The nuclear protein HMGB1 (high mobility group box 1) is secreted by monocytes-macrophages in response to inflammatory stimuli and serves as a danger-associated molecular pattern. Acetylation and phosphorylation of HMGB1 are implicated in the regulation of its nucleocytoplasmic translocation for secretion, although inflammatory stimuli are known to induce H 2 O 2 production. Here we show that H 2 O 2 -induced oxidation of HMGB1, which results in the formation of an intramolecular disulfide bond between Cys 23 and Cys 45 , is necessary and sufficient for its nucleocytoplasmic translocation and secretion. The oxidation is catalyzed by peroxiredoxin I (PrxI) and PrxII, which are first oxidized by H 2 O 2 and then transfer their disulfide oxidation state to HMGB1. The disulfide form of HMGB1 showed higher affinity for nuclear exportin CRM1 compared with the reduced form. Lipopolysaccharide (LPS)–induced HMGB1 secretion was greatly attenuated in macrophages derived from PrxI or PrxII knockout mice, as was the LPS-induced increase in serum HMGB1 levels.

In this study, we develop an in vivo dielectric imaging technique that measures capacitance using pin-type electrode arrays. Compared to normal tissues, cancer tissues exhibit higher capacitance values, allowing us to image the cancer region and monitor the chemotherapeutic effects of cancer in real-time. A comparison with the histopathological results shows that the in vivo dielectric imaging technique is able to detect small tumors (<3 mm) and tumor-associated changes. In addition, we demonstrate that cancer and inflammation may be distinguished by measuring the capacitance images at different frequencies. In contrast, the positron emission tomography using 2-[18F]-fluoro-2-deoxy-D-glucose was not capable of discriminating between cancer and inflammation.

The nuclear protein HMGB1 (high mobility group box 1) is secreted by monocytesmacrophages in response to inflammatory stimuli and serves as a danger-associated molecular pattern. Acetylation and phosphorylation of HMGB1 are implicated in the regulation of its nucleocytoplasmic translocation for secretion, although inflammatory stimuli are also known to induce H 2 O 2 production. Here we show that H 2 O 2 -induced oxidation of HMGB1 that results in formation of an intramolecular disulphide bond between Cys 23 and Cys 45 is necessary and sufficient for its nucleocytoplasmic translocation and secretion. The oxidation is catalysed by peroxiredoxin I (PrxI) and PrxII, which are first oxidized by H 2 O 2 and then transfer their disulphide oxidation state to HMGB1. The disulphide form of HMGB1 showed a higher affinity for the nuclear exportin CRM1 compared with the reduced form.Lipopolysaccharide (LPS)-induced HMGB1 secretion was greatly attenuated in macrophages derived from PrxI or PrxII knockout mice, as was the LPS-induced increase in serum HMGB1 levels in these mice.