PEG-BHD1028 Peptide Regulates Insulin Resistance and Fatty Acid ß-Oxidation, and Mitochondrial Biogenesis by Binding to Two Heterogeneous Binding Sites of Adiponectin Receptors, AdipoR1 and AdipoR2.

Adiponectin plays multiple critical roles in modulating various physiological processes by binding to its receptors. The functions of PEG-BHD1028, a potent novel peptide agonist to AdipoRs, was evaluated using in vitro and in vivo models based on the reported action spectrum of adiponectin. To confirm the design concept of PEG-BHD1028, the binding sites and their affinities were analyzed using the SPR (Surface Plasmon Resonance) assay. The results revealed that PEG-BHD1028 was bound to two heterogeneous binding sites of AdipoR1 and AdipoR2 with a relatively high affinity. In C2C12 cells, PEG-BHD1028 significantly activated AMPK and subsequent pathways and enhanced fatty acid ß-oxidation and mitochondrial biogenesis. Furthermore, it also facilitated glucose uptake by lowering insulin resistance in insulin-resistant C2C12 cells. PEG-BHD1028 significantly reduced the fasting plasma glucose level in db/db mice following a single s.c. injection of 50, 100, and 200 µg/Kg and glucose tolerance at a dose of 50 µg/Kg with significantly decreased insulin production. The animals received 5, 25, and 50 µg/Kg of PEG-BHD1028 for 21 days significantly lost their weight after 18 days in a range of 5-7%. These results imply the development of PEG-BHD1028 as a potential adiponectin replacement therapeutic agent.

Identification of Vaccinia-H1 Related Phosphatase as an Anticancer Target for 1,2,3,4,6-O-Pentagalloylglucose.

Protein tyrosine phosphatases are involved in diverse human diseases, including cancer, diabetes and inflammatory disorders. Loss of Vaccinia-H1 related phosphatase (VHR) has been shown to arrest at the G1-S and G2-M transitions of the cell cycle, and to increases cell death of prostate cancer cells through JNK activation, suggesting that VHR can be considered as an anticancer target. In this study, 658 natural products were screened through in vitro enzyme assay to identify VHR inhibitor. Among the VHR-inhibitory compounds, 1,2,3,4,6-O-pentagalloylglucose (PGG) was selected for further study as it has been reported to show antitumor effects against tumor model mice, but its direct target has not been identified. PGG inhibited the catalytic activity of VHR (Ki =53 nm) in vitro. Furthermore, the incubation of HeLa cervical cancer cells with PGG dramatically decreased cell viability and markedly increased the protein levels of the cleaved PARP, a hallmark of apoptosis. In addition, treatment of HeLa cells with PGG significantly reduced the protein levels of cyclin D1, Bcl-2 and STAT3 phosphorylation. Taken together, these results suggest that PGG could be a potential therapeutic candidate for the treatment of cervical cancer through VHR inhibition.

Development of an inverse distance weighted active infrared stealth scheme using the repulsive particle swarm optimization algorithm.

Treatments for detection by infrared (IR) signals are higher than for other signals such as radar or sonar because an object detected by the IR sensor cannot easily recognize its detection status. Recently, research for actively reducing IR signal has been conducted to control the IR signal by adjusting the surface temperature of the object. In this paper, we propose an active IR stealth algorithm to synchronize IR signals from the object and the background around the object. The proposed method includes the repulsive particle swarm optimization statistical optimization algorithm to estimate the IR stealth surface temperature, which will result in a synchronization between the IR signals from the object and the surrounding background by setting the inverse distance weighted contrast radiant intensity (CRI) equal to zero. We tested the IR stealth performance in mid wavelength infrared (MWIR) and long wavelength infrared (LWIR) bands for a test plate located at three different positions on a forest scene to verify the proposed method. Our results show that the inverse distance weighted active IR stealth technique proposed in this study is proved to be an effective method for reducing the contrast radiant intensity between the object and background up to 32% as compared to the previous method using the CRI determined as the simple signal difference between the object and the background.