Association between Interleukin-23 Receptor R381Q Gene.

The SNP (rs11209026, Arg381Gln, R381Q) in the IL-23 receptor (IL23R) confers protection against multiple inflammatory diseases, representing one of the most significant human genetic polymorphisms in inflammatory diseases. We, therefore, investigated the association between IL-23 R R381Q gene polymorphism and asthma. This case-control study was performed on 209 patients, and 200 healthy controls. Using PCR-RFLP, the R381Q variant was screened in the IL-23R gene of the patients and controls. Serum IgE levels were measured using ELISA technique. Eosinophil absolute count was done with Sesmex cell counter. Our results indicated that the genotype and allele frequencies of the IL-23R R381Q polymorphism is significantly different between asthmatic patients and control subjects (p<0.001; odd ratio= 0.266; 95%, CI=0.118-0.604. Moreover, the asthmatic patients had higher eosinophil count and total serum IgE levels than controls as expected (p<0.001). The present study suggested that R381Q polymorphism in IL-23 receptor may be a predisposing allele for asthma

Association between Interleukin-23 Receptor R381Q Gene Polymorphism and Asthma

The SNP (rs11209026, Arg381Gln, R381Q) in the IL-23 receptor (IL23R) confers protection against multiple inflammatory diseases, representing one of the most significant human genetic polymorphisms in inflammatory diseases. We, therefore, investigated the association between IL-23 R R381Q gene polymorphism and asthma. This case-control study was performed on 209 patients, and 200 healthy controls. Using PCR-RFLP, the R381Q variant was screened in the IL-23R gene of the patients and controls. Serum IgE levels were measured using ELISA technique. Eosinophil absolute count was done with Sesmex cell counter. Our results indicated that the genotype and allele frequencies of the IL-23R R381Q polymorphism is significantly different between asthmatic patients and control subjects (p<0.001; odd ratio= 0.266; 95%, CI= 0.118-0.604. Moreover, the asthmatic patients had higher eosinophil count and total serum IgE levels than controls as expected (p<0.001). The present study suggested that R381Q polymorphism in IL-23 receptor may be a predisposing allele for asthma

Association between Interleukin-23 Receptor R381Q Gene.

The SNP (rs11209026, Arg381Gln, R381Q) in the IL-23 receptor (IL23R) confers protection against multiple inflammatory diseases, representing one of the most significant human genetic polymorphisms in inflammatory diseases. We, therefore, investigated the association between IL-23 R R381Q gene polymorphism and asthma. This case-control study was performed on 209 patients, and 200 healthy controls. Using PCR-RFLP, the R381Q variant was screened in the IL-23R gene of the patients and controls. Serum IgE levels were measured using ELISA technique. Eosinophil absolute count was done with Sesmex cell counter. Our results indicated that the genotype and allele frequencies of the IL-23R R381Q polymorphism is significantly different between asthmatic patients and control subjects (p<0.001; odd ratio= 0.266; 95%, CI=0.118-0.604. Moreover, the asthmatic patients had higher eosinophil count and total serum IgE levels than controls as expected (p<0.001). The present study suggested that R381Q polymorphism in IL-23 receptor may be a predisposing allele for asthma

The Role of TIM-3 in Hepatocellular Carcinoma: A Promising Target for Immunotherapy?

One of the most common tumors in the world is hepatocellular carcinoma (HCC), and its mortality rates are still on the rise, so addressing it is considered an important challenge for universal health. Despite the various treatments that have been developed over the past decades, the prognosis for advanced liver cancer is still poor. Recently, tumor immunotherapy has opened new opportunities for suppression of tumor progression, recurrence, and metastasis. Besides this, investigation into this malignancy due to high immune checkpoint expression and the change of immunometabolic programming in immune cells and tumor cells is highly considered. Because anti-cytotoxic T lymphocyte–associated protein (CTLA)-4 antibodies and anti-programmed cell death protein (PD)-1 antibodies have shown therapeutic effects in various cancers, studies have shown that T cell immunoglobulin mucin-3 (TIM-3), a new immune checkpoint molecule, plays an important role in the development of HCC. In this review, we summarize the recent findings on signal transduction events of TIM-3, its role as a checkpoint target for HCC therapy, and the immunometabolic situation in the progression of HCC

TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines

IntroductionT-cell immunoglobulin and mucin domain-3 (TIM-3) is a transmembrane molecule first identified as an immunoregulator. This molecule is also expressed on leukemic cells in acute myeloid leukemia and master cell survival and proliferation. In this study, we aimed to explore the effect of TIM-3 interaction with its ligand galectin-9 (Gal-9) on glucose and lipid metabolism in AML cell lines.MethodsHL-60 and THP-1 cell lines, representing M3 and M5 AML subtypes, respectively, were cultured under appropriate conditions. The expression of TIM-3 on the cell surface was ascertained by flow cytometric assay. We used real-time PCR to examine the mRNA expression of GLUT-1, HK-2, PFKFB-3, G6PD, ACC-1, ATGL, and CPT-1A; colorimetric assays to measure the concentration of glucose, lactate, GSH, and the enzymatic activity of G6PD; MTT assay to determine cellular proliferation; and gas chromatography–mass spectrometry (GC-MS) to designate FFAs.ResultsWe observed the significant upregulated expression of GLUT-1, HK-2, PFKFB-3, ACC-1, CPT-1A, and G6PD and the enzymatic activity of G6PD in a time-dependent manner in the presence of Gal-9 compared to the PMA and control groups in both HL-60 and THP-1 cell lines (p &gt; 0.05). Moreover, the elevation of extracellular free fatty acids, glucose consumption, lactate release, the concentration of cellular glutathione (GSH) and cell proliferation were significantly higher in the presence of Gal-9 compared to the PMA and control groups in both cell lines (p &lt; 0.05).ConclusionTIM-3/Gal-9 ligation on AML cell lines results in aerobic glycolysis and altered lipid metabolism and also protects cells from oxidative stress, all in favor of leukemic cell survival and proliferation

TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines

Introduction: T-cell immunoglobulin and mucin domain-3 (TIM-3) is a transmembrane molecule first identified as an immunoregulator. This molecule is also expressed on leukemic cells in acute myeloid leukemia and master cell survival and proliferation. In this study, we aimed to explore the effect of TIM-3 interaction with its ligand galectin-9 (Gal-9) on glucose and lipid metabolism in AML cell lines. Methods: HL-60 and THP-1 cell lines, representing M3 and M5 AML subtypes, respectively, were cultured under appropriate conditions. The expression of TIM-3 on the cell surface was ascertained by flow cytometric assay. We used real-time PCR to examine the mRNA expression of GLUT-1, HK-2, PFKFB-3, G6PD, ACC-1, ATGL, and CPT-1A; colorimetric assays to measure the concentration of glucose, lactate, GSH, and the enzymatic activity of G6PD; MTT assay to determine cellular proliferation; and gas chromatography–mass spectrometry (GC-MS) to designate FFAs. Results: We observed the significant upregulated expression of GLUT-1, HK-2, PFKFB-3, ACC-1, CPT-1A, and G6PD and the enzymatic activity of G6PD in a time-dependent manner in the presence of Gal-9 compared to the PMA and control groups in both HL-60 and THP-1 cell lines (p > 0.05). Moreover, the elevation of extracellular free fatty acids, glucose consumption, lactate release, the concentration of cellular glutathione (GSH) and cell proliferation were significantly higher in the presence of Gal-9 compared to the PMA and control groups in both cell lines (p < 0.05). Conclusion: TIM-3/Gal-9 ligation on AML cell lines results in aerobic glycolysis and altered lipid metabolism and also protects cells from oxidative stress, all in favor of leukemic cell survival and proliferation.Isfahan University of Medical Science

Analysis of the expression of mir-34a, mir-199a, mir-30c and mir-19a in peripheral blood CD4+T lymphocytes of relapsing-remitting multiple sclerosis patients

Background: Multiple sclerosis is an immune-mediated inflammatory disease of central nervous system. MicroRNAs play important roles in autoimmune diseases such as MS. Objectives: The aim was to evaluate the expression pattern of miR-34a, miR-199a, miR-30c and miR-19a in peripheral blood derived CD4+ T lymphocytes of both relapsing and remitting phases of MS. Methods: Blood samples from 40 RRMS patients (20 in relapsing and 20 in remitting phase) and 20 healthy volunteers were taken. CD4+ T cells were isolated. The expression level of miR-34a, miR-199a, miR-30c and miR-19a, and the percentage of Th17 and Treg cells were measured. Expression of master transcription factors of Th17 and Treg cells and several targets of these miRNAs were also evaluated. Results: Data indicated an increased expression of miR-34a, miR-30c and miR-19a in relapsing phase and decreased expression of miR-199a in remitting phase. ROC curve data add other prestigious information of miR34a, miR-199a, miR-30c and miR-19a by defining relapsing and remitting phase and also healthy cases with high specificity and sensitivity at a proposed optimum cut-off point. Conclusion: Collectively, we showed a correlation between the four miRNAs with different phases of MS and their possible involvement in differentiation pathways of Th17 cells, as the most important players in MS

Induction of Apoptosis in Toxoplasma gondii Infected Hela Cells by Cisplatin and Sodium Azide and Isolation of Apoptotic Bodies and Potential Use for Vaccination against Toxoplasma gondii

Background: Toxoplasma gondii can infect a wide range of mammalians, especially humans. It controls several intracellular signals for the inhibition of apoptosis. This study aimed to investigate the apoptogenic effect of cisplatin and sodium azide on T. gondii infected HeLa cells and isolate apoptotic bodies (blebs) as a potent stimulator of the immune system. Methods: The cytotoxic properties of cisplatin and sodium azide (NaN3) on HeLa cells were evaluated by MTT assay. Moreover, the apoptogenic activity of cisplatin and NaN3 was studied using flow cytometry (Annexin V/PI double staining) and scanning electron microscopy (SEM). Finally, apoptotic bodies were separated by centrifugation. Results: MTT assay data showed that the survival rate of cells treated with different concentration of NaN3 was significantly reduced, compared to negative control groups. Concerning cisplatin, only concentration of 20 μM had not a significant impact on the cell viability; however, the other concentration of cisplatin significantly reduced cell viability, compared to negative control groups. The level of early apoptosis in uninfected HeLa cells was higher compared to infected HeLa cells treated with cisplatin and NaN3. Finally, apoptotic bodies were separated from T. gondii infected HeLa cells treated with cisplatin. Conclusion: Apoptosis was induced in both uninfected and infected HeLa cells with T. gondii and apoptotic bodies were isolated from infected cells. Therefore, further studies on apoptotic bodies are required in order to find a proper candidate for vaccine preparation against T. gondii infections

Prediction of probable impact of miR-34a and miR-215 on differentiation of naive CD4+ T cells to Th17 cells in multiple sclerosis

Background and aims: miRNAs, as a class of non-coding RNAs, take part in different cellular processes. Dysregulation of different miRNAs has been reported in numerous disorders to date. Multiple sclerosis (MS) is an autoimmune disease with high prevalence in Iran and Th17 cells play an important role in its pathogenesis. In the current study, we aimed to predict the possible role of miR-34a and miR-215 in the process of controlling Th17 differentiation, and hence, their possible impact on the onset and progression of MS. Methods: We investigated probable interactions of miRNAs and genes that participate in Th17 cells differentiation using miRwalk database as an integrative one which utilizes 10 different algorithms to predict miRNA-mRNA interaction. Results: Based on our findings, miR-34a and miR-215 were predicted to have a potential role in the induction of Th17 cells differentiation. Conclusion: Conclusively, miR-34a and miR-215 may up-regulate Th17 cells of MS patients. Since bioinformatics data have shown that these miRNAs suppress negative regulatory genes in Th17 cells differentiation, we suppose that down-regulation of these miRNAs could ameliorate MS symptoms. Therefore, several therapeutic approaches may be considered for these miRNAs besides their application as valuable prognostic/diagnostic biomarkers in detection of various stages of MS. Keywords: Multiple sclerosis, miRNA, Th17 cell