Damage intensity of gallic acid on prostatic cancer cells lineDu145 by alkaline electrophoresis

زمینه و هدف: سرطان پروستات شایع ترین سرطان در جامعه مردان است. عوامل بسیار زیادی منجر به بروز این بیماری می شود. در عین حال فاکتورهای متعددی به منظور پیشگیری و یا درمان این بیماری شناسایی شده اند. آنتی اکسیدان ها و مخصوصاً ترکیبات پلی فنلی مانند اسید گالیک دارای ظرفیت بالقوه ای از این ویژگی هستند. در این مطالعه با استفاده از تکنیک الکتروفورز قلیایی، اثر اسید گالیک را بر لاین سلول های سرطانی Du145 پروستات مورد مطالعه قرار دادیم. روش بررسی: در این مطالعه تجربی آزمایشگاهی، میزان زیست پذیری سلول های Du145 در مجاورت غلظت های مختلف گالیک اسید، به کمک روش رنگ سنجی تترازولیوم (MTT) اندازه گیری و غلظت مهارکنندگی 50 درصد رشد سلول‌ها (IC50) محاسبه شد. سه غلظت نزدیک به IC50 از داروی اسید گالیک برای 48 ساعت بر سلول های مذکور تیمار شد. پس از انجام الکتروفورز قلیایی تصاویر کامت های ایجاد شده با استفاده از نرم افزار CASP آنالیز شدند. یافته ها: با استفاده از آزمون MTT و بر اساس مدل پروبیت میزان IC50 اسید گالیک برای سلول های Du145 برابر 35 میکرومولار بدست آمد. در آزمون الکتروفورز قلیایی، برای سه غلظت 25،30 و 35 میکرومولار اسیدگالیک، نسبت طول کامت به قطر سلول به ترتیب برابر 1/3±6/7، 2/6±13/8 و 1/2±69/4 بود. نتیجه گیری: گالیک اسید به عنوان یک آنتی اکسیدان قدرتمند در غلظت های نزدیک به IC50 اثر مهاری شدیدی بر رشد سلول های سرطان پروستات (لاین Du145) داشته و با اثر تخریبی بر ژنوم این سلول ها می تواند آپوپتوز را در آنان القاء کند

The effect of carvacrol on the growth inhibition and genomic destruction in prostatic cancer cells using comet assay technique

زمینه و هدف: امروزه، سرطان ها یکی از بزرگترین نگرانی های جوامع بشری است. ترکیبات پلی فنلی و آنتی اکسیدان ها به عنوان یک فاکتور مهم و کلیدی در پیشگیری و یا درمان انواع سرطان ها به خوبی معرفی شده اند. این تحقیق با هدف بررسی اثر کارواکرول به عنوان یک ماده آنتی اکسیدانی قوی بر مهار رشد و میزان تخریب ژنوم رده سلول سرطانی PC3 پروستات انجام شده است. روش بررسی: در این مطالعه تجربی آزمایشگاهی، سلول های سرطانی PC3 پروستات با غلظت های مختلف کارواکرول تیمار و درصد زیست پذیری سلول ها به کمک روش رنگ سنجی تترازولیوم (MTT) اندازه گیری و سپس غلظت مهارکنندگی 50 درصد رشد سلول‌ها (IC50) محاسبه شد.در قدم بعدی، الکتروفورز قلیایی با توجه به IC50 برای سه غلظت 130، 230 و 360 میکرومولار از کارواکرول انجام و 100 عدد تصویر کامت های ایجاد شده با استفاده از نرم افزار CASP آنالیز گردید. یافته ها: بر اساس مدل پروبیت میزان IC50 کارواکرول برای سلول های PC3 360 میکرومولار بدست آمد. در آزمون الکتروفورز قلیایی، نسبت طول کامت به قطر سلول در غلظت های 130، 230 و 360 میکرومولار به ترتیب برابر 2/1±15/9، 4/2±38/7 و 2/0±65/3 درصد مشاهده شد. نتیجه گیری: کارواکرول به عنوان یک ترکیب پلی فنلی موثر در درمان سرطان ها به طور بالقوه ای می تواند ژنوم سلول های PC3 مشتق از سرطان پروستات را تخریب کند. تخریب ژنوم سلول های PC3 در غلظت های نزدیک به IC50 بسیار محسوس تر است

Molecular dynamics simulation study of the effect of hesperetin on pre-apoptotic factors of bad, bak, and bim

Background and Aim: Many compounds derived from medicinal plants, such as antioxidants and polyphenols have significant roles in prevention and treatment of various cancers. Activation of apoptosis related pathways is one of the mechanisms for inhibition of cancer progression. In this study, we investigated the effect of molecular dynamics simulation of hesperetin on the pre-apoptotic factors of Bad, Bak, and Bim. Material and Methods: In this study we collected data about 3 dimensional structure and Protein Data Bank (PDB) files of three apoptotic factors of Bad, Bak, and Bim from Protein Data Bank (http://www.rscb.org /pdb). Using VMD v1.9.2, AutoDock v.4.2, and Gromacs v.4.5.4 softwares, we started processes such as optimization, simulation, molecular docking and molecular dynamics calculations. Results: Binding of Bad molecule to hesperetin led to release of the highest amount of energy and reduced changes in the radius of gyration of Bad protein. But after binding of Bim and Bak proteins to hesperetin, changes in the radius of gyration, increased. The most frequent change in the secondary protein structure was related to increased amount of Bent structure and decreased amount of β-sheet structure in Bim molecule. Conclusion: Hesperetin can affect the activities of pre-apoptotic factors of Bad, Bak, and Bim by influencing their molecular dynamics. It seems that hesperetin has the highest effect on the activation of Bad molecule. Also, it can activate Bim protein and induce apoptosis via inducing alternations in the secondary structure of the protein

Effect of cinnamon supplementation on blood pressure and anthropometric parameters in patients with type 2 diabetes: A systematic review and meta-analysis of clinical trials

Background and aims: The present systematic review and meta-analysis was conducted to investigate the effect of cinnamon supplementation on blood pressure and anthropometric indices in patients with type 2 diabetes. Methods: PubMed, Embase, Scopus, Web of Science and Cochrane Library were systematically searched to find relevant records up to 22 August 2019. Standard mean difference (SMD) and 95 confidence interval (CI) were used to evaluate the effect of cinnamon supplementation on the outcomes of this study. In the case of heterogeneity, fixed and random effect models were used. The obtained data were analyzed by Stata 13. After excluding irrelevant records, 9 eligible articles were included. Results: This meta-analysis found a significant reduction in systolic blood pressure (SBP) (SMD: �0.532, 95 CI: -1.032, �0.033, P = 0.037) and diastolic blood pressure (DBP) (SMD: �0.681, 95% CI: -1.297, �0.065, P = 0.030) of patients with type 2 diabetes following cinnamon supplementation. Based on the results of the present study, cinnamon supplementation had no significant effect on the body weight (BW) (SMD: �0.309, 95% CI: -0.793, 0.175, P = 0.211), body mass index (BMI) (SMD: �0.550, 95% CI: -1.244, 0.144, P = 0.120). and waist circumference (WC) (SMD: �0.235, 95% CI: -0.518, 0.047, P = 0.103). Conclusions: Cinnamon supplementation significantly decreased SBP and DBP of patients with type 2 diabetes. Although cinnamon intake caused changes in anthropometric parameters, the observed changes were not statistically significant. © 2020 Diabetes Indi

Molecular Dynamics Mechanisms of the Inhibitory Effects of Abemaciclib, Hymenialdisine, and Indirubin on CDK-6

BACKGROUND: Cyclin-Dependent Kinases-6 (CDK-6) is a serine/threonine protein kinase with regular activity in the cell cycle. Some inhibitors, such as abemaciclib, hymenialdisine, and indirubin, cause cell arrest by decreasing its activity. OBJECTIVES: The purpose of this study was to evaluate the Molecular Dynamic (MD) effects of abemaciclib, hymenialdisine, and indirubin on the structure of CDK-6. METHODS: The PDB file of CDK-6 was obtained from the Protein Data Bank (http://www.rcsb.org). After the simulation of CDK-6 in the Gromacs software, 200 stages of molecular docking were run on CDK-6 in the presence of the inhibitors using AutoDock 4.2. The simulation of CDK-6 in the presence of inhibitors was performed after docking. RESULTS: Abemaciclib showed the greatest tendency to bind CDK-6 via binding 16 residues in the binding site with hydrogen bonds and hydrophobic bonding. CDK-6 docked to hymenialdisine and indirubin increased the Total Energy (TE) and decreased the radius of gyration (Rg). CDK-6 docked to hymenialdisine significantly decreased the coil secondary structure. CONCLUSION: CDK-6 is inhibited via high binding affinity to abemaciclib, hymenialdisine, and indirubin inhibitors and induces variation in the secondary structure and Rg in the CDK-6 docked to the three inhibitors. It seems that developing a drug with a binding tendency to CDK6 that is similar to those of abemaciclib, indirubin, and hymenialdisine can change the secondary structure of CDK6, possibly more potently, and can be used to develop anticancer drugs. However, additional studies are needed to confirm this argument

Medicinal plant compounds as promising inhibitors of coronavirus (COVID-19) main protease:an in silico study

The novel Coronavirus (COVID-19) has spread rapidly across the globe and has involved more than 215 countries and territories. Due to a lack of effective therapy or vaccine, urgent and concerted efforts are needed to identify therapeutic targets and medications. COVID-19 main protease represents a major target for drug treatment to inhibit viral function. The present study sought to evaluate medicinal plant compounds as potential inhibitors of the COVID-19 main protease using molecular docking and molecular dynamic analysis. The PDB files of COVID-19 main protease and some medicinal plant compounds were retrieved from the Protein Data Bank (http://www.rcsb.org) and Pubchem server, respectively. The Gromacs software was used for simulation studies, and molecular docking analysis was done using Autodock 4.2. The COVID-19 main protease simulation, compared with some phytochemicals docked to the COVID-19 main protease, were analyzed. Glabridin, catechin, and fisetin had the greatest tendency to interact with the COVID-19 main protease by hydrogen and hydrophobic interactions. Docking of these phytochemicals to COVID-19 main protease led to an increase in the radius of gyration (Rg), decrease in the Root mean square fluctuation (RMSF), and induced variation in COVID-19 main protease secondary structure. The high tendency interaction of glabridin, catechin, and fisetin to COVID-19 main protease induced conformational changes on this enzyme. These interactions can lead to enzyme inhibition. This simulated study indicates that these phytochemicals may be considered as potent inhibitors of the viral protease; however, more investigations are required to explore their potential medicinal use