Frequency of beta-thalassemia or beta-hemoglobinopathy carriers simultaneously affected with alpha-thalassemia in Iran.

BACKGROUND: Beta-thalassemias are prevalent heritable single gene disorders affecting the quantity of the hemoglobin molecule. Rarely, a co-inheritance of these impairments with alpha-thalassemia and/or a hemoglobinopathy occurs and makes an important double heterozygote or homozygous state. Thus finding these cases is essential for genetic counseling. The present study aimed to identify the prevalence of coexistent alpha-thalassemia mutations, hemoglobinopathies, and beta-thalassemia determinants. METHODS: This descriptive study was performed on 5760 patients. We used complete blood cell count, Hb electrophoresis, and HbA2 measurement for thalassemia carrier identification. Increased HbA2 (> or = 3.5%) is the standard diagnostic marker for beta-thalassemia, while normal HbA2 with low MCH and MCV can indicate an alpha-thalassemia carrier or atypical beta-thalassemia minor. Individuals with MCV < 80 fL, MCH < 27 pg, and hemoglobin < or = 15.3 g/dL in men or < or = 14 g/dL in women, were candidates for molecular thalassemia investigations. Patients with abnormal hemoglobin varieties in hemoglobin electrophoresis were referred to a genetics laboratory for hemoglobinopathy detection. RESULTS: 141 subjects out of 5760 were affected by alpha and beta-thalassemia or a beta-hemoglobinopathy simultaneously, including: 13 (11.1%) fetuses, 55 (38.2%) male cases, and 73 (50.7%) females. Among these 141 alpha-thalassemia patients, 92 cases (65.24%) were beta-thalassemia carriers and 3 (2.12%) were beta-thalassemia major, 43(30.49%) had beta-hemoglobinopathies, and 3 cases (2.12%) had co-inherited beta-thalassemia and variant hemoglobins. 31 beta-gene mutations were observed in this population, the most common being HbS Cd6 (A > T) (24%). These thalassemia determinants account for about 46% of all detected mutations. As for alpha-gene mutations, -3.7 detection was the most prevalent. CONCLUSIONS: The relatively high prevalence of co-inherited alpha-thalassemia and hemoglobinopathies among beta-thalassemia carriers indicates the importance of molecular analysis to diagnose these double heterozygous or sole homozygous cases for prenatal diagnostic purposes and putting forth strategies to prevent more complicated and dangerous combinations.

The effect of exercise training on the level of tissue IL-6 and vascular endothelial growth factor in breast cancer bearing mice.

OBJECTIVES: The goal of this study was assessing the prophylactic effect of exercise and its role as an adjuvant therapy on level of cytokines involved in angiogenesis in estrogen-dependent breast cancer. MATERIALS AND METHODS: Forty female BALB/c mice were randomly assigned to exercise-tumor-exercise (ETE), exercise-tumor-rest (ETR), rest-tumor-exercise (RTE) and rest-tumor-rest (RTR) groups. After orientation in the environment, two groups of mice performed continuous endurance exercise for 8 weeks, and thereafter estrogen-dependent MC4L2 cancer cells were injected to them. Then, one group of each of trained and non-trained mice performed endurance exercise 5 days per week for 6 weeks. Tumor volume was measured by a digital caliper weekly. Finally, the mice were sacrificed; tumor tissue was removed, immediately frozen and kept in -70°C. Tumor sample was homogenized; levels of cytokines were measured and quantified using ELISA. RESULTS: There was significant reduction in the level of interlukin-6 (IL-6) (P=0.001), Vascular endothelial growth factor (VEGF) (P=0.0001) and tumor volume (P=0.0001) among the groups performing endurance exercise after malignancy (RTE and ETE) in comparison with groups not performing endurance exercise (ETR and RTR), and these results were in agreement with tumor growth rate. CONCLUSION: Exercise can cause reduction in levels of pro-inflammatory cytokines in tumor tissue. Decreased IL-6 production could reduce the generation of VEGF, resulting in reduced intra-tumor angiogenesis. Due to reduction of the level of these cytokines in groups doing exercise before and after malignancy, exercise is presumed to be an adjuvant therapy in estrogen-receptor dependent tumors in addition to its effective prophylactic role.

Evaluation of the Effect of miR-26b Up-Regulation on HbF Expression in Erythroleukemic K-562 Cell Line.

BACKGROUND: The major hemoglobin in the fetus is hemoglobin F (HbF) (α2γ2), whereas in adult humans, hemoglobin A (α2ß2) is predominately expressed. Several studies have indicated that expression of the HbF subunit γ-globin might be regulated post-transcriptionally. This could be done by small non-coding RNAs called microRNAs which target mRNAs in a sequence-specific manner and lead to translational repression or mRNA decay. The aim of this study is to evaluate the effect of miR-26b up-regulation on γ-globin gene expression in K-562 cell line. METHODS: These cells were grown in RPMI 1640 and pre miR-26b and were transfected within K-562 cell line using lentiviral vector. After RNA extraction and cDNA synthesis in selected days, miRNA up-regulation was confirmed by miRNA real time PCR and then γand ßchain and GATA-1 expression were investigated by RT and QRT-PCR. RESULTS: The viability of cells before transfection was 90%. Three and 7 days after transfection, through the use of relative Q-PCR, the γ chain expression increased 3.7, 6.8 and 3.8 folds and GATA-1 expression increased 2.1, 6.0 and 8.0 in comparison with untransfected cells. CONCLUSION: The data suggest that miR-26b can be involved in the increase of γ-globin gene expression in K-562 cell line. We suggest that miR-26b may be a significant therapeutic target for increasing HbF levels in patients with sickle cell disease and ß-thalassemia.

The Effect of miR-210 Up-regulation on Proliferation and Survival of Mouse Bone Marrow Derived Mesenchymal Stem Cell.

BACKGROUND: Bone marrow derived mesenchymal stem cells (MSCs) are a population of multipotent progenitors which have the capacity of proliferation and differentiation into mesenchymal lineage cells. Hypoxia could promote the proliferation of MSCs. Micro-RNAs are endogenous RNAs that can play an important role in some processes such as proliferation and differentiation. MiR-210 could help for better proliferation of MSCs since this miRNA could activate HIF pathway. In current study we investigated if MSCs can preserve their differentiation and proliferation ability under normoxic conditions by upregulation of miR-210. MATERIALS AND METHODS: MSCs isolated from C57 BL/6 mice by flushing it's femurs into the cell culture media. After 72 hours, MSCs which are plastic adherent cells were attached to the flask and non-adherent cells were removed. Subsequently, MSCs induced to differentiate into osteocytes and adipocytes with specific differentiation media in order to confirm their identity and multipotency. Then miR-210 was inserted in Lentiviruse vectors and affected MSCs. In each passage, the number and viability of cells were evaluated. RESULTS: Comparison between miR-210 infected MSCs with control cells showed that miR-210 has ability to increase proliferation of MSCs significantly. CONCLUSION: We showed that miR-210 has ability to induce proliferation of MSCs without any negative effect on their differentiation abilities. Further studies are needed for evaluation of probable effects of miR-210 mechanisms on MSCs proliferation.

Evaluation of liver and kidney function in favism patients.

BACKGROUND: G6PD deficiency is the most common enzymopathy of red blood cells. The clinical symptoms of favism are jaundice, hematuria and haemolytic anaemia that seem to affect liver and kidney in long term. Thus we evaluate kidney and liver function of favism patients in an endemic area of the disease with a high rate of fava beans cultivation. METHODS: This study was performed on favism patients and healthy controls referring to Iranshahr central hospital. Liver and kidney function tests were performed. RESULTS: The results showed a statistically significant difference between these two groups (p <0.05) for liver function tests, (AST, ALT and ALP), but not for renal tests (BUN and creatinine) (p >0.05). CONCLUSION: Due to abnormalities were seen in the liver function tests of these patients, we suggest that these tests be regularly performed for favism patients who are constantly exposed to oxidant agents.

Anemia and thrombocytopenia in acute and chronic renal failure.

BACKGROUND: Acute renal failure describes as a syndrome by rapid decline in the ability of the kidney to eliminate waste products, regulate acid-base balance, and manage water homeostasis. When this impairment is prolonged and entered chronic phase, erythropoietin secretion by this organ is decreasing and toxic metabolic accumulates and causes hematological changes include decrease of HCT, MCV and RBC and platelet counts. This study evaluates present of anemia and thrombocytopenia in patients with acute and chronic renal failure. MATERIALS AND METHODS: This study conducted on 132 patients with renal impairment and also 179 healthy individuals as two separated control groups. Initially patients with renal problem were tested and after confirmation of impairment, patients were divided in two groups, acute with less than 3 months and chronic with more than 3 months renal failure, based on duration of the disease. Then complete blood count performed for each patient and finally obtained data were analyzed by SPSS software. RESULTS: Comparison between 96 patients with acute and 36 patients with chronic renal failure revealed that severity of anemia (HCT, Hb and MCV) between these two groups were statistically high in comparison with control groups (P > 0.05) but thrombocytopenia in patients with chronic renal failure was statistically different from control and the acute ones (P < 0.001). CONCLUSION: It was recommended that in patients with chronic renal failure, to prevent the risk of bleeding, platelet count should be checked periodically.