Application of PLK1 and HOXA13 Gene Expression Levels in Urine in the Diagnosis of Non-muscle Invasive Bladder Cancer.

Bladder cancer is the most common urinary tract neoplasm, affecting many people annually. Current diagnostic and surveillance methods for bladder cancer are frequently invasive and lack sensitivity and specificity. This study aimed to develop an accurate and non-invasive urine-based gene expression assay, including fibroblast growth factor receptor 3 (FGFR3), homeobox A13 (HOXA13), and polo-like kinase 1 (PLK1), to diagnose non-muscle-invasive bladder cancer (NMIBC) at stages Ta and T1. The samples were acquired from 62 patients with NMIBC, 31 control individuals, and 31 patients with non-cancerous genitourinary tract diseases. The expression levels of three relevant genes were determined using quantitative RT-PCR. In addition, the sensitivity and specificity of the data for these genes were computed. Our results showed that PLK1, HOXA13, and FGFR3 expressions of genes were significantly elevated in patients compared to the control groups (p = 0.0001; p = 0.039). The sensitivity and specificity for the FGFR3 gene were 55% and 76%, respectively (p = 0.39). These parameters for HOXA13 were 100% and 93% (p = 0.0001) and for PLK1 were 100% and 86% (p = 0.0001) for diagnosing and monitoring NMIBC. HOXA13 and PLK 1 exhibited adequate specificity and sensitivity for diagnosis. The results of this research showed that despite the higher expression of these genes in urine, only HOXA13 and PLK1 had sufficient and proper specificity and sensitivity, so the urinary expression of these two genes can be used in future studies for diagnosis and monitoring in cancer bladder.

Development of a novel liposomal nanoparticle formulation of cisplatin to breast cancer therapy.

Cisplatin is one of the conventional drugs used in chemotherapy which has a potent antitumor function. However, due to the dangerous side effects, including the damage to DNA of the normal cells, its clinical use is limited. The aim of this study was to prepare and characterize nanoliposome containing cisplatin. We optimized liposome formulations through the modification of the proportion of SPC80 (soybeanphospholipids with 75% phosphatidylcholine) and cholesterol content. Then, novel PEGylated liposomal formulations containing SPC80: cholesterol: DSPE-mPEG (at ratios of 85:10:5) were designed and developed to serve as a therapy to achieve more improved pharmaceutical efficiency. Zeta Sizer showed that PEGylated nanoliposomes had a mean diameter of 119.7 ± 2.1 nm, a zeta potential of -26.03 ± 1.34 mV, and entrapment efficiency of 96.65 ± 3%. The optimum formulations represented sustained, thermo-sensitive release, and augmented cellular uptake. The cytotoxic effect of the liposomal drug was higher than the free medication drug that confirmed the efficiency of cellular uptake. This study suggests that nanoliposome-loaded cisplatin plays a vital role in improving drug efficacy and the reduction of dosage.

Mild antagonistic effect of Valproic acid in combination with AZD2461 in MCF-7 breast cancer cells.

Background: Breast cancer (BC) is a complex disease, but current treatments are not efficient enough considering increased relapse and decreased survival rate among patients. Poly (ADP-ribose) polymerase inhibitors are recently developed anticancer agents which target cells with defects in homologous recombination (HR) pathway. This study wishes to assess whether the combination of AZD2461 as a newly developed PARP1 inhibitor and valproic acid (VPA), a histone deacetylase inhibitor could effectively reduce the growth of MCF-7 cells with no fundamental DNA repair defect. Methods: Both trypan blue dye exclusion assay and MTT viability test were used to evaluate cell death. γ-H2AX levels, as a marker of DNA repair, were measured using in cell ELISA method. The Student's t-test and non-parametric analysis of variance (ANOVA) were applied for our data analyses where p-value <0.05 was considered statistically significant. Results: As calculated by CompuSyn software, IC50 values for VPA and AZD2461 were 4.89 mM and 42.83 µM respectively following 48 hours treatment. Also, the trypan blue exclusion assay results showed a concentration- and time-dependent decrease when MCF-7 cells were treated with both agents (p<0.05). Combination analysis showed a mild antagonism (CI>1.1) while γ-H2AX levels found not to be significantly increased in MCF-7 cells co-treated with VPA+AZD2461 compared to each agent alone (p=0.29). Conclusion: Our findings revealed that the combination of VPA and AZD2461 could decrease cell viability of MCF-7 cells, but it was not able to significantly increase unrepaired DNA damage sites. The mechanism responsible for drugs combination was not of synergism or addition. Determining the type of involved cell death mechanisms might be followed in further studies.

Paclitaxel and curcumin coadministration in novel cationic PEGylated niosomal formulations exhibit enhanced synergistic antitumor efficacy.

BACKGROUND: The systemic administration of cytotoxic chemotherapeutic agents for cancer treatment often has toxic side effects, limiting the usage dose. To increase chemotherapeutic efficacy while reducing toxic effects, a rational design for synergy-based drug regimens is essential. This study investigated the augmentation of therapeutic effectiveness with the co-administration of paclitaxel (PTX; an effective chemotherapeutic drug for breast cancer) and curcumin (CUR; a chemosensitizer) in an MCF-7 cell line. RESULTS: We optimized niosome formulations in terms of surfactant and cholesterol content. Afterward, the novel cationic PEGylated niosomal formulations containing Tween-60: cholesterol:DOTAP:DSPE-mPEG (at 59.5:25.5:10:5) were designed and developed to serve as a model for better transfection efficiency and improved stability. The optimum formulations represented potential advantages, including extremely high entrapment efficiency (~ 100% for both therapeutic drug), spherical shape, smooth-surface morphology, suitable positive charge (zeta potential ~ + 15 mV for both CUR and PTX), sustained release, small diameter (~ 90 nm for both agents), desired stability, and augmented cellular uptake. Furthermore, the CUR and PTX kinetic release could be adequately fitted to the Higuchi model. A threefold and 3.6-fold reduction in CUR and PTX concentration was measured, respectively, when the CUR and PTX was administered in nano-niosome compared to free CUR and free PTX solutions in MCF-7 cells. When administered in nano-niosome formulations, the combination treatment of CUR and PTX was particularly effective in enhancing the cytotoxicity activity against MCF-7 cells. CONCLUSIONS: Most importantly, CUR and PTX, in both free form and niosomal forms, were determined to be less toxic on MCF-10A human normal cells in comparison to MCF-7 cells. The findings indicate that the combination therapy of PTX with CUR using the novel cationic PEGylated niosome delivery is a promising strategy for more effective breast cancer treatment.

Comparison of hematological parameters, iron levels, and oxidative stress in women with and without breast cancer: A case- control study.

Background: Iron is one of the nutrients that has recently received considerable attention because of its dual role in the incidence of breast cancer. The present study aimed at comparing hematological parameters, iron levels, and oxidative stress in women with and without breast cancer. Methods: The participants in this case-control study were 55 women, of whom 26 were new cases of breast cancer (confirmed by biopsy) as the case, and 29 without cancer (confirmed by mammography) as the control group. All participants underwent blood testing for complete blood count (CBC (free iron, ferritin, total iron binding capacity) TIBC (2, 2-diphenyl-1-picrylhydrazyl (DPPH), and Malondialdehyde (MDA). Results: The mean±SD age of the participants was 44.25±9.82 years, and there was no significant difference between groups. Also, no statistically significant difference was found between the 2 groups in variables, except the mean corpuscular volume of red cells (MCV), mean corpuscular hemoglobin concentration (MCHC), and mean cell hemoglobin (MCH). The use of iron supplements was significantly higher in the control than in the case group (p= 0. 01), with an odds ratio of 0.19% (95% CI: 0.45-0.7). The mean serum DPPH was significantly higher in the control than in the case group (p= 0. 006), but comparison of serum MDA showed no significant difference between the 2 groups. Conclusion: Iron deficiency anemia was greater in patients with breast cancer than in those without it. Moreover, iron supplementation appears to have a protective effect against breast cancer incidence. In addition, serum DPPH, as a total antioxidant index, was significantly higher in the control group.

Diode Laser Irradiation Effects on Miniscrew Stability and IL-1ß and TGF-ß1 Levels: A Split-Mouth Randomized Controlled Clinical Trial.

Introduction: This study aimed to assess the effect of low-level laser therapy (LLLT) on miniscrew stability and concentrations of interleukin-1ß (IL-1ß) and transforming growth factor-beta (TGF-ß1) in peri-miniscrew crevicular fluid in the course of orthodontic treatment. Methods: This randomized split-mouth double-blind clinical trial evaluated 18 patients requiring anterior retraction along with maximum anchorage. Miniscrews were placed between the maxillary second premolar and first molar. A diode laser was irradiated with a 980-nm wavelength and 100-mW output power in continuous-wave mode at four time points: T0 (1 hour after miniscrew placement), T1 (1 week later), T2 (at 1 month) and T3 (at 3 months) in one quadrant of the maxilla (laser group). The other quadrant of the maxilla underwent the pseudo-application of the laser (control group). The primary stability of miniscrews was measured by Periotest M and reported as Periotest value (PTV). Also, at each time point, samples were collected from the peri-miniscrew crevicular fluid one hour after laser irradiation to assess the concentration of IL-1ß and TGF-ß1. Results: The mean PTV (inverse of the stability) was smaller in the laser group compared with the control group at all time points; this difference was significant at T2 and T3. The mean concentration of IL-1ß in the laser group was lower than that in the control group at all time points, and this difference was significantly remarkable at T0 and T3. The mean concentration of TGF-ß1 in the laser group was lower than that in the control group at T0, T1 and T3; however, the difference was not statistically significant. Conclusion: The current results supported the efficacy of LLLT in increasing the miniscrew stability and decreasing the level of IL-1ß pro-inflammatory cytokine.

The effect of the dietary approaches to stop hypertension diet on total antioxidant capacity, superoxide dismutase, catalase, and body composition in patients with non-alcoholic fatty liver disease: a randomized controlled trial.

Aim: Non-alcoholic fatty liver disease (NAFLD) is a condition characterized by the accumulation of fat in the liver without excessive alcohol consumption. Lifestyle modifications, such as adopting a healthy diet, represent the standard treatment for NAFLD. However, the impact of the Dietary Approaches to Stop Hypertension (DASH) diet on oxidative stress biomarkers in patients with NAFLD remains unclear. Therefore, this study aimed to determine the effect of the DASH diet on total antioxidant capacity (TAC), catalase (CAT), superoxide dismutase (SOD) levels, and body composition in overweight and obese patients with NAFLD. Methods: A total of 70 overweight and obese patients aged 1870 years were randomly assigned to either the intervention (DASH diet, n = 35) or the control group (control diet, n = 35) for 12 weeks, with both groups following a calorie-restricted diet. Results: The mean age of participants was 43.1 ± 8.1 years in the DASH group and 45.1 ± 8.6 years in the control group. At the end of the study, a significant difference was observed in the mean TAC and SOD levels between the two groups (p = 0.02). After adjusting for potential confounding factors, such as age, sex, diabetes, smoking, physical activity, and baseline values, the DASH diet maintained its significant effects on TAC and SOD compared to the control diet (p = 0.03). However, there were no significant differences in CAT levels between the two groups. Moreover, a significant reduction in visceral fat (p = 0.01) and a marginally significant decrease in BMI (p = 0.06) were observed in the DASH group compared to the control group after adjusting for potential confounders. Conclusion: In conclusion, our study showed that following the DASH diet for 12 weeks in overweight and obese patients with NAFLD has beneficial effects on TAC, SOD, and visceral fat. These findings support the use of the DASH diet as a potential therapeutic intervention for the improvement of oxidative biomarkers in patients with NAFLD. Clinical trial registration: www.irct.ir/, identifier IRCT20170117032026N3.

Synthesis of a novel nanocomposite containing chitosan as a three-dimensional printed wound dressing technique: Emphasis on gene expression.

In this study, a highly porous three-dimensional (3D)-printed wound healing core/shell scaffold fabricated using poly-lactic acid (PLA). The core of scaffold was composed of hyaluronic acid (HA), copper carbon dots (Cu-CDs), rosmarinic acid, and chitosan hydrogel. Cu-CDs were synthesized using ammonium hydrogen citrate under hydrothermal conditions. Formulation containing 1 mg ml-1 concentration of Cu-CDs showed an excellent antibacterial activity against gram bacteria. At 0.25 mg ml-1 of Cu-CDs concentration, scaffold had a good biocompatibility as confirmed by cytotoxicity assay on L929 fibroblast stem cells. in vivo wound healing experiments on groups of rats revealed that after 15 days of treatment, the optimal formulation of composite scaffold significantly improves the wound healing process compared to the PLA scaffold. This finding was confirmed by histological analysis and the relative expression of PDGF, TGF-ß, and MMP-1 genes. The biocompatible antibacterial CU-CDS/PLA/HA/chitosan/rosmarinic acid nanocomposite is a promising wound healing scaffold which highly accelerates the process of skin regeneration.

Induction of apoptosis and modulation of homologous recombination DNA repair pathway in prostate cancer cells by the combination of AZD2461 and valproic acid.

Cancer therapies using defects in homologous recombination (HR) DNA repair pathway of tumor cells are not yet approved to be applicable in patients with malignancies other than BRCA1/2-mutated tumors. This study was designed to determine the efficacy of combination therapy of a histone deacetylase inhibitor, valproic acid (VPA) and a novel PARP inhibitor AZD2461 in both PC-3 (PTEN-mutated) and DU145 (PTEN-unmutated) prostate cancer cell lines. The Trypan blue dye exclusion assay and the tetrazolium-based colorimetric (MTT) assay were performed to measure the cytotoxicity while combination effects were assessed based on Chou-Talalay's principles. Flow-cytometric assay determined the type of cell death. The real-time PCR analysis was used to evaluate the alterations in mRNA levels of HR-related genes while their protein levels were measured using the ELISA method. γ-H2AX levels were determined as a marker of DNA damage. We observed a synergistic relationship between VPA and AZD2461 in all affected fractions of PC-3 cells (CI<0.9), but not in DU145 cells (CI>1.1). Annexin-V staining analysis revealed a significant induction of apoptosis when PC-3 cells were treated with VPA+AZD2461 (p<0.05). Both mRNA and protein levels of Rad51 and Mre11 were significantly decreased in PC-3 cells co-treated with VPA+AZD2461 while enhanced H2AX phosphorylation was found in PC-3 cells after 12 and 24 hours of co-treatment (p<0.05). Our findings established a preclinical rationale for selective targeting of HR repair pathways by a combination of VPA and AZD2461 as a mechanism for reducing the HR pathway sufficiency in PTEN-mutated prostate cancer cells.

Novel Poly(Adenosine Diphosphate-Ribose) Polymerase (PARP) Inhibitor, AZD2461, Down-Regulates VEGF and Induces Apoptosis in Prostate Cancer Cells

Background: Prostate cancer (Pca) is a heterogeneous disease, and current treatments are not based on molecular stratification. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors have recently been found to be remarkably toxic to cells with defects in homologous recombination, particularly cells with BRCA-mutated backgrounds. Therefore, this preliminary study was designed to evaluate whether PTEN expression status could have an impact on the sensitivity of invasive Pca cells to the PARP inhibitor, AZD2461. Methods: MTT viability test, Annexin V­FITC/propidium iodide double staining, and caspase3 activity assay were used to evaluate the apoptosis and relative expression of PTEN and VEGF in PC-3 and DU145 cell lines using real-time PCR. Results: MTT results showed that the inhibitory effects of AZD2461 were higher in PC-3 than DU145 cells (with IC50 of 36.48 and 59.03 µM at 48 hours of treatment, respectively). Flow cytometric analysis also showed the same results. When exposed to 40 µM of AZD2461, PC-3 (38.8%) and DU145 (28%) cells underwent apoptosis (p < 0.05). Treatment of cells by AZD2461 also caused a significant increase in apoptosis through caspase3 activation in both cell lines. VEGF mRNA levels in PC-3 cells significantly decreased compared to adjusted untreated cells (p < 0.05) in all measured times while displaying different alteration patterns in DU145 cells (p < 0.05). Conclusion: AZD2461 suppresses the growth of prostate tumor cells since AZD2461 monotherapy could prove to be efficacious, especially against cells not expressing PTEN besides activating the possible apoptosis-independent cell death pathways.

Carbon load in airway macrophages, DNA damage and lung function in taxi drivers exposed to traffic-related air pollution.

To evaluate the potential applicability of carbon load in airway macrophages as a marker of exposure to traffic-related air pollution (TRAP) and its association with parameters of comet assay as a marker of DNA damage, and pulmonary function tests (PFTs) in the group of taxi drivers in Iran. One hundred four male taxi drivers with at least 1-year job history were randomly selected from registered drivers in the taxi union. Airway macrophages were obtained via sputum induction, and then the area of airway macrophages occupied by carbon was measured. DNA damage was determined by comet assay. PFTs were measured by the spirometer. Most of the participants (89.4%) were non-smoker. In this study, 52.7% of non-smoker participants were able to give a sample of sputum with macrophage. Carbon content of airway macrophages was 0.2 µm2. There was no significant difference in pulmonary function and comet assay parameters in terms of smoking status. There was an inverse correlation between carbon load with each of comet assay and PFTs parameters, although not statistically significant. This study identified that long-term exposure to TRAP can be a risk factor for pulmonary disorders.

The effect of canola oil compared with sesame and sesame-canola oil on cardio-metabolic biomarkers in patients with type 2 diabetes: Design and research protocol of a randomized, triple-blind, three-way, crossover clinical trial.

BACKGROUND: Both canola and sesame oils consumption have been associated with favorable effects on cardio-metabolic biomarkers. However, to the best of our knowledge, no study has compared their effects on cardiovascular risk factors. The present study aimed to assess the effect of canola, sesame, and sesame-canola oils consumption on cardio-metabolic biomarkers in patients with type 2 diabetes mellitus (T2DM). METHODS: This study was a randomized, triple-blind, three-way, crossover clinical trial. The study participants included 102 individuals with T2DM. Their spouses were also included in the study. The participants were entered into a 4-week run-in period. After that, their regular dietary oil was replaced with canola, sesame, or sesame-canola oils (a blend of sesame and canola oils) in three 9-week phases, which were separated by two 4-week washout periods (sunflower oil was consumed during the run-in and the washout periods). Dietary, physical activity, blood pressure, and anthropometric measurements were assessed at the beginning, in the middle (week 4-5), and at the end of each treatment phase. Blood samples were taken at the beginning and at the end of each phase. Serum, plasma, buffy coat, and whole blood samples were extracted and kept at -80 ºC for further analysis. Serum fasting blood sugar (FBS), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were selected as the primary outcomes. RESULTS: 102 participants with T2DM were randomly assigned to one of the 6 rolling methods. Through them, 93 individuals (91.2%) completely participated in all phases. CONCLUSION: The present study will provide an exceptional opportunity to examine the effect of canola, sesame, and sesame-canola oil on cardio-metabolic markers in adults with and without T2DM. This trial will also provide a good medium for the investigation of gene-dietary oils interaction in the future.

Occupational exposure to particulate matters and telomere length.

Little is known about the possible association between occupational exposure to mineral particulate matters and change in leukocyte telomere length (LTL) as a hallmark of aging. The present study studied the relationship between occupational exposures to mineral dust and LTL in the exposed group of workers and compared to non-exposed workers. One hundred and ten male workers (80 exposed and 30 non-exposed) from different units of a ceramic factory were recruited in the study. Personal air samples were collected in the breathing zone of the workers for inhalable and respirable fractions. Relative LTL was measured in blood genomic DNA using the quantitative real-time PCR method and expressed as telomere/single copy gene ratio. Exposure to inhalable and respirable dusts in the exposed group was 22.66 ± 52.38 and 2.54 ± 9.34 mg/m3 respectively. Inhalable and respirable exposure values were highly correlated (r2 = 0.43; p < 0.001). Exposure to respirable and inhalable particles in 38.75% and 8.75% of exposed workers was higher than threshold limit value respectively. Mean LTL in the exposed workers (0.64 ± 0.06) was significantly shorter than the non-exposed workers (0.73 ± 0.07) (p < 0.001). Despite the significant difference in exposure intensity according to working units in the exposed group, there was no significant difference in LTL according to the working units (p = 0.60). In the adjusted regression models, but not crude models, marginally significant and positive association was found between both size fractions and LTL. The observed effect size for respirable particles was five times of that found for the inhalable fraction (beta 0.005 and 0.001 respectively). Mineral dust-and not only traffic-related air pollutant exposure-could be regarded as a risk factor in the process of cell aging. Our findings imply that early biological aging, as reflected in telomere shortening, may mediate the effects of occupational air pollution exposure on human health.

Metabolic Response to Omega-3 Fatty Acids and Vitamin E Co-Supplementation in Patients with Fibrocystic Breast Disease: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: There is scarce data on the effects of omega-3 fatty acids and vitamin E co-supplementation on metabolic status in patients with fibrocystic breast disease (FBD). The current study was carried out to determine the effects of omega-3 fatty acids and vitamin E co-supplementation on metabolic status in patients with FBD. METHODS: A randomized clinical trial was conducted on 56 patients with FBD. Participants were randomly divided into two groups to receive either 1000 mg omega-3 fatty acids plus 400 mg vitamin E (n = 28) or placebo (n = 28) for 12 weeks. Fasting blood samples were taken at the beginning of the study and after 12 weeks of intervention to determine inflammatory factors, biomarkers of oxidative stress, and metabolic profiles. RESULTS: After 12 weeks of intervention, changes in serum high-sensitivity C-reactive protein (-2171.4 ± 3189.1 vs. +696.9 ± 2774.8 ng/mL, P = 0.001) and plasma nitric oxide (+1.8 ± 4.0 vs. -0.1 ± 2.4 µmol/L, P = 0.04) in supplemented women were significantly different from those in the placebo group. In addition, compared to the placebo group, subjects who consumed omega-3 fatty acids plus vitamin E supplements had significantly decreased serum insulin concentrations (-3.2 ± 6.5 vs. -0.2 ± 1.7 µIU/mL, P = 0.01), the homeostasis model of assessment-estimated insulin resistance (-0.8 ± 1.7 vs. -0.02 ± 0.4, P = 0.03), serum triglycerides levels (-11.5 ± 47.3 vs. +10.6 ± 24.3 mg/dL, P = 0.03) and VLDL-cholesterol (-2.3 ± 9.5 vs. +2.1 ± 4.9 mg/dL, P = 0.03), as well as increased quantitative insulin sensitivity check index (+0.01 ± 0.01 vs. +0.001 ± 0.007, P = 0.001) and HDL-cholesterol (+3.4 ± 6.0 vs. -1.3 ± 4.3 mg/dL, P = 0.001). CONCLUSION: Overall, omega-3 fatty acids and vitamin E co-supplementation for 12 weeks had beneficial effects on inflammatory markers and metabolic profiles in patients with FBD.

Oxidative stress and DNA damage in the cord blood of preterm infants.

Preterm birth infants are more susceptible to oxidative stress and aftermaths unwanted outcomes such as DNA damage due to hyperoxic stress. In this study, we compared the DNA strand breaks as one of the results of DNA oxidation in white blood cells, malondialdehyde (oxidative stress marker), catalase and superoxide dismutase activity, and total antioxidant capacity (markers of antioxidant defense) in a cord blood plasma of a group of preterm (n=25) and full term births (n=25). The primary DNA damage and plasma oxidative stress markers were significantly higher in a preterm group (p<0.05). Cord plasma activity of superoxide dismutase was significantly lower in preterm infants (p≤0.001). However, there were no significant differences in the cord blood total antioxidant capacity, catalase activity and malondialdehyde in preterm and term infants. Among the oxidative stress markers, the malondialdehyde concentration showed the strongest effect size (1.54; 95%CI: 0.9-2.17). For comet parameters, the most powerful effect size was observed for tail length (5.24; 95% CI: 4.05-6.42). However, tail DNA percent and tail moment were also significantly higher in cases compared to controls. Significant negative correlation was observed between comet assay parameters and birth weight and gestational age when all cases and controls entered into the analysis. There was no significant association between the levels of oxidative stress markers and early DNA damage in cord blood plasma with future nutritional tolerance in preterm infants. In the present study, the primary DNA damage and plasma oxidative stress markers significantly were increased in a preterm group. Preterm babies are more prone to the outcomes related to the early DNA damage. Tail DNA percent does not depend on experimental conditions as other parameters (tail length and thus also tail moment) and can be used for comparison with other studies.

Oxidative stress and early DNA damage in workers exposed to iron-rich metal fumes.

Occupational exposure to metal fumes occurs routinely in many occupational settings. The inflammatory response to fumes and metals after exposure could lead to an increase in reactive oxygen species and level of DNA damage. In this study, the level of early DNA damage and oxidative stress was evaluated in a group of steel company (n = 30) and compared to the non-exposed (n = 28) subjects. All DNA damage markers in workers were significantly higher in exposed group in comparison with controls (p < 0.001). Stratified analysis based on smoking showed no significant differences between smoking and comet assay parameters. There was no significant difference between workers and controls in terms of HCT, TIBC, iron, and ferreting. However, HB in controls was significantly lower than exposed group (p < 0.001). A significant increase in catalase activity and MDA serum levels were observed in workers in comparison with controls. These findings suggest for the potential genotoxic effect of iron reach dust. Due to recent findings on the predictive potential of comet assay for cancer development, further, researches should be conducted to investigate the possible biochemical mechanism of such finding.

The effect of consumption of garlic tablet on proteins oxidation biomarkers in postmenopausal osteoporotic women: A randomized clinical trial.

BACKGROUND: Osteoporosis (OP) is one of the most prevalent metabolic bone diseases at higher ages, especially in postmenopausal women. OBJECTIVE: To determine the effect of consumption of garlic tablet on proteins oxidation biomarkers in postmenopausal osteoporotic women. METHODS: The present study was a double-blind randomized controlled clinical trial that included 42 postmenopausal women in Yazd during 2014-2015. Osteoporotic women were randomly assigned into two groups: the garlic group (GG) and the placebo group (PG). Participants in GG took two garlic tablets daily for 1 month and the participants in PG took placebo tablets in the same manner. After 30 days, the plasma level of carbonyl groups (PCO), total antioxidant capacity (TAC), and advanced oxidation protein products (AOPPs) were assessed by spectrophotometric assays. Also, Malondialdehyde (MDA) content was measured according to the procedure of Thiobarbituric Acid (TBA). Data were analyzed by SPSS version 18, using paired-samples t-test, independent-samples t-test, Wilcoxon, and Mann-Whitney U test. RESULTS: This study showed that garlic tablets had decreased PCO plasma levels (47.37±5.98 vs. 19.62±3.40 nM, p≤0.001, before and after the study, respectively), AOPPs (738.95±151.86 vs. 585.12±209.99 µM, p≤0.008, before and after the study, respectively), and increased TAC (11.34±10.80 vs. 47.93±17.80, p≤0.001, before and after the study, respectively). The parameters in placebo groups showed no significant differences before and after the study, respectively. The levels of MDA before taking the drug in comparison to before Garlic group was also reduced (1.30±1.04 vs. 0.92±0.81 µM, p=0.01, before and after the study, respectively). CONCLUSION: The role of oxidative stress in the pathophysiology of many diseases such as osteoporosis has been demonstrated. The present study showed that garlic consumption can reduce the oxidative stress. TRIAL REGISTRATION: The protocol of trial was registered at the Iranian clinical trial register (www.irct.ir) with ID: IRCT138811183273N1. FUNDING: This study funded by Shahid Sadoughi University of Medical Sciences (Yazd, Iran).

Primary DNA Damage in Dry Cleaners with Perchlorethylene Exposure.

BACKGROUND: Perchloroethylene is a halogenated solvent widely used in dry cleaning. International agency of research on cancer classified this chemical as a probable human carcinogen. OBJECTIVE: To evaluate the extent of primary DNA damage in dry cleaner workers who were exposed to perchloroethylene as compared to non-exposed subjects. The effect of exposure modifying factors such as use of personal protective equipment, perceived risk, and reported safe behaviors on observed DNA damage were also studied. METHODS: 59 exposed and non-exposed workers were selected from Yazd, Iran. All the 33 exposed workers had work history at least 3 months in the dry cleaning shops. Peripheral blood sampling was performed. Microscope examination was performed under fluorescent microscope (400×). Open comet software was used for image analysis. All biological analysis was performed in one laboratory. RESULTS: Primary DNA damage to leukocytes in dry cleaners was relatively high. The median tail length, %DNA in tail, and tail moment in exposed group were significantly higher than those in non-exposed group. There was no significant difference between smokers and nonsmokers in terms of tail length, tail moment, and %DNA in tail. There was no significant correlation between duration of employment in dry cleaning and observed DNA damage in terms of tail length, tail moment and %DNA in tail. Stratified analysis based on exposed and nonexposed category showed no significant relationship between age and observed DNA damage. CONCLUSION: Occupationally exposure to perchloroethylene can cause early DNA damage in dry cleaners.

In-vitro study of homocysteine and aspirin effects on fibrinolysis: measuring fibrinolysis parameters.

Some studies suggest that increased homocysteine in blood leads to alterations in coagulation and fibrinolysis; however, the precise mechanism is not clear. The aim of this study was to compare different concentrations of homocysteine and aspirin on fibrinolysis in the plasma of healthy individuals in vitro. Different concentrations of homocysteine (200, 100, and 50 µmol/l) and aspirin (100, 10, and 1 mg/l) were added to the healthy people plasma citrate. They were incubated at 37°C for 24 h. Then, fibrinolysis parameters were analyzed by the turbidimetric procedure at 405 nm. The independent-samples t-test was utilized to compare them (P < 0.05). Findings revealed that homocysteine at 200 µmol/l with aspirin 100 ml/g had significant changes in the lysis maximum velocity (0.150 ±â€Š0.002), half-lysis time (218 ±â€Š5.77), the total lysis time (446 ±â€Š5.77), and lag time in lysis (119 ±â€Š3.60), compared to homocysteine at 200 µmol/l lysis maximum velocity (0.110 ±â€Š0.002), half-lysis time (278 ±â€Š7.63), the total lysis time (515 ±â€Š14.29), and lag time in lysis (176 ±â€Š3.60), respectively (P < 0.05). Homocysteine at 200 µmol/l with aspirin 1 ml/g did not significantly change in either parameter (P > 0.05). Homocysteine at 50 µmol/l with aspirin (100, 10, and 1 mg/l) had significant changes in all fibrinolysis parameters (P < 0.05), compared to homocysteine at 50 µmol/l. The other concentrations were compared in the same way. Aspirin (more than 1 mg/l) had more effect on higher concentrations of homocysteine. Aspirin increased velocity of clot lysis and decreased lysis time of clot in the presence of homocysteine.

In-vitro study of methylglyoxal and aspirin effects on fibrinolysis parameters.

Methylglyoxal is a reactive α, ß dicarbonyl aldehyde compound that originates from various biochemical pathways. Some studies suggest that increased methylglyoxal in blood leads to changes in fibrinolysis; however, the precise mechanism is not clear. The aim of this study was to compare different concentrations of methylglyoxal and aspirin on fibrinolysis in the plasma of healthy individuals in vitro. Different concentrations of methylglyoxal (5, 50, 100, and 500 µmol/l) and aspirin (1, 10, and 100 mg/l) were added to the plasma citrate. They were incubated at 37°C for 24 h. Then, fibrinolysis parameters were analyzed by the turbidimetric procedure at 405 nm. The Independent Samples t-test was utilized to compare them (P < 0.05). Findings revealed that methylglyoxal at 500 µmol/l with aspirin 100 mg/l had significant changes in the maximum lysis velocity (0.163 ± 0.003), half-time lysis (240 ± 10.00), the total lysis time (485 ± 5.00), lag time in lysis (126 ± 5.77), compared with methylglyoxal at 500 µmol/l (0.104 ± 0.005), (276 ± 5.77), (570 ± 10.00), and (186 ± 5.77), respectively (P < 0.05). Methylglyoxal at 500 µmol/l with aspirin 1 mg/l did not significantly change in either parameter (P > 0.05). Methylglyoxal at 100 µmol/l with aspirin 1 mg/l did not significantly change in either fibrinolysis parameter (P > 0.05), compared with methylglyoxal at 100 µmol/l. Methylglyoxal at 5 µmol/l with aspirin (1, 10, 100  mg/l) changed in all fibrinolysis parameters (P < 0.05), compared with methylglyoxal at 5 µmol/l. The other concentrations were compared in the same way. Aspirin (more than 1 mg/l) had more effect on higher concentrations of methylglyoxal. It increased the velocity of lysis of the clot and shortened clot lysis.