Radiation-induced surge of macrophage foam cell formation, oxidative damage, and cytokine release is attenuated by a nanoformulation of curcumin

<p><b>Purpose:</b> We examined the potential of a dendrosomal nanoformulation of curcumin (DNC) for intervention of ionizing radiation (IR)-induced damage (particularly leading to atherosclerosis), employing an irradiated THP-1 macrophage model.</p> <p><b>Materials and methods:</b> Differentiated THP-1 macrophages were irradiated and treated with curcumin or DNC nanoformulation (and oxidized low density lipoprotein, ox-LDL, to promote foam cells). Chemical, biochemical, and genetics tools including viability and apoptosis, multiple ELISA, real-time PCR, Western blotting, enzyme activity, and fluorimetry assays were employed to illustrate IR damage as well as the DNC intervention potential.</p> <p><b>Results:</b> DNC <i>per se</i> at 10 μM exerted no cytotoxic effects on macrophages. However, it caused apoptosis in 2 Gy-irradiated macrophages which were treated with ox-LDL, chiefly through a caspase-dependent pathway involving caspase-3. Concurrently, 10 μM DNC prevented the IR-induced rise in lipid accumulation (72% decrease compared to IR control, <i>p</i> < .0001), dil-oxLDL uptake (78% decrease, <i>p</i> < .005), protein and mRNA expression of cholesterol influx genes, CD36 and SR-A, NF-κB activation (81% less binding activity, <i>p</i> < .001; and lower nuclear presence of p65), cytokine (monocyte chemoattractant protein-1 and interleukin-1β) release, reactive oxygen species (ROS), and oxidative damage to DNA (37% decrease in 8-OHdG, <i>p</i> < .05) and lipids (62% decrease in 8-isoprostane, <i>p</i> < .005). DNC facilitated the uptake of curcumin in irradiated macrophages, increased glutathione peroxidase expression and activity, restored glutathione (GSH) level, and upregulated the expression of a cholesterol efflux gene, ABCA1. Two other antioxidants, resveratrol and N-acetyl cycteine (NAC), could simulate some of the beneficial effects of DNC against IR-induced CD36 expression and lipid accumulation, which were obviated by buthionine sulfoximine (BSO) pre-treatment of macrophages. However, some modulatory effects of DNC, particularly on lipid accumulation and the expression of SR-A and ABCA1 genes, seemed to be independent of its antioxidant effect, since they were still observed in BSO-pretreated macrophages, depleted of GSH.</p> <p><b>Conclusions:</b> DNC treatment suppresses IR-induced oxidative damage, inflammation, and foam cell formation in macrophages through multiple mechanisms.</p

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Abstract The objective of this research was to investigate the influence of the over-expression of recombinant interferon-γ during high cell density cultivation on cellular characteristics of recombinant E. coli. Batch and fedbatch culture techniques were employed to grow Escherichia coli BL21 for production of human gamma-interferon in pET expression system. Final cell densities in batch and fed-batch cultivations were approximately 7 and 127 g cell dry weight (CDW) l -1 , respectively. In both systems, specific growth rate decreased and reached zero, 4 hours after the induction. It was found that high cell density and overexpression of interferon-γ had no substantial effects on cell lysis and plasmid stability. Plasmid content of the cells was nearly similar and remained constant during the post-induction period in both batch and fed-batch cultures (60 mg plasmid per g -1 CDW). In both systems, time profiles of acetate and lactate production were similar, lactate concentration was lower than that of acetate and the concentrations of both were lower than the inhibitory level. Maximum extracellular cAMP concentration occurred at the start of induction in fedbatch culture and was higher than the amount produced during the batch process. The size of E. coli cells reduced significantly as cell density increased and the morphology of the cells in high cell density changed from the usual rod shape to spherical, while the expression of interferon-γ remained almost constant

Vilsmeier Reagent: An Efficient Reagent for the Transformation of 2-Aminobenzamides into Quinazolin-4(3<i>H</i>)-one Derivatives

<div><p></p><p>Clean and easy preparation of quinazolin-4(3H)-one derivatives using 2-aminobenzamides and Vilsmeier reagent is described. 2-Aminobenzamides were converted into the corresponding quinazolinones under mild and efficient conditions, in good yields without undesirable by-products.</p> <p>[Supplementary materials are available for this article. Go to the publisher's online edition of <i>Synthetic Communications</i>® for the following free supplemental resource(s): Full experimental and spectral details.]</p> </div