ABSTRACT
BACKGROUND: Mesenchymal stem cells (MSCs) are of increased importance because of their capacity to counteract inflammation and suppress host immune responses. OBJECTIVES: The aim of the study was to compare the effectiveness of MSCs and hematopoietic stem cells (HSCs) in the treatment of rheumatoid arthritis (RA). MATERIAL AND METHODS: Paw swelling was assessed by measuring the thickness of the hind paws using a caliper. Cytokines - interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-ß), and IL-10 - and rheumatoid factor (RF) were measured using enzyme-linked immunosorbent assay (ELISA) kits. Oxidative stress biomarkers - malondialdehyde (MDA) and reduced glutathione (GSH) were assessed. Nuclear factor-kappaB (NF-κB) was detected by the western blot technique. Toll-like receptor-2 (TLR-2), matrix metalloproteinase-3 (MMP-3) and cartilage oligomeric matrix protein-1 (COMP-1) gene expression were assessed by the real-time quantitative analysis. Mesenchymal stem cells were isolated from the bone marrow (BM) of rats and HSCs were isolated from human umbilical cord blood (UCB). RESULTS: Paw edema, RA score, RF, cytokine assay, antioxidant state, NF-κB, TLR-2, MMP3, and COMP-1 showed improvement in the group that received MSCs compared to the group that received HSCs and the group that received methotrexate. CONCLUSIONS: Mesenchymal stem cells are very effective in reducing RA inflammation; they are superior to HSC and methotrexate treatment. Mesenchymal stem cells could become a better therapeutic opportunity for the treatment of RA.
Subject(s)
Arthritis, Rheumatoid/pathology , Cord Blood Stem Cell Transplantation/methods , Hematopoietic Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/methods , Animals , Anti-Inflammatory Agents , Antioxidants , Disease Models, Animal , Humans , Inflammation/pathology , Male , Oxidative Stress/physiology , Rats , Rats, WistarABSTRACT
Breast cancer is the most common invasive cancer in women worldwide. Sirtuin 1 (SIRT1) has recently been shown to have implications in regulating cancer cell growth and apoptosis. SIRT1 regulates Forkhead box O3a (FOXO3a) by both inhibiting FOXO3-induced apoptosis and potentiating the ability of FOXO3a to resist oxidative stress. Matrix metalloproteinase 2 (MMP2) participates in tumor invasion and metastasis by degrading extracellular matrix. SIRT1 up regulates MMP2 expression by its deacetylation activity. This study aimed to investigate the expression of SIRT1, FOXO3a and MMP2 in breast tissues of women with breast cancer. In addition, the effect of SIRT1 inhibition on both FOXO3a and MMP2 expression in breast cancer (MCF-7) cells was assessed. The expression levels of SIRT1, FOXO3a and MMP2 in the breast tissues were determined by real-time PCR in 60 patients with malignant tumor and in 24 patients with benign tumors. After SIRT1 inhibition, protein levels of SIRT1 and FOXO3a were assessed by Western Blot and levels of MMP2 by ELISA in MCF-7 cells. The expression levels of SIRT1, FOXO3a and MMP2 were significantly higher in breast cancer tissues compared to in benign breast tumor and adjacent normal tissues. SIRT1, MMP2 and FOXO3a expression were associated directly with each other. SIRT1 inhibition suppresses MMP2 and FOXO3a expression compared to control MCF7. Sirtinol (SIRT1 inhibitor) effectively induced inhibition of MMP2 and FOXO3a expression in MCF-7 cells, indicating the promising therapeutic strategy of targeting SIRT1 for breast cancer.
