Publications by authors named "Rasoul Baharlou"

22 Publications

  • Page 1 of 1

The impact of 17β-estradiol and progesterone therapy on peripheral blood mononuclear cells of asthmatic patients.

Mol Biol Rep 2021 Jan 14;48(1):297-306. Epub 2020 Dec 14.

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

There is a significant fluctuation in clinical symptoms of asthmatic females during their life course, suggesting that the reproductive status and the level of sex hormones may affect the development of asthma and its exacerbation. In this study, we aimed to assess the biological effects of 17β-estradiol (E2) and progesterone (P4), alone or in combination form, on the transcription factors and production of cytokines in peripheral blood mononuclear cells (PBMCs). PBMCs of the mild-to-moderate asthmatic patients and healthy controls (HCs) were treated with equivalent serum levels of E2 or P4 maintained during hormone replacement therapy (HRT). The expression levels of T-bet, GATA-3, RORγt, PU.1, and Foxp3 were assessed by quantitative PCR. We also measured the concentration of IL-4, IL-9, IL-10, IFN-γ, and TGF-β in cell culture supernatants using ELISA. IL-4 production and GATA-3 expression levels slightly increased when asthmatic PBMCs were treated with E2 (p < 0.01), P4 (p < 0.01), or E2 + P4 (p < 0.001) compared to the untreated cells. IL-9 secretion (p < 0.001) and PU.1 gene expression levels (p < 0.05) were slightly higher in asthmatic patients' PBMCs before treatment but hormone therapy did not affect the level of them. Although the untreated asthmatic PBMCs produced a lower amount of IFN-γ compared to HCs (p < 0.01), hormone treatment did not affect the levels of IFN-γ secretion in patient groups. Moreover, we did not observe any significant changes in IL-10 and TGF-β secretion in the supernatant of hormone treated cells. We found that the common applied HRT may faintly increase GATA-3 expression and IL-4 production levels in PBMCs of asthmatic patients and can slightly increase asthma severity.
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http://dx.doi.org/10.1007/s11033-020-06046-6DOI Listing
January 2021

Apoptotic effect of berberine via Bcl-2, ROR1, and mir-21 in patients with B-chronic lymphocytic leukemia.

Phytother Res 2020 Nov 10. Epub 2020 Nov 10.

Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran.

Berberine is a natural isoquinoline alkaloid that has been shown to inhibit the proliferation and induce apoptosis in a wide variety of tumor cells. However, the action mechanism of berberine in CLL cells is unknown. The previous study has shown that berberine leads to reduced viability and elevated levels of apoptosis in PBMCs of CLL patients. CLL cells are characterized by remarkable expression of Bcl-2 and ROR1 which leads to activation and survival and increases disease progression in patients. High-level expression of miR-21 in patients with CLL is associated with a higher risk of death. Here we investigated the anticancer effects of berberine upon peripheral blood mononuclear cells (PBMCs) of CLL patients. To evaluate the expression of anti-apoptotic proteins and ROR1 using flow cytometry and western blot, PBMCs were treated with 25 μM of berberine for 24 hr. The expression levels of mir-21 were evaluated by real-time PCR. Examination of treated cells demonstrated that berberine decreased Bcl-2 and ROR1 levels. Although western blot results did not show any change in Bax as a pro-apoptotic protein, an increased Bax/Bcl-2 ratio indicated that mitochondrial pathway is involved in berberine-induced apoptosis of CLL cells. Interestingly, berberine could reduce the expression of miR-21 in comparison to the untreated group. Our findings describe some of the molecular mechanisms of berberine by decreasing Bcl-2, ROR1, and mir-21 which may be considered as a novel apoptosis inducer in CLL cells.
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http://dx.doi.org/10.1002/ptr.6945DOI Listing
November 2020

Elevated serum levels of adiponectin and interlukin-28B after IFN/RIB therapy in hepatitis C virus-infected patients.

J Infect Dev Ctries 2019 05 31;13(5):434-444. Epub 2019 May 31.

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

Introduction: The interleukin 28B (IL28B) genotype is associated with changes of lipid metabolism in patients infected with hepatitis C virus (HCV). The association of steatosis with serum levels of adiponectin in chronic hepatitis C (CHC) patients has also been documented. This study aimed for the evaluation of serum levels of IL28B and adiponectin as well as the association of IL28B SNPs with different clinicopathological parameters in HCV-infected patients.

Methodology: All 142 HCV-infected patients received peg-interferon plus ribavirin. Detection of rs8099917 and rs12979860 IL-28B genotypes was done with specific primers. Serum IL28 and adiponectin levels were measured using commercial ELISA kits.

Results: Higher levels of both IL28 and adiponectin were found in patients. In Genotype 3a (G3a) -infected patients, IL28 and adiponectin serum levels were significantly higher than those infected with G1a. A correlation was found between increasing levels of AST and ALT in G3a-infected patients and the decrease in IL28 and adiponectin serum levels, respectively, in contrast to G1a-infected patients. Higher levels of both IL28 and adiponectin were associated with both CT allele of rs12979860 and TT allele of rs8099917 in patients in comparison with corresponding alleles in controls.

Conclusions: In contrast to other studies, this study showed higher serum adiponectin levels in HCV-infected patients compared to that in healthy controls. This finding is possibly due to adiponectin resistance caused by down-regulation of adiponectin receptors or tumorigenic effects of adiponectin. Our genotype-based analyses revealed, at least in part, the involvement of the viral factors in the outcome of HCV infection.
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http://dx.doi.org/10.3855/jidc.11190DOI Listing
May 2019

Cancer stem cells: A review from origin to therapeutic implications.

J Cell Physiol 2020 02 8;235(2):790-803. Epub 2019 Jul 8.

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

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are elucidated as cells that can perpetuate themselves via autorestoration. These cells are highly resistant to current therapeutic approaches and are the main reason for cancer recurrence. Radiotherapy has made a lot of contributions to cancer treatment. However, despite continuous achievements, therapy resistance and tumor recurrence are still prevalent in most patients. This resistance might be partly related to the existence of CSCs. In the present study, recent advances in the investigation of different biological properties of CSCs, such as their origin, markers, characteristics, and targeting have been reviewed. We have also focused our discussion on radioresistance and adaptive responses of CSCs and their related extrinsic and intrinsic influential factors. In summary, we suggest CSCs as the prime therapeutic target for cancer treatment.
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http://dx.doi.org/10.1002/jcp.29044DOI Listing
February 2020

Immunomodulatory Effects of Human Adipose Tissue-derived Mesenchymal Stem Cells on T Cell Subsets in Patients with Rheumatoid Arthritis.

Iran J Allergy Asthma Immunol 2019 Feb;18(1):114-119

Research Center for Non-Communicable Diseases, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.

Adipose-derived mesenchymal stem cells (Ad-MSCs) have been reported to suppress the effector T cell responses and have beneficial effects on various immune disorders, like rheumatoid arthritis (RA). This study was designed to investigate the effects of co-cultured Ad-MSCs on peripheral blood mononuclear cells (PBMCs) of RA patients and healthy individuals, through assessing transcription factors of T cell subsets. PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs with or without Phytohaemagglutinin (PHA). The quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of T-box 21 (T-bet), GATA-binding protein-3 (GATA3), retinoid-related orphan receptor γt (ROR-γt) and forkhead box P3 (Foxp3). Based on the results, Ad-MSCs greatly upregulated Th2 and Treg cell transcription factors, i.e., GATA3 and Foxp3 (p<0.05), and downregulated Th1 and Th17 transcription factors, i.e., T-bet and RORγt (p<0.05). These results demonstrate that Ad-MSCs can result in an immunosuppressive environment through inhibition of pro-inflammatory T cells and induction of T cells with a regulatory phenotype. Therefore, they might have important clinical implications for inflammatory and autoimmune diseases such as RA.
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February 2019

An antibody fragment against human delta-like ligand-4 for inhibition of cell proliferation and neovascularization.

Immunopharmacol Immunotoxicol 2018 Oct 5;40(5):368-374. Epub 2018 Sep 5.

d National Cell Bank of Iran, Pasteur Institute of Iran , Tehran , Iran.

Objectives: Angiogenesis targeting is an attractive approach for cancer treatment. Delta-like ligand 4 (DLL4) plays a pivotal role in neovascular development and its inhibitors have recently entered clinical trials for solid tumors. The aim of this study was to evaluate the possibilities of using anti-DLL4 antibody fragment as an angiogenesis maturation inhibitor.

Materials And Methods: In this study, a DLL4-specific Nanobody, named 3Nb3, was selected and assessed by western blotting and internalization assays. Functional assessments included MTT, apoptosis, and chicken chorioallantoic membrane (CAM) assays.

Results: Based on the results, 3Nb3 specifically binds to DLL4 and internalizes into MKN cell. Furthermore, 3Nb3 significantly inhibited the proliferation of cells and also neovascularization in the CAM.

Conclusions: These data demonstrated the potential of Nanobody for application in targeting DLL4. Our findings may provide a basis for the development of novel therapeutic techniques to inhibit growth and neovascularization of tumors.
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http://dx.doi.org/10.1080/08923973.2018.1505907DOI Listing
October 2018

Regulatory Effects of Estradiol on Peripheral Blood Mononuclear Cells Activation in Patients with Asthma.

Iran J Allergy Asthma Immunol 2018 Feb;17(1):9-17

Department of Student Research Committee, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.

Asthma prevalence and severity are greater in women than in men, and mounting evidence suggests this is in part related to female steroid sex hormones. Conflicting data are reported regarding pro- and anti-inflammatory properties of estradiol. This study was designed to clarify whether estradiol may contribute to enhanced T helper (Th) 17-associated cytokines production by peripheral blood mononuclear cells (PBMC) in asthmatic patients and healthy individuals. PBMCs from patients with asthma and healthy donors were cultured with 17-β estradiol (E2) and phytohemagglutinin (PHA). The quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure IL-6, IL-17, IL-23 and TGF-β. We observed a significant increased IL-17, IL-23 and TGF-β expression in PBMCs of patients compared to the healthy individuals. In addition, our findings indicated that IL-6 and IL-17 expressions in PBMCs were induced, following E2 treatment. Our results identified an impact of E2 in stimulation of Th17 phenotype, and upon hormonal oscillations and hormone replacement therapy (HRT), asthma inflammation may be mediated by Th17-associated cytokines.
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February 2018

Generation and characterization of an anti-delta like ligand-4 Nanobody to induce non-productive angiogenesis.

Anal Biochem 2018 03 12;544:34-41. Epub 2017 Dec 12.

Biotechnology Research Center, Venom & Biotherapeutics Molecules Laboratory, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

Antibody-based targeting of angiogenesis is a key approach for cancer treatment. Delta-like ligand 4 (DLL4) plays a pivotal role in tumor neovascular development and angiogenesis during tumor progression. It forecasts the prognosis of human malignancies and blocking its signaling can help to inhibit neovascularization and tumor metastasis. Nanobodies are the smallest antigen-binding domains of heavy chain antibodies in camelidae. The aim of this study was to develop a Nanobody against DLL4 and apply binding and functional approaches to target it. In this work, a Nanobody library against human recombinant DLL4 was developed. After panning, the periplasmic-extract (PE) of individual colonies were screened through ELISA. The interactions between Nanobody and DLL4 were assessed using immunohistochemistry and FACS. The functional assessment was carried out via tube formation assay. We selected a Nanobody (3Nb3) with a high binding signal to DLL4, associated with a binding affinity of 3.6 nM. It was demonstrated that 3Nb3 binds to native DLL4 on the surface of MKN cells and gastric carcinoma tissue, and also inhibits the maturation of capillary-like structures in HUVECs. The results were indicative of the potential of Nanobody for DLL4 identification and can broaden the scope for development of cancer diagnosis and treatment techniques.
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http://dx.doi.org/10.1016/j.ab.2017.12.014DOI Listing
March 2018

Genotype-related variations in proinflammatory and regulatory cytokine levels in treated and treatment-naive HCV-infected patients.

Med Microbiol Immunol 2018 Feb 17;207(1):65-74. Epub 2017 Nov 17.

Department of Microbiology and Immunology, Jahrom University of Medical Sciences, School of Medicine, Motahari Blvd, Jahrom, Iran.

Hepatitis C virus (HCV) modulates immune-related inflammatory responses to induce milder reactions leading to virus persistence. In this regard, the present study aimed to investigate the link between the HCV genotypes and the proinflammatory and regulatory cytokine levels. Ninety patients with hepatitis C infection (68 treatment-naive and 22 treated patients) and 76 healthy blood donors were studied. The serum levels of IFN-γ, IL-10, IL-17A, and IL-21 were measured by ELISA in the patients and healthy controls. IL-10, IL-17A, and IL-21 levels were significantly higher in HCV patients than in the healthy controls. The same cytokines were also higher in genotype 3a-infected patients compared with genotype 1a-infected patients. Interestingly, in treated patients, lower serum levels of IL-17A and IL-21 were detected in G3a-infected individuals, but not in those infected with G1a. G3a viral load displayed a significant correlation with IL-21 and IL-17A levels. In addition, G1a viral load correlated with IL-10 levels. In G3a-infected patients, a significant association was found between IL-17A serum levels and ALT. We found differences in IL-21 and IL-17A serum levels among HCV-infected patients which were genotype dependent. Since Th17-associated cytokines are associated with the progression of liver disease in HCV patients, IL-17A and IL-21 can be used as important biological markers for evaluating the immunopathogenesis of chronic hepatitis. Our results suggest that HCV G3a along with immune responses such as cytokines in HCV patients should be taken into account when interpreting clinical data and IFN-based therapeutic response.
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http://dx.doi.org/10.1007/s00430-017-0527-9DOI Listing
February 2018

Assessment of T helper 17-associated cytokines in third trimester of pregnancy.

Iran J Immunol 2017 Jun;14(2):172-179

Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Preeclampsia is a common pregnancy-specific disorder associated with significant maternal and fetal morbidity and mortality worldwide. It has been proposed that the imbalance between two CD4+ T cell subtypes, regulatory T cells (Treg) and T-helper 17 cells (Th17), is involved in the pathophysiology of preeclampsia.

Objectives: To determine the serum levels of IL-17, IL-21, IL-23 and TGF-β in patients with preeclampsia.

Methods: Blood samples were collected from 30 preeclampsia patients, 30 normotensive pregnant women and 30 healthy individuals with no history of malignancies or autoimmune disorders based on simple sampling. The serum levels of IL-17, IL-21, IL-23 and TGF-β were measured by the enzyme linked immunosorbent assay (ELISA).

Results: The serum levels of IL-17 and TGF-β were significantly higher in preeclampsia patients compared to normal pregnant group and healthy individuals (p>0.0001) but interestingly, the opposite was the case for IL-23 (p=0.005). However, there were no significant differences in IL-21 between preeclampsia and normal pregnant group.

Conclusions: Our results conclude that contrary to IL-21, serum levels of IL-17 and TGF-β significantly increased in preeclampsia compared to normal pregnant women, supporting an imbalance of cytokine profile in preeclamtic patients.
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http://dx.doi.org/IJIv14i2A8DOI Listing
June 2017

Human adipose tissue-derived mesenchymal stem cells in rheumatoid arthritis: Regulatory effects on peripheral blood mononuclear cells activation.

Int Immunopharmacol 2017 Jun 30;47:59-69. Epub 2017 Mar 30.

Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.

Background And Objectives: Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunomodulatory properties. The mechanisms by which MSCs inhibit the proliferation of pro-inflammatory T cells have not been fully elucidated yet. It is assumed that pro-inflammatory T-cells play an important role in the development of autoimmune diseases. We investigated the potential therapeutic effects of human adipose tissue derived (Ad)-MSCs on the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals, with a particular focus on Th17-associated cytokines.

Materials And Methods: PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs and HeLa with or without Phytohemagglutinin (PHA). Finally, IL-6, IL-17, IL-21, IL-23 and TGF-β levels were determined by ELISA and quantitative real-time RT-PCR on co-culture supernatants and PBMCs, respectively.

Results: In co-culture interaction, Ad-MSCs inhibited IL-17 secretion by PBMCs compared to unstimulated PBMCs cultured alone. In addition, IL-21 expressions in PBMCs of the patient group, and IL-17 and IL-21 in healthy group were inhibited by Ad-MSCs compared to PBMCs cultured alone. TGF-β expression in healthy individuals remarkably increased in both MSC-treated groups with and without PHA in comparison to PHA-stimulated and -unstimulated PBMCs.

Conclusions: This study demonstrates that human Ad-MSCs act as key regulators of immune tolerance by inhibiting the inflammation. Therefore, they can be attractive candidates for immunomodulatory cell-based therapy in RA.
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http://dx.doi.org/10.1016/j.intimp.2017.03.016DOI Listing
June 2017

Impact of HIV infection in patients infected with chronic HCV (genotypes 1a and 3a): virological and clinical changes.

Pathog Glob Health 2016 Oct - Dec;110(7-8):310-315. Epub 2016 Nov 10.

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

Background: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection has become a serious public health problem. The influence of HIV/HCV coinfection on plasma HCV RNA loads and clinical criteria which are usually regarded as a predictor of the progress of liver disease have not been reliably evaluated.

Objectives: This study investigated the impact of HIV infection on HCV RNA load and clinical indexes in Yazd and Tehran.

Materials And Methods: HCV/HIV-coinfected patients and HCV-monoinfected controls were examined and compared for plasma HCV RNA and related risk factors such as HCV genotypes, liver enzymes, and transmission routes.

Results: A total of 54 HCV/HIV-coinfected patients and 88 HCV-monoinfected controls were studied. The HCV RNA load mean was significantly higher in HCV/HIV-coinfected patients than in HCV-monoinfected patients (p < 0.001). HCV RNA load mean in patients infected with HCV without anti-HCV therapy was lower than HIV/HCV patients with and without highly active antiretroviral therapy that this difference was significant (p < 0.001). The HCV RNA levels were significantly higher in HIV/HCV genotype 3a coinfected patients than in genotype 3a monoinfected patients (p < 0.001). HIV RNA levels were lower in genotype 1a infected patients than in genotype 3a infected patients, but this difference was not significant statistically. The ALT mean levels were significantly higher in genotype 3a HIV/HCV-coinfected patients than in genotype 3a HCV-monoinfected patients (p < 0.001).

Conclusions: HIV/HCV coinfection leads to a significant increase in plasma HCV RNA. Further evaluations of the effects of ART and HIV infection on the course of HCV infection and the response to treatment against HCV infection in other and different genotypes are also needed. Moreover, HIV-infected patients should be screened regularly for HCV coinfection, particularly if they are in high-risk groups such as IDUs and recipients of blood transfusions.
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http://dx.doi.org/10.1080/20477724.2016.1253532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5189870PMC
June 2017

Elevated Levels of T-helper 17-associated Cytokines in Diabetes Type I Patients: Indicators for Following the Course of Disease.

Immunol Invest 2016 Oct 9;45(7):641-51. Epub 2016 Sep 9.

d Department of Student Research Committee, School of Medicine , Jahrom University of Medical Sciences , Jahrom , Iran.

Background: Type 1 diabetes (T1D) is thought to involve chronic inflammation, which is manifested by the activation and expression of different inflammatory mediators. Th1- and Th17-associated cytokines are factors that have been shown to exert profound pro-inflammatory activities and have been implicated in the pathogenesis of T1D in mice and humans.

Objectives: Therefore, the aim of this case control study was to determine the serum level of IL-17, IL-21, IL-27, transforming growth factor beta (TGF-β), and IFN-γ and their reciprocal relationship in Iranian T1D patients.

Patients And Methods: Blood samples were collected from 48 T1D patients and 49 healthy individuals with no history of malignancies or autoimmune disorders based on simple sampling. The serum levels of IL-17, IL-21, IL-27, TGF-β, and IFN-γ were measured by the enzyme linked immunosorbent assay (ELISA).

Results: The serum levels of IL-17 and IL-21 were significantly higher in T1D patients compared to the healthy individuals (p = 0.005 and 0.01, respectively), but interestingly, the opposite was the case for IL-27 (p < 0.0001). However, there were no significant differences in TGF-β and IFN-γ between both groups. In addition, IL-17/IFN-γ and IL-17/IL-27 ratios were higher in patients compared to the control group.

Conclusions: Our results indicated dominant Th17-associated IL-17, suggesting a shift from the Treg and Th1 phenotypes toward the Th17 phenotype. Therefore, it can promote inflammation in β cells in T1D. In addition, it suggests the role of Th17 and Th17/Th1 ratios as a potential contributor to β cells destruction and the Th17/Th1 response ratio may provide a novel biomarker for rapid T1D diagnosis before the destruction of β cells and progression of the disease to the clinical end stages.
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http://dx.doi.org/10.1080/08820139.2016.1197243DOI Listing
October 2016

Increased IL-17 and TGF-β serum levels in peripheral blood of patients with β-thalassemia major: implication for continual transfusions role in T helper17-mediated proinflammatory responses.

Turk J Med Sci 2016 Apr 19;46(3):749-55. Epub 2016 Apr 19.

Department of Student Research Committee, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.

Background/aim: Recent studies have shown that IL-17-producing CD4+ T helper (Th17) cells play an important role in proinflammatory processes. In this report we analyzed IL-17, IL-21, and TGF-β serum levels in the peripheral blood of Iranian beta-thalassemia major patients that clinically exhibited splenectomy and iron overload.

Materials And Methods: Blood samples were collected from 43 beta-thalassemia patients and 43 healthy individuals with no history of malignancies or autoimmune disorders. Then serum levels of IL-17, IL-21, and TGF-β were measured by enzyme linked immunosorbent assay (ELISA).

Results: The levels of IL-17 (P = 0.005) and TGF-β (P < 0.001) were significantly higher in the thalassemia patients compared to the healthy control. No significant differences in the level of serum IL-21 was observed between the patients and controls. There were no significant differences in serum levels of IL-17, IL-21, and TGF-β between patients with high or low serum levels of ferritin.

Conclusion: Multiple blood transfusions cause constant immune stimulation, as a result of repeated exposure to new alloantigens. This might have significant effects on the stimulation of cytokine producing cells in those patients and cytokine profile can be used as a related marker for assessing disease severity and consequently therapeutic intervention.
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http://dx.doi.org/10.3906/sag-1409-57DOI Listing
April 2016

Elevated IL-17 and TGF-β Serum Levels: A Positive Correlation between T-helper 17 Cell-Related Pro-Inflammatory Responses with Major Depressive Disorder.

Basic Clin Neurosci 2016 Apr;7(2):137-42

Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.

Introduction: Depression is a mental disorder that highly associated with immune system. Therefore, this study compares the serum concentrations of IL-21, IL-17, and transforming growth factor β (TGF-β) between patients with major depressive disorder and healthy controls.

Methods: Blood samples were collected from 41 patients with major depressive disorder and 40 healthy age-matched controls with no history of malignancies or autoimmune disorders. The subjects were interviewed face to face according to DSM-IV diagnostic criteria. Depression score was measured using completed Beck Depression Inventory in both groups. The serum concentrations of IL-21, IL-17, and TGF-β were assessed using ELISA.

Results: The mean score of Beck Depression score in the patient and control groups was 35.4±5.5 and 11.1±2.3. IL-17 serum concentrations in the patients and the control group were 10.03±0.6 and 7.6±0.6 pg/mL, respectively (P=0.0002). TGF-β level in the patients group was significantly higher than compare to the control group; 336.7±20.19 vs. 174.8±27.20 pg/mL, (P<0.0001). However, the level of IL-21 was not statistically different between the two groups 84.30±4.57 vs. 84.12±4.15 pg/mL (P>0.05).

Conclusion: Considering pro-inflammatory cytokines, current results support the association of inflammatory response and depressive disorder. So, it seems that pro-inflammatory factors profile can be used as indicator in following of depression progress and its treatment impacts.
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http://dx.doi.org/10.15412/J.BCN.03070207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892318PMC
April 2016

Reduced levels of T-helper 17-associated cytokines in the serum of patients with breast cancer: indicators for following the course of disease.

Cent Eur J Immunol 2016 24;41(1):78-85. Epub 2016 Mar 24.

Department of Student Research Committee, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.

Interleukin (IL)-17-producing CD4(+) T helper (Th17) cells that are known to produce IL-17 have recently been defined as a unique subset of proinflammatory helper cells. Interleukin 17 is an inflammatory cytokine with robust effects on many cells. It can play important roles in the pathogenesis of diverse groups of immune-mediated diseases. In this regard, the present case-control study aimed at determining serum levels of IL-17, IL-6, and transforming growth factor β (TGF-β) in Iranian breast cancer patients. Blood samples were collected from 55 patients with breast cancer and 34 healthy individuals with no history of malignancies or autoimmune disorders, based on simple sampling. The serum levels of IL-17, IL-6 and TGF-β were measured by enzyme-linked immunosorbent assay (ELISA). The serum level of IL-6 was significantly lower in patients with breast cancer compared with healthy individuals (p = 0.0003), and also the IL-17 was lower in the patient group than in controls (p = 0.01). Interestingly, the TGF-β serum level in patients was less than in controls (p < 0.0001). As most of the cases investigated in this study were in their early stages, it can be concluded that reduced IL-17, IL-6, and TGF-β can be used as predictors for clinical stage and prognosis of cancers such as breast carcinoma.
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http://dx.doi.org/10.5114/ceji.2016.58819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829824PMC
April 2016

HLA-DRB1 alleles of susceptibility and protection in Iranians with autoimmune hepatitis.

Hum Immunol 2016 Apr 11;77(4):330-5. Epub 2016 Jan 11.

Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. The aim of this study was to determine the frequency of HLA-DRB1 alleles in Iranian patients with AIH and investigate the association between HLA alleles and the different types of the disease. Fifty-four AIH patients and 100 age- and sex-matched healthy controls were subjected to low resolution HLA-DRB typing performed by polymerase chain reaction-sequence-specific primers (PCR-SSP) technique. The results revealed higher frequencies of HLA-DRB1(∗)03, and DRB1(∗)13 alleles in patients with AIH compared to controls. However, DRB1(∗)11 was less frequent in AIH patients. In type I AIH patients HLA-DRB1(∗)03, HLA-DRB1(∗)04, HLA-DRB1(∗)08, and HLA-DRB1(∗)13 were the most frequent alleles. While in type II, the most frequent alleles were HLA-DRB1(∗)07 and HLA-DRB1(∗)13. The seronegative patients showed more frequency of HLA-DRB1(∗)03 and HLA-DRB3. In contrary, the frequency of HLA-DRB1(∗)11, HLA-DRB1(∗)15 and HLA-DRB5 in type 1 was less than healthy individuals. These findings indicate the role of HLA-DRB haplotypes in AIH susceptibility and protection, in the Iranian population.
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http://dx.doi.org/10.1016/j.humimm.2016.01.007DOI Listing
April 2016

Distribution of IL-28B genotypes in patients with hepatitis C and healthy individuals in Jahrom city.

Gastroenterol Hepatol Bed Bench 2015 ;8(4):278-87

Department of Microbiology, Jahrom University of Medical Sciences, Jahrom, Iran.

Aim: The purpose of this study was to compare the distribution of interleukin (IL)-28B genotypes between Iranian healthy individuals and patients with chronic hepatitis C based on the genotype.

Background: Polymorphisms in the region of IL-28B gene have been identified as the strongest genetic pretreatment predictor of sustained virological response (SVR) in hepatitis C infection.

Patients And Methods: In this study, 147 patients with chronic hepatitis C and 80 healthy individuals were included. The IL-28B rs12979860 and rs8099917 polymorphisms were genotyped by PCR-RFLP method and the frequency of IL-28B polymorphisms with respect to HCV genotypes was also determined.

Results: The frequencies of rs12979860 TT, CC and CT genotypes in the chronic hepatitis C patients and healthy individuals were as follows: 10.8% vs. 11.3%, 38.7% vs. 46.2% and 50.3% vs. 42.5%. Also, the frequencies of rs8099917 TT, GG and GT genotypes in the chronic hepatitis C patients was 61.9%, 6.1% and 32% and in controls was 47.5%, 11.2% and 41.3%. The differences in the distribution of rs12979860 genotypes and alleles between HCV genotype 1 and HCV genotype 3a infected patients were statistically significant.

Conclusion: The rs12979860 C allele is the favorable allele for the spontaneous clearance of HCV. It seems that the impact of IL-28B polymorphism on the spontaneous clearance of HCV genotype 3 is more prominent than HCV genotype 1, which results in the observation of higher rs12979860 C allele frequency in chronic hepatitis C patients with HCV genotype 3 than HCV genotype 1.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600518PMC
October 2015

Increased interleukin-17 transcripts in peripheral blood mononuclear cells, a link between T-helper 17 and proinflammatory responses in bladder cancer.

Iran Red Crescent Med J 2015 Feb 3;17(2):e9244. Epub 2015 Feb 3.

Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, IR Iran.

Background: Interleukin (IL)-17-producing CD4+ T helper (Th17) cells thatare known by producing IL-17 have recently been defined as a unique subset of proinflammatory helper cells. IL-17 is an inflammatory cytokine with robust effect on many cells and it can play important roles in pathogenesis of diverse groups of immune-mediated diseases.

Objectives: The aim of this case-control study was to determine the gene expression of IL-6, IL-17, and transforming growth factor beta (TGF-β) in Iranian patients with bladder cancer.

Patients And Methods: Blood samples were collected from 37 patients with bladder cancer and 37 healthy individuals with no history of malignancies or autoimmune disorders, based of simple sampling. The expression of IL-6, IL-17, and TGF-β were measured by quantitative real-time polymerase chain reaction (qRT-PCR).

Results: The mean of IL-17 transcripts was significantly higher in patients with bladder cancer compared with healthy individuals (0.33 ± 0.06 vs. 0.42 ± 0.14, ) (P = 0.04), but their TGF-β was lower (12.53 ± 8.41 vs. 54.94 ± 17.95, ) (P = 0.04). However, the IL-6 transcripts level was similar in both groups (5.34 ± 2.40 vs. 8.07 ± 3.28, ) (P > 0.05) and there was not any significant difference between the noted cytokines expressions among patients with different stages and grades.

Conclusions: As most of the cases studied in this investigation were in stages I and II, IL-17 as a prominent proinflammatory cytokine may play an important role in recruiting and infiltrating of antitumor immune responses in early stages of bladder cancer. Furthermore, it can be used as predictor for the clinical stage and prognosis of cancers such as bladder carcinoma.
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http://dx.doi.org/10.5812/ircmj.9244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353256PMC
February 2015

Analytical assessment of interleukin - 23 and -27 cytokines in healthy people and patients with hepatitis C virus infection (genotypes 1 and 3a).

Hepat Mon 2014 Sep 27;14(9):e21000. Epub 2014 Sep 27.

Department of Social Medicine, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, IR Iran ; Young Researchers Club, Shahr-e-Qods branch, Islamic Azad University, Tehran, IR Iran.

Background: The immune system plays important roles in determining the outcomes of hepatitis C virus (HCV) infection. Interleukin-23 and -27 (IL-23 and IL-27) are two novel IL-12 cytokine family members known to enhance the T-lymphocyte response, but their precise involvement in HCV infection is not well known.

Objectives: We investigated the serum IL-27 and IL-23 levels in patients with HCV infection and in healthy individuals.

Patients And Methods: In this case-control study, we assessed IL-23 and IL-27 levels in serum of 37 healthy individuals and 64 patients with chronic HCV using Enzyme-linked immunosorbent assay (ELISA). The relationship of cytokines level with liver enzymes (ALT, AST, and ALP), HCV genotype and viral load were analyzed. The differences of these cytokine levels in the groups of treatment and no treatment was compared. HCV genotypes were classified by HCV-specific primers methods. HCV RNA loads were determined by fluorescence quantitative PCR.

Results: Serum level of IL-23 was higher in HCV infected patients compared to control group (P = 0.005). However, no significant difference was seen in IL-27 serum level between patients compared to the control group (P = 0.65). There was no significant difference in IL-23 and IL-27 level between genotype 1 HCV-infected- and 3a HCV-infected- patients. Positive moderate correlation between IL-23 and IL-27 with viral load was found in type 3a and 1 HCV-infected patient. Positive relative correlation was seen between ALT and IL-23 in 1a HCV-infected patients, which was higher than 3a HCV-infected patients; but there were no significant difference between serums liver enzymes with IL-23 and IL-27 in respect to genotype 3a and 1a HCV-infected patients.

Conclusions: These findings may reflect a vigorous pro-inflammatory reaction orchestrated by the host immune system against chronic HCV. Also, a better understanding of the involvement mechanism considering the correlation between other genotypes with inflammatory cytokines in various stages of disease can be obtained.
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http://dx.doi.org/10.5812/hepatmon.21000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221962PMC
September 2014

Reduced interleukin-17 and transforming growth factor Beta levels in peripheral blood as indicators for following the course of bladder cancer.

Immune Netw 2014 Jun 19;14(3):156-63. Epub 2014 Jun 19.

Department of Student Research Committee, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.

Interleukin (IL) 17 is produced by T-helper (Th) 17 with a vigorous effect on cells of the immune system playing important roles in pathogenesis of immune-mediated diseases, including autoimmune disorders and cancers. Therefore, the aim of current study was to determine the serum levels of IL-6, IL-17, and transforming growth factor beta (TGF-β) in Iranian bladder cancer patients, and to correlate them with disease status. Blood samples were collected from 40 bladder cancer patients and 38 healthy individuals with no history of malignancies or autoimmune disorders. The serum levels of IL-6, IL-17, and TGF-β were measured by the enzyme-linked immunosorbent assay (ELISA). The results showed that the levels of IL-17 (p<0.0001) and TGF-β (p<0.0001) were significantly lower in the patients compared to the controls. No significant differences in the level of serum IL-6 (p=0.16) was observed between the patients and controls. In addition, demographic characteristics between control and patients groups were not significantly different. As most of the cases studied in this investigation were in stage I and II, it is concluded that reduced Th17-related cytokines can be used as indicators for following the course and clinical stages of bladder carcinoma progress and immune response to cancer.
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http://dx.doi.org/10.4110/in.2014.14.3.156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079822PMC
June 2014

Molecular epidemiology of different hepatitis C genotypes in serum and peripheral blood mononuclear cells in jahrom city of iran.

Hepat Mon 2014 May 11;14(5):e16391. Epub 2014 May 11.

Department of Medical Lab Technology and Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

Background: The Hepatitis C Virus (HCV) is considered essentially hepatotropic, yet the virus compartments have also been found in important extra hepatic sites. Detection of HCV RNA in extra hepatic reservoirs such as peripheral blood mononuclear cells (PBMCs) is important for determining disease progression and treatment effectiveness.

Objectives: The present study aimed to determine different HCV genotypes in patients' plasma and PBMC specimens, in Jahrom city of Iran.

Patients And Methods: Blood samples of 137 patients with established HCV were collected at the Honari clinic. These patients were anti-HCV and plasma HCV RNA positive. After plasma RNA extraction and obtaining a pellet of approximately 3-5 × 10(6) PBMCs, Real-time PCR was performed, using specific-genotype primers. Finally, data analysis was done by the Statistical Package for Social Sciences (SPSS) software.

Results: Subtype 3 was the most common genotype in plasma (57.7%) and PBMCs (51.1%). Subtype 1a was detected in 36.5% and 30.7% of plasma samples and PBMCs, respectively whereas subtype 4 was not detected in any of the cases. There was a genotype difference between plasma and PBMCs of 12.4% of patients. In four patients no genotype was detected in their plasma but genotype 3 was detected in the PBMCs.

Conclusions: It is suggested that determination of the target genotype by plasma subtyping for choosing the proper antiviral therapy is essential but may result in therapy failure. HCV genotyping in PBMC samples, along with plasma specimens, might be more beneficial. Therefore determining the HCV genotype in PBMCs, before beginning the therapy is useful due to the possibility of occult infection detection.
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http://dx.doi.org/10.5812/hepatmon.16391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071316PMC
May 2014