Acute course of deferoxamine promoted neuronal differentiation of neural progenitor cells through suppression of Wnt/ß-catenin pathway: a novel efficient protocol for neuronal differentiation.

Neural progenitor cells (NPCs) are feasible therapeutically model cells in regenerative medicine. However, a number of obstacles oppose their applications including insufficiency in differentiation protocols. These complications should be overwhelmed to obtain a significant clinical application. Deferoxamine (DFO), as a small molecule with a clinically high-affinity to chelate intracellular Iron, has been granted orphan drug status for treatment of traumatic spinal cord injury, while its neuroprotective function is not well understood. The aim of the present study is evaluating whether DFO could modulate neuronal differentiation process of NPCs. A varies concentrations of DFO were used to promote neuronal differentiation of mouse and human NPCs with different serum condition as an extracellular source of Iron. Several neural markers were assessed by RT-qPCR and Western analysis. Meanwhile ß-catenin content was evaluated as key member of Wnt pathway. The maximal neuronal differentiation rate was observed when treating cells were treated with acute dosage of DFO (100 µM) for 6h in serum free condition. This treatment produced a significant increase in expression of neuronal markers and resulted in dramatically decrease in expression of glial markers. The protein content of ß-catenin was also decreased by this treatment. Despite of chronic concentration of DFO, which reduced the size of EBs apparently due to G1/S arrest of cell cycle as known features of DFO. Application of acute courses of DFO increased neuronal differentiation rate of NPCs in serum free conditions. We concluded that suppression of Wnt/ß-catenin pathway was induced through chelating of intracellular Iron due to DFO treatment. These findings help to understand therapeutic benefit of DFO as a neuroprotective agent.

Predictors of smoking cessation and duration: implication for smoking prevention.

BACKGROUND: There are few articles studding the factors associated with successful smoking cessation in Iranian smokers. The aim of this study is to clarify the association between socio-demographic factors and smoking behavior, such as number of failed smoking cessation and duration of abstinence in Iranian population. METHODS: A self-administered questionnaire survey of 673 participants was conducted in a local government health-care center. The questionnaire included items on socio-demographic information including, age, marital status, education, income, and job. Furthermore, information on smoking cigarettes including number of smoking per day, duration of smoking, cigarettes brand, nicotine concentration, and history of cessation was obtained. RESULTS: Mean ± SD of age and daily cigarette consumption were 39.7 ± 1.1 and 22.1 ± 1.1 respectively. Failure rate of smoking cessation was higher in the lower age group (odds ratios [OR] 2.9; 95% confidence intervals [CI] 1.1, 7.7) and less than 10 numbers smoking per day (OR 2.4; 95% CI 1.3, 4.5) and duration of smoking more than 30 years (OR 3.4; 95% CI 1.2, 9.3) and foreign cigarette brand (OR 1.8; 95% CI 1.1, 2.7). Length time of cessation was prominent in participants with lower age group (OR 5.4; 95% CI 1.3, 22.1), and less than 10 numbers smoking per day (OR 2.7; 95% CI 1.5, 4.9) and lower in smokers with duration of smoking more than 10 and 10-19 years (OR 0.32; 95% CI 0.12, 0.89), (OR 0.34; 95% CI 0.17, 0.76), respectively. CONCLUSIONS: The above results suggest that there are a significant association between socio-demographic factors and smoking-related behaviors in the Iranian population, consistent with previous reports world-wide. These factors should be considered to have appropriate public-health and policy response.