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  1. Lee BK, Tiong KH, Chang JK, Liew CS, Abdul Rahman ZA, Tan AC, et al.
    BMC Genomics, 2017 01 25;18(Suppl 1):934.
    PMID: 28198666 DOI: 10.1186/s12864-016-3260-7
    BACKGROUND: The drug discovery and development pipeline is a long and arduous process that inevitably hampers rapid drug development. Therefore, strategies to improve the efficiency of drug development are urgently needed to enable effective drugs to enter the clinic. Precision medicine has demonstrated that genetic features of cancer cells can be used for predicting drug response, and emerging evidence suggest that gene-drug connections could be predicted more accurately by exploring the cumulative effects of many genes simultaneously.

    RESULTS: We developed DeSigN, a web-based tool for predicting drug efficacy against cancer cell lines using gene expression patterns. The algorithm correlates phenotype-specific gene signatures derived from differentially expressed genes with pre-defined gene expression profiles associated with drug response data (IC50) from 140 drugs. DeSigN successfully predicted the right drug sensitivity outcome in four published GEO studies. Additionally, it predicted bosutinib, a Src/Abl kinase inhibitor, as a sensitive inhibitor for oral squamous cell carcinoma (OSCC) cell lines. In vitro validation of bosutinib in OSCC cell lines demonstrated that indeed, these cell lines were sensitive to bosutinib with IC50 of 0.8-1.2 μM. As further confirmation, we demonstrated experimentally that bosutinib has anti-proliferative activity in OSCC cell lines, demonstrating that DeSigN was able to robustly predict drug that could be beneficial for tumour control.

    CONCLUSIONS: DeSigN is a robust method that is useful for the identification of candidate drugs using an input gene signature obtained from gene expression analysis. This user-friendly platform could be used to identify drugs with unanticipated efficacy against cancer cell lines of interest, and therefore could be used for the repurposing of drugs, thus improving the efficiency of drug development.

  2. Kumar HK, Gan HM, Tan MH, Eng WW, Barton HA, Hudson AO, et al.
    J Genomics, 2017;5:12-15.
    PMID: 28138345 DOI: 10.7150/jgen.17863
    A total of eight Ensifer sp. strains were isolated from two pristine cave environments. One strain was isolated from a cave water pool located in the Wind Cave National Park, South Dakota, USA and the remaining seven strains were isolated from Lechuguilla Cave of Carlsbad Caverns National Park, New Mexico, USA. Whole genome sequencing and comparative genomic analyses of the eight isolates compared to various type strains from the genera Ensifer and Sinorhizobium demonstrates that although members in these genera can be phylogenetically separated into two distinct clades, the percentage of conserved proteins (POCP) between various type strains from Ensifer and Sinorhizobium are consistently higher than 50%, providing strong genomic evidence to support the classification of the genera Ensifer and Sinorhizobium into a single genus.
  3. Yong YL, Tan LT, Ming LC, Chan KG, Lee LH, Goh BH, et al.
    Front Pharmacol, 2016;7:538.
    PMID: 28119613 DOI: 10.3389/fphar.2016.00538
    In particular, neuropathic pain is a major form of chronic pain. This type of pain results from dysfunction or lesions in the central and peripheral nervous system. Capsaicin has been traditionally utilized as a medicine to remedy pain. However, the effectiveness and safety of this practice is still elusive. Therefore, this systematic review aimed to investigate the effect of topical capsaicin as a pain-relieving agent that is frequently used in pain management. In brief, all the double-blinded, randomized placebo- or vehicle-controlled trials that were published in English addressing postherpetic neuralgia were included. Meta-analysis was performed using Revman(®) version 5.3. Upon application of the inclusion and exclusion criteria, only six trials fulfilled all the criteria and were included in the review for qualitative analysis. The difference in mean percentage change in numeric pain rating scale score ranges from -31 to -4.3. This demonstrated high efficacy of topical capsaicin application and implies that capsaicin could result in pain reduction. Furthermore, meta-analysis was performed on five of the included studies. All the results of studies are in favor of the treatment using capsaicin. The incidence of side effects from using topical capsaicin is consistently higher in all included studies, but the significance of safety data cannot be quantified due to a lack of p-values in the original studies. Nevertheless, topical capsaicin is a promising treatment option for specific patient groups or certain neuropathic pain conditions such as postherpetic neuralgia.
  4. Oong XY, Ng KT, Tan JL, Chan KG, Kamarulzaman A, Chan YF, et al.
    PLoS One, 2017;12(1):e0170610.
    PMID: 28129386 DOI: 10.1371/journal.pone.0170610
    Reassortment of genetic segments between and within influenza B lineages (Victoria and Yamagata) has been shown to generate novel reassortants with unique genetic characteristics. Based on hemagglutinin (HA) and neuraminidase (NA) genes, recent surveillance study has identified reassortment properties in B/Phuket/3073/2013-like virus, which is currently used in the WHO-recommended influenza vaccine. To understand the potential reassortment patterns for all gene segments, four B/Phuket/3073/2013-like viruses and two unique reassortants (one each from Yamagata and Victoria) detected in Malaysia from 2012-2014 were subjected to whole-genome sequencing. Each gene was phylogenetically classified into lineages, clades and sub-clades. Three B/Phuket/3073/2013-like viruses from Yamagata lineage were found to be intra-clade reassortants, possessing PA and NA genes derived from Stockholm/12-like sub-clade, while the remaining genes from Wisconsin/01-like sub-clade (both sub-clades were within Yamagata Clade 3/Yam-3). However, the other B/Phuket/3073/2013-like virus had NS gene that derived from Stockholm/12-like sub-clade instead of Wisconsin/01-like sub-clade. One inter-clade reassortant had Yamagata Clade 2/Yam-2-derived HA and NP, and its remaining genes were Yam-3-derived. Within Victoria Clade 1/Vic-1 in Victoria lineage, one virus had intra-clade reassortment properties: HA and PB2 from Vic-1B sub-clade, MP and NS from a unique sub-clade "Vic-1C", and the remaining genes from Vic-1A sub-clade. Although random reassortment event may generate unique reassortants, detailed phylogenetic classification of gene segments showed possible genetic linkage between PA and NA genes in B/Phuket/3073/2013-like viruses, which requires further investigation. Understanding on reassortment patterns in influenza B evolution may contribute to future vaccine design.
  5. Lo TS, Lin YH, Chu HC, Cortes EF, Pue LB, Tan YL, et al.
    J Obstet Gynaecol Res, 2017 Jan;43(1):173-178.
    PMID: 27762470 DOI: 10.1111/jog.13158
    AIM: By investigating the association of urodynamics and urogenital nerve growth factor (NGF) levels in vaginal mesh surgery, we may be able to associate the likelihood of postoperative lower urinary tract symptoms developing as a result of synthetic mesh implanted for pelvic floor reconstructive surgery.

    METHODS: Thirty-eight female Sprague-Dawley rats were divided into three groups: mesh, sham (no mesh), and control. Urodynamic study and NGF analysis of the urogenital tissues were done and results were compared among all groups. The urodynamic studies of the mesh and sham groups were further divided into the 4th and 10th days. A P-value 

  6. Tan ET, Yong KW, Wong SH, D'Arcy BR, Al Jassim R, De Voss JJ, et al.
    J Agric Food Chem, 2016 Nov 09;64(44):8447-8453.
    PMID: 27737547
    Ingestion of indospicine-contaminated camel and horse meat has caused fatal liver injury to dogs in Australia, and it is currently not known if such contaminated meat may pose a human health risk upon dietary exposure. To date, indospicine-related research has tended to focus on analytical aspects, with little information on post-harvest management of indospicine-contaminated meat. In this study, indospicine degradation was investigated in both aqueous solution and also contaminated meat, under a range of conditions. Aqueous solutions of indospicine and indospicine-contaminated camel meat were microwaved (180 °C) or autoclaved (121 °C) with the addition of food-grade additives [0.05% (v/v) acetic acid or 0.05% (w/v) sodium bicarbonate] for 0, 15, 30, and 60 min. An aqueous sodium bicarbonate solution demonstrated the greatest efficacy in degrading indospicine, with complete degradation after 15 min of heating in a microwave or autoclave; concomitant formation of indospicine degradation products, namely, 2-aminopimelamic and 2-aminopimelic acids, was observed. Similar treatment of indospicine-contaminated camel meat with aqueous sodium bicarbonate resulted in 50% degradation after 15 min of heating in an autoclave and 100% degradation after 15 min of heating in a microwave. The results suggest that thermo-alkaline aqueous treatment has potential as a pragmatic post-harvest handling technique in reducing indospicine levels in indospicine-contaminated meat.
  7. Mohd-Sharif N, Shaibullah S, Givajothi V, Tan CS, Ho KL, Teh AH, et al.
    Acta Crystallogr F Struct Biol Commun, 2017 02 01;73(Pt 2):109-115.
    PMID: 28177322 DOI: 10.1107/S2053230X17001212
    TylP is one of five regulatory proteins involved in the regulation of antibiotic (tylosin) production, morphological and physiological differentiation in Streptomyces fradiae. Its function is similar to those of various γ-butyrolactone receptor proteins. In this report, N-terminally His-tagged recombinant TylP protein (rTylP) was overproduced in Escherichia coli and purified to homogeneity. The rTylP protein was crystallized from a reservoir solution comprising 34%(v/v) ethylene glycol and 5%(v/v) glycerol. The protein crystals diffracted X-rays to 3.05 Å resolution and belonged to the trigonal space group P3121, with unit-cell parameters a = b = 126.62, c = 95.63 Å.
  8. Tan SH, Normi YM, Leow AT, Salleh AB, Murad AM, Mahadi NM, et al.
    J. Biochem., 2017 02 01;161(2):167-186.
    PMID: 28175318 DOI: 10.1093/jb/mvw058
    The effectiveness of β-lactam antibiotics as chemotherapeutic agents to treat bacterial infections is gradually threatened with the emergence of antibiotic resistance mechanism among pathogenic bacteria through the production metallo-β-lactamase (MBL). In this study, we discovered a novel hypothetical protein (HP) termed Bleg1_2437 from the genome of alkaliphilic Bacillus lehensis G1 which exhibited MBL-like properties of B3 subclass; but evolutionary divergent from other circulating B3 MBLs. Domain and sequence analysis of HP Bleg1_2437 revealed that it contains highly conserved Zn2+-binding residues such as H54, H56, D58, H59, H131 and H191, important for catalysis, similar with the subclass B3 of MBL. Built 3-D Bleg1_2437 structure exhibited an αββα sandwich layer similar to the well-conserved global topology of MBL superfamily. Other features include a ceiling and floor in the model which are important for accommodation and orientation of β-lactam antibiotics docked to the protein model showed interactions at varying degrees with residues in the binding pocket of Bleg1_2437. Hydrolysis activity towards several β-lactam antibiotics was proven through an in vitro assay using purified recombinant Bleg1_2437 protein. These findings highlight the presence of a clinically important and evolutionary divergent antibiotics-degrading enzyme within the pools of uncharacterized HPs.
  9. Tan LT, Chan KG, Pusparajah P, Lee WL, Chuah LH, Khan TM, et al.
    Front Pharmacol, 2017;8:12.
    PMID: 28167913 DOI: 10.3389/fphar.2017.00012
    Cancer mortality and morbidity is projected to increase significantly over the next few decades. Current chemotherapeutic strategies have significant limitations, and there is great interest in seeking novel therapies which are capable of specifically targeting cancer cells. Given that fundamental differences exist between the cellular membranes of healthy cells and tumor cells, novel therapies based on targeting membrane lipids in cancer cells is a promising approach that deserves attention in the field of anticancer drug development. Phosphatidylethanolamine (PE), a lipid membrane component which exists only in the inner leaflet of cell membrane under normal circumstances, has increased surface representation on the outer membrane of tumor cells with disrupted membrane asymmetry. PE thus represents a potential chemotherapeutic target as the higher exposure of PE on the membrane surface of cancer cells. This feature as well as a high degree of expression of PE on endothelial cells in tumor vasculature, makes PE an attractive molecular target for future cancer interventions. There have already been several small molecules and membrane-active peptides identified which bind specifically to the PE molecules on the cancer cell membrane, subsequently inducing membrane disruption leading to cell lysis. This approach opens up a new front in the battle against cancer, and is of particular interest as it may be a strategy that may be prove effective against tumors that respond poorly to current chemotherapeutic agents. We aim to highlight the evidence suggesting that PE is a strong candidate to be explored as a potential molecular target for membrane targeted novel anticancer therapy.
  10. Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    Nurs Res, 2017 Mar-Apr;66(2):134-144.
    PMID: 28252574 DOI: 10.1097/NNR.0000000000000204
    BACKGROUND: Methadone is a substrate of the P-glycoprotein efflux transporter, which is encoded by ABCB1 (MDR1), and thus, ABCB1 polymorphisms may influence the transport of methadone at the blood-brain barrier, affecting its adverse effects.

    OBJECTIVES: This study investigated the association between ABCB1 polymorphisms and cold pressor pain responses among opioid-dependent patients on methadone maintenance therapy (MMT).

    METHODS: Malay male opioid-dependent patients receiving MMT (n = 148) were recruited. Cold pressor pain responses (pain threshold, pain tolerance, and pain intensity) were measured at 0, 2, 4, 8, 12, and 24 hours post-methadone dose. DNA was extracted from whole blood and genotyped for ABCB1 polymorphisms including 1236C>T (rs1128503), 2677G>T/A (rs2032582), and 3435C>T (rs1045642) using the allelic discrimination real-time polymerase chain reaction. Repeated-measure analysis of variance between-group analysis was used to compare the three cold pressor pain responses and ABCB1 polymorphisms (1236C>T, 2677G>T/A, and 3435C>T) according to genotypes and allelic additive models, genotype dominant and recessive models, haplotypes, and diplotypes.

    RESULTS: Patients with 2677 GG or 2677G allele had the lowest pain threshold compared with 2677G>T/A genotypes or alleles (p = .007 and .002, respectively). Haplotype analysis showed a significant association between ABCB1 haplotypes and pain threshold (p = .02). Patients with 2677G allele had the lowest pain tolerance compared to those with 2677T and 2677A alleles (2677G < 2677T < 2677A allele carriers; p = .05). In terms of pain intensity scores, patients with 2677 GG or 2677G allele had the highest scores compared to other 2677G>T/A genotypes or alleles (p = .04 and .008, respectively). Haplotype analysis revealed a significant difference between patients with CGC haplotype and those without this haplotype (p = .02).

    DISCUSSION: To the best of our knowledge, this study provides the first evidence that ABCB1 polymorphisms are associated with cold pressor pain responses among Malay male patients with opioid dependence on MMT. The results may provide an initial prediction on heightened pain sensitivity or hyperalgesia for individuals who are carriers of the ABCB1 polymorphisms.
  11. Lau SX, Leong YY, Ng WH, Ng AWP, Ismail IS, Yusoff NM, et al.
    Cell Biol Int, 2017 Jun;41(6):697-704.
    PMID: 28403524 DOI: 10.1002/cbin.10774
    Studies showed that co-transplantation of mesenchymal stem cells (MSCs) and cord blood-derived CD34+hematopoietic stem cells (HSCs) offered greater therapeutic effects but little is known regarding the effects of human Wharton's jelly derived MSCs on HSC expansion and red blood cell (RBC) generation in vitro. This study aimed to investigate the effects of MSCs on HSC expansion and differentiation. HSCs were co-cultured with MSCs or with 10% MSCs-derived conditioned medium, with HSCs cultured under standard medium served as a control. Cell expansion rates, number of mononuclear cell post-expansion and number of enucleated cells post-differentiation were evaluated. HSCs showed superior proliferation in the presence of MSC with mean expansion rate of 3.5 × 108 ± 1.8 × 107after day 7 compared to the conditioned medium and the control group (8.9 × 107 ± 1.1 × 108and 7.0 × 107 ± 3.3 × 106respectively, P 
  12. Hong W, Li J, Chang Z, Tan X, Yang H, Ouyang Y, et al.
    J Antibiot (Tokyo), 2017 Jul;70(7):832-844.
    PMID: 28465626 DOI: 10.1038/ja.2017.55
    The emergence of drug resistance in bacterial pathogens is a growing clinical problem that poses difficult challenges in patient management. To exacerbate this problem, there is currently a serious lack of antibacterial agents that are designed to target extremely drug-resistant bacterial strains. Here we describe the design, synthesis and antibacterial testing of a series of 40 novel indole core derivatives, which are predicated by molecular modeling to be potential glycosyltransferase inhibitors. Twenty of these derivatives were found to show in vitro inhibition of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Four of these strains showed additional activity against Gram-negative bacteria, including extended-spectrum beta-lactamase producing Enterobacteriaceae, imipenem-resistant Klebsiella pneumoniae and multidrug-resistant Acinetobacter baumanii, and against Mycobacterium tuberculosis H37Ra. These four compounds are candidates for developing into broad-spectrum anti-infective agents.
  13. Aziz NFHA, Abbasiliasi S, Ng HS, Phapugrangkul P, Bakar MHA, Tam YJ, et al.
    J Chromatogr B Analyt Technol Biomed Life Sci, 2017 Jun 15;1055-1056:104-112.
    PMID: 28458127 DOI: 10.1016/j.jchromb.2017.04.029
    The partitioning of β-mannanase derived from Bacillus subtilis ATCC 11774 in aqueous two-phase system (ATPS) was studied. The ATPS containing different molecular weight of polyethylene glycol (PEG) and types of salt were employed in this study. The PEG/salt composition for the partitioning of β-mannanase was optimized using response surface methodology. The study demonstrated that ATPS consists of 25% (w/w) of PEG 6000 and 12.52% (w/w) of potassium citrate is the optimum composition for the purification of β-mannanase with a purification fold (PF) of 2.28 and partition coefficient (K) of 1.14. The study on influences of pH and crude loading showed that ATPS with pH 8.0 and 1.5% (w/w) of crude loading gave highest PF of 3.1. To enhance the partitioning of β-mannanase, four ionic liquids namely 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF4), 1-ethyl-3-methylimidazolium tetrafluoroborate ([Emim]BF4), 1-butyl-3-methylimidazolium bromide ([Bmim]Br), 1-ethyl-3-methylimidazolium bromide ([Emim]Br) was added into the system as an adjuvant. The highest recovery yield (89.65%) was obtained with addition of 3% (w/w) of [Bmim]BF4. The SDS-PAGE analysis revealed that the β-mannanase was successfully recovered in the top phase of ATPS with the molecular size of 36.7kDa. Therefore, ATPS demonstrated a simple and efficient approach for recovery and purification of β-mannanase from fermentation broth in one single-step strategy.
  14. Saminathan M, Gan HM, Abdullah N, Wong CMVL, Ramiah SK, Tan HY, et al.
    J Appl Microbiol, 2017 Apr 23.
    PMID: 28434189 DOI: 10.1111/jam.13477
    AIMS: To evaluate the effects of condensed tannins (CTs) fractions of differing molecular weights (MWs) from a Leucaena leucocephala hybrid-Rendang on the rumen protozoal community in vitro.

    METHODS AND RESULTS: The effects of unfractionated CTs (F0) and CT fractions of different MWs (F1 > F2 > F3 > F4 > F5) on protozoal population and community were evaluated in vitro using rumen microbes and ground guinea grass as the substrate. Higher-MW CT fractions F1 and F2 significantly (P 

  15. Acharya UR, Sudarshan VK, Rong SQ, Tan Z, Lim CM, Koh JE, et al.
    Comput Biol Med, 2017 06 01;85:33-42.
    PMID: 28433870 DOI: 10.1016/j.compbiomed.2017.04.013
    An accurate detection of preterm labor and the risk of preterm delivery before 37 weeks of gestational age is crucial to increase the chance of survival rate for both mother and the infant. Thus, the uterine contractions measured using uterine electromyogram (EMG) or electro hysterogram (EHG) need to have high sensitivity in the detection of true preterm labor signs. However, visual observation and manual interpretation of EHG signals at the time of emergency situation may lead to errors. Therefore, the employment of computer-based approaches can assist in fast and accurate detection during the emergency situation. This work proposes a novel algorithm using empirical mode decomposition (EMD) combined with wavelet packet decomposition (WPD), for automated prediction of pregnant women going to have premature delivery by using uterine EMG signals. The EMD is performed up to 11 levels on the normal and preterm EHG signals to obtain the different intrinsic mode functions (IMFs). These IMFs are further subjected to 6 levels of WPD and from the obtained coefficients, eight different features are extracted. From these extracted features, only the significant features are selected using particle swarm optimization (PSO) method and selected features are ranked by Bhattacharyya technique. All the ranked features are fed to support vector machine (SVM) classifier for automated differentiation and achieved an accuracy of 96.25%, sensitivity of 95.08%, and specificity of 97.33% using only ten EHG signal features. Our proposed algorithm can be used in gynecology departments of hospitals to predict the preterm or normal delivery of pregnant women.
  16. Nidaullah H, Abirami N, Shamila-Syuhada AK, Chuah LO, Nurul H, Tan TP, et al.
    Vet World, 2017 Mar;10(3):286-292.
    PMID: 28435190 DOI: 10.14202/vetworld.2017.286-292
    AIM: The aim of this study was to determine the prevalence of various Salmonella serotypes in chickens, carcass contact surfaces as well as environmental samples collected from wet markets and small scale processing plant.

    MATERIALS AND METHODS: A total of 182 poultry and environmental samples were collected at random on separate occasions from wet markets and small scale processing plant, during the period of October 2014 to July 2015 in Penang and Perlis, Malaysia. The samples were analyzed for the presence of Salmonella using ISO 6579:2002 conventional culture-based method. Presumptive Salmonella colonies were subjected to various biochemical tests (such as triple sugar iron and lysine iron test), serologically confirmed using polyvalent O and H antisera and further serotyped at Public Health Laboratory, Ministry of Health, Perak, Malaysia.

    RESULTS: Salmonella serotypes were isolated from 161 out of 182 samples (88.46%) with 100% prevalence in the whole chicken carcass and chicken cuts - as well as transport crate, cage, drum, knife, chopping board, display table, floor, bench wash water, wash water, and drain water. Salmonella was isolated from 91.67%, 83.33%, and 66.67% of defeathering machines, drain swabs, and apron, respectively. 17 serotypes were isolated in this study with Salmonella Albany (57/161), Salmonella Corvallis (42/161), and Salmonella Brancaster (37/161) being the predominant serovars.

    CONCLUSION: The most carcass contact and environmental samples collected along the wet market chicken processing line were consistently contaminated with Salmonella. This indicates that Salmonella has established itself in poultry processing environments by colonizing the surfaces of the equipment and survives in these environments by establishing biofilms. Our results highlight the need of implementing strict hygiene and sanitation standards to reduce the incidence of Salmonella. The prevalence of Salmonella in poultry can be reduced effectively by identifying and eliminating the sources and contamination sites during slaughter and processing of poultry.

  17. Chong HT, Kamarulzaman A, Tan CT, Goh KJ, Thayaparan T, Kunjapan SR, et al.
    Ann Neurol, 2001 Jun;49(6):810-3.
    PMID: 11409437
    Nipah virus, a newly identified paramyxovirus caused a severe outbreak of encephalitis in Malaysia with high fatalities. We report an open-label trial of ribavirin in 140 patients, with 54 patients who were managed prior to the availability of ribavirin or refused treatment as control. There were 45 deaths (32%) in the ribavirin arm; 29 deaths (54%) occurred in the control arm. This represents a 36% reduction in mortality (p = 0.011). There was no associated serious side effect. This study suggests that ribavirin is able to reduce the mortality of acute Nipah encephalitis.
  18. Yong YK, Tan HY, Jen SH, Shankar EM, Natkunam SK, Sathar J, et al.
    J Transl Med, 2017 05 31;15(1):121.
    PMID: 28569153 DOI: 10.1186/s12967-017-1226-4
    BACKGROUND: Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks.

    METHODS: We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1β in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS-), dengue with warning signs (DWS+) and severe dengue (SD).

    RESULTS: Our results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P 

  19. Tan LT, Chan KG, Khan TM, Bukhari SI, Saokaew S, Duangjai A, et al.
    Front Pharmacol, 2017;8:276.
    PMID: 28567016 DOI: 10.3389/fphar.2017.00276
    Reactive oxygen species and other radicals potentially cause oxidative damage to proteins, lipids, and DNA which may ultimately lead to various complications including mutations, carcinogenesis, neurodegeneration, cardiovascular disease, aging, and inflammatory disease. Recent reports demonstrate that Streptomyces bacteria produce metabolites with potent antioxidant activity that may be developed into therapeutic drugs to combat oxidative stress. This study shows that Streptomyces sp. MUM212 which was isolated from mangrove soil in Kuala Selangor, Malaysia, could be a potential source of antioxidants. Strain MUM212 was characterized and determined as belonging to the genus Streptomyces using 16S rRNA gene phylogenetic analysis. The MUM212 extract demonstrated significant antioxidant activity through DPPH, ABTS and superoxide radical scavenging assays and also metal-chelating activity of 22.03 ± 3.01%, 61.52 ± 3.13%, 37.47 ± 1.79%, and 41.98 ± 0.73% at 4 mg/mL, respectively. Moreover, MUM212 extract was demonstrated to inhibit lipid peroxidation up to 16.72 ± 2.64% at 4 mg/mL and restore survival of Vero cells from H2O2-induced oxidative damages. The antioxidant activities from the MUM212 extract correlated well with its total phenolic contents; and this in turn was in keeping with the gas chromatography-mass spectrometry analysis which revealed the presence of phenolic compounds that could be responsible for the antioxidant properties of the extract. Other chemical constituents detected included hydrocarbons, alcohols and cyclic dipeptides which may have contributed to the overall antioxidant capacity of MUM212 extract. As a whole, strain MUM212 seems to have potential as a promising source of novel molecules for future development of antioxidative therapeutic agents against oxidative stress-related diseases.
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