Publications by authors named "Hamid-Reza Mohammadi-Motlagh"

22 Publications

  • Page 1 of 1

Serological and Molecular Tests for COVID-19: a recent update.

Iran J Immunol 2021 Mar;18(1):13-33

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

The COVID-19 pandemic is probably the most devastating worldwide challenge in recent century. COVID-19 leads to a mild to severe respiratory disease and affects different organs and has become a global concern since December 2019. Meanwhile, molecular biology and diagnostic laboratories played an essential role in diagnosis of the disease by introducing serological and molecular tests. Molecular-based techniques are reliable detection tools for SARS-CoV-2 and used for diagnosis of patients especially in the early stage of the disease. While, serological assays are considered as additional tools to verify the asymptomatic infections, tracing previous contacts of individuals, vaccine efficacy, and study the seroprevalance. The average time of the appearance of anti-SARS-CoV-2 antibodies in the patient's serum is 3-6 days after the onset of symptoms for both IgM and IgA and 10-18 days for IgG. Following the outbreak of COVID-19, FDA has approved and authorized a series of serological laboratory tests for early diagnosis. Serological assays have low-cost and provide fast results but have poor sensitivity in the early stage of the viral infection. Although the serological tests may not play an important role in the active case of COVID-19, it could be effective to determine the immunity of health care workers, and confirm late COVID-19 cases during the outbreak. In this review, we compared various laboratory diagnostic assays for COVID-19.
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http://dx.doi.org/10.22034/iji.2021.88660.1894DOI Listing
March 2021

The Antimicrobial Peptide, Nisin, Synergistically Enhances the Cytotoxic and Apoptotic Effects of Rituximab Treatment on Human Burkitt's Lymphoma Cell Lines.

Rep Biochem Mol Biol 2020 Oct;9(3):250-256

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Non-Hodgkin's lymphomas comprise the most common hematological cancers worldwide and consist of a heterogenous group of malignancies affecting the lymphoid system. Treatment of non-Hodgkin's lymphoma has been significantly enhanced with the addition of Rituximab to the standard chemotherapy regimen. However, even with the advancement of treatment patients continue to relapse and develop resistance to Rituximab, rendering subsequent treatments unsuccessful. The use of novel drugs with unique antitumor mechanisms has gained considerable attention. In this study, we explored the anti-cancer effects of the combined therapy of Rituximab and Nisin on human Burkitt's lymphoma cells.

Methods: The human Burkitt's lymphoma cells lines, Raji and Daudi, were treated with Nisin, Rituximab, or a combination of the two agents at various concentrations. Cytotoxicity following treatment was determined using cell viability assay. The degree of apoptosis was verified via flow cytometric analysis using FITC annexin V/PI staining.

Results: Our findings show that the combined treatment of Rituximab and Nisin results in a more significant reduction in the survival of Raji and Daudi Burkitt's lymphoma cells, compared to Nisin or Rituximab treatment alone. Additionally, our results indicate that Nisin can induce a significant degree of apoptosis in the Burkitt's lymphoma cells compared to the negative controls. However, the addition of Nisin to the Rituximab treatment synergistically enhances the apoptotic antitumor effect.

Conclusion: This study demonstrates the synergistic antitumor effect of Nisin treatment to enhance tumor cell apoptosis and the potential value of Nisin as an adjunct therapy in the treatment of lymphoma.
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http://dx.doi.org/10.29252/rbmb.9.3.250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816786PMC
October 2020

Immune microenvironment in different molecular subtypes of ductal breast carcinoma.

Breast Cancer Res Treat 2021 Jan 3;185(2):261-279. Epub 2020 Oct 3.

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

Purpose: Ductal breast carcinoma as a heterogeneous disease has different molecular subtypes associated with clinical prognosis and patients' survival. The role of immune system as a consistent part of the tumor microenvironment (TME) has been documented in progression of ductal breast carcinoma. Here, we aimed to describe the important immune cells and the immune system-associated molecules in Ductal Carcinoma In situ (DCIS) and Invasive Ductal Carcinoma (IDC) with special emphasis on their associations with different molecular subtypes and patients' prognosis.

Results: The immune cells have a dual role in breast cancer (BC) microenvironment depending on the molecular subtype or tumor grade. These cells with different frequencies are present in the TME of DCIS and IDC. The presence of regulatory cells including Tregs, MDSC, Th2, Th17, M2 macrophages, HLADR T cells, and Tγδ cells is related to more immunosuppressive microenvironment, especially in ER and TN subtypes. In contrast, NK cells, CTL, Th, and Tfh cells are associated to the anti-tumor activity. These cells are higher in ER BC, although in other subtypes such as TN or HER2 are associated with a favorable prognosis.

Conclusion: Determining the specific immune response in each subtype could be helpful in estimating the possible behavior of the tumor cells in TME. It is important to realize that different frequencies of immune cells in BC environment likely determine the patients' prognosis and their survival in each subtype. Therefore, elucidation of the distinct immune players in TME would be helpful toward developing targeted therapies in each subtype.
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http://dx.doi.org/10.1007/s10549-020-05954-2DOI Listing
January 2021

Saponins from Tribulus terrestris L. Extract Down-regulate the Expression of ICAM-1, VCAM-1 and E-selectin in Human Endothelial Cell Lines.

Int J Mol Cell Med 2020 ;9(1):73-83

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Atherosclerosis is an inflammatory disease in which intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin (SELE) are consistently expressed in the vascular endothelium. Several evidence support the crucial role of adhesion molecules in the development of atherosclerosis and plaque instability. Due to the anti-inflammatory activity of (TT), the present study investigated the effect of aqueous extract and saponin fraction of TT on the expression of , , and genes in endothelial cells during normal and lipopolysaccharide (LPS) induced conditions. Human umbilical vein endothelial cells (HUVEC) and human bone marrow endothelial cells (HBMEC) were cultured, stimulated by LPS, and treated with aqueous extract and saponin fraction of TT. Finally, the expression of , and genes were measured using quantitative real-time polymerase chain reaction. LPS-induced HUVECs and HBMECs significantly increased the expression of , , and in comparison with control groups (P<0.001). Treatment of LPS-induced HUVECs and HBMECs by aqueous extract and saponin fraction of TT decreased the expression of all three mentioned genes significantly (P<0.001) in comparison with LPS-induced cells. Taken together, our data suggest that TT has an anti-inflammatory effect. study about anti-inflammatory effect of this herb may provide new insights into the development of a herbal drug for the prevention/therapy of atherosclerosis.
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http://dx.doi.org/10.22088/IJMCM.BUMS.9.1.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422852PMC
January 2020

The immune system as a target for therapy of SARS-CoV-2: A systematic review of the current immunotherapies for COVID-19.

Life Sci 2020 Oct 1;258:118185. Epub 2020 Aug 1.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Aims: The immune response is essential for the control and resolution of viral infections. Following the outbreak of novel coronavirus disease (COVID-19), several immunotherapies were applied to modulate the immune responses of the affected patients. In this review, we aimed to describe the role of the immune system in response to COVID-19. We also provide a systematic review to collate and describe all published reports of the using immunotherapies, including convalescent plasma therapy, monoclonal antibodies, cytokine therapy, mesenchymal stem cell therapy, and intravenous immunoglobulin and their important outcomes in COVID-19 patients.

Material And Methods: A thorough search strategy was applied to identify published research trials in PubMed, Scopus, Medline, and EMBASE from Dec 1, 2019, to May 4, 2020, for studies reporting clinical outcomes of COVID-19 patients treated with immunotherapies along with other standard cares.

Key Findings: From an initial screen of 80 identified studies, 24 studies provided clinical outcome data on the use of immunotherapies for the treatment of COVID-19 patients, including convalescent plasma therapy (33 patients), monoclonal antibodies (55 patients), interferon (31 patients), mesenchymal stem cell therapy (8 patient), and immunoglobulin (63 patients). Except for nine severe patients who died after treatment, most patients were recovered from COVID-19 with improved clinical symptoms and laboratory assessment.

Significance: Based on the available evidence, it seems that treatment with immunotherapy along with other standard cares could be an effective and safe approach to modulate the immune system and improvement of clinical outcomes.
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http://dx.doi.org/10.1016/j.lfs.2020.118185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395832PMC
October 2020

In vivo anti-inflammatory efficacy of the combined Bowman-Birk trypsin inhibitor and genistein isoflavone, two biological compounds from soybean.

J Biochem Mol Toxicol 2019 Dec 8;33(12):e22406. Epub 2019 Oct 8.

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Soybean Bowman-Birk protease inhibitor (BBI) and genistein, two biological compounds from soybean, are well-known for their anti-inflammatory, antioxidant, and anticancer activities. The aim of this study was designing a BBI-genistein conjugate and then investigating its protective effect on lipopolysaccharide (LPS)-induced inflammation in BALB/c mice, compared with the effects of combination of BBI and genistein. BBI was purified from soybean and the BBI-genistein conjugate was synthesized. The BALB/c mice were intraperitoneally treated 2 hours before LPS induction. Our results showed that treatment with the combination of BBI and genistein greatly led to more reduced serum levels of tumor necrosis factor (TNF)-α and interferon (IFN)-γ compared with the treatments of BBI alone, the BBI-genistein conjugate, and genistein alone, respectively. Moreover, the expression of TNF-α and IFN-γ in the splenocytes was significantly downregulated along with improving host survival against the LPS-induced lethal endotoxemia in the same way. Our data support a new combined therapy using BBI and genistein, as natural anti-inflammatory agents, to develop a new drug for inflammatory diseases.
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http://dx.doi.org/10.1002/jbt.22406DOI Listing
December 2019

Study of gene expression and steviol glycosides accumulation in Stevia rebaudiana Bertoni under various mannitol concentrations.

Mol Biol Rep 2019 Feb 1;46(1):7-16. Epub 2018 Dec 1.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Stevia rebaudiana produces sweet steviol glycosides that are 300 times sweeter than sugar and have the beneficial effects on human health including anti-hyperglycaemic. Tissue culture is the best method with high efficacy to propagate stevia. Abiotic stress has an impact on steviol glycoside contents in stevia. Therefore, we investigated the effect of mannitol on the expression of four genes involved in the biosynthesis of stevia including UGT74G1, UGT76G1, kaurene oxidase and kaurene synthase genes and steviol glycosides accumulation in stevia under in vitro conditions. The highest expression of UGT76G1 gene occurred in the plants grown under 20 g/l mannitol. While for the kaurene synthase gene, the highest amount of gene expression was observed at 40 g/l mannitol. The results were different about kaurene oxidase gene. As the highest and lowest gene expression were seen in 50 and 30 g/l mannitol conditions respectively. There were the same results for UGT74G1 that means the most appropriate and also the most inopportune treatment for the gene expression were same as the condition for the kaurene oxidase gene. Compared with control, adding mannitol to media in all concentrations increases the expression of UGT76G1 gene. Estimation of steviol glycosides contents under different treatments of mannitol carried out by HPLC. According to the results, the highest amount of stevioside was produced under 20 g/l mannitol treatment. However, rebaudioside A was accumulated in its maximum amounts under 30 g/l mannitol. It can be concluded that adding mannitol to media in the certain concentration increases steviol glycoside contents in the stevia.
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http://dx.doi.org/10.1007/s11033-018-4250-4DOI Listing
February 2019

2-Methylpyridine-1-ium-1-sulfonate as an Inducer of Apoptosis and Cell Cycle Arrest: A comparative in vitro and Computational Study.

Nutr Cancer 2019 1;71(4):643-656. Epub 2018 Oct 1.

a Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.

"Let food be thy medicine and thy medicine be thy food" was expressed by Hippocrates and the health benefits of medicinal plants and natural products have been considered by humans since historic times. The current study aims to investigate the anti-cancer activity of 2-Methylpyridine-1-ium-1-sulfonate (MPS) isolated from bulbs of Allium hirtifolium. The MPS compound (in a dose-dependent manner) induced arrest the AGS cells in G1 and G2/M phases, and Caco-2 cells in G1 and S phases. These findings were associated with the down-regulation of cyclin D1, CDK4, and up-regulation of p21, p27 and p53. According to the morphological observations and DNA fragmentation assay, the MPS compound induced apoptosis in both cell lines, and also cause a significant increase in the expression of Bax/Bcl-2. In this context, our molecular docking results unveiled that the MPS compound has considerable affinity to interact with the minor groove of ctDNA and also with cell cycle kinases. To approve and find the accurate MPS mode of action against cancer cell lines (especially in gastrointestinal cancer) further studies is highly recommended.
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http://dx.doi.org/10.1080/01635581.2018.1506495DOI Listing
May 2020

Anti-angiogenesis effect of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive properties under experimental model.

Clin Exp Pharmacol Physiol 2018 04 4;45(4):370-376. Epub 2018 Feb 4.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Angiogenesis is a process through which new capillaries are formed from pre-existing ones, which contributes significantly to the pathogenesis of numerous diseases, such as cancer and chronic inflammatory disorders. The β-D-mannuronic acid (M2000) is a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive effects and is a matrix metalloproteinase (MMP) inhibitor. This research aimed to study the anti-angiogenesis effects of M2000 under in vitro and in vivo models. The cytotoxic and anti-proliferative effects of M2000 were examined using the trypan blue method and the MTT assay, respectively. The 3D collagen-cytodex model and the chick chorioallantoic membrane (CAM) assay were then used to evaluate the anti-angiogenesis property of M2000. Cytotoxicity assay revealed that M2000 (at concentrations of less than 100 μg/mL) had no cytotoxic effect on human umbilical vein endothelial cells (HUVECs). It was also illustrated that M2000 had little or no anti-proliferative effect on HUVECs. In addition, the anti-angiogenesis effects of M2000 were shown to be marginal in the in vitro model and both significant and dose-dependent in the in vivo status. This study showed that M2000 could be considered as an anti-angiogenic molecule which more likely exerts its activity mainly via indirect effects on endothelial cells and its anti-inflammatory effects may partly be attributable to its anti-angiogenic activity. Therefore, it could be recommended as a candidate for prevention and treatment of cancer, chronic inflammatory diseases, and other angiogenesis-related disorders.
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http://dx.doi.org/10.1111/1440-1681.12907DOI Listing
April 2018

2-Methylpyridine-1-ium-1-sulfonate from Allium hirtifolium: An anti-angiogenic compound which inhibits growth of MCF-7 and MDA-MB-231 cells through cell cycle arrest and apoptosis induction.

Biomed Pharmacother 2017 Sep 16;93:117-129. Epub 2017 Jun 16.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Natural products have well been recognized as sources of drugs in cancer treatment. Some medicinal plants contain the constituents with potent anti-angiogenic and anti-cancer effects, which have offered great hopes of being used as drugs for treating various cancers. The present study aims at identifying the anti-angiogenic effects of 2-Methylpyridine-1-ium-1-sulfonate (MPS) isolated from the ethyl acetate extract (EA) of Persian shallot (Allium hirtifolium). In a concentration-dependent manner, the MPS was able to inhibit endothelial cell migration and angiogenesis in both in vivo and in vitro assays, and also significantly suppressed proliferation of MCF-7 and MDA-MB-231 human breast cancer cell lines. Additionally, treatment with MPS showed a significant reduction in the vascular endothelial growth factor (VEGF) secretion level and production/activity of matrix metalloproteinases (MMP-2 and MMP-9) in the studied cells. The flow cytometry analysis indicated that MPS suppressed growth of MCF-7 and MDA-MB-231 cells at G0/G1 and S phases, respectively. Our results indicated that the induction of cell cycle arrest was correlated with the obvious changes in expression of p21, p27 and p53. According to the DNA fragmentation assay, MPS caused apoptosis in both cell lines, which confirms the results obtained with the growth assay. Moreover, the compound-mediated apoptosis accompanied with the increase in the Bax/Bcl-2 ratio and caspase-3 and -9 activities. Molecular docking results indicated that the MPS compound can surprisingly bind to VEGF and VEGF receptors and interacts with their critical amino acids. Finally, compounds with anticancer inhibitory activity (e.g. MPS) are abundant in nature and can be obtained from several sources. So, our data can be clinically developed for treating angiogenesis and cancer significantly.
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http://dx.doi.org/10.1016/j.biopha.2017.06.013DOI Listing
September 2017

A Highly Pure Sub-Fraction of Shallot Extract With Potent in vitro Anti-Angiogenic Activity.

Int J Mol Cell Med 2014 ;3(4):237-45

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Our previous studies showed that various extracts of Persian shallot (Allium hirtifolium) have anti- angiogenic effects. This study has been undertaken to isolate and identify the major effective anti- angiogeneic sub-fraction of shallot. After preparation of the 50% hydroalcoholic extract of shallot bulbs, the extract was successively fractionated into n- hexane, ethyl acetate, n- butanol and aqueous fractions. Anti-angiogenesis activity of fractions was examined by in vitro angiogenesis assay. The ethyl acetate fraction which had the most anti-angiogenesis activity was further fractionated to four sub- fractions by thin layer chromatography (TLC), silica gel column chromatography and then analyzed by High Performance TLC (HPTLC) with ethyl acetate-methanol- water as the solvent system. Our results showed that one of the four sub- fractions, as the major band in HPTLC, had the most anti- angiogenic activity. Purification and characterization of the major anti- angiogenic compound/compounds of shallot's extract may constitute one means by which diets rich in shallot confer protection against cancer and finally introduce new agents with pharmacological activities in shallot as a potential candidate in cancer therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293611PMC
January 2015

In vitro inhibition of angiogenesis by heat and low pH stable hydroalcoholic extract of Peganum harmala seeds via inhibition of cell proliferation and suppression of VEGF secretion.

Pharm Biol 2015 Jun 4;53(6):855-61. Epub 2014 Dec 4.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran .

Context: Progression of cancer cells is completely dependent on its angiogenesis. Inhibition of tumor angiogenesis has shed new light on cancer treatment. As a result, anti-angiogenesis therapy represents one of the most significant advances in clinical oncology. Peganum harmala L. (Zygophyllaceae) is a native plant from the eastern Iranian region, which is used as a traditional folk medicine. Although some biological properties of this plant are determined, its effect on angiogenesis is still unclear.

Objective: We investigated the anti-angiogenic effects of heat and low pH stable hydroalcoholic extract of P. harmala seeds on endothelial cells (ECs) proliferation and VEGF secretion.

Materials And Methods: Dried Peganum seeds were purchased from Kermanshah Traditional Bazar in 2011. Hydroalcoholic extract of dried seeds (0, 10, 20, 40, 60, 80, 100, 120, and 150 μg/ml) was used for in vitro evaluation of its cytotoxicity, anti-proliferative, and anti-angiogenic effects on ECs. In vitro effect of the extract on VEGF secretion was assayed using ELISA.

Results: Treatment with hydroalcoholic extract at seven different concentrations resulted in significant decrease of ECs proliferation and angiogenesis with an ID50 of ∼ 85 μg/ml. VEGF secretion was (inhibited) decreased by the extracts at concentrations higher than 10 μg/ml.

Discussion And Conclusion: Herbal plant extracts still attract attention owing to their fewer side effects comparing to synthetic drug agents. Current study indicated that hydroalcoholic extract of P. harmala seeds contains a potent anti-angiogenic component, which exerts its inhibitory effect mainly through down-regulation of essential mediators such as VEGF.
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http://dx.doi.org/10.3109/13880209.2014.946057DOI Listing
June 2015

Comparative Evaluation of Cytotoxic and Apoptogenic Effects of Several Coumarins on Human Cancer Cell Lines: Osthole Induces Apoptosis in p53-Deficient H1299 Cells.

Adv Pharmacol Sci 2014 3;2014:847574. Epub 2014 Sep 3.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran.

Natural products are excellent resources for finding lead structures for the development of chemotherapeutic agents. Coumarins are a class of natural compounds found in a variety of plants. In this study, we evaluated the cytotoxic potential of coumarins isolated from Prangos ferulacea (L.) Lindl. in PC3, SKNMC, and H1299 (p53 null) human carcinoma cell lines. Osthole proved to be an outstanding potent cytotoxic agent especially against PC3 cells. Isoimperatorin exhibited moderate inhibitory effect against SKNMC and PC3 cell lines. Oxypeucedanin and braylin did not display any cytotoxic activity. In the next set of experiments, the apoptotic potentials of osthole and isoimperatorin were investigated. Induction of apoptosis by isoimperatorin was accompanied by an increase in activation of caspase-3, -8, and -9 in SKNMC cells and caspase-3 and -9 in PC3 cells. Moreover, isoimperatorin induced apoptosis by upregulating Bax and Smac/DIABLO genes in PC3 and SKNMC cells. Osthole induced apoptosis by downregulating antiapoptotic Bcl-2 in only PC3 cells and upregulating the proapoptotic genes Bax and Smac/DIABLO in PC3, SKNMC, and H1299 cells. The effects of osthole on H1299 cells are important because the loss of p53 has been associated with poor clinical prognosis in cancer treatment.
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http://dx.doi.org/10.1155/2014/847574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168038PMC
October 2014

Osthole attenuates doxorubicin-induced apoptosis in PC12 cells through inhibition of mitochondrial dysfunction and ROS production.

Biomed Res Int 2014 12;2014:156848. Epub 2014 Jun 12.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah 6714869914, Iran.

Doxorubicin (DOX) is a potent, broad-spectrum chemotherapeutic drug used for treatment of several types of cancers. Despite its effectiveness, it has a wide range of toxic side effects, many of which most likely result from its inherent prooxidant activity. It has been reported that DOX has toxic effects on normal tissues, including brain tissue. In the current study, we investigated the protective effect of osthole isolated from Prangos ferulacea (L.) Lindl. on oxidative stress and apoptosis induced by DOX in PC12 as a neuronal model cell line. PC12 cells were pretreated with osthole 2 h after treatment with different concentrations of DOX. 24 h later, the cell viability, mitochondrial membrane potential (MMP), the activity of caspase-3, the expression ratio of Bax/Bcl-2, and the generation of intracellular ROS were detected. We found that pretreatment with osthole on PC12 cells significantly reduced the loss of cell viability, the activity of caspase-3, the increase in Bax/Bcl-2 ratio, and the generation of intracellular ROS induced by DOX. Moreover, pretreatment with osthole led to an increase in MMP in PC12 cells. In conclusion, our results indicated that pretreatment with nontoxic concentrations of osthole protected PC12 cells from DOX-mediated apoptosis by inhibition of ROS production.
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http://dx.doi.org/10.1155/2014/156848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075090PMC
March 2015

Low Concentrations of Flavonoid - Rich Fraction of Shallot Extract Induce Delayed - Type Hypersensitivity and TH1 Cytokine IFNγ Expression in BALB/c Mice.

Int J Mol Cell Med 2014 ;3(1):16-25

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. ; Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Flavonoids are potentially immunomodulatory factors and it may be inferred that these phytochemicals contribute to immunomodulatory properties of the Allium family. In the present study, we investigated the potential mechanism underlying the immunomodulatory effect of shallot and its ethyl acetate (EA) fraction as flavonoid-rich sources. Ex vivo, effects of a hydroalcoholic extract of shallot, its fractions and quercetin on lymphocyte viability were evaluated. The proliferative effects of the fractions were examined using naive mouse lymphocytes to determine the fraction with highest impact/ activity. In addition, in a mouse model, both delayed- type hypersensitivity (DTH) responses and production of a key cytokine (interferon [IFN]-ᵧ) were evaluated. Both the shallot extract and its fractions inhibited lymphocytes cell growth and survival in a concentration- dependent manner. The findings also showed that the extract and especially the ethyl acetate (EA) fraction could induce lymphocyte proliferation. The evaluation of the extract and its EA fraction on DTH responses indicated that both caused a significant increase in DTH response. Furthermore, they triggered significant increases in IFNγ and decreases in interleukin (IL)-4 production by splenic mononuclear cells. Because of the significant immunomodulatory activity displayed in these studies, it is plausible that shallot could have a potential use as an immunomodulatory agent in clinical settings.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927387PMC
February 2014

New procedure for epidermal cell isolation using kiwi fruit actinidin, and improved culture of melanocytes in the presence of leukaemia inhibitory factor and forskolin.

Cell Prolif 2013 Jun 10;46(3):348-55. Epub 2013 May 10.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Objectives: Conventional isolation of epidermis from the dermis and disruption of epidermal sheets to liberate the cells, are performed using proteolytic enzymes such as thermolysin or collagenase. Selective population expansion of melanocytes is achieved by suppressing proliferation of keratinocytes and fibroblasts in epidermal cell suspensions, using phorbol esters and cholera toxin. Here, we introduce a new procedure for isolation of epidermal cells, using proteolytic activity of kiwi fruit actinidin, and also an improved growth medium for melanocytes in the presence of leukaemia inhibitory factor (LIF) and forskolin.

Materials And Methods: Dermo-epidermal separation and epidermal sheet cell dispersion were performed using actinidin compared to conventional proteases including collagenase, thermolysin or trypsin. Thereafter, melanocyte culture was performed in two common media and one modified medium to discover optimization for these cells.

Results: We found that dermo-epidermal separation and epidermal sheet cell dispersion using kiwi fruit actinidin were considerably better than previously used methods, both from the aspect of less fibroblast and keratinocyte contamination, and of more viable native cells. Also, melanocytes proliferated better in phorbol ester- and cholera toxin-free proliferation medium supplemented with LIF and forskolin.

Conclusion: Less contamination and higher numbers of viable cells were actinidin preferential for separation of epidermis and isolation of epidermal cells. Supplementation of LIF and forskolin to new medium increased proliferation potential of melanocytes in comparison to exogenous mitogens.
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http://dx.doi.org/10.1111/cpr.12028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6496922PMC
June 2013

Anticancer and anti-inflammatory activities of shallot (Allium ascalonicum) extract.

Arch Med Sci 2011 Feb 8;7(1):38-44. Epub 2011 Mar 8.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Introduction: Alliumplants are an important part of the diet of many populations and there is a long-held belief in their health-enhancing properties such as cancer prevention. In this study, the anticancer and anti-inflammatory activities of the aqueous extract of the Allium ascalonicum bulbs have been studied.

Material And Methods: The antiproliferative and anti-growth activity of the aqueous extract of A. ascalonicum was examined in vitro on different tumor cell lines. Furthermore, the acetic acid-induced vascular permeability as an in vivo assay was used for studying anti-inflammatory activity of the extract.

Results: The aqueous extract of A. ascalonicum had the most anti-growth activity on the cancer cell lines; Jurkat and K562 against Wehi 164 with lower cytotoxic preference. The extract also showed much less cytotoxicity against the normal cell (HUVEC) line and significant anti-inflammatory activity in vivo.

Conclusions: It is of interest that the extract of this plant has shown much less cytotoxicity against the normal cell line, and, if this also occurs in vivo, the use of this plant clinically for the treatment of cancer patients would have some scientific support. The results of these assays indicated that A. ascalonicum can be a candidate for prevention and treatment of many diseases related to inflammation and malignancy.
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http://dx.doi.org/10.5114/aoms.2011.20602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258679PMC
February 2011

Diagnostic value of chemical shift artifact in distinguishing benign lymphadenopathy.

Eur J Radiol 2011 Nov 4;80(2):594-7. Epub 2010 Nov 4.

Department of Radiology, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Purpose: Today, distinguishing metastatic lymph nodes from secondary benign inflammatory ones via using non-invasive methods is increasingly favorable. In this study, the diagnostic value of chemical shift artifact (CSA) in magnetic resonance imaging (MRI) was evaluated to distinguish benign lymphadenopathy.

Subjects And Methods: A prospective intraindividual internal review board-approved study was carried out on 15 men and 15 women having lymphadenopathic lesions in different locations of the body who underwent contrast-enhanced dynamic MR imaging at 1.5 T. Then, the imaging findings were compared with pathology reports, using the statistics analyses.

Results: Due to the findings of the CSA existence in MRI, a total of 56.7% of the studied lesions (17 of 30) were identified as benign lesions and the rest were malignant, whereas the pathology reports distinguished twelve malignant and eighteen benign cases. Furthermore, the CSA findings comparing the pathology reports indicated that CSA, with confidence of 79.5%, has a significant diagnostic value to differentiate benign lesions from malignant ones.

Conclusion: Our study demonstrated that CSA in MR imaging has a suitable diagnostic potential nearing readiness for clinical trials. Furthermore, CSA seems to be a feasible tool to differentiate benign lymph nodes from malignant ones; however, further studies including larger numbers of patients are required to confirm our results.
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http://dx.doi.org/10.1016/j.ejrad.2010.10.005DOI Listing
November 2011

Tranilast could has potential therapeutic value in the treatment of psoriasis.

Med Hypotheses 2011 Feb 27;76(2):217-9. Epub 2010 Oct 27.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Psoriasis is a common chronic skin disease characterized by recurrent erythromatous skin plaques that exhibit epidermal hyperplasia, variable inflammatory cell infiltrate, and abnormalities of the dermal vascularization. The involvement of angiogenic growth factors such as vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs) and inflammatory cytokines such as IFNγ, IL-1, IL-2, TNFα, TGFα and β, IL-6, IL-8, amphiregulin and monocyte chemoattractant protein 1 (MCP-1) have been known to play pathogenic roles in traumatic psoriatic skin. However, anti-angiogenic and anti-inflammatory cytokines regimens might favorably affect the psoriasis disease process. Tranilast is an anti-allergic drug now emerging as anti-angiogenesis and anti-inflammatory effects. In vitro and in vivo experiments have also been strongly showed that tranilast would treat skin psoriasis by inhibition of involving factors. Herein, we hypothesize that local administration of tranilast may be potentially clinically useful in psoriasis.
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http://dx.doi.org/10.1016/j.mehy.2010.09.034DOI Listing
February 2011

In vitro and ex vivo antiangiogenic activity of Salvia officinalis.

Phytother Res 2010 Oct;24(10):1526-31

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, IR Iran.

Angiogenesis is a key process in the promotion of cancer and its metastasis. Herein, the antiangiogenic activity of Salvia officinalis extract and its fractions was investigated. S. officinalis aerial parts were extracted with ethanol and its successive hexane, ethyl acetate, n-butanol and aqueous fractions were evaluated for their antiangiogenic activities using human umbilical vein endothelial cells (HUVEC) capillary tube formation and rat aorta models in a three-dimensional collagen matrix. Furthermore, antimigrative effects of the fractions were assessed using a wound healing model. The ethanol extract of S. officinalis (ESO) potently inhibited capillary tube formation in HUVEC and rat aorta models of angiogenesis, and its hexane fraction (HSO) exerted the highest inhibitory effect. In addition, the ethanol extract of S. officinalis and its hexane fraction showed a dose-dependent inhibitory activity on the migration of the endothelial cells in the wound healing model. Furthermore, ESO inhibited endothelial cell proliferation at 50-200 μg/mL in a dose-dependent manner. These findings indicated some new pharmacological activities of S. officinalis such as antiangiogenic in vitro and ex vivo, and antimigrative activity in vitro. Therefore, S. officinalis could be a candidate as a useful herb with therapeutic or preventive activity against angiogenesis related disorders.
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http://dx.doi.org/10.1002/ptr.3168DOI Listing
October 2010

In vitro and in vivo anti-angiogenesis effect of shallot (Allium ascalonicum): a heat-stable and flavonoid-rich fraction of shallot extract potently inhibits angiogenesis.

Toxicol In Vitro 2010 Sep 4;24(6):1655-61. Epub 2010 Jun 4.

School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

This study has been undertaken to elucidate the anti-angiogenic properties of shallot extract in vitro and in vivo and also to define the responsible fraction and its stability. After preparation of the extract of shallot bulbs with 50% ethanol, the extract was successively fractionated into n-hexane, ethyl acetate, n-butanol and aqueous fractions. The ethyl acetate fraction was further fractionated to three subfractions using thin layer chromatography. Anti-angiogenic activity of fractions and subfractions were examined on human umbilical vein endothelial cells (HUVECs) in collagen matrix and chicken chorioallantoic membrane (CAM) models. Among the fractions, ethyl acetate fraction and one of its subfractions potently inhibited angiogenesis in vitro and in vivo. Furthermore, ethyl acetate fraction sustained its inhibitory effect significantly even after treatment in high thermal and low pH conditions. These findings provided a useful basis for further investigations on shallot as a useful herb with therapeutic or preventive activity against angiogenesis related disorders.
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http://dx.doi.org/10.1016/j.tiv.2010.05.022DOI Listing
September 2010

Inhibition of corneal neovascularization with propolis extract.

Arch Med Res 2009 Jan;40(1):59-61

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Neovascularization of the normally avascular cornea is seen in many pathological conditions including trauma, corneal transplantation, inflammation and eye diseases. Various growth factors and proteinases are involved in corneal neovascularization. Data supporting a causal role for vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are extensive. Inhibition of angiogenesis is a main strategy for treating corneal neovascularization. Several findings have shown that corneal neovascularization can be reduced by using anti-VEGF and anti-MMPs agents. Efficacy of a propolis extract has been demonstrated for reducing angiogenesis in vitro and in vivo. Propolis extracts containing artepillin C and caffeic acid phenyl ester significantly reduced the number of newly formed vessels and expression of MMPs and VEGF production from various cells. So far, propolis extract is a potential candidate as an anti-angiogenic agent and can inhibit cell proliferation, migration and capillary tube formation. We hypothesize that topical application of propolis is potentially useful for inhibiting corneal neovascularization and restoration of corneal clarity.
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http://dx.doi.org/10.1016/j.arcmed.2008.10.004DOI Listing
January 2009