Publications by authors named "Ehsan Aali"

9 Publications

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Improvement of cytotoxicity of mitoxantrone and daunorubicin by candidone, tephrosin, and bavachinin.

Mol Biol Rep 2021 Nov 25;48(11):7105-7111. Epub 2021 Sep 25.

Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.

Background: Flavonoids have been demonstrated to have the ability of sensitizing cancer cells to chemotherapy and inverse multidrug resistance via various mechanisms, such as modulating of pumps. The therapeutic effect of candidone, tephrosin, and bavachinin in treatment of cancer, particularly to overcome multidrug resistance (MDR) is largely unknown. The capacity of these agents in sensitization of MDR cells is investigated in the current work.

Methods And Results: We analyzed the impact of candidone, tephrosin, and bavachinin, as chemosensitizer on cell cytotoxicity, P-gp and ABCG2 mRNA expression level on two multidrug resistant cells, ABCG2 overexpressing human epithelial breast cancer cell line (MCF7/MX), and P-gp overexpressing human gastric adenocarcinoma cell line (EPG85.257RDB). The inhibitory concentration of 50% (IC50) of daunorubicin in EPG85.257RDB cells in combination with IC10 of Bavachinin, Tephrosin, and Candidone were 6159 ± 948, 4186 ± 665, 730 ± 258 nM, and this data in MCF7/MX cell were 1773 ± 534, 7160 ± 405 and 3340 ± 622 nM respectively. These three flavonoids dose-dependently decreased the viability of MCF7/MX and EPG85.257RDB and significantly (p < 0.05) decreased IC50 of daunorubicin and mitoxantrone except Tephrosin in MCF7/MX cells. Candidone and Bavachinin were the most potent chemosensitizer in EPG85.257RDB and MCF7/MX cells respectively. Flavonoids did not reduce mRNA expression of P-gp and ABCG2 after 72 h treatment, except Candidone in EPG85.257RDB and Bavachinin in MCF7/MX cells.

Conclusions: This effect is not time-dependent, and flavonoids have their own patterns that are cell-dependent. In general, tephrosin, candidone, and bavachinin had the potential of sensitizing MDR cells to mitoxantrone and daunorubicin.
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http://dx.doi.org/10.1007/s11033-021-06700-7DOI Listing
November 2021

Cardioprotective Effects of Mebudipine in a Rat Model of Doxorubicin-Induced Heart Failure.

Iran J Med Sci 2021 03;46(2):136-143

Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: Mebudipine, a dihydropyridine calcium-channel blocker (CCB), shows greater time- and voltage-dependent inhibitory effects than nifedipine. Its significant negative chronotropic effects without having considerable negative inotropic properties may make it a suitable candidate for the pharmacotherapy of heart failure (HF). This study aimed to investigate the possible beneficial action of mebudipine in a rat model of HF.

Methods: The present study carried out in the Department of Pharmacology at the Iran University of Medical Sciences during the years of 2009-2011. An experimental model of HF was induced in male Wistar rats using doxorubicin (DOX). The rats were divided into five groups with seven animals in each group: normal control group, DOX-induced HF control groups, and treatment groups. The animals were administered DOX for 15 days. A consistent deterioration occurred after a four-week rest period. The animals were then treated with intraperitoneal mebudipine (0.5 mg/kg) and intraperitoneal amlodipine (0.35 mg/kg), as well as an equal volume of distilled water for 15 days. The plasma levels of big endothelin-1 (BET-1), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), as well as the clinical status (heart rate and blood pressure), were assessed before and after treatment. Statistical analysis was performed with SPSS software using parametric and nonparametric ANOVA.

Results: Mebudipine and amlodipine reversed the increased plasma BET-1 values in the treated animals when compared with the HF control group (0.103 and 0.112 vs 0.231 pg/mL, respectively). The increased plasma levels of AST, ALT, CK-MB, and LDH were also reversed in the HF animals that received mebudipine or amlodipine.

Conclusion: The administration of mebudipine to HF animals, akin to amlodipine, palliated the clinical and biochemical signs of the disease in the present study. The abstract was presented in the Iranian Congress of Physiology and Pharmacology as a poster and published in the Scientific Information Database as a supplement (2015; Vol 22).
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http://dx.doi.org/10.30476/ijms.2019.82057.0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966930PMC
March 2021

The Antihelminthic Drug, Mebendazole, Induces Apoptosis in Adult T-Cell Leukemia/Lymphoma Cancer Cells: Trial.

Int J Hematol Oncol Stem Cell Res 2020 Oct;14(4):257-264

Department of Pharmacology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

Adult T-cell leukemia/lymphoma (ATLL) is a poor prognostic Hematopoietic malignancy with various therapeutic challenges, which had been classified as non-Hodgkin lymphoma. The Drug switching, as a novel, innovative and promising approach, is an opportunity to overcoming on therapeutic challenges of hard-treating disease, . ATLL. Our aim is evaluating the antiproliferative and apoptotic effect of Mebendazole (MBZ) on ATLL cancer cells in conditions. We used Jurkat cell-line as ATLL cancer cells. After treatment of MBZ in different concentrations on jurkat cells, the cell viabilities were determined by MTT assay. After IC value determination, the 24-, 48- and 72-h treatments had been performed in IC concentration and control to evaluating the quantitative apoptosis rate by Annexin/PI Flowcytometry and qualitative apoptosis by DAPI Nuclear staining. Also, Glucose spectrophotometry were performed to evaluate the reduced amount of glucose uptake through MBZ treatment. MBZ inhibits proliferation of jurkat cells and IC value had been estimated 10 μM (). According to the flowcytometric results, increasing in drug concentration is associated with decrease cell viability and the percentage of full-apoptosis. However, it inversely correlates with percentage of early-apoptosis rate. Also, the microscopic captures of DAPI Nuclear staining confirms the flowcytometry results in qualitative manner. In addition, it was found that inhibition of glucose uptake was inversely correlated with increased MBZ concentration (). MBZ potentially inhibits the proliferation of ATLL cancer cells in condition. MBZ inhibits the growth of Jurkat cells by inducing apoptosis. Also, we suggest that indirectly inhibition of Glucose transporting occurs by MBZ, which could induce apoptosis in cancer cells.
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http://dx.doi.org/10.18502/ijhoscr.v14i4.4482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876428PMC
October 2020

Control of Hyperglycemia Using Differentiated and Undifferentiated Mesenchymal Stem Cells in Rats with Type 1 Diabetes.

Cells Tissues Organs 2020 7;209(1):13-25. Epub 2020 Jul 7.

Razi Drug Research Center and Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran,

Due to their ability in self-renewing and differentiation into a wide variety of tissues, mesenchymal stem cells (MSCs) exhibit outstanding potential for regenerative medicine. This study was aimed at investigating different aspects of MSC therapy in controlling hyperglycemia in streptozotocin-induced diabetes rats. Using an islet cell differentiation protocol, bone marrow (BM) MSCs were differentiated into insulin-producing cells (IPCs). The differentiation process was evaluated by immunocytochemistry, reverse transcriptase PCR, and dithizone staining. Diabetic animals in 4 diabetic individual groups received normal saline, BM-MSCs, coadministration of BM-MSCs with supernatant, and IPCs. Blood glucose and insulin levels were monitored during the experiment. Immunohistochemical analysis of the pancreas was performed at the end of the experiment. Administration of BM-MSCs could not reverse glucose and insulin levels in experimental animals as efficiently as cotransplantation of BM-MSCs with supernatant. The effect of coadministration of BM-MSCs with supernatant and transplantation of IPCs on controlling hyperglycemia is comparable. Immunohistochemical analysis showed that number and size of islets per section were significantly increased in groups receiving IPCs and BM-MSC-supernatant compared to the MSC group of animals. In conclusion, coadministration of BM-MSCs with supernatant could be used as efficiently as IPC transplantation in controlling hyperglycemia in diabetic rats.
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http://dx.doi.org/10.1159/000507790DOI Listing
March 2021

Investigating the effect of vitamin D vaginal suppository on sexual function among postmenopausal women: study protocol for a randomized controlled trial.

BMC Womens Health 2020 02 18;20(1):27. Epub 2020 Feb 18.

Psychology Department, Nottingham Trent University, Nottingham, UK.

Background: Menopause is associated with changes in sexual function which are partly due to vaginal atrophy in response to estrogen reduction. Estrogen administration temporarily reduces the symptoms of vaginal dryness, but long-term exposure to this drug is likely to be associated with serious complications. Considering the promising results of previous studies concerning the effect of vitamin D on vaginal dryness, the proposed study will investigate the effect of vitamin D vaginal suppository on the sexual function of postmenopausal women.

Methods: In a randomized, controlled clinical trial, 105 postmenopausal women will be randomly assigned to three groups receiving vitamin D vaginal suppository, placebo vaginal suppository, or control (no intervention). Vitamin D vaginal suppositories contain 1000 units of vitamin D3. The timing of the use of vitamin D vaginal suppositories and placebo suppositories will be every night in the first 2 weeks, and every other night in the following 6 weeks (8 weeks in total). The primary outcome will be the sexual function of participants which will be assessed using the Female Sexual Function Index (FSFI) before and immediately after the intervention, and at 1 and 2 months after the end of the intervention. The side effects of these suppositories will be examined as a secondary consequence of the study. Data will be analyzed using SPSS software version 25. In the case of normal distribution of data, the mean score of sexual function will be compared between the groups using a repeated measurements ANOVA. If statistical analysis leads to significant results, the post-hoc test will be used to determine the differences between the groups. Comparison of demographic and fertility characteristics of the women will be carried out using statistical tests such as chi-squares and t-tests. A significance level of p < .05 will be used for statistical analyses.

Discussion: If vitamin D vaginal suppositories improve sexual function among premenopausal women with long-term effects and minimum side effects, the suppositories will be considered a safe complementary and alternative choice for alleviating sexual dysfunction among this group.

Trial Registration: IRCT20180704040346N1 at 2018-10-13 prospectively registered.
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http://dx.doi.org/10.1186/s12905-020-00899-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029522PMC
February 2020

Enhancing the Therapeutic Efficacy of Daunorubicin and Mitoxantrone with Bavachinin, Candidone, and Tephrosin.

Evid Based Complement Alternat Med 2019 7;2019:3291737. Epub 2019 Nov 7.

Department of Pharmacology, Qazvin University of Medical Sciences, Qazvin, Iran.

The capability of flavonoids in sensitizing cancer cells was demonstrated in numerous works to chemotherapy and converse multidrug resistance by modulating efflux pumps and apoptosis mechanisms. Three flavonoids, namely, bavachinin, tephrosin, and candidone, have been recently introduced to cancer treatment research presenting various activities, such as antibacterial, immunomodulatory, cell death, and anticancer. Less information exists regarding the therapeutic significance of these flavonoids in cancer treatment, especially in overcoming multidrug resistance (MDR). Here, we tempted to investigate the potency of these agents in reversing MDR by analyzing their effects as chemosensitizers on cell cytotoxicity, P-gp and ABCG2 protein expression levels, and their function on two multidrug-resistant cell lines, P-gp-overexpressing human gastric adenocarcinoma cell line (EPG85.257RDB) and ABCG2-overexpressing human epithelial breast cancer cell line (MCF7/MX). The inhibitory concentration of 10% (IC) of bavachinin, tephrosin, and candidone in EPG85.257RDB cells was 1588.7 ± 202.2, 264.8 ± 86.15, and 1338.6 ± 114.11 nM, respectively. Moreover, these values in MCF7/MX cell were 2406.4 ± 257.63, 38.8 ± 4.28, and 27.9 ± 5.59 nM, respectively. Expression levels of ABCG2 and P-gp were not significantly downregulated by these flavonoids. Maximum levels of daunorubicin and mitoxantrone accumulations and minimum rates of drug efflux in both cell lines were detected 48 hrs posttreatment with tephrosin and bavachinin, respectively. Chemosensitization to mitoxantrone and daunorubicin treatments was, respectively, achieved in MCF7/MX and EPG85.257RDB cells in response to IC of bavachinin and tephrosin, independently. These effects did not follow time-dependent manner, and each flavonoid had its cell-dependent patterns. Overall, bavachinin, tephrosin, and candidone showed potency to sensitize MDR cells to daunorubicin and mitoxantrone and could be considered as attractive MDR modulators for cancer treatment. However, their action was time and cell specific.
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http://dx.doi.org/10.1155/2019/3291737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877970PMC
November 2019

Association Study of the Rs2230806 Genetic Variation with Lipid Profile and Coronary Artery Disease Risk in an Iranian Population.

Open Access Maced J Med Sci 2018 Feb 11;6(2):274-279. Epub 2018 Feb 11.

Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran.

Background: plays essential roles in the biogenesis of high -density lipoprotein - cholesterol. Variations in the ABCA1 gene may influence the risk of coronary artery disease (CAD).

Aim: Present study aimed to investigate the association of rs2230806 (R219K) polymorphism of gene with the development and severity of CAD in an Iranian population.

Materials And Methods: Our study population consisted of 100 patients with angiographically confirmed CAD and 100 controls. The genotyping of mutation of gene was determined by PCR - RFLP method. Lipid profile was determined using routine colourimetric assays. Statistical analysis was done by SPSS - 16.

Results: The genotypic (P = 0.024) and allelic (P = 0.001) distribution of the polymorphism were significantly different between the two groups. In a univariate analysis (with genotype RR as the reference), the genotype (OR = 0.46, 95%CI = 0.25-0.86, P = 0.020) and genotype (OR = 0.27, 95%CI = 0.11 - 0.66, P = 0.005) was significantly associated with a decreased risk of CAD. A multiple logistic regression analysis revealed that smoking (0.008), diabetes (P = 0.023), triglyceride (P = 0.001), HDL - cholesterol (P = 0.002) and genotype (P = 0.009) were significantly and independently associated with the risk of CAD. The association between different genotypes of polymorphism with lipid profile was not significant in both groups (P > 0.05). The polymorphism was significantly associated with severity of CAD (P < 0.05).

Conclusion: The carriage of K allele of polymorphism has a protective effect on CAD risk and correlates with a decreased severity of CAD. This protective effect seems to be mediated independently of plasma lipid levels.
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http://dx.doi.org/10.3889/oamjms.2018.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839431PMC
February 2018

A comparative study of mesenchymal stem cell transplantation with its paracrine effect on control of hyperglycemia in type 1 diabetic rats.

J Diabetes Metab Disord 2014 11;13(1):76. Epub 2014 Aug 11.

Razi Drug Research Center and Department of Pharmacology, Iran University of Medical Sciences, Tehran, Iran ; Department of Tissue Engineering and Cell Therapy, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran ; Endocrine and Metabolism Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: Many studies suggested mesenchymal stem cells (MSCs) transplantation as a new approach to control hyperglycemia in type 1 diabetes mellitus through differentiation mechanism. In contrary others believed that therapeutic properties of MSCs is depends on paracrine mechanisms even if they were not engrafted. This study aimed to compare these two approaches in control of hyperglycemia in STZ-induced diabetic rats.

Methods: Animals were divided into five groups: normal; diabetic control; diabetic received MSCs; diabetic received supernatant of MSCs; diabetic received co-administration of MSCs with supernatant. Blood glucose, insulin levels and body weight of animals were monitored during experiment. Immunohistochemical and immunofluorescence analysis were performed to monitor functionality and migration of labeled-MSCs to pancreas.

Results: First administration of MSCs within the first 3 weeks could not reduce blood glucose, but second administration significantly reduced blood glucose after week four compared to diabetic controls. Daily injection of supernatant could not reduce blood glucose as efficient as MSCs. Interestingly; Co-administration of MSCs with supernatant significantly reduced blood glucose more than other treated groups. Insulin levels and body weight were significantly increased in MSCs + supernatant-treated animals compared to other groups. Immunohistological analysis showed an increase in number and size of islets per section respectively in supernatant, MSCs and MSCs + supernatant-treated groups.

Conclusion: Present study exhibited that repeated-injection of MSCs reduced blood glucose and increased serum insulin levels in recipient rats. Injection of supernatant could not reverse hyperglycemia as efficient as MSCs. Interestingly; co-administration of MSCs with supernatant could reverse hyperglycemia more than either group alone.
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http://dx.doi.org/10.1186/2251-6581-13-76DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329572PMC
February 2015

Effect of 17β-estradiol on mediators involved in mesenchymal stromal cell trafficking in cell therapy of diabetes.

Cytotherapy 2015 Jan 20;17(1):46-57. Epub 2014 Nov 20.

Razi Drug Research Center and Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Cell Therapy, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background Aims: Mesenchymal stromal cells (MSCs) have shown great promise for cell therapy of a wide range of diseases such as diabetes. However, insufficient viability of transplanted cells reaching to damaged tissues has limited their potential therapeutic effects. Expression of estrogen receptors on stem cells may suggest a role for 17β-estradiol (E2) in regulating some functions in these cells. There is evidence that E2 enhances homing of stem cells. Induction of hypoxia-inducible factor-1α (HIF-1α) by E2 and the profound effect of HIF-1α on migration of cells have previously been demonstrated. We investigated the effect of E2 on major mediators involved in trafficking and subsequent homing of MSCs both in vitro and in vivo in diabetic rats.

Methods: E2 has been selected to improve the poor migration capacity of MSCs toward sites of injury. MSCs were incubated with different concentrations of E2 for varying periods of time to investigate whether estradiol treatment could be effective to enhance the efficiency of MSC transplantation.

Results: E2 significantly enhanced the viability of the cells that were blocked by ICI 182,780 (estrogen receptor antagonist). E2 also increased HIF-1α, CXC chemokine receptor 4 and C-C chemokine receptor 2 protein and messenger RNA levels measured by Western blot and reverse transcription-polymerase chain reaction. The enzymatic activity of matrix metalloproteinase 2 and metalloproteinase 9 was elevated in E2-treated cells through the use of gelatin zymography. Finally, the improved migration capacity of E2-treated MSCs was evaluated with the use of a Boyden chamber and in vivo migration assays.

Conclusions: Our data support that conditioning of MSCs with E2 promotes migration of cells in cultured MSCs in vitro and in a diabetic rat model in vivo through regulation of major mediators of cell trafficking.
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http://dx.doi.org/10.1016/j.jcyt.2014.06.009DOI Listing
January 2015
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