Displaying publications 21 - 30 of 30 in total

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  1. Lim SW, Tan KJ, Azuraidi OM, Sathiya M, Lim EC, Lai KS, et al.
    Sci Rep, 2021 12 17;11(1):24206.
    PMID: 34921182 DOI: 10.1038/s41598-021-03624-x
    MYB proteins are highly conserved DNA-binding domains (DBD) and mutations in MYB oncoproteins have been reported to cause aberrant and augmented cancer progression. Identification of MYB molecular biomarkers predictive of cancer progression can be used for improving cancer management. To address this, a biomarker discovery pipeline was employed in investigating deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in predicting damaging and potential alterations on the properties of proteins. The nsSNP of the MYB family; MYB, MYBL1, and MYBL2 was extracted from the NCBI database. Five in silico tools (PROVEAN, SIFT, PolyPhen-2, SNPs&GO and PhD-SNP) were utilized to investigate the outcomes of nsSNPs. A total of 45 nsSNPs were predicted as high-risk and damaging, and were subjected to PMut and I-Mutant 2.0 for protein stability analysis. This resulted in 32 nsSNPs with decreased stability with a DDG score lower than - 0.5, indicating damaging effect. G111S, N183S, G122S, and S178C located within the helix-turn-helix (HTH) domain were predicted to be conserved, further posttranslational modifications and 3-D protein analysis indicated these nsSNPs to shift DNA-binding specificity of the protein thus altering the protein function. Findings from this study would help in the field of pharmacogenomic and cancer therapy towards better intervention and management of cancer.
  2. Moo CL, Osman MA, Yang SK, Yap WS, Ismail S, Lim SH, et al.
    Sci Rep, 2021 10 21;11(1):20824.
    PMID: 34675255 DOI: 10.1038/s41598-021-00249-y
    Antimicrobial resistance remains one of the most challenging issues that threatens the health of people around the world. Plant-derived natural compounds have received considerable attention for their potential role to mitigate antibiotic resistance. This study was carried out to assess the antimicrobial activity and mode of action of a monoterpene, 1,8-cineol (CN) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Results showed that resazurin microplate assay and time-kill analysis revealed bactericidal effects of CN at 28.83 mg/mL. Zeta potential showed that CN increased the surface charge of bacteria and an increase of outer membrane permeability was also detected. CN was able to cause leakage of proteins and nucleic acids in KPC-KP cells upon exposure to CN and ethidium bromide influx/efflux experiment showed the uptake of ethidium bromide into the cell; this was attributed to membrane damage. CN was also found to induce oxidative stress in CN-treated KPC-KP cells through generation of reactive oxygen species which initiated lipid peroxidation and thus damaging the bacterial cell membrane. Scanning and transmission electron microscopies further confirmed the disruption of bacterial cell membrane and loss of intracellular materials. In this study, we demonstrated that CN induced oxidative stress and membrane damage resulting in KPC-KP cell death.
  3. Voon W, Hum YC, Tee YK, Yap WS, Salim MIM, Tan TS, et al.
    Sci Rep, 2022 Nov 10;12(1):19200.
    PMID: 36357456 DOI: 10.1038/s41598-022-21848-3
    Computer-aided Invasive Ductal Carcinoma (IDC) grading classification systems based on deep learning have shown that deep learning may achieve reliable accuracy in IDC grade classification using histopathology images. However, there is a dearth of comprehensive performance comparisons of Convolutional Neural Network (CNN) designs on IDC in the literature. As such, we would like to conduct a comparison analysis of the performance of seven selected CNN models: EfficientNetB0, EfficientNetV2B0, EfficientNetV2B0-21k, ResNetV1-50, ResNetV2-50, MobileNetV1, and MobileNetV2 with transfer learning. To implement each pre-trained CNN architecture, we deployed the corresponded feature vector available from the TensorFlowHub, integrating it with dropout and dense layers to form a complete CNN model. Our findings indicated that the EfficientNetV2B0-21k (0.72B Floating-Point Operations and 7.1 M parameters) outperformed other CNN models in the IDC grading task. Nevertheless, we discovered that practically all selected CNN models perform well in the IDC grading task, with an average balanced accuracy of 0.936 ± 0.0189 on the cross-validation set and 0.9308 ± 0.0211on the test set.
  4. Lim EC, Lim SW, Tan KJ, Sathiya M, Cheng WH, Lai KS, et al.
    Life (Basel), 2022 Jul 09;12(7).
    PMID: 35888106 DOI: 10.3390/life12071018
    Dysregulation of fibroblast growth factors is linked to the pathogenesis of bladder cancer. The role of FGF1 and FGF3 is evident in bladder cancer; however, the role of FGF4 is vague. Despite being reported that FGF4 interacts with FGF1 and FGF3 in MAPK pathways, its pathogenesis and mechanism of action are yet to be elucidated. Therefore, this study aimed to elucidate pathogenic nsSNPs and their role in the prognosis of bladder cancer by employing in-silico analysis. The nsSNPs of FGF4 were retrieved from the NCBI database. Different in silico tools, PROVEAN, SIFT, PolyPhen-2, SNPs&GO, and PhD-SNP, were used for predicting the pathogenicity of the nsSNPs. Twenty-seven nsSNPs were identified as “damaging”, and further stability analysis using I-Mutant 2.0 and MUPro indicated 22 nsSNPs to cause decreased stability (DDG scores < −0.5). Conservation analysis predicted that Q97K, G106V, N164S, and N167S were highly conserved and exposed. Biophysical characterisation indicated these nsSNPs were not tolerated, and protein-protein interaction analysis showed their involvement in the GFR-MAPK signalling pathway. Furthermore, Kaplan Meier bioinformatics analyses indicated that the FGF4 gene deregulation affected the overall survival rate of patients with bladder cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of FGF4 may serve as potential targets for diagnoses and therapeutic interventions focusing on bladder cancer.
  5. Varijakzhan D, Loh JY, Yap WS, Yusoff K, Seboussi R, Lim SE, et al.
    Mar Drugs, 2021 Apr 27;19(5).
    PMID: 33925365 DOI: 10.3390/md19050246
    Marine sponges are sessile invertebrates that can be found in temperate, polar and tropical regions. They are known to be major contributors of bioactive compounds, which are discovered in and extracted from the marine environment. The compounds extracted from these sponges are known to exhibit various bioactivities, such as antimicrobial, antitumor and general cytotoxicity. For example, various compounds isolated from Theonella swinhoei have showcased various bioactivities, such as those that are antibacterial, antiviral and antifungal. In this review, we discuss bioactive compounds that have been identified from marine sponges that showcase the ability to act as antibacterial, antiviral, anti-malarial and antifungal agents against human pathogens and fish pathogens in the aquaculture industry. Moreover, the application of such compounds as antimicrobial agents in other veterinary commodities, such as poultry, cattle farming and domesticated cats, is discussed, along with a brief discussion regarding the mode of action of these compounds on the targeted sites in various pathogens. The bioactivity of the compounds discussed in this review is focused mainly on compounds that have been identified between 2000 and 2020 and includes the novel compounds discovered from 2018 to 2021.
  6. Md Sharif S, Yap WS, Fun WH, Yoon EL, Abd Razak NF, Sararaks S, et al.
    Nurs Rep, 2021 Oct 26;11(4):859-880.
    PMID: 34968274 DOI: 10.3390/nursrep11040080
    BACKGROUND: While the global maternal mortality ratio (MMR) shows a decreasing trend, there is room for improvement. Midwifery education has been under scrutiny to ensure that graduates acquire knowledge and skills relevant to the local context.

    OBJECTIVE: To review the basic professional midwifery qualification and pre-practice requirements in countries with lower MMR compared with Malaysia.

    METHODS: A rapid review of country-specific Ministry of Health and Midwifery Association websites and Advanced Google using standardised key words. English-language documents reporting the qualifications of midwives or other requirements to practise midwifery from countries with a lower MMR than Malaysia were included.

    RESULTS: Sixty-three documents from 35 countries were included. The minimum qualification required to become a midwife was a bachelor's degree. Most countries require registration or licensing to practise, and 35.5% have implemented preregistration national midwifery examinations. In addition, 13 countries require midwives to have nursing backgrounds.

    CONCLUSION: In countries achieving better maternal outcomes than Malaysia, midwifes often have a degree or higher qualification. As such, there is a need to reinvestigate and revise the midwifery qualification requirements in Malaysia.

  7. Foo LS, Larkin JR, Sutherland BA, Ray KJ, Yap WS, Hum YC, et al.
    Magn Reson Med, 2021 04;85(4):2188-2200.
    PMID: 33107119 DOI: 10.1002/mrm.28565
    PURPOSE: To assess the correlation and differences between common amide proton transfer (APT) quantification methods in the diagnosis of ischemic stroke.

    METHODS: Five APT quantification methods, including asymmetry analysis and its variants as well as two Lorentzian model-based methods, were applied to data acquired from six rats that underwent middle cerebral artery occlusion scanned at 9.4T. Diffusion and perfusion-weighted images, and water relaxation time maps were also acquired to study the relationship of these conventional imaging modalities with the different APT quantification methods.

    RESULTS: The APT ischemic area estimates had varying sizes (Jaccard index: 0.544 ≤ J ≤ 0.971) and had varying correlations in their distributions (Pearson correlation coefficient: 0.104 ≤ r ≤ 0.995), revealing discrepancies in the quantified ischemic areas. The Lorentzian methods produced the highest contrast-to-noise ratios (CNRs; 1.427 ≤ CNR ≤ 2.002), but generated APT ischemic areas that were comparable in size to the cerebral blood flow (CBF) deficit areas; asymmetry analysis and its variants produced APT ischemic areas that were smaller than the CBF deficit areas but larger than the apparent diffusion coefficient deficit areas, though having lower CNRs (0.561 ≤ CNR ≤ 1.083).

    CONCLUSION: There is a need to further investigate the accuracy and correlation of each quantification method with the pathophysiology using a larger scale multi-imaging modality and multi-time-point clinical study. Future studies should include the magnetization transfer ratio asymmetry results alongside the findings of the study to facilitate the comparison of results between different centers and also the published literature.

  8. Chai CY, Maran S, Thew HY, Tan YC, Rahman NMANA, Cheng WH, et al.
    Biology (Basel), 2022 Nov 02;11(11).
    PMID: 36358305 DOI: 10.3390/biology11111604
    The Harvey rat sarcoma (HRAS) proto-oncogene belongs to the RAS family and is one of the pathogenic genes that cause cancer. Deleterious nsSNPs might have adverse consequences at the protein level. This study aimed to investigate deleterious nsSNPs in the HRAS gene in predicting structural alterations associated with mutants that disrupt normal protein-protein interactions. Functional and structural analysis was employed in analyzing the HRAS nsSNPs. Putative post-translational modification sites and the changes in protein-protein interactions, which included a variety of signal cascades, were also investigated. Five different bioinformatics tools predicted 33 nsSNPs as "pathogenic" or "harmful". Stability analysis predicted rs1554885139, rs770492627, rs1589792804, rs730880460, rs104894227, rs104894227, and rs121917759 as unstable. Protein-protein interaction analysis revealed that HRAS has a hub connecting three clusters consisting of 11 proteins, and changes in HRAS might cause signal cascades to dissociate. Furthermore, Kaplan-Meier bioinformatics analyses indicated that the HRAS gene deregulation affected the overall survival rate of patients with breast cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of HRAS may serve as potential targets for different proteomic studies, diagnoses, and therapeutic interventions focusing on cancer.
  9. Tang CN, Wan Abdullah WMAN, Wee CY, Balia Yusof ZN, Yap WS, Cheng WH, et al.
    Biology (Basel), 2023 Mar 10;12(3).
    PMID: 36979122 DOI: 10.3390/biology12030430
    Vacuolar processing enzyme (VPE) is a cysteine protease responsible for vacuolar proteins' maturation and regulation of programmed cell death (PCD). Four isoforms of Arabidopsis thaliana VPEs were identified previously, but only the functions of βVPE, γVPE, and δVPE were determined. The specific function of a gene is linked to the cis-acting elements in the promoter region. A promoter analysis found repetitive drought-related cis-elements in αVPE, which highlight its potential involvement in drought regulation in A. thaliana. The further co-expression network portraying genes interacting with αVPE substantiated its drought-regulation-related function. Expression of αVPE was upregulated after drought treatment in A. thaliana. To confirm the role of αVPE, a loss of function study revealed that αVPE knockout mutants remained green compared with WT after drought treatment. The mutants had reduced proline activity, decreased sucrose content, and lower MDA content, but increased photosynthetic pigments, indicating that αVPE negatively regulates drought tolerance in A. thaliana. Taken together, our findings serve as important evidence of the involvement of αVPE in modulating drought tolerance in A. thaliana.
  10. Foo LS, Larkin JR, Sutherland BA, Ray KJ, Yap WS, Goh CH, et al.
    Quant Imaging Med Surg, 2023 Dec 01;13(12):7879-7892.
    PMID: 38106293 DOI: 10.21037/qims-23-510
    BACKGROUND: When an ischemic stroke happens, it triggers a complex signalling cascade that may eventually lead to neuronal cell death if no reperfusion. Recently, the relayed nuclear Overhauser enhancement effect at -1.6 ppm [NOE(-1.6 ppm)] has been postulated may allow for a more in-depth analysis of the ischemic injury. This study assessed the potential utility of NOE(-1.6 ppm) in an ischemic stroke model.

    METHODS: Diffusion-weighted imaging, perfusion-weighted imaging, and chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) data were acquired from five rats that underwent scans at 9.4 T after middle cerebral artery occlusion.

    RESULTS: The apparent diffusion coefficient (ADC), cerebral blood flow (CBF), and apparent exchange-dependent relaxations (AREX) at 3.5 ppm and NOE(-1.6 ppm) were quantified. AREX(3.5 ppm) and NOE(-1.6 ppm) were found to be hypointense and exhibited different signal patterns within the ischemic tissue. The NOE(-1.6 ppm) deficit areas were equal to or larger than the ADC deficit areas, but smaller than the AREX(3.5 ppm) deficit areas. This suggested that NOE(-1.6 ppm) might further delineate the acidotic tissue estimated using AREX(3.5 ppm). Since NOE(-1.6 ppm) is closely related to membrane phospholipids, NOE(-1.6 ppm) potentially highlighted at-risk tissue affected by lipid peroxidation and membrane damage. Altogether, the ADC/NOE(-1.6 ppm)/AREX(3.5 ppm)/CBF mismatches revealed four zones of increasing sizes within the ischemic tissue, potentially reflecting different pathophysiological information.

    CONCLUSIONS: Using CEST coupled with ADC and CBF, the ischemic tissue may thus potentially be separated into four zones to better understand the pathophysiology after stroke and improve ischemic tissue fate definition. Further verification of the potential utility of NOE(-1.6 ppm) may therefore lead to a more precise diagnosis.

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