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Background: Colorectal cancer (CRC) is considered as one of the most common malignancy and the fourth leading cause of cancer-related deaths, worldwide. Here, we aimed to investigate the expression of miR–663b and miR–650 in CRC tissue and plasma specimens. Methods: In this case–control study, tumor specimens, non-tumoral adjacent tissues, and matched-plasma samples were obtained from forty patients with CRC living in the northwestern of Iran. Plasma of healthy patients was also collected as control. Total RNA was extracted from all specimens and studied by real-time PCR. Furthermore, the correlation between the expression of microRNAs and clinico-pathological features were also studied. Results: Our data illustrated that miR-650 and miR-663b are down-regulated and up-regulated in tumor samples compared to non-tumoral margins, respectively (p < 0.001). However, the results did not show any significant difference in patient's plasmas compared to controls. Further analysis disclosed that the expression of miR-663b is significantly associated with tumor size, lymph node metastasis, and tumor stage, while miR-650 is remarkably related to TNM stage, lymph node metastasis, distant metastasis, tumor size, and age. (p < 0.05) Furthermore, receiver operating characteristic (ROC) analyses revealed that miR-650 and miR-663b are potential biomarkers in differentiating CRC patients from healthy controls. Conclusion: In conclusion, our data illustrated the potential of miR-650 and miR-663b as biomarkers in colorectal cancer. However, further studies are needed to confirm the employment of these microRNAs in the diagnosis and/or prognosis of colorectal malignancies. [ABSTRACT FROM AUTHOR]

AbstractMultiple sclerosis (MS) is a condition characterized by inflammation in the central nervous system (CNS), impacting sensory, motor, and cognitive abilities. Globally, around three million individuals are affected by MS, with up to 97,000 cases in Iran attributed to genetic predispositions along with various environmental factors like smoking. Cognitive impairment affects a significant portion of patients, ranging from 45% to 70%. This study investigates the impact of regular aerobic swimming exercise for four weeks, mild cognitive impairment induced by encephalomyelitis, and their combination on the expression of microRNA-142-3p and its correlation with the release of brain-derived neurotrophic factor (BDNF) in relation to spatial memory. Twenty-one C57BL/6 mice were divided into three groups. RT-PCR was used for microRNA expression analysis, and BDNF levels were assessed via western blotting. Clinical scores and animal weights were monitored daily. EAE induction led to an increase in microRNA-142-3p expression and a decrease in BDNF levels compared to the control group. Exercise inversed them significantly, and improved spatial memory. Our findings indicate that engaging in regular swimming exercise can counteract the up-regulation of miR-142-3p in brain tissue, which likely contributes to mild cognitive impairment induced by MS. Additionally, the increase in BDNF following exercise appears to be associated with miR-142-3p and the enhancement of cognitive function. Thus, the therapeutic benefits of exercise, particularly in releasing BDNF to improve cognitive function in MS patients, warrant consideration. Lifestyle modifications have the potential to effectively modulate environmental influences and ethnicity, underscoring their significance in MS management. [ABSTRACT FROM AUTHOR]

Background. Recurrent pregnancy loss is defined as at least two consecutive clinical pregnancy losses before 20th week of gestation. In this study, we investigated microRNA-1 and microRNA-1229 in recurrent miscarriage patients before and after lymphocyte therapy in comparison to control group. Methods. First, a written and informed consent will be obtained from the target population of this study, who are people with RPL referring to Waliasr International Hospital. According to the standard protocol, the number of 2×107 is injected subcutaneously to patients. Real-time PCR technique will be used to check the expression level of microRNA-1 and microRNA-1229. Results. The gene expression level of micro-RNA 1 in RPL women before of lymphocyte therapy was 2.030±1.445 and the gene expression level of the same microRNA after the lymphocyte therapy of the mother was 1.101±0.4780. Also, the expression level of micro-RNA 1229 in these women was reported to be 2.100±0.6296 before treatment and 1.247±0.9631 after treatment with lymphocytes. This level of gene expression in control group, for micro-RNA 1 and micro-RNA 1229 genes is 1.000±0.08334 and 1.000±0.08091, respectively. Conclusion. The results of our study showed a noticeable decrease in the gene expression of microRNAs under study, both microRNAs 1 and 1229, in women with a history of three consecutive injections of the father's subcutaneous lymphocytes. Practical Implications. This study can show the therapeutic effect of lymphocyte for patients with recurrent miscarriage so that this treatment can be used along with other treatment methods. [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 & Objective: Lung transplantation is a promising therapy for patients with end-stage lung disease. Pulmonary surfactant is a lipid and protein complex which has a key role in lung function. Molecular mechanisms mediating in rejection of lung transplantation related to surfactants are not still comprehensively understood. In this study, we applied bioinformatics approaches to identify genes and molecular mechanisms involved in surfactant function in rejection of lung transplantation. Materials & Methods: At first, transcriptomics data was extracted and analyzed to construct the protein-protein interaction network and gene regulatory network using Cytoscape. Then, networks analysis were performed to determine hubs, bottlenecks, clusters, and regulatory motifs to identify critical genes and molecular mechanisms involve in surfactant function in rejection of lung transplantation. Finally, critical genes selected for repuposing drugs. Results: Analyzing the constructed PPIN and GRN identified SCD, FN1, ICAM1, ITGB8, FOXC1, SIX1, FHL2, KRT5, TFAP2A, GAS5, MALAT1, and lnrCXCR4 as critical genes. Enrichment analysis showed the genes are enriched for pulmonary surfactant metabolism dysfunction, defective CSF2RB causes pulmonary surfactant metabolism dysfunction 4 and 5, Interleukin-4 and Interleukin-13 signaling may be the mechanisms for surfactant function in rejection of lung transplantation. We predicted some candidate drugs for preventing of lung transplantation rejection such as Sunitinib, Gemcitabine, Oxaliplatin, Hyaluronic acid. Conclusion: Following our model validation using the existing experimental data, our model suggested critical molecules and candidate medicines involve in surfactant function in rejection of lung transplantation for furtur investigations. [ABSTRACT FROM AUTHOR]

Background and Objectives: The role of microRNAs (miRNAs) in tuberculosis infection is well established. As microRNAs are able to change expression profiles according to different conditions, they can be useful biomarkers. Iranians and Afghans with tuberculosis were studied for three immune-related miRNAs (miR-let-7f, miR-125a, and miR-125b). Materials and Methods: A total of 60 Iranian and Afghan patients with active pulmonary TB were enrolled in the Pulmonary Department of the Pasteur Institute of Iran. Serum and sputum samples were collected simultaneously from all participants. A Real-time PCR was conducted to detect differentially expressed miRNAs. Results: Iranian (P<0.0001) and Afghan (P<0.0001) serum samples and Afghan (P<0.0001) sputum samples overexpressed miR-125a, whereas Iranian sputum samples showed downregulation (P=0.0039). In both Iranian (P<0.0001; P=0.0007) and Afghan (P<0.0001; P<0.0001) serum and sputum samples, miR-125b was overexpressed. Furthermore, miR-let-7f downregulation was observed in serum and sputum samples (P<0.0001), whereas Iranian sputum samples had no statistically significant differences (P=0.348). Conclusion: Overexpression of miR-125a and miR-125b has been detected in Iranian and Afghan samples. In both races, miR-let-7f downregulation has been confirmed. Identification of miRNA profiles under different conditions opens the door to evaluating potential new biomarkers for diagnosis, disease monitoring, and therapeutic markers in TB infection. [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: Acute lymphoblastic leukemia (ALL) is a malignancy that leads to altered blast cell proliferation, survival, and maturation and eventually to the lethal accumulation of leukemic cells. Recently, dysregulated expression of various micro-RNAs (miRNAs) has been reported in hematologic malignancies, especially ALL. Cytomegalovirus infection can induce ALL in otherwise healthy individuals, so a more detailed evaluation of its role in ALL-endemic areas like Iran is required. Methods: In this cross-sectional study, 70 newly diagnosed adults with ALL were recruited. The expression level of microRNA-155(miR-155) and microRNA-92(miR-92) was evaluated by real-time SYBR Green PCR. The correlations between the miRNAs mentioned above and the severity of disease, CMV infection, and acute graft vs. host disease after hematopoietic stem cell transplantation (HSCT) were assessed. B cell and T cell ALL distinction in the level of miRNAs was provided. Results: After the statistical analysis, our results indicated a marked increase in the expression of miR-155 and miR-92 in ALL patients vs. healthy controls (*P = 0.002–*P = 0.03, respectively). Also, it was shown that the expression of miR-155 and miR-92 was higher in T cell ALL compared to B cell ALL (P = 0.01–P = 0.004, respectively), CMV seropositivity, and aGVHD. Conclusion: Our study suggests that the plasma signature of microRNA expression may act as a powerful marker for diagnosis and prognosis, providing knowledge outside cytogenetics. Elevation of miR-155 in plasma can be a beneficial therapeutic target for ALL patients, with consideration of higher plasma levels of miR-92 and miR-155 in CMV + and post-HSCT aGVHD patients. [ABSTRACT FROM AUTHOR]

Background: Circulating microRNAs (miRNAs) can help to predict the chemotherapy response in breast cancer with promising results. The aim of the present study was to investigate the relationships between the miR-199a, miR-663a, and miR-663b expression and chemotherapy response in metastatic breast cancer patients. Methods: This study is a case-control study performed at Yasuj University of Medical Sciences (2018-2021). The expression levels of miR-663a, miR-663b, and miR-199a in the serum of 25 patients with metastatic breast cancer versus 15 healthy individuals were determined by the real-time polymerase chain reaction method. The response to treatment was followed up in a 24-month period. All patients were treated with second-line medications. Two or more combinations of these drugs were used: gemcitabine, Navelbine®, Diphereline®, Xeloda®, letrozole, Aromasin®, and Zolena®. Statistical analyses were performed in SPSS 21.0 and GraphPad Prism 6 software. The expression levels were presented as mean±SD and analyzed by Student's t test. Results: The results and clinicopathological features of patients were analyzed by t test. The statistical analysis showed that miR-663a expression was related to human epidermal growth factor receptor 2 (HER2) status and was significantly lower in the HER2+ than HER2- group (P=0.027). Moreover, the expression of miR-199a and miR-663b was significantly correlated with the response to treatment, in which the expression of miR-199a was higher in the poor-response group (P=0.049), while the higher expression of miR-663b was seen in the good-response group (P=0.009). Conclusion: These findings state that the high plasma level of miR-199a and the low plasma level of miR-663b may be related to chemoresistance in patients with metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is considered the second-deadliest and third-most common malignancy worldwide. Studying the carcinogenic mechanism of bacteria or their role in aggravating cancer can be precious. Fusobacterium nucleatum (F. nucleatum) is one of the important bacteria in the occurrence and spread of CRC. In this study, we investigated the expression levels of miR-21, miR-17-5P, miR-155, and the relative frequency of F. nucleatum in biopsy samples from patients with CRC. Method: DNA and RNA samples were extracted using a tissue extraction kit, and then cDNAs were synthesized using a related kit. Based on the sequence of miR-17-5P, miR-21, and miR-155 genes, F. nucleatum specific 16srRNA and bacterial universal16srRNA specific primers were selected, and the expression levels of the target genes were analyzed using the Real-Time PCR method. Results: The expression level of miR-21, miR-17-5P, and miR-155 genes showed a significant increase in the cancer group. Also, the expression of the mentioned miRNAs was significantly raised in the positive samples for F. nucleatum presence. The relative frequency of F. nucleatum in the cancer group was significantly increased compared to the control group. Conclusion: Due to the changes in the expression of genes involved in causing CRC in the presence of F. nucleatum, it is possible to prompt identification and provide therapeutic solutions to cancer patients by studying their microbial profiles and the expression changes of different selected genes. [ABSTRACT FROM AUTHOR]

Background: Non-Hodgkin lymphoma (NHL) is the eleventh leading cause of cancer-related death in the world. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL. Up to winter 2021-2022, the death toll caused by the coronavirus disease 2019 (COVID-19) has exceeded 5.6 million worldwide. Possible molecular mechanisms involved in the systemic inflammation, and cytokine storm in COVID-19 patients are still not fully understood. MicroRNA-155 (miR-155) plays a role in the post-transcriptional gene regulation of hematopoiesis, oncogenesis, and inflammation. The present study aimed to evaluate the expression of miR-155 in patients with DLBCL and/or COVID-19. Methods: A cross-sectional study was conducted from July to December 2020 in Tehran (Iran) to evaluate the expression of miR-155 in adult patients diagnosed with DLBCL and/or COVID-19. The real-time polymerase chain reaction technique was used to evaluate the expression of miR-155 in the sera of 92 adults who were either healthy or suffering from DLBCL and/or COVID-19. Relative quantification of gene expression was calculated in terms of cycle threshold (Ct) value. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant. Results: The expression of miR-155 was not associated with the sex or age of the participants. In comparison with healthy individuals (-ΔCt: -1.92±0.25), the expression of miR-155 increased in patients with COVID-19 (1.95±0.14), DLBCL (2.25±0.16), or both (4.33±0.65). Conclusion: The expression of miR-155 increased in patients with DLBCL and/or COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: Asthenozoospermia (AZS), sperm immobility, is one of the major cause of men infertility. Evidence suggested that microRNAs (miRNAs) play a critical role in spermatogenesis process. However, the association of miRNAs polymorphisms with idiopathic male infertility remains unknown. Therefore, we investigated correlation between miR- 196a2 rs11614913 polymorphism and idiopathic AZS among Iranian Azeri men. Materials and Methods: In this study, 50 men with idiopathic AZS (case group) as well as 50 age and ethnically matched healthy men (control group) were enrolled from East Azerbaijan, Iran. The proteinase K method was used to extract the genomic DNA from sperm samples. Finally, genotyping was conducted using tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS PCR) method. Results: The frequency of TT, TC, and CC genotypes were 12%, 54%, and 34%, respectively, in patients with AZS; whereas the figures were 8%, 40%, and 52% in healthy controls, respectively. We found a significant difference between case and control groups in term of CC genotype frequency (P = 0.016). Conclusion: We found a significant correlation between miR- 196a2 rs11614913 polymorphism and AZS in Iranian Azeri men [ABSTRACT FROM AUTHOR]

Background: Cancer cells have a higher demand for iron to grow and proliferate. A new complex of iron nanoparticles and thiosemicarbazones was synthesized. Confirmation tests included UV-visible, scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), Fourier transform infrared (FTIR), X-ray diffraction (XRD) and zeta potential. Methods: MTT assay, flow cytometry and qRT-PCR were used to investigate anti-proliferative effect, amount of apoptosis and the effect of Fe3O4@Glu/BTSC on changes in gene expression of microRNA let-7c (let-7c), respectively. The specifications of Fe3O4@Glu/BTSC were confirmed at 5 nm. Results: Fe3O4@Glu/BTSC was more effective than BTSC and Fe3O4 on A549 cells (IC50 = 166.77 µg/mL) but its effect on healthy cells was smaller (CC50 = 189.15 µg/mL). The drug selectivity index (SI) was calculated to be 1.13. The initial apoptosis rate was 46.33% for Fe3O4@Glu/BTSC, 28.27% for BTSC and 26.02% for Fe3O4. BTSC and BTSC@Fe3O4 inhibited the cell cycle progression in the Sub-G1 and S phases. let-7c expression was 6.9 times higher in treated cells compared to the control group. The expression rate was 2.2 with BTSC compared to the control group and 1.6 times for Fe3O4. Conclusion: Fe3O4@Glu/BTSC has proper anti-proliferative effects against lung cancer cells by increasing the expression of let-7c and inhibiting the cell cycle with the apoptosis activation pathway. [ABSTRACT FROM AUTHOR]

This study was focused on identifying the effects of single nucleotide polymorphisms (SNPs) located on an entire region of the let-7c miRNA gene with consideration of its ability to promote litter size in Markhoz goats. The Markhoz goat, the native breed in Iran, is important for its reproductive traits, such as litter size. DNA polymorphism of let-7c miRNA gene was revealed and considered for further studies for its effect on litter size in Markhoz goats. PCR-SSCP analysis investigated different band patterns for this miRNA; however, sequencing results have detected only an A to T substitution located five nucleotides downstream of the let-7c miRNA gene. The chi-squared test showed that the let-7c miRNA gene locus was out of the Hardy–Weinberg equilibrium (HWE) and has significant effect (p < 0.05). Furthermore, the least-square analysis indicated that the let-7c miRNA gene does not affect prolificacy in the Markhoz goat (p > 0.05). In sum, all loci failed to have a significant effect on the litter size trait (p > 0.05). Moreover, years of kidding and parity had no significant impact on let-7c_S (p > 0.05); however, the let-7c_B affected the litter size trait significantly (p < 0.05). Additionally, binary logistic regression and chi-square analysis revealed that allele A of the detected SNP within 3′ UTR region of the let-7c gene had a non-significant effect on litter size in the studied goats (p > 0.05). [ABSTRACT FROM AUTHOR]

Background. If the pregnancy attempt fails, it may become a stressful event. Therefore, in many cases, problem solving can lead to greater satisfaction and cohesion of couples and prevent psychological and social harm to families. The aim of this study was to determine the significant difference in the expression of miR-146a miRNA in maternal blood between the control and observation groups and to determine whether the miRNA can be used as diagnostic biomarkers or not. Methods. The present study is a basic and descriptive survey in terms of data analysis. The samples included pregnant women referred to Tabriz University of Jahad from September 2019 to February 2021. We used Exel, Spss v.21 and Roc software for data analysis. Data were prepared in Exel software with reference gene and by calculating CT. Were used in Roc software. Results. The results showed a difference between the control and observation groups. Early detection of recurrent miscarriage should be used in these mothers. Conclusion. Through using diagnostic kits of the studied miRNAs, effective steps can be taken for early detection, prevention of abortion, and reducing the heavy psychological, economic, and social burden on families. Therefore, it is suggested that diagnostic kits be made for these biomarkers and used in infertility centers. Practical Implications. Among the practical implications of this study, we can mention the diagnosis and prevention of abortion, which can reduce the burden on families and society. [ABSTRACT FROM AUTHOR]

Background. Micro-ribonucleic acids (miRs) take part in post-transcriptional gene regulation. MiR-155 regulates hematopoiesis, oncogenesis, and immunologic and inflammatory processes. We investigated the expression levels of miR-155 in sera of patients with Burkitt’s lymphoma, diffuse large B-cell lymphoma (DLBCL), and rheumatoid arthritis. Methods. In this cross-sectional observation, we used real-time polymerase chain reaction to evaluate expression of miR-155 in sera of 92 Iranian adults who were healthy or had Burkitt’s lymphoma, DLBCL, or rheumatoid arthritis. The relative quantification of gene expression was calculated in terms of cycle threshold values (Ct). We conducted Pearson’s and Spearman’s correlations, Fisher's exact test, and one-way analysis of variance and Games-Howell post-hoc test, with the level of significance of 0.05. Results. The expression of miR-155 was independent of sex and age in each study group. In comparison with healthy subjects(-ΔCt: -2.29 ±SD: 1.92), miR-155 expression increased in DLBCL (2.49±1.01), and rheumatoid arthritis (2.30±1.34) patients, but did not change in adults with Burkitt’s lymphoma (-1.29±2.11). Conclusion. MiR-155 was significantly elevated in the sera of patients with DLBCL, and rheumatoid arthritis. Further studies with larger sample sizes are needed to assess the diagnostic, and therapeutic applications of miR-155 in these patients. Practical Implications. The expression of miR-155 increases in sera of patients suffering from DLBCL, and rheumatoid arthritis. The expression of miR-155 was independent of sex and age of patients in this study. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most common form of arthritis associated with gradual joint destruction. The current treatment aims to alleviate pain and inflammation and improve the quality of life. Crocin is an active ingredient in saffron, with anti-inflammatory properties. MicroRNAs are small, non-coding RNAs that regulate gene expression. We aimed to evaluate the effect of crocin on the gene expression of microRNA-146a, microRNA-155, microRNA-223, and microRNA-21 in OA patients and compare it with a placebo. This study was approved and registered in the Iranian Registry of Clinical Trials (2015021910507N2) and ClinicalTrials.gov identifier: NCT03375814. Forty OA patients were randomly divided into two equal groups, receiving either crocin or placebo. Peripheral blood samples were collected before and four months after the intervention. The pain was assessed using the visual analog scale, and laboratory tests included C-reactive protein and erythrocyte sedimentation rate. The expression levels of microRNA-146a, microRNA-155, microRNA-223, and microRNA-21 genes were evaluated by SYBR Green real-time PCR. The results showed that the gene expression levels of microRNA-21 and microRNA-155 in patients receiving crocin were significantly decreased and increased, respectively. No significant changes were observed in microRNA-146a and microRNA-223 gene expression levels. In conclusion, crocin's anti-inflammatory role might be partly attributed to its effects on the gene expression of microRNA-21 and microRNA-155. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common cancer in women. Micro RNAs have emerged as a biomarker for the diagnosis and treatment of breast cancer. Objectives: The purpose of the present study was to evaluate miR-191, miR-22, and epidermal growth factor receptor (EGFR) mRNA in peripheral blood and tissues of patients with breast cancer. Methods: A number of l00 peripheral blood samples (50 patient blood samples and 50 healthy blood samples) were collected. Also, 100 tissue samples were simultaneously collected from affected patients by a specialist including 50 samples from the center of the tumor and 50 samples from the side tissues of tumors. Immediately, RNA extraction and cDNA synthesis were performed and polymerase chain reaction (real-time polymerase chain reaction) was performed. Results: The data obtained from the present study showed that the blood and tissue levels of miR-191 and EGFR mRNA were significantly increased in breast cancer samples compared to the group of healthy samples and the blood and tissue levels of miR-22 were significantly decreased in breast cancer samples compared to the group of healthy samples. The miR-191 was increased in patients compared to normal individuals up to 2.3 (blood) and 2.16 (tissue) times, respectively. The miR-22 was decreased in patients compared to normal individuals up to 1.46 (blood) and 1.28 (tissue) times, respectively. Also, EGFR expression was increased in patients compared to normal individuals up to 70.2 (blood) and 24.2 (tissue) times, respectively. The present study can play role indetermin-ing the prognosis of breast cancer and in obtaining molecular diagnostic biomarkers in peripheral blood and tissues of patients with breast cancer. [ABSTRACT FROM AUTHOR]

This study evaluated the inhibitory effects of bilirubin on colony formation and cell migration of melanoma and non-melanoma skin cancer cell lines SK-MEL-3 and A431, compared with normal human dermal fibroblasts (HDF). The IC50 obtained from the MTT assay was 125, 100, and 75 μM bilirubin for HDF, A431, and SK-MEL-3 cells, respectively. The colony formation and cell migration of cancer cells, treated with 100 μM bilirubin, were reduced significantly (p < 0.05). Bilirubin decreased cell adhesion and inhibited cell colonization via inducing apoptosis and cell death. Also by interaction with migration main factors, bilirubin caused inhibition the cell migration. [ABSTRACT FROM AUTHOR]

Water ferns of the genus Azolla and the filamentous cyanobacteria Nostoc azollae constitute a model symbiosis that enabled the colonization of the water surface with traits highly desirable for the development of more sustainable crops: their floating mats capture CO2 and fix N2 at high rates using light energy. Their mode of sexual reproduction is heterosporous. The regulation of the transition from the vegetative phase to the spore forming phase in ferns is largely unknown, yet a prerequisite for Azolla domestication, and of particular interest as ferns represent the sister lineage of seed plants. Sporocarps induced with far red light could be crossed so as to verify species attribution of strains from the Netherlands but not of the strain from the Anzali lagoon in Iran; the latter strain was assigned to a novel species cluster from South America. Red-dominated light suppresses the formation of dissemination stages in both gametophyte- and sporophyte-dominated lineages of plants, the response likely is a convergent ecological strategy to open fields. FR-responsive transcripts included those from MIKCC homologues of CMADS1 and miR319-controlled GAMYB transcription factors in the fern, transporters in N. azollae , and ycf2 in chloroplasts. Loci of conserved microRNA (miRNA) in the fern lineage included miR172, yet FR only induced miR529 and miR535, and reduced miR319 and miR159. Phylogenomic analyses of MIKCC TFs suggested that the control of flowering and flower organ specification may have originated from the diploid to haploid phase transition in the homosporous common ancestor of ferns and seed plants. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the expression of four up/down-regulated inflammatory miRNAs and their mRNA targets in the serum samples of COVID-19 patients with different grades. Also, we investigated the relative expression of these miRNAs and mRNAs during hospitalization. Methods: In this cross-sectional study, 5 mL of blood sample were taken from COVID-19 patients with different grades and during hospitalization from several health centers of Yazd, Tehran, and Zahedan province of Iran from December 20, 2020 to March 2, 2021. The relative expression of miRNAs and mRNAs was evaluated by q-PCR. Results: We found that the relative expression of hsa-miR-31-3p, hsa-miR-29a-3p, and hsa-miR-126-3p was significantly decreased and the relative expression of their mRNA targets (ZMYM5, COL5A3, and CAMSAP1) was significantly increased with the increase of disease grade. Conversely, the relative expression of hsa-miR-17-3p was significantly increased and its mRNA target (DICER1) was significantly decreased with the increase of disease grade. This pattern was exactly seen during hospitalization of COVID-19 patients who did not respond to treatment. In COVID-19 patients who responded to treatment, the expression of selected miRNAs and their mRNA targets returned to the normal level. A negative significant correlation was seen between (1) the expression of hsa-miR-31-3p and ZMYM5, (2) hsa-miR-29a-3p and COL5A3, (3) hsa-miR-126-3p and CAMSAP1, and (4) hsa-miR-17-3p and DICER1 in COVID-19 patients with any grade (P < 0.05) and during hospitalization. Conclusions: In this study, we gained a more accurate understanding of the expression of up/down-regulated inflammatory miRNAs in the blood of COVID-19 patients. The obtained data may help us in the diagnosis and prognosis of COVID-19. Trial registration: The ethics committee of Zahedan University of Medical Sciences, Zahedan, Iran. (Ethical Code: IR.ZAUMS.REC.1399.316) was registered for this project. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that myeloid cell leukemia-1 (Mcl-1) is the target gene for microRNA -101 (miRNA-101), and decreased levels of miRNA-101 are associated with elevated levels of Mcl-1 and lung cancer survival. The objective of the present study was to investigate the effect of miRNA-101 on the sensitivity of A549 lung cancer cells to etoposide. Methods: The study was conducted during 2018 and 2019 at Arak University of Medical Sciences, Arak, Iran. The effect of miRNA- 101 on Mcl-1 expression was assessed using reverse transcriptionquantitative polymerase chain reaction 3-(4, 5-Dimethylthiazol- 2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and trypan blue exclusion assays were performed to determine the effect of treatments on cell survival and proliferation, respectively. The interaction between miRNA-101 and etoposide was evaluated using the combination index analysis of Chou-Talalay. Apoptosis was quantified using ELISA cell death assay. ANOVA and Bonferroni's tests were used to determine statistical differences between the groups (P<0.05). GraphPad Prism software (version 6.01) was used for data analysis. Results: The results showed that miRNA-101 clearly inhibited the expression of Mcl-1 and reduced the growth of A549 cells, relative to blank control and negative control miRNA (P<0.05). Transfection of miRNA-101 synergistically enhanced the sensitivity of the A549 cells to etoposide. Apoptosis assay data also showed that miRNA-101 triggered apoptosis and augmented the etoposide-mediated apoptosis. Conclusion: Up-regulation of miRNA-101 inhibited cell survival and proliferation, and sensitized A549 cells to etoposide by suppressing Mcl-1 expression. miRNA-101 replacement therapy can be considered as an effective therapeutic strategy in non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Mustard gas (sulfur mustard, SM), a highly vesicating chemical warfare agent, was first deployed in warfare in 1917 and recently during the Iraq–Iran war (1980s) and Syrian conflicts (2000s); however, the threat of exposure from stockpiles and old artillery shells still looms large. Whereas research has been long ongoing on SM‐induced toxicity, delineating the precise molecular pathways is still an ongoing area of investigation; thus, it is important to attempt novel approaches to decipher these mechanisms and develop a detailed network of pathways associated with SM‐induced toxicity. One such avenue is exploring the role of microRNAs (miRNAs) in SM‐induced toxicity. Recent research on the regulatory role of miRNAs provides important results to fill in the gaps in SM toxicity–associated mechanisms. In addition, differentially expressed miRNAs can also be used as diagnostic markers to determine the extent of toxicity in exposed individuals. Thus, in our review, we have summarized the studies conducted so far in cellular and animal models, including human subjects, on the expression profiles and roles of miRNAs in SM‐ and/or SM analog–induced toxicity. Further detailed research in this area will guide us in devising preventive strategies, diagnostic tools, and therapeutic interventions against SM‐induced toxicity. [ABSTRACT FROM AUTHOR]

Background: In recent years, the role of micro-RNAs in the cancer pathophysiology has attracted a great deal of scientific attention. MiRNAs regulate a variety of cellular functions, such as apoptosis, differentiation and migration by targeting oncogenic or tumor suppressor genes. We conducted the current study to assess the expression of miR-107, Krüppel-like factor 4 (KLF4) and death-associated protein kinase (DAPK1) genes in malignant and normal colon tissues and also colorectal cancer (CRC) model cells exposed to oxaliplatin and 5-FU chemotherapy agents. Method: In this case-control study, the tissue samples from CRC patients were collected during colonoscopy process in 2013-2016 at Imam Reza hospital. Subsequently, the expression levels of miR-107, KLF4, and DAPK1 were detected with quantitative Real-Time PCR. Furthermore, in the in vitro phase of this study, we investigated the changes in the expression level of miR-107, KLF4 and DAPK1 transcripts after oxaliplatin and 5-FU treatment. Results: Unlike miR-107, the expression levels of KLF4 and DAPK1 genes decreased in the tumor samples compared to those in the marginal specimens. In addition, both oxaliplatin and 5-FU significantly increased the expression level of miR-107. There were significant correlations between the expression levels of miR-107, KLF4, and DAPK1genes and clinicopathological features, for instance lymph node metastasis and cell differentiation. Conclusion: The current study suggested a tumor suppressor role for KLF4 and DAPK1 in CRC. The altered expression of miR-107, KLF-4, and DAPK1 genes in CRC tumors and healthy tissues could be utilized for CRC diagnosis and prognosis. Furthermore, the studied genes could be considered as potential therapeutic targets in CRC. [ABSTRACT FROM AUTHOR]

Objective: Thirteen million cancer deaths and 21.7 million new cancer cases are expected in the world by 2030. Breast cancer is considered as the main cause of cancer mortality in women aged 20-59 years. microRNAs (miRNAs) regulate gene expression at the post-transcriptional level and they are highly expressed in malignancies,including breast cancer. The role of miRNAs in the pathogenesis of breast cancer is not fully understood. In the present study,for the first time,the impact of hsa-miR-423 rs6505162 on breast cancer risk was investigated in the central province of Iran,Isfahan. Materials and Methods: This case-control study was conducted on 153 clinicopathological proven breast cancer patients and 153 sex-matched healthy women with no history of any cancer type and relative patients. The patients and controls were genotyped and association of their clinical characteristics with hsa-miR-423 rs6505162 genotype was analyzed. Results: The findings indicated that CC genotype of hsa-miR-423 rs6505162 was associated with the increased risk of breast cancer [odds ratio (OR)=2.37,95% confidence interval (CI)=1.29-4.35 and P=0.0023,CC vs. AA]. Conclusion: The data suggested that hsa-miR-423 rs6505162 could be considered as a novel risk factor in breast cancer pathogenesis in Isfahan province of Iran. [ABSTRACT FROM AUTHOR]

Background: The optimal dose of anticoagulant warfarin varies among patients to achieve the target international normalised ratio. Although genetic variations related to warfarin pharmacokinetics and vitamin K cycle are important factors associated with warfarin dose requirements, these variations do not completely explain the large interindividual variability observed in the most populations, suggesting that additional factors may contribute to this variability. microRNAs have recently been introduced as regulators of drug function genes, and therefore, may be involved in drug responses. In this study, we aimed to evaluate the possible association between variants in the seed region of microRNAs, which target the genes involved in the action of warfarin and warfarin dose requirement.Methods: 526 samples were collected from Iranian patients. Four selected polymorphisms in the seed region of microRNAs (rs2910164, rs66683138, rs12416605 and rs35770269 in miR-146a, miR-3622a, miR-938 and miR-449c, respectively) were genotyped by PCR-restriction fragment length polymorphism method.Results: rs2910164 C/G in the seed region of miR-146a was associated with warfarin dose requirement (p<0.001); the patients with GG genotype had the higher mean dose of warfarin (40.6 mg/week, compared with 33.9 and 31.8 mg/week for GC and CC genotypes, respectively). The association of other polymorphisms with warfarin dose requirement was not statistically significant.Conclusion: rs2910164 C/G in the seed region of miR-146a is associated with warfarin maintenance dose, likely by disrupting interaction between miR-146a and ATP-binding cassette subfamily B member 1 gene, ABCB1. Therefore, this polymorphism may possibly be a potential factor for assessment of warfarin dose requirements. [ABSTRACT FROM AUTHOR]

Objectives: Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of apparently mature B-type lymphocytes in the lymphohematopoietic organs. Methylation in promoters of tumor suppressor genes is one of the mechanisms that causes blood malignancy. In this study, we evaluated the promoter DNA methylation status of miR-129-2 tumor suppressor gene and its association with clinical and laboratory parameters of patients with CLL. Methods: We studied the promoter DNA methylation frequency of the miR-129-2 gene in 50 patients with CLL and 50 healthy controls using methylation-specific polymerase chain reaction methods. Statistical analysis was performed using SPSS-18 software, and a p-value < 0.050 was considered statistically significant. Results: The frequency ofpromoter DNA methylation ofthe miR-129-2 gene was significantly higher in the CLL group compared with control group (38.0% vs. 0.0%, p < 0.001; χ² = 23.457). The promoter DNA methylation frequency of miR-129-2 gene was not significantly different between the two sexes (p = 0.236). A significant but weak correlation was seen between the methylated state of the miR-129-2 gene and organomegaly (p = 0.019, r = 0.330) as well as hemoglobin levels (p = 0.020, r = -0.233). However, binary logistic regression analysis indicated organomegaly as the only clinical biomarker with a statistically significant association with the hypermethylated miR-129-2 gene state (p = 0.046). Conclusions: The high frequency of promoter DNA methylation of the miR-129-2 gene in the CLL group compared to the control group, as well as its significant association with organomegaly, suggests the importance of this epigenetic biomarker in the pathogenesis and prognosis of CLL disease. [ABSTRACT FROM AUTHOR]

Background: Cutaneous Leishmaniasis (CL) is an emerging uncontrollable and neglected infectious disease worldwide including Iran. The aim of this study was to investigate the expression profile of apoptosis-related miRNA and its target gene in macrophages. Methods: This study was carried out in the Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran from January 2016 to November 2018.Applying literature reviews, bioinformatics software, and microarray expression analysis, we selected miRNA-24-3p interfering in apoptosis pathway. The expression profile of this miRNA and target gene were investigated in Leishmania major (MRHO/IR/75/ER)-infected primary and RAW 264.7 macrophages (IBRC-C10072) compared with non-infected macrophages (control group) using quantitative Real-time PCR. Results: Results of bioinformatics analysis showed that miR-24-3p as anti-apoptotic miRNA inhibits pro-apoptotic genes (Caspases 3 and 7). Microarray expression data presented in Gene Expression Omnibus (GEO) revealed a significant difference in the expression level of selected miRNA and its target gene between two groups. QRT-PCR results showed that the expression of miR-24-3p was upregulated in L. major infectioned macrophages that approved the results of bioinformatics and microarray analysis. Conclusion: Parasite can alter miRNAs expression pattern in the host cells to establish infection and its survival. Alteration in miRNAs levels likely plays an important role in regulating macrophage functions following L. major infection. These results could highlight current understanding and new insights concerning the gene expression in macrophages during leishmaniasis and will help to development of novel strategies for control and treatment of CL. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (SCC) is the most common oral malignancy. Some evidence indicated that there is a correlation between microRNA single nucleotide polymorphisms and the risk of oral cancer. The aim of the current study was to investigate the association between mir-499 polymorphism with the risk of oral cavity and oropharyngeal SCC in a subset of Iranian Population. Materials and Methods: In this case–control pilot study total of 112 participants including 56 histopathlogically confirmed oral and oropharyngeal SCC patients and 56 age- and sex-matched controls were included The mir-499 rs3746444 T/C polymorphism was detected using polymerase chain reaction-restriction fragment length polymorphism method. The comparisons of the distribution of the allele and genotype frequencies were performed using Chi-square test, and P < 0.05 was considered as statistically significant. Results: The result of the present study indicated that the frequency distribution of mir-499 was not significantly different between cases and controls (P > 0.05). We also did not find any significant association between the risk of the cancer and mir-499 polymorphisms in the recessive (Odds ratio [OR]: 6.60; 95% confidence interval [CI]: 0.77–56.74; P = 0.11) and dominant (OR: 1; 95% CI: 0.37–2.74; P = 1) inheritance models even after adjustment for smoking. Conclusion: The results of the present study indicated that the polymorphisms of mir-499 are not associated with the risk of oral and oropharyngeal SCC in Iranian population. However, further large scale studies are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Background: miRNA is one of those biomarkers that have different types. Hsa-miR-15 is one of the molecules, which expressed in the heart tissue. MiRNAs are small non-coding RNA that regulates complex cardiac signaling and transcription pathways in cardiac during different condition. The aim of this study was to compare hsa-miR-15 gene expression changes in myocardial infarction patients with healthy individuals. Methods: In this case-control study, which was included 88 patients with myocardial infarction and 19 healthy individuals who had been referred to the Shahid Madani hospital of Tabriz. After total RNA extraction and cDNA synthesis, the hsa-miR-15 gene expression changes were assessed using Real-time PCR method. For data analysis, we have used independent t-test. Results: The hsa-miR-15 gene expression changes increased in the patients with myocardial infarction compared to healthy individuals. The level of hsa-miR-15 gene expression was shown a statistically significant difference between groups (p >0/05). Conclusion: The hsa-miR-15gene expression increased in the patient with myocardial infarction and may be used as a biomarker in early diagnosis of myocardial infarction. [ABSTRACT FROM AUTHOR]

Background: Usually, chemoradiotherapy can be used for the treatment of locally advanced colorectal cancer (CRC) before surgery. On the other hand, some studies have shown that fractional radiation of tumor cells leads to chemoresistance. The aim of this study was to evaluate the chemoresistance of radioresistant sub-line (RR sub-line). Methods: This study was done in Hamadan University of Medical Sciences in 2017-2018. MTT assay and sub-G1 fraction analysis by flow cytometry were used to evaluate crossresistance of RR sub-line to gefitinib and regorafenib. Real-time PCR was used to investigate the role of four miRNAs and their target genes in the cross-resistance of RR sub-line. The t test and repeated measures test were used for the assessment of statistical significance between groups. Results: The IC50 of gefitinib and regorafenib for RR sub-line were significantly higher than those of the parental cell line. On the other hand, the resistance index of RR sub-line for gefitinib and regorafenib were 1.92 and 1.44, respectively. The sub-G1 fraction of RR sub-line following treatment with gefitinib and regorafenib was significantly lower than that of the parental cell line (P=0.012 and P=0.038, respectively). The expression of miR-9, Let-7e, and Let-7b in RRsub-line was significantly lower than that of the parental cell line. However, NRAS, IGF1R, NFKB1, and CCND1 found to be upregulated in RR sub-line in comparison with the parental cell line. Conclusion: We can conclude that the acquired RR sub-line was cross-resistance to gefitinib and regorafenib. Furthermore, miR-9/NFKB1, let-7b/CCND1, let-7e/NRAS, and IGF1R played essential roles in the chemoradioresistance of CRC. [ABSTRACT FROM AUTHOR]

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

Background: MicroRNAs (miRNAs) are a group of small non-coding RNAs that bind to the target mRNA and regulate gene expression. Recently circulating microRNAs were investigated as markers of diseases and therapeutic targets. Although various studies analyze the miRNA expression in liver disease, these studies on PFIC are few. Progressive familial intrahepatic cholestasis (PFIC) is a rare liver disease with autosomal recessive inheritance. Most children with PFIC progress to cirrhosis and liver failure and consequently need to have a liver transplant. The aim of this study is the investigation of the miR-19b and miR-let7b expression levels in Iranian PFIC children., Methods: 25 PFIC patients, 25 healthy children and 25 Biliary Atresia patients were considered as case and two control groups respectively. Blood samples were obtained and Liver function tests (LFTs) were measured. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for miR-19b and miR-let7b. The U6 gene is used as an internal control., Results: qPCR on PFIC patients' samples demonstrated that the miR-19b and the miR-let7b expression were significantly decreased in patients compared to the control groups, with a p-value<0.0001 and p-value=0.0006 receptively., Conclusion: In conclusion, circulating micro-RNA like miR-19b and miR-let7b have a potential opportunity to be a non-invasive diagnostic marker or therapeutic target for PFIC in the future., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

MicroRNAs (miRNAs) regulate genes expression by directly binding to the 3′ untranslated region (3′UTR) of specific target mRNAs. Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) are proposed to be important in the development of breast cancer (BC). In the present study, we conducted a case-control study with 266 BCE patients and 288 control women to examine the possible association of miRNAs polymorphisms (miR-100 rs1834306, miR-124-1 rs531564, miR-218-2 rs11134527, miR-301b rs384262, miR-605 rs2043556, and miR-4293 rs12220909) with BC susceptibility. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The findings showed miR-218-2 rs11134527 variant increased the risk of BC (OR = 7.70, 95%CI = 3.84–15.43, P < .0001, GA vs GG and OR = 6.86, 95%CI = 3.47–13.57, P < .0001, A vs G). Regarding miR-301b rs384262 polymorphism, we observed that this variant significantly increased the risk of BC (OR = 3.12, 95%CI = 2.20–4.45, P < .0001, AG vs AA and OR = 2.22, 95%CI = 1.68–2.93, P < .0001, G vs A). Our findings did not support an association between miR-100 rs1834306, miR-124-1 rs531564, miR-605 rs2043556 and miR-4293 rs12220909 polymorphism and the risk of BC. In conclusion, the finding showed that miR-218-2 rs11134527 and miR-301b rs384262 variant might contribute to increase the risk of BC in a sample of Iranian population. Additional studies with larger sample sizes and different ethnicities are necessary to confirm our finding. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to find the relationship between rs1799964 in TNF-α gene as well as rs1051208 of RAF1 gene SNPs on GC in an Iranian population. Background: Gastric cancer (GC) is the second leading cause of cancer-related death worldwide after lung cancer. Tumor necrosis factor (TNF) is one of the most important factors in the pathogenesis of this cancer. Single nucleotide polymorphisms have a principle role in gene expression of TNF-α and miRNAs which may lead to gastric cancer. Methods: In a case-control study, we investigated the risk of GC in 198 Iranians. For this purpose, 5 mL of peripheral blood was collected in EDTA -containing tube and genomic DNA was isolated. Genotyping of SNPs was also performed by PCR-RFLP; to approve the outcome, 10% of genotyping results with RFLP were sequenced. Results: The comparison between case and control groups revealed a significant association between the rs1051208 C allele of RAF1 gene and GC (P = 0.04). We did not observe any remarkable association between TNF-α -1031 in gastric cancer patients and the healthy control group. Conclusion: The results indicated that C allele in RAF1 gene plays a role in susceptibility to gastric cancer. Therefore, SNPs are among notable biomarkers for predicting susceptibility to dreadful diseases, especially cancers. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the third major cause of cancer death worldwide. Hepatitis B virus (HBV) and HBx gene play an important role in the development of HCC by influencing signaling pathways. Since there is no detectable symptom in the early phase of HCC, there is need to find new HCC-specific markers with high sensitivity for early detection and diagnosis of HCC. On the other hand, by the advent and development of bioinformatic sciences, it is now possible to predict miRNAs as biomarkers, and their targets. Therefore, in the present study, based on the results of the bioinformatic software applications with different algorithm, we selected the miRNA targeting HBx and NOTCH1 mRNAs according to higher score, suitable connection with target gene and confirming them in more softwares. Materials and Methods: First, the sequences of NOTCH1 and HBx genes were retrieved from NCBI. Afterwards, several software applications such as TargetScan, mirWalk, miRBase, Miranda, PicTar, miRVir, and DIANA were applied to predict miRNAs. Results: Based on the high scoring by bioinformatics softwares and suitable targeting, miR-34a were selected to target NOTCH1 and miR-6510, miR-5193 and miR-214 were chosen to targetHBX gene. Conclusion: Because of tumor suppression roles of miR-214 and miR-34a, they probably could be used as therapeutic strategy in cancer researches. It is also seems that the miR-5193 could act as a specific marker in Hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Context: A number of single nucleotide polymorphisms (SNPs) in ERBB4 gene have been linked to increase the risk of breast cancer. However, no study has been dedicated to analyze the significance of microRNA-related SNP rs1972820, located in ERBB4 3'-untranslated region (UTR), in breast tumors.Aims: Here, we investigated the frequency and association between rs1972820 and breast cancer.Subjects and Methods: The rs1972820 genotypes in 182 samples were collected from 96 healthy people, and 86 breast cancer patients were determined using tetra-primer amplification refractory mutation system-polymerase chain reaction. The frequency of genotypes was analyzed to find the association between rs1972820 and breast cancer risk.Statistical Analysis Used: Conditional logistic regression, odds ratios (ORs), the associated 95% confidence intervals (CIs), and Armitage's test were used in this study.Results: In silico analysis suggested that rs1972820 located in the 3'UTR of ERBB4 gene affects the binding affinity of miR-3144-3p a potential oncomiRNA. Statistical analysis showed a significant association between SNP rs1972820 G allele and reduced breast cancer risk, odds ratio = 0.443 (95% CI: 0.196-0.998).Conclusions: rs1972820 SNP allele is significantly associated with the reduced risk of breast cancer and could be considered as a potential marker for breast cancer predisposition in population of Isfahan. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) associated gastric carcinoma (EBVaGC) is a subtype of gastric cancer with distinct histological and molecular features. The study aimed to assess the EBV DNA copy number and the prevalence of EBVaGC in gastric cancer samples taken from Iranian patients. The next aim was to assess whether the DNA and microRNAs EBV are present in plasma. EBV load was analyzed in 68 gastric cancer biopsies and compared with the results of EBV-encoded small RNA in situ hybridization (EBER-ISH) test in these patients. After the detection of 6 EBV miRNAs in gastric tissue by stem-loop RT-PCR, plasma samples were evaluated for the viral load and EBV miRNAs. Four gastric cancer cases were EBER -ISH positive (5.8%), with a significantly higher viral load than the remaining cases, 47,781 vs. 1909 copies/μg of tissue DNA. Here, was also found a significant difference in plasma EBV load between EBER-positive and EBER-negative cases. Although EBV miRNAs were detectable in all the EBER-positive tumors, the test did not detect any of these miRNAs among the plasma samples tested. Our data indicate that the prevalence of EBVaGC among Iranian patients with gastric cancer is lower than the global prevalence and although none of the EBV miRNAs were detected in plasma, evaluation of EBV microRNAs in tumor tissue, especially miR-BART7-3p, may constitute useful biomarkers for diagnosis of EBVaGC., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Type 2 diabetes is the most prevalent metabolic disease worldwide. The disease is characterised by high blood glucose levels and recently it has been shown that changes in the plasma levels of several miRNAs (miRNA) are associated with the disease. Interestingly, alterations in circulating miRNAs occur years before the onset of the disease and demonstrate predictive power. In this study, we carried out RT-qPCR to examine the plasma levels of two type 2 diabetes specific miRNAs, miR-30d-5p and miR-126-3p in an Iranian population of non-diabetic control individuals, subjects with intermediate hyperglycaemia and type 2 diabetic individuals with hyperglycaemia. We found that the plasma levels of miR-30d and miR-126 increase by 3.1 and 11.16 times, respectively, in individuals with intermediate hyperglycaemia compared to non-diabetic controls. However, no significant changes in the expression of these two miRNAs have been observed between type 2 diabetic individuals and non-diabetic subjects. Our results confirm that alterations in the plasma levels of miR-30d-5p and miR-126-3p could be used as diagnostic markers of type 2 diabetes in the Iranian population as well.

Beet curly top Iran virus(BCTIV) is a new member of geminiviruses causing leaf curl disease in a wide range of crops. These DNA viruses can both induce and be themselves targeted by gene silencing machinery. In animals, miRNAs were found to limit viral establishment by direct interference with viral replication or by targeting viral transcripts. However, such mechanisms have not been yet reported for plant viruses. In this work, we investigated the possible binding of tomato encoded miRNA/miRNA* sequences to the viral genome and/or transcripts of BCTIV.In silicoanalysis showed that several miRNA/miRNA* species including mir319, mir1919 and mir159 can potentially target both the genome and transcribed ORFs of the BCTIV. In addition, the identified miRNAs* also were predicted to bind host genes from various metabolic pathways. This may suggest a novel role for plant miRNA/miRNA* in host-virus interactions and defence response. [ABSTRACT FROM PUBLISHER]

Beet curly top Iran virus (BCTIV) is a member of genus Becurtovirus, family Geminiviridae, which constrains host crop production in various geographical regions in Iran. This virus causes significant crop loss in sugar beet and has been also reported from other hosts including tomato. Various plant factors such as resistance genes and microRNA pathways were found to be involved in plant-geminivirus interaction. Ty resistant hybrids were found to confer resistance to both monopartite and bipartite begomoviruses through increasing cytosine methylation of the viral genome. In this study we investigated the response of various tomato cultivars and Ty resistant hybrids to BCTIV infection. In addition, the effect of the virus on the regulation of microRNA target genes in plant development was investigated. Based on the evaluated disease severity index and coefficient of infection, Ty resistant hybrids were grouped as moderately susceptible plants and produced leaf curling symptoms after BCTIV infection. However, no clear symptom was observed in the cultivar Super Chief. In addition, a significantly lower level of virus accumulation was observed in Super Chief plants compared to the susceptible cultivar, Grosse Lisse. Expression analysis of miRNA target genes in infected plants showed that AGO1 was induced in both cultivars. However, MYB33 and AP2 were differentially regulated in the susceptible and moderately resistant cultivars. The importance of regulation of these miRNA target genes in viral symptom development is discussed. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRs) are involved in the autoimmune and neurological diseases, including multiple sclerosis (MS), through modulating post-transcriptional gene regulation. Accumulating evidence indicates that miR-10, miR-24a, miR-124, and miR-21 play an imperative role in MS pathogenesis. Therefore, the current research aimed to analyze the expression of the selected miRNAs for MS in Iranian population., Methods and Results: Blood sample of 75 relapsing-remitting MS (RRMS) patients and 75 healthy individuals suffering no neurodegenerative illness was collected. Subsequently, the isolation of peripheral blood mononuclear cells (PBMCs) was performed by employing Ficoll-Hypaque density gradient method. Afterward, total RNA was extracted and subjected to qRT-PCR analysis. The obtained results evidenced that the relative expression of miR-10 (P = 0.0002), miR-21 (P = 0.0014), and miR-124 (P = 0.0091) significantly decreased in RRMS patients compared to healthy participants. On the contrary, no notable change was observed between the studies groups regarding miR-24a expression levels (P = 0.107). ROC curve analysis estimated an area under the curve (AUC) value equal to 0.75 with P = 0.0006 for miR-10, while it was decreased for miR-21 (AUC = 0.67 and P = 0.0054) and miR-124 (AUC = 0.66 and P = 0.012)., Conclusion: The change in miR-10, miR-124, and miR-21 expression patterns was implied to participate in MS development. Further large scale observational studies are recommended., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: MicroRNAs are a class of small noncoding ribonucleic acids that perform a critical role in adjustment of gene expression. miRNAs-155 (miR-155) participates in controlling inflammation. Periodontitis is defined as inflammatory disorder of tissues surrounding the teeth. In this study, the expression levels of miR-155 and its target genes, tumor necrotizing factor alpha (TNF-α), and interleukin-6 (IL-6) were evaluated in a group of Iranian patients. Materials and Methods: This sectional study was performed on 10 healthy controls and 10 individuals with chronic periodontitis by means of polymerase chain reaction (PCR) test. For each individual, clinical parameters including probing depth and clinical attachment loss and blood samples were measured. Levels of miR-155, TNF-α, and IL-6 were quantified using real-time PCR (α=0/05) and the results were analyzed by Mann–Whitney U test. Results: The level of miR-155 was significantly higher in patients with chronic periodontitis (P < 0.001). A positive correlation was observed between the level of miR-155 and clinical parameters (P < 0.05). Level of miR-155 in tissue samples was correlated with blood samples although the expression level was higher in blood samples. Conclusion: As the expression level of miR-155, TNF-α, and IL-6 genes was higher in subjects with chronic periodontitis than healthy individuals, it might suggest a role for miR-155 in patients with chronic periodontitis. [ABSTRACT FROM AUTHOR]

Background: Autophagy induction has been shown to differ in magnitude depending on the mycobacterial species. However, few studies have investigated the specific autophagic capacity of different Mycobacterium tuberculosis (Mtb) strains in alveolar epithelial cells (ATs). This study aimed to elucidate the host autophagic response to different Mtb strains in ATs responsible for TB in the capital of Iran, Tehran., Methods: A549 cells were infected with three different Mtb clinical isolates (Beijing, NEW1, and CAS1/Delhi) and the reference strain H37Rv. Following RNA extraction, the expression of eight ATG genes, four mycobacterial genes, and three miRNAs was evaluated using quantitative RT-PCR., Results: The results revealed that all four strains influenced the autophagy pathway in various ways at different magnitudes. The Beijing and H37Rv strains could inhibit autophagosome formation, whereas the CAS and NEW1 strains induced autophagosome formation. The expression of genes involved in the fusion of autophagosomes to lysosomes (LAMP1) indicated that all the studied strains impaired the autophagolysosomal fusion; this result is not unexpected as Mtb can block the autophagolysomal fusion. In addition, the Beijing and H37RV strains prevented the formation of autophagic vacuoles, besides mycobacterial targeting of lysosomes and protease activity., Conclusion: This preliminary study improved our understanding of how Mtb manages to overcome the host immune system, such as autophagy, and evaluated the genes used by specific strains during this process. Further studies with a large number of Mtb strains, encompassing the other main Mtb lineages, are inevitable.