Displaying publications 41 - 60 of 69 in total

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  1. Loh SW, Ng WL, Yeo KS, Lim YY, Ea CK
    PLoS One, 2014;9(7):e103915.
    PMID: 25079219 DOI: 10.1371/journal.pone.0103915
    H3K9 methylation is one of the essential histone post-translational modifications for heterochromatin formation and transcriptional repression. Recently, several studies have demonstrated that H3K9 methylation negatively regulates the type I interferon response.
  2. Chew YL, Chan EW, Tan PL, Lim YY, Stanslas J, Goh JK
    PMID: 21306653 DOI: 10.1186/1472-6882-11-12
    Many medicinal plants from Leguminosae family can be found easily in Malaysia. These plants have been used as traditional medicines by local ethnic groups, where they are prepared as decoction, pastes for wound infections, and some have been eaten as salad. This paper focused on the assessment of antioxidant potential, antibacterial activity and classes of phytochemicals of nine plants from the Leguminosae family.
  3. Lim YY, Prang KH, Cysique L, Pietrzak RH, Snyder PJ, Maruff P
    Behav Res Methods, 2009 Nov;41(4):1190-200.
    PMID: 19897828 DOI: 10.3758/BRM.41.4.1190
    Verbal memory tests-although important to the neuropsychological assessment of memory-are biased to many cultures. In the present article, we highlighted the limitations associated with the direct translation of tests and word matching, as well as the lack of ecological validity and cultural appropriateness when tests developed in one culture are used in another. To overcome these limitations, a verbal memory paradigm was developed that framed the memory assessment with a shopping-list format, but that developed culturally specific stimuli for the different language groups. The aim of the present study was to determine the equivalence of this shopping list memory test in different cultural and language groups. Eighty-three adults from English-, French-, Malay-, and Chinese-speaking cultures participated in four experiments. The results of all the experiments indicated that performance of verbal list learning is equivalent, irrespective of the language used. These results support the use of this methodology for minimizing cross-cultural test bias, and have important implications for testing culturally and linguistically diverse individuals.
  4. Wang Y, Lim YY, He Z, Wong WT, Lai WF
    PMID: 33559482 DOI: 10.1080/10408398.2021.1882381
    The last decide has witnessed a growing research interest in the role of dietary phytochemicals in influencing the gut microbiota. On the other hand, recent evidence reveals that dietary phytochemicals exhibit properties of preventing and tackling symptoms of Alzheimer's disease, which is a neurodegenerative disease that has also been linked with the status of the gut microbiota over the last decade. Till now, little serious discussions, however, have been made to link recent understanding of Alzheimer's disease, dietary phytochemicals and the gut microbiota together and to review the roles played by phytochemicals in gut dysbiosis induced pathologies of Alzheimer's disease. Deciphering these connections can provide insights into the development and future use of dietary phytochemicals as anti-Alzheimer drug candidates. This review aims at presenting latest evidence in the modulating role of phytochemicals in the gut microbiota and its relevance to Alzheimer's disease and summarizing the mechanisms behind the modulative activities. Limitations of current research in this field and potential directions will also be discussed for future research on dietary phytochemicals as anti-Alzheimer agents.
  5. Choong YS, Lim YY, Soong JX, Savoo N, Guida C, Rhyman L, et al.
    Hormones (Athens), 2021 Sep;20(3):557-569.
    PMID: 33782920 DOI: 10.1007/s42000-021-00278-2
    PURPOSE: Diabetes mellitus is a common condition in the clinically obese. Bariatric surgery is one of the ways to put type 2 diabetes in remission. Recent findings propose the appetite-regulator peptide tyrosine tyrosine (PYY) as a therapeutic option for patients with type 2 diabetes. This novel gut hormone restores impaired insulin and glucagon secretion in pancreatic islets and is implicated in type 2 diabetes reversal after bariatric surgery. The current study elucidates the interactions between PYY and the NPY1R and NPY4R receptors using computational methods.

    METHODS: Protein structure prediction, molecular docking simulation, and molecular dynamics (MD) simulation were performed to elucidate the interactions of PYY with NPY1R and NPY4R.

    RESULTS: The predicted binding models of PYY-NPY receptors are in agreement with those described in the literature, although different interaction partners are presented for the C-terminal tail of PYY. Non-polar interactions are predicted to drive the formation of the protein complex. The calculated binding energies show that PYY has higher affinity for NPY4R (ΔGGBSA = -65.08 and ΔGPBSA = -87.62 kcal/mol) than for NPY1R (ΔGGBSA = -23.11 and ΔGPBSA = -50.56 kcal/mol).

    CONCLUSIONS: Based on the constructed models, the binding conformations obtained from docking and MD simulation for both the PYY-NPY1R and PYY-NPY4R complexes provide a detailed map of possible interactions. The calculated binding energies show a higher affinity of PYY for NPY4R. These findings may help to understand the mechanisms behind the improvement of diabetes following bariatric surgery.

  6. Rahumatullah A, Balachandra D, Noordin R, Baharudeen Z, Lim YY, Choong YS, et al.
    Sci Rep, 2021 01 28;11(1):2502.
    PMID: 33510342 DOI: 10.1038/s41598-021-82125-3
    Antibodies have different chemical properties capable of targeting a diverse nature of antigens. Traditionally, immune antibody libraries are perceived to be disease-specific with a skewed repertoire. The complexity during the generation of a combinatorial antibody library allows for a skewed but diverse repertoire to be generated. Strongyloides stercoralis is a parasite that causes strongyloidiasis, a potentially life-threatening disease with a complex diagnosis that impedes effective control and treatment of the disease. This study describes the isolation of monoclonal antibodies against S. stercoralis NIE recombinant protein using an immune antibody phage display library derived from lymphatic filaria-infected individuals. The isolated antibody clones showed both lambda and kappa light chains gene usage, with diverse amino acid distributions. Structural analysis showed that electropositivity and the interface area could determine the binding affinity of the clones with NIE. The successful identification of S. stercoralis antibodies from the filarial immune library highlights the breadth of antibody gene diversification in an immune antibody library that can be applied for closely related infections.
  7. Lim CC, Chan SK, Lim YY, Ishikawa Y, Choong YS, Nagaoka Y, et al.
    Mol Immunol, 2021 07;135:191-203.
    PMID: 33930714 DOI: 10.1016/j.molimm.2021.04.016
    The murine double minute 2 (MDM2) protein is a major negative regulator of the tumour suppressor protein p53. Under normal conditions, MDM2 constantly binds to p53 transactivation domain and/or ubiquinates p53 via its role as E3 ubiquitin ligase to promote p53 degradation as well as nuclear export to maintain p53 levels in cells. Meanwhile, amplification of MDM2 and appearance of MDM2 spliced variants occur in many tumours and normal tissues making it a prognostic indicator for human cancers. The mutation or deletion of p53 protein in half of human cancers inactivates its tumour suppressor activity. However, cancers with wild type p53 have its function effectively inhibited through direct interaction with MDM2 oncoprotein. Here, we described the construction of a MDM2 spliced variant (rMDM215kDa) consisting of SWIB/MDM2 domain and its central region for antibody generation. Biopanning with a human naïve scFv library generated four scFv clones specific to rMDM215kDa. Additionally, the selected scFv clones were able to bind to the recombinant full length MDM2 (rMDM2-FL). Computational prediction showed that the selected scFv clones potentially bind to exon 7-8 of MDM2 while leaving the MDM2/SWIB domain free for p53 interaction. The developed antibodies exhibit good specificity can be further investigated for downstream biomedical and research applications.
  8. Ng WL, Marinov GK, Liau ES, Lam YL, Lim YY, Ea CK
    RNA Biol, 2016 09;13(9):861-71.
    PMID: 27362560 DOI: 10.1080/15476286.2016.1207036
    Circular RNAs (circRNAs) constitute a large class of RNA species formed by the back-splicing of co-linear exons, often within protein-coding transcripts. Despite much progress in the field, it remains elusive whether the majority of circRNAs are merely aberrant splicing by-products with unknown functions, or their production is spatially and temporally regulated to carry out specific biological functions. To date, the majority of circRNAs have been cataloged in resting cells. Here, we identify an LPS-inducible circRNA: mcircRasGEF1B, which is predominantly localized in cytoplasm, shows cell-type specific expression, and has a human homolog with similar properties, hcircRasGEF1B. We show that knockdown of the expression of mcircRasGEF1B reduces LPS-induced ICAM-1 expression. Additionally, we demonstrate that mcircRasGEF1B regulates the stability of mature ICAM-1 mRNAs. These findings expand the inventory of functionally characterized circRNAs with a novel RNA species that may play a critical role in fine-tuning immune responses and protecting cells against microbial infection.
  9. Lee WK, Lim YY, Leow AT, Namasivayam P, Ong Abdullah J, Ho CL
    Carbohydr Polym, 2017 May 15;164:23-30.
    PMID: 28325321 DOI: 10.1016/j.carbpol.2017.01.078
    Agar is a jelly-like biopolymer synthesized by many red seaweeds as their major cell wall component. Due to its excellent rheological properties, it has been exploited commercially for applications in food, cosmetic, pharmaceutical, biomedical and biotechnology industries. Despite its multiple uses, the biosynthesis of this phycocolloid is not fully understood. The current knowledge on agar biosynthesis is inferred from plant biochemistry and putative pathways for ulvan and alginate biosynthesis in green and brown seaweeds, respectively. In this review, the gaps in our current knowledge on agar biosynthetic pathway are discussed, focusing on the biosynthesis of agar precursors, elongation of agar polysaccharide chain and side chain modification. The development of molecular markers for the screening of desired seaweeds for industrial exploitation is also discussed.
  10. Ong KS, Mawang CI, Daniel-Jambun D, Lim YY, Lee SM
    Expert Rev Anti Infect Ther, 2018 11;16(11):855-864.
    PMID: 30308132 DOI: 10.1080/14787210.2018.1535898
    INTRODUCTION: Biofilm formation is a strategy for microorganisms to adapt and survive in hostile environments. Microorganisms that are able to produce biofilms are currently recognized as a threat to human health. Areas covered: Many strategies have been employed to eradicate biofilms, but several drawbacks from these methods had subsequently raised concerns on the need for alternative approaches to effectively prevent biofilm formation. One of the main mechanisms that drives a microorganism to transit from a planktonic to a biofilm-sessile state, is oxidative stress. Chemical agents that could target oxidative stress regulators, for instance antioxidants, could therefore be used to treat biofilm-associated infections. Expert commentary: The focus of this review is to summarize the function and limitation of the current anti-biofilm strategies and will propose the use of antioxidants as an alternative method to treat, prevent and eradicate biofilms. Studies have shown that water-soluble and lipid-soluble antioxidants can reduce and prevent biofilm formation, by influencing the expression of genes associated with oxidative stress. Further in vivo work should be conducted to ensure the efficacy of these antioxidants in a biological environment. Nevertheless, antioxidants are promising anti-biofilm agents, and thus is a potential solution for biofilm-associated infections in the future.
  11. Tan HL, Kai D, Pasbakhsh P, Teow SY, Lim YY, Pushpamalar J
    Colloids Surf B Biointerfaces, 2020 Apr;188:110713.
    PMID: 31884080 DOI: 10.1016/j.colsurfb.2019.110713
    Electrospinning is a common method to prepare nanofiber scaffolds for tissue engineering. One of the common cellulose esters, cellulose acetate butyrate (CAB), has been electrospun into nanofibers and studied. However, the intrinsic hydrophobicity of CAB limits its application in tissue engineering as it retards cell adhesion. In this study, the properties of CAB nanofibers were improved by fabricating the composite nanofibers made of CAB and hydrophilic polyethylene glycol (PEG). Different ratios of CAB to PEG were tested and only the ratio of 2:1 resulted in smooth and bead-free nanofibers. The tensile test results show that CAB/PEG composite nanofibers have 2-fold higher tensile strength than pure CAB nanofibers. The hydrophobicity of the composite nanofibers was also reduced based on the water contact angle analysis. As the hydrophilicity increases, the swelling ability of the composite nanofiber increases by 2-fold with more rapid biodegradation. The biocompatibility of the nanofibers was tested with normal human dermal fibroblasts (NHDF). The cell viability assay results revealed that the nanofibers are non-toxic. In addition to that, CAB/PEG nanofibers have better cell attachment compared to pure CAB nanofibers. Based on this study, CAB/PEG composite nanofibers could potentially be used as a nanofiber scaffold for applications in tissue engineering.
  12. Pong LY, Yew PN, Lee WL, Lim YY, Sharifah SH
    Chin Med, 2020;15:49.
    PMID: 32467721 DOI: 10.1186/s13020-020-00329-7
    Background: Dengue fever is currently endemic in tropical and subtropical countries worldwide and effective drug against DENV infection is still unavailable. Porcupine dates, which are traditionally used to treat dengue fever, might contain potential anti-dengue compounds. Two porcupine dates, black date (BD) and powdery date (PD) from Himalayan porcupine (Hystrix brachyura), were investigated for their antiviral activities against DENV-2 in vitro.

    Methods: The methanol crude extracts (MBD and MPD) were prepared from the raw material of porcupine dates. The tannin-rich fractions (BDTF and PDTF) were isolated from their methanol crude extracts using column chromatography. The presence of tannins in BDTF and PDTF extracts was determined by fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) analyses. The cytotoxicity and anti-DENV-2 activities including virus yield inhibition, virucidal, virus attachment and pre-treatment assays of the extracts were examined in Vero cells.

    Results: Our findings revealed that all the extracts of porcupine dates exhibited antiviral activity against DENV-2 in Vero cells. The IC50 of BDTF and PDTF were 25 µg/mL and 11 µg/mL respectively, while their methanol crude extracts demonstrated lower antiviral efficacy (IC50 ≈ 101-107 µg/mL). BDTF and PDTF also exerted a similar higher virucidal effect (IC50 of 11 µg/mL) than methanol crude extracts (IC50 ≈ 52-66 µg/mL). Furthermore, all the extracts inhibited the attachment of DENV-2 by at least 80%. Pre-treatments of cells with BDTF and PDTF markedly prevented DENV-2 infection when compared to methanol crude extracts.

    Conclusion: This study suggests that porcupine dates possess antiviral properties against DENV-2, which is attributed to its tannin compounds.

  13. Tong KL, Tan KE, Lim YY, Tien XY, Wong PF
    Mol Cell Biochem, 2022 Dec;477(12):2703-2733.
    PMID: 35604519 DOI: 10.1007/s11010-022-04455-8
    Atherosclerosis is the major cause of coronary artery disease (CAD) which includes unstable angina, myocardial infarction, and heart failure. The onset of atherogenesis, a process of atherosclerotic lesion formation in the intima of arteries, is driven by lipid accumulation, a vicious cycle of reactive oxygen species (ROS)-induced oxidative stress and inflammatory reactions leading to endothelial cell (EC) dysfunction, vascular smooth muscle cell (VSMC) activation, and foam cell formation which further fuel plaque formation and destabilization. In recent years, there is a surge in the number of publications reporting the involvement of circular RNAs (circRNAs) in the pathogenesis of cardiovascular diseases, cancers, and metabolic syndromes. These studies have advanced our understanding on the biological functions of circRNAs. One of the most common mechanism of action of circRNAs reported is the sponging of microRNAs (miRNAs) by binding to the miRNAs response element (MRE), thereby indirectly increases the transcription of their target messenger RNAs (mRNAs). Individual networks of circRNA-miRNA-mRNA associated with atherogenesis have been extensively reported, however, there is a need to connect these findings for a complete overview. This review aims to provide an update on atherogenesis-related circRNAs and analyze the circRNA-miRNA-mRNA interactions in atherogenesis. The atherogenic mechanisms and clinical relevance of each atherogenesis-related circRNA were systematically discussed for better understanding of the knowledge gap in this area.
  14. Ng WL, Marinov GK, Chin YM, Lim YY, Ea CK
    Sci Rep, 2017 09 25;7(1):12227.
    PMID: 28947785 DOI: 10.1038/s41598-017-12550-w
    Circular RNAs (circRNAs) have recently emerged as a large class of novel non-coding RNA species. However, the detailed functional significance of the vast majority of them remains to be elucidated. Most functional characterization studies targeting circRNAs have been limited to resting cells, leaving their role in dynamic cellular responses to stimuli largely unexplored. In this study, we focus on the LPS-induced cytoplasmic circRNA, mcircRasGEF1B, and combine targeted mcircRasGEF1B depletion with high-throughput transcriptomic analysis to gain insight into its function during the cellular response to LPS stimulation. We show that knockdown of mcircRasGEF1B results in altered expression of a wide array of genes. Pathway analysis revealed an overall enrichment of genes involved in cell cycle progression, mitotic division, active metabolism, and of particular interest, NF-κB, LPS signaling pathways, and macrophage activation. These findings expand the set of functionally characterized circRNAs and support the regulatory role of mcircRasGEF1B in immune response during macrophage activation and protection against microbial infections.
  15. Choong YS, Lee YV, Soong JX, Law CT, Lim YY
    Adv Exp Med Biol, 2017;1053:221-243.
    PMID: 29549642 DOI: 10.1007/978-3-319-72077-7_11
    The use of monoclonal antibody as the next generation protein therapeutics with remarkable success has surged the development of antibody engineering to design molecules for optimizing affinity, better efficacy, greater safety and therapeutic function. Therefore, computational methods have become increasingly important to generate hypotheses, interpret and guide experimental works. In this chapter, we discussed the overall antibody design by computational approches.
  16. Lim CS, Goh SL, Kariapper L, Krishnan G, Lim YY, Ng CC
    Clin Chim Acta, 2015 Aug 25;448:206-10.
    PMID: 26164385 DOI: 10.1016/j.cca.2015.07.008
    Development of indirect enzyme-linked immunosorbent assays (ELISAs) often utilizes synthetic peptides or recombinant proteins from Escherichia coli as immobilized antigens. Because inclusion bodies (IBs) formed during recombinant protein expression in E. coli are commonly thought as misfolded aggregates, only refolded proteins from IBs are used to develop new or in-house diagnostic assays. However, the promising utilities of IBs as nanomaterials and immobilized enzymes as shown in recent studies have led us to explore the potential use of IBs of recombinant Epstein-Barr virus viral capsid antigen p18 (VCA p18) as immobilized antigens in ELISAs for serologic detection of nasopharyngeal carcinoma (NPC).
  17. Piyarathna IE, Lim YY, Edla M, Thabet AM, Ucgul M, Lemckert C
    Sensors (Basel), 2023 Jan 26;23(3).
    PMID: 36772411 DOI: 10.3390/s23031372
    In recent years, harvesting energy from ubiquitous ultralow-frequency vibration sources, such as biomechanical motions using piezoelectric materials to power wearable devices and wireless sensors (e.g., personalized assistive tools for monitoring human locomotion and physiological signals), has drawn considerable interest from the renewable energy research community. Conventional linear piezoelectric energy harvesters (PEHs) generally consist of a cantilever beam with a piezoelectric patch and a proof mass, and they are often inefficient in such practical applications due to their narrow operating bandwidth and low voltage generation. Multimodal harvesters with multiple resonances appear to be a viable solution, but most of the previously proposed designs are unsuitable for ultralow-frequency vibration. This study investigated a novel multimode design, which included a bent branched beam harvester (BBBH) to enhance PEHs' bandwidth output voltage and output power for ultralow-frequency applications. The study was conducted using finite element method (FEM) analysis to optimize the geometrical design of the BBBH on the basis of the targeted frequency spectrum of human motion. The selected design was then experimentally studied using a mechanical shaker and human motion as excitation sources. The performance was also compared to the previously proposed V-shaped bent beam harvester (VBH) and conventional cantilever beam harvester (CBH) designs. The results prove that the proposed BBBH could harness considerably higher output voltages and power with lower idle time. Its operating bandwidth was also remarkably widened as it achieved three close resonances in the ultralow-frequency range. It was concluded that the proposed BBBH outperformed the conventional counterparts when used to harvest energy from ultralow-frequency sources, such as human motion.
  18. Ida J, Chan SK, Glökler J, Lim YY, Choong YS, Lim TS
    Molecules, 2019 Mar 19;24(6).
    PMID: 30893817 DOI: 10.3390/molecules24061079
    G-quadruplexes are made up of guanine-rich RNA and DNA sequences capable of forming noncanonical nucleic acid secondary structures. The base-specific sterical configuration of G-quadruplexes allows the stacked G-tetrads to bind certain planar molecules like hemin (iron (III)-protoporphyrin IX) to regulate enzymatic-like functions such as peroxidase-mimicking activity, hence the use of the term DNAzyme/RNAzyme. This ability has been widely touted as a suitable substitute to conventional enzymatic reporter systems in diagnostics. This review will provide a brief overview of the G-quadruplex architecture as well as the many forms of reporter systems ranging from absorbance to luminescence readouts in various platforms. Furthermore, some challenges and improvements that have been introduced to improve the application of G-quadruplex in diagnostics will be highlighted. As the field of diagnostics has evolved to apply different detection systems, the need for alternative reporter systems such as G-quadruplexes is also paramount.
  19. Piyarathna IE, Thabet AM, Ucgul M, Lemckert C, Lim YY, Tang ZS
    Sensors (Basel), 2023 Jun 01;23(11).
    PMID: 37299984 DOI: 10.3390/s23115257
    Piezoelectric energy harvesting systems have been drawing the attention of the research community over recent years due to their potential for recharging/replacing batteries embedded in low-power-consuming smart electronic devices and wireless sensor networks. However, conventional linear piezoelectric energy harvesters (PEH) are often not a viable solution in such advanced practices, as they suffer from a narrow operating bandwidth, having a single resonance peak present in the frequency spectrum and very low voltage generation, which limits their ability to function as a standalone energy harvester. Generally, the most common PEH is the conventional cantilever beam harvester (CBH) attached with a piezoelectric patch and a proof mass. This study investigated a novel multimode harvester design named the arc-shaped branch beam harvester (ASBBH), which combined the concepts of the curved beam and branch beam to improve the energy-harvesting capability of PEH in ultra-low-frequency applications, in particular, human motion. The key objectives of the study were to broaden the operating bandwidth and enhance the harvester's effectiveness in terms of voltage and power generation. The ASBBH was first studied using the finite element method (FEM) to understand the operating bandwidth of the harvester. Then, the ASBBH was experimentally assessed using a mechanical shaker and real-life human motion as excitation sources. It was found that ASBBH achieved six natural frequencies within the ultra-low frequency range (<10 Hz), in comparison with only one natural frequency achieved by CBH within the same frequency range. The proposed design significantly broadened the operating bandwidth, favouring ultra-low-frequency-based human motion applications. In addition, the proposed harvester achieved an average output power of 427 μW at its first resonance frequency under 0.5 g acceleration. The overall results of the study demonstrated that the ASBBH design can achieve a broader operating bandwidth and significantly higher effectiveness, in comparison with CBH.
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