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Fulltext Synthesis, structural and antioxidant studies of some novel N-ethyl phthalimide esters

Chidan Kumar CS, Loh WS, Chandraju S, Win YF, Tan WK, Quah CK, et al.

PLoS One, 2015;10(3):e0119440.
PMID: 25742494 DOI: 10.1371/journal.pone.0119440

A series of N-ethyl phthalimide esters 4(a-n) were synthesized and characterized by spectroscopic studies. Further, the molecular structure of majority of compounds were analysed by single crystal X-ray diffraction studies. The X-ray analysis revealed the importance of substituents on the crystal stability and molecular packing. All the synthesized compounds were tested for in vitro antioxidant activity by DPPH radical scavenging, FRAP and CUPRAC methods. Few of them have shown good antioxidant activity.
Fulltext Genome Sequence Analysis Reveals Evidence of Quorum-Sensing Genes Present in Aeromonas hydrophila Strain M062, Isolated from Freshwater

Chan KG, Tan WS, Chang CY, Yin WF, Mumahad Yunos NY

Genome Announc, 2015;3(2).
PMID: 25767237 DOI: 10.1128/genomeA.00100-15

Aeromonas hydrophila has emerged worldwide as a human pathogen. Here, we report the draft whole-genome sequence of a freshwater isolate from Malaysia, A. hydrophila strain M062, and its N-acylhomoserine lactone genes are also reported here.
Phytochemical investigation of Gynura bicolor leaves and cytotoxicity evaluation of the chemical constituents against HCT 116 cells

Teoh WY, Tan HP, Ling SK, Abdul Wahab N, Sim KS

Nat Prod Res, 2016;30(4):448-51.
PMID: 25738869 DOI: 10.1080/14786419.2015.1017726

Gynura bicolor (Compositae) is a popular vegetable in Asia and believed to confer a wide range of benefits including anti-cancer. Our previous findings showed that the ethyl acetate extract of G. bicolor possessed cytotoxicity and induced apoptotic and necrotic cell death in human colon carcinoma cells (HCT 116). A combination of column chromatography had been used to purify chemical constituents from the ethyl acetate and water extract of G. bicolor leaves. Eight chemical constituents 5-p-trans-coumaroylquinic acid (I), 4-hydroxybenzoic acid (II), rutin (III), kampferol-3-O-rutinoside (IV), 3,5-dicaffeoylquinic acid (V), kampferol-3-O-glucoside (VI), guanosine (VII) and chlorogenic acid (VIII) were isolated from G. bicolor grown in Malaysia. To our best knowledge, all chemical constituents were isolated for the first time from G. bicolor leaves except rutin (III). 3,5-dicaffeoylquinic acid (V), guanosine (VII) and chlorogenic acid (VIII) demonstrated selective cytotoxicity (selective index>3) against HCT 116 cancer cells compared to CCD-18Co human normal colon cells.
The complete mitogenome of the endangered white-clawed freshwater crayfish Austropotamobius pallipes (Lereboullet, 1858) (Crustacea: Decapoda: Astacidae)

Grandjean F, Tan MH, Gan HY, Gan HM, Austin CM

Mitochondrial DNA A DNA Mapp Seq Anal, 2016 09;27(5):3329-30.
PMID: 25738217 DOI: 10.3109/19401736.2015.1018207

The Austropotamobius pallipes complete mitogenome has been recovered using Next-Gen sequencing. Our sample of A. pallipes has a mitogenome of 15,679 base pairs (68.44% A + T content) made up of 13 protein-coding genes, 2 ribosomal subunit genes, 22 transfer RNAs, and a 877 bp non-coding AT-rich region. This is the first mitogenome sequenced for a crayfish from the family Astacidae and the 4(th) for northern hemisphere genera.
Fulltext Effective equine immunization protocol for production of potent poly-specific antisera against Calloselasma rhodostoma, Cryptelytrops albolabris and Daboia siamensis

Sapsutthipas S, Leong PK, Akesowan S, Pratanaphon R, Tan NH, Ratanabanangkoon K

PLoS Negl Trop Dis, 2015 Mar;9(3):e0003609.
PMID: 25774998 DOI: 10.1371/journal.pntd.0003609

Snake envenomation has been estimated to affect 1.8 million people annually with about 94,000 deaths mostly in poor tropical countries. Specific antivenoms are the only rational and effective therapy for these cases. Efforts are being made to produce effective, affordable and sufficient antivenoms for these victims. The immunization process, which has rarely been described in detail, is one step that needs to be rigorously studied and improved especially with regard to the production of polyspecific antisera. The polyspecific nature of therapeutic antivenom could obviate the need to identify the culprit snake species. The aim of this study was to produce potent polyspecific antisera against 3 medically important vipers of Thailand and its neighboring countries, namely Cryptelytrops albolabris "White lipped pit viper" (CA), Calleoselasma rhodostoma "Malayan pit viper" (CR), and Daboia siamensis "Russell's viper" (DS). Four horses were immunized with a mixture of the 3 viper venoms using the 'low dose, low volume multi-site' immunization protocol. The antisera showed rapid rise in ELISA titers against the 3 venoms and reached plateau at about the 8th week post-immunization. The in vivo neutralization potency (P) of the antisera against CA, CR and DS venoms was 10.40, 2.42 and 0.76 mg/ml, respectively and was much higher than the minimal potency limits set by Queen Soavabha Memorial Institute (QSMI). The corresponding potency values for the QSMI monospecific antisera against CA, CR and DS venoms were 7.28, 3.12 and 1.50 mg/ml, respectively. The polyspecific antisera also effectively neutralized the procoagulant, hemorrhagic, necrotic and nephrotoxic activities of the viper venoms. This effective immunization protocol should be useful in the production of potent polyspecific antisera against snake venoms, and equine antisera against tetanus, diphtheria or rabies.
New insights into seaweed polyphenols on glucose homeostasis

Murugan AC, Karim MR, Yusoff MB, Tan SH, Asras MF, Rashid SS

Pharm Biol, 2015 Aug;53(8):1087-97.
PMID: 25630358 DOI: 10.3109/13880209.2014.959615

CONTEXT: Polyphenol-rich marine macroalgae are gaining dietary importance due to their influence over diabetes mellitus and the role as a vital source of high-value nutraceuticals. Their assorted beneficial effects on human health include competitive inhibition of digestive enzymes, varying the activity of hepatic glucose-metabolizing enzymes, lowering the plasma glucose levels, and lipid peroxidation, delaying the aging process.
OBJECTIVE: In this paper, we review the health beneficial effects of polyphenols and phlorotannins from brown seaweeds with special emphasis on their inhibitory effects on carbohydrate-metabolizing enzymes.
METHODS: A survey of literature from databases such as Sciencedirect, Scopus, Pubmed, Springerlink, and Google Scholar from the year 1973 to 2013 was done to bring together the information relating to drug discovery from brown seaweeds as a source for diabetes treatment.
RESULTS: Over the past two decades, 20 different bioactive polyphenols/phlorotannins have been isolated and studied from 10 different brown algae. Discussion of the positive effect on the inhibition of enzymes metabolizing carbohydrates in both in vitro and in vivo experiments are included.
CONCLUSION: Despite the recent advancements in isolating bioactive compounds from seaweeds with potential health benefit or pharmaceutical behavior, studies on the polyphenol effectiveness on glucose homeostasis in human beings are very few in response to their functional characterization. Added research in this area is required to confirm the close connection of polyphenol rich seaweed-based diet consumption with glucose homeostasis and the exciting possibility of prescribing polyphenols to treat the diabetes pandemic.
The complete mitogenome of the hermit crab Clibanarius infraspinatus (Hilgendorf, 1869), (Crustacea; Decapoda; Diogenidae) - a new gene order for the Decapoda

Gan HY, Gan HM, Tan MH, Lee YP, Austin CM

Mitochondrial DNA A DNA Mapp Seq Anal, 2016 11;27(6):4099-4100.
PMID: 25629489

The complete mitochondrial genome of the hermit crab Clibanarius infraspinatus was recovered by genome skimming using Next-Gen sequencing. The Clibanarius infraspinatus mitogenome has 16,504 base pairs (67.94% A + T content) made up of 13 protein-coding genes, 2 ribosomal subunit genes, 22 transfer RNAs and a putative 1500 bp non-coding AT-rich region. The Clibanarius infraspinatus mitogenome sequence is the first for the family Diogenidae and the second for the superfamily Paguroidea and exhibits a translocation of the ND3 gene not previously reported for the Decapoda.
Ten-year mortality in older patients attending the emergency department after a fall

Tan MP, Kamaruzzaman SB, Zakaria MI, Chin AV, Poi PJ

Geriatr Gerontol Int, 2015 Jan 22.
PMID: 25613422 DOI: 10.1111/ggi.12446

METHODS: Information on sociodemographics, dependency using the Barthel index and fall characteristics were collected from consecutive patients attending the ED over a 6-month period. Barthel score was reassessed at 12 months. Ten-year mortality data were obtained through the National Registry Department.
RESULTS: A total of 198 participants, with a mean age (standard deviation) of 76.2 years (6.3 years) and 74% women, were recruited. Of these, 70% sustained falls indoors, while 49% of falls occurred between 06.00 to 12.00 hours. Total Barthel scores were significantly lower at 1-year follow up compared with baseline (median [interquartile range], 20 [2] vs 18 [5], P
Fulltext Developing a primary care research agenda through collaborative efforts - a proposed "6E" model

Tan NC, Ng CJ, Rosemary M, Wahid K, Goh LG

Asia Pac Fam Med, 2014;13(1):17.
PMID: 25606021 DOI: 10.1186/s12930-014-0017-9

Primary care research is at a crossroad in South Pacific. A steering committee comprising a member of WONCA Asia Pacific Regional (APR) council and the President of Fiji College of General Practitioners garnered sponsorship from Fiji Ministry of Health, WONCA APR and pharmaceutical agencies to organize the event in October 2013. This paper describes the processes needed to set up a national primary research agenda through the collaborative efforts of local stakeholders and external facilitators using a test case in South Pacific.
The complete mitogenome of the minute mudskipper, Periophthalmus minutus Eggert, 1935 (Perciformes: Gobiidae: Oxudercinae)

Gan HM, Tan MH, Lee YP, Hammer MP, Austin CM

Mitochondrial DNA A DNA Mapp Seq Anal, 2016 11;27(6):4187-4188.
PMID: 25600740

The mitogenome of an Australian sample of the mudskipper, Periophthalmus minutus, was recovered from partial sequencing using the MiSeq sequencer. This mudskipper has a mitogenome of 16,506 base pairs (55% A + T content) made up of two ribosomal subunit genes, 13 protein-coding genes, 22 transfer RNAs, and a 838 bp non-coding AT-rich region. This is the first sequenced mitogenome for the genus Periophthalmus and the fifth for the subfamily Oxudercinae.
Long-term outcome of native tissue reconstructive vaginal surgery for advanced pelvic organ prolapse at 86 months: Hysterectomy versus hysteropexy

Lo TS, Pue LB, Hung TH, Wu PY, Tan YL

J Obstet Gynaecol Res, 2015 Jul;41(7):1099-107.
PMID: 25808989 DOI: 10.1111/jog.12678

To evaluate and compare the long-term outcome of sacrospinous ligament fixation (SSF) in combination with various other compartment defect native tissue repairs with hysterectomy or hysteropexy.
A descriptive study of nasogastric tube feeding among geriatric inpatients in Malaysia: utilization, complications, and caregiver opinions

Nordin N, Kamaruzzaman SB, Chin AV, Poi PJ, Tan MP

J Nutr Gerontol Geriatr, 2015;34(1):34-49.
PMID: 25803603 DOI: 10.1080/21551197.2014.998326

The strong emphasis on feeding in Asian cultures may influence decisions for nasogastric (NG) tube feeding in geriatric inpatients. We evaluated the utility, complications, and opinions of caregivers toward NG tube feeding in an acute geriatric ward in a teaching hospital in Kuala Lumpur. Consecutive patients aged 65 years and older receiving NG tube feeding were included. Sociodemographic, clinical, and laboratory indices were recorded. Opinion on NG tube feeding were evaluated through face-to-face interviews with caregivers, recruited through convenience sampling. Of 432 patients admitted, 96 (22%), age ± standard deviation = 80.8 ± 7.4 years, received NG tube feeding. The complication and mortality rates were 69% and 38%, respectively. Diabetes (odds ratio [95% confidence interval] = 3.34 [1.07, 10.44], aspiration pneumonia (8.15 [2.43, 27.24]), impaired consciousness (3.13 [1.05, 9.36]), and albumin ≤26 g/dl (4.43 [1.46, 13.44]) were independent predictors of mortality. Other relatives were more likely than spouses (23.5 [3.59, 154.2]) and caregivers with tertiary education more likely than those with no formal education ( 18 [1.23, 262.7]) to agree to NG feeding. Sixty-four percent of caregivers felt NG tube feeding was appropriate at the end of life, mostly due to the fear of starvation. NG tube feeding is widely used in our setting, despite high complication and mortality rates, with likely influences from cultural emphasis on feeding.
Fulltext Understanding the physicochemical properties of mitragynine, a principal alkaloid of Mitragyna speciosa, for preclinical evaluation

Ramanathan S, Parthasarathy S, Murugaiyah V, Magosso E, Tan SC, Mansor SM

Molecules, 2015 Mar 18;20(3):4915-27.
PMID: 25793541 DOI: 10.3390/molecules20034915

Varied pharmacological responses have been reported for mitragynine in the literature, but no supportive scientific explanations have been given for this. These studies have been undertaken without a sufficient understanding of the physicochemical properties of mitragynine. In this work a UV spectrophotometer approach and HPLC-UV method were employed to ascertain the physicochemical properties of mitragynine. The pKa of mitragynine measured by conventional UV (8.11 ± 0.11) was in agreement with the microplate reader determination (8.08 ± 0.04). Mitragynine is a lipophilic alkaloid, as indicated by a logP value of 1.73. Mitragynine had poor solubility in water and basic media, and conversely in acidic environments, but it is acid labile. In an in vitro dissolution the total drug release was higher for the simulated gastric fluid but was prolonged and incomplete for the simulated intestinal fluid. The hydrophobicity, poor water solubility, high variability of drug release in simulated biological fluids and acid degradable characteristics of mitragynine probably explain the large variability of its pharmacological responses reported in the literature. The determined physicochemical properties of mitragynine will provide a basis for developing a suitable formulation to further improve its solubility, stability and oral absorption for better assessment of this compound in preclinical studies.
Fulltext Analysis of Pectate Lyase Genes in Dickeya chrysanthemi Strain L11, Isolated from a Recreational Lake in Malaysia: a Draft Genome Sequence Perspective

Chan KG, Kher HL, Chang CY, Yin WF, Tan KH

Genome Announc, 2015;3(2).
PMID: 25792063 DOI: 10.1128/genomeA.00145-15

Dickeya chrysanthemi is well known as a plant pathogen that caused major blackleg in the European potato industry in the 1990s. D. chrysanthemi strain L11 was discovered in a recreational lake in Malaysia. Here, we present its draft genome sequence.
Fulltext Low efficacy of delthamethrin-treated net against Singapore Aedes aegypti is associated with kdr-type resistance

Pang SC, Chiang LP, Tan CH, Vythilingam I, Lam-Phua SG, Ng LC

Trop Biomed, 2015 Mar;32(1):140-50.
PMID: 25801264 MyJurnal

There has been a worldwide surge in the number and severity of dengue in the past decades. In Singapore, relentless vector control efforts have been put in to control the disease since the 1960's. Space spraying, fogging, chemical treatment and source reduction are some commonly used methodologies for controlling its vectors, particularly Aedes aegypti. Here, as we explored the use of a commercially available delthamethrin-treated net as an alternative strategy and the efficacy of the treated net was found to be limited. Through bioassays and molecular studies, the failure of the treated net to render high mortality rate was found to be associated with the knockdown resistance (kdr) mutation. This is the first report of kdr- mutations in Singapore's Ae. aegypti. At least one point mutation, either homozygous or heterozygous, at amino acid residue V1016G of DIIS6 or F1269C of DIIIS6 was detected in 93% of field strains of Ae. aegypti. Various permutations of wild type and mutant amino acids of the four alleles were found to result in varying degree of survival rate among local field Ae. aegypti when exposed to the deltamethrin treated net. Together with the association of higher survival rate with the presence of both V1016G and F1269C, the data suggest the role of these mutations in the resistance to the deltamethrin. The high prevalence of these mutations were confirmed in a country wide survey where 70% and 72% of the 201 Ae. aegypti analysed possessed the mutations at residues 1016 and 1269 respectively. The highest mutated frequency combination was found to be heterozygous alleles (VG/FC) at both residues 1016 and 1269 (37.8%), followed by homozygous mutation at allele 1269 (24.4%) and homozygous mutation at allele 1016 (22.9%). The kdr- type of resistance among the vector is likely to undermine the effectiveness of pyrethroids treated materials against these mosquitoes.
Relationship Between Metabolites Composition and Biological Activities of Phyllanthus niruri Extracts Prepared by Different Drying Methods and Solvents Extraction

Mediani A, Abas F, Khatib A, Tan CP, Ismail IS, Shaari K, et al.

Plant Foods Hum Nutr, 2015 Jun;70(2):184-92.
PMID: 25800644 DOI: 10.1007/s11130-015-0478-5

The study investigated the changes in the metabolite, antioxidant and α-glucosidase inhibitory activities of Phyllanthus niruri after three drying treatments: air, freeze and oven dryings. Water extracts and extracts obtained using different solvent ratios of ethanol and methanol (50, 70, 80 and 100%) were compared. The relationships among the antioxidant, α-glucosidase inhibitory activity and metabolite levels of the extracts were evaluated using partial least-square analysis (PLS). The solvent selectivity was assessed based on the phytochemical constituents present in the extract and their concentrations quantitatively analyzed using high performance liquid chromatography. The freeze-dried P. niruri samples that were extracted with the mixture of ethanol or methanol with low ratio of water showed higher biological activity values compared with the other extracts. The PLS results for the ethanolic with different ratio and water extracts demonstrated that phenolic acids (chlorogenic acid and ellagic acid) and flavonoids were highly linked to strong α-glucosidase inhibitory and antioxidant activities.
The complete mitogenome of the giant clam Tridacna squamosa (Heterodonta: Bivalvia: Tridacnidae)

Gan HM, Gan HY, Tan MH, Penny SS, Willan RC, Austin CM

Mitochondrial DNA A DNA Mapp Seq Anal, 2016 09;27(5):3220-1.
PMID: 25648928 DOI: 10.3109/19401736.2015.1007355

The complete mitochondrial genome of the commercially and ecologically important and internationally vulnerable giant clam Tridacna squamosa was recovered by genome skimming using the MiSeq platform. The T. squamosa mitogenome has 20,930 base pairs (62.35% A+T content) and is made up of 12 protein-coding genes, 2 ribosomal subunit genes, 24 transfer RNAs, and a 2594 bp non-coding AT-rich region. The mitogenome has a relatively large insertion in the atp6 gene. This is the first mitogenome to be sequenced from the genus Tridacna, and the family Tridacnidae and represents a new gene order.
The complete mitogenome of the Norway lobster Nephrops norvegicus (Linnaeus, 1758) (Crustacea: Decapoda: Nephropidae)

Gan HM, Tan MH, Gan HY, Lee YP, Austin CM

Mitochondrial DNA A DNA Mapp Seq Anal, 2016 09;27(5):3179-80.
PMID: 25648918 DOI: 10.3109/19401736.2015.1007325

The clawed lobster Nephrops norvegicus is an important commercial species in European waters. We have sequenced the complete mitochondrial genome of the species from a partial genome scan using Next-Gen sequencing. The N. norvegicus has a mitogenome of 16,132 base pairs (71.22% A+ T content) comprising 13 protein-coding genes, 2 ribosomal subunit genes, 21 transfer RNAs, and a putative 1259 bp non-coding AT-rich region. This mitogenome is the second fully characterized for the family Nephropidae and the first for the genus Nephrops. The mitogenome gene order is identical to the Maine lobster, Homarus americanus with the exception of the possible loss of the trnI gene.
Fulltext Characterisation of genotype VII Newcastle disease virus (NDV) isolated from NDV vaccinated chickens, and the efficacy of LaSota and recombinant genotype VII vaccines against challenge with velogenic NDV

Roohani K, Tan SW, Yeap SK, Ideris A, Bejo MH, Omar AR

J Vet Sci, 2015;16(4):447-57.
PMID: 25643805 DOI: 10.4142/jvs.2015.16.4.447

A Newcastle disease virus (NDV) isolate designated IBS002 was isolated from a commercial broiler farm in Malaysia. The virus was characterised as a virulent strain based on the multiple basic amino acid motif of the fusion (F) cleavage site (112)RRRKGF(117) and length of the C-terminus extension of the hemagglutinin-neuraminidase (HN) gene. Furthermore, IBS002 was classified as a velogenic NDV with mean death time (MDT) of 51.2 h and intracerebral pathogenicity index (ICPI) of 1.76. A genetic distance analysis based on the full-length F and HN genes showed that both velogenic viruses used in this study, genotype VII NDV isolate IBS002 and genotype VIII NDV isolate AF2240-I, had high genetic variations with genotype II LaSota vaccine. In this study, the protection efficacy of the recombinant genotype VII NDV inactivated vaccine was also evaluated when added to an existing commercial vaccination program against challenge with velogenic NDV IBS002 and NDV AF2240-I in commercial broilers. The results indicated that both LaSota and recombinant genotype VII vaccines offered full protection against challenge with AF2240-I. However, the LaSota vaccine only conferred partial protection against IBS002. In addition, significantly reduced viral shedding was observed in the recombinant genotype VII-vaccinated chickens compared to LaSota-vaccinated chickens.
Fulltext Ornamental exterior versus therapeutic interior of Madagascar periwinkle (Catharanthus roseus): the two faces of a versatile herb

Nejat N, Valdiani A, Cahill D, Tan YH, Maziah M, Abiri R

ScientificWorldJournal, 2015;2015:982412.
PMID: 25667940 DOI: 10.1155/2015/982412

Catharanthus roseus (L.) known as Madagascar periwinkle (MP) is a legendary medicinal plant mostly because of possessing two invaluable antitumor terpenoid indole alkaloids (TIAs), vincristine and vinblastine. The plant has also high aesthetic value as an evergreen ornamental that yields prolific blooms of splendid colors. The plant possesses yet another unique characteristic as an amiable experimental host for the maintenance of the smallest bacteria found on earth, the phytoplasmas and spiroplasmas, and serves as a model for their study. Botanical information with respect to synonyms, vernacular names, cultivars, floral morphology, and reproduction adds to understanding of the plant while the geography and ecology of periwinkle illustrate the organism's ubiquity. Good agronomic practices ensure generous propagation of healthy plants that serve as a source of bioactive compounds and multitudinous horticultural applications. The correlation between genetic diversity, variants, and TIA production exists. MP is afflicted with a whole range of diseases that have to be properly managed. The ethnobotanical significance of MP is exemplified by its international usage as a traditional remedy for abundant ailments and not only for cancer. TIAs are present only in micro quantities in the plant and are highly poisonous per se rendering a challenge for researchers to increase yield and reduce toxicity.

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