Displaying publications 1 - 20 of 44 in total

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  1. Lee KH, Abas F, Alitheen NB, Shaari K, Lajis NH, Ahmad S
    Molecules, 2011 Nov 23;16(11):9728-38.
    PMID: 22113581 DOI: 10.3390/molecules16119728
    Our preliminary screening had shown that the curcumin derivative [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] or BDMC33 exhibited improved anti-inflammatory activity by inhibiting nitric oxide synthesis in activated macrophage cells. In this study, we further investigated the anti-inflammatory properties of BDMC33 on PGE(2 )synthesis and cyclooxygenase (COX) expression in IFN-γ/LPS-stimulated macrophages. We found that BDMC33 significantly inhibited PGE(2) synthesis in a concentration-dependent manner albeit at a low inhibition level with an IC(50) value of 47.33 ± 1.00 µM. Interestingly, the PGE(2) inhibitory activity of BDMC33 is not attributed to inhibition of the COX enzyme activities, but rather BDMC33 selectively down-regulated the expression of COX-2. In addition, BDMC33 modulates the COX expression by sustaining the constitutively COX-1 expression in IFN-γ/LPS-treated macrophage cells. Collectively, the experimental data suggest an immunodulatory action of BDMC33 on PGE(2) synthesis and COX expression, making it a possible treatment for inflammatory disorders with minimal gastrointestinal-related side effects.
  2. Wright A, De Livera A, Lee KH, Higgs C, Nicholson M, Gibbs L, et al.
    BMC Public Health, 2022 Dec 27;22(1):2434.
    PMID: 36575409 DOI: 10.1186/s12889-022-14836-9
    BACKGROUND: Population surveys across the world have examined the impact of the COVID-19 pandemic on mental health. However, few have simultaneously examined independent cross-sectional data with longitudinal data, each of which have different strengths and weaknesses and facilitate the investigation of distinct research questions. This study aimed to investigate psychological distress and life satisfaction during the first and second lockdowns in the state of Victoria, Australia, and the social factors that may be affected by lockdowns and could affect mental health.

    METHODS: The VicHealth Victorian Coronavirus Wellbeing Impact Study included two 20-min opt-in online panel surveys conducted in May and September 2020 in Victoria, each with a sample of 2000 adults aged 18 + . A two-part study design was used: a repeated cross-sectional study of respondents who participated in Survey One and Survey Two, followed by a longitudinal nested cohort study. The primary exposures were social solidarity, social connectedness and staying connected with family and friends. Using logistic regression modelling, we explored the associations between our exposures and primary outcomes of psychological distress and life satisfaction with and without adjustment for covariates, both cross-sectionally and longitudinally. The results from the multivariable models were summarised using adjusted Odds Ratios (aOR), 95% Confidence Intervals (CI).

    RESULTS: Cross-sectional results indicated that the percentage of participants with low life satisfaction was significantly higher in the second survey sample (53%) compared to the first (47%). The percentage of participants with high psychological distress was higher but not significantly different between the two survey samples (14% first survey vs 16% second survey). Longitudinal study results indicated that lower social connectedness was significantly associated with higher psychological distress (aOR:3.3; 95% CI: 1.3-8.4) and lower life satisfaction (aOR:0.2; 95% CI: 0.1-0.4). Younger adults had higher psychological distress compared to older adults (aOR:6.8; 95% CI:1.5-31.1). Unemployment at the time of the first survey was significantly associated with lower life satisfaction at the second survey (aOR:0.5; 95% CI: 0.3-0.9).

    CONCLUSION: This study supports the findings of other international studies. It also highlights the need to promote increased social connection and maintain it at times of isolation and separation, particularly amongst younger adults.

  3. Park JY, Ngan HY, Park W, Cao Z, Wu X, Ju W, et al.
    J Gynecol Oncol, 2015 Jan;26(1):68-74.
    PMID: 25609163 DOI: 10.3802/jgo.2015.26.1.68
    The Asian Society of Gynecologic Oncology International Workshop 2014 on gynecologic oncology was held in Asan Medical Center, Seoul, Korea on the 23rd to 24th August 2014. A total of 179 participants from 17 countries participated in the workshop, and the up-to-date findings on the management of gynecologic cancers were presented and discussed. This meeting focused on the new trends in the management of cervical cancer, fertility-sparing management of gynecologic cancers, surgical management of gynecologic cancers, and recent advances in translational research on gynecologic cancers.
  4. Ang QQ, Wing YK, He Y, Sulaiman AH, Chiu NY, Shen YC, et al.
    Int J Clin Pract, 2009 Jul;63(7):1041-9.
    PMID: 19570122 DOI: 10.1111/j.1742-1241.2009.02107.x
    Reports from non-Asian populations indicate that painful physical symptoms (PPS) are associated with poorer clinical and functional outcomes in major depressive disorder (MDD). The purpose of this study is to report comparative changes in disease severity, treatment patterns and quality of life observed in East Asian patients with MDD, with and without PPS, as assessed prospectively over a 3-month observation period.
  5. Lee KH, Chai VY, Kanachamy SS, Say YH
    Ethn Dis, 2015;25(1):65-71.
    PMID: 25812254
    Our study investigated the association of UCP1 -3826A/G and UCP3 -55C/T single nucleotide polymorphisms (SNPs) with obesity and its related traits among multi-ethnic Malaysians.
  6. Lee KH, Chow YL, Sharmili V, Abas F, Alitheen NB, Shaari K, et al.
    Int J Mol Sci, 2012;13(3):2985-3008.
    PMID: 22489138 DOI: 10.3390/ijms13032985
    Our preliminary screening has shown that curcumin derivative BDMC33 [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] exerted promising nitric oxide inhibitory activity in activated macrophages. However, the molecular basis and mechanism for its pharmacological action is yet to be elucidated. The aim of this study was to investigate the anti-inflammatory properties of BDMC33 and elucidate its underlying mechanism action in macrophage cells. Our current study demonstrated that BDMC33 inhibits the secretion of major pro-inflammatory mediators in stimulated macrophages, and includes NO, TNF-α and IL-1β through interference in both nuclear factor kappaB (NF-κB) and mitogen activator protein kinase (MAPK) signaling cascade in IFN-γ/LPS-stimulated macrophages. Moreover, BDMC33 also interrupted LPS signaling through inhibiting the surface expression of CD-14 accessory molecules. In addition, the inhibitory action of BDMC33 not only restricted the macrophages cell (RAW264.7), but also inhibited the secretion of NO and TNF-α in IFN-γ/LPS-challenged microglial cells (BV-2). The experimental data suggests the inflammatory action of BDMC33 on activated macrophage-like cellular systems, which could be used as a future therapeutic agent in the management of chronic inflammatory diseases.
  7. Chow YL, Lee KH, Vidyadaran S, Lajis NH, Akhtar MN, Israf DA, et al.
    Int Immunopharmacol, 2012 Apr;12(4):657-65.
    PMID: 22306767 DOI: 10.1016/j.intimp.2012.01.009
    The increasing prevalence of neurodegenerative diseases has prompted investigation into innovative therapeutics over the last two decades. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the therapeutic choices to control and suppress the symptoms of neurodegenerative diseases. However, NSAIDs-associated gastropathy has hampered their long term usage despite their clinical advancement. On the natural end of the treatment spectrum, our group has shown that cardamonin (2',4'-dihydroxy-6'-methoxychalcone) isolated from Alpinia rafflesiana exerts potential anti-inflammatory activity in activated macrophages. Therefore, we further explored the anti-inflammatory property of cardamonin as well as its underlying mechanism of action in IFN-γ/LPS-stimulated microglial cells. In this investigation, cardamonin shows promising anti-inflammatory activity in microglial cell line BV2 by inhibiting the secretion of pro-inflammatory mediators including nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). The inhibition of NO and PGE(2) by cardamonin are resulted from the reduced expression of inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2), respectively. Meanwhile the suppressive effects of cardamonin on TNF-α, IL-1β and IL-6 were demonstrated at both protein and mRNA levels, thus indicating the interference of upstream signal transduction pathway. Our results also validate that cardamonin interrupts nuclear factor-kappa B (NF-κB) signalling pathway via attenuation of NF-κB DNA binding activity. Interestingly, cardamonin also showed a consistent suppressive effect on the cell surface expression of CD14. Taken together, our experimental data provide mechanistic insights for the anti-inflammatory actions of cardamonin in BV2 and thus suggest a possible therapeutic application of cardamonin for targeting neuroinflammatory disorders.
  8. Mok JS, Chang P, Lee KH, Kam TS, Goh SH
    J Ethnopharmacol, 1992 Jun;36(3):219-23.
    PMID: 1434680
    Among several alkaloids, including dimeric indoles, isolated from Uncaria callophylla, gambirine which is an alkaloid unique to this plant, has been found to be another hypotensive principle from the plant. Intravenous injections of gambirine in the dose range of 0.2 to 10.0 mg/kg caused a dose-related fall in both systolic and diastolic blood pressures as well as heart rate. At all doses gambirine showed a prompt onset of action and at the higher doses (5.0-10 mg/kg), marked persistence of hypotension accompanied by severe bradycardia were observed. In addition, higher doses of gambirine produced a more marked decrease in diastolic than systolic pressure while at lower doses both decreased equally. It is suggested that the hypotensive effect of gambirine may be peripheral in origin and is associated, at least in part, with a cardiac action.
  9. Soo RA, Cho BC, Kim JH, Ahn MJ, Lee KH, Zimina A, et al.
    J Thorac Oncol, 2023 Dec;18(12):1756-1766.
    PMID: 37865896 DOI: 10.1016/j.jtho.2023.08.017
    INTRODUCTION: Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases.

    METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response.

    RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population.

    CONCLUSIONS: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.

  10. Tejamaya M, Phanprsit W, Kim J, Tsai FJ, Muto G, Miller D, et al.
    Ind Health, 2022 Dec 01;60(6):589-598.
    PMID: 35022363 DOI: 10.2486/indhealth.2021-0227
    The types of workplaces and occupations with coronavirus 2019 (COVID-19) clusters vary between countries and periods. We aimed to characterize major occupational groups with mass outbreaks of COVID-19 infections in several Asia-Pacific countries. Data on the major occupations or workplaces reporting COVID-19 cases in workplaces from January 2020 to July 2021 was collected from industrial hygiene professionals in nine countries. The proportion of workers accounted for 39.1 to 56.6% of the population in each country. The number of workers covered in the national statistics varies among nations based on their definition of a worker. None of the countries examined here have systematically collected occupational data on COVID-19 illnesses and deaths classified by type of industry, occupation, or job. Most countries experienced COVID-19 clusters among health and social care workers (HSCW) in hospitals or long-term care facilities. The types of occupations or workplaces with virus clusters in some participating countries included prisons, call centers, workplaces employing immigrants, garment facilities, grocery stores, and the military, which differed among countries, except for a few common occupations such as HSCW and those populated by immigrants. Further study is necessary in order to seek ways to control infection risks, including revisions to industrial-health-related laws.
  11. Lee KH, Abas F, Mohamed Alitheen NB, Shaari K, Lajis NH, Israf DA, et al.
    Int J Rheum Dis, 2015 Jul;18(6):616-27.
    PMID: 24832356 DOI: 10.1111/1756-185X.12341
    Synovial fibroblast has emerged as a potential cellular target in progressive joint destruction in rheumatoid arthritis development. In this study, BDMC33 (2,6-bis[2,5-dimethoxybenzylidene]cyclohexanone), a curcumin analogue with enhanced anti-inflammatory activity has been synthesized and the potency of BDMC33 on molecular and cellular basis of synovial fibroblasts (SF) were evaluated in vitro.
  12. Lee PM, Lee KH
    Biochem Biophys Res Commun, 1989 Apr 28;160(2):780-7.
    PMID: 2719696
    Gangliosides and glycophorin are receptors for wheat germ agglutinin. The competitive binding of these molecules to wheat germ agglutinin is studied by electron spin resonance spectroscopy with spin labels attached to the oligosaccharide chains of gangliosides. Evidence shows that glycophorin is more accessible to wheat germ agglutinin binding than gangliosides. The interactions of gangliosides and glycophorin in liposomes is disrupted on low level binding of WGA.
  13. Lee PM, Lee KH, Siaw YS
    J Chem Technol Biotechnol, 1993;58(1):65-70.
    PMID: 7763937
    Aminoacylase I (EC. 3.5.1.14) was immobilized by covalent crosslinking to alginate molecules with 1-ethyl-3-(3-dimethyl-aminopropyl)-carbodiimide HCl followed by calcium alginate bead formation for the production of L-phenylalanine from the racemic mixtures of N-acetyl-DL-phenylalanine. Different concentrations of the coupling reagent were tested and the coupling process was optimized. The immobilized and the partially purified aminoacylase were characterized in terms of the activity, operational stability, thermal stability, pH and temperature optima and kinetic constants, Km and Vmax. The activity of the enzyme covalently immobilized in calcium alginate beads was enhanced by about 75% compared to that of free enzyme. The beads showed stable activity under operational conditions, they lost about 40% of their activity after four reaction cycles. The immobilized aminoacylase was more stable over a broader pH range. Thus this simple method provides irreversible immobilization of aminoacylase to give a biocatalyst with good operational stability and enhanced activity.
  14. Ng HS, Tan GYT, Lee KH, Zimmermann W, Yim HS, Lan JC
    J Biosci Bioeng, 2018 Oct;126(4):507-513.
    PMID: 29764763 DOI: 10.1016/j.jbiosc.2018.04.008
    The α- and γ-mangostins from Garcinia mangostana pericarps (GMP) exhibit antioxidant, anti-bacterial, anti-inflammatory and anti-tumor properties. The extraction yields α- and γ-mangostins are often limited by the presence of the GMP cell walls. Therefore, the extraction and recovery of mangostins from GMP with an Aspergillus niger cellulase-assisted aqueous micellar biphasic system (CA-AMBS) was developed for enhanced yield of mangostins. Effects of the concentration of cellulase, the incubation time and the temperature of the system on the recovery of mangostins were investigated. The optimum condition for the recovery of α- and γ-mangostins was obtained with the addition of 0.5% (w/w) cellulase incubated at 40°C for 2 h. High log partition coefficients of α-mangostins (log Kα 4.79 ± 0.02) and γ-mangostins (log Kγ 4.02 ± 0.02) were achieved. High yields of α-mangostins (73.4%) and γ-mangostins (14.0%) were obtained from the micelle-rich bottom phase with final concentrations of 3.67 mg/mL and 0.70 mg/mL, respectively. The back-extraction of mangostins was performed with the addition of 30% (w/w) of isopropanol and 0.05 M of KCl at pH 9 to the bottom phase of the CA-AMBS. The yields of the α- and γ-mangostins from GMP were considerably enhanced with the CA-AMBS and the direct recovery of mangostins was demonstrated without additional downstream processing steps.
  15. Lee KH, Hui KP, Tan WC, Lim TK
    Singapore Med J, 1993 Oct;34(5):385-7.
    PMID: 8153680
    Noninvasive oximetry provides continuous monitoring of arterial oxygen saturation and hence, early detection of hypoxia. This has proved to be a useful adjunct to patients' safety, and is considered indispensable in certain settings. However, errors may be present in the pulse oximeter estimation (SpO2) of arterial oxygen saturation (SaO2), which may be due to various parameters. We have studied a multi-ethnic population where the skin pigmentation is different, and also under different conditions comparing SpO2 with SaO2. Our results showed that SpO2 estimation of SaO2 amongst the three racial groups (Chinese, Malays, and Indians) varied significantly (ANOVA, p < 0.05). The over-estimation was more pronounced by hypoxic conditions and jaundice. Haemoglobin and systolic blood pressure did not affect the difference between SpO2 and SaO2.
  16. Wan SA, Tiong IK, Chuah SL, Cheong YR, Singh BSM, Lee KH, et al.
    Med J Malaysia, 2023 Mar;78(2):207-212.
    PMID: 36988532
    INTRODUCTION: Osteoporosis and osteoporotic fracture pose a major public health problem in our ageing population, and particularly concerning is the increased morbidity and mortality associated with osteoporotic hip fractures. While overall diagnosis and treatment for osteoporosis have improved, osteoporosis in men remains underdiagnosed and undertreated. We aim to describe the difference in clinical characteristics between elderly men and women with osteoporotic hip fractures in Sarawak General Hospital.

    MATERIALS AND METHODS: All patients diagnosed with osteoporotic hip fracture admitted to Sarawak General Hospital from June 2019 to March 2021 were recruited, and demographic data and clinical features were obtained.

    RESULTS: There were 140 patients with osteoporotic hip fracture, and 40 were men (28.6%). The mean age for males was 74.1 ± 9.5 years, while the mean age for females was 77.4 ± 9.1 years (p=0.06). The types of fracture consisted of neck of femur=78, intertrochanteric=61 and subtrochanteric=1. More men were active smokers (15% vs 1%, p<0.001). There were 20 men with secondary osteoporosis (50%), while 13 women (13%) had secondary osteoporosis (p<0.001). The causes of secondary osteoporosis among the men were hypogonadism, COPD, glucocorticoid-induced osteoporosis, renal disease, androgen deprivation therapy, thyroid disorder, prostate cancer and previous gastrectomy. There were two deaths among the men and four deaths among the women during the inpatient and 3 months follow-up period. There was no statistical significance between the mortality rates between male patients (5%) and female patients (4%) (p=0.55).

    CONCLUSION: There were more females with osteoporotic hip fractures, and there were significantly more males with secondary osteoporotic hip fractures.

  17. Lee KH, Lee PM, Siaw YS
    J Chem Technol Biotechnol, 1993;57(1):27-32.
    PMID: 7763683
    Aminoacylase I (EC 3.5.1.14) encapsulated in calcium alginate beads stabilized with poly-L-lysine was used for the production of L-phenylalanine by the hydrolysis of a racemic mixture of N-acetyl-DL-phenylalanine. The immobilized aminoacylase was studied with respect to operational stability, thermal stability, effects of pH and temperature and kinetic constants. The leakage of enzyme from the stabilized beads was eliminated. The immobilized enzyme retained high biological activity. The Km and Vmax values for the stabilized beads were 11.11 mmol dm-3 and 0.076 mumol min-1 respectively. The optimum pH and temperature for the hydrolysis were 6.5 and 55 degrees C respectively. Scanning electron micrographs revealed crosslinked structures on the surface of the beads. The operational performances of the beads in a batch reaction and a packed-bed bioreactor for continuous reaction were investigated. With batch reaction, only about 5% of enzyme activity was lost within ten reaction cycles and there was no significant loss of activity over 600 h of continuous operation after equilibrium was reached, and a conversion yield of about 80% was obtained.
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