Displaying publications 1 - 20 of 105 in total

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  1. Lim JCW, Sagineedu SR, Yong ACH, Sidik SM, Wong WSF, Stanslas J
    Naunyn Schmiedebergs Arch Pharmacol, 2021 Jan;394(1):95-105.
    PMID: 32840650 DOI: 10.1007/s00210-020-01966-3
    SRS27, an andrographolide analogue, had been proven to have therapeutic properties at a dose of 3 mg/kg in both in vitro and in vivo asthma models of our previous study. The present study focuses on the pharmacokinetic and toxicity profile of this compound to provide further evidence for the development of this compound as an anti-asthma agent. A simple pharmacokinetic study was performed in female BALB/c mice to measure blood plasma concentration of the compound at therapeutic dose. At a single dose of 3 mg/kg, SRS27 had a relatively short half-life but was able to achieve a concentration range of 13-19 μM that is related to its in vitro bioactivities. With regard to toxicity profile, SRS27 appears to be safe, as no histopathological changes were observed in the liver, kidneys and ovaries of SRS27-treated female BALB/c mice. In addition, there was no significant change in the mean body weight and organ weight of the animals in the SRS27-treated groups compared with the vehicle-treated control group at the end of the treatment. This fully supports the absence of any significant changes in peripheral blood leukocyte counts of SRS27-treated mice. Rewardingly, this acute toxicity study also revealed that SRS27 has a wide therapeutic window as no toxicity symptoms were detected with a dose up to 60 mg/kg daily when tested for 14 days. These results provide strong justification for further investigation of SRS27 as a potential new anti-asthma agent.
  2. Loh C. Y., Tang, T. F., Wong, W. F., Looi, Chung Yeng
    MyJurnal
    Introduction: The Hedgehog (Hh) pathway serves as a major regulator in organ development, stem cell maintenance, cell proliferation, and cell differentiation. This pathway is highly regulated and aberrant activation will promote tumorigenesis. Hh pathway notably Sonic Hedgehog pathway was reported to be upregulated and promote tumorigenesis in various human malignancies including colorectal, gastric, lung, prostate, and breast. This review was aimed to discuss the current understanding of Hh pathway activation in different types of human cancers and discuss the development of the therapeutic applications targeting Hh pathway. Methods: A systematic review was conducted using the electronic research database PubMed Central (PMC) from 2014-2019. The search was limited to studies that are relevant to both Hh signalling pathway and human cancers. A total of 50 articles were selected and their references cited were searched and reviewed. Results: The results regarding the role of Hh signalling in pancreatic cancer and colorectal cancer are controversial with some reporting tumor promoting activities whereas others tumor suppressive activity. Besides, results from other studies suggesting that Hh signalling pathway plays an oncogenic role by inducing tumor cells proliferation, promoting metastasis and maintaining cancer stem cells in human cancers such as lung, stomach, and breast. To date, Glasdegib (PF-04449913) is the only Hh targeting small molecule inhibitor being studied at FDA Phase 3 clinical trial. Identification of the right tumors and minimization of the side effects remain as the main obstacles in the development of Hh signalling inhibitors. Conclusion: In conclusion, advancement in our understanding of Hh pathway has provided us opportunity to develop novel therapeutic strategies to fight human cancers with activated Hh pathway but more studies need to be conducted to solve the controversial regarding the role of Hh pathway in certain cancers.
  3. Wong WK, Chua HS
    Knee Surg Relat Res, 2020 Apr 16;32(1):20.
    PMID: 32660589 DOI: 10.1186/s43019-020-00032-9
    BACKGROUND: In an ever-aging society that as a whole has become more affluent, significant emphasis has been accorded to an improved quality of life. Knee osteoarthritis is ever-increasingly treated with total knee arthroplasty. The benefits and satisfaction experienced by those who have undergone total knee replacements (TKR) are well documented in the literature. The issue arises when osteoarthritis of the affected knee is more complex than simple osteoarthritis, i.e. the patient has complex primary osteoarthritis. This collective term encompasses conditions such as massive bone loss, ligamentous laxity, coronal defects and those with contractures. There are various classifications to describe massive bone loss but we utilized the Anderson Orthopaedic Research Institute (AORI) classification. Numerous treatment options are available and we report the use of metaphyseal sleeves as a highly successful treatment option.

    METHODS: We retrospectively reviewed all the patients at our centre who underwent primary TKR using the metaphyseal sleeves. Patients were assessed on symptoms and functional status, and radiographs were also taken to assess for osseointegration. Only patients who completed 2 years of follow up were included in our study.

    RESULTS: The updated (2011) Knee Society Score (KSS) was used in conjunction with radiological assessments at each follow up. Mean KSS scores improved from 53.83 preoperatively to 193.39 postoperatively. All patients demonstrated increasing osseointegration throughout follow up.

    CONCLUSION: The metaphyseal sleeve is an excellent treatment option for complex primary osteoarthritic knees with good results objectively, functionally and radiologically and would be a great choice for all orthopaedic surgeons to include in their armamentarium.

  4. Hong W, Wang Y, Chang Z, Yang Y, Pu J, Sun T, et al.
    Sci Rep, 2015;5:15328.
    PMID: 26471125 DOI: 10.1038/srep15328
    It is an urgent need to develop new drugs for Mycobacterium tuberculosis (Mtb), and the enzyme, dihydrofolate reductase (DHFR) is a recognised drug target. The crystal structures of methotrexate binding to mt- and h-DHFR separately indicate that the glycerol (GOL) binding site is likely to be critical for the function of mt-DHFR selective inhibitors. We have used in silico methods to screen NCI small molecule database and a group of related compounds were obtained that inhibit mt-DHFR activity and showed bactericidal effects against a test Mtb strain. The binding poses were then analysed and the influence of GOL binding site was studied by using molecular modelling. By comparing the chemical structures, 4 compounds that might be able to occupy the GOL binding site were identified. However, these compounds contain large hydrophobic side chains. As the GOL binding site is more hydrophilic, molecular modelling indicated that these compounds were failed to occupy the GOL site. The most potent inhibitor (compound 6) demonstrated limited selectivity for mt-DHFR, but did contain a novel central core (7H-pyrrolo[3,2-f]quinazoline-1,3-diamine), which may significantly expand the chemical space of novel mt-DHFR inhibitors. Collectively, these observations will inform future medicinal chemistry efforts to improve the selectivity of compounds against mt-DHFR.
  5. Abdullah S, Wong WF, Tan CT
    Mult Scler Int, 2017;2017:1359761.
    PMID: 28203460 DOI: 10.1155/2017/1359761
    Background. There have been inconsistent reports on the prevalence and pathogenicity of anti-Aquaporin 4 (AQP4) in patients presented with idiopathic inflammatory demyelinating diseases (IIDDs). Objective. To estimate the prevalence of anti-AQP4 antibody in patients with IIDDs presented to University Malaya Medical Centre in terms of patients' clinical and radiological presentations and prognoses. Methods. Retrospective data review of IIDDs patients presented from 2005 to 2015. Patients were classified into classical multiple sclerosis (CMS), opticospinal (OS) presentation, optic neuritis (ON), transverse myelitis (TM), brainstem syndrome (BS), and tumefactive MS. Anti-Aquaporin 4 antibody was tested using the Indirect Immunofluorescence Test (IIFT) cell-based assay. Statistical analysis was done using the SPSS version 20. Results. Anti-AQP4 antibody was detected in 53% of patients presented with IIDDs. CMS was more common in the seronegative group, 27/47 (57.45%; p < 0.001). Conversely, OS involvement was more common in the seropositive group, 26/53 (49.06%; p < 0.001). Longitudinally extensive spinal cord lesions (LESCLs) on MRI were also more common in the seropositive group, 29/40 (72.50%; p = 0.004). Only 2/40 (5.00%) had MRI evidence of patchy or multiple short-segment spinal cord lesions in the AQP4-positive group (p = 0.003). The relapse rate and Expanded Disability Status Scale (EDSS) were also higher in the seropositive group (5.43 versus 3.17, p = 0.005; 4.07 versus 2.51, p = 0.006, resp.). Typical clinical presentations that defined NMO were also seen in the seronegative patients, but in a lower frequency. Conclusion. Our cohort of patients had a higher prevalence of seropositivity of anti-AQP4 antibody as compared to those in Western countries. This was also associated with a more typical presentation of opticospinal involvement with LESCLs on MRI, a higher rate of relapse, and EDSS.
  6. Wong WL, Tan WB, Lim LH
    J. Helminthol., 2006 Mar;80(1):87-90.
    PMID: 16469180
    Hard structures of helminths have often been used for taxonomic identification but are usually not clearly defined when treated with conventional methods such as ammonium picrate-glycerin for monogeneans and glycerin for nematodes. The present study reports a rapid and simple technique to better resolve the hard parts of selected monogeneans and nematodes using 5-10% alkaline sodium dodecyl sulphate (SDS). In comparison with established methods, SDS-treated worms become more transparent. In monogeneans treated with SDS, clear details of the hooks, hook filaments, anchors, bars and the sclerotized copulatory organs could be observed. In SDS-treated nematodes, spicules and ornamentations of the buccal capsules could be clearly seen.
  7. Jiamsakul A, Lee MP, Nguyen KV, Merati TP, Cuong DD, Ditangco R, et al.
    Int J Tuberc Lung Dis, 2018 02 01;22(2):179-186.
    PMID: 29506614 DOI: 10.5588/ijtld.17.0348
    SETTING: Tuberculosis (TB) is the most common human immunodeficiency virus (HIV) related opportunistic infection and cause of acquired immune-deficiency syndrome related death. TB often affects those from a low socio-economic background.

    OBJECTIVE: To assess the socio-economic determinants of TB in HIV-infected patients in Asia.

    DESIGN: This was a matched case-control study. HIV-positive, TB-positive cases were matched to HIV-positive, TB-negative controls according to age, sex and CD4 cell count. A socio-economic questionnaire comprising 23 questions, including education level, employment, housing and substance use, was distributed. Socio-economic risk factors for TB were analysed using conditional logistic regression analysis.

    RESULTS: A total of 340 patients (170 matched pairs) were recruited, with 262 (77.1%) matched for all three criteria. Pulmonary TB was the predominant type (n = 115, 67.6%). The main risk factor for TB was not having a university level education (OR 4.45, 95%CI 1.50-13.17, P = 0.007). Burning wood or coal regularly inside the house and living in the same place of origin were weakly associated with TB diagnosis.

    CONCLUSIONS: These data suggest that lower socio-economic status is associated with an increased risk of TB in Asia. Integrating clinical and socio-economic factors into HIV treatment may help in the prevention of opportunistic infections and disease progression.

  8. Do TC, Boettiger D, Law M, Pujari S, Zhang F, Chaiwarith R, et al.
    HIV Med, 2016 08;17(7):542-9.
    PMID: 27430354 DOI: 10.1111/hiv.12358
    OBJECTIVES: The aim of the study was to assess the prevalence and characteristics associated with current smoking in an Asian HIV-positive cohort, to calculate the predictive risks of cardiovascular disease (CVD), coronary heart disease (CHD) and myocardial infarction (MI), and to identify the impact that simulated interventions may have.

    METHODS: Logistic regression analysis was used to distinguish associated current smoking characteristics. Five-year predictive risks of CVD, CHD and MI and the impact of simulated interventions were calculated utilizing the Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D) algorithm.

    RESULTS: Smoking status data were collected from 4274 participants and 1496 of these had sufficient data for simulated intervention calculations. Current smoking prevalence in these two groups was similar (23.2% vs. 19.9%, respectively). Characteristics associated with current smoking included age > 50 years compared with 30-39 years [odds ratio (OR) 0.65; 95% confidence interval (CI) 0.51-0.83], HIV exposure through injecting drug use compared with heterosexual exposure (OR 3.03; 95% CI 2.25-4.07), and receiving antiretroviral therapy (ART) at study sites in Singapore, South Korea, Malaysia, Japan and Vietnam in comparison to Thailand (all OR > 2). Women were less likely to smoke than men (OR 0.11; 95% CI 0.08-0.14). In simulated interventions, smoking cessation demonstrated the greatest impact in reducing CVD and CHD risk and closely approximated the impact of switching from abacavir to an alternate antiretroviral in the reduction of 5-year MI risk.

    CONCLUSIONS: Multiple interventions could reduce CVD, CHD and MI risk in Asian HIV-positive patients, with smoking cessation potentially being the most influential.

  9. Zeehaida M, Zairi NZ, Tan ZN, Wong WK, Lim BH
    Trop Biomed, 2009 Dec;26(3):366-8.
    PMID: 20237453
    The screening for anti-amoebic antibody among a group of donors was to obtain negative control serum samples for an on-going antigen development assay in diagnosis of amoebic liver abscess. Out of 200 samples, 125 (62.5%) were negative, whereas 44 (21.5%) had IHA titer of less than 1:128 and 31 (16.0%) of the samples had significant IHA titers of 1:128 or more, in which 2 serum samples gave titers of 1:4096.
  10. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    PMID: 33465186 DOI: 10.1140/epjc/s10052-020-08701-5
    A search is presented for supersymmetric partners of the top quark (top squarks) in final states with two oppositely charged leptons (electrons or muons), jets identified as originating from b quarks, and missing transverse momentum. The search uses data from proton-proton collisions at s = 13 TeV collected with the CMS detector, corresponding to an integrated luminosity of 137 fb - 1 . Hypothetical signal events are efficiently separated from the dominant top quark pair production background with requirements on the significance of the missing transverse momentum and on transverse mass variables. No significant deviation is observed from the expected background. Exclusion limits are set in the context of simplified supersymmetric models with pair-produced lightest top squarks. For top squarks decaying exclusively to a top quark and a lightest neutralino, lower limits are placed at 95 % confidence level on the masses of the top squark and the neutralino up to 925 and 450 GeV , respectively. If the decay proceeds via an intermediate chargino, the corresponding lower limits on the mass of the lightest top squark are set up to 850 GeV for neutralino masses below 420 GeV . For top squarks undergoing a cascade decay through charginos and sleptons, the mass limits reach up to 1.4 TeV and 900 GeV respectively for the top squark and the lightest neutralino.
  11. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2020;80(8):752.
    PMID: 32852485 DOI: 10.1140/epjc/s10052-020-8168-3
    A data sample of events from proton-proton collisions with at least two jets, and two isolated same-sign or three or more charged leptons, is studied in a search for signatures of new physics phenomena. The data correspond to an integrated luminosity of

    137




    fb


    -
    1




    at a center-of-mass energy of

    13

    TeV

    , collected in 2016-2018 by the CMS experiment at the LHC. The search is performed using a total of 168 signal regions defined using several kinematic variables. The properties of the events are found to be consistent with the expectations from standard model processes. Exclusion limits at 95% confidence level are set on cross sections for the pair production of gluinos or squarks for various decay scenarios in the context of supersymmetric models conserving or violating R parity. The observed lower mass limits are as large as

    2.1

    TeV

    for gluinos and

    0.9

    TeV

    for top and bottom squarks. To facilitate reinterpretations, model-independent limits are provided in a set of simplified signal regions.
  12. Sirunyan AM, CMS Collaboration, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2021;81(1):13.
    PMID: 33493254 DOI: 10.1140/epjc/s10052-020-08739-5
    A search for dark matter particles is performed using events with a Z boson candidate and large missing transverse momentum. The analysis is based on proton-proton collision data at a center-of-mass energy of 13 Te , collected by the CMS experiment at the LHC in 2016-2018, corresponding to an integrated luminosity of 137 fb - 1 . The search uses the decay channels Z → e e and Z → μ μ . No significant excess of events is observed over the background expected from the standard model. Limits are set on dark matter particle production in the context of simplified models with vector, axial-vector, scalar, and pseudoscalar mediators, as well as on a two-Higgs-doublet model with an additional pseudoscalar mediator. In addition, limits are provided for spin-dependent and spin-independent scattering cross sections and are compared to those from direct-detection experiments. The results are also interpreted in the context of models of invisible Higgs boson decays, unparticles, and large extra dimensions.
  13. Sirunyan AM, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Eur Phys J C Part Fields, 2021;81(8):723.
    PMID: 34780581 DOI: 10.1140/epjc/s10052-021-09472-3
    A search for charged Higgs bosons produced in vector boson fusion processes and decaying into vector bosons, using proton-proton collisions at s = 13 TeV at the LHC, is reported. The data sample corresponds to an integrated luminosity of 137 fb - 1 collected with the CMS detector. Events are selected by requiring two or three electrons or muons, moderate missing transverse momentum, and two jets with a large rapidity separation and a large dijet mass. No excess of events with respect to the standard model background predictions is observed. Model independent upper limits at 95% confidence level are reported on the product of the cross section and branching fraction for vector boson fusion production of charged Higgs bosons as a function of mass, from 200 to 3000 GeV . The results are interpreted in the context of the Georgi-Machacek model.
  14. Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, Erö J, et al.
    Eur Phys J C Part Fields, 2021;81(8):688.
    PMID: 34780582 DOI: 10.1140/epjc/s10052-021-09348-6
    A search is presented for a heavy vector resonance decaying into a Z boson and the standard model Higgs boson, where the Z boson is identified through its leptonic decays to electrons, muons, or neutrinos, and the Higgs boson is identified through its hadronic decays. The search is performed in a Lorentz-boosted regime and is based on data collected from 2016 to 2018 at the CERN LHC, corresponding to an integrated luminosity of 137 fb - 1 . Upper limits are derived on the production of a narrow heavy resonance Z ' , and a mass below 3.5 and 3.7 Te is excluded at 95% confidence level in models where the heavy vector boson couples predominantly to fermions and to bosons, respectively. These are the most stringent limits placed on the Heavy Vector Triplet Z ' model to date. If the heavy vector boson couples exclusively to standard model bosons, upper limits on the product of the cross section and branching fraction are set between 23 and 0.3 fb for a Z ' mass between 0.8 and 4.6 Te , respectively. This is the first limit set on a heavy vector boson coupling exclusively to standard model bosons in its production and decay.
  15. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2020 Apr 03;124(13):131802.
    PMID: 32302170 DOI: 10.1103/PhysRevLett.124.131802
    A search is presented for a narrow resonance decaying to a pair of oppositely charged muons using sqrt[s]=13  TeV proton-proton collision data recorded at the LHC. In the 45-75 and 110-200 GeV resonance mass ranges, the search is based on conventional triggering and event reconstruction techniques. In the 11.5-45 GeV mass range, the search uses data collected with dimuon triggers with low transverse momentum thresholds, recorded at high rate by storing a reduced amount of trigger-level information. The data correspond to integrated luminosities of 137 and 96.6  fb^{-1} for conventional and high-rate triggering, respectively. No significant resonant peaks are observed in the probed mass ranges. The search sets the most stringent constraints to date on a dark photon in the ∼30-75 and 110-200 GeV mass ranges.
  16. Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Phys Rev Lett, 2024 Feb 09;132(6):061801.
    PMID: 38394587 DOI: 10.1103/PhysRevLett.132.061801
    The first search for scalar leptoquarks produced in τ-lepton-quark collisions is presented. It is based on a set of proton-proton collision data recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138  fb^{-1}. The reconstructed final state consists of a jet, significant missing transverse momentum, and a τ lepton reconstructed through its hadronic or leptonic decays. Limits are set on the product of the leptoquark production cross section and branching fraction and interpreted as exclusions in the plane of the leptoquark mass and the leptoquark-τ-quark coupling strength.
  17. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Jul 28;131(4):041803.
    PMID: 37566864 DOI: 10.1103/PhysRevLett.131.041803
    A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138  fb^{-1} collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, κ_{2V}, excluding κ_{2V}=0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.
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