The footprint of TGF-ß in airway remodeling of the mustard lung.

Mustard lung is a major pulmonary complication in individuals exposed to sulfur mustard (SM) gas during the Iran-Iraq war. It shares common pathological and clinical features with some chronic inflammatory lung disorders, particularly chronic obstructive pulmonary disease (COPD). Airway remodeling, which is one of the main causes of lung dysfunction and the dominant phenomenon of chronic pulmonary diseases, is seen in the mustard lung. Among all mediators involved in the remodeling process, the transforming growth factor (TGF)-ß plays a pivotal role in lung fibrosis and consequently in the airway remodeling. Regarding the high levels of this mediator detected in mustard lung patients, in the present study, we have discussed the possible roles of TGF-ß in airway remodeling (including epithelial layer damage, subepithelial fibrosis and angiogenesis). Finally, based on TGF-ß targeting, we have reviewed new airway remodeling therapeutic approaches.

The Induction of Metformin Inhibitory Effects on Tumor Cell Growth in Hypoxic Condition.

It is aimed to evaluate the actual anti-cancerous effects of metformin on cancer cells in hypoxic condition. Non-cancerous cells (HEK293) and cancer cells (MCF-7) were cultured in both hypoxia and normoxia conditions and treated with different concentrations of metformin. The proliferation, apoptosis, and necrosis rate were assessed using MTT test and Annexin V assay. The S6K1 phosphorylation was assessed using western blotting. Zymography was used to measure the activity of metalloproteinase-9 (MMP-9). Metformin treatment inhibited proliferation of cancer cells in the optimal concentration of 10 mM under hypoxia condition, while it showed no effects on non-cancerous cell viability. The statistical analysis of MTT assay indicated that the pro-apoptotic function of metformin for cancer cells under hypoxia condition compared to normoxia was significant with different metformin concentrations (p<0.01). However, the effect of metformin treatments for non-cancerous cells under hypoxia condition compared to normoxia was not significant. Western-blot analysis indicated a significant decrease in S6K1 phosphorylation in cancer cells under hypoxia condition (p<0.05). Nevertheless, there was no considerable difference between normoxia and hypoxia conditions in non-cancerous cells. MMP-9 zymography analysis revealed that the highest inhibition of MMP-9 activity was observed in hypoxia condition by 20mM of metformin concentration only in cancer cell. The results indicate that in hypoxia condition metformin exerts its anti-cancerous function by inhibiting proliferation and tumor progression and inducing cell apoptosis more effectively than normoxia condition. In line with cancer cell conditions, most importantly hypoxic condition, metformin can be considered as a potential anti-cancerous drug.

Study of curcumin immunomodulatory effects on reactive astrocyte cell function.

Multiple sclerosis (MS) is considered an inflammatory and neurodegenerative disease of the central nervous system (CNS) which most often presents as relapsing-remitting episodes. Recent evidence suggests that activated astrocytes play a dual functional role in CNS inflammatory disorders such as MS. In this study, we tried to induce anti-inflammatory functions of astrocytes by curcumin. The effects of curcumin were examined on human a astrocyte cell line (U373-MG) induced by lipopolysaccharide (LPS) in vitro. Matrix metalloproteinase (MMP)-9 activity was assessed by gelatin zymography. Cytokine levels were evaluated by quantitative ELISA method and mRNA expression was measured by real-time PCR. We found that curcumin decreased the release of IL-6 and reduced MMP-9 enzyme activity. It down-regulated MCP-1 mRNA expression too. However, curcumin did not have significant effects on the expression of neurotrophin (NT)-3 and insulin-like growth factor (IGF)-1 mRNAs. Results suggest that curcumin might beneficially affect astrocyte population in CNS neuroinflammatory environment lean to anti-inflammatory response and help to components in respects of CNS repair. Our findings offer curcumin as a new therapeutic agent with the potential of regulating astrocyte-mediated inflammatory diseases in the CNS.