Effects of bone marrow mesenchymal stem cells on the cardiac function and immune system of mice with endotoxemia.

The present study aimed to investigate the effects of bone marrow mesenchymal stem cells (MSCs) on the cardiac function and immune system of mice with endotoxemia. The mice were divided into the following groups: Control group, endotoxemia group, lipopolysaccharide (LPS) treatment group, LPS and MSC treatment group (LPS + MSC group) and MSC group. Following treatment with LPS, the cardiac function of the mice was examined at after 2, 6 and 24 h, and on day 7. An enzyme­linked immunofluorescent assay was used to analyze the serum and the levels of cytokines in the myocardium, and western blotting was used to investigate any changes in the levels of signaling proteins associated with the myocardium. A 3­(4,5­dimethyl­2­thiazolyl)­2,5­diphenyl­2H­tetrazolium bromide assay was used to investigate the growth rate of the splenic cells at after 24 h and on day 7, and the humoral immune function and phagocytosis of the macrophages in the mice were also examined. The cardiac function of the mice with endotoxemia declined, although this impairment was circumvented following treatment with MSCs. The levels of interleukin (IL)­1ß, IL­6, tumor necrosis factor­α and IL­10 in the serum and the myocardium increased following stimulation by LPS, although these declined as a result of MSC treatment. The expression levels of Toll­like receptor 4, p65­nuclear factor­κB and phosphorylated p38 in the mouse myocardium were enhanced following stimulation by LPS, which subsequently decreased as a result of MSC treatment. Compared with the control group, the growth rate of the splenic cells, humoral immune function and the level of phagocytosis of macrophages were all increased, although these parameters declined following treatment with MSCs. Taken together, the present study revealed that the MSCs inhibited the inflammatory reaction in the mice with endotoxemia, and improved cardiac function. By contrast, the cellular and humoral immunity were depressed, and phagocytosis of the macrophages, which were enhanced following simulation with LPS, were decreased following treatment with MSCs. However, no overexpression of the anti­inflammatory factor, IL­10, was observed. The present study hypothesized that MSCs exert a bifunctional role in endotoxemia, by inhibiting inflammatory factors, including IL­1 and IL­6, and inhibiting the compensatory expression of IL­10 following LPS stimulation. This avoids the possibility of excessive inhibition of immunological function, as this results in immunosuppression, and a higher ratio of IL­10 to TNF­α is indicative of a poor prognosis in patients with sepsis.

The binding behavior of itraconazole with hemoglobin: studies from multi-spectroscopic techniques.

The interactions between hemoglobin (Hb) and itraconazole (ITZ) are investigated in details using UV-vis spectra, circular dichroism spectroscopy, steady state fluorescence, three-dimensional fluorescence spectra, synchronous fluorescence and time-resolved fluorescence spectra at molecular level. The UV-vis studies represent that ITZ can access into heme group and lead to it explored in aqueous medium. CD spectra suggest ITZ could combine with amino acid residues in polypeptide chain and cause a partial unfolding of Hb (reducing of the α-helix content). Steady state fluorescence/synchronous fluorescence (taking into account inner filter effects) and three-dimensional fluorescence/time-resolved fluorescence spectroscopy results reveal that ITZ alters polarity and conformation around the fluorophore molecule. The interaction processes are static quenching mechanisms. The negative of ΔH(0) and ΔS(0) indicate that hydrogen bonds and van der Waals are the main force.