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| 1 | Hepatitis C virus NS5A promotes insulin resistance through IRS-1 serine phosphorylation and increased gluconeogenesis显示文摘AIM: To investigate the mechanisms of insulin resistance in human hepatoma cells expressing hepatitis C virus(HCV) nonstructural protein 5A(NS5A).METHODS: The human hepatoma cell lines,Huh7 and Huh7.5,were infected with HCV or transientlytransfected with a vector expressing HCV NS5 A. The effect of HCV NS5 A on the status of the critical players involved in insulin signaling was analyzed using realtime quantitative polymerase chain reaction and Western blot assays. Data were analyzed using Graph Pad Prism version 5.0.RESULTS: To investigate the effect of insulin treatment on the players involved in insulin signaling pathway,we analyzed the status of insulin receptor substrate-1(IRS-1) phosphorylation in HCV infected cells or Huh7.5 cells transfected with an HCV NS5 A expression vector. Our results indicated that there was an increased phosphorylation of IRS-1(Ser307) in HCV infected or NS5 A transfected Huh7.5 cells compared to their respective controls. Furthermore,an increased phosphorylation of Akt(Ser473) was observed in HCV infected and NS5 A transfected cells compared to their mock infected cells. In contrast,we observed decreased phosphorylation of Akt Thr308 phosphorylation in HCV NS5 A transfected cells. These results suggest that Huh7.5 cells either infected with HCV or ectopically expressing HCV NS5 A alone have the potential to induce insulin resistance by the phosphorylation of IRS-1 at serine residue(Ser307) followed by decreased phosphorylation of Akt Thr308,Fox01 Ser256 and GSK3β Ser9,the downstream players of the insulin signalingpathway. Furthermore,increased expression of PECK and glucose-6-phosphatase,the molecules involved in gluconeogenesis,in HCV NS5 A transfected cells was observed.CONCLUSION: Taken together,our results suggest the role of HCV NS5 A in the induction of insulin resistance by modulating various cellular targets involved in the insulin signaling pathway. | Fahed Parvaiz Sobia Manzoor Jawed Iqbal Mehuli Sarkar-Dutta Muhammad Imran Gulam Waris | 2015 | World Journal of Gastroenterology2015，21，43： | 7 |
| 2 | LMI Consensus Condition for Discrete-time Multi-agent Systems显示文摘This paper examines a consensus problem in multiagent discrete-time systems, where each agent can exchange information only from its neighbor agents. A decentralized protocol is designed for each agent to steer all agents to the same vector. The design condition is expressed in the form of a linear matrix inequality. Finally, a simulation example is presented and a comparison is made to demonstrate the effectiveness of the developed methodology. | Magdi S.Mahmoud Gulam Dastagir Khan | 2018 | IEEE/CAA Journal of Automatica Sinica2018，5，2： | 6 |
| 3 | Toward point-of-care assessment of patient response:a portable tool for rapidly assessing cancer drug efficacy using multifrequency impedance cytometry and supervised machine learning显示文摘We present a novel method to rapidly assess drug efficacy in targeted cancer therapy,where antineoplastic agents are conjugated to antibodies targeting surface markers on tumor cells.We have fabricated and characterized a device capable of rapidly assessing tumor cell sensitivity to drugs using multifrequency impedance spectroscopy in combination with supervised machine learning for enhanced classification accuracy.Currently commercially available devices for the automated analysis of cell viability are based on staining,which fundamentally limits the subsequent characterization of these cells as well as downstream molecular analysis.Our approach requires as little as 20μL of volume and avoids staining allowing for further downstream molecular analysis.To the best of our knowledge,this manuscript presents the first comprehensive attempt to using high-dimensional data and supervised machine learning,particularly phase change spectra obtained from multi-frequency impedance cytometry as features for the support vector machine classifier,to assess viability of cells without staining or labelling. | Karan Ahuja Gulam M.Rather Zhongtian Lin Jianye Sui Pengfei Xie Tuan Le Joseph R.Bertino Mehdi Javanmard | 2019 | Microsystems & Nanoengineering2019，5，1： | 4 |
| 4 | Attenuation of MET-mediated migration and invasion in hepatocellular carcinoma cells by SOCS1显示文摘AIM To investigate the role of suppressor of cytokine signaling 1(SOCS1)in regulating MET-mediated invasive potential of hepatocellular carcinoma(HCC)cells.METHODSStable derivatives of mouse(Hepa1-6)and human(hep3B,Hep G2)HCC cell lines expressing SOCS1or control vector were evaluated for their ability to migrate towards hepatocyte growth factor(HGF)in the transwell migration assay,invade extracellular matrix in response to HGF stimulation in a 3-D invasion assay by confocal microscopy,and to undergo anchorageindependent proliferation in semisolid agar.Following intravenous and intrasplenic inoculation into NOD.scid.gamma mice,the ability of Hepa cells to form othotopic tumors was evaluated.Following HGF stimulation of Hepa and Hep3B cells,expression of proteins implicated in epithelial-to-mesenchymal transition was evaluated by western blot and qR T-PCR.RESULTS SOCS1 expression in mouse and human HCC cells inhibited HGF-induced migration through matrigel.In the 3-D invasion assay,HGF stimulation induced invasion of HCC cells across type-Ⅰcollagen matrix,and SOCS1expression significantly reduced the depth of invasion.SOCS1 expression also reduced the number and size of colonies formed by anchorage-independent growth in semisolid agar.Following intravenous inoculation,control Hepa cell formed large tumor nodules that obliterated the liver whereas the SOCS1-expressing Hepa cells formed significantly smaller nodules.Tumors formed by SOCS1-expressing cells showed reduced phosphorylation of STAT3 and ERK that was accompanied by reduced levels of MET protein expression.HGF stimulated Hepa cells expressing SOCS1 showed increased expression of E-cadherin and decreased expression of EGR1,SNAI1and ZEB1.Comparable results were obtained with Hep3B cells.SOCS1 expressing HCC cells also showed reduced levels of EGR1 and SNAI1 transcripts.CONCLUSION Our findings indicate that loss of SOCS1-dependent control over epithelial-to-mesenchymal transition may contribute to MET-mediated migration,invasion and metastatic growth of HCC. | Yirui Gui Md Gulam Musawwir Khan Diwakar Bobbala Claire Dubois Sheela Ramanathan Caroline Saucier Subburaj Ilangumaran | 2017 | World Journal of Gastroenterology2017，23，36： | 3 |
| 5 | Evaluation of a locked nucleic acid form of antisense oligo targeting HIF-1α in advanced hepatocellular carcinoma显示文摘BACKGROUND Hypoxia-inducible factor 1α(HIF-1α) is a gene that regulates tumor survival,neovascularization and invasion. Overexpression of HIF-1α correlates with poor prognosis in hepatocellular carcinoma(HCC). RO7070179 is a HIF-1α inhibitor that decreases HIF-1α mRNA and its downstream targets, it could be a potential treatment in HCC.AIM To evaluate safety and preliminary activity of RO7070179 in patients with previously treated HCC, with focus on a patient with prolonged response to RO7070179.METHODS In the preclinical study of RO7070179 in a HCC xenograft model, the mice wereseparated into 4 groups with each group received doses of 0, 3, 10 and 30 mg/kg for total 10 doses. HCC patients who failed at least one line of systemic treatment,received RO7070179 as a weekly infusion, each cycle is 6 wk. We evaluated the safety and HIF-1α mRNA levels of RO7070179.RESULTS Preclinical evaluation of RO7070179 in orthotopic HCC xenograft model showed no significant differences in HCC tumor weight between the 3 and 10 mg/kg groups. However, dose of 10 mg/kg of RO7070179, has shown 76% reduction of the amount of HIF-1α mRNA in HCC tissue. In the phase 1 b study of RO7070179 in previously treated HCC patients, 8 out of 9 were evaluable: 1 achieved PR and1 SD. The patient with PR responded after 2 cycles treatments, which has been maintained for 12 cycles. This patient also showed reduction in perfusion of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) after 1 cycle of treatment. After 1 cycle of treatment, both patients with PR and SD showed decrease in HIF-1α mRNA at the root of biopsies(each biopsy was divided into 2 specimens, the tip and the root).CONCLUSION RO7070179 can reduce HIF-1α mRNA level in HCC patients with SD or PR. It is well tolerated at 10 mg/kg, with transaminitis as the dose of increased toxicity.This study indicates that RO7070179 might benefit HCC patients, and an early signal for clinical benefit can potentially be predicted through changes in either m RNA level or DCE-MRI within 1 cycle of therapy. | Jennifer Wu Merly Contratto Krishna P Shanbhogue Gulam A Manji Bert H O'Neil Anne Noonan Robert Tudor Ray Lee | 2019 | World Journal of Clinical Oncology2019，10，3： | 2 |
| 6 | Evaluation of a 2D diode array for IMRT quality assurance显示文摘 | Daniel Létourneau Misbah Gulam Di Yan Mark Oldham John W. Wong | 2003 | Radiotherapy and Oncology2003，，2： | 2 |
| 7 | Evaluation of a 2D diode array for IMRT quality assurance显示文摘 | Daniel Letourneau Misbah Gulam Di Yan | 2004 | Radiotherapy and Oncolo gy2004，，： | 1 |
| 8 | Detection of Escherichia coli O157:H7 by multiplex PCR and their characterization by plasmid profiling, antimlcrobial resistance, RAPD and PFGE analyses 显示文摘 | Son Radu Ooi Wai Ling Gulam Rusul | 2001 | Journal of Microbiological Methods2001，，46： | 1 |
| 9 | Evaluation of a 2D diode array for IMRT quality assurance 显示文摘 | Letoumeau D Gulam M | 2004 | Radiother Oncol2004，70，2： | 1 |
| 10 | A Brief Primer on Good Samaritan Law for Health Care Professionals显示文摘 | Hyder Gulam John Devereux | | 0，，03： | 1 |
| 11 | Growth and characterization of gel grown single crystals of bis-glycine hydrogen chloride (BGHC)显示文摘 | K. Ambujam K. Rajarajan S. Selvakumar J. Madhavan Gulam Mohamed P. Sagayaraj | 2005 | Optical Materials2005，，6： | 1 |
| 12 | Lipase enzyme immobilization on synthetic beaded macroporous copolymers for kinetic resolution of chiral drugs intermediates显示文摘 | RAJINDER P GULAM NQ | 2008 | Process Biochemistry2008，43，4： | 1 |
| 13 | Prevalenceand antibiotic resistance of Salmonella serovars in ducks,duckrearing and processing environments in Penang,Malaysia显示文摘 | Frederick Adzitey Gulam Rusul Nurul Huda | 2012 | Food Research International2012，45，2： | 1 |
| 14 | Mechanisms of cholesterol removal by lactobacilli under conditions that mimic the human gastrointestinal tract 显示文摘 | Huey-Shi Lye Gulam Rusul Rahmat-Ali Min-Tze Liong | 2010 | International Dairy Journal2010，，20： | 1 |
| 15 | Clinical outcome of dia- betes patients hospitalized with foot ulcers, Dares Salaam, Tanzania 显示文摘 | Gulam Abbas Z Lutale J K Morbach S | 2002 | Diabet Med2002，19，7： | 1 |
| 16 | Factors as- sociated with difficult neuraxial blockade 显示文摘 | Ruzman T Gulam D Harsanji Drenjancevic I | 2014 | Lecal Reg Anesth2014，，7： | 1 |
| 17 | Lipaseenzymeimmobilizationonsyntheticbeadedmacroporoucopolymersfor kineticresolutionofchiraldrugsintermediates显示文摘 | INDUB RAJINDERP GULAM N Q | | 0，，： | 1 |
| 18 | Evaluation of a 2D diode array for IMRT quality assurance显示文摘 | LETOURNEAU D GULAM M YAN D | 2004 | Radiotherapy and Oncolo- gy2004，70，2： | 1 |
| 19 | A single 8,5'-cyclo-2'-deoxyadenosine lesion in a TATA box prevents binding of the TATA binding protein and strongly reduces transcription in vivo显示文摘 | Marietta C Gulam H Brooks PJ | | 0，，： | 1 |
| 20 | Evaluation of a 2D diode array for IMRT quality assurance显示文摘 | Letoumeaau D Gulam M Yan D | 2004 | Radiother Oncol2004，70，2： | 1 |
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