Synthesis and biological characterization of Mn0.5Zn0.5EuxDyxFe1.8-2xO4 nanoparticles by sonochemical approach.

Metallic nanoparticles (NPs) possess unique properties which makes them attractive candidates for various applications especially in field of experimental medicine and drug delivery. Many approaches were developed to synthesize divers and customized metallic NPs that can be useful in many areas such as, experimental medicine, drug design, drug delivery, electrical and electronic engineering, electrochemical sensors, and biochemical sensors. Among different metallic nanoparticles, manganese (Mn) NPs are the most prominent materials, in the present study, we have synthetized unique Mn0.5Zn0.5DyxEuxFe1.8-2xO4 NPs by using ultrasonication method (x ≤ 0.1). The structure, and surface morphology of Mn0.5Zn0.5DyxEuxFe1.8-2xO4 NPs was characterized by XRD, SEM, TEM and EDX methods. We have examined the biological effects of Mn0.5Zn0.5DyxEuxFe1.8-2xO4 NPs on both normal (HEK-293) and cancerous (HCT-116) cells. We have found that the treatment of Mn0.5Zn0.5DyxEuxFe1.8-2xO4 NPs post 48 h, showed significant decline in cancer cells population as revealed by MTT assay. The IC50 value of Mn0.5Zn0.5DyxEuxFe1.8-2xO4 NPs was ranged between (2.35 µg/mL to 2.33 µg/mL). To check the specificity of the actions, we found that the treatment of Mn0.5Zn0.5DyxEuxFe1.8-2xO4 NPs did not produce any effects on the normal cells, which suggest that Mn0.5Zn0.5DyxEuxFe1.8-2xO4 NPs selectively targeted the cancerous cells. The anti-bacterial properties of Mn0.5Zn0.5DyxEuxFe1.8-2xO4 NPs were also evaluated by MIC and MBC assays. We suggest that Mn0.5Zn0.5DyxEuxFe1.8-2xO4 NPs produced by sonochemical method possess potential anti-cancer and anti-bacterial capabilities.

Cigarette toxin 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces experimental pancreatitis through α7 nicotinic acetylcholine receptors (nAChRs) in mice.

Clinical studies have shown that cigarette smoking is a dose-dependent and independent risk factor for acute pancreatitis. Cigarette smoke contains nicotine which can be converted to the potent receptor ligand and toxin, NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]. Previously, we have shown that NNK induces premature activation of pancreatic zymogens in rats, an initiating event in pancreatitis, and this activation is prevented by pharmacologic inhibition of nicotinic acetylcholine receptors (nAChR). In this study, we determined whether NNK mediates pancreatitis through the α7 isoform of nAChR using α7nAChR knockout mice. PCR analysis confirmed expression of non-neuronal α7nAChR in C57BL/6 (WT) mouse and human acinar cells. NNK treatment stimulated trypsinogen activation in acini from WT but not α7nAChR-/- mice. NNK also stimulated trypsinogen activation in human acini. To further confirm these findings, WT and α7nAChR-/- mice were treated with NNK in vivo and markers of pancreatitis were measured. As observed in acini NNK treatment induced trypsinogen activation in WT but not α7nAChR-/- mice. NNK also induced other markers of pancreatitis including pancreatic edema, vacuolization and pyknotic nuclei in WT but not α7nAChR-/- animals. NNK treatment led to increased neutrophil infiltration, a marker of inflammation, in WT mice and to a significantly lesser extent in α7nAChR-/- mice. We also examined downstream targets of α7nAChR activation and found that calcium and PKC activation are involved down stream of NNK stimulation of α7nAChR. In this study we used genetic deletion of the α7nAChR to confirm our previous inhibitor studies that demonstrated NNK stimulates pancreatitis by activating this receptor. Lastly, we demonstrate that NNK can also stimulate zymogen activation in human acinar cells and thus may play a role in human disease.