Prognostic correlation of NOTCH1 and SF3B1 mutations with chromosomal abnormalities in chronic lymphocytic leukemia patients.

BACKGROUND AND AIM: Chronic lymphocytic leukemia (CLL) is a monoclonal malignancy of B lymphocytes. Since common mutations in NOTCH1 and SF3B1, along with other possible chromosomal alterations, change disease severity and survival of patients with CLL, we aimed to evaluate the correlation of common mutations in NOTCH1 and SF3B1 as the poor prognostic markers with chromosomal abnormalities and clinical hematology. METHOD: This retrospective study was performed on the peripheral blood of 51 patients diagnosed before chemotherapy with CLL. G-banding karyotype and FISH were performed. For NOTCH1, exon 34 and for SF3B1, exons 14,15,16 were assessed using Sanger sequencing. RESULTS: The mutation frequency of NOTCH1 and SF3B1 with the pathogenic clinical status was 6:51 (11.76%), and variants obtained from both genes were 9:51 (17.64%). The frequency of SF3B1 mutation (K666E) was higher than in previous studies (p-value <.05). There was a significant correlation between NOTCH1 mutations and del17p13 (p-value = .068), also SF3B1 mutations with del11q22 (p-value = .095) and del13q14 (p-value = .066). Up to 90% of the specific stimuli used for the G-banding karyotype successfully identified the malignant clone. There was a significant relationship between the cluster of differentiation 38 (CD38) expression level and NOTCH1 mutations (p-value = .019) and a significant correlation between Binet classification and the SF3B1 (p-value = .096). CONCLUSION: The correlation of NOTCH1 and SF3B1 mutations with chromosomal abnormalities and CD38 expression may reveal the overall patient's survival rate. The mutations may be effective in the clonal expansion and progression of CLL, particularly in the diagnosis stage, as well as the control and management of the treatment.

Soy protein and genistein improves renal antioxidant status in experimental nephrotic syndrome.

BACKGROUND AND OBJECTIVES: Nephrotic syndrome is a chronic disease especially common in the childhood and adolescence. Reactive oxygen species (ROS) and free radicals have significant role in the pathogenesis of nephrotic syndrome. The aim of this study was to evaluate the effect of soy protein and genistein (main isoflavone of soybean) on renal antioxidant status of nephrotic rats. METHODS: This study was done for 8 weeks on 40 adult male Sprague-Dawley rats divided into four groups of 10 rats each. Study groups included: 1-Control, 2-Nephrotic syndrome, 3-Nephrotic syndrome+soy protein diet and 4-Nephrotic syndrome+soy protein diet+genistein. Urine protein and urine creatinine were measured. After homogenization of kidney, total antioxidant capacities (TAC), activities of catalase enzyme, the concentration of malondialdehydes (MDA) and carbolynated proteins were determined spectrophotometrically. Pathological examination was done on kidneys with light microscope. Cell viability was evaluated with MTT assay on WEHI-164 fibro sarcoma cell line. The MMP2 enzyme activity was evaluated in different concentrations of genistein. RESULTS: Total antioxidant capacity was significantly increased in soy genistein. Catalase activity was significantly increased in soy and soy genistein groups. Protein carbonyl and MDA were significantly lower in soy and soy genistein groups. The scores of pathological examination showed significant improvement in soy and soy genistein groups. Genistein decreased the proliferation of the WEHI-164 fibrosarcoma cell line. CONCLUSION: It seems that soy protein decreases kidney damages in nephrotic syndrome. Adding genistein to soy protein causes improvements in antioxidant status of kidney tissue. Genistein decreases proliferation of cell.

Effects of imatinib mesylate in mouse models of multiple sclerosis and in vitro determinants.

Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS), This autoimmune disease is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. Imatinib mesylate is a selective protein tyrosine kinase inhibitor with immunomodulatory properties that abrogates multiple signal transduction pathways in immune cells. In the present research, our aim was to test the therapeutic efficacy of imatinib in experimental model of MS. We performed EAE induction in 23 female C57 mice by myelin oligodendrocyte glycoprotein-35-55 (MOG35-55) in Complete Freund's Adjuvant (CFA) emulsion and used imatinib for treatment of EAE. The clinical evaluation and histopathology were assessed. Also for in vitro analysis, we used U-87 MG, C6 and WEHI-164 cell lines to evaluate the inhibitory effects of imatinib in cell proliferation, as well as pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) and matrix metalloproteinase (MMP) secretion. Our findings demonstrated that this drug had beneficial effects on EAE by attenuation in the severity and a delay in the onset of disease. In vitro, imatinib inhibited cell proliferation, MMP-2 expression and activity and also attenuated the production of proinflammatory cytokines. Imatinib with its potential therapeutic effects and immunomodulatory properties may be considered, after additional necessary tests and trials, for treatment of MS.

The role of different subsets of regulatory T cells in immunopathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease and a systemic inflammatory disease which is characterized by chronic joint inflammation and variable degrees of bone and cartilage erosion and hyperplasia of synovial tissues. Considering the role of autoreactive T cells (particularly Th1 and Th17 cells) in pathophysiology of RA, it might be assumed that the regulatory T cells (Tregs) will be able to control the initiation and progression of disease. The frequency, function, and properties of various subsets of Tregs including natural Tregs (nTregs), IL-10-producing type 1 Tregs (Tr1 cells), TGF-ß-producing Th3 cells, CD8(+) Tregs, and NKT regulatory cells have been investigated in various studies associated with RA and collagen-induced arthritis (CIA) as experimental model of this disease. In this paper, we intend to submit the comprehensive information about the immunobiology of various subsets of Tregs and their roles and function in immunopathophysiology of RA and its animal model, CIA.