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Fulltext miRNAS as potential biomarkers in head and neck squamous cell carcinoma diagnostics

Cheah Yoke Kqueen, Yaghma Masood, Nurul Syakima Ab Mutalib, Sethu Thakachy Subha, Norhafizah Mohtarrudin

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):9-9.
MyJurnal

MicroRNAs (miRNAs) are small noncoding RNAs that involved in various normal and cancer-related cellular pro-cesses. Studies on expression profiling of miRNAs have been performed and the data showed that some miRNAs are up-regulated or down-regulated in cancer. miRNAs play a crucial role in HNSCC development, metastasis, prognosis and survival rate. Several studies have been conducted previously to investigate that use of miRNAs as the biomark-ers in disease diagnostic/prognostic and potential therapeutic targets management that may improve the outcomes of HNSCC. Our previous study revealed that upregulation of oncogenic miRNAs including hsa-miR-181a-2*, hsa-miR-29b-1*, hsa-miR-181a, hsa-miR-181b, hsa-miR-744, hsa-miR-1271 and hsa-miR-221* were able to distinguish HNSCC from normal samples. These miRNAs may contribute in a simple profiling strategy to identify individuals at higher risk of developing head and neck cancers, thus helping in the elucidation of the molecular mechanisms involved in head and neck cancer pathogenesis.
Fulltext Whole genome sequence data of an Antarctic bacterium, Arthrobacter sp. ES1 from the Schirmacher Oasis, East Antarctica

Teoh CP, Yusof NA, Budiman C, Cheah YK, Wong CMVL

Data Brief, 2023 Jun;48:109052.
PMID: 36942092 DOI: 10.1016/j.dib.2023.109052

Arthrobacter is a coryneform bacterium in the family of Micrococcaceae. Arthrobacter species isolated from hostile environments are capable of producing interesting bioactive compounds, some of which may be a new class of antibiotics. Here, we present the complete genome sequence of Arthrobacter sp. ES1 isolated from Schirmacher Oasis in East Antarctica. Genomic DNA sequencing was performed using the Illumina MiSeq sequencer. Arthrobacter sp. ES1 has a genome size of 3,964,927 bp and a GC content of 65.73%. The raw genome sequences have been deposited in the NCBI Sequence Read Archive database under the accession number, SRR20664316.
Fulltext Whole genome sequence and annotation dataset of rare actinobacteria, Barrientosiimonas humi gen. nov., sp. nov. 39T from Antarctica

Chong SY, Azmi AA, Cheah YK

Data Brief, 2023 Dec;51:109657.
PMID: 37876741 DOI: 10.1016/j.dib.2023.109657

Barrientosiimonas humi gen. nov., sp. nov. 39T is a rare actinobacteria strain isolated from the less explored extreme environment of the Antarctic soil. Here, we present the whole genome sequencing and annotation data from the high-quality draft genome of B. humi from Antarctica. The extracted genomic deoxyribonucleic acid (DNA) was sequenced using the PacBio Sequel sequencing platform, followed by the Illumina HiSeq sequencing system. Subsequently, the assembly data from Canu 1.7 and Pilon were subjected to bioinformatics analysis for genome annotation to analyze the entire genomic information of the sequences. Different bioinformatics analysis approaches were used to disclose a high-quality draft genome basis for B. humi and provided a better understanding of its biological and molecular functions. Note that 83,639 reads were predicted from its 3.6Mb genome size, with a guanine-cytosine content (GC) content of 72.39%. The genome was assembled into two contigs, where the larger contig represents the chromosome and the smaller contig represents the plasmid. It is composed of 3,381 coding genes, with about 95% of them being functionally annotated. It consists of 3,318 coding sequences, one tmRNA gene, 57 tRNA genes, and five repeated regions. B. humi was evident, sharing a close sequence similarity with the species Demetria terragena and the family Dermacoccaceae. Gene Ontology (GO) functional classification indicated cell and cell parts were highly represented among the cellular component category; catalytic activity and binding were the most enriched processes within the molecular function category; metabolic and cellular processes were the most represented in the biological process category. Clusters of Orthologous Group (COG) functional classification revealed metabolism-related genes were highly enriched and mostly mapped to amino acid transport metabolism, transcription, energy production, and conversion. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional classification reported that the metabolism process was the most represented KEGG pathway. There were 52 biosynthetic gene clusters involved in secondary metabolites biosynthesis, indicating B. humi has antibacterial, antifungal, cytotoxic, and inhibitor bioactivities. The dataset of the whole-genome sequence of B. humi has been deposited in the European Nucleotide Archive (ENA) repository under the accession number PRJEB44986 / ERP129097. The dataset of the genome annotation of B. humi had been deposited in Zenodo. The reported genomic sequence data for B. humi contributes comprehensive data to the current molecular information of the species, serving as a significant approach that facilitates the advancement of medicine.
Virulotyping of Salmonella enterica subsp. enterica isolated from indigenous vegetables and poultry meat in Malaysia using multiplex-PCR

Khoo CH, Cheah YK, Lee LH, Sim JH, Salleh NA, Sidik SM, et al.

Antonie Van Leeuwenhoek, 2009 Nov;96(4):441-57.
PMID: 19565351 DOI: 10.1007/s10482-009-9358-z

The increased occurrence of Salmonella occurrence in local indigenous vegetables and poultry meat can be a potential health hazards. This study is aimed to detect the prevalence of twenty different virulence factors among Salmonella enterica strains isolated from poultry and local indigenous vegetables in Malaysia via an optimized, rapid and specific multiplex PCR assay. The assay encompasses a total of 19 Salmonella pathogenicity islands genes and a quorum sensing gene (sdiA) in three multiplex reaction sets. A total of 114 Salmonella enterica isolates belonging to 38 different serovars were tested. Each isolate in under this study was found to possess up to 70% of the virulence genes tested and exhibited variable pathogenicity gene patterns. Reproducibility of the multiplex PCR assay was found to be 100% and the detection limit of the optimized multiplex PCR was tested with lowest detectable concentration of DNA 0.8 pg microl(-1). This study demonstrated various Salmonella pathogenicity island virulence gene patterns even within the same serovar. This sets of multiplex PCR system provide a fast and reliable typing approach based on Salmonella pathogenicity islands, thus enabling an effective monitoring of emerging pathogenic Salmonella strains as an additional tool in Salmonella surveillance studies.
Fulltext Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata

Chew SY, Brown AJP, Lau BYC, Cheah YK, Ho KL, Sandai D, et al.

J Biomed Sci, 2021 Jan 02;28(1):1.
PMID: 33388061 DOI: 10.1186/s12929-020-00700-8

BACKGROUND: Emergence of Candida glabrata, which causes potential life-threatening invasive candidiasis, has been widely associated with high morbidity and mortality. In order to cause disease in vivo, a robust and highly efficient metabolic adaptation is crucial for the survival of this fungal pathogen in human host. In fact, reprogramming of the carbon metabolism is believed to be indispensable for phagocytosed C. glabrata within glucose deprivation condition during infection.
METHODS: In this study, the metabolic responses of C. glabrata under acetate growth condition was explored using high-throughput transcriptomic and proteomic approaches.
RESULTS: Collectively, a total of 1482 transcripts (26.96%) and 242 proteins (24.69%) were significantly up- or down-regulated. Both transcriptome and proteome data revealed that the regulation of alternative carbon metabolism in C. glabrata resembled other fungal pathogens such as Candida albicans and Cryptococcus neoformans, with up-regulation of many proteins and transcripts from the glyoxylate cycle and gluconeogenesis, namely isocitrate lyase (ICL1), malate synthase (MLS1), phosphoenolpyruvate carboxykinase (PCK1) and fructose 1,6-biphosphatase (FBP1). In the absence of glucose, C. glabrata shifted its metabolism from glucose catabolism to anabolism of glucose intermediates from the available carbon source. This observation essentially suggests that the glyoxylate cycle and gluconeogenesis are potentially critical for the survival of phagocytosed C. glabrata within the glucose-deficient macrophages.
CONCLUSION: Here, we presented the first global metabolic responses of C. glabrata to alternative carbon source using transcriptomic and proteomic approaches. These findings implicated that reprogramming of the alternative carbon metabolism during glucose deprivation could enhance the survival and persistence of C. glabrata within the host.
Fulltext Torque Teno Virus and Hepatitis: A review on correlation.

Siti Nurzulaikha Hazanudin, Cheah Yoke Kqueen, Rasnaizam Rasdi, Zamberi Sekawi, Zulkefley Othman

Life Sciences, Medicine and Biomedicine, 2019;3(2):0-0.
MyJurnal

Torque teno virus (TTV) is one of the “orphan” virus that have been discovered almost two decades ago, with little information on the relationship of the infection to any diseases. It is one of the 45% of commensal virus which was found throughout the population and becoming one of the most extensively studied viruses on its prevalence among various level of health status. From healthy blood donors to patients who suffered severe illness, TTV infection level seems to be high and the findings has triggered an interest from the researcher. Even though the study on TTV prevalence is actively performed, the actual pathogenesis of TTV to any specific diseases is yet to be ascertained. Many suggestions on the possible association of TTV infection with severe diseases such as acute respiratory diseases, liver-related diseases and even cancer have been discussed. However, one type of diseases which might have an association with TTV is hepatitis. Albeit, it remains a theory as the actual pathogenicity of TTV is not fully understood.
The effects of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone on proinflammatory signaling pathways and CLP-induced lethal sepsis in mice

Tham CL, Lam KW, Rajajendram R, Cheah YK, Sulaiman MR, Lajis NH, et al.

Eur J Pharmacol, 2011 Feb 10;652(1-3):136-44.
PMID: 21114991 DOI: 10.1016/j.ejphar.2010.10.092

We previously showed that 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC), suppressed the synthesis of various proinflammatory mediators. In this study we explain the mechanism of action of BHMC in lipopolysaccharide (LPS)-induced U937 monocytes and further show that BHMC prevents lethality of CLP-induced sepsis. BHMC showed dose-dependent inhibitory effects on p38, JNK and ERK 1/2 activity as determined by inhibition of phosphorylation of downstream transcription factors ATF-2, c-Jun and Elk-1 respectively. Inhibition of these transcription factors subsequently caused total abolishment of AP-1-DNA binding. BHMC inhibited p65 NF-κB nuclear translocation and DNA binding of p65 NF-κB only at the highest concentration used (12.5μM) but failed to alter phosphorylation of JNK, ERK1/2 and STAT-1. Since the inhibition of p38 activity was more pronounced we evaluated the possibility that BHMC may bind to p38. Molecular docking experiments confirmed that BHMC fits well in the highly conserved hydrophobic pocket of p38 MAP kinase. We also show that BHMC was able to improve survival from lethal sepsis in a murine caecal-ligation and puncture (CLP) model.
Fulltext The Role of Breast Cancer Stem Cell-Related Biomarkers as Prognostic Factors

Ko CCH, Chia WK, Selvarajah GT, Cheah YK, Wong YP, Tan GC

Diagnostics (Basel), 2020 Sep 19;10(9).
PMID: 32961774 DOI: 10.3390/diagnostics10090721

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide, and its incidence is on the rise. A small fraction of cancer stem cells was identified within the tumour bulk, which are regarded as cancer-initiating cells, possess self-renewal and propagation potential, and a key driver for tumour heterogeneity and disease progression. Cancer heterogeneity reduces the overall efficacy of chemotherapy and contributes to treatment failure and relapse. The cell-surface and subcellular biomarkers related to breast cancer stem cell (BCSC) phenotypes are increasingly being recognised. These biomarkers are useful for the isolation of BCSCs and can serve as potential therapeutic targets and prognostic tools to monitor treatment responses. Recently, the role of noncoding microRNAs (miRNAs) has extensively been explored as novel biomarker molecules for breast cancer diagnosis and prognosis with high specificity and sensitivity. An in-depth understanding of the biological roles of miRNA in breast carcinogenesis provides insights into the pathways of cancer development and its utility for disease prognostication. This review gives an overview of stem cells, highlights the biomarkers expressed in BCSCs and describes their potential role as prognostic indicators.
Fulltext The Interplay between MicroRNAs and Cellular Components of Tumour Microenvironment (TME) on Non-Small-Cell Lung Cancer (NSCLC) Progression

Lee SS, Cheah YK

J Immunol Res, 2019;2019:3046379.
PMID: 30944831 DOI: 10.1155/2019/3046379

Cellular components of the tumour microenvironment (TME) are recognized to regulate the hallmarks of cancers including tumour proliferation, angiogenesis, invasion, and metastasis, as well as chemotherapeutic resistance. The linkage between miRNA, TME, and the development of the hallmarks of cancer makes miRNA-mediated regulation of TME a potential therapeutic strategy to complement current cancer therapies. Despite significant advances in cancer therapy, lung cancer remains the deadliest form of cancer among males in the world and has overtaken breast cancer as the most fatal cancer among females in more developed countries. Therefore, there is an urgent need to develop more effective treatments for NSCLC, which is the most common type of lung cancer. Hence, this review will focus on current literature pertaining to antitumour or protumourigenic effects elicited by nonmalignant stromal cells of TME in NSCLC through miRNA regulation as well as current status and future prospects of miRNAs as therapeutic agents or targets to regulate TME in NSCLC.
Fulltext Tear Samples for Protein Extraction: Comparative Analysis of Schirmer's Test Strip and Microcapillary Tube Methods

Tham ML, Mahmud A, Abdullah M, Md Saleh R, Mohammad Razali A, Cheah YK, et al.

Cureus, 2023 Dec;15(12):e50972.
PMID: 38259376 DOI: 10.7759/cureus.50972

INTRODUCTION: Tear sampling is an attractive option for collecting biological samples in ophthalmology clinics, as it offers a non-invasive alternative to other invasive techniques. However, there are many tear sampling methods still in consideration. This study explores the suitability of Schirmer's test strip and microcapillary tube as reliable and satisfactory methods for tear sampling.
METHODS: Tear samples were collected from eight healthy volunteers using the standard Schirmer's test strip method with or without anesthesia and microcapillary tubes. The total tear protein concentrations were analyzed via spectrophotometry and bicinchoninic acid (BCA) protein assay. The protein profile was determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The optimal wetting length of Schirmer's strip and suitable buffer solutions were compared. Discomfort levels reported by participants and the ease of execution for ophthalmologists were also evaluated.
RESULTS: Tear samples exhibited typical protein profiles as shown by SDS-PAGE. The mean total protein obtained from an optimum wetting length of 20 mm using Schirmer's strip without anesthesia in phosphate-buffered saline (PBS) yielded substantial quantities of protein as measured by nanophotometer (220.20 ± 67.43 µg) and the BCA protein assay (210.34 ± 59.46 µg). This method collected a significantly higher quantity of protein compared to the microcapillary tube method (p=0.004) which was much more difficult to standardize. The clinician found it harder to utilize microcapillary tubes, while participants experienced higher insecurity and less discomfort with the microcapillary tube method. PBS used during the tear protein extraction process eluted higher tear protein concentration than ammonium bicarbonate, although the difference was not statistically significant. Using anaesthesia did not ease the sampling procedure substantially and protein quantity was maintained.
CONCLUSION: Good quality and quantity of protein from tear samples were extracted with the optimized procedure. Schirmer's strip test in the absence of local anesthesia provided a standard, convenient, and non-invasive method for tear collection.
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.
Synthesis of a DNA-targeting nickel (II) complex with testosterone thiosemicarbazone which exhibits selective cytotoxicity towards human prostate cancer cells (LNCaP)

Heng MP, Sinniah SK, Teoh WY, Sim KS, Ng SW, Cheah YK, et al.

Spectrochim Acta A Mol Biomol Spectrosc, 2015 Nov 5;150:360-72.
PMID: 26057090 DOI: 10.1016/j.saa.2015.05.095

Testosterone thiosemicarbazone, L and its nickel (II) complex 1 were synthesized and characterized by using FTIR, CHN, (1)H NMR, and X-ray crystallography. X-ray diffraction study confirmed the formation of L from condensation of testosterone and thiosemicarbazide. Mononuclear complex 1 is coordinated to two Schiff base ligands via two imine nitrogens and two tautomeric thiol sulfurs. The cytotoxicity of both compounds was investigated via MTT assay with cisplatin as positive reference standard. L is more potent towards androgen-dependent LNCaP (prostate) and HCT 116 (colon). On the other hand, complex 1, which is in a distorted square planar environment with L acting as a bidentate NS-donor ligand, is capable of inhibiting the growth of all the cancer cell lines tested, including PC-3 (prostate). It is noteworthy that both compounds are less toxic towards human colon cell CCD-18Co. The intrinsic DNA binding constant (Kb) of both compounds were evaluated via UV-Vis spectrophotometry. Both compounds showed Kb values which are comparable to the reported Kb value of typical classical intercalator such as ethidium bromide. The binding constant of the complex is almost double compared with ligand L. Both compounds were unable to inhibit the action topoisomerase I, which is the common target in cancer treatment (especially colon cancer). This suggest a topoisomerase I independent-cell death mechanism.
Simulation of improper food hygiene practices: A quantitative assessment of Vibrio parahaemolyticus distribution

Malcolm TTH, Chang WS, Loo YY, Cheah YK, Radzi CWJWM, Kantilal HK, et al.

Int J Food Microbiol, 2018 Nov 02;284:112-119.
PMID: 30142576 DOI: 10.1016/j.ijfoodmicro.2018.08.012

Kitchen mishandling practices contribute to a large number of foodborne illnesses. In this study, the transfer and cross-contamination potential of Vibrio parahaemolyticus from bloody clams to ready-to-eat food (lettuce) was assessed. Three scenarios were investigated: 1) direct cross-contamination, the transfer of V. parahaemolyticus from bloody clams to non-food contact surfaces (hands and kitchen utensils) to lettuce (via slicing), was evaluated; 2) perfunctory decontamination, the efficacy of two superficial cleaning treatments: a) rinsing in a pail of water, and b) wiping with a kitchen towel, were determined; and 3) secondary cross-contamination, the microbial transfer from cleaning residuals (wash water or stained kitchen towel) to lettuce was assessed. The mean of percent transfer rates through direct contact was 3.6%, and an average of 3.5% of total V. parahaemolyticus was recovered from sliced lettuce. The attempted treatments reduced the transferred population by 99.0% (rinsing) and 94.5% (wiping), and the relative amount of V. parahaemolyticus on sliced lettuce was reduced to 0.008%. V. parahaemolyticus exposure via secondary cross-contamination was marginal. The relative amount of V. parahaemolyticus recovered from washed lettuce was 0.07%, and the transfers from stained kitchen towel to lettuce were insubstantial. Our study highlights that V. parahaemolyticus was readily spread in the kitchen, potentially through sharing of non-food contact surfaces. Results from this study can be used to better understand and potentially raising the awareness of proper handling practices to avert the spread of foodborne pathogens.
Profiling of recovery efficiencies for three standard protocols (FDA-BAM, ISO-11290, and modified USDA) on temperature-injured Listeria monocytogenes

Lee HY, Chai LC, Pui CF, Wong WC, Mustafa S, Cheah YK, et al.

J Microbiol Biotechnol, 2011 Sep;21(9):954-9.
PMID: 21952372

There have been a number of studies conducted in order to compare the efficiencies of recovery rates, utilizing different protocols, for the isolation of L. monocytogenes. However, the severity of multiple cell injury has not been included in these studies. In the current study, L. monocytogenes ATCC 19112 was injured by exposure to extreme temperatures (60°C and -20°C) for a one-step injury, and for a two-step injury the cells were transferred directly from a heat treatment to frozen state to induce a severe cell injury (up to 100% injury). The injured cells were then subjected to the US Food and Drug Administration (FDA), the ISO-11290, and the modified United States Department of Agriculture (mUSDA) protocols, and plated on TSAyeast (0.6% yeast), PALCAM agar, and CHROMAgar Listeria for 24 h or 48 h. The evaluation of the total recovery of injured cells was also calculated based on the costs involved in the preparation of media for each protocol. Results indicate that the mUSDA method is best able to aid the recovery of heat-injured, freeze-injured, and heat-freeze-injured cells and was shown to be the most cost effective for heat-freeze-injured cells.
Fulltext Potential ability of phytochemical in inhibition of invadopodia formation and HIF-1α in cancer metastasis

Hamad Ali Hamad, Banulata Gopalsamy, Cheah Yoke Kqueen, Nur Fariesha Md Hashim

Malaysian Journal of Medicine and Health Sciences, 2019;15(202):71-80.
MyJurnal

Cancer metastasis is a multistep process, which results in cancer cells disseminating to other organs. The crucial metastasis step involves cancer invasion which occurs via actin-protrusion by invasive malignant cells, termed as invadopodia. In solid tumours, invadopodia formation increases as a result of hypoxia which is found to be resis- tant against chemotherapy and radiotherapy. Phytochemicals have been potentially identified as a prime source of effective conventional drugs for metastasis treatments, which target cancer cell invasion, particularly molecular components of the invadopodia formation. The Hypoxia-Inducible Factor-1α (HIF-1α) is an essential target in terms of treatment for hypoxic tumour, as well as helping to identify the mode of action for the drugs, particularly phy- tochemical compounds. The aim of this review is to highlight the current development with regards to the ability of phytochemicals in targeting cancer metastasis, as well as phytochemical compounds which are able to inhibit HIF-1α and invadopodia formation. The use of phytochemicals for targeting hypoxic cancer cells may open new prospects for reducing cancer metastasis.
Fulltext Physiologically Relevant Alternative Carbon Sources Modulate Biofilm Formation, Cell Wall Architecture, and the Stress and Antifungal Resistance of Candida glabrata

Chew SY, Ho KL, Cheah YK, Sandai D, Brown AJP, Than LTL

Int J Mol Sci, 2019 Jun 28;20(13).
PMID: 31261727 DOI: 10.3390/ijms20133172

Flexibility in carbon metabolism is pivotal for the survival and propagation of many human fungal pathogens within host niches. Indeed, flexible carbon assimilation enhances pathogenicity and affects the immunogenicity of Candida albicans. Over the last decade, Candida glabrata has emerged as one of the most common and problematic causes of invasive candidiasis. Despite this, the links between carbon metabolism, fitness, and pathogenicity in C. glabrata are largely unexplored. Therefore, this study has investigated the impact of alternative carbon metabolism on the fitness and pathogenic attributes of C. glabrata. We confirm our previous observation that growth on carbon sources other than glucose, namely acetate, lactate, ethanol, or oleate, attenuates both the planktonic and biofilm growth of C. glabrata, but that biofilms are not significantly affected by growth on glycerol. We extend this by showing that C. glabrata cells grown on these alternative carbon sources undergo cell wall remodeling, which reduces the thickness of their β-glucan and chitin inner layer while increasing their outer mannan layer. Furthermore, alternative carbon sources modulated the oxidative stress resistance of C. glabrata as well as the resistance of C. glabrata to an antifungal drug. In short, key fitness and pathogenic attributes of C. glabrata are shown to be dependent on carbon source. This reaffirms the perspective that the nature of the carbon sources available within specific host niches is crucial for C. glabrata pathogenicity during infection.
Physicochemical, morphological and cellular uptake properties of lutein nanodispersions prepared by using surfactants with different stabilizing mechanisms

Tan TB, Chu WC, Yussof NS, Abas F, Mirhosseini H, Cheah YK, et al.

Food Funct, 2016 Apr 20;7(4):2043-51.
PMID: 27010495 DOI: 10.1039/c5fo01621e

In this study, we prepared a series of lutein nanodispersions via the solvent displacement method, by using surfactants with different stabilizing mechanisms. The surfactants used include Tween 80 (steric stabilization), sodium dodecyl sulfate (SDS; electrostatic stabilization), sodium caseinate (electrosteric stabilization) and SDS-Tween 80 (electrostatic-steric stabilization). We then characterized the resulting lutein nanodispersions in terms of their particle size, particle size distribution, zeta potential, lutein content, flow behavior, apparent viscosity, transmittance, color, morphological properties and their effects on cell viability and cellular uptake. The type of surfactant used significantly (p < 0.05) affected the physical properties of the nanodispersions, but the chemical properties (lutein content) remained unaffected. Transmission electron microscopy (TEM) images obtained from this study demonstrated that the solvent displacement method was capable of producing lutein nanodispersions containing spherical particles with sizes ranging from 66.20-125.25 nm, depending on the type of surfactant used. SDS and SDS-Tween 80 surfactants negatively affected the viability of the HT-29 cells used in this study. Thus, for the cellular uptake determination, only Tween 80 and sodium caseinate surfactants were used. The cellular uptake of the lutein nanodispersion stabilized by sodium caseinate was higher than that which was stabilized by Tween 80. All things considered, the type of surfactant with different stabilizing mechanisms did produce lutein nanodispersions with different characteristics. These findings would aid in future selection of surfactants in order to produce nanodispersions with desirable properties.
Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NC 6H 4Me-4] for R = Me, Et and iPr, induce apoptosis, cell cycle arrest and inhibit cell invasion of HT-29 colon cancer cells through modulation of the nuclear factor-κB activation pathway and ubiquitination

Ooi KK, Yeo CI, Ang KP, Akim AM, Cheah YK, Halim SN, et al.

J Biol Inorg Chem, 2015 Jul;20(5):855-73.
PMID: 26003312 DOI: 10.1007/s00775-015-1271-5

The phosphanegold(I) carbonimidothioates, Ph3PAu{SC(OR)=NC6H4Me-4} for R = Me (1), Et (2) and iPr (3), feature linear P-Au-S coordination geometries and exhibit potent in vitro cytotoxicity against HT-29 colon cancer cells in both monolayer and multi-cellular spheroid models (e.g., IC50 = 11.9 ± 0.4 and 20.3 ± 0.3 μM for 2, respectively). Both intrinsic and extrinsic pathways of apoptosis are demonstrated by human apoptosis PCR array analysis, caspase activities, DNA fragmentation and cell apoptotic assays. Compounds 1-3 induce an extrinsic pathway that leads to down-regulation of NFκB. Compound 2 also exhibits an extrinsic apoptotic pathway involving the activation of both p53 and p73, whereas 3 activates p53 only. Lys48- and Lys63-linked polyubiquitination are also promoted by 1-3. Each of cytotoxic Ph3PAu{SC(OR)=NC6H4Me-4}, for R = Me (1), Et (2) and iPr (3), induce an intrinsic apoptotic pathway as well as an extrinsic pathway leading to down-regulation of NFκB. Lys48- and Lys63-linked polyubiquitination are promoted by 1-3 and these are able to inhibit cell invasion and to suppress the activity of TrxR.
Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N((i)Pr)CH2CH2OH] for R = Ph, Cy and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways

Jamaludin NS, Goh ZJ, Cheah YK, Ang KP, Sim JH, Khoo CH, et al.

Eur J Med Chem, 2013 Sep;67:127-41.
PMID: 23856069 DOI: 10.1016/j.ejmech.2013.06.038

The synthesis and characterisation of R3PAu[S2CN((i)Pr)CH2CH2OH], for R = Ph (1), Cy (2) and Et (3)4, is reported. Compounds 1-3 are cytotoxic against the doxorubicin-resistant breast cancer cell line, MCF-7R, with 1 exhibiting greater potency and cytotoxicity than either of doxorubicin and cisplatin. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis by 1, and necrosis by 2 and 3, are demonstrated, by both extrinsic and intrinsic pathways. Compound 1 activates the p53 gene, 2 activates only the p73 gene, whereas 3 activates both the p53 and p73 genes. Compounds 1 and 3 activate NF-κB, and each inhibits topoisomerase I.
Fulltext Phenotype microarrays reveal metabolic dysregulations of neurospheres derived from embryonic Ts1Cje mouse model of Down syndrome

Seth EA, Lee HC, Yusof HHBM, Nordin N, Cheah YK, Ho ETW, et al.

PLoS One, 2020;15(7):e0236826.
PMID: 32730314 DOI: 10.1371/journal.pone.0236826

Down syndrome (DS), is the most common cause of intellectual disability, and is characterized by defective neurogenesis during perinatal development. To identify metabolic aberrations in early neurogenesis, we profiled neurospheres derived from the embryonic brain of Ts1Cje, a mouse model of Down syndrome. High-throughput phenotypic microarray revealed a significant decrease in utilisation of 17 out of 367 substrates and significantly higher utilisation of 6 substrates in the Ts1Cje neurospheres compared to controls. Specifically, Ts1Cje neurospheres were less efficient in the utilisation of glucose-6-phosphate suggesting a dysregulation in the energy-producing pathway. T Cje neurospheres were significantly smaller in diameter than the controls. Subsequent preliminary study on supplementation with 6-phosphogluconic acid, an intermediate of glucose-6-phosphate metabolism, was able to rescue the Ts1Cje neurosphere size. This study confirmed the perturbed pentose phosphate pathway, contributing to defects observed in Ts1Cje neurospheres. We show for the first time that this comprehensive energetic assay platform facilitates the metabolic characterisation of Ts1Cje cells and confirmed their distinguishable metabolic profiles compared to the controls.

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