Review Article
Ahmad Mobed
Abstract
Tuberculosis (TB) is believed to be one of the leading causes of death in the world; nevertheless, Bacillus Calmette-Guérin (BCG) is the solitary vaccine utilized to prevent TB. Despite the protective effect of this vaccine in children, its efficiency remains under question in adults. We conducted ...
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Tuberculosis (TB) is believed to be one of the leading causes of death in the world; nevertheless, Bacillus Calmette-Guérin (BCG) is the solitary vaccine utilized to prevent TB. Despite the protective effect of this vaccine in children, its efficiency remains under question in adults. We conducted the present study to provide an overview of DNA based vaccines against TB and highlight the vaccine delivery advances and limitations. This study also aimed to bring a review of mycobacterial antigens, including heat shock protein 65 (Hsp65), antigen 85A (Ag85A), early secretory antigenic target 6 (EAST-6), antigen 85B (Ag85B), and heat shock protein X (HspX) as the most extensively considered antigens in the development of vaccines against M. tuberculosis.
Original Article
Hong Ouyang; Jie Cheng; Jingdong Du; Huiyun Gan; Zheng Lu
Abstract
Background: T helper 17 (Th17) cells and the related cytokines, interleukin (IL)- 17 and IL-23, were proved to play pivotal roles during the development of allergic rhinitis (AR). IL-27, an anti-inflammatory cytokine, has been reported to promote the production of IL-12R and induce Th1 cell responses. ...
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Background: T helper 17 (Th17) cells and the related cytokines, interleukin (IL)- 17 and IL-23, were proved to play pivotal roles during the development of allergic rhinitis (AR). IL-27, an anti-inflammatory cytokine, has been reported to promote the production of IL-12R and induce Th1 cell responses. However, its effect on Th17 responses was not fully understood. Objective: We conducted the present research to explore the role of IL-27 in the regulation of Th17 responses in AR. Methods: Thirty confirmed AR patients and 20 controls were recruited for the study. The mRNA expression and protein levels of IL-27 were analyzed employing quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively, and their correlations with Th17 cytokines were analyzed. We utilized ELISA and qPCR to analyze the effect of IL-27 on the differentiation of Th17 cells and the production of IL-17 and IL-23 from peripheral blood mononuclear cells (PBMCs). Results: We found that the IL-27 levels in AR were downregulated and negatively related to IL-17 and IL-23 levels. The recombinant IL-27 inhibited the mRNA expression of RORγt and the protein expression of IL-17 and IL-23 in PBMCs through MEK, NF-κB, and JNK pathways. Conclusion: Our data demonstrated that IL-27 suppressed Th17 responses through MEK, NF-κB, and JNK pathways.
Original Article
Xiaoling Liu; Xiaojia Liu; Yu Ren; Hongxin Yang; Xiaolei Sun; Haiyun Huang
Abstract
Background: Vitamin D supplementation has been proven to be effective in the treatment of allergic rhinitis (AR). Objective: We conducted the present study to explore the role and efficacy of vitamin D adjuvant therapy for the treatment of inflammation in patients with AR. Methods: Out of 127 patients ...
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Background: Vitamin D supplementation has been proven to be effective in the treatment of allergic rhinitis (AR). Objective: We conducted the present study to explore the role and efficacy of vitamin D adjuvant therapy for the treatment of inflammation in patients with AR. Methods: Out of 127 patients with potential eligible AR, 60 were randomly assigned into two groups and were finally included in our analysis (n=30 for each intervention). The patients with potential eligible AR were randomly allocated to intervention with desloratadine citrate disodium (DCD, 8.8 mg/day) without and with vitamin D3 nasal drops (1.5х106 IU, once/week) for four weeks. Thirty healthy control subjects were included in our study. We assessed the changes in the serum 25(OH)D, peripheral blood eosinophils, interleukin (IL)-4 levels, and nasal symptoms. Serum 25(OH)D, peripheral blood eosinophils, and IL-4 levels were detected respectively with liquid chromatography-tandem mass spectrometry (LC-MS/MS), a blood detector, and enzyme-linked immunosorbent assay. Results: Our patients who received vitamin D3 adjuvant therapy had a higher serum 25(OH)D level (47.57 ± 2.83 vs. 31.51 ± 2.95 ng/ml, p=0.000) and lower AR symptoms score (2.07 ± 1.89 vs. 3.37 ± 1.50, p=0.005), serum IL-4 (10.38 ± 3.41 vs. 12.79 ± 5.40 pg/ml, p=0.043), and peripheral blood eosinophils (0.34 ± 0.09 vs. 0.41 ± 0.10 109/l, p=0.003) compared with DCD single treatment. The efficacy rates of DCD with and without vitamin D3 in AR were 97% and 84%, respectively. Conclusion: Nasal vitamin D3 combined with DCD could improve the clinical symptoms of AR. Vitamin D3 adjunct therapy showed significant effects on inhibiting inflammation in patients with AR. We concluded that vitamin D3 supplementation could be an effective adjuvant therapy in AR patients.
Original Article
Yuying Ji; Rui Cao; Guangxin Lv; Yuanyuan Jin; Jing Chen
Abstract
Background: In a previous study, the unrecognized role of gMYL6 in the up-regulation of human NK cells development and cytotoxicity was reported. Objective: To further elucidate the mechanism of action of small recombinant fragments of gMYL6 enhancing the NK cells activity. Methods: Mononuclear cells ...
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Background: In a previous study, the unrecognized role of gMYL6 in the up-regulation of human NK cells development and cytotoxicity was reported. Objective: To further elucidate the mechanism of action of small recombinant fragments of gMYL6 enhancing the NK cells activity. Methods: Mononuclear cells were isolated from umbilical cord blood (UCB) by density-gradient centrifugation and NK cells were propagated and cultured. The small peptides from the gMYL6, with the ability to enhance the cytotoxicity of NK cells were screened by CCK-8 method and one of the most powerful peptides was identified for the next study. Flow cytometry was used to assess the proliferation and apoptosis of K562 cells, as well as the cell cycle arrest. The apoptosis of target cells was observed by AO/EB fluorescence staining, and the degree of apoptosis was assessed by flow cytometry. Protein imprinting method was also used to explore the pathway of small peptides to enhance the NK cells' activity. On the other hand, Real-time Quantitative PCR Detecting System was used to verify the mechanism of K562 cells suppression. Results: Small D peptide significantly increased NK cells cytotoxicity and induced both cell cycle arrest at G2/M and apoptosis of K562 cells. Conclusion: Small D peptide could be a novel promising peptide for cancer immunotherapy since it was shown to promote the cytotoxicity of cord blood-derived NK cells.
Original Article
Keyu Sun; Zichen Xie; Yang Li; Yanyan Li; Jianfeng Song; Zhefeng Meng
Abstract
Background: There is a close relationship between neutrophil extracellular traps (NETs) and venous thromboembolism (VTE). The regulatory role and mechanism of glucocorticoids (GC) in the formation of NETs are unclear. Objective: This study was conducted to assess the effect of GC on the formation ...
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Background: There is a close relationship between neutrophil extracellular traps (NETs) and venous thromboembolism (VTE). The regulatory role and mechanism of glucocorticoids (GC) in the formation of NETs are unclear. Objective: This study was conducted to assess the effect of GC on the formation of NETs. Methods: We constructed a mouse VTE model and treated them with GC to observe the effect of GC on the formation of NETs. In this regard, peripheral blood neutrophils were isolated, and the effect and mechanism of GC in neutrophil activation were analyzed. Results: Following LPS treatment, the colony-forming ability of neutrophils and their ability to form NETs increased significantly. The analysis of cytokine changes by RT-PCR combined with ELISA showed that the level of inflammatory factors in LPS-activated neutrophils increased significantly; however, these factors were significantly inhibited after GC treatment, and the inhibitory effect was positively correlated with the concentration of GC. LPS treatment was able to activate the production of ROS and lipid peroxides, however, this activation was significantly inhibited after GC treatment, and the inhibition increased with increasing doses of GC. Further examination of the changes in NF-κB signaling activation revealed that LPS-induced NF-κB signaling was significantly inhibited after GC treatment, and this inhibition increased with increasing the GC concentration. Conclusion: Glucocorticoids were able to inhibit neutrophil activation and reduce the formation of NETs. The research results provided a new research direction for clinical antithrombotic treatment.
Original Article
Niloufar Sadat Miri; Payam Saadat; Abbas Azadmehr; Morteza Oladnabi; Abdolreza Daraei
Abstract
Background: Neuroinflammation and immunopathology in Parkinson's disease (PD) are believed to be associated with genetic and environmental factors. Objective: We conducted the current study to evaluate the Toll-like receptors (TLR4 and TLR9) genes polymorphism in patients with Parkinson's disease ...
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Background: Neuroinflammation and immunopathology in Parkinson's disease (PD) are believed to be associated with genetic and environmental factors. Objective: We conducted the current study to evaluate the Toll-like receptors (TLR4 and TLR9) genes polymorphism in patients with Parkinson's disease in northern Iran. Methods: We extracted DNA from peripheral blood samples of 100 sporadic cases of Parkinson's disease and 100 healthy-matched controls with the mean age of 69.98 and 71.94 years, respectively. Subsequently, single-nucleotide polymorphisms (SNPs) of TLR4 and TLR9 were genotyped using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Results were confirmed employing Sanger sequencing. For the analysis of our data, we used SNPStats and SPSS 22 software. Results: Our findings indicated that the allele distribution for rs352140 of TLR9 gene was significantly different in the PD group compared with the healthy controls (p=0.02). Moreover, rs352140 T allele was observed to be correlated with PD reduced risk (TT + TC vs. CC). The dominant rs352140 model was approved as the most acceptable inheritance model for fitting the data (OR 0.41, 95% CI 0.23-0.75, p=0.0031). Additionally, haplotype analysis revealed a significant correlation between TLR9 polymorphisms and Parkinson's disease. Conclusion: The results of this study indicated that rs352140T of TLR9 gene was a protective factor in Parkinson's disease. Furthermore, this SNP could be regarded as a prognostic factor. However, this conclusion should be confirmed by further investigations.
Original Article
Nayyereh Saadati; Mandana khodashahi; Zahra Rezaieyazdi; Maryam Sahebari; Zeinab Saremi; Saeed Mohammadian Haftcheshmeh; Houshang Rafatpanah; Maryam Salehi
Abstract
Background: Rheumatoid arthritis (RA) is described as a systemic and chronic autoimmune disease characterized by inflammatory polyarthritis. Lymphocyte-activation gene 3 (LAG3) is a membrane glycoprotein expressed on activated, exhausted, and regulatory T cells. LAG3 plays a major role in the function ...
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Background: Rheumatoid arthritis (RA) is described as a systemic and chronic autoimmune disease characterized by inflammatory polyarthritis. Lymphocyte-activation gene 3 (LAG3) is a membrane glycoprotein expressed on activated, exhausted, and regulatory T cells. LAG3 plays a major role in the function of Treg cells. LAG3 also has a soluble form (sLAG3) with a controversial role. Objective: To evaluate the serum level of sLAG3 in rheumatoid arthritis patients in comparison with healthy subjects and assess its association with the disease activity. Methods: This cross-sectional study was performed on 105 patients with RA referred to Ghaem hospital of Mashhad, Iran. We divided the participants into four groups: 1) 35 untreated patients with newly diagnosed RA, 2) 35 active RA patients, 3) 35 patients in the remission phase of the disease, and 4) 35 healthy individuals matched in terms of age and sex. After completing the interview and questionnaire, the sLAG3 was evaluated by commercial ELISA. Results: The serum level of sLAG3 significantly increased in RA patients (76.78 ng/ml) as compared with the healthy participants (51.67, p=0.002). However, there was no significant difference between RA patients in the remission phase of the disease (114.11 ng/ml) and those with moderate to high disease activity (63.06 ng/ml, p=0.076). Conclusion: This study provided insights into the role of sLAG3 in the immunopathogenesis of RA disease, but further investigations are also warranted.
Case Report
Farhad Abolnezhadian; Sara Iranparast; Fatemeh Ahmadpour
Abstract
Combined immunodeficiencies (CIDs) are a heterogeneous group of disorders characterized by various gene mutations. The mutations in the STK4 (Serine Threonine Kinase 4) gene, which has a role in the regulation of apoptosis and proliferation, can be a cause of immunodeficiency. In the current paper, we ...
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Combined immunodeficiencies (CIDs) are a heterogeneous group of disorders characterized by various gene mutations. The mutations in the STK4 (Serine Threonine Kinase 4) gene, which has a role in the regulation of apoptosis and proliferation, can be a cause of immunodeficiency. In the current paper, we reported a case of identical twin brothers with a novel STK4 mutation, one of whom showed clinical manifestations associated with this mutation with a delay of two years. The mutation in the STK4 gene was identified employing Whole Exome Sequencing (WES), and we described the probable reasons for this delay. We found that the STK4 genetic defect caused almost the same clinical symptoms of immunodeficiency in the twin brothers. Meanwhile, the severity of the disease was higher in one of them, which may be due to extra genetic defect in LRBA, and likely differences in the percentage of B lymphocyte population and CD4+/ CD8+ state.
