Adropin, a peptide hormone expressed in liver and brain, is known to improve insulin resistance and endothelial dysfunction. Serum levels of adropin are negatively associated with the severity of coronary artery disease. However, it remains unknown whether adropin could modulate atherogenesis. We assessed the effects of adropin on inflammatory molecule expression and human THP1 monocyte adhesion in human umbilical vein endothelial cells (HUVECs), foam cell formation in THP1 monocyte-derived macrophages, and the migration and proliferation of human aortic smooth muscle cells (HASMCs) in vitro and atherogenesis in Apoe−/− mice in vivo. Adropin was expressed in THP1 monocytes, their derived macrophages, HASMCs, and HUVECs. Adropin suppressed tumor necrosis factor α-induced THP1 monocyte adhesion to HUVECs, which was associated with vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 downregulation in HUVECs. Adropin shifted the phenotype to anti-inflammatory M2 rather than pro-inflammatory M1 via peroxisome proliferator-activated receptor γ upregulation during monocyte differentiation into macrophages. Adropin had no significant effects on oxidized low-density lipoprotein-induced foam cell formation in macrophages. In HASMCs, adropin suppressed the migration and proliferation without inducing apoptosis via ERK1/2 and Bax downregulation and phosphoinositide 3-kinase/Akt/Bcl2 upregulation. Chronic administration of adropin to Apoe−/− mice attenuated the development of atherosclerotic lesions in the aorta, with reduced the intra-plaque monocyte/macrophage infiltration and smooth muscle cell content. Thus, adropin could serve as a novel therapeutic target in atherosclerosis and related diseases.

No abstract

BackgroundNeopterin, a metabolite of GTP, is produced by activated macrophages and is abundantly expressed within atherosclerotic lesions in human aorta and carotid and coronary arteries. We aimed to clarify the influence of neopterin on both vascular inflammation and atherosclerosis, as neither effect had been fully assessed.Methods and ResultsWe investigated neopterin expression in coronary artery lesions and plasma from patients with coronary artery disease. We assessed the atheroprotective effects of neopterin in vitro using human aortic endothelial cells, human monocyte‐derived macrophages, and human aortic smooth muscle cells. In vivo experiments included a study of aortic lesions in apolipoprotein E–deficient mice. Neopterin expression in coronary artery lesions and plasma was markedly increased in patients with versus without coronary artery disease. In human aortic endothelial cells, neopterin reduced proliferation and TNF‐α (tumor necrosis factor α)–induced upregulation of MCP‐1 (monocyte chemotactic protein 1), ICAM‐1 (intercellular adhesion molecule 1), and VCAM‐1 (vascular cell adhesion molecule 1). Neopterin attenuated TNF‐α–induced monocyte adhesion to human aortic endothelial cells and the inflammatory macrophage phenotype via NF‐κB (nuclear factor‐κB) downregulation. Neopterin suppressed oxidized low‐density lipoprotein–induced foam cell formation associated with CD36 downregulation and upregulation of ATP‐binding cassette transporters A1 and G1 in human monocyte‐derived macrophages. In human aortic smooth muscle cells, neopterin suppressed angiotensin II–induced migration and proliferation via c‐Src/Raf‐1/ERK1/2 downregulation without inducing apoptosis. Exogenous neopterin administration and endogenous neopterin attenuation with its neutralizing antibody for 4 weeks retarded and promoted, respectively, the development of aortic atherosclerotic lesions in apolipoprotein E–deficient mice.ConclusionsOur results indicate that neopterin prevents both vascular inflammation and atherosclerosis and may be induced to counteract the progression of atherosclerotic lesions. Consequently, neopterin could be of use as a novel therapeutic target for atherosclerotic cardiovascular diseases.

Boron nitride nanotube (BNNT)@mesoporous silica hybrids with controllable surface zeta potential were fabricated for intracellular delivery of doxorubicin. The materials showed higher suspension ability, doxorubicin intracellular endocytosis efficiency, and LNcap prostate cancer cell killing ability compared with naked BNNTs.

Our data demonstrate no toxic effects up to concentrations of 20 µg/ml, once more confirming biosafety of BNNTs, and again highlighting that nanoparticle aspect ratio plays a key role in the biocompatibility evaluation.

The interaction between boron nitride nanotubes (BNNTs) layer and mesenchymal stem cells (MSCs) is evaluated for the first time in this study. BNNTs layer supports the attachment and growth of MSCs and exhibits good biocompatibility with MSCs. BNNTs show high protein adsorption ability, promote the proliferation of MSCs and increase the secretion of total protein by MSCs. Especially, BNNTs enhance the alkaline phosphatase (ALP) activity as an early marker of osteoblasts, ALP/total protein and osteocalcin (OCN) as a late marker of osteogenic differentiation, which shows that BNNTs can enhance osteogenesis of MSCs. The release of trace boron and the stress on cells exerted by BNNTs with a fiber structure may account for the enhanced differentiation of MSCs into osteoblasts. Therefore BNNTs are potentially useful for bone regeneration in orthopedic applications.

Boron nitride nanotubes@NaGdF4:Eu composites with core@shell structures were fabricated giving the opportunity to trace, target and thus to manipulate BNNTs in vitro. The composites show a significantly higher cellular uptake and chemotherapy drug intracellular delivery ability in the presence of an external magnetic field than that in its absence.

We constructed a modified form of the VS ribozyme containing an imidazole ring in place of adenine at position 756. The novel ribozyme is active in both cleavage and ligation reactions. The reaction is efficient, although relatively slow. The results are consistent with a role for nucleobase catalysis in the catalytic mechanism of this ribozyme.