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In vitro modulation of probiotic bacteria on the biofilm of Candida glabrata

Chew SY, Cheah YK, Seow HF, Sandai D, Than LT

Anaerobe, 2015 Aug;34:132-8.
PMID: 26028405 DOI: 10.1016/j.anaerobe.2015.05.009

A conspicuous new concept of pathogens living as the microbial societies in the human host rather than free planktonic cells has raised considerable concerns among scientists and clinicians. Fungal biofilms are communities of cells that possess distinct characteristic such as increased resistance to the immune defence and antimycotic agents in comparison to their planktonic cells counterpart. Therefore, inhibition of the biofilm may represent a new paradigm for antifungal development. In this study, we aim to evaluate the in vitro modulation of vulvovaginal candidiasis (VVC)-causing Candida glabrata biofilms using probiotic lactobacilli strains. Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 were shown to have completely inhibited C. glabrata biofilms and the results were corroborated by scanning electron microscopy (SEM), which revealed scanty structures of the mixed biofilms of C. glabrata and probiotic lactobacilli strains. In addition, biofilm-related C. glabrata genes EPA6 and YAK1 were downregulated in response to the probiotic lactobacilli challenges. The present study suggested that probiotic L. rhamnosus GR-1 and L. reuteri RC-14 strains inhibited C. glabrata biofilm by partially impeding the adherence of yeast cells and the effect might be contributed by the secretory compounds produced by these probiotic lactobacilli strains. Further investigations are required to examine and identify the biofilm inhibitory compounds and the mechanism of probiotic actions of these lactobacilli strains.
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.
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 Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata

Chew SY, Ho KL, Cheah YK, Ng TS, Sandai D, Brown AJP, et al.

Sci Rep, 2019 02 26;9(1):2843.
PMID: 30808979 DOI: 10.1038/s41598-019-39117-1

The human fungal pathogen Candida glabrata appears to utilise unique stealth, evasion and persistence strategies in subverting the onslaught of host immune response during systemic infection. However, macrophages actively deprive the intracellular fungal pathogen of glucose, and therefore alternative carbon sources probably support the growth and survival of engulfed C. glabrata. The present study aimed to investigate the role of the glyoxylate cycle gene ICL1 in alternative carbon utilisation and its importance for the virulence of C. glabrata. The data showed that disruption of ICL1 rendered C. glabrata unable to utilise acetate, ethanol or oleic acid. In addition, C. glabrata icl1∆ cells displayed significantly reduced biofilm growth in the presence of several alternative carbon sources. It was also found that ICL1 is crucial for the survival of C. glabrata in response to macrophage engulfment. Disruption of ICL1 also conferred a severe attenuation in the virulence of C. glabrata in the mouse model of invasive candidiasis. In conclusion, a functional glyoxylate cycle is essential for C. glabrata to utilise certain alternative carbon sources in vitro and to display full virulence in vivo. This reinforces the view that antifungal drugs that target fungal Icl1 have potential for future therapeutic intervention.
Complete genome sequence data of tropical thermophilic bacterium Parageobacillus caldoxylosilyticus ER4B

Ching XJ, Najimudin N, Cheah YK, Wong CMVL

Data Brief, 2022 Feb;40:107764.
PMID: 35024395 DOI: 10.1016/j.dib.2021.107764

Parageobacillus caldoxylosilyticus, or previously identified as Geobacillus caldoxylosilyticus, is a thermophilic Gram-positive bacterium which can easily withstand growth temperatures ranging from 40 °C to 70 °C. Here, we present the first complete genome sequence of Parageobacillus caldoxylosilyticus ER4B which was isolated from an empty oil palm fruit bunch compost in Malaysia. Whole genome sequencing was performed using the PacBio RSII platform. The genome size of strain ER4B was around 3.9Mbp, with GC content of 44.31%. The genome consists of two contigs, in which the larger contig (3,909,276bp) represents the chromosome, while the smaller one (54,250bp) represents the plasmid. A total of 4,164 genes were successfully predicted, including 3,972 protein coding sequences, 26 rRNAs, 91 tRNAs, 74 miscRNA, and 1 tmRNA. The genome sequence data of strain ER4B reported here may contribute to the current molecular information of the species. It may also facilitate the discovery of molecular traits related to thermal stress, thus, expanding our understanding in the acclimation or adaptation towards extreme temperature in bacteria.
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.
Fulltext Optimization of process parameters in preparation of tocotrienol-rich red palm oil-based nanoemulsion stabilized by Tween80-Span 80 using response surface methodology

Chong WT, Tan CP, Cheah YK, B Lajis AF, Habi Mat Dian NL, Kanagaratnam S, et al.

PLoS One, 2018;13(8):e0202771.
PMID: 30142164 DOI: 10.1371/journal.pone.0202771

Red palm oil (RPO) is a natural source of Vitamin E (70-80% tocotrienol). It is a potent natural antioxidant that can be used in skin-care products. Its antioxidant property protects skin from inflammation and aging. In our work, a tocotrienol-rich RPO-based nanoemulsion formulation was optimized using response surface methodology (RSM) and formulated using high pressure homogenizer. Effect of the concentration of three independent variables [surfactant (5-15 wt%), co-solvent (10-30 wt%) and homogenization pressure (500-700 bar)] toward two response variables (droplet size, polydispersity index) was studied using central composite design (CCD) coupled to RSM. RSM analysis showed that the experimental data could be fitted into a second-order polynomial model and the coefficients of multiple determination (R2) is 0.9115. The optimized formulation of RPO-based nanoemulsion consisted of 6.09 wt% mixed surfactant [Tween 80/Span 80 (63:37, wt)], 20 wt% glycerol as a co-solvent via homogenization pressure (500 bar). The optimized tocotrienol-rich RPO-based nanoemulsion response values for droplet size and polydispersity index were 119.49nm and 0.286, respectively. The actual values of the formulated nanoemulsion were in good agreement with the predicted values obtained from RSM, thus the optimized compositions have the potential to be used as a nanoemulsion for cosmetic formulations.
Association of Cholesteryl Ester Transfer Protein and Endothelial Nitric Oxide Synthase Gene Polymorphisms With Coronary Artery Disease in the Multi-Ethnic Malaysian Population

Chu WC, Aziz AF, Nordin AJ, Cheah YK

Clin Appl Thromb Hemost, 2016 Sep;22(6):581-8.
PMID: 25667236 DOI: 10.1177/1076029615571628

Genetic variants of cholesteryl ester transfer protein (CETP) and endothelial nitric oxide synthase (eNOS) influence high-density lipoprotein cholesterol (HDL-C) metabolism and nitric oxide (NO) synthesis, respectively, and might increase the risk of coronary artery disease (CAD). This study is to investigate the relationship between genetic polymorphisms and the risk of CAD and to evaluate their potential interactions. A total of 237 patients with CAD and 101 controls were genotyped. The association of the polymorphism with the risk of CAD varied among the ethnic groups. Moreover, the concomitant presence of both CETP B1 and eNOS 4a alleles significantly increased the risk of CAD in the Malay group (OR = 33.8, P < .001) and the Indian group (OR = 10.9, P = .031) but not in the Chinese group. This study has identified a novel ethnic-specific gene-gene interaction and suggested that the combination of CETP B1 allele and eNOS 4a allele significantly increases the risk of CAD in Malays and Indians.
Prevalence of COVID-19 among healthcare workers in the paediatric department: Estimates from a multicenter cross-sectional survey in Negeri Sembilan

David NCE, Juliana H, Chok M, Gan YZ, Tan YC, Nur Adlina MN, et al.

Med J Malaysia, 2023 Jan;78(1):80-86.
PMID: 36715196

INTRODUCTION: The COVID-19 pandemic has reached a phase where many have been infected at least once. Healthcare workers were not spared from being infected. This study aimed to determine the period prevalence of COVID-19 among the paediatric healthcare workers in Negeri Sembilan as the country transitioned into an endemic phase of the pandemic. Additionally, we investigate potential sociodemographic and occupational characteristics associated with SARS-CoV-2 infection among healthcare workers.
MATERIALS AND METHODS: A cross-sectional study was conducted among the healthcare workers in the paediatric department at three public specialist hospitals in Negeri Sembilan between 15 and 21 April 2022. Data were collected through a self-administered questionnaire.
RESULTS: Out of the 504 eligible healthcare workers, 493 participated in this study (response rate 97.8%). The overall prevalence of COVID-19 (11 March 2020-15 April 2022) among healthcare workers was 50.9%. The majority (80.1%) were infected during the Omicron wave two months before the survey. Household contacts accounted for 35.9% of infection sources. The proportion of non-doctors in the COVID-19-infected group was significantly higher compared to the non-infected group (74.1% vs 64.0%, p=0.016). The COVID-19-infected group had a higher proportion of schoolgoing children (44.6% vs 30.6%, p=0.001) and children who attended pre-school/sent to the babysitter (49.0% vs 24.4%, p<0.001). There were no significant differences between infection rates among the healthcare workers working in the tertiary hospital and the district hospitals. There were also no significant differences in the proportion of COVID-19- infected doctors and nurses when analysed by seniority.
CONCLUSION: Our study provided an estimate on the prevalence of COVID-19 among paediatric healthcare workers in Negeri Sembilan and the factors associated with infection, which captures the extent and magnitude of this pandemic on the state's paediatric department. Most infections resulted from household contact, with a higher proportion of infected healthcare workers having young children.
Fulltext Evaluation of DNA and RNA extraction methods

Edwin Shiaw CS, Shiran MS, Cheah YK, Tan GC, Sabariah AR

Med J Malaysia, 2010 Jun;65(2):133-7.
PMID: 23756798 MyJurnal

This study was done to evaluate various DNA and RNA extractions from archival FFPE tissues. A total of 30 FFPE blocks from the years of 2004 to 2006 were assessed with each modified and adapted method. Extraction protocols evaluated include the modified enzymatic extraction method (Method A), Chelex-100 extraction method (Method B), heat-induced retrieval in alkaline solution extraction method (Methods C and D) and one commercial FFPE DNA Extraction kit (Qiagen, Crawley, UK). For RNA extraction, 2 extraction protocols were evaluated including the enzymatic extraction method (Method 1), and Chelex-100 RNA extraction method (Method 2). Results show that the modified enzymatic extraction method (Method A) is an efficient DNA extraction protocol, while for RNA extraction, the enzymatic method (Method 1) and the Chelex-100 RNA extraction method (Method 2) are equally efficient RNA extraction protocols.
Fulltext Induction of cell cycle arrest and apoptosis in caspase-3 deficient MCF-7 cells by Dillenia suffruticosa root extract via multiple signalling pathways

Foo JB, Yazan LS, Tor YS, Armania N, Ismail N, Imam MU, et al.

BMC Complement Altern Med, 2014;14:197.
PMID: 24947113 DOI: 10.1186/1472-6882-14-197

Dillenia suffruticosa root dichloromethane extract (DCM-DS) has been reported to exhibit strong cytotoxicity towards breast cancer cells. The present study was designed to investigate the cell cycle profile, mode of cell death and signalling pathways of DCM-DS-treated human caspase-3 deficient MCF-7 breast cancer cells.
Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple-negative breast cancer cells

Foo JB, Saiful Yazan L, Tor YS, Wibowo A, Ismail N, Armania N, et al.

J Ethnopharmacol, 2016 Jul 1;187:195-204.
PMID: 27131434 DOI: 10.1016/j.jep.2016.04.048

Dillenia suffruticosa is traditionally used for treatment of cancerous growth including breast cancer in Malaysia.
Induction of cell cycle arrest and apoptosis by betulinic acid-rich fraction from Dillenia suffruticosa root in MCF-7 cells involved p53/p21 and mitochondrial signalling pathway

Foo JB, Saiful Yazan L, Tor YS, Wibowo A, Ismail N, How CW, et al.

J Ethnopharmacol, 2015 May 26;166:270-8.
PMID: 25797115 DOI: 10.1016/j.jep.2015.03.039

Dillenia suffruticosa (Family: Dilleniaceae) or commonly known as "Simpoh air" in Malaysia, is traditionally used for treatment of cancerous growth including breast cancer.
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.
Fulltext Identification of Potential Chemical Substrates as Fuel for Hypoxic Tumors That May Be Linked to Invadopodium Formation in Hypoxia-Induced MDA-MB-231 Breast-Cancer Cell Line

Hamad HA, Enezei HH, Alrawas A, Zakuan NM, Abdullah NA, Cheah YK, et al.

Molecules, 2020 Aug 26;25(17).
PMID: 32858793 DOI: 10.3390/molecules25173876

Hypoxia plays a significant role in solid tumors by the increased expression of hypoxia-inducible factor-1α (HIF-1α), which is known to promote cancer invasion and metastasis. Cancer-cell invasion dynamically begins with the degradation of the extracellular matrix (ECM) via invadopodia formation. The chemical substrates that are utilized by hypoxic cells as fuel to drive invadopodia formation are still not fully understood. Therefore, the aim of the study was to maintain MDA-MB-231 cells under hypoxia conditions to allow cells to form a large number of invadopodia as a model, followed by identifying their nutrient utilization. The results of the study revealed an increase in the number of cells forming invadopodia under hypoxia conditions. Moreover, Western blot analysis confirmed that essential proteins for hypoxia and invadopodia, including HIF-1α, vascular endothelial growth factor (VEGF), metallopeptidase-2 (MMP-2), and Rho guanine nucleotide exchange factor 7 (β-PIX), significantly increased under hypoxia. Interestingly, phenotype microarray showed that only 11 chemical substrates from 367 types of substrates were significantly metabolized in hypoxia compared to in normoxia. This is thought to be fuel for hypoxia to drive the invasion process. In conclusion, we found 11 chemical substrates that could have potential energy sources for hypoxia-induced invadopodia formation of these cells. This may in part be a target in the hypoxic tumor and invadopodia formation. Additionally, these findings can be used as potential carrier targets in cancer-drug discovery, such as the usage of dextrin.
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.
Fulltext Management of T1DM in children and adolescents in primary care

Hong Y, Hassan N, Cheah YK, Jalaludin MY, Kasim ZM

Malays Fam Physician, 2017;12(2):18-22.
PMID: 29423125

The Clinical Practice Guidelines on the Management of Type 1 Diabetes Mellitus in Children & Adolescents was developed by a multidisciplinary development group and approved by the Ministry of Health Malaysia in 2015. A systematic review of 15 clinical questions was conducted using the evidence retrieved mainly from MEDLINE and Cochrane databases. Critical appraisal was done using the Critical Appraisal Skills. Recommendations were formulated on the accepted 136 evidences using the principles of Grading Recommendations, Assessment, Development and Evaluation tailored to the local setting. Type 1 diabetes mellitus is a chronic disease, which usually occurs at an early age, and is associated with various complications including retinopathy, nephropathy, neuropathy and cardiovascular morbidity. Good glycaemic control early in the disease results in lower frequency of chronic diabetes complications, which in turn reduces the healthcare cost. Accurate classification of diabetes and optimum management with the aim to achieve glycaemic targets is of utmost importance.
A bismuth diethyldithiocarbamate compound promotes apoptosis in HepG2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the NF-κB activation pathway

Ishak DH, Ooi KK, Ang KP, Akim AM, Cheah YK, Nordin N, et al.

J Inorg Biochem, 2014 Jan;130:38-51.
PMID: 24176918 DOI: 10.1016/j.jinorgbio.2013.09.018

The compound with R=CH2CH3 in Bi(S2CNR2)3 (1) is highly cytotoxic against a range of human carcinoma, whereas that with R=CH2CH2OH (2) is considerably less so. Both 1 and 2 induce apoptosis in HepG2 cells with some evidence for necrosis induced by 2. Based on DNA fragmentation, caspase activities and human apoptosis PCR-array analysis, both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. While both compounds activate mitochondrial and FAS apoptotic pathways, compound 1 was also found to induce another death receptor-dependent pathway by induction of CD40, CD40L and TNF-R1 (p55). Further, 1 highly expressed DAPK1, a tumour suppressor, with concomitant down-regulation of XIAP and NF-κB. Cell cycle arrest at the S and G2/M phases correlates with the inhibition of the growth of HepG2 cells. The cell invasion rate of 2 is 10-fold higher than that of 1, a finding correlated with the down-regulation of survivin and XIAP expression by 1. Compounds 1 and 2 interact with DNA through different binding motifs with 1 interacting with AT- or TA-specific sites followed by inhibition of restriction enzyme digestion; 2 did not interfere with any of the studied restriction enzymes.
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 Validity of self-reported weight and height: a cross-sectional study among Malaysian adolescents

Kee CC, Lim KH, Sumarni MG, Teh CH, Chan YY, Nuur Hafizah MI, et al.

BMC Med Res Methodol, 2017 Jun 02;17(1):85.
PMID: 28577547 DOI: 10.1186/s12874-017-0362-0

BACKGROUND: Self-reported weight and height are commonly used in lieu of direct measurements of weight and height in large epidemiological surveys due to inevitable constraints such as budget and human resource. However, the validity of self-reported weight and height, particularly among adolescents, needs to be verified as misreporting could lead to misclassification of body mass index and therefore overestimation or underestimation of the burden of BMI-related diseases. The objective of this study was to determine the validity of self-reported weight and height among Malaysian secondary school children.

METHODS: Both self-reported and directly measured weight and height of a subgroup of 663 apparently healthy schoolchildren from the Malaysian Adolescent Health Risk Behaviour (MyAHRB) survey 2013/2014 were analysed. Respondents were required to report their current body weight and height via a self-administrative questionnaire before they were measured by investigators. The validity of self-reported against directly measured weight and height was examined using intraclass correlation coefficient (ICC), the Bland-Altman plot and weighted Kappa statistics.

RESULTS: There was very good intraclass correlation between self-reported and directly measured weight [r = 0.96, 95% confidence interval (CI): 0.93, 0.97] and height (r = 0.94, 95% CI: 0.90, 0.96). In addition the Bland-Altman plots indicated that the mean difference between self-reported and direct measurement was relatively small. The mean difference (self-reported minus direct measurements) was, for boys: weight, -2.1 kg; height, -1.6 cm; BMI, -0.44 kg/m2 and girls: weight, -1.2 kg; height, -0.9 cm; BMI, -0.3 kg/m2. However, 95% limits of agreement were wide which indicated substantial discrepancies between self-reported and direct measurements method at the individual level. Nonetheless, the weighted Kappa statistics demonstrated a substantial agreement between BMI status categorised based on self-reported weight and height and the direct measurements (kappa = 0.76, 95% CI: 0.67, 0.84).

CONCLUSION: Our results show that the self-reported weight and height were consistent with direct measurements and therefore can be used in assessing the nutritional status of Malaysian school children from the age of 13 to 17 years old in epidemiological studies and for surveillance purposes when direct measurements are not feasible, but not for assessing nutritional status at the individual level.

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