MyMedR

Fulltext Early diagnosis of Dengue infection using a commercial Dengue Duo rapid test kit for the detection of NS1, IGM, and IGG

Wang SM, Sekaran SD

Am J Trop Med Hyg, 2010 Sep;83(3):690-5.

PMID: 20810840 DOI: 10.4269/ajtmh.2010.10-0117

A commercial Dengue Duo rapid test kit was evaluated for early dengue diagnosis by detection of dengue virus NS1 antigen and immunoglobulin M (IgM)/IgG antibodies. A total of 420 patient serum samples were subjected to real-time reverse transcription-polymerase chain reaction (RT-PCR), in-house IgM capture enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition assay, and the SD Dengue Duo rapid test. Of the 320 dengue acute and convalescent sera, dengue infection was detected by either serology or RT-PCR in 300 samples (93.75%), as compared with 289 samples (90.31%) in the combined SD Duo NS1/IgM. The NS1 detection rate is inversely proportional, whereas the IgM detection rate is directly proportional to the presence of IgG antibodies. The sensitivity and specificity in diagnosing acute dengue infection in the SD Duo NS1/IgM were 88.65% and 98.75%, respectively. The assay is sensitive and highly specific. Detection of both NS1 and IgM by SD Duo gave comparable detection rate by either serology or RT-PCR.

Fulltext Evaluation of a commercial SD dengue virus NS1 antigen capture enzyme-linked immunosorbent assay kit for early diagnosis of dengue virus infection

Wang SM, Sekaran SD

J Clin Microbiol, 2010 Aug;48(8):2793-7.

PMID: 20573879 DOI: 10.1128/JCM.02142-09

Early definitive diagnosis of dengue virus infection may help in the timely management of dengue virus infection. We evaluated the Standard Diagnostics (SD, South Korea) dengue virus nonstructural protein NS1 antigen enzyme-linked immunosorbent assay (SD dengue NS1 Ag ELISA) for the detection of dengue virus NS1 antigen in patients' sera, using a total of 399 serum samples in a comparison with real-time reverse transcription (RT)-PCR, an in-house IgM capture (MAC)-ELISA, and a hemagglutination inhibition (HI) assay. Of the 320 dengue sera, 205 (64%) tested positive for NS1 antigen compared to 300 (93.75%) by either MAC-ELISA or RT-PCR, 161 (50.31%) by RT-PCR, and 226 (70.36%) by MAC-ELISA only. The assay was able to detect NS1 antigen in convalescent-phase sera until day 14 of infection. The NS1 detection rate is inversely proportional while the IgM detection rate is directly proportional to the presence of IgG antibodies. The overall sensitivity and specificity of the SD dengue NS1 Ag ELISA in the detection of "confirmed dengue virus" sera are 76.76% and 98.31%, respectively. This suggests that the SD kit is highly specific and sensitive for the detection of NS1 antigen. However, caution is needed when the kit is used as a single assay, as detection in samples that contained the virus was only about 81.97%. Combining this assay with an IgM and/or IgG assay will increase the sensitivity of detection, especially in areas with a higher prevalence of secondary dengue virus infections.

Fulltext RNA interference mediated inhibition of dengue virus multiplication and entry in HepG2 cells

Alhoot MA, Wang SM, Sekaran SD

PLoS One, 2012;7(3):e34060.

PMID: 22457813 DOI: 10.1371/journal.pone.0034060

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.

Fulltext Inhibition of dengue virus entry and multiplication into monocytes using RNA interference

Alhoot MA, Wang SM, Sekaran SD

PLoS Negl Trop Dis, 2011 Nov;5(11):e1410.

PMID: 22140591 DOI: 10.1371/journal.pntd.0001410

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.

Fulltext Antimetastatic effects of Phyllanthus on human lung (A549) and breast (MCF-7) cancer cell lines

Lee SH, Jaganath IB, Wang SM, Sekaran SD

PLoS One, 2011;6(6):e20994.

PMID: 21698198 DOI: 10.1371/journal.pone.0020994

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.

Detection and Quantification of Chikungunya Virus by Real-Time RT-PCR Assay

Wang SM, Ali UH, Sekaran SD, Thayan R

Methods Mol Biol, 2016;1426:105-17.

PMID: 27233265 DOI: 10.1007/978-1-4939-3618-2_10

Real-time PCR assay has many advantages over conventional PCR methods, including rapidity, quantitative measurement, low risk of contamination, high sensitivity, high specificity, and ease of standardization (Mackay et al., Nucleic Acids Res 30:1292-1305, 2002). The real-time PCR system relies upon the measurement of a fluorescent reporter during PCR, in which the amount of emitted fluorescence is directly proportional to the amount of the PCR product in a reaction (Gibsons et al., Genome Res 6:995-1001, 1996). Here, we describe the use of SYBR Green I-based and TaqMan(®) real-time reverse transcription polymerase chain reaction (RT-PCR) for the detection and quantification of Chikungunya virus (CHIKV).

Antibodies against prM protein distinguish between previous infection with dengue and Japanese encephalitis viruses

Cardosa MJ, Wang SM, Sum MS, Tio PH

BMC Microbiol, 2002 May 5;2:9.

PMID: 12019028

In Southeast Asia, dengue viruses often co-circulate with other flaviviruses such as Japanese encephalitis virus, and due to the presence of shared antigenic epitopes it is often difficult to use serological methods to distinguish between previous infections by these flaviviruses.

Fulltext Inhibition of dengue virus entry into target cells using synthetic antiviral peptides

Alhoot MA, Rathinam AK, Wang SM, Manikam R, Sekaran SD

Int J Med Sci, 2013;10(6):719-29.

PMID: 23630436 DOI: 10.7150/ijms.5037

Despite the importance of DENV as a human pathogen, there is no specific treatment or protective vaccine. Successful entry into the host cells is necessary for establishing the infection. Recently, the virus entry step has become an attractive therapeutic strategy because it represents a barrier to suppress the onset of the infection. Four putative antiviral peptides were designed to target domain III of DENV-2 E protein using BioMoDroid algorithm. Two peptides showed significant inhibition of DENV when simultaneously incubated as shown by plaque formation assay, RT-qPCR, and Western blot analysis. Both DET4 and DET2 showed significant inhibition of virus entry (84.6% and 40.6% respectively) using micromolar concentrations. Furthermore, the TEM images showed that the inhibitory peptides caused structural abnormalities and alteration of the arrangement of the viral E protein, which interferes with virus binding and entry. Inhibition of DENV entry during the initial stages of infection can potentially reduce the viremia in infected humans resulting in prevention of the progression of dengue fever to the severe life-threatening infection, reduce the infected vector numbers, and thus break the transmission cycle. Moreover these peptides though designed against the conserved region in DENV-2 would have the potential to be active against all the serotypes of dengue and might be considered as Hits to begin designing and developing of more potent analogous peptides that could constitute as promising therapeutic agents for attenuating dengue infection.

Fulltext Cytokine factors present in dengue patient sera induces alterations of junctional proteins in human endothelial cells

Appanna R, Wang SM, Ponnampalavanar SA, Lum LC, Sekaran SD

Am J Trop Med Hyg, 2012 Nov;87(5):936-42.

PMID: 22987650 DOI: 10.4269/ajtmh.2012.11-0606

Plasma leakage in severe dengue has been postulated to be associated with skewed cytokine immune responses. In this study, the association of cytokines with vascular permeability in dengue patients was investigated. Human serum samples collected from 48 persons (13 with dengue fever, 29 with dengue hemorrhagic fever, and 6 healthy) were subjected to cytokines analysis by using Luminex Multiplex Technology. Selected serum samples from patients with dengue hemorrhagic fever sera and recombinant human cytokines were then tested for roles on inducing vascular permeability by treatment of human umbilical vein endothelial cells. Confocal immunofluorescence staining indicated morphologic alteration of human umbilical vein endothelial cells treated with serum samples from patients with dengue hemorrhagic fever compared with serum samples from healthy persons. The findings suggest that cytokines produced during dengue hemorrhagic infections could induce alterations in the vascular endothelium, which may play a fundamental role in the pathophysiology of dengue.

Fulltext Dengue infection and miscarriage: a prospective case control study

Tan PC, Soe MZ, Si Lay K, Wang SM, Sekaran SD, Omar SZ

PLoS Negl Trop Dis, 2012;6(5):e1637.

PMID: 22590658 DOI: 10.1371/journal.pntd.0001637

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.

Molecular Epidemiology of Chikungunya Virus by Sequencing

Thayan R, Yusof MA, Saat Z, Sekaran SD, Wang SM

Methods Mol Biol, 2016;1426:11-9.

PMID: 27233257 DOI: 10.1007/978-1-4939-3618-2_2

Molecular surveillance of Chikungunya virus (CHIKV) is important as it provides data on the circulating CHIKV genotypes in endemic countries and enabling activation of measures to be taken in the event of a pending outbreak. Molecular surveillance is carried out by first detecting CHIKV in susceptible humans or among field-caught mosquitoes. This is followed by sequencing a selected region of the virus which will provide evidence on the source of the virus and possible association of the virus to increased cases of Chikungunya infections.

Robust molecular bowl-based metal-organic frameworks with open metal sites: size modulation to increase the catalytic activity

Liu L, Han ZB, Wang SM, Yuan DQ, Ng SW

Inorg Chem, 2015 Apr 20;54(8):3719-21.

PMID: 25849722 DOI: 10.1021/acs.inorgchem.5b00185

Herein, two stable lead(II) molecular-bowl-based metal-organic frameworks and their micro- and nanosized forms with open metal sites were presented. These materials could act as Lewis acid catalysts to cyanosilylation reaction. Moreover, the catalytic performances are size-dependent, with the catalyst with nanosized form being 1 order of magnitude more efficient than those with micro- and millisized forms.

Loss of Transfected Human Brain Micro-Vascular Endothelial Cell Integrity during Herpes Simplex Virus Infection

Lee SH, Atiya N, Wang SM, Manikam R, Raju CS, Sekaran SD

Intervirology, 2018;61(4):193-203.

PMID: 30541013 DOI: 10.1159/000495180

OBJECTIVE: Herpes simplex virus infection through the neuronal route is the most well-studied mode of viral encephalitis that can persists in a human host for a lifetime. However, the involvement of other possible infection mechanisms by the virus remains underexplored. Therefore, this study aims to determine the temporal effects and mechanisms by which the virus breaches the human brain micro-vascular endothelial cells of the blood-brain barrier.

METHOD: An electrical cell-substrate impedance-sensing tool was utilized to study the real-time cell-cell barrier or morphological changes in response to the virus infection.

RESULTS: Herpes simplex virus, regardless of type (i.e., 1 or 2), reduced the cell-cell barrier resistance almost immediately after virus addition to endothelial cells, with negligible involvement of cell-matrix adhesion changes. There is no exclusivity in the infection ability of endothelial cells. From 30 h after HSV infection, there was an increase in cell membrane capacitance with a subsequent loss of cell-matrix adhesion capability, indicating a viability loss of the infected endothelial cells.

CONCLUSION: This study shows for the first time that destruction of human brain micro-vascular endothelial cells as an in vitro model of the blood-brain barrier could be an alternative invasion mechanism during herpes simplex virus infection.

Human Papilloma Virus (HPV) self-sampling: do women accept it?

Abdullah NN, Daud S, Wang SM, Mahmud Z, Mohd Kornain NK, Al-Kubaisy W

J Obstet Gynaecol, 2018 Apr;38(3):402-407.

PMID: 29385850 DOI: 10.1080/01443615.2017.1379061

This study aims to determine the acceptability of Human Papilloma Virus (HPV) self-sampling and the factors associated with willingness to buy HPV self-sampling kit in the future. A total of 164 women aged 28-60 years old from Obstetrics & Gynaecology clinics at a teaching hospital performed HPV self-sampling using the Digene HC2 DNA collection kit. After samples were taken, the participants were given self-administered questionnaires. The majority of the participants were Malay (93.9%), had attained tertiary education (65.2%) and were employed (70.1%). The acceptability was good. More than half of the participants felt that self-sampling was easy. Only 1.2% felt that the procedure was difficult to perform. Most reported no pain at all during the procedure (66.9%). The commonest concern was getting a good sample (90.1%). A number of Pap smears were found to be significantly associated with the willingness to buy the HPV self-sampling kit. HPV self-sampling has the potential to be included in the cervical cancer screening programme. Impact Statement What is already known on this subject: HPV self-sampling is acceptable in some developed and developing countries. It is acceptable because it was easy to perform with very minimal pain or discomfort. Studies on the acceptance of self-screening are needed to plan a policy on self-sampling in the future. What the results of this study add: Our study adds new findings to the body of knowledge on self-sampling in the local population. We found that more women are willing to do the self-sampling at the clinic rather than at home. Although more than 90% expressed willingness to do self-sampling in the future, only 70% of them were willing to purchase the kit. Cost is a potential barrier to women who have the interest to perform the self-sampling. Given the global economic challenges, cost is inevitably an important predictor that we have to consider. What the implications are of these findings for clinical practice and/or further research: Future research should examine women from the rural areas and those who are resilient to Pap smear screening. In clinical practice, clinicians should acknowledge that cost is a potential barrier for women who are willing to do self-sampling. Self-sampling could be an option for women with no financial constraint to buy the kit. However, clinicians should counsel women so that they can make an informed choice in determining their screening method.

Fulltext A Systematic Review on Attenuation of PCSK9 in Relation to Atherogenesis Biomarkers Associated with Natural Products or Plant Bioactive Compounds in In Vitro Studies: A Critique on the Quality and Imprecision of Studies

Zulkapli R, Yusof MYPM, Abd Muid S, Wang SM, Firus Khan AY, Nawawi H

Int J Environ Res Public Health, 2022 Oct 08;19(19).

PMID: 36232177 DOI: 10.3390/ijerph191912878

A systematic review was performed to identify all the related publications describing PCSK9 and atherogenesis biomarkers attenuation associated with a natural product and plant bioactive compounds in in vitro studies. This review emphasized the imprecision and quality of the included research rather than the detailed reporting of the results. Literature searches were conducted in Scopus, PubMed, and Science Direct from 2003 until 2021, following the Cochrane handbook. The screening of titles, abstracts, and full papers was performed by two independent reviewers, followed by data extraction and validity. Study quality and validity were assessed using the Imprecision Tool, Model, and Marker Validity Assessment that has been developed for basic science studies. A total of 403 articles were identified and 31 of those that met the inclusion criteria were selected. 13 different atherogenesis biomarkers in relation to PCSK9 were found, and the most studied biomarkers are LDLR, SREBP, and HNF1α. In terms of quality, our review suggests that the basic science study in investigating atherogenesis biomarkers is deficient in terms of imprecision and validity.

Fulltext Clinical and immunological markers of dengue progression in a study cohort from a hyperendemic area in Malaysia

Rathakrishnan A, Klekamp B, Wang SM, Komarasamy TV, Natkunam SK, Sathar J, et al.

PLoS One, 2014;9(3):e92021.

PMID: 24647042 DOI: 10.1371/journal.pone.0092021

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.

Fulltext Dengue patients exhibit higher levels of PrM and E antibodies than their asymptomatic counterparts

Yeo AS, Rathakrishnan A, Wang SM, Ponnampalavanar S, Manikam R, Sathar J, et al.

Biomed Res Int, 2015;2015:420867.

PMID: 25815314 DOI: 10.1155/2015/420867

Dengue virus infection is a common tropical disease which often occurs without being detected. These asymptomatic cases provide information in relation to the manifestation of immunological aspects. In this study, we developed an ELISA method to compare neutralizing effects of dengue prM and E antibodies between dengue patients and their asymptomatic household members. Recombinant D2 premembrane (prM) was constructed, cloned, and tested for antigenicity. The recombinant protein was purified and tested with controls by using an indirect ELISA method. Positive dengue serum samples with their asymptomatic pair were then carried out onto the developed ELISA. In addition, commercially available recombinant envelope (E) protein was used to develop an ELISA which was tested with the same set of serum samples in the prM ELISA. Asymptomatic individuals showed preexisting heterotypic neutralizing antibodies. The recombinant prM was antigenically reactive in the developed ELISA. Dengue patients had higher prM and E antibodies compared to their household members. Our study highlights the neutralizing antibodies levels with respect to dengue prM and E between dengue patients and asymptomatic individuals.

Fulltext Cytokine expression profile of dengue patients at different phases of illness

Rathakrishnan A, Wang SM, Hu Y, Khan AM, Ponnampalavanar S, Lum LC, et al.

PLoS One, 2012;7(12):e52215.

PMID: 23284941 DOI: 10.1371/journal.pone.0052215

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.

Fulltext Lack of clinical manifestations in asymptomatic dengue infection is attributed to broad down-regulation and selective up-regulation of host defence response genes

Yeo AS, Azhar NA, Yeow W, Talbot CC, Khan MA, Shankar EM, et al.

PLoS One, 2014;9(4):e92240.

PMID: 24727912 DOI: 10.1371/journal.pone.0092240

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.

Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC

Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.

Phys Rev Lett, 2024 Jan 12;132(2):021803.

PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803

The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140 fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.

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