The Association of Pre-diagnostic Inflammatory Markers and Adipokines and the Risk of Non-Hodgkin Lymphoma Development in Egypt.

Non-Hodgkin lymphoma (NHL) is an etiologically, clinically, and histologically heterogeneous group of lymphoproliferative disorders. Immune dysfunction is a well-known risk factor and dysregulation of cytokines may mediate disease progression. Obesity is one of the important relations connecting immune system abnormalities and lymphomagenesis. We conducted a study to find out the association between obesity as measured by body mass index (BMI), and risk of non-Hodgkin lymphoma (NHL) development by assessment the of inflammatory cytokines levels, (IL-6, IL-10, IFN-gamma and CRP) and adipokines levels (leptin and adiponectin). Also, to predict the effect of higher BMI on the incidence of NHL. The study included 180 NHL patients and 172 healthy controls. The inflammatory markers (IL-6, IL-10, IFN-γ & CRP) together with adiponectin were assessed by ELISA technique. IL-6, IL-10, CRP, IFN-γ and Adiponectin were statistically higher in cases than control. A positive significant difference of Leptin (p-value 0.001) was found with higher levels in patients with BMI (≥ 25 kg/m2) than in patients with < 25 kg/m2. IL-6, IL-10, CRP, IFN-γ and Adiponectin could be implicated in lymphomagenesis in Egyptian NHL. The study results support the hypothesis that obesity has a major role in the development of NHL. An association between Leptin and NHL risk with higher levels in patients with BMI (≥ 25 kg/m2) was proved.

CRISPR-mediated gene modification of hematopoietic stem cells with beta-thalassemia IVS-1-110 mutation.

BACKGROUND: ß-Thalassemias represent a group of genetic disorders caused by human hemoglobin beta (HBB) gene mutations. The radical curative approach is to correct the mutations causing the disease. CRISPR-CAS9 is a novel gene-editing technology that can be used auspiciously for the treatment of these disorders. The study aimed to investigate the utility of CRISPR-CAS9 for gene modification of hematopoietic stem cells in ß-thalassemia with IVS-1-110 mutation. METHODS AND RESULTS: We successfully isolated CD34+ cells from peripheral blood of ß-thalassemia patients with IVS-1-110 mutation. The cells were transfected with Cas9 endonuclease together with guide RNA to create double-strand breaks and knock out the mutation. The mutation-corrected CD34+ cells were subjected to erythroid differentiation by culturing in complete media containing erythropoietin. CONCLUSION: CRISPR/Cas-9 is an effective tool for gene therapy that will broaden the spectrum of therapy and potentially improve the outcomes of ß-thalassemia.

The effect of bone marrow-derived mesenchymal stem cells on chemotherapy induced ovarian failure in albino rats.

OBJECTIVES: Chemotherapy targets rapidly dividing tissues in the body. It destroys the progenitor cells in gonads resulting in premature ovarian failure. Studies have suggested that bone marrow-derived stem cells can generate oocytes in chemotherapy treated female rats after transplantation. The present study aimed to assess mechanism of homing, the action of injected BM-MSCs on ovarian function after ovarian damage. EXPERIMENTAL DESIGN: Seventy two female albino rats were randomly allocated into Control and CTX group, The Experimental protocol was lasted for 12 weeks during which serum FSH and E2 were monitored twice at the end of the 2nd week (12 rats) and 8th week (6 rats). Stem cells identification and homing were evaluated by Flowcytometry and tagging of stem cells with iron oxide particles respectively. Also, histopathological examination was done to evaluate both degeneration (6 rats at 4th week) and regeneration (6 rats at 12th week) of ovarian tissue together with assessment of the levels of TNF-α in ovarian homogenate and IGF-I as a growth factor in ovarian tissue. PRINCIPAL OBSERVATIONS: Partial improvement of E2 and FSH levels as well as ovarian architecture. Elevation of ovarian TNF- α levels and of IGF-I immunohistochemical expressions in ovarian tissues of BM-MSCs injected rats were noticed following homing of BM- MSCs in the ovarian stroma in both control and chemotherapy groups. CONCLUSION: Injected BM- MSCs can home in the stroma of the injured ovaries. IGF-I and TNF- α may have a role in the attraction of stem cells in vivo.

Association between matrix metalloproteinase 2 (MMP2) promoter polymorphisms and the susceptibility to non-Hodgkin's lymphoma in Egyptians.

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases capable of extracellular matrix degradation. MMP2 is the key molecule that control invasion, tumor growth, and metastasis, and has been associated with poor prognosis in several tumors. Several epidemiological studies have focused on the associations between MMP2 promoter polymorphisms and cancer susceptibility; however, little is known about their role in hematological malignancies. The present study aimed to investigate the association of MMP2 -735C/T and -1306C/T promoter polymorphisms with B-NHL susceptibility and their clinicopathological characteristics. The study included 100 B-NHL patients and 100 healthy controls. Genotyping of MMP2 -735C/T and MMP2 -1306C/T was done by polymerase chain reaction restricted fragment length polymorphism (PCR-RFLP) technique. MMP2 -735C/T heteromutant genotype (CT) was detected in 23 % of patients, and the homomutant genotype (TT) was detected in 7 % of patients. The polymorphic allele, T allele, was associated with susceptibility to B-NHL (OR = 2.8:95 %CI = 1.48-5.28). For MMP2 -1306C/T, the frequencies of the polymorphic variants were 5 % for the heteromutant genotype (CT) and 3 % for the homomutant genotype (TT). The polymorphic allele, T allele, conferred almost fourfold increased risk of B-NHL (OR = 3.8, 95 %CI = 1.05-13.9), and the risk elevated to be almost eight folds when confined to diffuse large B-cell lymphoma (DLBCL) (OR = 7.9, 95 %CI = 1.67-32.27). MMP2 -735C/T polymorphic genotypes were correlated with advanced clinical stages of the disease (stages III and IV). In conclusion, the study revealed that the variant alleles of MMP2 -735C/T and MMP2 -1306C/T can be considered as molecular risk factors for B-NHL among Egyptians.