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      • KCI등재

        Value of 3-Dimensional CT Virtual Anatomy Imaging in Complex Foreign Body Retrieval from Soft Tissues

        Xiu-Jun Yang,Guang-Fu Xing,Chang-Wen Shi,Wei Li 대한영상의학회 2013 Korean Journal of Radiology Vol.14 No.2

        Objective: To investigate the value of 3-dimensional (3D) CT virtual anatomy imaging (VAI) in the complex foreign body (FB) retrieval of the soft tissues. Materials and Methods: Four hundred and seventy-five patients with radiopaque FB(s) diagnosed by radiograph underwent contrast-enhanced 3D CT examination. VAI was reconstructed by volume-rendering opacity software, by sliding down the lowest threshold from -600 to 100 HU. The imaging was grouped into three groups: A (axial and multi-planar reformation [MPR] images), B (standard 3D imaging with axial and MPR images), and C (VAI with axial and MPR images). They were analyzed to reveal the type, size, number, location, complications, and the interventional removability of the object, with the comparisons in the management and clinical outcomes on the patient follow-up studies. The data were subjected to chi-square tests, with p value < 0.05 indicating significant statistical difference. Results: The FB shape, size, number, site distribution and vessels around FB, as well as the FB-associated vascular complications and the FB interventional removability were assessed more accurately in Group C than in Group B or Group A (p < 0.005). There was no significant difference in disclosing the type and depth of the FB among the three groups (p > 0.75). On the basis of the 3D CT, especially the enhanced 3D CT VAI, the followings were processed: the recommendation of interventional removal in 286 (60.47%) and non-intervention in 187 (39.53%) of the 473 patients with soft-tissue FB(s); in 352 (56.50%) of the 623 radiopaque FBs patients, 258 (54.55%) patients accurately detected on 3D CT and the successful removal by intervention (343 FBs) or surgery (9 FBs) without any sequela; and 215 (45.45%) patients with 271 FBs lost in the follow-up, with their departure from the hospital. Conclusion: The 3D CT, especially 3D enhanced CT VAI, has great incremental value in further diagnosis and management of complex FB extraction from soft tissues.

      • SCIESCOPUSKCI등재

        Morphological, Phylogenetic and Biological Characteristics of Ectropis obliqua Single-Nucleocapsid Nucleopolyhedrovirus

        Ma Xiu-cui,Xu Hai-Jun,Tang Mei-Jun,Xiao Qiang,Hong Jian,Zhang Chuan-Xi The Microbiological Society of Korea 2006 The journal of microbiology Vol.44 No.1

        The tea looper caterpillar, Ectropis obliqua, is one of the major pests of tea bushes. E. obliqua single-nucleocapsid nucleopolyhedrovirus (EcobSNPV) has been used as a commercial pesticide for biocontrol of this insect. However only limited genetic analysis for this important virus has been done up to now. EcobSNPV was characterized in this study. Electron microscopy analysis of the occlusion body showed polyhedra of 0.7 to $1.7\;{\mu}m$ in diameter containing a single nucleocapsid per envelope of the virion. A 15.5 kb genomic fragment containing EcoRI-L, EcoRI-N and HindIII-F fragments, was sequenced. Analysis of the sequence revealed that the fragment contained eleven potential open reading frames (ORFs): lef-1, egt, 38.7k, rrl, polyhedrin, orfl629, pk-1, hoar and homologues to Spodoptera exigua multicapsid NPV (SeMNPV) ORFs 15, 28, and 29. Gene arrangement and phylogeny analysis suggest that EcobSNPV is closely related to the previously described Group II NPV. Bioassays on lethal concentration $(LC_{50}\;and\;LC_{90})$ and lethal time $(LT_{50}\;and\;LT({90})$ were conducted to test the susceptibility of E. obliqua larvae to the virus.

      • Nrf2 Overexpression Predicts Prognosis and 5-FU Resistance in Gastric Cancer

        Hu, Xiu-Feng,Yao, Jun,Gao, She-Gan,Wang, Xin-Shuai,Peng, Xiu-Qing,Yang, Yan-Tong,Feng, Xiao-Shan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

        Objective: NF-E2-related factor 2 (Nrf2) is activated in several human malignancies. However, the role of Nrf2 in gastric cancer (GC) remains incompletely understood. In this study, we therefore analyzed associations of Nrf2 expression status with clinical features and chemotherapeutic resistance in GC. Materials and Methods: A total of 186 samples from GC patients who underwent gastrectomy were used for prognostic assessment. A further 142 samples from GC cases who received first-line combination chemotherapy were applied for investigation of chemoresistance. The Nrf2 expression was evaluated by immunohistochemistry in GC samples, and its relationship with clinicopathological parameters and chemotherapy sensitivity was analyzed. The effect of Nrf2 gene silencing on chemotherapy resistance was also examined by cell viability assay in vivo. Results: Of the 186 patients with GC, 104/186 (55.9%) showed high expression for Nrf2. The overexpression of Nrf2 was an independent predictor of overall survival [OS, hazard ratio (HR) 3.9; P=0.011] and disease-free survival (DFS, HR 4.3; P=0.002). The gene silencing of Nrf2 reduced resistance to cell death induced by 5-FU in GC cell lines. Conclusion: Our data show that Nrf2 is an independent prognostic factor in GC. Furthermore, Nrf2 confers resistance to chemotherapeutic drug 5-FU in GC cells. Taken together, Nrf2 is a potential prognostic marker and predictive for 5-FU resistance in GC.

      • An integrated study of tyrosinase inhibition by rutin: progress using a computational simulation.

        Si, Yue-Xiu,Yin, Shang-Jun,Oh, Sangho,Wang, Zhi-Jiang,Ye, Sen,Yan, Li,Yang, Jun-Mo,Park, Yong-Doo,Lee, Jinhyuk,Qian, Guo-Ying Adenine Press 2012 Journal of biomolecular structure & dynamics Vol.29 No.5

        <P>Tyrosinase inhibition studies have recently gained the attention of researchers due to their potential application values. We simulated docking (binding energies for AutoDock Vina: -9.1 kcal/mol) and performed a molecular dynamics simulation to verify docking results between tyrosinase and rutin. The docking results suggest that rutin mostly interacts with histidine residues located in the active site. A 10 ns molecular dynamics simulation showed that one copper ion at the tyrosinase active site was responsible for the interaction with rutin. Kinetic analyses showed that rutin-mediated inactivation followed a first-order reaction and mono- and biphasic rate constants occurred with rutin. The inhibition was a typical competitive type with K(i) = 1.100.25 mM. Measurements of intrinsic and ANS-binding fluorescences showed that rutin showed a relatively strong binding affinity for tyrosinase and one possible binding site that could be a copper was detected accompanying with a hydrophobic exposure of tyrosinase. Cell viability testing with rutin in HaCaT keratinocytes showed that no toxic effects were produced. Taken together, rutin has the potential to be a potent anti-pigment agent. The strategy of predicting tyrosinase inhibition based on hydroxyl group number and computational simulation may prove useful for the screening of potential tyrosinase inhibitors.</P>

      • The effect of thiobarbituric acid on tyrosinase: inhibition kinetics and computational simulation.

        Yin, Shang-Jun,Si, Yue-Xiu,Wang, Zhi-Jiang,Wang, Su-Fang,Oh, Sangho,Lee, Sanghyuk,Sim, Seon-Mi,Yang, Jun-Mo,Qian, Guo-Ying,Lee, Jinhyuk,Park, Yong-Doo Adenine Press 2011 Journal of biomolecular structure & dynamics Vol.29 No.3

        <P>Tyrosinase plays various roles in organisms and much research has focused on the regulation of tyrosinase activity. We studied the inhibitory effect of thiobarbituric acid (TBA) on tyrosinase. Our kinetic study showed that TBA inhibited tyrosinase in a reversible noncompetitive manner (K(i) 5 14.0 ± 8.5 mM and IC?????? 5 8.0 ± 1.0 mM). Intrinsic and ANS-binding fluorescences studies were also performed to gain more information regarding the binding mechanism. The results showed that no tertiary structural changes were obviously observed. For further insight, we predicted the 3D structure of tyrosinase and simulated the docking between tyrosinase and TBA. The docking simulation was successful with significant scores (binding energy for AutoDock4: -5.52 kcal/mol) and suggested that TBA was located in the active site. The 11 ns molecular dynamics simulation convinced that the four HIS residues (residue numbers: 57, 90, 250, and 282) were commonly responsible for the interaction with TBA. Our results provide a new inhibition strategy that works using an antioxidant rather than targeting the copper ions within the tyrosinase active site.</P>

      • Mixed-type inhibition of tyrosinase from Agaricus bisporus by terephthalic acid: computational simulations and kinetics.

        Yin, Shang-Jun,Si, Yue-Xiu,Chen, Yong-Fu,Qian, Guo-Ying,L?, Zhi-Rong,Oh, Sangho,Lee, Jinhyuk,Lee, Sanghyuk,Yang, Jun-Mo,Lee, Dong-Youn,Park, Yong-Doo Kluwer Academic/Plenum 2011 The Protein Journal Vol.30 No.4

        <P>Tyrosinase inhibition studies are needed due to the agricultural and medicinal applications. For probing effective inhibitors of tyrosinase, a combination of computational prediction and enzymatic assay via kinetics were important. We predicted the 3D structure of tyrosinase from Agaricus bisporus, used a docking algorithm to simulate binding between tyrosinase and terephthalic acid (TPA) and studied the reversible inhibition of tyrosinase by TPA. Simulation was successful (binding energies for Autodock4 = -1.54 and Fred2.0 = -3.19 kcal/mol), suggesting that TPA interacts with histidine residues that are known to bind with copper ions at the active site. TPA inhibited tyrosinase in a mixed-type manner with a K ( i ) = 11.01 2.12 mM. Measurements of intrinsic and ANS-binding fluorescences showed that TPA induced no changes in tertiary structure. The present study suggested that the strategy of predicting tyrosinase inhibition based on hydroxyl groups and orientation may prove useful for screening of potential tyrosinase inhibitors.</P>

      • KCI등재
      • Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice

        Jiang, Shu-Heng,Li, Jun,Dong, Fang-Yuan,Yang, Jian-Yu,Liu, De-Jun,Yang, Xiao-Mei,Wang, Ya-Hui,Yang, Min-Wei,Fu, Xue-Liang,Zhang, Xiao-Xin,Li, Qing,Pang, Xiu-Feng,Huo, Yan-Miao,Li, Jiao,Zhang, Jun-Feng Elsevier 2017 Gastroenterology Vol.153 No.1

        <P><B>Background & Aims</B></P> <P>Desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors.</P> <P><B>Methods</B></P> <P>We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras<SUP>G12D/+</SUP>/Trp53<SUP>R172H/+</SUP>/Pdx1-Cre (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples. We also analyzed expression levels of proteins involved in 5-HT synthesis and degradation by immunohistochemical analysis of a tissue microarray containing 311 PDAC specimens, and associated expression levels with patient survival times. 5-HT level in 14 matched PDAC tumor and non-tumor tissues were analyzed by ELISA. PDAC cell lines were incubated with 5-HT and cell survival and apoptosis were measured. We analyzed expression of the 5-HT receptor HTR2B in PDAC cells and effects of receptor agonists and antagonists, as well as HTR2B knockdown with small hairpin RNAs. We determined the effects of 5-HT stimulation on gene expression profiles of BxPC-3 cells. Regulation of glycolysis by 5-HT signaling via HTR2B was assessed by immunofluorescence and immunoprecipitation analyses, as well as by determination of the extracellular acid ratio, glucose consumption, and lactate production. Primary PDACs, with or without exposure to SB204741 (a selective antagonist of HTR2B), were grown as xenograft tumors in mice, and SB204741 was administered to tumor-bearing KPC mice; tumor growth and metabolism were measured by imaging analyses.</P> <P><B>Results</B></P> <P>In immunohistochemical analysis of a tissue microarray of PDAC specimens, increased levels of TPH1 and decreased level of MAOA, which regulate 5-HT synthesis and degradation, correlated with stage and size of PDACs and shorter patient survival time. We found levels of 5-HT to be increased in human PDAC tissues compared with non-tumor pancreatic tissues, and PDAC cell lines compared with non-transformed pancreatic cells. Incubation of PDAC cell lines with 5-HT increased proliferation and prevented apoptosis. Agonists of HTR2B, but not other 5-HT receptors, promoted proliferation and prevented apoptosis of PDAC cells. Knockdown of HTR2B in PDAC cells, or incubation of cells with HTR2B inhibitors, reduced their growth as xenograft tumors in mice. We observed a correlation between 5-HT and glycolytic flux in PDAC cells; levels of metabolic enzymes involved in glycolysis, the phosphate pentose pathway, and hexosamine biosynthesis pathway increased significantly in PDAC cells following 5-HT stimulation. 5-HT stimulation led to formation of the HTR2B–LYN–p85 complex, which increased PI3K–Akt–mTOR signaling and the Warburg effect by increasing protein levels of MYC and HIF1A. Administration of SB204741 to KPC mice slowed growth and metabolism of established pancreatic tumors and prolonged survival of the mice.</P> <P><B>Conclusions</B></P> <P>Human PDACs have increased levels of 5-HT, and PDAC cells increase expression of its receptor, HTR2B. These increases allow for tumor glycolysis under metabolic stress and promote growth of pancreatic tumors and PDAC xenograft tumors in mice.</P>

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