Displaying publications 1 - 20 of 69 in total

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  1. Tan KE, Ng WL, Marinov GK, Yu KH, Tan LP, Liau ES, et al.
    Sci Rep, 2021 Jul 13;11(1):14392.
    PMID: 34257379 DOI: 10.1038/s41598-021-93781-w
    Epstein-Barr virus (EBV) has been recently found to generate novel circular RNAs (circRNAs) through backsplicing. However, comprehensive catalogs of EBV circRNAs in other cell lines and their functional characterization are still lacking. In this study, we have identified a list of putative EBV circRNAs in GM12878, an EBV-transformed lymphoblastoid cell line, with a significant majority encoded from the EBV latent genes. A novel EBV circRNA derived from the exon 5 of LMP-2 gene which exhibited highest prevalence, was further validated using RNase R assay and Sanger sequencing. This circRNA, which we term circLMP-2_e5, can be universally detected in a panel of EBV-positive cell lines modelling different latency programs. It ranges from lower expression in nasopharyngeal carcinoma (NPC) cells to higher expression in B cells, and is localized to both the cytoplasm and the nucleus. We provide evidence that circLMP-2_e5 is expressed concomitantly with its cognate linear LMP-2 RNA upon EBV lytic reactivation, and may be produced as a result of exon skipping, with its circularization possibly occurring without the involvement of cis elements in the short flanking introns. Furthermore, we show that circLMP-2_e5 is not involved in regulating cell proliferation, host innate immune response, its linear parental transcripts, or EBV lytic reactivation. Taken together, our study expands the current repertoire of putative EBV circRNAs, broadens our understanding of the biology of EBV circRNAs, and lays the foundation for further investigation of their function in the EBV life cycle and disease development.
  2. Ten LC, Chin YM, Tai MC, Chin EF, Lim YY, Suthandiram S, et al.
    Sci Rep, 2017 01 31;7:41400.
    PMID: 28139690 DOI: 10.1038/srep41400
    Large consortia efforts and genome-wide association studies (GWASs) have linked a number of genetic variants within the 6p21 chromosomal region to non-Hodgkin lymphoma (NHL). Complementing these efforts, we genotyped previously reported SNPs in the human leukocyte antigen (HLA) class I (rs6457327) and class II (rs9271100, rs2647012 and rs10484561) regions in a total of 1,145 subjects (567 NHL cases and 578 healthy controls) from two major ethnic groups in Malaysia, the Malays and the Chinese. We identified a NHL-associated (PNHL_add = 0.0008; ORNHL_add = 0.54; 95% CI = 0.37-0.77) and B-cell associated (PBcell_add = 0.0007; ORBcell_add = 0.51; 95% CI = 0.35-0.76) SNP rs2647012 in the Malaysian Malays. In silico cis-eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. Minor allele rs2647012-T is linked to higher expression of HLA-DQB1, rendering a protective effect to NHL risk. Our findings suggest that the HLA class II region plays an important role in NHL etiology.
  3. Yu KH, Shi CH, Wang B, Chow SH, Chung GT, Lung RW, et al.
    Genome Res, 2021 Dec;31(12):2340-2353.
    PMID: 34663689 DOI: 10.1101/gr.275348.121
    Circular RNAs (circRNAs) are abundantly expressed in cancer. Their resistance to exonucleases enables them to have potentially stable interactions with different types of biomolecules. Alternative splicing can create different circRNA isoforms that have different sequences and unequal interaction potentials. The study of circRNA function thus requires knowledge of complete circRNA sequences. Here we describe psirc, a method that can identify full-length circRNA isoforms and quantify their expression levels from RNA sequencing data. We confirm the effectiveness and computational efficiency of psirc using both simulated and actual experimental data. Applying psirc on transcriptome profiles from nasopharyngeal carcinoma and normal nasopharynx samples, we discover and validate circRNA isoforms differentially expressed between the two groups. Compared with the assumed circular isoforms derived from linear transcript annotations, some of the alternatively spliced circular isoforms have 100 times higher expression and contain substantially fewer microRNA response elements, showing the importance of quantifying full-length circRNA isoforms.
  4. Lim YY, Chin YM, Tai MC, Fani S, Chang KM, Ong TC, et al.
    Leuk Lymphoma, 2015 Jan;56(1):163-8.
    PMID: 24684230 DOI: 10.3109/10428194.2014.907895
    We evaluated the association of two IL10 single nucleotide polymorphisms (SNPs) (rs1800896 and rs1800871) with non-Hodgkin lymphoma (NHL) risk in the three major races of the Malaysian population (Malay, Chinese and Indian; 317 cases and 330 controls). Our initial screening demonstrated that rs1800871 but not rs1800896 was significantly associated with increased NHL risk in Malays (pMalay-Rec = 0.007) and Chinese only (pChinese-Rec = 0.039). Subsequent combined analysis of the Malay and Chinese revealed significant association of rs1800871 with all (ALL) NHL subtypes (pMeta-ALL-NHL-Rec = 0.001), ALL B-cell subtypes (pMeta-ALL-B-cell-Rec = 0.003), diffuse large B-cell lymphoma (DLBCL) subtype (pMeta-DLBCL-Rec = 0.002) and ALL T-cell subtypes (pMeta-ALL-T-cell-Rec = 0.031). SNP rs1800896 showed increased risk only in follicular lymphoma (FL) (pMeta-FL-Dom = 0.0004). We also detected a male-specific association of rs1800871 with increased NHL risk (pMeta-Male-ALL-NHL-Rec = 0.006) in the combined analysis. To our knowledge, this is the first report on the association of IL10 promoter SNPs with NHL susceptibility in the three major races of Malaysia.
  5. Yeo KS, Tan MC, Wong WY, Loh SW, Lam YL, Tan CL, et al.
    Sci Rep, 2016 Sep 27;6:34125.
    PMID: 27671354 DOI: 10.1038/srep34125
    TNF-induced signaling mediates pleiotropic biological consequences including inflammation, immunity, cell proliferation and apoptosis. Misregulation of TNF signaling has been attributed as a major cause of chronic inflammatory diseases and cancer. Jumonji domain-containing protein 8 (JMJD8) belongs to the JmjC family. However, only part of the family members has been described as hydroxylase enzymes that function as histone demethylases. Here, we report that JMJD8 positively regulates TNF-induced NF-κB signaling. Silencing the expression of JMJD8 using RNA interference (RNAi) greatly suppresses TNF-induced expression of several NF-κB-dependent genes. Furthermore, knockdown of JMJD8 expression reduces RIP ubiquitination, IKK kinase activity, delays IκBα degradation and subsequently blocks nuclear translocation of p65. In addition, JMJD8 deficiency enhances TNF-induced apoptosis. Taken together, these findings indicate that JMJD8 functions as a positive regulator of TNF-induced NF-κB signaling.
  6. Tan MC, Wong WY, Ng WL, Yeo KS, Mohidin TB, Lim YY, et al.
    PLoS One, 2017;12(1):e0170352.
    PMID: 28114392 DOI: 10.1371/journal.pone.0170352
    Influenza virus is estimated to cause 3-5 million severe complications and about 250-500 thousand deaths per year. Different kinds of anti-influenza virus drugs have been developed. However, the emergence of drug resistant strains has presented a big challenge for efficient antiviral therapy. Indole derivatives have been shown to exhibit both antiviral and anti-inflammatory activities. In this study, we adopted a cell-based system to screen for potential anti-IAV agents. Four indole derivatives (named 525A, 526A, 527A and 528A) were subjected to the antiviral screening, of which 526A was selected for further investigation. We reported that pre-treating cells with 526A protects cells from IAV infection. Furthermore, 526A inhibits IAV replication by inhibiting the expression of IAV genes. Interestingly, 526A suppresses the activation of IRF3 and STAT1 in host cells and thus represses the production of type I interferon response and cytokines in IAV-infected cells. Importantly, 526A also partially blocks the activation of RIG-I pathway. Taken together, these results suggest that 526A may be a potential anti-influenza A virus agent.
  7. Chew YL, Lim YY, Stanslas J, Ee GC, Goh JK
    PMID: 25371595
    BACKGROUND: Flowers of Bauhinia kockiana were investigated for their anticancer properties.

    METHODS: Gallic acid (1), and methyl gallate (2), were isolated via bioassay-directed isolation, and they exhibited anticancer properties towards several cancer cell lines, examined using MTT cell viability assay. Pyrogallol (3) was examined against the same cancer cell lines to deduce the bioactive functional group of the phenolic compounds.

    RESULTS: The results showed that the phenolic compounds could exhibit moderate to weak cytotoxicity towards certain cell lines (GI50 30 - 86 µM), but were inactive towards DU145 prostate cancer cell (GI50 > 100 µM).

    CONCLUSION: It was observed that pyrogallol moiety was one of the essential functional structures of the phenolic compounds in exhibiting anticancer activity. Also, the carboxyl group of compound 1 was also important in anticancer activity. Examination of the PC-3 cells treated with compound 1 using fluorescence microscopy showed that PC-3 cells were killed by apoptosis.

  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.

  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.

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