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  1. Candida parapsilosis-specific monoclonal antibodies and their use for detection of Candida antigens in experimental systemic candidiasis
    Wong SF, Mak JW
    Hybridoma (Larchmt), 2010 Dec;29(6):539-46.
    PMID: 21117988 DOI: 10.1089/hyb.2010.0049
    Candida parapsilosis has emerged as one of the most common causes of bloodstream infection worldwide. The diagnosis of invasive candidiasis etiological agents to the species level remains a laboratory and clinical challenge. Thus, specific monoclonal antibodies to detect systemic candidiasis and to identify Candida virulence factors and associated pathogenesis through immunohistochemistry would be very useful. Inbred Balb/c mice were immunized with C. parapsilosis antigens, and blood was checked for the presence of reactive antibodies using ELISA. Fusion was performed using the harvested spleen cells and NS1 myeloma cells, and the clones were screened for the presence of antibody producing hybrid cells by dot-blot. The 1B11 clone secreted IgG2a monoclonal antibody that was reactive with the C. parapsilosis antigen at MW of 59 kDa and cross-reacted with C. tropicalis but not with other fungal and bacterial antigens tested. Another 3D1 clone secreted IgG1 monoclonal antibody that was reactive with C. parapsilosis antigen at MW of 30 kDa. The 3D1 monoclonal antibody was found to be species specific. Experimental systemic candidiasis in rats was induced through intravenous injection of C. parapsilosis, and all the vital organs were collected for immunohistochemistry study. These monoclonal antibodies were reactive against surface epitopes on the yeast cells, pseudohyphae, and immune complexes in tissue sections. Sandwich ELISAs using these antibodies were developed and were able to detect circulating antigens in experimental candidiasis in rats at 0.2 μg/μL. These monoclonal antibodies may have potential as primary capture antibodies for the development of rapid diagnostic test for human systemic fungal infection.
  2. Fulltext Environmental health and building related illnesses
    Ambu, Stephen, Chu, Wan-Loy, Mak, Joon-Wah, Wong, Shew-Fung, Chan, Li-Li, Wong, Siew-Tung
    International e-Journal of Science, Medicine & Education, 2008;2(3):-.
    MyJurnal
    Malaysia has good environmental laws to protect the outdoor environment and public health. However there are no laws governing indoor air quality (IAQ) and the knowledge among the public about its importance is also lacking. Environmental professionals think it is not a priority and this influences the policy decisions in the country. Therefore there is a need to create awareness by way of research, education and other promotional activities. What is much needed at this time is the establishment of standards for the conduct of risk assessment studies. To establish standards we need reliable data which can be used to develop appropriate guidelines for the purpose of mitigation and adaptation programmes. IAQ can have significant influence on health resulting in drop in productivity and economy of a country. It has been estimated that in the US, building related illnesses (BRI) symptoms have a relationship with decrease (3 to 5%) in work performance in an affected population resulting in an annual loss of US$60 billion in revenue. However, based on efficient management programmes they have also projected that the potential annual savings can be in the region of US$10 to 30 billion. This establishes that fact that good management programmes based on efficient guidelines is of economic value to a country and wellbeing of the population. The IMU has embarked on a research programme to collect the much-needed data for the framing of a good IAQ guideline for Malaysia.
  3. Fulltext Effect of cathepsin D and prostate specific antigen on latent transforming growth factor-beta in breast cancer cell lines
    Wong SF, Seow HF, Lai LC
    Malays J Pathol, 2003 Dec;25(2):129-34.
    PMID: 16196369
    Transforming growth factor-beta (TGFbeta) is present, predominantly in latent forms, in normal and malignant breast tissue. The mechanisms by which latent TGFbeta is activated physiologically remain largely an enigma. The objective of this study was to assess whether the proteases, cathepsin D and prostate specific antigen (PSA) could activate latent TGFbeta1 and TGFbeta2 in conditioned media of the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 human breast cancer cell lines, newly purchased from ATCC. Both of the cell lines were seeded in 6-well plates 2 days prior to treatment with varying concentrations of cathepsin D and PSA. Active TGFbeta1 and TGFbeta2 in the media were then measured by ELISA after 4, 8, 24 and 72 hours of treatment. TGFbeta1 and TGFbeta2 mRNA expression of both cell lines were measured by RT-PCR to determine whether any increase in level of active TGFbeta1 and TGFbeta2 was due to increased production. There was a significant increase in only active TGFbeta2 levels in the MDA-MB-231 cell line with both treatments. Cathepsin D and PSA did not have any effect on TGFbeta1 and TGFbeta2 mRNA expression. Cathepsin D and PSA were unable to activate latent TGFbeta1 and TGFbeta2 in these two breast cancer cell lines. A constant level of TGFbeta2 mRNA in the control and treated MDA-MB-231 cells suggests that the increase in level of active TGFbeta2 was not a result of increased production but was likely to be due to activation by a mechanism independent of cathepsin D and PSA.
  4. Potential use of a monoclonal antibody for the detection of Candida antigens in an experimental systemic candidiasis model
    Wong SF, Mak JW, Pook CK
    Hybridoma (Larchmt), 2008 Oct;27(5):361-73.
    PMID: 18823263 DOI: 10.1089/hyb.2008.0021
    The Candida species are the most common fungal pathogens of systemic candidiasis. The diagnosis of invasive candidiasis remains a laboratory and clinical challenge. Thus, development of diagnostic assays to detect systemic candidiasis and to identify Candida virulence factors and associated pathogenesis through immunohistochemistry using specific monoclonals and polyclonals will be useful. Inbred Balb/c mice were immunized with C. albicans antigens, and blood was checked for the presence of reactive antibodies using ELISA. Fusion was performed using the harvested spleen cells and NS1 myeloma cells, and the clones were screened for the presence of antibody producing hybrid cells by dot-blot. Western blot analysis showed that the L2D10 monoclonal antibody was reactive against the antigens with molecular weight of 20 kDa. Experimental systemic candidiasis in mice was induced through intravenous injection of C. albicans and all the vital organs were collected for immunohistochemistry study. The monoclonal antibody reacted to surface epitopes on the yeast cells, germ tubes, and hyphae, and to immune complexes. It was used with the polyclonal antibody in a sandwich ELISA for the detection of circulating antigens in experimental candiadiasis in mice. Antibody levels were also determined using the ELISA method, and the antibody levels of C. albicans infected mice were increased compared with uninfected animals. The monoclonal antibody was used in immunoperoxidase and immunofluorescence techniques for the detection of fungal infection in tissue sections and was found to be more sensitive than conventional periodic acid Schiff or silver staining techniques. This monoclonal antibody may serve as potential primary capture antibodies for the development of a rapid diagnostic test for human systemic fungal infection.
  5. Culture and molecular identification of fungal contaminants in edible bird nests
    Chen JX, Wong SF, Lim PK, Mak JW
    Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2015;32(12):2138-47.
    PMID: 26429550 DOI: 10.1080/19440049.2015.1101494
    Widespread food poisoning due to microbial contamination has been a major concern for the food industry, consumers and governing authorities. This study is designed to determine the levels of fungal contamination in edible bird nests (EBNs) using culture and molecular techniques. Raw EBNs were collected from five house farms, and commercial EBNs were purchased from five Chinese traditional medicine shops (companies A-E) in Peninsular Malaysia. The fungal contents in the raw and commercial EBNs, and boiled and unboiled EBNs were determined. Culturable fungi were isolated and identified. In this study, the use of these methods revealed that all EBNs had fungal colony-forming units (CFUs) that exceeded the limit set by Standards and Industrial Research Institute of Malaysia (SIRIM) for yeast and moulds in EBNs. There was a significant difference (p < 0.05) in the number of types of fungi isolated from raw and commercial EBNs, but no significant difference in the reduction of the number of types of fungi after boiling the EBNs (p > 0.05). The types of fungi isolated from the unboiled raw EBNs were mainly soil, plant and environmental fungi, while the types of fungi isolated from the boiled raw EBNs, unboiled and boiled commercial EBNs were mainly environmental fungi. Aspergillus sp., Candida sp., Cladosporium sp., Neurospora sp. and Penicillum sp. were the most common fungi isolated from the unboiled and boiled raw and commercial EBNs. Some of these fungi are mycotoxin producers and cause opportunistic infections in humans. Further studies to determine the mycotoxin levels and methods to prevent or remove these contaminations from EBNs for safe consumption are necessary. The establishment and implementation of stringent regulations for the standards of EBNs should be regularly updated and monitored to improve the quality of the EBNs and consumer safety.
  6. Fulltext Differential expression of the angiogenesis growth factors in psoriasis vulgaris
    Liew SC, Das-Gupta E, Chakravarthi S, Wong SF, Lee N, Safdar N, et al.
    BMC Res Notes, 2012;5:201.
    PMID: 22537619 DOI: 10.1186/1756-0500-5-201
    Angiogenesis has been reported to be one of the contributory factors to the pathogenesis of psoriasis vulgaris. This study aims to compare the expression of different angiogenesis growth factors namely (1) the vascular endothelial growth factor (VEGF) subfamily: A, B, C, D and placenta growth factor (PlGF); (2) nerve growth factor (NGF) and (3) von Willebrand factor (vWFr) in the skins of patients with psoriasis vulgaris and non-psoriatic volunteers.

    Study site: Dermatology Department of Hospital Kuala Lumpur, Kuala Lumpur and Tuanku Ja’afar Hospital, Seremban, Malaysia
  7. Meta-analysis: the association between HIV infection and extrapulmonary tuberculosis
    Naing C, Mak JW, Maung M, Wong SF, Kassim AI
    Lung, 2013 Feb;191(1):27-34.
    PMID: 23180033 DOI: 10.1007/s00408-012-9440-6
    BACKGROUND: Extrapulmonary tuberculosis has been an AIDS-defining condition. Individual studies that highlight the association between HIV and extrapulmonary TB are available. Our objectives were to synthesis evidence on the association between extrapulmonary tuberculosis and HIV and to explore the effective preventive measures of these two diseases.

    METHODS: This is a meta-analysis of observational studies reporting effect estimates on how HIV is associated with extrapulmonary tuberculosis. We searched for the eligible studies in the electronic databases using search terms related to HIV and extrapulmonary tuberculosis. Where possible, we estimated the summary odds ratios using random effects meta-analysis. We stratified analysis by the type of study design. We assessed heterogeneity of effect estimates within each group of studies was assessed using I (2) test.

    RESULTS: Nineteen studies (7 case control studies and 12 cohort studies) were identified for the present study. The pooled analysis shows a significant association between HIV and extrapulmonary tuberculosis (summary odds ratio: 1.3; 95 % confidence interval (CI) 1.05-1.6; I (2): 0 %). In a subgroup analysis with two studies, a significant association was found between CD4+ count less than 100 and the incidence of extrapulmonary tuberculosis (summary OR: 1.31; 95 % CI 1.02-1.68; I (2): 0 %).

    CONCLUSIONS: Findings show evidence on the association between extrapulmonary tuberculosis and HIV, based on case control studies. Further studies to understand the mechanisms of interaction of the two pathogens are recommended.

  8. Molecular identification of house dust mites and storage mites
    Wong SF, Chong AL, Mak JW, Tan J, Ling SJ, Ho TM
    Exp Appl Acarol, 2011 Oct;55(2):123-33.
    PMID: 21468750 DOI: 10.1007/s10493-011-9460-6
    Mites are known causes of allergic diseases. Currently, identification of mites based on morphology is difficult if only one mite is isolated from a (dust) sample, or when only one gender is found, or when the specimen is not intact especially with the loss of the legs. The purpose of this study was to use polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of the ITS2 gene, to complement the morphological data for the identification of mites to the species level. For this, six species were cultured: Dermatophagoides pteronyssinus, D. farinae, Blomia tropicalis, Tyrophagus putrescentiae, Aleuroglyphus ovatus and Glycycometus malaysiensis. Genomic DNA of the mites was extracted, quantified, amplified and digested individually with restriction enzymes. Hinf I and Ple I differentiated the restriction patterns of D. pteronyssinus and D. farinae. Bfa I and Alu I enzymes differentiated B. tropicalis and G. malaysiensis. Ple I enzyme was useful for the differentiation between T. putrescentiae and A. ovatus. Bfa I was useful for the differentiation of G. malaysiensis from the rest of the species. In conclusion, different species of mites can be differentiated using PCR-RFLP of ITS2 region. With the established PCR-RFLP method in this study, identification of these mites to the species level is possible even if complete and intact adult specimens of both sexes are not available. As no study to date has reported PCR-RFLP method for the identification of domestic mites, the established method should be validated for the identification of other species of mites that were not included in this study.
  9. Potential Residual Contaminants in Edible Bird's Nest
    Yeo BH, Tang TK, Wong SF, Tan CP, Wang Y, Cheong LZ, et al.
    Front Pharmacol, 2021;12:631136.
    PMID: 33833681 DOI: 10.3389/fphar.2021.631136
    Edible bird's nest (EBN) is recognized as a nourishing food among Chinese people. The efficacy of EBN was stated in the records of traditional Chinese medicine and its activities have been reported in many researches. Malaysia is the second largest exporter of EBNs in the world, after Indonesia. For many years, EBN trade to China was not regulated until August 2011, when a safety alert was triggered for the consumption of EBNs. China banned the import of EBNs from Malaysia and Indonesia due to high level of nitrite. Since then, the Malaysia government has formulated Malaysia Standards for swiftlet farming (MS 2273:2012), edible bird's nest processing plant design and management (MS 2333:2010), and edible bird's nest product quality (MS 2334:2011) to enable the industry to meet the specified standards for the export to China. On the other hand, Indonesia's EBN industry formulated a standard operating procedure (SOP) for exportation to China. Both countries can export EBNs to China by complying with the standards and SOPs. EBN contaminants may include but not limited to nitrite, heavy metals, excessive minerals, fungi, bacteria, and mites. The possible source of contaminants may come from the swiftlet farms and the swiftlets or introduced during processing, storage, and transportation of EBNs, or adulterants. Swiftlet house design and management, and EBN processing affect the bird's nest color. Degradation of its optical quality has an impact on the selling price, and color changes are tied together with nitrite level. In this review, the current and future prospects of EBNs in Malaysia and Indonesia in terms of their quality, and the research on the contaminants and their effects on EBN color changes are discussed.
  10. Fulltext Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment
    Looi CK, Chung FF, Leong CO, Wong SF, Rosli R, Mai CW
    J Exp Clin Cancer Res, 2019 Apr 15;38(1):162.
    PMID: 30987642 DOI: 10.1186/s13046-019-1153-8
    BACKGROUND: Pancreatic cancer is one of the most lethal type of cancers, with an overall five-year survival rate of less than 5%. It is usually diagnosed at an advanced stage with limited therapeutic options. To date, no effective treatment options have demonstrated long-term benefits in advanced pancreatic cancer patients. Compared with other cancers, pancreatic cancer exhibits remarkable resistance to conventional therapy and possesses a highly immunosuppressive tumor microenvironment (TME).

    MAIN BODY: In this review, we summarized the evidence and unique properties of TME in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. We reviewed the current strategies and future perspectives of combination therapies that (1) promote T cell priming through tumor associated antigen presentation; (2) inhibit tumor immunosuppressive environment; and (3) break-down the desmoplastic barrier which improves tumor infiltrating lymphocytes entry into the TME.

    CONCLUSIONS: It is imperative for clinicians and scientists to understand tumor immunology, identify novel biomarkers, and optimize the position of immunotherapy in therapeutic sequence, in order to improve pancreatic cancer clinical trial outcomes. Our collaborative efforts in targeting pancreatic TME will be the mainstay of achieving better clinical prognosis among pancreatic cancer patients. Ultimately, pancreatic cancer will be a treatable medical condition instead of a death sentence for a patient.

  11. Fulltext Production of Biodegradable Palm Oil-Based Polyurethane as Potential Biomaterial for Biomedical Applications
    Yeoh FH, Lee CS, Kang YB, Wong SF, Cheng SF, Ng WS
    Polymers (Basel), 2020 Aug 17;12(8).
    PMID: 32824514 DOI: 10.3390/polym12081842
    Being biodegradable and biocompatible are crucial characteristics for biomaterial used for medical and biomedical applications. Vegetable oil-based polyols are known to contribute both the biodegradability and biocompatibility of polyurethanes; however, petrochemical-based polyols were often incorporated to improve the thermal and mechanical properties of polyurethane. In this work, palm oil-based polyester polyol (PPP) derived from epoxidized palm olein and glutaric acid was reacted with isophorone diisocyanate to produce an aliphatic polyurethane, without the incorporation of any commercial petrochemical-based polyol. The effects of water content and isocyanate index were investigated. The polyurethanes produced consisted of > 90% porosity with interconnected micropores and macropores (37-1700 µm) and PU 1.0 possessed tensile strength and compression stress of 111 kPa and 64 kPa. The polyurethanes with comparable thermal stability, yet susceptible to enzymatic degradation with 7-59% of mass loss after 4 weeks of treatment. The polyurethanes demonstrated superior water uptake (up to 450%) and did not induce significant changes in pH of the medium. The chemical changes of the polyurethanes after enzymatic degradation were evaluated by FTIR and TGA analyses. The polyurethanes showed cell viability of 53.43% and 80.37% after 1 and 10 day(s) of cytotoxicity test; and cell adhesion and proliferation in cell adhesion test. The polyurethanes produced demonstrated its potential as biomaterial for soft tissue engineering applications.
  12. Gene expression changes in human bronchial epithelial cells (BEAS-2B) and human pulmonary alveolar epithelial cells (HPAEpiC) after interaction with Cladosporium sphaerospermum
    Lo SG, Wong SF, Mak JW, Choo KK, Ng KP
    Med Mycol, 2020 Apr 01;58(3):333-340.
    PMID: 31309220 DOI: 10.1093/mmy/myz061
    Cladosporium is one of the most abundant spore. Fungi of this genus can cause respiratory allergy and intrabronchial lesion. We studied the differential expression of host genes after the interaction of Cladosporium sphaerospermum conidia with Human Bronchial Epithelial Cells (BEAS-2B) and Human Pulmonary Alveolar Epithelial Cells (HPAEpiC). C. sphaerospermum conidia were harvested and co-cultured with BEAS-2B cells or HPAEpiC cells for 48 hours respectively. This culture duration was chosen as it was associated with high germination rate. RNA was extracted from two biological replicates per treatment. RNA of BEAS-2B cells was used to assess changes in gene expression using AffymetrixGeneChip® Human Transcriptome Array 2.0. After co-culture with Cladosporium spores, 68 individual genes were found differentially expressed (P ≤ 0.05) and up-regulated ≥ 1.5 folds while 75 genes were found differentially expressed at ≤ -1.5 folds compared with controls. Reverse transcription and qPCR were performed on the RNA collected from both BEAS-2B cells and HPAEpiC cells to validate the microarray results with 7 genes. Based on the findings, infected pulmonary epithelial cells exhibited an increase in cell death-related genes and genes associated with innate immunity.
  13. Fulltext Correlation of serum cartilage oligomeric matrix protein (COMP) and interleukin-16 (IL-16) levels with disease severity in primary knee osteoarthritis: A pilot study in a Malaysian population
    Das Gupta E, Ng WR, Wong SF, Bhurhanudeen AK, Yeap SS
    PLoS One, 2017;12(9):e0184802.
    PMID: 28910372 DOI: 10.1371/journal.pone.0184802
    OBJECTIVE: The aim of this study was to investigate the correlations between serum cartilage oligomeric matrix protein (COMP), interleukin-16 (IL-16) and different grades of knee osteoarthritis (KOA) in Malaysian subjects.

    METHODS: Ninety subjects were recruited comprising 30 with Kellgren-Lawrence (K-L) grade 2 KOA, 27 with K-L grade 3 KOA, 7 with grade 4 KOA, and 30 healthy controls. All subjects completed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Serum COMP and IL-16 levels were measured using ELISA and their values log transformed to ensure a normal distribution.

    RESULTS: There was no significant differences in levels of log serum COMP and IL-16 between healthy controls and KOA patients. There were no significant differences in the log serum COMP and IL-16 levels within the different K-L grades in the KOA patients. In KOA patients, log serum IL-16 levels significantly correlated with the WOMAC score (p = 0.001) and its subscales, pain (p = 0.005), stiffness (p = 0.019) and physical function (p<0.0001). Serum IL-16 levels were significantly higher in Malaysian Indians compared to Malays and Chinese (p = 0.024).

    CONCLUSIONS: In this multi-ethnic Malaysian population, there was no difference in serum COMP and IL-16 levels between healthy controls and patients with KOA, nor was there any difference in serum COMP or IL-16 levels across the various K-L grades of KOA. However, there were significant inter-racial differences in serum IL-16 levels.
  14. Fulltext Dengue fever and insecticide resistance in Aedes mosquitoes in Southeast Asia: a review
    Gan SJ, Leong YQ, Bin Barhanuddin MFH, Wong ST, Wong SF, Mak JW, et al.
    Parasit Vectors, 2021 Jun 10;14(1):315.
    PMID: 34112220 DOI: 10.1186/s13071-021-04785-4
    Dengue fever is the most important mosquito-borne viral disease in Southeast Asia. Insecticides remain the most effective vector control approach for Aedes mosquitoes. Four main classes of insecticides are widely used for mosquito control: organochlorines, organophosphates, pyrethroids and carbamates. Here, we review the distribution of dengue fever from 2000 to 2020 and its associated mortality in Southeast Asian countries, and we gather evidence on the trend of insecticide resistance and its distribution in these countries since 2000, summarising the mechanisms involved. The prevalence of resistance to these insecticides is increasing in Southeast Asia, and the mechanisms of resistance are reported to be associated with target site mutations, metabolic detoxification, reduced penetration of insecticides via the mosquito cuticle and behavioural changes of mosquitoes. Continuous monitoring of the status of resistance and searching for alternative control measures will be critical for minimising any unpredicted outbreaks and improving public health. This review also provides improved insights into the specific use of insecticides for effective control of mosquitoes in these dengue endemic countries.
  15. Gene expression profiling of giant fibroadenomas of the breast
    Yin Lee JP, Thomas AJ, Lum SK, Shamsudin NH, Hii LW, Mai CW, et al.
    Surg Oncol, 2021 Jun;37:101536.
    PMID: 33677364 DOI: 10.1016/j.suronc.2021.101536
    INTRODUCTION: Fibroadenomas of the breast present as two phenotypic variants. The usual variety is 5 cm or less in diameter and there is another large variant called giant fibroadenoma which is greater than 5 cm in diameter. Despite of its large size, it is not malignant. The aim of our study is to determine whether this large variant is different from the usual fibroadenoma in terms of its biological pathways and biomarkers.

    METHODS: mRNA was extracted from 44 fibroadenomas and 36 giant fibroadenomas, and transcriptomic profiling was performed to identify up- and down-regulated genes in the giant fibroadenomas as compared to the fibroadenomas.

    RESULTS: A total of 40 genes were significantly up-regulated and 18 genes were significantly down-regulated in the giant fibroadenomas as compared to the fibroadenomas of the breast. The top 5 up-regulated genes were FN1, IL3, CDC6, FGF8 and BMP8A. The top 5 down-regulated genes were TNR, CDKN2A, COL5A1, THBS4 and BMPR1B. The differentially expressed genes (DEGs) were found to be associated with 5 major canonical pathways involved in cell growth (PI3K-AKT, cell cycle regulation, WNT, and RAS signalling) and immune response (JAK-STAT signalling). Further analyses using 3 supervised learning algorithms identified an 8-gene signature (FN1, CDC6, IL23A, CCNA1, MCM4, FLT1, FGF22 and COL5A1) that could distinguish giant fibroadenomas from fibroadenomas with high predictive accuracy.

    CONCLUSION: Our findings demonstrated that the giant fibroadenomas are biologically distinct to fibroadenomas of the breast with overexpression of genes involved in the regulation of cell growth and immune response.

  16. 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.
  17. Fulltext A novel strategy for community screening of SARS-CoV-2 (COVID-19): Sample pooling method
    Lim KL, Johari NA, Wong ST, Khaw LT, Tan BK, Chan KK, et al.
    PLoS One, 2020;15(8):e0238417.
    PMID: 32857823 DOI: 10.1371/journal.pone.0238417
    The rapid global spread of the coronavirus disease (COVID-19) has inflicted significant health and socioeconomic burden on affected countries. As positive cases continued to rise in Malaysia, public health laboratories experienced an overwhelming demand for COVID-19 screening. The confirmation of positive cases of COVID-19 has solely been based on the detection of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) using real-time reverse transcription polymerase chain reaction (qRT-PCR). In efforts to increase the cost-effectiveness and efficiency of COVID-19 screening, we evaluated the feasibility of pooling clinical Nasopharyngeal/Oropharyngeal (NP/OP) swab specimens during nucleic acid extraction without a reduction in sensitivity of qRT-PCR. Pools of 10 specimens were extracted and subsequently tested by qRT-PCR according to the WHO-Charité protocol. We demonstrated that the sample pooling method showed no loss of sensitivity. The effectiveness of the pooled testing strategy was evaluated on both retrospective and prospective samples, and the results showed a similar detection sensitivity compared to testing individual sample alone. This study demonstrates the feasibility of using a pooled testing strategy to increase testing capacity and conserve resources, especially when there is a high demand for disease testing.
  18. Fulltext COVID-19 Sample Pooling: From RNA Extraction to Quantitative Real-time RT-PCR
    Voon K, Johari NA, Lim KL, Wong ST, Khaw LT, Wong SF, et al.
    Bio Protoc, 2021 May 05;11(9):e4005.
    PMID: 34124305 DOI: 10.21769/BioProtoc.4005
    The COVID-19 pandemic requires mass screening to identify those infected for isolation and quarantine. Individually screening large populations for the novel pathogen, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is costly and requires a lot of resources. Sample pooling methods improve the efficiency of mass screening and consume less reagents by increasing the capacity of testing and reducing the number of experiments performed, and are therefore especially suitable for under-developed countries with limited resources. Here, we propose a simple, reliable pooling strategy for COVID-19 testing using clinical nasopharyngeal (NP) and/or oropharyngeal (OP) swabs. The strategy includes the pooling of 10 NP/OP swabs for extraction and subsequent testing via quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), and may also be applied to the screening of other pathogens.
  19. Human cytokeratin 1 plays a role in the interaction of Pteropine orthoreovirus with Hek293 cells but not HeLa cells
    Siew ZY, Tan YF, Iswara RP, Wong SF, Wong ST, Tan BK, et al.
    Microbes Infect, 2024;26(1-2):105243.
    PMID: 38380604 DOI: 10.1016/j.micinf.2023.105243
    Pteropine orthoreovirus (PRV) causes respiratory tract infections in humans. Despite its emergence as a zoonotic and respiratory virus, little is known about its cell tropism, which hampers progress in fully understanding its pathogenesis in humans. Hek293 cells are most susceptible to PRV infection, while HeLa cells are the least. Human cytokeratin 1 (CK1) was identified as the protein that interacts with PRV. The immunofluorescence assay and qPCR results revealed prior treatment with anti-CK1 may provide Hek293 cells protection against PRV. The KRT1-knockout Hek293 cells were less susceptible to PRV infection. Further study into the pathogenesis of PRV in humans is needed.
  20. Fulltext Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival
    Tiong KH, Tan BS, Choo HL, Chung FF, Hii LW, Tan SH, et al.
    Oncotarget, 2016 Sep 06;7(36):57633-57650.
    PMID: 27192118 DOI: 10.18632/oncotarget.9328
    Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.
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