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.

Concomitant overexpression of mir-182-5p and mir-182-3p raises the possibility of IL-17-producing Treg formation in breast cancer by targeting CD3d, ITK, FOXO1, and NFATs: A meta-analysis and experimental study.

T cells are polarized toward regulatory T cells (Tregs) in tumor microenvironment by the shuttling of microRNAs that target T cell-activating signaling pathways. We evaluated the expression of the miR-182 cluster (miR-96, 182, and 183) in peripheral blood mononuclear cells (PBMCs) of patients with breast cancer (BC), and T cell polarization by the expression of FOXO1, NFATs, ITK, TCR/CD3 complex, and IL-2/IL-2RA. Twenty-six microRNAs overexpressed in tumor tissues and sera of these patients were extracted by a meta-analysis. Then, the expression of the miR-182 cluster was investigated in PBMCs and sera of these patients and correlated with their targets in PBMCs. Finally, miR-182 was cloned into Jurkat cells to evaluate its effects on T cell polarization. FOXO1, CD3d, ITK, NFATc3, NFATc4, and IL-2RA were targeted by miR-182, due to which their expression decreased in PBMCs of patients. Although IL-6, IL-17, and TGF-ß increased after miR-182 transduction, IL-2 dramatically decreased. We revealed CD4+ FOXP3+ T cell differentiation in the miR-182-transduced group. Although miR-182 has inhibitory effects on T cells by the inhibition of FOXO1, TCR/CD3 complex, NFATs, and IL-2/IL-2RA signaling pathways, it increases FOXP3, TGF-ß, and IL-17 expression to possibly drive T cell deviation toward the transitional state of IL-17-producing Tregs and Treg formation in the end.

Preventive effects of oxytocin and oxytocin receptor in breast cancer pathogenesis.

AIM: Modifications of oxytocin (OT) concentration and OT receptor (OXTR) expression level have different effects on breast cancer-derived cells. This study was conducted to evaluate OT variation in breast cancer patients and to evaluate OXTR expression changes in breast cancer tissues. METHODS: The plasma concentrations of OT in both breast cancer patients and healthy individuals' samples were assessed. OXTR variations were then assessed in both cancerous and noncancerous breast tissues. RESULTS: OT had an increase in breast cancer patients and expression of OXTR in contralateral breast was more than cancerous tissues. CONCLUSION: Despite the high levels of OT concentration in breast cancer patients, it seems that a lower expression of OXTR in cancerous tissues can be effective in the breast cancer progression.

Advances in synthetic biology of oleaginous yeast Yarrowia lipolytica for producing non-native chemicals.

Oleaginous yeast Yarrowia lipolytica is an important industrial host for the production of enzymes, oils, fragrances, surfactants, cosmetics, and pharmaceuticals. More recently, improved synthetic biology tools have allowed more extensive engineering of this yeast species, which lead to the production of non-native metabolites. In this review, we summarize the recent advances of genome editing tools for Y. lipolytica, including the application of CRISPR/Cas9 system and discuss case studies, where Y. lipolytica was engineered to produce various non-native chemicals: short-chain fatty alcohols and alkanes as biofuels, polyunsaturated fatty acids for nutritional and pharmaceutical applications, polyhydroxyalkanoates and dicarboxylic acids as precursors for biodegradable plastics, carotenoid-type pigments for food and feed, and campesterol as a precursor for steroid drugs.

The diversity in the expression profile of caveolin II transcripts, considering its new transcript in breast cancer.

Most studies have revealed the effects of caveolins in cancer inhibition. However, due to a lack of reports about their new transcripts, their presence and their effects on different cancers are unclear. This study was conducted to evaluate the cavolin-2 (cav-2) transcripts expression changes in tumoral and corresponding tissues and in contralateral breast, to investigate their variation associated with the variation of caveolin-1 (cav-1) expression in breast cancer. There were 40 breast-derived tumoral, corresponding, and contralateral tissues obtained from the patients with breast cancer. The RNA and proteins were extracted from these samples. So, cav-1 and cav-2 transcripts' variation were assessed in whole tumoral, corresponding, and contralateral breast. Also, their expression modifications were evaluated via the Western blotting technique. The results derived from this study verified the presence of transcript III of cav-2 for the first time, which was reported only in the gene bank, but we could not detect and validate any protein associated with these transcripts. Also, the decreasing trend of cav-1 and the cav-2 (transcripts I and II) were observed in tumoral tissues compared to unaffected tissues especially in stages I and II. It seems that the descending expression levels of cav-1 and cav-2 (transcript I, II) besides the lasting expression of cav-2 (transcript III) are associated with the incidence and promotion of breast cancer, especially in the initial stages of breast cancer. So, this may show a potential in determining the patients who can undergo the prophylactic mastectomy. Moreover, the results of the study demonstrated that transcript III may be a candidate as a non-coding RNA.

Enhanced production of nisin by co-culture of Lactococcus lactis sub sp. lactis and Yarrowia lipolytica in molasses based medium.

Nisin is a safe, approved and commercial bacteriocin that is produced by Lactococcus lactis subsp. lactis. Since lactate accumulation in fermentation medium reduces L. lactis growth and nisin production, Yarrowia lipolytica, a lactate consuming yeast and L. lactis subsp. lactis, were simultaneously cultured in a molasses based medium. Y. lipolytica is not able to consume sucrose as carbon source, but rather consumes lactate and hence decrease lactic acid titer by 10% in the medium. Lactic acid consumption, 15% increased pH value and stimulated L. lactis growth. In the mixed culture, nisin production and L. lactis growth were 50% and 49% higher than that of pure culture, respectively. Also the results showed that specific growth rate of L. lactis increased 4 times more than that of the pure culture.

Acute Myeloid Leukemia as the Main Cause of Pancytopenia in Iranian Population.

BACKGROUND & OBJECTIVE: Pancytopenia is the reduction in the number of all 3 major cellular elements of blood and leads to anemia, leukopenia, and thrombocytopenia. A wide variety of etiologies result in pancytopenia including leukemia, aplastic anemia, and megaloblastic anemia. The current study identified the different etiologies of pancytopenia based on bone marrow examination in Iranian patients with pancytopenia. METHODS: A total of 683 cases of pancytopenia with various etiologies were selected for this retrospective study. Bone marrow biopsy was performed with the standard technique using Jamshidi needle. The inclusion criteria for patients with pancytopenia were hemoglobin (Hb) <10 g/dL, total leukocyte count (TLC) <4 x 109/L, and platelet count <140 x 109/L. RESULTS: In the present study acute leukemia was the first most common etiology detected in 235 (35.4%) patients in which acute myeloid leukemia (AML) comprised the majority of cases 142 (21.4%), followed by myelodysplastic syndrome (MDS) 100 (15%). In patients less than 20 years old, acute leukemia was also the commonest cause identified in 56 (57.7%) cases in which acute lymphoblastic leukemia (ALL) with 38.7% was the most common etiology; however in adults (>45 year old), AML accounted for the majority of cases 76 (53.5%). CONCLUSION: Since acute leukemia was the commonest etiology in both young and adults in which AML accounted for the majority of cases with pancytopenia in Iranian population, there was an urgent need to identify the underlying molecular or genetic mechanism of this malignancy for better further medical management and patients` survival.

Coexistence of splenic hemangioma and vascular malformation of the vertebrae.

BACKGROUND: Cavernous hemangioma is an encapsulated mass of dilated, endothelial lined vascular channels filled with slowly flowing blood. Cavernous hemangioma of the spleen is a rare condition with less than 100 reports so far. Hemangioma of the vertebral is a benign vascular legion around one or two vertebrae. These are usually asymptomatic and discovered incidentally. In this study we reported an extreme rare case of splenic hemangioma coexistence with vascular malformation of the vertebrae. To our knowledge this is the first report of coexistence of splenic hemangioma and hemangioma of the vertebra. CASE PRESENTATION: A 20-year-old iranian male with splenomegaly, abdominal pain, diarrhea and pancytopenia who was first highly suspicious for malignancy referred to our center for evaluation of the diagnostic workup. After full examination we detected a very rare case with a giant, solitary cavernous hemangioma of the spleen and multiple hemangiomas in his vertebrae. Histopathology of the spleen showed a large cavernous hemangioma occupying almost the entire spleen with large areas of infarction necrosis with multiple hemangiomas of the vertebrae. CONCLUSION: It is extremely rare to have a splenic hemangioma concurrent with vertebra hemangioma and this is clinically very important to consider splenic hemangioma in differential diagnosis of splenomegaly for a better therapeutic management in related patients.