Displaying publications 21 - 40 of 61 in total

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  1. Fulltext 16S rRNA Gene Sequencing for Deciphering the Colorectal Cancer Gut Microbiome: Current Protocols and Workflows
    Osman MA, Neoh HM, Ab Mutalib NS, Chin SF, Jamal R
    Front Microbiol, 2018;9:767.
    PMID: 29755427 DOI: 10.3389/fmicb.2018.00767
    The human gut holds the densest microbiome ecosystem essential in maintaining a healthy host physiology, whereby disruption of this ecosystem has been linked to the development of colorectal cancer (CRC). The advent of next-generation sequencing technologies such as the 16S rRNA gene sequencing has enabled characterization of the CRC gut microbiome architecture in an affordable and culture-free approach. Nevertheless, the lack of standardization in handling and storage of biospecimens, nucleic acid extraction, 16S rRNA gene primer selection, length, and depth of sequencing and bioinformatics analyses have contributed to discrepancies found in various published studies of this field. Accurate characterization of the CRC microbiome found in different stages of CRC has the potential to be developed into a screening tool in the clinical setting. This mini review aims to concisely compile all available CRC microbiome studies performed till end of 2016 and to suggest standardized protocols that are crucial in developing a gut microbiome screening panel for CRC.
  2. Challenges and future direction of molecular research in air pollution-related lung cancers
    Shahadin MS, Ab Mutalib NS, Latif MT, Greene CM, Hassan T
    Lung Cancer, 2018 04;118:69-75.
    PMID: 29572006 DOI: 10.1016/j.lungcan.2018.01.016
    Hazardous air pollutants or chemical release into the environment by a variety of natural and/or anthropogenic activities may give adverse effects to human health. Air pollutants such as sulphur dioxide (SO2), nitrogen oxides (NOx), carbon monoxide (CO), heavy metals and particulate matter (PM) affect number of different human organs, especially the respiratory system. The International Agency for Research on Cancer (IARC) reported that ambient air pollution is a cause of lung cancer. Recently, the agency has classified outdoor air pollution as well as PM air pollution as Group 1 carcinogens. In addition, several epidemiological studies have shown a positive association between air pollutants to lung cancer risks and mortality. However, there are only a few studies examining the molecular effects of air pollution exposure specifically in lung cancer due to multiple challenges to mimic air pollution exposure in basic experimentation. Another major issue is the lack of adequate adjustments for exposure misclassification as air pollution may differ temporo-spatially and socioeconomically. Thus, the purpose of this paper is to review the current molecular understanding of air pollution-related lung cancer and potential future direction in this challenging yet important research field.
  3. Fulltext Integrated Characterization of MicroRNA and mRNA Transcriptome in Papillary Thyroid Carcinoma
    Mohamad Yusof A, Jamal R, Muhammad R, Abdullah Suhaimi SN, Mohamed Rose I, Saidin S, et al.
    Front Endocrinol (Lausanne), 2018;9:158.
    PMID: 29713312 DOI: 10.3389/fendo.2018.00158
    The incidence rate of papillary thyroid carcinoma (PTC) has rapidly increased in the recent decades, and the microRNA (miRNA) is one of the potential biomarkers in this cancer. Despite good prognosis, certain features such as lymph node metastasis (LNM) and BRAF V600E mutation are associated with a poor outcome. More than 50% of PTC patients present with LNM and BRAF V600E is the most common mutation identified in this cancer. The molecular mechanisms underlying these features are yet to be elucidated. This study aims to elucidate miRNA-genes interaction networks in PTC with or without LNM and to determine the association of BRAF V600E mutation with miRNAs and genes expression profiles. Next generation sequencing was performed to characterize miRNA and gene expression profiles in 20 fresh frozen tumor and the normal adjacent tissues of PTC with LNM positive (PTC LNM-P) and PTC without LNM (PTC LNN). BRAF V600E was genotyped using Sanger sequencing. Bioinformatics integration and pathway analysis were performed to determine the regulatory networks involved. Based on network analysis, we then investigated the association between miRNA and gene biomarkers, and pathway enrichment analysis was performed to study the role of candidate biomarkers. We identified 138 and 43 significantly deregulated miRNAs (adjusted p value 
  4. Fulltext Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis
    Ab Mutalib NS, Othman SN, Mohamad Yusof A, Abdullah Suhaimi SN, Muhammad R, Jamal R
    PeerJ, 2016;4:e2119.
    PMID: 27350898 DOI: 10.7717/peerj.2119
    Background. Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy originating from the follicle cells in the thyroid. Despite a good overall prognosis, certain high-risk cases as in those with lymph node metastasis (LNM) have progressive disease and poorer prognosis. MicroRNAs are a class of non-protein-coding, 19-24 nucleotides single-stranded RNAs which regulate gene expression and these molecules have been shown to play a role in LNM. The integrated analysis of miRNAs and gene expression profiles together with transcription factors (TFs) has been shown to improve the identification of functional miRNA-target gene-TF relationships, providing a more complete view of molecular events underlying metastasis process. Objectives. We reanalyzed The Cancer Genome Atlas (TCGA) datasets on PTC to identify differentially expressed miRNAs/genes in PTC patients with LNM-positive (LNM-P) versus lymph node negative (LNN) PTC patients and to investigate the miRNA-gene-TF regulatory circuit that regulate LNM in PTC. Results. PTC patients with LNM (PTC LNM-P) have a significantly shorter disease-free survival rate compared to PTC patients without LNM (PTC LNN) (Log-rank Mantel Cox test, p = 0.0049). We identified 181 significantly differentially expressed miRNAs in PTC LNM-P versus PTC LNN; 110 were upregulated and 71 were downregulated. The five topmost deregulated miRNAs were hsa-miR-146b, hsa-miR-375, hsa-miR-31, hsa-miR-7-2 and hsa-miR-204. In addition, 395 miRNAs were differentially expressed between PTC LNM-P and normal thyroid while 400 miRNAs were differentially expressed between PTC LNN and normal thyroid. We found four significant enrichment pathways potentially involved in metastasis to the lymph nodes, namely oxidative phosphorylation (OxPhos), cell adhesion molecules (CAMs), leukocyte transendothelial migration and cytokine-cytokine receptor interaction. OxPhos was the most significantly perturbed pathway (p = 4.70E-06) involving downregulation of 90 OxPhos-related genes. Significant interaction of hsa-miR-301b with HLF, HIF and REL/NFkB transcription factors were identified exclusively in PTC LNM-P versus PTC LNN. Conclusion. We found evidence of five miRNAs differentially expressed in PTC LNM-P. Alteration in OxPhos pathway could be the central event in metastasis to the lymph node in PTC. We postulate that hsa-miR-301b might be involved in regulating LNM in PTC via interactions with HLF, HIF and REL/NFkB. To the best of our knowledge, the roles of these TFs have been studied in PTC but the precise role of this miRNA with these TFs in LNM in PTC has not been investigated.
  5. Fulltext Circular RNAs: Potential Regulators of Treatment Resistance in Human Cancers
    Jeyaraman S, Hanif EAM, Ab Mutalib NS, Jamal R, Abu N
    Front Genet, 2019;10:1369.
    PMID: 32047511 DOI: 10.3389/fgene.2019.01369
    Circular RNAs (circRNAs) which were once considered as "junk" are now in the spotlight as a potential player in regulating human diseases, especially cancer. With the development of high throughput technologies in recent years, the full potential of circRNAs is being uncovered. CircRNAs possess some unique characteristics and advantageous properties that could benefit medical research and clinical applications. CircRNAs are stable with covalently closed loops that are resistant to ribonucleases, have disease stage-specific expressions and are selectively abundant in different types of tissues. Interestingly, the presence of circRNAs in different types of treatment resistance in human cancers was recently observed with the involvement of a few key pathways. The activation of certain pathways by circRNAs may give new insights to treatment resistance management. The potential usage of circRNAs from this aspect is very much in its infancy stage and has not been fully validated. This mini-review attempts to highlight the possible role of circRNAs as regulators of treatment resistance in human cancers based on its intersection molecules and cancer-related regulatory networks.
  6. LOC285629 regulates cell proliferation and motility in colorectal cancer cells
    Nasir SN, Abu N, Ab Mutalib NS, Ishak M, Sagap I, Mazlan L, et al.
    Clin Transl Oncol, 2018 Jun;20(6):775-784.
    PMID: 29098557 DOI: 10.1007/s12094-017-1788-x
    PURPOSE: Colorectal cancer (CRC) is one of the most widely diagnosed cancers in men and women worldwide. With the advancement of next-generation sequencing technologies, many studies have highlighted the involvement of long non-coding RNAs (lncRNAs) in cancer development. Growing evidence demonstrates that lncRNAs play crucial roles in regulating gene and protein expression and are involved in various cancers, including CRC. The field of lncRNAs is still relatively new and a lot of novel lncRNAs have been discovered, but their functional roles are yet to be elucidated. This study aims to characterize the expression and functional roles of a novel lncRNA in CRC.

    METHOD: Several methods were employed to assess the function of LOC285629 such as gene silencing, qPCR, proliferation assay, BrdU assay, transwell migration assay, ELISA and protein profiler.

    RESULTS: Via in silico analyses, we identified significant downregulation of LOC285629, a novel lncRNA, across CRC stages. LOC285629 expression was significantly downregulated in advanced stages (Stage III and IV) compared to Stage I (Kruskal-Wallis Test; p = 0.0093). Further in-house validation showed that the expression of LOC285629 was upregulated in colorectal cancer tissues and cell lines compared to the normal counterparts, but was downregulated in advanced stages. By targeting LOC285629, the viability, proliferative abilities, invasiveness and resistance of colorectal cancer cells towards 5-fluorouracil were reduced. It was also discovered that LOC285629 may regulate cancer progression by targeting several different proteins, namely survivin, BCL-xL, progranulin, PDGF-AA, enolase 2 and p70S6 K.

    CONCLUSION: Our findings suggest that LOC285629 may be further developed as a potential therapeutic target for CRC treatment.

  7. Gene Mutations as Emerging Biomarkers and Therapeutic Targets for Relapsed Acute Myeloid Leukemia
    Aziz H, Ping CY, Alias H, Ab Mutalib NS, Jamal R
    Front Pharmacol, 2017;8:897.
    PMID: 29270125 DOI: 10.3389/fphar.2017.00897
    It is believed that there are key differences in the genomic profile between adult and childhood acute myeloid leukemia (AML). Relapse is the significant contributor of mortality in patients with AML and remains as the leading cause of cancer death among children, posing great challenges in the treatment of AML. The knowledge about the genomic lesions in childhood AML is still premature as most genomic events defined in children were derived from adult cohorts. However, the emerging technologies of next generation sequencing have narrowed the gap of knowledge in the biology of AML by the detection of gene mutations for each sub-type which have led to the improvement in terms of prognostication as well as the use of targeted therapies. In this review, we describe the recent understanding of the genomic landscape including the prevalence of mutation, prognostic impact, and targeted therapies that will provide an insight into the pathogenesis of AML relapse in both adult and childhood cases.
  8. Fulltext Methylation Profile of Cancer Testis Antigens in Colorectal Cancer
    Abu N, Rus Bakarurraini NAA, Nasir SN, Ishak M, Baharuddin R, Jamal R, et al.
    Iran J Immunol, 2023 Mar 14;20(1):83-91.
    PMID: 36932973 DOI: 10.22034/iji.2023.92600.2171
    BACKGROUND: Cancer testis antigens (CTAs) are a class of immune-stimulating antigens often overexpressed in many types of cancers. The usage of the CTAs as immunotherapy targets have been widely investigated in different cancers including melanoma, hematological malignancies, and colorectal cancer. Studies have indicated that the epigenetic regulation of the CTAs such as the methylation status may affect the expression of the CTAs. However, the report on the methylation status of the CTAs is conflicting. The general methylation profile of the CTAs, especially in colorectal cancer, is still elusive.

    OBJECTIVE: To determine the methylation profile of the selected CTAs in our colorectal cancer patients.

    METHODS: A total of 54 pairs of colorectal cancer samples were subjected to DNA methylation profiling using the Infinium Human Methylation 450K bead chip.

    RESULTS: We found that most of the CTAs were hypomethylated, and CCNA1 and TMEM108 genes were among the few CTAs that were hypermethylated.

    CONCLUSION: Overall, our brief report has managed to show the overall methylation profile in over the 200 CTAs in colorectal cancer and this could be used for further refining any immunotherapy targets.

  9. Fulltext Extracellular Vesicle-derived circular RNAs confers chemoresistance in Colorectal cancer
    Hon KW, Ab-Mutalib NS, Abdullah NMA, Jamal R, Abu N
    Sci Rep, 2019 Nov 11;9(1):16497.
    PMID: 31712601 DOI: 10.1038/s41598-019-53063-y
    Chemo-resistance is associated with poor prognosis in colorectal cancer (CRC), with the absence of early biomarker. Exosomes are microvesicles released by body cells for intercellular communication. Circular RNAs (circRNAs) are non-coding RNAs with covalently closed loops and enriched in exosomes. Crosstalk between circRNAs in exosomes and chemo-resistance in CRC remains unknown. This research aims to identify exosomal circRNAs associated with FOLFOX-resistance in CRC. FOLFOX-resistant HCT116 CRC cells (HCT116-R) were generated from parental HCT116 cells (HCT116-P) using periodic drug induction. Exosomes were characterized using transmission electron microscopy (TEM), Zetasizer and Western blot. Our exosomes were translucent cup-shaped structures under TEM with differential expression of TSG101, CD9, and CD63. We performed circRNAs microarray using exosomal RNAs from HCT116-R and HCT116-P cells. We validated our microarray data using serum samples. We performed drug sensitivity assay and cell cycle analysis to characterize selected circRNA after siRNA-knockdown. Using fold change >2 and p 
  10. Fulltext Rapid methods for the detection of foodborne bacterial pathogens: principles, applications, advantages and limitations
    Law JW, Ab Mutalib NS, Chan KG, Lee LH
    Front Microbiol, 2014;5:770.
    PMID: 25628612 DOI: 10.3389/fmicb.2014.00770
    The incidence of foodborne diseases has increased over the years and resulted in major public health problem globally. Foodborne pathogens can be found in various foods and it is important to detect foodborne pathogens to provide safe food supply and to prevent foodborne diseases. The conventional methods used to detect foodborne pathogen are time consuming and laborious. Hence, a variety of methods have been developed for rapid detection of foodborne pathogens as it is required in many food analyses. Rapid detection methods can be categorized into nucleic acid-based, biosensor-based and immunological-based methods. This review emphasizes on the principles and application of recent rapid methods for the detection of foodborne bacterial pathogens. Detection methods included are simple polymerase chain reaction (PCR), multiplex PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), loop-mediated isothermal amplification (LAMP) and oligonucleotide DNA microarray which classified as nucleic acid-based methods; optical, electrochemical and mass-based biosensors which classified as biosensor-based methods; enzyme-linked immunosorbent assay (ELISA) and lateral flow immunoassay which classified as immunological-based methods. In general, rapid detection methods are generally time-efficient, sensitive, specific and labor-saving. The developments of rapid detection methods are vital in prevention and treatment of foodborne diseases.
  11. Fulltext Discovery on Antibiotic Resistance Patterns of Vibrio parahaemolyticus in Selangor Reveals Carbapenemase Producing Vibrio parahaemolyticus in Marine and Freshwater Fish
    Lee LH, Ab Mutalib NS, Law JW, Wong SH, Letchumanan V
    Front Microbiol, 2018;9:2513.
    PMID: 30410472 DOI: 10.3389/fmicb.2018.02513
    Vibrio parahaemolyticus, a Gram-negative halophilic bacterium is often associated with fish and fishery products, thus causing gastroenteritis in humans upon ingestion of contaminated food. V. parahaemolyticus has become a globally well-known pathogen with yearly reported cases in many countries. This study aimed to discover the antibiotic resistance patterns of V. parahaemolyticus as well as detect Carbapenem resistant isolates from marine and freshwater fish in Selangor. A total of 240 freshwater and marine fish samples collected from wet market and supermarket in Selangor were tested for the presence of V. parahaemolyticus. All the fish samples were determined positive for V. parahaemolyticus using conventional microbiological culture-based method. The toxR gene were detected via polymerase chain reaction (PCR) in 165/240 (69%) isolates. The two-virulence factor of V. parahaemolyticus, thermostable direct hemolysin (tdh) and TDH-related hemolysin (trh) was screened via PCR. As such, four isolates were trh+and none were tdh+. Majority of the isolates presented high resistance to ampicillin (88%), amikacin (64%), and kanamycin (50%). In addition, this study identified 19-imipenem resistant isolates isolated from freshwater and marine fish samples. Further analysis of these 19-imipenem resistant isolates revealed that the resistance toward imipenem was plasmid mediated after plasmid curing assay. The multiple antibiotics resistance index was >0.2 for 70% of the isolates. In summary, the results confirm the presence of V. parahaemolyticus in freshwater and marine fish samples in Selangor, Malaysia. To our best knowledge, this is the first report discovering the antibiotic resistant patterns and Carbapenem-resistant isolates of V. parahaemolyticus isolated from marine and freshwater fish samples in Selangor.
  12. Fulltext Single Cell Transcriptome in Colorectal Cancer-Current Updates on Its Application in Metastasis, Chemoresistance and the Roles of Circulating Tumor Cells
    Tieng FYF, Baharudin R, Abu N, Mohd Yunos RI, Lee LH, Ab Mutalib NS
    Front Pharmacol, 2020;11:135.
    PMID: 32174835 DOI: 10.3389/fphar.2020.00135
    Colorectal cancer (CRC) is among the most common cancer worldwide, a challenge for research, and a model for studying the molecular mechanisms involved in its development. Previously, bulk transcriptomics analyses were utilized to classify CRC based on its distinct molecular and clinicopathological features for prognosis and diagnosis of patients. The introduction of single-cell transcriptomics completely turned the table by enabling the examination of the expression levels of individual cancer cell within a single tumor. In this review, we highlighted the importance of these single-cell transcriptomics analyses as well as suggesting circulating tumor cells (CTCs) as the main focus of single-cell RNA sequencing. Characterization of these cells might reveal the intratumoral heterogeneity present in CRC while providing critical insights into cancer metastasis. To summarize, we believed the analysis of gene expression patterns of CTC from CRC at single-cell resolution holds the potential to provide key information for identification of prognostic and diagnostic markers as well as the development of precise and personalized cancer treatment.
  13. Fulltext Molecular characterization of serous ovarian carcinoma using a multigene next generation sequencing cancer panel approach
    Ab Mutalib NS, Syafruddin SE, Md Zain RR, Mohd Dali AZ, Mohd Yunos RI, Saidin S, et al.
    BMC Res Notes, 2014;7:805.
    PMID: 25404506 DOI: 10.1186/1756-0500-7-805
    High grade serous ovarian cancer is one of the poorly characterized malignancies. This study aimed to elucidate the mutational events in Malaysian patients with high grade serous ovarian cancer by performing targeted sequencing on 50 cancer hotspot genes.
  14. Fulltext Diversity and antimicrobial activities of actinobacteria isolated from tropical mangrove sediments in Malaysia
    Lee LH, Zainal N, Azman AS, Eng SK, Goh BH, Yin WF, et al.
    ScientificWorldJournal, 2014;2014:698178.
    PMID: 25162061 DOI: 10.1155/2014/698178
    The aim of this study was to isolate and identify Actinobacteria from Malaysia mangrove forest and screen them for production of antimicrobial secondary metabolites. Eighty-seven isolates were isolated from soil samples collected at 4 different sites. This is the first report to describe the isolation of Streptomyces, Mycobacterium, Leifsonia, Microbacterium, Sinomonas, Nocardia, Terrabacter, Streptacidiphilus, Micromonospora, Gordonia, and Nocardioides from mangrove in east coast of Malaysia. Of 87 isolates, at least 5 isolates are considered as putative novel taxa. Nine Streptomyces sp. isolates were producing potent antimicrobial secondary metabolites, indicating that Streptomyces isolates are providing high quality metabolites for drug discovery purposes. The discovery of a novel species, Streptomyces pluripotens sp. nov. MUSC 135(T) that produced potent secondary metabolites inhibiting the growth of MRSA, had provided promising metabolites for drug discovery research. The biosynthetic potential of 87 isolates was investigated by the detection of polyketide synthetase (PKS) and nonribosomal polyketide synthetase (NRPS) genes, the hallmarks of secondary metabolites production. Results showed that many isolates were positive for PKS-I (19.5%), PKS-II (42.5%), and NRPS (5.7%) genes, indicating that mangrove Actinobacteria have significant biosynthetic potential. Our results highlighted that mangrove environment represented a rich reservoir for isolation of Actinobacteria, which are potential sources for discovery of antimicrobial secondary metabolites.
  15. Molecular characterization of Antarctic actinobacteria and screening for antimicrobial metabolite production
    Lee LH, Cheah YK, Mohd Sidik S, Ab Mutalib NS, Tang YL, Lin HP, et al.
    World J Microbiol Biotechnol, 2012 May;28(5):2125-37.
    PMID: 22806035 DOI: 10.1007/s11274-012-1018-1
    The present study aimed to isolate actinobacteria from soil samples and characterized them using molecular tools and screened their secondary metabolites for antimicrobial activities. Thirty-nine strains from four different location of Barrientos Island, Antarctica using 12 types of isolation media was isolated. The isolates were preceded to screening of secondary metabolites for antimicrobial and antifungal activities. Using high-throughput screening methods, 38% (15/39) of isolates produced bioactive metabolites. Approximately 18% (7/39), 18% (7/39), 10% (4/39) and 2.5% (1/39) of isolates inhibited growth of Candida albicans ATCC 10231(T), Staphylococcus aurues ATCC 51650(T), methicillin-resistant Staphylococcus aurues (MRSA) ATCC BAA-44(T) and Pseudomonas aeruginosa ATCC 10145(T), respectively. Molecular characterization techniques like 16S rRNA analysis, Enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR), Random amplified polymorphic DNA (RAPD) and composite analyses were used to characterize the actinobacteria strains. Analysis of 16S rRNA sequences is still one of the most powerful methods to determine higher taxonomic relationships of Actinobacteria. Both RAPD and ERIC-PCR fingerprinting have shown good discriminatory capability but RAPD proved to be better in discriminatory power than ERIC-PCR. Our results demonstrated that composite analysis of both fingerprinting generally increased the discrimination ability and generated best clustering for actinobacteria strains in this study.
  16. Genome sequence of Streptomyces pluripotens MUSC 135(T) exhibiting antibacterial and antioxidant activity
    Ser HL, Tan WS, Ab Mutalib NS, Cheng HJ, Yin WF, Chan KG, et al.
    Mar Genomics, 2015 Dec;24 Pt 3:281-3.
    PMID: 26452302 DOI: 10.1016/j.margen.2015.09.010
    Isolated from intertidal soil, Streptomyces pluripotens MUSC 135(T) produces a broad-spectrum bacteriocin against the pathogens methicillin-resistant Staphylococcus aureus (MRSA) ATCC BAA-44(T), Salmonella typhi ATCC 19430(T) and Aeromonas hydrophila ATCC 7966(T). Along with antibacterial activity, fermentation studies on strain MUSC 135(T) revealed production of antioxidant(s). The high quality draft genome of MUSC 135(T) comprises 7,480,269 bp with G+C content of 70.00%. Through bioinformatics analysis, 72 gene clusters identified in the genome were associated with the production of secondary metabolites, which may shed light on the identity of these bioactive compounds.
  17. Fulltext MicroRNA-200c and microRNA-31 regulate proliferation, colony formation, migration and invasion in serous ovarian cancer
    Ibrahim FF, Jamal R, Syafruddin SE, Ab Mutalib NS, Saidin S, MdZin RR, et al.
    J Ovarian Res, 2015;8:56.
    PMID: 26260454 DOI: 10.1186/s13048-015-0186-7
    Serous epithelial ovarian cancer (SEOC) is a highly metastatic disease and its progression has been implicated with microRNAs. This study aimed to identify the differentially expressed microRNAs in Malaysian patients with SEOC and examine the microRNAs functional roles in SEOC cells.
  18. Fulltext Diversity of Streptomyces spp. from mangrove forest of Sarawak (Malaysia) and screening of their antioxidant and cytotoxic activities
    Law JW, Chan KG, He YW, Khan TM, Ab Mutalib NS, Goh BH, et al.
    Sci Rep, 2019 12 03;9(1):15262.
    PMID: 31792235 DOI: 10.1038/s41598-019-51622-x
    Streptomycetes have been the center of attraction within scientific community owing to their capability to produce various bioactive compounds, for instance, with different antimicrobial, anticancer, and antioxidant properties. The search for novel Streptomyces spp. from underexplored area such as mangrove environment has been gaining attention since these microorganisms could produce pharmaceutically important metabolites. The aim of this study is to discover the diversity of Streptomyces spp. from mangrove in Sarawak and their bioactive potentials - in relation to antioxidant and cytotoxic activities. A total of 88 Streptomyces isolates were successfully recovered from the mangrove soil in Kuching, state of Sarawak, Malaysia. Phylogenetic analysis of all the isolates and their closely related type strains using 16S rRNA gene sequences resulted in 7 major clades in the phylogenetic tree reconstructed based on neighbour-joining algorithm. Of the 88 isolates, 18 isolates could be considered as potentially novel species according to the 16S rRNA gene sequence and phylogenetic analyses. Preliminary bioactivity screening conducted on the potential novel Streptomyces isolates revealed significant antioxidant activity and notable cytotoxic effect against tested colon cancer cell lines (HCT-116, HT-29, Caco-2, and SW480), with greater cytotoxicity towards SW480 and HT-29 cells. This study highlighted that the Sarawak mangrove environment is a rich reservoir containing streptomycetes that could produce novel secondary metabolites with antioxidant and cytotoxic activities.
  19. Identification of differentially expressed circular RNAs in chemoresistant colorectal cancer
    Abu N, Hon KW, Jeyaraman S, Yahaya A, Abdullah NM, Mustangin M, et al.
    Epigenomics, 2019 06;11(8):875-884.
    PMID: 31020847 DOI: 10.2217/epi-2019-0042
    Aim: Chemoresistance in colorectal cancer (CRC) has become a burden in treating the disease effectively. Circular RNAs (circRNAs) are a type of noncoding RNA that were found to be important in cellular homeostasis. The involvement of circRNAs in relation to chemoresistance in other types of cancers has also been reported. This study aims to identify the differentially expressed circRNAs between chemoresistant and chemosensitive CRC cells. Materials & methods: We developed a chemoresistant cell line model and profiled the circRNAs via microarray. We further validated the expression of two circRNAs in 25 formalin-fixed paraffin-embedded (FFPE) tissue specimens (13 nonresponders and 12 responders) via quantitative polymerase chain reaction (qPCR).  Results & conclusion: We found that there were 773 upregulated and 732 downregulated circRNAs between the chemoresistant and chemosensitive HCT-116 cells. We found that hsa_circ_32883 could be a promising biotarget.
  20. Fulltext Targeting Gut Microbial Biofilms-A Key to Hinder Colon Carcinogenesis?
    Chew SS, Tan LT, Law JW, Pusparajah P, Goh BH, Ab Mutalib NS, et al.
    Cancers (Basel), 2020 Aug 13;12(8).
    PMID: 32823729 DOI: 10.3390/cancers12082272
    Colorectal cancer (CRC) is a global public health issue which poses a substantial humanistic and economic burden on patients, healthcare systems and society. In recent years, intestinal dysbiosis has been suggested to be involved in the pathogenesis of CRC, with specific pathogens exhibiting oncogenic potentials such as Fusobacterium nucleatum, Escherichia coli and enterotoxigenic Bacteroides fragilis having been found to contribute to CRC development. More recently, it has been shown that initiation of CRC development by these microorganisms requires the formation of biofilms. Gut microbial biofilm forms in the inner colonic mucus layer and is composed of polymicrobial communities. Biofilm results in the redistribution of colonic epithelial cell E-cadherin, increases permeability of the gut and causes a loss of function of the intestinal barrier, all of which enhance intestinal dysbiosis. This literature review aims to compile the various strategies that target these pathogenic biofilms and could potentially play a role in the prevention of CRC. We explore the potential use of natural products, silver nanoparticles, upconverting nanoparticles, thiosalicylate complexes, anti-rheumatic agent (Auranofin), probiotics and quorum-sensing inhibitors as strategies to hinder colon carcinogenesis via targeting colon-associated biofilms.
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