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Undoubtfully, the normal immune system can make a potential response to variable pathogens and neutralize or kill them depending on the type of infection through innate and acquired immunity. Cytokines have poly-peptide nature and are considered as signaling molecules that could amplify or alleviate immune responses besides their other biological functions. Interleukin 38 (IL-38) is a member of the IL-1 family cytokine that, however, its anti-inflammatory role has been observed in different autoimmune diseases like systemic lupus erythematosus (SLE), psoriasis, and Sjogren's syndrome; there is a controversy about the cytokine pro-inflammatory function. In the current review, we skimmed IL-38 structure, signaling mechanism, and its immunological functions, IL-38-producing immune cells. Also, we argued about the role of this cytokine in viral infections including hepatitis B (HBV), hepatitis C (HCV), influenza (Flu), and COVID-19. Also, it illustrated the IL-38 protective effects on sepsis. Moreover, we explained the modulatory role of IL-38 in the COVID-19 cytokine storm.

Background Small non-coding RNAs have emerged as essential modulators of viral infections such as hepatitis C virus (HCV). Cellular miRNAs directly regulate the viral infectivity and indirectly by targeting virus-host factors. The current study investigates the inhibitory effect of let-7b miRNA on HCV replication in the Hepatocarcinoma cell line (Huh7.5). Methods and results The algorithm-based search revealed that let-7b, a high score microRNA, has target sequences on the HCV genome. The Huh7.5 cells were stably transduced with let-7b lentiviral vectors (Huh7.5/let-7b) and mock (Huh7.5/scrambled). The expression of the let-7b level was assessed by real-time PCR assay and Red fluorescence microscope. A dual-luciferase assay was conducted to evaluate the liver-specific let-7b and HCV genome interaction. In the next step, for establishing HCVcc, Full-length HCV-RNA was transduced to naive Huh7.5, Huh7.5/scrambled, and Huh7.5/let-7b cells. The results of in silico analysis and dual-luciferase reporter assay exhibited a specific interaction of HCV-NS5B and let-7b. Real-time PCR analysis revealed that in contrast to infected naive Huh7.5 cells and Huh7.5/scrambled, a significant decrease in HCV-RNA load was seen in Huh7.5/let-7b cells. On the other hand, the Flow Cytometry test showed that let-7b could significantly induce the apoptosis pathway in Huh7.5/let-7b. Conclusions The results also suggest that let-7b, as a target of the HCV genome, potentially reduces HCV replication and raises cell apoptosis rate. We suggest that let-7b directly downregulates HCV replication and may serve as a unique antiviral therapy.

Staphylococcus aureus is an important human opportunistic pathogen that can have a major influence on public health. Here, we aimed to evaluate different aspects of the immune response to a novel multi-epitope fusion protein (HMS) based on HlaH35L, MntC, and SACOL0723 proteins in comparison to the individual antigens. For this purpose, specific total IgG, IgG1, and IgG2a isotypes and the cytokines related to Th1, Th2, and Th17 were assessed. The Bio-efficiency of the fusion protein was evaluated by opsonic killing activity. The HMS fusion protein elicited a high specific IgG level and also induced a higher level of Th1, Th2, and Th17-related cytokines which were more polarized towards the Th1 and Th17 compared to individual antigens. The HMS-specific antisera also significantly promoted phagocytosis of S. aureus COL strain by mouse macrophages. In conclusion, the fusion protein might be an effective vaccine for potential protective immunity against a lethal infection of S. aureus in mice.

From December 2019, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was started as a cluster of pneumonia cases in Wuhan, Hubei Province, China. The disturbing statistics of SARS-CoV-2 promoted scientists to develop an effective vaccine against this infection. NOM protein is a multi-epitope protein that designed based on Nucleocapsid, ORF3a, and Membrane proteins of SARS-CoV-2. Flagellin is a structural protein that binds to the Toll-like receptor 5 and can enhance the immune response to a particular antigen. In this study, NOM protein as vaccine candidate was linked to the carboxyl and amino terminals of flagellin adjuvant derived from Salmonella enterica subsp. enterica serovar Dublin. Then, informatics evaluations were performed for both NOM protein and NOM protein linked to flagellin (FNOM). The interaction between the NOM and FNOM proteins with the TLR5 were assessed using docking analysis. The FNOM protein, which compared to the NOM protein, had a more suitable 3D structure and a stronger interaction with TLR5, was selected for experimental study. The FNOM and Spike (S) proteins expressed and then purified by Ni-NTA column as vaccine candidates. For analysis of immune response, anti-FNOM and anti-S proteins total IgG and IFN-γ, TNF-α, IL-6, IL-10, IL-22 and IL-17 cytokines were evaluated after vaccination of mice with vaccine candidates. The results indicated that the specific antisera (Total IgG) raised in mice that received FNOM protein formulated with S protein were higher than mice that received FNOM and S proteins alone. Also, IFN-γ and TNF-α levels after the spleen cells stimulation were significantly increased in mice that received the FNOM protein formulated with S protein compared to other groups. Immunogenic evaluations showed that, the FNOM chimeric protein could simultaneously elicit humoral and cell-mediated immune responses. Finally, it could be concluded that the FNOM protein formulated with S protein could be considered as potential vaccine candidate for protection against SARS-CoV-2 in the near future.

This study seeks to evaluate the effects of Iranian green propolis (IGP) and Leishmania heat shock protein (HSP) 70 as adjuvants, each combined with Leishmania glycoprotein (Gp) 63 as an antigen, o...

Little is known about the clinical significance of the peripheral blood CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) and T helper-17 (Th17) cells in lymphoma patients. In this study, the prognostic and clinical significance of peripheral blood Tregs and Th17 cells were evaluated in lymphoma patients during different phases. The frequency of Tregs and Th17 lymphocytes was measured by flow cytometry method in 47 classical Hodgkin's lymphoma (cHL) and 48 diffuse large B cell lymphoma (DLBCL) patients. Our results showed that the frequency of Tregs and absolute Treg count was significantly reduced in relapsed patients compared to patients at the remission phase, as well as with newly diagnosed untreated patients in both groups. Patients who reached complete remission had elevated frequency of CD4+ FOXP3+ lymphocytes, Tregs, absolute Treg count, Treg/CD4 and Treg/Th17 ratio in the cHL group and CD4+ CD25+ cells in DLBCL group. The frequency of Tregs, absolute Treg count and Treg/Th17 ratio in cHL patients and CD4+ FOXP3+ and CD4+ CD25+ cells in DLBCL patients positively associated with survival rate. Moreover, the percentage of Tregs and absolute Treg count positively correlated with white blood cell, platelet count and ESR level in cHL patients and with white blood cell count in DLBCL patients. The initial number of Tregs/Th17 cells and also the Treg/Th17 ratio was not associated with changes in disease-free survival (DFS) in both groups. Therefore, higher frequency of peripheral blood Tregs and Treg/Th17 ratio might be associated with a favorable outcome in lymphoma patients, better response to chemotherapy and lower rate of relapse.

Purpose: Given the challenge in the diagnosis of bacterial meningitis (BM), we assessed different cytokines in the cerebrospinal fluid (CSF) of antibiotics pre-treated patients.Materials and method...

A decrease in T cell count or reduced T cell function can be indicative of T cell immunodeficiency. In the present study, T-cell function was assessed using Carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution test after stimulation with commonly used Phytohaemagglutinin (PHA) or anti-CD3/anti-CD28 coated beads in pediatric patients with recurrent infections. Seven infants with recurrent infections and seven sex/age-matched healthy infants were included in this study. A blood cell count, immunophenotyping, and serum immunoglobulin level were performed. The proliferation of T cells was also assessed with CFSE dilution after stimulation with PHA or anti-CD3/anti-CD28 coated beads. This study showed increased IgA, IgG, and IgM levels in patients compared to the controls. In contrast to the controls, the immunophenotyping results showed a significant decline in the number of CD4+ T cells in patients. Although there was no difference in CD3+ T cell proliferation between patients and controls, the CD4+ and CD8+ T cell proliferation rates were significantly decreased in patients when stimulated with PHA. As a mitogen with the potential for maximum proliferation of T cells, PHA is better able to distinguish between patients with recurrent infections and controls than anti-CD3/anti-CD28, which mimics only the TCR pathway for stimulation of T cells.

Staphylococcus aureus infections are now one of the most common causes of surgical drainage, bacteremia, and hospital-acquired infections. The emergence of antibiotic resistance has increased mortality and costs of treatment. The design of a new vaccine against S. aureus would have a great beneficial impact on public health. In the current report, we design and introduce a novel epitope-based fusion protein (Hla, MntC and SACOL0723) and investigate its biological activities. Three known antigenic proteins from S. aureus were analyzed for the prediction of immunogenic B and T-cell epitopes and validated using bioinformatics tools. The affinity and the map of interactions between the receptor and ligand were evaluated via docking protocols. Functional activity of the recombinant protein was assessed by western blot and opsonophagocytosis tests and determining the bacterial burden from the infected tissues. To determine the type of induced immunity, cytokines profile and isotyping ELISA was performed. Based on in silico analysis, seven epitopes rich domain including highly scored T and B-cell epitopes were selected. The study results indicated that the high titer of specific antibodies raised against the vaccine candidate could opsonize the bacteria and decrease the viable bacterial cells. The fusion protein was able to elicit a mixture of Th1, Th2, and Th17 immune responses more towards Th1 and Th17. In conclusion, the fusion protein formulated with alum could be considered as a potential vaccine candidate for protection against S. aureus in the near future.

Visceral leishmaniasis (VL) is a life threatening disease in which a variety of cytokines regulating the immune responses can determine its outcome. As based on their region in the gene, some single nucleotide polymorphisms (SNP) can influence the expression of their corresponding proteins, this study aimed to investigate the association between SNP in the IL-10, IL-12, IFN-γ genes and susceptibility to VL. The study was carried out on 120 patients with VL, 67 patients’ families (family group), and 102 healthy individuals with positive leishmanin skin test as positive control group. SNPs in IL-10 (−592, −819, −1082), IL-12 (+1188) were analyzed using PCR-RFLP and allele specific polymerase chain reaction (ASPCR) was used to analyze SNPs in IFN-γ (+874 A/T). The results showed that at position +874 of IFN-γ, AT genotype was significantly more frequent in patients than that in families and controls, but TT genotype was significantly more frequent in families than in patients. Distributions of IFN-γ alleles were not significantly different between the study groups. As for IL-12 and IL-10 genotypes and alleles, no significant difference was observed between the groups. Although a strong linkage disequilibrium was observed between alleles −592, −819 and −1082 of IL-10, distributions of the most common haplotypes and haplogenotypes reconstructed from IL-10 alleles were not significantly different between the study groups. It could be suggested that heritage of AT genotype at position +874 of IFN-γ may predispose and TT genotype can resist individual to VL in an endemic area in the southwest of Iran.

Plasmacytoma variant translocation 1 (PVT1) is a newly discovered long non-coding RNA, which has not been previously studied in the inflammatory responses of the peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD).This cross-sectional study was conducted on 15 CAD patients and 15 non-CAD (NCAD) individuals. The PVT1 expression was assessed in the PBMCs of the participants using a real-time polymerase chain reaction. Interleukin (IL)-10, IL-22, and matrix metalloproteinase-9 (MMP-9) were measured in the plasma and supernatant of cultured PBMCs in the presence or absence of lipopolysaccharide (LPS) using flow cytometry and enzyme-linked immunosorbent assay.An increased expression of PVT1 was observed in the untreated PBMCs of CAD patients, compared to the NCAD group. The PVT1 was significantly up-regulated after LPS treatment in the PBMCs of both groups. Plasma MMP-9 levels were found to be higher in CAD patients than in the control individuals. The level of IL-10 and IL-22 production by the non-treated PBMCs of CAD cases was significantly lower than the NCAD group. Overall, in the examined population, PVT1 expression was negatively correlated with IL-10 secretion. Moreover, the results showed a significant negative correlation between PVT1 expression and IL-10 production by untreated cells.The PVT1 expression augmented in the PBMCs of CAD patients, which could be associated with the decreased IL-10 generation by the PBMCs of these patients.

Adipokines are peptides that regulate endothelial function, inflammation, blood pressure, and hemostasis. We measured Leptin, Adiponectin, Resistin and Adipsin in a cohort of 36 STEMI patients. Serum levels of Adipokines were measured in three time-points by a multiplex assay. A significant difference in Adipsin concentration between day-5 (T5) and day-180 (T180) post-MI was observed. Resistin levels decreased significantly from day 0 (T0) to T5 and T180. Adiponectin/Resistin ratio increased from T0 to T180. Leptin at T0 and T5 were higher in non- smokers. Adipsin at T0 was inversely correlated with heart rate, respiratory rate and pulse rate. Adiponectin/Resistin ratio at T180 negatively correlated with respiratory-rate. Adiponectin/Resistin ratio at T180 was higher in patients with grade-1 atrioventricular (AV) block. Anteroseptal hypokinesia (AH) correlated with Resistin at T0 and Adipsin at T5 while Leptin at T0 and T5 correlated with AH. Adiponectin/Resistin ratio at T180 was; however, lower in patients with AH. A decreasing trend in Resistin and its T0 association with AH plus correlation of Leptin at T0 and T5 with AH show the effect of Adipokines on mechanical complications after MI. We suggest that Adipokine networks have both beneficial and harmful effects and may be new cardiac biomarkers and/or drug targets.

One of the most prevalent malignancies, which have severe effects on women's health, is breast cancer. Quercetin, a flavonoid found in vegetables, tea, and fruits, is known to have bioactive properties, such as anti-inflammatory, anti-oxidant, as well as anti-cancer. Long non-coding RNAs (lncRNAs) have been recognized to function as primary regulators of diverse cellular processes, including differentiation, development, and cell fate.

The role of T-helper lymphocytes especially T helper 2 (Th2) subsets in lymphoid malignancies is debatable and unknown.Herein, we evaluated the polarization of the IFN-γThe proportion of IFN-γTaken together, higher peripheral blood IFN-γ

Radioactive iodine (RAI)-induced thyrocyte destruction may lead to uncontrolled inflammation. This study was designed to evaluate the prophylactic and therapeutic immunomodulatory effects of omega-3 fatty acids in patients with differentiated thyroid cancer scheduled for RAI ablation. A total of 85 patients were divided into two groups based on radioiodine dosage after thyroidectomy: high-dose with 150 mCi and intermediate-dose with 100 mCi. Then patients in each group were randomly divided into three subgroups: G1 with RAI ablation only, G2 treated with omega-3 for 30 days before RAI ablation, and G3 treated with omega-3 for 30 days after RAI ablation. Serum cytokine levels were determined with the cytometric bead assay at different time points. Within-group comparisons showed transient elevation of IL-13 after pretreatment with omega-3, significant reductions in Th1+Th17/Th2+Th22 ratio after high-dose RAI ablation, and decreased Th1+Th17/Th2+Th22 and Th1+Th17/Th2+Th9+Th22 ratios after intermediate-dose RAI ablation in G2. Between-group comparisons showed that IL-10 level in G3 was significantly higher than in G1 1 week after high-dose RAI ablation, whereas Th1+Th17/Th2+Th22 and Th1+Th17/Th2+Th9+Th22 ratios were significantly lower in G3 than G2 1 month after intermediate-dose RAI ablation. However, cytokine changes 1 week and 1 month after RAI ablation when adjusted for baseline values showed no differences among groups. Despite observing within-group changes in some cytokines, we found no real changes attributable to a prophylactic or therapeutic anti-inflammatory effect of omega-3. Because of the specific effect of radioactive iodine on thyroid cells, extensive systemic inflammation may not be induced after RAI ablation.

AIMS Given the involvement of IL-9 in the immune responses to parasitic infections, we aimed to determine alterations in the levels of IL-9+CD4+ T cells and the cytokines influencing their differentiations and functions following treatment in paediatric visceral leishmaniasis (VL). METHODS AND RESULTS Eighteen VL and 20 healthy children were included. The levels of IL-9+CD4+ T cells and cytokines influencing their differentiations and functions were measured in the blood and PBMC culture supernatant at the onset of diagnosis and 1 and 2 weeks and 2 months after treatment, using flow cytometer. IL-9+CD4+ T cells, IL-2 and TNF-α were significantly higher in the blood of VL patients than those in the controls; however, following treatment, IL-9+CD4+ T cells down-regulated and IL-33 and IFN-γ significantly up-regulated. After ex vivo stimulation, although the released cytokines were not significantly different between the study groups, the levels of IL-2, IL-9 and IFN-γ significantly decreased. CONCLUSIONS The higher frequency of IL-9+CD4+ T cells and its decline following treatment implies their roles in the immunopathogenesis of VL; however, at the diagnosis onset, lower levels of serum IL-9 and its higher level in the culture supernatant may confer in vivo dysfunction of IL-9+CD4+ T cells in the acute phase of human VL.

Staphylococcus aureus is an important human opportunistic pathogen that can have a major influence on public health. Here, we aimed to evaluate different aspects of the immune response to a novel multi-epitope fusion protein (HMS) based on Hla

Background: Plasmacytoma variant translocation 1 (PVT1) is a newly discovered long non-coding RNA (lncRNA), and it has not been previously studied in the inflammatory responses of peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD). Methods: This cross-sectional study was conducted in 15 CAD patients and 15 non-CAD (NCAD) individuals. PVT1 expression in PBMCs of the participants was measured, using real-time PCR. Interleukin (IL)-10, IL-22 and MMP-9 in the plasma and supernatant of the cultured PBMCs in the presence or absence of lipopolysaccharide (LPS) was assessed, using flowcytometry and ELISA.Results: An increased expression of PVT1 was observed in untreated PBMCs of CAD patients compared to the NCAD group. There was a significant up-regulation of PVT1 after LPS treatment in PBMCs of both groups. Plasma matrix metalloproteinase-9 (MMP-9) levels were found to be higher in CAD patients compared to the controls. The level of IL-10 and IL-22 production from the non-treated PBMCs of CAD was significantly lower compared to the NCAD group. In the total examined population, PVT1 expression was negatively correlated with IL-10 secretion. The results also showed a significant negative correlation between PVT1 expression and IL-10 produced by untreated cells. Conclusions: PVT1 expression is increased in PBMCs of CAD patients and this increased expression could be associated with decreased IL-10 production from PBMCs of these patients.

SUMMARY OBJECTIVE: This study aimed to investigate the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) expression and its role in cytokine production from peripheral blood mononuclear cells (PBMCs) in patients with coronary artery disease (CAD) and non-CAD participants (NCAD). METHODS: Blood samples were taken from 15 patients with CAD and 15 NCAD individuals. The plasma was used for biochemical analyses. MALAT1 and CD36 expressions were evaluated in the isolated peripheral blood mononuclear cells (PBMCs) by real-time PCR. Furthermore, the levels of inflammatory cytokines e.g. interleukin (IL)-6, IL-10, and IL-22 were measured in the supernatants of the cultured PBMCs by flow cytometry. RESULTS: The levels of MALAT1 and CD36 were not significantly different between the CAD and NCAD groups. However, a lower level of MALAT1 and CD36 was observed in PBMCs of vitamin D deficient (

Regarding the role of micro RNAs (miRNA) in the proliferation and differentiation of T cells as well as the controversy around the role of bacteria in the pathogenesis of abdominal aortic aneurysm (AAA), the effects of Helicobacter pylori (Hp) and Lactobacillus acidophilus (La) were investigated in the induction of miRNAs and apoptosis in CD4+ memory T (Tem) cells of AAA patients and controls. Signature atherosclerosis miRNAs 21, 92a, 146a, 155, 326 and 663 were measured in the sera and tissues of AAA patients and control. PBMCs separately and in co-culture with HUVEC were treated with Hp-water-extract (HpWE) and La-conditioned-medium (LaCM). Apoptosis and miRNA levels were assessed in the isolated Tem by flowcytometry and real-time-PCR. In single-culture, HpWE increased apoptosis and miR-155 and LaCM decreased apoptosis and increased miR-21. In co-culture, apoptosis decreased in both groups in response to CagA+HpWE. Also, all miRNAs increased in patients Tem but in controls, only miR- 146a and 21 showed changes. Although, apoptosis was similar in Tem of patients and controls, the effects of Hp and La were different on the induction of apoptosis and miRNAs and also these bacteria showed different impacts in single and co-culture conditions. Beyond the direct effects of these bacteria on the pathogenesis of diseases, their effects on miRNAs expression may shed light on their roles in the development and the prevention of AAA.

Little is known about the clinical significance of the peripheral blood CD4

Toll-like receptors (TLRs) are among the players of inflammation during atherosclerosis. We assessed the effects of Eritoran, a TLR-4 antagonist, on lipopolysaccharide (LPS)-induced cytokines production by Peripheral Blood Mononuclear Cells (PBMCs) of patients with high-stenosis (HS) (n = 6) and healthy controls (HCs) (n = 6) co-cultured with Human Umbilical Vein Endothelial Cells (HUVECs). LPS stimulation significantly increased the levels of IL-6 (P = 0.007 and P = 0.005), TNF-α (P = 0.006 and P = 0.005), IL-2 (P = 0.007 and P = 0.002), IFN-γ (P = 0.006 and P = 0.003), IL-17A (P = 0.004 and P = 0.003), IL-17F (P = 0.005 and P = 0.003), IL-5 (P = 0.007 and P = 0.005), IL-13 (P = 0.006 and P = 0.005), IL-9 (P = 0.005 and P = 0.005) and IL-21 (P = 0.007 and P = 0.005) in HUVECs co-cultured with HC and HS PBMCs as compared with un-stimulated co-culture condition, respectively. Eritoran treatment (50 μg/mL and 100 μg/mL) significantly reduced the levels of LPS-induced IL-6 (P = 0.007 and P = 0.006; P = 0.007 and P = 0.007), TNF-α (P = 0.005 and P = 0.003; P = 0.007 and P = 0.005), IL-2 (P = 0.007 and P = 0.005; P = 0.005 and P = 0.004), IFN-γ (P = 0.007 and P = 0.005; P = 0.005 and P = 0.004), IL-17A (P = 0.005 and P = 0.002; P = 0.005 and P = 0.002), IL-17F (P = 0.006 and P = 0.006; P = 0.005 and P = 0.005), IL-5 (P = 0.007 and P = 0.006; P = 0.007 and P = 0.007), IL-9 (P = 0.005 and P = 0.005; P = 0.005 and P = 0.005) and IL-21 (P = 0.007 and P = 0.007; P = 0.005 and P = 0.005) in stimulated HUVECs co-cultured with HC and HS PBMCs, compared to un-treated condition, respectively. Our results demonstrate that attenuating effect of Eritoran on the inflammatory responses to LPS is higher in PBMCs of patients with high stenosis, suggesting its potential role in ameliorating inflammatory conditions in atherosclerosis.

Classic galactosemia is an autosomal recessive disorder of galactose metabolism, which can result in life-threatening complications due to mutations within the GALT gene. Definite diagnosis of classic galactosemia is established by the detection of pathogenic mutations in the GALT gene. Herein we are reporting a novel missense mutation (c.516A>T; p.Glu172Asp) in exon 6 of the GALT gene in the homozygous state in a 2-year-old female infant. Screening-test for galactosemia was abnormal in this patient. We evaluated the GALT protein structure using molecular docking analysis. Accordingly, we identified that the Glu172 is one of the galactose 1-phosphate binding sites, and a substitution mutation in this position can disrupt the active site of GALT protein.

Considering the collaboration between immune responses and medications for the improvement of visceral leishmaniasis (VL), this study investigated the levels of T helper (Th) 22 and the corresponding cytokines in the acute phase of VL and their alterations following treatment. The study was conducted on 18 patients with confirmed VL and 20 healthy sex and age matched children as the controls. The levels of Th22 cells and the cytokines driving their differentiations and functions in the blood and peripheral blood mononuclear cells (PBMC) cultured supernatants, were assessed using flow cytometry method. The results revealed significantly higher levels of Th22, IL-21 and IL-6 in the patients' blood than those in the controls. Additionally, higher levels of IL-21 and IL-22 were observed in the cultured supernatants of VL patients' PBMCs, compared to the controls. Upon treatment, Th22 and IL-6 were down-regulated and conversely, IL-21, IL-22, IL-23 and IL-33 were significantly up-regulated in the patients' blood at different time points. Receiver operating characteristic (ROC) curve analysis indicated that for the differential diagnosis of VL, plasma IL-21 is more sensitive and specific than Th22 and the above mentioned cytokines. The higher proportions of Th22 and IL-21 in the VL patients and their alterations post treatment confer their roles in the immunopathogenesis of VL. So, Th22 and IL-21 in the patients' blood can be considered as biomarkers to be used for the differential diagnosis of VL. Nevertheless, further studies are warranted to clarify their particular mechanisms in this process.

Visceral leishmaniasis (VL) is an infectious disease caused by an intracellular protozoan belonging to Leishmania species. Interleukin (IL)-22 plays an important role in inflammatory response, chemotaxis, regulation of cellular proliferation and tissue repair. Considering the role of IL-22 in control of leishmaniasis and the effect of its single nucleotide polymorphisms (SNPs) on respective function and production, this study aimed to investigate the probable association of IL-22 SNPs with VL. The study was carried out on 110 patients with VL, 102 healthy individuals with negative leishmanin skin test (negative control group (NCG)), and 144 healthy individuals with positive leishmanin skin test (LSTPG). Four SNPs in IL-22 including rs2227501, rs2227503, rs2227513 and rs1026786 were analyzed by polymerase chain reaction-restricted fragment length polymorphism (PCR– RFLP) in the study groups. The frequency of A allele and AA genotype at rs1026786 were significantly higher in the LSTPG group than in the patients (P = 0.013 and P = 0.001, respectively). Conversely, the frequency of AG genotype was significantly higher in the patients and the NCG than in the LSTPG group (P = 0.0001 and P = 0.002, respectively). For rs2227503, the frequency of AG genotype was significantly higher in the LSTPG group than in the NCG (P = 0.025). The haplotype TGAA frequency was significantly higher in the NCG, compared to patients and LSTPG group (P = 0.004 and P = 0.023, respectively). The frequencies of haplotypes TAAG and TGAG were significantly higher in the patients than in the LSTPG group (P = 0.046 and P = 0.014, respectively). The TAAA/TAAG frequency was significantly higher in the patients than in the LSTPG group (P = 0.013). Inheritance of rs1026786 A allele and AA genotype of IL-22 could be a possible protective factor against VL, whereas the inheritance of the haplotypes TAAG and TGAG may predispose Iranian population to the disease.

Brucella is an obligate intracellular gram negative bacterium and the causative agent of brucellosis. Interleukin-2 (IL-2) is a cytokine involved in cell-mediated immunity response secreted by activated T-cells and considered as the growth factor for T-cells. Previous reports have revealed that gene polymorphisms of cytokines can affect susceptibility to Brucella infection. The goal of this study was to investigate the relationship between IL-2 gene polymorphisms (positions +114 and −384) and susceptibility to brucellosis. A total of 173 brucellosis patients and 75 healthy animal husbandmen who had Brucella infected animals and consumed their contaminated dairy products, as control group, were included in this study. All participants were genotyped for IL-2 gene polymorphisms at positions +114 (G/T) and −384 (G/T), using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The frequency of TT genotype at the position +114 was significantly higher in the controls, compared with the patients. But, there was no significant difference between the groups regarding TG and GG genotypes as well as T and G alleles. Furthermore, at position −384, the frequencies of G allele and GG genotype were higher in the controls compared with patients, however, they were not significantly different Additionally, TT/TT haplogenotype (+114/−384) was significantly higher in the controls, compared with the patients. Conclusively, it is suggested that the inheritance of TT genotype (position +114) and TT/TT haplogenotype (+114/−384) of IL-2 gene could be considered as one of the genetic factors responsible for resistance to brucellosis.

Inflammation and oxidative stress are important risk factors affecting various cells in the formation of atherosclerosis. MicroRNAs (miRs) are regulators of inflammation and atherogenesis. The expressions of endothelial cell (EC)-specific miR-10a and miR-21 and monocyte-specific miR-33a and miR-221 were investigated using coculture of the ECs and monocytes upon exposure to H2O2 as an oxidative stressor, and endotoxin/lipopolysaccharide (LPS) as a microbial stressor. Human umbilical endothelial cells (HUVECs) and peripheral blood mononuclear cells (or monocytes) were cocultured in M199 complete medium and were incubated with LPS (20 ng/mL) or H2O2 (1%) for 8 hours at 37°C. The HUVECs and monocytes were then separated from the cellular mix using a magnetic bead negative selection technique. The relative expression of miRs was determined by real-time polymerase chain reaction. In both cell types, H2O2 induced miR10a ( P = 0.05) and LPS induced miR21 ( P = 0.0003) compared to the untreated controls. Coculture increased miR-10a and miR-21 expression in monocytes ( P = 0.0008 and