Selenium Supplementation Alter the Frequency of Th17 but not Th1/Th2 Lymphocytes in Diffuse Large B Cell Lymphoma Patients.

BACKGROUND: Selenium (Se) is a micronutrient, which has recently been proven to have a positive effect on the immune system of cancer patients, but the underlying mechanism is not clearly defined. In this randomized controlled trial, we evaluated the effect of three-month Se supplementation on the profile of CD4+ T-helper subsets including IFN-γ+/IL-4- Th1, IFN-γ-/IL-4+ Th2, and CD4+IL-17+ Th17 cells in sixteen diffuse large B cell lymphoma (DLBCL) patients at stable remission phase who consumed Se (Se+) compared to the fourteen control patients who did not receive Se (Se-). METHODS: The frequency of IFN-γ+/IL-4- Th1, IFN-γ-/IL-4+ Th2, and CD4+IL-17+ Th17 lymphocytes was determined using a four-color flow cytometry method. RESULTS: The results revealed that three-month Se supplementation significantly decreased the proportion of CD4+IL-17+ Th17 lymphocytes but not IFN-γ+/IL-4- Th1 and IFN-γ-/IL-4+ Th2 subtypes in DLBCL patients at stable remission. Change in the percentage of IFN-γ+/IL-4- Th1, IFN-γ-/IL-4+ Th2, and CD4+IL-17+ Th17 cells did not significantly differ between Se+ and Se- groups. No positive correlation was observed between changes in different Th subpopulations in both Se+ and Se- groups. CONCLUSIONS: Taken together, three-month Se supplementation can reduce the proportion of CD4+IL-17+ Th17 cells in DLBCL patients at stable remission phase. Larger population and longer follow-up of patients is necessary to specify the clinical significance of Se supplementation on the popularity of T-helper cells in DLBCL patients.

Eugenol: A New Option in Combination Therapy with Sorafenib for the Treatment of Undifferentiated Thyroid Cancer.

Thyroid cancer (TC) is the most common endocrine malignancy. Thyroidectomy and radiotherapy are common treatment modalities for patients with undifferentiated TC (UTC), and sorafenib is usually recommended to prevent a recurrence. However, malignant cells may evade chemotherapy-induced apoptosis, and combination therapy was developed to achieve better outcomes. This study investigated whether eugenol in combination with sorafenib was more effective than either substance individually in triggering apoptosis in the UTC. The IC50 of sorafenib and eugenol was determined in a UTC cell line (8305C) by MTT assay, and their synergistic effect in combination therapy was investigated. Flow cytometry was used to evaluate the rate of apoptosis in treated cells. To confirm that cell death occurred through apoptosis, immunoblotting was used to determine the relative cleavage of caspase-8 and caspase-9. The IC50 of sorafenib was 20 µM, and that of eugenol was 2100 µM. The sorafenib-eugenol combination (1:105) showed synergistic effects at concentrations equal to or less than their IC50. The rate of apoptosis induction was higher in cells treated with eugenol or the eugenol-sorafenib combination compared to sorafenib-treated cells. The relative intensity of cleaved/un cleaved forms of caspase-8 increased in eugenol-treated cells compared to sorafenib-treated cells.Sorafenib and eugenol at concentrations equal to or less than their IC50 had a synergistic effect in 8305C cells. The most potent apoptotic effect was achieved with sorafenib and eugenol at their IC50. Lower doses of sorafenib could be used with eugenol to improve its efficacy while reducing its side effects.

Immunomodulatory Effects of Omega-3 Fatty Acids in Patients with Differentiated Thyroid Cancer Before or After Radioiodine Ablation.

BACKGROUND: Thyroid cancer and radioactive iodine (RAI) ablation for postsurgical management may lead to uncontrolled inflammation. OBJECTIVE: This study was intended to assess the prophylactic and therapeutic immunomodulatory effects of omega-3 fatty acids in patients with differentiated thyroid cancer (DTC). METHODS: A total of 85 patients with DTC were allocated into two groups based on RAI dosage after thyroidectomy. Patients in each group were randomly distributed 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. Fifteen healthy individuals were included as controls. Serum cytokine levels including IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, TNF-α and IFN-γ were determined by cytometric bead assay. RESULTS: IL-4, IL-6, IL-21 and IL-22 levels in patients with DTC were higher than in the healthy controls. Regardless of RAI dosage, IL-6 showed an increasing trend after RAI ablation. IL-4, IL-22, and IL-17A remained at considerably higher levels than in the healthy controls after RAI ablation. Within-group comparisons showed a significant reduction in Th1+Th17/Th2+Th22 ratio in G2 patients 1 week after RAI ablation. Between-group comparisons showed increased IL-10 levels in G3 compared with G1 patients one week after high-dose RAI ablation. In G3, Th1+Th17/Th2+Th22 and Th1+Th17/Th2+Th9+Th22 ratios were remarkably lesser than in G2 patients 1 month after intermediate-dose RAI ablation. CONCLUSION: Our results showed better anti-inflammatory effects of omega-3 when it was used therapeutically after RAI ablation in patients with DTC than when it was used prophylactically before RAI.

The impact of selenium on regulatory T cell frequency and immune checkpoint receptor expression in patients with diffuse large B cell lymphoma (DLBCL).

For many decades, selenium (Se) has been known as a potential anti-cancer agent that can also improve the function of immune cells in a variety of solid tumors. However, there is no report on the role of Se on CD4+ T cell subsets like CD4+CD25+FOXP3+ regulatory T cells (Tregs) in lymphoma patients. In this randomized clinical trial, we investigated the effect of 3-month Se consumption on the frequency of CD4+CD25+FOXP3+ Tregs and the expression of immune checkpoint receptors in thirty-two non-Hodgkin lymphoma (NHL) patients (16 patients with Se (Se+) and 16 without Se (Se-) consumption) with diffuse large B-cell lymphoma (DLBCL) subtype at stable remission. The change in the frequency of Tregs and expression of immune checkpoint receptors including CTLA-4, LAG-3, TIM-3, and PD-L1 genes were evaluated after 3 months in both groups using flow cytometry and SYBR Green Real-time PCR method, respectively. The results showed that the frequency of CD4+CD25+FOXP3+ Tregs and expression of immune checkpoint receptors did not significantly change after 3-month Se consumption in DLBCL patients. However, alteration in the frequency of CD4+CD25-FOXP3+ Treg subsets was positively correlated with change in CTLA-4, LAG-3, and TIM-3 expression in the Se+ group. Three-month Se supplementation did not prevent relapse in Se+ group. Taken together, Se supplementation alone did not affect the frequency of CD4+CD25+FOXP3+ Tregs, expression of checkpoint receptors, and prevention of relapse in DLBCL patients at stable remission phase but might influence the functional properties of other Treg subsets like CD4+CD25-FOXP3+ Tregs.

Vitamin D status influences cytokine production and MALAT1 expression from the PBMCs of patients with coronary artery disease and healthy controls.

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 (<15 ng/ml) CAD and NCAD participants. Furthermore, the vitamin D deficient (<15 ng/ml) group showed a significantly higher plasma level of IL-6, IL-10, and IL-22 compared to the non-deficient (≥15 ng/ml) group. In addition, significant positive correlations were found between CD36, IL-22, and fasting blood sugar (FBS) with MALAT1. CONCLUSION: Given that in vitamin D deficient individuals a decreased level of MALAT1 was associated with CD36 expression and increased IL-22 production, vitamin D supplementation may play a role in reducing MALAT1/CD36/IL-22 mediated complications such as T2DM and CAD, especially in vitamin D deficiency.

Vitamin D status influences cytokine production and MALAT1 expression from the PBMCs of patients with coronary artery disease and healthy controls

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 (<15 ng/ml) CAD and NCAD participants. Furthermore, the vitamin D deficient (<15 ng/ml) group showed a significantly higher plasma level of IL-6, IL-10, and IL-22 compared to the non-deficient (≥15 ng/ml) group. In addition, significant positive correlations were found between CD36, IL-22, and fasting blood sugar (FBS) with MALAT1. CONCLUSION: Given that in vitamin D deficient individuals a decreased level of MALAT1 was associated with CD36 expression and increased IL-22 production, vitamin D supplementation may play a role in reducing MALAT1/CD36/IL-22 mediated complications such as T2DM and CAD, especially in vitamin D deficiency.

RESUMO OBJETIVO: O objetivo deste estudo foi investigar a expressão do RNA longo não codificante lncRNA MALAT1 e o seu papel na produção de citocinas a partir de células mononucleares do sangue periférico (PBMCs) em pacientes com doença arterial coronariana (DAC) e participantes sem DAC (NDAC). MÉTODOS: Amostras de sangue foram coletadas de 15 pacientes com DAC e 15 indivíduos NCAD. O plasma foi usado para análises bioquímicas. As expressões de MALAT1 e CD36 foram avaliadas nas células mononucleares do sangue periférico (PBMCs) isoladas por PCR em tempo real. Além disso, os níveis de citocinas inflamatórias, como a interleucina (IL)-6, IL-10 e IL-22 foram medidas no sobrenadante da cultura de PBMCs por citometria de fluxo. RESULTADOS: Os níveis de MALAT1 e CD36 não foram significativamente diferentes entre os grupos DAC e NDAC. No entanto, um nível inferior de MALAT1 e CD36 foi observado nas PBMCs de participantes com deficiência de vitamina D (< 15 ng/ml) tanto no grupo DAC quanto no NDAC. Além disso, o grupo com deficiência de vitamina D (< 15 ng/ml) apresentou um nível plasmático significativamente maior de IL-6, IL-10 e IL-22 em comparação com o grupo sem a deficiência (≥15 ng/ml). Além disso, foram encontradas correlações positivas significativas entre CD36, IL-22, e glicemia de jejum (GJ) e o MALAT1. CONCLUSÃO: Dado que em indivíduos com deficiência de vitamina D a diminuição do nível de MALAT1 foi associada com a expressão de CD36 e produção aumentada de IL-22, a suplementação de vitamina D pode ter um papel importante na redução de complicações mediadas por MALAT1/CD36/IL-22, tais como DMT2 e DAC, especialmente em casos de deficiência de vitamina D.

Effects of omega-3 fatty acids on serum levels of T-helper cytokines in children with asthma.

BACKGROUND: There has been a considerable interest in the potential therapeutic value of dietary supplementation with ω-3 fatty acids in patients with asthma. OBJECTIVES: This cross-sectional study was designed to identify the effect of ω-3 fatty acids on symptom score, pulmonary function and serum T-helper cytokine concentrations in children with mild to moderate persistent asthma. METHODS: A total of 39 patients among 50 volunteers completed this 3-month study. They took a soft gel capsule containing 180mg EPA and 120mg DHA daily. Pulmonary function was evaluated in 28 eligible patients by spirometry, and serum levels of Th1, Th2, Th9, Th17 and Th22 cytokines were measured by multiplex cytometric bead assay before and after treatment. RESULTS: After treatment with ω-3, symptom score improved in 28 (72%) patients. The results of spirometry showed remarkable improvement in FEV1/FVC (P=0.044) and PEF (P<0.0001) after treatment, but considering a cut-off of 80%, real improvement was observed in 32% of patients with PEF<80% which raised above the cut-off after ω-3 treatment (P=0.004) whereas, FEV1/FVC changes were above the cut-off value in 89% of the patients. After treatment, IL-17A and TNF-α levels decreased significantly (both P=0.049). CONCLUSION: Oral administration of natural anti-inflammatory products such as ω-3 is a promising complementary approach to managing asthma.

Susceptibility patterns and cross-resistance of antibiotics against Pseudomonas aeruginosa isolated from burn patients in the South of Iran.

Pseudomonas aeruginosa plays a prominent role in serious infections in burn patients. Rapid acquisition of multi-drug resistance leads to high morbidity and mortality, especially in burn centers. Ten antibiotics, which were widely used in our burn patients were selected. MICs for imipenem, mropenem, cefepime, ceftazidime, cafoparazone/sulbactam, ticarcillin/clavulanate, piperacillin/tazobactam, ciprofloxacin, tobramycin and amikacin to 70 strains of P. aeruginosa, which were isolated from burn patients were determined by the E-test method (AB Biodisk, Sweden). Extended-spectrum beta-lactamase, group I inducible beta-lactamases and metallo-beta-lactamase activities were also determined. Imipenem and meropenum were the most active in vitro antibacterial agents followed by ciprofloxacin (p<0.05), whereas, ticarcillin/clavulanate was the least active. Almost all (98-100%) of the resistant isolates also showed cross-resistance to cefepime. The majority of imipenem and meropenem resistant isolates (85-100% and 76-100%) demonstrated cross-resistance to all the other antibiotics. ESBLs were detected in only three (4.3%) isolates, whereas, inducible beta-lactamase was observed in eight (11.4%) isolates. Metallo-beta-lactamase was detected in none of the isolates. Almost all of the antibiotic resistant isolates also showed cross-resistance to the majority of penicillins and cephalosporins with or without beta-lactamase inhibitors, from which ticarcillin/clavulanate demonstrated this phenomenon at the highest level.