Publications by authors named "Kurosh Kalantar"

31 Publications

Proportion of T follicular helper cells in peripheral blood of rheumatoid arthritis patients: a systematic review and meta-analysis.

Expert Rev Clin Immunol 2021 Apr 15:1-14. Epub 2021 Apr 15.

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

Alterations in the levels and activity of Tfh may lead to impaired immune tolerance and autoimmune diseases. The aim of this study was to investigate the proportion and types of Tfh cells in the peripheral blood (PB) of RA patients.Comprehensive databases were searched for studies evaluating the proportion of Tfh cells in the PB of patients with RA compared to healthy control (HCs).The proportion of Tfh cells in RA patients was significantly higher than in HCs (SMD 0.699, [0.513, 0.884], p < 0.0001). Furthermore, Tfh cells proportion in untreated-RA and early-RA patients was markedly greater than HCs, when comparisons done without considering the definition markers, and also when Tfh cells were defined by the specified definition markers. While the proportion of Tfh cells by all definitions was higher in active-RA compared to HCs, analysis of two definitions, CD4CXCR5 and CD4CXCR5ICOS, didn't show significant differences. Furthermore, higher proportion of Tfh cells defined by all definitions and a specified definition (CD4CXCR5PD-1) was observed when SRA compared to SRA patients.The results demonstrate that circulating Tfh are highly elevated in RA patients highlights its potential use as a biomarker and a target for RA therapy.
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http://dx.doi.org/10.1080/1744666X.2021.1915770DOI Listing
April 2021

Interleukin-27 gene variant rs153109 is associated with enhanced cytokine serum levels and susceptibility to Behçet's disease in the Iranian population.

Eur Cytokine Netw 2020 Dec;31(4):140-146

Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran, Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.

Behcet's disease (BD) is a systemic vasculitis, characterized by recurrent oral aphthous, genital ulcers, ocular lesions, and other organ involvement. Interleukin (IL)-27 with its pro- and anti-inflammatory effects might be an important effective cytokine in this disease. The aim of this study was to investigate the association of IL-27 serum concentration and a single-nucleotide polymorphism (SNP) rs153109 (-964 A > G) with the risk and clinical features of the patients with BD. IL-27 Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the IL-27 serum levels were measured using enzyme-linked immunosorbent assay (ELISA). It is shown that AG, GG, and AG + GG genotypes, as well as G allele of rs153109, can significantly increase the risk of BD in total and in male individuals. Significantly higher frequencies of AG and GG genotypes and G allele were observed in total and male patients with an active form of BD. AG and GG genotypes were associated with joint (p = 0.046) and vascular (p = 0.02) involvement. The frequency of the G allele was higher in all patients, as well as in female patients with vascular involvement (p = 0.02). Serum cytokine analysis indicated an increased level of IL-27 in BD patients compared to healthy subjects (p = 0.038). Additionally, a higher level of IL-27 was detected in patients carrying the rs153109 GG genotype (p = 0.04) and those with renal (p = 0.009) and skin (p = 0.05) involvement. In conclusion, this study underscores the involvement of IL-27 rs153109 variants and increased serum level in BD susceptibility and pathogenesis.
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http://dx.doi.org/10.1684/ecn.2020.0458DOI Listing
December 2020

Variations in IL-22, IL-27 and IL-35 serum levels in untreated and treated hepatitis C patients.

Eur Cytokine Netw 2020 Dec;31(4):134-139

Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Hepatitis C virus (HCV) is the leading cause of chronic liver diseases including hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. We aimed to assess serum levels of interleukin (IL)-22, IL-27 and IL-35 in patients with hepatitis C and healthy controls to investigate their possible relationship with viral genotypes and liver enzyme levels.

Method: A total of 30 newly diagnosed hepatitis C patients with no history of antiviral therapy and 30 healthy individuals participated in this study. Serum levels of IL-22, IL-27 and IL-35 were determined by ELISA in peripheral blood samples from patients prior to and following treament with pan-genotypic direct-acting anti-viral therapy. Serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were measured to determine any possible association between hepatic enzymes and cytokine serum levels concentrations.

Result: The results show elevated serum levels of of IL-35 in HCV-infected patients compared to treated cases and healthy controls, whereas there was no significant difference in IL-22 and IL-27 serum levels among the three groups. Additionally, the cytokine levels were not significantly correlated with certain genotypes and levels of liver enzymes.

Conclusion: Our findings indicate a potential role for IL-35 in chronic HCV infection and therapeutic management of patients with hepatitis C infection.
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http://dx.doi.org/10.1684/ecn.2020.0455DOI Listing
December 2020

The role of FOXP3 rs3761548 and rs2294021 polymorphisms in pediatrics acute lymphoblastic leukemia: association with risk and response to therapy.

Mol Biol Rep 2021 Feb 30;48(2):1139-1150. Epub 2021 Jan 30.

Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, 71345-1798, Iran.

FOXP3 X-linked gene has crucial roles in the development and function of regulatory T cells. We investigated the association of FOXP3 rs3761548, rs3761549 and rs2294021 single nucleotide polymorphisms (SNPs) with acute lymphoblastic leukemia (ALL) susceptibility and response to therapy. Genotyping was performed in 247 patients and 210 healthy subjects. We observed a higher frequency of rs3761548 A carriers and rs2294021 C carriers (p < 0.04) in male patients, and lower frequencies of rs3761548 AC genotype (p = 0.04) and rs2294021 CT genotype (p = 0.01) in female patients compared to controls. ACC (p = 0.04) and ATC haplotypes (p = 0.002) were associated with susceptibility to ALL. There was a significant correlation between the genotypes of rs3761548 and rs2294021 SNPs with event-free survival (EFS) and overall survival (OS). The rs3761548 A genotype in male patients was associated with increased risk of relapse (p < 0.0001), shorter EFS, increased death rate (p = 0.002) and shorter OS compared to C genotype (p = 0.001). Similar significant results were observed for the relation of rs2294021 C genotype with response to therapy in male patients. In females, patients with rs3761548 AC genotype had longer EFS (p = 0.02) and those with rs2294021 CT had longer EFS and OS (p < 0.005). According to haplotype analysis, patients carrying ACC or ATC haplotypes had the highest number of WBCs and shorter EFS or OS, and patients with CCT haplotype had the lowest number of WBCs and longer EFS or OS. These results provided evidence for the impact of these polymorphisms on susceptibility and response to therapy in children with ALL.
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http://dx.doi.org/10.1007/s11033-021-06154-xDOI Listing
February 2021

Identification of immunoreactive proteins in secretions of Leishmania infantum promastigotes: an immunoproteomic approach.

East Mediterr Health J 2020 Dec 9;26(12):1548-1555. Epub 2020 Dec 9.

Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran.

Background: In the Mediterranean region, Leishmania infantum is the main cause of visceral leishmaniasis. Dogs with canine visceral leishmaniasis are an important reservoir of visceral leishmaniasis. Control of canine visceral leishmaniasis could disrupt transmission of visceral leishmaniasis to humans. The secreted antigens of Leishmania promastigotes are potential stimuli of the host immune system. Proteomic techniques facilitate the identification of new protein markers.

Aims: This study aimed to identify immunoreactive proteins in the secretions of L. infantum promastigotes which could be possible targets for the diagnosis and treatment of canine visceral leishmaniasis and the development of vaccines against the disease.

Methods: Secretions of L. infantum promastigotes were obtained from the cultivation of 6 × 10 promastigotes in serum- free RPMI-1640 medium during a period of 72 h. After deionization and lyophilization, two-dimensional gel electrophoresis was used for protein separation followed by Western blotting. Thirteen common and repeatable immunoreactive spots were analysed by mass spectrometry.

Results: Nine proteins were identified by spectrometry. Most of these proteins were involved in metabolism pathways, survival and pathogenicity of Leishmania parasites. Phospholipase C, immune inhibitor A, chitin-binding protein and a single peptide match to chain A crystal structure of selenomethionine were observed in the secretions of L. infantum promastigotes.

Conclusions: The proteins identified in metabolism pathways, survival and pathogenicity of Leishmania parasites are possible targets that could be used for the diagnosis and treatment of canine visceral leishmaniasis and the development of vaccines against the disease in the future.
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http://dx.doi.org/10.26719/emhj.20.114DOI Listing
December 2020

Therapeutic Effect of Carvacrol-loaded Albumin Nanoparticles on Arthritic Rats.

Iran J Pharm Res 2020 ;19(1):312-320

Department of Chemistry, Payame Noor University, Shiraz, Iran.

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. Carvacrol, an important natural terpenoid product in aromatic plants such as , has shown anti-inflammatory effects in animal models of arthritis. However, its poor water solubility and high volatility have limited its application. In the present study in order to overcome this problem, we encapsulated carvacrol in the bovine serum albumin (BSA) nanoparticles and examined its therapeutic and immunomodulatory effects in adjuvant-induced arthritis (AIA). Carvacrol-loaded BSA nanoparticles were prepared by desolvation method. Nanoparticles had encapsulation efficiency (EE) of 67.7 ± 6.9% and loading capacity (LC) of 26.6 ± 2%. The size of particles was 148 ± 25 nm and they had monomodal distribution. After arthritis induction, the rats were treated intraperitoneally with nanoparticle for every 3 days until day 28. The treatment of the rats with 375 mg/mL carvacrol-loaded BSA nanoparticle significantly decreased clinical severity score (27.5 ± 9.8%, = 0.008), erythrocyte sedimentation rate (33.4 ± 10%, = 0.02), nitric oxide production (82.3 ± 2.6%, = 0.004) and interleukin (IL)-17 gene expression (55.1 ± 8.2%, = 0.003) compared to the untreated arthritic group. A higher reduction in inflammation severity in arthritic rats treated with carvacrol-loaded BSA in comparison to those treated with carvacrol alone was observed. In conclusion, encapsulation of carvacrol in nanoparticles reduced arthritis signs and release of NO and IL-17 inflammatory cytokine and therefore is suggested to be considered as a good approach for improving the therapeutic applications of carvacrol in RA.
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http://dx.doi.org/10.22037/ijpr.2019.15494.13131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462511PMC
January 2020

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System.

Front Immunol 2020 22;11:1582. Epub 2020 Jul 22.

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

Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro- and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.
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http://dx.doi.org/10.3389/fimmu.2020.01582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387426PMC
August 2020

IL-18 in Blood Serum of Hepatitis C Patients Might be of Predictive Value for Individual Outcomes.

Infect Disord Drug Targets 2020 Jul 7. Epub 2020 Jul 7.

Department of Immunology, Shiraz University of Medical Sciences, Shiraz. Iran.

Objective: Pro- inflammatory cytokines including Interleukin (IL)-18 have been shown to be involved in the clearance of Hepatitis C virus (HCV) infection. However, changes in the balance of pro- and anti-inflammatory cytokines production during the immune response, can elicit a variety of liver damage. Therefore, it is of interest to study IL-18 serum levels in hepatitis patients and its correlation with HCV infection.

Methods: Twenty-nine newly diagnosed HCV+ patients with no history of antiviral therapy, and 17 healthy controls were enrolled in our study. Biochemical markers of liver disease were evaluated by biochemistry assay kits. Serum concentrations of IL-18 were determined with the ELISA method before and after treatment with pangenotypic direct-acting antivirals (DAAs) treatment.

Results: Our results showed statistically significant difference in serum levels of IL-18 in HCV+ patients (692.261 ± 48.76) compared to healthy controls (520.00 ± 44.73) (P=0.021). However, there was no significant difference in IL-18 serum levels between treated group compared to untreated patients (P=0.74). No significant correlations were detected between the level of IL-18 and liver enzyme levels.

Conclusion: According to our study, IL-18 might be a disease marker associated with HCV infection; however, this conclusion requires further investigation.
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http://dx.doi.org/10.2174/1871526520666200707113401DOI Listing
July 2020

Decreased levels of interleukin 27 in the serum of vitiligo patients.

An Bras Dermatol 2020 Sep - Oct;95(5):570-574. Epub 2020 Jun 16.

Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Background: Vitiligo is a common skin disorder in which melanocytes are destroyed by auto-reactive immune responses. The loss of melanocytes results in the appearance of depigmented areas in different parts of the body. Cytokines have remarkable roles in the pathogenesis of vitiligo, such as IL-1, IL-6, and TNF-α; interleukin 27 (IL-27) is a new member of the IL-6/IL-12 family, mainly released by activated antigen-presenting cells. IL-27 has been suggested to function as a pro-inflammatory as well as an anti-inflammatory cytokine. Altered concentrations of IL-27 have been shown in various auto-immune diseases such as multiple sclerosis, rheumatoid arthritis, and psoriasis. No studies have been conducted to determine the expression of this cytokine in vitiligo patients.

Objective: The objective of this study was to determine the serum concentration of IL-27 in vitiligo patients and compare it with normal individuals.

Methods: The serum concentration of IL-27 in 79 vitiligo patients was evaluated in comparison to 45 healthy controls using ELISA assay.

Results: Results showed decreased concentration of IL-27 in vitiligo patients as compared with healthy subjects (p=0.026). Furthermore, no correlation between IL-27 concentrations and disease parameters such as vitiligo severity and the extension of the depigmented area was observed.

Study Limitation: A larger sample size would be more recommended for this study.

Conclusion: The reduction in the serum levels of IL-27 in vitiligo patients compared to normal subjects suggested the possible anti-inflammatory role of this cytokine in vitiligo. Thus, IL-27 may be considered as a new target for the manipulation of the immune system in vitiligo patients.
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http://dx.doi.org/10.1016/j.abd.2020.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563000PMC
November 2020

Pro-inflammatory Effects of Influenza Type A Virus PB1-F2 Protein-derived Peptide in Lipopolysaccharide-treated Macrophages.

Iran J Allergy Asthma Immunol 2020 May 17;19(S1):74-82. Epub 2020 May 17.

Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St. Albans, VIC, Australia AND Department of Medicine-Western Health, The University of Melbourne, St. Albans, VIC, Australia.

Influenza A virus (IAV) has the potential to cause pandemics with considerable health and socio-economic burdens. A viral protein, polymerase basic 1- frame2 (PB1-F2), as a virulence factor, has pro-apoptotic activity and contributes to viral pathogenesis by delaying viral clearance and inducing inflammation. Macrophages are susceptible to IAV infection and produce high levels of inflammatory cytokines and chemokines. In the present study, the pro-inflammatory effects of PB1-F2 derived peptide was evaluated by measuring the expression of key inflammatory mediators in murine macrophage cell line J774.1. PB1-F2 treated macrophages were examined for nitric oxide (NO) production, inflammatory cytokines, and enzymes expression and pro-inflammatory cytokines secretion using Griess reagent, real-time polymerase chain reaction (PCR) and ELISA, respectively. Our results have shown that PB1-F2 peptide at non-cytotoxic concentrations (0.1-0.8 µmol/mL) had no effect on NO production. When applied to Lipopolysaccharide (LPS)-treated macrophages, PB1-F2 peptide at 0.8 μmol/mLincreasedinducible NO synthase (iNOS), cyclooxygenase (COX)-2, and interleukin (IL)-6 genes expression to 2.02, 3.81, and 3.65 folds, respectively. PB1-F2 at concentrations of 0.4 and 0.8 µm/mL increased tumor necrosis factor (TNF)-α transcription by 4.15 and 5.55 fold. At posttranslational level, TNF-α increased from 166.5±13.88 in LPS-treated cells to 773.6±95.27 and 1485±76.31 at concentrations of 0.4 and 0.8 μmol/mL in PB1-F2 peptide, respectively. However, PB1-F2 Peptide did not have any significant effect on IL-6 production. These findings suggest that PB1-F2 peptide may partly exert its enhancing role in viral pathogenicity through the induction of inflammatory mediators in macrophages. Hence, targeting PB1-F2 peptide would be helpful in the reduction of viral infection complications.
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http://dx.doi.org/10.18502/ijaai.v19i(s1.r1).2863DOI Listing
May 2020

Decreased serum levels of IL-27and IL-35 in patients with Graves disease.

Arch Endocrinol Metab 2020 Apr 6. Epub 2020 Apr 6.

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

Objectives: Graves' disease (GD) is an autoimmune disease causing the overproduction of the thyroid hormone from thyroid gland. This disease is mainly the result of the production of antibodies against TSH receptors. Cytokines play an important role in orchestrating the pathophysiology in autoimmune thyroid disease. The regulatory role of IL-12 on TH1 cells has been proven. IL-27 and IL-35, members of IL-12 cytokine family, are two cytokines that have been newly discovered. IL-35 has been identified as a novel immunosuppressive and anti-inflammatory cytokine while IL-27 has both inflammatory and anti-inflammatory functions. The objective of the current study was to examine the changes in the serum level of the foregoing cytokines in GD patients in comparison to healthy controls.

Materials And Methods: In this study, serum levels of IL-27 and IL-35 were determined by an ELISA method; anti TPO and anti Tg were measured by an RIA method in 40 new cases of Graves's disease. The findings were compared with 40 healthy controls.

Results: The results showed a significant difference between IL-27 and IL-35 regarding their serum levels with P values of 0.0001 and 0.024, respectively; anti TPO and anti Tg levels of the cases were also significantly different from controls (p < 0.001).

Conclusion: The reduction in the serum levels of IL-27 and IL-35 in GD patients compared to normal subjects suggests the possible anti-inflammatory role of these cytokines in GD.
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http://dx.doi.org/10.20945/2359-3997000000227DOI Listing
April 2020

Leishmanial selenoproteins and the host immune system: towards new therapeutic strategies?

Trans R Soc Trop Med Hyg 2020 07;114(7):541-544

Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, 7134845794, Iran.

Optimum levels of selenoproteins are essential for starting and managing the host immune responses against pathogens. According to the expression of selenoproteins in Leishmania parasites, and since high levels of selenoproteins lead to adverse effects on immune cells and their functions, Leishmania parasites might then express selenoproteins such as selenomethionine in their structure and/or secretions able to challenge the host immune system. Finally, this adaptation may lead to evasion of the parasite from the host immune system. The expression of selenoproteins in Leishmania parasites might then induce the development of infection. We therefore suggest these molecules as new therapeutic candidates for the treatment of leishmaniasis.
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http://dx.doi.org/10.1093/trstmh/traa013DOI Listing
July 2020

Chitin binding protein as a possible RNA binding protein in Leishmania parasites.

Pathog Dis 2020 02;78(1)

Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Leishmaniasis includes a broad spectrum of pathological outcomes in humans caused by protozoan parasites from the genus Leishmania. In recent years, proteomic techniques have introduced novel proteins with critical functions in Leishmania parasites. Based on our report of a Chitin binding protein (CBP) in our previous immunoproteomic study, this article suggests that CBP might be an RNA binding protein (RBP) in Leishmania parasites. RBPs, as key regulatory factors, have a role in post-transcriptional gene regulation. The presence of RBPs in Leishmania parasites has not been considered so far; however, this study aims to open a new venue regarding RBPs in Leishmania parasites. Confirming CBP as an RBP in Leishmania parasites, exploring other RBPs and their functions might lead to interesting issues in leishmaniasis. In fact, due to the regulatory role of RBPs in different diseases including cancers and their further classification as therapeutic targets, the emerging evaluation of CBP and RBPs from Leishmania parasites may allow the discovery of novel and effective drugs against leishmaniasis.
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http://dx.doi.org/10.1093/femspd/ftaa007DOI Listing
February 2020

Fas, FasL and Foxp3 gene expression in post-liver transplant autoimmune hepatitis patients with and without acute rejection.

Clin Exp Hepatol 2019 May 13;5(2):103-108. Epub 2019 May 13.

Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.

Aim Of The Study: In this study we investigated Fas, FasL and Foxp3 expression in relation to liver graft rejection and its severity in autoimmune hepatitis (AIH) patients.

Material And Methods: Twenty-three AIH patients including five post-transplant patients with acute rejection (AR) and 18 patients without AR (non-AR) were studied for Fas, FasL and Foxp3 gene expression in peripheral blood mononuclear cells on days 1, 3 and 7 after transplantation by real-time PCR. The relationships between gene expression and clinical features were determined.

Results: Real-time PCR showed various Fas gene expression levels with no significant difference between the days in AR patients ( = 0.52). In non-AR patients, Fas level increased from 0.98 ±0.24 fold on the first day to 1.89 ±0.42 fold on day 3 after transplantation ( < 0.01). In this group of patients, we also found a significant increase in FasL expression on day 7 (29.91 ±6.89 fold) compared to day 1 (13.50 ±7.44 fold, < 0.05). Foxp3 gene expression in both groups showed decreased levels during the first week after transplantation. The decreased Foxp3 expression in AR patients was correlated with rejection activity index ( = 0.86, < 0.0001).

Conclusions: Increased Fas and FasL gene expression levels in non-AR patients and decreased Foxp3 gene expression in both groups suggested the important role of these molecules in the alloreactive response after liver transplantation in AIH patients. Foxp3 expression might be useful for monitoring rejection severity.
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http://dx.doi.org/10.5114/ceh.2019.85076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728859PMC
May 2019

Tumor Cell Death via Apoptosis and Improvement of Activated Lymphocyte Cytokine Secretion by Extracts from Euphorbia Hebecarpa and Euphorbia Petiolata.

Asian Pac J Cancer Prev 2019 07 1;20(7):1979-1988. Epub 2019 Jul 1.

Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Immunomodulatory materials from natural herbs and the characterization of their immune enhancement effects may have tremendous potential as cancer treatment. The aim of the present study was to investigate the apoptosis-inducing activities of Euphorbia hebecarpa Boiss and Euphorbia petiolata Banks & Sol. plant extracts and their effects on cytokine secretion by lymphocytes. Materials and Methods: We assessed the apoptosis-inducing effect of the plants’ hexane extracts on previously determined sensitive cell lines (HeLa for E. hebecarpa and K562 for E. petiolata) by flow cytometry and measurement of caspase 3 activation. The apoptosis-related gene expressions were examined by real-time PCR. The effects of the extracts on lymphocyte proliferation and cytokine secretion were examined. Results: Flow cytometry analysis showed that the inhibitory effect of the extracts on tumor cell growth was due to cell apoptosis. The plant extracts at the 100 μg/ml dose induced apoptosis in HeLa (98.5 ± 0.1%) and K562 (57.7 ± 1.9%) cells. The extracts increased caspase 3 activation (≈2-fold>control). Real-time PCR showed Fas and Bax gene upregulation and Bcl-2 downregulation, which resulted in an increased Bax/Bcl-2 expression ratio. The extracts increased lymphocyte proliferation and increased levels of IFN-γ production in the presence and absence of mitogen (p < 0.05). They significantly increased IL-4 and decreased IL-10 secretion by mitogen-stimulated lymphocytes. E. hebecarpa also increased IL-17 release. Conclusion: These results have shown that both extracts possess antitumor activity by inducing apoptosis, possibly through both intrinsic and extrinsic pathways. In addition, they induced secretion of different T helper subset related cytokines that are effective in the immune response against cancer.
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http://dx.doi.org/10.31557/APJCP.2019.20.7.1979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745218PMC
July 2019

An immunoproteomic approach to identifying immunoreactive proteins in amastigotes using sera of dogs infected with canine visceral leishmaniasis.

Pathog Glob Health 2019 05 17;113(3):124-132. Epub 2019 May 17.

c Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences , Shiraz , Iran.

Visceral leishmaniasis (VL), the most severe form of leishmaniasis, is caused by and . The infected dogs with canine visceral leishmaniasis (CVL) are important reservoirs for VL in humans, so the diagnosis, treatment and vaccination of the infected dogs will ultimately decrease the rate of human VL. Proteomics and immunoproteomics techniques have facilitated the introduction of novel drug, vaccine and diagnostic targets. Our immunoproteomic study was conducted to identify new immunoreactive proteins in amastigote form of . The strain of (MCAN/IR/07/Moheb-gh) was obtained from CVL-infected dogs. J774 macrophage cells were infected with the promastigotes. The infected macrophages were ruptured, and pure amastigotes were extracted from the macrophages. After protein extraction, two-dimensional gel electrophoresis was employed for protein separation followed by Western blotting. Western blotting was performed, using symptomatic and asymptomatic sera of the infected dogs with CVL. Thirteen repeatable immunoreactive spots were identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Some, including prohibitin, ornithine aminotransferase, annexin A4, and apolipoprotein A-I, have been critically involved in metabolic pathways, survival, and pathogenicity of parasites. Further investigations are required to confirm our identified immunoreactive proteins as a biomarker for CVL.
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http://dx.doi.org/10.1080/20477724.2019.1616952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586132PMC
May 2019

Inhibition of interferon-γ production and T-bet expression by menthol treatment of human peripheral blood mononuclear cells.

Immunopharmacol Immunotoxicol 2019 Apr 6;41(2):267-276. Epub 2019 May 6.

a Department of Immunology , Shiraz University of Medical Sciences , Shiraz , Iran.

(L.) Huds., has shown anti-inflammatory effects. To evaluate the immunomodulatory effects of menthol, the major constituent of on T cells as the main cells affecting the inflammatory responses. Effect of menthol on: proliferation and viability of the peripheral blood human mononuclear cells (PBMCs) by BrdU and propidium iodide (PI) staining, respectively, interferone (IFN)γ and interleukin (IL)-4 cytokine production in lymphocytes stimulated with phytohemagglutinin (PHA) and phorbol myristate acetate/calcium ionophore (PMA/CI) by ELISA; intracellular staining of CD4 cells for IFNγ expression by flow cytometry and gene expressions of T heper (Th) cell transcription factors was measured using real time-PCR. Menthol dose-dependently inhibited lymphocytes proliferation from 88.7% at 50 μg/ml to 3.63% at 800 μg/ml (p < .05). According to the results of PI staining, this inhibitory effect was not due to cell death. Menthol dose-dependently decreased IFNγ but not IL-4 production in culture of PHA- and PMA/CI-stimulated lymphocytes to more than 80% at 800 µg/ml. In flow cytometry analysis, menthol reduced the number of IFN-γ-expressing CD4T cells stimulated either with PHA or PMA/CI. Treatment of PBMCs with 800 μg/ml of menthol decreased levels of T-bet from 14.5 ± 2.26 fold in untreated control to 2.76 ± 1.74 fold (p < .001). Foxp-3 expression decreased to nearly half, but GATA3 did not significantly change. Ratios of T-bet to GATA3 and T-bet to Foxp3 gene expressions were dose-dependently declined. Decreased IFNγ expression plus T-bet down-regulation suggested the inhibitory effect of menthol on Th1 cells differentiation and hence imply its possible therapeutic usefulness in inflammatory diseases.
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http://dx.doi.org/10.1080/08923973.2019.1588294DOI Listing
April 2019

Influence of forkhead box protein 3 polymorphisms (rs2232365, rs3761548) with the outcome of pregnancy: A meta-analysis.

J Cell Physiol 2019 Feb 19. Epub 2019 Feb 19.

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

Dysfunction of regulatory T cells (Tregs) may contribute to certain immune-related pregnancy complications. Forkhead box protein 3 (FOXP3) is the key transcription factor of Treg. We performed a systematic review and meta-analysis to evaluate the possible association between FOXP3 polymorphisms -924A/G (rs2232365) and -3279C/A (rs3761548) and immune-related pregnancy complications. After reviewing 78 fully published studies, 10 studies fulfilled previously defined eligibility criteria and were used for meta-analysis. Two single nucleotide polymorphisms showed a significant correlation with increased or reduced risk for immune-related pregnancy complications. For rs3761548, women with allele A were significantly at a higher risk than women carrying allele C (odds ratio = 1.29, 95% confidence interval: 1.20-1.38; p = 0.001). For rs2232365, women with GG or AG genotype were at a higher risk than women with genotype AA, thereby, allele G was significantly associated with a higher risk than allele A. Our meta-analysis supports the notion that immune-related pregnancy complications might be linked to genetic variations in the FOXP3 gene.
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http://dx.doi.org/10.1002/jcp.28328DOI Listing
February 2019

The Importance of Checking Leishmania Promastigotes Viability in the Proteomics Analysis of Secretions.

Turkiye Parazitol Derg 2018 Dec;42(4):245-248

Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Objective: The aim of the present study was to compare the efficacy of checking the viability of Leishmania promastigote by flow cytometry using propidium iodide (PI) and microscopic method using trypan blue (TB) before proteomics analysis of the secretions.

Methods: The promastigotes (6×109) of Leishmania infantum in the exponential growth phase were transferred to serum-free media. Then, the viability of promastigotes was checked and compared with flow cytometry and microscopic method at 0, 2, 3, 4, 5, and 72 h.

Results: Flow cytometry did not show many dead cells at 0 to 4 h, and the viability was approximately 98%. The percentage of the dead promastigotes increased to 8% at 5 h and 17% at 72 h. Meanwhile, the microscopic method using TB did not show any dead cell after 4 and 72 h, and the viability was 100%.

Conclusion: The present study confirms the importance of flow cytometry using PI in checking the viability of Leishmania promastigotes, especially before the proteomics analysis of the secretions. It also shows that flow cytometry using PI is more sensitive than microscopic method using TB.
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http://dx.doi.org/10.5152/tpd.2018.5834DOI Listing
December 2018

Pyrin and Hematopoietic Interferon-Inducible Nuclear Protein Domain Proteins: Innate Immune Sensors for Cytosolic and Nuclear DNA.

Crit Rev Immunol 2019;39(4):275-288

Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.

The innate immune system is the first line of defense against microbial pathogens. The response of innate immunity is initiated by molecules known as pattern recognition receptors (PRRs). Such responses are often triggered by nucleic acids that are delivered to the cytoplasm or nucleus of cells. The ability to recognize foreign nucleic acids in these two locations is an important defense mechanism of the human innate immune system. Several PRRs are located in the cytosol or nucleus and detect foreign DNAs. The pyrin and hematopoietic interferon-inducible nuclear (PYHIN) domain protein is a family of PRRs that includes interferon-inducible protein 16, absent in melanoma 2, PYHIN 1 (or interferon-inducible protein X, as it is also known), myeloid cell nuclear differentiation antigen, and pyrin domain only protein 3. These nuclear and cytosolic sensors play an essential part in host defense of intracellular pathogens. In addition, members of the PYHIN family are critical regulators of immune response, apoptosis, cell growth, differentiation, and transcription. In this review, we summarize important characteristics of these innate immune sensors and their roles in several diseases. A better understanding of the role of DNA sensors in the nucleus and cytoplasm will lead to the development of novel therapeutic approaches to control infections and associated diseases.
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http://dx.doi.org/10.1615/CritRevImmunol.2020033114DOI Listing
August 2020

An update on immune dysregulation in obesity-related insulin resistance.

Scand J Immunol 2019 Apr 29;89(4):e12747. Epub 2019 Jan 29.

Department of Immunology, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.

Obesity is associated with chronic low-grade inflammation of the adipose tissue (AT) that might develop into systemic inflammation, insulin resistance (IR) and an increased risk of type 2 diabetes mellitus (T2DM) in severe obese rodents and humans. In the lean state, small normal adipocytes and AT macrophages interact with each other to maintain metabolic homeostasis but during obesity, enlarged adipocytes secrete inflammatory mediators and express immune receptors to recruit immune cells and aggravate the inflammation. The better understanding of the obesity-related inflammatory milieu and the sequential events leading to IR could be helpful in designing new preventive and therapeutic strategies. The present review will discuss the cellular and molecular abnormalities participating in the pathogenesis of obesity in obese individuals as well as high-fat diet (HFD)-fed mice, a mouse model of obesity.
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http://dx.doi.org/10.1111/sji.12747DOI Listing
April 2019

A multicenter-based study on epidemiology, antibiotic susceptibility and risk factors of toxigenic Clostridium difficile in hospitalized patients in southwestern Iran.

Infez Med 2018 Dec;26(4):308-315

Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran.

Clostridium difficile (recently Clostridioides difficile) is a leading cause of hospital- and antimicrobial-associated diarrhea (AAD). The present study was carried out to investigate the prevalence of toxigenic C. difficile, antibiotic resistance and its associated risk factors in Iranian hospitalized patients. This cross-sectional study was conducted from October 2017 to June 2018 in three teaching hospitals in southwestern Iran. During this period, a total of 215 non duplicated nosocomial AAD samples were collected from the hospitalized patients older than two years of age. Presumptive C. difficile isolates were identified by standard microbiologic methods and confirmed by specific PCR primers. The minimum inhibitory concentrations (MICs) were determined by the agar dilution method. PCR was carried out to determine the presence of toxin genes (tcdA, and tcdB). In all, from the 215 diarrheal samples, the frequency of C. difficile culture-positive samples was 21.4% (n = 46). Of the 46 C. difficile isolates, 43 carried both toxins, two isolates only had the tcdB gene, and one was negative for both toxins. Overall, all isolates of C. difficile were susceptible to metronidazole and vancomycin. The MIC50/MIC90 of metronidazole and vancomycin were 0.75/2 μg/mL, 0.25/0.75 μg/mL, respectively. The findings of this study show the prevalence of CDI in hospitalized patients in southwestern Iran, highlighting the importance of active surveillance of CDI in hospitals. Meanwhile, all of the tested isolates were susceptible to metronidazole and vancomycin, which encourages the use of these antibiotics as the drug of choice for initial treatment of CDI in our region.
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December 2018

Recombinant NS3 Protein Induced Expression of Immune Modulatory Elements in Hepatic Stellate Cells During Its Fibrotic Activity.

Viral Immunol 2018 10 3;31(8):575-582. Epub 2018 Oct 3.

1 Stem Cell Technology Research Center, Shiraz University of Medical Sciences , Shiraz, Iran .

There is a growing body of studies that show the important role of NS3 protein from hepatitis C virus in fibrosis. However, mechanisms of the effects of this protein on immune modulation of stellate cells remain to be investigated. Herein, the effect of NS3 protein on the expression level of suppressor of cytokine signaling (SOCS)1/3 and interleukin-24 (IL-24)-related genes was investigated in hepatic stellate cell (HSC), LX-2. Recombinant NS3 protein was added to LX-2 HSC culture. Leptin and standard medium treatments were also included in experiments as positive and negative controls, respectively. Total RNA was extracted from each well at 6, 12, and 24 h after NS3 addition. The expression levels of the fibrotic (transforming growth factor beta 1 [TGF-β], alpha-smooth muscle actin [α-SMA], and COL1A1), inflammatory (IL-6 and IL-24), IL-20R, IL-22R, and immunosuppressive genes (SOCS1 and SOCS3) were evaluated by real-time polymerase chain reaction (PCR). Recombinant NS3 protein induced activated phenotypes of LX-2 with a significant increase in the expression level of α-SMA COL1A1 (p < 0.0001) and TGF-β. Moreover, this exposure led to a meaningful elevation in the expression of IL-6. Furthermore, compared with leptin (control), after the stellate cell treatment with NS3, SOCS1 and SOCS3 gene expression induced at a comparable level. Compared with the control sample, the NS3 protein significantly increased the expression level of IL-24 and its related receptors, IL-20R and IL-22R. This study not only confirmed the previously proved inflammatory and fibrotic effect of this protein but also indicated that high expression levels of SOCS1, SOCS3, and IL-24 have a significant effect on HSC activation. Therefore, these two molecules can be used as a potential therapeutic target candidate.
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http://dx.doi.org/10.1089/vim.2018.0018DOI Listing
October 2018

Inhibition of LPS-induced inflammatory responses by Satureja hortensis extracts in J774.1 macrophages.

J Immunoassay Immunochem 2018 18;39(3):274-291. Epub 2018 Jun 18.

a Department of Immunology , Shiraz University of Medical Sciences , Shiraz , Iran.

Macrophages are among the main cells involved in generation of inflammation. To investigate the anti-inflammatory effect of Satureja hortensis (summer savory), lipopolysaccharide (LPS)-activated J774.1 macrophages were treated with various extracts, and the expression and release of various inflammatory molecules by macrophages were examined. We showed that dichloromethane and hexane extracts reduced nitric oxide (NO) production more efficiently than other extracts. Both extracts decreased gene expression of inducible NO synthase (iNOS) (<0.44 fold of control), cyclooxygenase (COX)-2 (<0.29 fold), interleukin (IL)-1β (<0.41 fold), IL-6 (<0.25 fold) and tumor necrosis factor (TNF)-α (<0.2 fold). The extracts reduced IL-6 and IL-1β proteins production from macrophages. Surface intensity of expression of intercellular adhesion molecule (ICAM)-1 decreased to 845 ± 28.1 (dichloromethane) and 715 ± 48.6 (hexane) compared to the control (902 ± 73.1). These findings showed that Satureja hortensis, by influencing macrophages and related mediators, could contribute to reduction of inflammation and might be useful as an anti-inflammatory agent.
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http://dx.doi.org/10.1080/15321819.2018.1480495DOI Listing
August 2018

Investigation of Dracocephalum kotschyi Plant Extract on the Effective Inflammatory Transcription Factors and Mediators in Activated Macrophages.

Antiinflamm Antiallergy Agents Med Chem 2018 ;17(1):39-49

Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Dracocephalum kotschyi is traditionally used for its anti-inflammatory effects. We aimed to investigate the effects of ethyl acetate extract of D. kotschyi on the expression of key inflammatory mediators and main signaling molecules involved in the regulation of inflammation.

Methods: Lipopolysaccharide (LPS)-stimulated J774.1 mouse macrophages were cultured in the presence of the plant extract and examined by the real time-PCR for gene expressions of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. Cytokine levels and phosphorylated forms of stressactivated protein kinases/c-Jun N-terminal kinase (SAPK/JNK), signal transducer and activator of transcription (STAT)-3, p38, IκB-α and nuclear factor (NF)-κB p65 were determined using ELISA.

Results: The extract significantly reduced the expression of key mediators of inflammation. iNOS expression level decreased from 138±8.5 fold in LPS-only treated cells to 6.5±2.6 fold after treatment with 25 µg/ml of the extract (p<0.001). Similarly, COX-2 expression decreased from 632 ±98.8 fold in control to 124 ±24.6 fold (p<0.01). Treatment of cells with the extract significantly reduced IL-1β and TNF-α cytokines at both gene and protein expression levels. The extract at 25 µg/ml caused significant decreases in phospho- SAPK/JNK and phospho-STAT3 levels in macrophages (p<0.01). Proteins of phospho-p38, NFκB-p65 and phospho-NF-κB p65 had a reduced level in treated cells (p<0.05). No significant change in phospho-IκB level was observed.

Conclusion: These findings suggested that D. kotschyi with inhibition of NF-κB, SAPK/JNK, STAT-3 and p-38 might have reduced the expression levels of key inflammatory mediators and thus possibly have potential beneficial impact on inflammatory diseases.
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http://dx.doi.org/10.2174/1871523017666180608081656DOI Listing
February 2019

Achievement amastigotes of and investigation of pathological changes in the tissues of infected golden hamsters.

J Parasit Dis 2018 Jun 5;42(2):187-195. Epub 2018 Mar 5.

3Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

is an agent of visceral leishmaniasis (VL). Amastigote form is a more appropriate target for investigations on vaccines, treatment, and diagnosis. This study aimed to achieve the amastigotes of in the golden hamster and J774 macrophages and report the pathological changes that occur in the liver and spleen of the hamsters with VL. 4 male golden hamsters were infected with promastigotes. After 5 months, the hamsters were euthanized and touch and pathology smears were prepared from the livers and spleens. Then, these tissues were homogenized and centrifuged at 100×. Supernatants were collected and centrifuged at 2000× and the pellets were collected. In the next part of our study, J774 macrophages were infected with promastigotes. Then, the infected macrophages were ruptured. Centrifuge stages were done same the previous part. The amastigotes were observed in touch and pathology smears. A load of amastigotes in the livers was more than the spleens in both types of smears. Although the livers' structure had undergone pathological changes, the spleens were unchanged. Also, the macrophage infectivity ratio was up to 95%. Our results present a simple and accessible way of achieving a lot of pure and real amastigotes for different fields in Also, it seems that the pathological changes occurring in the spleen and the liver of animals with VL are different and probably can be attributed to the genetic and immune process of the infected animals.
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http://dx.doi.org/10.1007/s12639-018-0981-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962490PMC
June 2018

Using proteomics as a powerful tool to develop a vaccine against Mediterranean visceral leishmaniasis.

J Parasit Dis 2018 Jun 19;42(2):162-170. Epub 2018 Mar 19.

3Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Visceral leishmaniasis (VL) is a tropical infectious disease, which is called Mediterranean visceral leishmaniasis (MVL) in the Mediterranean area. In spite of many attempts, no effective commercial vaccine exists for MVL. To find new targets for developing antileishmanial vaccines, knowing parasite antigens that provoke the immune system are on demand. Nowadays, proteomics methods are defined as approaches for analysis of protein profiling of different cells. Within this framework, detection of new antigens is becoming more facilitated. In this review, we aimed to introduce possible targets using proteomics so; they could be used as candidates for developing vaccines against MVL. It can shed new light in the near future on the development of promising vaccines for MVL.
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http://dx.doi.org/10.1007/s12639-018-0986-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962495PMC
June 2018

Anti-inflammatory activity of extract on macrophages mediated by inhibition of inflammatory mediators and cytokines expression.

Res Pharm Sci 2018 Feb;13(1):73-81

Department of Immunology, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.

(Boraginaceae) is an important remedy used for various illnesses. In this study, we investigated the anti-inflammatory effects of in the J774.1A macrophage cell line. We prepared ethyl acetate, dichloromethane and hexane extracts from flowers and examined their possible cytotoxic effects using MTT assay. Lipopolysaccharide (LPS)-stimulated macrophages were treated with the extracts after which we measured nitric oxide (NO) production by Griess method. Inducible NO synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 gene expressions were examined by real time-PCR. IL-1β and IL-6 cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). The hexane extract with a half maximal inhibitory concentration (IC) of 39.8 μg/mL most effectively reduced NO production. Real time-PCR analysis indicated reduced levels of iNOS ((0.05 ± 0.006 relative fold change (RFC)) and COX2 (0.06 ± 0.002 RFC) gene expressions with the 100 μg/mL hexane extract ( < 0.001). IL1-β, TNF-α, and IL-6 gene expression levels decreased at all concentrations of the extract (less than ≈ 0.28 RFC). Treatment of LPS-stimulated cells with 100 μg/mL of the extract reduced IL-1β secretion to 27.9 ± 0.21 pg/mL and IL-6 to 555 ± 166 pg/mL. In conclusion, hexane extract showed the greatest reduction in macrophage NO secretion compared to other extracts. This extract could modulate the inflammatory mode of the macrophages by causing reductions in iNOS and COX2 enzymes as well as IL-1β, IL-6, and TNF-α cytokine levels. The results of this study have shown the anti-inflammatory effects of this plant. Further studies regarding its therapeutic potential in inflammatory disorders are recommended.
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http://dx.doi.org/10.4103/1735-5362.220970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772084PMC
February 2018

Seroepidemiological Study of Infection among Psychiatric Patients in Mashhad, Northeast of Iran.

Iran J Parasitol 2017 Jan-Mar;12(1):117-122

Dept. of Parasitology and Mycology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Psychiatric patients have an increased risk of some infections like toxoplasmosis. Investigations on infection among psychiatric patients have been limited in Mashhad, Northeast of Iran. In this case-control study, prevalence of T. gondii was investigated by serological method.

Methods: This case-control study was performed among psychiatric patients admitted to Avicenna Hospital in Mashhad, Northeast of Iran. Three hundred and fifty inpatients and 350 controls were examined in 2012-2013 for detection of IgG and IgM antibodies against in their blood sera by ELISA. Socio-demographic and clinical manifestations of the patients were obtained.

Results: Anti- IgG antibodies was found in 164 (46.85%) of 350 psychiatric inpatients and 120 (34.28%) of 350 controls. Seventeen (4.85%) of psychiatric individuals and 3 (0.85%) of control group were IgM+/IgG- indicating acute form of toxoplasmosis. There were no statistically significant differences between the case and control groups. In patient group, schizophrenic patients had the highest positive rate (46.28%) and bipolar mood disorder had the second most prevalent rate (20%). Of 162 schizophrenia patients, 65 (40.1%) had latent infection which was higher than that observed in controls.

Conclusion: The prevalence of infection among psychiatric patients suffering from schizophrenia was more in Mashhad, compared with control group.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522687PMC
August 2017

Effect of MicroRNA-21 Transfection on In-vitro Differentiation of Human Naive CD4+ T Cells to Regulatory T Cells.

Iran J Allergy Asthma Immunol 2017 Jun;16(3):235-244

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

Regulatory T cells (Tregs) are important components of the immune system that modulate responses of other cells. These cells are involved in peripheral tolerance mechanisms, so defect in development and function of these cells can result in autoimmune disease. Increasing evidence supports the role of microRNAs-21 (miR-21) in the regulation of forkhead box P3 (Foxp3) expression in Tregs. We aimed to determine whether miR-21 transfection to naive CD4+ T cells can be useful in generation of iTregs in-vitro. We investigated in-vitro differentiation of miR-21-transfected naive CD4+ T cells to iTregs and compared these iTregs to cytokine-differentiated iTregs and control group. We showed that expression of Foxp3, transforming growth factor beta (TGF-β), and interleukin-10 (IL-10) are increased in iTregs generated after miR-21 transfection in comparison with cytokine-differentiated iTregs and control group. Our findings demonstrate that miR-21 has positive role in in-vitro generation of induced regulatory T-cells (iTregs).
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June 2017