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Search Results: 1 - 10 of 121148 matches for " Seok Mui Wang "
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Inhibition of Dengue Virus Entry and Multiplication into Monocytes Using RNA Interference
Mohammed Abdelfatah Alhoot,Seok Mui Wang,Shamala Devi Sekaran
PLOS Neglected Tropical Diseases , 2011, DOI: 10.1371/journal.pntd.0001410
Abstract: Background Dengue infection ranks as one of the most significant viral diseases of the globe. Currently, there is no specific vaccine or antiviral therapy for prevention or treatment. Monocytes/macrophages are the principal target cells for dengue virus and are responsible for disseminating the virus after its transmission. Dengue virus enters target cells via receptor-mediated endocytosis after the viral envelope protein E attaches to the cell surface receptor. This study aimed to investigate the effect of silencing the CD-14 associated molecule and clathrin-mediated endocytosis using siRNA on dengue virus entry into monocytes. Methodology/Principal Findings Gene expression analysis showed a significant down-regulation of the target genes (82.7%, 84.9 and 76.3% for CD-14 associated molecule, CLTC and DNM2 respectively) in transfected monocytes. The effect of silencing of target genes on dengue virus entry into monocytes was investigated by infecting silenced and non-silenced monocytes with DENV-2. Results showed a significant reduction of infected cells (85.2%), intracellular viral RNA load (73.0%), and extracellular viral RNA load (63.0%) in silenced monocytes as compared to non-silenced monocytes. Conclusions/Significance Silencing the cell surface receptor and clathrin mediated endocytosis using RNA interference resulted in inhibition of the dengue virus entry and subsequently multiplication of the virus in the monocytes. This might serve as a novel promising therapeutic target to attenuate dengue infection and thus reduce transmission as well as progression to severe dengue hemorrhagic fever.
RNA Interference Mediated Inhibition of Dengue Virus Multiplication and Entry in HepG2 Cells
Mohammed Abdelfatah Alhoot, Seok Mui Wang, Shamala Devi Sekaran
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034060
Abstract: Background Dengue virus-host cell interaction initiates when the virus binds to the attachment receptors followed by endocytic internalization of the virus particle. Successful entry into the cell is necessary for infection initiation. Currently, there is no protective vaccine or antiviral treatment for dengue infection. Targeting the viral entry pathway has become an attractive therapeutic strategy to block infection. This study aimed to investigate the effect of silencing the GRP78 and clathrin-mediated endocytosis on dengue virus entry and multiplication into HepG2 cells. Methodology/Principal Findings HepG2 cells were transfected using specific siRNAs to silence the cellular surface receptor (GRP78) and clathrin-mediated endocytosis pathway. Gene expression analysis showed a marked down-regulation of the targeted genes (87.2%, 90.3%, and 87.8% for GRP78, CLTC, and DNM2 respectively) in transfected HepG2 cells when measured by RT-qPCR. Intracellular and extracellular viral RNA loads were quantified by RT-qPCR to investigate the effect of silencing the attachment receptor and clathrin-mediated endocytosis on dengue virus entry. Silenced cells showed a significant reduction of intracellular (92.4%) and extracellular viral RNA load (71.4%) compared to non-silenced cells. Flow cytometry analysis showed a marked reduction of infected cells (89.7%) in silenced HepG2 cells compared to non-silenced cells. Furthermore, the ability to generate infectious virions using the plaque assay was reduced 1.07 log in silenced HepG2 cells. Conclusions/Significance Silencing the attachment receptor and clathrin-mediated endocytosis using siRNA could inhibit dengue virus entry and multiplication into HepG2 cells. This leads to reduction of infected cells as well as the viral load, which might function as a unique and promising therapeutic agent for attenuating dengue infection and prevent the development of dengue fever to the severe life-threatening DHF or DSS. Furthermore, a decrease of viremia in humans can result in the reduction of infected vectors and thus, halt of the transmission cycle.
Antimetastatic Effects of Phyllanthus on Human Lung (A549) and Breast (MCF-7) Cancer Cell Lines
Sau Har Lee,Indu Bala Jaganath,Seok Mui Wang,Shamala Devi Sekaran
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0020994
Abstract: Current chemotherapeutic drugs kill cancer cells mainly by inducing apoptosis. However, they become ineffective once cancer cell has the ability to metastasize, hence the poor prognosis and high mortality rate. Therefore, the purpose of this study was to evaluate the antimetastatic potential of Phyllanthus (P. niruri, P. urinaria, P. watsonii, and P. amarus) on lung and breast carcinoma cells.
Dengue Infection and Miscarriage: A Prospective Case Control Study
Peng Chiong Tan ,May Zaw Soe,Khaing Si Lay,Seok Mui Wang,Shamala Devi Sekaran,Siti Zawiah Omar
PLOS Neglected Tropical Diseases , 2012, DOI: 10.1371/journal.pntd.0001637
Abstract: Background Dengue is the most prevalent mosquito borne infection worldwide. Vertical transmissions after maternal dengue infection to the fetus and pregnancy losses in relation to dengue illness have been reported. The relationship of dengue to miscarriage is not known. Method We aimed to establish the relationship of recent dengue infection and miscarriage. Women who presented with miscarriage (up to 22 weeks gestation) to our hospital were approached to participate in the study. For each case of miscarriage, we recruited 3 controls with viable pregnancies at a similar gestation. A brief questionnaire on recent febrile illness and prior dengue infection was answered. Blood was drawn from participants, processed and the frozen serum was stored. Stored sera were thawed and then tested in batches with dengue specific IgM capture ELISA, dengue non-structural protein 1 (NS1) antigen and dengue specific IgG ELISA tests. Controls remained in the analysis if their pregnancies continued beyond 22 weeks gestation. Tests were run on 116 case and 341 control sera. One case (a misdiagnosed viable early pregnancy) plus 45 controls (39 lost to follow up and six subsequent late miscarriages) were excluded from analysis. Findings Dengue specific IgM or dengue NS1 antigen (indicating recent dengue infection) was positive in 6/115 (5·2%) cases and 5/296 (1·7%) controls RR 3·1 (95% CI 1·0–10) P = 0·047. Maternal age, gestational age, parity and ethnicity were dissimilar between cases and controls. After adjustments for these factors, recent dengue infection remained significantly more frequently detected in cases than controls (AOR 4·2 95% CI 1·2–14 P = 0·023). Interpretation Recent dengue infections were more frequently detected in women presenting with miscarriage than in controls whose pregnancies were viable. After adjustments for confounders, the positive association remained.
Development of conventional and real-time multiplex PCR assays for the detection of nosocomial pathogens
Anbazhagan, Deepa;Mui, Wang Seok;Mansor, Marzida;Yan, Gracie Ong Siok;Yusof, Mohd Yasim;Sekaran, Shamala Devi;
Brazilian Journal of Microbiology , 2011, DOI: 10.1590/S1517-83822011000200006
Abstract: nosocomial infections are major clinical threats to hospitalised patients and represent an important source of morbidity and mortality. it is necessary to develop rapid detection assays of nosocomial pathogens for better prognosis and initiation of antimicrobial therapy in patients. in this study, we present the development of molecular methods for the detection of six common nosocomial pathogens including escherichia coli, staphylococcus aureus, streptococcus pneumoniae, klebsiella pneumoniae, pseudomonas aeruginosa and acinetobacter spp. conventional multiplex pcr and sybr green based real time pcr assays were performed using genus and species specific primers. blind testing with 300 clinical samples was also carried out. the two assays were found to be sensitive and specific. eubacterial pcr assay exhibited positive results for 46 clinical isolates from which 43 samples were detected by real time pcr assay. the sensitivity of the assay is about 93.7% in blind test isolates. the pcr results were reconfirmed using the conventional culture method. this assay has the potential to be a rapid, accurate and highly sensitive molecular diagnostic tool for simultaneous detection of escherichia coli, staphylococcus aureus, streptococcus pneumoniae, klebsiella pneumoniae, pseudomonas aeruginosa and acinetobacter spp. this assay has the potential to detect nosocomial pathogens within 5 to 6 hours, helping to initiate infection control measures and appropriate treatment in paediatric and elderly (old aged) patients, pre-and post surgery patients and organ transplant patients and thus reduces their hospitalization duration .
Cytokine Expression Profile of Dengue Patients at Different Phases of Illness
Anusyah Rathakrishnan, Seok Mui Wang, Yongli Hu, Asif M. Khan, Sasheela Ponnampalavanar, Lucy Chai See Lum, Rishya Manikam, Shamala Devi Sekaran
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0052215
Abstract: Background Dengue is an important medical problem, with symptoms ranging from mild dengue fever to severe forms of the disease, where vascular leakage leads to hypovolemic shock. Cytokines have been implicated to play a role in the progression of severe dengue disease; however, their profile in dengue patients and the synergy that leads to continued plasma leakage is not clearly understood. Herein, we investigated the cytokine kinetics and profiles of dengue patients at different phases of illness to further understand the role of cytokines in dengue disease. Methods and Findings Circulating levels of 29 different types of cytokines were assessed by bead-based ELISA method in dengue patients at the 3 different phases of illness. The association between significant changes in the levels of cytokines and clinical parameters were analyzed. At the febrile phase, IP-10 was significant in dengue patients with and without warning signs. However, MIP-1β was found to be significant in only patients with warning signs at this phase. IP-10 was also significant in both with and without warning signs patients during defervescence. At this phase, MIP-1β and G-CSF were significant in patients without warning signs, whereas MCP-1 was noted to be elevated significantly in patients with warning signs. Significant correlations between the levels of VEGF, RANTES, IL-7, IL-12, PDGF and IL-5 with platelets; VEGF with lymphocytes and neutrophils; G-CSF and IP-10 with atypical lymphocytes and various other cytokines with the liver enzymes were observed in this study. Conclusions The cytokine profile patterns discovered between the different phases of illness indicate an essential role in dengue pathogenesis and with further studies may serve as predictive markers for progression to dengue with warning signs.
Clinical and Immunological Markers of Dengue Progression in a Study Cohort from a Hyperendemic Area in Malaysia
Anusyah Rathakrishnan, Benjamin Klekamp, Seok Mui Wang, Thamil Vaani Komarasamy, Santha Kumari Natkunam, Jameela Sathar, Azliyati Azizan, Aurora Sanchez-Anguiano, Rishya Manikam, Shamala Devi Sekaran
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0092021
Abstract: Background With its elusive pathogenesis, dengue imposes serious healthcare, economic and social burden on endemic countries. This study describes the clinical and immunological parameters of a dengue cohort in a Malaysian city, the first according to the WHO 2009 dengue classification. Methodology and Findings This longitudinal descriptive study was conducted in two Malaysian hospitals where patients aged 14 and above with clinical symptoms suggestive of dengue were recruited with informed consent. Among the 504 participants, 9.3% were classified as non-dengue, 12.7% without warning signs, 77.0% with warning signs and 1.0% with severe dengue based on clinical diagnosis. Of these, 37% were misdiagnosed as non-dengue, highlighting the importance of both clinical diagnosis and laboratory findings. Thrombocytopenia, prolonged clotting time, liver enzymes, ALT and AST served as good markers for dengue progression but could not distinguish between patients with and without warning signs. HLA-A*24 and -B*57 were positively associated with Chinese and Indians patients with warning signs, respectively, whereas A*03 may be protective in the Malays. HLA-A*33 was also positively associated in patients with warning signs when compared to those without. Dengue NS1, NS2A, NS4A and NS4B were found to be important T cell epitopes; however with no apparent difference between with and without warning signs patients. Distinction between the 2 groups of patients was also not observed in any of the cytokines analyzed; nevertheless, 12 were significantly differentially expressed at the different phases of illness. Conclusion The new dengue classification system has allowed more specific detection of dengue patients, however, none of the clinical parameters allowed distinction of patients with and without warning signs. While the HLA-A*33 may be predictive marker for development of warning signs; larger studies will be needed to support this findings.
Lack of Clinical Manifestations in Asymptomatic Dengue Infection Is Attributed to Broad Down-Regulation and Selective Up-Regulation of Host Defence Response Genes
Adeline S. L. Yeo, Nur Atiqah Azhar, Wanyi Yeow, C. Conover Talbot, Mohammad Asif Khan, Esaki M. Shankar, Anusyah Rathakrishnan, Azliyati Azizan, Seok Mui Wang, Siew Kim Lee, Mun Yik Fong, Rishya Manikam, Shamala Devi Sekaran
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0092240
Abstract: Objectives Dengue represents one of the most serious life-threatening vector-borne infectious diseases that afflicts approximately 50 million people across the globe annually. Whilst symptomatic infections are frequently reported, asymptomatic dengue remains largely unnoticed. Therefore, we sought to investigate the immune correlates conferring protection to individuals that remain clinically asymptomatic. Methods We determined the levels of neutralizing antibodies (nAbs) and gene expression profiles of host immune factors in individuals with asymptomatic infections, and whose cognate household members showed symptoms consistent to clinical dengue infection. Results We observed broad down-regulation of host defense response (innate, adaptive and matrix metalloprotease) genes in asymptomatic individuals as against symptomatic patients, with selective up-regulation of distinct genes that have been associated with protection. Selected down-regulated genes include: TNF α (TNF), IL8, C1S, factor B (CFB), IL2, IL3, IL4, IL5, IL8, IL9, IL10 and IL13, CD80, CD28, and IL18, MMP8, MMP10, MMP12, MMP15, MMP16, and MMP24. Selected up-regulated genes include: RANTES (CCL5), MIP-1α (CCL3L1/CCL3L3), MIP-1β (CCL4L1), TGFβ (TGFB), and TIMP1. Conclusion Our findings highlight the potential association of certain host genes conferring protection against clinical dengue. These data are valuable to better explore the mysteries behind the hitherto poorly understood immunopathogenesis of subclinical dengue infection.
Fourier Coefficients of Automorphic Forms and Integrable Discrete Series
Goran Mui
Mathematics , 2015,
Abstract: Let $G$ be the group of $\mathbb R$--points of a semisimple algebraic group $\mathcal G$ defined over $\mathbb Q$. Assume that $G$ is connected and noncompact. We study Fourier coefficients of Poincar\' e series attached to matrix coefficients of integrable discrete series. We use these results to construct explicit automorphic cuspidal realizations, which have appropriate Fourier coefficients $\neq 0$, of integrable discrete series in families of congruence subgroups. In the case of $G=Sp_{2n}(\mathbb R)$, we relate our work to that of Li [15]. For $\mathcal G$ quasi--split over $\mathbb Q$, we relate our work to the result about Poincar\' e series due to Khare, Larsen, and Savin [16].
Improving Islet Engraftment by Gene Therapy
Xiaojie Wang,Mark Meloche,C. Bruce Verchere,Dawei Ou,Alice Mui,Garth L. Warnock
Journal of Transplantation , 2011, DOI: 10.1155/2011/594851
Abstract: Islet cell transplantation is currently the only feasible long-term treatment option for patients with type 1 diabetes. However, the majority of transplanted islets experience damage and apoptosis during the isolation process, a blood-mediated inflammatory microenvironment in the portal vein upon islet infusion, hypoxia induced by the low oxygenated milieu, and poor-revascularization-mediated lack of nutrients, and impaired hormone modulation in the local transplanted site. Strategies using genetic modification methods through overexpression or silencing of those proteins involved in promoting new formation of blood vessels or inhibition of apoptosis may overcome these hurdles and improve islet engraftment outcomes.
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