Atypical memory B cells increase in the peripheral blood of patients with breast cancer regardless of lymph node involvement.

BACKGROUND: Breast cancer is the most common cancer in females. The immune system has a crucial role in the fight against cancer. B and T cells, the two main components of the adaptive immunity, are critical players that specifically target tumor cells. However, B cells, in contrast to T cells, and their role in cancer inhibition or progression is less investigated. Accordingly, in this study, we assessed and compared the frequency of naïve and different subsets of memory B cells in the peripheral blood of patients with breast cancer and healthy women. RESULTS: We found no significant differences in the frequencies of peripheral CD19+ B cells between the patients and controls. However, there was a significant decrease in the frequency of CD19+IgM+ B cells in patients compared to the control group (P=0.030). Moreover, the patients exhibited higher percentages of atypical memory B cells (CD19+CD27‒IgM‒, P=0.006) and a non-significant increasing trend in switched memory B cells (CD19+CD27+IgM‒, P=0.074). Further analysis revealed a higher frequency of atypical memory B cells (aMBCs) in the peripheral blood of patients without lymph node involvement as well as those with a tumor size greater than 2cm or with estrogen receptor (ER) negative/progesterone receptor (PR) negative tumors, compared with controls (P=0.030, P=0.040, P=0.031 and P=0.054, respectively). CONCLUSION: Atypical memory B cells (CD19+CD27‒IgM‒) showed a significant increase in the peripheral blood of patients with breast cancer compared to the control group. This increase seems to be associated with tumor characteristics. Nevertheless, additional research is necessary to determine the precise role of these cells during breast cancer progression.

Association of Interleukin-4 Receptor α Chain I50V Gene Variant (rs1805010) and Asthma in Iranian Population: A Case-control Study.

Background: Asthma is one of the respiratory disorders caused by chronic airway inflammation. IL-4 has been identified as one of the participating interleukins in the severity of asthma. Objective: A case-control study was conducted to determine the association of rs1805010, a single nucleotide polymorphism in the interleukin 4 receptor α chain, with asthma and immunoglobulin E and IL-17A serum levels in Iranian populations. Methods: ELISA was used to investigate the relationship between three different varieties of SNP I50V and serum IL-17A levels, as well as total IgE levels. Based on GINA criteria, patients were classified into mild, moderate, and severe groups based on the association between SNP I50V, IL-17A, and total IgE. In order to analyze the data, the student-t-test and the one-way ANOVA were used. Results: The SNP I50V was associated with asthma in a significant way (p = 0.001). IL-17A and total IgE levels were significantly higher in asthmatic patients than in control participants (p 0.05 and p 0.021, respectively), but neither showed any association with SNP I50V in the asthmatic patients. Conclusion: Asthma patients have a higher prevalence of the I allele, reflecting the significance of Th2 cells. Although total IgE and IL-17A levels increased in both disease subgroups, total IgE level augmentation correlates directly with disease severity, while IL-17A level enhancement does not.

Lactobacillus rhamnosus and Lactobacillus delbrueckii Ameliorate the Expression of miR-125a and miR-146a in Systemic Lupus Erythematosus Patients.

The microRNAs are non-coding RNA molecules involved in physiological and pathological processes, causing autoimmune diseases such as systemic lupus erythematosus (SLE). Probiotics are living microorganisms that possess beneficial effects on the host immune system and modulate it. The effect of Lactobacillus rhamnosus and Lactobacillus delbrueckii on the expression of miR-125a and miR-146a was studied in peripheral blood mononuclear cells (PBMCs) from newly diagnosed lupus patients in this in vitro study. During this study, 20 recently diagnosed SLE patients and 20 healthy individuals participated. Ficoll method was used to isolate the PBMCs from whole blood, which were cultured for 48 h with Lactobacillus rhamnosus and Lactobacillus delbrueckii. In the next step, total RNA containing microRNA was extracted. cDNA was synthesized for miR-125a and miR-146a genes and analyzed by real-time PCR. Results were presented as fold changes. As compared to healthy controls, SLE patients expressed lower levels of miR-125a and miR-146a. PBMCs treated with Lactobacillus rhamnosus, Lactobacillus delbrueckii, or both probiotics had significantly higher levels of miR-125a and miR-146a compared to the untreated group. Treatment of PBMCs with both L. rhamnosus and L. delbrueckii upregulated the expression of miR-125a and miR-146a in treated cells compared with untreated cells in SLE patients (p = 0.02, p = 0.001). Lactobacillus rhamnosus and Lactobacillus delbrueckii modify lupus patients' immune responses and disease effects by regulating miR-125a and miR-146a.

Expression of miR-21 &IL-4 in endometriosis.

BACKGROUND: Endometriosis characterized with existence of endometrial-like tissue outside the uterus. Fibrosis of ectopic lesions is an important feature of endometriosis. IL-4 induces fibrosis via fibroblast proliferation, collagen production and myofibroblast differentiation. Increasing of miR-21 expression promotes fibroblast activation and fibrosis expansion. The aim of study was to evaluate the expression of miR-21 and its relationship with IL-4 gene expression in endometrial ectopic and eutopic tissues of endometriosis patients. METHODS AND RESULTS: Ectopic and eutopic tissue samples were taken from 20 women with endometriosis, and control samples were taken from the endometrium of 20 endometriosis-free women. The relative expression of IL-4 and miR-21 evaluated by Real Time PCR. IL-4 relative gene expression was significantly increased in ectopic tissue compared to eutopic (p = 0.025) and control tissue (p = 0.021). The relative expression of miR-21 gene in ectopic tissue was increased compared to eutopic (p = 0.850) and control tissue (p = 0.978) but these differences were not significant. Also, the correlation between IL-4 and miR-21 relative gene expression was not significant (p = 0.083). CONCLUSION: The increased expression of miR-21 in endometrium of women with endometriosis may upregulate the IL-4 gene expression and lead to fibrosis. Further studies may suggest miR-21 and IL-4 as candidates for diagnosis of endometriosis.

Identification of Potential Biomarkers in the Peripheral Blood Mononuclear Cells of Relapsing-Remitting Multiple Sclerosis Patients.

Multiple sclerosis (MS) is described as an immune disorder with inflammation and neurodegeneration. Relapsing-remitting MS (RRMS) is one of the most common types of MS. The diagnostic manner for this disorder typically includes the usage of magnetic resonance imaging (MRI); however, this is not always a very precise diagnostic method. Identification of molecular biomarkers in RRMS body fluids samples compared to healthy subjects can be useful to indicate the normal and pathogenic biological processes or pharmacological responses to drug interaction. In this regard, this study evaluated different miRNAs in isolated peripheral blood mononuclear cells (PBMCs) of RRMS compared to controls and their correlations with altered T regulatory type 1 (Tr1) cells, osteopontin (OPN), and interleukin 10 (IL-10) levels. The frequency of Tr1 cells was measured using flow cytometry. Also, the expressions of different miRNAs were evaluated via quantitative real-time polymerase chain reaction (RT-qPCR) and plasma levels of IL-10 and OPN were tested by enzyme-linked immunosorbent assay (ELISA). The obtained results showed the Tr1 cells' frequency, Let7c-5p, and miR-299-5p levels decreased in RRMS patients to about 59%, 0.69%, and 20% of HCs, respectively, (P < 0.05). The miR-106a-5p levels increased about 7.5-fold in RRMS patients in comparison to HCs (P < 0.05). Moreover, the results showed that there was an increased negative association between Tr1 frequency and plasma-OPN levels in RRMS patients in comparison to HCs and also, we found a moderate positive correlation between plasma-IL-10 and miR-299-5p expression of RRMS patients. Overall, it may be possible to use these biomarkers to improve the diagnostic process. These biomarkers may also be considered for clinical and therapeutic studies in the future.

Evaluation of Expression of LRBA and CTLA-4 Proteins in Common Variable Immunodeficiency Patients.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease with a heterogeneous genetic background. Lipopolysaccharide-responsive beige-like anchor (LRBA), as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have important regulatory roles in the immune responses. Here, we have investigated the expression of LRBA and CTLA-4 proteins in CVID patients with at least one presentation of early-onset occurrence, autoimmunity, or enteropathy. In this study, 20 newly diagnosed CVID patients without infection only phenotype, and ten healthy individuals were enrolled. The expressions of LRBA and CTLA-4 proteins were assessed by western blotting and flow cytometry, respectively. The patients were divided into two groups of autoimmunity-positive (11 cases) and autoimmunity-negative (9 patients). LRBA and CTLA-4 expressions were significantly lower in autoimmune-positive patients than in healthy individuals (P = .03 and P = .03, respectively). Autoimmune-negative patients had lower expression of LRBA and CTLA-4 than the control group, although it was not significant. There was a positive correlation between the expressions of LRBA and CTLA-4 in both groups of patients (P < .05). Furthermore, the highest frequency of LRBA (85.7%) and CTLA-4 (71.4%) defects was detected in those with concomitant presence of autoimmunity, enteropathy, and early-onset occurrence. Concurrent presence of autoimmunity, enteropathy, and early-onset occurrence in CVID patients could be indicative of a lack of expression in LRBA and CTLA-4 proteins. This could be helpful in early diagnosis and initiation of appropriate treatment in these patients prior to genetic confirmation.

Association of the single nucleotide polymorphism C1858T of the PTPN22 gene with unexplained recurrent pregnancy loss: A case-control study.

BACKGROUND: Lymphoid-tyrosine-phosphatase which is encoded by the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene plays a pivotal role in the regulation of immune responses by dephosphorylating several signaling intermediates of immune cells. OBJECTIVE: Since a balanced immune response has been shown to be important during pregnancy, the purpose of this research was to compare the frequency of the PTPN22 C1858T polymorphism in women with unexplained recurrent pregnancy loss (URPL) vs. in a control group for the first time. MATERIALS AND METHODS: Genomic DNA from 200 individuals with URPL and 200 individuals without URPL (the control group) at the infertility center in Yazd, Iran was isolated using the salting-out method. The PTPN22 C1858T polymorphism of the two groups was analyzed using polymerase chain reaction-restriction fragment length polymorphism. Genotype frequencies in the women with URPL and the fertile control group were compared using the Chi-square test. RESULTS: There were significant differences in the frequency of the PTPN22 1858T polymorphism in the URPL individuals vs. the healthy controls, i.e. 32.0% and 21.5%, respectively (p = 0.01). CONCLUSION: Our findings suggest that the PTPN22 1858T polymorphism could play a role in recurrent pregnancy loss. Therefore, genotyping of the mentioned polymorphism can help clinicians to predict the probable risk of URPL.

Investigating the Association between IL-27 and Susceptibility to Preeclampsia among Iranian Women.

BACKGROUND: Preeclampsia (PE) is one of the most serious disorders of human pregnancy with a high rate of mortality for the fetus and mother. Several etiological factors are involved in the onset of this disease. Upregulation of IL-27 has been reported in placental tissue recovered from preeclamptic women, but the role of IL-27 has not yet been investigated in PE. The aim of the study was to investigate the association of IL-27 rs153109 and rs17855750 gene polymorphisms with PE; also, protein levels and susceptibility and severity of PE in Iranian women were evaluated. METHODS: This case-control study was performed on 199 PE patients and 228 healthy women as the control group. IL-27 rs153109 and rs17855750 SNPs were genotyped using a PCR-RFLP method. Moreover, the levels of IL-27 were determined in 40 PE and 45 healthy women using ELISA method. RESULTS: Statistical analysis indicated that there were no differences in genotype, allele and genotype combination frequencies in the SNPs between cases and controls. The plasma level of IL-27 was elevated in the mild form of the disease compared with controls (p-value: 0.006). CONCLUSIONS: The effect of IL-27 in preeclampsia is not due to the studied cytokine polymorphisms, but the level of IL-27 might be associated with the severity of preeclampsia in Iranian women.

Association of M55L and Q192R polymorphisms of paraoxonase 1 gene (PON1) with recurrent pregnancy loss risk: A case-control study.

BACKGROUND: Recurrent pregnancy loss (RPL) refers to the incidence of two or more abortions before the first half of pregnancy. Oxidative stress has been hypothesized to play a central role in RPL. OBJECTIVE: To investigate the relationship between Q192R and L55M polymorphisms of PON1 as antioxidant enzyme and the risk of RPL. MATERIALS AND METHODS: In this case-control study, 110 women with RPL (case) and 110 healthy fertile women (control) referred to the Research and Clinical Center for Infertility, Shiraz, Iran were enrolled. Genomic DNA was extracted from the peripheral blood in all participants. Polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: Statistical analysis of Q192R polymorphism showed a significant difference for the RR genotype between the case and control group (OR = 11, CI = 1.39-86.87, p = 0.005) but none for the QR and QQ genotypes. No significant association was observed between the R and Q allelic frequency in the RPL participants compared to the control group (p = 0.53). Also, statistical analysis of the L55M polymorphism for MM genotype in the case group compared with the control group showed a significant difference (OR = 3.59, CI = 0.97-13.30, p = 0.042), but none for the LM and LL genotypes. CONCLUSION: The findings showed a significant correlation between the Q192R polymorphisms and the L55M PON1 enzyme and RPL in this study population.

Immunomodulatory effects of vitamin D3 on gene expression of MDGF, EGF and PDGFB in endometriosis.

RESEARCH QUESTION: Endometriosis, an inflammatory disease, is assumed to be associated with an increased production of growth-related cytokines. Based on the emerging immunomodulatory role of vitamin D3 in different inflammatory conditions, this study aimed to examine its modulatory effect on the expression levels of the genes for platelet-derived growth factor-B (PDGFB), monocyte/macrophage-derived growth factor (MDGF, also known as PPBP) and epidermal growth factor (EGF) in peritoneal fluid mononuclear cells (PFMC) in women with and without endometriosis. DESIGN: PFMC from 10 women with endometriosis and 10 control participants were treated with vitamin D3.The gene expression levels of PDGFB, MDGF and EGF were measured 6, 24 and 48 h following vitamin D3 administration using real-time PCR. RESULTS: Gene expression levels of EGF and PDGFB were higher in the PFMC of women with endometriosis than the control group (P = 0.006, P < 0.001, respectively). Although MDGF expression showed an increase in the endometriosis group compared with non-endometriotic controls, no significant difference was found. Vitamin D3 significantly decreased EGF expression at 6, 24 and 48 h (P < 0.001, P < 0.001 and P = 0.007, respectively), MDGF at 24 and 48 h (P < 0.001 and P = 0.009, respectively) and PDGFB at 6 h (P = 0.047) in the endometriosis group. Vitamin D3 treatment had no significant effect on expression of the genes in the PFMC of non-endometriotic women. CONCLUSIONS: The study concluded that PDGFB and EGF gene expression increases in endometriosis, and vitamin D3 could markedly decrease this expression, suggesting its therapeutic potential in endometriosis.

Effect of Atorvastatin, Curcumin, and Quercetin on miR-21 and miR-122 and their correlation with TGFß1 expression in experimental liver fibrosis.

AIMS: Liver fibrosis is an inflammatory and fibrogenic process that occurs following chronic liver damage. TGFß1 is the key inducer of fibrosis. MiR-21 and miR-122 are two miRNAs that their expression changes during fibrosis. In the present study, we investigate the effects of curcumin, quercetin, and atorvastatin on the expression levels of miR-21 and miR-122 and evaluated their correlation with TGFß1 expression in bile duct ligation (BDL)-induced fibrotic rats. MATERIALS AND METHODS: Thirty two adult male Wistar rats were divided into 8 groups (n = 8 for each): Sham, Sham + curcumin (100 mg/kg/day), Sham + quercetin (30 mg/kg/day), Sham + atorvastatin (15 mg/kg/day), BDL, BDL + curcumin, BDL + quercetin, BDL + atorvastatin and treated for four weeks via oral gavage. The expression of miR-21, miR-122, and TGFß1 was evaluated via RT-qPCR. KEY FINDINGS: The expression levels of TGFß1 and miR-21 were significantly increased in the BDL group compared to the Sham group (P < 0.05), but the expression of miR-122 was significantly decreased in the BDL group compared to the Sham group (P < 0.05). Curcumin, quercetin, and atorvastatin treatment lead to down-regulation of miR-21 and TGFß1 and up-regulation of miR-122 in the BDL groups. There was no significant difference between these drugs in altering gene expression and all had the same effects. Moreover, a direct significant correlation was observed between mir-21 and TGFß1 and an inverse significant correlation between mir-122 and TGFß1 expression. SIGNIFICANCE: In summary, targeting these molecular pathways may partially prevent the progression of liver fibrosis.

The balance of regulatory and stimulatory B cell subsets in breast cancer draining lymph nodes correlates with tumor prognostic factors.

AIMS: B cells can promote or inhibit immune responses against breast cancer. We investigated changes in the frequency of B cells with stimulatory or regulatory capacity in breast tumor draining lymph nodes during cancer progression. MAIN METHODS: We isolated mononuclear cells from fresh axillary lymph nodes (LNs) of 44 patients with breast cancer and stained lymphocytes with antibodies against CD19, CD80, CD86, CD39 and CD73. To assess programmed death-1 (PD-1) and PD-ligand 1 (PD-L1) expression, lymphocytes were briefly stimulated, stained for CD19, PD-1 and PD-L1, and examined with flow cytometry. KEY FINDINGS: The frequency of CD80+ B cells was higher in nonmetastatic lymph nodes, while the percentage of CD86+ B cells showed a positive relationship with higher tumor grade and higher numbers of involved LNs. A small proportion of unstimulated B cells expressed PD-1 or PD-L1 but these molecules were rapidly upregulated on B cells following activation. The frequency of stimulated PD-L1+ B cells showed an inverse association with estrogen and progesterone receptor expression and a nonsignificant positive association with tumor grade. In addition, the percentage of unstimulated PD-1+ B cells was higher in patients with higher-grade tumors. CD73 expression on B cells was associated with lower numbers of involved LNs, and the frequency of CD39+ B cells was higher in patients with larger tumors. SIGNIFICANCE: CD86+, CD39+, PD-1+ and PD-L1+ B cells showed associations with poor prognostic factors, therefore their potential role in the suppression of the immune responses against breast cancer should be evaluated in greater detail.

Resveratrol suppresses interleukin-6 expression through activation of sirtuin 1 in hypertrophied H9c2 cardiomyoblasts.

Inflammatory cytokine, interleukin-6 (IL-6), plays an important role in the pathogenesis of cardiac hypertrophy. Recent studies have documented that resveratrol exhibits cardioprotective effects. The present study attempts to explore whether resveratrol suppreses IL-6 in hypertrophied H9c2 cardiomyoblasts through histone deacetylase, sirtuin 1 (SIRT1). To induce hypertrophy, the cells were incubated with angiotensin II (Ang II). Treatment groups were treated with different doses (1, 10, 25, 50, 75, and 100 µM) of resveratrol (R). Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell size was determined using crystal violet staining. Gene expression was assessed by real-time polymerase chain reaction technique. Enzyme-linked immunosorbent assay was used to measure IL-6 concentration. The results showed that cell area and ANP messenger RNA (mRNA) levels decreased significantly in R25+Ang, R50+Ang, and R100+Ang groups, as compared with Ang group. Therefore, 10, 20, 30, 40, and 50 µM of resveratrol were used to to evaluate its anti-inflammatory effects. The results revealed that Ang II upregulated IL-6 at both mRNA and protein levels (p < .001 vs. normal) and resveratrol (50 µM) decreased IL-6 mRNA (p < .01) and protein (p < .05) significantly in comparison to Ang group. However, in groups in which the cells were pretreated with SIRT1 inhibitor, EX-527, the response of resveratrol was partially reversed. Transcription levels of IL-6 receptor components (gp130 and gp80) did not change significantly among the experimental groups. The current data suggests that resveratrol protects H9c2 cells against Ang II-induced hypertrophy by suppression of IL-6 through SIRT1 activation.

The association between vitamin D status and metabolic syndrome and its components among female teachers residing in Yazd city

Background: Studies trying to find the association between vitamin D status and metabolic syndrome (MetS) have led to inconsistent results, and community-based data for individuals living in the Middle East are limited. Objectives: To find out if MetS and its components are associated with vitamin D status among female teachers residing in Yazd city during winter 2015. Materials and methods: A total of 276 female teachers (case group, n = 124 and control group, n = 152) aged 20-60 years were included. Weight, height, waist circumference, blood pressure, daily energy intake, physical activity, serum 25 hydroxy vitamin D (25(OH)D3), fasting blood glucose, triglycerides and high-density lipoprotein cholesterol (HDL-C) levels were assessed. Logistic regression was used to examine the odds ratio of MetS according to vitamin D status. Results: Mean serum 25(OH)D3 was 32.79 ± 18.62 ng/ml and 33.73 ± 20.20, in females with and without MetS, respectively (P > 0.142). Compared to those with 25(OH)D3of < 20 ng/ml, the odds ratio for MetS was 1.01 (95% CI: 0.48-2.13) and 0.95 (95% CI: 0.56-1.60) for those with serum 25(OH)D3 levels of 20-29 ng/ml and ≥ 30 ng/ml, respectively (P trend = 0.84). The association remained insignificant after adjusting for potential confounders. Furthermore, vitamin D status was not associated with MetS components (P > 0.05). Conclusion: Although several studies have claimed the association between vitamin D status and MetS, we could not find a similar connection in a sample of Iranian female teachers. Prospective studies are needed to determine the possible effect of vitamin D in the development of MetS, particularly in the Yazd province

Antecedentes: Los estudios en busca de una asociación entre el estado de vitamina D y el síndrome metabólico (SM) han dado resultados no concluyentes, y los datos sobre comunidades de personas residentes en Oriente Próximo son limitados. Objetivos: Averiguar si existe asociación entre el SM y sus componentes y el estado de vitamina D en profesoras residentes en la ciudad de Yazd durante el invierno de 2015. Materiales y métodos: Se incluyó a un total de 276 profesoras (grupos de casos, n = 124 y grupo de control, n = 152) de 20-60 años de edad. Se determinaron el peso, la talla, el perímetro de la cintura, la presión arterial, la ingesta diaria de energía, la actividad física y los niveles de 25-hidroxivitamina D (25(OH)D3), glucosa en ayunas, triglicéridos y colesterol de las proteínas de alta densidad (C-HDL). Se utilizó regresión logística para determinar la razón de probabilidades de SM en función del estado de vitamina D. Resultados: La concentración sérica media de 25(OH)D3 era de 32,79 ± 18,62 ng/ml y 33,73 ± 20,20 en las mujeres con y sin SM, respectivamente (P > 0,142). En comparación con las que tenían < 20 ng/ml de 25(OH)D3, la razón de probabilidades de SM era 1,01 (IC al 95%, 0,48-2,13) y 0,95 (IC al 95%, 0,56-1,60) en las que tenían valores de 20-29 ng/ml y ≥ 30 ng/ml, respectivamente (tendencia de P = 0,84). La asociación seguía siendo no significativa después del ajuste por posibles factores de confusión. Además, el estado de vitamina D no se asociaba con los componentes del SM (P > 0,05). Conclusión: Aunque varios estudios han informado de una asociación entre el estado de la vitamina D y el SM, no pudimos hallar una relación similar en una muestra de profesoras iraníes. Se necesitan estudios prospectivos para determinar el posible efecto de la vitamina D en el desarrollo del SM, especialmente en la provincia de Yazd

The association between vitamin D status and metabolic syndrome and its components among female teachers residing in Yazd city.

BACKGROUND: Studies trying to find the association between vitamin D status and metabolic syndrome (MetS) have led to inconsistent results, and community-based data for individuals living in the Middle East are limited. OBJECTIVES: To find out if MetS and its components are associated with vitamin D status among female teachers residing in Yazd city during winter 2015. MATERIALS AND METHODS: A total of 276 female teachers (case group, n=124 and control group, n=152) aged 20-60 years were included. Weight, height, waist circumference, blood pressure, daily energy intake, physical activity, serum 25 hydroxy vitamin D (25(OH)D3), fasting blood glucose, triglycerides and high-density lipoprotein cholesterol (HDL-C) levels were assessed. Logistic regression was used to examine the odds ratio of MetS according to vitamin D status. RESULTS: Mean serum 25(OH)D3 was 32.79±18.62ng/ml and 33.73±20.20, in females with and without MetS, respectively (P>0.142). Compared to those with 25(OH)D3of <20ng/ml, the odds ratio for MetS was 1.01 (95% CI: 0.48-2.13) and 0.95 (95% CI: 0.56-1.60) for those with serum 25(OH)D3 levels of 20-29ng/ml and ≥30ng/ml, respectively (P trend=0.84). The association remained insignificant after adjusting for potential confounders. Furthermore, vitamin D status was not associated with MetS components (P>0.05). CONCLUSION: Although several studies have claimed the association between vitamin D status and MetS, we could not find a similar connection in a sample of Iranian female teachers. Prospective studies are needed to determine the possible effect of vitamin D in the development of MetS, particularly in the Yazd province.

Empirically derived dietary patterns and serum inflammatory markers in Iranian female teachers: A cross-sectional study.

AIM: To examine the relationship between dietary patterns and inflammatory markers including serum high sensitivity C-reactive protein (hs-CRP) and interleukin 17A (IL-17A) in females. METHODS: In the present cross-sectional study in female teachers living in Yazd, central Iran, data on anthropometric measurements and general information were gathered. A food frequency questionnaire was completed by participants and then, subjects were invited to give blood samples. Major dietary patterns were derived using principal component analysis and serum inflammatory markers were compared according to quintiles of dietary patterns scores. RESULTS: In total, 320 subjects aged 40.38 ± 8.08 years were included. Three dietary patterns were derived: (i) 'traditional' with a high intake of poultry, salt, eggs, other vegetables and red meat; (ii) 'vegetables and fruits' with a higher intake of tomatoes, yoghurt drinks, green leafy vegetables, dried fruits, fruits, other vegetables and organ meats and (iii) 'dairy and saturated fat' with a high loading of high-fat dairy products, butter, low-fat dairy, margarine, eggs, other vegetables and green leafy vegetables. Participants in the highest quintile of the 'vegetables and fruits' dietary pattern had significantly lower serum hs-CRP levels compared to those in the lowest quintile (3.6 ± 0.4 mg/L vs 2.6 ± 0.4 mg/L, respectively; P < 0.05). None of the dietary patterns were associated with circulating IL-17 levels. CONCLUSIONS: Higher consumption of fruits and vegetables is inversely associated with serum hs-CRP but not IL-17 levels. Studies investigating the dietary patterns in association with IL-17 in other populations are recommended.

The Dietary Approaches to Stop Hypertension (DASH)-Style Diet and an Alternative Mediterranean Diet are Differently Associated with Serum Inflammatory Markers in Female Adults.

BACKGROUND: Studies on the association between a priori dietary patterns and serum highly sensitive C-reactive protein (hs-CRP) have led to inconsistent results, and we are not aware of any study on interleukin 17A (IL-17A) as an inflammatory marker associated with autoimmune diseases. OBJECTIVE: The present study aimed to investigate the association between Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean dietary patterns with circulating hs-CRP and IL-17A levels. METHODS: In this cross-sectional study, female teachers (aged 20-50 years) who lived in Yazd, Iran, were randomly selected from elementary, guidance, and high schools from September 2015 to February 2016. Anthropometric data, as well as general information and dietary food intakes, were gathered, and each participant gave 1 blood sample. Participants were categorized into tertiles based on the DASH and the Mediterranean diet calculated scores. The associations between the dietary patterns and serum hs-CRP and IL-17A levels were assessed in the crude and multivariable models. In total, 320 female teachers aged 40.38 (8.08) years were included. RESULTS: The DASH diet was associated with lower serum hs-CRP levels in the crude ( P = .05) and the fully adjusted models ( P = .02), while it was not significantly associated with IL-17A levels. The participants with the highest adherence to the Mediterranean diet had significantly lower circulating IL-17A levels ( P = .04) even controlling for all confounders ( P = .02); however, there was not a significant relationship between this diet and hs-CRP levels. CONCLUSIONS: The DASH and the Mediterranean dietary patterns might be differently associated with inflammatory markers. Further prospective studies are recommended to confirm our results.

Prophylactic DNA vaccine targeting Foxp3+ regulatory T cells depletes myeloid-derived suppressor cells and improves anti-melanoma immune responses in a murine model.

Regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) are the two important and interactive immunosuppressive components of the tumor microenvironment that hamper anti-tumor immune responses. Therefore, targeting these two populations together might be beneficial for overcoming immune suppression in the tumor microenvironment. We have recently shown that prophylactic Foxp3 DNA/recombinant protein vaccine (Foxp3 vaccine) promotes immunity against Treg in tumor-free conditions. In the present study, we investigated the immune modulatory effects of a prophylactic regimen of the redesigned Foxp3 vaccine in the B16F10 melanoma model. Our results indicate that Foxp3 vaccination continuously reduces Treg population in both the tumor site and the spleen. Surprisingly, Treg reduction was associated with a significant decrease in the frequency of MDSC, both in the spleen and in the tumor environment. Furthermore, Foxp3 vaccination resulted in a significant reduction of arginase-1(Arg-1)-induced nitric oxide synthase (iNOS), reactive oxygen species (ROS) and suppressed MDSC activity. Moreover, this concurrent depletion restored production of inflammatory cytokine IFN-γ and enhanced tumor-specific CTL response, which subsequently resulted in the reduction of tumor growth and the improved survival rate of vaccinated mice. In conclusion, our results revealed that Foxp3 vaccine promotes an immune response against tumor by targeting both Treg and MDSC, which could be exploited as a potential immunotherapy approach.

Evaluation of the effects of anti-psychotic drugs on the expression of CD68 on the peripheral blood monocytes of Alzheimer patients with psychotic symptoms.

INTRODUCTION: Previous studies approved the important roles of CD68, as scavenger receptors, in Alzheimer's disease (AD). The aim of this study was to evaluate the effect of treatment with anti-psychotic drugs and vitamin B12 on the expression levels of CD68 in monocytes of psychotic AD patients. MATERIAL AND METHODS: Expression of CD68 on the monocytes was evaluated in the following groups: 1. age and sex matched healthy controls (Group 1), 2. non-psychotic AD patients (Group 2), 3. psychotic AD patients (Group 3), 4. psychotic AD patients treated with Risperidone (Group 4), 5. psychotic AD patients treated with Risperidone plus vitamin B12 (Group 5), 6. psychotic AD patients treated with Quetiapine (Group 6), psychotic AD patients treated with Quetiapine plus vitamin B12 (Group 7). The expression of CD68 has been performed using flow cytometry technique. RESULTS: The results showed that CD68 levels were significantly increased in AD patients in comparison to healthy controls and in psychotic AD patients in comparison to non-psychotic AD patients. Treatment with anti-psychotic drugs decreased the expression of CD68. Expression of CD68 has a positive correlation with pain, dementia and mental disorders symptoms in psychotic AD patients. DISCUSSION: CD68 may play key roles in the pathogenesis of AD and its complications may be via induction of inflammation. Therefore, it may be concluded that CD68 may be considered as a risk factor for development of AD and also psychotic symptoms in the patients.

Association of PD-1.5 C/T, but Not PD-1.3 G/A, with Malignant and Benign Brain Tumors in Iranian Patients.

Programmed death-1 (PD-1) negatively regulates the immune response. The aims of this study were to assess the association of two single nucleotide polymorphisms in the PD-1 gene, PD-1.5 (+7785 C/T-rs2227981) and PD-1.3 (+7146 G/A- rs11568821), with benign and malignant brain tumors. Patients with brain tumors (96 patients with benign and 56 with malignant brain tumors) and 150 healthy control individuals were included. PCR-RFLP was performed for genotyping. It was revealed that the genotype and allele frequencies of PD-1.5 C/T polymorphism were significantly different between all brain tumor patients and the control group. The frequencies of the CT genotype and T allele were higher in brain tumor patients. In contrast, the frequency of PD-1.3 G/A genotypes and alleles showed no significant difference between all brain tumor patients and controls. Patients were then divided into malignant and benign groups. The results revealed a significant difference in both patients groups compared with the controls only at PD-1.5 C/T position. Arlequin analysis showed the GC haplotype was the most frequent haplotype in the whole group of patients and controls, and the GT haplotype was significantly different between patient and control groups. In conclusion, we demonstrate that PD-1.5 C/T polymorphism, but not PD-1.3 G/A, is associated with brain tumors in Iranian patients.