Publications by authors named "Majid Khoshmirsafa"

26 Publications

  • Page 1 of 1

Acute and post-acute phase of COVID-19: Analyzing expression patterns of miRNA-29a-3p, 146a-3p, 155-5p, and let-7b-3p in PBMC.

Int Immunopharmacol 2021 Apr 6;97:107641. Epub 2021 Apr 6.

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

Background: When a new pathogen, such as severe acute respiratory syndrome coronavirus 2, appears all novel information can aid in the process of monitoring and in the diagnosis of the coronavirus disease (COVID-19). The aim of the current study is to elucidate the specific miRNA profile which can act as new biomarkers for distinguishing acute COVID-19 disease from the healthy group and those in the post-acute phase of the COVID-19 disease.

Methods: The expression level of selected miRNAs including let-7b-3p, miR-29a-3p, miR-146a-3p and miR-155-5p were evaluated in peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, in both the acute and post-acute COVID-19 phase of the disease and healthy groups, by real-time PCR assays. Specificity and sensitivity of miRNAs was tested by receiver operating characteristic (ROC) analysis in COVID-19 patients.

Results: The expression level of all miRNAs in COVID-19 patients was significantly higher than in the healthy group. Therefore, the expression pattern of miR-29a-3p, miR-146a-3p and let-7b-3p in the post-acute COVID-19 phase was significantly different from the acute COVID-19 phase. ROC analyses demonstrated that miR-29a-3p, -155-5p and -146a-3p may serve as the novel biomarker for COVID-19 diagnosis with high specificity and sensitivity. In addition, miR-29a-3p, and -146a-3p can maybe act as novel biomarkers for distinguishing acute from post-acute phase of COVID-19 disease.

Discussion: The difference in miRNA expression pattern between COVID-19 patients and those in the healthy group, and between acute COVID-19 with post-acute COVID-19, suggested that cellular miRNAs could be used as promising biomarkers for diagnosis and monitoring of COVID-19.
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http://dx.doi.org/10.1016/j.intimp.2021.107641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023203PMC
April 2021

High frequency of concurrent anti-C1q and anti-dsDNA but not anti-C3b antibodies in patients with Lupus Nephritis.

J Immunoassay Immunochem 2021 Mar 31:1-18. Epub 2021 Mar 31.

Department of Rheumatology, Iran University of Medical Sciences, Tehran, Iran.

Lupus Nephritis (LN) in patients with Systemic Lupus Erythematosus (SLE) is one of the most serious and prevalent manifestations. The procedure of renal biopsy is harmful and accompanied by potential hazards. Therefore, introducing reliable biomarkers to predict LN is exceedingly worthwhile. In the present study, we compared the diagnostic values of circulating autoantibodies against dsDNA, C1q, C3b, SSA, SSB, and Sm alone or in combination to predict LN. This study evaluated the abovementioned autoantibodies in 40 healthy controls (HCs) and 95 SLE patients with different kidney involvements, including absent (n = 40), inactive (n = 20), and active (n = 35) LN using EIA method. The frequency and odds ratio of anti-dsDNA (71.4%, OR = 4.2), anti-C1q (62.9%, OR = 5.1), and the simultaneous existence of anti-C1q and anti-dsDNA (51.4%, OR = 6) antibodies were significantly higher in the active LN group compared with both inactive and absent LN groups. Moreover, the levels of anti-C1q and anti-dsDNA antibodies positively correlated with disease activity in patients with SLE. The prevalence of these autoantibodies was associated with the severity of LN biopsies. These data suggest that anti-C1q and anti-dsDNA antibodies and also their simultaneous presence may be valuable diagnostic biomarkers for LN prediction in patients with SLE.
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http://dx.doi.org/10.1080/15321819.2021.1895215DOI Listing
March 2021

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

Bibliometric analysis of global scientific research on Coronavirus (COVID-19).

Med J Islam Repub Iran 2020 23;34:51. Epub 2020 May 23.

Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Since the outbreak of the novel coronavirus disease from Wuhan, China, in early December 2019, many scientists focused on this infection to find a way to deal with it. Due to the dramatic scientific growth in this field, we conducted a scientometric study to gain a better understanding of the scientific literature on COVID-19. We extracted all COVID-19 documents indexed in the Scopus from December 1, 2019, to April 1, 2020, without any language limitation and determined their bibliometric characteristics, including document type, open accessibility status, citation counting, H-index, top cited documents, the most productive countries, institutions and journals, international collaboration, the most frequent terms and keywords, journal bibliographic coupling and cocitations. A total of 923 documents on COVID-19 were retrieved, of which 418 were original articles. All documents had received 2551 citations with an average citation of 2.76 per document and an h-index of 23. China ranked first with 348 documents, followed by the United States (n = 160). The Lancet and BMJ Clinical Research Ed published the most documents (each with 74 documents) and 2 institutions (University of Hong Kong and Huazhong University of Science and Technology) ranked first in this regard. In addition, the present study analyzed the top 25 highly-cited documents (those that had received 70% of all citations). This study highlighted the focused subjects on various aspects of COVID-19 literature such as pathogenesis, epidemiology, transmission, diagnosis, treatment, prevention, and its complications.
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http://dx.doi.org/10.34171/mjiri.34.51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481853PMC
May 2020

The effect of smoking on latent tuberculosis infection susceptibility in high risk individuals in Iran.

J Immunoassay Immunochem 2020 Sep 16;41(5):885-895. Epub 2020 Aug 16.

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

Tuberculosis has been declared as a global emergency. Latent tuberculosis infection (LTBI) is a state in which host immunity cannot completely eradicate . Cigarette smoke increases the risk of respiratory infections, such a TB, as it has adverse effects on respiratory immune function. In this cross-sectional study, which was performed from 2016 to 2017, 31 patients with newly diagnosed lung cancer, 63 Chronic obstructive pulmonary disease (COPD), 46 with problems in respiratory system, and 40 healthy subjects were studied. Demographic data of all subjects were recorded a questionnaire. IGRAs (Interferon-γ release assays) were used to determine LTBI. We showed that smoking has significant odds ratio for COPD patients (OR: 4.58, 95% CI: 1.93-10.87). Also, the concordance of smoking with COPD (OR: 22, 95% CI: 2.7-179.2), lung cancer (OR: 10, 95% CI: 1.03-97), and other respiratory diseases (OR: 4.54, 95% CI: 1.93-10.87) is a significant risk factor for the presence of LTBI whereas the existence of LTBI in the study groups did not show any significant odds ratio. This study is the first to analyze the relationship between smoking in patients with respiratory diseases and LTBI susceptibility in Iran by IGRAs, which proposes cigarette smoking as a powerful risk factor for LTBI.
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http://dx.doi.org/10.1080/15321819.2020.1806075DOI Listing
September 2020

Expansion of Single Cell Transcriptomics Data of SARS-CoV Infection in Human Bronchial Epithelial Cells to COVID-19.

Biol Proced Online 2020 23;22:16. Epub 2020 Jul 23.

Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 19 (COVID-19) that was emerged as a new member of coronaviruses since December 2019 in Wuhan, China and then after was spread in all continentals. Since SARS-CoV-2 has shown about 77.5% similarity to SARS-CoV, the transcriptome and immunological regulations of SARS-CoV-2 was expected to have high percentage of overlap with SARS-CoV.

Results: In this study, we applied the single cell transcriptomics data of human bronchial epithelial cells (2B4 cell line) infected with SARS-CoV, which was annotated in the Expression Atlas database to expand this data to COVID-19. In addition, we employed system biology methods including gene ontology (GO) and Reactome pathway analyses to define functional genes and pathways in the infected cells with SARS-CoV. The transcriptomics analysis on the Expression Atlas database revealed that most genes from infected 2B4 cell line with SARS-CoV were downregulated leading to immune system hyperactivation, induction of signaling pathways, and consequently a cytokine storm. In addition, GO:0016192 (vesicle-mediated transport), GO:0006886 (intracellular protein transport), and GO:0006888 (ER to Golgi vesicle-mediated transport) were shown as top three GOs in the ontology network of infected cells with SARS-CoV. Meanwhile, R-HAS-6807070 (phosphatase and tensin homolog or PTEN regulation) showed the highest association with other Reactome pathways in the network of infected cells with SARS-CoV. PTEN plays a critical role in the activation of dendritic cells, B- and T-cells, and secretion of proinflammatory cytokines, which cooperates with downregulated genes in the promotion of cytokine storm in the COVID-19 patients.

Conclusions: Based on the high similarity percentage of the transcriptome of SARS-CoV with SARS-CoV-2, the data of immunological regulations, signaling pathways, and proinflammatory cytokines in SARS-CoV infection can be expanded to COVID-19 to have a valid platform for future pharmaceutical and vaccine studies.
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http://dx.doi.org/10.1186/s12575-020-00127-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377208PMC
July 2020

JAK Inhibition as a New Treatment Strategy for Patients with COVID-19.

Int Arch Allergy Immunol 2020 11;181(6):467-475. Epub 2020 May 11.

Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

After the advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the outbreak of coronavirus disease 2019 (COVID-19) commenced across the world. Understanding the Immunopathogenesis of COVID-19 is essential for interrupting viral infectivity and preventing aberrant immune responses before a vaccine can be developed. In this review, we provide the latest insights into the roles of angiotensin-converting enzyme II (ACE2) and Ang II receptor-1 (AT1-R) in this disease. Novel therapeutic strategies, including recombinant ACE2, ACE inhibitors, AT1-R blockers, and Ang 1-7 peptides, may prevent or reduce viruses-induced pulmonary, cardiac, and renal injuries. However, more studies are needed to clarify the efficacy of these therapeutics. Furthermore, considering the common role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in AT1-R expressed on peripheral tissues and cytokine receptors on the surface of immune cells, potential targeting of this pathway using JAK inhibitors (JAKinibs) is suggested as a promising approach in patients with COVID-19 who are admitted to hospitals. In addition to antiviral therapy, potential ACE2- and AT1-R-inhibiting strategies, and other supportive care, we suggest other potential JAKinibs and novel anti-inflammatory combination therapies that affect the JAK-STAT pathway in patients with COVID-19. Since the combination of MTX and baricitinib leads to outstanding clinical outcomes, the addition of baricitinib to MTX might be a potential strategy.
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http://dx.doi.org/10.1159/000508247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270061PMC
June 2020

Evaluating the Immunoreactivity of Ailanthus Altissima (The Tree of Heaven) Pollen Extract in Atopic Patients.

Iran J Allergy Asthma Immunol 2020 Apr 16;19(2):132-138. Epub 2020 Apr 16.

Department of Immunology, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.

IgE-mediated hypersensitivity reaction to pollens is a common health problem in atopic patients. In this regard, the assessment of the allergenicity of highly pollinating plants would be demanding. Based on the increment of Ailanthus altissima (A. altissima) tree in some parts of Iran and considering its probable role in respiratory allergy, in this study, we aimed to investigate its IgE-immunoreactivity and in diagnostic applications. One hundred and twenty-five allergic rhinitis patients who were diagnosed as high IgE responders and demonstrated seasonal rhinitis or rhinoconjunctivitis, as well as 20 healthy controls (HCs) with no allergic symptoms, were enrolled in this study. Total protein extract was prepared from A. altissima pollens and subjected to quality control experiments and finally used in ELISA and western blotting studies. Approximately 24% of the atopic patients (30 from 125) showed positive immunoreactivity to A. altissima extract. The median (IQR) of absorbance (450 nm) of the specific IgE against A. altissima pollen extract in HCs and positive groups were 0.33 (0.28-0.42) and 0.59 (0.36-0.79), respectively (p<0.001). Receiver operating characteristics (ROC) curve analysis of the specific ELISA results, revealed a cut-off value of 0.46 and a sensitivity of 70% and specificity of 100%. Western blotting with the sera positive cases revealed that the main immunoreactive proteins range from 10 to 70 kDa. This study revealed that some of A. altissima pollen proteins ranging from 10 to 70 kDa show IgE-reactivity in atopic patients and may play a role in their allergic reaction symptoms.
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http://dx.doi.org/10.18502/ijaai.v19i2.2763DOI Listing
April 2020

Local eosinophils are associated with increased IgA subclass levels in the sinonasal mucosa of chronic rhinosinusitis with polyp patients.

Allergy Asthma Clin Immunol 2020 25;16:30. Epub 2020 Apr 25.

1Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: Chronic rhinosinusitis (CRS) describes an inflammatory condition affecting the sinonasal mucosa. As the immune system players such as immunoglobulins play prominent roles in the development of CRS, we aimed to investigate the expression of IgA subclasses and factors involved in IgA class switching in the sinonasal mucosa of CRS patients.

Methods: Specimens were collected from the sinonasal mucosa of the healthy controls and CRS patients. Histological assessments were performed by H&E and immunohistochemistry. Real-time PCR and ELISA methods were applied to measure gene expression and protein levels extracted from tissue samples, respectively.

Results: We observed that total IgA and subclass-positive cells were higher in the patient groups than controls. There was a significant correlation between the number of eosinophils and total IgA and subclasses-positive cells (Pv < 0.0001). The expression of CXCL13, BAFF, AID, and germline transcripts were increased in CRSwNP patients. In contrast to IgA2 levels, IgA1 levels were significantly increased in the sinonasal tissue of CRSwNP patients (Pv < 0.01). TGF-β was significantly elevated in the sinonasal tissue of patients with CRSsNP.

Conclusions: Increased protein levels of IgA subclasses and related antibody-producing cells were associated with elevated eosinophils in CRSwNP patients which may result in eosinophil pathological functions. Several therapeutic approaches might be developed to modulate the IgA production to ameliorate the inflammatory mechanisms in CRSwNP patients.
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http://dx.doi.org/10.1186/s13223-020-00428-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183627PMC
April 2020

Comparison of Diagnostic Tests with Oral Food Challenge in a Clinical Trial for Adult Patients with Sesame Anaphylaxis.

Iran J Allergy Asthma Immunol 2020 Feb 1;19(1):27-34. Epub 2020 Feb 1.

Department of Allergy and Clinical Immunology, Rasool-E-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.

Sesame food allergy (SFA); especially anaphylaxis, is a life-threatening condition. The accurate diagnosis of SFA is done by skin prick test (SPT), skin prick to prick (SPP) or specific IgE (sIgE) and is confirmed by oral food challenge (OFC). Since there are few studies evaluating and comparing the utility of these methods for diagnosis of sesame anaphylaxis in adult patients, we aimed to compare OFC with diagnostic tests, including SPT, SPP, and sesames IgE; using ImmunoCAP considering the sensitivity and specificity issues in patients with sesame anaphylaxis. Twenty patients with sesame anaphylaxis were diagnosed based on OFC. Then SPT, SPP, and sIgE were evaluated. Sixteen patients had positive OFC; while 4 patients had negative results. Out of 16 OFC+ patients, 7 patients were SPT+, 15 patients were SPP+, and 2 patients had detectable sIgE. A positive SPT indicated 44% sensitivity and 50% specificity. A positive SPP showed 87.5% sensitivity and 75% specificity. A positive ImmunoCAP test demonstrated 12.5% sensitivity and 75% specificity. The AUC of SPP was significant for the diagnosis of sesame anaphylaxis (p=0.038). In conclusion, when the OFC is not possible, the SPP test with natural sesame seed may be applicable in patients with a convincing history instead of the artificial or commercial extracts of sesame used for SPT. Positive SPP is a good alternative diagnostic method for patients with sesame anaphylaxis. Also, the poor sensitivity of SPT and sIgE may indicate the poor discriminative capability of these tests.
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http://dx.doi.org/10.18502/ijaai.v19i1.2415DOI Listing
February 2020

A Truncated Snail1 Transcription Factor Alters the Expression of Essential EMT Markers and Suppresses Tumor Cell Migration in a Human Lung Cancer Cell Line.

Recent Pat Anticancer Drug Discov 2019 ;14(2):158-169

Immunology Asthma & Allergy Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Epithelial-to-Mesenchymal Transition (EMT) is necessary for metastasis. Zinc- finger domain-containing transcription factors, especially Snail1, bind to E-box motifs and play a crucial role in the induction and regulation of EMT.

Objective: We hypothesized if C-terminal region of Snail1 (CSnail1) may competitively bind to E-box and block cancer metastasis.

Methods: The CSnail1 gene coding sequence was inserted into the pIRES2-EGFP vector. Following transfection of A549 cells with the designed construct, EMT was induced with TGF-β1 and the expression of essential EMT markers was evaluated by real-time PCR and immunoblotting. We also monitored cell migration.

Results: CSnail1 inhibited TGF-β1-induced N-cadherin and vimentin mRNA expression and increased β-catenin expression in transfected TGF-β1-treated A549 cells. A similar finding was obtained in western blotting. CSnail1 also blocked the migration of transfected cells in the scratch test.

Conclusion: Transfection of A549 cells with CSnail1 alters the expression of essential EMT markers and consequently suppresses tumor cell migration. These findings confirm the capability of CSnail1 in EMT blocking and in parallel to current patents could be applied as a novel strategy in the prevention of metastasis.
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http://dx.doi.org/10.2174/1574892814666190527111429DOI Listing
February 2020

Comparison of clinical and immunological features and mortality in common variable immunodeficiency and agammaglobulinemia patients.

Immunol Lett 2019 06 3;210:55-62. Epub 2019 May 3.

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Common Variable Immunodeficiency (CVID) and agammaglobulinemia are two of the main types of symptomatic primary antibody deficiencies. The pathogenic origins of these two diseases are different; agammaglobulinemia is a group of inherited disorders that usually are caused by mutations in the gene encoding Bruton Tyrosine Kinase (BTK) protein while CVID is a heterogeneous disorder mainly without monogenic cause. However, both diseases share a characteristic of frequent bacterial infections, a decline in serum immunoglobulin levels, and abnormality in antibody responses. The demographics and immunologic parameters, clinical manifestation, and mortality statistics from 297 patients with CVID and agammaglobulinemia followed up over 2 decades in the Children's Medical Center of Iran. Age at onset of symptom in agammaglobulinemia was earlier than CVID but the course of disease in CVID patients was longer than agammaglobulinemia patients. Pulmonary infections were the most prevalent clinical manifestations in both groups of patients. Lymphadenopathy, hepatomegaly, and splenomegaly were significantly higher in CVID patients than agammaglobulinemia patients and there was a significant association between these complications and mortality in CVID patients. Among 297 patients, 128 patients (88 CVID and 40 agammaglobulinemia) deceased. The predominant causes of death in CVID patients were infections, chronic lung disease, and malignancy while in agammaglobulinemia patients were infections and respiratory failure. Infections, especially respiratory infections were the most common complication and cause of death in both CVID and agammaglobulinemia groups and recent treatment advances even Immunoglobulin replacement cannot completely control these complications. Thus prompt recognition and specific management of these complications are worthwhile.
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http://dx.doi.org/10.1016/j.imlet.2019.05.001DOI Listing
June 2019

Serum levels of adiponectin and vitamin D correlate with activity of Rheumatoid Arthritis.

Mol Biol Rep 2019 Apr 27;46(2):2505-2512. Epub 2019 Mar 27.

Department of Rheumatology, Iran University of Medical Sciences, Tehran, Iran.

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which numerous cells and mediators affect inflammatory conditions and disease severity. To compare the serum levels of adiponectin, vitamin D, copper, and zinc in patients with RA and to investigate the relationship between these parameters and RA severity. Ninety patients with RA and 30 healthy controls participated in this cross-sectional case-control study between November 2016 and April 2017; according to the ACR/EULAR criteria for RA. Serum levels of adiponectin were determined by ELISA; copper and zinc by colorimetric spectrophotometry; and vitamin D by HPLC. Kruskal-Wallis and Spearman tests were performed using SPSS software and data were depicted by GraphPad Prism software. Compared with healthy controls, the serum level of adiponectin was significantly increased, whereas vitamin D was significantly decreased in patients with RA. Adiponectin and vitamin D levels were inversely correlated in RA subgroups (P < 0.001, r = - 0.410). Adiponectin and vitamin D correlated with RA severity. Furthermore, no significant difference was found in copper and zinc levels between RA groups and controls. The definitive roles of adiponectin, vitamin D, copper, and zinc are not completely determined in RA development. Based on disease activity, these parameters can modulate inflammatory conditions, thus they have the potential to be used as promising therapeutic biomarkers to follow up the severity of disease, as well as the progression and treatment success in patients with RA.
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http://dx.doi.org/10.1007/s11033-019-04682-1DOI Listing
April 2019

Levels of total IgA and IgA subclasses in the serum of chronic rhinosinusitis patients.

Med J Islam Repub Iran 2018 30;32:94. Epub 2018 Sep 30.

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

Different inflammatory mechanisms take part in the immunopathogenesis of chronic rhinosinusitis (CRS). Immunoglobulin (Ig) A is the first-line defense in the airway tracts and other mucosal sites, but little is reported regarding its serum level in CRS patients. The purpose of current study is to determine the serum levels of total IgA, and its subclasses (IgA1, and IgA2) in CRS with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and control groups. In this case-control study the serum levels of total IgA and IgA subclasses were determined by Nephelometry and ELISA methods, respectively. The difference of the median concentrations was analyzed with the Kruskal-Wallis test. Collected data were analyzed using SPSS and presented by GraphPad Prism software. A total of 10 CRSwNP patient, 10 CRSsNP patients and 10 healthy controls participated in our study. The mean age of the groups were 38.2±12.6, 25.6±10.54, and 30.1±9.5, respectively. The concentrations of total IgA were 156(120-165), 165 (149-173), and 172 (152.8-184.3) mg/dl, respectively. The concentrations of IgA1 were 107 (77.9-169.9), 156.1(112.8-175.6), and 130.4 (118.8- 175.2) mg/dl, respectively. The concentrations of IgA2 were 26.11 (18.41-38.11), 26.96 (15.48-38.39), and 23.2 (18.42-31.78) mg/dl, respectively. There was no significant difference in total IgA (p=0.120), IgA1 (p=0.397) and IgA2 (p=0.925) serum levels among three groups. Our study showed there is no difference in total IgA and IgA subclasses in the serum of CRS patients in comparison to healthy controls.
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http://dx.doi.org/10.14196/mjiri.32.94DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376997PMC
September 2018

A Review of Preclinical Experiments Toward Targeting M2 Macrophages in Prostate Cancer.

Curr Drug Targets 2019 ;20(7):789-798

Department of Medical Laboratory Science, Faculty of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran.

Prostate cancer is malignant cancer leading to high mortality in the male population. The existence of suppressive cells referred to as tumor-associated macrophages (TAM) is a major obstacle in prostate cancer immunotherapy. TAMs contribute to the immunosuppressive microenvironment that promotes tumor growth and metastasis. In fact, they are main regulators of the complicated interactions between tumor and surrounding microenvironment. M2 macrophages, as a type of TAMs, are involved in the growth and progression of prostate cancer. Recently, they have gained remarkable importance as therapeutic candidates for solid tumors. In this review, we will discuss the roles of M2 macrophages and worth of their potential targeting in prostate cancer treatment. In the following, we will introduce important factors resulting in M2 macrophage promotion and also experimental therapeutic agents that may cause the inhibition of prostate cancer tumor growth.
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http://dx.doi.org/10.2174/1389450120666190123141553DOI Listing
July 2020

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

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

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

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

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

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

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

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

Elevated expression of miR-21 and miR-155 in peripheral blood mononuclear cells as potential biomarkers for lupus nephritis.

Int J Rheum Dis 2019 Mar 5;22(3):458-467. Epub 2018 Nov 5.

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

Aim: Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE). There is a great interest in using microRNAs (miRNAs) as diagnostic and prognostic biomarkers in autoimmune diseases.

Materials And Methods: This study evaluated miR-16, miR-21, miR-141, miR-146a, and miR-155 expression levels in peripheral blood mononuclear cells (PBMCs) of 55 female SLE patients with absent, inactive, or active nephritis, and 30 healthy controls (HCs) using quantitative polymerase chain reaction.

Results: MiR-21 and miR-155 levels were significantly greater in the active nephritis group than in the absent, inactive or HC groups. Moreover, receiver operating characteristic and logistic regression analyses revealed miR-21 and miR-155 were significant risk factors for LN.

Conclusion: Overexpression of miR-21 and miR-155 in PBMCs may participate in LN pathophysiology and these miRNAs could be used as biomarkers for the condition.
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http://dx.doi.org/10.1111/1756-185X.13410DOI Listing
March 2019

Characterization of a multi-epitope peptide with selective MHC-binding capabilities encapsulated in PLGA nanoparticles as a novel vaccine candidate against Toxoplasma gondii infection.

Vaccine 2018 10 1;36(41):6124-6132. Epub 2018 Sep 1.

Department of Parasitology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

No effective human vaccine against Toxoplasma gondii (T. gondii) has yet been developed; however, a protective vaccine using immunogenic peptides in a safe delivery vehicle system offers promise. Here, we employed bioinformatics to design a multimeric recombinant T. gondii vaccine using predicted T and B cell epitopes of SAG1, AMA1, ROP2, and GRA4 proteins based on their binding capabilities to common major histocompatibility complex (MHC) molecules. Furthermore, we encapsulated the expressed protein in poly lactic-co-glycolic acid (PLGA) nanoparticles as a delivery vehicle and also used alum as an adjuvant to determine the vaccine potency of this multimeric antigen. BALB/c mice were vaccinated and then challenged with T. gondii RH strain, and the survival rate and cytokine profiles were studied. Mice vaccinated with the multi-epitope-based vaccine, both with and without PLGA, had greater Th1 immune responses, survival rates, specific antibody titers, and IFN-γ and IL-2 levels than controls, while the alum-adsorbed vaccine stimulated a Th2-type humoral immune response.
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http://dx.doi.org/10.1016/j.vaccine.2018.08.068DOI Listing
October 2018

Frequency of CD4 and CD8 T cells in Iranian chronic rhinosinusitis patients.

Allergy Asthma Clin Immunol 2018 5;14:47. Epub 2018 Jul 5.

1Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: Chronic Rhinosinusitis (CRS) is a persistent inflammatory disease affecting paranasal sinuses. CRS is categorized into two distinct subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Although several immune cells are involved in the CRS pathogenesis, the role of T cells is not fully understood. The objective of the present study was to evaluate the frequency of CD4 and CD8 T cells and macrophages in the sinonasal mucosa of CRS patients, as well as to investigate the specific transcription factors for Th1, Th2, Th17, and Treg cells.

Methods: In this study, 15 healthy controls, 12 CRSsNP, and 23 CRSwNP patients participated. CD4, CD8, and CD68 cells were investigated in the sinonasal tissues using immunohistochemistry. The expression of transcription factors related to Th subsets (T-bet, GATA3, Ror-γt, and FoxP3) was evaluated using real-time PCR. Furthermore, CRSwNP patients were defined as eosinophilic when eosinophils consisted of more than 10% of total inflammatory cells. The Kruskal-Wallis, Mann-Whitney, and Spearman tests were used in statistical analyses.

Results: The median (range) age of the studied groups was: 32 (14-67) for CRSwNP, 28 (10-43) for CRSsNP, and 27 (17-44) for controls. The number of eosinophils in CRSwNP patients was higher than two other groups, whereas neutrophils were elevated in both CRSwNP and CRSsNP groups in comparison to controls. The frequency of CD4 and CD8 T cells, macrophages, and total inflammatory cells were significantly increased in CRSwNP and CRSsNP patients compared with controls. The mRNA expression of GATA3 was increased in CRSwNP patients while mRNA expression of Ror-γt was elevated in CRSsNP patients. No significant difference was observed in T-bet mRNA expression among three groups. Both CRSwNP and CRSsNP patients showed decreased FoxP3 mRNA expression in comparison to controls.

Conclusion: The frequency of CD4 and CD8 T cells was elevated in CRS patients. In addition, we demonstrated Th2 dominance in CRSwNP patients and Th17 dominance in CRSsNP patients, implicating different mechanisms may underlie the disease. Better CRS classification and targeted therapeutic strategies may be achievable by determining the pattern of infiltrating inflammatory cells. Therefore, further experimental investigations on T cells are needed.
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http://dx.doi.org/10.1186/s13223-018-0270-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034261PMC
July 2018

Anti-Oxidants as Chemopreventive Agents in Prostate Cancer: A Gap Between Preclinical and Clinical Studies.

Recent Pat Anticancer Drug Discov 2018 ;13(2):224-239

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

Background: Tumor cells may be expressed as a result of oxidative stress. The extent of oxidative stress correlates with the aggressive and metastatic potency of cancer.

Objective: One simple way to control prostate cancer is through chemoprevention which refers to the administration of natural or synthetic agents to block, reverse, or delay the process of carcinogenesis. The most chemopreventive agents are antioxidants in nature.

Methods: In this review, we summarized the effects of dietary antioxidants with a focus on their molecular mechanisms and possible roles in the treatment of prostate cancer cells. We also reported the recent outcomes of laboratory and/or clinical trials of antioxidants in prostate cancer patients.

Results: Numerous pre-clinical studies showed that antioxidants protect DNA against being damaged by Reactive Oxygen Species (ROS), thereby genetic mutations causing cancer are likely to be prevented. However, the clinical trial results showed that antioxidants have yielded mixed outcomes or benefitted only a subgroup of the population.

Conclusion: A greater understanding of the molecular events associated with antioxidants will enhance the development of treatment and could result in better strategies for the chemoprevention of prostate cancer. Recent patents also suggest that anti-oxidant compounds can be effective for the prevention and the treatment of prostate cancer.
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http://dx.doi.org/10.2174/1574892813666180213164700DOI Listing
October 2018

Comparative assessment of recombinant and native immunogenic forms of Fasciola hepatica proteins for serodiagnosis of sheep fasciolosis.

Parasitol Res 2018 Jan 4;117(1):225-232. Epub 2017 Dec 4.

Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran.

Laboratory diagnosis of sheep fasciolosis is commonly performed by coprological examinations; however, this method may lead to false negative results during the acute phase of the infection. Furthermore, the poor sensitivity of coprological methods is considered to be a paradox in the chronic phase of the infection. In this study, we compared the immunoreactivity of native and recombinant forms of Fasciola hepatica excretory/secretory antigens and determined their capabilities for the development of F. hepatica-specific immunoassays. Immunoreactivity and specificity of recombinant and native forms of F. hepatica antigens, including fatty acid binding protein (FABP), glutathione-S-transferase (GST), and cathepsin L-1 (CL1), in parallel with native forms of FABP and GST, were studied for serodiagnosis of the chronic form of sheep fasciolosis, individually or in combination with each other by enzyme-linked immunosorbent assays (ELISA). The correlation of the findings was assessed by receiver-operator characteristic (ROC); furthermore, the specificity and sensitivity were assessed by Youden's J. Serologic cross-reactivity was evaluated using samples from healthy sheep (n = 40), Fasciola-infected sheep (n = 30), and sheep with other parasitic infections (n = 43). The FABPs were determined to be greater than 95% sensitive for F. hepatica serodiagnosis. The most desirable diagnostic recombinant antigen was rCL1, which showed 100% sensitivity and 97% specificity in ELISA and was capable of discriminating the positive and negative samples by maximum Youden's J results. We conclude that rCL1 can be used for routine serodiagnosis of chronic fasciolosis. Thus, it could be advantageous in development of immunoassays for screening of ovine herds in fasciolosis-endemic areas and as a reliable agent for detection of fasciolosis in non-endemic regions.
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http://dx.doi.org/10.1007/s00436-017-5696-3DOI Listing
January 2018

Is mannose-binding lectin serum concentration a reliable predictor for recurrent vulvovaginal candidiasis?

Mycoses 2019 Feb 18;62(2):106-111. Epub 2018 Dec 18.

Department of Medical Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Recurrent vulvovaginal candidiasis (RVVC) is a common opportunistic, mucosal fungal infection, predominantly caused by the fungus Candida albicans. Mannose-binding lectin (MBL) is an acute-phase protein that plays a key role in the innate immunity defence against infectious disease. This study was conducted to evaluate the relationship between the MBL serum level and the relative expression of MBL mRNA in RVVC using real-time PCR for the first time. The case-control study included 40 female participants suffering from RVVC and 40 healthy individuals. The MBL serum level was measured using a commercial ELISA kit. The relative mRNA expression of the MBL gene was quantified using real-time PCR. Data analysis was carried out by spss software. The MBL concentration was significantly higher in the participants suffering from RVVC compared to the control group (0.330 ng/mL vs 0.253 ng/mL). The prognostic value (P < .001) for RVVC diagnosis has been calculated. Quantitative RT-PCR results from 35 samples showed a low to significant values for mRNA levels corresponding to MBL gene expression (1-352 folds) (P < .001). The results of this study suggest that MBL plays a main role in the innate immunity and it is also affected by environmental factors and other genetic variations. Therefore, the MBL gene expression profile does not reflect precise phenotypic levels in the serum.
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http://dx.doi.org/10.1111/myc.12723DOI Listing
February 2019

Evaluation of a new protocol for wheat desensitization in patients with wheat-induced anaphylaxis.

Immunotherapy 2017 06;9(8):637-645

Department of Allergy & Clinical Immunology, Iran University of Medical Sciences, Tehran, Iran.

Aim: New approaches such as oral immunotherapy (OIT) may be useful in IgE-mediated anaphylaxis to wheat.

Patients & Methods: 12 patients underwent OIT protocol that comprised of two phases: the first with semolina flour and the second with spaghetti. Total and specific wheat IgE were assayed by ELISA before and after OIT and 18 months later. Skin prick tests were also performed.

Results: Patients successfully tolerated 50 g of wheat. The median baseline total IgE was decreased after up-dosing phase and decreased after follow-up (p < 0.01). The median baseline wheat-specific IgE was increased after up-dosing and decreased after follow-up (p < 0.001).

Conclusion: The efficiency and safety of our OIT protocol were shown on wheat allergic patients but further investigation is needed.
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http://dx.doi.org/10.2217/imt-2017-0011DOI Listing
June 2017

The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells.

Cell Commun Signal 2017 06 21;15(1):23. Epub 2017 Jun 21.

Department of immunology, school of medicine, Iran University of Medical Sciences, Tehran, Iran.

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays critical roles in orchestrating of immune system, especially cytokine receptors and they can modulate the polarization of T helper cells. This pathway is regulated by an array of regulator proteins, including Suppressors of Cytokine Signaling (SOCS), Protein Inhibitors of Activated STATs (PIAS) and Protein Tyrosine Phosphatases (PTPs) determining the initiation, duration and termination of the signaling cascades. Dysregulation of the JAK-STAT pathway in T helper cells may result in various immune disorders. In this review, we represent how the JAK-STAT pathway is generally regulated and then in Th cell subsets in more detail. Finally, we introduce novel targeted strategies as promising therapeutic approaches in the treatment of immune disorders. Studies are ongoing for identifying the other regulators of the JAK-STAT pathway and designing innovative therapeutic strategies. Therefore, further investigation is needed.
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http://dx.doi.org/10.1186/s12964-017-0177-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480189PMC
June 2017

Evaluation of anti-Cathepsin L1: a more reliable method for serodiagnosis of human fasciolosis.

Trans R Soc Trop Med Hyg 2016 09 19;110(9):542-550. Epub 2016 Oct 19.

Immunology Research center, Iran University of Medical Sciences, Tehran, Iran

Background: Coprological examinations are commonly used for diagnosis of fasciolosis. However, these methods are not useful during the acute phase of the infection and also show poor sensitivity during its chronic phase. In this study we compared the immunoreactivity of the native and recombinant forms of Fasciola hepatica excretory/secretory antigens and determined the most appropriate one for development of F. hepatica-specific immunoassays.

Methods: The coding sequences of previously-determined immunogenic proteins including cathepsin L1 (CL1), fatty acid binding protein (FABP) and glutathione-S-transferase (GST) were cloned and expressed in E. coli BL-21 cells. Native forms of FABP and GST were also purified. We evaluated the immunoreactivity of the native and recombinant proteins by ELISA using sera from 40 healthy individuals, 15 fasciolosis patients, and 57 patients with other infectious diseases.

Results: All of the studied proteins showed high sensitivity and specificity for F. hepatica serodiagnosis. However, CL1 was more sensitive and specific (100%) than the others for the detection of F. hepatica-specific antibodies. Notably, both FABP and GST showed significant cross-reactivity with hydatidosis patients' sera while CL1 did not.

Conclusions: Cathepsin L1 has acceptable sensitivity and specificity for serodiagnosis of F. hepatica and its application could be advantageous in immunoassay development.
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http://dx.doi.org/10.1093/trstmh/trw063DOI Listing
September 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