Nafiseh Esmaeil - Academia.edu (original) (raw)

Papers by Nafiseh Esmaeil

Research paper thumbnail of P64: Increased Proportion of Tc17 and Th17 Cells and their Significant Reduction after Thymectomy may be Related to Disease Progression in Myastenia Gravis

The Neuroscience Journal of Shefaye Khatam, Apr 10, 2018

Myas thenia gravis (MG) is an autoimmune disease mediated by auto-antibodies agains t the neuromu... more Myas thenia gravis (MG) is an autoimmune disease mediated by auto-antibodies agains t the neuromuscular junction. The thymus has an important role in the pathogenesis of MG because mos t of the patients have thymic pathology and thymectomy (TE) can reduce the severity of the disease. In the present s tudy, the frequency of Th17 and Tc17 cells were s tudied in MG patients (pre and 6 months pos t-TE) and healthy controls. We recruited 12 MG patients from the

Research paper thumbnail of INTERCELLULAR ADHESION MOLECULE-1 & REACTIVE OXYGEN SPECIES IN FEMALES WITH UNEXPLAINED INFERTILITY

Mansoura Medical Journal, Dec 1, 2000

Research paper thumbnail of Apamin as a BBB Shuttle and Its Effects on T Cell Population During the Experimental Autoimmune Encephalomyelitis-Induced Model of Multiple Sclerosis

Neurotoxicity Research, Sep 6, 2021

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system presente... more Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system presented by autoimmune manifestations. This study aimed at investigating the effects of apamin administration on the activated T cell population in an experimental autoimmune encephalomyelitis (EAE) MS model. Thirty mice underwent EAE induction and were then randomly divided into 5 groups. Three groups received 10, 50, and 100 µg/kg apamin; the fourth group received 1 mg/kg dexamethasone; and the fifth group received the equivalent amount of PBS (phosphate-buffered saline) intraperitoneally. Peripheral CD4 + cell and memory T cell distribution was measured with a flow cytometer every week. Also, CD4 + and CD8 + cell infiltration to the brain was assessed with immunohistochemistry. It was observed that the group receiving 50 µg/kg apamin had a lower EAE score in comparison with the groups receiving 100 µg/kg apamin (p 0.014). Also, peripheral blood memory cells with CD44 + , CD62L - , and CD4 + markers were decreased in apamin-administered groups. Regarding the infiltrated CD8 + cells, a significant decrease (p 0.002) was observed in the group receiving 50 µg/kg apamin compared with the control group. These results indicate that 50-µg/kg doses of apamin had an effective treatment over 14 days; it reduced both the severity of symptoms and the infiltration of CD8 + cells into the CNS. Moreover, it increased myelin density and decreased the circulation of CD62L - , CD44L - , and CD44 + memory T cells. So, it appears that apamin plays a critical role in regulating immunity and reducing the complications of autoimmune MS.

Research paper thumbnail of Supplementation of carvacrol attenuates hippocampal tumor necrosis factor-alpha level, oxidative stress, and learning and memory dysfunction in lipopolysaccharide-exposed rats

Advanced Biomedical Research, 2022

Research paper thumbnail of P64: Increased Proportion of Tc17 and Th17 Cells and their Significant Reduction after Thymectomy may be Related to Disease Progression in Myastenia Gravis

The Neuroscience Journal of Shefaye Khatam, 2018

Myas thenia gravis (MG) is an autoimmune disease mediated by auto-antibodies agains t the neuromu... more Myas thenia gravis (MG) is an autoimmune disease mediated by auto-antibodies agains t the neuromuscular junction. The thymus has an important role in the pathogenesis of MG because mos t of the patients have thymic pathology and thymectomy (TE) can reduce the severity of the disease. In the present s tudy, the frequency of Th17 and Tc17 cells were s tudied in MG patients (pre and 6 months pos t-TE) and healthy controls. We recruited 12 MG patients from the Shariati Hospital, Tehran, Iran, and the Alzahra Hospital, Isfahan, Iran, and 12 ageand sex-matched HC from the outpatient service of our ins titution (Department of Immunology, Isfahan Medical School, Isfahan, Iran) from April 2016 to May 2017. The frequency of Tc17 cells in pre-TE patients was significantly higher than HC (p <0.05) and after thymectomy Tc17 cells significantly decreased compared to the pre-TE (p <0.05). The frequency of Th17 cells in pre-TE patients was significantly higher than HC (p <0.05) and after t...

Research paper thumbnail of The Role of Distinct Subsets of Macrophages in the Pathogenesis of MS and the Impact of Different Therapeutic Agents on These Populations

Frontiers in Immunology, Aug 20, 2021

Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (C... more Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS). Besides the vital role of T cells, other immune cells, including B cells, innate immune cells, and macrophages (MФs), also play a critical role in MS pathogenesis. Tissue-resident MФs in the brain's parenchyma, known as microglia and monocytederived MФs, enter into the CNS following alterations in CNS homeostasis that induce inflammatory responses in MS. Although the neuroprotective and anti-inflammatory actions of monocyte-derived MФs and resident MФs are required to maintain CNS tolerance, they can release inflammatory cytokines and reactivate primed T cells during neuroinflammation. In the CNS of MS patients, elevated myeloid cells and activated MФs have been found and associated with demyelination and axonal loss. Thus, according to the role of MФs in neuroinflammation, they have attracted attention as a therapeutic target. Also, due to their different origin, location, and turnover, other strategies may require to target the various myeloid cell populations. Here we review the role of distinct subsets of MФs in the pathogenesis of MS and different therapeutic agents that target these cells.

Research paper thumbnail of Contradictory Effect of Lymphocyte Therapy and Prednisolone Therapy on CD3+CD8+CD56+ Natural Killer T Population in Women with Recurrent Spontaneous Abortion

Journal of Human Reproductive Sciences

Research paper thumbnail of Evaluation of Urokinase Plasminogen Activator Receptor, Soluble Urokinase Plasminogen Activator Receptor, and β1 Integrin in Patients with Hodgkin′s Lymphoma

Advanced Biomedical Research, 2017

Background: The objective of this study is to indicate the role of urokinase plasminogen activato... more Background: The objective of this study is to indicate the role of urokinase plasminogen activator receptor (uPAR), soluble uPAR (suPAR), and β1 integrin in tumor growth and invasion of lymph nodes from Hodgkin's lymphoma (HL) patients. Materials and Methods: In this study, 25 lymph nodes from HL patients were analyzed for the expression of β1 integrin and uPAR on mononuclear cells using two-color fl ow cytometry and immunohistochemical analysis. Moreover, the levels of suPAR in the serum samples of HL patients were measured and compared with 32 healthy controls. Results: Flowcytometry and immunohistochemical results indicated no signifi cant association of uPAR expression with tumor size, different stages, or different histological subtypes of HL; however, an increased expression of β1 integrin was detected in the advanced stages of HL. Higher expression of β1 integrin was detected in nodular sclerosis compared to lymphocyte predominant. No signifi cant difference was observed between the serum levels of suPAR in patients with different stages of HL and healthy controls. Moreover, the levels of suPAR were signifi cantly higher in nodular sclerosis in comparison with other subtypes. Conclusions: This study showed that the levels of suPAR and β1 integrin varied between different histological subtypes of HL. Although uPAR may play only a minor role in the growth and metastasis of lymphoma, β1 integrin may be important in predicting prognosis and metastasis in HL.

Research paper thumbnail of Increased Proportion of Tc17 and Th17 Cells and Their Significant Reduction after Thymectomy May Be Related to Disease Progression in Myasthenia Gravis

Neuroimmunomodulation, 2017

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against the neuromuscu... more Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against the neuromuscular junction. The thymus has an important role in the pathogenesis of MG because most patients have thymic pathology, and thymectomy (TE) can reduce the severity of the disease. In this study, the frequency of Th17 and Tc17 cells was studied in 12 MG patients (pre-TE and 6 months post-TE) and in 12 healthy controls (HC). The frequency of Tc17 cells in the pre-TE patients was significantly higher than in the HC (p &amp;amp;lt; 0.05), and after TE, these cells had significantly decreased compared to before TE (p &amp;amp;lt; 0.05). The frequency of Th17 cells in pre-TE patients was significantly higher than in the HC (p &amp;amp;lt; 0.05), and after TE, these cells had significantly decreased compared to before TE (p &amp;amp;lt; 0.05). Our findings indicated a possible role of Tc17 and Th17 in MG pathogenesis.

Research paper thumbnail of Human recombinant soluble PD1 can interference in T cells and Treg cells function in response to MDA-MB-231 cancer cell line

PubMed, 2023

Objectives: PD1/PDL1 pathway targeting using antibodies shows immune related adverse events in pa... more Objectives: PD1/PDL1 pathway targeting using antibodies shows immune related adverse events in patients with tumors. The masking of PD1 ligand by soluble human PD-1 (shPD-1) probably inhibits the PD1/PDL1 interaction between T cells and tumor cells. Accordingly, the goal of this study was to produce human recombinant PD-1-secreting cells and find out how soluble human PD-1 affects T lymphocyte function. Methods: An inducible construct of the human PD-1 secreting gene under hypoxia condition was synthesized. The construct was transfected into the MDA-MB-231 cell line. In six groups exhausted T lymphocytes were co-cultured with transfected or non-transfected MDA-MB-231 cell lines. The effect of shPD-1 on IFNγ production, Treg cell's function, CD107a expression, apoptosis, and proliferation was assessed by ELISA and flow cytometry, respectively. Results: The results of this study showed that shPD-1 inhibits PD-1/PD-L1 interaction and enhances T lymphocyte responses through a significant increase in IFNγ production and CD107a expression. In addition, in the presence of shPD-1, the percentage of Treg cells decreased, while MDA-MB-231 cell apoptosis increased. Conclusions: We concluded that the human PD-1 secreting construct induced under hypoxia condition inhibits the interaction of PD-1/PD-L1 and enhances T lymphocyte responses in tumor environments and chronic infections.

Research paper thumbnail of Therapeutic potential of silymarin as a natural iron‐chelating agent in β‐thalassemia intermedia

Clinical Case Reports, 2022

Abnormal iron accumulation in vital organs is one of the major complications of β‐thalassemia int... more Abnormal iron accumulation in vital organs is one of the major complications of β‐thalassemia intermedia (β‐TI). Silymarin, a flavonolignan isolated from Silybum marianum, significantly decreases the serum ferritin levels of β‐TI patients. This finding suggests silymarin as a safe and effective natural iron‐chelating agent for the treatment of iron‐overloaded conditions.

Research paper thumbnail of Phycocyanin C a Natural Product with Impressive Therapeutic Efficacy for Inhibition of Breast Tumors’ Growth and Metastasis in Vivo

Middle East Journal of Cancer, Oct 18, 2020

Background: Several studies have reported the anticancer effect of phycocyanin C, a natural extra... more Background: Several studies have reported the anticancer effect of phycocyanin C, a natural extract isolated from the algae Arthrospira platensis. However, its therapeutic effects on the growth of breast cancer and its metastasis have not been determined yet. Method: In this case-control study, we employed phycocyanin C for the treatment of 4T1 breast tumor as an applicable experimental animal model for human mammary cancer and metastasis. BALB/c mice were injected subcutaneously (s.c) into the 4 th abdominal mammary fat pad with 1×10 6 4T1 cells. We randomly divided the mice into two groups; one group of mice were injected with PBS as the control, and the other group was intraperitoneally injected with phycocyanin C (80 mg/kg daily for 20 days). Tumor growth and metastasis were assessed in both groups. Results: Phycocyanin C significantly inhibited 4T1 breast tumors growth (P<0.05). The mean tumors volumes at the control group were 2.73 times higher than those of the treatment group. In addition, phycocyanin C treatment could significantly inhibit the formation of metastasis colonies at vital organs like spleen, liver, and lung. Moreover, the survival rate of the tumor-bearing mice increased after about 22 days by phycocyanin C treatment in comparison with the control. Conclusion: This is the first report demonstrating the anticancer effects of phycocyanin C on 4T1 breast tumor in vivo. Overall, our findings provided convincing evidence for the application of phycocyanin C as an anticancer therapeutic agent.

Research paper thumbnail of Elevated Serum Levels of Cell Death Circulating Biomarkers, M30 and M65, In Patients with β-Thalassemia Major

Hemoglobin, Apr 19, 2013

Deposition of iron in visceral organs, mainly in the liver, causes tissue damage in β-thalassemia... more Deposition of iron in visceral organs, mainly in the liver, causes tissue damage in β-thalassemia major (β-TM) patients. Keratin 18 (K18) represents one of the major caspase substrates during apoptosis of hepatocytes. To better characterize the hepatic apoptosis and/or necrosis in β-thal patients, the circulating levels of M65 (soluble intact K18) and M30 (the caspases-generated K18 fragment) were measured in 40 β-TM patients and compared with 40 healthy controls. The ratio of M30/M65 (caspase-cleaved to total K18) was also determined in thalassemic and normal subjects. Results of the ELISA assays revealed that the serum levels of hepatocyte death markers, M65 and M30, were significantly increased in β-thal patients compared to healthy controls (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). M30 serum levels were also positively correlated with the serum levels of liver transaminases including aspartate aminotransferase (AST) (r = 0.337, p = 0.047) and alanine aminotransferase (ALT) (r =0.391, p = 0.02).

Research paper thumbnail of Producing Soluble Human Programmed Cell Death Protein-1: A Natural Supporter for CD4+T Cell Cytotoxicity and Tumor Cells Apoptosis

PubMed, Dec 1, 2019

Background: Programmed cell death protein-1 (PD-1)/PD-L1 pathway is one of the immune checkpoint ... more Background: Programmed cell death protein-1 (PD-1)/PD-L1 pathway is one of the immune checkpoint pathways involved in the regulation of the immune responses and the suppression of anti-tumor defense. PD-1/PD-L1 blocking antibodies improve immune responses such as cytotoxic activity of CD8+/CD4+T cells and increase mortality of tumor cells as well; however, their use is accompanied by adverse side effects. Objectives: We aimed to produce a native blocker of human PD-1/PD-L1, for developing T cells cytotoxicity and tumor cells apoptosis. Materials and methods: We designed and cloned soluble human PD-1-GFP-pcDNA3.1/hygro construct in Escherichia coli strain TOP10 cells and then transfected this construct into the HEK cells. The concentration of the secreted shPD-1 in the supernatant was measured and the supernatant was used for blocking PD-L1 on the MDA-MB-231 cells. The cytotoxicity of CD8+/CD4+T cells and the apoptosis of MDA-MB-231 cells, under the influence of shPD-1 in the co-culture of T cells with the MDA-MB-231 cells, were evaluated using flow cytometry technique. Results: The GFP expression in the transfected cells illustrated the successful designing, transfection, and production of shPD-1. Soluble human PD-1 concentration in the supernatant of the transfected HEK cells was significantly higher than the untransfected cells. In addition, shPD-1 significantly blocked PD-L1 on the MDA- MB-231 cells, improved the cytotoxicity of CD4+T cells, and increased the apoptosis of MDA-MB-231 cells. Conclusion: Overall, increased CD4+T cell cytotoxicity and tumor cells apoptosis under the influence of shPD-1, confirmed the effectiveness of shPD-1 as a natural blocker of PD-L1and as an augmenter of the anti-tumorimmune responses.

Research paper thumbnail of Optimization of In Vitro Expansion and Activation of Human Natural Killer Cells against Breast Cancer Cell Line

PubMed, Mar 11, 2020

Background: Regarding to the increase of cancer deaths in recent years and disability of common t... more Background: Regarding to the increase of cancer deaths in recent years and disability of common therapies to eradicate cancers, as well as expansion of Natural Killer (NK) cell therapy, it seems so vital to find new useful therapies against cancers. Breast cancer is the second main cause of cancer death among women. As it is impossible for a majority of patients to receive NK cell therapy, an attempt was made to establish a low-cost and efficient method for expanding and activating NK cells against breast cancer cell line (MCF7). Methods: NK cells were isolated from Peripheral Blood Mononuclear Cells (PBMCs) applying either MACS based NK cell enrichment kit or antibodies and complement as cytotoxic method. Then, the NK cells were cultured in Stem Cell Growth Medium (SCGM) with feeder layer (irradiated PBMCs) along with PHA or OKT3. IL-2, IL-15 and IL-21 were used to expand NK cells and finally their cytotoxic activity was investigated by flow cytometry. Results: Highly pure NK cells were obtained and no significant difference between the two isolation methods was found. Using IL-2 plus IL-15, the number of NK cells increased up to100 fold after 16 days. No significant effect was observed after IL-21 treatment. Conclusion: Our data indicated that cytotoxicity method can be considered a low-cost alternative for NK cell isolation kits. It seems that culturing NK cells for 14 days in either PHA or OKT3 supplemented SCGM medium would be more effective than culturing for 16 days in the presence of IL-21.

Research paper thumbnail of Comparison of Phenotypic Characterization between Differentiated Osteoblasts from Stem Cells and Calvaria Osteoblasts In vitro

PubMed, Feb 1, 2013

Background: Characteristics of differentiated osteoblasts from adipose derived stem cells (ADSCs)... more Background: Characteristics of differentiated osteoblasts from adipose derived stem cells (ADSCs) in compared with isolated osteoblasts from normal bone such as calvaria are unknown. The aim of this study was determination and comparison of phenotypic characterization between differentiated osteoblasts from stem cells and calvaria osteoblasts in vitro. Methods: In this study, mesenchymal stem cells were isolated from adipose tissue of human by enzymatic digestion and were differentiated into osteoblasts using osteogenic medium. Characteristics of these cells at first, second, third and fourth weeks were comprised with calvaria osteoblasts that were isolated from human calvaria by explanation culture method. To screen the characteristics of both calvaria and the differentiated osteoblasts, we used western blot to identify protein levels, von Kossa staining for mineral matrix detection and alkaline phosphatase (ALP) assay kit (Sigma) for ALP activity measurement. Difference between calvaria and differentiated osteoblast cells were analyzed by one-way ANOVA and P < 0.05 was considered as statistically significant. Results: Alkaline phosphatase activity, collagen and mineral material production in differentiated osteoblasts at third week were more significantly than calvaria cells (P < 0.05). Our results indicated that there was no significant different in osteocalcin (OC) production between differentiated osteoblast at first, second and third weeks and calvaria cells but declined at fourth week (P < 0.05). Conclusions: Our survey showed that cellular traits of differentiated osteoblasts presented better than calvaria osteoblasts in vitro conditions. Therefore, we suggest that ADSCs could be used in next studies for bone tissue engineering.

Research paper thumbnail of Immunoregulatory Effects of Human Amnion Epithelial Cells on Natural Killer and T Cells in Women with Recurrent Spontaneous Abortion (RSA)

Turkish journal of immunology, 2019

Introduction: Unexplained Recurrent Spontaneous Abortion (URSA) is the most common immunological ... more Introduction: Unexplained Recurrent Spontaneous Abortion (URSA) is the most common immunological complication during pregnancy. It has been found that the cells such as human amnion epithelial cells (hAECs) have the potency to modulate immune responses in vitro and in vivo. In the present study, we assessed the immunomodulatory effect of hAECs on NK cells and T cells in women with URSA. Materials and Methods: Peripheral Blood mononuclear cells (PBMC) were obtained from 14 URSA patients and co-cultured with isolated hAECs. NK cells and T cells were identified using anti-CD56 and anti-CD3 monoclonal antibodies (mAb). The expression of the activating receptor CD69 and the degranulation marker CD107a on NK cells and T cells were detected using specific mAb and analyzed by flow cytometry. Results: We found that CD69 activating receptor expression on NK cells and T cells was significantly decreased by incubation with hAECs in a dose-dependent manner (p=0.049). Also, the degranulation marker CD107a was significantly downregulated on NK cells and T cells following incubation with hAEC (p=0.003). Conclusion: Our results suggest hAECs have immune regulatory effects on activation and cytotoxicity of NK and T cells. Potential therapeutic application of hAECs for dysregulated NK and T cells immunity should be investigated in the future.

Research paper thumbnail of Potential Therapeutic Effects of Human Amniotic Epithelial Cells on Gynecological Disorders Leading to Infertility or Abortion

Stem cell reviews and reports, Nov 4, 2022

Research paper thumbnail of Prophylactic Autologous Cancer Cells Immunization Inhibits Triple Negative Breast Tumors’ Growth and Metastasis in 4T1 Tumor-Bearing BALB/c Mice

Journal of Tumor, 2019

cancer cells. Tumor induction was performed with 4T1 cells injection at the 4th mammary fat pad o... more cancer cells. Tumor induction was performed with 4T1 cells injection at the 4th mammary fat pad of each mouse. Tumor diameter and the number of macroscopic metastatic nodules on the lungs' surface were investigated two weeks after the last immunization. We found that the immunization of mice with homogenized 4T1 cancer cells and IFA significantly inhibited 4T1 tumors' growth. Also, metastatic colonies in the lungs significantly decreased in mice which immunized with 4T1 cancer cells and IFA. Overall, the effective induction of immune response by the vaccine used in our study seems to have prevented cancer cells migration and metastasis to other organs. However, precise immunological studies are required to determine the mechanism of such a vaccine.

Research paper thumbnail of Seroprevalence of Toxocara Canis In Asthmatic Children and its Relation to the Severity of Diseases

Medicinski arhiv, 2018

Background: Toxocariasis is a common parasitic infection worldwide even in developed countries. T... more Background: Toxocariasis is a common parasitic infection worldwide even in developed countries. Through this health problem, the immune system is triggered and the antibody is produced, leading to some hypersensitive situations like asthma. In the present study, we tried to show a correlation between Toxocara Canis (T. canis) seropositivity and asthma in Isfahan city. Methods: This research is a cross-sectional study involving 40 asthmatics and 46 non-asthmatic cases aged 2-18 years. In all cases, T. canis IgG level was measured using enzyme-linked immunosorbent assay (ELISA) and compared between two groups. Results: The seroprevalence of IgG anti-T. canis antibodies were 45%in the asthmatic patients and 21.7% in the controls (P= 0.022). The more severe asthmatic patients had significantly more risk for T. canis seropositivity (P= 0.019). In the asthmatic patients, there was a significant correlation between Toxocara seropositivity and going to park or playground (P= 0.001). Conclusion: In this study, we found a significantly positive serology of T. canis in asthmatic children especially in more severe disease. To verify the etiologic role of Toxocara in asthma, more advanced studies are needed.

Research paper thumbnail of P64: Increased Proportion of Tc17 and Th17 Cells and their Significant Reduction after Thymectomy may be Related to Disease Progression in Myastenia Gravis

The Neuroscience Journal of Shefaye Khatam, Apr 10, 2018

Myas thenia gravis (MG) is an autoimmune disease mediated by auto-antibodies agains t the neuromu... more Myas thenia gravis (MG) is an autoimmune disease mediated by auto-antibodies agains t the neuromuscular junction. The thymus has an important role in the pathogenesis of MG because mos t of the patients have thymic pathology and thymectomy (TE) can reduce the severity of the disease. In the present s tudy, the frequency of Th17 and Tc17 cells were s tudied in MG patients (pre and 6 months pos t-TE) and healthy controls. We recruited 12 MG patients from the

Research paper thumbnail of INTERCELLULAR ADHESION MOLECULE-1 & REACTIVE OXYGEN SPECIES IN FEMALES WITH UNEXPLAINED INFERTILITY

Mansoura Medical Journal, Dec 1, 2000

Research paper thumbnail of Apamin as a BBB Shuttle and Its Effects on T Cell Population During the Experimental Autoimmune Encephalomyelitis-Induced Model of Multiple Sclerosis

Neurotoxicity Research, Sep 6, 2021

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system presente... more Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system presented by autoimmune manifestations. This study aimed at investigating the effects of apamin administration on the activated T cell population in an experimental autoimmune encephalomyelitis (EAE) MS model. Thirty mice underwent EAE induction and were then randomly divided into 5 groups. Three groups received 10, 50, and 100 µg/kg apamin; the fourth group received 1 mg/kg dexamethasone; and the fifth group received the equivalent amount of PBS (phosphate-buffered saline) intraperitoneally. Peripheral CD4 + cell and memory T cell distribution was measured with a flow cytometer every week. Also, CD4 + and CD8 + cell infiltration to the brain was assessed with immunohistochemistry. It was observed that the group receiving 50 µg/kg apamin had a lower EAE score in comparison with the groups receiving 100 µg/kg apamin (p 0.014). Also, peripheral blood memory cells with CD44 + , CD62L - , and CD4 + markers were decreased in apamin-administered groups. Regarding the infiltrated CD8 + cells, a significant decrease (p 0.002) was observed in the group receiving 50 µg/kg apamin compared with the control group. These results indicate that 50-µg/kg doses of apamin had an effective treatment over 14 days; it reduced both the severity of symptoms and the infiltration of CD8 + cells into the CNS. Moreover, it increased myelin density and decreased the circulation of CD62L - , CD44L - , and CD44 + memory T cells. So, it appears that apamin plays a critical role in regulating immunity and reducing the complications of autoimmune MS.

Research paper thumbnail of Supplementation of carvacrol attenuates hippocampal tumor necrosis factor-alpha level, oxidative stress, and learning and memory dysfunction in lipopolysaccharide-exposed rats

Advanced Biomedical Research, 2022

Research paper thumbnail of P64: Increased Proportion of Tc17 and Th17 Cells and their Significant Reduction after Thymectomy may be Related to Disease Progression in Myastenia Gravis

The Neuroscience Journal of Shefaye Khatam, 2018

Myas thenia gravis (MG) is an autoimmune disease mediated by auto-antibodies agains t the neuromu... more Myas thenia gravis (MG) is an autoimmune disease mediated by auto-antibodies agains t the neuromuscular junction. The thymus has an important role in the pathogenesis of MG because mos t of the patients have thymic pathology and thymectomy (TE) can reduce the severity of the disease. In the present s tudy, the frequency of Th17 and Tc17 cells were s tudied in MG patients (pre and 6 months pos t-TE) and healthy controls. We recruited 12 MG patients from the Shariati Hospital, Tehran, Iran, and the Alzahra Hospital, Isfahan, Iran, and 12 ageand sex-matched HC from the outpatient service of our ins titution (Department of Immunology, Isfahan Medical School, Isfahan, Iran) from April 2016 to May 2017. The frequency of Tc17 cells in pre-TE patients was significantly higher than HC (p <0.05) and after thymectomy Tc17 cells significantly decreased compared to the pre-TE (p <0.05). The frequency of Th17 cells in pre-TE patients was significantly higher than HC (p <0.05) and after t...

Research paper thumbnail of The Role of Distinct Subsets of Macrophages in the Pathogenesis of MS and the Impact of Different Therapeutic Agents on These Populations

Frontiers in Immunology, Aug 20, 2021

Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (C... more Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS). Besides the vital role of T cells, other immune cells, including B cells, innate immune cells, and macrophages (MФs), also play a critical role in MS pathogenesis. Tissue-resident MФs in the brain's parenchyma, known as microglia and monocytederived MФs, enter into the CNS following alterations in CNS homeostasis that induce inflammatory responses in MS. Although the neuroprotective and anti-inflammatory actions of monocyte-derived MФs and resident MФs are required to maintain CNS tolerance, they can release inflammatory cytokines and reactivate primed T cells during neuroinflammation. In the CNS of MS patients, elevated myeloid cells and activated MФs have been found and associated with demyelination and axonal loss. Thus, according to the role of MФs in neuroinflammation, they have attracted attention as a therapeutic target. Also, due to their different origin, location, and turnover, other strategies may require to target the various myeloid cell populations. Here we review the role of distinct subsets of MФs in the pathogenesis of MS and different therapeutic agents that target these cells.

Research paper thumbnail of Contradictory Effect of Lymphocyte Therapy and Prednisolone Therapy on CD3+CD8+CD56+ Natural Killer T Population in Women with Recurrent Spontaneous Abortion

Journal of Human Reproductive Sciences

Research paper thumbnail of Evaluation of Urokinase Plasminogen Activator Receptor, Soluble Urokinase Plasminogen Activator Receptor, and β1 Integrin in Patients with Hodgkin′s Lymphoma

Advanced Biomedical Research, 2017

Background: The objective of this study is to indicate the role of urokinase plasminogen activato... more Background: The objective of this study is to indicate the role of urokinase plasminogen activator receptor (uPAR), soluble uPAR (suPAR), and β1 integrin in tumor growth and invasion of lymph nodes from Hodgkin's lymphoma (HL) patients. Materials and Methods: In this study, 25 lymph nodes from HL patients were analyzed for the expression of β1 integrin and uPAR on mononuclear cells using two-color fl ow cytometry and immunohistochemical analysis. Moreover, the levels of suPAR in the serum samples of HL patients were measured and compared with 32 healthy controls. Results: Flowcytometry and immunohistochemical results indicated no signifi cant association of uPAR expression with tumor size, different stages, or different histological subtypes of HL; however, an increased expression of β1 integrin was detected in the advanced stages of HL. Higher expression of β1 integrin was detected in nodular sclerosis compared to lymphocyte predominant. No signifi cant difference was observed between the serum levels of suPAR in patients with different stages of HL and healthy controls. Moreover, the levels of suPAR were signifi cantly higher in nodular sclerosis in comparison with other subtypes. Conclusions: This study showed that the levels of suPAR and β1 integrin varied between different histological subtypes of HL. Although uPAR may play only a minor role in the growth and metastasis of lymphoma, β1 integrin may be important in predicting prognosis and metastasis in HL.

Research paper thumbnail of Increased Proportion of Tc17 and Th17 Cells and Their Significant Reduction after Thymectomy May Be Related to Disease Progression in Myasthenia Gravis

Neuroimmunomodulation, 2017

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against the neuromuscu... more Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against the neuromuscular junction. The thymus has an important role in the pathogenesis of MG because most patients have thymic pathology, and thymectomy (TE) can reduce the severity of the disease. In this study, the frequency of Th17 and Tc17 cells was studied in 12 MG patients (pre-TE and 6 months post-TE) and in 12 healthy controls (HC). The frequency of Tc17 cells in the pre-TE patients was significantly higher than in the HC (p &amp;amp;lt; 0.05), and after TE, these cells had significantly decreased compared to before TE (p &amp;amp;lt; 0.05). The frequency of Th17 cells in pre-TE patients was significantly higher than in the HC (p &amp;amp;lt; 0.05), and after TE, these cells had significantly decreased compared to before TE (p &amp;amp;lt; 0.05). Our findings indicated a possible role of Tc17 and Th17 in MG pathogenesis.

Research paper thumbnail of Human recombinant soluble PD1 can interference in T cells and Treg cells function in response to MDA-MB-231 cancer cell line

PubMed, 2023

Objectives: PD1/PDL1 pathway targeting using antibodies shows immune related adverse events in pa... more Objectives: PD1/PDL1 pathway targeting using antibodies shows immune related adverse events in patients with tumors. The masking of PD1 ligand by soluble human PD-1 (shPD-1) probably inhibits the PD1/PDL1 interaction between T cells and tumor cells. Accordingly, the goal of this study was to produce human recombinant PD-1-secreting cells and find out how soluble human PD-1 affects T lymphocyte function. Methods: An inducible construct of the human PD-1 secreting gene under hypoxia condition was synthesized. The construct was transfected into the MDA-MB-231 cell line. In six groups exhausted T lymphocytes were co-cultured with transfected or non-transfected MDA-MB-231 cell lines. The effect of shPD-1 on IFNγ production, Treg cell's function, CD107a expression, apoptosis, and proliferation was assessed by ELISA and flow cytometry, respectively. Results: The results of this study showed that shPD-1 inhibits PD-1/PD-L1 interaction and enhances T lymphocyte responses through a significant increase in IFNγ production and CD107a expression. In addition, in the presence of shPD-1, the percentage of Treg cells decreased, while MDA-MB-231 cell apoptosis increased. Conclusions: We concluded that the human PD-1 secreting construct induced under hypoxia condition inhibits the interaction of PD-1/PD-L1 and enhances T lymphocyte responses in tumor environments and chronic infections.

Research paper thumbnail of Therapeutic potential of silymarin as a natural iron‐chelating agent in β‐thalassemia intermedia

Clinical Case Reports, 2022

Abnormal iron accumulation in vital organs is one of the major complications of β‐thalassemia int... more Abnormal iron accumulation in vital organs is one of the major complications of β‐thalassemia intermedia (β‐TI). Silymarin, a flavonolignan isolated from Silybum marianum, significantly decreases the serum ferritin levels of β‐TI patients. This finding suggests silymarin as a safe and effective natural iron‐chelating agent for the treatment of iron‐overloaded conditions.

Research paper thumbnail of Phycocyanin C a Natural Product with Impressive Therapeutic Efficacy for Inhibition of Breast Tumors’ Growth and Metastasis in Vivo

Middle East Journal of Cancer, Oct 18, 2020

Background: Several studies have reported the anticancer effect of phycocyanin C, a natural extra... more Background: Several studies have reported the anticancer effect of phycocyanin C, a natural extract isolated from the algae Arthrospira platensis. However, its therapeutic effects on the growth of breast cancer and its metastasis have not been determined yet. Method: In this case-control study, we employed phycocyanin C for the treatment of 4T1 breast tumor as an applicable experimental animal model for human mammary cancer and metastasis. BALB/c mice were injected subcutaneously (s.c) into the 4 th abdominal mammary fat pad with 1×10 6 4T1 cells. We randomly divided the mice into two groups; one group of mice were injected with PBS as the control, and the other group was intraperitoneally injected with phycocyanin C (80 mg/kg daily for 20 days). Tumor growth and metastasis were assessed in both groups. Results: Phycocyanin C significantly inhibited 4T1 breast tumors growth (P<0.05). The mean tumors volumes at the control group were 2.73 times higher than those of the treatment group. In addition, phycocyanin C treatment could significantly inhibit the formation of metastasis colonies at vital organs like spleen, liver, and lung. Moreover, the survival rate of the tumor-bearing mice increased after about 22 days by phycocyanin C treatment in comparison with the control. Conclusion: This is the first report demonstrating the anticancer effects of phycocyanin C on 4T1 breast tumor in vivo. Overall, our findings provided convincing evidence for the application of phycocyanin C as an anticancer therapeutic agent.

Research paper thumbnail of Elevated Serum Levels of Cell Death Circulating Biomarkers, M30 and M65, In Patients with β-Thalassemia Major

Hemoglobin, Apr 19, 2013

Deposition of iron in visceral organs, mainly in the liver, causes tissue damage in β-thalassemia... more Deposition of iron in visceral organs, mainly in the liver, causes tissue damage in β-thalassemia major (β-TM) patients. Keratin 18 (K18) represents one of the major caspase substrates during apoptosis of hepatocytes. To better characterize the hepatic apoptosis and/or necrosis in β-thal patients, the circulating levels of M65 (soluble intact K18) and M30 (the caspases-generated K18 fragment) were measured in 40 β-TM patients and compared with 40 healthy controls. The ratio of M30/M65 (caspase-cleaved to total K18) was also determined in thalassemic and normal subjects. Results of the ELISA assays revealed that the serum levels of hepatocyte death markers, M65 and M30, were significantly increased in β-thal patients compared to healthy controls (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). M30 serum levels were also positively correlated with the serum levels of liver transaminases including aspartate aminotransferase (AST) (r = 0.337, p = 0.047) and alanine aminotransferase (ALT) (r =0.391, p = 0.02).

Research paper thumbnail of Producing Soluble Human Programmed Cell Death Protein-1: A Natural Supporter for CD4+T Cell Cytotoxicity and Tumor Cells Apoptosis

PubMed, Dec 1, 2019

Background: Programmed cell death protein-1 (PD-1)/PD-L1 pathway is one of the immune checkpoint ... more Background: Programmed cell death protein-1 (PD-1)/PD-L1 pathway is one of the immune checkpoint pathways involved in the regulation of the immune responses and the suppression of anti-tumor defense. PD-1/PD-L1 blocking antibodies improve immune responses such as cytotoxic activity of CD8+/CD4+T cells and increase mortality of tumor cells as well; however, their use is accompanied by adverse side effects. Objectives: We aimed to produce a native blocker of human PD-1/PD-L1, for developing T cells cytotoxicity and tumor cells apoptosis. Materials and methods: We designed and cloned soluble human PD-1-GFP-pcDNA3.1/hygro construct in Escherichia coli strain TOP10 cells and then transfected this construct into the HEK cells. The concentration of the secreted shPD-1 in the supernatant was measured and the supernatant was used for blocking PD-L1 on the MDA-MB-231 cells. The cytotoxicity of CD8+/CD4+T cells and the apoptosis of MDA-MB-231 cells, under the influence of shPD-1 in the co-culture of T cells with the MDA-MB-231 cells, were evaluated using flow cytometry technique. Results: The GFP expression in the transfected cells illustrated the successful designing, transfection, and production of shPD-1. Soluble human PD-1 concentration in the supernatant of the transfected HEK cells was significantly higher than the untransfected cells. In addition, shPD-1 significantly blocked PD-L1 on the MDA- MB-231 cells, improved the cytotoxicity of CD4+T cells, and increased the apoptosis of MDA-MB-231 cells. Conclusion: Overall, increased CD4+T cell cytotoxicity and tumor cells apoptosis under the influence of shPD-1, confirmed the effectiveness of shPD-1 as a natural blocker of PD-L1and as an augmenter of the anti-tumorimmune responses.

Research paper thumbnail of Optimization of In Vitro Expansion and Activation of Human Natural Killer Cells against Breast Cancer Cell Line

PubMed, Mar 11, 2020

Background: Regarding to the increase of cancer deaths in recent years and disability of common t... more Background: Regarding to the increase of cancer deaths in recent years and disability of common therapies to eradicate cancers, as well as expansion of Natural Killer (NK) cell therapy, it seems so vital to find new useful therapies against cancers. Breast cancer is the second main cause of cancer death among women. As it is impossible for a majority of patients to receive NK cell therapy, an attempt was made to establish a low-cost and efficient method for expanding and activating NK cells against breast cancer cell line (MCF7). Methods: NK cells were isolated from Peripheral Blood Mononuclear Cells (PBMCs) applying either MACS based NK cell enrichment kit or antibodies and complement as cytotoxic method. Then, the NK cells were cultured in Stem Cell Growth Medium (SCGM) with feeder layer (irradiated PBMCs) along with PHA or OKT3. IL-2, IL-15 and IL-21 were used to expand NK cells and finally their cytotoxic activity was investigated by flow cytometry. Results: Highly pure NK cells were obtained and no significant difference between the two isolation methods was found. Using IL-2 plus IL-15, the number of NK cells increased up to100 fold after 16 days. No significant effect was observed after IL-21 treatment. Conclusion: Our data indicated that cytotoxicity method can be considered a low-cost alternative for NK cell isolation kits. It seems that culturing NK cells for 14 days in either PHA or OKT3 supplemented SCGM medium would be more effective than culturing for 16 days in the presence of IL-21.

Research paper thumbnail of Comparison of Phenotypic Characterization between Differentiated Osteoblasts from Stem Cells and Calvaria Osteoblasts In vitro

PubMed, Feb 1, 2013

Background: Characteristics of differentiated osteoblasts from adipose derived stem cells (ADSCs)... more Background: Characteristics of differentiated osteoblasts from adipose derived stem cells (ADSCs) in compared with isolated osteoblasts from normal bone such as calvaria are unknown. The aim of this study was determination and comparison of phenotypic characterization between differentiated osteoblasts from stem cells and calvaria osteoblasts in vitro. Methods: In this study, mesenchymal stem cells were isolated from adipose tissue of human by enzymatic digestion and were differentiated into osteoblasts using osteogenic medium. Characteristics of these cells at first, second, third and fourth weeks were comprised with calvaria osteoblasts that were isolated from human calvaria by explanation culture method. To screen the characteristics of both calvaria and the differentiated osteoblasts, we used western blot to identify protein levels, von Kossa staining for mineral matrix detection and alkaline phosphatase (ALP) assay kit (Sigma) for ALP activity measurement. Difference between calvaria and differentiated osteoblast cells were analyzed by one-way ANOVA and P < 0.05 was considered as statistically significant. Results: Alkaline phosphatase activity, collagen and mineral material production in differentiated osteoblasts at third week were more significantly than calvaria cells (P < 0.05). Our results indicated that there was no significant different in osteocalcin (OC) production between differentiated osteoblast at first, second and third weeks and calvaria cells but declined at fourth week (P < 0.05). Conclusions: Our survey showed that cellular traits of differentiated osteoblasts presented better than calvaria osteoblasts in vitro conditions. Therefore, we suggest that ADSCs could be used in next studies for bone tissue engineering.

Research paper thumbnail of Immunoregulatory Effects of Human Amnion Epithelial Cells on Natural Killer and T Cells in Women with Recurrent Spontaneous Abortion (RSA)

Turkish journal of immunology, 2019

Introduction: Unexplained Recurrent Spontaneous Abortion (URSA) is the most common immunological ... more Introduction: Unexplained Recurrent Spontaneous Abortion (URSA) is the most common immunological complication during pregnancy. It has been found that the cells such as human amnion epithelial cells (hAECs) have the potency to modulate immune responses in vitro and in vivo. In the present study, we assessed the immunomodulatory effect of hAECs on NK cells and T cells in women with URSA. Materials and Methods: Peripheral Blood mononuclear cells (PBMC) were obtained from 14 URSA patients and co-cultured with isolated hAECs. NK cells and T cells were identified using anti-CD56 and anti-CD3 monoclonal antibodies (mAb). The expression of the activating receptor CD69 and the degranulation marker CD107a on NK cells and T cells were detected using specific mAb and analyzed by flow cytometry. Results: We found that CD69 activating receptor expression on NK cells and T cells was significantly decreased by incubation with hAECs in a dose-dependent manner (p=0.049). Also, the degranulation marker CD107a was significantly downregulated on NK cells and T cells following incubation with hAEC (p=0.003). Conclusion: Our results suggest hAECs have immune regulatory effects on activation and cytotoxicity of NK and T cells. Potential therapeutic application of hAECs for dysregulated NK and T cells immunity should be investigated in the future.

Research paper thumbnail of Potential Therapeutic Effects of Human Amniotic Epithelial Cells on Gynecological Disorders Leading to Infertility or Abortion

Stem cell reviews and reports, Nov 4, 2022

Research paper thumbnail of Prophylactic Autologous Cancer Cells Immunization Inhibits Triple Negative Breast Tumors’ Growth and Metastasis in 4T1 Tumor-Bearing BALB/c Mice

Journal of Tumor, 2019

cancer cells. Tumor induction was performed with 4T1 cells injection at the 4th mammary fat pad o... more cancer cells. Tumor induction was performed with 4T1 cells injection at the 4th mammary fat pad of each mouse. Tumor diameter and the number of macroscopic metastatic nodules on the lungs' surface were investigated two weeks after the last immunization. We found that the immunization of mice with homogenized 4T1 cancer cells and IFA significantly inhibited 4T1 tumors' growth. Also, metastatic colonies in the lungs significantly decreased in mice which immunized with 4T1 cancer cells and IFA. Overall, the effective induction of immune response by the vaccine used in our study seems to have prevented cancer cells migration and metastasis to other organs. However, precise immunological studies are required to determine the mechanism of such a vaccine.

Research paper thumbnail of Seroprevalence of Toxocara Canis In Asthmatic Children and its Relation to the Severity of Diseases

Medicinski arhiv, 2018

Background: Toxocariasis is a common parasitic infection worldwide even in developed countries. T... more Background: Toxocariasis is a common parasitic infection worldwide even in developed countries. Through this health problem, the immune system is triggered and the antibody is produced, leading to some hypersensitive situations like asthma. In the present study, we tried to show a correlation between Toxocara Canis (T. canis) seropositivity and asthma in Isfahan city. Methods: This research is a cross-sectional study involving 40 asthmatics and 46 non-asthmatic cases aged 2-18 years. In all cases, T. canis IgG level was measured using enzyme-linked immunosorbent assay (ELISA) and compared between two groups. Results: The seroprevalence of IgG anti-T. canis antibodies were 45%in the asthmatic patients and 21.7% in the controls (P= 0.022). The more severe asthmatic patients had significantly more risk for T. canis seropositivity (P= 0.019). In the asthmatic patients, there was a significant correlation between Toxocara seropositivity and going to park or playground (P= 0.001). Conclusion: In this study, we found a significantly positive serology of T. canis in asthmatic children especially in more severe disease. To verify the etiologic role of Toxocara in asthma, more advanced studies are needed.