Displaying publications 41 - 60 of 181 in total

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  1. Fulltext Water extract of brewers' rice induces apoptosis in human colorectal cancer cells via activation of caspase-3 and caspase-8 and downregulates the Wnt/β-catenin downstream signaling pathway in brewers' rice-treated rats with azoxymethane-induced colon carcinogenesis
    Tan BL, Norhaizan ME, Huynh K, Heshu SR, Yeap SK, Hazilawati H, et al.
    BMC Complement Altern Med, 2015;15:205.
    PMID: 26122204 DOI: 10.1186/s12906-015-0730-4
    Brewers' rice, is locally known as temukut, is a mixture of broken rice, rice bran, and rice germ. The current study is an extension of our previous work, which demonstrated that water extract of brewers' rice (WBR) induced apoptosis in human colorectal cancer (HT-29) cells. We also identified that brewers' rice was effective in reducing the tumor incidence and multiplicity in azoxymethane (AOM)-injected colon cancer rats. Our present study was designed to identify whether WBR confers an inhibitory effect via the regulation of upstream components in the Wnt signaling pathway in HT-29 cells. To further determine whether the in vitro mechanisms of action observed in the HT-29 cells inhibit the downstream signaling target of the Wnt/β-catenin pathway, we evaluated the mechanistic action of brewers' rice in regulating the expressions and key protein markers during colon carcinogenesis in male Sprague-Dawley rats.
  2. Fulltext Potential recombinant vaccine against influenza A virus based on M2e displayed on nodaviral capsid nanoparticles
    Yong CY, Yeap SK, Ho KL, Omar AR, Tan WS
    Int J Nanomedicine, 2015;10:2751-63.
    PMID: 25897220 DOI: 10.2147/IJN.S77405
    Influenza A virus poses a major threat to human health, causing outbreaks from time to time. Currently available vaccines employ inactivated viruses of different strains to provide protection against influenza virus infection. However, high mutation rates of influenza virus hemagglutinin (H) and neuraminidase (N) glycoproteins give rise to vaccine escape mutants. Thus, an effective vaccine providing protection against all strains of influenza virus would be a valuable asset. The ectodomain of matrix 2 protein (M2e) was found to be highly conserved despite mutations of the H and N glycoproteins. Hence, one to five copies of M2e were fused to the carboxyl-terminal end of the recombinant nodavirus capsid protein derived from Macrobrachium rosenbergii. The chimeric proteins harboring up to five copies of M2e formed nanosized virus-like particles approximately 30 nm in diameter, which could be purified easily by immobilized metal affinity chromatography. BALB/c mice immunized subcutaneously with these chimeric proteins developed antibodies specifically against M2e, and the titer was proportional to the copy numbers of M2e displayed on the nodavirus capsid nanoparticles. The fusion proteins also induced a type 1 T helper immune response. Collectively, M2e displayed on the nodavirus capsid nanoparticles could provide an alternative solution to a possible influenza pandemic in the future.
  3. Fulltext Infectious hematopoietic necrosis virus: advances in diagnosis and vaccine development
    Yong CY, Ong HK, Tang HC, Yeap SK, Omar AR, Ho KL, et al.
    PeerJ, 2019;7:e7151.
    PMID: 31341728 DOI: 10.7717/peerj.7151
    The aquaculture of salmonid fishes is a multi-billion dollar industry with production over 3 million tons annually. However, infectious hematopoietic necrosis virus (IHNV), which infects and kills salmon and trout, significantly reduces the revenue of the salmon farming industry. Currently, there is no effective treatment for IHNV infected fishes; therefore, early detection and depopulation of the infected fishes remain the most common practices to contain the spread of IHNV. Apart from hygiene practices in aquaculture and isolation of infected fishes, loss of fishes due to IHNV infection can also be significantly reduced through vaccination programs. In the current review, some of the diagnostic methods for IHNV, spanning from clinical diagnosis to cell culture, serological and molecular methods are discussed in detail. In addition, some of the most significant candidate vaccines for IHNV are also extensively discussed, particularly the DNA vaccines.
  4. Fulltext An Influenza A Vaccine Based on the Extracellular Domain of Matrix 2 Protein Protects BALB/C Mice Against H1N1 and H3N2
    Ong HK, Yong CY, Tan WS, Yeap SK, Omar AR, Razak MA, et al.
    Vaccines (Basel), 2019 08 19;7(3).
    PMID: 31430965 DOI: 10.3390/vaccines7030091
    Current seasonal influenza A virus (IAV) vaccines are strain-specific and require annual reconstitution to accommodate the viral mutations. Mismatches between the vaccines and circulating strains often lead to high morbidity. Hence, development of a universal influenza A vaccine targeting all IAV strains is urgently needed. In the present study, the protective efficacy and immune responses induced by the extracellular domain of Matrix 2 protein (M2e) displayed on the virus-like particles of Macrobrachium rosenbergii nodavirus (NvC-M2ex3) were investigated in BALB/c mice. NvC-M2ex3 was demonstrated to be highly immunogenic even in the absence of adjuvants. Higher anti-M2e antibody titers corresponded well with increased survival, reduced immunopathology, and morbidity of the infected BALB/c mice. The mice immunized with NvC-M2ex3 exhibited lower H1N1 and H3N2 virus replication in the respiratory tract and the vaccine activated the production of different antiviral cytokines when they were challenged with H1N1 and H3N2. Collectively, these results suggest that NvC-M2ex3 could be a potential universal influenza A vaccine.
  5. Fulltext Targeted inactivation of Salmonella Agona metabolic genes by group II introns and in vivo assessment of pathogenicity and anti-tumour activity in mouse model
    Gwee CP, Khoo CH, Yeap SK, Tan GC, Cheah YK
    PeerJ, 2019;7:e5989.
    PMID: 30671294 DOI: 10.7717/peerj.5989
    The fight against cancer has been a never-ending battle. Limitations of conventional therapies include lack of selectivity, poor penetration and highly toxic to the host. Using genetically modified bacteria as a tumour therapy agent has gained the interest of scientist from the past few decades. Low virulence and highly tolerability of Salmonella spp. in animals and humans make it as the most studied pathogen with regards to anti-tumour therapy. The present study aims to construct a genetically modified S. Agona auxotroph as an anti-tumour agent. LeuB and ArgD metabolic genes in ΔSopBΔSopD double knockout S. Agona were successfully knocked out using a Targetron gene knockout system. The knockout was confirmed by colony PCR and the strains were characterized in vitro and in vivo. The knockout of metabolic genes causes significant growth defect in M9 minimal media. Quadruple knockout ΔSopBΔSopDΔLeuBΔArgD (BDLA) exhibited lowest virulence among all of the strains in all parameters including bacterial load, immunity profile and histopathology studies. In vivo anti-tumour study on colorectal tumour bearing-BALB/c mice revealed that all strains of S. Agona were able to suppress the growth of the large solid tumour as compared with negative control and ΔLeuBΔArgD (LA) and BDLA auxotroph showed better efficacy. Interestingly, higher level of tumour growth suppression was noticed in large tumour. However, multiple administration of bacteria dosage did not increase the tumour suppression efficacy. In this study, the virulence of BDLA knockout strain was slightly reduced and tumour growth suppression efficacy was successfully enhanced, which provide a valuable starting point for the development of S. Agona as anti-tumour agent.
  6. Fulltext Transcriptome analysis of chicken intraepithelial lymphocyte natural killer cells infected with very virulent infectious bursal disease virus
    Boo SY, Tan SW, Alitheen NB, Ho CL, Omar AR, Yeap SK
    Sci Rep, 2020 10 27;10(1):18348.
    PMID: 33110122 DOI: 10.1038/s41598-020-75340-x
    The infectious bursal disease (IBD) is an acute immunosuppressive viral disease that significantly affects the economics of the poultry industry. The IBD virus (IBDV) was known to infect B lymphocytes and activate macrophage and T lymphocytes, but there are limited studies on the impact of IBDV infection on chicken intraepithelial lymphocyte natural killer (IEL-NK) cells. This study employed an mRNA sequencing approach to investigate the early regulation of gene expression patterns in chicken IEL-NK cells after infection with very virulent IBDV strain UPM0081. A total of 12,141 genes were expressed in uninfected chicken IEL-NK cells, and most of the genes with high expression were involved in the metabolic pathway, whereas most of the low expressed genes were involved in the cytokine-cytokine receptor pathway. A total of 1,266 genes were differentially expressed (DE) at 3 day-post-infection (dpi), and these DE genes were involved in inflammation, antiviral response and interferon stimulation. The innate immune response was activated as several genes involved in inflammation, antiviral response and recruitment of NK cells to the infected area were up-regulated. This is the first study to examine the whole transcriptome profile of chicken NK cells towards IBDV infection and provides better insight into the early immune response of chicken NK cells.
  7. Fulltext In Vitro Evaluation of Curcumin-Encapsulated Chitosan Nanoparticles against Feline Infectious Peritonitis Virus and Pharmacokinetics Study in Cats
    Ng SW, Selvarajah GT, Hussein MZ, Yeap SK, Omar AR
    Biomed Res Int, 2020;2020:3012198.
    PMID: 32596292 DOI: 10.1155/2020/3012198
    Feline infectious peritonitis (FIP) is an important feline viral disease, causing an overridden inflammatory response that results in a high mortality rate, primarily in young cats. Curcumin is notable for its biological activities against various viral diseases; however, its poor bioavailability has hindered its potential in therapeutic application. In this study, curcumin was encapsulated in chitosan nanoparticles to improve its bioavailability. Curcumin-encapsulated chitosan (Cur-CS) nanoparticles were synthesised based on the ionic gelation technique and were spherical and cuboidal in shape, with an average particle size of 330 nm and +42 mV in zeta potential. The nanoparticles exerted lower toxicity in Crandell-Rees feline kidney (CrFK) cells and enhanced antiviral activities with a selective index (SI) value three times higher than that of curcumin. Feline-specific bead-based multiplex immunoassay and qPCR were used to examine their modulatory effects on proinflammatory cytokines, including tumour necrosis factor (TNF)α, interleukin- (IL-) 6, and IL-1β. There were significant decrements in IL-1β, IL-6, and TNFα expression in both curcumin and Cur-CS nanoparticles. Based on the multiplex immunoassay, curcumin and the Cur-CS nanoparticles could lower the immune-related proteins in FIP virus (FIPV) infection. The single- and multiple-dose pharmacokinetics profiles of curcumin and the Cur-CS nanoparticles were determined by high-performance liquid chromatography (HPLC). Oral delivery of the Cur-CS nanoparticles to cats showed enhanced bioavailability with a maximum plasma concentration (Cmax) value of 621.5 ng/mL. Incorporating chitosan nanoparticles to deliver curcumin improved the oral bioavailability and antiviral effects of curcumin against FIPV infection. This study provides evidence for the potential of Cur-CS nanoparticles as a supplementary treatment of FIP.
  8. Functionalizing TiO2 with graphene oxide for enhancing photocatalytic degradation of methylene blue (MB) in contaminated wastewater
    Kurniawan TA, Mengting Z, Fu D, Yeap SK, Othman MHD, Avtar R, et al.
    J Environ Manage, 2020 Sep 15;270:110871.
    PMID: 32721315 DOI: 10.1016/j.jenvman.2020.110871
    Methylene blue is a refractory pollutant commonly present in textile wastewater. This study tests the feasibility of TiO2/graphene oxide (GO) composite in enhancing photocatalytic degradation of MB in synthetic wastewater with respect to scientific and engineering aspects. To enhance its removal, we vary the composition of the composite based on the TiO2 weight. Under UV-vis irradiation, the effects of photocatalyst's dose, pH, and reaction time on MB removal by the composites are evaluated under optimum conditions, while any changes in their physico-chemical properties before and after treatment are analyzed by using TEM, SEM, XRD, FTIR and BET. The photodegradation pathways of the target pollutant by the composite and its removal mechanisms are also elaborated. It is found that the same composite with a 1:2 wt ratio of GO/TiO2 has the largest surface area of 104.51 m2/g. Under optimum reactions (0.2 g/L of dose, pH 10, and 5 mg/L of pollutant's concentration), an almost complete MB removal could be attained within 4 h. This result is higher than that of the TiO2 alone (30%) under the same conditions. Since the treated effluents could meet the strict discharge standard limit of ≤0.2 μg/L set by China's regulation, subsequent biological treatments are unnecessary for completing biodegradation of remaining oxidation by-products in the wastewater effluents.
  9. In vitro characterization of chicken bone marrow-derived dendritic cells following infection with very virulent infectious bursal disease virus
    Yasmin AR, Yeap SK, Tan SW, Hair-Bejo M, Fakurazi S, Kaiser P, et al.
    Avian Pathol, 2015;44(6):452-62.
    PMID: 26305169 DOI: 10.1080/03079457.2015.1084997
    Infectious bursal disease is caused by infectious bursal disease virus (IBDV), an immunosuppressive virus that targets immune cells such as B cells and macrophages. However, the involvement of dendritic cells (DCs) during IBDV infection is not well understood. In this study the in vitro effects of live and inactivated very virulent IBDV (vvIBDV) UPM0081 on bone marrow-derived DCs (BM-DC) were characterized and compared with BM-DC treated with lipopolysaccharide (LPS). Morphologically, BM-DC treated with LPS and vvIBDV showed stellate shape when compared to immature BM-DC. In addition, LPS-treated and both live and inactivated vvIBDV-infected BM-DC expressed high levels of double positive CD86 and major histocompatibility complex class II antigens (>20%). vvIBDV-infected BM-DC showed significantly higher numbers of apoptotic cells compared to LPS. Replication of vvIBDV was detected in the infected BM-DC as evidenced by the increased expression of VP3 and VP4 IBDV antigens based on flow cytometry, real-time polymerase chain reaction and immunofluorescence tests. Levels of different immune-related genes such as interleukin-1β (IL-1β), CXCLi2 (IL-8), IL-18, interferon gamma (IFN-γ, IL-12α, CCR7 and Toll-like receptor-3 (TLR3) were measured after LPS and vvIBDV treatments. However, marked differences were noticed in the onset and intensity of the gene expression between these two treatment groups. LPS was far more potent than live and inactivated vvIBDV in inducing the expression of IL-1β, IL-18 and CCR7 while expression of Th1-like cytokines, IFN-γ and IL-12α were significantly increased in the live vvIBDV treatment group. Meanwhile, the expression of TLR3 was increased in live vvIBDV-infected BM-DC as compared to control. Inactivated vvIBDV-treated BM-DC failed to stimulate IFN-γ, IL-12α and TLR3 expressions. This study suggested that BM-DC may serve as another target cells during IBDV infection which require further confirmation via in vivo studies.
  10. Fulltext Pressurized hot water extraction of hydrosable tannins from Phyllanthus tenellus Roxb
    Mohd Jusoh NH, Subki A, Yeap SK, Yap KC, Jaganath IB
    BMC Chem, 2019 Dec;13(1):134.
    PMID: 31891160 DOI: 10.1186/s13065-019-0653-0
    Background: Safety, environmental and economic setbacks are driving industries to find greener approaches to extract bioactive compounds from natural resources. Pressurized hot water extraction (PHWE) is among the solvent free and efficient methods for extracting bioactive compounds.

    Experimental: In this study, the suitability of PHWE for extracting bioactive compounds such as phenolics, hydrolysable tannins and flavonoids from Phyllanthus tenellus was investigated by UPLC-qTOF-MS.

    Results: Solvent properties of water are significantly increased through imposing temperature at 121 °C and pressure at 15 p.s.i. Pressurized hot water extraction obtained 991-folds higher hydrolysable tannins than methanol extraction.

    Conclusion: The extraction yields of hydrolysable tannins with PHWE was almost double of absolute methanol extraction.

  11. Fulltext Brewers' rice modulates oxidative stress in azoxymethane-mediated colon carcinogenesis in rats
    Tan BL, Norhaizan ME, Huynh K, Yeap SK, Hazilawati H, Roselina K
    World J Gastroenterol, 2015 Aug 7;21(29):8826-35.
    PMID: 26269672 DOI: 10.3748/wjg.v21.i29.8826
    To investigate the mechanistic action of brewers' rice in regulating the Wnt/nuclear factor-kappa B (NF-κB)/Nrf2-signaling pathways during colon carcinogenesis in male Sprague-Dawley rats.
  12. Fulltext Protective efficacy of inactivated Newcastle disease virus vaccines prepared in two different oil-based adjuvants
    Aljumaili OA, Bello MB, Yeap SK, Omar AR, Ideris A
    Onderstepoort J Vet Res, 2020 Sep 28;87(1):e1-e7.
    PMID: 33054260 DOI: 10.4102/ojvr.v87i1.1865
    Despite the availability of Newcastle disease (ND) vaccines for more than six decades, disease outbreaks continue to occur with huge economic consequences to the global poultry industry. The aim of this study is to develop a safe and effective inactivated vaccine based on a recently isolated Newcastle disease virus (NDV) strain IBS025/13 and evaluate its protective efficacy in chicken following challenge with a highly virulent genotype VII isolate. Firstly, high titre of IBS025/13 was exposed to various concentrations of binary ethylenimine (BEI) to determine the optimal conditions for complete inactivation of the virus. The inactivated virus was then prepared in form of a stable water-in-oil emulsion of black seed oil (BSO) or Freund's incomplete adjuvant (FIA) and used as vaccines in specific pathogen-free chicken. Efficacy of various vaccine preparations was also evaluated based on the ability of the vaccine to protect against clinical disease, mortality and virus shedding following challenge with highly virulent genotype\VII NDV isolate. The results indicate that exposure of NDV IBS025/13 to 10 mM of BEI for 21 h at 37 °C could completely inactivate the virus without tempering with the structural integrity of the viral hemagglutin-neuraminidase protein. More so, the inactivated vaccines adjuvanted with either BSO- or FIA-induced high hemagglutination inhibition antibody titre that protected the vaccinated birds against clinical disease and in some cases virus shedding, especially when used together with live attenuated vaccines. Thus, genotype VII-based NDV-inactivated vaccines formulated in BSO could substantially improve poultry disease control particularly when combined with live attenuated vaccines.
  13. Fulltext Identification of Reference Genes in Chicken Intraepithelial Lymphocyte Natural Killer Cells Infected with Very-virulent Infectious Bursal Disease Virus
    Boo SY, Tan SW, Alitheen NB, Ho CL, Omar AR, Yeap SK
    Sci Rep, 2020 05 22;10(1):8561.
    PMID: 32444639 DOI: 10.1038/s41598-020-65474-3
    Due to the limitations in the range of antibodies recognising avian viruses, quantitative real-time PCR (RT-qPCR) is still the most widely used method to evaluate the expression of immunologically related genes in avian viruses. The objective of this study was to identify suitable reference genes for mRNA expression analysis in chicken intraepithelial lymphocyte natural killer (IEL-NK) cells after infection with very-virulent infectious bursal disease virus (vvIBDV). Fifteen potential reference genes were selected based on the references available. The coefficient of variation percentage (CV%) and average count of these 15 genes were determined by NanoString technology for control and infected samples. The M and V values for shortlisted reference genes (ACTB, GAPDH, HMBS, HPRT1, SDHA, TUBB1 and YWHAZ) were calculated using geNorm and NormFinder. GAPDH, YWHAZ and HMBS were the most stably expressed genes. The expression levels of three innate immune response related target genes, CASP8, IL22 and TLR3, agreed in the NanoString and RNA sequencing (RNA-Seq) results using one or two reference genes for normalisation (not HMBS). In conclusion, GAPDH and YWHAZ could be used as reference genes for the normalisation of chicken IEL-NK cell gene responses to infection with vvIBDV.
  14. Quantitative Proteomics Analysis Revealed Compromised Chicken Dendritic Cells Function at Early Stage of Very Virulent Infectious Bursal Disease Virus Infection
    Yasmin AR, Omar AR, Farhanah MI, Hiscox AJ, Yeap SK
    Avian Dis, 2019 06 01;63(2):275-288.
    PMID: 31251527 DOI: 10.1637/11936-072418-Reg.1
    Chicken dendritic cells (DCs) have been demonstrated to be susceptible to infectious bursal disease virus (IBDV), a causative agent of acute and immunosuppressed disease in young chicks known as infectious bursal disease. Further functional characterization of IBDV-infected DCs of chickens is required to provide a better understanding on the influence of the virus on chicken bone marrow-derived dendritic cells (BM-DCs) following very virulent (vv) IBDV infection. Membrane proteins of BM-DCs were extracted and the proteins were further denatured and reduced before performing labeling with isobaric tags for relative and absolute quantitation. The differential expression protein profiles were identified and quantified using liquid chromatography coupled with tandem mass spectrometry, and later validated using flow cytometry and real-time reverse transcriptase PCR. The analysis has identified 134 differentially regulated proteins from a total of 283 proteins (cutoff values of ≤0.67, ≥1.5, and ProtScore >1.3 at 95% confidence interval), which produced high-yield membrane fractions. The entry of vvIBDV into the plasma membrane of BM-DCs was observed at 3 hr postinfection by the disruption of several important protein molecule functions, namely apoptosis, RNA/DNA/protein synthesis, and transport and cellular organization, without the activation of proteins associated with signaling. At the later stage of infection, vvIBDV induced expression of several proteins, namely CD200 receptor 1-A, integrin alpha-5, HSP-90, cathepsin, lysosomal-associated membrane protein, and Ras-related proteins, which play crucial roles in signaling, apoptosis, stress response, and antigen processing as well as in secretion of danger-associated proteins. These findings collectively indicated that the chicken DCs are expressing various receptors regarded as potential targets for pathogen interaction during viral infection. Therefore, fundamental study of the interaction of DCs and IBDV will provide valuable information in understanding the role of professional antigen-presenting cells in chickens and their molecular interactions during IBDV infection and vaccination.
  15. Molecular Characterization of QX-Like and Variant Infectious Bronchitis Virus Strains in Malaysia Based on Partial Genomic Sequences Comprising the S-3a/3b-E-M-Intergenic Region-5a/5b-N Gene Order
    Khanh NP, Tan SW, Yeap SK, Satharasinghe DA, Hair-Bejo M, Bich TN, et al.
    Avian Dis, 2017 Dec;61(4):442-452.
    PMID: 29337625 DOI: 10.1637/11637-032817-Reg.1
    Infectious bronchitis virus (IBV) is one of the major poultry pathogens of global importance. However, the prevalence of IBV strains in Malaysia is poorly characterized. The partial genomic sequences (6.8 kb) comprising the S-3a/3b-E-M-intergenic region-5a/5b-N gene order of 11 Malaysian IBVs isolated in 2014 and 2015 were sequenced using next-generation sequencing technology. Phylogenetic and pairwise sequence comparison analysis showed that the isolated IBVs are divided into two groups. Group 1 (IBS124/2015, IBS125/2015, IBS126/2015, IBS130/2015, IBS131/2015, IBS138/2015, and IBS142/2015) shared 90%-95% nucleotide and deduced amino acid similarities to the QX-like strain. Among these isolates, IBS142/2015 is the first IBV detected in Sarawak state located in East Malaysia (Borneo Island). Meanwhile, IBV isolates in Group 2 (IBS037A/2015, IBS037B/2015, IBS051/2015, and IBS180/2015) were 91.62% and 89.09% identical to Malaysian variant strain MH5365/95 (EU086600) at nucleotide and amino acid levels, respectively. In addition, all studied IBVs were distinctly separate from Massachusetts (70%-72% amino acid similarity) and European strains including 793/B, Italy-02, and D274 (68%-73% amino acid similarity). Viruses in Group 1 have the insertion of three amino acids at positions 23, 121, and 122 of the S1 protein and recombinant events detected at nucleotide position 4354-5864, with major parental sequence derived from QX-like (CK-CH-IBYZ-2011) and a minor parental sequence derived from Massachusetts vaccine strain (H120). This study demonstrated coexistence of the IBV Malaysian variant strain along with the QX-like strain in Malaysia.
  16. Fulltext Nano and Microparticles as Potential Oral Vaccine Carriers and Adjuvants Against Infectious Diseases
    Jazayeri SD, Lim HX, Shameli K, Yeap SK, Poh CL
    Front Pharmacol, 2021;12:682286.
    PMID: 34149426 DOI: 10.3389/fphar.2021.682286
    Mucosal surfaces are the first site of infection for most infectious diseases and oral vaccination can provide protection as the first line of defense. Unlike systemic administration, oral immunization can stimulate cellular and humoral immune responses at both systemic and mucosal levels to induce broad-spectrum and long-lasting immunity. Therefore, to design a successful vaccine, it is essential to stimulate the mucosal as well as systemic immune responses. Successful oral vaccines need to overcome the harsh gastrointestinal environment such as the extremely low pH, proteolytic enzymes, bile salts as well as low permeability and the low immunogenicity of vaccines. In recent years, several delivery systems and adjuvants have been developed for improving oral vaccine delivery and immunogenicity. Formulation of vaccines with nanoparticles and microparticles have been shown to improve antigen stability, availability and adjuvanticity as well as immunostimulatory capacity, target delivery and specific release. This review discusses how nanoparticles (NPs) and microparticles (MPs) as oral carriers with adjuvant characteristics can be beneficial in oral vaccine development.
  17. Fulltext Identification and Analysis of microRNAs in Chlorella sorokiniana Using High-Throughput Sequencing
    Azaman SNA, Satharasinghe DA, Tan SW, Nagao N, Yusoff FM, Yeap SK
    Genes (Basel), 2020 09 25;11(10).
    PMID: 32992970 DOI: 10.3390/genes11101131
    Chlorella is a popular microalga with robust physiological and biochemical characteristics, which can be cultured under various conditions. The exploration of the small RNA content of Chlorella could improve strategies for the enhancement of metabolite production from this microalga. In this study, stress was introduced to the Chlorella sorokiniana culture to produce high-value metabolites such as carotenoids and phenolic content. The small RNA transcriptome of C. sorokiniana was sequenced, focusing on microRNA (miRNA) content. From the analysis, 98 miRNAs were identified in cultures subjected to normal and stress conditions. The functional analysis result showed that the miRNA targets found were most often involved in the biosynthesis of secondary metabolites, followed by protein metabolism, cell cycle, and porphyrin and chlorophyll metabolism. Furthermore, the biosynthesis of secondary metabolites such as carotenoids, terpenoids, and lipids was found mostly in stress conditions. These results may help to improve our understanding of regulatory mechanisms of miRNA in the biological and metabolic process of Chlorella species. It is important and timely to determine the true potential of this microalga species and to support the potential for genetic engineering of microalgae as they receive increasing focus for their development as an alternative source of biofuel, food, and health supplements.
  18. Bursal immunopathology responses of specific-pathogen-free chickens and red jungle fowl infected with very virulent infectious bursal disease virus
    Farhanah MI, Yasmin AR, Khanh NP, Yeap SK, Hair-Bejo M, Omar AR
    Arch Virol, 2018 Aug;163(8):2085-2097.
    PMID: 29626271 DOI: 10.1007/s00705-018-3841-7
    Very virulent infectious bursal disease virus (vvIBDV) targets B lymphocytes in the bursa of Fabricius (BF), causing immunosuppression and increased mortality rates in young birds. There have been few studies on the host immune response following vvIBDV infection at different inoculum doses in chickens with different genetic backgrounds. In this study, we characterized the immune responses of specific-pathogen-free (SPF) chickens and Malaysian red jungle fowl following infection with vvIBDV strain UPM0081 at 103.8 and 106.8 times the 50% embryo infectious dose (EID50). The viral burden, histopathological changes, immune cell populations, and expression of immune-related genes were measured and compared between infected and uninfected bursa at specific intervals. The populations of KUL1+, CD3+CD4+ and CD3+CD8+ cells were significantly increased in both types of chickens at 3 dpi, and there was significant early depletion of IgM+ B cells at 1 dpi in the red jungle fowl. vvIBDV infection also induced differential expression of genes that are involved in Th1 and pro-inflammatory responses, with groups receiving the higher dose (106.8 EID50) showing earlier expression of IFNG, IL12B, IL15, IL6, CXCLi2, IL28B, and TLR3 at 1 dpi. Although both chicken types showed equal susceptibility to infection, the red jungle fowl were clinically healthier than the SPF chickens despite showing more depletion of IgM+ B cells and failure to induce IFNB activation. In conclusion, high-dose vvIBDV infection caused an intense early host immune response in the infected bursa, with depletion of IgM+ B cells, bursal lesions, and cytokine expression as a response to mitigate the severity of the infection.
  19. Fulltext The effects of different velogenic NDV infections on the chicken bursa of Fabricius
    Kristeen-Teo YW, Yeap SK, Tan SW, Omar AR, Ideris A, Tan SG, et al.
    BMC Vet Res, 2017 May 31;13(1):151.
    PMID: 28569155 DOI: 10.1186/s12917-017-1071-y
    BACKGROUND: Virulent Newcastle disease virus (NDV) was reported to cause rapid depletion of chicken bursa of Fabricius. Severe pathological condition of the organ is commonly associated with high levels of virus replication, intense inflammatory response and also the degree of apoptosis. In this study, the responses of chicken bursa of Fabricius infected with two different strains of velogenic NDV, namely AF2240 and IBS002, were investigated by observing cell population changes, oxidative stress, viral replication and cytokine expression in the organ. Subsequently, apoptosis of enriched bursal IgM+ cells was determined to help us elucidate possible host pathogen relationships between the chicken bursa of Fabricius and NDV infection.

    RESULTS: The depletion of IgM+ cells and infiltration of macrophages were observed to be higher in bursa infected with AF2240 as compared to IBS002. In line with the increment of the macrophage population, higher nitric oxide (NO) and malondialdehyde (MDA) contents which indicated higher oxidative stress were also detected in bursa infected with NDV AF2240. In addition, higher pro-inflammatory cytokines and chemokine gene expression such as chicken CXCLi2, IL-18 and IFN-γ were observed in AF2240 infected bursa. Depletion of IgM+ cells was further confirmed with increased cell death and apoptosis of the cells in AF2240 infected bursa as compared to IBS002. However, it was found that the viral load for NDV strain IBS002 was comparatively higher than AF2240 although the magnitude of the pro- inflammatory cytokines expression and cell apoptosis was lower than AF2240.

    CONCLUSION: The results of our study demonstrated that infection of NDV strains AF2240 and IBS002 caused apoptosis in bursa IgM+ cells and its severity was associated with increased expression of pro-inflammatory cytokines/chemokine, macrophage infiltration and oxidative stress as the infection duration was prolonged. However, of the two viruses, we observed that NDV AF2240 induced a greater magnitude of apoptosis in chicken bursa IgM+ cells in comparison to IBS002. This might be due to the high level of oxidative stress and inflammatory cytokines/chemokine as well as lower IL10 expression which subsequently led to a high rate of apoptosis in the chicken bursa of Fabricius although the detected viral load of AF2240 was lower than IBS002.

  20. Differential activation of intraepithelial lymphocyte-natural killer cells in chickens infected with very virulent and vaccine strains of infectious bursal disease virus
    Jahromi MZ, Bello MB, Abdolmaleki M, Yeap SK, Hair-Bejo M, Omar AR
    Dev Comp Immunol, 2018 10;87:116-123.
    PMID: 29886054 DOI: 10.1016/j.dci.2018.06.004
    To gain insights into the role of CD3-/28.4+ intraepithelial lymphocytes-natural killer (CD3-/28.4+IEL-NK) cells during infectious bursal disease virus (IBDV) infection, characterisation of the cells was performed following infection with different strains of the virus. In vitro treatment with IL-18 or ionomycin/PMA successfully stimulated and activated the cells via a significant increase in the expression of CD69, B-Lec, CHIR-AB1 and NK-lysin. Similarly, chickens infected with the vaccine strain of IBDV also up-regulated the expression of CD69, B-Lec, CHIR-AB1 and NK-lysin in CD3-/28.4+ IEL-NK cells up to 3 days post infection (dpi) and down-regulated the expression of the inhibitory receptor B-NK at 3 dpi. On the contrary, infection with the very virulent IBDV (vvIBDV) strain lead to a reduced activation of the cells by down-regulating the expression of the CD69, CHIR-AB1 and NK-lysin especially at 1 dpi. These findings altogether demonstrate the differential activation of CD3-/28.4+IEL-NK cells in chicken following infection with the vaccine or very virulent strains of IBDV. The study therefore provides an important clue into the differential pathogenesis of IBDV infection in chicken. Further studies are however required to determine the functional importance of these findings during IBDV vaccination and infection.
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