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 deacetyl ase 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 an d the tetrazolium-based colorimetric (MTT) assay were performed to measure the cytotoxicity while combination effects were assessed based on Chou-Talalay's princi- ples. Flow-cytometric assay determined the type of cell deat h. 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 (CI1.1). 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

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 ttest, 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)

The Effects of Dark Chocolate Consumption on Oxidative Stress and Blood Pressure in Patients with Metabolic Syndrome: A Randomized Clinical Trial

Background: Consumption of dark chocolate has been often hypothesized to have a role in the prevention of chronic diseases. The objective of this study was to investigate the effects of consumption of dark chocolate (DC) on serum oxidative stress and blood pressure (BP) in patients with metabolic syndrome (MetS). Methods: An 8-week parallel randomized clinical trial involving 114 patients with MetS was conducted on stable medication in 2014. Participants were randomly assigned to three groups: 1) consume 40 g/d DC (40G), 2) consume 20 g/d DC (20G), and 3) consume no DC as the control group (CG). BP, radical scavenging activity of 1-diphenyl-2-picrylhydrazyl (DPPH), and malondialdehyde (MDA) were measured at baseline and after 8 weeks of intervention. Results: Mean age, weight, and body mass index (BMI) of participants were 51.38 &plusmn; 6.95 y, 77.34 &plusmn; 12.86 kg, and 28.65 &plusmn; 4.4 kg/m2, respectively. No significant differences were found among the three groups in relation to these variables after the intervention. The mean change of systolic blood pressure in 40G, 20G, and CG were 0.31 &plusmn; 1.81, 0.37 &plusmn; 1.65, and 0.26 &plusmn; 1.56 mmHg (P = 0.3), respectively. These figures for diastolic blood pressure were obtained as 0.08 &plusmn; 1.03, -0.02 &plusmn; 1.12, and 0.22 &plusmn; 1.03 mmHg. No significant changes were observed in MDA and DPPH between three groups. Conclusion: Even daily intake of 40 g of DC with 76% purity for an 8-week period had no effect on body weight, BMI, BP, and oxidative stress in patients with MetS

Diode Laser Irradiation Effects on Miniscrew Stability and IL-1β and TGF-β1 Levels: A Split-Mouth Randomized Controlled Clinical Trial: Diode Laser Effects on Miniscrew Stability

Introduction: This study aimed to assess the effect of low-level laser therapy (LLLT) on miniscrew stability and concentrations of interleukin-1β (IL-1β) and transforming growth factor-beta (TGF-β1) 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 mini-screws 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-1β and TGF-β1. 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-1β 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-β1 in the laser group was lower than that in the control group at T0, T1, and T3; however, the difference was not statistically significant. Conclusions: The current results supported the efficacy of LLLT in increasing the miniscrew stability and decreasing the level of IL-1β pro-inflammatory cytokin

The Effect of Chamomile Tea versus Black Tea on Glycemic Control and Blood Lipid Profiles in Depressed Patients with Type 2 Diabetes: A Randomized Clinical Trial

Background: According to traditional beliefs, chamomile products have anti-depression effect. The aim of this study was to investigate the effects of chamomile tea on glycemic control, depression status and lipid profiles in type 2 diabetes (T2D) with depression. Methods: This randomized clinical trial was carried out on 74 depressed patients with T2D. Participants were randomly divided into two 37-people groups, chamomile tea (CG) and black tea group (BG). The CG received 3 cups of chamomile tea daily and the BG received 3 cups of black tea daily half an hour after meals for 12 weeks. To examine the status of depression, Beck II test was utilized. Anthropometric measurements, 24-h dietary recalls, glycosylated hemoglobin A1c (HbA1c) and blood lipids profile were measured at the baseline and at the end of the intervention. Results: The HbA1c mean was significantly reduced in CG after the intervention, when compared with BG (7.15 &plusmn; 1.23% vs. 7.98 &plusmn; 1.76%, P = 0.02). In the same vein, the mean changes in CG and BG were -0.74 &plusmn; 1.29 and 0.04 &plusmn; 1.07 (P = 0.006), respectively. No significant changes were observed in mean of serum lipids within and between groups. The Beck score also showed a significant reduction in the CG after the intervention (P < 0.001) and also, the mean changes showed a significant difference between the two groups. Conclusions: The results of this study demonstrated that drinking three cups of chamomile tea daily for 12 weeks by T2D suffering from depression lead to improve glycemic control and depression state. Therefore, drinking this kind of tea by these patients is recommende

Evaluation of Laboratory Factors in Patients with Covid 19 in Yazd, Maybod, and Ardakan Cities in 2020

Introduction: This new viral syndrome named as Coronavirus disease 2019 (COVID-19) by WHO. Some laboratory parameters change in the patients with covid-19. This study was conducted with the aim of evaluating laboratory parameters in the patients with COVID-19. Methods: A cross-sectional-analytical study was conducted in the hospitals of Shahid Sadoughi of Yazd, Imam Jafar Sadegh of Meibod and Shahid Ziaei of Ardakan between April and May 2019. The study population was patients with Covid-19 with a positive PCR test, 275 people were included in the study using the available sampling method. The checklist of this study included demographic information, hospitalization information and test values (CBC, diff, ESR, AST, ALT, Cr, Urea, LDH, PT, PTT, INR). Data were analyzed by SPSS software version 17 and the significance level was considered less than 0.05. Results: A significant difference was observed between the values of WBC, Lymphocyte, Neutrophil, ESR, Urea, Creatinine, LDH, AST tests in the two groups that died and recovered. Among the patients who were hospitalized in the general departments, ICU or both, a significant difference was found between the patients who recovered and those who died (P=0.000). Significantly, more number of hospitalization days and older age were observed in deceased patients (P=0.000). Conclusion: In the present study, we came to the conclusion that in addition to increasing the level of WBC, neutrophil, urea, creatinine, LDH and AST in deceased patients, a decrease in lymphocytes was also observed and these results can be used in future crises of Covid-19

Comparison of the Effects of Green Tea and Melissa Officinalis on Weight and Blood Pressure in Welders: A Single-blind, Crossover Clinical Trial

Background: Considering the effectiveness of green tea and Melissa officinalis in reducing weight and blood pressure in past studies, this study aimed to compare the effects of green tea and Melissa officinalis on blood pressure and weight in welders. Methods: This is a single-blind crossover clinical trial. Twenty welders from a workshop entered the study. Green tea and Melissa officinalis infusions (4 g/d) were provided 2 times a day for 4 weeks in random order with a 3-week washout. Measurements were performed at the beginning and the end of each intervention. The environmental pollution of the workshop was measured by the professional health engineer at the beginning. Results: The diet and black tea intake were not different during the interventions (P > 0.05). Physical activity was not different throughout the study, although the intensity of physical activity was higher in the Melissa officinalis period (12.31 &plusmn; 12.89 versus 60.00 &plusmn; 33.95 min/ week; P = 0.06). Weight, body mass index and diastolic blood pressure decreased during the period of Melissa officinalis consumption and there was a slight increase during the green tea period (P > 0.05). Conclusions: It is likely that one month of consumption of Melissa officinalis is as effective as green tea in changing weight and blood pressure, and therefore they can be a good alternative to each othe