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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: After breast cancer, cervix neoplasm is the most common disease among young women. Nowadays, natural substances are used in the treatment of diseases, because of the known side effects of the chemical drugs. Dunaliella is a green alga that lives in the saltwater lakes of Iran and is abundant in antioxidant substances. This paper aimed to study the effect of Dunaliella extract on the expression of the anti-apoptotic BCL-2 gene in Hela cell line. Expression of this gene is increased during cancer. It is expected that gene expression will be reduced if the alga extract is effective. Methods: Hela was prepared from the Center for Genetic and Biological Reserves of Iran and cultured. After culture, cells were divided into two treatment and control groups. Different concentrations of algae extract were applied to the treatment group for 48 hours. Then its toxicity was measured using MTT assay and IC50 was determined. RNA was extracted from cells of two groups, to determine the relative amount of gene expression at a concentration of IC50. Then Real-time PCR was used. Results: The result of Real-time PCR showed that the relative expression of BCL-2, in treatment group cells that were affected by algae extract, was four times lower than the control group. Since the P-value is less than 0.05 (Pvalue = 0), this decrease is significant. Conclusion: After 48 hours, at a concentration of IC50 of algae extract, the relative expression of BCL-2 was four times lower than control group. [ABSTRACT FROM AUTHOR]

In this paper, an attempt was made to find out two empirical relationships incorporating linear multivariate regression (LMR) and gene expression programming (GEP) for predicting the blast-induced ground vibration (BIGV) at the Sarcheshmeh copper mine in south of Iran. For this purpose, five types of effective parameters in the blasting operation including the distance from the blasting block, the burden, the spacing, the specific charge, and the charge per delay were considered as the input data while the output parameter was the BIGV. The correlation coefficient and root mean squared error for the LMR were 0.70 and 3.18 respectively, while the values for the GEP were 0.91 and 2.67 respectively. Also, for evaluating the validation of these two methods, a feed-forward artificial neural network (ANN) with a 5-20-1 structure has been used for predicting the BIGV. Comparisons of these parameters revealed that both methods successfully suggested two empirical relationships for predicting the BIGV in the case study. However, the GEP was found to be more reliable and more reasonable. [ABSTRACT FROM AUTHOR]

Background & Objective: Iran is located in the esophageal cancer geographical belt. As multiple genetic alterations are responsible for the molecular pathogenesis of esophageal squamous cell cancer (ESCC), the role and frequency of HER2 expression, MMR deficiency, and PI3KCA mutation are not well defined. Methods: We carried out HER2/neu expression, dMMR/MSI high, and PI3KCA mutation analysis in specimens of patients with ESCC. We accessed archival tissue blocks related to specimens of 68 ESCC cases at the time of surgery following neoadjuvant chemoradiation. These patients underwent surgery during 2013-2018 at the Cancer Institute of Iran affiliated with the Tehran University of Medical Sciences in Tehran. Results: None of the patients showed HER2 expression, dMMR/MSI high, or PI3K mutations. Conclusion: dMMR/MSI-H and PI3KCA mutation and HER2 expression may not be reliable andfrequent targets for systemic therapy in patients with esophageal SCC. [ABSTRACT FROM AUTHOR]

Introduction: Levels of the human epidermal growth factor receptor 2 (HER2) gene are low in normal breast tissue, but half of the patients with breast cancer exhibit higher levels of this receptor. The differential expression of the HER2 gene in normal and malignant cells makes it an excellent biomarker for therapeutic purposes. In this study, we evaluated the degree of HER2 overexpression in patients and its relationship with age and the occurrence of metastases. Materials & Methods: In this retrospective, registry-based, two-center cohort study, information on 1500 breast cancer patients recruited from Shahid Mostafa Khomeini Hospital in Ilam Province was collected from 2020 to 2023. Results: The likelihood of metastasis in cancer patients with HER2 gene expression was three times higher (adjusted OR: 2.82; 95% CI: 1.79-3.29; P=0.001). Additionally, the involvement of lymph nodes (adjusted OR: 2.01; 95% CI: 0.87-3.79; P=0.03) was significantly associated with increased metastasis. Conclusion: This study demonstrates that HER2 gene expression and the number of involved lymph nodes are significant prognostic factors that increase the risk of metastasis. Therefore, implementing comprehensive breast cancer screenings can play an important role in the treatment and prevention of metastasis in breast cancer patients. [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 and Aim: Acinetobacter baumannii (A. baumannii) is an important bacterium that can cause multidrug-resistant nosocomial infections in the patients who are admitted to different hospital wards. Various factors play role in the resistance of this bacterium to antibiotics, one of the most important of which is the presence of drug efflux pumps. This study aimed to investigate the presence of the AdeABC efflux system and its role in drug resistance by inactivating them. Materials and Methods: Clinical samples were collected from three hospitals in Tehran, Iran for one year. The initial diagnosis and identification of A. baumannii was done by culture and biochemical methods. Finally, the identified prototypes were confirmed by molecular method. To investigate the role of antibiotic efflux pump in the drug resistance, minimum inhibitory concentration (MIC) for ciprofloxacin in the presence and absence of an efflux pump inhibitor, carbonyl cyanide 3- chlorophenylhydrazone (CCCP), was determined by microdilution method. Additionally, the presence of adeB, adeR, and adeS genes related to the AdeABC depletion system was investigated by PCR. Results: The results showed that more than 98% of the isolated bacteria had adeB, adeR, and adeS genes in the AdeABC depletion system. Approximately, 47.18% of these bacteria displayed a fourfold reduction in ciprofloxacin MIC levels in the presence of CCCP. Conclusion: Administration of a suitable antibiotic along with a safe efflux pump inhibitor for the treatment of A. baumannii infections can help to reduce the material and spiritual damages caused by the resistant bacteria. [ABSTRACT FROM AUTHOR]

Introduction: Our aim was to investigate the expression of miRNAs, C-reactive protein as a blood inflammation marker, and alanine aminotransferase as a tissue inflammation marker, in recovered and not-recovered COVID-19 patients. Methods: This cross-sectional project was conducted at three medical centers in Iran from December to March 2021. In total, 20 confirmed cases of COVID-19 with grade III severity and 20 healthy subjects were enrolled in the study. Subsequently, the neuroinflammatory expression of miRNAs (miR-199, miR-203, and miR-181), C-reactive protein, and alanine aminotransferase was investigated during hospitalization from week 0 to week 2. Results: Among COVID-19 subjects who did not recover, the expression levels of miR-199, miR-203, and miR-181 were decreased, while the levels of C-reactive protein and alanine aminotransferase increased during hospitalization. Conversely, in recovered COVID-19 subjects, the relative expression of miR-199, miR-203, and miR-181 increased and the levels of C-reactive protein and alanine aminotransferase decreased during hospitalization. Conclusion: The expression pattern of neuroinflammatory miRNAs depends on whether the COVID-19 patient is recovering or deteriorating. Their expression is downregulated in COVID-19 patients who do not recover and upregulated in those who do recover. [ABSTRACT FROM AUTHOR]

Background and Objective. Multiple sclerosis (MS) is a progressive disease of the nervous system that leads to demyelination of the nerves and is more common in young adults, especially women. Environmental factors that trigger MS pathogeneses are genetic susceptibility and viral infections. The viral infections are considered to be of particular relevance. Along with viruses belonging to the Herpesviridae family such as varicella zoster virus (VZV), human herpes virus-6 (HHV-6), and particularly Epstein–Barr virus (EBV), the expression of the env gene of human endogenous retrovirus (HERV-W) like MSRV is expected to be one of the risk factors for bringing up MS and disease progression. The present study aimed to investigate the correlation between EBV infection and HERV-W env in a case group (MS patients) and a control group (healthy individuals). Materials and Methods. 130 subjects were enrolled in a case-control study at two tertiary university hospitals from Tabriz (Imam and Razi), Iran. Of these, 65 subjects were MS patients serving as the case group, and 65 subjects were healthy individuals serving as the control group. After DNA extraction from all samples, the EBER region of EBV genome was used as the primer for the detection of EBV. RNA was extracted from PBMCs, and cDNA synthesis was performed by using Sina Gene kit. Subsequently, each sample was analysed by RT-PCR with two sets of primers to detect specifically multiple sclerosis retroviruses (MSRV) env, and RT-PCR was repeated for each HERV-W env. Positive sample was used in order to confirm the result. Results. In the case group, 19 (29.2%) patients were male and 46 (70.8%) patients were female. Nevertheless, in the control group, 21 (32.3%) subjects were male and 44 (67.7%) subjects were female. No significant difference was found between groups in gender (p = 0.70). The mean range in control and case groups was 33/38 ± 9/85 and 33.18 ± 8.65, respectively. No significant difference was found between groups in age (p = 0.902). 4 (6.2%) patients in case groups were found to be positive for EBV DNA (p = 0.119). Expression of the env gene of HERVs was observed in 10 (15.38%) and two (3.07%) specimens in the case and control groups (p = 0.030), separately. A comparison of the prevalence of the HERV ENV genome between the two study groups showed a significant difference (p = 0.005). Conclusion. The results of this study failed to show any difference between MS patients and healthy controls in the rate of EBV infection. It can be concluded that the expression of HERV-W/env genes may be involved in the development of MS in these patients. [ABSTRACT FROM AUTHOR]

The incidence of urothelial carcinoma is increasing worldwide (including in Iran). Bladder cancer can be classified in various manners according to the standardized histomorphology set by the World Health Organization (WHO). Various genetic modifications occurring at the DNA level and the resulting variations in RNA expression give rise to different subcategories that have important implications for diagnosis, prognosis, and treatment. The molecular basis of these morphologic variances is now better understood because of recent developments in molecular biology. With updates on the genetic and clinical characteristics, we highlight the histologic traits of the divergent differentiation and subtypes recognized by the most recent WHO classification (5th edition). Molecular subtypes of lower and upper tract cancer can be used to characterize their clinical behaviors and determine therapeutic responses to neoadjuvant chemotherapy. In this overview article, we also present a preliminary analysis of our ongoing data collection on molecular features of urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Recurrent Pregnancy Loss and Recurrent Implantation Failure are major limiting factors in the establishment of pregnancy. Recurrent Pregnancy loss is defined as the failure of two or more clinically recognized pregnancies. A considerable proportion of infertile couples undergoing IVF treatment experiencing recurrent implantation failure (RIF) fail repeatedly to implant following at least three IVF cycles. MicroRNAs (miRNAs) can serve as reliable non-invasive diagnostic and prognostic biomarkers for pregnancy-related complications. Therefore, this study aimed to quantify miR-23a-3p expression level in the plasma of patients with idiopathic recurrent pregnancy loss (iRPL) and recurrent implantation failure compared to healthy subjects to evaluate its potential diagnostic value in iRPL and RIF patients. Material & Methods: This study is a cross-sectional descriptive study. A total of 120 plasma samples were obtained from 40 women with a history of at least two consecutive iRPL, 40 women with RIF, and 40 healthy women without a history of miscarriage to evaluate the expression level of the circulating miR-23a-3p by quantitative real-time polymerase chain reaction (qPCR) technique. All participants were recruited from Assisted Reproductive Technology (ART) and Stem Cell Research Center, Tabriz, Iran, September 2019-March 2020. Statistical analysis was performed using SPSS (version 22). Diagnostic efficiency of the circulating miRNAs was determined by Receiver Operatig Characteristic curve analysis using Graphpad Prism version 9.1.1. Findings: Our results showed that the miR-23a-3p expression level in plasma of iRPL patients was lower than those in healthy controls but without a statistically significant difference (P=0.113). We also found that miR-23a-3p plasma level in patients with RIF tended to be lower compared to healthy participants; however, it was not statistically significant (P=0.974). Discussion & Conclusion: The current study provides evidence indicating that downregulation of miR-23a-3p may be associated with iRPL and RIF. Therefore, further research is needed, such as using different geographic regions, large sample sizes, and other techniques (microarray). [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common cancers all over the world, and dysbiosis in the gut microbiota may play a role in colorectal carcinogenesis. Bacteroides fragilis can lead to tumorigenesis by changing signaling pathways, including the WNT/β-catenin pathway. Therefore, in the present study, we investigated the correlation between the enterotoxigenic B. fragilis amount and the expression of signaling pathway genes involved in CRC. Materials and methods: B. fragilis was determined in 30 tumors and adjacent healthy tissues by the qPCR method. Next, the relationship between enterotoxigenic B. fragilis and the expression of signaling pathway genes, including CCND1, TP53, BCL2, BAX, WNT, TCF, AXIN, APC, and CTNNB1 was investigated. Additionally, possible correlations between clinicopathological features of the tumor samples and the abundance of B. fragilis were analyzed. Results: The results showed that B. fragilis was detected in 100% of tumor samples and 86% of healthy tissues. Additionally, enterotoxigenic B. fragilis colonized 47% of all samples, and bft-1 toxin was the most frequently found isotype among the samples. The analysis showed that the high level of B. fragilis has a significant relationship with the high expression of AXIN, CTNNB1, and BCL2 genes. On the other hand, our results did not show any possible correlation between this bacterium and the clinicopathological features of the tumor sample. Conclusion: B. fragilis had a higher abundance in the tumor samples than in healthy tissues, and this bacterium may lead to CRC by making changes in cellular signaling pathways and genes. Therefore, to better understand the physiological effects of B. fragilis on the inflammatory response and CRC, future research should focus on dissecting the molecular mechanisms by which this bacterium regulates cellular signaling pathways. [ABSTRACT FROM AUTHOR]

Prangos ferulacea plant is very popular in Iran due to its unique properties in treating diseases and its special flavor. To check the characteristics of this plant, first, its extract was extracted using the maceration method. Its chemical composition was investigated using high-performance liquid chromatography (HPLC) that p-coumaric was identified as its main compound, and Fourier-transform infrared spectroscopy (FTIR) showed the presence of functional groups related to phenolic, flavonoid, tannins, and carboxylic acids such as caffeic acid and coumaric acid composition. Total phenol content (TPC), total flavonoid content (TFC), and beta-carotene were equal to 202.04 ± 5.46mg gallic acid equivalent (GAE)/g dry weight, 1,909.46 ± 13 µg quercetin (QE)/g of dry weight, and 2.91 mg/100 g. The antioxidant property of the extract was evaluated using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2' -azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS) free radical scavenging and ferric reducing antioxidant power assay (FRAP). According to the IC50 obtained for DDPH (274 ± 7.2µg/mL) and ABTS (120.45 ± 9.6µg/mL) and FRAP values [1.92 ± 0.05 µg ascorbic acid equivalent (AAE)/g of extract], this extract had high antioxidant properties. Cytotoxicity was evaluated against the survival of HT 29 cells that IC50 was 82.15 ± 0.02µg/mL. The antimicrobial property of the extract was calculated using disk diffusion agar (DDA), well diffusion agar (WDA), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). Listeria monocytogenes has the highest sensitivity to this extract and inhibition zone based on DDA and WDA method and with an MIC and MBC equal to 16 and 128 mg/mL has the least resistance. The morphology change of L. monocytogenes strain was proved through scanning electron microscope (SEM) and confocal laser scanning microscopy (CLSM). The extract caused a significant reduction in the transcription of genes involved in the film formation ability of L. monocytogenes. The obtained results fully prove the very practical and pragmatic characteristics of P. ferulacea. [ABSTRACT FROM AUTHOR]

Background & Objective: Dicer a member of the RNase III endonucleases has a crucial function in the development of miRNAs that affects gene expression in different kinds of cancers. The present research focused on examining the expression level of Dicer and its relation with clinicopathological features in children with Acute Lymphoblastic Leukemia (ALL) among the population in the northwest region of Iran. Materials & Methods: In a case-control study, 140 samples (70 patients and 70 healthy controls of similar age and sex rates) from 2019 to 2021 were included in the Dicer mRNA expression levels assessment. Quantitative Real-Time PCR analyses were utilized to determine expression levels of Dicer in samples and the demographic and clinicopathologic features and the relationship of these variables were evaluated. Results: Average Dicer expression □ct values were 2.8267 and up-regulated compared to healthy samples (P=0.000). No significant relationships have been found among gene expression, demographical and clinicopathological parameters. Also, demographical and clinicopathological factors were not correlated with the mRNA expression level of the gene except age (r=0.148, P=0.001). Conclusion: The current research shows that the expression of Dicer is significantly upregulated in ALL patients, which suggests that it could have a vital function in ALL pathology. It will also theoretically be seen in the potential as a new intervention objective for ALL cases. [ABSTRACT FROM AUTHOR]

Verticillium wilt is a major threat to many crops, among them alfalfa (Medicago sativa). The model plant Medicago truncatula, a close relative of alfalfa was used to study the genetic control of resistance towards a new Verticillium alfalfae isolate. The accidental introduction of pathogen strains through global trade is a threat to crop production and such new strains might also be better adapted to global warming. Isolates of V. alfalfae were obtained from alfalfa fields in Iran and characterized. The Iranian isolate AF1 was used in a genome-wide association study (GWAS) involving 242 accessions from the Mediterranean region. Root inoculations were performed with conidia at 25°C and symptoms were scored regularly. Maximum Symptom Score and Area under Disease Progess Curve were computed as phenotypic traits to be used in GWAS and for comparison to a previous study with French isolate V31.2 at 20°C. This comparison showed high correlation with a shift to higher susceptibility, and similar geographical distribution of resistant and susceptible accessions to AF1 at 25°C, with resistant accessions mainly in the western part. GWAS revealed 30 significant SNPs linked to resistance towards isolate AF1. None of them were common to the previous study with isolate V31.2 at 20°C. To confirm these loci, the expression of nine underlying genes was studied. All genes were induced in roots following inoculation, in susceptible and resistant plants. However, in resistant plants induction was higher and lasted longer. Taken together, the use of a new pathogen strain and a shift in temperature revealed a completely different genetic control compared to a previous study that demonstrated the existence of two major QTLs. These results can be useful for Medicago breeding programs to obtain varieties better adapted to future conditions. [ABSTRACT FROM AUTHOR]

The current study assesses the collapse sensitivity classes of loess soils using gene expression programming (GEP) and ordinal logistic regression (OLR). The crucial variable to forecast the possible development of loess caves in the Golestan Province (northeast of Iran) is the collapse sensitivity factor (Is). A database of 62 records, including the mechanical and physical characteristics of soils, was used. Oedometer tests were used to estimate the parameters of the collapse coefficient, the time needed for 90% settlement (T90%), and collapse sensitivity. The database includes 10 inputs (grain size, porosity, initial water content, precipitation, climatic data, liquid limit, calcium carbonate content, vegetation, and degree of soil saturation) and one output (collapse sensitivity classes). This is a complicated approach due to the complexity of setting up and performing such kinds of tests in the laboratory. The likelihood of soil classification ranks as severe, moderately severe, moderate, and small sensitivity was inspected using OLR and GEP. This study demonstrated that the OLR approach could effectively differentiate among more than 70% of distinct groups. Furthermore, experimental data reported from Semnan, Sarakhs, and Mashhad also attests to the accuracy of the OLR model. The sensitivity analysis indicated that silt fraction imparts the maximum effect on the collapse sensitivity classes. The trial-and-error method was used to determine the configurations of the GEP model prior to developing an ideal model. The performance of the GEP model to estimate the collapse sensitivity categories in a trustworthy, strong, and useful way is well documented by comparison between the results of the GEP and the experimental findings, which are affordable. [ABSTRACT FROM AUTHOR]

Objective(s): This research was designed to study the prevalence of OqxAB efflux pump genes and also to investigate the relationship between efflux pump and resistance to antibiotics, especially to fluoroquinolones, evaluate the expression levels of OqxAB genes, and molecular typing of Klebsiella pneumoniae isolated from hospitalized patients in Hamadan hospitals, west of Iran. Materials and Methods: In a cross-sectional study, 100 clinical strains of K. pneumoniae were isolated from hospitalized patients in three major teaching hospitals from January to June 2021. The antibiotic susceptibility of isolates was evaluated by the disk-diffusion agar method. The frequency of genes encoding oqxA and oqxB of efflux pump genes was investigated by PCR, and the expression of the oqxA efflux pump gene was investigated by the Real-time PCR method. The genetic relationship of K. pneumoniae isolates was analyzed by the Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR technique. Results: According to our results, the multi-drug resistance phenotype (MDR) in 65% and high prevalence resistance to ciprofloxacin in 89% of K. pneumoniae isolates was detected. The higher prevalence of oqxA (95%) and oqxB (98%) was also detected. There was a significant relationship between ciprofloxacin resistance and the oqxB gene as well as between ceftriaxone and chloramphenicol resistance and the oqxA gene. The expression of the oqxA gene was higher in ciprofloxacin-resistant isolates. Conclusion: The results of this study suggest a potential reservoir for the spread of OqxAB genes among hospital-acquired bacteria. Infection control strategies should be used prudently to reduce the spread of resistant strains of K. pneumoniae in hospitals. [ABSTRACT FROM AUTHOR]

Background: The B-cell-specific Moloney murine leukemia virus integration site1 (BMI-1) is one of the famous members of the Polycomb ring finger group, which plays a crucial role in the gene transcription regulation through histone changes. Hence, it is believed to be necessary to further clarify the effects of the BMI-1 clinical. Method: This cross-sectional study was conducted on 70 acute myeloid leukemia (AML), 70 chronic myeloid leukemia (CML), and 20 healthy individuals, as the control group. We used real-time quantitative polymerase chain reaction in order to assess the BMI-1 level expression and its effect on prognosis in AML patients in the Molecular Pathology Research Center. Results: The results of the present work indicated that the BMI-1 overexpression was significantly higher in the AML and CML patients compared with that in the healthy controls (P < 0.001). Furthermore, a significant relationship was observed between the BMI-1 overexpression and poor prognosis in the AML patients (Hazard ratio=1.749, P < 0.001, 95% confidence interval = 1.31-2.32). Additionally, BMI-1 high was found in chronic and blastic phase in the CML patients (P < 0.001). Conclusion: We concluded that investigation of BMI-1 gene expression pattern will be conducive to the prognosis and treatment of myeloid leukemia. [ABSTRACT FROM AUTHOR]

Background: and Aim Acinetobacter baumannii causes various nosocomial infections and has a high antibiotic resistance. Probiotics can produce metabolites with antimicrobial properties. This study aims to evaluate the antimicrobial ability of probiotics against nosocomial pathogens by inhibiting the ompA gene expression effective in biofilm formation in Acinetobacter baumannii. Methods & Materials: The antimicrobial properties of probiotics against nosocomial pathogens were evaluated phenotypically. The polymerase chain reaction (PCR) technique was used to identify the ompA gene in Acinetobacter baumannii. After treatment with Bacillus licheniformis supernatant, the ompA gene expression was compared before and after treatment with real-time PCR technique. Ethical Considerations This study was approved by the ethics committee of Islamic Azad University, Qom branch (Code: IR.IAU.QOM.REC.1398.004). Results: Among the study probiotics, Bacillus licheniformis supernatant had the best antimicrobial properties against nosocomial isolates of Acinetobacter baumannii A52, Acinetobacter baumannii ATCC19606, Kelebsiella pneumonia ATCC70063, and Pseudomonas aeruginosa PAO1. Bacillus licheniformis supernatant also significantly reduced the biofilm formation and ompA gene expression in Acinetobacter baumannii. Conclusion: Bacillus licheniformis can produce substances with antimicrobial and antibiofilm properties. It can be used for controlling the causative agents of nosocomial infections. [ABSTRACT FROM AUTHOR]

Background: Lifestyle intervention may have a critical effect on the association between genetics and obesity. This study aimed to investigate changes in FTO and IRX3 gene expression in obese and overweight male adolescents undergoing a lifestyle intervention and the role of FTO genotype in this interaction.Methods: This study was a field trial of 62 adolescents from boys' high schools in Tehran, Iran. Two schools were randomly allocated as the intervention (n = 30) and control (n = 32) schools. The rs9930506 SNP in FTO was genotyped at baseline and the level of FTO and IRX3 expression in peripheral blood mononuclear cells (PBMCs). Anthropometric measurements were assessed at baseline and after 18 weeks of intensive lifestyle intervention.Results: Our results showed that IRX3 expression in the intervention group was significantly up-regulated compared to baseline (P = 0.007) and compared to the control group (P = 0.011).The intervention group had significantly up-regulated transcripts of IRX3 only in rs9930506 risk allele carriers of the intervention group compared to risk allele carriers of the control group (P = 0.017). Moreover, our data showed that the FTO expression was up-regulated in AA genotype carriers and down-regulated in AG/GG genotype carriers (P = 0.017).Conclusion: Lifestyle modification may exert its effects on obesity through changes in the expression level of the FTO and IRX3 genes. However, FTO genotype plays a role in the extent of the effect of lifestyle changes on gene expression. Further studies are crucial to have a better understanding of the interaction between lifestyle, genetics and anthropometric measurements. Trial registration This paper reports a comprehensive intervention study (Interactions of Genetics, Lifestyle and Anthropometrics study or IGLA study), which is retrospectively registered in the Iranian Registry of Clinical Trials as IRCT2016020925699N2. Date registered: April 24, 2016. ( https://www.irct.ir/searchresult.php?id=25699&number=2 ). [ABSTRACT FROM AUTHOR]

Background & Objective: Acute myeloid leukemia (AML) is a hematopoietic malignancy caused by genetic abnormalities. Currently, molecular and genetic factors are routinely used as diagnostic and prognostic markers. FLT-3 is one of the most known diagnostic factors in AML. MDR1 gene belongs to the ATP binding cassette family; it is known as one of the chemotherapy-resistant causes of AML. We aimed to study FLT-3ITD mutations and their association with MDR1 gene expression in AML individuals. Methods: For investigation, 80 AML individuals and 20 healthy controls were selected. This study was done in the Cancer molecular Pathology Research Center of Mashhad University of Medical Sciences (MUMS), Iran during 2017-2019. FLT3-ITD mutation was assessed by polymerase chain reaction (PCR); Real-time quantitative PCR was performed to measure the amount of MDR1 gene expression. Bone marrow and blood smears of patients were evaluated in terms of morphology. SPSS 16.0 was used for data analysis. Results: FLT3-ITD mutation and MDR1 overexpression were found in 18.8% and 23.8% of AML patients, respectively. Statistical analysis did not show any relationship or association between these two markers. Cuplike morphology was observed in blast cells in 21.25% of AML cases, which was associated with the presence of FLT3-ITD mutation. Conclusion: FLT-3 and MDR1 function independently. Survival studies to determine the exact role of MDR1 overexpression in drug resistance issues would be suggested. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one of the most prevalent types of cancer in Iranian women and the second cause of death in women worldwide. Gene mutations are the key determinants of the disease; therefore, the genetic study of this disease is of paramount importance. One of the genetic evaluation methods of this disease is microarray technology, which allows the examination of the simultaneous expression of thousands of genes. Clustering is the method for analyzing high-dimension data, which we used in the present research for collecting similar genes in separated clusters. Method: A descriptive and inferential statistical analysis was carried out to evaluate unsupervised learning models of gene expression analysis and five bi-clustering methods (including PLAID (PL), Fabia, Bimax, Cheng & Church (CC), and Xmotif) were compared. For this purpose, we obtained the microarray gene expression data for lapatinib-resistant breast cancer cell lines from previously published research. The enrichment efficacy of the clusters was evaluated with gene ontology, and the results of these five models were compared with the Jaccard index, variance stability, least-square error, and goodness of fit indices. Furthermore, the results of the best model were assessed for building a genes sets network with Bayesian networks. Results: After preprocessing, clustering was performed on the data with the dimension (4710 x 18) of the genes. Four models, except for CC, successfully found bi-clusters in the data set. The data evaluation revealed that the results of the models were almost the same, but the PL model performed better than the others, finding 11 bi-clusters; this model was used to build the network of gene sets. Conclusion: According to the results, the PL method was suitable for clustering the data. Accordingly, it could be recommended for data analysis. In addition, the gene sets network formed on gene expression data was incompetent. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is a complex disease characterized by clonal expansion of undifferentiated myeloid precursors, resulting in impaired hematopoiesis and bone marrow failure. Different genetic and environmental factors are believed to be involved in the pathogenesis of AML. Notch signaling with a tumor suppressing plays a role in myeloproliferative disorder and is a negative regulator of myeloid progenitor commitment. Crosstalk between Notch signaling and CXCR4 axis is a matter of debate in AML. Method: In the current case-control study, we evaluated the expression level of CXCR4, JAG1, and MIB1, which are all involved or related to Notch signaling in adult AML patients. Blood samples were obtained from 25 AML and 17 healthy individuals and the expression level of the selected genes was evaluated via the real-time polymerase chain reaction. Results: Our results revealed the increased expression of JAG1, but decreased expression of CXCR4 in AML patients in Iranian population of AML patients. Moreover, some gender-associated effects on the expression of JAG1 and CXCR4 were detected, which may be related to sex hormones. The expression level of MIB1 did not change significantly. The correlation analysis showed no correlations between the age of the patients and the expression levels of the genes. Conclusion: Herein, for the first time, we suggested some new evidence regarding the complex role of Notch signaling-related genes (CXCR4 and JAG1) in the pathogenesis of AML in Iranian patients. [ABSTRACT FROM AUTHOR]

Background: Obesity is a major public health concern in developed and even developing countries worldwide. Adiponectin is a protein secreted by adipose tissue that modulates many metabolic processes and plays a vital role in obesity. This study aimed to determine the association of four variants of the ADIPOQ gene with serum adiponectin, cortisol levels and obesity status. Methods: This case-control study was performed on 164 obese individuals compared by 156 control from the Tehran Lipid and Glucose Study (TLGS). Standard procedures obtained anthropometric measures and metabolic parameters. Cortisol and adiponectin levels were measured by ELISA method. rs1501299, rs266729, rs17300539, and rs17366743 on the ADIPOQ gene were genotyped using the PCR-RFLP. The correlation between adiponectin gene SNPs and obesity were calculated by Additive, dominant, and recessive genetic models. Pearson's or Spearman's found correlations between adiponectin levels and metabolic and anthropometric variables. Data were analyzed using SPSS software Version 20. Results: Adiponectin and cortisol levels were significantly lower in obese subjects compared to the control group (p < 0.05). There was a significant negative correlation between serum adiponectin level and BMI, waist circumference (WC), waist-hip ratio, hip circumference (HC), Fasting blood sugar (FBS) Triglyceride (TG), Total cholesterol (TC), Systolic blood pressure (SBP), Diastolic blood pressure (DBP) (r = − 0.147, r = − 0.324, r = 0.371, r = − 0.179, r = − 0.299, r = − 0.277, r = − 0.041, r = − 0.134, and r = − 0.149, respectively). A positive correlation was found between adiponectin and high-density lipoprotein cholesterol (HDL-C) (r = 0.29), but no significant correlations were found between adiponectin and Low-density lipoprotein cholesterol(LDL-C) and cortisol. ADIPOQ variant rs1501299 was significantly associated with cortisol levels in subjects with BMI ≥ 25 (P-value =0.039). Conclusions: Adiponectin and cortisol levels were associated with obesity. No ADIPOQ gene variants and haplotypes were associated with cortisol, Adiponectin, and obesity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gastric cancer is one of the lethal cancers and there is no effective treatment for these patients and still, 5-year survival rate is about 25% to 30%. Finding reliable biomarkers for early-stage diagnosis, targeted therapy, and survival prediction is a priority in this cancer. OBJECTIVES: In this study we were trying to know about the molecular classification of gastric cancers in a group of patients from the South of Iran. PATIENTS AND METHODS: In a cross sectional study, 50 specimens of gastric cancer were selected that have enough tissue to be stained by immunohistochemistry (IHC). IHC was performed for Her-2, mismatch repair genes (MLH-1, MSH-2, MSH-6, and PMS-2), and PDL-1. Frequency of positive makers was compared with survival and outcome. RESULTS AND CONCLUSION: In our study, deficient MMR (dMMR) was detected in 4 patients (8.0%). PD-L1 expression in tumor cells (TC) was observed in 1 of 4 cases (25%) with PMS2 loss. However, PD-L1 in TCs and TILs (tumor infiltrating lymphocytes) was negative in 1 case with MLH1 loss and in 3 of 4 cases with PMS2 loss, which was not statistically significant. All of our 50 cases were positive for MSH2 and MSH6, 24% of which showed TCs with PDL-1 expression and 32% of them in TIL. HER2 was positive in 2 (2/50, 4.0%) cases, among which all of the cases were positive for PD-L1 expression in TCs and TILs, respectively. However, in HER2-negative group, 26.2% (11/42) and 28.6% (12/42) of tumors were positive for PD-L1 in TCs and TILs, respectively. The expression rate of PD-L1 in HER2 negative TCs was significantly higher than that in HER2 positive TCs (P = .033). Immunohistochemistry for Her-2 was equivocal in 6 cases (12.0%) none of which expressed PD-L1 in tumor cells. In our study minimum and maximum survival times from detection of gastric cancer were 1 and 87 months, respectively. The mean ± SD and median ± SD of overall survival time were 30.69 ± 4.88 and 18 ± 1.45 months, respectively. One and 3-year survival rates of 40% and 24%, respectively. PD-L1 expression was not associated with survival, but its expression was associated with intestinal type Lauren classification and negative HER-2. PD-L1 positivity in tumor cells or tumor infiltrating lymphocytes was not an independent prognostic factor in gastric cancer. [ABSTRACT FROM AUTHOR]

Background Esophageal Squamous Cell Carcinoma (ESCC) is the seventh most common and lethal malignancy worldwide with a high incidence in Iran. Esophageal cancer has a poor prognosis and low 5-years survival rate. Despite several studies on esophageal cancer, its underlying mechanism remains unclear. Therefore, it is significant to analyze the molecular factors involved in disease for introducing effective diagnosis and therapeutic approaches. Accordingly, the aberrant expression of miRNA was demonstrated in the etiology of esophageal cancer, and applying them as detecting biomarkers was further considered by researchers. This study aimed to evaluate the expression level of miRNA-138 in the tumor tissues of ESCC and normal adjacent tissues. Objective In total, 35 samples of tumor and normal tissues of the esophagus were collected from ESCC patients. Methods Then, RNA extraction was conducted and the expression level of miRNA-138 was assessed in the collected tissue samples, applying real-time RT-PCR. Moreover, the relationship between the miRNA- 138 expression level and the patient’s clinical characteristics was assessed. Results According to the obtained results, the expression of miR-138 was significantly downregulated in the tumor tissues of ESCC, compared to normal adjacent tissues (P<0.05). Additionally, the level of miRNA-138 downregulation was significantly correlated with tumor differentiation degree and metastasis status (P<0.05). Conclusion The significant downregulation of miRNA-138 in the tumor samples of ESCC indicated the role of this epigenetic alteration in esophageal carcinogenesis. Therefore, applying the miRNA-138 could be considered as a potential molecular biomarker for ESCC diagnosis and screening. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to develop combination approach for the treatment of Escherichia coli-producing extended-spectrum β-lactamases (ESBLs) isolated from intensive care unit (ICU)-acquired urinary tract infections (UTIs). Materials and Methods: The observational study was conducted between January 5, 2018- June 5, 2019 to isolate and detect E. coli from UTI patients admitted to ICUs in Shahid Rajaee hospital, Gachsaran, Iran. Morphological, biochemical and molecular methods were conducted to identify E. coli isolates. Phenotypic confirmation of E. coli producing ESBL was performed using ESBL disc diffusion test according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The combination index assay set-up was based on CLSI guidelines to investigate antibacterial susceptibilities to vancomycin alone and in combination with trimethoprim and interpreted with the fractional inhibitory concentration (FIC) index. Eventually, the expression levels of blaCTX-M-33 gene were determined by real-time quantitative reverse transcription–polymerase chain reaction. Results: A total of 90 ICU-acquired UTIs occurred among 255 patients. The combination index assay results showed that vancomycin/trimethoprim combination would be reduced its minimal inhibitory concentration90 value. The vancomycin/trimethoprim combination revealed partial synergistic and indifferent effects (FIC = 0.52–1.50) in the isolates of E. coli-producing ESBL. The results of gene expression analysis indicated that vancomycin/trimethoprim combination caused downregulation of blaCTX-M-33 gene at negligible levels by 55.56–58.82-fold and stopped drug resistant. Conclusion: Vancomycin/trimethoprim combination may diminish resistance in the E. coli-producing ESBL isolated from ICU-acquired UTI patients. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis is one of the ten most important neglected tropical diseases worldwide. Understanding the distribution of vectors of visceral and cutaneous leishmaniasis (VL/CL) is one of the significant strategic frameworks to control leishmaniasis. In this study, the extent of the bioclimatic variability was investigated to recognize a rigorous cartographic of the spatial distribution of VL/CL vectors as risk-maps using ArcGIS modeling system. Moreover, the effect of bioclimatic diversity on the fold change expression of genes possessing vaccine traits (SP15 and LeIF) was evaluated in each bioclimatic region using real-time PCR analysis.Methods: The Inverse Distance Weighting interpolation method was used to obtain accurate geography map in closely-related distances. Bioclimatic indices were computed and vectors spatial distribution was analyzed in ArcGIS10.3.1 system. Species biodiversity was calculated based on Shannon diversity index using Rv.3.5.3. Expression fold change of SP15 and LeIF genes was evaluated using cDNA synthesis and RT-qPCR analysis.Results: Frequency of Phlebotomus papatasi was predominant in plains areas of Mountainous bioclimate covering the CL hot spots. Mediterranean region was recognized as an important bioclimate harboring prevalent patterns of VL vectors. Semi-arid bioclimate was identified as a major contributing factor to up-regulate salivary-SP15 gene expression (P = 0.0050, P < 0.05). Also, Mediterranean bioclimate had considerable effect on up-regulation of Leishmania-LeIF gene in gravid and semi-gravid P. papatasi population (P = 0.0109, P < 0.05).Conclusions: The diversity and spatial distribution of CL/VL vectors associated with bioclimatic regionalization obtained in our research provide epidemiological risk maps and establish more effectively control measures against leishmaniasis. Oscillations in gene expression indicate that each gene has its own features, which are profoundly affected by bioclimatic characteristics and physiological status of sand flies. Given the efficacy of species-specific antigens for vaccine production, it is essential to consider bioclimatic factors that have a fundamental role in affecting the regulatory regions of environmentally responsive loci for genes used in vaccine design. [ABSTRACT FROM AUTHOR]

Background: Iran is one of the high-risk countries for esophageal squamous cell carcinoma (ESCC). Human papillomavirus (HPV) has been reported as one of the etiologic, pathogenetic, and prognostic factors in this tumor, especially in high-risk geographic areas. Previous reports from our geographic area, that is, the South of Iran failed to show any evidence of HPV in the cases of ESCC by molecular methods. Objectives: In this study, we evaluated P16 and P53 immunohistochemistry (IHC) expression in the cases of esophageal ESCC from Fars province in the South of Iran to find the presence of any correlation between clinicopathologic findings with P16 and P53 expression by IHC as etiologic and prognostic biomarkers. We also tried to compare the results from other geographic areas of Iran and the world. Results: P16 and P53 expression were found in 42.9% and 66.12% of ESCCs, respectively. No statistically significant correlation was found between clinicopathologic findings and P16 pr P53 expression. Conclusion: Although P16 and P53 expression in ESCC in the South of Iran is significant, there is no statistically significant correlation between clinicopathologic findings and outcome in ESCC and expression of these 2 proteins to be considered as biomarkers. Results from other geographic areas of Iran and the world are also very controversial and inconsistent. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis is a prevalent tropical disease caused by more than 20 Leishmania species (Protozoa, Kinetoplastida and Trypanosomatidae). Among different clinical forms of the disease, cutaneous leishmaniasis is the most common form, with an annual 0.6-1 million new cases reported worldwide. This disease's standard treatment is pentavalent antimonial (SbV) that have been used successfully since the first half of the 20th century as a first-line drug. However, treatment failure is an increasing problem that is persistently reported from endemic areas. It is important to define and standardize tests for drug resistance in cutaneous leishmaniasis. SbV must be reduced to its trivalent active form (SbIII). This reduction occurs within the host macrophage, and the resultant SbIIIenters amastigotes via the aquaglyceroporin1 (AQP1) membrane carrier. Overexpression of AQP1 results in hypersensitivity of the parasites to SbIII, but resistant phenotypes accompany reduced expression, inactivation mutations, or deletion of AQP1. Hence, in this study, a phylogenetic analysis using barcode gene COXII and kDNA minicircle and expression analysis of AQP1 were performed in treatment failure isolates to assess the isolates' molecular characteristics and to verify possible association with drug response. Methods: Samples in this study were collected from patients with cutaneous leishmaniasis referred to the Diagnosis Laboratory Center in Isfahan Province, Iran, from October 2017 to December 2019. Among them, five isolates (code numbers 1-5) were categorized as treatment failures. The PCR amplification of barcode gene COXII and kDNA minicircle were done and subsequently analyzed using MEGA (10.0.5) to perform phylogenetics analysis of Treatment failures (TF) and Treatment response (TR) samples. Relative quantification of the AQP1 gene expression of TF and TR samples was assessed by real-time PCR. Results: All samples were classified as L. major. No amplification failure was observed in the cases of barcode gene COXII and kDNA minicircle amplification. Having excluded the sequences with complete homology using maximum parsimony with the Bootstrap 500 method, four major groups were detected to perform phylogenetic analysis using COXII. The phylogenetic analysis using the barcode target of minicircle showed that all five treatment failure isolates were grouped in a separate sub-clade. Conclusions: We concluded that the barcode gene COXII and the minicircle kDNA were suitable for identification, differentiation and phylogenetic analysis in treatment failure clinical isolates of Leishmania major. Also, AQP1 gene expression analyses showed that treatment failure isolates had less expression than TR isolates. The isolate with TF and overexpression of the AQP1 gene of other molecular mechanisms such as overexpression of ATP-binding cassette may be involved in the TR, such as overexpression of ATP-binding cassette which requires further research. [ABSTRACT FROM AUTHOR]

Background: Campylobacter jejuni (C. jejuni) is a leading cause of acute gastroenteritis in human worldwide. The aim of study was to assess the distribution of sialylated lipooligosaccharide (LOS) classes and capsular genotypes in C. jejuni isolated from Iranian children with gastroenteritis. Furthermore, the level of dnaK gene expression in C. jejuni strains with selected capsular genotypes and LOS classes was intended. Moreover, a comprehensive study of C. jejuni MLST-genotypes and inclusive comparison with peer sequences worldwide was intended.Methods: Twenty clinical C. jejuni strains were isolated from fecal specimens of 280 children aged 0-5 years, suspected of bacterial gastroenteritis, which admitted to 3 children hospitals from May to October, 2018. Distribution of sialylated LOS classes and specific capsular genotypes were investigated in C. jejuni of clinical origin. The expression of dnaK in C. jejuni strains was measured by Real-Time-PCR. MLST-genotyping was performed to investigate the clonal relationship of clinical C. jejuni strains and comparison with inclusive sequences worldwide.Results: C. jejuni HS23/36c was the predominant genotype (45%), followed by HS2 (20%), and HS19 and HS4 (each 10%). A total of 80% of isolates were assigned to LOS class B and C. Higher expression level of dnaK gene was detected in strains with HS23/36c, HS2 and HS4 capsular genotypes and sialylated LOS classes B or C. MLST analysis showed that isolates were highly diverse and represented 6 different sequence types (STs) and 3 clonal complexes (CCs). CC21 and CC257 were the most dominant CCs (75%) among our C. jejuni strains. No new ST and no common ST with our neighbor countries was detected.Conclusions: The C. jejuni isolates with LOS class B or C, and capsular genotypes of HS23/36, HS2, HS4 and HS19 were dominant in population under study. The CC21 and CC257 were the largest CCs among our isolates. In overall picture, CC21 and CC353 complexes were the most frequently and widely distributed clonal complexes worldwide, although members of CC353 were not detected in our isolates. This provides a universal picture of movement of dominant Campylobacter strains worldwide. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide and has a poor prognosis. The breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes are the key tumor suppressor genes responding in the cases of DNA damage. They repair double-strand DNA breaks to maintain gene stability. Mutations in BRCA1 and BRCA2 lead to genetic instability and develop different cancers, mainly familial breast and ovarian cancers. This study aimed to investigate the expression profiles of BRCA1 and BRCA2 genes in OSCC through the use of immunohistochemistry (IHC) technique. Method: In this retrospective study, a total of 60 samples (20 samples of each grade) were collected from the archive of pathology department of Taleghani educational hospital, Tehran, Iran, from 2000-2017. IHC staining was performed for all tissue samples. Results: BRCA1 immunoreactivity was positive in the cytoplasm and nuclear of 56 and 24 samples, respectively. None of the cancer cells showed nuclear BRCA2 expression; however, BRCA2 cytoplasmic staining existed in 17 cases. Chi-square test showed statistically significant differences between BRCA1 staining (P=0.001) and histological grade, and between BRCA2 expression (P=0.001) and histological grade in the research groups. Conclusion: Altered subcellular localization of BRCA1/2 and immunostaining of the cancer cells at the invasive front may indicate the critical role of BRCA1/2 in the development of OSCC. Early detection of BRCA mutation carriers by IHC has a significant impact on successful treatment. [ABSTRACT FROM AUTHOR]

In order to understand and adequately manage hydrological stress, it is necessary to simulate groundwater levels accurately. In this research, gene expression programming (GEP) and M5 model tree (M5) are used to simulate monthly groundwater levels. The models are combined with wavelet transform to produce two hybrid models: wavelet gene expression programming (WGEP) and wavelet M5 model tree (WM5). For the simulation, groundwater level, temperature and precipitation values from three observation wells and one meteorological station, located in Iran, are used. The results indicate that the hybrid models, WGEP and WM5, lead to a better performance than the simple models, GEP and M5. The performance of the two hybrid models is similar. It is also observed that selecting a suitable time lag for inputs plays an important role in the accuracy of the simple models. The selection of a suitable decomposition level strongly affects the accuracy of hybrid models. [ABSTRACT FROM AUTHOR]

Background: Flower development and sufficient fruit set are important parameters with respect to walnut yield. Knowledge about flowering genes of fruit trees can help to conduct better molecular breeding programs. Therefore, this study was carried out to investigate the expression pattern of some flowering genes (FT, SOC1, CAL, LFY and TFL1) in Persian walnut (cv. Chandler) during the growing season and winter dormancy. Results: The results showed that walnut flower induction and initiation in Shahmirzad, Iran occurred in early June and late September, respectively. After meeting chilling and heat requirement, flower differentiation and anthesis occurred in late-March and mid-April to early-May, respectively. Study of flowering gene expression showed that the expression of the FT gene increased in three stages including before breaking of bud dormancy, from late March to late April (coincided with flower differentiation and anthesis) and from late May to mid-June (coincided with flower induction). Like FT, the expression of SOC1 gene increased during flower induction and initiation (mid-May to early-August) as well as flower anthesis (mid-April to early-May). LFY and CAL genes as floral meristem identity genes are activated by FT and SOC1 genes. In contrast with flowering stimulus genes, TFL1 showed overexpression during winter dormancy which prevented flowering. Conclusion: The expression of FT gene activated downstream floral meristem identity genes including SOC1, CAL and LFY which consequently led to release bud dormancy as well as flower anthesis and induction. Also, TFL1 as a flowering inhibitor gene in walnut showed overexpression during the bud dormancy. Chilling accumulation reduced TFL1 gene expression and increased the expression of flowering genes which ultimately led to overcome dormancy. [ABSTRACT FROM AUTHOR]

A precise forecast of streamflow in intermittent rivers is of major difficulties and challenges in watershed management, particularly in arid and semiarid regions. The present research study introduces an ensemble gene expression programming (EGEP) modeling approach to 1- and 2-day ahead streamflow forecasts that meet both accuracy and simplicity criteria of an applied model. Three main components of the proposed EGEP approach which are capable of producing a parsimonious model include (i) creating a population of suitable solutions using classic genetic programming (GP) instead of a single solution, (ii) combining the solutions throughout gene expression programming, and (iii) parsimony selection based upon trade-off analysis between the complexity and accuracy of the best-evolved solutions at the holdout validation set. The EGEP model was trained and verified using the streamflow measurements from the Shahrchay River lying northwest of Iran. Several statistical indicators were computed for verification of the ensemble models' accuracy with that of classic GP and artificial neural network models developed as the benchmarks. Our results revealed that the EGEP outperforms the benchmarks. It is an explicit, simple, and precise approach and, therefore, worthy to be used in practice. [ABSTRACT FROM AUTHOR]

Background and Aim recombinant DNA technique is a powerful and appropriate method for the production of protein biopolymers with specificity in amino acid sequence and spatial chemistry. Elastin-Like Polypeptide (ELP) is a biocompatible, biodegradable and non-immunological biopolymer used in various biotechnology studies. The ELP tag is a cheap, fast and non-chromatographic technique for purifying target proteins. In this study, pET expression vector was designed for the combination of ELP gene sequences and target recombinant protein in order to produce recombinant fusion protein with the ELP tag. Methods & Materials MOD gene was transformed to E. coli-BL21 (DE3) cells after designing and synthesis among the XbaI and XhoI restriction sites in the pET-32a (+) vector of the clone. Then, colonies were isolated based on plasmid size and examined by cutting using restriction enzymes. The final recombinant colonies was verified using polymerase chain reaction method and DNA sequencing. Ethical Considerations The Research Ethics Committee of Arak University of Medical Sciences approved all ethical considerations ofworking on laboratory animals (Code: 92-146-11). Results Replacing the MOD sequence in the pET-32a vector (+) eliminated the components expressing the fusion tags (Thioredoxin, Histidine, and S-tag), the identification site of protease enzyme (tobacco etch virus), and multiple cloning site. In addition, it added specific restriction enzyme identification sequences of ELP gene and target gene. As a result, in the optimized pET-MODvector, 466 nucleotides reduced in size and the secondary structure was improved. Conclusion Considering the improvement of spatial structure and reduction of pET-MOD vector size, as well as the possibility of the fusion of recombinant protein with the ELP tag, it is possible to use this vector for ELPyation of the target protein. [ABSTRACT FROM AUTHOR]

Background: Studies on the association between the prothrombin G20210A variant and coronary artery disease (CAD) risk are inconclusive. This study aimed to investigate the possible association between the G20210A variant in the prothrombin gene and documented CAD and its severity. Methods: This study enrolled 1460 patients who were consecutively admitted for elective coronary angiography. Via the standard angiographic techniques, coronary angiographies were done and the presence and severity of CAD were determined through the clinical vessel score and the Gensini score. Prothrombin G20210A genotypes were identified using PCR-RFLP. Results: This cross-sectional study was performed on 953 men and 507 women at a mean age of 58.21±10.33 years. The median and the interquartile range for the Gensini score were not statistically significantly different between the wild (GG) and mutant (AA+GA) genotypes (P=0.440). The association between the G20210A polymorphism and the severity of CAD with respect to the vessel score also showed no significant linear trend of higher numbers of diseased vessels (P= 0.765 for the Mantel-Haenszel test of linear trend) in the AA+GA genotype as compared with the GG genotype. Conclusion: Our data failed to confirm the hypothesis that the G20210A variant mutation may be a significant determinant of CAD risk or its severity. [ABSTRACT FROM AUTHOR]

Background: In recent years, prostate cancer prevails as one of the lead cancers affecting men. Currently, prostate cancer research involves the phytochemical study of plants with anti-tumour effects. This study compares the anti-tumour effects of three plant species indigenous to Iran and their interaction with cluster of differentiation (CD)-82 protein, a therapeutic target found in prostate cancer cells. Methods: The extracts of Hypericum perforatum, Achillea millefolium, and Aloe vera were prepared and their toxicological, cellular and gene expression responses were evaluated in PC-3 human prostate cancer cells and normal human chondrocyte cell line C28/I2. They were exposed to different concentrations of the plants (10 mg/mL, 5 mg/mL, 1 mg/mL, 100 μg/mL, 10 μg/mL, and 1 μg/mL) at three exposure time points (24, 48, 72 hours) to determine cancer cell cytotoxicity and gene expression profiles. Results: Half-maximal inhibitory concentration (IC50) in PC-3 cells ranged from 0.6 to 8.5 mg/mL for H. perforatum extract, from 0.4 to 7.5 mg/mL for A. Millefolium extract, and from 0.2 to 8.0 mg/mL for A. vera extract in a timedependent manner. A. vera extract caused the highest cell death levels in PC-3 cells (94%) and C28/I2 cells (57%) after 48 hours. A 1.97-, 3.00-, and 3.48-fold increase in relative gene expression of CD82 was observed for H. perforatum, A. millefolium, and A. vera extracts, respectively. Conclusions: A. vera and A. millefolium extracts are a selective inhibitor of prostate cancer cells and a potent activator of CD82 expression. [ABSTRACT FROM AUTHOR]

Background: Early-onset inflammatory bowel disease (IBD) is classified into Crohn's disease (CD), ulcerative colitis (UC) and unclassified disorders, which has a chronic, relapsing course and can result in substantial long-term morbidity. IBD is a multifactorial disorder with genetic susceptibility, immunological predisposition and environmental triggers. The objective of this study was to generally determine the prevalence of IL10R mutation in IBD patients in Isfahan, Iran. We performed sequencing of all exons in IL10RA and IL10RB in a cohort of IBD patients and healthy controls. Methods: Total DNA contents of 76 patients and 50 healthy controls were extracted from whole blood and polymerase chain reaction (PCR) amplifications and sequencing of whole exons in IL10R were performed. Results: Overall, we determined 13 single nucleotide polymorphisms (SNPs) in all IL10R genes. Of them, rs3135932 and rs2229113 of the IL10RA1 gene, in exons 4 and 7, respectively, were significantly associated with IBD occurrence in patients. Conclusions: Our results also confirmed that early-onset IBD could be attributed to a synergistic effect of several variant alleles of the genes encoding IL10 receptors. These variants, alone, could only give rise to a sub-clinical manifestation of IBD. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare the expression of miR-21 gene in stages II-IV of formalin-fixed paraffin-embedded (FFPE) tissue in patients with colon cancer and introduce miR-21 as a potential molecular marker for detection of colon cancer in the early stages. Introduction: Currently, identification of key molecules involved in the pathogenesis of cancer is one of the areas under consideration. miRNAs, are small RNAs which have been identified in many cancers. In this study, we investigated the expression of miR-21 in three pathologic stages in patients with colon cancer in the north of Iran. Patients and methods: A total of 40 FFPE samples were obtained from patients with stages II, III, and IV from hospitals in Mazandaran and Golestan provinces. After extraction of RNA, treatment with DNase I and cDNA synthesis was performed and miR-21 expression was assessed by qPCR. Then, the data were analyzed using statistical software R (3.4.3). Results: The expression of miR-21 in stage II was significantly different from stage IV. However, no significant difference was observed between the other stages. In stage II, the level of miR-21 expression was higher in men than women. Moreover, in the second pathological stage, miR-21 expression was reduced in patients with adjacent lymphoid tissue engagement. In addition, the expression of miR-21 in grade I was significantly higher than grade II. Conclusion: The results of this study suggest that miR-21 can be a diagnostic marker for early stages of colon cancer, especially in men. It can also be considered as a good candidate for targeted treatment of colon cancer in the early stages of the disease. Furthermore, for the first time, we suggested that miR-21 can be a good molecular marker for classification of the stages of colon cancer. [ABSTRACT FROM AUTHOR]

Background: Antibiotic resistant strains of Pseudomonas aeruginosa are the cause of Gram negative nosocomial infections especially among the immunosuppressed patients. The bacteria contains las I and las R genes that play very important roles in the pathogenesis and mechanisms of aggression. These genes can be influenced by the quorum sensing (QS) system and such mechanism is becoming clinically important worldwide. This study aimed to investigate the preventive effects of green coffee extract (GCE) on the expression of pathogenesis-related genes, las I and las R in P. aeruginosa. Methods: A total of fifty four P. aeruginosa strains were isolated out of 100 clinical samples collected from the infectious wards in different hospitals (Tehran province) using conventional microscopic and biochemical methods. Susceptibility of the isolates to different antibiotics, GCE and chlorogenic acid were elucidated. Multiplex polymerase chain reaction (PCR) and real-time PCR were performed to detect and quantify the expression levels of las I and las R genes. The presence of chlorogenic acid in GCE was confirmed by HPLC. Results: Antibiotic susceptibility tests revealed multidrug resistance among the clinical isolates of those 40 strains were resistant to ciprofloxacin (74.07%), 43 to ceftazidime (79.26%), 29 to amikacin (53.7%), 42 to ampicillin (77.77%), 17 to colistin (31.48%), 40 to gentamicin (74.77%), and 50 to piperacillin (92.59%). PCR outcomes exhibited that the frequency of las I and las R genes were 100% in resistant and sensitive strains isolated from clinical and standard strains of P. aeruginosa (ATCC 15449). Real-time PCR analyses revealed that GCE significantly prevented the expression of las I and las R genes in P. aeruginosa. GCE at concentration level as low as 2.5 mg/mL could prevent the expression of lasI and lasR genes in P. aeruginosa clinical isolates. Conclusion: The presence and expression levels of las I and las R genes in P. aeruginosa isolates were investigated when the bacteria was exposed to GCE. Our results tend to suggest that genes involved in pathogenesis of:Pseudomonas aeruginosa are down regulated by quorum sensing effect of chlorogenic acid and therefore GCE could be useful as an adjuvant in combating multidrug resistance strains of Pseudomonas aeruginosa. [ABSTRACT FROM AUTHOR]

The mustard lung is a late consequence of exposure to sulfur mustard (SM) in veterans who had participated in the Iraq-Iran war. Three mechanisms are contributed in the pathogenesis of mustard lung including oxidative stress, protease-antiprotease imbalance, and dysregulated immune response. In the context of the immune response, the role of the inflammasome complex and their inflammatory cytokines are important. This study aims to investigate the inflammasome pathway and their inflammatory cytokine (i.e IL-1 and IL-18) in the peripheral blood of mustard lung patients as well as chronic obstructive pulmonary disease (COPD) patients. This research was conducted as a cross-sectional analytical study on 15 SM patients and was compared with 15 COPD patients and 15 healthy controls. The real-time polymerase chain reaction was used to assess gene expression levels of inflammasome components (NLRP1, NLRP3, NLRC4, and ASC), inflammatory cytokines (IL-1β, IL-18, and IL-1βR), and IL-37 as an anti-inflammatory cytokine. Finally, the data were analyzed by SPSS version 21 software. The gene expression level of molecules involved in inflammasome pathway showed a slight increase in the peripheral blood of SM and COPD patients compared to the control group. However, this difference was not statistically significant. Only IL-37 and NLRP1 had a significant increase in mustard lung and COPD patients; compared to healthy controls (p<0.05). Due to the normal expression of genes involved in the inflammasome pathway, it can be stated that the inflammasome pathway is not active in the blood of mustard lung patients. [ABSTRACT FROM AUTHOR]

BACKGROUND Colorectal cancer (CRC) is one of the most common cancers among men and women worldwide. Cancer metastasis is the main cause of death in patients with cancer. NEBL (nebulette, Gene ID: 10529) protein interacts with thin filaments in the cell and may functionally destabilize focal adhesion composition. There are some studies on NEBL gene expression alteration in cancer. In the presented study we aimed to analyze NEBL gene expression in patients with colorectal cancer to explore possible association of this gene with clinicopathological features in CRC. METHODS Sixty-seven fresh samples of colorectal tumors and adjacent normal tissues were collected from Iranian patients with CRC. Real time polymerase chain reaction was performed to measure the level of NEBL gene expression and its association with clinico-pathological features. RESULTS A significant overexpression with 3 fold increse was seen in NEBL mRNA level in tumoral tissues compared with the adjacent normal tissues. In addition there was a significant association between NEBL gene expression with lymph node metastasis in patients with CRC. CONCLUSION The overexpression of NEBL has the capacity to be considred as a prognostic biomarker in patients with CRC. [ABSTRACT FROM AUTHOR]

Aim: In this study, we determined the gene expression analysis of IL-17 gene family for early detection of subclinical inflammation among IBD patients. Background: Cytokines have a vital role in the pathogenesis of inflammatory bowel disease (IBD). Interleukin-17 is the signature cytokine of the recently identified T helper 17 (Th17) cell subset. IL-17F is mainly involved in mucosal host defense mechanisms whereas the functions of IL-17B remain largely elusive. Methods: In this cross-sectional study, IBD patients divided into two active and inactive groups. Peripheral blood mononuclear cells (PBMCs) from 38 IBD patients which 20 inactive samples and 18 active individuals were collected. Changes of IL-17 F and IL-17B mRNA expression level evaluated by quantitative-real time-PCR. Results: mRNA expression level of IL-17B and IL-17F in CD, UC, active and inactive groups have been assessed and there were no significant differences (P>0.05). Patients were classified into five different categories as follows: i) 5-ASA; ii) 5-ASA + Pred; iii) 5-ASA + AZA; iv) 5-ASA + Pred + AZA; v) 5-ASA + Pred + AZA + IFX according to medication usage, expression of IL-17F and IL-17B had no differences (p>0.05). Conclusion: Evaluation of IL-17B and IL-17F mRNA expression level illustrate no difference among active and inactive patients. Therefore, IL-17B and IL-17F are not biomarkers in an Iranian IBD patients. [ABSTRACT FROM AUTHOR]

Background: Wound healing is often impaired in diabetic animals and humans. Matrix metalloproteases act as pro-inflammatory agents in physiological wound healing pathways by stimulating cytokines including the interleukins, IL6, IL1A and IL1B, and the tumor necrosis factor and transforming growth factor beta1. Botanicals are traditionally used to assist healing of different types of wounds, because they produce fewer side effects. Our specific aim here was to develop a plant-based recipe supporting effective wound healing in diabetic animals. Methods: Plant materials from Adiantum capillus-veneris, Commiphora molmol, Aloe Vera, and henna were collected for this study, and oven-dried at 60 °C. The dried leaves and resins were then crumbled into a powder and mixed in equal parts with Vaseline as a preservative. This mixture was used as an ointment on wounds induced in 60 diabetic and non-diabetic rats that were divided into 6 subgroups receiving agent or control treatments. Necrotic tissue surrounding the wound was periodically removed during wound healing. RNA was extracted from the healing region of the wound at days 7, 14 and 21 for cDNA synthesis to monitor changes in Tgfb1, Mmp3, Mmp9, Il6 and Tnf a expression using real-time PCR. Results: The expression of the Mmp3, the Tnf a, and the Tgfb1 genes from wound tissue were significantly different (p < 0.05) between diabetic and non-diabetic (control) rats treated with the herbal mixture after 14 and 21 days. There was no significant difference (p > 0.05) of the Mmp9 gene expression in diabetic and non-diabetic rats treated only with Vaseline after 7, 14, and 21 days. But, the expression of the Mmp9 gene decreased significantly (p < 0.05) in diabetic rats after 14 days in comparison to non-diabetic rats, when the herbal mixture was added to Vaseline. Conclusions: Our study presents an herbal treatment that alters the gene expression signature at wounds induced in the rat model for type I diabetes in a manner consistent with accelerated healing, and demonstrates that this herbal treatment might be effective to treat wounds in diabetic patients. [ABSTRACT FROM AUTHOR]

Aim: We aimed to study the expression of CD24 and CD133 in colorectal cancer and normal adjacent tissues to assess a relationship between these markers and clinic-pathological characteristics and patient's survival. Background: Cancer stem cells are a group of tumor cells that have regeneration and multi-order differentiation capabilities. Patients and methods: Expression of CD24 and CD133 was studied in a paraffin block of colorectal cancer and normal tissues near tumors with the immuneohistochemical method in patients who were referred to Imam Khomeini Hospital in Sari. Results: A total of 50 samples (25 males and 25 females) with a mean age of 67.57±13.9 years old with range 28-93 years, included 3 mucinous carcinoma and 47 adenocarcinoma. Expression of CD133 marker was negative in 29 cases and positive in 21 cases. Expression of CD24 in tissue near tumor cells was found in 30% of available samples. The relationship between expressing CD24 with treatment (surgery and chemotherapy) was significant and its relationship with patient's survival was insignificant statistically. However, there was a clear difference as mean survival age of patients based on CD24 expression was 26.64±18.15 for negative cases and 41.75±28.76 months for positive cases. CD24 and CD133 expressions and their coexpression with other clinic-pathological factors were not significant. Conclusion: During this study, the relationship between CD24 and treatment type was significant. To confirm this result, various studies with high sample numbers and other stem cell markers are recommended. [ABSTRACT FROM AUTHOR]

Background: The main objective of the present work was to compare the effects of the gonadotropin-releasing hormone agonist (GnRH-a) and GnRH antagonist (GnRH-ant) on the gene expression profiles of oocytes obtained from Iranian infertile couples undergoing in vitro fertilization (IVF). Methods: Fifty infertile couples who underwent IVF between June 2012 and November 2013 at the Infertility Center of Tehran Women General Hospital, Tehran University of Medical Sciences, were included in this study. We included women that had undergone IVF treatment because of male factor, tubal factor, or unexplained infertility. The women randomly underwent controlled ovarian stimulation (COS) with either the GnRH-a (n = 26) or the GnRH-ant (n = 24). We obtained 50 germinal vesicle (GV) oocytes donated by women in each group. After the sampling, pool of 50 GV oocytes for each group was separately analyzed by quantitative polymerase chain reaction (qPCR). Result: The expression levels of Adenosine triphosphatase 6 (ATPase 6), Bone morphogenetic protein 15 (BMP15), and Neuronal apoptosis inhibitory protein (NAIP) genes were significantly upregulated in the GnRH-ant group compared to the GnRH-a group, with the fold change of 3.990 (SD ± 1.325), 6.274 (SD ± 1.542), and 2.156 (SD ± 1.443), respectively, (P < 0.001). Growth differentiation factor 9 (GDF9) mRNA did not have any expression in the GnRH-a group; however, GDF9 mRNA was expressed in the GnRH-ant group. Finally, it was found that the genes involved in the DNA repairing and cell cycle checkpoint did not have any expression in either group. Conclusion: The present study showed, for the first time, the expression levels of genes involved in the cytoplasmic maturity (BMP15, GDF9), adenosine triphosphate production (ATPase 6), and antiapoptotic process (NAIP), in human GV oocytes were significantly higher in the GnRH-anta group than in the GnRH-a group in COS. Higher expression level of these genes when GnRH-ant protocol is applied, this protocol seems to be a more appropriate choice for women with poly cystic ovarian syndrome, because it can probably improve the expression of the aforementioned genes. [ABSTRACT FROM AUTHOR]

Background The main objective of the present work was to compare the effects of the gonadotropin-releasing hormone agonist (GnRH-a) and GnRH antagonist (GnRH-ant) on the gene expression profiles of oocytes obtained from Iranian infertile couples undergoing in vitro fertilization (IVF). Methods Fifty infertile couples who underwent IVF between June 2012 and November 2013 at the Infertility Center of Tehran Women General Hospital, Tehran University of Medical Sciences, were included in this study. We included women that had undergone IVF treatment because of male factor, tubal factor, or unexplained infertility. The women randomly underwent controlled ovarian stimulation (COS) with either the GnRH-a (n = 26) or the GnRH-ant (n = 24). We obtained 50 germinal vesicle (GV) oocytes donated by women in each group. After the sampling, pool of 50 GV oocytes for each group was separately analyzed by quantitative polymerase chain reaction (qPCR). Result The expression levels of Adenosine triphosphatase 6 (ATPase 6), Bone morphogenetic protein 15 (BMP15), and Neuronal apoptosis inhibitory protein (NAIP) genes were significantly upregulated in the GnRH-ant group compared to the GnRH-a group, with the fold change of 3.990 (SD ± 1.325), 6.274 (SD ± 1.542), and 2.156 (SD ± 1.443), respectively, (P < 0.001). Growth differentiation factor 9 (GDF9) mRNA did not have any expression in the GnRH-a group; however, GDF9 mRNA was expressed in the GnRH-ant group. Finally, it was found that the genes involved in the DNA repairing and cell cycle checkpoint did not have any expression in either group. Conclusion The present study showed, for the first time, the expression levels of genes involved in the cytoplasmic maturity (BMP15, GDF9), adenosine triphosphate production (ATPase 6), and antiapoptotic process (NAIP), in human GV oocytes were significantly higher in the GnRHanta group than in the GnRH-a group in COS. Higher expression level of these genes when GnRH-ant protocol is applied, this protocol seems to be a more appropriate choice for women with poly cystic ovarian syndrome, because it can probably improve the expression of the aforementioned genes. [ABSTRACT FROM AUTHOR]

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