Displaying publications 1 - 20 of 46 in total

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  1. Kamariah K, Satgunasingam N, Nasri NM, Ng KY
    Med J Malaysia, 1993 Mar;48(1):40-5.
    PMID: 7688063
    Eighty-nine patients who had hydatidiform moles evacuated at the General Hospital, Kuala Lumpur, were followed with serum beta hCG determinations from October 1988 to June 1991. A regression curve for serum beta hCG, as measured by RIA, was derived from the results of 47 of the patients who demonstrated spontaneous regression of serum beta hCG titres. All 47 patients had normal serum titres at 135 days after evacuation. The mean time taken to reach normal level was 82.6 days, while the range was 39 to 135 days (5 to 19 weeks).
  2. Wong CM, Ganesh R, Ng KY
    Med J Malaysia, 1999 Mar;54(1):117-9.
    PMID: 10972015
    Diagnosis of ectopic pregnancy prior to rupture is an arduous task even with the availability of many new investigative methods and imaging modalities. Above all, a high index of suspicion is necessary when dealing with women who present in early pregnancy with abdominal pain and vaginal bleeding. With the increased use of ovulation induction agents, the probability of heterotropic pregnancy should be kept in mind. The use of transvaginal ultrasonography (TVS) will help in earlier diagnosis because of its advantages over transabdominal ultrasonography (TAS).
  3. Asokan S, Chew EK, Ng KY, Thanaletchimy N, Asmiati A, Kong NM
    J Obstet Gynaecol Res, 2000 Jun;26(3):199-201.
    PMID: 10932982
    Ruptured splenic artery aneurysm during pregnancy is a rare event with high maternal and fetal mortality rate. A case of ruptured splenic artery aneurysm in the post partum period is presented. The literature is reviewed on pathophysiology, clinical presentation and management of this rare and potentially fatal entity.
  4. Baharum H, Morita H, Tomitsuka A, Lee FC, Ng KY, Rahim RA, et al.
    Mar Biotechnol (NY), 2011 Oct;13(5):845-56.
    PMID: 21181422 DOI: 10.1007/s10126-010-9344-5
    Type III polyketide synthases (PKSs) produce an array of metabolites with diverse functions. In this study, we have cloned the complete reading frame encoding type III PKS (SbPKS) from a brown seaweed, Sargassum binderi, and characterized the activity of its recombinant protein biochemically. The deduced amino acid sequence of SbPKS is 414 residues in length, sharing a higher sequence similarity with bacterial PKSs (38% identity) than with plant PKSs. The Cys-His-Asn catalytic triad of PKS is conserved in SbPKS with differences in some of the residues lining the active and CoA binding sites. The wild-type SbPKS displayed broad starter substrate specificity to aliphatic long-chain acyl-CoAs (C(6)-C(14)) to produce tri- and tetraketide pyrones. Mutations at H(331) and N(364) caused complete loss of its activity, thus suggesting that these two residues are the catalytic residues for SbPKS as in other type III PKSs. Furthermore, H227G, H227G/L366V substitutions resulted in increased tetraketide-forming activity, while wild-type SbPKS produces triketide α-pyrone as a major product. On the other hand, mutant H227G/L366V/F93A/V95A demonstrated a dramatic decrease of tetraketide pyrone formation. These observations suggest that His(227) and Leu(366) play an important role for the polyketide elongation reaction in SbPKS. The conformational changes in protein structure especially the cavity of the active site may have more significant effect to the activity of SbPKS compared with changes in individual residues.
  5. Wong KT, Ng KY, Ong KC, Ng WF, Shankar SK, Mahadevan A, et al.
    Neuropathol. Appl. Neurobiol., 2012 Aug;38(5):443-53.
    PMID: 22236252 DOI: 10.1111/j.1365-2990.2011.01247.x
    To investigate if two important epidemic viral encephalitis in children, Enterovirus 71 (EV71) encephalomyelitis and Japanese encephalitis (JE) whose clinical and pathological features may be nonspecific and overlapping, could be distinguished.
  6. Baharum H, Chu WC, Teo SS, Ng KY, Rahim RA, Ho CL
    Phytochemistry, 2013 Aug;92:49-59.
    PMID: 23684235 DOI: 10.1016/j.phytochem.2013.04.014
    Vanadium-dependent haloperoxidases belong to a class of vanadium enzymes that may have potential industrial and pharmaceutical applications due to their high stability. In this study, the 5'-flanking genomic sequence and complete reading frame encoding vanadium-dependent bromoperoxidase (GcVBPO1) was cloned from the red seaweed, Fracilaria changii, and the recombinant protein was biochemically characterized. The deduced amino acid sequence of GcVBPO1 is 1818 nucleotides in length, sharing 49% identity with the vanadium-dependent bromoperoxidases from Corralina officinalis and Cor. pilulifera, respectively. The amino acid residues associated with the binding site of vanadate cofactor were found to be conserved. The Km value of recombinant GcVBPO1 for Br(-) was 4.69 mM, while its Vmax was 10.61 μkat mg(-1) at pH 7. Substitution of Arg(379) with His(379) in the recombinant protein caused a lower affinity for Br(-), while substitution of Arg(379) with Phe(379) not only increased its affinity for Br(-) but also enabled the mutant enzyme to oxidize Cl(-). The mutant Arg(379)Phe was also found to have a lower affinity for I(-), as compared to the wild-type GcVBPO1 and mutant Arg(379)His. In addition, the Arg(379)Phe mutant has a slightly higher affinity for H2O2 compared to the wild-type GcVBPO1. Multiple cis-acting regulatory elements associated with light response, hormone signaling, and meristem expression were detected at the 5'-flanking genomic sequence of GcVBPO1. The transcript abundance of GcVBPO1 was relatively higher in seaweed samples treated with 50 parts per thousand (ppt) artificial seawater (ASW) compared to those treated in 10 and 30 ppt ASW, in support of its role in the abiotic stress response of seaweed.
  7. Ng KT, Ng KY, Khong WX, Chew KK, Singh PK, Yap JK, et al.
    PLoS One, 2013;8(12):e80884.
    PMID: 24312505 DOI: 10.1371/journal.pone.0080884
    HIV-1 subtype B and CRF01_AE are the predominant infecting subtypes among men who have sex with men (MSM) in Singapore. The genetic history, population dynamics and pattern of transmission networks of these genotypes remain largely unknown. We delineated the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and the recently characterized CRF51_01B strains circulating among the MSM population in Singapore. A total of 105 (49.5%) newly-diagnosed treatment-naïve MSM were recruited between February 2008 and August 2009. Phylogenetic reconstructions of the protease gene (HXB2: 2239 - 2629), gp120 (HXB2: 6942 - 7577) and gp41 (HXB2: 7803 - 8276) of the env gene uncovered five monophyletic transmission networks (two each within subtype B and CRF01_AE and one within CRF51_01B lineages) of different sizes (involving 3 - 23 MSM subjects, supported by posterior probability measure of 1.0). Bayesian coalescent analysis estimated that the emergence and dissemination of multiple sub-epidemic networks occurred between 1995 and 2005, driven largely by subtype B and later followed by CRF01_AE. Exponential increase in effective population size for both subtype B and CRF01_AE occurred between 2002 to 2007 and 2005 to 2007, respectively. Genealogical estimates suggested that the novel CRF51_01B lineages were probably generated through series of recombination events involving CRF01_AE and multiple subtype B ancestors. Our study provides the first insight on the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and CRF51_01B viral strains circulating among MSM in Singapore.
  8. Lim BK, Ng KY, Omar J, Omar SZ, Gunapalaiah B, Teoh YL, et al.
    Med J Malaysia, 2014 Feb;69(1):2-8.
    PMID: 24814620
    INTRODUCTION: Cervical cancer is the third most common cancer in women worldwide. The HPV-16/18 AS04- adjuvanted vaccine (Cervarix©) has previously been shown to be highly immunogenic with a clinically acceptable safety profile. This phase IIIb, double-blind, randomized (1:1) and placebo controlled trial (NCT00345878) was designed to evaluate the vaccine immunogenicity against HPV-16 and HPV-18 as well as its safety and reactogenicity in Malaysian women.

    METHODS: Healthy women aged 18-35 years received intramuscularly three doses of either the vaccine (HPV group) or aluminium hydroxide (ALU group) at 0, 1, and 6 months. Antibody titers were measured by an enzyme-linked immunosorbent assay (ELISA).

    RESULTS: A total of 271 eligible subjects were enrolled and 266 subjects completed the study. Initially seronegative subjects in the HPV group showed 100% seroconversion one month post-dose-3 for anti HPV-16 and anti-HPV-18 antibodies with geometric mean titers of 11107.5 (95% CI: 9727.3-12683.4) EL.U/mL and 4273.5 (95% CI: 3771.8-4841.9) EL.U/mL, respectively. Over 96% of subjects in both groups received all three vaccine doses. Solicited local (pain) and general symptoms (myalgia, fatigue, arthralgia and headache) were commonly reported in both HPV and ALU groups. Eight serious adverse events were reported throughout the study (five in the HPV group; three in the ALU group), all considered by investigators to be unrelated to vaccination.

    CONCLUSION: The HPV-16/18 AS04-adjuvanted vaccine was immunogenic and generally well tolerated in Malaysian women aged 18-35 years.
  9. Chye SM, Tiong YL, Yip WK, Koh RY, Len YW, Seow HF, et al.
    Environ Toxicol, 2014 Sep;29(9):981-90.
    PMID: 23172806 DOI: 10.1002/tox.21828
    para-Phenylenediamine (p-PD) is a suspected carcinogen, but it has been widely used as a component in permanent hair dyes. In this study, the mechanism of p-PD-induced cell death in normal Chang liver cells was investigated. The results demonstrated that p-PD decreased cell viability in a dose-dependent manner. Cell death via apoptosis was confirmed by enhanced DNA damage and increased cell number in the sub-G1 phase of the cell cycle, using Hoechst 33258 dye staining and flow cytometry analysis. Apoptosis via reactive oxygen species generation was detected by the dichlorofluorescin diacetate staining method. Mitogen-activated protein kinase (MAPK) activation was assessed by western blot analysis and revealed that p-PD activated not only stress-activated protein kinase (SAPK)/c-Jun N-terminal kinases (JNK) and p38 MAPK but also extracellular signal-regulated kinase (ERK). Cytotoxicity and apoptosis induced by p-PD were markedly enhanced by ERK activation and selectively inhibited by ERK inhibitor PD98059, thus indicating a negative role of ERK. In contrast, inhibition of p38 MAPK activity with the p38-specific inhibitor SB203580 moderately inhibited cytotoxicity and apoptosis induction by p-PD. Similarly, SP600125, an inhibitor of SAPK/JNK, moderately inhibited cytotoxicity and apoptosis induced by p-PD, thus implying that p38 MAPK and SAPK/JNK had a partial role in p-PD-induced apoptosis. Western blot analysis revealed that p-PD significantly increased phosphorylation of p38 and SAPK/JNK and decreased phosphorylation of ERK. In conclusion, the results demonstrated that SAPK/JNK and p38 cooperatively participate in apoptosis induced by p-PD and that a decreased ERK signal contributes to growth inhibition or apoptosis.
  10. Ng KT, Ng KY, Chen JH, Ng OT, Kamarulzaman A, Tee KK
    Clin Infect Dis, 2014 Sep 15;59(6):910-1.
    PMID: 24944233 DOI: 10.1093/cid/ciu480
  11. Yew MY, Koh RY, Chye SM, Othman I, Ng KY
    PMID: 25308934 DOI: 10.1186/1472-6882-14-391
    Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the senile population with manifestation of motor disability and cognitive impairment. Reactive oxygen species (ROS) is implicated in the progression of oxidative stress-related apoptosis and cell death of the midbrain dopaminergic neurons. Its interplay with mitochondrial functionality constitutes an important aspect of neuronal survival in the perspective of PD. Edible bird's nest (EBN) is an animal-derived natural food product made of saliva secreted by swiftlets from the Aerodamus genus. It contains bioactive compounds which might confer neuroprotective effects to the neurons. Hence this study aims to investigate the neuroprotective effect of EBN extracts in the neurotoxin-induced in vitro PD model.
  12. Koh RY, Sim YC, Toh HJ, Liam LK, Ong RS, Yew MY, et al.
    Mol Med Rep, 2015 Oct;12(4):6293-9.
    PMID: 26239257 DOI: 10.3892/mmr.2015.4152
    The chemotherapeutic agents used to treat nasopharyngeal cancer (NPC) exhibit low efficacy. Strobilanthes crispa Blume is widely used for its anticancer, diuretic and anti‑diabetic properties. The present study aimed to determine the cytotoxic and apoptogenic effects of S. crispa on CNE‑1 NPC cells. A 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5 diphenyl tetrazolium bromide assay was used to evaluate the cytotoxic effects of S. crispa against CNE‑1 cells. The rate of apoptosis was determined using propidium iodide staining and caspase assays. Ethyl acetate, hexane and chloroform extracts of S. crispa leaves all exhibited cytotoxic effects on CNE‑1 cells, at a half maximal inhibitory concentration (IC50) of 119, 123.5 and 161.7 µg/ml, respectively. In addition, hexane, chloroform and ethyl acetate extracts of S. crispa stems inhibited CNE‑1 cell proliferation, at a IC50 of 49.4, 148.3 and 163.5 µg/ml, respectively. Flow cytometric analysis revealed an increased proportion of cells in the sub G1 phase and a decreased proportion of cells in the G2/M phase, following treatment with the extracts. However, the extracts did not alter the activities of caspase ‑3/7, ‑8 and ‑9. No cytotoxic effect was observed when the cells were treated with the methanol and water extracts of S. crispa stems and leaves. In conclusion, the S. crispa extracts were cytotoxic against CNE‑1 cells and these extracts were able to induce apoptosis, independent of caspase activation.
  13. Reena K, Ng KY, Koh RY, Gnanajothy P, Chye SM
    Environ Toxicol, 2017 Jan;32(1):265-277.
    PMID: 26784575 DOI: 10.1002/tox.22233
    para-Phenylenediamine (PPD) has long been used in two-thirds of permanent oxidative hair dye formulations. Epidemiological studies and in vivo studies have shown that hair dye is a suspected carcinogen of bladder cancer. However, the toxicity effects of PPD to human bladder remains elusive. In this study, the effects of PPD and its involvement in the apoptosis pathways in human urothelial cells (UROtsa) was investigated. It was demonstrated that PPD decreased cell viability and increased the number of sub-G1 hypodiploid cells in UROtsa cells. Cell death due to apoptosis was detected using Annexin V binding assay. Further analysis showed PPD generated reactive oxygen species (ROS), induced mitochondrial dysfunction through the loss of mitochondrial membrane potential and increased caspase-3 level in UROtsa cells. Western blot analysis of PPD-treated UROtsa cells showed down-regulation of phosphorylated proteins from NF-κB, mTOR, and Wnt pathways. In conclusion, PPD induced apoptosis via activation of ROS-mediated mitochondrial pathway, and possibly through inhibition of NF-κB, mTOR, and Wnt pathways. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 265-277, 2017.
  14. Lee SWH, Ng KY, Chin WK
    Sleep Med Rev, 2017 02;31:91-101.
    PMID: 26944909 DOI: 10.1016/j.smrv.2016.02.001
    Recent epidemiological studies have suggested that there is an association between glycemic control and sleep disturbances in patients with type 2 diabetes, but the extent is unclear. A systematic literature search was performed in nine electronic databases from inception until August 2015 without any language restriction. The search identified 20 studies (eight studies reporting duration of sleep and 15 studies evaluating sleep quality), and 15 were included in the meta-analysis. Short and long sleep durations were associated with an increased hemoglobin A1c (HbA1c) (weighted mean difference (WMD): 0.23% [0.10-0.36], short sleep; WMD: 0.13% [0.02-0.25], long sleep) compared to normal sleep, suggesting a U-shaped dose-response relationship. Similarly, poor sleep quality was associated with an increased HbA1c (WMD: 0.35% [0.12-0.58]). Results of this study suggest that amount of sleep as well as quality of sleep is important in the metabolic function of type 2 diabetes patients. Further studies are needed to identify for the potential causal role between sleep and altered glucose metabolism.
  15. Ng KY, Leong MK, Liang H, Paxinos G
    Brain Struct Funct, 2017 Sep;222(7):2921-2939.
    PMID: 28478550 DOI: 10.1007/s00429-017-1439-6
    Melatonin, through its different receptors, has pleiotropic functions in mammalian brain. Melatonin is secreted mainly by the pineal gland and exerts its effects via receptor-mediated and non-receptor-mediated actions. With recent advancement in neuroanatomical mapping, we may now understand better the localizations of the two G protein-coupled melatonin receptors MT1 and MT2. The abundance of these melatonin receptors in respective brain regions suggests that receptor-mediated actions of melatonin might play crucial roles in the functions of central nervous system. Hence, this review aims to summarize the distribution of melatonin receptors in the brain and to discuss the putative functions of melatonin in the retina, cerebral cortex, reticular thalamic nucleus, habenula, hypothalamus, pituitary gland, periaqueductal gray, dorsal raphe nucleus, midbrain and cerebellum. Studies on melatonin receptors in the brain are important because cumulative evidence has pointed out that melatonin receptors not only play important physiological roles in sleep, anxiety, pain and circadian rhythm, but might also be involved in the pathogenesis of a number of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and Huntington's disease.
  16. Koh RY, Lim FP, Ling LSY, Ng CPL, Liew SF, Yew MY, et al.
    Oncol Lett, 2017 Oct;14(4):4957-4964.
    PMID: 29085507 DOI: 10.3892/ol.2017.6821
    Cancer is a major public health concern not only in developed countries, but also in developing countries. It is one of the leading causes of mortality worldwide. However, current treatments may cause severe side effects and harm. Therefore, recent research has been focused on identifying alternative therapeutic agents extracted from plant-based sources in order to develop novel treatment options for cancer. Strobilanthes crispa Blume is a plant native to countries including Madagascar and Indonesia. It has been used as an anti-diabetic, diuretic and laxative in traditional folk medicine. Furthermore, S. crispa has potential in treating cancer, as evidenced in previous studies. In the present study, the cytotoxic and apoptotic activities of S. crispa crude extracts were investigated in liver and breast cancer cell lines. Hexane, ethyl acetate, chloroform, methanol and water extracts prepared from the leaves, and stems of S. crispa were evaluated for their cytotoxicity on HepG-2 and MDA-MB-231 cells using an MTT assay. The anti-proliferative properties of stem hexane (SH) extract on both cell lines were analysed using cell doubling time determination and cell cycle analysis, while the apoptogenic properties was determined through the detection of caspase-8. Among the extracts tested, SH extract exhibited the lowest half maximal inhibitory concentrations in both the cell lines. The SH extract induced morphological changes in HepG-2 and MDA-MB-231 cells, and significantly delayed cell population doubling time. Furthermore, it altered cell cycle profile and significantly increased caspase-8 activity in HepG-2 cells, but not in MDA-MB-231 cells. In conclusion, the SH extract of S. crispa possesses potent anticancer properties and may be a suitable chemotherapeutic target.
  17. Ng KY, Awang N
    Environ Monit Assess, 2018 Jan 06;190(2):63.
    PMID: 29306973 DOI: 10.1007/s10661-017-6419-z
    Frequent haze occurrences in Malaysia have made the management of PM10 (particulate matter with aerodynamic less than 10 μm) pollution a critical task. This requires knowledge on factors associating with PM10 variation and good forecast of PM10 concentrations. Hence, this paper demonstrates the prediction of 1-day-ahead daily average PM10 concentrations based on predictor variables including meteorological parameters and gaseous pollutants. Three different models were built. They were multiple linear regression (MLR) model with lagged predictor variables (MLR1), MLR model with lagged predictor variables and PM10 concentrations (MLR2) and regression with time series error (RTSE) model. The findings revealed that humidity, temperature, wind speed, wind direction, carbon monoxide and ozone were the main factors explaining the PM10 variation in Peninsular Malaysia. Comparison among the three models showed that MLR2 model was on a same level with RTSE model in terms of forecasting accuracy, while MLR1 model was the worst.
  18. Chong FP, Ng KY, Koh RY, Chye SM
    Cell Mol Neurobiol, 2018 Jul;38(5):965-980.
    PMID: 29299792 DOI: 10.1007/s10571-017-0574-1
    Alzheimer's disease (AD) is characterized by progressive memory loss and cognitive function deficits. There are two major pathological hallmarks that contribute to the pathogenesis of AD which are the presence of extracellular amyloid plaques composed of amyloid-β (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. Despite extensive research that has been done on Aβ in the last two decades, therapies targeting Aβ were not very fruitful at treating AD as the efficacy of Aβ therapies observed in animal models is not reflected in human clinical trials. Hence, tau-directed therapies have received tremendous attention as the potential treatments for AD. Tauopathies are closely correlated with dementia and immunotherapy has been effective at reducing tau pathology and improving cognitive deficits in animal models. Thus, in this review article, we discussed the pathological mechanism of tau proteins, the key factors contributing to tauopathies, and therapeutic approaches for tauopathies in AD based on the recent progress in tau-based research.
  19. Chia KY, Ng KY, Koh RY, Chye SM
    CNS Neurol Disord Drug Targets, 2018;17(9):671-679.
    PMID: 29546836 DOI: 10.2174/1871527317666180315161626
    BACKGROUND & OBJECTIVE: Protein misfolding and aggregation have been considered the common pathological hallmarks for a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). These abnormal proteins aggregates damage mitochondria and induce oxidative stress, resulting in neuronal cell death. Prolonged neuronal damage activates microglia and astrocytes, development of inflammation reaction and further promotes neurodegeneration. Thus, elimination of abnormal protein aggregates without eliciting any adverse effects are the main treatment strategies. To overcome this, recent studies have deployed single- chain fragment variable antibodies (scFvs) to target the pathological protein aggregates, such as amyloid-beta (Aβ) peptides, α-synuclein (α-syn) and Huntingtin (Htt). To date scFv has been effective at inhibiting abnormal protein aggregates formation in both in vitro and in vivo model system of AD, PD and HD.

    CONCLUSION: Currently active research is still ongoing to improve the scFv gene delivery technology, to further enhance brain penetration, intracellular stability, solubility and efficacy of scFv intrabody.

  20. Tan HY, Ng KY, Koh RY, Chye SM
    Cell Mol Neurobiol, 2020 Jan;40(1):25-51.
    PMID: 31435851 DOI: 10.1007/s10571-019-00724-1
    The progressive loss of structure and functions of neurons, including neuronal death, is one of the main factors leading to poor quality of life. Promotion of functional recovery of neuron after injury is a great challenge in neuroregenerative studies. Melatonin, a hormone is secreted by pineal gland and has antioxidative, anti-inflammatory, and anti-apoptotic properties. Besides that, melatonin has high cell permeability and is able to cross the blood-brain barrier. Apart from that, there are no reported side effects associated with long-term usage of melatonin at both physiological and pharmacological doses. Thus, in this review article, we summarize the pharmacological effects of melatonin as neuroprotectant in central nervous system injury, ischemic-reperfusion injury, optic nerve injury, peripheral nerve injury, neurotmesis, axonotmesis, scar formation, cell degeneration, and apoptosis in rodent models.
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