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

Phenotypic and genotypic assay for detection of extended spectrum B-lactamases production by Klebsiella pnemoniae isolates in Emam Reza Hospital in Tabriz, Iran.

Objectives of this study were to investigate the prevalence of K. pneumoniae producing ESBLs, to evaluate the susceptibility of K. pneumoniae producing ESBLs towards non-beta-lactam antibiotics and to study the dominant ESBLs gene in Emam Reza hospital. K. pneumoniae producing ESBLs identified by phenotypic and genotypic methods. Polymerase Chain Reaction (PCR) performed for detection of blaSHV, TEM and CTX-M. The findings showed that 43.69%, 13.59%, 7.77%, 11.65% and 23.3% were from UTI, ICUs, surgery ward, lesion infections and RTI, respectively. The results showed that 43.7% of isolates were ESBLs produces. The findings revealed that 26.7%, 6.7%, 20% and 0% of K.pneumoniae producing ESBLs were resistant to amikacin, ciprofloxacin, cotrimoxazol and imipenem, respectively. Thirty-nine blaSHV, seven blaTEM and seven blaCTX-M identified among K.pneumoniae producing ESBLs. The results reflected in cold month resistant to third generation cephalosporins were more than warm months. Generally, frequency of blaSHV was more than blaCTX-M and blaTEM

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

The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways

Abstract Acute myeloid leukemia (AML) comprises a multifarious and heterogeneous array of illnesses characterized by the anomalous proliferation of myeloid cells in the bone marrow microenvironment (BMM). The BMM plays a pivotal role in promoting AML progression, angiogenesis, and metastasis. The immune checkpoints (ICs) and metabolic processes are the key players in this process. In this review, we delineate the metabolic and immune checkpoint characteristics of the AML BMM, with a focus on the roles of BMM cells e.g. tumor-associated macrophages, natural killer cells, dendritic cells, metabolic profiles and related signaling pathways. We also discuss the signaling pathways stimulated in AML cells by BMM factors that lead to AML progression. We then delve into the roles of immune checkpoints in AML angiogenesis, metastasis, and cell proliferation, including co-stimulatory and inhibitory ICs. Lastly, we discuss the potential therapeutic approaches and future directions for AML treatment, emphasizing the potential of targeting metabolic and immune checkpoints in AML BMM as prognostic and therapeutic targets. In conclusion, the modulation of these processes through the use of directed drugs opens up new promising avenues in combating AML. Thereby, a comprehensive elucidation of the significance of these AML BMM cells' metabolic and immune checkpoints and signaling pathways on leukemic cells can be undertaken in the future investigations. Additionally, these checkpoints and cells should be considered plausible multi-targeted therapies for AML in combination with other conventional treatments in AML. Video Abstrac