Displaying publications 1 - 20 of 104 in total

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  1. Kassim M, Mansor M, Kamalden TA, Shariffuddin II, Hasan MS, Ong G, et al.
    Shock, 2014 Aug;42(2):154-60.
    PMID: 24667629 DOI: 10.1097/SHK.0000000000000179
    Excessive free radical production by immune cells has been linked to cell death and tissue injury during sepsis. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death that has been identified in several pathological conditions. Caffeic acid phenethyl ester (CAPE) is an active component of honeybee products and exhibits antioxidant, anti-inflammatory, and immunomodulatory activities. The present study examined the ability of CAPE to scavenge peroxynitrite in RAW 264.7 murine macrophages stimulated with lipopolysaccharide/interferon-γ that was used as an in vitro model. Conversion of 123-dihydrorhodamine to its oxidation product 123-rhodamine was used to measure peroxynitrite production. Two mouse models of sepsis (endotoxemia and cecal ligation and puncture) were used as in vivo models. The level of serum 3-nitrotyrosine was used as an in vivo marker of peroxynitrite. The results demonstrated that CAPE significantly improved the viability of lipopolysaccharide/interferon-γ-treated RAW 264.7 cells and significantly inhibited nitric oxide production, with effects similar to those observed with an inhibitor of inducible nitric oxide synthase (1400W). In addition, CAPE exclusively inhibited the synthesis of peroxynitrite from the artificial substrate SIN-1 and directly prevented the peroxynitrite-mediated conversion of dihydrorhodamine-123 to its fluorescent oxidation product rhodamine-123. In both sepsis models, CAPE inhibited cellular peroxynitrite synthesis, as evidenced by the absence of serum 3-nitrotyrosine, an in vivo marker of peroxynitrite. Thus, CAPE attenuates the inflammatory responses that lead to cell damage and, potentially, cell death through suppression of the production of cytotoxic molecules such as nitric oxide and peroxynitrite. These observations provide evidence of the therapeutic potential of CAPE treatment for a wide range of inflammatory disorders.
  2. Sekaran SD, Rathakrishnan A, Yeo ASL
    JUMMEC, 2014;17(2):23-32.
    MyJurnal
    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.
  3. Mahboob T, Azlan AM, Tan TC, Samudi C, Sekaran SD, Nissapatorn V, et al.
    Asian Pac J Trop Med, 2016 Sep;9(9):866-871.
    PMID: 27633300 DOI: 10.1016/j.apjtm.2016.07.008
    OBJECTIVE: To examine the acanthamoebicidal effects of ethyl acetate, aqueous and butanol fractions of dried flower buds of Lonicera japonica (L. japonica) Thunb. (Flos Lonicerae) in vitro.

    METHODS: Acanthamoeba triangularis isolates were obtained from environmental water samples and identified by PCR. They were exposed to ethyl acetate, water and butanol fractions of L. japonica Thunb. at concentrations ranging from 0.5 mg/mL to 1.5 mg/mL. The extracts were evaluated for growth inhibition at 24, 48 and 72 h, respectively. Chlorogenic acid at a concentration of 1 mg/mL was examined for inhibition of encystment.

    RESULTS: Ethyl acetate fraction at a concentration of 1.5 mg/mL evoked a significant reduction of trophozoite viability by 48.9% after 24 h, 49.2% after 48 h and 33.7% after 72 h chlorogenic acid, the major active constituent of L. japonica Thunb. at the concentration of 1 mg/mL reduced the cysts/trophozoite ratio by 100% after 24 h, 84.0% after 48 h and 72.3% after 72 h. This phenolic compound at concentration of 1 mg/mL concurrent with 0.6% hydrogen peroxide inhibited hydrogen peroxide-induced encystment by 92.8% at 72 h.

    CONCLUSIONS: Results obtained from this study show that ethyl acetate fraction at 1.5 mg/mL is the most potent fraction of L. japonica Thunb. and its major constituent chlorogenic acid showed the remarkable inhibition of encystment at a concentration of 1 mg/mL.

  4. 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.
  5. Sambanthamurthi R, Tan Y, Sundram K, Hayes KC, Abeywardena M, Leow SS, et al.
    Br J Nutr, 2011 Dec;106(11):1664-75.
    PMID: 21736778 DOI: 10.1017/S0007114511002133
    It is well established that plant phenolics elicit various biological activities, with positive effects on health. Palm oil production results in large volumes of aqueous by-products containing phenolics. In the present study, we describe the effects of oil palm phenolics (OPP) on several degenerative conditions using various animal models. OPP reduced blood pressure in a NO-deficient rat model, protected against ischaemia-induced cardiac arrhythmia in rats and reduced plaque formation in rabbits fed an atherogenic diet. In Nile rats, a spontaneous model of the metabolic syndrome and type 2 diabetes, OPP protected against multiple aspects of the syndrome and diabetes progression. In tumour-inoculated mice, OPP protected against cancer progression. Microarray studies on the tumours showed differential transcriptome profiles that suggest anti-tumour molecular mechanisms involved in OPP action. Thus, initial studies suggest that OPP may have potential against several chronic disease outcomes in mammals.
  6. Lau SM, Chua TH, Sulaiman WY, Joanne S, Lim YA, Sekaran SD, et al.
    Parasit Vectors, 2017 Mar 21;10(1):151.
    PMID: 28327173 DOI: 10.1186/s13071-017-2091-y
    BACKGROUND: Dengue remains a serious public health problem in Southeast Asia and has increased 37-fold in Malaysia compared to decades ago. New strategies are urgently needed for early detection and control of dengue epidemics.

    METHODS: We conducted a two year study in a high human density dengue-endemic urban area in Selangor, where Gravid Ovipositing Sticky (GOS) traps were set up to capture adult Aedes spp. mosquitoes. All Aedes mosquitoes were tested using the NS1 dengue antigen test kit. All dengue cases from the study site notified to the State Health Department were recorded. Weekly microclimatic temperature, relative humidity (RH) and rainfall were monitored.

    RESULTS: Aedes aegypti was the predominant mosquito (95.6%) caught in GOS traps and 23% (43/187 pools of 5 mosquitoes each) were found to be positive for dengue using the NS1 antigen kit. Confirmed cases of dengue were observed with a lag of one week after positive Ae. aegypti were detected. Aedes aegypti density as analysed by distributed lag non-linear models, will increase lag of 2-3 weeks for temperature increase from 28 to 30 °C; and lag of three weeks for increased rainfall.

    CONCLUSION: Proactive strategy is needed for dengue vector surveillance programme. One method would be to use the GOS trap which is simple to setup, cost effective (below USD 1 per trap) and environmental friendly (i.e. use recyclable plastic materials) to capture Ae. aegypti followed by a rapid method of detecting of dengue virus using the NS1 dengue antigen kit. Control measures should be initiated when positive mosquitoes are detected.

  7. Lau SM, Vythilingam I, Doss JI, Sekaran SD, Chua TH, Wan Sulaiman WY, et al.
    Trop Med Int Health, 2015 Oct;20(10):1271-80.
    PMID: 26094839 DOI: 10.1111/tmi.12555
    To determine the effectiveness of using sticky traps and the NS1 dengue antigen kit for the surveillance of Aedes mosquitoes for dengue control.
  8. Pourshahrestani S, Zeimaran E, Kadri NA, Gargiulo N, Jindal HM, Naveen SV, et al.
    ACS Appl Mater Interfaces, 2017 Sep 20;9(37):31381-31392.
    PMID: 28836753 DOI: 10.1021/acsami.7b07769
    Chitosan-based hemostats are promising candidates for immediate hemorrhage control. However, they have some disadvantages and require further improvement to achieve the desired hemostatic efficiency. Here, a series of 1% Ga2O3-containing mesoporous bioactive glass-chitosan composite scaffolds (Ga-MBG/CHT) were constructed by the lyophilization process and the effect of various concentrations of Ga-MBG (10, 30, and 50 wt %) on the hemostatic function of the CHT scaffold was assessed as compared to that of Celox Rapid gauze (CXR), a current commercially available chitosan-coated hemostatic gauze. The prepared scaffolds exhibited >79% porosity and showed increased water uptake compared to that in CXR. The results of coagulation studies showed that pure CHT and composite scaffolds exhibited increased hemostatic performance with respect to CXR. Furthermore, the composite scaffold with the highest Ga-MBG content (50 wt %) had increased capability to enhancing thrombus generation, blood clotting, and platelet adhesion and aggregation than that of the scaffold made of pure CHT. The antibacterial efficacy and biocompatibility of the prepared scaffolds were also assessed by a time-killing assay and an Alamar Blue assay, respectively. Our results show that the antibacterial effect of 50% Ga-MBG/CHT was more pronounced than that of CHT and CXR. The cell viability results also demonstrated that Ga-MBG/CHT composite scaffolds had good biocompatibility, which facilitates the spreading and proliferation of human dermal fibroblast cells even with 50 wt % Ga-MBG loading. These results suggest that Ga-MBG/CHT scaffolds could be a promising hemostatic candidate for improving hemostasis in critical situations.
  9. 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).
  10. Jindal HM, Chandramathi S, Sekaran SD, Suresh K
    Trop Biomed, 2020 Sep 01;37(3):626-636.
    PMID: 33612777 DOI: 10.47665/tb.37.3.626
    Hand hygiene is the topmost crucial procedure to prevent hospital-acquired infections. Choosing an effective hand disinfectant is necessary in enforcing good hand hygiene practice especially in hospital settings. The aim of the study was to investigate the efficacy of Aaride AGT-1 as a hand disinfectant for the inhibition of pathogenic microorganisms' transmission among both patients and personnel in the health care system compared to other commercially available disinfectants. In the present study, a new hand disinfectant Aaride AGT-1 was tested against several bacterial and viral pathogens to evaluate its antimicrobial activity profile. The results revealed that Aaride AGT-1 displayed the highest antibacterial activity against five pathogenic bacteria including MRSA when compared to other commercially available hand sanitizers. Aaride AGT-1 showed the lowest percentage needed to inhibit the growth of bacterial pathogens. In addition, results obtained from time killing assay revealed that Aaride AGT-1 demonstrated the best killing kinetics, by eradicating the bacterial cells rapidly within 0.5 min with 6 log reduction (>99.99% killing). Also, Aaride AGT1 was able to reduce 100% plaque formed by three viruses namely HSV-1, HSV-2 and EV-71. In conclusion, Aaride AGT-1 is capable of killing wide-spectrum of pathogens including bacteria and viruses compared to other common disinfectants used in hospital settings. Aaride AGT-1's ability to kill both bacteria and viruses contributes as valuable addition to the hand disinfection portfolio.
  11. Saeidi A, Chong YK, Yong YK, Tan HY, Barathan M, Rajarajeswaran J, et al.
    Cell Immunol, 2015 Sep;297(1):19-32.
    PMID: 26071876 DOI: 10.1016/j.cellimm.2015.05.005
    The role of T-cell immunosenescence and functional CD8(+) T-cell responses in HIV/TB co-infection is unclear. We examined and correlated surrogate markers of HIV disease progression with immune activation, immunosenescence and differentiation using T-cell pools of HIV/TB co-infected, HIV-infected and healthy controls. Our investigations showed increased plasma viremia and reduced CD4/CD8 T-cell ratio in HIV/TB co-infected subjects relative to HIV-infected, and also a closer association with changes in the expression of CD38, a cyclic ADP ribose hydrolase and CD57, which were consistently expressed on late-senescent CD8(+) T cells. Up-regulation of CD57 and CD38 were directly proportional to lack of co-stimulatory markers on CD8(+) T cells, besides diminished expression of CD127 (IL-7Rα) on CD57(+)CD4(+) T cells. Notably, intracellular IFN-γ, perforin and granzyme B levels in HIV-specific CD8(+) T cells of HIV/TB co-infected subjects were diminished. Intracellular CD57 levels in HIV gag p24-specific CD8(+) T cells were significantly increased in HIV/TB co-infection. We suggest that HIV-TB co-infection contributes to senescence associated with chronic immune activation, which could be due to functional insufficiency of CD8(+) T cells.
  12. Gundamaraju R, Vemuri RC, Singla RK, Manikam R, Rao AR, Sekaran SD
    Pharmacogn Mag, 2014 Aug;10(Suppl 3):S557-62.
    PMID: 25298674 DOI: 10.4103/0973-1296.139782
    The myocardium is generally injured in the case of reperfusion injury and arterial damage is caused by hypertension. In reference to these statements, the present study was focused. Cardiac glycosides were said to have protective effects against myocardial infarction and hypertension. Strophanthus hispidus was thus incorporated in the study.
  13. 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.
  14. Tang YQ, Jaganath IB, Manikam R, Sekaran SD
    Int J Med Sci, 2014;11(6):564-77.
    PMID: 24782645 DOI: 10.7150/ijms.7704
    Melanoma is the most fatal form of skin cancer. Different signalling pathways and proteins will be differentially expressed to pace with the tumour growth. Thus, these signalling molecules and proteins are become potential targets to halt the progression of cancer. The present works were attempted to investigate the underlying molecular mechanisms of anticancer effects of Phyllanthus (P.amarus, P.niruri, P.urinaria and P.watsonii) on skin melanoma, MeWo cells.
  15. Tan WC, Jaganath IB, Manikam R, Sekaran SD
    Int J Med Sci, 2013;10(13):1817-29.
    PMID: 24324358 DOI: 10.7150/ijms.6902
    Nucleoside analogues such as acyclovir are effective antiviral drugs against herpes simplex virus infections since its introduction. However, with the emergence of acyclovir-resistant HSV strains particularly in immunocompromised patients, there is a need to develop an alternative antiherpetic drug and plants could be the potential lead. In this study, the antiviral activity of the aqueous extract of four Phyllanthus species were evaluated against herpes simplex virus type-1 (HSV-1) and HSV-2 in Vero cells by quantitative PCR. The protein expressions of untreated and treated infected Vero cells were studied by 2D-gel electrophoresis and Western blot. This is the first study that reported the antiviral activity of P. watsonii. P. urinaria was shown to demonstrate the strongest antiviral activity against HSV-1 and HSV-2, with SI >33.6. Time-of-addition studies suggested that the extract may act against the early infection stage and the replication stage. Protein expression studies indicated that cellular proteins that are involved in maintaining cytoskeletal structure could be potential target for development of antiviral drugs. Preliminary findings indicated that P. urinaria demonstrated potent inhibitory activity against HSV. Hence, further studies such as in vivo evaluation are required for the development of effective antiherpetic drug.
  16. Lee SH, Jaganath IB, Manikam R, Sekaran SD
    BMC Complement Altern Med, 2013 Oct 20;13:271.
    PMID: 24138815 DOI: 10.1186/1472-6882-13-271
    BACKGROUND: Lung cancer constitutes one of the malignancies with the greatest incidence and mortality rates with 1.6 million new cases and 1.4 million deaths each year. Prognosis remains poor due to deleterious development of multidrug resistance resulting in less than 15% lung cancer patients reaching five years survival. We have previously shown that Phyllanthus induced apoptosis in conjunction with its antimetastastic action. In the current study, we aimed to determine the signaling pathways utilized by Phyllanthus to exert its antimetastatic activities.

    METHODS: Cancer 10-pathway reporter array was performed to screen the pathways affected by Phyllanthus in lung carcinoma cell line (A549) to exert its antimetastatic effects. Results from this array were then confirmed with western blotting, cell cycle analysis, zymography technique, and cell based ELISA assay for human total iNOS. Two-dimensional gel electrophoresis was subsequently carried out to study the differential protein expressions in A549 after treatment with Phyllanthus.

    RESULTS: Phyllanthus was observed to cause antimetastatic activities by inhibiting ERK1/2 pathway via suppression of Raf protein. Inhibition of this pathway resulted in the suppression of MMP2, MMP7, and MMP9 expression to stop A549 metastasis. Phyllanthus also inhibits hypoxia pathway via inhibition of HIF-1α that led to reduced VEGF and iNOS expressions. Proteomic analysis revealed a number of proteins downregulated by Phyllanthus that were involved in metastatic processes, including invasion and mobility proteins (cytoskeletal proteins), transcriptional proteins (proliferating cell nuclear antigen; zinc finger protein), antiapoptotic protein (Bcl2) and various glycolytic enzymes. Among the four Phyllanthus species tested, P. urinaria showed the greatest antimetastatic activity.

    CONCLUSIONS: Phyllanthus inhibits A549 metastasis by suppressing ERK1/2 and hypoxia pathways that led to suppression of various critical proteins for A549 invasion and migration.

  17. 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.
  18. 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.
  19. 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.
  20. Anbazhagan D, Mansor M, Yan GO, Md Yusof MY, Hassan H, Sekaran SD
    PLoS One, 2012;7(7):e36696.
    PMID: 22815678 DOI: 10.1371/journal.pone.0036696
    Quorum sensing is a term that describes an environmental sensing system that allows bacteria to monitor their own population density which contributes significantly to the size and development of the biofilm. Many gram negative bacteria use N-acyl-homoserine lactones as quorum sensing signal molecules. In this study, we sought to find out if the biofilm formation among clinical isolates of Acinetobacter spp. is under the control of autoinducing quorum sensing molecules.
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