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Fulltext Interleukin-1 Receptor Antagonist and Interleukin-4 Genes Variable Number Tandem Repeats Are Associated with Adiposity in Malaysian Subjects

Kok YY, Ong HH, Say YH

J Obes, 2017;2017:4104137.
PMID: 28293435 DOI: 10.1155/2017/4104137

Interleukin-1 receptor antagonist (IL1RA) intron 2 86 bp repeat and interleukin-4 (IL4) intron 3 70 bp repeat are variable number tandem repeats (VNTRs) that have been associated with various diseases, but their role in obesity is elusive. The objective of this study was to investigate the association of IL1RA and IL4 VNTRs with obesity and adiposity in 315 Malaysian subjects (128 M/187 F; 23 Malays/251 ethnic Chinese/41 ethnic Indians). The allelic distributions of IL1RA and IL4 were significantly different among ethnicities, and the alleles were associated with total body fat (TBF) classes. Individuals with IL1RA I/II genotype or allele II had greater risk of having higher overall adiposity, relative to those having the I/I genotype or I allele, respectively, even after controlling for ethnicity [Odds Ratio (OR) of I/II genotype = 12.21 (CI = 2.54, 58.79; p = 0.002); II allele = 5.78 (CI = 1.73, 19.29; p = 0.004)]. However, IL4 VNTR B2 allele was only significantly associated with overall adiposity status before adjusting for ethnicity [OR = 1.53 (CI = 1.04, 2.23; p = 0.03)]. Individuals with IL1RA II allele had significantly higher TBF than those with I allele (31.79 ± 2.52 versus 23.51 ± 0.40; p = 0.005). Taken together, IL1RA intron 2 VNTR seems to be a genetic marker for overall adiposity status in Malaysian subjects.
Comparison of Cell-based and Nanoparticle-based Therapeutics in Treating Atherosclerosis

Goh WX, Kok YY, Wong CY

Curr Pharm Des, 2023;29(35):2827-2840.
PMID: 37936453 DOI: 10.2174/0113816128272185231024115046

Today, cardiovascular diseases are among the biggest public health threats worldwide. Atherosclerosis, a chronic inflammatory disease with complex aetiology and pathogenesis, predispose many of these conditions, including the high mortality rate-causing ischaemic heart disease and stroke. Nevertheless, despite the alarming prevalence and absolute death rate, established treatments for atherosclerosis are unsatisfactory in terms of efficacy, safety, and patient acceptance. The rapid advancement of technologies in healthcare research has paved new treatment approaches, namely cell-based and nanoparticle-based therapies, to overcome the limitations of conventional therapeutics. This paper examines the different facets of each approach, discusses their principles, strengths, and weaknesses, analyses the main targeted pathways and their contradictions, provides insights on current trends as well as highlights any unique mechanisms taken in recent years to combat the progression of atherosclerosis.
Fulltext An Analysis of Health Science Students' Preparedness and Perception of Interactive Virtual Laboratory Simulation

Kok YY, Er HM, Nadarajah VD

Med Sci Educ, 2021 Dec;31(6):1919-1929.
PMID: 34518785 DOI: 10.1007/s40670-021-01364-1

The achievement of learning goals via laboratory practical depends on both extrinsic and intrinsic factors. They could be limited by laboratory time, incurred cost, safety, self-efficacy, inadequate prior preparation by learners, and different learning styles. Hence, virtual laboratory simulation (vLAB) may be an appropriate e-learning tool to overcome these restrictions. In this study, student's perception of the usefulness of vLAB was determined by using deoxyribonucleic acid (DNA) gel electrophoresis and polymerase chain reaction (PCR) as case examples. The perception of Year 2 and 3 health science undergraduate students' (N = 87) was studied using a questionnaire consisting of 12 items, rated on a 5-point Likert-scale. The attainment of learning outcomes was assessed using pre-and post-tests containing multiple-choice questions (MCQs). In addition, student's experience and learning from the vLAB were further explored using qualitative analysis. Although there was no significant difference between the mean scores of the pre-and post-tests, results showed that all participants perceived vLAB well, with a median score of 4 (Agree) for all items in the questionnaire. It provides a meaningful learning experience and an authentic environment where students feel safe to practice what they have learnt in lectures. Moreover, vLAB facilitates individualised learning and enhances self-efficacy among students. In conclusion, vLAB prepares students for physical laboratory sessions by activating the prehension dimension of Kolb's learning cycle, therefore complementing and strengthening the attainments of health sciences laboratory learning goals and outcomes.
Distribution of Microplastics and Nanoplastics in Aquatic Ecosystems and Their Impacts on Aquatic Organisms, with Emphasis on Microalgae

Wan JK, Chu WL, Kok YY, Lee CS

Rev Environ Contam Toxicol, 2018 Jun 06.
PMID: 29872923 DOI: 10.1007/398_2018_14

Plastics, with their many useful physical and chemical properties, are widely used in various industries and activities of daily living. Yet, the insidious effects of plastics, particularly long-term effects on aquatic organisms, are not properly understood. Plastics have been shown to degrade to micro- and nanosize particles known as microplastics and nanoplastics, respectively. These minute particles have been shown to cause various adverse effects on aquatic organisms, ranging from growth inhibition, developmental delay and altered feeding behaviour in aquatic animals to decrease of photosynthetic efficiency and induction of oxidative stress in microalgae. This review paper covers the distribution of microplastics and nanoplastics in aquatic ecosystems, focusing on their effects on microalgae as well as co-toxicity of microplastics and nanoplastics with other pollutants. Besides that, this review paper also discusses future research directions which could be taken to gain a better understanding of the impacts of microplastics and nanoplastics on aquatic ecosystems.
Influence of polystyrene microplastic and nanoplastic on copper toxicity in two freshwater microalgae

Wan JK, Chu WL, Kok YY, Lee CS

Environ Sci Pollut Res Int, 2021 Mar 01.
PMID: 33646549 DOI: 10.1007/s11356-021-12983-x

There has been increasing concern over the toxic effects of microplastics (MP), nanoplastics (NP), and copper (Cu) on microalgae. However, the combined toxicity of the metal in the presence of polystyrene (PS) MP/NP on microalgae has not been well studied, particularly after long-term exposure (i.e., longer than 4 days). The primary aim of the present study was to investigate the effect of PS MP and NP on Cu toxicity on two freshwater microalgae, namely Chlorella sp. TJ6-5 and Pseudokirchneriella subcapitata NIES-35 after acute exposure for 4 days and up to 16 days. The results showed that both microalgae were sensitive to Cu, but tolerant to MP/NP. However, MP/NP increased the toxicity of Cu at EC50 in both microalgae, which was only noticeable in chronic exposure. Single and combined treatment of MP/NP and Cu induced higher oxidative stress and caused morphological and ultrastructural changes in both microalgae. The adsorption of Cu to MP and NP was low (0.23-14.9%), with most of the Cu present in free ionic form (81.6-105.8%). The findings on different sensitivity of microalgae to Cu in the presence of MP/NP may have significant implication as microalgae are likely to be exposed to a mixture of both MP/NP and Cu in the environment. For example, in air-blasting technology, MP and NP are used as abrasive medium to remove Cu-containing antifouling paints on hulls of ship and submerged surfaces. Wastewater treatment plants receive household wastes containing MP and NP, as well as stormwater runoffs and industrial wastes contaminated with heavy metals.
In Situ Gelling Ophthalmic Drug Delivery System: An Overview and Its Applications

Sheshala R, Kok YY, Ng JM, Thakur RR, Dua K

Recent Pat Drug Deliv Formul, 2015;9(3):237-48.
PMID: 26205681

Ophthalmic drug delivery system is very interesting and challenging due to the normal physiologically factor of eyes which reduces the bioavailability of ocular products. The development of new ophthalmic dosage forms for existing drugs to improve efficacy and bioavailability, patient compliance and convenience has become one of the main trend in the pharmaceuticals industry. The present review encompasses various conventional and novel ocular drug delivery systems, methods of preparation, characterization and recent research in this area. Furthermore, the information on various commercially available in situ gel preparations and the existing patents of in situ drug delivery systems i.e. in situ gel formation of pectin, in situ gel for therapeutic use, medical uses of in situ formed gels and in situ gelling systems as sustained delivery for front of eye are also covered in this review.
Green synthesis of graphene-silver nanocomposites and its application as a potent marine antifouling agent

Yee MS, Khiew PS, Chiu WS, Tan YF, Kok YY, Leong CO

Colloids Surf B Biointerfaces, 2016 Dec 01;148:392-401.
PMID: 27639489 DOI: 10.1016/j.colsurfb.2016.09.011

Fouling of marine surfaces has been a perpetual problem ever since the days of the early sailors. The tenacious attachment of seaweed and invertebrates to man-made surfaces, notably on ship hulls, has incurred undesirable economic losses. Graphene receives great attention in the materials world for its unique combination of physical and chemical properties. Herein, we present a novel 2-step synthesis method of graphene-silver nanocomposites which bypasses the formation of graphene oxide (GO), and produces silver nanoparticles supported on graphene sheets through a mild hydrothermal reduction process. The graphene-Ag (GAg) nanocomposite combines the antimicrobial property of silver nanoparticles and the unique structure of graphene as a support material, with potent marine antifouling properties. The GAg nanocomposite was composed of micron-scaled graphene flakes with clusters of silver nanoparticles. The silver nanoparticles were estimated to be between 72 and 86nm (SEM observations) while the crystallite size of the silver nanoparticles (AgNPs) was estimated between 1 and 5nm. The nanocomposite also exhibited the SERS effect. GAg was able to inhibit Halomonas pacifica, a model biofilm-causing microbe, from forming biofilms with as little as 1.3wt.% loading of Ag. All GAg samples displayed significant biofilm inhibition property, with the sample recording the highest Ag loading (4.9wt.% Ag) associated with a biofilm inhibition of 99.6%. Moreover, GAg displayed antiproliferative effects on marine microalgae, Dunaliella tertiolecta and Isochrysis sp. and inhibited the growth of the organisms by more than 80% after 96h. The marine antifouling properties of GAg were a synergy of the biocidal AgNPs anchored on the stable yet flexible graphene sheets, providing maximum active contact surface areas to the target organisms.
Fulltext Anti-tumour promoting activity and antioxidant properties of girinimbine isolated from the stem bark of Murraya koenigii S

Kok YY, Mooi LY, Ahmad K, Sukari MA, Mat N, Rahmani M, et al.

Molecules, 2012 Apr 20;17(4):4651-60.
PMID: 22522395 DOI: 10.3390/molecules17044651

Girinimbine, a carbazole alkaloid isolated from the stem bark of Murraya koenigii was tested for the in vitro anti-tumour promoting and antioxidant activities. Anti-tumour promoting activity was determined by assaying the capability of this compound to inhibit the expression of early antigen of Epstein-Barr virus (EA-EBV) in Raji cells that was induced by the tumour promoter, phorbol 12-myristate 13-acetate. The concentration of this compound that gave an inhibition rate at fifty percent was 6.0 µg/mL and was not cytotoxic to the cells. Immunoblotting analysis of the expression of EA-EBV showed that girinimbine was able to suppress restricted early antigen (EA-R). However, diffused early antigen (EA-D) was partially suppressed when used at 32.0 µg/mL. Girinimbine exhibited a very strong antioxidant activity as compared to a-tocopherol and was able to inhibit superoxide generation in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced differentiated premyelocytic HL-60 cells more than 95%, when treated with the compound at 5.3 and 26.3 µg/mL, respectively. However girinimbine failed to scavenge the stable diphenyl picryl hydrazyl (DPPH)-free radical.
Fulltext Natural Bioactive Compounds from Macroalgae and Microalgae for the Treatment of Alzheimer's Disease: A Review

Lee JY, Wong CY, Koh RY, Lim CL, Kok YY, Chye SM

Yale J Biol Med, 2024 Jun;97(2):205-224.
PMID: 38947104 DOI: 10.59249/JNKB9714

Neuroinflammation, toxic protein aggregation, oxidative stress, and mitochondrial dysfunction are key pathways in neurodegenerative diseases like Alzheimer's disease (AD). Targeting these mechanisms with antioxidants, anti-inflammatory compounds, and inhibitors of Aβ formation and aggregation is crucial for treatment. Marine algae are rich sources of bioactive compounds, including carbohydrates, phenolics, fatty acids, phycobiliproteins, carotenoids, fatty acids, and vitamins. In recent years, they have attracted interest from the pharmaceutical and nutraceutical industries due to their exceptional biological activities, which include anti-inflammation, antioxidant, anticancer, and anti-apoptosis properties. Multiple lines of evidence have unveiled the potential neuroprotective effects of these multifunctional algal compounds for application in treating and managing AD. This article will provide insight into the molecular mechanisms underlying the neuroprotective effects of bioactive compounds derived from algae based on in vitro and in vivo models of neuroinflammation and AD. We will also discuss their potential as disease-modifying and symptomatic treatment strategies for AD.
Fulltext Educational resource for antimicrobial resistance and stewardship for dentistry programmes: a research protocol

Ang CY, Dhaliwal JS, Muharram SH, Akkawi ME, Hussain Z, Rahman H, et al.

BMJ Open, 2021 07 07;11(7):e048609.
PMID: 34233993 DOI: 10.1136/bmjopen-2021-048609

INTRODUCTION: Antimicrobial resistance (AMR) is a global public and patient safety issue. With the high AMR risk, ensuring that the next generation of dentists that have optimal knowledge and confidence in the area of AMR is crucial. A systematic approach is vital to design an AMR content that is comprehensive and clinically relevant. The primary objective of this research study will be to implement a consensus-based approach to elucidate AMR content and curriculum priorities for professional dentistry programmes. This research aims to establish consensus along with eliciting opinion on appropriate AMR topics to be covered in the Bachelor of Dental Surgery syllabus.
METHODS AND ANALYSIS: A three-phase approach to validate content for curriculum guidelines on AMR will be adopted. First, literature review and content analysis were conducted to find out the available pertinent literature in dentistry programmes. A total of 23 potential literature have been chosen for inclusion within this study following literature review and analysis in phase 1. The materials found will be used to draft curriculum on antimicrobials for dentistry programmes. The next phase involves the validation of the drafted curriculum content by recruiting local and foreign experts via a survey questionnaire. Finally, Delphi technique will be conducted to obtain consensus on the important or controversial modifications to the revised curriculum.
ETHICS AND DISSEMINATION: An ethics application is currently under review with the Institute of Health Science Research Ethics Committee, Universiti Brunei Darussalam. All participants are required to provide a written consent form. Findings will be used to identify significant knowledge gaps on AMR aspect in a way that results in lasting change in clinical practice. Moreover, AMR content priorities related to dentistry clinical practice will be determined in order to develop need-based educational resource on microbes, hygiene and prudent antimicrobial use for dentistry programmes.
Fulltext Impact of Microplastics and Nanoplastics on Human Health

Yee MS, Hii LW, Looi CK, Lim WM, Wong SF, Kok YY, et al.

Nanomaterials (Basel), 2021 Feb 16;11(2).
PMID: 33669327 DOI: 10.3390/nano11020496

Plastics have enormous impacts to every aspect of daily life including technology, medicine and treatments, and domestic appliances. Most of the used plastics are thrown away by consumers after a single use, which has become a huge environmental problem as they will end up in landfill, oceans and other waterways. These plastics are discarded in vast numbers each day, and the breaking down of the plastics from micro- to nano-sizes has led to worries about how toxic these plastics are to the environment and humans. While, there are several earlier studies reported the effects of micro- and nano-plastics have on the environment, there is scant research into their impact on the human body at subcellular or molecular levels. In particular, the potential of how nano-plastics move through the gut, lungs and skin epithelia in causing systemic exposure has not been examined thoroughly. This review explores thoroughly on how nanoplastics are created, how they behave/breakdown within the environment, levels of toxicity and pollution of these nanoplastics, and the possible health impacts on humans, as well as suggestions for additional research. This paper aims to inspire future studies into core elements of micro- and nano-plastics, the biological reactions caused by their specific and unusual qualities.
Fulltext Potential Application of Algae in Biodegradation of Phenol: A Review and Bibliometric Study

Radziff SBM, Ahmad SA, Shaharuddin NA, Merican F, Kok YY, Zulkharnain A, et al.

Plants (Basel), 2021 Dec 06;10(12).
PMID: 34961148 DOI: 10.3390/plants10122677

One of the most severe environmental issues affecting the sustainable growth of human society is water pollution. Phenolic compounds are toxic, hazardous and carcinogenic to humans and animals even at low concentrations. Thus, it is compulsory to remove the compounds from polluted wastewater before being discharged into the ecosystem. Biotechnology has been coping with environmental problems using a broad spectrum of microorganisms and biocatalysts to establish innovative techniques for biodegradation. Biological treatment is preferable as it is cost-effective in removing organic pollutants, including phenol. The advantages and the enzymes involved in the metabolic degradation of phenol render the efficiency of microalgae in the degradation process. The focus of this review is to explore the trends in publication (within the year of 2000-2020) through bibliometric analysis and the mechanisms involved in algae phenol degradation. Current studies and publications on the use of algae in bioremediation have been observed to expand due to environmental problems and the versatility of microalgae. VOSviewer and SciMAT software were used in this review to further analyse the links and interaction of the selected keywords. It was noted that publication is advancing, with China, Spain and the United States dominating the studies with total publications of 36, 28 and 22, respectively. Hence, this review will provide an insight into the trends and potential use of algae in degradation.
Fulltext Protocol for a three-phase prospective study to develop educational resource of antimicrobial resistance and stewardship for medical programme

Dhaliwal JS, Mohamad Yusra MAM, Muharram SH, Akkawi ME, Hussain Z, Rahman H, et al.

BMJ Open, 2022 Feb 28;12(2):e049867.
PMID: 35228275 DOI: 10.1136/bmjopen-2021-049867

INTRODUCTION: Antimicrobial resistance (AMR) is one of the critical medical issues of the 21st century. Medical professionals are the primary prescribers of antimicrobials; their undergraduate education of antimicrobial stewardship (AMS) is considered one of the fundamental approaches in combating the issue of AMR. This education level provides a platform to bridge any gaps in their knowledge and competency in AMS. This study aims to develop an educational resource on microbes, hygiene and prudent antimicrobial use for the undergraduate medical programme. The guideline produced will then be assimilated into the existing curriculum which will help to improve the quality of education which in turn will improve rationale as the use of antimicrobials in the future.
METHODS AND ANALYSIS: A three-step approach consensus approach will be adopted for this study for the development of a validated medical curriculum guideline on AMR. A preliminary curriculum for the programme will be drafted from reviews of published literature including syllabi as well as national and international guidelines. A total of 26 potential sources were found to be relevant, and selected for this study. Subsequently, the drafted curriculum will be subjected for validation via online surveys by various infectious disease experts. Finally, a Delphi technique will be employed to obtain consensus on heterogeneous findings to the revised curriculum. The quantitative and qualitative responses will be analysed and discussed among the panel of researchers.
ETHICS AND DISSEMINATION: This study protocol has been approved by the Institute of Health Sciences Research Ethics Committee of Universiti Brunei Darussalam (Reference: UBD/PAPRSBIHSREC/2020/124). Informed consent declaration will be collected prior to data collections as indication of agreement of participation in the study. Results will be made available to medical educators and also researchers on AMR and stewardship. The results also will be disseminated at feedback sessions to officers at Ministry of Health and Ministry of Education, Brunei Darussalam.
Fulltext Inhibitory activities of microalgal extracts against Epstein-Barr virus DNA release from lymphoblastoid cells

Kok YY, Chu WL, Phang SM, Mohamed SM, Naidu R, Lai PJ, et al.

J Zhejiang Univ Sci B, 2011 May;12(5):335-45.
PMID: 21528487 DOI: 10.1631/jzus.B1000336

This study aimed to assess the inhibitory activities of methanol extracts from the microalgae Ankistrodesmus convolutus, Synechococcus elongatus, and Spirulina platensis against Epstein-Barr virus (EBV) in three Burkitt's lymphoma (BL) cell lines, namely Akata, B95-8, and P3HR-1. The antiviral activity was assessed by quantifying the cell-free EBV DNA using real-time polymerase chain reaction (PCR) technique. The methanol extracts from Ankistrodesmus convolutus and Synechococcus elongatus displayed low cytotoxicity and potent effect in reducing cell-free EBV DNA (EC(50)<0.01 µg/ml) with a high therapeutic index (>28000). After fractionation by column chromatography, the fraction from Synechococcus elongatus (SEF1) reduced the cell-free EBV DNA most effectively (EC(50)=2.9 µg/ml, therapeutic index>69). Upon further fractionation by high performance liquid chromatography (HPLC), the sub-fraction SEF1'a was most active in reducing the cell-free EBV DNA (EC(50)=1.38 µg/ml, therapeutic index>14.5). This study suggests that microalgae could be a potential source of antiviral compounds that can be used against EBV.

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