Displaying publications 21 - 33 of 33 in total

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  1. Fulltext Discovery of the fish host of the 'planktonic' caligid Caligus undulatus Shen & Li, 1959 (Crustacea: Copepoda: Siphonostomatoida)
    Ohtsuka S, Nawata M, Nishida Y, Nitta M, Hirano K, Adachi K, et al.
    Biodivers Data J, 2020;8:e52271.
    PMID: 32565681 DOI: 10.3897/BDJ.8.e52271
    The siphonostomatoid copepod Caligus undulatus Shen & Li, 1959 has been widely reported from plankton samples obtained from neritic and oceanic waters off coasts of the Indo-West Pacific and Atlantic Oceans. Until now, its fish host has remained unknown. This copepod belongs to an intriguing group of congeners that, despite being part of a chiefly parasitic group, are consistently found as zooplankters. Quite unexpectedly, in October 2019, a fish host of C. undulatus was discovered in the Seto Inland Sea, Japan-namely, the Japanese sardinella Sardinella zunasi (Bleeker, 1854). Both juvenile (chalimus) and adult individuals of this caligid were observed as parasites of the fish host. The discovery suggests that the species has an alternative life cycle as previously proposed for other purportedly 'planktonic' congeners and might frequently switch hosts during the adult stage. Thus, the C. undulatus group is newly proposed as a species group in the genus, in which five species are known as planktonic. Some hypotheses on the modified life cycle of caligids also briefly discussed.
  2. Fulltext Identification of NRAS Diagnostic Biomarkers and Drug Targets for Endometrial Cancer-An Integrated in Silico Approach
    Alessandro L, Low KE, Abushelaibi A, Lim SE, Cheng WH, Chang SK, et al.
    Int J Mol Sci, 2022 Nov 18;23(22).
    PMID: 36430761 DOI: 10.3390/ijms232214285
    The diagnosis of endometrial cancer involves sequential, invasive tests to assess the thickness of the endometrium by a transvaginal ultrasound scan. In 6−33% of cases, endometrial biopsy results in inadequate tissue for a conclusive pathological diagnosis and 6% of postmenopausal women with non-diagnostic specimens are later discovered to have severe endometrial lesions. Thus, identifying diagnostic biomarkers could offer a non-invasive diagnosis for community or home-based triage of symptomatic or asymptomatic women. Herein, this study identified high-risk pathogenic nsSNPs in the NRAS gene. The nsSNPs of NRAS were retrieved from the NCBI database. PROVEAN, SIFT, PolyPhen-2, SNPs&GO, PhD-SNP and PANTHER were used to predict the pathogenicity of the nsSNPs. Eleven nsSNPs were identified as “damaging”, and further stability analysis using I-Mutant 2.0 and MutPred 2 indicated eight nsSNPs to cause decreased stability (DDG scores < −0.5). Post-translational modification and protein−protein interactions (PPI) analysis showed putative phosphorylation sites. The PPI network indicated a GFR-MAPK signalling pathway with higher node degrees that were further evaluated for drug targets. The P34L, G12C and Y64D showed significantly lower binding affinity towards GTP than wild-type. Furthermore, the Kaplan−Meier bioinformatics analyses indicated that the NRAS gene deregulation affected the overall survival rate of patients with endometrial cancer, leading to prognostic significance. Findings from this could be considered novel diagnostic and therapeutic markers.
  3. Fulltext In-silico identification of deleterious non-synonymous SNPs of TBX1 gene: Functional and structural impact towards 22q11.2DS
    Almakhari M, Chen Y, Kong AS, Moradigaravand D, Lai KS, Lim SE, et al.
    PLoS One, 2024;19(6):e0298092.
    PMID: 38905172 DOI: 10.1371/journal.pone.0298092
    The TBX1 gene plays a critical role in the development of 22q11.2 deletion syndrome (22q11.2DS), a complex genetic disorder associated with various phenotypic manifestations. In this study, we performed in-silico analysis to identify potentially deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) within the TBX1 gene and evaluate their functional and structural impact on 22q11.2DS. A comprehensive analysis pipeline involving multiple computational tools was employed to predict the pathogenicity of nsSNPs. This study assessed protein stability and explored potential alterations in protein-protein interactions. The results revealed the rs751339103(C>A), rs780800634(G>A), rs1936727304(T>C), rs1223320618(G>A), rs1248532217(T>C), rs1294927055 (C>T), rs1331240435 (A>G, rs1601289406 (A>C), rs1936726164 (G>A), and rs911796187(G>A) with a high-risk potential for affecting protein function and stability. These nsSNPs were further analyzed for their impact on post-translational modifications and structural characteristics, indicating their potential disruption of molecular pathways associated with TBX1 and its interacting partners. These findings provide a foundation for further experimental studies and elucidation of potential therapeutic targets and personalized treatment approaches for individuals affected by 22q11.2DS.
  4. The impact of ocean acidification and cadmium toxicity in the marine crab Scylla serrata: Biological indices and oxidative stress responses
    Thangal SH, Nandhinipriya R, Vasuki C, Gayathri V, Anandhan K, Yogeshwaran A, et al.
    Chemosphere, 2023 Oct 17.
    PMID: 37858766 DOI: 10.1016/j.chemosphere.2023.140447
    Ocean acidification (OA) and heavy metals pollution in marine environments are potentially threatening marine life. The interactive effect of OA and heavy metals could be more vulnerable to marine organisms than individual exposures. In the current study, the effect of OA on the toxicity of cadmium (Cd) in the crab Scylla serrata was evaluated. Crab instars (0.07 cm length and 0.1 g weight) were subjected to pH 8.2, 7.8, 7.6, 7.4, 7.2, and 7.0 with and without 0.01 mg l-1 of Cd for 60 days. We notice a significant decrease in growth, molting, protein, carbohydrate, amino acid, lipid, alkaline phosphatase, and haemocytes of crabs under OA + Cd compared to OA treatment. In contrast, the growth, protein, amino acid, and haemocyte levels were significantly affected by OA, Cd, and its interactions (OA + Cd). However, superoxide dismutase, catalase, lipid peroxidation, glutamic oxaloacetate transaminase, glutamic pyruvate transaminase, and accumulation of Cd in crabs were considerably elevated in OA + Cd treatments compared to OA alone treatments. The present investigation showed that the effect of Cd toxicity might be raised under OA on S. serrata. Our study demonstrated that ocean acidification significantly affects the biological indices and oxidative stress responses of S. serrata exposed to Cd toxicity.
  5. Effects of Mesua ferrea leaf and fruit extracts on growth and morphology of Staphylococcus aureus
    Aruldass CA, Marimuthu MM, Ramanathan S, Mansor SM, Murugaiyah V
    Microsc Microanal, 2013 Feb;19(1):254-60.
    PMID: 23332129 DOI: 10.1017/S1431927612013785
    Mesua ferrea is traditionally used for treating bleeding piles, fever, and renal diseases. It has been reported to have antimircobial activity. In the present study, antibacterial efficacy of leaf and fruit extracts on the growth and morphology of Staphylococcus aureus is evaluated. Both extracts display good antibacterial activity against S. aureus with a minimum inhibition concentration of 0.048 mg/mL. Both extracts are bacteriostatic at a minimum bacteriostatic concentration of 0.39 mg/mL. The bacteriostatic activity lasts for 24 h, and then cells start to grow as normal as shown in time-kill analysis. Scanning electron microscopy study indicated potential detrimental effect of the extracts of leaf and fruits of M. ferrea on the morphology of S. aureus. The treatment with the extracts caused extensive lysis of the cells, leakage of intracellular constituents, and aggregation of cytoplasmic contents forming an open meshwork of the matrix.
  6. Fulltext Mutations in the tail domain of MYH3 contributes to atrial septal defect
    Maran S, Ee R, Faten SA, Sy Bing C, Khaw KY, Erin Lim SH, et al.
    PLoS One, 2020;15(4):e0230982.
    PMID: 32315303 DOI: 10.1371/journal.pone.0230982
    Atrial septal defect (ASD) is one of the most common congenital heart defects diagnosed in children. Sarcomeric genes has been attributed to ASD and knockdown of MYH3 functionally homologues gene in chick models indicated abnormal atrial septal development. Here, we report for the first time, a case-control study investigating the role of MYH3 among non-syndromic ASD patients in contributing to septal development. Four amplicons which will amplifies the 40 kb MYH3 were designed and amplified using long range-PCR. The amplicons were then sequenced using indexed paired-end libraries on the MiSeq platform. The STREGA guidelines were applied for planning and reporting. The non-synonymous c. 3574G>A (p.Ala1192Thr) [p = 0.001, OR = 2.30 (1.36-3.87)] located within the tail domain indicated a highly conserved protein region. The mutant model of c. 3574G>A (p.Ala1192Thr) showed high root mean square deviation (RMSD) values compared to the wild model. To our knowledge, this is the first study to provide compelling evidence on the pathogenesis of MYH3 variants towards ASD hence, suggesting the crucial role of non-synonymous variants in the tail domain of MYH3 towards atrial septal development. It is hoped that this gene can be used as panel for diagnosis of ASD in future.
  7. Fulltext Predicting Deleterious Non-Synonymous Single Nucleotide Polymorphisms (nsSNPs) of HRAS Gene and In Silico Evaluation of Their Structural and Functional Consequences towards Diagnosis and Prognosis of Cancer
    Chai CY, Maran S, Thew HY, Tan YC, Rahman NMANA, Cheng WH, et al.
    Biology (Basel), 2022 Nov 02;11(11).
    PMID: 36358305 DOI: 10.3390/biology11111604
    The Harvey rat sarcoma (HRAS) proto-oncogene belongs to the RAS family and is one of the pathogenic genes that cause cancer. Deleterious nsSNPs might have adverse consequences at the protein level. This study aimed to investigate deleterious nsSNPs in the HRAS gene in predicting structural alterations associated with mutants that disrupt normal protein-protein interactions. Functional and structural analysis was employed in analyzing the HRAS nsSNPs. Putative post-translational modification sites and the changes in protein-protein interactions, which included a variety of signal cascades, were also investigated. Five different bioinformatics tools predicted 33 nsSNPs as "pathogenic" or "harmful". Stability analysis predicted rs1554885139, rs770492627, rs1589792804, rs730880460, rs104894227, rs104894227, and rs121917759 as unstable. Protein-protein interaction analysis revealed that HRAS has a hub connecting three clusters consisting of 11 proteins, and changes in HRAS might cause signal cascades to dissociate. Furthermore, Kaplan-Meier bioinformatics analyses indicated that the HRAS gene deregulation affected the overall survival rate of patients with breast cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of HRAS may serve as potential targets for different proteomic studies, diagnoses, and therapeutic interventions focusing on cancer.
  8. Fulltext Antimicrobial Potential of Aqueous Extract of Giant Sword Fern and Ultra-High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry Analysis
    Venmathi Maran BA, Palaniveloo K, Mahendran T, Chellappan DK, Tan JK, Yong YS, et al.
    Molecules, 2023 Aug 15;28(16).
    PMID: 37630329 DOI: 10.3390/molecules28166075
    Vibriosis and parasitic leech infestations cause the death of various farmed fish, such as groupers, hybrid groupers, sea bass, etc., in Malaysia and other Southeast Asian countries. In the absence of natural control agents, aquaculture operators rely on toxic chemicals to control Vibrio infections and parasitic leeches, which can have a negative impact on the environment and health. In the present study, we investigated the antivibrio and antiparasitic activities of the aqueous extract of giant sword fern (GSF) (Nephrolepis biserrata, Nephrolepidaceae, locally known as "Paku Pedang") against four Vibrio spp. and the parasitic leech Zeylanicobdella arugamensis, as well as its metabolic composition using the ultra-high-performance liquid chromatography-high-resolution mass spectrometry system (UHPLC-HRMS). The data show that the aqueous extract of GSF at a concentration of 100 mg/mL exhibits potent bactericidal activity against V. parahaemolyticus with a zone of inhibition of 19.5 mm. In addition, the extract showed dose-dependent activity against leeches, resulting in the complete killing of the parasitic leeches within a short period of 11-43 min when tested at concentrations ranging from 100 to 25 mg/mL. The UHPLC-HRMS analysis detected 118 metabolites in the aqueous extract of GSF. Flavonoids were the primary metabolites, followed by phenolic, aromatic, fatty acyl, terpenoid, vitamin and steroidal compounds. Notably, several of these metabolites possess antibacterial and antiparasitic properties, including cinnamaldehyde, cinnamic acid, apigenin, quercetin, cynaroside, luteolin, naringenin, wogonin, 6-gingerol, nicotinamide, abscisic acid, daidzein, salvianolic acid B, etc. Overall, our study shows the significant antibacterial and antiparasitic potential of the GSF aqueous extract, which demonstrates the presence of valuable secondary metabolites. Consequently, the aqueous extract is a promising natural alternative for the effective control of Vibrio infections and the treatment of parasitic leeches in aquaculture systems.
  9. Fulltext Functional and structural analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the MYB oncoproteins associated with human cancer
    Lim SW, Tan KJ, Azuraidi OM, Sathiya M, Lim EC, Lai KS, et al.
    Sci Rep, 2021 12 17;11(1):24206.
    PMID: 34921182 DOI: 10.1038/s41598-021-03624-x
    MYB proteins are highly conserved DNA-binding domains (DBD) and mutations in MYB oncoproteins have been reported to cause aberrant and augmented cancer progression. Identification of MYB molecular biomarkers predictive of cancer progression can be used for improving cancer management. To address this, a biomarker discovery pipeline was employed in investigating deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in predicting damaging and potential alterations on the properties of proteins. The nsSNP of the MYB family; MYB, MYBL1, and MYBL2 was extracted from the NCBI database. Five in silico tools (PROVEAN, SIFT, PolyPhen-2, SNPs&GO and PhD-SNP) were utilized to investigate the outcomes of nsSNPs. A total of 45 nsSNPs were predicted as high-risk and damaging, and were subjected to PMut and I-Mutant 2.0 for protein stability analysis. This resulted in 32 nsSNPs with decreased stability with a DDG score lower than - 0.5, indicating damaging effect. G111S, N183S, G122S, and S178C located within the helix-turn-helix (HTH) domain were predicted to be conserved, further posttranslational modifications and 3-D protein analysis indicated these nsSNPs to shift DNA-binding specificity of the protein thus altering the protein function. Findings from this study would help in the field of pharmacogenomic and cancer therapy towards better intervention and management of cancer.
  10. Fulltext In-Silico Analysis of Deleterious SNPs of FGF4 Gene and Their Impacts on Protein Structure, Function and Bladder Cancer Prognosis
    Lim EC, Lim SW, Tan KJ, Sathiya M, Cheng WH, Lai KS, et al.
    Life (Basel), 2022 Jul 09;12(7).
    PMID: 35888106 DOI: 10.3390/life12071018
    Dysregulation of fibroblast growth factors is linked to the pathogenesis of bladder cancer. The role of FGF1 and FGF3 is evident in bladder cancer; however, the role of FGF4 is vague. Despite being reported that FGF4 interacts with FGF1 and FGF3 in MAPK pathways, its pathogenesis and mechanism of action are yet to be elucidated. Therefore, this study aimed to elucidate pathogenic nsSNPs and their role in the prognosis of bladder cancer by employing in-silico analysis. The nsSNPs of FGF4 were retrieved from the NCBI database. Different in silico tools, PROVEAN, SIFT, PolyPhen-2, SNPs&GO, and PhD-SNP, were used for predicting the pathogenicity of the nsSNPs. Twenty-seven nsSNPs were identified as “damaging”, and further stability analysis using I-Mutant 2.0 and MUPro indicated 22 nsSNPs to cause decreased stability (DDG scores < −0.5). Conservation analysis predicted that Q97K, G106V, N164S, and N167S were highly conserved and exposed. Biophysical characterisation indicated these nsSNPs were not tolerated, and protein-protein interaction analysis showed their involvement in the GFR-MAPK signalling pathway. Furthermore, Kaplan Meier bioinformatics analyses indicated that the FGF4 gene deregulation affected the overall survival rate of patients with bladder cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of FGF4 may serve as potential targets for diagnoses and therapeutic interventions focusing on bladder cancer.
  11. Fulltext A whole genome analyses of genetic variants in two Kelantan Malay individuals
    Wan Juhari WK, Md Tamrin NA, Mat Daud MH, Isa HW, Mohd Nasir N, Maran S, et al.
    Hugo J, 2014 Dec;8(1):4.
    PMID: 27090252 DOI: 10.1186/s11568-014-0004-0
    BACKGROUND: The sequencing of two members of the Royal Kelantan Malay family genomes will provide insights on the Kelantan Malay whole genome sequences. The two Kelantan Malay genomes were analyzed for the SNP markers associated with thalassemia and Helicobacter pylori infection. Helicobacter pylori infection was reported to be low prevalence in the north-east as compared to the west coast of the Peninsular Malaysia and beta-thalassemia was known to be one of the most common inherited and genetic disorder in Malaysia.

    RESULT: By combining SNP information from literatures, GWAS study and NCBI ClinVar, 18 unique SNPs were selected for further analysis. From these 18 SNPs, 10 SNPs came from previous study of Helicobacter pylori infection among Malay patients, 6 SNPs were from NCBI ClinVar and 2 SNPs from GWAS studies. The analysis reveals that both Royal Kelantan Malay genomes shared all the 10 SNPs identified by Maran (Single Nucleotide Polymorphims (SNPs) genotypic profiling of Malay patients with and without Helicobacter pylori infection in Kelantan, 2011) and one SNP from GWAS study. In addition, the analysis also reveals that both Royal Kelantan Malay genomes shared 3 SNP markers; HBG1 (rs1061234), HBB (rs1609812) and BCL11A (rs766432) where all three markers were associated with beta-thalassemia.

    CONCLUSIONS: Our findings suggest that the Royal Kelantan Malays carry the SNPs which are associated with protection to Helicobacter pylori infection. In addition they also carry SNPs which are associated with beta-thalassemia. These findings are in line with the findings by other researchers who conducted studies on thalassemia and Helicobacter pylori infection in the non-royal Malay population.

  12. Fulltext Clinical comparison of HMPV and RSV infections in hospitalised Malaysian children: A propensity score matched study
    Ng DC, Liew CH, Tan KK, Awang EHB, Nazri FNBA, Maran AKT, et al.
    Clin Respir J, 2024 Mar;18(3):e13747.
    PMID: 38529669 DOI: 10.1111/crj.13747
    INTRODUCTION: Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are significant contributors to the burden of acute respiratory infections in children, but data on hMPV from Southeast Asia are limited despite its potential for serious disease. This study aimed to compare the clinical presentation, resource utilisation and outcomes between hMPV and RSV infections in hospitalised Malaysian children.

    METHODS: This retrospective, observational study included children aged ≤12 years old hospitalised with hMPV or RSV, confirmed via direct fluorescent antibody (DFA) methods, between 1 July to 30 October 2022 at Hospital Tuanku Ja'afar Seremban, Malaysia. Demographic, clinical presentation, resource utilisation and outcome data were analysed. Propensity score matching was used to balance cohorts based on key demographic and clinical characteristics.

    RESULTS: This study included 192 patients, comprising 112 with hMPV and 80 with RSV. hMPV patients were older (median age 20.5 vs. 9.4 months, p 

  13. Fulltext Modeling the significance of dynamic capability on the performance of microfinance institutions
    The HV, Yang M, Fazal SA, Maran, Gao J, Yang Q, et al.
    PLoS One, 2023;18(5):e0285814.
    PMID: 37220166 DOI: 10.1371/journal.pone.0285814
    According to strategic management theory, dynamic capability plays a significant role in enhancing organizational performance. Using a cross-sectional research design, the current study quantitatively assesses the mediating effect of dynamic capability on the relationships of total quality management, customer intellectual capital, and human resource management practice with the performance of microfinance institutions. An online survey involving 120 members of Induk Koperasi Kredit, a credit union association in West Kalimantan, Indonesia, is conducted. All the data are subjected to variance-based partial least squares structural equation modeling (PLS-SEM) analysis. The obtained results demonstrate the significant and positive influence of total quality management and human resource management practice on dynamic capability. Furthermore, dynamic capability is found to mediate the relationship between total quality management and human resource management practice on the performance of microfinance institutions. However, this study is unable to conclude that total quality management and human resource management practice have any significant impact on the performance of microfinance institutions. Nonetheless, this study demonstrates the crucial need for microfinance institutions to enhance their management activities via dynamic capability to enhance performance. This is one of the earliest studies conducted during the COVID-19 pandemic to examine the capabilities and performance of microfinance institutions in Indonesia. Notably, the performance of microfinance institutions can be further sustained by improving customers' intellectual and dynamic capabilities.
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