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Workers in the iron casting industries are exposed to various chemicals, especially graphite in furnace process. This study aims to investigate the toxic effects of graphite particles on human lung cells. Particle characteristics were confirmed by electron microscope and light scattering. Cell viability and oxidative stress markers were measured. The expression of oxidative repair genes, namely OGG1, MTH1, and ITPA, was evaluated. The average particle size was determined to be 172.1 ± 11.96 nm. The median inhibition concentration (IC50) of graphite particles was 46.75 µg/mL. Notably, 25 and 50 µg/mL concentrations resulted in significant GSH depletion and MDA production. The high concentration of graphite particles (200 µg/mL) led to OGG1 suppression and increased MTH1 expression. Based on these findings, graphite exposure may induce toxicity in human lung cells by increasing oxidative stress. Further research is necessary to fully understand the mechanisms underlying graphite toxicity. [ABSTRACT FROM AUTHOR]

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Background: Ovarian granulosa cells (GCs) are essential for follicular development. Ovarian advanced glycation endproducts (AGEs) accumulation is related to GCs dysfunction. Alpha-lipoic acid (ALA) illustrates therapeutic capabilities for infertility-related disorders. Therefore, this study assessed the effects of ALA on AGEs-induced GCs hormonal dysfunction. Methods: The study was conducted from October 2021 to September 2022 at the Department of Medical Genetics, Shiraz University of Medical Sciences. Isolated GCs (n=50) were divided into control, human glycated albumin (HGA), HGA+ALA, and ALA treatments. Steroidogenic enzymes and AGE receptor (RAGE) genes were assessed by qRT-PCR. Steroid hormones and RAGE protein were evaluated using ELISA and Western blotting. Data were analyzed using GraphPad Prism software (ver. 9), and P<0.05 was considered significant. Results: Our findings showed that HGA treatment significantly (P=0.0001) increased RAGE (by 140.66%), STAR (by 117.65%), 3β-HSD (by 165.68%), and 17β-HSD (by 122.15%) expression, while it decreased CYP19A1 (by 68.37%) expression. RAGE protein level (by 267.10%) was also increased in HGA-treated GCs. A significant decrease in estradiol (by 59.66%) and a slight and sharp elevation in progesterone (by 30.40%) and total testosterone (by 158.24%) levels was also observed. ALA treatment ameliorated the HGA-induced changes in steroidogenic enzyme mRNA levels (P=0.001) and steroid hormone secretion (P=0.010). Conclusion: This work shows that ALA therapy likely corrects hormonal dysfunctions caused by AGEs in luteinized GCs. This effect is probably achieved by decreased RAGE expression. Clinical research is needed to understand how AGEs and ALA interact in the ovary, which might lead to a more targeted ovarian dysfunction therapy. [ABSTRACT FROM AUTHOR]

Background: Odontogenic cysts and tumors develop from the dental follicle of asymptomatic impacted teeth. Odontogenic tissues express the epidermal growth factor receptor family (EGFR), which mediates cell proliferation, survival, and neoplastic differentiation. The present study aimed to compare the immunohistochemical expression of EGFR and human epidermal growth factor receptor 2 (HER2) in the dental follicle of impacted wisdom teeth with normal and abnormal radiographic size. Methods: In this analytical study, immunohistochemical staining of EGFR and HER2 was performed on 30 normal and 30 abnormal follicles of impacted third molars. Follicles with a width of <2.5 mm were considered normal, whereas those with a width of ≥2.5 mm were regarded as abnormal. The immunoreactive score (IRS) was used to report the expression levels of EGFR and HER2. The obtained data were analyzed using SPSS software. Age and sex were compared in normal and abnormal groups with independent t test and Chi square test, respectively. P<0.05 was considered statistically significant. Results: The EGFR and HER2 overall expression was high in all normal and abnormal follicles. The comparison of the percentage of stained cells and intensity of EGFR and HER2 staining in normal and abnormal follicles were not significantly different (P=0.73, P=0.63, P=0.95, respectively). Conclusion: Due to the high expression of EGFR and HER2 in normal and abnormal follicles, as well as the lack of significant differences in these two groups, the radiographic size of dental follicles might not indicate the potential capabilities of their cells, and more research in this field is recommended. [ABSTRACT FROM AUTHOR]

Drought stress is one of the major limiting factors for the production of tomato in Iran. In this study, the efficiency of selenate and Se nanoparticle (SeNP) foliar application on tomato plants was assessed to vestigate mitigating the risk associated with water-deficit conditions. Tomato plants were treated with SeNPs at the concentrations of 0 and 4 mg L−1; after the third sprays, the plants were exposed to water-deficit conditions. The foliar spraying with SeNPs not only improved growth, yield, and developmental switch to the flowering phase but also noticeably mitigated the detrimental risk associated with the water-deficit conditions. Gene expression experiments showed a slight increase in expression of microRNA-172 (miR-172) in the SeNP-treated plants in normal irrigation, whereas miR-172 displayed a downregulation trend in response to drought stress. The bZIP transcription factor and CRTISO genes were upregulated following the SeNP and drought treatments. Drought stress significantly increased the H2O2 accumulation that is mitigated with SeNPs. The foliar spraying with Se or SeNPs shared a similar trend to alleviate the negative effect of drought stress on the membrane integrity. The applied supplements also conferred drought tolerance through noticeable improvements in the non-enzymatic (ascorbate and glutathione) and enzymatic (catalase and peroxidase) antioxidants. The SeNP-mediated improvement in drought stress tolerance correlated significantly with increases in the activity of phenylalanine ammonia-lyase, proline, non-protein thiols, and flavonoid concentrations. SeNPs also improved the fruit quality regarding K, Mg, Fe, and Se concentrations. It was concluded that foliar spraying with SeNPs could mitigate the detrimental risk associated with the water-deficit conditions. [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]

Introduction: Coronary artery bypass surgery (CABG) is a common procedure for patients with coronary artery disease. This study aimed to investigate the effect of selected physical exercises on the expression of FGF-2 and VEGF-A in patients post-CABG. Material & Methods: In this semi-experimental study, 20 male patients from Afshar Hospital (Yazd City) who had undergone CABG were selected and randomly divided into two groups: a combined training group and a control group. The combined training group performed an 8-week program consisting of endurance training (15-20 minutes at 50-60% of HRmax) and resistance training (10-20 minutes, including three upper limb and two lower limb movements, each with three sets of 10 repetitions at 3060% of 1RM), conducted three times per week. Gene expression of Fibroblast Growth Factor 2 (FGF-2) and Vascular Endothelial Growth Factor A (VEGF-A) was measured using Real-Time PCR. Data were analyzed using paired t-tests and one-way ANOVA with a significance level set at P<0.05. Results: An increase in the expression of VEGF and FGF-2 genes was observed in the combined training group post-test compared to pre-test (p=0.019). Additionally, there was a significant difference in VEGF gene expression between the control and training groups (p=0.016). Significant differences were also found in FGF-2 expression between the combined exercise group and both the healthy control and patient control groups (p=0.001 for both). Conclusion: The results suggest that combined exercises may enhance physiological adaptations and improve the functional capacity of the heart and vessels in CABG patients by increasing growth factor expression. [ABSTRACT FROM AUTHOR]

Background. Helicobacter pylori are the principal causative factor in the etiological factors of chronic, active, or type B gastritis; peptic and duodenal ulcers; stomach carcinoma; and epithelial tissue lymphoid malignancies. It infects more than half of the population worldwide. To reduce H. pylori production, pharmacological therapy of H. pylori diseases typically involves using threefold treatment methods. However, as a result of such therapy, antimicrobial resistance is commonly developed. Alternative therapeutics for H. pylori diseases are thus of particular interest. Methods. Thyme essential oils (EOs) obtained from T. caramanicus Jalas plants in Iran were tested for antibacterial activity against H. pylori obtained from 320 poultry specimens in this investigation. Antibacterial activity was measured using inhibition zones, minimum inhibitory concentrations (MICs), and minimum bactericidal concentrations (MBCs). The impact of T. caramanicus Jalas essential oils on H. pylori isolate cagA, vacA, and babA2 gene expression was evaluated using a quantitative real‐time PCR method (p < 0.05). Results. The chemical content of these EOs varied significantly according to chromatographic examination. Thymol, carvacrol, and terpinene‐4‐ol are the most abundant components in these EOs. H. pylori was recognized as a Helicobacter species with a 175‐bp PCR product of 16S rRNA in 20/20 (100%). According to PCR results, all 20 (100%) isolates belonged to H. pylori. The EOs inhibited H. pylori in a dose‐dependent manner, with T. caramanicus Jalas being the most effective, followed by pterygium EOs in decreasing order. At 8 mg/mL of T. caramanicus Jalas EOs, IZs against H. pylori were 27.4 ± 0.42 mm, and at 8 mg/mL of pterygium, IZs against H. pylori were 1 ± 0.02. T. caramanicus Jalas essential oils were used to treat all bacteria, and the findings showed that T. caramanicus Jalas had a substantial inhibitory impact on the expression of cagA, vacA, and babA2 virulence‐related genes (p < 0.05). Conclusions. In a dose‐dependent manner, the EOs of T. caramanicus Jalas EO demonstrated a high degree of antimicrobial property against H. pylori bacteria. The most efficient EOs were those from T. caramanicus Jalas with relative concentrations of thymol and carvacrol, followed by the coumarin‐dominated pterygium EO with reduced antibacterial activity. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is the second most common type of leukemia in children. Although prognostic and diagnostic tests of AML patients have improved, there is still a great demand for new reliable clinical biomarkers for AML. Read-through fusion transcripts (RTFTs) are complex transcripts of adjacent genes whose molecular mechanisms are poorly understood. This is the first report of the presence of the PPP1R1B::STARD3 fusion transcript in an AML patient. Here, we investigated the presence of PPP1R1B::STARD3 RTFT in a case of AML using paired-end RNA sequencing (RNA-seq). Case presentation: A Persian 12-year-old male was admitted to Dr. Sheikh Hospital of Mashhad, Iran, in September 2019 with the following symptoms, including fever, convulsions, hemorrhage, and bone pain. The patient was diagnosed with AML (non-M3-FAB subtype) based on cell morphologies and immunophenotypical features. Chromosomal analysis using the G-banding technique revealed t (9;22) (q34;q13). Conclusions: Single-cell RNA sequencing (scRNA-seq) analysis suggested that the PPP1R1B promoter may be responsible for the PPP1R1B::STARD3 expression. Alterations in the level of lipid metabolites implicate cancer development, and this fusion can play a crucial role in the cholesterol movement in cancer cells. PPP1R1B::STARD3 may be considered a candidate for targeted therapies of the cholesterol metabolic and the PI3K/AKT signaling pathways involved in cancer development and progression. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine whether mammographic and sonographic features of malignant breast lesions are correlated with tumor histologic grade, hormonal receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67 status. Materials and Methods: In this retrospective study, imaging and histopathological findings of 187 biopsy-proven breast cancer cases from November 2019 to February 2021 were reviewed. The Chi-square test was used to examine the potential correlation between mammographic and sonographic characteristics with histopathological features such as hormonal receptor, HER2 status, Ki-67 labeling index, and histological grade. Results: We observed that microlobulated margin as well as oval/round morphology in mammograms correlate with triple-negative intrinsic subtype (P = 0.006 and P = 0.004). The presence of calcification in sonography was significantly higher in the luminal-B subtype (P = 0.002). Furthermore, ill-defined margins in mammography were significantly higher in amplified HER2 expression (P = 0.004) in the same manner as an oval/round shape in higher levels of Ki-67 (P = 0.030). Conclusion: Mammography and sonography features may reflect the biological behavior of various subtypes of breast cancer and can detect more aggressive breast cancers that can mimic benign or less malignant appearing lesions. These findings may be an excellent predictor for some subtypes like triple-negative breast cancer. Studying the range of these imaging characteristics may help in better understanding the prognosis, choosing a treatment strategy, and predicting response to treatment. [ABSTRACT FROM AUTHOR]

Background: Occult hepatitis B infection (OBI) refers to the presence of hepatitis B virus (HBV) DNA in the serum or liver of individuals who tested negative for HBV surface antigen (HBsAg). This study aimed to determine seropositivity for antibodies against HBV core antigen (anti-HBc) and the frequency of OBI among the HBsAg non-reactive blood donors in Mashhad, northeastern Iran. Methods: In this cross-sectional study, serum samples of HBsAg-negative blood donors were examined for anti-HBc during June and August 2018. Anti-HBc-positive samples were tested for antibodies against HBsAg (anti-HBs), and those with negative results were classified as isolated anti-HBc cases. The presence of HBV DNA in the C, S, and X gene regions was assessed by a qualitative real-time polymerase chain reaction method in all HBsAg-negative samples. OBI subjects were detected by the presence of at least one HBV genomic region. Results: Of 540 HBsAg-negative donors, 29 (5.4%; 95% confidence interval: 3.6--7.6%) showed seroreactivity for anti-HBc, of whom 18 individuals were also seropositive for anti-HBs. All donors showed negative results for all three HBV genes regardless of their serum anti-HBc status. Conclusion: Based on our findings, we suggest routine screening of Iranian blood donation volunteers for serum anti-HBc and anti-HBs but not HBV DNA. [ABSTRACT FROM AUTHOR]

A tomato‐infecting virus known as Beet curly top Iran virus (BCTIV) cause a significant disease for tomato plants and several other plant species around the world. Chitosan polysaccharide is a natural biopolymer that has been utilised as an exo‐elicitor to enhance plant defence mechanisms against a variety of plant diseases. This study investigates the efficacy of chitosan in combating BCTIV disease on tomato plants and modulating the host–virus interaction under greenhouse conditions. Twenty‐four hours before the virus inoculation, tomato plants were sprayed with a protective chitosan solution at different concentrations (0.5, 1, 1.5, and 2 mg/mL). Tomato plants were inoculated with a BCTIV infectious clone using an Agrobacterium‐inoculation method. The findings clearly demonstrated a reduction in the severity of the disease in chitosan‐treated plants as compared to Mock‐plants, with the percentage decreasing from 61.53% to 75.28% in 1.5 mg/mL treated plants and from 9.01% to 28.43% in 0.5 mg/mL treated plants. In addition, the utilisation of chitosan has the potential to deactivate the accumulation of BCTIV within the host tissues. The virus accumulation was greatly alleviated in 1, 1.5, and 2 mg/mL‐treated plants by 71.29%, 90.11%, and 93.14%, respectively, and over the mock plants. Furthermore, it was found that chitosan applied at all tested concentrations increased the relative expression and mRNA accumulation of genes related to resistance, including the pathogenesis‐related protein gene PR‐1, the HSP90 gene, and the AGO2a antiviral gene. These genes reached their maximum by 22.9‐, 12.93‐, and 4.44‐fold increases, respectively, over the untreated control. According to gas chromatography–mass spectroscop (GC‐MS) fractionation profile, chitosan increased 28 bioactive metabolic components, such as n‐hexadecanoic acid, heptanone, 1,2‐dimethylbenzene, dicarboxylic acid, and cis‐11‐octadecenoic acid methyl‐ester, to improve metabolic pathways. Results reported here revealed that foliar application of chitosan decreases the rate of the disease severity and virus accumulation in BCTIV‐infected tomato plants. This effect is associated with increased gene expression and defence‐related factors, enhancing tomato resistance to BCTIV infection. Consequently, chitosan treatments could be part of an integrated approach for reducing the severity of BCTIV disease in tomato and other host plants. [ABSTRACT FROM AUTHOR]

Objectives: Urinary tract infection (UTI) is a common complication during pregnancy that can have severe consequences for both the mother and the fetus. ESBL-producing strains of E. coli present a significant challenge in terms of treatment during pregnancy. This study aims to identify pregnant women carrying beta-lactamase-producing E. coli and assess the antibiotic resistance patterns of these isolates. Methods: This cross-sectional study investigated the presence of broad-spectrum beta-lactamase-producing E. coli isolates in pregnant women attending medical centers affiliated with Kashan University of Medical Sciences. Vaginal colonization, associated complications, and antibiotic resistance profiles were assessed. The antibiogram test using the disc diffusion method was employed to determine colonization and antibiotic susceptibility, while PCR testing was used to detect genes associated with beta-lactamase production. Results: Among the 175 samples collected, 51 samples tested positive for E. coli, with 15 of these samples containing ESBL-producing isolates. A significant correlation was observed between the frequency distribution of E. coli isolates and factors such as age, history of urinary tract infections, body mass index, and previous abortions in pregnant women. Among the 15 ESBL-producing E. coli isolates, the blaSHV, blaTEM, and blaCTX-M resistance genes were detected in 12 (80%), 9 (60%), and 1 (6.66%) isolates, respectively. Conclusion: The prevalence of ESBL-producing E. coli in pregnant women underscores the urgent need for public health interventions to combat antibiotic resistance. [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]

Background: High-risk Human Papillomavirus (HPV) genotypes are found in malignant oral epithelial lesions, and HPV infection is proposed as a risk factor for initiating Squamous cell carcinoma (SCC) in the head and neck region. This study suggests a practical approach to detect HPV in HPVassociated oral epithelial dysplasia (HAOED). Methods: Fifty-four oral epithelial dysplasia specimens were examined, comprising twenty-seven cases diagnosed with highgrade dysplasia and twenty-seven cases diagnosed with lowgrade dysplasia using a binary grading system. To assess the cases for HPV, the specimens were examined for p16 protein using an immunohistochemical (IHC) study, and then, the Chromatin In Situ Hybridization (CISH) test was performed for all positive cases. Chromatin Immunoprecipitation-Polymerase Chain Reaction (ChIP-PCR) was performed on CISH-positive specimens to assess the outcome. This cross-sectional study was conducted in 2020 at Tehran University of Medical Science. SPSS software version 22.0 was used to perform the Chi square or Fisher's exact test to examine the relationship between variables (statistically significant level P<0.05). Results: The expression of p16 protein was not associated with the severity of epithelial dysplasia (81.5% in low-grade and 59.2% in high-grade cases) (P=0.16). Moreover, according to the CISH test result, 9.25% of all specimens were positive (P>0.99), and in the nine cases, undergone the ChIP-PCR study, two cases (22.2%) showed positivity for HPV-16, while one case (11.1%) demonstrated positivity for HPV-51. Conclusion: Regarding HAOED, here, we proposed a step-bystep combination approach using different diagnostic methods, including IHC for p16 protein, CISH, and ChIP-PCR based on a complementary algorithm. [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]

Autism spectrum disorders (ASDs) are described as generalized developmental disorders, with an average age of onset of 36 months. Genetic and environmental factors may contribute to this multifactorial disorder. The present study aimed to investigate the association of three GRIN2B polymorphisms, including rs1019385, rs1024893, and rs3764028, with ASDs. Based on the results, there was a significant difference regarding the genotype frequency of rs3764028 polymorphism between the control and case (ASD) groups (P = 0.027). According to the recessive model, this variant was associated with ASDs (P = 0.23). None of the eight haplotype models with frequencies above 0.5 showed significant differences between the case and control groups in terms of allelic frequency. The present results showed that the rs376028 variant was directly related to the phenotypic symptoms of ASDs. [ABSTRACT FROM AUTHOR]

Teucrium persicum Boiss. an Iranian endemic plant is used in Iranian traditional medicine. E-cadherin transmembrane protein participates in adherens junctions and is the main partner for β-catenin protein. The GC-MS analysis was used to detect the chemical constituents of the methanolic extract. Its effects on the transcription of the E-cadherin encoding gene, cellular levels, and localization of E-cadherin protein in PC-3 cells were investigated. About 70 chemical constituents were identified. Indirect immunofluorescence microscopy and western blotting results revealed the restoration of E-cadherin protein at cell adhesion contact sites in cells treated with T. persicum extract. Gene expression studies revealed that the extract increased the transcription of the E-cadherin encoding gene in PC-3 cells. These results suggest that T. persicum extract may contain potent compounds that provide further support for the anticancer properties of T. persicum. Surely, detailed molecular investigations are needed to find the mechanism(s) behind these effects. [ABSTRACT FROM AUTHOR]

Background and aims: MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are well‐known types of noncoding RNAs (ncRNAs), which have been known as the key regulators of gene expression. They can play critical roles in viral infection by regulating the host immune response and interacting with genes in the viral genome. In this regard, ncRNAs can be employed as biomarkers for viral diseases. The current study aimed to evaluate peripheral blood mononuclear cell (PBMC) ncRNAs (lncRNAs‐homeobox C antisense intergenic RNA [HOTAIR], ‐H19, X‐inactive‐specific transcript [XIST], plasmacytoma variant translocation 1 [PVT‐1], and miR‐34a) as diagnostic biomarkers to differentiate severe COVID‐19 cases from mild ones. Methods: Candidate ncRNAs were selected according to previous studies and assessed by real‐time polymerase chain reaction in the PBMC samples of patients with severe coronavirus disease 2019 (COVID‐19) (n = 40), healthy subjects (n = 40), and mild COVID‐19 cases (n = 40). Furthermore, the diagnostic value of the selected ncRNAs was assessed by analyzing the receiver‐operating characteristic (ROC). Results: The results demonstrated that the expression pattern of the selected ncRNAs was significantly different between the studied groups. The levels of HOTAIR, XIST, and miR‐34a were remarkably overexpressed in the severe COVID‐19 group in comparison with the mild COVID‐19 group, and in return, the PVT‐1 levels were lower than in the mild COVID‐19 group. Interestingly, the XIST expression level in men with severe COVID‐19 was higher compared to women with mild COVID‐19. ROC results suggested that HOTAIR and PVT‐1 could serve as useful biomarkers for screening mild COVID‐19 from severe COVID‐19. Conclusions: Overall, different expression patterns of the selected ncRNAs and ROC curve results revealed that these factors can contribute to COVID‐19 pathogenicity and can be considered diagnostic markers of COVID‐19 severe outcomes. [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: Uncovering the roles and characteristics of pathogenesis-related molecules can help us develop novel management methods in parasitology. In this study, we studied the expression levels of Strongyloides stercoralis heat shock protein70 (HSP70) (Sst-hsp-70) and astacin (Sst-ast) as pathogenesis-related genes as well as the expression of S. ratti HSP70 and HSP17.1 (Sra-hsp-70, Sra-hsp-17.1) in the larvae and adult stages of S. stercoralis. Methods: A hyperinfection isolate of S. stercoralis from Gilan Province, northern Iran was cultivated on nutrient agar. After a couple of days, parasites in different stages of life were collected, and total RNA was extracted. The expression levels of astacin and HSP genes were compared by real-time PCR. Results: Statistically higher expression levels of Sst-ast, Sst-hsp-70, and Sra-hsp-70 genes in L3 larvae than in adults were observed. However, the expression level of Sra-hsp-17.1 was non-significantly lower in the larval stage than in adult worms. Conclusion: Higher expression levels of Sst-ast, Sst-hsp-70, and Sra-hsp-70 genes in the larval stages of S. stercoralis suggest the potential role of these enzymes in parasite cutaneous invasion and pathogenesis. However, higher expression of Srahsp-17.1 in adult forms is probably involved in resistance and survival mechanisms. The similarity in gene expression between S. stercoralis and S. ratti can provide helpful hints to better understand strongyloidiasis from various perspectives, including pathogenesis, proper diagnosis, and targeted treatment. [ABSTRACT FROM AUTHOR]

Background and Objective: Bisphenol A [BPA; 2,2-bis-(4 hydroxyphenyl) propane] is an environmental estrogenic and endocrine-disrupting compound that exerts its destructive effects through increasing oxidative stress, but the mechanisms underlying this effect have not yet been fully explained. This study evaluates BPA toxicity in muscle cells and the therapeutic potential of adiponectin (APN) and quercetin (QUER). Materials & Methods: Confluent L6 rat muscle cells were exposed to BPA (50 and 100 μM) with APN (10 and 100 ng/ml) and QUER (10 and 25 mM) for 24 and 48 hours. Cell viability, pro-oxidant/antioxidant balance (PAB), catalase (CAT) activity, and KEAP1/Nrf2 gene expression were analyzed using desired methods. Results: BPA in high doses (100 mM) significantly reduced the viability of the muscle cells, while APN and QUER increased cell survival in a time-dependent manner. The effect of QUER also was dose-dependent, while APN in high doses decreased the viability of the muscle cells. APN and QUER also reduced BPA-associated oxidative stress. These changes were significant in the case of QUER. The CAT activity was reduced in BPA-treated cells, which was notably increased with APN and QUER treatment. A decrease in Nrf2 gene expression of BPA-treated muscle cells improved by treatment with QUER and APN in a dose-dependent manner. Conclusion: Our results hinted that APN and QUER could modulate BPA-induced oxidative stress in muscle cells through KEAP1/Nrf2 pathways. Accordingly, it can also be concluded that APN in low doses and QUER may significantly reduce muscle toxicity caused by BPA. [ABSTRACT FROM AUTHOR]

Background & Objective: Toll-like receptors (TLRs) are proteins that play key roles in inflammation. METH and buprenorphine (BUP) both modulate pain, but the exact mechanism underlying their antinociceptive effects is unknown. As a result, the expression of TLR1 and TLR2 genes was examined in METH rats that had been treated with or without BUP. Materials & Methods: A total of 77 rats were classified into 11 subtypes (n = 7): control (saline), BUP 6 or 10 mg/kg, METH (10 mg/kg), METH+BUP 6 or 10 mg/kg, or withdrawal groups. The treatments were intraperitoneally administered for 5 or 14 days. RT-PCR evaluated genes expressed in the brain stem area. Results: The results showed that TLR1 gene expression in the METH group (10 mg/kg; 5 days) considerably improved compared with the control group. Furthermore, BUP injection (10 mg/kg) acutely decreased TLR2 gene expression compared with the METH group. In the METH + BUP (10 mg/kg; 14 days) group, TLR1 expression was higher than in the METH group. The coadministration of METH+BUP (10 mg/kg) acutely decreased TLR2 gene expression compared with METH. Conclusion: There are limited changes in these genes, and their role in METH consumption and inflammation is unclear. Due to the presence of these two genes in the inflammatory pain and addiction signaling pathways, they may have more clear roles in other parts of the nervous system. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the third mostcommoncancer that frequently spreads to other parts of thebody, with a low chance of recovery and a high mortality rate. Long non-coding RNAsare considered significant prognostic and diagnostic indicators because they are dysregulated in various cancers and have distinctive expression patterns and high tissue- and cell-specificity. VLDLR-AS1 lncRNA deregulation has been associated with several malignancies. Objectives: This study aimed to evaluate the expression levels of VLDLR-AS1 in CRC. It was the first time this assessment was conducted. Methods:We studied 188 samples, including 94 tumor samples and 94 paired adjacent non-tumor tissues. Total RNA was extracted, and its quantity and purity were assessed. TaKaRa PrimeScript 1st Strand cDNA Synthesis Kit (Kusatsu, Japan) was used for the reaction. The StepOnePlus Real-Time PCR System (Applied Biosystems) was set up to assess the relative expression of VLDLR-AS1. Results: According to the qRT-PCR data, the VLDLR-AS1 expression levels in CRC tissues were significantly lower than in tumor margins (P < 0.0001). In addition, receiver operating characteristic curve analysis demonstrated that VLDLR-AS1 expression can discriminate between tumor and non-tumor samples with the sensitivity and specificity of 72.34% and 51.06%, respectively (P = 0.03, AUC = 0.6274). However, no significant association was found between the expression levels of VLDLR-AS1 and clinicopathological features in CRC patients. Conclusions: The results of this study indicated that VLDLR-AS1 lncRNA is significantly downregulated in the tumor tissues of CRC patients compared to healthy tumor margin tissues. This evidence shows the potential of this gene as a promising biomarker for the early detection of CRC development. [ABSTRACT FROM AUTHOR]

Squeezing is a well-known geotechnical phenomenon in the excavation of underground spaces, especially tunnels. Squeezing occurs under different geotechnical conditions in weak rock masses. A study was carried out to develop a mathematical and practical model to predict squeezing so that risk mitigation measures can be taken if necessary. A mathematical model based on a gene expression programming algorithm was developed using a database of 115 squeezing case histories. Four model performance evaluation criteria – specificity, sensitivity, accuracy and Matthew's correlation coefficient – and the receiver operating characteristic curve were then assessed based on a testing dataset. The accuracy of the model was also compared with that of previously developed models. Found to be able to determine squeezing with acceptable accuracy, the model was then used to investigate squeezing-prone areas in the Beheshtabad water-conveyance tunnel in Iran. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the combined effects of resveratrol (RES) and saroglitazar (SARO) on a high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in a rat model. Methods: In this animal study, rats were treated with RES, SARO, or a combination of both. Male rats were fed with an HFD to induce nonalcoholic steatohepatitis (NASH) and then divided into 4 groups: RES treatment, SARO treatment, combined RES and SARO treatment, and no treatment. Various parameters were measured, including body and liver weight, liver enzymes, gene expression of inflammatory markers and reactive oxygen species (ROS), protein expression levels of transforming growth factor-beta (TGF-β) and p-Smad3, and liver histology. Results: The combination of RES and SARO significantly reduced blood and hepatic lipids, attenuated weight gain, and decreased inflammatory cytokine production in a NAFLD study. The combination diminished hepatic lipid accumulation, oxidative stress, and TGF-β1 expression, suggesting antifibrotic effects. Histological evaluations showed antisteatotic and antifibrotic outcomes of the combined treatment. Improved glycemic index, blood lipids, and reduced NASH indicators (i.e., aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were observed after 6 weeks. The treatment also decreased ROS and NOX family expression, lessening oxidative stress. The inhibition of the TGF-β-Smad3 pathway in HFD-induced rats resulted in reduced NASH(P< 0.05). Conclusions: The results indicated that the group receiving the combination of RES and SARO showed a more efficient reduction in fibrosis and steatosis in the NASH model induced by an HFD than the groups receiving RES or SARO alone. [ABSTRACT FROM AUTHOR]

Introduction: Coronary artery disease (CAD) is the main cause of death and is characterized by atherosclerosis in coronary arteries. Inflammation plays a crucial role in the progression and development of atherosclerosis. Methods: The present study consisted of 132 Iranian individuals who underwent coronary angiography, 65 patients with CAD, and 67 controls. The matrix metalloproteinase-9 (MMP-9), TNF-α, IL-6, and vitamin D serum levels were measured by the ELISA technique. The gene expression of MMP-9 and tissue inhibitors of metalloproteinase (TIMP-1) was estimated by realtime PCR assay. Results: A considerable increase in levels and PBMC gene expression of MMP-9 and serum levels of IL-6 and TNF-α were found in CAD patients compared with controls. A significant decrease was detected in vitamin D levels of CAD patients in comparison with controls. A considerable direct correlation was found between MMP-9 levels and MMP-9 and TIMP1 gene expression in CAD patients. MMP-9 levels positively correlated with LDL-C in CAD patients. The correlation between TIMP1 gene expression and IL-6 levels was also negatively significant. There were positive correlations between MMP-9 levels with IL-6 and TNF-α serum levels in CAD patients. Conclusion: This study showed that the interaction between MMPs, TIMP1, and cytokines could play a role in the pathogenesis of atherosclerosis. The present study suggested that high levels of TNF-α and IL-6 and vitamin D deficiency in our studied patients could disturb the MMP-9/TIMP-1 balance and lipid metabolism, leading to plaque formation/ rupture in predisposed CAD patients. [ABSTRACT FROM AUTHOR]

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

Background: The utilization of molecular techniques in detecting cancer has resulted in an improved prediction of outcomes. Oral squamous cell carcinoma (OSCC) is a prevalent illness that is frequently detected in its late stages. Therefore, finding molecular biomarkers that lead to the early detection of OSCC is of great importance. Objectives: This study aimed at evaluating the expression levels of long non-coding RNA (lncRNA) gastric carcinoma highly expressed transcript 1 (GHET1) and lncRNA ZXF2 in OSCC patients and their relationship with clinical pathology variables due to biomarker discovery and early diagnosis of OSCC. Methods: Tissue sampling was performed after selecting 30 OSCC patients and 30 healthy individuals from Emam-Khomeini Hospital, Tehran, Iran. Then, RNA extraction and cDNA synthesis were performed from these samples, using the relevant kits and their quantity and quality were measured, using nanodrop and agarose gel electrophoresis, respectively. For molecular biomarker identification and validation, real-time PCR(RT-PCR) was utilized to assess the expression of lncRNA GHETl and lncRNAZXF2. Data analysis was done, using GraphPad prism V.8 software. Results: The results showed that the expressions of both lncRNA GHETl and lncRNA ZXF2 in OSCC tumor tissue increased compared to normal tissue (P< 0.0001). Receiver operating characteristic (ROC) analysis indicated that lncRNA GHETl and lncRNA ZXF2 have the capability to be employed as biomarkers for OSCC detection. However, no significant relationship was observed between lncRNA GHETl and lncRNA ZXF2 expressions with clinicopathological variables such as tumor stage and grade as well as patients' age. Conclusions: LncRNA GHETl and lncRNA ZXF2 have the potential to be used as biomarkers in the early detection of OSCC and evaluating their expression in clinical settings are recommended. The use of these biomarkers in the early detection of OSCC can prevent the high mortality rate of OSCC patients. In the current study, the important role of the studied lncRNAs in OSCC diagnosis was shown. However, further studies are needed to confirm this. [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]

Background: Cichorium intybus L. (Kasni) distillate is widely used in Eastern countries as a safe herbal drink to improve male fertility. However, the potential effects on fertility parameters and possible adverse effects have not been studied experimentally. The current study aims to evaluate the impact of Cichorium intybus L. distillate (CD) on male mice fertility. Methods: In the present study (Shiraz, Iran), 30 male mice (3035 g) were divided into three groups. 10 mice received distilled water (DW) for five weeks as the control group. Another 10 mice, named group CD1/2, received chicory distillate of 1/2 dilution, and the other 10 mice received chicory distillate of CD1/4 dilution as CD1/4 group, ad libitum for three weeks, and they received DW for two weeks afterward. Experimental mice were sacrificed on day 35, and sperm analysis and sera collection were performed for further investigation of FSH, LH, testosterone, and some liver and kidney function parameters. We used the left testis for stereological analysis, and the right one was excised to investigate the expression of the androgen receptor gene. For statistical analysis using SPSS 18.0, mean±SD values were analyzed by one-way analysis of variance (ANOVA) with Dunnett's analysis as post hoc to compare between groups. In stereological investigations, the Kruskal-Wallis method was used for pairwise comparisons to compare groups. The P value was considered statistically significant at P<0.05. Results: Treatment with CD1/2 resulted in the elevation of serum FSH (P=0.002), LH (P=0.009), testosterone (P=0.034), seminiferous tubule epithelium volume (P=0.029) and length (P=0.028), and Leydig cells number (P=0.009) in comparison with the control group. Administrating CD1/2 (P=0.038) and CD1/4 (P=0.013) significantly increased sperm count compared to the control group. Conclusion: The results revealed that using chicory distillate can improve hormone levels and sperm count in male mice. [ABSTRACT FROM AUTHOR]

Background & Objective: Heat shock proteins (HSPs) have garnered significant interest as a potential host factor in COVID-19. By exerting control over HSP levels, the invading virus can effectively manipulate the destiny of host cells, capitalizing on their essential roles in cellular pathways and viral life cycles. Within this investigation, we present novel findings elucidating the variations in HSP27 protein and mRNA expression between patients exhibiting mild symptoms and those manifesting moderate-to-severe symptoms of COVID-19, juxtaposed against a control cohort. Materials & Methods: A total of 102 patient samples were included in the study, comprising 54 individuals with moderate-to-severe COVID-19 symptoms and 48 with mild symptoms. Additionally, 42 samples from healthy individuals constituted the control group. HSP27 protein levels were quantified using ELISA, while the transcript content was assessed using Real-Time PCR. Results: Our initial findings revealed a statistically significant reduction in serum HSP27 levels among patients displaying mild COVID-19 symptoms when compared to the control group (P< 0.05). Nonetheless, this disparity did not achieve statistical significance in patients with moderate-to-severe symptoms. In contrast, the transcriptomic profile of HSP27 exhibited striking similarity across all groups, including mild, moderate-to-severe, and controls (P= 0.25 and P= 0.56, respectively). Conclusion: The present study, to date, is the first to investigate HSP27 gene expression levels in COVID-19 patients. Conducting further studies on HSP27 is of considerable help to clarify the importance of this molecule in SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Mycoremediation, a subset of bioremediation, is considered an advanced method to eliminate environmental contaminations. To identify tolerant fungi to copper contamination and study the related gene expression, sampling was carried out from the soil of "Sarcheshmeh Copper Mine," which is one of the biggest open-cast copper mines in the world. A total of 71 fungal isolates were obtained and purified. Afterward, the inhibitory effect of different concentrations (1000, 1500, 3500, 4000, and 5500 ppm) of copper sulfate on mycelial growth was evaluated. Results indicated that only 5500 ppm of copper sulfate inhibited fungal growth compared to the control. Based on the bioassay experiments, three isolates including S3-1, S3-21, and S1-7, which were able to grow on solid and broth medium containing 5500 ppm of copper sulfate at different pH conditions, were selected and identified using molecular approaches. Also, laccase and metallothionein gene expression has been assessed in these isolates. According to the molecular identification using ITS1-5.8S- ITS2 region, isolates S3-1 and S1-7 were identified as Pleurotus eryngii, and isolate S3-21 belonged to the genus Sarocladium. In addition, P. eryngii showed laccase gene expression reduction after 8 days of exposure to copper sulfate. While in the genus Sarocladium, it increased (almost 2 times) from 6 to 8 days. Besides, metallothionein gene expression has increased from 6 to 8 days of copper sulfate treatment compared to the control which reveals its role in copper tolerance of all studied isolates. In this study, Pleurotus eryngii and Sarocladium sp. are introduced as heavy metal tolerant fungi and the related gene expression to copper tolerance was studied for the first time in Iran. [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]

Objectives Febrile seizure is a neuroinflammatory disease involving feverinduced seizures affecting children in the early stages of life. TNFα is a pro-inflammatory cytokine reported to be elevated in FS. Specific promoter variants of TNFα could be associated with its elevated cytokine expression and susceptibility to FS. The present study analyzed the association of specific TNFα variants, including TNFα -238 G/A (a genetic variant; G: Guanine, A: Adenine) (rs361525), TNFα -308 G/A (rs1800629), and TNFα -376 G/A (rs1800750) promoter polymorphisms, with FS susceptibility, and TNFα serum levels in an Iranian population. Materials & Methods Sixty-eight FS patients and 136 controls were enrolled. The SSPPCR method was utilized to analyze TNFα promoter genotypes. This research also confirmed the genotyping results by sequencing samples of ten patients and normal controls. Results The GG (a genetic sequence; G: Guanine) genotype of -238 SNP was associated with the increased risk of FS [OR = 12.65, 95% CI (2.83-56.60), P-value = 0.0012]. The AA (a genetic sequence; A: Adenine) genotype in the-308 region was increased in patients with FS and associated with the disease [OR = 4.62, 95% CI (1.46-14.56), P-value = 0.028]. The increased occurrence of heterozygous AG in the -376 SNP among control groups has been linked to a decreased risk of FS [OR = 0.22, 95% CI (0.11-0.43), P-value = 0.0001]. This study revealed that AGA (a genetic sequence; G: Guanine, A: Adenine) (-238/ -308/ -376) haplotype with the highest frequency in controls was associated with a decreased risk of FS, while GAA (a genetic sequence; G: Guanine, A: Adenine) (-238/ -308/ -376) carriers were more susceptible to FS. Conclusion The current study suggested that TNFα gene promoter variants at rs361525, rs1800629, and rs1800750 could be associated with the susceptibility to FS and altered serum levels of TNFα. [ABSTRACT FROM AUTHOR]

Background: Excessive extracellular matrix (ECM) deposition in adipose tissue is a hallmark of fibrosis, leading to disrupted adipose tissue homeostasis and metabolic dysfunction. Hesperetin, a flavonoid compound, has shown promising anti-inflammatory, anti-obesity and anti-diabetic properties. Therefore, we investigated the anti-fibrotic effects of hesperetin, through targeting ECM components and matrix metalloproteinase enzymes. Methods: 3T3-L1 cells were cultured in DMEM, containing 10% FBS and 1% penicillin/streptomycin. Cells were treated with a range of hesperetin concentrations, and the cell viability was determined using MTT assay. Subsequently, the expression of genes encoding collagen VI, osteopontin, matrix metalloproteinase-2 (Mmp-2) and Mmp-9 was analyzed using specific primers and real-time PCR technique. To evaluate protein levels of collagen VI and osteopontin, Western blotting was performed. Results: Hesperetin affected the viability of 3T3-L1 adipocytes with IC50 of 447.4 µM, 339.2 µM and 258.8 µM (24 h, 48 and 72 h, respectively). Hesperetin significantly reduced the gene and protein expression of both collagen VI and osteopontin in 3T3-L1 pre-adipocytes, in a time- and dose-dependent manner. Hesperetin was also able to cause a remarkable decline in gene expression of Mmp2 and Mmp9. Conclusion: Hesperetin could potently reduce the production of markers of adipose tissue fibrosis and might be considered a potential anti-fibrotic compound in obesity. Thus, hesperetin has the potency to be used for the treatment of obesity-associated fibrosis. [ABSTRACT FROM AUTHOR]

Background: Tobacco smoke contains various toxins that negatively affect the human reproductive system. Caffeic acid phenethyl ester (CAPE), a potent antioxidant, has protective effects on the reproductive system against oxygen-free radicals, methotrexate, and pesticides. Herein, the effect of CAPE on some key markers of endometrial receptivity has been evaluated. Methods: A cross-sectional study was conducted during 2018-2019 in the Department of Clinical Biochemistry, School of Medicine, Fasa University of Medical Sciences (Fasa, Iran). Primary endometrial cells were divided into five groups, namely control, nicotine, CAPE, vehicle, and nicotine+CAPE. Real-time polymerase chain reaction (PCR) and methylation-specific PCR were performed to evaluate gene expressions and methylation, respectively. Appropriate doses of CAPE and nicotine were determined using the MTT assay. Data were analyzed using SPSS software (version 16.0) with a one-way analysis of variance. P<0.01 was considered statistically significant. The fold change was calculated using the 2-ΔΔCT method. Results: Treatment of cells with nicotine significantly reduced the expression of C-X-C motif chemokine ligand 12 (CXCL12), fibroblast growth factor 2 (FGF2), and vascular endothelial growth factor A (VEGF-A) genes (P<0.0001). However, the expression levels increased significantly when treated with nicotine+CAPE (P<0.0001). Despite the reduced CXCL12 gene expression in cells treated with nicotine, CXCL12 was unmethylated in all study groups, indicating that the methylation status of the CXCL12 gene was not affected by nicotine or CAPE. Conclusion: CAPE can be a suitable agent to protect female smokers from the harmful effects of nicotine. This manuscript is available as a preprint on the Research Gate website: https://www.researchgate.net/scientific-contributions/Amin-Namdari-2172473868 [ABSTRACT FROM AUTHOR]

Background: Autophagy is a conservative mechanism for cell survival as the main response of cells to stress conditions. The present study aimed to assess the effect of docetaxel on the survival, fertilization, and expression of autophagy-related genes in vitrified oocytes. Methods: The study was conducted in 2018 at the Stem Cells Technology Research Center, Shiraz University of Medical Sciences (Shiraz, Iran). Denuded oocytes were randomly selected and assigned to five groups, namely control (n=133), docetaxel (n=136), docetaxel+cryoprotectants (n=146), docetaxel+vitrification (n=138), and vitrification (n=145). The effect of vitrification on the expression of autophagy-related gene 5 (ATG5) and Beclin-1 was determined using a real-time polymerase chain reaction. Data were analyzed using SPSS software (version 26.0) and GraphPad Prism 9. Results: Survival and fertilization rates in each experimental group were significantly reduced compared to the control group (P=0.001). After in vitro fertilization of oocytes, the 2-cell formation rate was significantly reduced in the docetaxel+vitrification and vitrification groups compared to the control and docetaxel groups (P=0.001 and P=0.001, respectively). Pre-incubation of oocytes with docetaxel reduced gene expression levels of Beclin-1 and ATG5 in the docetaxel+cryoprotectants and docetaxel+vitrification groups (P=0.001 and P=0.019, respectively). The expression level of these genes was also reduced in the docetaxel group compared to the control group (P=0.001). Conclusion: Incubation of mouse metaphase II oocytes with docetaxel prior to vitrification reduced the expression of autophagy-related genes and increased survival and fertilization rates compared to untreated oocytes. [ABSTRACT FROM AUTHOR]

Background: Significant economic consequences can lead to various problems and complications, including medical complications. Coronary artery disease (CAD), a serious health threat with increasing prevalence, is a major cause of death and mortality worldwide. This study aimed to investigate the effects of a special training program on cytochrome P450 (CYP) gene expression and reactive oxygen species (ROS) levels in patients with coronary artery bypass surgery. Methods: This semi-experimental study was conducted on 16 patients who underwent coronary artery surgery in Babol City, Iran. The patients were selected using a random sampling method and divided into 2 groups: experimental and control groups. The experimental group engaged in an exercise program consisting of 3 sessions per week for a duration of 8 weeks. The expression levels of CYP and ROS genes were measured by the real-time polymerase chain reaction (PCR) method. The analysis was performed by comparing covariances and means. Results: ROS gene expression levels significantly decreased in the experimental group than in the control group (P=0.003). However, there was no significant difference in P450 levels between the experimental and control groups (P=0.99). Conclusion: Special exercises reduced ROS expression and increased P450 expression in patients who had coronary bypass surgery. There is a probability that special exercises, can effectively prevent heart damage by increasing antioxidant capacity and reducing ROS. [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]

Systemic lupus erythematosus (SLE) is an autoimmune disease in which the immune system abnormally reacts against cells and tissues leading to inflammation. Epigenetic alterations, including DNA methylation and histone modification, have critical effects on autoimmune disease and SLE pathogenesis via dysregulation of critical genes. The purpose of this study was to evaluate the epigenetic-related gene expression of DNA methyltransferase (DNMT) and histone deacetylase 1 (HDAC1) in Iranian patients with SLE. This matched case–control study included 16 people with SLE and 16 healthy people who were referred to the Rafsanjani rheumatology clinic, in southeast Iran. The expression of DNMT and HDAC1 genes was measured through a real-time PCR assay of blood samples. DNMT gene expression did not differ significantly between SLE and healthy groups (P = 0.21). In contrast, HDAC1 gene expression was enhanced in the SLE group, but this enhancement failed to reach statistical significance (P = 0.94). The results of this study suggest that overexpression of HDAC1 could serve as a diagnostic for SLE disease. Additional studies with larger sample sizes are required to confirm our findings. Evaluation of other genes related to SLE disease is essential and may help to make an accurate diagnosis of the disease. [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]

Introduction Finding biomarkers for highly lethal cancers is a priority. Objective The current study was designed to understand the clinical significance of vascular endothelial growth factor (VEGF), latent membrane protein 1 (LMP1), and tumor necrosis factor-α (TNF-α) expression as the biomarkers, and evaluate their correlation with each other, in nasopharyngeal carcinoma (NPC) in the province of Guilan, North of Iran. Methods Gene expression was evaluated in 25 formalin-fixed paraffin-embedded (FFPE) blocks from cases of confirmed NPC and 20 FFPE samples of non-NPC by quantifying messenger ribonucleic acid (mRNA) and protein levels, using real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) methods, respectively. Furthermore, the correlations among the protein levels of different genes, along with the patients' demographic characteristics were assessed. Results Our findings on mRNA and protein levels demonstrated that the expression of the LMP1 gene in the NPC group was significantly elevated compared with that of the non-NPC group. In addition, the protein levels in the NPC group indicated a positive and significant correlation between LMP1 and VEGF expression. It was noted that both protein and mRNA levels showed no significant differences in the expression of TNF-α and VEGF genes between the NPC and control groups. Furthermore, there was no significant relationship between the expression of these proteins and the demographic characteristics of NPC patients. Conclusion Overall, a significant increase in LMP1 expression was observed in NPC patients, which may serve as a diagnostic biomarker for NPC. Also, LMP1 might be involved in NPC progression by inducing VEGF gene expression. [ABSTRACT FROM AUTHOR]

Background & Aims: Liver cancer is one of the deadliest cancers and the most common cancers worldwide. Nanoparticles due to their wide applications in diagnostics, imaging and drug delivery, have attracted significant attentions (6). Upon a previous studies, the green-route mediated production of metal nanoparticles inhibits the progression of cancer cell lines (9, 10). Inprevios study the inhibition of the breast cancer cells were conducted by silver chloride nanoparticles synthesized by Onopordum acanthium L. extract through inducing apoptosis pathway (11). Lnc RNA GAS5 is a tumor suppressor, it’s an expression in some malignant tumors decrease. In liver Cancer Cells (HCC) The GAS5 gene Expression is reduced, which identifies the poor prognosis of this gene (5). However, a limited number of reports have been investigated on the cytotoxic effect of silver chloride nanoparticles on cancer cells, so in this study, we aimed to investigate it. In our study, we investigated the silver chloride nanoparticles synthesized by O. acanthium L. extract, as well as its anticancer effects on liver cancer and normal cell lines. The aim of this study was investigating the cytotoxicity effect of silver chloride nanoparticles and evaluation of LncRNA GAS 5 gene expression in liver cancer cells. Methods: Brifly, 100 mL of a solution of 1 mM silver nitrate was prepared in distilled water. Then, 5 mL of solution of O. acanthium L. extract (4 mg/mL) and KCl salt (1 mM) were drop wise added to the stirred silver nitrate solution. Subsequentely, the resulted solution was stirred at room temperature for 24 hours. This solution was then centrifuged at 13,000 rpm for 10 minutes; the supernatant was discarded and then centrifuged again with distilled water (11). In this study, HepG2 and HEK293 cells were obtained from the Pasteur Institute Cell Bank of Tehran and treated with silver chloride nanoparticles after 24 hours. Cell viability percentage of nanoparticles were determined by MTT (3-(4, 5- Dimethyltetrazollium Bromide) assay toward HepG2 and HEK293 cells. The HepG2 and HEK293 cell lines were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) (Gibco, Scotland) medium with 10% FBS serum and 1% streptomycin antibiotic (Gibco, Scotland). The cells were then stored at 37 ° C with 5% CO2 in a humidified cell culture. To evaluate the in vitro cell viability, the colorimetric MTT method was assessed for investigating the appropriate lethal dose of silver chloride nanoparticles. Afterward, they were treated with silver chloride nanoparticles in various concentrations (0, 3.125, 6.25, 12.5, 25, 50, 100, 200 and 400 μg/mL) for 24 hours. Nanoparticles were added to the cells (1 × 104 cells per well) cultured on 96-well plate, which were incubated an overnight at 37 °C. Thereafter, MTT solution (100 μl of 0.05 mg/well) was added to the plate. Subsequently, dimethyl sulfoxide (DMSO) solvent we added of to each well to solubilize the formazan crystals. Finally, the optical density of the treated and untreated cells was evaluated with the ELISA reader (Eppendorf, Germany) at the wavelength of 570 nm. Finally, the viability of the cells was calculated according to the following formula: percentage of cell viability (%) = OD value of sample / OD value of control × 100. Levels of LncRNA GAS5 gene expression in HepG2 liver cancer cell were quantified using quantitative real-time reverse transcription-PCR (qRT-PCR) technique. To assess the qRT-PCR method, total cellular RNA extraction was carried out using the RNA extraction kit based on to the instructions in the Qiagen kit (Qiagen, Germany). To synthesis of transcriptional complementary DNA (cDNA), PrimeScriptTM RT Kit (Takara, Japan) was carried out (12). GAS5 and GAPDH primers were then conducted using NCBI primer blast in this study (Table 1). Subsequently, qRT-PCR method was evaluated by 100 ng of cDNA, SYBER Green PCR Master Mix (2X), followed by 2mM each of reverse and forward primers in final volume to 20 μL with nuclease free water. Also, the data was investigated by ABI StepOne using the Applied Biosystems qRT-PCR (ABI 7300 system, Applied Biosystems). Statistical significance between treatment and untreated groups were evaluated by One-way analysis of variance (ANOVA) with SPSS software version 22 and the Tukey post hoc. Data were expressed as mean ± the standard deviation of three replicates from three independent experiments. and P ˂0.05 was considered significance level. Results: The results showed that silver chloride nanoparticles decrease significantly the cell viability of cancerous HepG2 cells as compared to normal HEK293 cell line. In this regard, silver chloride nanoparticles were able to increase cell toxicity in a dosedependent manner, as shown in Figure 1 and 2. Also, IC50 concentration of silver chloride nanoparticles toward HepG2 and HEK293 cells was 49 and 160 μg/mL, respectively. To conduct the effect of IC50 dose of nanoparticles on cell lines, we investigated HepG2 and HEK293 cells treated with 0, 3.125, 6.25, 12.5, 25, 50, 100, 200 and 400 μg/mL of nanoparticles for overnight using MTT assay. At concentration of 12.5, 25, 50, 100, 200, and 400 µg/mL of silver chloride nanoparticles, the viability of HepG2 was reduced to (79.85±6.44 )%, (63.68±7.05) %,(46.87 ± 4.7)%, (31.83 ± 4.44)%, (18.63± 6.1) %, and (18.63± 6.1) (P < 0.001), respectively (Figure 1). At concentration of 50, 100, 200, and 400 µg/mL of silver chloride nanoparticles, the viability of HEK293 was reduced to (80.28±6.1 )%, (69.91±6.13) %,(43.67 ± 7.76)%, and (24.99 ± 4.42)% (P < 0.001), respectively (Figure 2). In order to determine the effect of silver chloride nanoparticles on cancerous cells, alterations in the mRNA expression levels of LncRNA GAS5 gene in HepG2 cells were carried out using qRT-PCR technique followed by the exposure to nanoparticle. According to our study, the results of real time PCR displayed that the expression of LncRNA GAS5 was up-regulated by a 4.6±0.34 (p˂0.001) fold as compared to control gene. Conclusion: In summary, the effect of silver chloride nanoparticles against HepG2 and HEK293 cells showed that these nanoparticles have high cytotoxicity. Also, increase in LncRNA GAS5 gene expression level reveals the triggering apoptosis in HepG2 cells. silver chloride nanoparticles can be considered as a promising strategy for the treatment of liver cancer. Thus, for the liver cancer therapy, further in vivo investigations are required to determine the efficacy of the silver chloride nanoparticles. [ABSTRACT FROM AUTHOR]

Background & Aims: Aging is a process of deterioration over time. On the other hand, the prevalence of heart diseases has increased with the increase in life expectancy. Important genes that play a role in the aging process are related to telomerase activity, which plays an important role in heart health. are considered a strong stimulant for the telomere system. Also, coenzyme Q10 is a fat-soluble vitamin, which improves cardiovascular function. The general purpose of this research is to investigate the effect of six weeks of aerobic training along with Q10 supplementation on TRF1 and TRF2 gene expression. Heart tissue was from aged male Wistar rats. Methods: The current study was a developmental study and its method was an experimental one. The statistical population of the current study was 17 old Wistar male mice aged 88 to 96 weeks with an average weight of 404 grams from Razi Vaccine and Serum Research Company. This research was conducted in the physiology laboratory of Shahid Rajaei Tarbiat University. All mice had the same environmental conditions in terms of air temperature (25±2) degrees Celsius, relative humidity (55±5) and day-night cycle (12-12 hours) of light and darkness. The samples were randomly divided into 5 groups including 3 groups of three (exercise sham-supplement sham-control) and two groups of four (aerobic exercise-aerobic exercise and supplement). Laboratory animals were used and approved by the research ethics committee of the Research Institute of Physical Education and Sports Sciences (Ethics ID: IR.SSRC.REC.1401.051) and conducted in the laboratory of the Faculty of Sports Sciences of Tarbiat University, Shahid Rajaei. This study was conducted with a post-test design for measuring TRF1 and TRF2 and a pre-test-post-test design for measuring Vpeak and lee index. The independent variables of the research included aerobic exercise and Q10 supplement, and the dependent variables included TRF1 gene and TRF2 gene. At the beginning of the study, the animals were familiarized with the environment and trained on a treadmill for two weeks. Finally, after the last familiarization session and after 48 hours of rest, Vpeak [the maximum amount of VO2 (oxygen consumption) during an exercise test is increasing in which all VO2max criteria are not fulfilled (11) and the Lee index of all subjects were measured. The incremental test started with a speed of 5 m/min and a speed equivalent to 5 m/min was added every three minutes. The time to reach fatigue was determined by the mice's inability to run on the treadmill. Based on the maximum speed obtained, the training protocol was designed for six weeks and five sessions per week for the training groups, and then the training protocols were started (1, 2). Vpeak is measured every two weeks to determine training intensity (14). The program of moderate intensity aerobic training (MICT) is as follows: in the first week, it was performed with an intensity of 65% of Vpeak for 15 minutes, and in the sixth week, it reached an intensity of 70% of Vpeak in 30 minutes: the subjects before starting the protocol with an intensity of -40 50% of Vpeak was heated for 5 minutes and cooled down after completing the protocol. The sham group was given sesame oil by gavage to give stress. The aerobic exercisesupplement group was given 20 mg of fat-soluble Q10 supplement per kilogram of body weight combined with 0.5 cc of sesame oil by gavage for 42 days. The bodyweight was given to the aerobic exercise group. The supplement was prepared from its manufacturing company called Nano Kimia Salamat (15, 16). 48 hours after the end of the protocols and the last training session, Vpeak and Lee's index were measured, and also the height and weight of the mice were measured every week. Nasoanal length[cm]] ×1000 was used. 48 hours after the last training session, the samples were anesthetized with a combination of xylazine 5 to 10 mg/kg and ketamine 50 to 100 mg/kg. Then the heart tissue was extracted and washed with PBS and transferred to a negative 80 centigrade freezer and then transferred to the laboratory for tissue analysis using standard kits for gene expression by PCR method (2, 3, 17). Specialized laboratory processes were performed to measure the expression level of TRF1 and TRF2 genes and to measure telomere length using Real time-PCR method. Quantitative real time-PCR was used to measure the gene expression levels using special primers. Amplification of TRF2 and TRF1 genes as well as GAPDH reference gene was done to measure gene expression by real time PCR based on the standard method. To measure the decrease or increase in the expression of TRF1 and TRF2 genes, its expression was compared with the expression of internal control genes. For this purpose, F and R primers and cDNA were added to the master mix and the final volume was prepared for Real time PCR reaction. The primers used were prepared from Cinagen company, made in Iran. (18, 19) Then the real time PCR process was performed using the QIAGEN machine and each reaction was performed in duplicate. After the reaction, the raw data was extracted and the amount was calculated. Expression of genes was done using method 2-ΔΔCt. (20) After collecting the raw data, the Shapiro-Wilk test was used to check the normality of the data distribution. Then, in order to statistically analyze the data and compare between the groups two-way ANOVA test was used, and because the groups were unequal, the Scheffe test was used. Correlated T-test was used to check the changes of stabilizing variables. All statistical calculations were done using SPSS26 software at a significant level of P≤0.05. Excel2013 software was used to draw graphs. Results: Based on the obtained results, there was a significant difference between the groups after six weeks of aerobic training along with Q10 supplementation on TRF1 and TRF2 gene expression. (P≤0.05) Conclusion: In general, the present study showed that aerobic exercise along with Q10 supplementation increases the expression of TRF1 and TRF2 genes in heart tissue. Therefore, according to the above result, it is possible to cautiously recommend aerobic exercise along with Q10 supplementation for the elderly. [ABSTRACT FROM AUTHOR]

Background and Aim: Nowadays, non-albicans Candida are common in human pathogens, and some of these cases were found in milk. Therefore, as well as the lack of accurate estimates of its global prevalence and severity, the present study aims to assess the demographic features of non-albicans Candida (NAC) spp. and determine the species distribution of NAC. It also evaluated the in vitro Azole susceptibility of NAC species and identified the erg11 gene and erg11 expression in fluconazole-resistant isolates of NAC spp., in Iran. Materials and Methods: In the present study, non-albicans Candida, including Candida glabrata, Candia krusei, Candida parapsilosis, and Candida tropicalis, were isolated and identified from 14 farms (raw milk) and human patients using culture methods, Real-Time PCR and sequencing. The resistance and susceptibility of the samples to azole were examined and erg11 expression was evaluated by RT-qPCR. The results were analyzed by REST Software to compare the levels of erg11 gene expression involved in drug resistance of NAC. Results: 74 and 52 NAC strains were isolated in 262 collected milk samples and human samples. Based on ITS sequencing, 0.76% were identified as C. glabrata, 2.29% as C. tropicalis, 4.19% as C. parapsilosis, and 19.8% as C. krusei. The expression of the erg11 gene in the NAC was increased in samples isolated from humans compared to samples isolated from livestock (P>0.05), while no significant difference was found in the case of Candida glabrata isolated from both sources (P<0.05). All NAC isolates were sensitive to flucytosine. Conclusion: non-albicans Candida (NAC) isolates from cows' milk have antifungal resistance genes while they had not taken any antifungal drugs. The resistance gene is transferred from antifungal agents in crop protection medications. Clinical isolates also had increased resistance to antifungal activity. Also, using Azole antibiotics can increase resistance gene level activity. This phenomenon should be considered for treatment program protocols. [ABSTRACT FROM AUTHOR]

Citrus tristeza virus (CTV) is one of the economically destructive viruses affecting citrus trees worldwide, causing significant losses in fruit production. Comparative genomic studies have shown genetic diversity in various regions of the genome of CTV isolates, which has classified the virus into several genotypes. In recent years, some orange citrumelo-tolerant rootstocks showed yellowing, decline, and vein clearing in northern Iran (Mazandaran province, Sari). We confirmed the presence of CTV in the symptomatic trees by reverse transcription PCR (RT-PCR). The complete genome of a Sari isolate of CTV (Sari isolate) was sequenced using next-generation sequencing (NGS) technology. In addition, phylogenetic analysis, differential gene expression of the virus and identification of its variants in a population were studied. We obtained the final contigs of the virus (nt) and annotated all genomes to viral ORFs, untranslated regions (UTRs), intergenic regions, and 5' and 3' ends of the genome. Phylogenetic analysis of the Sari isolate and other genotypes of CTV showed that the Sari isolates were placed in a distinct cluster without a sister group. Based on the number of specific transcripts (TPM) in CTV RNA -Seq, P13 was the most highly expressed gene related to the host range of the virus and its systemic infection. The ORFs of the polyprotein, P33, and P18 showed variation in a single population of the sari isolate. The CTV has a potential for variation in a population in a host, and these variations may contribute to the best fit of the CTV in different situations. In Iran, whole genome sequencing of the CTV was performed for the first time, and we gained new insights into CTV variation in a population. [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]