Publications by authors named "Ali Khodadadi"

71 Publications

Effect of water-soluble PM on the production of TNF-α by human monocytes and induction of apoptosis in A549 human lung epithelial cells.

J Environ Health Sci Eng 2021 Jun 7;19(1):143-150. Epub 2021 Jan 7.

Environmental Technologies Research Center (ETRC), Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Long-term exposure to airborne particles of 10 µm and less in size (PM) in dust can lead to increased risk of diseases such as respiratory, cardiovascular, lung cancer and atherosclerosis. The aim of the study was to evaluate the effects of water-soluble PM particles in the Middle East Dust (MED) storm in Ahvaz, Iran, on the production of TNF-α by human monocytes. In addition, we assessed the level of induction of apoptosis in isolated A549 human pulmonary epithelial cells. For this purpose, isolated human blood monocytes (250,000 to 300,000 cell/ ml) as well as isolated human pulmonary A549 epithelial cells (100,0000 cell/ ml) were exposed to various concentrations (62.5, 125, 250, 500 µg/ml) of water-soluble PM particles for different incubation periods (12, 24, 48 h). The results showed that exposure to PM particles increased the production of TNF-α in human monocytes and promoted apoptosis induction in A549 cells, in both concentration and incubation of period-dependent manner. In conclusion, airborne dust particles in Ahvaz city contain active compounds capable of increasing production of the pro-inflammatory cytokine, TNF-α, and inducing apoptosis of lung epithelial cells.
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http://dx.doi.org/10.1007/s40201-020-00588-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172754PMC
June 2021

Role of breast cancer-derived exosomes in metabolism of immune cells through PD1-GLUT1-HK2 metabolic axis.

Tissue Cell 2021 Jun 15;71:101576. Epub 2021 Jun 15.

Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address:

Tumor cells modulate immune responses by secreting exosomes. Tumor exosomes can affect the metabolism of immune cells and increase immune inhibitory molecules such as programmed cell death protein 1 (PD-1). PD-1 inhibits the glycolysis pathway in immune cells. We investigated the role of tumor exosomes in how metabolic changes occur through the PD1-GLUT1-HK2 metabolic axisin peripheral blood mononuclear cells (PBMCs). The MDA-MB-231 cell line was cultured, serum samples from breast cancer patients were collected, and exosomes purified from serum samples and the MDA-MB-231 cell line. PBMCs were treated with purified exosomes for 72 h and, the expression of PD1-GLUT1-HK2 genes was measured by real-time PCR. Our study results showed relative expression of the HK2 gene in both groups treated with MDA-MB-231 cell line exosomes and serum exosomes of breast cancer patients was significantly increased compared to the control group (p < 0.0001). Also, the relative expression of the PD1 gene and GLUT1 gene showed a significant increase compared to the control group only in the group treated with MDA-MB-231 cell line exosomes (p < 0.0001). Therefore, Breast cancer exosomes increased the expression of key genes in the glycolysis pathway, increasing the glycolysis pathway in PBMCs. Increased expression of PD-1 could not prevent the expression of critical genes in the glycolysis pathway as in previous studies.
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http://dx.doi.org/10.1016/j.tice.2021.101576DOI Listing
June 2021

Tranilast: a potential anti-Inflammatory and NLRP3 inflammasome inhibitor drug for COVID-19.

Immunopharmacol Immunotoxicol 2021 Jun 21;43(3):247-258. Epub 2021 May 21.

Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

SARS-CoV-2 is a type of beta-CoV that develops acute pneumonia, which is an inflammatory condition. A cytokine storm has been recognized as one of the leading causes of death in patients with COVID-19. ALI and ARDS along with multiple organ failure have also been presented as the consequences of acute inflammation and cytokine storm. It has been previously confirmed that SARS-CoV, as another member of the beta-CoV family, activates NLRP3 inflammasome and consequently develops acute inflammation in a variety of ways through having complex interactions with the host immune system using structural and nonstructural proteins. Numerous studies conducted on Tranilast have further demonstrated that the given drug can act as an effective anti-chemotactic factor on controlling inflammation, and thus, it can possibly help the improvement of the acute form of COVID-19 by inhibiting some key inflammation-associated transcription factors such as NF-κB and impeding NLRP3 inflammasome. Several studies have comparably revealed the direct effect of this drug on the prevention of inappropriate tissue's remodeling; inhibition of neutrophils, IL-5, and eosinophils; repression of inflammatory cell infiltration into inflammation site; restriction of factors involved in acute airway inflammation like IL-33; and suppression of cytokine IL-13, which increase mucosal secretions. Therefore, Tranilast may be considered as a potential treatment for patients with the acute form of COVID-19 along with other drugs.
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http://dx.doi.org/10.1080/08923973.2021.1925293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146296PMC
June 2021

Effect of 5-aminolevulinic acid on gene expression and presence of NKG2D receptor on NK cells.

Int Immunopharmacol 2021 Apr 29;97:107677. Epub 2021 Apr 29.

Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address:

Natural killer (NK) cells are involved in innate and acquired immunity, stimulating and enhancing immune responses via secretion of IFN-γ and TNF-α. NKG2D is among the most important NK's stimulant receptors, the ligands of which are elevated on cancerous and virus-infected cells. We analyzed effect of 5-ALA on gene expression and receptor presentation of NKG2D, which is present on peripheral blood NK cells. Mononuclear cells were isolated from the venous blood samples of healthy individuals. RNA extraction and cDNA synthesis were performed after exposure of samples to 5-ALA, and gene expression was evaluated using Real-Time PCR, and the receptor presence rate on the cell surface was evaluated by flow-cytometry analysis. The results showed the gene expression of NKG2D and the presence of its receptor on NK cells were increased.5-ALA can be used to activate NK cells in their killing activity, preventing the growth and metastasis of cancerous cells.
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http://dx.doi.org/10.1016/j.intimp.2021.107677DOI Listing
April 2021

Application of different negative binomial parameterizations to develop safety performance functions for non-federal aid system roads.

Accid Anal Prev 2021 Jun 15;156:106103. Epub 2021 Apr 15.

Virginia Tech Transportation Institute, 3500 Transportation Research Plaza, Building 1 R207, Blacksburg, VA 24061, United States. Electronic address:

Safety performance functions (SPFs) are the main building blocks in understanding the relationships between crash risk factors and crash frequencies. Many research efforts have focused on high-volume roadways that typically experience more crashes. A few studies have documented SPFs for non-federal aid system (NFAS) roads including rural minor collectors, rural local roads, and urban local roads. NFAS roads are characterized by unique features such as lower speeds, and shorter segment lengths, and they usually experience fewer crashes given the low exposure of these roads. As a result, there is a clear need to investigate the associated safety issues of NFAS roadways and generate distinct SPFs for them. The main objective of this study is to bridge the gap in the literature and develop SPFs for NFAS roads. This study examined the application of traditional negative binomial and zero-favored negative binomial models (i.e., negative binomial-Lindley). Both groups of models were formulated by different variance and dispersion structures. Using crash, roadway inventory, and traffic volume data from 2014 to 2018 in Virginia, the results showed that the NB-L models perform better than the traditional NB models. Furthermore, an appropriate variance structure along with a reasonably chosen dispersion function can further improve the model performance.
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http://dx.doi.org/10.1016/j.aap.2021.106103DOI Listing
June 2021

Leukemia Inhibitory Factor Suppresses NKG2D mRNA Expression and Presentation on Human Natural Killer Cells.

Iran J Allergy Asthma Immunol 2021 Feb 11;20(1):98-105. Epub 2021 Feb 11.

Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran AND Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Leukemia inhibitory factor (LIF) is a multi-functional cytokine secreted from cells such as lymphocytes and hepatocytes. This study aimed to evaluate the effect of LIF on natural killer group 2 member D (NKG2D) receptors' expression and presentation on natural killer (NK) cells.  For this purpose, peripheral blood mononuclear cells taken from 4 young male healthy blood donors were isolated and the effect of LIF (25 ng/mL) after 12, 24, and 48 hours of incubation, on NKG2D receptors expression and presentation was investigated using flow cytometry and real-time-polymerase chain reaction (PCR). All of the steps of the experiment were performed in duplicate. After periods of 12, 24, and 48 hours, LIF reduced both the expression and presentation of the NKG2D receptor on NK cells. The results suggest that this cytokine has a direct modulating activity on the body's immune response through suppression of NKG2D receptor expression and presentation on NK cells.
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http://dx.doi.org/10.18502/ijaai.v20i1.5416DOI Listing
February 2021

Quantifying the automated vehicle safety performance: A scoping review of the literature, evaluation of methods, and directions for future research.

Accid Anal Prev 2021 Mar 8;152:106003. Epub 2021 Feb 8.

Zachry Department of Civil & Environmental Engineering, Texas A&M University, Texas, USA.

Vehicle automation safety must be evaluated not only for market success but also for more informed decision-making about Automated Vehicles' (AVs) deployment and supporting policies and regulations to govern AVs' unintended consequences. This study is designed to identify the AV safety quantification studies, evaluate the quantification approaches used in the literature, and uncover the gaps and challenges in AV safety evaluation. We employed a scoping review methodology to identify the approaches used in the literature to quantify AV safety. After screening and reviewing the literature, six approaches were identified: target crash population, traffic simulation, driving simulator, road test data analysis, system failure risk assessment, and safety effectiveness estimation. We ran two evaluations on the identified approaches. First, we investigated each approach in terms of its input (required data, assumptions, etc.), output (safety evaluation metrics), and application (to estimate AVs' safety implications at the vehicle, transportation system, and society levels). Second, we qualitatively compared them in terms of three criteria: availability of input data, suitability for evaluating different automation levels, and reliability of estimations. This review identifies four challenges in AV safety evaluation: (a) shortcomings in AV safety evaluation approaches, (b) uncertainties in AV implementations and their impacts on AV safety, (c) potential riskier behavior of AV passengers as well as other road users, and (d) emerging safety issues related to AV implementations. This review is expected to help researchers and rulemakers to choose the most appropriate quantification method based on their goals and study limitations. Future research is required to address the identified challenges in AV safety evaluation.
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http://dx.doi.org/10.1016/j.aap.2021.106003DOI Listing
March 2021

A novel mutation in RFXANK gene and low B cell count in a patient with MHC class II deficiency: a case report.

Immunol Res 2020 08;68(4):225-231

Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Recurrence of severe microbial infections results from a primary immunodeficiency disorder known as major histocompatibility complex class II deficiency or bare lymphocyte syndrome type II. Immunologic function is severely impaired due to the absence of MHC class II molecules on the surface of immune cells. Here, we report a 5-year-old boy with a novel homozygous mutation in RFXANK gene that negatively affects the proper expression of MHC class II molecules by antigen presenting cells. The frame shift mutations in RFXANK gene and negative HLA-DR proteins expression on peripheral blood mononuclear cells were identified and confirmed by whole exome sequencing, Sanger sequencing, and flow cytometry. The patient was referred with long-term severe prolonged diarrhea, fever, coughing, and vomiting. Also, antibiotic resistance, normal T cell, and NK cell counts with low B cell count and reduced serum immunoglobulin level were observed. The patient did not give a dramatic response to intravenous immunoglobulin infusion. The significancy of this report is the novelty of mutation and low B cell count which is not commonly expected in such patients. The final diagnosis of BLS type II is based on WES, Sanger sequencing, and flow cytometric evaluation. Moreover, it seems that the only therapeutic choice is hematopoietic stem cell transplantation.
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http://dx.doi.org/10.1007/s12026-020-09141-9DOI Listing
August 2020

Interleukin-22 and intestinal homeostasis: Protective or destructive?

IUBMB Life 2020 08 4;72(8):1585-1602. Epub 2020 May 4.

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

Interleukin (IL)-22 is a member of IL-10 family cytokines with various immunologic functions. As its name implies, IL-22 is known to be secreted mainly by Th22 cells, a recently discovered lineage of CD4+ T cells. Also, Th17, Th1, natural killer cells, γδT cells, and innate immune cells along with some nonlymphoid cells have been confirmed as secondary cellular sources of IL-22. Different cell types such as bronchial and intestinal epithelial cells, keratinocytes, hepatocytes, dermal fibroblasts, and tubular epithelial cells are affected by IL-22. Both pathologic and protective roles have been attributed to IL-22 in maintaining gut homeostasis and inflammation. According to the latest fast-growing investigations, IL-22 is significantly involved in various pathologies including allergic diseases, infection, autoimmunity, and cancer development. Regulating gut immune responses, barrier integrity, and inflammation is dependent on a diverse complex of cytokines and mediators which are secreted by mucosal immune cells. Several investigations have been designed to recognize the role of IL-22 in gastrointestinal immunity. This article tries to discuss the latest knowledge on this issue and clarify the potential of IL-22 to be used in the future therapeutic approaches of intestinal disorders including inflammatory bowel diseases and colon cancer.
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http://dx.doi.org/10.1002/iub.2295DOI Listing
August 2020

Spermatogenesis Recovery Potentials after Transplantation of Adipose Tissue-Derived Mesenchymal Stem Cells Cultured with Growth Factors in Experimental Azoospermic Mouse Models.

Cell J 2020 Jan 29;21(4):401-409. Epub 2019 Jul 29.

Cancer, Environmental and Petroleum Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Objective: Approximately 1% of the male population suffers from obstructive or non-obstructive azoospermia. Previous in vitro studies have successfully differentiated mesenchymal stem cells (MSCs) into germ cells. Because of immunemodulating features, safety, and simple isolation, adipose tissue-derived MSCs (AT-MSCs) are good candidates for such studies. However, low availability is the main limitation in using these cells. Different growth factors have been investigated to overcome this issue. In the present study, we aimed to comparatively assess the performance of AT-MSCs cultured under the presence or absence of three different growth factors, epidermal growth factor (EGF), leukemia inhibitory factor (LIF) and glial cell line-derived neurotrophic factor (GDNF), following transplantation in testicular torsion-detorsion mice.

Materials And Methods: This was an experimental study in which AT-MSCs were first isolated from male Naval Medical Research Institute (NMRI) mice. Then, the mice underwent testicular torsion-detorsion surgery and received bromodeoxyuridine (BrdU)-labeled AT-MSCs into the lumen of seminiferous tubules. The transplanted cells had been cultured in different conditioned media, containing the three growth factors and without them. The expression of germ cell-specific markers was evaluated with real-time polymerase chain reaction (PCR) and western-blot. Moreover, immunohistochemical staining was used to trace the labeled cells.

Results: The number of transplanted AT-MSCs resided in the basement membrane of seminiferous tubules significantly increased after 8 weeks. The expression levels of and genes in the transplanted testicles by AT-MSCs cultured in the growth factors-supplemented medium was greater than those in the control group (P<0.001 and P<0.05, respectively). The expression levels of the and genes did not significantly differ from the control group.

Conclusion: Our findings showed that the use of EGF, LIF and GDNF to culture AT-MSCs can be very helpful in terms of MSC survival and localization.
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http://dx.doi.org/10.22074/cellj.2020.6055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722443PMC
January 2020

Flood in the South-West of Iran in 2019; Causes, Problems, Actions and Lesson Learned.

Bull Emerg Trauma 2019 Apr;7(2):199-200

Ph.D. Candidate of Health in Disasters and Emergencies, Student Research Committee, Department of Health in Disasters and Emergencies, Health Human Resources Research Center, School of Management and Medical Informatics, Shiraz University of Medical Sciences, Shiraz, Iran.

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http://dx.doi.org/10.29252/beat-070219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555208PMC
April 2019

Effects of Quercetin-Loaded Nanoparticles on MCF-7 Human Breast Cancer Cells.

Medicina (Kaunas) 2019 Apr 22;55(4). Epub 2019 Apr 22.

Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background and objectives: Previous studies have shown anti-tumor activity of quercetin (QT). However, the low bioavailability of QT has restricted its use. This study aimed to assess the toxic effect of QT encapsulated in solid lipid nanoparticles (QT-SLNs) on the growth of MCF-7 human breast cancer cells. Materials and Methods: MCF-7 and MCF-10A (non-tumorigenic cell line) cell lines treated with 25 µmol/mL of QT or QT-SLNs for 48 h. Cell viability, colony formation, oxidative stress, and apoptosis were evaluated to determine the toxic effects of the QT-SLNs. The QT-SLNs with appropriate characteristics (particle size of 85.5 nm, a zeta potential of -22.5 and encapsulation efficiency of 97.6%) were prepared. The QT-SLNs showed sustained QT release until 48 h. Cytotoxicity assessments indicated that QT-SLNs inhibited MCF-7 cells growth with a low IC (50% inhibitory concentration) value, compared to the free QT. QT-SLNs induced a significant decrease in the viability and proliferation of MCF-7 cells, compared to the free QT. QT-SLN significantly increased reactive oxygen species (ROS) level and MDA contents and significantly decreased antioxidant enzyme activity in the MCF-7 cells. Following QT-SLNs treatment, the expression of the protein significantly decreased, whereas Bx expression showed a significant increase in comparison with free QT-treated cells. Furthermore, The QT-SLNs significantly increased apoptotic and necrotic indexes in MCF-7 cells. Viability, proliferation, oxidative stress and apoptosis of MCF-10A cells were not affected by QT or QT-SLNs. According to the results of this study, SLN significantly enhanced the toxic effect of QT against human breast cancer cells.
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http://dx.doi.org/10.3390/medicina55040114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524048PMC
April 2019

Survivin as a diagnostic and therapeutic marker for thyroid cancer.

Pathol Res Pract 2019 Apr 18;215(4):619-625. Epub 2019 Jan 18.

Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address:

Thyroid cancer (TC) is known as the most prevalent form of endocrine malignancy. With regard to high heterogeneity of the nodules, problem of discriminating between benign and malignant ones in terms of pathological characteristics, as well as lack of appropriate molecular markers; significant efforts are being made to identify molecular markers that able to detect tumorous lesions. Survivin, the newest member of the family of proteins inhibiting cell apoptosis, has been recently considered as a novel molecule marker for cancer. Studies on TC have also demonstrated distinctive expression of survivin and its splice variants in cancer cells compared to normal ones. Therefore, detection of survivin expression and its new splice variants can be utilized to identify tumor nodules and distinguish them from non-cancerous ones, along with other routine laboratory methods.
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http://dx.doi.org/10.1016/j.prp.2019.01.025DOI Listing
April 2019

Determination of the dose enhancement exclusively in tumor tissue due to the presence of GNPs.

Appl Radiat Isot 2019 Mar 30;145:39-46. Epub 2018 Nov 30.

Department of Medical Radiation, Engineering Faculty, Central Tehran Branch, Islamic Azad University, Tehran, Iran.

Purpose: The purpose of this study is to investigate the differences between obtained percentage dose enhancements in areas around nanoparticles in GNPs (gold nanoparticles) enriched medium and percentage dose enhancements in the entire GNPs enriched medium including nanoparticles region.

Methods And Materials: To verify the accuracy of Ir-192 source simulation, the obtained values of air kerma strength, dose rate constants, and radial dose functions were compared against previously published results. Then a 1 cm × 1 cm× 1 cm tumor volume loaded with different diameters of GNPs were considered at a source to the tumor center of 1 cm. Finally, dose enhancements were obtained for 50, 100 and 200 nm GNPs as a function of various concentrations of the radiosensitizer and depth in phantom.

Results: Calculations showed that dose enhancement could be customized by varying the size of nanoparticles, concentrations and radial distance from the source. The highest PDE (The ratio of the increased deposited dose in the tumor region to the dose deposition in the no nano gold-containing structure) was acquired by 50 nm nanoparticles, 30 mg/g concentrations and in the highest distance from the source. (PDE) and (PDE) due to the presence of 7-30 mg/g concentration of GNPs ranged from 3-18.19% and 3.45-21.13%, respectively. The results of this study revealed that the correlation is significant at the 0.01 level and there is a non-negligible difference (up to 3%) between (D)and (D).

Conclusion: By considering exclusively determination of dose enhancement in the just tumor tissue, calculating (D) Instead of D may be a strategy for clinical use of nanoparticles in the radiation therapy. The results showed that with the increasing trend of dose enhancement in the GNPs loaded-tumor, dose enhancement decreases with an increase in the size of GNPs.
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http://dx.doi.org/10.1016/j.apradiso.2018.11.013DOI Listing
March 2019

Effect of dehydroepiandrosterone on meiotic spindle structure and oocyte quality in mice.

Iran J Basic Med Sci 2018 Oct;21(10):1020-1025

Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran.

Objectives: Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances in women with diminished ovarian reserve (DOR) and to reduce miscarriage rates by 50-80%. This study, therefore, assesses effects of DHEA on number of retrieved oocytes and meiotic spindles.

Materials And Methods: A randomized, prospective, controlled study was conducted on eight groups, four groups of young mice and four elderly. All young and old groups received different oral doses (35, 50, 75 mg/kg) of DHEA for 3 months. Meiotic spindle assessment was done by immunocytochemical techniques using a confocal laser microscope (Leica TCS-4D).

Results: Statistical surveys showed that in control young groups 80% (=0.0845) and in the old control group 73.3% (=0.000) of the meiotic spindles have a normal shape and structure; the difference was meaningful. The young with 50 mg/kg of DHEA in 85.4% and the young with 75 mg/kg of DHEA in 84.2% were normal in shape and structure. Statistical analysis showed that the difference was meaningless (=0.845). The old group with 30 mg/kg of DHEA in 81.1%, the old with 50 mg/kg of DHEA in 83.9%, and the old with 75 mg/kg of DHEA in 79.0% showed normal shape and structure. The meiotic spindle disruption ratio in old mice showed a significant difference (=0.000) in comparison with others in young groups. Statistical analysis showed that difference between DHEA and control groups is meaningful. But this difference was meaningless between DHEA groups.

Conclusion: Results showed that DHEA has a positive and improvement effect on the meiotic spindle in old mice.
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http://dx.doi.org/10.22038/IJBMS.2018.27111.6629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281067PMC
October 2018

Overexpression of Regulatory T Cell-Related Markers (FOXP3, CTLA-4 and GITR) by Peripheral Blood Mononuclear Cells from Patients with Breast Cancer

Asian Pac J Cancer Prev 2018 Nov 28;19(11):3019-3025. Epub 2018 Nov 28.

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

Background: Regulatory T (Treg) cells are immunosuppressor lymphocytes that play a critical role in the establishment and progression of cancers. A number of markers, especially FOXP3, CTLA-4 and GITR influence the function of Treg cells. This investigation aimed to evaluate the expression of a number of important Treg cell-related markers by peripheral blood mononuclear cells (PBMCs) from newly-diagnosed women with breast cancer. Methods: The fresh PBMCs were obtained from 20 women with breast cancer and 20 healthy individuals. The PBMCs from both groups were cultured for 32 hours in the presence or absence of PHA (10 μg/ml). After total RNA extraction from cultured PBMCs, the expression of the FOXP3, CTLA-4 and GITR transcripts was assessed using real time-PCR. Results: The mRNA expression of FOXP3, CTLA-4 and GITR in unstimulated PBMCs from patients with breast cancer were significantly higher than healthy control group (P<0.05, P<0.03 and P<0.04, respectively). Similarly, the expression of FOXP3, CTLA-4 and GITR transcripts in PHA-stimulated PBMCs from patients with breast cancer were significantly increased in comparison with healthy individuals (P<0.01, P<0.005 and P<0.01, respectively). Conclusion: The increased expression of FOXP3, CTLA-4 and GITR represent higher activity of Treg cells in patients with breast cancer that may play an important role in the tumor establishment and development.
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http://dx.doi.org/10.31557/APJCP.2018.19.11.3019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318404PMC
November 2018

Ellagic acid mitigates sodium arsenite-induced renal and hepatic toxicity in male Wistar rats.

Pharmacol Rep 2018 Aug 5;70(4):712-719. Epub 2018 Feb 5.

Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address:

Background: The aim of this study was to investigate the effect of ellagic acid (EA) on arsenic-induced renal and hepatic toxicity in rats.

Methods: A total number of 35 male Wistar rats were randomly divided into five experimental groups. Group 1 received normal saline (po). Group 2 received sodium arsenite (SA, 10mg/kg, po) for 21days. Group 3 received EA (30mg/kg, po) for 14days. Groups 4 and 5 received SA 7days prior to EA (10 and 30mg/kg respectively) treatment and continued up to 21days simultaneous with SA administration. Various biochemical, histological and molecular biomarkers were measured in kidney and liver.

Results: Treatment with EA (more potently at dose of 30mg/kg) restored the SA-induced alterations in serum creatinine (Cr) and blood urine nitrogen (BUN) levels as well as the changes in aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations (all p<0.001). Elevated levels of malondialdehyde (MDA) and nitric oxide (NO) in renal and hepatic tissue was reduced by EA treatment (all p<0.001). Treatment with EA enhanced the glutathione (GSH) content in liver (p<0.001) and up-regulated renal and hepatic superoxide dismutase (SOD) and glutathione peroxidase (GPx) mRNA expression (all p<0.001). The SA-induced histopathological alterations in kidney and liver were reduced by EA treatment.

Conclusion: In conclusion, the presence of EA with SA alleviated its toxic effects and EA treatment might be an effective strategy for the management of arsenic-induced renal and hepatic damage.
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http://dx.doi.org/10.1016/j.pharep.2018.02.007DOI Listing
August 2018

STAT3 and apoptosis challenges in cancer.

Int J Biol Macromol 2018 Oct 18;117:993-1001. Epub 2018 May 18.

Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Several studies have processed conceivable evidence for the vital role of Signal Transducer and Activator of Transcription 3 (STAT3) in cancer transformation and carcinogenesis. Therefore, one of the important factors in formation of cancer is STAT3 and for design of novel anticancer drugs is a suitable target. On the other hand, apoptosis pathway has a critical role in the cancers pathogenesis. Generally, increasing developments have been existed to expression, production, phosphorylation or activation of STAT3 in the effective or responsible cells of most of the cancers. In return, apoptosis process in this cells have been suffered inhibition, decrease in expression, produce or activation in some related factors which lead to debilitation or inhibition of the process. Further understanding of the STAT3 related signaling and apoptosis pathway can lead to the invention of novel approaches for therapies in unstudied disease. In this manuscript, review and highlight recent knowledge of the STAT3 pathway and its connection with apoptosis process in cancers and discuss STAT3-targeting agents to therapeutic developments.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.05.121DOI Listing
October 2018

Expression of Salmonella typhimurium and Escherichia coli flagellin protein and its functional characterization as an adjuvant.

Microb Pathog 2018 May 9;118:87-90. Epub 2018 Mar 9.

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

Background: Flagellin is the major structural protein monomer of bacterial flagella. Flagellin through binding to its receptor and activation of antigen presenting cells stimulates the innate and adaptive immune responses. Flagellin is used as an effective systemic or mucosal adjuvant to stimulate the immune system. Recently, the therapeutic and protective role of flagellin in some infectious diseases and cancers has been investigated. In this study, we cloned the fliC genes from Salmonella typhimurium and Escherichia coli into pET-28a vector and investigated their expression in the prokaryotic system.

Methods: The fliC genes of S. typhimurium and E. coli were amplified by PCR with a specific oligonucleotide primer set. thse were cloned into the pET-28a vector and the recombinant pET-28a-fliC plasmids were successfully transformed into the E. coli strain BL-21(DE3). The expression of flagellin proteins in the prokaryotic cells were evaluated. Finally, Transcription of TNF-α mRNA was confirmed using Real-time PCR.

Results: The expression of proteins in the prokaryotic cells were approved by SDS-PAGE and western blotting method. Further, the functional characterization of flagellin proteins were evaluated using their ability to induce increased m-RNA expression of pro-inflammatory cytokine.

Conclusions: The flagellin proteins were expressed in the prokaryotic system. These proteins can be used to link target antigens as an effective adjuvant for future DNA vaccine studies. Purified recombinant proteins in this study can also be used for therapeutic and prophylactic purposes.
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http://dx.doi.org/10.1016/j.micpath.2018.03.016DOI Listing
May 2018

Valsartan attenuates bleomycin-induced pulmonary fibrosis by inhibition of NF-κB expression and regulation of Th1/Th2 cytokines.

Immunopharmacol Immunotoxicol 2018 Jun 15;40(3):225-231. Epub 2018 Feb 15.

c Department of Immunology, Faculty of Medicine , Ahvaz Jundishapur University of Medical Sciences (AJUMS) , Ahvaz , Iran.

Objective: Pulmonary fibrosis (PF) is a chronic respiratory system disease. The role of inflammation and angiotensin in the development and progression of PF has previously been demonstrated. Alternation in antifibrotic/profibrotic mediators and NF-κB activation have important roles in PF development. NF-κB, a nuclear factor, induces the transcription of inflammatory and pro-inflammatory cytokines. The aim of this study was to evaluate the effect of valsartan as an angiotensin receptor blocker on IL-4, INF-γ, and NF-κB expression in the treatment of PF.

Materials And Methods: Rats were divided into five groups: groups I (bleomycin) and II (control) received a single injection of bleomycin (7.5 IU/kg) or vehicle, respectively. Groups III-V received valsartan (20, 40, and 80 mg/kg, respectively) orally a week before and for 3 weeks after the bleomycin injection. Serum levels of IL-4 and INF- γ were then measured. Relative NF-κB expression was investigated by real-time PCR.

Results: Histopathological examination showed the anti-inflammation effect of valsartan. Bleomycin significantly increased IL-4 serum level and decreased that of INF-γ in the serum. Valsartan could restore their levels to normal. Valsartan raised the decreased ratio of INF-γ/IL-4. Exposure to bleomycin elevated NF-κB expression; and valsartan decreased the increased gene expression.

Discussion: Valsartan as an angiotensin receptor antagonist presumably by blocking angiotensin receptor causes to ameliorated PF, which was at least partly due to antifibrotic/profibrotic cytokine regulation and reduced NF-κB expression.

Conclusions: Valsartan showed a significant protective effect against bleomycin-induced PF.
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http://dx.doi.org/10.1080/08923973.2018.1431924DOI Listing
June 2018

Anticancer Activity of Curcumin-Loaded PLGA Nanoparticles on PC3 Prostate Cancer Cells.

Iran J Pharm Res 2017 ;16(3):868-879

Cell and Molecular Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Curcumin (Cur) has been found to be very efficacious against many different types of cancer cells. However, the major disadvantage associated with the use of Cur is its low systemic bioavailability. Our present work investigated the toxic effect of encapsulation of Cur in PLGA (poly lactic-coglycolic acid) nanospheres (NCur) on PC3 human cancer prostate cell. In the present study, we have investigated the effects of NCur on growth, autophagia, and apoptosis in PC3 cells, respectively, by MTT assay, fluorescence microscopy, and Flow cytometry. MTT assays revealed that the NCur at the concentration of 25 µg/mL for 48 h were able to exert a more pronounced effect on the PC3 cells as compared to free Cur. Apoptotic index was significantly increased in NCur-treated cells compared to free Cur. The percentage of autophagic cells (LC3-II positive cells) was also significantly increased in NCur treatment in comparison to free Cur. These data indicate that the NCur has considerable cytotoxic activity more than Cur on PC3 cell lines, which is mediated by induction of both apoptotic and autophagic processes. Thus, NCur has high potential as an adjuvant therapy for clinical application in prostate cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610743PMC
January 2017

Defining a standard and weighted mathematical index for maturation of dendritic cells.

Immunology 2018 04 24;153(4):532-544. Epub 2017 Nov 24.

Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada.

The concept of dendritic cell (DC) maturation generally refers to the changes in morphology and function of DCs. Conventionally, DC maturity is based on three criteria: loss of endocytic ability, gain of high-level capacity to present antigens and induce proliferation of T cells, and mobility of DCs toward high concentrations of CCL19. Impairment of DC maturation has been suggested as the main reason for infectivity or chronicity of several infectious agents. In the case of hepatitis C virus, this has been a matter of controversy for the last two decades. However, insufficient attention has been paid to the method of ex vivo maturation as the possible source of such controversies. We previously reported striking differences between DCs matured with different methods, so we propose the use of a standard quantitative index to determine the level of maturity in DCs as an approach to compare results from different studies. We designed and formulated a mathematically calculated index to numerically define the level of maturity based on experimental data from ex vivo assays. This introduces a standard maturation index (SMI) and weighted maturation index (WMI) based on strictly standardized mean differences between different methods of generating mature DCs. By calculating an SMI and a WMI, numerical values were assigned to the level of maturity achieved by DCs matured with different methods. SMI and WMI could be used as a standard tool to compare diversely generated mature DCs and so better interpret outcomes of ex vivo and in vivo studies with mature DCs.
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http://dx.doi.org/10.1111/imm.12856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838426PMC
April 2018

The protective effect of Buffalo's milk against toluene induced-nephrotoxicity in rats.

J Nephropathol 2017 Jul 17;6(3):174-179. Epub 2016 Dec 17.

Department of Occupational Health, Engineering, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background: Toluene is widely used in different activities of industrial, commercial and household applications. It can cause damage to the human body. Buffalos' milk has a good nutritive value.

Objectives: The aim of this study is to examine the negative effects of toluene on kidney tissues and to investigate the protective effects of buffalo's milk against toluene-induced nephrotoxicity in rats.

Materials And Methods: Forty adult male Wistar rats (180-220 g weight) were randomly assigned to eight groups (n = 5). Animals in groups I to IV received oral gavage 1 mL distilled water (DHO) and groups V to VIII received oral gavage 1 mL buffalo's milk. Ten minutes later, animals were received toluene (i.p) at doses of 300 mg/kg (groups I and V), 600 mg/kg (groups of II and VI), and 900 mg/kg (groups of III and VII), respectively. The animals in groups IV (control) and VIII were injected vehicle (corn oil) only. The experiment repeated for seven consecutive days. Twenty-four hours after the last administration, animals were killed with overdose of sodium pentobarbital. Blood samples were analyzed for blood urea nitrogen (BUN) and creatinine (Cr). One part of the kidney tissues were excised for measuring the activities of superoxide dismutase (SOD), glutathione reductase (GR) and catalase (CAT) and the level of malondialdehyde (MDA). Another parts were excised for histopatholgical examination.

Results: Administration of toluene to male rats produced dose-dependent damage in the kidney. This was noted by elevation of BUN, Cr and MDA levels. In contrast, diminished the CAT, GR and SOD enzyme activities in rats treated with toluene when compared to those in control animals. Histopathological manifestations were also observed in dose related manner in toluene-treated rats. Buffalo's milk had no effect on the biochemical parameters and kidney morphology when compared to those in control. However, it was able to prevent rat kidney against toluene toxicity.

Conclusions: The results of this study demonstrated that toluene damages kidney tissue and is a nephrotoxic substance. Buffalo's milk was able to prevent the renal damage as an antioxidant and a nephroprotective agent.
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http://dx.doi.org/10.15171/jnp.2017.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607980PMC
July 2017

Therapeutic effects of ellagic acid on memory, hippocampus electrophysiology deficits, and elevated TNF-α level in brain due to experimental traumatic brain injury.

Iran J Basic Med Sci 2017 Apr;20(4):399-407

Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Golestan Blvd, Ahvaz, Iran.

Objectives: Cognitive defects such as learning and memory impairment are amongst the most repetitious sequelae after sever and moderate traumatic brain injury (TBI). It was suggested that ellagic acid (EA), an innate phenol product, display neuroprotective properties against oxidative and inflammatory damages after brain injury. The object of the current study was therapeutic properties of EA on blood-brain barrier (BBB) interruption and elevated content of TNF-α in brain tissue followed by neurologic aftereffects, cognitive and brain electrophysiology deficits as outcomes of diffuse TBI in rat.

Materials And Methods: TBI was induced by a 200 g weight falling by a 2-m height through a free-falling tube onto the head of anesthetized rat. TBI rats treated immediately after trauma with EA (100 mg/kg, IP) once every 8 hr until 48 hr later. Neurologic outcomes, passive avoidance task (PAT), hippocampal long-term potentiation (LTP), BBB permeability and content of TNF-α in brain tissue were evaluated.

Results: TBI induced significant impairments in neurological score, BBB function, PAT and hippocampal LTP in TBI+Veh group in compare with Sham+Veh (<0.001). EA treatment decreased neurologic severity score (NSS), restored increased BBB permeability, cognitive and hippocampal LTP abnormalities, and elevated brain content of TNF-α due to TBI significantly (<0.001).

Conclusion: Our findings propose that EA can restore NSS, cognitive and LTP deficits and prevent brain inflammation may by restore BBB permeability as well as lowering brain content of TNF-α following TBI.
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http://dx.doi.org/10.22038/IJBMS.2017.8581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425922PMC
April 2017

Design of Indigenous ELISA Using Tachyzoites from the RH Strain of and Comparison with Commercial Kits in Ahvaz, Southwest of Iran, 2015.

Jundishapur J Microbiol 2016 Oct 13;9(10):e36666. Epub 2016 Sep 13.

Department of Epidemiology and Biostatistics, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran.

Background: is one of the most common causes of latent infections in humans worldwide. Detecting anti- antibodies in serum using serological tests is a common method to diagnose toxoplasmosis.

Objectives: In the present study, an indigenous ELISA kit was prepared using tachyzoites from the RH strain of , and its sensitivity and specificity were compared with those of commercial kits.

Methods: To produce antigens, 0.02 mL of locally isolated RH strain parasites along with 10 tachyzoites were injected into the peritoneal cavities of 50 laboratory mice (BALB/C). Parasites were collected after 4 days. After filtering and washing, the concentration of protein in sonicated tachyzoites was calculated using the Lowry protein assay. The dilution of antigen, serum and alkaline phosphatase conjugate was assessed in designing an indigenous ELISA method; then ELISA was performed based on these dilutions, and its sensitivity was determined using 200 serum samples. In addition, the specificity of the assay was evaluated using 40 serum samples from patients with tuberculosis, leukemia or hydatid cyst.

Results: Indigenous ELISA was used to examine 100 serum samples containing anti- IgG, with a sensitivity of 98% (commercial kits: 100%). Another 100 serum samples containing anti- IgM were also tested, with a sensitivity of 99% (commercial kits: 100%). When 40 serum samples from patients with leukemia, hydatid cyst or tuberculosis were examined using anti- IgG, the specificity was 100%, identical to commercial kits. However, the specificity of a similar test with anti- IgM was just 28.6% for serum samples from leukemia patients, 21.4% for hydatid cyst and 16.7% for tuberculosis.

Conclusions: We found that purified locally isolated soluble crude antigens of the RH strain of from the peritoneal cavity of mice may be one of the most promising antigens for detection of human toxoplasmosis in routine screening.
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http://dx.doi.org/10.5812/jjm.36666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136452PMC
October 2016

Neuroprotective Effects of Ellagic Acid in a Rat Model of Parkinson's Disease.

Acta Med Iran 2016 Aug;54(8):494-502

Department of Immunology, Cancer, Petroleum, and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Antioxidants have protective effects against free radicals-induced neural damage in Parkinson's disease (PD). We examined the effects of ellagic acid (EA) on locomotion, pallidal local EEG, and its frequency bands' power and also cerebral antioxidant contents in a rat model of PD induced by 6-hydroxidopamine (6-OHDA). 6-OHDA (16 µg/2µ l) was injected into the right medial forebrain bundle (MFB) in MFB-lesioned rat's brain. Sham group received vehicle instead of 6-OHDA. PD-model was confirmed by rotational test using apomorphine injection. EA (50 mg/kg/2 ml, by gavages) was administered in PD+EA group. One group of MFB-lesioned rats received pramipexole (PPX; 2 mg/kg/2 ml, by gavages) as a positive control group (PD+PPX group). Motor activity was assessed by stride length, rotarod, and cylinder tests. Pallidal local EEG was recorded in freely moving rats. The levels of malondialdehyde (MDA) besides Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured in both striatum and hippocampus tissues. MFB lesion caused significant reduction of stride-length (P<0.001), bar decent latency (P<0.001) and frequency bands' power of pallidal EEG (P<0.001). Use of 6-OHDA caused a reduction in the GPx (P<0.001) and SOD (P<0.001) activities while increased significantly the levels of MDA (P<0.001) in MFB-lesioned rats. EA significantly restored all above parameters. The results show that EA can improve the motor impairments and electrophysiological performance in the MFB-lesioned rats via raising the cerebral antioxidant contents. Therefore, EA can protect the brain against free radicals-induced neural damage and may be beneficial in the treatment of PD.
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August 2016

The Effect of G2 Adjuvant on Gene Expression and Delivery of NKG2D Receptor on NK Cells in Peripheral Blood.

Cancer Biother Radiopharm 2016 May;31(4):119-24

1 Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran .

Introduction: Natural killer (NK) cells are a subset of lymphocytes in humans that release cytokines such as tumor necrosis factor alpha and interferon gamma-γ during infection. NKG2D is one of the most important stimulating NK receptors binding MIC-A, MIC-B, and ULBPs, which leads to activation of NK cells against tumor cells. In this study, the authors evaluated the effect of G2 adjuvant on gene expression and delivery of NKG2D receptor on NK cells in peripheral blood.

Materials And Methods: Peripheral blood mononuclear cells were isolated from venous blood obtained from healthy volunteers after adding G2 adjuvant within 12, 24, and 48 hours of incubation. Then, total RNA was extracted from the cells, cDNA synthesis was performed, and gene expression was evaluated by real-time PCR. In addition, NK cells were stained with the appropriate monoclonal antibodies, and the receptors expressed on cell surface were quantified.

Results: G2 adjuvant leads to upregulation of gene expression and increases the expression of NKG2D receptor on the surface of NK cells after incubation.

Conclusion: The findings of this study demonstrated that G2 adjuvant can increase NK cell cytotoxicity. It may play an important role in killing tumor cells, preventing tumor growth and metastasis.
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http://dx.doi.org/10.1089/cbr.2015.1883DOI Listing
May 2016

The effect of the melatonin on cryopreserved mouse testicular cells.

Int J Reprod Biomed 2016 Jan;14(1):23-8

Department of Anatomy, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: After improvements in various cancer treatments, life expectancy has been raised, but success in treatment causes loss of fertility in many of the survived young men. Cryopreservation of immature testicular tissues or cells introduced as the only way to preserve fertility. However, freezing has some harmful effects. Melatonin, a pineal gland hormone, has receptors in reproductive systems of different species. It is assumed that melatonin has free radical scavenger properties.

Objective: The aim of this study was to evaluate the effects of melatonin on the cryopreserved testicular cells in mouse.

Materials And Methods: Cells from 7- 10 days old NMRI mice testes were isolated using two step enzymatic digestion. The testicular cells were divided into two groups randomly and cryopreserved in two different freezing media with and without the addition of 100 µm melatonin. Finally, apoptosis of the cells was assayed by flow cytometry. Also, lactate dehydrogenase activity test was performed to assess the cytotoxicity.

Results: The results of lactate dehydrogenase showed the nearly cytotoxic effect of melatonin. The results of flow cytometry showed increase in apoptosis in the cryopreserved cells in the media containing melatonin compared to the control group.

Conclusion: The present study shows that melatonin has an apoptotic effect on cryopreserved mouse testicular cells.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837917PMC
January 2016

Comparison of colony formation of human spermatogonial stem cells (SSCs) with and without collagen.

J Pak Med Assoc 2016 Mar;66(3):285-91

Department of Urology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Objective: To investigate the effects of collagen and growth factors on in vitro proliferation of human spermatogonial stem cells obtained from patients with non-obstructive azoospermia.

Methods: The experimental cross-sectional study was conducted from February 2013 to April 2015 after obtaining approval from the ethics committee of Ahvaz Jundishapur University of Medical Sciences, Iran. Testicular sperm extractions of non-obstructive azoospermic patients were obtained from the Clinical Urology and Embryology, In Vitro Fertilization Department of Imam Khomeini Hospital. Spermatogonial stem cells and Sertoli cells, obtained from human testis biopsies by a two-step enzymatic digestion method, were purified using fluorescence- activated cell-sorting and daturastramonium-lectin, and were cultured separately. To investigate a more direct influential factor on colony formation, one control and two experimental groups were formed. Group 1 acted as the control in which spermatogonial stem cells were co-cultured with Sertoli cells alone. In group 2 they were co-cultured with Sertoli cells and growth factors such as leukaemia inhibitory factor, epidermal growth factor and glial cell-derived neurotrophic factor, and in group 3 with Sertoli cells along with growth factors in the presence of collagen-coated dishes. Number and diameter of the colonies were evaluated after 7 weeks.

Results: Specimens obtained related to 21 patients. Number and diameter of the colonies in group 3 (18±2.6 and 276.6±45.5) were significantly more than both groups 1 (3.5±1 and D1:81.6±12) and group 2(11±2.2 and 165.2±32.5) (p<0.05 each). Also, the number and diameter of colony in group 2 were significantly better than the control group (p<0.05).Expression profile of the VASA, promyelocytic leukaemia zinc-finger (PLZF), Octamer-binding transcription factor 4 (OCT4) and integrin a6 (INTGa6) were detected in all groups. Based on cytochemical findings, OCT4 was expressed in the colonies of all three groups.

Conclusions: According to positive effects of collagen and growth factors on the colonisation of spermatogonial stem cells, it seems that using the cells may lead to better colonisation of this type of stem cells.
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March 2016

Effects of Exendine-4 on The Differentiation of Insulin Producing Cells from Rat Adipose-Derived Mesenchymal Stem Cells.

Cell J 2016 17;17(4):720-9. Epub 2016 Jan 17.

Cell and Molecular Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Objective: To evaluate the effect of Exendine-4 (EX-4), a Glucagon-like peptide 1 (GLP-1) receptor agonist, on the differentiation of insulin-secreting cells (IPCs) from rat adipose-derived mesenchymal stem cells(ADMSCs).

Materials And Methods: In this experimental study, ADMSCs were isolated from rat adi- pose tissue and exposed to induction media with or without EX-4. After induction, the existence of IPCs was confirmed by morphology analysis, expression pattern analysis of islet-specific genes (Pdx-1, Glut-2 and Insulin) and insulin synthesis and secretion.

Results: IPCs induced in presence of EX-4 were morphologically similar to pancre- atic islet-like cells. Expression of Pdx-1, Glut-2 and Insulin genes in EX-4 treated cells was significantly higher than the cells exposed to differentiation media without EX-4. Compared to EX-4 untreated ADMSCs, insulin release from EX-4 treated ADMSCs showed a nearly 2.5 fold (P<0.05) increase when exposed to a high glucose (25 mM) medium. The percentage of insulin positive cells in the EX-4 treated group was ap- proximately 4-fold higher than in the EX-4 untreated ADMSCs.

Conclusion: The present study has demonstrated that EX-4 enhances the differen- tiation of ADMSCs into IPCs. Improvement of this method may help the formation of an unlimited source of cells for transplantation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746422PMC
http://dx.doi.org/10.22074/cellj.2016.3844DOI Listing
February 2016