Neuraminidase inhibitors reduce nitric oxide production in influenza virus-infected and gamma interferon-activated RAW 264.7 macrophages

The influenza virus (influenza) infection causes an intense infiltration of pulmonary tissues by macrophages, which abundantly generate a free radical, nitric oxide (NO) resulting in lung damage. Neuraminidase inhibitors (NIs) restrict influenza virus replication but whether they can suppress NO production within macrophages is unknown. RAW 264.7 macrophages were exposed to interferon-gamma (IFN-gamma), live influenza (A/PR/8/34) or a combination of both and were treated with NIs (oseltamivir or zanamivir). Results revealed that the drugs reduced a synergy between influenza and IFN-gamma in NO synthesis within the cells at all of the used concentrations (0.01, 0.1, 1 microg/ml). In contrast to zanamivir, this effect occurred in a concentration-dependent manner with oseltamivir treatment. On the other hand, all concentrations of zanamivir significantly suppressed NO production in comparison to that upon the combined exposure only (p < 0.05). Both compounds also considerably decreased NO generation in the IFN-gamma-stimulated macrophages, and zanamivir in the influenza-infected cells as well. However, neither of the drugs inhibited iNOS mRNA expression in the cells containing these stimulants. Additionally, the data indicate that a prodrug oseltamivir can be activated in vitro within the macrophage cultures. These findings are important for designing treatment approaches to limit pulmonary inflammation during influenza infection.     

A comparison of bone regeneration with human mesenchymal stem cells and muscle-derived stem cells and the critical role of BMP

Adult multipotent stem cells have been isolated from a variety of human tissues including human skeletal muscle, which represent an easily accessible source of stem cells. It has been shown that human skeletal muscle-derived stem cells (hMDSCs) are muscle-derived mesenchymal stem cells capable of multipotent differentiation. Although hMDSCs can undergo osteogenic differentiation and form bone when genetically modified to express BMP2; it is still unclear whether hMDSCs are as efficient as human bone marrow mesenchymal stem cells (hBMMSCs) for bone regeneration. The current study aimed to address this question by performing a parallel comparison between hMDSCs and hBMMSCs to evaluate their osteogenic and bone regeneration capacities. Our results demonstrated that hMDSCs and hBMMSCs had similar osteogenic-related gene expression profiles and had similar osteogenic differentiation capacities in vitro when transduced to express BMP2. Both the untransduced hMDSCs and hBMMSCs formed very negligible amounts of bone in the critical sized bone defect model when using a fibrin sealant scaffold; however, when genetically modified with lenti-BMP2, both populations successfully regenerated bone in the defect area. No significant differences were found in the newly formed bone volumes and bone defect coverage between the hMDSC and hBMMSC groups. Although both cell types formed mature bone tissue by 6 weeks post-implantation, the newly formed bone in the hMDSCs group underwent quicker remodelling than the hBMMSCs group. In conclusion, our results demonstrated that hMDSCs are as efficient as hBMMSCs in terms of their bone regeneration capacity; however, both cell types required genetic modification with BMP in order to regenerate bone in vivo.