Displaying publications 21 - 40 of 69 in total

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  1. Fulltext Caffeoylquinic acids in leaves of selected Apocynaceae species: Their isolation and content
    Wong SK, Lim YY, Ling SK, Chan EW
    Pharmacognosy Res, 2014 Jan;6(1):67-72.
    PMID: 24497746 DOI: 10.4103/0974-8490.122921
    Three compounds isolated from the methanol (MeOH) leaf extract of Vallaris glabra (Apocynaceae) were those of caffeoylquinic acids (CQAs). This prompted a quantitative analysis of their contents in leaves of V. glabra in comparison with those of five other Apocynaceae species (Alstonia angustiloba, Dyera costulata, Kopsia fruticosa, Nerium oleander, and Plumeria obtusa), including flowers of Lonicera japonica (Japanese honeysuckle), the commercial source of chlorogenic acid (CGA).
  2. Fulltext Choices of chromatographic methods as stability indicating assays for pharmaceutical products: A review
    Chew YL, Khor MA, Lim YY
    Heliyon, 2021 Mar;7(3):e06553.
    PMID: 33855234 DOI: 10.1016/j.heliyon.2021.e06553
    Stability indicating assay describes a technique which is used to analyse the stability of drug substance or active pharmaceutical ingredient (API) in bulk drug and pharmaceutical products. Stability indicating assay must be properly validated as per ICH guidelines. The important components in a stability indicating assay include sensitivity, specificity, accuracy, reliability, reproducibility and robustness. A validated assay is able to measure the concentration changes of drug substance/API with time and make reliable estimation of the quantity of the degradation impurities. The drug substance is separated and resolved from the impurities. Pros and cons of HPLC, GC, HPTLC, CE and SFC were discussed and reviewed. Stability indicating assay may consist of the combination of chromatographic separation and spectroscopic detection techniques. Hyphenated system could demonstrate parallel quantitative and qualitative analysis of drug substances and impurities. Examples are HPLC-DAD, HPLC-FL, GC-MS, LC-MS and LC-NMR. The analytes in the samples are separated in the chromatography while the impurities are chemically characterised by the spectroscopy in the system. In this review, various chromatographic methods which had been employed as stability indicating assays for drug substance and pharmaceutical formulation were systematically reviewed, and the application of hyphenated techniques in impurities characterisation and identification were also discussed with supporting literatures.
  3. CircRNA-miRNA interactions in atherogenesis
    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.
  4. Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy
    Lim YY, Zaidi AMA, Miskon A
    Molecules, 2023 Mar 24;28(7).
    PMID: 37049685 DOI: 10.3390/molecules28072920
    Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands' roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy.
  5. Fulltext Composing On-Program Triggers and On-Demand Stimuli into Biosensor Drug Carriers in Drug Delivery Systems for Programmable Arthritis Therapy
    Lim YY, Zaidi AMA, Miskon A
    Pharmaceuticals (Basel), 2022 Oct 27;15(11).
    PMID: 36355502 DOI: 10.3390/ph15111330
    Medication in arthritis therapies is complex because the inflammatory progression of rheumatoid arthritis (RA) and osteoarthritis (OA) is intertwined and influenced by one another. To address this problem, drug delivery systems (DDS) are composed of four independent exogenous triggers and four dependent endogenous stimuli that are controlled on program and induced on demand, respectively. However, the relationships between the mechanisms of endogenous stimuli and exogenous triggers with pathological alterations remain unclear, which results in a major obstacle in terms of clinical translation. Thus, the rationale for designing a guidance system for these mechanisms via their key irritant biosensors is in high demand. Many approaches have been applied, although successful clinical translations are still rare. Through this review, the status quo in historical development is highlighted in order to discuss the unsolved clinical difficulties such as infiltration, efficacy, drug clearance, and target localisation. Herein, we summarise and discuss the rational compositions of exogenous triggers and endogenous stimuli for programmable therapy. This advanced active pharmaceutical ingredient (API) implanted dose allows for several releases by remote controls for endogenous stimuli during lesion infections. This solves the multiple implantation and local toxic accumulation problems by using these flexible desired releases at the specified sites for arthritis therapies.
  6. Computer-Aided Antibody Design: An Overview
    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.
  7. Corrigendum to "Biosynthesis of agar in red seaweeds: A review" [Carbohydr. Polym. 164 (2017) 23-30]
    Lee WK, Lim YY, Leow AT, Namasivayam P, Ong Abdullah J, Ho CL
    Carbohydr Polym, 2017 08 01;169:533.
    PMID: 28504177 DOI: 10.1016/j.carbpol.2017.03.085
  8. Critical analysis of current methods for assessing the in vitro antioxidant and antibacterial activity of plant extracts
    Tan JB, Lim YY
    Food Chem, 2015 Apr 1;172:814-22.
    PMID: 25442625 DOI: 10.1016/j.foodchem.2014.09.141
    Natural product research is an active branch of science, driven by the increased value placed on individual health and well-being. Many naturally-occurring phytochemicals in plants, fruits and vegetables have been reported to exhibit antioxidant and antibacterial activity; often touted as being beneficial for human health. In vitro screening is a common practice in many research laboratories as a means of rapidly assessing these properties. However, the methods used by many are not necessarily optimal; a result of poor standardization, redundant assays and/or outdated methodology. This review primarily aims to give a better understanding in the selection of in vitro assays, with emphasis placed on some common assays such as the total phenolic content assay, free radical scavenging activity, disc-diffusion and broth microdilution. This includes a discussion on the reasons for choosing a particular assay, its strengths and weaknesses, ways to improve the accuracy of results and alternative assays.
  9. Fulltext CuZn Complex Used in Electrical Biosensors for Drug Delivery Systems
    Lim YY, Miskon A, Zaidi AMA
    Materials (Basel), 2022 Nov 01;15(21).
    PMID: 36363264 DOI: 10.3390/ma15217672
    This paper is to discuss the potential of using CuZn in an electrical biosensor drug carrier for drug delivery systems. CuZn is the main semiconductor ingredient that has great promise as an electrochemical detector to trigger releases of active pharmaceutical ingredients (API). This CuZn biosensor is produced with a green metal of frameworks, which is an anion node in conductive polymers linked by bioactive ligands using metal-polymerisation technology. The studies of Cu, Zn, and their oxides are highlighted by their electrochemical performance as electrical biosensors to electrically trigger API. The three main problems, which are glucose oxidisation, binding affinity, and toxicity, are highlighted, and their solutions are given. Moreover, their biocompatibilities, therapeutic efficacies, and drug delivery efficiencies are discussed with details given. Our three previous investigations of CuZn found results similar to those of other authors' in terms of multiphases, polymerisation, and structure. This affirms that our research is on the right track, especially that related to green synthesis using plant extract, CuZn as a nanochip electric biosensor, and bioactive ligands to bind API, which are limited to the innermost circle of the non-enzymatic glucose sensor category.
  10. Current anti-biofilm strategies and potential of antioxidants in biofilm control
    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. Fulltext Detection of Cytoplasmic and Nuclear Circular RNA via RT-qPCR
    Tan KE, Ng WL, Ea CK, Lim YY
    Bio Protoc, 2023 Sep 05;13(17):e4798.
    PMID: 37849784 DOI: 10.21769/BioProtoc.4798
    Circular RNA (circRNA) is an intriguing class of non-coding RNA that exists as a continuous closed loop. With the improvements in high throughput sequencing, biochemical analysis, and bioinformatic algorithms, studies on circRNA expression became abundant in recent years. However, functional studies of circRNA are still limited. Subcellular localization of circRNA may provide some clues in elucidating its biological functions by performing subcellular fractionation assay. Notably, circRNAs that are predominantly found in the cytoplasm are more likely to be involved in post-transcriptional gene regulation, e.g., acting as micoRNA sponge, whereas nuclear-retained circRNAs are predicted to play a role in transcriptional regulation. Subcellular fractionation could help researchers to narrow down and prioritize downstream experiments. The majority of the currently available protocols describe the steps for subcellular fractionation followed by western blot analysis for protein molecules. Here, we present a protocol for the subcellular fractionation of cells to detect circRNA via RT-qPCR with divergent primers. Moreover, detailed steps for the generation of specific circRNAs-enriched cDNA included in this protocol will enhance the amplification and detection of low-abundance circRNAs. This will be useful for researchers studying low-abundance circRNAs. Key features This protocol builds upon the method developed by Gagnon et al. (2014) and extends its application to circRNA study. Protocol for amplification of low levels of circRNA expression. Analysis takes into consideration the ratio of cytoplasmic RNA concentration to nuclear RNA concentration.
  12. Development and structural characterisation of human scFv targeting MDM2 spliced variant MDM215kDa
    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.
  13. Dietary phytochemicals that influence gut microbiota: Roles and actions as anti-Alzheimer agents
    Wang Y, Lim YY, He Z, Wong WT, Lai WF
    Crit Rev Food Sci Nutr, 2021 Feb 09.
    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.
  14. Effects of Aminocarboxylate Ligands of Surface Active Copper(II) Complexes on the Hydrolysis of p-Nitrophenyldiphenylphosphate
    Ship CP, Zainudin A, Lim YY
    J Colloid Interface Sci, 1999 Sep 1;217(1):211-213.
    PMID: 10441432
    The rate of hydrolysis of p-nitrophenyldiphenylphosphate in the presence of micellized [Cu(C(12)tmed)(L)](+) where C(12)tmed is N,N,N'-trimethyl-N'-dodecylethylenediamine and L is the anion part of the amino acid has been investigated. It was found that the observed maximum rate obtained under the excess surfactant over the substrate condition depends very much on the ability of the amino acid ligand to form a mixed-chelate complex with the [Cu(C(12)tmed)](2+) moiety. In general, a chelating ligand with better coordination ability gives a slower rate because of the reduction in the supply of Cu-OH nucleophile in the micelle. Copyright 1999 Academic Press.
  15. Effects of aminoacids on the autooxidation of 3,5-di-tert-butylcatechol in the presence of surface-active copper(II) complexes
    Lim YY, Liew LP
    J Colloid Interface Sci, 2002 Nov 15;255(2):425-7.
    PMID: 12505092
    The rate of autooxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) in the presence of micelles formed from mixing equal concentrations of [Cu(C(12)-tmed)Br(2)] (where C(12)-tmed is N,N,N'-trimethyl-N'-dodecylethylenediamine) and several amino acids has been investigated. It was found that the rate in air-saturated solution is very much dependent on pH, which affects the availability of copper(II) coordination site for the catechol and the degree of micellization. At a given pH, the rates in [Cu(C(12)-tmed)Br(2)] micellar media are greatly enhanced in the presence sodium halide.
  16. Electrospun cellulose acetate butyrate/polyethylene glycol (CAB/PEG) composite nanofibers: A potential scaffold for tissue engineering
    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.
  17. Enhancing the Bandwidth and Energy Production of Piezoelectric Energy Harvester Using Novel Multimode Bent Branched Beam Design for Human Motion Application
    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. Enzymatic synthesis of quercetin oleate esters using Candida antarctica lipase B
    Saik AY, Lim YY, Stanslas J, Choo WS
    Biotechnol Lett, 2017 Feb;39(2):297-304.
    PMID: 27812823 DOI: 10.1007/s10529-016-2246-5
    OBJECTIVES: To investigate the lipase-catalyzed acylation of quercetin with oleic acid using Candida antarctica lipase B.

    RESULTS: Three acylated analogues were produced: quercetin 4'-oleate (C33H42O8), quercetin 3',4'-dioleate (C51H74O9) and quercetin 7,3',4'-trioleate (C69H106O10). Their identities were confirmed with UPLC-ESI-MS and (1)H NMR analyses. The effects of temperature, duration and molar ratio of substrates on the bioconversion yields varied across conditions. The regioselectivity of the acylated quercetin analogues was affected by the molar ratio of substrates. TLC showed the acylated analogues had higher lipophilicity (152% increase) compared to quercetin. Partition coefficient (log P) of quercetin 4'-oleate was higher than those of quercetin and oleic acid. Quercetin 4'-oleate was also stable over 28 days of storage.

    CONCLUSIONS: Quercetin oleate esters with enhanced lipophilicity can be produced via lipase-catalyzed reaction using C. antarctica lipase B to be used in topical applications.

  19. Extraction methods of butterfly pea (Clitoria ternatea) flower and biological activities of its phytochemicals
    Jeyaraj EJ, Lim YY, Choo WS
    J Food Sci Technol, 2021 Jun;58(6):2054-2067.
    PMID: 33967304 DOI: 10.1007/s13197-020-04745-3
    Clitoria ternatea or commonly known as 'Butterfly pea' has been used traditionally in Ayurvedic medicine in which various parts of the plants are used to treat health issues such as indigestion, constipation, arthritis, skin diseases, liver and intestinal problems. The flowers of C. ternatea are used worldwide as ornamental flowers and traditionally used as a food colorant. This paper reviews the recent advances in the extraction and biological activities of phytochemicals from C. ternatea flowers. The application of maceration or ultrasound assisted extraction greatly increased the yield (16-247% of increase) of phytochemicals from C. ternatea flowers. Various phytochemicals such as kaempferol, quercetin and myricetin glycosides as well as anthocyanins have been isolated from C. ternatea flowers. Clitoria ternatea flower extracts were found to possess antimicrobial, antioxidant, anti-inflammatory, cytotoxic and antidiabetic activities which are beneficial to human health. Clitoria ternatea flower is a promising candidate for functional food applications owing to its wide range of pharmacotherapeutic properties as well as its safety and effectiveness.
  20. Fulltext Factors associated with poor academic achievement among urban primary school children in Malaysia
    Ong LC, Chandran V, Lim YY, Chen AH, Poh BK
    Singapore Med J, 2010 Mar;51(3):247-52.
    PMID: 20428748
    The aim of this study was to identify factors associated with poor academic achievement during the early school years.
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