Adipose sirtuin 6 drives macrophage polarization toward M2 through IL-4 production and maintains systemic insulin sensitivity in mice and humans

Song, Mi-Young,Kim, Sang Hoon,Ryoo, Ga-Hee,Kim, Mi-Kyung,Cha, Hye-Na,Park, So-Young,Hwang, Hong Pil,Yu, Hee Chul,Bae, Eun Ju,Park, Byung-Hyun Nature Publishing Group UK 2019 Experimental and molecular medicine Vol.51 No.5

<▼1><P>Adipose tissue inflammation is a reproducible feature of obesity and obesity-linked insulin resistance. Although sirtuin 6 (Sirt6) deficiency has previously been implicated in diet-induced obesity and systemic insulin resistance, the adipocyte-specific role of Sirt6 in the regulation of adipose tissue inflammation and systemic metabolic dysfunction in mice fed normal chow and in humans remains elusive. Here, using <I>Adipoq-Cre</I>-mediated adipocyte-specific Sirt6 knockout (aS6KO) mice, we explored whether adipocyte Sirt6 inhibits adipose tissue inflammation and its underlying mechanism. aS6KO mice fed normal chow gained more body weight and fat mass than wild-type mice and exhibited glucose intolerance and systemic insulin resistance. Measurement of plasma and tissue cytokines and flow cytometric analysis of adipose stromal vascular cells indicated a decrease in alternatively activated M2 macrophages in the adipose tissue of aS6KO mice. Mechanistically, Sirt6 regulated the expression of the canonical type 2 cytokine IL-4 by adipocytes in a cell autonomous manner, which in turn affects M2 macrophage polarization. Consistent with animal experimental data, the degree of obesity and insulin resistance demonstrated by the body mass index, fasting blood glucose and HbA1c correlated negatively with the expression of Sirt6 in human visceral fat tissues. Collectively, these results suggest that adipocyte Sirt6 regulates body weight gain and insulin sensitivity independent of diet, and the increased IL-4 production by Sirt6 and resultant M2 polarization of adipose tissue macrophages may attenuate proinflammatory responses in adipose tissue.</P></▼1><▼2><P><B>Obesity and diabetes: A control protein in fat</B></P><P>A protein in adipose tissue (composed of fat cells) helps protect against inflammation and the development of resistance to insulin that develops in obesity and can lead to type 2 diabetes. Researchers in South Korea, led by Eun Ju Bae at Woosuk University, Wanju, and Byung-Hyun Park at Chonbuk National University, Jeonju, investigated the role of Sirt6 in mice and in human adipose tissue. Deleting the mouse gene that codes for Sirt6 in adipocytes promoted the impaired response to insulin and associated increase in blood glucose levels that are two key aspects of diabetes. Changes in biochemical signaling pathways controlling immune cells called macrophages were implicated in these effects and suggest an anti-inflammatory role for Sirt6. Analysis of human adipose tissue supported these findings. The research will help understand how obesity promotes type 2 diabetes.</P></▼2>

Bio-conversion of Liquiritin and Liquiritin Apioside from Glycyrrhiza uralensis Root to Liquiritigenin during Nuruk Fermentation

Byung-Jhip HA,Chang-Sub KU,Dong-Jun BAE,Kyu-Sang HWANG,Chang-Ho KIM,Dong-IL JANG 한국생물공학회 2009 한국생물공학회 학술대회 Vol.2009 No.4

In-Hospital Medical Complications and Long-Term Mortality After Ischemic Stroke

Bae, Hee-Joon,Yoon, Doo-Sang,Lee, Juneyoung,Kim, Byung-Kun,Koo, Ja-Seong,Kwon, Ohyun,Park, Jong-Moo Ovid Technologies Wolters Kluwer -American Heart A 2005 Stroke Vol.36 No.11

<P>BACKGROUND AND PURPOSE: Inhospital medical complications account for a considerable portion of deaths during the early stage of stroke. However, relatively few studies have examined their long-term effects on mortality in stroke patients. METHODS: We prospectively and consecutively collected data on 579 patients with acute ischemic stroke from November 1998 to February 2001. Mortality was confirmed using national death certificate data from 1999 to 2003. RESULTS: During admission, one or more medical complications requiring intervention developed in 160 of these 579 patients (27.6%). For these 160 subjects, the 30-day, 90-day, 1-year, 2-year, 3-year, and 4-year mortalities were 16.3, 29.4, 46.9, 55.6, 61.3, and 70.7%, whereas the mortality figures for those without such complications (n=419) were 1.4, 3.8, 8.8, 15.0, 19.1, and 22.4 (P<0.001 with log-rank test). To eliminate the short-term effects of these complications and thus reveal their long-term effects, we investigated differences in mortality versus the presence of inhospital complications at more than 30 days, 90 days, 1 year, 2 years, and 3 years after stroke, respectively. Cox's proportional hazard regression analysis was applied at these times after stroke and showed that all hazard ratios of medical complications in terms of mortality were statistically larger than one, regardless of adjusting for effects of potential predictors on mortality. CONCLUSIONS: Our study shows that stroke patient mortality is influenced by inhospital medical complications significantly up to the chronic stage. This finding suggests that the appropriate prevention and management of inhospital complications could improve short-term and long-term prognoses after stroke.</P>

Enhanced Expression of Recombinant Proteins by the Partial Polyhedrin-fused Expression System in Insect Cells

Sung Min Bae,Hee Jung Kim,Tae Young Shin,Jae Bang Choi,Yeon Ho Je,Byung Rae Jin,Soo Dong Woo 한국응용곤충학회 2014 한국응용곤충학회 학술대회논문집 Vol.2014 No.04

Polyhedrin is the major component of the nuclear viral occlusions produced during replication of the baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV). To enhance the production efficiency of foreign protein in baculovirus expression system, the effects of various polyhedrin fragments were investigated by fusion expressing them with the enhanced green fluorescent protein (EGFP). Recombinant viruses were generated to express EGFP fused with polyhedrin fragments based on the previously reported minimal region for self-assembly and the KRKK nuclear localization signal (NLS). The marked increase of EGFP by these fusion expressions was confirmed through protein and fluorescence intensity analyses. Among the fusion-expressed protein in nucleus and cytoplasm, the most hyper-expression was observed in the fusion of amino acids 19 to 110 and 32 to 59 of polyhedrin. Also these fragments, some degradation of only the fused polyhedrin was observed in the fusion of amino acids 19 to 85 and 32 to 85. The production of E2 protein, which is a major antigen of classical swine fever virus, was dramatically increased by fusion expression with polyhedrin amino acids 19 to 110, and its preliminary immunogenicity was verified using experimental guinea pigs. The production of luciferase was approximately two folds increased by fusion expression with polyhedrin amino acids 32 to 59, and its activity was measured using Luminometer. This study suggests a new option for higher expression of useful foreign recombinant protein using the partial polyhedrin fusion expression in baculovirus.

SPA0355 attenuates ischemia/reperfusion-induced liver injury in mice

Bae, Ui-Jin,Yang, Jae Do,Ka, Sun-O,Koo, Jeung-Hyun,Woo, Seong Ji,Lee, Young-Rae,Yu, Hee Chul,Cho, Baik Hwan,Zhao, Hui-Yuan,Ryu, Jae-Ha,Lee, Sang-Myeong,Jeon, Raok,Park, Byung-Hyun Nature Publishing Group 2014 Experimental and molecular medicine Vol.46 No.8

<P>Hepatic ischemia/reperfusion (I/R) injury leads to oxidative stress and acute inflammatory responses that cause liver damage and have a considerable impact on the postoperative outcome. Much research has been performed to develop possible protective techniques. We aimed to investigate the efficacy of SPA0355, a synthetic thiourea analog, in an animal model of hepatic I/R injury. Male C57BL/6 mice underwent normothermic partial liver ischemia for 45 min followed by varying periods of reperfusion. The animals were divided into three groups: sham operated, I/R and SPA0355 pretreated. Pretreatment with SPA0355 protected against hepatic I/R injury, as indicated by the decreased levels of serum aminotransferase and reduced parenchymal necrosis and apoptosis. Liver synthetic function was also restored by SPA0355 as reflected by the prolonged prothrombin time. To gain insight into the mechanism involved in this protection, we measured the activity of nuclear factor-κB (NF-κB), which revealed that SPA0355 suppressed the nuclear translocation and DNA binding of NF-κB subunits. Concomitantly, the expression of NF-κB target genes such as <I>IL-1</I>β<I>, IL-6, TNF-</I>α and <I>iNOS</I> was significantly downregulated. Lastly, the liver antioxidant enzymes superoxide dismutase, catalase and glutathione were upregulated by SPA0355 treatment, which correlated with the reduction in serum malondialdehyde. Our results suggest that SPA0355 pretreatment prior to I/R injury could be an effective method to reduce liver damage.</P>

Novel Threadlike Structures May Be Present on the Large Animal Organ Surface: Evidence in Swine Model

Bae, Kyoung-Hee,Park, Sang Hyun,Lee, Byung-Cheon,Nam, Min-Ho,Yoon, Ji Woong,Kwon, Hee-Min,Yoon, Seung Zhoo Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

<P><I>Background</I>. The types of embryonic development probably provoke different paths of novel threadlike structure (NTS) development. The authors hypothesized that NTS may be easily observed on the surface of swine intestines by using trypan blue staining method and visualization under an optical microscope. <I>Methods</I>. General anesthesia was administered to 2 Yorkshire pigs. The abdominal walls of the pigs were carefully dissected along the medial alba. NTSs were identified on organ surfaces under a stereoscopic microscope after trypan blue staining. Isolated NTS specimens obtained from the large intestine were subjected to 4′,6-diamidino-2-phenylindole (DAPI) staining and observed using the polarized light microscopy to confirm whether the obtained structure fits the definition of NTS. <I>Results</I>. We found elastic, semitransparent threadlike structures (forming a network structure) that had a milky-white color <I>in situ </I>and <I>in vivo</I> in swine large intestines. The samples showed distinct extinction of polarized light at every 90 degrees, and nucleus was shown to be rod shaped by DAPI staining, indicating that they meet the criteria of NTS. <I>Conclusion</I>. We used a swine model to demonstrate that NTS may be present on large animal organ surfaces. Our results may permit similar studies by using human specimens.</P>

Photo-Related Stress Effects in a-SiGe:H Thin Film Transistors for Infrared Image Sensors

Sang Youn Han,Kyung Sook Jeon,Junho Song,Ho Sik Jeon,Byung Seong Bae IEEE 2013 Journal of display technology Vol.9 No.1

<P>The effects of photo-related stress on the electrical performances of a-SiGe:H thin-film transistors (TFTs) were investigated in comparison with a-Si:H TFTs. Compared with a-Si:H TFTs, the a-SiGe:H TFTs show better stability to the light stress because the number of electrons involved in the creation of dangling bonds are smaller in a-SiGe:H TFTs, resulting in less light-induced degradation. However, a larger threshold voltage shift from the positive gate bias was observed due to the higher number of weak bonds in a-SiGe:H TFTs, which leads to a higher gate bias instability than is observed for a-Si:H TFTs. The temperature dependences of the electrical properties in a-SiGe:H TFTs were observed, and they indicated that a-SiGe:H TFTs follow a thermally activated behavior pattern. Based on the thermally activated behavior, a new model predicting the lifetime of a-SiGe:H TFT image sensors was proposed. The instability of the drain current with respect to the stress time under an electrical bias and light was estimated. Based on the calculated lifetime, the a-SiGe:H TFTs are predicted to be reliable for long-term applications in image sensors.</P>

Apamin attenuated cerulein-induced acute pancreatitis by inhibition of JNK pathway in mice.

Bae, Gi-Sang,Heo, Kwang-Ho,Park, Kyoung-Chel,Choi, Sun Bok,Jo, Il-Joo,Seo, Seung-Hee,Kim, Dong-Goo,Shin, Joon-Yeon,Kang, Dae-Gil,Lee, Ho-Sub,Song, Ho-Joon,Shin, Byung-Cheul,Park, Sung-Joo Plenum Pub. Corp.] 2013 Digestive diseases and sciences Vol.58 No.10

<P>We have previously reported that bee venom (BV) has a protective role against acute pancreatitis (AP). However, the effects of apamin, the major compound of BV, on AP have not been determined. The aim of this study was to evaluate the effects of apamin on cerulein-induced AP.</P>

Anti-viral Effect of Lactobacillus plantarum DC 412K Isolated from Kimchi on the Avian Influenza Virus

Byung-Jhip Ha,Dong-Jun Bae,Chang-Sub Ku,Chang-Ho Kim,Dong-Il Jang,Haan-Woo Sung 한국생물공학회 2008 한국생물공학회 학술대회 Vol.2008 No.4

Polyhedrin Fusion Expression of CSFV E2 Protein for the Enhanced Production in a Baculovirus Expression System

Sung Min Bae,Bit Na Rae Yun,Tae Young Shin,Jae Bang Choi,Yeon Ho Je,Byung Rae Jin,Soo Dong Woo 한국응용곤충학회 2010 한국응용곤충학회 학술대회논문집 Vol.2010 No.10

The Classical Swine Fever Virus (CSFV) is a member of the Pestivirus genus of the Flaviviridae. The polyprotein composed of eight nonstructural and four structural proteins (nucleocapsid protein C and three envelope glycoprotein E0, E1 and E2). E2, the most immunogenic of the CSFV glycoproteins, induces a protective immune response in swine. The objective of this study was to enhance production of E2 protein by fusion with partial polyhedrin of nucleopolyhedrovirus in insect cells. We generated various E2 form by fusion with different combinations of the partial polyhedrin and deletion of the C-terminal transmembrane region (TMR). Expression of the E2 protein was identified by SDS-PAGE and Western blot analysis using anti-CSFV E2 monoclonal antibodies. The fusion expression of an E2 protein with the partial polyhedrin markedly increased expression levels. Also, expression of E2 proteinlacking TMR region was higher than that of intact E2 protein. As a result, the fusion expression of E2 protein lacking the C-terminal TMR with partial polyhedrin was significantly increased in insect cells. These suggest that the fusion of target foreign protein with partial polyhedrin could enhance significantly the production of target protein.