Displaying publications 1 - 20 of 250 in total

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  1. Che Hamzah AM, Chew CH, Al-Trad EI, Puah SM, Chua KH, A Rahman NI, et al.
    Sci Rep, 2024 Feb 12;14(1):3485.
    PMID: 38347106 DOI: 10.1038/s41598-024-54182-x
    Despite the importance of methicillin-resistant Staphylococcus aureus (MRSA) as a priority nosocomial pathogen, the genome sequences of Malaysian MRSA isolates are currently limited to a small pool of samples. Here, we present the genome sequence analyses of 88 clinical MRSA isolates obtained from the main tertiary hospital in Terengganu, Malaysia in 2016-2020, to obtain in-depth insights into their characteristics. The EMRSA-15 (ST22-SCCmec IV) clone of the clonal complex 22 (CC22) lineage was predominant with a total of 61 (69.3%) isolates. Earlier reports from other Malaysian hospitals indicated the predominance of the ST239 clone, but only two (2.3%) isolates were identified in this study. Two Indian-origin clones, the Bengal Bay clone ST772-SCCmec V (n = 2) and ST672 (n = 10) were also detected, with most of the ST672 isolates obtained in 2020 (n = 7). Two new STs were found, with one isolate each, and were designated ST7879 and ST7883. From the core genome phylogenetic tree, the HSNZ MRSA isolates could be grouped into seven clades. Antimicrobial phenotype-genotype concordance was high (> 95%), indicating the accuracy of WGS in predicting most resistances. Majority of the MRSA isolates were found to harbor more than 10 virulence genes, demonstrating their pathogenic nature.
  2. Jones SU, Chew CH, Yeo CC, Abdullah FH, Othman N, Kee BP, et al.
    Int Microbiol, 2023 Nov;26(4):841-849.
    PMID: 36805382 DOI: 10.1007/s10123-023-00335-3
    Methicillin-susceptible Staphylococcus aureus (MSSA) is an important nosocomial pathogen worldwide. This study aims to investigate the in vitro biofilm-forming ability of clinical MSSA isolated from various sources in the main public tertiary referral hospital in Terengganu, Malaysia and to detect the presence of biofilm-associated and regulatory genes among these isolates. A total of 104 MSSA isolates [pus (n = 75), blood (n = 24), respiratory secretions (n = 2), eye (n = 2), and urine (n = 1)] were investigated for slime production and biofilm formation using Congo red agar and crystal violet microtitre plate, respectively. Fifteen MSSA isolates with varying degrees of biofilm formation were selected for validation via a real-time cell analyser. All isolates were screened for microbial surface components recognising adhesive matrix molecules (MSCRAMM) and accessory gene regulator (agr) using polymerase chain reaction assay. A total of 76.0% (79/104) isolates produced slime layer, while all isolates developed biofilm as follows: 52.8% (55/104) strong biofilm producers, 40.4% (42/104) intermediate biofilm producers, and 6.7% (7/104) weak biofilm producers. A total of 98.1% (102/104) isolates carried at least one of the screened MSCRAMM gene(s) with the eno gene detected at the highest rate (87.5%, 91/104), while the sasG gene was significantly associated with strong biofilm production (p = 0.015). Three agr groups, 1, 2, and 3, were detected among the MSSA isolates with a predominance of agr-3 (32.7%, 34/104). In conclusion, biofilm formation varied greatly among clinical MSSA isolates, and the presence of sasG gene and agr-1 may play important role in initiating MSSA infections via biofilm formation.
  3. Lin GSS, Ng YS, Ghani NRNA, Chua KH
    BMC Oral Health, 2023 Sep 25;23(1):690.
    PMID: 37749537 DOI: 10.1186/s12903-023-03389-x
    BACKGROUND: The integration of artificial intelligence (AI) in dentistry has the potential to revolutionise the field of dental technologies. However, dental technicians' views on the use of AI in dental technology are still sparse in the literature. This qualitative study aimed to explore the perceptions of dental technicians regarding the use of AI in their dental laboratory practice.

    METHODS: Twelve dental technicians with at least five years of professional experience and currently working in Malaysia agreed to participate in the one-to-one in-depth online interviews. Interviews were recorded, transcribed verbatim and translated. Thematic analysis was conducted to identify patterns, themes, and categories within the interview transcripts.

    RESULTS: The analysis revealed two key themes: "Perceived Benefits of AI" and "Concerns and Challenges". Dental technicians recognised the enhanced efficiency, productivity, accuracy, and precision that AI can bring to dental laboratories. They also acknowledged the streamlined workflow and improved communication facilitated by AI systems. However, concerns were raised regarding job security, professional identity, ethical considerations, and the need for adequate training and support.

    CONCLUSION: This research sheds light on the potential benefits and challenges associated with the integration of AI in dental laboratory practices. Understanding these perceptions and addressing the challenges can support the effective integration of AI in dental laboratories and contribute to the growing body of literature on AI in healthcare.

  4. Lau TV, Puah SM, Tan JMA, Merino S, Puthucheary SD, Chua KH
    Microb Pathog, 2023 Apr;177:106059.
    PMID: 36878334 DOI: 10.1016/j.micpath.2023.106059
    Aeromonas dhakensis possesses dual flagellar systems for motility under different environments. Flagella-mediated motility is necessary for biofilm formation through an initial attachment of bacteria to the surface, but this has not been elucidated in A. dhakensis. This study investigates the role of polar (flaH, maf1) and lateral (lafB, lafK and lafS) flagellar genes in the biofilm formation of a clinical A. dhakensis strain WT187 isolated from burn wound infection. Five deletion mutants and corresponding complemented strains were constructed using pDM4 and pBAD33 vectors, respectively, and analyzed for motility and biofilm formation using crystal violet staining and real-time impedance-based assays. All mutants were significantly reduced in swimming (p 
  5. Nallappan D, Ong KC, Palanisamy UD, Chua KH, Kuppusamy UR
    Arch Physiol Biochem, 2023 Feb;129(1):186-197.
    PMID: 32813560 DOI: 10.1080/13813455.2020.1808019
    AIM: A high-fat diet (HFD) can lead to obesity and related metabolic disorders. This study evaluated the preventive efficacy of myricetin derivative-rich fraction (MD) from Syzygium malaccense leaf extract against HFD-induced obesity, hyperglycaemia, and oxidative stress in C57BL/6J mice.

    METHODS: HFD-fed mice were administered MD (50 mg/kg, 100 mg/kg, and 150 mg/kg) or 2 mg/kg metformin (positive control) orally for 16 weeks. Normal diet and HFD-fed control groups received normal saline.

    RESULTS: MD dose of 50 mg/kg was better than 100 mg/kg and 150 mg/kg in significantly reducing weight-gain, glucose intolerance, insulin resistance, lipid accumulation in liver and kidney, and improving the serum lipid profile. Lowered protein carbonyls and lipid hydroperoxides in urine and tissue homogenates and elevated reduced glutathione, ferric reducing antioxidant power (FRAP), and Trolox equivalent antioxidant capacity (TEAC) levels in tissue homogenates indicated amelioration of oxidative stress.

    CONCLUSION: MD has therapeutic value in the prevention and management of obesity, hyperglycaemia, and oxidative stress.

  6. Subramaniam S, Ong KC, Sabaratnam V, Chua KH, Kuppusamy UR
    Int J Med Mushrooms, 2023;25(4):27-42.
    PMID: 37075082 DOI: 10.1615/IntJMedMushrooms.2023047595
    Ganoderma neo-japonicum Imazeki is a medicinal mushroom consumed by the indigenous people in Malaysia as a remedy for diabetes. This study aims to validate the efficacy of G. neo-japonicum polysaccharides (GNJP) on obesity-induced type 2 diabetes mellitus (T2DM) in C57BL/6J mice. Mice were divided into seven groups; normal diet (ND)-control, high-fat-diet (HFD)-control, HFDGNJP-treated (50, 100, 200 mg/kg b.w.), HFDMET (metformin 50 mg/kg; positive-control) and ND-GNJP (200 mg/kg b.w.). Mice were administered GNJP or metformin orally for 10 weeks (thrice/week) and sacrificed after an oral glucose tolerance test. Body weight, serum biochemicals, liver histology, adipocyte gene expressions, glucose and insulin levels were measured. HFD caused obesity, dyslipidemia, and diabetes in the untreated groups. GNJP (50 mg/kg b.w.) supplementation prevented weight gain and liver steatosis, improved serum lipid profile and glucose tolerance and attenuated hyperglycemia and hyperinsulinemia more effectively when compared with the other treatment groups. The prevention of obesity and lipid dysregulation is plausibly attributed to the increased hormone-sensitive lipase and reduced Akt-1 and Ppary gene expressions while the up-regulation of AdipoQ (adiponectin), Prkag2 and Slc2a4 genes served to sensitize insulin and improve glucose uptake. Thus, supplementation with an appropriate dose of GNJP has promising efficacies in preventing HFD aka obesity-induced T2DM and associated metabolic abnormalities.
  7. Ng HK, Puah SM, Teh CSJ, Idris N, Chua KH
    PeerJ, 2023;11:e15304.
    PMID: 37214089 DOI: 10.7717/peerj.15304
    BACKGROUND: Acinetobacter baumannii was reported to have resistance towards carbapenems and the ability to form an air-liquid biofilm (pellicle) which contributes to their virulence. The GacSA two-component system has been previously shown to play a role in pellicle formation. Therefore, this study aims to detect the presence of gacA and gacS genes in carbapenem-resistant Acinetobacter baumannii (CRAB) isolates recovered from patients in intensive care units and to investigate their pellicle forming ability.

    METHODS: The gacS and gacA genes were screened in 96 clinical CRAB isolates using PCR assay. Pellicle formation assay was performed in Mueller Hinton medium and Luria Bertani medium using borosilicate glass tubes and polypropylene plastic tubes. The biomass of the pellicle was quantitated using the crystal violet staining assay. The selected isolates were further assessed for their motility using semi-solid agar and monitored in real-time using real-time cell analyser (RTCA).

    RESULTS: All 96 clinical CRAB isolates carried the gacS and gacA genes, however, only four isolates (AB21, AB34, AB69 and AB97) displayed the ability of pellicle-formation phenotypically. These four pellicle-forming isolates produced robust pellicles in Mueller Hinton medium with better performance in borosilicate glass tubes in which biomass with OD570 ranging from 1.984 ± 0.383 to 2.272 ± 0.376 was recorded. The decrease in cell index starting from 13 hours obtained from the impedance-based RTCA showed that pellicle-forming isolates had entered the growth stage of pellicle development.

    CONCLUSION: These four pellicle-forming clinical CRAB isolates could be potentially more virulent, therefore further investigation is warranted to provide insights into their pathogenic mechanisms.

  8. Tee MZ, Er YX, Easton AV, Yap NJ, Lee IL, Devlin J, et al.
    Microbiome, 2022 Dec 07;10(1):214.
    PMID: 36476263 DOI: 10.1186/s40168-022-01385-x
    BACKGROUND: While microbiomes in industrialized societies are well characterized, indigenous populations with traditional lifestyles have microbiomes that are more akin to those of ancient humans. However, metagenomic data in these populations remains scarce, and the association with soil-transmitted helminth infection status is unclear. Here, we sequenced 650 metagenomes of indigenous Malaysians from five villages with different prevalence of helminth infections.

    RESULTS: Individuals from villages with higher prevalences of helminth infections have more unmapped reads and greater microbial diversity. Microbial community diversity and composition were most strongly associated with different villages and the effects of helminth infection status on the microbiome varies by village. Longitudinal changes in the microbiome in response to albendazole anthelmintic treatment were observed in both helminth infected and uninfected individuals. Inference of bacterial population replication rates from origin of replication analysis identified specific replicating taxa associated with helminth infection.

    CONCLUSIONS: Our results indicate that helminth effects on the microbiota were highly dependent on context, and effects of albendazole on the microbiota can be confounding for the interpretation of deworming studies. Furthermore, a substantial quantity of the microbiome remains unannotated, and this large dataset from an indigenous population associated with helminth infections is a valuable resource for future studies. Video Abstract.

  9. Chai HC, Chua KH
    Diagnostics (Basel), 2022 Nov 29;12(12).
    PMID: 36552996 DOI: 10.3390/diagnostics12122989
    Blood remains the specimen of preference for malaria diagnosis, whether it is for microscopic, nucleic acid-based or biomarker detection of Plasmodium present in a patient. However, concerning the disadvantages of blood drawing, specimens that can be non-invasively collected under non-hygienic settings would come in handy for malaria diagnosis in endemic areas with limited resources. Although the current approaches using saliva or urine might not be as sensitive and specific as using blood, the potential of these two specimens should not be underestimated and efforts in developing diagnostic methods for Plasmodium detection specifically in these two specimens should continue without giving up. This review not only compiles and summarizes the sensitivity and specificity achieved by various detection approaches when using these samples for malaria diagnosis, it also intends to enhance the possibility of using saliva and urine for diagnostic purposes by describing how Plasmodium nucleic acid and antigens may likely be present in these samples. This review may hopefully encourage and motivate researchers in developing saliva- and urine-based diagnostic methods for Plasmodium detection to facilitate the control and eradication of malaria. In summary, the presence of Plasmodium DNA and antigens in urine and saliva makes these two specimens relevant and useful for malaria diagnosis.
  10. Al-Trad EI, Che Hamzah AM, Puah SM, Chua KH, Kwong SM, Yeo CC, et al.
    Pathogens, 2022 Nov 23;11(12).
    PMID: 36558739 DOI: 10.3390/pathogens11121406
    Staphylococcus hominis is a coagulase-negative Staphylococcus (CoNS) commensal capable of causing serious systemic infections in humans. The emergence of multidrug-resistant S. hominis strains is of concern but little is known about the characteristics of this organism, particularly from Malaysia. Here, we present the comparative genome analysis of S. hominis ShoR14, a multidrug-resistant, methicillin-resistant blood isolate from Terengganu, Malaysia. Genomic DNA of S. hominis ShoR14 was sequenced on the Illumina platform and assembled using Unicycler v0.4.8. ShoR14 belonged to sequence type (ST) 1 which is the most prevalent ST of the S. hominis subsp. hominis. Comparative genomic analysis with closely related strains in the database with complete genome sequences, led to the discovery of a novel variant of the staphylococcal chromosome cassette mec (SCCmec) type VIII element harboring the mecA methicillin-resistance gene in ShoR14 and its possible carriage of a SCCfus element that encodes the fusidic acid resistance gene (fusC). Up to seven possible ShoR14 plasmid contigs were identified, three of which harbored resistance genes for tetracycline (tetK), chloramphenicol (catA7), macrolides, lincosamides, and streptogramin B (ermC). Additionally, we report the discovery of a novel mercury-resistant transposon, Tn7456, other genomic islands, and prophages which make up the S. hominis mobilome.
  11. Puah SM, Puthucheary SDA, Chua KH
    Jpn J Infect Dis, 2022 Jan 31.
    PMID: 35095023 DOI: 10.7883/yoken.JJID.2021.477
    Genus Plesiomonas, represented by a single species, P. shigelloides is a Gram-negative bacillus associated with gastrointestinal and extraintestinal disease in humans. In this study, 44 clinical isolates (gastrointestinal n=41; extraintestinal n=3) were genetically confirmed as P. shigelloides using the hug gene. All 20 virulence genes were detected in gastrointestinal isolates, ranging from 7.7% to 100%, however, only 12 genes were detected in extra-gastrointestinal isolates, ranging from 33.3% to 100%. The phlA gene was significantly (p=0.0216) associated with gastrointestinal isolates. The results of this study suggest that the presence of phlA may play a role in gastrointestinal-related infections. On the other hand, pilF, tolC and fur were detected in both gastrointestinal and extraintestinal clinical isolates and further investigations are warrants to elucidate their role in the pathogenesis of P. shigelloides.
  12. Puah SM, Fong SP, Kee BP, Puthucheary SD, Chua KH
    Microb Pathog, 2022 Jan;162:105345.
    PMID: 34896547 DOI: 10.1016/j.micpath.2021.105345
    Recently, Elizabethkingia species have gained attention as a cause of life-threatening infections. The identification via phenotypic methods of three important species- Elizabethkingia meningoseptica, E. anophelis and E. miricola is difficult. Our objectives were to re-assess 30 archived Flavobacterium meningosepticum isolates using 16S rRNA gene sequencing, ERIC-PCR, and biofilm formation assay. Twenty-four isolates were re-identified as E. anophelis and 6 as E. miricola. All of them had the ability to form biofilm as shown in microtiter plate assay based on crystal violet staining. Overall, E. anophelis had a higher specific biofilm formation index compared to E. miricola. A total of 42% (10 out of 24) of E. anophelis were classified as strong, 29% (7 out of 24) as moderate and 29% (7 out of 24) as weak biofilm producers. E. miricola, 17% (1 out of 6) isolates were strong biofilm producers, 50% (3 out of 6) moderate and 33% (2 out of 6) were weak producers. E. anophelis from tracheal secretions were significantly associated with (p = 0.0361) strong biofilm formation. In summary, this study showed that the isolates originally identified as F. meningosepticum were re-classified using the 16S rRNA gene as one of two Elizabethkingia species. The ability of E. anophelis to form strong biofilm in endotracheal tubes indicates their probable role in the pathogenesis of Elizabethkingia infections.
  13. Kuan SW, Chua KH, Tan EW, Tan LK, Loch A, Kee BP
    PeerJ, 2022;10:e13265.
    PMID: 35441061 DOI: 10.7717/peerj.13265
    Cardiomyopathy (CMP) constitutes a diverse group of myocardium diseases affecting the pumping ability of the heart. Genetic predisposition is among the major factors affecting the development of CMP. Globally, there are over 100 genes in autosomal and mitochondrial DNA (mtDNA) that have been reported to be associated with the pathogenesis of CMP. However, most of the genetic studies have been conducted in Western countries, with limited data being available for the Asian population. Therefore, this study aims to investigate the mutation spectrum in the mitochondrial genome of 145 CMP patients in Malaysia. Long-range PCR was employed to amplify the entire mtDNA, and whole mitochondrial genome sequencing was conducted on the MiSeq platform. Raw data was quality checked, mapped, and aligned to the revised Cambridge Reference Sequence (rCRS). Variants were named, annotated, and filtered. The sequencing revealed 1,077 variants, including 18 novel and 17 CMP and/or mitochondrial disease-associated variants after filtering. In-silico predictions suggested that three of the novel variants (m.8573G>C, m.11916T>A and m.11918T>G) in this study are potentially pathogenic. Two confirmed pathogenic variants (m.1555A>G and m.11778G>A) were also found in the CMP patients. The findings of this study shed light on the distribution of mitochondrial mutations in Malaysian CMP patients. Further functional studies are required to elucidate the role of these variants in the development of CMP.
  14. Chai HC, Chua KH
    Diagnostics (Basel), 2021 Nov 30;11(12).
    PMID: 34943481 DOI: 10.3390/diagnostics11122244
    Pathogens may change the odor and odor-related biting behavior of the vector and host to enhance pathogen transmission. In recent years, volatile biomarker investigations have emerged to identify odors that are differentially and specifically released by pathogens and plants, or the pathogen-infected or even cancer patients. Several studies have reported odors or volatile biomarkers specifically detected from the breath and skin of malaria-infected individuals. This review will discuss the potential use of these odors or volatile biomarkers for the diagnosis of malaria. This approach not only allows for the non-invasive mean of sample collection but also opens up the opportunity to develop a biosensor for malaria diagnosis in low-resource settings.
  15. Mahendran R, Lim SK, Ong KC, Chua KH, Chai HC
    Clin Exp Nephrol, 2021 Nov;25(11):1163-1172.
    PMID: 34254206 DOI: 10.1007/s10157-021-02111-x
    BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic kidney disorder that impairs renal functions progressively leading to kidney failure. The disease affects between 1:400 and 1:1000 ratio of the people worldwide. It is caused by the mutated PKD1 and PKD2 genes which encode for the defective polycystins. Polycystins mimic the receptor protein or protein channel and mediate aberrant cell signaling that causes cystic development in the renal parenchyma. The cystic development is driven by the increased cyclic AMP stimulating fluid secretion and infinite cell growth. In recent years, natural product-derived small molecules or drugs targeting specific signaling pathways have caught attention in the drug discovery discipline. The advantages of natural products over synthetic drugs enthusiast researchers to utilize the medicinal benefits in various diseases including ADPKD.

    CONCLUSION: Overall, this review discusses some of the previously studied and reported natural products and their mechanisms of action which may potentially be redirected into ADPKD.

  16. Azazi A, Haron FN, Chua KH, Lim YAL, Lee PC, Chew CH
    Trop Biomed, 2021 Sep 01;38(3):265-275.
    PMID: 34362869 DOI: 10.47665/tb.38.3.067
    Malaria caused by Plasmodium knowlesi species has become a public health concern, especially in Malaysia. Plasmodium knowlesi parasite which originates from the macaque species, infects human through the bite of the Anopheles mosquitoes. Research on malaria vaccine has been a continuous effort to eradicate the malaria infection, yet there is no vaccine against P. knowlesi malaria to date. Apical membrane antigen 1 (AMA1) is a unique surface protein of all apicomplexan parasites that plays a crucial role in parasite-host cell invasion and thus has been a long-standing malaria vaccine candidate. The selection of protective epitopes in silico has led to significant advances in the design of the vaccine. The present study aimed to employ bioinformatics tools to predict the potential immunogenic B- and T-cell epitopes in designing malaria vaccine targeting P. knowlesi AMA1 (PkAMA1). B-cell epitopes were predicted using four bioinformatics tools, i.e., BepiPred, ABCpred, BcePred, and IEDB servers whereas T-cell epitopes were predicted using two bioinformatics servers, i.e., NetMHCpan4.1 and NetMHCIIpan-4.0 targeting human major histocompatibility complex (MHC) class I and class II molecules, respectively. The antigenicity of the selected epitopes computed by both B- and T-cell predictors were further analyzed using the VaxiJen server. The results demonstrated that PkAMA1 protein encompasses multi antigenic regions that have the potential for the development of multi-epitope vaccine. Two B- and T-cell epitopes consensus regions, i.e., NSGIRIDLGEDAEVGNSKYRIPAGKCP (codons 28-54) and KTHAASFVIAEDQNTSY RHPAVYDEKNKT (codons 122-150) at domain I (DI) of PkAMA1 were reported. Advancement of bioinformatics in characterization of the target protein may facilitate vaccine development especially in vaccine design which is costly and cumbersome process. Thus, comprehensive B-cell and T-cell epitope prediction of PkAMA1 offers a promising pipeline for the development and design of multi-epitope vaccine against P. knowlesi.
  17. Lau MF, Chua KH, Sabaratnam V, Kuppusamy UR
    Biotechnol Appl Biochem, 2021 Aug;68(4):902-917.
    PMID: 32856730 DOI: 10.1002/bab.2013
    Ganoderma neo-japonicum is a well-known medicinal mushroom in Asian countries. However, scientific validations on its curative activities are confined to cirrhosis and diabetes. In this study, the anticancer properties of G. neo-japonicum were evaluated using cellular and computational models. The ethanolic extract (EtOH) with a promising inhibitory effect was fractionated into four different fractions: hexane (Hex), chloroform (Chl), butanol (Btn), and aqueous (Aq). The active fractions were then subjected to cell apoptosis assessment and phytochemical profiling. Molecular docking was conducted to elucidate the affinity of selected constituents towards antiapoptotic Bcl-2 protein. The butanol fraction showed the highest antioxidant activities as well as total phenolic content. Both hexane and chloroform fractions exerted a potent cytotoxic effect on colonic carcinoma cells through the induction of apoptosis. Phytochemical analysis revealed that the chloroform fraction is terpenoid enriched whereas the hexane fraction comprises predominantly sterol constituents. Stellasterol and 1,25-dihydroxyvitamin D3 3-glycoside were demonstrated to have a high affinity towards Bcl-2 protein. Overall, G. neo-japonicum can be considered as a compelling therapeutic candidate for cancer treatment.
  18. Nallappan D, Chua KH, Ong KC, Chong CW, Teh CSJ, Palanisamy UD, et al.
    Food Funct, 2021 Jul 05;12(13):5876-5891.
    PMID: 34019055 DOI: 10.1039/d1fo00539a
    Obesity is a driving factor in the onset of metabolic disorders. This study aims to investigate the effects of the myricetin derivative-rich fraction (MD) from Syzygium malaccense leaf extract on high-fat diet (HFD)-induced obesity and its associated complications and its influence on uncoupling protein-1 (UCP-1) and gut microbiota in C57BL/6J mice. Mice were randomly assigned into four groups (n = 6) and given a normal diet (ND) or high-fat diet (HFD) for 10 weeks to induce obesity. The HFD groups (continued with HFD) were administered 50 mg kg-1 MD (treatment), 50 mg kg-1 metformin (positive control) and normal saline (HFD and ND controls) daily for four weeks via oral gavage. The ten-week HFD-feeding resulted in hyperglycemia and elevated urinary oxidative indices. The subsequent MD administration caused significant weight reduction without appetite suppression and amelioration of insulin resistance, steatosis and dyslipidemia. Besides, MD significantly reduced lipid hydroperoxides and protein carbonyls in tissue homogenates and urine and elevated Trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP) and reduced glutathione (GSH) and thus, alleviated oxidative stress. The weight reduction was correlated with downregulation of inflammatory markers and the increased UCP-1 level, suggesting weight loss plausibly through thermogenesis. The Akkermansia genus (reflects improved metabolic status) in the HFD50 group was more abundant than that in the HFD group while the non-enzymatic antioxidant markers were strongly associated with UCP-1. In conclusion, MD ameliorates obesity and its related complications possibly via the upregulation of UCP-1 and increased abundance of Akkermansia genus and is promising as a therapeutic agent in the treatment of obesity and its associated metabolic disorders.
  19. Goh XT, Lim YAL, Lee PC, Nissapatorn V, Chua KH
    Mol Biochem Parasitol, 2021 07;244:111390.
    PMID: 34087264 DOI: 10.1016/j.molbiopara.2021.111390
    The present study aimed to examine the genetic diversity of human malaria parasites (i.e., P. falciparum, P. vivax and P. knowlesi) in Malaysia and southern Thailand targeting the 19-kDa C-terminal region of Merozoite Surface Protein-1 (MSP-119). This region is essential for the recognition and invasion of erythrocytes and it is considered one of the leading candidates for asexual blood stage vaccines. However, the genetic data of MSP-119 among human malaria parasites in Malaysia is limited and there is also a need to update the current sequence diversity of this gene region among the Thailand isolates. In this study, genomic DNA was extracted from 384 microscopy-positive blood samples collected from patients who attended the hospitals or clinics in Malaysia and malaria clinics in Thailand from the year 2008 to 2016. The MSP-119 was amplified using PCR followed by bidirectional sequencing. DNA sequences identified in the present study were subjected to Median-joining network analysis with sequences of MSP-119 obtained from GenBank. DNA sequence analysis revealed that PfMSP-119 of Malaysian and Thailand isolates was not genetically conserved as high number of haplotypes were detected and positive selection was prevalent in PfMSP-119, hence questioning its suitability to be used as a vaccine candidate. A novel haplotype (Q/TNG/L) was also detected in Thailand P. falciparum isolate. In contrast, PvMSP-119 was highly conserved, however for the first time, a non-synonymous substitution (A1657S) was reported among Malaysian isolates. As for PkMSP-119, the presence of purifying selection and low nucleotide diversity indicated that it might be a potential vaccine target for P. knowlesi.
  20. Jolly JJ, Mohd Fozi NF, Chin KY, Wong SK, Chua KH, Alias E, et al.
    Exp Ther Med, 2021 Jul;22(1):680.
    PMID: 33986845 DOI: 10.3892/etm.2021.10112
    A three-dimensional ex vivo bone cell culture system mimicking the skeletal system is useful for bone tissue engineering and as drug discovery platforms. The present study aimed to establish a three-dimensional skeletal culture system using native bovine bone scaffolds and human bone cells. Bovine bone scaffolds were cultured with human foetal osteoblasts 1.19 and human peripheral blood mononuclear cells for 21 days under standard culture conditions. The following groups were established: Decalcified unseeded bone scaffold (DUBS) as baseline control, decalcified seeded bone scaffold (DSBS) to mimic osteoporosis condition and undecalcified seeded bone scaffold to mimic normal condition. The scaffold's porosity and cell attachment on the scaffolds were determined using scanning electron microscopy. Histological evaluation was used to examine changes in trabecular bone structure. Dual-energy X-ray absorptiometry analysis was performed to determine the bone mineral density (BMD) and bone mineral content (BMC) of the scaffolds. A compression test was performed to examine the total biomechanical strength of the scaffolds. The trabecular thickness and number increased, while the trabecular separationwas reduced slightly in DSBS than in DUBS (P>0.05). The BMD and BMC increased significantly (P<0.05), while the compressive strength only increased slightly in DSBS than in DUBS (P>0.05). In conclusion, the ex vivo skeletal microenvironment comprising native bovine bone scaffolds seeded with bone cells is structurally, functionally and mechanically comparable with natural bone. This system may be used as a platform to understand bone physiology and screen for potential drug candidates.
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