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  1. Fulltext In silico evidence of de novo interactions between ribosomal and Epstein - Barr virus proteins
    Sim EU, Talwar SP
    BMC Mol Cell Biol, 2019 08 15;20(1):34.
    PMID: 31416416 DOI: 10.1186/s12860-019-0219-y
    BACKGROUND: Association of Epstein-Barr virus (EBV) encoded latent gene products with host ribosomal proteins (RPs) has not been fully explored, despite their involvement in the aetiology of several human cancers. To gain an insight into their plausible interactions, we employed a computational approach that encompasses structural alignment, gene ontology analysis, pathway analysis, and molecular docking.

    RESULTS: In this study, the alignment analysis based on structural similarity allows the prediction of 48 potential interactions between 27 human RPs and the EBV proteins EBNA1, LMP1, LMP2A, and LMP2B. Gene ontology analysis of the putative protein-protein interactions (PPIs) reveals their probable involvement in RNA binding, ribosome biogenesis, metabolic and biosynthetic processes, and gene regulation. Pathway analysis shows their possible participation in viral infection strategies (viral translation), as well as oncogenesis (Wnt and EGFR signalling pathways). Finally, our molecular docking assay predicts the functional interactions of EBNA1 with four RPs individually: EBNA1-eS10, EBNA1-eS25, EBNA1-uL10 and EBNA1-uL11.

    CONCLUSION: These interactions have never been revealed previously via either experimental or in silico approach. We envisage that the calculated interactions between the ribosomal and EBV proteins herein would provide a hypothetical model for future experimental studies on the functional relationship between ribosomal proteins and EBV infection.

  2. Fulltext Patterns and Determinants of Attitudes towards Genetic Risk of Cancer: Case Study in a Malaysian Public University
    Sim EU, Ting SH
    Biomed Res Int, 2018;2018:4682431.
    PMID: 30112391 DOI: 10.1155/2018/4682431
    Genetic risk to cancer is a knowledge largely confined to experts and the more educated sectors of the developed western countries. The perception of genetic susceptibility to cancer among the masses is fragmented, particularly in developing countries. As cancer diseases affect developing countries as much as developed nations, it is imperative to study perception and reception of genetic risk to cancer in Southeast Asia. Here, we report on a novel case study to gauge the awareness and attitudes towards genetic determination of cancer among the undergraduates of a Malaysian public university. A total of 272 university undergraduate students completed an online questionnaire. On causes of cancer, the respondents believed that cancer is caused by lifestyle and environmental factors, but those with science background were more likely to associate it with genetic factors. The results on awareness of genetic profiling of cancer risk showed that there are significant differences between those with science and nonscience background but there are no significant differences for gender and socioeconomic background. As for attitudes towards cancer risk, female respondents, those from middle socioeconomic status and science background, are more likely to believe in genetic determinism of cancer. The findings have implications on target population segmentation in strategic health communication on cancer.
  3. Over-expression of cyclo-oxygenase-2 predicts poor survival of patients with nasopharyngeal carcinoma: a meta-analysis
    Sim CC, Sim EU
    J Laryngol Otol, 2020 Apr;134(4):338-343.
    PMID: 32172705 DOI: 10.1017/S0022215120000614
    OBJECTIVES: The conclusive prognostic significance of cyclo-oxygenase-2 has been determined in various cancers but not in nasopharyngeal carcinoma. Therefore, this study aimed to evaluate the relationship of cyclo-oxygenase-2 expression with the survival outcome and treatment response of nasopharyngeal carcinoma patients via a systematic meta-analysis approach.

    METHODS: A meta-analysis was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses ('PRISMA') checklist. The primary clinical characteristics of patients, and hazard ratios with 95 per cent confidence intervals of overall survival data, were tabulated from eligible studies. The relationship of cyclo-oxygenase-2 expression with survival outcome (expressed as hazard ratio) and treatment response (expressed as odds ratio) in nasopharyngeal carcinoma patients was analysed, and explained with the aid of forest plot charts.

    RESULTS AND CONCLUSION: The pooled hazard ratio for overall survival was 2.02 (95 per cent confidence interval = 1.65-2.47). This indicates that the over-expression of cyclo-oxygenase-2 is significantly associated with the poor survival of nasopharyngeal carcinoma patients. The pooled odds ratio of 0.98 (95 per cent confidence interval = 0.27-3.49) reveals that over-expression of cyclo-oxygenase-2 was not significantly related to the treatment outcome.

  4. Fulltext The roles of ribosomal proteins in nasopharyngeal cancer: culprits, sentinels or both
    Sim EU, Lee CW, Narayanan K
    Biomark Res, 2021 Jun 30;9(1):51.
    PMID: 34193301 DOI: 10.1186/s40364-021-00311-x
    Ribosomal protein genes encode products that are essential for cellular protein biosynthesis and are major components of ribosomes. Canonically, they are involved in the complex system of ribosome biogenesis pivotal to the catalysis of protein translation. Amid this tightly organised process, some ribosomal proteins have unique spatial and temporal physiological activity giving rise to their extra-ribosomal functions. Many of these extra-ribosomal roles pertain to cellular growth and differentiation, thus implicating the involvement of some ribosomal proteins in organogenesis. Consequently, dysregulated functions of these ribosomal proteins could be linked to oncogenesis or neoplastic transformation of human cells. Their suspected roles in carcinogenesis have been reported but not specifically explained for malignancy of the nasopharynx. This is despite the fact that literature since one and half decade ago have documented the association of ribosomal proteins to nasopharyngeal cancer. In this review, we explain the association and contribution of dysregulated expression among a subset of ribosomal proteins to nasopharyngeal oncogenesis. The relationship of these ribosomal proteins with the cancer are explained. We provide information to indicate that the dysfunctional extra-ribosomal activities of specific ribosomal proteins are tightly involved with the molecular pathogenesis of nasopharyngeal cancer albeit mechanisms yet to be precisely defined. The complete knowledge of this will impact future applications in the effective management of nasopharyngeal cancer.
  5. Induction of protein expression within Escherichia coli vector for entry into mammalian cells
    Chen Q, Lee CW, Sim EU, Narayanan K
    Hum Gene Ther Methods, 2014 Feb;25(1):40-7.
    PMID: 24134118 DOI: 10.1089/hgtb.2012.188
    Direct protein delivery into the cytosol of mammalian cells by invasive Escherichia coli (E. coli) bacterial vector will bypass the need to achieve nuclear entry and transcription of DNA, a major hurdle that is known to seriously limit gene transfer. The bacterial vector is induced to express the protein during its growth phase, before presentation for entry into mammalian cells and release of its content into the cellular environment. For this class of vector, crossing the plasma membrane becomes the primary step that determines the success of protein delivery. Yet, how the mechanics of protein expression within the vector affect its entry into the host is poorly understood. We found the vector's effectiveness to enter HeLa cells diminished together with its viability when phage N15 protelomerase (TelN) expression was induced continuously in the invasive E. coli despite producing an abundant amount of functional protein. By comparison, shorter induction, even as little as 3 hr, produced sufficient amounts of functional TelN and showed more effective invasion of HeLa cells, comparable to that of uninduced invasive E. coli. These results demonstrate that brief induction of protein expression during vector growth is essential for optimal entry into mammalian cells, an important step for achieving bacteria-mediated protein delivery.
  6. Escherichia coli bactofection using Lipofectamine
    Narayanan K, Lee CW, Radu A, Sim EU
    Anal Biochem, 2013 Aug 15;439(2):142-4.
    PMID: 23608053 DOI: 10.1016/j.ab.2013.04.010
    Successful gene delivery into mammalian cells using bactofection requires entry of the bacterial vector via cell surface integrin receptors followed by release of plasmid DNA into the cellular environment. We show, for the first time, that addition of the DNA transfection reagent Lipofectamine improves entry of invasive Escherichia coli into HeLa cells and enhances up to 2.8-fold green fluorescent protein (GFP) expression from a reporter plasmid. The addition of Lipofectamine may be applicable to other bacterial vectors to increase their DNA delivery efficiency into mammalian cells.
  7. Fulltext The uS8, uS4, eS31, and uL14 Ribosomal Protein Genes Are Dysregulated in Nasopharyngeal Carcinoma Cell Lines
    Sim EU, Ng KL, Lee CW, Narayanan K
    Biomed Res Int, 2017;2017:4876954.
    PMID: 28791303 DOI: 10.1155/2017/4876954
    The association of ribosomal proteins with carcinogenesis of nasopharyngeal carcinoma (NPC) has been established in a limited subset of ribosomal protein genes. To date, three ribosomal protein genes, eL27 (L27), eL41 (L41), and eL43 (L37a), have been found to be differentially expressed in cell lines derived from NPC tumors. This raises the possibility of more ribosomal protein genes that could be associated with NPC. In this study, we investigated the expression profiles of eight ribosomal protein genes, uS8 (S8), uS4 (S9), eS31 (S27a), eL6 (L6), eL18 (L18), uL14 (L23), eL24 (L24), and eL30 (L30), in six NPC-derived cell lines (HONE-1, SUNE1, HK1, TW01, TW04, and C666-1). Their expression levels were compared with that of a nonmalignant nasopharyngeal epithelial cell line (NP69) using quantitative real-time PCR (RT-qPCR) assay. Of the eight genes studied, the expressions of four ribosomal protein genes uS8 (S8), uS4 (S9), eS31 (S27a), and uL14 (L23) were found to be significantly downregulated in NPC cell lines relative to NP69. Our findings provide novel empirical evidence of these four ribosomal protein genes as NPC-associated genetic factors and reinforce the relevance of ribosomal proteins in the carcinogenesis of nasopharyngeal cancer.
  8. Fulltext Early detection of C-reactive protein and von Willebrand factor levels in Malaysian patients with acute coronary syndrome
    Tiong WN, Sim EU, Fong AY, Ong TK
    J Cardiovasc Dis Res, 2013 Mar;4(1):3-6.
    PMID: 24023462 DOI: 10.1016/j.jcdr.2012.08.004
    BACKGROUND: Diagnosing acute coronary syndrome (ACS) remains a challenge in patients presenting at early phase of hospitalization. We hypothesized that inflammatory markers of plaque rupture could accurately identifying ACS patients from stable coronary artery diseases (CAD).

    MATERIALS AND METHODS: The serum and peripheral blood gene expression levels of C-reactive protein (CRP) and von Willebrand factor (vWF) in multiethnic Malaysian patients (n = 7) admitted with early hospitalization of ACS was evaluated. Nine patients with stable coronary artery disease without previous history of ACS were enrolled as controls.

    RESULTS: Serum and peripheral blood mRNA levels of CRP and vWF were significantly higher in ACS compared to control groups (P 

  9. Short homologies efficiently generate detectable homologous recombination events
    Osahor AN, Tan CY, Sim EU, Lee CW, Narayanan K
    Anal Biochem, 2014 Oct 1;462:26-8.
    PMID: 24929088 DOI: 10.1016/j.ab.2014.05.030
    When recombineering bacterial artificial chromosomes (BACs), it is common practice to design the ends of the donor molecule with 50 bp of homology specifying its insertion site. We demonstrate that desired recombinants can be produced using intermolecular homologies as short as 15 bp. Although the use of shorter donor end regions decreases total recombinants by several fold, the frequency of recombinants with correctly inserted donor molecules was high enough for easy detection by simple polymerase chain reaction (PCR) screening. This observation may have important implications for the design of oligonucleotides for recombineering, including significant cost savings, especially for high-throughput projects that use large quantities of primers.
  10. Differential expression of a subset of ribosomal protein genes in cell lines derived from human nasopharyngeal epithelium
    Sim EU, Ang CH, Ng CC, Lee CW, Narayanan K
    J Hum Genet, 2010 Feb;55(2):118-20.
    PMID: 19927161 DOI: 10.1038/jhg.2009.124
    Extraribosomal functions of human ribosomal proteins (RPs) include the regulation of cellular growth and differentiation, and are inferred from studies that linked congenital disorders and cancer to the deregulated expression of RP genes. We have previously shown the upregulation and downregulation of RP genes in tumors of colorectal and nasopharyngeal carcinomas (NPCs), respectively. Herein, we show that a subset of RP genes for the large ribosomal subunit is differentially expressed among cell lines derived from the human nasopharyngeal epithelium. Three such genes (RPL27, RPL37a and RPL41) were found to be significantly downregulated in all cell lines derived from NPC tissues compared with a nonmalignant nasopharyngeal epithelial cell line. The expression of RPL37a and RPL41 genes in human nasopharyngeal tissues has not been reported previously. Our findings support earlier suspicions on the existence of NPC-associated RP genes, and indicate their importance in human nasopharyngeal organogenesis.
  11. Investigating the decay rates of Escherichia coli relative to Vibrio parahemolyticus and Salmonella Typhi in tropical coastal waters
    Lee CW, Ng AY, Bong CW, Narayanan K, Sim EU, Ng CC
    Water Res, 2011 Feb;45(4):1561-70.
    PMID: 21146847 DOI: 10.1016/j.watres.2010.11.025
    Using the size fractionation method, we measured the decay rates of Escherichia coli, Salmonella Typhi and Vibrio parahaemolyticus in the coastal waters of Peninsular Malaysia. The size fractions were total or unfiltered, <250 μm, <20 μm, <2 μm, <0.7 μm, <0.2 μm and <0.02 μm. We also carried out abiotic (inorganic nutrients) and biotic (bacterial abundance, production and protistan bacterivory) measurements at Port Dickson, Klang and Kuantan. Klang had highest nutrient concentrations whereas both bacterial production and protistan bacterivory rates were highest at Kuantan. We observed signs of protist-bacteria coupling via the following correlations: Protistan bacterivory-Bacterial Production: r = 0.773, df = 11, p < 0.01; Protist-Bacteria: r = 0.586, df = 12, p < 0.05. However none of the bacterial decay rates were correlated with the biotic variables measured. E. coli and Salmonella decay rates were generally higher in the larger fraction (>0.7 μm) than in the smaller fraction (<0.7 μm) suggesting the more important role played by protists. E. coli and Salmonella also decreased in the <0.02 μm fraction and suggested that these non-halophilic bacteria did not survive well in seawater. In contrast, Vibrio grew well in seawater. There was usually an increase in Vibrio after one day incubation. Our results confirmed that decay or loss rates of E. coli did not match that of Vibrio, and also did not correlate with Salmonella decay rates. However E. coli showed persistence where its decay rates were generally lower than Salmonella.
  12. Fulltext Human Ribosomal Proteins RPeL27, RPeL43, and RPeL41 Are Upregulated in Nasopharyngeal Carcinoma Cell Lines
    Sim EU, Chan SL, Ng KL, Lee CW, Narayanan K
    Dis Markers, 2016;2016:5179594.
    PMID: 28018022 DOI: 10.1155/2016/5179594
    Apart from their canonical role in ribosome biogenesis, there is increasing evidence of ribosomal protein genes' involvement in various cancers. A previous study by us revealed significant differential expression of three ribosomal protein genes (RPeL27, RPeL41, and RPeL43) between cell lines derived from tumor and normal nasopharyngeal epithelium. However, the results therein were based on a semiquantitative assay, thus preliminary in nature. Herein, we provide findings of a deeper analysis of these three genes in the context to nasopharyngeal carcinoma (NPC) tumorigenesis. Their expression patterns were analyzed in a more quantitative manner at transcript level. Their protein expression levels were also investigated. We showed results that are contrary to previous report. Rather than downregulation, these genes were significantly overexpressed in NPC cell lines compared to normal control at both transcript and protein levels. Nevertheless, their association with NPC has been established. Immunoprecipitation pulldown assays indicate the plausible interaction of either RPeL27 or RPeL43 with POTEE/TUBA1A and ACTB/ACTBL2 complexes. In addition, RPeL43 is shown to bind with MRAS and EIF2S1 proteins in a NPC cell line (HK1). Our findings support RPeL27, RPeL41, and RPeL43 as potential markers of NPC and provide insights into the interaction targets of RPeL27 and RPeL43 proteins.
  13. RFP-based method for real-time tracking of invasive bacteria in a heterogeneous population of cells
    Akinsola RO, Adewoyin M, Lee CW, Sim EU, Narayanan K
    Anal Biochem, 2021 12 01;634:114432.
    PMID: 34695391 DOI: 10.1016/j.ab.2021.114432
    Quantification of bacterial invasion into eukaryotic cells is a prerequisite to unfold the molecular mechanisms of this vector's function to obtain insights for improving its efficiency. Invasion is traditionally quantified by antibiotic protection assays that require dilution plating and counting of colony-forming units rescued from infected cells. However, to differentiate between attached and internalized bacteria vector, this assay requires supplementation by a time-consuming and tedious immunofluorescence staining, making it laborious and reduces its reliability and reproducibility. Here we describe a new red fluorescent protein (RFP)-based high-throughput and inexpensive method for tracking bacterial adherence and internalization through flow cytometry to provide a convenient and real-time quantification of bacterial invasiveness in a heterogeneous population of cells. We invaded MCF-7, A549, and HEK-293 cells with the E. coli vector and measured RFP using imaging flow cytometry. We found high cellular infection of up to 70.47% in MCF-7 compared to 27.4% and 26.2% in A549 and HEK-293 cells, respectively. The quantitative evaluation of internalized E. coli is rapid and cell-dependent, and it distinctively differentiates between attached and cytosolic bacteria while showing the degree of cellular invasiveness. This imaging flow cytometry approach can be applied broadly to study host-bacteria interaction.
  14. Rapid preparation of adherent mammalian cells for basic scanning electron microscopy (SEM) analysis
    Osahor A, Deekonda K, Lee CW, Sim EU, Radu A, Narayanan K
    Anal Biochem, 2017 10 01;534:46-48.
    PMID: 28693990 DOI: 10.1016/j.ab.2017.07.008
    Sample preparation for scanning electron microscope analysis involves reagents and equipment that are expensive and often hazardous. Here we demonstrate a circumvention of Osmium tetroxide and critical point drying, greatly reducing the duration, complexity and cost of the process. We captured early stage interactions of invasive-bacteria and HeLa cells during the process of bacteria-mediated gene delivery and illustrate sufficient clarity can be obtained using this procedure to preserve and clearly visualize relevant cellular structures. This protocol is significantly cheaper and easier to adapt compared to conventional methods, and will allow routine preparation/viewing of eukaryotic or bacterial samples for basic morphological studies.
  15. Fulltext Expression trend of selected ribosomal protein genes in nasopharyngeal carcinoma
    Ma XR, Sim EU, Ling TY, Tiong TS, Subramaniam SK, Khoo AS
    Malays J Med Sci, 2012 Oct;19(4):23-30.
    PMID: 23613646 MyJurnal
    Ribosomal proteins are traditionally associated with protein biosynthesis until recent studies that implicated their extraribosomal functions in human diseases and cancers. Our previous studies using GeneFishing™ DEG method and microarray revealed underexpression of three ribosomal protein genes, RPS26, RPS27, and RPL32 in cancer of the nasopharynx. Herein, we investigated the expression pattern and nucleotide sequence integrity of these genes in nasopharyngeal carcinoma to further delineate their involvement in tumourigenesis. The relationship of expression level with clinicopathologic factors was also statistically studied.
  16. Fulltext Increased serum levels of interleukin-6 and von Willenbrand Factor in early phase of acute coronary syndrome in a young and multiethnic Malaysian population
    Tiong WN, Fong AY, Sim EU, Chan HC, Ong TK, Chang BC, et al.
    Heart Asia, 2012;4(1):146-50.
    PMID: 27326052 DOI: 10.1136/heartasia-2012-010131
    Interleukin-6 (IL6; proinflammatory marker), von Willebrand Factor (vWF; endothelial dysfunction marker) and P-selectin (platelet activation marker), may play important roles in defining the pathogenesis of vulnerable plaques in acute coronary syndrome (ACS). This study aims to investigate the expression and relationship of these markers in early phases of ACS in a young and multiethnic Malaysian population.
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