an-optimized-protocol-for-efficient-radiolabeling-gold-nanoparticles

An Optimized Protocol for the Efficient Radiolabeling of Gold Nanoparticles by Using a <sup>125</sup>I-labeled Azide Prosthetic Group

Here, we demonstrate a detailed protocol for the radiosynthesis of a 125I-labeled azide prosthetic group and its application to the efficient ...

Korea Atomic Energy Research Institute

Isoegomaketone (IK) is an essential oil component of Perilla frutescens (L.) Britt., and there have been no studies investigating its biological activities. We found that IK inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages, and moreover, when IK was injected into animals prior to LPS administration, NO serum levels decreased in a dose-dependent manner. These results indicate that IK possesses anti-inflammatory activity both in vitro and in vivo. IK suppressed the phosphorylation of STAT-1 and the production of IFN-beta. Treatment with IK also inhibited the activation of NF-kappaB and activator protein-1, but more IK was required for inhibition than for STAT-1 inhibition, indicating that downregulation of inducible nitric oxide synthase gene expression by IK is mainly attributed to the blockade of STAT-1 activation. Furthermore, IK also induced the expression of heme oxygenase-1 (HO-1) through the activation of nuclear factor E2-related factor 2. Treatment with SnPP, a selective inhibitor of HO-1, reversed the IK-induced suppression of STAT-1 phosphorylation and NO production. Taken together, IK isolated from P. frutescens inhibits NO production in LPS-treated RAW 264.7 macrophages through simultaneous induction of HO-1 and inhibition of the IFN-beta-STAT-1 pathway.

Isoegomaketone inhibits lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages through the heme oxygenase-1 induction and inhibition of the interferon-beta-STAT-1 pathway.

The aim of this study was to investigate the protective ability of blackberry extract (BE) against oxidative stress in carbon tetrachloride (CCl(4))-treated rats. The results showed that treatment with BE attenuated lipid peroxidation that was increased by CCl(4) and also markedly recovered the activity of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), that were decreased by CCl(4). BE also elevated the protein expression levels of NF-E2-related factor-2 (Nrf2), CuZnSOD, MnSOD, GPx-1/2, and heme oxygenase-1 (HO-1), but not that of catalase. Furthermore, the administration of BE significantly attenuated the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that were increased by CCl(4). Therefore, the present study suggests that BE possesses significant protective effects against in vivo oxidative stress.

Blackberry extract attenuates oxidative stress through up-regulation of Nrf2-dependent antioxidant enzymes in carbon tetrachloride-treated rats.

The anti-inflammatory activities of a prepared isoegomaketone 3a and its derivatives 3b-3f were evaluated in RAW 264.7 cells. Among these, the compound 3d was displayed the most potent inhibitory activities against production of nitric oxide, monocyte chemoattractant protein-1 and interleukin-6. Based on these results, the abilities of compounds 3a-3f to modulate NF-κB and AP-1-mediated gene transcription using a luciferase reporter assay were investigated. The transcriptional activities of NF-κB and AP-1 decreased when pretreated with 3a-3f. Interestingly, at 10 μM, compound 3d markedly suppressed the lipopolysaccharide-induced NF-κB and activator protein-1 DNA binding activities. Some preliminary structure-activity relationships were proposed that may provide a direction for further study.

Biological evaluation of isoegomaketone isolated from Perilla frutescens and its synthetic derivatives as anti-inflammatory agents.

Genistein was irradiated with γ-irradiation at doses of 0, 10, 30, 50, 100, and 150 kGy. We observed that the decrease in the genistein peak after gamma irradiation was concomitant with the appearance of several new peaks. 150 kGy gamma-irradiated genistein did not exert cytotoxicity in macrophages, and inhibited inducible nitric oxide synthase-mediated nitric oxide production and pro-inflammatory cytokines level, such as tumor necrosis factor-α, interleukin-6 and interleukin-1β, in lipopolysaccharide (LPS)-induced macrophages. The treatment of LPS-stimulated macrophages with 150 kGy gamma-irradiated genistein resulted in a significant decrease in cyclooxygenase-2 levels, as well as the expression of cell surface molecules, such as CD80 and CD86. Furthermore, we also found that the anti-inflammatory action of 150 kGy gamma-irradiated genistein occurred through an inhibition of mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2, p38 and c-Jun N-terminal kinase) and nuclear factor-κB signaling pathways based on a toll-like receptor 4 in macrophages, which may be speculated that several radiolysis products of genistein transformed by gamma-irradiation induce the inhibition of pro-inflammatory mediators. From these findings, it seems likely that gamma-irradiated genistein could play a potent role in the treatment of inflammatory disease as a value-added product in the medical industry.

Anti-inflammatory effect of gamma-irradiated genistein through inhibition of NF-κB and MAPK signaling pathway in lipopolysaccharide-induced macrophages.

Herein we report the radiosynthesis of a pyridine derived azide prosthetic group for iodine radioisotope labeling of dibenzocyclooctyne (DBCO) conjugated molecules. The radiolabeling of the stannylated precursor 2 was conducted using [(125)I]NaI and chloramine-T to give (125)I-labeled azide ([(125)I]1) with high radiochemical yield (72±8%, n=4) and radiochemical purity (>99%). Using (125)I-labeled azide ([(125)I]1), cyclic RGD peptide and near infrared fluorescent molecule were efficiently labeled with modest to good radiochemical yields. The biodistribution study and SPECT/CT images showed that [(125)I]1 underwent rapid renal clearance. These results clearly demonstrated that [(125)I]1 could be used as an useful radiotracer for in vivo pre-targeted imaging as well as efficient in vitro radiolabeling of DBCO containing molecules.

Synthesis and evaluation of an (125)I-labeled azide prosthetic group for efficient and bioorthogonal radiolabeling of cyclooctyne-group containing molecules using copper-free click reaction.

In this report, we present a rapid and highly efficient method for radioactive iodine labeling of trans-cyclooctene group conjugated biomolecules using inverse-electron-demand Diels-Alder reaction. Radioiodination reaction of the tetrazine structure was carried out using the stannylated precursor 2 to give (125)I-labeled azide ([(125)I]1) with high radiochemical yield (65±8%) and radiochemical purity (>99%). For radiolabeling application of [(125)I]1, trans-cyclooctene derived cRGD peptide and human serum albumin were prepared. These substrated were reacted with [(125)I]1 under mild condition to provide the radiolabeled products [(125)I]6 and [(125)I]8, respectively, with excellent radiochemical yields. The biodistribution study of [(125)I]8 in normal ICR mice showed significantly lower thyroid uptake values than that of (125)I-labeled human serum albumin prepared by a traditional radiolabeling method. Therefore [(125)I]8 will be a useful radiolabeled tracer in various molecular imaging and biological studies. Those results clearly demonstrate that [(125)I]1 will be used as a valuable prosthetic group for radiolabeling of biomolecules.

Article	Year
Isoegomaketone inhibits lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages through the heme oxygenase-1 induction and inhibition of the interferon-beta-STAT-1 pathwa... Journal of agricultural and food chemistry\| PubMed ID: 20030328	2010
Blackberry extract attenuates oxidative stress through up-regulation of Nrf2-dependent antioxidant enzymes in carbon tetrachloride-treated rats. Journal of agricultural and food chemistry\| PubMed ID: 21888405	2011
Biological evaluation of isoegomaketone isolated from Perilla frutescens and its synthetic derivatives as anti-inflammatory agents. Archives of pharmacal research\| PubMed ID: 21910048	2011
Anti-inflammatory effect of gamma-irradiated genistein through inhibition of NF-κB and MAPK signaling pathway in lipopolysaccharide-induced macrophages. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association\| PubMed ID: 25447760	2014
Synthesis and evaluation of an (125)I-labeled azide prosthetic group for efficient and bioorthogonal radiolabeling of cyclooctyne-group containing molecules using copper-free click reaction. Bioorganic & medicinal chemistry letters\| PubMed ID: 26748695	2016
Highly efficient method for (125)I-radiolabeling of biomolecules using inverse-electron-demand Diels-Alder reaction. Bioorganic & medicinal chemistry\| PubMed ID: 27134118	2016

Dae Seong Choi

Biography

JoVE Journal Publications

Other Publications