Genes In Blood Mononuclear Cells Research Articles

<i>TLR9</i> gene expression in immune cells of patients with psoriasis

Background. Psoriasis (skin lesions and psoriatic arthritis PA) is a chronic inflammatory autoimmune disease that can be triggered by excessive activation of endosomal toll-like receptors (TLRs), mainly TLR9. Elevated TLR9 levels are observed in both PA and psoriasis. Therefore, studying the expression pattern of the TLR9 gene may help select therapies for patients with PA and psoriasis.
 Aim. To study the expression pattern of the TLR9 gene in blood mononuclear cells of PA and psoriasis patients without joint involvement for possible use in the transition to targeted therapy.
 Materials and methods. Mononuclear cells were isolated from the peripheral blood of 31 patients with psoriasis vulgaris without joint involvement, 45 patients with PA, and 20 healthy volunteers. TLR9 gene expression was analyzed by real-time polymerase chain reaction.
 Results. A comparison of expression levels in PA patients and healthy volunteers showed that the expression level of TLR9 in PA patients was 591 times higher than that in healthy volunteers. The expression level of TLR9 in psoriasis patients without joint involvement was also significantly (423-fold) higher than that in healthy subjects.
 Conclusion. TLR9 gene expression in mononuclear cells of psoriasis patients with severe skin lesions is similar to that in PA patients. High levels of TLR9 gene expression may be a marker of possible joint involvement in patients with psoriasis and indicate the need to reconsider the therapeutic approach to a particular patient.

Reduced expression of the tumor necrosis factor gene in blood mononuclear cells in radiologically isolated syndrome – validation of transcriptome analysis results

Radiologically isolated syndrome (RIS) is a nosological form in which magnetic resonance imaging (MRI) reveals lesions of the white matter of the brain and/or spinal cord characteristic of multiple sclerosis (MS) in individuals in the absence of clinical symptoms of the disease. Among the studies devoted to RIS, the number of works aimed at studying the molecular mechanisms underlying its formation is very small. Previously, using next generation sequencing (NGS), we for the first time revealed significant differences in the expression profiles of several genes in peripheral blood mononuclear cells (MNCs) of individuals with RIS and healthy controls.Objective: to conduct a validation analysis of changes in the expression of the CCR2, CX3CR1, and TNF genes that were observed during NGS in the MNCs of individuals with RIS compared with healthy individuals.Patients and methods. Analysis of the expression of the CCR2, CX3CR1, and TNF genes was performed on independent validation cohorts (in MNCs of 14 subjects with RIS and 14 without RIS) by reverse transcription followed by real-time PCR. Results and discussion. In MNCs of subjects with RIS, the TNF gene expression was significantly reduced compared to healthy controls (p=0.035; FC=0.78). No significant differences in expression levels were found for other genes.Conclusion. The obtained data shows that disturbances of TNF gene expression preceding the clinical manifestations of MS, at least in individuals with RIS, which can lead to further dysregulation of several processes.

Identification of miRNA-mRNA-TF regulatory networks in peripheral blood mononuclear cells of type 1 diabetes

BackgroundType 1 diabetes (T1D) is a T lymphocyte-mediated and B lymphocyte-assisted autoimmune disease. We aimed to identify abnormally expressed genes in peripheral blood mononuclear cells (PBMCs) of T1D and explore their possible molecular regulatory network.MethodsExpression datasets were downloaded from the Gene Expression Omnibus (GEO) database. Then, the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRNAs) were identified, and functional enrichment and immune cell infiltration analysis were performed. The starBase, miRTarBase, TarBase, JASPAR, ENCODE, and TRRUST databases constructed the miRNA-mRNA-TF regulatory network. The ROC curves were plotted to evaluate the sensitivity and specificity of miRNAs and mRNAs.ResultA total of 216 DEGs directly or indirectly related to type I diabetes mellitus, natural killer cell-mediated cytotoxicity, Th1, and Th2 cell differentiation, and the IL-17 and TNF signaling pathways were obtained. The miRNA-mRNA-TF network indicates that miR-320a and SOX5 are the only miRNAs and TFs that both target ADM and RRAGD. The ROC curves showed that ADM (0.9375), RRAGD (0.8958), and hsa-mir-320a (0.9417) had high accuracy in T1D diagnosis.ConclusionThe constructed regulatory networks, including miR-320a/ADM/SOX5 and miR-320a/RRAGD/SOX5, may provide new insight into the mechanisms of development and progression in T1D.

Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu's Arteritis.

To explore the relationships between Toll-like receptors (TLRs) and the activation and differentiation of T-cells in Takayasu’s arteritis (TAK), using real-time fluorescence quantitative polymerase chain reaction, mRNA abundance of 29 target genes in peripheral blood mononuclear cells (PBMCs) were detected from 27 TAK patients and 10 healthy controls. Compared with the healthy control group, the untreated TAK group and the treated TAK group had an increased mRNA level of TLR2 and TLR4. A sample-to-sample matrix revealed that 80% of healthy controls could be separated from the TAK patients. Correlation analysis showed that the inactive-treated TAK group exhibited a unique pattern of inverse correlations between the TLRs gene clusters (including TLR1/2/4/6/8, BCL6, TIGIT, NR4A1, etc) and the gene cluster associated with T-cell activation and differentiation (including TCR, CD28, T-bet, GATA3, FOXP3, CCL5, etc). The dynamic gene co-expression network indicated the TAK groups had more active communication between TLRs and T-cell activation than healthy controls. BCL6, CCL5, FOXP3, GATA3, CD28, T-bet, TIGIT, IκBα, and NR4A1 were likely to have a close functional relation with TLRs at the inactive stage. The co-expression of TLR4 and TLR6 could serve as a biomarker of disease activity in treated TAK (the area under curve/sensitivity/specificity, 0.919/100%/90.9%). The largest gene co-expression cluster of the inactive-treated TAK group was associated with TLR signaling pathways, while the largest gene co-expression cluster of the active-treated TAK group was associated with the activation and differentiation of T-cells. The miRNA sequencing of the plasma exosomes combining miRDB, DIANA-TarBase, and miRTarBase databases suggested that the miR-548 family miR-584, miR-3613, and miR-335 might play an important role in the cross-talk between TLRs and T-cells at the inactive stage. This study found a novel relation between TLRs and T-cell in the pathogenesis of autoimmune diseases, proposed a new concept of TLR-co-expression signature which might distinguish different disease activity of TAK, and highlighted the miRNA of exosomes in TLR signaling pathway in TAK.

Minimum redundancy maximal relevance gene selection of apoptosis pathway genes in peripheral blood mononuclear cells of HIV-infected patients with antiretroviral therapy-associated mitochondrial toxicity

BackgroundWe previously identified differentially expressed genes on the basis of false discovery rate adjusted P value using empirical Bayes moderated tests. However, that approach yielded a subset of differentially expressed genes without accounting for redundancy between the selected genes.MethodsThis study is a secondary analysis of a case–control study of the effect of antiretroviral therapy on apoptosis pathway genes comprising of 16 cases (HIV infected with mitochondrial toxicity) and 16 controls (uninfected). We applied the maximum relevance minimum redundancy (mRMR) algorithm on the genes that were differentially expressed between the cases and controls. The mRMR algorithm iteratively selects features (genes) that are maximally relevant for class prediction and minimally redundant. We implemented several machine learning classifiers and tested the prediction accuracy of the two mRMR genes. We next used network analysis to estimate and visualize the association among the differentially expressed genes. We employed Markov Random Field or undirected network models to identify gene networks related to mitochondrial toxicity. The Spinglass model was used to identify clusters of gene communities.ResultsThe mRMR algorithm ranked DFFA and TNFRSF1A, two of the upregulated proapoptotic genes, on the top. The overall prediction accuracy was 86%, the two mRMR genes correctly classified 86% of the participants into their respective groups. The estimated network models showed different patterns of gene networks. In the network of the cases, FASLG was the most central gene. However, instead of FASLG, ABL1 and LTBR had the highest centrality in controls.ConclusionThe mRMR algorithm and network analysis revealed a new correlation of genes associated with mitochondrial toxicity.

Genome-wide mRNA profiling identifies the NRF2-regulated lymphocyte oxidative stress status in patients with silicosis

BackgroundThe immunomodulatory abnormalities of silicosis are related to the lymphocyte oxidative stress state. The potential effect of antioxidant therapy on silicosis may depend on the variation in nuclear factor erythroid 2-related factor 2 (NRF2)-regulated antioxidant genes in peripheral blood mononuclear cells (PBMCs). As NRF2 is a redox-sensitive transcription factor, its possible roles and underlying mechanism in the treatment of silicosis need to be clarified.MethodsNinety-two male patients with silicosis and 87 male healthy volunteers were randomly selected. PBMCs were isolated from fresh blood from patients with silicosis and healthy controls. The lymphocyte oxidative stress state was investigated by evaluating NRF2 expression and NRF2-dependent antioxidative genes in PBMCs from patients with silicosis. Key differentially expressed genes (DEGs) and signaling pathways were identified utilizing RNA sequencing (RNA-Seq) and bioinformatics technology. Gene set enrichment analysis was used to identify the differences in NRF2 signaling networks between patients with silicosis and healthy controls.ResultsThe number of monocytes was significantly higher in patients with silicosis than that of healthy controls. Furthermore, RNA-Seq findings were confirmed using quantitative polymerase chain reaction and revealed that NRF2-regulated DEGs were associated with glutathione metabolism, transforming growth factor-β, and the extracellular matrix receptor interaction signaling pathway in PBMCs from patients with silicosis. The top 10 hub genes were identified by PPI analysis: SMAD2, MAPK3, THBS1, SMAD3, ITGB3, integrin alpha-V (ITGAV), von Willebrand factor (VWF), BMP4, CD44, and SMAD7.ConclusionsThese findings suggest that NRF2 signaling regulates the lymphocyte oxidative stress state and may contribute to fibrogenic responses in human PBMCs. Therefore, NRF2 might serve as a novel preventive and therapeutic candidate for silicosis.

Predicting the allergenicity of legume proteins using a PBMC gene expression assay

BackgroundFood proteins differ in their allergenic potential. Currently, there is no predictive and validated bio-assay to evaluate the allergenicity of novel food proteins. The objective of this study was to investigate the potential of a human peripheral blood mononuclear cell (PBMC) gene expression assay to identify biomarkers to predict the allergenicity of legume proteins.ResultsPBMCs from healthy donors were exposed to weakly and strongly allergenic legume proteins (2S albumins, and 7S and 11S globulins from white bean, soybean, peanut, pea and lupine) in three experiments. Possible biomarkers for allergenicity were investigated by exposing PBMCs to a protein pair of weakly (white bean) and strongly allergenic (soybean) 7S globulins in a pilot experiment. Gene expression was measured by RNA-sequencing and differentially expressed genes were selected as biomarkers. 153 genes were identified as having significantly different expression levels to the 7S globulin of white bean compared to soybean. Inclusion of multiple protein pairs from 2S albumins (lupine and peanut) and 7S globulins (white bean and soybean) in a larger study, led to the selection of CCL2, CCL7, and RASD2 as biomarkers to distinguish weakly from strongly allergenic proteins. The relevance of these three biomarkers was confirmed by qPCR when PBMCs were exposed to a larger panel of weakly and strongly allergenic legume proteins (2S albumins, and 7S and 11S globulins from white bean, soybean, peanut, pea and lupine).ConclusionsThe PBMC gene expression assay can potentially distinguish weakly from strongly allergenic legume proteins within a protein family, though it will be challenging to develop a generic method for all protein families from plant and animal sources. Graded responses within a protein family might be of more value in allergenicity prediction instead of a yes or no classification.

Differential expression of apoptosis related genes in the peripheral blood mononuclear cells of acute lymphoblastic/lymphocytic leukemia (ALL) patients

Apoptosis is the cell’s intrinsic death program which plays a crucial role in the regulation of many normal physiological processes in the body’s tissues. In leukemia patients, the extent of cancer cell susceptibility to apoptosis is correlated with clinical responses to chemotherapy and disease prognosis. The aim of this study was evaluation of the expression of apoptosis related genes in the peripheral blood mononuclear cells (PBMCs) of acute lymphoblastic/lymphocytic leukemia (ALL) patients. Peripheral blood samples were obtained from 20 patients with ALL and 20 healthy individuals. PBMCs were isolated using Ficoll-Paque density gradient centrifugation method. After RNA extraction and cDNA synthesis, gene expression levels of apoptosis related genes including caspase-3, 8, 9, BAX, and BAK genes were measured by real-time RT-PCR technique. Gene expression analysis showed that the expression levels of the initiator caspases-8 and -9 are increased in the PBMCs of adult ALL patients when compared with that in PBMCs of healthy individuals. Increased gene expression levels of the proapoptotic protein BAK was also detected in PBMCs of ALL patients. In contrast, decreased expression levels of the proapoptotic BAX and the executioner caspase-3 were observed in the PBMCs of ALL patients. These results suggest that the expression of genes involved in both extrinsic and intrinsic signaling pathways of apoptosis are induced in PBMCs of ALL patients while the gene expression of other proapoptotic molecule, BAK, and the executioner caspase-3 diminished in PBMCs cells of ALL patients. This findings indicate that resistance to apoptosis may be one of the hallmarks of ALL cells.

RNA Sequencing for Gene Expression Profiles in Peripheral Blood Mononuclear Cells with Ankylosing Spondylitis RNA.

Several previous studies have attempted to investigate the regulatory mechanisms underlying gene expression in ankylosing spondylitis (AS). However, the specific molecular pathways underlying this condition remain unclear. Previous research used next-generation RNA sequencing to identify a series of differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) when compared between patients with AS and healthy controls, thus implying that these DEGs may be related to AS. Furthermore, by screening these DEGS, it may be possible to facilitate clinical diagnosis and optimize treatment strategies. In order to test this hypothesis, we recruited 15 patients with AS and 15 healthy controls. We randomly selected five subjects from each group of patients for RNA sequencing analysis. Sequence reads were generated by an Illumina HiSeq2500 platform and mapped on to the human reference genome using HISAT2. We successfully identified 973 significant DEGs (p < 0.05) in PBMCs. When compared with controls, 644 of these genes were upregulated (with a fold change (FC) > 2) in AS patients and 329 were downregulated (FC < 0.5). Our analysis identified numerous genes related to immune response. Gene Ontology (GO) analysis indicated that these DEGs were significantly related to the positive regulation of epidermal growth factor-activated receptor activity, the positive regulation of the ERBB (erb-b2 receptor tyrosine kinase) signaling pathway, the differentiation of trophoblast giant cells, oxygen transport, immune-related pathways, and inflammation-related pathways. The DEGs were also closely related to the TNF and NF-κB signaling pathways. Six DEGs were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curve analysis indicated that IL6 may represent a useful biomarker for diagnosing AS. The development of new biomarkers may help us to elucidate the specific mechanisms involved in the development and progression of AS.

Expression Profile Analysis of Selenium-Related Genes in Peripheral Blood Mononuclear Cells of Patients with Keshan Disease.

Keshan disease (KD) is an endemic cardiomyopathy, which mainly occurs in China. Selenium deficiency is believed to play an important role in the pathogenesis of KD, but the molecular mechanism of selenium-induced damage remains unclear. To identify the key genes involved in selenium-induced damage, we compared the expression profiles of selenium-related genes between patients with KD and normal controls. Total RNA was isolated, amplified, labeled, and hybridized to Agilent human 4 × 44 K whole genome microarrays. Selenium-related genes were screened using the Comparative Toxicogenomics Database. The microarray data were subjected to single-gene and gene ontology (GO) expression analysis using R Studio and Gene Set Enrichment Analysis (GSEA) software. Quantitative real-time PCR was conducted to validate the microarray results. We identified 16 upregulated and 11 downregulated selenium-related genes in patients. These genes are involved in apoptosis, metabolism, transcription regulation, ion transport, and growth and development. Of the significantly enriched GO categories in KD patients, we identified four apoptosis-related, two metabolism-related, four growth and development-related, and four ion transport-related GOs. Based on our results, we suggest that selenium might contribute to the development of KD through dysfunction of selenium-related genes involved in apoptosis, metabolism, ion transport, and growth and development in the myocardium.

Modulation of the IL-6/STAT3 Signaling Axis in CD4+ T Cells As a Potential Immune Mechanism of Action of Azacytidine in High-Risk Myelodysplastic Syndromes

Modulation of the IL-6/STAT3 Signaling Axis in CD4+ T Cells As a Potential Immune Mechanism of Action of Azacytidine in High-Risk Myelodysplastic Syndromes

Methylation of Specific CpG Sites in IL-1β and IL1R1 Genes is Affected by Hyperglycaemia in Type 2 Diabetic Patients

ABSTRACTObjective: Type 2 diabetes (T2D), which is the most common metabolic disorder in the world, results from insulin resistance of target tissues and reduced production of insulin from pancreatic β cells with genetic and environmental factors both playing roles in the pathogenesis. The aim of this study was to investigate the effect of blood glucose levels on DNA methylation of IL-1β and IL1R1 genes in the peripheral blood mononuclear cells (PBMCs) of non-diabetic, type 2 pre-diabetic and diabetic individuals.Methods: In this case-control study, 54 non-diabetic, pre-diabetic and type 2 diabetic individuals were enrolled and categorized based on their fasting plasma glucose (FPG) and glycated hemoglobin (A1C) levels. DNA was extracted from PBMCs and subjected to bisulfite treatment. The methylation status of two CpG sites in the IL-1β gene and three CpG sites in IL1R1 gene was then determined using Sanger sequencing.Results: Our results show that the methylation of IL-1β gene is decreased and the methylation of IL1R1 gene is increased in diabetic individuals with hyperglycemia. Further analysis revealed that both CpG sites in IL-1β gene are affected by hyperglycemia and display decreased methylation while only one CpG site in IL1R1 gene is affected by hyperglycemia.Conclusion: We propose that the DNA methylation status of the CpG sites cg18773937 and cg23149881 in IL-1β gene and the CpG site cg13399261 in IL1R1 gene could serve as an epigenetic marker of chronic inflammation and T2D development. These CpG sites can also be considered for studies on metabolic memory.

Susceptibility of Specific HLA DRB1*15 AlleleAmong Chronic Hepatitis B Infected Bangladeshi Patients

Background: The outcome of hepatitis B virus (HBV) infection may be influenced by host factors like Human Leukocyte Antigen (HLA).The expression of HLA genes in peripheral blood mononuclear cells (PBMCs) may reflect the molecular mechanism underlying different HBV infection outcomes.&#x0D; Objective: The purpose of the present study was to explore whether HLA DRB1*15 allele confer susceptibility to chronic hepatitis B infected Bangladeshi patients.&#x0D; Method: This cross sectional study was carried out in the Department of Virology, Bangabandhu Sheikh Mujib Medical University (BSMMU) during July 2012 to June 2013 for a period of one year.Evaluation of HLA DRB1*15 allele distribution among 30 chronic hepatitis B infected (HBV) Bangladeshi patients compared them with 30 healthy individuals.HLA DRB1*15 allele distribution was detected by conventional PCR followed by agarose gel electrophoresis, using commercial low-resolution DRB1*15 allele polymerase chain reaction sequence specific priming kit.&#x0D; Result: A total of 30 chronic hepatitis B infected (HBV) Bangladeshi patients were evaluated together with 30 healthy controls. The study revealed a significant increase of DRB1*15 allele (46.7% vs 20%; RR= 3.5; X2 = 7.2; P&lt;0.05) compared to healthy controls. This is the first report on HLA DRB1*15 allele associations among chronic hepatitis B (HBV) infected Bangladeshi patients.&#x0D; Conclusion: The present study reveals that HLA DRB1*15 allele was more frequent in chronic hepatitis B infected Bangladeshi patients compared to healthy individuals. Thus, HLA DRB1*15 allele of HLA class II molecules significantly affect the outcome of hepatitis B infection.&#x0D; Bangladesh Journal of Medical Science Vol.18(4) 2019 p.783-788

Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes.

Calcium (Ca2+) is an important ion in physiology and is found both outside and inside cells. The intracellular concentration of Ca2+ is tightly regulated as it is an intracellular signal molecule and can affect a variety of cellular processes. In immune cells Ca2+ has been shown to regulate e.g. gene transcription, cytokine secretion, proliferation and migration. Ca2+ can enter the cytoplasm either from intracellular stores or from outside the cells when Ca2+ permeable ion channels in the plasma membrane open. The Ca2+ release-activated (CRAC) channel is the most prominent Ca2+ ion channel in the plasma membrane. It is formed by ORAI1-3 and the channel is opened by the endoplasmic reticulum Ca2+ sensor proteins stromal interaction molecules (STIM) 1 and 2. Another group of Ca2+ channels in the plasma membrane are the voltage-gated Ca2+ (CaV) channels. We examined if a change in immunological tolerance is accompanied by altered ORAI, STIM and CaV gene expression in peripheral blood mononuclear cells (PBMCs) in pregnant women and in type 1 diabetic individuals. Our results show that in pregnancy and type 1 diabetes ORAI1-3 are up-regulated whereas STIM1 and 2 are down-regulated in pregnancy but only STIM2 in type 1 diabetes. Expression of L-, P/Q-, R- and T-type voltage-gated Ca2+ channels was detected in the PBMCs where the CaV2.3 gene was up-regulated in pregnancy and type 1 diabetes whereas the CaV 2.1 and CaV3.2 genes were up-regulated only in pregnancy and the CaV1.3 gene in type 1 diabetes. The results are consistent with that expression of ORAI, STIM and CaV genes correlate with a shift in immunological status of the individual in health, as during pregnancy, and in the autoimmune disease type 1 diabetes. Whether the changes are in general protective or in type 1 diabetes include some pathogenic components remains to be clarified.

Changes in peroxisome proliferator-activated receptor alpha target gene expression in peripheral blood mononuclear cells associated with non-alcoholic fatty liver disease

ObjectiveTo identify differences in the expression of peroxisome proliferator-activated receptor alpha (PPARα) target genes in human peripheral blood mononuclear cells (PBMCs) associated with non-alcoholic fatty liver disease (NAFLD) among Chinese individuals.MethodsThirty healthy subjects were selected as the control group (CN), and 43 patients newly diagnosed with NAFLD were subdivided into two groups, non-obese group (NF, n = 21) and obese group (OF, n = 22). Expression of PPARα and its target genes was determined in PBMCs. The levels of liver cell damage markers, total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), glucose, and insulin were determined in serum.ResultsCompared to the CN group, the blood pressure and homeostasis model assessment for insulin resistance (HOMA-IR) were increased in the other groups (P < 0.05), while the systolic blood pressure (SBP) and liver cell damage markers were significantly increased in the OF group (P < 0.05). In the OF group, PPARα target gene expression was 2.03–3.31 times higher than that in the CN group, and a negative correlation was found between PPARα target gene expression and abdominal circumference (AC), body mass index (BMI), diastolic blood pressure (DBP). Additionally, solute carrier family 25 (carnitine/acylcarnitine translocase) member 20 (SLC25A20) and acyl-coenzyme A dehydrogenase 2 long chain (ACADVL) were negatively correlated with HOMA-IR; PPARα, acetyl-coenzyme A dehydrogenase 2 (ACAA2), and carnitine palmitoyltransferase 1A (CPT1A) were positively correlated with HOMA-IR.ConclusionThere is an up-expression of PPARα target genes in the PBMCs of NAFLD patients, possibly leading to changes in β-oxidation and insulin resistance.

The circadian rhythm of glucocorticoid administration entrains clock-controlled genes in blood mononuclear cells: a DREAM trial ancillary study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Circulatory TGF-beta1 is significantly higher in early stage of pulmonary sarcoidosis.

Introduction: The pathogenesis of pulmonary fibrosis in sarcoidosis is not known. We hypothesized that higher levels of circulatory growth factors are present in early stages of pulmonary sarcoidosis and may be associated with pulmonary fibrosis. Methods: Age and sex-matched subjects with sarcoidosis stage 0-1 (n=18), stage 4-5 (n=13) and healthy controls (n=5) had their serum TGF-β1, FGF, and VEGF levels measured as well as their gene expressions determined in peripheral blood mononuclear cells. Results: TGF-β1 levels were significantly higher in patients with stage 0-1 sarcoidosis compared with normal healthy control patients (25,488 vs. 13800 pg/ml, P=0.05). Patients with sarcoidosis stage 4 had a 1.3-fold higher peripheral blood mononuclear cells (PBMC) gene expression of TGF-β1 compared with subjects at stage 0-1 (P= 0.041). The serum levels of FGF, and VEGF had a trend towards higher levels in sarcoidosis subjects compared to normal controls. Conclusion: These results suggest that cell growth factors levels are high in early stages of sarcoidosis. These findings should be validated in larger studies. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 213-217).

Quercetin reduces the transcriptional activity of NF-kB in stable coronary artery disease

ObjectiveThe aim of this study was to determine the effect of quercetin on the indicators of chronic systemic inflammation (CSI) in stable coronary artery disease (CAD). MethodsThis study included 85 patients with CAD, stable angina pectoris, functional class (FC) II, and heart failure (НF) 0-І. Each patient was prescribed beta-blockers, statins, and aspirin. In addition, a total of 30 patients, forming the study group received quercetin at a daily dose of 120mg for two months, while the remaining 55 patients made up the control group. The levels of cytokines, such as tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-10 (IL-10) in serum and the expression of the inhibitor of kappa B α (IkBα) gene in blood mononuclear cells, were determined. ResultsThe increased levels of IL-1β and TNF-α, as well as a moderate increase in IL-10 levels, were detected in the serum of patients with CAD. The expression of the IkBα gene (2–δСt) did not differ significantly between the groups. Under the influence of quercetin, levels of IL-1β and TNF-α were reduced and IL-10 levels tended to decrease. In contrast, the serum levels of these cytokines did not change significantly in the control group. The administration of quercetin decreased the expression of the IkBα gene (0.0092±0.0033 against 0.0261±0.0166, р=0.003; 2–δδСt, 2.82±1.39 times) in contrast to the control group. ConclusionQuercetin showed anti-inflammatory properties in patients with CAD, indicating a decrease in transcriptional activity of the nuclear factor of transcription kappa B (NF-kB).

Transient Receptor Potential Ion Channels in the Etiology and Pathomechanism of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling condition of unknown cause having multi-system manifestations. Our group has investigated the potential role of transient receptor potential (TRP) ion channels in the etiology and pathomechanism of this illness. Store-operated calcium entry (SOCE) signaling is the primary intracellular calcium signaling mechanism in non-excitable cells and is associated with TRP ion channels. While the sub-family (Canonical) TRPC has been traditionally associated with this important cellular mechanism, a member of the TRPM sub-family group (Melastatin), TRPM3, has also been recently identified as participating in SOCE in white matter of the central nervous system. We have identified single nucleotide polymorphisms (SNPs) in TRP genes in natural killer (NK) cells and peripheral blood mononuclear cells (PBMCs) in CFS/ME patients. We also describe biochemical pathway changes and calcium signaling perturbations in blood cells from patients. The ubiquitous distribution of TRP ion channels and specific locations of sub-family group members such as TRPM3 suggest a contribution to systemic pathology in CFS/ME.

Comparative Evaluation of IL-16 mRNA level and rs1131445 polymorphism of IL-16 gene in Peripheral Blood Mononuclear Cells of patients with Inflammatory Bowel Diseases

Aberrant immune response in a gene cally susceptible host is acknowledged in the pathogenesis of In ammatory Bowel Diseases (IBD) including Crohn’s disease (CD) and Ulcerative colitis (UC). Here we aimed to evaluate IL-16 mRNA level, as the immune component and rs1131445 polymorphism of IL- 16 gene, as the gene c susceptibility component of IBD development in PBMC sample. A total of 97 IBD patients (13 CD and 84 UC) and 100 healthy controls were included. Peripheral Blood Mononuclear Cells (PBMCs) were extracted. Polymorphism evaluation was performed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) and the results were confirmed by sequencing method. Comparative Real- time PCR method was used for IL-16 mRNA assessment. A 3.92-fold increase was observed in the expression level of IL-16 in PBMC of IBD patients compared to the controls (p&lt;0.0001). IL-16 expression was not signi cantly di erent in di erent IBD forms and pathological phases. Distribu on of rs1131445 polymorphism was not significantly different between controls and pa ents (P=0.825). Distribu on of CC genotype was signi cantly higher in CD patients (P=0.016). Although IL-16 mRNA level was considerably lower in CC genotype, this difference was not statistically significant (p=0.537). Lower IL-16 mRNA level was observed in CC genotype of rs1131445 SNP which was not in accordance with the expectations and needs to be further investigated. These data suggest that IL-16 level could be considered as a prognostic marker in Iranian IBD patients.