Effect of PM2.5 exposure on adhesion molecules and systemic nitric oxide in healthy adults: The role of metals, PAHs, and oxidative potential.

Since there is limited evidence on the impact of PM2.5 content on cardiovascular biomarkers, we conducted a cross-sectional study on 89 healthy adults from October 12 to November 21, 2021. We measured daily PM2.5 in two distinct regions during different time windows: a high-traffic urban area and an industrial suburb. The concentrations of metals, PAHs, and oxidative potential (OP) were determined using ICP-MS, GC-MS, and dithiothreitol (DTT), respectively. Systemic biomarkers, including NO, sICAM-1, sVCAM-1, MDA, and CRP, were quantified in each subject simultaneously. A generalized linear model was used to examine the association between PM2.5 toxicity and each health endpoint. Our findings indicated that daily PM2.5 concentrations exceeded the WHO-recommended level by approximately sevenfold. We found that PM2.5 exposure was associated with adverse cardiovascular outcomes. Moreover, exposure to PM2.5 mass, total PAHs, and certain trace metals (Ni, Fe, V, As, and Pb) resulted in a decline in serum NO levels. At lag 3, exposure to PM2.5 mass resulted in a significant decrease in NO levels [1.32% (95% CI: -2.27, -0.12)] and total PAHs [2.05% (95% CI: -3.93, -0.12)]. In contrast, OP exhibited a mild correlation with NO level increases. Positive associations were observed between PM2.5 and its chemical constituents (PAHs, As, Cu, OP) and adhesion molecules at different lag times. An increase of 0.16 ppb in PAH concentrations at an interquartile range was associated with a 4.74% decline (95% CI, -7.80, -0.55) in the sVCAM-1 level. However, our study did not reveal any significant trend between pollutants and other biomarkers (sICAM-1, MDA, and CRP). Consequently, our findings suggest that different PM2.5 chemical compositions exhibit diverse behavior in biological responses.

Unraveling the link between PTBP1 and severe asthma through machine learning and association rule mining method.

Severe asthma is a chronic inflammatory airway disease with great therapeutic challenges. Understanding the genetic and molecular mechanisms of severe asthma may help identify therapeutic strategies for this complex condition. RNA expression data were analyzed using a combination of artificial intelligence methods to identify novel genes related to severe asthma. Through the ANOVA feature selection approach, 100 candidate genes were selected among 54,715 mRNAs in blood samples of patients with severe asthmatic and healthy groups. A deep learning model was used to validate the significance of the candidate genes. The accuracy, F1-score, AUC-ROC, and precision of the 100 genes were 83%, 0.86, 0.89, and 0.9, respectively. To discover hidden associations among selected genes, association rule mining was applied. The top 20 genes including the PTBP1, RAB11FIP3, APH1A, and MYD88 were recognized as the most frequent items among severe asthma association rules. The PTBP1 was found to be the most frequent gene associated with severe asthma among those 20 genes. PTBP1 was the gene most frequently associated with severe asthma among candidate genes. Identification of master genes involved in the initiation and development of asthma can offer novel targets for its diagnosis, prognosis, and targeted-signaling therapy.

Carcinogenic and non-carcinogenic risk of exposure to metal fume in different types of welding processes.

The international agency for cancer research (IARC) has classified welding fumes as definitive carcinogens. The aim of the present study was to assess health risk due to exposure to welding fumes in different welding types. In this study, exposure to fumes of iron (Fe), chromium (Cr), and nickel (Ni) in the breathing zone air of 31 welder engaged in arc, argon and CO2 welding was assessed. Carcinogenic and non-carcinogenic risk assessments due to exposure to fumes were performed using the method proposed by the Environmental Protection Agency (EPA) by Monte Carlo simulation. The results showed that in the CO2 welding, concentration of Ni, Cr, and Fe was lower than the 8-h Time-Weighted Average Threshold Limit Value (TWA-TLV), recommended by the American Conference of Governmental Industrial Hygienists (ACGIH). In argon welding, Cr and Fe concentrations were higher than the TWA-TLV. In arc welding, concentrations of Ni and Fe were more than the TWA-TLV. In addition, the risk of non-carcinogenicity due to exposure to Ni and Fe in all three types of welding was more than standard level (HQ>1). The results indicated that the welders are at health risk due to exposure to metal fumes. Preventive exposure control measures such as local ventilation need to be implemented in welding workplaces.

Micronucleus assay of DNA damage among welders: Effects of welding processes.

Metal fumes, gases, noise, and radiation are hazardous occupational exposures that may be encountered by welders. We have evaluated DNA damage among welders; the buccal micronucleus cytome (BMCyt) assay was used. Thirty-four exposed welders (cases) and an equal number of non-welders (controls) participated in this study. Cell types including basal, early and late differentiated cells with micronucleus (MN), dense chromatin, karyorrhectic, pyknotic, karyolitic, and binucleated cells (NBUD) were measured. Damage levels among, arc, argon, and CO2 welders were statistically significantly higher, compared to the control group. Results showed that mean of MN and NBUDs as indicators of DNA damages among arc, argon and CO2 welding's were significantly higher compared to control group. Also, the mean of DNA damage levels were statistically higher among the arc welders than among the argon or CO2 welders; and levels were higher among the argon welders than the CO2 welders. Preventative measures need to be implemented to reduce exposure to harmful agents during welding.

Economic Burden of Asthma in Northwest Iran.

Background: The economic burden of asthma is a major public health concern. This study estimates the economic burden of asthma in Northwest of Iran. Methods: A longitudinal study was conducted between 2017 and 2018 in Tabriz (Iran) using the Persian version of the Work Productivity and Activity Impairment (WPAI) questionnaire. Direct and indirect costs associated with asthma were estimated based on the societal perspective, prevalence-based approach, and bottom-up method. Annual indirect costs were estimated using the human capital (HC) method. The structural equation model was used to evaluate the relationship between costs, sex, and asthma severity. Results: A total of 621 patients with asthma were enrolled in the study. Significant differences were found between female and male patients for the mean cost of radiology (P=0.006), laboratory (P=0.028), and diagnostic (P=0.017) tests at baseline, and for laboratory (P=0.012), and diagnostic (P=0.027) tests at one-year follow-up. The more severe asthma, the more significant the costs for annual physician office visits (P=0.040) and medications (P=0.013). As asthma severity increased, significantly higher expenditures were observed in women for days lost from work at baseline (P=0.009) and one-year follow-up (P=0.001), and in men for productivity loss at work due to impairment at baseline (P=0.045). A significant association between indirect costs and the cost of impairment-related lost productivity at work (ß=3.29, P<0.001), and between severe asthma and indirect costs (ß=32.36, P<0.001) was observed. Conclusion: High costs are incurred by Iranian asthma patients, especially because of impairment-related productivity loss at work associated with asthma exacerbation.

Male-biased association of endothelial nitric oxide synthase Asp298Glu substitution (NOS3-c.894G/T) with asthma risk and severity.

OBJECTIVE: The nitric-oxide pathway plays a crucial role in the pathogeneses of asthma and NOS3-encoded endothelial nitric oxide synthase is one of the main components of the pathway. Variants of NOS3 are known to contribute to asthma development and pathophysiology. METHODS: We investigated the association of NOS3-c.894G/T (rs1799983) with asthma risk and severity by studying frequencies of its genotypes and alleles in 555 asthmatics (93 intermittent, 240 mild, 158 moderate, and 64 severe asthma cases) and 351 control participants using the PCR-FRLP method, logistic regression analysis and generalized ordered logit estimates. RESULTS: GT genotype (ORadj: 1.39; CI: 1.04-1.85; p = 0.026), dominant model GT + TT (ORadj: 1.41; CI: 1.07-1.87; p = 0.015), and T allele (ORadj: 1.32; CI: 1.05-1.67; p = 0.018) was associated with increased ORs in asthmatics. Also, the frequency of GT + TT (ORadj: 1.55; CI: 1.01-2.38; p = 0.044) was significantly higher in males. Furthermore, GT genotype (ORadj: 1.39; CI: 1.04-1.85; p = 0.024), GT + TT (ORadj: 1.42; CI: 1.07-1.87; p = 0.014), and T allele (ORadj: 1.32; CI: 1.05-1.66; p = 0.018) in total population and GT + TT (ORadj: 1.56; CI: 1.02-2.37; p = 0.04) in males were significantly associated with increased risk of severe, moderate, mild, intermittent asthma vs. controls. Also, GT genotype (ORadj: 1.39; CI: 1.02-1.91; p = 0.039) was significantly more frequent in severe, moderate grades vs. lower severity grades in the total population. Frequencies of GT genotype (ORadj: 1.77; CI: 1.05-3.00; p = 0.032) and GT + TT (ORadj: 1.74; CI: 1.04-2.90; p = 0.036) in total population and GT genotype (ORadj: 2.40; CI: 1.16-4.97; p = 0.018) and GT + TT (ORadj: 2.30; CI: 1.12-4.74; p = 0.023) in male subpopulation were significantly higher in severe cases compared to lower grades. CONCLUSIONS: NOS3-c.894G/T may be associated with asthma risk and its severer grades, with greater effects in men.

Association of the Toll-like receptor 4 and NOX4 gene and protein levels in asthmatic patients with metabolic syndrome: A case-control study.

Background: Understanding the contributing of influence inflammatory biomarkers in asthmatic patients with metabolic syndrome is more important. Whereby, the present study considering the important association of NADPH oxidase4 (NOX4) and Toll- like receptor4 (TLR4) in the respiratory inflammatory responses in asthmatic patients with metabolic syndrome (AS-MetS) and asthmatic (AS) patients. Materials and Methods: In this case-control study, 30 AS and 34 AS-MetS patients were enrolled. The Peripheral blood mononuclear cells (PBMCs) mRNA and protein levels of TLR4 and NOX4 were measured by qRT-PCR and western blot, respectively. Then their correlation was evaluated. Results: The significant down-regulation of mRNA and protein PBMCs expression levels of TLR4 were observed in the AS-MetS group in comparison to AS one (P=0.03), but the NOX4 expression was non-significant. Additionally, the significant correlation was exhibited between mRNA expression levels of NOX4 and TLR4 in both AS-MetS (r= 0.440, P=0.009) and AS groups (r=0.909, P=0.0001). The association between TLR4 mRNA level and triglyceride in AS-MetS group (r=0.454, P=0.008,) and also white blood cells (WBC) in AS group (r= -0.507, P=0.006,) were significant. Conclusion: The metabolic syndrome can significantly influence the expressions of TLR4 in AS-MetS. This study indicated that TLR4 and NOX4 altogether may provide valuable molecular knowledge of their relation with metabolic syndrome criteria for finding major pathways in different phenotype of asthma.

Sex-specific association of exposure to air pollutants and Nrf2 gene expression and inflammatory biomarkers in exhaled breath of healthy adolescents.

Studies investigating the nuclear factor erythroid 2-related factor 2 (Nrf2) expression levels in the respiratory system of healthy subjects are scarce. Moreover, separate studies on the health-related outcomes of air pollution for each sex are limited. The current panel study investigated sex-specific Nrf2 expression levels and related oxidative stress and inflammatory responses among healthy adolescents exposed to PM2.5, PM10, O3, and PM2.5-bounded metals in a high traffic region. Forty-nine healthy nonsmoking subjects participated in the study for five consecutive months (Nov. 2019 to Feb. 2020). Each subject was asked to provide 1 mL of exhaled breath condensate (EBC). Data were analyzed using linear mixed-effects models. The results showed that PM10, PM2.5, O3, and PM2.5-bounded metals were negatively linked to Nrf2 expression level in EBC of females with -58.3% (95% CI: 79.5, -15.4), -32.1% (95% CI: -50.3, -7.1), -76.2% (95% CI: -92.6, -23.9), and -1.9 (95% CI: -3.4, -0.4), respectively. While our results presented no significant association between the studied pollutants and Nrf2 gene expression in males, significant associations were observed between the pollutants and total nitric oxide (NOx), interleukins 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in the EBC of females. In the case of males, only EBC cytokines showed a significant association with air pollutants. Overall, this study suggests that exposure to ambient air pollutants may affect the respiratory system with biologically different mechanisms in males and females. PM2.5 concentration had a positive correlation with exhaled TNF-α and IL6 values in females while positive correlation with TNF-α and negative correlation with IL6 values in males. O3 had a negative correlation with TNF-α in males.

Female-biased association of NOS2-c.1823C>T (rs2297518) with co-susceptibility to metabolic syndrome and asthma.

The nitric oxide (NO) pathway contributes to the pathogeneses of metabolic syndrome (MetS) and asthma. NOS2 encodes inducible-NO synthase, which is an important enzyme of the pathway, and its variations could affect the risk of asthma and MetS and thereby co-susceptibility to them. This study aims to estimate the association of NOS2-c.1823C>T with risk of asthma, MetS, and asthma with MetS condition (ASMetS), and with asthma stages: intermittent, mild, moderate, and severe asthma. The study included asthmatics (n = 555), MetS (n = 334), and ASMetS cases (n = 232) and 351 controls, which were genotyped by the PCR-RFLP method. The T allele was significantly associated with an increased risk of asthma and MetS in the sample population and females. CT genotype and CT+TT model were significantly associated with increased risk of ASMetS in females. A significant association between CT genotype and increased risk of ASMetS in the sample population and females was found in ASMetS versus MetS. In the sample population and among females, the T allele was significantly associated with severe asthma. The rs2297518 single nucleotide polymorphism of NOS2 contributes to the risk of MetS, asthma, and co-susceptibility to them, and this contribution may be stronger in females compared to males.

MicroRNA-Based Biomarkers in Lung Cancer: Recent Advances and Potential Applications.

INTRODUCTION: MicroRNAs (miRNAs) are a group of small noncoding RNAs (ncRNAs) that post-transcriptionally control the expression of genes by binding and degrading their target mRNAs. miRNAs can function as possible tumor suppressors or oncogenes in various cancers. Lately, miRNAs application as a biomarker (prognosis and diagnosis) for different diseases has gained much attention. miRNAs exist in a stable form in several biological materials, including tissue, plasma, and serum. The noninvasive and easy screening of miRNAs in serum, blood, tissue, and other body fluids and acceptable stability make microRNA a noticeable factor as biomarkers in human malignancies. MATERIALS AND METHODS: In this review, we searched some online databases like Web of Science, Embase, and PubMed to find eligible manuscripts up to the end of 2021. RESULTS: Abnormal expressions of these molecules are associated with the incidence of many illnesses like cancer. Therefore, they are candidates as a molecular tool for noninvasive tumor prognosis and diagnosis. In the current study, we introduce important miRNAs that may be used as prognostic and diagnostic markers in lung cancer patients. CONCLUSION: We summarized the latest reports about critical miRNAs related to the diagnosis and prognosis in lung patients.

A Review of Substrates for Solid-State Fermentation of Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), for Basidiome Production and Effect on Bioactive Compounds.

Mushrooms in the genus Ganoderma have been collected and used as medicine since ancient times. However, commercial basidiome production has only recently been achieved. The solid substrates for basidiome production usually consist of lignocellulosic materials as the major component and the supplements (e.g., different types of bran and flour) as the minor segment. Research on substrates for solid-state fermentation with the purpose of basidiome production has focused on investigating locally available agrowaste materials, and their suitability is judged by the economic outputs. This review summarizes the formulations of the substrates and discusses their effects on the yield of basidiome or its bioactive compounds. Through a comprehensive look, this review concludes that future research focused on various treatments to modulate extracellular enzyme production may bring more options to the table for innovative solid substrate formulation.

Regulatory Effect of let-7f Transfection in Non-Small Cell Lung Cancer on its Candidate Target Genes.

Background: Let-7f has essential impacts on biological processes; however, its biological and molecular functions in lung cancer pathogenesis have yet been remained unclear. We aimed to investigate the expression level of let-7f and its candidate target genes both in lung cancer tissues and A549 cell line. Methods: Bioinformatics databases were first used to select candidate target genes of let-7f. Then the relative gene and protein expressions of let-7f and its target genes, including HMGA2, ARID3B, SMARCAD1, and FZD3, were measured in lung tissues of NSCLC patients and A549 cell line using qRT-PCR and Western blotting. The electroporation method was used to transfect A549 cells with let-7f mimic and microRNA inhibitor. The impact of let-7f transfection on the viability of A549 cells was assessed using MTT assay. The expression data of studied genes were analyzed statistically. Results: Results indicated significant downregulated expression level of let-7f-5p (p = 0.0013) and upregulated level of the HMGA2 and FZD3 in NSCLC cases (p < 0.05). In A549 cells, after transfection with let-7f mimic, the expression of both mRNA and protein levels of HMGA2, ARID3B, SMARCAD1, and FZD3 decreased. Also, the overexpression of let-7f significantly inhibited the A549 cell proliferation and viability (p = 0.017). Conclusion: Our findings exhibited the high value of let-7f and HMGA2 as biomarkers for NSCLC. The let-7f, as a major tumor suppressor regulatory factor via direct targeting genes (e.g. HMGA2), inhibits lung cancer cell viability and proliferation and could serve as a marker for the early diagnostic of NSCLC.

Combination Therapy with KRAS and P38α siRNA Suppresses Colorectal Cancer Growth and Development in SW480 Cell Line.

PURPOSE: Colorectal cancer (CRC) is one of the most prevalence malignancies in a different society with a high rate of death. The KRAS and p38α axes have critical roles in the development, migration, and growth of numerous tumors, such as colorectal malignancy. KRAS mutation acts as an oncogene in various cancers and is correlated with the poor prognosis in colorectal tumors. Also, p38α plays different roles and exhibits tissue-dependent activity. In some tissues act as an oncogene while in others act as a tumor suppressor. In this research, we try to understand the effect of the P38α and KRAS genes suppression by specific siRNAs on the SW480 cell line progression. METHODS: We evaluate the impact of the P38α and KRAS gene knockdown by special siRNA on the growth and development of the SW480 cell line. SW480 cell line was treated with KRAS and P38α siRNAs, and the cell viability, gene expression, migration ability, and rate of apoptosis were evaluated with MTT assay, real-time PCR, scratch test, and flow cytometry. RESULTS: After treatment of the cancer cell with KRAs and P38α siRNAs, cell viability reduced to 29.16%. Also, the expression levels of the KRAS and P38α genes reduced to 26.34% and 16.06%, respectively. Apoptosis rate after combination therapy with KRAS and P38α siRNAs increased to 72.1. Also, we found that these siRNAs suppress cell migration in SW480 cell lines. CONCLUSION: The current study showed that combination therapy with p38α and KRAS siRNA may be considered a novel therapy for colorectal tumor in future.

The oxidative and neurotoxic potentials of the ambient PM2.5 extracts: The efficient multi-solvent extraction method.

The health effects of ambient air particulate matter with a diameter of ≤2.5 µm (PM2.5) on the central nervous system are well known and the induced oxidative stress has been shown as their main neuropathologic outcome. Ambient air PM2.5 sampling methods mostly use air sampler systems that collect PM2.5 on filters, which is followed by a PM2.5 extraction approach. Inefficient extraction may lead to compositional bias and unreal interpretation of the results. This study aimed to compare our proposed multi-solvent extraction (MSE) approach for PM2.5 extraction with a conventional aqueous extraction (AqE) method using the analysis of oxidative effects and cytotoxicity in the human neuroblastoma SH-SY5Y cell line. Ambient PM2.5 samples were collected from an urban traffic location in Tehran city, the capital of Iran, using a high-volume sampler. The developed MSE method was proved to have superior advantages over the AqE method including an increased extraction efficiency (as much as 96 against 48% for PMms and PMaq, respectively), and decreased artifacts and compositional biases. Ambient PM2.5, besides PMms and PMaq were analyzed for water-soluble ions, metals, and major elements. Dithiothreitol, ascorbic acid, lipid peroxidation, and cell viability assays on SH-SY5Y cells represented the significantly higher oxidative potential for PMms compared to PMaq. The increased cytotoxicity may occur because of the increased oxidative potential of PMms and possibly is associated with higher efficiency of the MSE over the AqE method for removal of total redox-active PM components.

Association Between NOX4 And Nrf2 Genes in Non-Small-Cell Lung Carcinoma: A Case-Control Study.

BACKGROUND: Epithelial malignancy in lung cancer, which is initiated with myofibroblast differentiation and remodeling, promotes hypoxia and intracellular ROS generation most affected by the prototypical enzyme, NADPH oxidase 4 (NOX4). In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) acts as a critical transcription factor by stimulating antioxidant proteins as redox homeostasis regulators. The aim of this study was to investigate a possible correlation between lung tissue NOX4 and Nrf2 genes (NOX4 and Nrf2) mRNA expression and bronchoalveolar lavage fluid (BALF) protein expression in non-small-cell lung carcinoma (NSCLC) patients. METHODS: Samples from 25 patients with various NSCLC types and stages and 20 healthy controls were collected. NOX4 and Nrf2 mRNA were measured by qRT-PCR, and protein by western blot analysis. RESULTS: NOX4 mRNA and protein expression was significantly up-regulated in NSCLC patients' lung tissues and BALFs (p= 0.03 and 0.01, respectively). In addition, by adjusting for age, sex, and NSCLC types and stages, a significant and positive correlation was observed between NOX4 and Nrf2 mRNA expression (r= 0.927, p= 0.001). This was also true when not adjusted as above (r= 0.944, p< 0.001). CONCLUSION: NOX4 mRNA and protein expression is significantly up-regulated in NSCLC patients' lung tissues and BALFs, and NOX4 and Nrf2 mRNA expression is positively correlated in NSCLC tissues.

Polymorphism (-499C/G) in DDAH2 promoter may act as a protective factor for metabolic syndrome: A case-control study in Azar-Cohort population

ABSTRACT Objective: Globally developing metabolic syndrome (MetS) prevalence as a major health problem can be related to multiple factors of genetic and environmental. Dimethylaminohydrolase 2 (DDAH2) is the main enzyme implicated in the cardiovascular system, which regulates the nitric oxide pathway. This study investigated the association of DDAH2 polymorphism −499C/G (rs805305) with the risk of MetS among the Azar-Cohort population. Subjects and methods: The occurrence of SNP rs805305 in the DDAH2 gene was tested using the PCR-RFLP method in 332 MetS cases and 294 healthy controls. Afterward, the association of the allele and genotypes with the risk of MetS and its components were examined. Results: The G allele and GC genotype were significantly associated with a reduced risk of MetS (P ≤ 0.001). Also, the dominant genetic model (GG+GC) significantly decreased the risk of MetS (P = 0.001), however, in sex subtypes MetS risk was significantly reduced in males before and in females after adjustment for age (P ≤ 0.02). Conclusion: The −499C/G polymorphism of DDAH2 may play a protective role and reduce MetS risk among the Azar-Cohort population.

Acute responses of airway oxidative stress, inflammation, and hemodynamic markers to ambient PM2.5 and their trace metal contents among healthy adolescences: A panel study in highly polluted versus low polluted regions.

Particulate air pollutants are known contributors to global cardiorespiratory mortality through several pathways. We examined the effects of varied exposure to PM2.5 and trace metals on biological markers of airway inflammation, oxidative stress, and hemodynamic function of young individuals living in two different exposure settings. We enrolled and followed a panel of 97 healthy nonsmoking participants aged 15-18 years living in a highly polluted metropolitan city of Tabriz (TBZ) and a much less polluted semi-urban town of Hadishahr (HDS). For five consecutive months, the subjects were examined by a physician, and fractional exhaled nitric oxide levels (FENO) were measured. Samples of exhaled breath condensation (EBC) were obtained for measuring interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and total nitric oxide (NOx). We measured daily outdoor PM2.5 mass concentration in a fixed station in each location for all this period. The PM-metal content was analyzed by ICP-MS. The linear mixed-effects regression models were applied for data analysis. The averages of PM2.5 mass and total metals in TBZ were nearly two and four times higher than in HDS, respectively. In TBZ, an increased IQR of PM2.5 mass during 0-5 days was -correlated with a significant rise in diastolic blood pressure, heart rate, TNF-α, FENO, and NOx and reduction of IL-6. Moreover, exposure to low PM2.5 concentration is significantly -correlated with an elevation in diastolic blood pressure in HDS. We also observed that exposure to metal constituents in the highly polluted region is correlated with increased TNF-α and IL-6 with 131.80% (95% CI: 56.01, 244.39) and 47.51% (95% CI: 33.01, 62.05) per IQR of Hg, respectively. This study suggests that exposure to ambient PM2.5 and their metal contents in highly polluted areas may incite significant changes in airway inflammation, oxidative stress, and hemodynamic parameters in healthy subjects.

Polymorphism (-499C/G) in DDAH2 promoter may act as a protective factor for metabolic syndrome: A case-control study in Azar-Cohort population.

OBJECTIVE: Globally developing metabolic syndrome (MetS) prevalence as a major health problem can be related to multiple factors of genetic and environmental. Dimethylaminohydrolase 2 (DDAH2) is the main enzyme implicated in the cardiovascular system, which regulates the nitric oxide pathway. This study investigated the association of DDAH2 polymorphism -499C/G (rs805305) with the risk of MetS among the Azar-Cohort population. METHODS: The occurrence of SNP rs805305 in the DDAH2 gene was tested using the PCR-RFLP method in 332 MetS cases and 294 healthy controls. Afterward, the association of the allele and genotypes with the risk of MetS and its components were examined. RESULTS: The G allele and GC genotype were significantly associated with a reduced risk of MetS (P ≤ 0.001). Also, the dominant genetic model (GG+GC) significantly decreased the risk of MetS (P = 0.001), however, in sex subtypes MetS risk was significantly reduced in males before and in females after adjustment for age (P ≤ 0.02). CONCLUSION: The -499C/G polymorphism of DDAH2 may play a protective role and reduce MetS risk among the Azar-Cohort population.

Association of NOS3-c.894G>T transversion with susceptibility to metabolic syndrome in Azar-cohort population: A case-control study and in silico analysis of the SNP molecular effects.

OBJECTIVES: We investigated whether NOS3-c.894G>T transversion (rs1799983), which causes the substitution of glutamate with aspartate (E298D) in the oxygenase domain of endothelial nitric oxide synthase (eNOS), is associated with susceptibility to metabolic syndrome (MetS) risk in Iranian-Azerbaijanis. MATERIALS AND METHODS: The frequencies of the alleles and genotypes were compared in the 300 cases and 300 controls using PCR-RFLP assay. Also, higher-order MetS interaction with the genotypes, gender, age, and body mass index (BMI) was evaluated by classification and regression tree (CART) analysis. In silico analysis was done to introduce a hypothesis describing the molecular effects of NOS3-c.894G>T. RESULTS: The T allele (OR:1.46; CI:1.054-2.04; P=0.02), GT genotype (OR:1.44; CI:1.02-2.03; P=0.03), and dominant model (TT+GT vs GG, OR:1.48; CI:1.06-2.06; P=0.01) were found to be associated with increased risk of MetS. In the male subpopulation TT genotype (OR:7.19; CI:1.53-33.70; P=0.01) was discovered to be associated with increased odds of MetS. CART analysis showed that NOS3-c.894G>T genotypes and BMI significantly contribute to modulating MetS risk. Furthermore, in silico investigation revealed that c.894G>T may alter eNOS function through affecting interactions of its oxygenase domain with proteins such as B2R, b-actin, CALM1, CAV1, GIT1, HSP90AA1, NOSIP, and NOSTRIN. CONCLUSION: We showed that NOS3-c.894G>T was associated with an increased risk of MetS in Iranian-Azerbaijanis, and BMI modulates the effects of NOS3-c.894G>T genotypes on MetS risk. Also, in silico analysis found that NOS3-c.894G>T may affect the interaction of the eNOS oxygenase domain with its several functional partners.

Terminalia Catappa Extract (TCE) Reduces Proliferation of Lung and Breast Cancer Cell by Modulating miR-21 and miR-34a Expressions.

BACKGROUND: After cardiovascular illness, cancer is the one of the main and second cause of death in the worldwide. Despite significant advances in this field, low survival, drug resistance, and side effects of chemotherapy remain an unsolved problem. Due to the high mortality rate among cancer patients, finding the new substance to treatment with low side effects is important. Previous studies have been informed that positive effects of herbal medicines on cancer patients, which are very efficient in the treatment of cancer. METHODS: In this study, the antitumor effect of ethanolic Terminalia catappa leaf extract (TCE) on MCF-7, MDA-231, and A549 cell lines was examined. For this reason, the effects of TCE on cell migration, gene expression, and growth were investigated by scratch, test, real-time PCR (qPCR) qPCR, and MTT tests respectively. RESULTS: As a reported by the MTT outcomes, TCE significantly decreased the viability of A549, MCF-7, and MDA-231 cells (P < 0.05).  Moreover, genes expression patterns that are related to proliferation (miR-21, miR-34a), migration (MMP-13, Vimentin), and apoptosis (Cas-3, Cas-8, Cas-9, Bcl-2, Bax) also have changed significantly after treatment with TCE. Also, in the A549 cell line, Bax (p value: 0.029), Cas-9 (p value: 0.00023), miR-34a (p value: 0.031), Bcl-2 (p value: 0.0076), MMP-13 (p value: 0.041), Cas-3 (p value: 0.00051) and in MCF-7 cell line Bax (p value: 0.0004), Cas-3 (p value: 0.0003), Cas-9(p value: 0.037), miR-34a (p value: 0.005), Bcl-2(pvalue:0.0007), mir-21(p value:0.016), MMP-13(p value: 0.011) and in MDA-231 cell line Bax(p value<0.0001), Cas-3(p value: 0.003), Cas-9(p value: 0.0004). mir-34a (p value:0.0019), Bcl-2(p value:0.0023), MMP-13(p value: 0.032) have significantly changed compare to control group. CONCLUSION: The outcomes of this research determined that T. Catappa might be a potential source of antitumor compounds and could be a candidate for further research.
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