Publications by authors named "Hedayatollah Shirzad"

72 Publications

Increased Indoleamine 2, 3-Dioxygenase expression modulates Th1/Th17/Th22 and Treg pathway in humans with Helicobacter Pylori-Infected gastric mucosa.

Hum Immunol 2021 Jan 28;82(1):46-53. Epub 2020 Oct 28.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:

Introduction And Purpose: Indoleamine 2, 3- dioxygenase (IDO) plays an importantrole in immunosuppressive pathway, as inhibits responsesof T cells and promotes immune tolerance. Host responsetoHelicobacter pylori (H. pylori) is involved in the infection persistenceand it is also associatedwith different clinical outcomes. The aim of this study was to investigate the role of IDO in H. pylori-infected patients with gastritis diseases and peptic ulcer diseases (PUD) through the assessment of the relationship among IDO protein expression and the numbers of T helper (Th)-1, Th17, Th22, and T regulator (Treg) cells.

Materials And Methods: Antrum biopsy was obtained from H. pylori-negative patients (n = 48) and H. pylori-positive subjects (55 patients with gastritis and 47 patients with PUD), for performing H. pylori status and histopathological assessments. IDO protein expression was evaluated by Western blotting.

Results: IDO protein expression was significantly higher in gastric biopsies from H. pylori-positive subjects compared to the H. pylori-negative subjects, and also in H. pylori-positive subjects with gastritis disease compared to H. pylori-positive subjects with PUD. Moreover, in H. pylori-positive subjects, a positive correlation was observed between IDO protein expression and the frequency of Treg cells. In addition, a negative correlation was observed between IDO protein expression and the number of Th1, Th17, and Th22.

Conclusion: Increased IDO protein expression is able to change the number of Th1, Th17, Th22, and Treg cells and these changes are possibly associated with an increase in the risk of PUD development in H. pylori-infected patients.
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http://dx.doi.org/10.1016/j.humimm.2020.10.005DOI Listing
January 2021

Up-regulated CCL18, CCL28 and CXCL13 Expression is Associated with the Risk of Gastritis and Peptic Ulcer Disease in Helicobacter Pylori infection.

Am J Med Sci 2021 01 28;361(1):43-54. Epub 2020 Jul 28.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:

Background: Helicobacter pylori (H. pylori) infection causes inflammation and increases the risk of developing peptic ulcer disease (PUD); however, the exact molecular mechanisms of PUD development remain unclear. The aim of this study was to investigate the expression of CCL18, CCL28, and CXCL13 in H. pylori-positive subjects in comparison with H. pylori-negative subjects, and to determine its association with different clinical outcomes and virulence factors.

Methods: In total, 55 H. pylori-positive subjects with gastritis, 47 H. pylori-positive subjects with PUD, and 48 H. pylori-negative subjects were enrolled in this study. CCL18, CCL28, and CXCL13 expression were determined using real time polymerase chain reaction (PCR). The virulence factors of H. pylori such as cytotoxin-associated gene A (cagA), outer inflammatory protein A (oipA), blood group antigen-binding adhesin (babA), and vacuolating cytotoxin A (VacA) genes were evaluated using PCR.

Results: CCL18, CCL28, and CXCL13 expression in H. pylori-positive subjects were significantly higher than H. pylori-negative subjects. CCL18 and CXCL13 expression in H. pylori-positive subjects with oipA and babA2were significantly higher than H. pylori-positive subjects with oipA¯ and babA2¯. CCL18 and CXCL13 expression were found to be significantly elevated in H. pylori-positive subjects with gastritis compared with H. pylori-positive subjects with PUD. CCL28 expression was significantly higher in H. pylori-positive subjects with PUD compared with H. pylori-positive subjects with gastritis.

Conclusions: The increased of CCL18 and CXCL13 may be involved in the pathogenesis of H. pylori-associated gastritis, while the increased of CCL28 may be involved in the pathogenesis of H. pylori-associated PUD.
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http://dx.doi.org/10.1016/j.amjms.2020.07.030DOI Listing
January 2021

The protective effects of resveratrol on ulcerative colitis via changing the profile of Nrf2 and IL-1β protein.

Mol Biol Rep 2020 Sep 4;47(9):6941-6947. Epub 2020 Sep 4.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with increasing incidence and prevalence in developed countries. The presence of inflammatory cytokines is considered the main detrimental factor in severe types of IBD. The Nrf2 transcription factor plays an important role in reducing the expression of inflammatory agents such as interleukin (IL)-1β and increasing reparative factors such as IL-11. Resveratrol, a plant-derived phenolic compound, reduces the damage in chronic experimentally induced colitis. Twenty patients with UC and also 20 healthy controls were recruited in this study. The proteins expression of Nrf2 and IL-1β was assessed in colonic biopsies by Western blotting. Caco-2 cells were challenged with TNF-α (in vitro simulation of UC), in the presence or not of 190 nM (24 h) and 75 nM (48 h) Resveratrol. Then, Nrf2 and IL-1β in gene and protein expression were measured by real time-PCR and Western blotting in different treatments. Finally, IL-11 proteins expression was measured in culture supernatant by ELISA. A significant increase of IL-1β protein was detected in inflamed colonic tissues from UC patients compared with the control individuals. In Caco-2 cells challenged with TNF-α, protein expression of IL-1β and p-Nrf2 showed an increase, while gene expression of Nrf2 did not show a significant difference. After treatment with Resveratrol, both IL-1β mRNA and protein levels were reduced, while IL-11 protein levels showed any increase. The p-Nrf2 is a dominant form which is prevalent in inflamed tissues from UC patients. Resveratrol can reverse the inflammatory effects of TNF-α by reducing IL-1β and increasing IL-11 production.
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http://dx.doi.org/10.1007/s11033-020-05753-4DOI Listing
September 2020

Ghrelin induces autophagy and CXCR4 expression via the SIRT1/AMPK axis in lymphoblastic leukemia cell lines.

Cell Signal 2020 02 3;66:109492. Epub 2019 Dec 3.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:

T cell acute lymphoblastic leukemia (T-ALL) is one of the most frequent malignancies in children, and the CXCR4 receptor plays an important role in the metastasis of this malignancy. Ghrelin is a hormone with various functions including stimulation of the release of growth hormone and autophagy in cancer cells. Moreover, SIRT1 and AMPK (AMP-activated protein kinase) stimulate expression of proteins involved in autophagy. On the other hand, autophagic cell death can be an alternative target for cancer therapy, in the absence of apoptosis. The relationship between ghrelin and the SIRT1/AMPK axis and the resulting effects on autophagy, apoptosis, proliferation, and expression of CXCR4 and the ghrelin receptor (GHS-R1a), in Jurkat and Molt-4 human lymphoblastic cell lines was not previously clear. Here we demonstrate that SIRT1 expression is upregulated during the induction of autophagy by ghrelin, an effect that is inhibited by inactivation of SIRT1/AMPK axis. In addition, ghrelin can affect CXCR4 and GHS-R1a expression. In conclusion, this work reveals that ghrelin induces autophagy, invasion, and downregulation of ghrelin receptor expression via the SIRT1/AMPK axis in lymphoblastic cell lines. However, in these cell lines ghrelin-induced autophagy does not lead to cell death due to weak induction of apoptosis.
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http://dx.doi.org/10.1016/j.cellsig.2019.109492DOI Listing
February 2020

T-bet Cells Polarization in Patients Infected with Helicobacter pylori Increase the Risk of Peptic Ulcer Development.

Arch Med Res 2019 04 7;50(3):113-121. Epub 2019 Aug 7.

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

Background: Peptic ulcer disease (PUD) is a common disease worldwide moreover known as stomach ulcer or peptic ulcer. Increased the number of T CD4 helper cells in response to gastric infection by Helicobacter pylori (H. pylori) play an important role in the development of PUD. The aim of this study was to determine the frequency of T-bet cells in H. pylori-infection, its interaction with Th17/Treg cells and its association with the clinical consequences of the infection.

Methods: A total of 63 patients with PUD, 89 patients with gastritis and 48 H. pylori-negative subjects were enrolled in this study. The number of T-bet cells were determined by immunohistochemistry.

Results: The numbers of T-bet cells and INF-γ expression in infected patients were significantly higher than uninfected. Moreover, the number of T-bet cells and INF-γ expression in infected patients with PUD were significantly higher than infected patients with gastritis. Additionally, the number of T-bet cells and INF-γ expression were found to be inversely correlated with degree of H. pylori density and chronic inflammation score (CIS) in infected patients with gastritis disease, but this correlation was positive in the infected patients with PUD. The number of T-bet cells was found to be positively correlated with the number of Th17 cells and inversely correlated with the number of Treg cells in infected patients with gastritis and PUD.

Conclusion: Abnormal hyper-activation of T-bet cells during H. pylori-infection may lead to tissue damage caused by immunopathologic reactions.
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http://dx.doi.org/10.1016/j.arcmed.2019.07.005DOI Listing
April 2019

Circulating mesenchymal stem cells, stromal derived factor (SDF)-1 and IP-10 levels increased in clinically active multiple sclerosis patients but not in clinically stable patients treated with beta interferon.

Mult Scler Relat Disord 2019 Oct 12;35:233-238. Epub 2019 Aug 12.

MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Mesenchymal stem cells (MSCs) have the capacity to migrate into the inflammatory regions in response to chemokines such as, IP-10 and SDF-1α and function as anti-inflammatory and immunomodulatory cells.

Methods: In this study we investigated the MSCs frequency in peripheral blood of Relapsing-Remitting Multiple Sclerosis (RRMS) patients in clinically active and not on disease-modifying therapy (DMT) (n = 22) and clinically stable on DMT (Interferon-β (IFN-β) therapy) for at least 6 months (n = 22) in comparison to sex and age-matched healthy controls (n = 25) using flow cytometry. The serum and gene expression levels of IP-10 and SDF-1a were also measured in studied groups by ELISA and Real time- PCR.

Results: We obtained significant high levels of circulating CD45CD34 CD90 and CD45CD34 CD105 cells in clinically active patients, not on DMT and patients under IFNβ therapy compared with control group. Furthermore, a significant increase in the percentage of circulating CD45CD34 CD105 CD90 cells was found in clinically active patients and not on DMT compared with control group. Serum analysis of IP-10 and SDF-1α showed a significant increase in IP10 concentration in both clinically active not on DMT (P = 0.02) and on DMT (P = 0.005) RRMS patients in comparison with controls. The expression level of SDF-1α mRNA significantly increased in clinically active not on DMT (P = 0.03), while decreased in patients under IFNβ therapy (P = 0.04). The mRNA expression of IP-10 only increased in patients on DMT compared with controls (P = 0.05).

Conclusion: Circulating MSCs, IP-10 and SDF-1α levels, increased in RRMS patients with clinically active not on DMT and IFN-β therapy reduced circulating MSCs and SDF-1α levels.
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http://dx.doi.org/10.1016/j.msard.2019.08.013DOI Listing
October 2019

Role of Th22 cells in Helicobacter pylori-related gastritis and peptic ulcer diseases.

Mol Biol Rep 2019 Dec 29;46(6):5703-5712. Epub 2019 Jul 29.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Helicobacter pylori (H. pylori) has been shown to be one of the leading causes of peptic ulcer diseases (PUDs) and gastritis. T helper-22 (Th22) cells and its most important cytokine, interleukin-22 (IL-22) are importantly active in inflammation and inflammatory tissues. Since inflammation is one of the main attributes of infection caused by H. pylori and resulting complications (gastritis and gastrointestinal ulcer), this study was designed to evaluate the Th22 cells count and the IL-22 protein expression in people suffering from PUD and gastritis. The present study was conducted on 55 patients with gastritis, 47 patients with PUD and 48 uninfected subjects. After preparation of section and extraction of protein from antral biopsies, immunohistochemistry and western blot methods were used to evaluate the Th22 cells and IL-22 protein expression level, respectively. According to findings, the Th22 cells count and the IL-22 protein expression level in the infected subjects were siginficantly more than in the uninfected subjects. It should be noted that the Th22 cells count and the IL-22 protein expression level in the infected subjects with PUD were significantly greater than those in the infected subjects with gastritis. In addition, the Th22 cells count had positive correlation with the density of H. pylori, chronic inflammation score and acute inflammatory score in the infected subjects with PUD. The Th22 cells count had positive correlation with the Th17 cells count and inverse correlation with the Treg cells count in the infected subjects with PUD and gastritis. Our data demonstrated that abnormal hyper-activation of Th22 cells as well as its correlation with the Th17 cells during infection caused by H. pylori might damage tissues through immunopathological responses.
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http://dx.doi.org/10.1007/s11033-019-05004-1DOI Listing
December 2019

Local Expression of Mucosal YKL-40; Correlation of YKL-40 with Clinical Manifestations and Immunopathogenesis of Moderate/Severe Persistent Allergic Rhinitis Patients.

Immunol Invest 2020 Feb 3;49(1-2):46-57. Epub 2019 Jul 3.

Clinical Biochemistry Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.

YKL-40 is an important protein that plays a critical role in chronic inflammation in hypersensitivity disease. In this study, the expression of YKL-40 was investigated among patients with moderate/severe persistent allergic rhinitis (M/S PAR), patients with mild (M) PAR and healthy individuals. Moreover, the association between YKL-40 and immunopathogenesis of M/S PAR was meticulously surveyed. For this purpose, surgical samples were tested by real-time polymerase chain reaction to evaluate YKL-40 mRNA expression. The presence and location of YKL-40 protein in the tissue samples were determined by immunohistochemistry. Additionally, we measured the number of eosinophils per field in the tissue samples, blood eosinophils, total serum IgE, specific serum IgE, total nasal syndrome score (TNSS) and YKL-40 serum levels. The data indicated that production of YKL-40 in patients with M/S PAR increased significantly when compared with the control group. Furthermore, local production of YKL-40 correlated with specific IgE, nasal eosinophil count and TNSS. The results of the present study indicate that YKL-40, for its correlation with allergic clinical manifestations and symptom severity in M/S PAR patients, should be considered as a trigger factor in AR.
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http://dx.doi.org/10.1080/08820139.2019.1634096DOI Listing
February 2020

Pterostilbene increases Fas expression in T-lymphoblastic leukemia cell lines.

Res Pharm Sci 2019 Feb;14(1):55-63

Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, I.R. Iran.

Treatment of acute lymphoblastic leukemia (ALL) has been promising in last decades, but side effects still persist and searching for the least toxic agents continue. Pterostilbene (PTE) is a natural compound with several anti-cancer and anti-oxidant properties. Fas, as a member of death inducing family of tumor necrosis factor (TNF) receptors with an intracellular death domain, can initiate the extrinsic apoptosis signaling pathway. Here after the half maximal inhibitory concentration (IC) determination in cell lines, we searched for PTE effects on Fas, both in mRNA and surface levels in two ALL cell lines, Jurkat and Molt-4. After harvesting cells in optimum situations, MTS assay was used to determine IC concentrations. Real-time polymerase chain reaction (RT-PCR) and flow cytometry were performed for Fas mRNA and surface expression variations after exposure to PTE. The findings showed that PTE decreases cell viability with different extent in two ALL cell lines. In addition to inducing apoptosis, it can increase Fas in both gene and cell surface expression in the same concentrations. Pterostilbene as a natural anti-cancer agent can increase Fas expression both in mRNA and surface levels that results in apoptosis signal transduction improvement which sensitizes cells to apoptosis by immune effector cells. As a result, abnormal cells removal would be more efficiently with the minimum side effects on normal cells.
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http://dx.doi.org/10.4103/1735-5362.251853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407337PMC
February 2019

Differential Expression of Fas in Moderate/Severe and Mild Persistent Allergic Rhinitis and Its Correlation With Pathological Parameters.

Am J Rhinol Allergy 2019 May 16;33(3):286-293. Epub 2019 Jan 16.

4 Department of Biostatistics, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background And Aims: The roles of Fas in immune system are multifaceted, and the interaction between Fas receptor and Fas ligand is essential for maintaining the immune tolerance. We aimed to assess the level of the expression of Fas receptor on nasal inferior turbinate mucosa in patients with mild persistent allergic rhinitis (M PAR) and moderate to severe (M/S) PAR and determined the relationship between disease severity and production of Fas.

Methods: A total of 70 patients with M/S PAR, 70 patients with M PAR, and 70 healthy individuals were enrolled in this study. We obtained biopsies of nasal inferior turbinate mucosa from the participants. The expression of Fas mRNA was evaluated by real-time polymerase chain reaction. The presence and location of Fas were determined by immunohistochemistry. The number of eosinophils per field, blood eosinophils, total serum IgE levels, and specific serum IgE levels were measured. Clinical manifestations of patients were assessed by Total Nasal Syndrome Score (TNSS).

Results: The expression of Fas in patients with M/S PAR was decreased significantly compared to the control group and patients with M PAR. Local mucosal expression of Fas was correlated with specific IgE, nasal eosinophil count, and TNSS.

Conclusion: According to the results of this study, there might be a relationship between the expression of Fas receptor on nasal turbinate mucosa and the severity of persistent allergic rhinitis.
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http://dx.doi.org/10.1177/1945892418824246DOI Listing
May 2019

The relationship between IL-17A and IL-22 expression and clinical severity in patients with moderate/severe persistent allergic rhinitis.

Am J Otolaryngol 2019 Mar - Apr;40(2):173-178. Epub 2018 Dec 18.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Purpose: Several reactions leading to numerous effects are regulated by IL-22. However, the relationship between IL-22 and immunopathogensis of allergic rhinitis (AR) has been rarely investigated. The aim of the present study was to investigate the levels of IL-22 and IL-17A in AR patients and their association with clinical severity of persistent allergic rhinitis (PAR).

Materials And Methods: Thirty mild persistent allergic rhinitis (M PAR) patients, thirty moderate/severe persistent allergic rhinitis (M/S PAR) patients, and thirty healthy controls were enrolled in this study. Local production of IL-22 and IL-17A in PAR patients and healthy controls' nasal mucosa was examined by immunohistochemistry (IHC) and real-time polymerase chain reaction (RT-PCR) techniques. Serum levels of IL-22, IL-17A, specific immunoglobulin E (sIgE), and total IgE (tIgE) in PAR patients and healthy controls were determined by ELISA. In addition, blood eosinophil, nasal eosinophils per field, and total nasal syndrome score (TNSS) were also assessed.

Results: In comparison with healthy controls, production of IL-22 and IL-17A in M/S PAR patients increased significantly. Furthermore, serum levels as well as the mean number of IL-22 and IL-17A cells in nasal mucosa correlated with sIgE, nasal eosinophil count, and TNSS.

Conclusion: The results of the present study provide the first evidence that local production of IL-22 might be expressed in PAR patients. The expression of IL-22 and IL-17A, and their correlations with clinical parameters in PAR patients suggest the role of these cytokines in the events involved in the development of PAR.
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http://dx.doi.org/10.1016/j.amjoto.2018.12.009DOI Listing
June 2019

Correlation of interleukin 6 and transforming growth factor β1 with peripheral blood regulatory T cells in rheumatoid arthritis patients: a potential biomarker.

Cent Eur J Immunol 2018 30;43(3):281-288. Epub 2018 Oct 30.

Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Introduction: Proinflammatory cytokines and regulatory T cells (Tregs) are considered as important factors involved in autoimmunity development especially in rheumatoid arthritis (RA).

Aim Of The Study: To investigate the frequency of peripheral blood Tregs and related cytokines in RA patients and to determine the possible correlation between Treg percentage and interleukin 6 (IL-6) and transforming growth factor 1 (TGF-1) as indicators in assessment of Treg function and mechanisms preceding autoimmunity in RA.

Material And Methods: Thirty-seven Iranian RA patients with a moderate (3.2-5.1) disease activity score (DAS) and the same number of healthy age- and sex-matched individuals were enrolled. Frequency of peripheral blood Tregs (CD4FoxP3CD25) was determined by flow cytometry. Serum levels of IL-6 and TGF-1 and their expression levels in peripheral blood mononuclear cells (PBMCs) were evaluated by ELISA and Q-PCR, respectively.

Results: Rheumatoid arthritis patients showed significantly lower peripheral blood Treg frequencies compared to healthy individuals. Additionally, Treg (%) showed a significant inverse correlation between serum concentrations of IL-6 and mRNA expression of PBMCs, whereas there was no significant correlation between Treg (%) and TGF-1 levels.

Conclusions: The current study revealed that Treg numbers were reduced in peripheral blood of RA patients. This reduction inversely correlated with IL-6 levels, which may lead to persistent autoimmune and inflammatory conditions in RA patients.
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http://dx.doi.org/10.5114/ceji.2018.80047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305606PMC
October 2018

Correlation between expression of MMP-9 and MMP-3 in Helicobacter pylori infected patients with different gastroduodenal diseases.

Arab J Gastroenterol 2018 Dec 30;19(4):148-154. Epub 2018 Nov 30.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:

Background And Study Aims: Helicobacter pylori (H. pylori) has been implicated in the pathogenesis of most important gastro-duodenal diseases, such as gastritis, peptic ulcer disease (PUD) and gastric cancer. H. pylori upregulates the expression and activity of several matrix metalloproteinases (MMPs) in the gastric mucosa, but the role of MMP-3 and MMP-9 in infected patients with H. pylori have not been clearly defined yet. We examined mucosal MMP-3 and MMP-9 mRNA levels in gastric mucosa of H. pylori infected patients and evaluated the effects of virulence factors cagA and vacA allelic variants on these levels. We also determined correlation between mucosal MMP-3 and MMP-9 mRNA levels and types of disease.

Patients And Methods: Total RNA was extracted from gastric biopsies of 50 H. pylori-infected patients and 50 H. pylori-negative patients. Mucosal MMP-3 and MMP-9 mRNA expression level in H. pylori-infected and non-infected gastric biopsies were determined by real time-polymerase chain reaction (PCR). Presence of vacA (vacuolating cytotoxin A) and cagA (cytotoxin associated gene A) virulence factors were evaluated using PCR.

Results: The levels of MMP-3 in gastric mucosa were not different between H. pylori-positive and H. pylori-negative patients. There was no correlation between MMP-3 mRNA expression and virulence factor (cagA and vacA allelic variants) and the different types of disease (gastritis and PUD) in infected patients. But MMP-9 mRNA expression was significantly higher in biopsies of H. pylori-infected patients compared to H. pylori-negative patients. Also mucosal MMP-9 mRNA expression in H. pylori-infected patients was significantly associated with cagA status PUD.

Conclusion: Our results suggest that MMP-9 might be involved in the pathogenesis of H. pylori. PUD could be associated with cag PAI-dependent MMP-9 upregulation.
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http://dx.doi.org/10.1016/j.ajg.2018.11.001DOI Listing
December 2018

The effect of Fisch. & C.A.Mey extract on the viability and the proliferation of MDA-MB-231 cell line.

Biosci Rep 2019 01 11;39(1). Epub 2019 Jan 11.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

Some medicinal herbs and compounds are known to target cancer cells, but the success of them as anticancer compounds depends to a large extent on their ability to activate pathways that kill cancer cells by arresting cell cycle and inducing apoptosis. The aim of the present study was to determine the anticancer effects of on the breast cancer cells to reveal the underlying mechanism of its anti-breast cancer properties. In this experimental study, triple negative breast cancer cell line (MDA-MB-231) was cultivated in RPMI-1640 medium. Hydroalcoholic extract (70:30) of aerial parts of the plant was prepared. The cultured cells were treated with different concentrations (0-1000 μg/ml) of extract for 24 and 48 h. Toxicity of the extract on MDA-MB-231 cells was examined using MTT (3-[4,5-dimethyl-2-thiazolyl]-2, 5 diphenyl tetrazolium bromide) test. The Annexin V-FITC Apoptosis Detection Kit was used to evaluate apoptosis and necrosis. Flow cytometry technique was employed to differentiate different phases of the cell cycle in the cells. Data were analyzed by GraphPad Prism and SPSS software. After 24 and 48 h, the IC50 values were respectively 76.78 (95% CI = 60.75-97.05; = 0.8588) and 59.71 (95% CI = 46.25-77.09; = 0.8543) μg/ml for The extract exhibited antiproliferative effects against MDA-MB-231 cells in a dose-dependent manner. Annexin V-FITC/PI assay confirmed that the extract was able to induce apoptosis in MDA-MB-231 cells. Moreover, treatment with the extract resulted in cell cycle arrest at G1 phase. Therefore, could induce apoptosis and cycle arrest in the MDA-MB-231 cell line. It might be a good resource of natural products for producing anti-breast cancer drugs.
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http://dx.doi.org/10.1042/BSR20181538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328893PMC
January 2019

Differential expression of CCL18 in moderate/severe and mild persistent allergic rhinitis and its correlation with disease parameters.

J Immunoassay Immunochem 2018 13;39(5):485-495. Epub 2018 Aug 13.

d Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran.

Background And Aims: This study aimed to assess the level of the expression of CCL-18 on nasal inferior turbinate mucosa in patients with mild (M) and moderate-to-severe (M/S) persistent allergic rhinitis (PAR).

Methods: The participants in this case-controlled study were divided into three groups: patients with M/S PAR, patients with M PAR, and the healthy control group. Biopsies of nasal inferior turbinate mucosa were obtained from the participants. Expression of CCL-18 mRNA was evaluated by real-time PCR. The serum levels of CCL-18 were determined by ELISA. Total serum IgE levels and specific serum IgE levels were measured. The clinical manifestations were assessed using the total nasal syndrome score (TNSS).

Results: Gene expression and the serum level of CCL-18 in patients with M/S PAR increased significantly compared to the control group and patients with M PAR. The serum level of CCL-18 was found to correlate with TNSS in patients with M/S PAR. There was a statistical correlation between the serum level of CCL-18 and the total serum IgE in the treatment groups.

Conclusion: The results of the study indicate that there could be a relationship between the expression of CCL-18 in nasal turbinate mucosa and the severity of allergic rhinitis.
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http://dx.doi.org/10.1080/15321819.2018.1506931DOI Listing
October 2018

The Role of Inflammatory Cytokines in Creating T Cell Exhaustion in Cancer.

Cancer Biother Radiopharm 2018 Sep 13;33(7):267-273. Epub 2018 Jul 13.

1 Department of Microbiology and Immunology, Faculty of Medicine, Shahrekord University of Medical Sciences , Shahrekord, Iran .

Secreted inflammatory cytokines are considered as critical mediators in the tumor microenvironment. Cancer cells play a significant role in the differentiation of effector T cells to exhausted T cells through mediator production. Effector T cells that undergo tumor microenvironment become terminally differentiated into exhausted T cells. These changes create an opportunity for tumorigenesis and invasion of cancer cells. Despite having some characteristics of effector T cells, the exhausted T cells lose their antitumor properties. In this article, the phenotypes and function of exhausted T cells were reviewed and the expression pattern of inflammatory cytokines in tumor tissues and peripheral blood of cancer patients were described. Additionally, the effects of inflammatory cytokines on intracellular factors and signals of T lymphocyte cells were explained. In conclusion, the authors referred to probable approaches that could be used to improve the antitumor activity of T cells and intervention into T cell exhaustion.
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http://dx.doi.org/10.1089/cbr.2018.2449DOI Listing
September 2018

The regulatory role of Nrf2 in antioxidants phase2 enzymes and IL-17A expression in patients with ulcerative colitis.

Pathol Res Pract 2018 Aug 23;214(8):1149-1155. Epub 2018 Jun 23.

Department of Pathology, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background: Reactive oxygen species (ROS) is one of the pathogenic factors responsible for intestinal injury in Ulcerative colitis (UC). Nuclear factor erythroid-2 related factor 2 (Nrf2) plays a critical role against ROS factors to conserve epithelial integrity. This study aimed to localize Nrf2 and IL-17A protein in the inflamed mucosa of patients with ulcerative colitis. The gene expression of Nrf2 was also correlated with GST-A4 and PRDX1.

Materials And Methods: A total of 20 patients and 20 healthy controls with definite UC based on the clinical criteria were enrolled for this study. The expression pattern of Nrf2 and IL-17A protein was compared in inflamed and non-inflamed colonic biopsies by immunohistochemical staining. Nrf2, GST-A4 and PRDX1 gene expression were determined by real-time polymerase chain reaction (RT-PCR).

Results: In inflamed colonic biopsies, an increased level of Nrf2 protein factor was detected in epithelial cells. Conversely, IL-17A protein was presented more in mononuclear cells in mucosa and lamina propria regions. A significant increase of Nrf2, GST-A4 gene expression was observed in both mild and severe patients with ulcerative colitis. GST-A4 gene expression indicated a high exponential rate in logistic regression.

Conclusion: Oxidative stress in inflamed colonic tissue can induce Nrf2 gene expression. The performance of Nrf2 transcription factor may lead to the induction of GST-A4 and PRDX1. IL-17A is less detected in intestinal inflammation, presenting Nrf2 factor. The present findings suggest that Nrf2 function in the gut plays a role in arresting both inflammatory response and oxidative damages of UC.
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http://dx.doi.org/10.1016/j.prp.2018.06.001DOI Listing
August 2018

The role of T helper 1-cell response in Helicobacter pylori-infection.

Microb Pathog 2018 Oct 21;123:1-8. Epub 2018 Jun 21.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:

Helicobacter pylori (H. pylori) is a human pathogen affecting over 50% of the world population. This pathogen is usually associated with chronic inflammation of the gastric mucosa that can lead to peptic ulcer disease (PUD) and gastric cancer (GC), especially in susceptible individuals. These outcomes have been attributed to the interaction of several factors, including host genetic susceptibility, local innate and adaptive immune responses, virulence factors of H. pylori, and environmental factors. T helper (Th) cell subsets and their signature cytokines especially IFN-γ, contribute to anti-bacterial response, but at the mean time sustaining chronic inflammatory responses in the site of infection. It has been acknowledged that H. pylori-infection results in a Th1-dominant response and that inflammation of the gastric mucosa depends mainly on Th1 cell responses. But, the mechanism of the role of Th1 cell responses in H. pylori-infection has not yet been clearly explained. In this review, we will focus on the role of Th1 involved in H. pylori-infection, its interaction with Th17/Treg cells and its association with the clinical consequences of the infection.
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http://dx.doi.org/10.1016/j.micpath.2018.06.033DOI Listing
October 2018

Intensified Th9 Response is Associated with the Immunopathogenesis of Active Ulcerative Colitis.

Immunol Invest 2018 Oct 21;47(7):700-711. Epub 2018 Jun 21.

c Department of Internal Medicine , Shahrekord University of Medical Sciences , Shahrekord , Iran.

Background: Ulcerative colitis (UC) is a chronic inflammatory disorder of the large intestine histologically characterized by indistinct sustained inflammatory responses. Genetical susceptibility and environmental factors' effects play the roles in disease occurrence and it can be life threatening if remains untreated. It seems that intensification of inflammatory responses in this condition is not restricted to a specific cell line of T lymphocytes. Our aim was to determine the number of T helper 9 (Th9) cells in inflamed colonic biopsies of UC patients. We also correlated it with interleukin (IL)-9 protein level in addition to certain genes expressions associated with Th9 phenotype.

Methods: Expression of CD4 and IL-9 were evaluated by immunohistochemical staining. Enzyme linked immunosorbent assay (ELISA) was performed to determine the colonic expression of IL-9 protein and finally mRNA expressions of interferon regulatory factor 4 (Irf4), Smad2, and Smad3 were measured by real-time polymerase chain reaction (RT-PCR) as critical transcription factors of Th9 differentiation.

Results: Number of Th9 cells was significantly increased in inflamed samples as compared with normal tissues. Also quantitative measurement of IL-9 by ELISA and mRNA expressions of Irf4, Smad2, and Smad3 showed notable correlative enhancements in patient's samples.

Conclusion: Function and number of Th9 cells are up-regulated in the inflamed mucosa of UC patients as with the protein secretion of IL-9 and mRNA expressions of Irf4, Smad2, and Smad3, so Th9 cells and IL-9 may become remarkable therapeutic targets for IBD treatment in the future.
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http://dx.doi.org/10.1080/08820139.2018.1486411DOI Listing
October 2018

The expression analysis of Fra-1 gene and IL-11 protein in Iranian patients with ulcerative colitis.

BMC Immunol 2018 06 18;19(1):17. Epub 2018 Jun 18.

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Background: Fra-1 (fosl1) belongs to the activator protein1 (AP-1) family inducing IL-11 expression in oxidative stress condition. IL-11 plays a pivotal role in protecting epithelial barriers integrity. In this study, we investigated the Fra-1 gene expression in the inflamed mucosa of patients with ulcerative colitis (UC) as well as its relation to IL-11 expression.

Materials And Methods: We enrolled 20 patients and 20 healthy controls with definite UC based on the clinical criteria. Fra-1 gene expression in inflamed and non-inflamed colonic biopsies was determined by real-time polymerase chain reaction (RT-PCR). The IL-11 protein concentration was measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. Pearson correlation was applied to calculate the relation between Fra-1 and IL-11.

Results: An increased level of Fra-1 gene expression was observed in patients with mild ulcerative colitis. The protein concentration of IL-11 was also increased in mild UC patients. Conversely, a significant decrease of IL-11 protein level was detected in severe UC patients compared to control group.

Conclusion: Oxidative stress in inflamed intestinal biopsies can induce fra-1 gene expression. Our findings suggest that Fra-1 transcription factor leads to the production of IL-11 protein in UC patients.
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http://dx.doi.org/10.1186/s12865-018-0257-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006762PMC
June 2018

A screening of growth inhibitory activity of Iranian medicinal plants on prostate cancer cell lines.

Biomedicine (Taipei) 2018 Jun 28;8(2). Epub 2018 May 28.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background: Prostate cancer has been known as one of the most common malignancy in the men and it is therefore very important to prevent and treat this cancer. In this study, the anticancer effects of 20 species of medicinal plants in Iran, especially those grown in Chaharmahal and Bakhtiari province, were investigated on prostate cancer cell lines to identify potential natural alternatives for the development of prostate cancer anticancer drugs.

Methods: The plants were gathered from Chaharmahal va Bakhtyari and their aerial parts extracted through maceration method using ethanol 70%. Anti-proliferative activity of extracts on PC-3, DU145 and HDF cell lines was evaluated by MTT assay 48 hours after treatment.

Results: Euphorbia szovitsii Fisch. & C.A.Mey. and Achillea wilhelmsii had anti-proliferative activity more than other plants on PC-3. Also IC50s for Urtica dioica, Euphorbia szovitsii Fisch. & C.A.Mey. and Medicago sativa were lower amount among the examined plants on Du-145.

Conclusion: According to our result, Euphorbia szovitsii Fisch. & C.A.Mey., U. dioica and Medicago sativa with good anti-proliferative activity can serve as an effective source of natural products to develop new antiprostate cancer drugs.
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http://dx.doi.org/10.1051/bmdcn/2018080208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992925PMC
June 2018

Alteration in CD8 T cell subsets in enterovirus-infected patients: An alarming factor for type 1 diabetes mellitus.

Kaohsiung J Med Sci 2018 May 20;34(5):274-280. Epub 2018 Jan 20.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Type 1 diabetes is a multi-factorial disease that can develop due to the combination of genetic and environmental factors. Viruses, particularly enteroviruses, are major environmental candidates in the pathogenesis of type 1 diabetes, even though the mechanisms of pathogenicity of these viruses and their effects on the immune system have not been understood very well yet. Previous studies show that any imbalance in the population of different lymphocyte subsets could develop autoimmune diseases. Our theory is that enteroviral infection causes an impairment in the distribution of lymphocyte subtypes and consequently results in the diabetes onset in some individuals. Therefore, in this project, we evaluated the distribution of T CD8+ lymphocytes and their subsets in type 1 diabetes patients. This study was conducted to investigate the relationship between enteroviral infection and type 1 diabetes mellitus in an Iranian population, and suggestion a predicting approach for susceptible subjects.
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http://dx.doi.org/10.1016/j.kjms.2017.12.010DOI Listing
May 2018

Th9 Cells: Probable players in ulcerative colitis pathogenesis.

Int Rev Immunol 2018 19;37(4):192-205. Epub 2018 Apr 19.

a Department of Microbiology and Immunology , Faculty of Medicine, Shahrekord University of Medical Sciences , Shahrekord , Iran.

T lymphocytes represent an important part of adaptive immune system undertaking different functions to regulate immune responses. CD4+ T cells are the most important activator cells in inflammatory conditions. Depending on the type of induced cells and inflamed sites, expression and activity of different subtypes of helper T cells are changed. Recent studies have confirmed the existence of a new subset of helper T lymphocytes called Th9. Naive T cells can differentiate into Th9 subtypes if they are exposed simultaneously by interleukin (IL) 4 and transforming growth factor β and also secondary activation of a complicated network of transcription factors such as interferon regulatory factor 4 (IRF4) and Smads which are essential for adequate induction of this phenotype. Th9 cells specifically produce interleukin 9 and their probable roles in promoting intestinal inflammation are being investigated in human subjects and experimental models of ulcerative colitis (UC). Recently, infiltration of Th9 cells, overexpression of IL-9, and certain genes associated with Th9 differentiation have been demonstrated in inflammatory microenvironment of UC. Intestinal oversecretion of IL-9 protein is likely to break down epithelial barriers and compromise tolerance to certain commensal microorganisms which leads to inflammation. Th9 pathogenicity has not yet been adequately explored in UC and they are far from being considered as inflammatory cells in this milieu, therefore precise understanding the role of these newly identified cells in particular their potential role in gut pathogenesis may enable us to develop novel therapeutic approaches for inflammatory bowel disease. So, this article tries to discuss the latest knowledge on the above-mentioned field.
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http://dx.doi.org/10.1080/08830185.2018.1457659DOI Listing
April 2019

The Inhibitory Effect of Epigallocatechin Gallate on the Viability of T Lymphoblastic Leukemia Cells is Associated with Increase of Caspase-3 Level and Fas Expression.

Indian J Hematol Blood Transfus 2018 Apr 1;34(2):253-260. Epub 2017 Aug 1.

6Department of Medical Laboratory Technology, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Acute lymphoblastic leukemia is the most prevalent cancer in children. Novel components to help struggle aggressive malignancies and overcome some side effects of conventional treatments could be a promising strategy. Epigallocatechingallate (EGCG), have attracted the attention of scientists for prevention or treatment of some cancers. Jurkat cells were incubated with the different concentrations of EGCG (30-100 µm) for 24, 48, and 72 h and cell viability was investigated using MTS test. Apoptosis and the level of caspase 3 alterations were evaluated using flowcytometry and expression of Fas by Real Time PCR. EGCG decreased viability of cells with an inhibition concentration (IC50) of 82.8 ± 3.1, 68.8 ± 4 and 59.7 ± 4.8 μM in 24,48 and 72 h. 50, 70 and 100 µM concentrations of EGCG induced apoptosis in about 31, 40 and 71% of the cells, respectively. The mean value of caspase 3 positive cells in the presence of 50, 70 and 100 µm concentrations of EGCG was 19.3 ± 2.9, 29.5 ± 3.1 and 61.2 ± 3.4 respectively compared to 7.8 ± 1.1 in control with a significant difference at 100 µm concentration. Treatment with EGCG for 48 h enhanced the expression of Fas reaching to a significant level at 100 µM concentration. EGCG is effective in decrease cell viability, apoptosis induction and enhancement of caspase 3 and expression level in jurkat cells. A comprehensive understanding of molecular events and pharmacokinetics of the component and experiments in animal models are required for dose determination and its interaction with other components of combination chemotherapy.
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http://dx.doi.org/10.1007/s12288-017-0854-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884976PMC
April 2018

Recent Findings in Molecular Basis of Inflammation and Anti-inflammatory Plants.

Curr Pharm Des 2018 ;24(14):1551-1562

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Inflammation is one of the most important body responses provided by the immune system since it ensures survival when tissues are affected by injuries or infections. The inflammatory response is an important process for maintenance of normal tissue homeostasis. In contrast to acute inflammation, chronic inflammation does not have a useful impact. Prevention and suppression of inflammation are necessary to reduce patient suffering and to preserve the integrity of multiple organs. Unfortunately, commercial available anti-inflammatory drugs are not free from side effects. Hence, there is an urgent need for introducing potent, nontoxic or less toxic antiinflammatory drugs. Recently, substantial progress has been made in the understanding of inflammatory mechanisms which may open new avenues for the preparation of novel anti-inflammatory drugs. Medicinal plants are also promising sources for preparation of such novel drugs. Taking into consideration the anti-inflammatory activities of a large group of medicinal plants, this article, in addition to describing recent advances in progress in understanding the molecular basis of inflammation, presents the most important medicinal plants with antiinflammatory activity.
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http://dx.doi.org/10.2174/1381612824666180403122003DOI Listing
October 2019

Analysis of the expression of mir-34a, mir-199a, mir-30c and mir-19a in peripheral blood CD4+T lymphocytes of relapsing-remitting multiple sclerosis patients.

Gene 2018 Jun 15;659:109-117. Epub 2018 Mar 15.

Department of Cellular Biotechnology at Cell Science research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Electronic address:

Background: Multiple sclerosis is an immune-mediated inflammatory disease of central nervous system. MicroRNAs play important roles in autoimmune diseases such as MS.

Objectives: The aim was to evaluate the expression pattern of miR-34a, miR-199a, miR-30c and miR-19a in peripheral blood derived CD4+ T lymphocytes of both relapsing and remitting phases of MS.

Methods: Blood samples from 40 RRMS patients (20 in relapsing and 20 in remitting phase) and 20 healthy volunteers were taken. CD4+ T cells were isolated. The expression level of miR-34a, miR-199a, miR-30c and miR-19a, and the percentage of Th17 and Treg cells were measured. Expression of master transcription factors of Th17 and Treg cells and several targets of these miRNAs were also evaluated.

Results: Data indicated an increased expression of miR-34a, miR-30c and miR-19a in relapsing phase and decreased expression of miR-199a in remitting phase. ROC curve data add other prestigious information of miR-34a, miR-199a, miR-30c and miR-19a by defining relapsing and remitting phase and also healthy cases with high specificity and sensitivity at a proposed optimum cut-off point.

Conclusion: Collectively, we showed a correlation between the four miRNAs with different phases of MS and their possible involvement in differentiation pathways of Th17 cells, as the most important players in MS.
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http://dx.doi.org/10.1016/j.gene.2018.03.035DOI Listing
June 2018

In vitro immunomodulatory activity of celastrol against influenza A virus infection.

Immunopharmacol Immunotoxicol 2018 Jun 1;40(3):250-255. Epub 2018 Mar 1.

c Cellular and Molecular Research Center, Basic Health Sciences Institute , Shahrekord University of Medical Sciences , Shahrekord , Iran.

Context: The influenza A virus (IAV) causes severe respiratory disease that remains a leading reason for morbidity and mortality. Previous studies have indicated that influenza complications in addition to viral replication are due to overproduction of pro-inflammatory cytokines. Therefore, a new compound is needed to be used with current antiviral drugs to modulate overproduction of pro-inflammatory cytokines in IAV infection.

Objective: This study investigated the effect of celastrol on mRNA expression and concentration levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-6 (IL6) that are induced by influenza A/Puerto Rico/8/34 (H1N1; PR8) in Madin-Darby Canine Kidney (MDCK) cells. The effect of this compound on virus titration and viral mRNA expression was also investigated.

Methods: Confluent MDCK cells were infected with influenza virus (H1N1; PR8) and treated with celastrol at different concentrations. After incubation, mRNA expression and concentrations of TNFα and IL6 were investigated using real-time polymerase chain reaction (PCR) and ELISA. The viral mRNA expression and virus titration were investigated using real-time PCR and 50% tissue culture infectious dose (TCID) assay, respectively.

Results: mRNA expression and concentrations of TNFα and IL6 increased significantly in control virus compared to cell control, and decreased significantly when compared with control virus after celastrol treatment. Viral mRNA expression and virus titration did not decrease after celastrol treatment.

Conclusion: Due to reducing mRNA expression and concentrations of TNFα and IL6, celastrol can serve as a suitable choice to control cytokine-induced inflammation in IAV infection, and therefore it can be used with current antiviral drugs.
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http://dx.doi.org/10.1080/08923973.2018.1440591DOI Listing
June 2018

Up-regulated Th17 cell function is associated with increased peptic ulcer disease in Helicobacter pylori-infection.

Infect Genet Evol 2018 06 23;60:117-125. Epub 2018 Feb 23.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:

Background: During Helicobacter pylori (H. pylori) infection CD4 T cells in the gastric lamina propria are hyporesponsive and polarized by Th1/Th17 cell responses controlled by Treg cells. The objective of this study was to determine the number of Th17 cells in gastric mucosa of patients with gastritis and peptic ulcer and determined the relationship between main virulence factor of H. pylori and Th17 cells.

Methods And Materials: A total of 89 H. pylori-infected gastritis patients, 63 H. pylori-infected peptic ulcer patients and 48 H. pylori-negative non-ulcer dysplasia patients were enrolled in this study. The number of Th17 was determined by immunohistochemistry. IL-8 and IL-17A expressions were determined by real-time polymerase chain reaction (qPCR). Also, the grade of chronic and active inflammation was investigated for involvement according to the density of neutrophils and mononuclear in gastric mucosal crypts, from one to all crypts.

Results: The number of Th17 cells and the expression of IL-8 and IL-17A in infected patients were significantly higher than uninfected subjects. The number of Th17 cells and the expression of IL-8 and IL-17A in infected patients with peptic ulcer were significantly higher than patients with gastritis. Additionally, the numbers of Th17 cells as well as the expression of IL-8 and IL-17A were positively correlated with the degree of H. pylori density in infected patients with peptic ulcer, while this correlation was negative in infected patients with gastritis. The numbers of Th17 cells as well as the expression of IL-8 and IL-17A were positively correlated with the degree of chronic inflammation.

Conclusion: The predominant Th17 cell responses may play a role in the pathogenesis of peptic ulcers disease in infected patients.
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http://dx.doi.org/10.1016/j.meegid.2018.02.020DOI Listing
June 2018

Study of the tumor microenvironment during breast cancer progression.

Cancer Cell Int 2017 22;17:123. Epub 2017 Dec 22.

Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.

Background: Different cells and mediators in the tumor microenvironment play important roles in the progression of breast cancer. The aim of this study was to determine the composition of the microenvironment during tumor progression in order to discover new related biomarkers and potentials for targeted therapy.

Methods: In this study, breast cancer biopsies from four different stages, and control breast biopsies were collected. Then, the mRNA expression of several markers related to different CD4 T cell subsets including regulatory T cells (Treg), T helper (Th) type 1, 2 and 17 were determined. In addition, we investigated the expression of two inflammatory cytokines (TNF-α and IL-6) and inflammatory mediators including FASL, IDO, SOCS1, VEGF, and CCR7.

Results: The results showed that the expression of Th1 and Th17 genes was decreased in tumor tissues compared to control tissues. In addition, we found that the gene expression related to these two cell subsets decreased during cancer progression. Moreover, the expression level of TNF-α increased with tumor progression.

Conclusion: We conclude that the expression of genes related to immune response and inflammation is different between tumor tissues and control tissues. In addition, this difference was perpetuated through the different stages of cancer.
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http://dx.doi.org/10.1186/s12935-017-0492-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741925PMC
December 2017

Interaction between Gallic acid and Asparaginase to potentiate anti-proliferative effect on lymphoblastic leukemia cell line.

Biomed Pharmacother 2017 Dec 6;96:1045-1054. Epub 2017 Dec 6.

Pathology and Hematology Department, Shahrekord University of Medical Sciences, Shahrekord, Iran; Medical Plant Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:

Background: Treatment of acute lymphoblastic leukemia (ALL) fails in some cases and the side effects cause mortality in certain patients. Gallic acid (GA), a polyhydroxyphenolic compound has biological functions including anti-proliferative properties. The aim of the present study was to investigate the growth inhibition effects of GA in combination with asparaginase (ASP), as a component of combination chemotherapy, in a lymphoblastic leukemia cell line.

Methods: Jurkat cells were incubated with different concentrations of GA with or without ASP. Proliferation inhibition was investigated using MTS test. The level of apoptosis alterations were evaluated using flow cytometry. The expression of Fas gene level and surface expression were investigated by quantitative real time PCR and flow cytometry respectively.

Results: GA at 50μM concentration and ASP at 0.5 IU/ml inhibited 50% cell proliferation in 48 hours. GA also increased the inhibitory effect of ASP and some combinations had synergistic results. The increase of cell apoptosis and Fas expression were observed in GA-treated cells compared to control. GA increased the effect of ASP on proliferation inhibition, induction of apoptosis and Fas expression.

Conclusion: GA is an effective component in proliferation inhibition, apoptosis induction and enhancement of Fas expression level in Jurkat cell line. GA in some combination with ASP increases the effect of the latter on the cells. The study of the mechanism of these effects could be a further step towards target therapy. This study is a preliminary phase to the use of GA and should be carried out by more comprehensive study and animal models.
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http://dx.doi.org/10.1016/j.biopha.2017.11.122DOI Listing
December 2017