Displaying publications 1 - 20 of 103 in total

  1. Tang YQ, Lee SH, Sekaran SD
    JUMMEC, 2014;17(2):1-8.
    The plants of the genus Phyllanthus (Euphorbiaceae) are distributed in most tropical and subtropical regions of world. This plant has been long used as a traditional medicine to treat problems such as stomach, intestinal infections, kidney and urinary bladder disturbances, diabetes, and hepatitis B. There has been considerable interest in these plants in recent years. This review discusses the antiviral and anticancer aspects of Phyllanthus species. Scientific studies have demonstrated that extracts and purified isolated compounds (flavonoids, lignans, phenols, and terpenes) obtained from these plants possess antiviral effects against herpes simplex (HSV) and dengue virus infections (DENV). These observations are associated with the disruption of essential proteins needed during viral cycle, thus halting the viral replication. In addition, the Phyllanthus species have also been shown to exert inhibitory effects against selected cancers types. In these studies anti-proliferative, anti-metastatic, anti-angiogenic effects and induced apoptosis of human cancers cell lines were observed. These may be explained by the disruption of multiple survival pathways and differential protein expression. CONLCUSION:As a conclusion, tThe Phyllanthus plant possesses multiple medicinal properties, including antiviral and anticancer activities which may potentially be used as a medicinal source for many disease locally.
  2. Jindal MH, Le CF, Mohd Yusof MY, Sekaran SD
    JUMMEC, 2014;17(1):1-7.
    Antimicrobial peptides (AMPs) have gained increasing attention as a potential candidate in the development of novel antimicrobial agent. Designing AMPs with enhanced antimicrobial activity while reducing the cell toxicity level is desired especially against the antibiotic-resistant microbes. Various approaches towards the design of AMPs have been described and physicochemical properties of AMPs represent the primary factors determining the antimicrobial potency of AMPs. The most common parameters include net charge and hydrophobicity, which greatly influence the antimicrobial activity of AMPs. Moreover, certain amino acids would have critical importance in affecting the antimicrobial activity as well as cell cytotoxicity of AMPS. In this review, net charge, hydrophobicity, and specific amino acid residues were discussed as factors contributing to the antimicrobial activity of AMPs.
  3. Sekaran SD
    Dengue is an arthropod borne disease that has become important worldwide. There is still no specific drug available for treatment and also no protective vaccine that can be used. As such, specific diagnosis is essential to enable good management and prevention of large outbreaks. Diagnosis today in many countries is still based on serology though the detection of NS1 has slowly become incorporated. Diagnosis is critical for early intervention with specific preventive health measures to prevent fatalities and also to curtail spread and reduce economic losses. Serological assays mainly detect IgM which now as a single test is invalid unless a second sample is taken to confirm. As such to effectively diagnose dengue at all stages of infection, assays with two or more markers are required or two samples taken a few days apart. Other commonly used tests include NS1 detection, nucleic acid amplification and IgG detection. However the sensitivities of the current commercial kits vary quite considerably and have to be interpreted with caution. Hence knowledge of this disease is essential when conducting diagnostics for dengue.
  4. Rathakrishnan A, Sekaran SD
    Expert Opin Med Diagn, 2013 Jan;7(1):99-112.
    PMID: 23530846 DOI: 10.1517/17530059.2012.718759
    Dengue is of major concern around the world. Having no pathognomonic features that reliably distinguish it from other febrile illnesses, laboratory diagnosis is important for confirmation. Ideally, a dengue diagnostic test should be sensitive, specific and applicable from the onset of disease to 10 days post-infection.
  5. Sekaran SD, Artsob H
    Expert Opin Med Diagn, 2007 Dec;1(4):521-30.
    PMID: 23496358 DOI: 10.1517/17530059.1.4.521
    Flaviviruses constitute a genus of viruses that are important etiologic agents of human disease, causing clinical disease ranging from fever to severe manifestations, such as encephalitis and hemorrhagic fever. Serology is presently the most frequently used means of diagnosing flavivirus infections. However, other diagnostic tests may be employed, such as molecular detection, virus isolation and antigen-capture procedures. The applicability of the latter three diagnostic procedures can be expected to vary depending upon the infecting flavivirus, as some flaviviruses, such as dengue, display high and long-term viremias, whereas other flaviviruses produce no, or barely detectable, viremias. Molecular diagnostic techniques have been successfully applied to the diagnosis of flavivirus infections and have the advantage of rapidity, sensitivity and specific identification of the infecting virus. However, it is important to ensure that the right detection tools are employed (for example, appropriate primers and probes to detect the specific virus) and that the laboratory maintains a high proficiency in their testing procedures. Some of the studies that have been employed in the diagnosis of flavivirus infections are reviewed in this article. It seems that there is the potential to develop testing algorithms that successfully employ molecular diagnostics alone or in conjunction with other laboratory techniques for the diagnosis of acute human flavivirus infections.
  6. Sekaran SD, Rathakrishnan A, Yeo ASL
    JUMMEC, 2014;17(2):23-32.
    Dengue is one of the highest occurring vector-borne diseases. It is caused by dengue viruses 1- 4. Currently, the disease is classified into dengue with or without warning signs and severe dengue based on WHO 2009 dengue classification. As of today, neither specific drugs nor commercial vaccine exist for dengue. The best treatment yet would be support, management and proper medical care. With no pathognomonic features that could differentiate it from other febrile illnesses, clinical diagnosis alone is insufficient. Yet, despite the current advances and existence of various laboratory diagnostic methods of dengue, a consensus singular method has not been established. There are several hypotheses or theories regarding the vaguely understood immunopathogenesis of dengue. Amongst these are the viral factors, host-immune factors and host-genetic factors. In addition to these, the occurrence of asymptomatic dengue has further complicated the disease. However, these individuals provide opportunities in the search for protective factors against dengue.
  7. Thergarajan G, Sekaran SD
    Expert Rev Mol Diagn, 2023;23(8):643-651.
    PMID: 37417532 DOI: 10.1080/14737159.2023.2234815
    INTRODUCTION: Every year, a significant rise in dengue incidence observed is responsible for 10% of fever episodes in children and adolescents in endemic countries. Considering that the symptoms of dengue are similar to those of many other viruses, early diagnosis of the disease has long been difficult, and lack of sensitive diagnostic tools may be another factor contributing to a rise in dengue incidence.

    AREAS COVERED: This review will highlight dengue diagnostics strategies and discuss other possible targets for dengue diagnosis. Understanding the dynamics of the immune response and how it affects viral infection has enabled informed diagnosis. As more technologies emerge, precise assays that include some clinical markers need to be included.

    EXPERT OPINION: Future diagnostic strategies will require the use both viral and clinical markers in a serial manner with the use of artificial intelligence technology to determine from the first point of illness to better determine severity status and management. A definitive endpoint is not in the horizon as the disease as well as the virus is constantly evolving and hence many developed assays need to be constantly changing some of their reagents periodically as newer genotypes and probably too serotypes emerge.

  8. Komarasamy TV, Sekaran SD
    J Oleo Sci, 2012;61(4):227-39.
    PMID: 22450124
    Melanoma incidence and mortality have risen dramatically in recent years. No effective treatment for metastatic melanoma exists; hence currently, an intense effort for new drug evaluation is being carried out. In this study, we investigated the effects of a palm oil-derived nanopolymer called Bio-12 against human malignant melanoma. The nanopolymers of Bio-12 are lipid esters derived from a range of fatty acids of palm oil. Our study aims to identify the anti-proliferative properties of Bio-12 against human malignant melanoma cell line (MeWo) and to elucidate the mode of actions whereby Bio-12 brings about cell death. Bio-12 significantly inhibited the growth of MeWo cells in a concentration- and time- dependent manner with a median inhibitory concentration (IC₅₀) value of 1/25 dilution after 72 h but was ineffective on human normal skin fibroblasts (CCD-1059sk). We further investigated the mode of actions of Bio-12 on MeWo cells. Cell cycle flow cytometry demonstrated that MeWo cells treated with increasing concentrations of Bio-12 resulted in S-phase arrest, accompanied by the detection of sub-G1 content, indicative of apoptotic cell death. Induction of apoptosis was further confirmed via caspase (substrate) cleavage assay which showed induction of early apoptosis in MeWo cells. In addition, DNA strand breaks which are terminal event in apoptosis were evident through increase of TUNEL positive cells and formation of a characteristic DNA ladder on agarose gel electrophoresis. Moreover, treatment of MeWo cells with Bio-12 induced significant increase in lactate dehydrogenase (LDH) activity. These results show that Bio-12 possesses the ability to suppress proliferation of human malignant melanoma MeWo cells and this suppression is at least partly attributed to the initiation of the S-phase arrest, apoptosis and necrosis, suggesting that it is indeed worth for further investigations.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. Tang YQ, Jaganath IB, Sekaran SD
    PLoS One, 2010;5(9):e12644.
    PMID: 20838625 DOI: 10.1371/journal.pone.0012644
    Phyllanthus is a traditional medicinal plant that has been used in the treatment of many diseases including hepatitis and diabetes. The main aim of the present work was to investigate the potential cytotoxic effects of aqueous and methanolic extracts of four Phyllanthus species (P.amarus, P.niruri, P.urinaria and P.watsonii) against skin melanoma and prostate cancer cells.
  14. Osman O, Fong MY, Sekaran SD
    J Gen Virol, 2009 Mar;90(Pt 3):678-686.
    PMID: 19218214 DOI: 10.1099/vir.0.005306-0
    The full-length genomes of two DENV-1 viruses isolated during the 2005-2006 dengue incidents in Brunei were sequenced. Twenty five primer sets were designed to amplify contiguous overlapping fragments of approximately 500-600 base pairs spanning the entire sequence of the genome. The amplified PCR products were sent to a commercial laboratory for sequencing and the nucleotides and the deduced amino acids were determined. Sequence analysis of the envelope gene at the nucleotide and amino acid levels between the two isolates showed 92 and 96 % identity, respectively. Comparison of the envelope gene sequences with 68 other DENV-1 viruses of known genotypes placed the two isolates into two different genotypic groups. Isolate DS06/210505 belongs to genotype V together with some of the recent isolates from India (2003) and older isolates from Singapore (1990) and Burma (1976), while isolate DS212/110306 was clustered in genotype IV with the prototype Nauru strain (1974) and with some of the recent isolates from Indonesia (2004) and the Philippines (2002, 2001). In the full-length genome analysis at the nucleotide level, isolate DS06/210505 showed 94 % identity to the French Guyana strain (1989) in genotype V while isolate DS212/110306 had 96 % identity to the Nauru Island strain (1974) in genotype IV. This work constitutes the first complete genetic characterization of not only Brunei DENV-1 virus isolates, but also the first strain from Borneo Island. This study was the first to report the isolation of dengue virus in the country.
  15. Kumari N, Navaratnam P, Sekaran SD
    J Infect Dev Ctries, 2008 Jun 01;2(3):193-9.
    PMID: 19738350
    BACKGROUND: Streptococcus pneumoniae is a major human pathogen. The emergence of penicillin resistant strains since the 1970s has been life threatening and the evolution of the bacteria have enabled itself to develop resistance to many other antibiotics such as the macrolides and the fluoroquinolones. This study aims to characterize S. pneumoniae isolates for the presence of penicillin and macrolide resistance genes.

    METHODOLOGY: One hundred and twenty clinical isolates of S. pneumoniae were obtained from patients of University Malaya Medical Centre (UMMC). The strains were screened using a multiplex real-time PCR method for the presence of alterations in the genes encoding the penicillin binding proteins: pbp2b, macrolide resistance determinant ermB and the pneumolysin gene, ply. Dual-labelled Taqman probes were used in the real-time detection method comprising three different genes labeled with individual fluorophores at different wavelengths. One hundred and twenty isolates from bacterial cultures and isolates directly from blood cultures samples were analyzed using this assay.

    RESULTS: A multiplex PCR comprising the antibiotic resistance genes, ermB and and pneumolysin gene (ply), a S. pneumoniae species specific gene, was developed to characterize strains of S. pneumoniae. Out of the 120 pneumococcal isolates, 58 strains were categorized as Penicillin Sensitive Streptococcus pneumoniae (PSSP), 36 as Penicillin Intermediate Streptococcus pneumoniae (PISP) and 26 as Penicillin Resistant Streptococcus pneumoniae (PRSP). All the 58 PSSP strains harboured the pbp2b gene while the 36 PISP and 26 PRSP strains did not harbour this gene, thus suggesting reduced susceptibility to penicillin. Resistance to erythromycin was observed in 47 of the pneumococcal strains while 15 and 58 were intermediate and sensitive to this drug respectively. Susceptibility testing to other beta-lactams (CTX and CRO) also showed reduced susceptibility among the strains within the PISP and PRSP groups but most PSSP strains were sensitive to other antibiotics.

    CONCLUSION: The characterization of pneumococcal isolates for penicillin and erythromycin resistance genes could be useful to predict the susceptibility of these isolates to other antibiotics, especially beta-lactams drugs. We have developed an assay with a shorter turnaround time to determine the species and resistance profile of Streptococcus pneumoniae with respect to penicillin and macrolides using the Real Time PCR format with fluorescent labeled Taqman probes, hence facilitating earlier and more definitive antimicrobial therapy which may lead to better patient management.

  16. Desa MN, Sekaran SD, Vadivelu J, Parasakthi N
    Epidemiol Infect, 2008 Jul;136(7):940-2.
    PMID: 17678563
    Choline-binding proteins (CBP) have been associated with the pathogenesis of Streptococcus pneumoniae. We screened, using PCR, for the presence of genes (cbpA, D, E, G) encoding these proteins in 34 isolates of pneumococci of known serotypes and penicillin susceptibility from invasive and non-invasive disease. All isolates harboured cbpD and cbpE whereas cbpA and cbpG were found in 47% and 59% respectively; the latter were more frequent in vaccine-associated types and together accounted for 77% of these isolates. No association was observed with penicillin susceptibility but 85% of non-invasive isolates were positive for these genes.
  17. Jahanshahi P, Sekaran SD, Adikan FR
    Med Biol Eng Comput, 2015 Aug;53(8):679-87.
    PMID: 25791696 DOI: 10.1007/s11517-015-1262-2
    Evaluation of binding between analytes and its relevant ligands on surface plasmon resonance (SPR) biosensor is of considerable importance for accurate determination and screening of an interference in immunosensors. Dengue virus serotype 2 was used as a case study in this investigation. This research work compares and interprets the results obtained from analytical analysis with the experimental ones. Both the theoretical calculations and experimental results are verified with one sample from each category of dengue serotypes 2 (low, mid, and high positive), which have been examined in the database of established laboratorial diagnosis. In order to perform this investigation, the SPR angle variations are calculated, analyzed, and then validated via experimental SPR angle variations. Accordingly, the error ratios of 5.35, 6.54, and 3.72% were obtained for the low-, mid-, and high-positive-specific immune globulins of patient serums, respectively. In addition, the magnetic fields of the biosensor are numerically simulated to show the effect of different binding mediums.
  18. Le CF, Fang CM, Sekaran SD
    PMID: 28167546 DOI: 10.1128/AAC.02340-16
    Antimicrobial peptides (AMPs) are expressed in various living organisms as first-line host defenses against potential harmful encounters in their surroundings. AMPs are short polycationic peptides exhibiting various antimicrobial activities. The principal antibacterial activity is attributed to the membrane-lytic mechanism which directly interferes with the integrity of the bacterial cell membrane and cell wall. In addition, a number of AMPs form a transmembrane channel in the membrane by self-aggregation or polymerization, leading to cytoplasm leakage and cell death. However, an increasing body of evidence has demonstrated that AMPs are able to exert intracellular inhibitory activities as the primary or supportive mechanisms to achieve efficient killing. In this review, we focus on the major intracellular targeting activities reported in AMPs, which include nucleic acids and protein biosynthesis and protein-folding, protease, cell division, cell wall biosynthesis, and lipopolysaccharide inhibition. These multifunctional AMPs could serve as the potential lead peptides for the future development of novel antibacterial agents with improved therapeutic profiles.
  19. Tan HY, Nagoor NH, Sekaran SD
    Trop Biomed, 2010 Dec;27(3):430-41.
    PMID: 21399583 MyJurnal
    The major outer membrane protein (OmpH) of 4 local Malaysian strains of Pasteurella multocida serotype B:2 were characterized in comparison to ATCC strains. Three major peptide bands of MW 26, 32 and 37 kDa were characterized using SDSPAGE. Two of these fragments, the 32 kDa and 37 kDa were observed to be more reactive with a mouse polyclonal antiserum in all of the local isolates as well as the ATCC strains in a Western blot. However, the 32 kDa fragment was found to cross react with other Gram negative bacteria. Therefore, the 37 kDa OmpH was selected as vaccine candidate. The 37 kDa ompH gene of the isolated strain 1710 was cloned into an Escherichia coli expression vector to produce large amounts of recombinant OmpH (rOmpH). The 37 kDa ompH gene of strain 1710 was sequenced. In comparison to a reference strain X-73 of the ompH of P. multocida, 39bp was found deleted in the 37 kDa ompH gene. However, the deletion did not shift the reading frame or change the amino acid sequence. The rOmpH was used in a mice protection study. Mice immunized and challenged intraperitoneally resulted 100% protection against P. multocida whilst mice immunized subcutaneously and challenged intraperitoneally only resulted 80% protection. The rOmpH is therefore a suitable candidate for vaccination field studies. The same rOmpH was also used to develop a potential diagnostic kit in an ELISA format.
  20. Gebriel AM, Subramaniam G, Sekaran SD
    Trop Biomed, 2006 Dec;23(2):194-207.
    PMID: 17322822 MyJurnal
    The detection of leptospires in patient blood in the first week of the disease using PCR provides an early diagnostic tool. PCR using two sets of primers (G1/G2 and B64-I/B64-II) tested with samples seeded with 23 leptospiral strains from pathogenic and non-pathogenic strains was able to amplify leptospiral DNA from pathogenic strains only. Of the 39 antibody negative samples collected from patients suspected for leptospirosis, only 1 sample (2.6%) was PCR positive. Using LSSP-PCR, the G2 primers allowed the characterization of Leptopira species to 10 different genetic signatures which may have epidemiological value in determining species involved in outbreaks. Leptospiral outer membrane proteins from three strains were purified and reacted against patients sera and gave rise to different profiles for pathogenic and non-pathogenic strains. Lymphocytes of mice injected with OMPs proliferated and released IFN(-3) when stimulated in vitro using Leptospira OMP as antigens. This suggests that an immune response could be established using leptospiral OMPs as a putative vaccine. OMPs were also used in a Dot-ELISA to detect antibodies against Leptospira pathogens in humans.
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links