of Proto-Indo-Iranian or prehistoric mitochondrial profiles which survived relatively recent external contributions to the Iranian gene pool., (Copyright © 2011 S. Karger AG, Basel.)

To determine the genetic relationship of Iranian viruses, the haemagglutinin (HA) genes from ten isolates of H9N2 viruses isolated from commercial chickens in Iran during 1998-2002 were amplified and sequenced. Sequence analysis and phylogenetic studies were conducted by comparing each isolate with those of the available H9N2 strains at GenBank. All these ten isolates had the same sequence -R-S-S-R/G-L- of proteolytic cleavage site of the HA. Nucleotide sequence comparisons of HA gene from Iranian isolates showed 95.2-99.1% identity within the group. Five isolates had leucine (L) at position 226 instead of glutamine (Q). Phylogenetic analysis showed that all our isolates belonged to the G1-like sublineage. Also these isolates showed some degree of homology with other H9N2 isolates e.g., 94.3-96.9% with qu/HK/G1/97, 96.1-98.6% with pa/Chiba/1/97, 95.6-98.2% with pa/Narita/92A/98, and 94.0-96.3% with HK/1073/99. On the basis of phylogenetic and molecular characterization evidence, we concluded that the H9N2 subtype influenza viruses circulating in chicken flocks in Iran since 1998-2002 had a common origin. The results of this study indicated that all Iranian viruses have the potential to emerge as highly pathogenic influenza virus, and considering the homology of these isolates with human H9N2 strains, it seems that the potential of these avian influenza isolates to infect human should not be overlooked.

Bioinformatics and traditional medicine can be used in discovery and design of novel candidate drugs to efficient cancer chemotherapy. In this study, similarity search tools employed to screen and introduce novel herbs with antitumor property. Several novel herbs have been selected by using logical computational algorithms and assayed on six cancerous cell lines. Complementary assays involved hemolytic and antifungal MIC tests have been performed to determine selectivity and their biocompatibility with RBC of herbal extracts. Final findings may point at selective activity of herbal extracts Rheum ribes, Ficus bengalensis, Morus alba, Musa sapientum, Arnebia decumbens, Citrus limon, Fraxinus excelsior, Rumex acetosella, Arnebia echioides in inducing cytotoxicity on cancerous cell lines. In the present research, in vitro results confirmed predicted findings from our in silico work. Complementary assays including antifungal MIC and hemolytic tests were carried out also to determine selectivity of herbal extracts. Findings resulted from hemolytic test showed that candidate herbal extracts did not induce hemolysis similar to negative control, also antifungal test results indicated that six herbal extracts had antifungal activity in concentration of 250 microg/ml.

The combustion of crude oil produces a wide range of pollutants, including gases, volatile organic compounds, polycyclic aromatic hydrocarbons, acid compounds (e.g., sulfuric acid), and soot. Several of these pollutants have been linked with the deterioration and blackening of monuments. The paper reports the results of an investigation on the causes of the soiling of cultural remains at important archaeological sites in the provinces of Khuzestan and Fars, in southern Iran, assumed to be an effect of the Persian Gulf oil well fires of 1991. Different analytical techniques were applied to characterize the mineralogical composition of the damage layers, investigate the deposition of atmospheric particles, measure the anion concentrations, and identify and quantify the carbon components. The results showed that the black deposits on the surfaces of the Iranian monuments considered are mainly microbiotic crusts produced by cyanobacterial growth. No evidence was found of the deposition of particulate matter (smoke) produced by the Kuwait oil fires during the Gulf War.