Displaying publications 1 - 20 of 37 in total

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  1. Zainol MKM, Linforth RJC, Winzor DJ, Scott DJ
    Eur Biophys J, 2021 Dec;50(8):1103-1110.
    PMID: 34611772 DOI: 10.1007/s00249-021-01572-y
    This investigation of the temperature dependence of DppA interactions with a subset of three dipeptides (AA. AF and FA) by isothermal titration calorimetry has revealed the negative heat capacity ([Formula: see text]) that is a characteristic of hydrophobic interactions. The observation of enthalpy-entropy compensation is interpreted in terms of the increased structuring of water molecules trapped in a hydrophobic environment, the enthalpic energy gain from which is automatically countered by the entropy decrease associated with consequent loss of water structure flexibility. Specificity for dipeptides stems from appropriate spacing of designated DppA aspartate and arginine residues for electrostatic interaction with the terminal amino and carboxyl groups of a dipeptide, after which the binding pocket closes to become completely isolated from the aqueous environment. Any differences in chemical reactivity of the dipeptide sidechains are thereby modulated by their occurrence in a hydrophobic environment where changes in the structural state of entrapped water molecules give rise to the phenomenon of enthalpy-entropy compensation. The consequent minimization of differences in the value of ΔG0 for all DppA-dipeptide interactions thus provides thermodynamic insight into the biological role of DppA as a transporter of all dipeptides across the periplasmic membrane.
  2. Yuvaraj R, Murugappan M, Ibrahim NM, Sundaraj K, Omar MI, Mohamad K, et al.
    Int J Psychophysiol, 2014 Dec;94(3):482-95.
    PMID: 25109433 DOI: 10.1016/j.ijpsycho.2014.07.014
    In addition to classic motor signs and symptoms, individuals with Parkinson's disease (PD) are characterized by emotional deficits. Ongoing brain activity can be recorded by electroencephalograph (EEG) to discover the links between emotional states and brain activity. This study utilized machine-learning algorithms to categorize emotional states in PD patients compared with healthy controls (HC) using EEG. Twenty non-demented PD patients and 20 healthy age-, gender-, and education level-matched controls viewed happiness, sadness, fear, anger, surprise, and disgust emotional stimuli while fourteen-channel EEG was being recorded. Multimodal stimulus (combination of audio and visual) was used to evoke the emotions. To classify the EEG-based emotional states and visualize the changes of emotional states over time, this paper compares four kinds of EEG features for emotional state classification and proposes an approach to track the trajectory of emotion changes with manifold learning. From the experimental results using our EEG data set, we found that (a) bispectrum feature is superior to other three kinds of features, namely power spectrum, wavelet packet and nonlinear dynamical analysis; (b) higher frequency bands (alpha, beta and gamma) play a more important role in emotion activities than lower frequency bands (delta and theta) in both groups and; (c) the trajectory of emotion changes can be visualized by reducing subject-independent features with manifold learning. This provides a promising way of implementing visualization of patient's emotional state in real time and leads to a practical system for noninvasive assessment of the emotional impairments associated with neurological disorders.
  3. Yuvaraj R, Murugappan M, Ibrahim NM, Sundaraj K, Omar MI, Mohamad K, et al.
    J Neural Transm (Vienna), 2015 Feb;122(2):237-52.
    PMID: 24894699 DOI: 10.1007/s00702-014-1249-4
    Parkinson's disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3-AF4, F7-F8, F3-F4, FC5-FC6, T7-T8, P7-P8, and O1-O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities.
  4. Yuvaraj R, Murugappan M, Ibrahim NM, Omar MI, Sundaraj K, Mohamad K, et al.
    J Integr Neurosci, 2014 Mar;13(1):89-120.
    PMID: 24738541 DOI: 10.1142/S021963521450006X
    Deficits in the ability to process emotions characterize several neuropsychiatric disorders and are traits of Parkinson's disease (PD), and there is need for a method of quantifying emotion, which is currently performed by clinical diagnosis. Electroencephalogram (EEG) signals, being an activity of central nervous system (CNS), can reflect the underlying true emotional state of a person. This study applied machine-learning algorithms to categorize EEG emotional states in PD patients that would classify six basic emotions (happiness and sadness, fear, anger, surprise and disgust) in comparison with healthy controls (HC). Emotional EEG data were recorded from 20 PD patients and 20 healthy age-, education level- and sex-matched controls using multimodal (audio-visual) stimuli. The use of nonlinear features motivated by the higher-order spectra (HOS) has been reported to be a promising approach to classify the emotional states. In this work, we made the comparative study of the performance of k-nearest neighbor (kNN) and support vector machine (SVM) classifiers using the features derived from HOS and from the power spectrum. Analysis of variance (ANOVA) showed that power spectrum and HOS based features were statistically significant among the six emotional states (p < 0.0001). Classification results shows that using the selected HOS based features instead of power spectrum based features provided comparatively better accuracy for all the six classes with an overall accuracy of 70.10% ± 2.83% and 77.29% ± 1.73% for PD patients and HC in beta (13-30 Hz) band using SVM classifier. Besides, PD patients achieved less accuracy in the processing of negative emotions (sadness, fear, anger and disgust) than in processing of positive emotions (happiness, surprise) compared with HC. These results demonstrate the effectiveness of applying machine learning techniques to the classification of emotional states in PD patients in a user independent manner using EEG signals. The accuracy of the system can be improved by investigating the other HOS based features. This study might lead to a practical system for noninvasive assessment of the emotional impairments associated with neurological disorders.
  5. Yuvaraj R, Murugappan M, Mohamed Ibrahim N, Iqbal M, Sundaraj K, Mohamad K, et al.
    Behav Brain Funct, 2014;10:12.
    PMID: 24716619 DOI: 10.1186/1744-9081-10-12
    While Parkinson's disease (PD) has traditionally been described as a movement disorder, there is growing evidence of disruption in emotion information processing associated with the disease. The aim of this study was to investigate whether there are specific electroencephalographic (EEG) characteristics that discriminate PD patients and normal controls during emotion information processing.
  6. Yuvaraj R, Murugappan M, Omar MI, Ibrahim NM, Sundaraj K, Mohamad K, et al.
    Int J Neurosci, 2014 Jul;124(7):491-502.
    PMID: 24168328 DOI: 10.3109/00207454.2013.860527
    Although an emotional deficit is a common finding in Parkinson's disease (PD), its neurobiological mechanism on emotion recognition is still unknown. This study examined the emotion processing deficits in PD patients using electroencephalogram (EEG) signals in response to multimodal stimuli.
  7. Tharmathurai S, Muhammad-Ikmal MK, Razak AA, Che-Hamzah J, Azhany Y, Fazilawati Q, et al.
    J Glaucoma, 2021 May 01;30(5):e205-e212.
    PMID: 33710066 DOI: 10.1097/IJG.0000000000001830
    PRCIS: Depression increases with severity of visual field defect in older adults with primary open-angle glaucoma (POAG).

    PURPOSE: This study aimed to determine the prevalence of depression among patients with POAG and examine the relationship between depression and the severity of POAG in older adults.

    MATERIALS AND METHODS: Three hundred and sixty patients with POAG aged 60 years or above were recruited from 2 tertiary centers located in an urban and suburban area. The participants were stratified according to the severity of their glaucoma based on the scores from the modified Advanced Glaucoma Intervention Study (AGIS) to mild, moderate, severe, and end stage. Face-to-face interviews were performed using the Malay Version Geriatric Depression Scale 14 (mGDS-14) questionnaire. Depression is diagnosed when the score is ≥8. One-way analysis of variance was used to compare the subscores between the groups. Multifactorial analysis of variance was also applied with relevant confounding factors.

    RESULTS: Depression was detected in 16% of older adults with POAG; a higher percentage of depression was seen in those with end stage disease. There was a significant increase in the mean score of mGDS-14 according to the severity of POAG. There was evidence of an association between depression and severity of visual field defect (P<0.001). There was a significant difference in mGDS-14 score between the pairing of severity of POAG [mild-severe (P=0.003), mild-end stage (P<0.001), moderate-severe (P<0.001), and moderate-end stage (P<0.001)] after adjustment to living conditions, systemic disease, and visual acuity.

    CONCLUSION: Ophthalmologists should be aware that older adults with advanced visual field defects in POAG may have depression. The detection of depression is important to ensure adherence and persistence to the treatment of glaucoma.

  8. Tasyriq M, Najmuldeen IA, In LL, Mohamad K, Awang K, Hasima N
    PMID: 22997533
    In continuation of our interest towards the elucidation of apoptotic pathways of cytotoxic phytocompounds, we have embarked upon a study on the anticancer effects of 7α-hydroxy-β-sitosterol (CT1), a rare natural phytosterol oxide isolated from Chisocheton tomentosus. CT1 was found to be cytotoxic on three different human tumor cell lines with minimal effects on normal cell controls, where cell viability levels were maintained ≥80% upon treatment. Our results showed that cell death in MCF-7 breast tumor cells was achieved through the induction of apoptosis via downregulation of the ERK1/2 signaling pathway. CT1 was also found to increase proapoptotic Bax protein levels, while decreasing anti-apoptotic Bcl-2 protein levels, suggesting the involvement of the intrinsic pathway. Reduced levels of initiator procaspase-9 and executioner procaspase-3 were also observed following CT1 exposure, confirming the involvement of cytochrome c-mediated apoptosis via the mitochondrial pathway. These results demonstrated the cytotoxic and apoptotic ability of 7α-hydroxy-β-sitosterol and suggest its potential anti-cancer use particularly on breast adenocarcinoma cells.
  9. Taha H, Hadi AH, Nordin N, Najmuldeen IA, Mohamad K, Shirota O, et al.
    Chem Pharm Bull (Tokyo), 2011;59(7):896-7.
    PMID: 21720044
    Pseuduvarines A (1) and B (2), two new dioxoaporphine alkaloids with an amino moiety, were isolated from the stem bark of Pseuduvaria rugosa and their structures were elucidated by combination of 2D-NMR spectroscopic analysis. Pseuduvarines A (1) and B (2) showed cytotoxicity against MCF7, HepG2, and HL-60 (1: IC₅₀, 0.9, 21.7, and >50.0 µM, respectively, 2: IC₅₀ >50.0, 15.7, and 12.4 µM, respectively).
  10. Sivasothy Y, Hadi AH, Mohamad K, Leong KH, Ibrahim H, Sulaiman SF, et al.
    Bioorg Med Chem Lett, 2012 Jun 1;22(11):3831-6.
    PMID: 22546674 DOI: 10.1016/j.bmcl.2012.02.064
    The rhizomes of Zingiber spectabile yielded a new dimeric flavonol glycoside for which the name kaempferol-3-O-(4″-O-acetyl)-α-L-rhamnopyranoside-(I-6,II-8)-kaempferol-3-O-(4″-O-acetyl)-α-L-rhamnopyranoside; spectaflavoside A (1) was proposed, along with kaempferol and its four acetylrhamnosides (2-6), demethoxycurcumin (7) and curcumin (8). The structure of spectaflavoside A was elucidated by spectroscopic methods including, 1D and 2D NMR techniques. This is the first report on the occurrence of a dimeric flavonol glycoside in the Zingiberaceae and the second in nature. Spectaflavoside A was found to be a potent iron chelating agent.
  11. Samat NA, Abdul Murad NA, Mohamad K, Abdul Razak MR, Mohamed Ibrahim N
    Front Neurosci, 2017;11:712.
    PMID: 29326545 DOI: 10.3389/fnins.2017.00712
    Background: Cognitive impairment is prevalent in Parkinson's disease (PD), affecting 15-20% of patients at diagnosis. α-synuclein expression and genetic polymorphisms of Apolipoprotein E (ApoE) have been associated with the presence of cognitive impairment in PD although data have been inconsistent. Objectives: To determine the prevalence of cognitive impairment in patients with PD using Montreal Cognitive Assessment (MoCA), Comprehensive Trail Making Test (CTMT) and Parkinson's disease-cognitive rating scale (PDCRS), and its association with plasma α-synuclein and ApoE genetic polymorphisms. Methods: This was across-sectional study involving 46 PD patients. Patients were evaluated using Montreal cognitive assessment test (MoCA), and detailed neuropsychological tests. The Parkinson's disease cognitive rating scale (PDCRS) was used for cognitive function and comprehensive trail making test (CTMT) for executive function. Blood was drawn for plasma α-synuclein measurements and ApoE genetic analysis. ApoE polymorphism was detected using MutaGELAPoE from ImmunDiagnostik. Plasma α-synuclein was detected using the ELISA Technique (USCN Life Science Inc.) according to the standard protocol. Results: Based on MoCA, 26 (56.5%) patients had mild cognitive impairment (PD-MCI) and 20 (43.5%) had normal cognition (PD-NC). Based on the PDCRS, 18 (39.1%) had normal cognition (PDCRS-NC), 17 (37%) had mild cognitive impairment (PDCRS-MCI), and 11 (23.9%) had dementia (PDCRS-PDD). In the PDCRS-MCI group, 5 (25%) patients were from PD-NC group and all PDCRS-PDD patients were from PD-MCI group. CTMT scores were significantly different between patients with MCI and normal cognition on MoCA (p = 0.003). Twenty one patients (72.4%) with executive dysfunction were from the PD-MCI group; 17 (77.3%) with severe executive dysfunction and 4 (57.1%) had mild to moderate executive dysfunction. There were no differences in the plasma α-synuclein concentration between the presence or types of cognitive impairment based on MoCA, PDCRS, and CTMT. TheApoEe4 allele carrier frequency was significantly higher in patients with executive dysfunction (p = 0.014). Conclusion: MCI was prevalent in our PD population. PDCRS appeared to be more discriminatory in detecting MCI and PDD than MoCA. Plasma α-synuclein level was not associated with presence nor type of cognitive impairment, but the ApoEe4 allele carrier status was significantly associated with executive dysfunction in PD.
  12. Qureshi AK, Mukhtar MR, Hirasawa Y, Hosoya T, Nugroho AE, Morita H, et al.
    Chem Pharm Bull (Tokyo), 2011;59(2):291-3.
    PMID: 21297315
    Two new indole alkaloids, neolamarckines A and B (1, 2) were isolated from the leaves of Neolamarckia cadamba (Rubiaceae). Structural elucidation of 1 and 2 was performed by combination of 2D-NMR and circular dichroism (CD) spectra, and chemical correlations. Neolamarckine A (1) showed inhibition of inducible nitric oxide synthase (iNOS) dose dependently.
  13. Najmuldeen IA, Hadi AH, Awang K, Mohamad K, Ketuly KA, Mukhtar MR, et al.
    J Nat Prod, 2011 May 27;74(5):1313-7.
    PMID: 21428417 DOI: 10.1021/np200013g
    Three new limonoids, chisomicines A-C (1-3), have been isolated from the bark of Chisocheton ceramicus. Their structures were determined by 2D NMR, CD spectroscopic methods, and X-ray analysis. Chisomicine A (1) exhibited NO production inhibitory activity in J774.1 cells stimulated by LPS dose-dependently at high cell viability.
  14. Najmuldeen IA, Hadi AH, Awang K, Mohamad K, Ng SW
    PMID: 21581023 DOI: 10.1107/S1600536808033163
    The asymmetric unit of the title compound, C(29)H(50)O(2), contains two mol-ecules; one mol-ecule is linked to the other by two O-H⋯O hydrogen bonds, whereas only one of the hydr-oxy groups of the second mol-ecule is involved in hydrogen bonding. This gives rise to a chain that runs along the a axis of the monoclinic unit cell.
  15. Nagoor NH, Shah Jehan Muttiah N, Lim CS, In LL, Mohamad K, Awang K
    PLoS One, 2011;6(8):e23661.
    PMID: 21858194 DOI: 10.1371/journal.pone.0023661
    The aim of this study was to determine the cytotoxic and apoptotic effects of erythrocarpine E (CEB4), a limonoid extracted from Chisocheton erythrocarpus on human oral squamous cell carcinoma. Based on preliminary dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, CEB4 treated HSC-4 cells demonstrated a cytotoxic effect and inhibited cell proliferation in a time and dose dependent manner with an IC(50) value of 4.0±1.9 µM within 24 h of treatment. CEB4 was also found to have minimal cytotoxic effects on the normal cell line, NHBE with cell viability levels maintained above 80% upon treatment. Annexin V-fluorescein isothiocyanate (FITC), poly-ADP ribose polymerase (PARP) cleavage and DNA fragmentation assay results showed that CEB4 induces apoptosis mediated cell death. Western blotting results demonstrated that the induction of apoptosis by CEB4 appeared to be mediated through regulation of the p53 signalling pathway as there was an increase in p53 phosphorylation levels. CEB4 was also found to up-regulate the pro-apoptotic protein, Bax, while down-regulating the anti-apoptotic protein, Bcl-2, suggesting the involvement of the intrinsic mitochondrial pathway. Reduced levels of initiator procaspase-9 and executioner caspase-3 zymogen were also observed following CEB4 exposure, hence indicating the involvement of cytochrome c mediated apoptosis. These results demonstrate the cytotoxic and apoptotic ability of erythrocarpine E, and suggest its potential development as a cancer chemopreventive agent.
  16. Mohd-Zin SW, Marwan AI, Abou Chaar MK, Ahmad-Annuar A, Abdul-Aziz NM
    Scientifica (Cairo), 2017;2017:5364827.
    PMID: 28286691 DOI: 10.1155/2017/5364827
    Spina bifida is among the phenotypes of the larger condition known as neural tube defects (NTDs). It is the most common central nervous system malformation compatible with life and the second leading cause of birth defects after congenital heart defects. In this review paper, we define spina bifida and discuss the phenotypes seen in humans as described by both surgeons and embryologists in order to compare and ultimately contrast it to the leading animal model, the mouse. Our understanding of spina bifida is currently limited to the observations we make in mouse models, which reflect complete or targeted knockouts of genes, which perturb the whole gene(s) without taking into account the issue of haploinsufficiency, which is most prominent in the human spina bifida condition. We thus conclude that the need to study spina bifida in all its forms, both aperta and occulta, is more indicative of the spina bifida in surviving humans and that the measure of deterioration arising from caudal neural tube defects, more commonly known as spina bifida, must be determined by the level of the lesion both in mouse and in man.
  17. Mohd Said MS, Bin Shudim SS, Mohamad K, Shaharir SS, Kong NCT, Ali RA
    Egyptian Rheumatologist, 2016;38:189-194.
    DOI: 10.1016/j.ejr.2015.12.001
    Aim of the work This work aimed to determine the frequency of subclinical memory dysfunction in a group of Malaysian systemic lupus erythematosus (SLE) patients and to study its relation to clinical characteristics, laboratory investigations and disease activity. Patients and methods Fifteen SLE patients attending the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and not known to have neuropsychiatric lupus were recruited. These patients were assessed using the Wechsler Memory Scale. Disease activity was assessed using the SLE disease activity index 2000 (SLEDAI-2K). Results The median age of the patients was 28 years (25–37 years) and they were 14 females and one male. Their median disease duration was 9.3 years (4.8–10 years). Their median SLEDAI-2K was 4 (0–6). Memory dysfunction was identified in 7/15 (46.7%) SLE patients and was significantly associated with lower serum thyroxine levels (median 12.27; 11.8–13.3 μg/dl) (p = 0.027) compared to those without memory impairment (15.48; 14.39–16.56 μg/dl). Auditory memory impairment was associated with the education level as the auditory memory index was significantly lower in patients with secondary education (n = 7, median 88; 86.5–91.5) compared to those who received tertiary education (n = 8, median 103; 97.5–119.5) (p = 0.025) while visual memory was influenced by disease duration (p = 0.016). There was no association between overall memory dysfunction and disease duration, number of relapses, clinical manifestations and SLEDAI-2K scores. Conclusion There is a high frequency of subclinical memory dysfunction among SLE patients. A remarkable association is present with lower thyroxine. Auditory memory impairment is related to the level of education and visual memory to disease duration. © 2015 The Authors
  18. Mohamad K, Yusoff M, Awang K, Ahmad K, Ng SW
    PMID: 21583174 DOI: 10.1107/S1600536809015955
    In the mol-ecule of pinnatane A, C(30)H(48)O(3), isolated from the bark of Walsura pinnata Hassk, the four cyclo-hexane rings adopt chair conformations; the carboxyl and hydr-oxy substituents occupy axial positions. The cyclo-hexene ring is envelope-shaped. Adjacent mol-ecules are linked by O-H⋯O hydrogen bonds into a chain running along the c axis.
  19. Mohamad K, Martin MT, Najdar H, Gaspard C, Sévenet T, Awang K, et al.
    J Nat Prod, 1999 Jun;62(6):868-72.
    PMID: 10395505
    Nine 3,4-secoapotirucallanes, argentinic acids A-I, were isolated from the bark of Aglaia argentea and transformed to their methyl esters 1-9. The structures were determined by spectral and chemical means. Compounds 1-8 showed moderate cytotoxic activity against KB cells (IC50 1.0-3.5 microg/mL).
  20. Looi CY, Moharram B, Paydar M, Wong YL, Leong KH, Mohamad K, et al.
    PMID: 23837445 DOI: 10.1186/1472-6882-13-166
    Centratherum anthelminticum (L.) Kuntze (scientific synonyms: Vernonia anthelmintica; black cumin) is one of the ingredients of an Ayurvedic preparation, called "Kayakalp", commonly applied to treat skin disorders in India and Southeast Asia. Despite its well known anti-inflammatory property on skin diseases, the anti-cancer effect of C. anthelminticum seeds on skin cancer is less documented. The present study aims to investigate the anti-cancer effect of Centratherum anthelminticum (L.) seeds chloroform fraction (CACF) on human melanoma cells and to elucidate the molecular mechanism involved.
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