Overexpression of miR-490-5p/miR-490-3p Potentially Induces IL-17-Producing T Cells in Patients With Breast Cancer

Objective: Breast cancer (BC) is the most prevalent female cancer globally and this is also true in Iranian women. Alteration in circulating microRNAs affects the fate of immune cells, affecting immunological response to neoplasia. Materials and Methods: We investigated the expression of miR-490-5p and miR-490-3p in peripheral blood mononuclear cells (PBMCs) and plasma of patients with BC. Moreover, the correlation of these microRNAs with the expression levels of CD3d, interleukin 2 (IL-2), IL-2 receptor chain alpha (IL-2RA), forkhead box O1 (FOXO1) and nuclear factor of activated T cells 5 (NFAT5) were investigated. Results: Two groups, including 42 patients with BC, aged 22-75 years with stage I, II, III disease without administration of immunosuppressive chemotherapy regimens/radiotherapy and 40 healthy controls aged 27-70 years, participated. Overexpression and higher circulation levels of miR-490-5p and miR-490-3p were found in the patients with consequent down-regulation of all targets investigated in PBMCs. Furthermore, there was a significant negative correlation between the overexpression of these microRNAs and a reduction in levels of CD3d, IL-2, and IL-2RA in patients with BC. Conclusion: These results suggest that down-regulation of the target genes by miR-490 may predispose and facilitate the production of Th17 lymphocytes and IL-17-producing Tregs. The variation in miR-490-5p/-3p and the investigated targets in the PBMCs of BC patients may be used as non-invasive diagnostic markers

Th1/Th2 cytokines in Type 1 diabetes: Relation to duration of disease and gender

Background: T-cells are important in the pathogenesis of Type 1 diabetes (T1D). However, the exact role of T-cell subpopulations in this pathway remains unknown. The purpose of this study was to assess the expression pattern of T helper 1 (Th1) interferon-gamma (IFN-γ) and Th2 interleukin-4 (IL-4) cytokines and their relationship with sex and disease duration in T1D patients. Materials and Methods: This study was conducted on 21 T1D patients and 22 healthy subjects. Gene expression analysis of peripheral blood mononuclear cells (PBMCs) was performed using real-time reverse transcriptase polymerase chain reaction. Results: IFN-γ gene expression was significantly lower in T1D patients compared with controls (P < 0.05). Conversely, IL-4 mRNAs were significantly increased in the PBMCs from patients as compared to controls (P < 0.05). There was no significant difference in the expression of IL-4 and IFN-γ between men and women with T1D (P > 0.05) while IL-4 mRNA expression in male patients was about 1.9 folds higher than female patients. Moreover, IFN-γ mRNA expression in female patients was about 1.8 folds lower than male patients. Patients were divided into two groups regarding their disease duration: <10 years and >10 years. A significant increase in the IL-4 expression was observed between two groups of patients compared to controls (P < 0.0001). Conversely, there was a significant difference in the expression of IFN-γ only between patients with more than 10 years of disease duration (P = 0.02). Conclusion: These data propose supplementary implications for the role of Th1/Th2 imbalance in T1D immunopathogenesis. Moreover, factors such as sex and disease duration may have some influence on cytokine mRNA expression

Association of the gene expression variation of tumor necrosis factor-α and expressions changes of dopamine receptor genes in progression of diabetic severe foot ulcers

Objective(s):Regulation of pro-inflammatory factors such as TNF-, which are secreted by the immune cells through induction of their several receptors including dopamine receptors (especially DRD2 and DRD3) is one of the noticeable problems in diabetic severe foot ulcer healing. This study was conducted to evaluate the alteration of TNF- in plasma as well as DRD2 and DRD3 changes in PBMCs of diabetics with severe foot ulcers. Materials and Methods: Peripheral blood samples were collected from 31 subjects with ulcers, 29 without ulcers, and 25 healthy individuals. Total mRNA was extracted from PBMCs for the study of DRD2, DRD3, and TNF- gene expression variations. Expression patterns of these genes were evaluated by real-time PCR. Consequently, concentration of TNF- was investigated in plasma. Results: Significant decrease in gene expression and plasma concentration of TNF- in PBMCs was observed in both patient groups at P Conclusion: We concluded that DRD2 and DRD3 expression alteration and presence of new DRD3 transcripts can be effective in reduction of TNF-α expression as a pro-inflammatory factor. Performing complementary studies, may explain that variations in DRD2 and DRD3 are prognostic and effective markers attributed to the development of diabetes severe foot ulcers

Low-Dose Atorvastatin has Promoting Effect on Melanoma Tumor Growth and Angiogenesis in Mouse Model

Background: Preclinical evidence indicates that statins possess diverse antineoplastic effects in different types of tumors. However, clinical studies have yielded conflicting results regarding the potential of statins to either increase or decrease the risk of cancer. Our objective was to examine the relationship between the dose of a treatment and its impact on melanoma tumor growth and angiogenesis in an in vivo setting. Materials and Methods: Melanoma cells were injected into C57BL6 mice in four groups. They received 0, 1, 5, and 10 mg/kg of atorvastatin daily. Three others received the mentioned doses one week before the inoculation of melanoma animals. At the end of the third week, the animals were euthanized in a humane manner, and both blood samples and tumor specimens were collected for subsequent analysis. Results: The tumor size was 1.16 ± 0.25 cm3 in a group treated with therapeutic dose of atorvastatin and was significantly larger than that in the control group (0.42 ± 0.08 cm3). However, there were no significant differences between the two other doses and the control group (0.72 ± 0.22, 0.46 ± 0.08 cm3 in atorvastatin-treated groups with 5 and 10 mg/kg). The vascular density of the tumors was significantly increased in the lowest dose of the atorvastatin treatment group, similar to the results of tumor size (P < 0.05). Conclusion: Atorvastatin, at low therapeutic concentrations, has been observed to stimulate tumor growth and exhibit pro-angiogenic effects. Therefore, it is advised to exercise caution and recommend clinically relevant doses of statins to patients with cancer