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Huang, Jin,Kang, Saeromi,Park, Soo-Jin,Im, Dong-Soon Elsevier 2017 Cellular signalling Vol.39 No.-
<P><B>Abstract</B></P> <P>Non-alcoholic fatty liver disease is the most commonly occurring chronic liver disease, and hepatic steatosis, a condition defined as extensive lipid accumulation in hepatocytes, is associated with liver dysfunction and metabolic diseases, such as, obesity and type II diabetes. Apelin is an adipokine that acts on a G protein-coupled receptor named APJ, and has been established to play pivotal roles in various physiological conditions. However, the function of apelin in hepatocytes has not been fully investigated. In order to assess the functional roles of apelin and APJ in hepatocytes, we used an in vitro model of liver X receptor (LXR)-mediated hepatocellular steatosis. In Hep3B human hepatoma cells, T0901317 (a specific LXR activator) induced lipid accumulation and this was inhibited by apelin. T0901317 also induced the expression of SREBP-1c, a key transcription factor for lipogenesis. Apelin not only inhibited SREBP-1c induction at the mRNA and protein levels but also induced lipolytic PPARα expression. Furthermore, these protective effects of apelin were inhibited by apelin F13A (a specific APJ antagonist). Furthermore, silencing of APJ by siRNA transfection also inhibited the actions of apelin. Specific inhibitors of cellular signaling components showed inhibition of lipid accumulation by apelin was mediated through G<SUB>i/o</SUB> proteins, AMPK, and SREBP-1c suppression during the early stage and through AMPK, ERKs, and PPARα induction during the late stage. In addition, the protective effect of apelin was confirmed in mouse primary hepatocytes. Our observations suggest apelin-APJ signaling in hepatocytes functions to protect against lipid accumulation in liver through two signaling pathways, that is, via AMPK activation and PPARα induction.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Apelin protected liver X receptor-mediated steatosis through APJ in human and mouse hepatocytes </LI> <LI> Early signaling by apelin was APJ➔Gi/o➔p38 MAPK and PI3K➔AMPK➔suppression of SREBP-1c➔lipogenesis suppression. </LI> <LI> Later signaling by apelin was APJ➔Gi/o➔PI3K and ERK➔PPARα induction➔enhanced lipolysis. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Ginsenoside Rg<sub>3</sub> promotes inflammation resolution through M2 macrophage polarization
Kang, Saeromi,Park, Soo-Jin,Lee, Ae-Yeon,Huang, Jin,Chung, Hae-Young,Im, Dong-Soon The Korean Society of Ginseng 2018 Journal of Ginseng Research Vol.42 No.1
Background: Ginsenosides have been reported to have many health benefits, including anti-inflammatory effects, and the resolution of inflammation is now considered to be an active process driven by M2-type macrophages. In order to determine whether ginsenosides modulate macrophage phenotypes to reduce inflammation, 11 ginsenosides were studied with respect to macrophage polarization and the resolution of inflammation. Methods: Mouse peritoneal macrophages were polarized into M1 or M2 phenotypes. Reverse transcription-polymerase chain reaction, Western blotting, and measurement of nitric oxide (NO) and prostaglandin $E_2$ levels were performed in vitro and in a zymosan-induced peritonitis C57BL/6 mouse model. Results: Ginsenoside $Rg_3$ was identified as a proresolving ginseng compound based on the induction of M2 macrophage polarization. Ginsenoside $Rg_3$ not only induced the expression of arginase-1 (a representative M2 marker gene), but also suppressed M1 marker genes, such as inducible NO synthase, and NO levels. The proresolving activity of ginsenoside $Rg_3$ was also observed in vivo in a zymosan-induced peritonitis model. Ginsenoside $Rg_3$ accelerated the resolution process when administered at peak inflammatory response into the peritoneal cavity. Conclusion: These results suggest that ginsenoside $Rg_3$ induces the M2 polarization of macrophages and accelerates the resolution of inflammation. This finding opens a new avenue in ginseng pharmacology.
Huang, Yong,Tong, Dedi,Zhu, Shan,Wu, Lehao,Mao, Qi,Ibrahim, Zuhaib,Lee, W. P. Andrew,Brandacher, Gerald,Kang, Jin U. Williams & Wilkins 2015 Plastic and reconstructive surgery Vol.135 No.4
BACKGROUND:: Evolution in microsurgical techniques and tools has paved the way for supermicrosurgical anastomoses, with vessel diameters often approaching below 0.8 mm in the clinical realm and even smaller (0.2 to 0.3 mm) in murine models. Several imaging and monitoring devices have been introduced for postoperative monitoring, but intraoperative guidance, assessment, and predictability have remained limited to binocular optical microscopy and the surgeon’s experience. The authors present a high-resolution, real-time, three-dimensional imaging modality for intraoperative evaluation of luminal narrowing, thrombus formation, and flow alterations. METHODS:: An imaging modality that provides immediate, in-depth, high-resolution, three-dimensional structure view and flow information of the anastomosed site, called phase-resolved Doppler optical coherence tomography, was developed. Twenty-two mouse femoral artery anastomoses and 17 mouse venous anastomoses were performed and evaluated. Flow status, vessel inner lumen three-dimensional structure, and early thrombus detection were analyzed based on imaging results. Predictions formed correlated with actual long-term surgical outcomes. Eventually, four cases of mouse orthotopic limb transplantation were carried out, and predicted long-term patency based on imaging results was confirmed by actual results. RESULTS:: The assessments based on high-resolution three-dimensional visualization of the vessel flow status and inner lumen provided by phase-resolved Doppler optical coherence tomography show 92 percent sensitivity and 90 percent specificity for arterial anastomoses and 90 percent sensitivity and 86 percent specificity for venous anastomoses. CONCLUSIONS:: Phase-resolved Doppler optical coherence tomography is an effective evaluation tool for microvascular anastomosis. It can predict the long-term vessel patency with high sensitivity and specificity.
Kang, Saeromi,Huang, Jin,Lee, Bo-Kyung,Jung, Young-Suk,Im, Eunok,Koh, Jung-Min,Im, Dong-Soon Elsevier 2018 Biochimica et biophysica acta, Molecular and cell Vol.1863 No.2
<P>Protective effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on non-alcoholic fatty liver disease has been demonstrated. FFA4 (also known as GPR120; a G protein-coupled receptor) has been suggested to be a target of n-3 PUFA. FFA4 expression in hepatocytes has also been reported from liver biopsies in child fatty liver patients. In order to assess the functional role of FFA4 in hepatic steatosis, we used an in vitro model of liver X receptor (LXR)-mediated hepatocellular steatosis. FFA4 expression was confirmed in Hep3B and HepG2 human hepatoma cells. T0901317 (a specific LXR activator) induced lipid accumulation and docosahexaenoic acid (DHA; a representative n-3 PUFA) inhibited lipid accumulation. This DHA-induced inhibition was blunted by treatment of AH7614 (a FFA4 antagonist) and by transfection of FFA4 siRNA. SREBP-lc (a key transcription factor of lipogenesis) was induced by treatment with T0901317, and SREBP-lc induction was also inhibited by DHA at mRNA and protein levels. DHA-induced suppression of SREBP-lc expression was also blunted by FFA4-knockdown. Furthermore, DHA inhibited T0901317-induced lipid accumulation in primary hepatocytes from wild type mice, but not in those from FFA4 deficient mice. In addition, DHA-induced activations of G(q/11) proteins, CaMKK, and AMPK were found to be signaling components of the steatosis protective pathway. The results of this study suggest that n-3 PUFA protect hepatic steatosis by activating FFA4 in hepatocytes, and its signaling cascade sequentially involves FFA4, G(q/11) proteins, CaMKK, AMPK, and SREBP-lc suppression.</P>
Shen, Kang,Huang, Xin-En,Lu, Yan-Yan,Wu, Xue-Yan,Liu, Jin,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12
Objective: This study was designed to investigate treatment efficacy and side effects of concomitant Aisu$^{(R)}$ (docetaxel) with three-dimensional conformal external beam radiotherapy for the treatment of inoperable patients with esophageal cancer. Methods: Inoperable patients were treated with three-dimensional conformal external beam radiotherapy (5/week, 2 GY/day, and total dose 60GY) plus docetaxel ($30-45mg/m^2$, iv, d1, 8). Results: Twenty eight patients met the study eligibility criteria and the response rate was evaluated according to RICIST guidelines. Among 28 patients, 2 achieved CR, 22 PR, 3 SD and 1 patient was documented PD. Mild gastrointestinal reaction and bone marrow suppression were also documented. All treatment related side effects were tolerable. Conclusion: Three-dimensional conformal external beam radiotherapy combined with docetaxel is an active and safe regimen for inoperable patients with esophageal cancer.
Cho, Han Jin,Lim, Do Young,Kwon, Gyoo Taik,Kim, Ji Hee,Huang, Zunnan,Song, Hyerim,Oh, Yoon Sin,Kang, Young-Hee,Lee, Ki Won,Dong, Zigang,Park, Jung Han Yoon MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.2
<P>Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has been shown to have anti-tumor properties. In the present study, we investigated whether BITC inhibits the development of prostate cancer in the transgenic adenocarcinoma mouse prostate (TRAMP) mice. Five-week old, male TRAMP mice and their nontransgenic littermates were gavage-fed with 0, 5, or 10 mg/kg of BITC every day for 19 weeks. The weight of the genitourinary tract increased markedly in TRAMP mice and this increase was suppressed significantly by BITC feeding. H and E staining of the dorsolateral lobes of the prostate demonstrated that well-differentiated carcinoma (WDC) was a predominant feature in the TRAMP mice. The number of lobes with WDC was reduced by BITC feeding while that of lobes with prostatic intraepithelial neoplasia was increased. BITC feeding reduced the number of cells expressing Ki67 (a proliferation marker), cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 in the prostatic tissue. <I>In vitro</I> cell culture results revealed that BITC decreased DNA synthesis, as well as CDK2 and CDK4 activity in TRAMP-C2 mouse prostate cancer cells. These results indicate that inhibition of cell cycle progression contributes to the inhibition of prostate cancer development in TRAMP mice treated with BITC.</P>
Fault-Tolerant Control of Five-Phase Induction Motor Under Single-Phase Open
Kong, Wubin,Huang, Jin,Kang, Min,Li, Bingnan,Zhao, Lihang The Korean Institute of Electrical Engineers 2014 Journal of Electrical Engineering & Technology Vol.9 No.3
This paper deals with fault-tolerant control of five-phase induction motor (IM) drives under single-phase open. By exploiting a decoupled model for five-phase IM under fault, the indirect field-oriented control ensures that electromagnetic torque oscillations are reduced by particular magnitude ratio currents. The control techniques are developed by the third harmonic current injection, in order to improve electromagnetic torque density. Furthermore, Proportional Resonant (PR) regulator is adopted to realize excellent current tracking performance in the phase frame, compared with Proportional Integral (PI) and hysteresis regulators. The analysis and experimental results confirm the validity of fault-tolerant control under single-phase open.