Browse publications by year: 2017

  1. Vijayarathna S, Oon CE, Chen Y, Kanwar JR, Sasidharan S
    Biomed Pharmacother, 2017 May;89:499-514.
    PMID: 28249252 DOI: 10.1016/j.biopha.2017.02.075
    Medicinal plants have been accepted as a gold mine, with respect to the diversity of their phytochemicals. Many medicinal plants extracts are potential anticancer agents. Polyalthia longifolia var. angustifolia Thw. (Annonaceae) is one of the most significant native medicinal plants and is found throughout Malaysia. Hence, the present study was intended to assess the anticancer properties of P. longifolia leaf methanolic extract (PLME) and its underlying mechanisms. The Annexin V/PI flow cytometry analysis showed that PLME induces apoptosis in HeLa cells in dose-dependent manner whereas the PI flow cytometric analysis for cell cycle demonstrated the accumulation of cells at sub G0/G1, G0/G1 and G2/M phases. Investigation with JC-1 flow cytometry analysis indicated increase in mitochondria membrane potential depolarisation corresponding to increase in PLME concentrations. PLME was also shown to influence intracellular reactive oxygen species (ROS) by exerting anti-oxidant (half IC50) and pro-oxidant (IC50and double IC50) affect against HeLa cells. PLME treatment also displayed DNA damage in HeLa cells in concentration depended fashion. The proteomic profiling array exposed the expression of pro-apoptotic and anti-apoptotic proteins upon PLME treatment at IC50concentration in HeLa cells. Pro-apoptotic proteins; BAX, BAD, cytochrome c, caspase-3, p21, p27 and p53 were found to be significantly up-regulated while anti-apoptotic proteins; BCL-2 and BCL-w were found to be significantly down-regulated. This investigation postulated the role of p53 into mediating apoptosis, cell cycle arrest and mitochondrial potential depolarisation by modulating the redox status of HeLa cells.
    MeSH terms: HeLa Cells; Humans; Plant Extracts/pharmacology*; Plant Extracts/chemistry; Apoptosis/drug effects*; Reactive Oxygen Species; Plant Leaves/chemistry*; Annonaceae/chemistry*; Membrane Potential, Mitochondrial/drug effects*; Cell Cycle Checkpoints/drug effects*
  2. Hegedűs B, Kós PB, Bálint B, Maróti G, Gan HM, Perei K, et al.
    J Biotechnol, 2017 Jan 10;241:76-80.
    PMID: 27851894 DOI: 10.1016/j.jbiotec.2016.11.013
    Sulfanilic acid (4-aminobenzenesulfonic acid) is a sulfonated aromatic amine widely used in chemical industries for synthesis of various organic dyes and sulfa drugs. There are quite a few microbial co-cultures or single isolates capable of completely degrading this compound. Novosphingobium resinovorum SA1 was the first single bacterium which could utilize sulfanilic acid as its sole carbon, nitrogen and sulfur source. The strain has versatile catabolic routes for the bioconversion of numerous other aromatic compounds. Here, the complete genome sequence of the N. resinovorum SA1 strain is reported. The genome consists of a circular chromosome of 3.8 Mbp and four extrachromosomal elements between 67 and 1 759.8 kbp in size. Three alternative 3-ketoadipate pathways were identified on the plasmids. Sulfanilic acid is decomposed via a modified 3-ketoadipate pathway and the oxygenases involved form a phylogenetically separate branch on the tree. Sequence analysis of these elements might provide a genetic background for deeper insight into the versatile catabolic metabolism of various aromatic xenobiotics, including sulfanilic acid and its derivatives. Moreover, this is also a good model strain for understanding the role and evolution of multiple genetic elements within a single strain.
    MeSH terms: DNA, Bacterial/analysis; DNA, Bacterial/genetics; Sulfanilic Acids/analysis; Sulfanilic Acids/metabolism*; Genome, Bacterial/genetics*; Sequence Analysis, DNA; Alphaproteobacteria/genetics*; Alphaproteobacteria/metabolism
  3. Yogarajah T, Ong KC, Perera D, Wong KT
    Arch Virol, 2017 Mar;162(3):727-737.
    PMID: 27878462 DOI: 10.1007/s00705-016-3157-4
    Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are closely related enteroviruses that cause hand, foot and mouth disease (HFMD) in children. Serious neurological complications almost always occur in EV-A71 infection, but are rare in CV-A16 infection. Based on the hypothesis that this may be because EV-A71 infects neuronal cells more easily than CV-A16, we compared virus infection, replication and spread of EV-A71 and CV-A16 in SK-N-SH cells. We found that CV-A16 invariably showed significantly lower replication and caused less necrotic cell death in SK-N-SH cells, compared with EV-A71. This was not due to a lower proportion of CV-A16-infected cells, since both viruses showed similar proportions of infected cells at all time points analyzed. Furthermore, reduced replication of CV-A16 in SK-N-SH cells does not appear to be due to limited viral receptor availability, which might limit viral entry, because experiments with viral RNA-transfected cells showed the same results as for live virus infections. On the other hand, no differences were observed between EV-A71 and CV-A16 in RD cells and results were generally similar in RD cells for both viruses. Taken together, our findings suggest that the poor growth of CV-A16 and EV-A71in SK-N-SH cells, compared with RD cells, may be due to cell type-specific restrictions on viral replication and spread. Furthermore, the lower viral replication and necrotic cell death in CV-A16-infected SK-N-SH cells, compared with EV-A71-infected SK-N-SH cells, is consistent with the lower prevalence of neurotropism observed in CV-A16-associated HFMD outbreaks. Nonetheless, in vivo data and more extensive comparisons of different viral strains are essential to confirm our findings.
    MeSH terms: Child; Disease Outbreaks; Enterovirus Infections; Enterovirus; Hand, Foot and Mouth Disease; Humans; Receptors, Virus; RNA, Viral; Virus Replication; Prevalence; Cell Death; Enterovirus A, Human
  4. Foo SC, Yusoff FM, Ismail M, Basri M, Yau SK, Khong NMH, et al.
    J Biotechnol, 2017 Jan 10;241:175-183.
    PMID: 27914891 DOI: 10.1016/j.jbiotec.2016.11.026
    Natural antioxidants from sustainable sources are favoured to accommodate worldwide antioxidant demand. In addition to bioprospecting for natural and sustainable antioxidant sources, this study aimed to investigate the relationship between the bioactives (i.e. carotenoid and phenolic acids) and the antioxidant capacities in fucoxanthin-producing algae. Total carotenoid, phenolic acid, fucoxanthin contents and fatty acid profile of six species of algae (five microalgae and one macroalga) were quantified followed by bioactivity evaluation using four antioxidant assays. Chaetoceros calcitrans and Isochrysis galbana displayed the highest antioxidant activity, followed by Odontella sinensis and Skeletonema costatum which showed moderate bioactivities. Phaeodactylum tricornutum and Saccharina japonica exhibited the least antioxidant activities amongst the algae species examined. Pearson correlation and multiple linear regression showed that both carotenoids and phenolic acids were significantly correlated (p<0.05) with the antioxidant activities, indicating the influence of these bioactives on the algal antioxidant capacities.
    MeSH terms: Antioxidants/metabolism*; Antioxidants/chemistry; Biotechnology; Carotenoids/analysis; Carotenoids/metabolism*; Fatty Acids/metabolism; Phenols/analysis; Phenols/metabolism*; Xanthophylls/metabolism*; Xanthophylls/chemistry; Microalgae/metabolism*; Microalgae/chemistry
  5. Subramani B, Subbannagounder S, Ramanathanpullai C, Palanivel S, Ramasamy R
    Exp Biol Med (Maywood), 2017 03;242(6):645-656.
    PMID: 28092181 DOI: 10.1177/1535370216688568
    Redox homeostasis plays a crucial role in the regulation of self-renewal and differentiation of stem cells. However, the behavioral actions of mesenchymal stem cells in redox imbalance state remain elusive. In the present study, the effect of redox imbalance that was induced by either hydrogen peroxide (H2O2) or ascorbic acid on human cardiac-resident (hC-MSCs) and non-resident (umbilical cord) mesenchymal stem cells (hUC-MSCs) was evaluated. Both cells were sensitive and responsive when exposed to either H2O2 or ascorbic acid at a concentration of 400 µmol/L. Ascorbic acid pre-treated cells remarkably ameliorated the reactive oxygen species level when treated with H2O2. The endogenous antioxidative enzyme gene (Sod1, Sod2, TRXR1 and Gpx1) expressions were escalated in both MSCs in response to reactive oxygen species elevation. In contrast, ascorbic acid pre-treated hUC-MSCs attenuated considerable anti-oxidative gene (TRXR1 and Gpx1) expressions, but not the hC-MSCs. Similarly, the cardiogenic gene (Nkx 2.5, Gata4, Mlc2a and β-MHC) and ion-channel gene ( IKDR, IKCa, Ito and INa.TTX) expressions were significantly increased in both MSCs on the oxidative state. On the contrary, reduced environment could not alter the ion-channel gene expression and negatively regulated the cardiogenic gene expressions except for troponin-1 in both cells. In conclusion, redox imbalance potently alters the cardiac-resident and non-resident MSCs stemness, cardiogenic, and ion-channel gene expressions. In comparison with cardiac-resident MSC, non-resident umbilical cord-MSC has great potential to tolerate the redox imbalance and positively respond to cardiac regeneration. Impact statement Human mesenchymal stem cells (h-MSCs) are highly promising candidates for tissue repair in cardiovascular diseases. However, the retention of cells in the infarcted area has been a major challenge due to its poor viability and/or low survival rate after transplantation. The regenerative potential of mesenchymal stem cells (MSCs) repudiate and enter into premature senescence via oxidative stress. Thus, various strategies have been attempted to improve the MSC survival in 'toxic' conditions. Similarly, we investigated the response of cardiac resident MSC (hC-MSCs) and non-resident MSCs against the oxidative stress induced by H2O2. Supplementation of ascorbic acid (AA) into MSCs culture profoundly rescued the stem cells from oxidative stress induced by H2O2. Our data showed that the pre-treatment of AA is able to inhibit the cell death and thus preserving the viability and differentiation potential of MSCs.
    MeSH terms: Ascorbic Acid/pharmacology; Cell Differentiation/drug effects*; Cell Differentiation/physiology; Fluorescent Antibody Technique; Humans; Hydrogen Peroxide/pharmacology; Ion Channels/metabolism*; Myocardium/metabolism; Blotting, Western; Gene Expression/physiology; Oxidative Stress/drug effects*; Oxidative Stress/physiology; Reverse Transcriptase Polymerase Chain Reaction; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells/drug effects; Mesenchymal Stromal Cells/metabolism; Mesenchymal Stromal Cells/physiology*
  6. Soh JY, Chiang WC, Huang CH, Woo CK, Ibrahim I, Heng K, et al.
    World Allergy Organ J, 2017;10(1):3.
    PMID: 28232856 DOI: 10.1186/s40413-016-0136-x
    BACKGROUND: Galacto-oligosaccharides (GOS) are prebiotics added to commercial milk formula of infants and mothers. In recent years, cases of allergy related to GOS in atopic children have been reported in the South East Asian region.

    CASE PRESENTATIONS: We describe a series of pregnant (n = 4) and lactating mothers (n = 2) who developed anaphylactic reactions after consumption of maternal milk formula containing GOS. All six subjects had pre-existing atopy and a positive skin prick test to GOS and 5/5 of the subjects who were tested had positive basophil activation tests to GOS. All of the mothers and their babies had normal neonatal outcomes after the reactions.

    CONCLUSIONS: The supplementation of GOS into milk and beverages in the Asian region should take into account the rare chance of allergenicity of GOS in the atopic population.

  7. Chai HH, Ho WK, Graham N, May S, Massawe F, Mayes S
    Genes (Basel), 2017 Feb 22;8(2).
    PMID: 28241413 DOI: 10.3390/genes8020084
    Bambara groundnut (Vigna subterranea (L.) Verdc.) is an underutilised legume crop, which has long been recognised as a protein-rich and drought-tolerant crop, used extensively in Sub-Saharan Africa. The aim of the study was to identify quantitative trait loci (QTL) involved in agronomic and drought-related traits using an expression marker-based genetic map based on major crop resources developed in soybean. The gene expression markers (GEMs) were generated at the (unmasked) probe-pair level after cross-hybridisation of bambara groundnut leaf RNA to the Affymetrix Soybean Genome GeneChip. A total of 753 markers grouped at an LOD (Logarithm of odds) of three, with 527 markers mapped into linkage groups. From this initial map, a spaced expression marker-based genetic map consisting of 13 linkage groups containing 218 GEMs, spanning 982.7 cM (centimorgan) of the bambara groundnut genome, was developed. Of the QTL detected, 46% were detected in both control and drought treatment populations, suggesting that they are the result of intrinsic trait differences between the parental lines used to construct the cross, with 31% detected in only one of the conditions. The present GEM map in bambara groundnut provides one technically feasible route for the translation of information and resources from major and model plant species to underutilised and resource-poor crops.
    MeSH terms: Genetic Markers; Hybridization, Genetic; Fabaceae; Genetic Linkage; RNA; Soybeans; Africa South of the Sahara; Crops, Agricultural; Quantitative Trait Loci; Droughts; Vigna
  8. Sangok FE, Maie N, Melling L, Watanabe A
    Sci Total Environ, 2017 Jun 01;587-588:381-388.
    PMID: 28242223 DOI: 10.1016/j.scitotenv.2017.02.165
    To understand the variations in the decomposability of tropical peat soil following deforestation for an oil palm plantation, a field incubation experiment was conducted in Sarawak, Malaysia. Peat soils collected from three types of primary forest, namely Mixed Peat Swamp (MPS; Gonystylus-Dactylocladus-Neoscrotechinia association), Alan Batu (ABt; Shorea albida-Gonstylus-Strenonurus association), and Alan Bunga (ABg; Shorea albida association), were packed in polyvinyl chloride pipes and installed in an oil palm plantation. Carbon dioxide (CO2) and methane (CH4) fluxes from soil were monthly measured for 3years. Environmental variables including soil temperature, soil moisture content, and groundwater table were also monitored. The pH, loss on ignition, and total carbon (C) content were similar among the three soils, while total N content was larger in the MPS than in the ABg soils. Based on13C nuclear magnetic resonance (NMR) spectroscopy, C composition of the MPS and ABg soils was characterized by the largest proportion of C present as alkyl C and O-alkyl C, respectively. The C composition of the ABt soil was intermediate between the MPS and ABg soils. The CO2fluxes from the three soils ranged from 78 to 625mgCm-2h-1with a negative correlation to groundwater level. The CH4fluxes ranged from -67 to 653μgCm-2h-1. Both total CO2and CH4fluxes were larger in the order ABg>ABt>MPS (P<0.05). Annual rate of peat decomposition as was estimated from cumulative C loss differed up to 2 times, and the rate constant in exponential decay model was 0.033y-1for the MPS soil and 0.066y-1for the ABg soil. The field incubation results of the three forest peat soils seem to reflect the difference in the labile organic matter content, represented by polysaccharides.
    MeSH terms: Carbon; Carbon Dioxide; Conservation of Natural Resources; Malaysia; Methane; Magnetic Resonance Spectroscopy; Polysaccharides; Polyvinyl Chloride; Soil; Temperature; Wetlands; Dipterocarpaceae; Gene-Environment Interaction; Groundwater; Forests
  9. Permala J, Tarning J, Nosten F, White NJ, Karlsson MO, Bergstrand M
    PMID: 28242661 DOI: 10.1128/AAC.02491-16
    Intermittent preventive treatment (IPT) is used to reduce malaria morbidity and mortality, especially in vulnerable groups such as children and pregnant women. IPT with the fixed dose combination of piperaquine (PQ) and dihydroartemisinin (DHA) is being evaluated as a potential mass treatment to control and eliminate artemisinin-resistant falciparum malaria. This study explored alternative DHA-PQ adult dosing regimens compared to the monthly adult dosing regimen currently being studied in clinical trials. A time-to-event model describing the concentration-effect relationship of preventive DHA-PQ administration was used to explore the potential clinical efficacy of once-weekly adult dosing regimens. Loading dose strategies were evaluated and the advantage of weekly dosing regimen was tested against different degrees of adherence. Assuming perfect adherence, three tablets weekly dosing regimen scenarios maintained malaria incidence of 0.2 to 0.3% per year compared to 2.1 to 2.6% for all monthly dosing regimen scenarios and 52% for the placebo. The three tablets weekly dosing regimen was also more forgiving (i.e., less sensitive to poor adherence), resulting in a predicted ∼4% malaria incidence per year compared to ∼8% for dosing regimen of two tablets weekly and ∼10% for monthly regimens (assuming 60% adherence and 35% interindividual variability). These results suggest that weekly dosing of DHA-PQ for malaria chemoprevention would improve treatment outcomes compared to monthly administration by lowering the incidence of malaria infections, reducing safety concerns about high PQ peak plasma concentrations and being more forgiving. In addition, weekly dosing is expected to reduce the selection pressure for PQ resistance.
    MeSH terms: Antimalarials/administration & dosage; Antimalarials/pharmacokinetics; Antimalarials/therapeutic use*; Computer Simulation; Drug Administration Schedule; Drug Therapy, Combination; Humans; Quinolines/administration & dosage; Quinolines/pharmacokinetics*; Quinolines/therapeutic use*; Malaria, Falciparum/drug therapy; Malaria, Falciparum/prevention & control*; Treatment Outcome; Chemoprevention/methods; Artemisinins/administration & dosage; Artemisinins/pharmacokinetics*; Artemisinins/therapeutic use*
  10. Jafarzadeh S, Alias AK, Ariffin F, Mahmud S, Najafi A, Ahmad M
    J Food Sci Technol, 2017 Jan;54(1):105-113.
    PMID: 28242909 DOI: 10.1007/s13197-016-2441-3
    This study aimed to provide novel biopolymer-based antimicrobial films as food packaging that may assist in reducing environmental pollution caused by the accumulation of synthetic food packaging. The blend of ZnO nanorods (ZnO-nr) and nanokaolin in different ratios (1:4, 2:3, 3:2 and 4:1) was incorporated into semolina, and nanocomposite films were prepared using solvent casting. The resulting films were characterized through field-emission scanning electron microscopy and X-ray diffraction. The mechanical, optical, physical, and antimicrobial properties of the films were also analyzed. The water vapor permeability of the films decreased with increasing ZnO-nr percentage, but their tensile strength and modulus of elasticity increased with increasing nanokaolin percentage. The UV transmittance of the semolina films were greatly influenced by an increase in the amount of ZnO-nr. The addition of ZnO-nr: nanokaolin at all ratios (except 1:4) into semolina reduced UV transmission to almost 0%. Furthermore, the ZnO-nr/nanokaolin/semolina films exhibited a strong antimicrobial activity against Staphylococcus aureus. These properties suggest that the combination of ZnO-nr and nanokaolin are potential fillers in semolina-based films to be used as active packaging for food and pharmaceuticals.
  11. Mohd Nor N'N, Abbasiliasi S, Marikkar MN, Ariff A, Amid M, Lamasudin DU, et al.
    J Food Sci Technol, 2017 Jan;54(1):164-173.
    PMID: 28242914 DOI: 10.1007/s13197-016-2448-9
    This paper reports on the extraction, partial characterization and the potential application of crude polysaccharides from defatted coconut residue as a prebiotic. The coconut residue was defatted and extracted to obtain the crude polysaccharides and its physicochemical properties were determined. The crude polysaccharides were assessed for monosaccharide composition, total carbohydrate content, reducing sugar concentration and protein content determination. The functional group and structural elucidation of crude polysaccharides was also done using Fourier transform infrared spectra analysis. The product was then subjected to artificial human gastric juice treatment to determine digestibility. Finally, an in vitro proliferation and acid production by two probiotic bacteria namely Lactobacillus casei Shirota and Lactobacillus bulgaricus were included in this study. It was found that the defatted coconut residue contained ash (0.54%), moisture (55.42%), protein (1.69%), crude fat (17.26%) and carbohydrate (25.73%). The percentage of crude polysaccharides extracted was 0.73 ± 0.04. The two fractions of monosaccharides obtained were glucose and fructose. Total carbohydrate content of DCR was 13.35% (w/v). The quantitative value of the reducing sugars obtained was 20.71%. Protein content in the crude polysaccharides was 0.009% and the peaks which indicated the presence of protein were observed at around 1640 cm(-1) (amide I) and 1530 cm(-1) (amide II). DCR crude polysaccharides were highly resistant (88%) to hydrolysis when subjected to artificial human gastric juice. The product was found to markedly stimulate two tested probiotics to proliferate and produce organic acids. All the above findings are supportive of the fact that polysaccharides extracted from DCR, an industrial waste, have a vast potential to be exploited as novel prebiotics.
    MeSH terms: Cocos; Fourier Analysis; Fructose; Gastric Juice; Glucose; Humans; Hydrolysis; Industrial Waste; Lactobacillus casei; Monosaccharides; Polysaccharides; Spectroscopy, Fourier Transform Infrared; Probiotics; Lactobacillus delbrueckii; Prebiotics
  12. Siti Rashima R, Maizura M, Kang WM, Fazilah A, Tan LX
    J Food Sci Technol, 2017 Jan;54(1):228-235.
    PMID: 28242920 DOI: 10.1007/s13197-016-2454-y
    The effects of sodium chloride (NaCl) (3.5%) solution and polysaccharides, such as carboxymethyl cellulose (CMC) (0.1, 0.3 and 0.5%) and gum arabic (5, 10 and 15%), on the physicochemical properties, antioxidant capacity and sensory characteristics of bitter gourd juice were investigated. An increase in the concentration of CMC and gum arabic significantly was observed to increase the lightness (L value) and the viscosity (mPas) of bitter gourd juice at all levels. Increased concentrations of gum arabic significantly increased the total soluble solids. The bitter gourd fruit treated with NaCl solution produced the highest lightness (L value) and scavenging activity of free radical 2,2-diphenyl-1-picrylhydrazyl of bitter gourd juice. Increased concentration of gum arabic up to 15% significantly increased the total phenolic content. The addition of 5% gum arabic effectively reduced the bitterness of the bitter gourd juice. Viscosity of the juice resulted in negative correlation for bitterness.
    MeSH terms: Antioxidants; Biphenyl Compounds; Carboxymethylcellulose Sodium; Free Radicals; Fruit; Gum Arabic; Phenols; Polysaccharides; Sodium Chloride; Viscosity; Momordica charantia
  13. Wong CW, Tan HH
    J Food Sci Technol, 2017 Feb;54(2):564-571.
    PMID: 28242955 DOI: 10.1007/s13197-017-2501-3
    This paper presents the enzymatic liquefaction process for honey jackfruit optimized with Pectinex® Ultra SP-L and Celluclast® 1.5 L individually or in combinations at different concentrations (0-2.5% v/w) and incubation time (0-2.5 h). Treatment with combinations of enzymes showed a greater effect in the reduction of viscosity (83.9-98.8%) as compared to single enzyme treatment (64.8-87.3%). The best parameter for enzymatic liquefaction was obtained with 1.0% (v/w) Pectinex® Ultra SP-L and 0.5% (v/w) Celluclast® 1.5 L for 1.5 h. Spray drying process was carried out using different inlet temperatures (140-180 °C) and maltodextrin concentrations (10-30% w/w). Results indicated that the spray-dried honey jackfruit powder produced at 160 °C with 30% w/w maltodextrin gave the highest product yield (66.90%) with good powder qualities in terms of water activity, solubility, moisture content, hygroscopicity, color and bulk density. The spray-dried honey jackfruit powder could potentially be incorporated into various food products.
    MeSH terms: Color; Desiccation; Honey; Polysaccharides; Powders; Solubility; Temperature; Viscosity; Water; Wettability; Artocarpus; Bays
  14. Wong JG, Lai XJ, Sarafian RY, Wong HS, Smith JB
    Int Med Case Rep J, 2017;10:51-54.
    PMID: 28243154 DOI: 10.2147/IMCRJ.S107648
    We report a case of a Caucasian female who developed active polypoidal choroidal vasculopathy (PCV) at the edge of a stable choroidal nevus and was successfully treated with verteporfin photodynamic therapy. No active polyp was detectable on indocyanine green angiography 2 years after treatment, and good vision was maintained. Indocyanine green angiography is a useful investigation to diagnose PCV and may be underutilized. Unlike treatment of choroidal neovascularization secondary to choroidal nevus, management of PCV secondary to nevus may not require intravitreal anti-vascular endothelial growth factor therapy. Photodynamic monotherapy may be an effective treatment of secondary PCV.
    MeSH terms: Angiography; Choroid; Female; Indocyanine Green; Nevus; Photochemotherapy; Polyps; Porphyrins; Choroidal Neovascularization; Vascular Endothelial Growth Factor A
  15. Baharudin R, Ab Mutalib NS, Othman SN, Sagap I, Rose IM, Mohd Mokhtar N, et al.
    Front Pharmacol, 2017;8:47.
    PMID: 28243201 DOI: 10.3389/fphar.2017.00047
    Resistance to 5-Fluorouracil (5-FU) is a major obstacle to the successful treatment of colorectal cancer (CRC) and posed an increased risk of recurrence. DNA methylation has been suggested as one of the underlying mechanisms for recurrent disease and its contribution to the development of drug resistance remains to be clarified. This study aimed to determine the methylation phenotype in CRC for identification of predictive markers for chemotherapy response. We performed DNA methylation profiling on 43 non-recurrent and five recurrent CRC patients using the Illumina Infinium HumanMethylation450 Beadchip assay. In addition, CRC cells with different genetic backgrounds, response to 5-FU and global methylation levels (HT29 and SW48) were treated with 5-FU and DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-azadC). The singular and combined effects of these two drug classes on cell viability and global methylation profiles were investigated. Our genome-wide methylation study on the clinical specimens showed that recurrent CRCs exhibited higher methylation levels compared to non-recurrent CRCs. We identified 4787 significantly differentially methylated genes (P < 0.05); 3112 genes were hyper- while 1675 genes were hypomethylated in the recurrent group compared to the non-recurrent. Fifty eight and 47 of the significantly hypermethylated and hypomethylated genes have an absolute recurrent/non-recurrent methylation difference of ≥20%. Most of the hypermethylated genes were involved in the MAPK signaling pathway which is a key regulator for apoptosis while the hypomethylated genes were involved in the PI3K-AKT signaling pathway and proliferation process. We also demonstrate that 5-azadC treatment enhanced response to 5-FU which resulted in significant growth inhibition compared to 5-FU alone in hypermethylated cell lines SW48. In conclusion, we found the evidence of five potentially biologically important genes in recurrent CRCs that could possibly serve as a new potential therapeutic targets for patients with chemoresistance. We postulate that aberrant methylation of CCNEI, CCNDBP1, PON3, DDX43, and CHL1 in CRC might be associated with the recurrence of CRC and 5-azadC-mediated restoration of 5-FU sensitivity is mediated at least in part by MAPK signaling pathway.
    MeSH terms: Genetic Background; Cell Line; Cell Survival; Colonic Neoplasms; Fluorouracil; Humans; Neoplasm Recurrence, Local; Phenotype; Colorectal Neoplasms; Signal Transduction; Apoptosis; Drug Resistance, Neoplasm; DNA Methylation; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt
  16. Paul S, Ali MY, Rumpa NE, Tanvir EM, Hossen MS, Saha M, et al.
    PMID: 28243309 DOI: 10.1155/2017/4686104
    This study was undertaken to investigate the toxicological profile of a methanolic extract of Garcinia pedunculata fruit in rats by conducting hematological, biochemical, and histopathological examinations. Long Evans rats were divided into four groups, each with 6 animals, and were treated with three oral doses (250, 500, and 1000 mg/kg) once daily for 21 days. The extract did not cause significant changes in body and relative organ weight, percent water content, or hematological parameters at any administered doses. However, a significant dose-dependent positive effect in serum lipid profile and all atherogenic indices including the cardiac risk ratio, Castelli's risk index-2, and the atherogenic coefficient were observed. Significant increases in the levels of iron and decreases in serum alkaline phosphatase, alanine transaminase, and lactate dehydrogenase activities and the levels of serum glucose were noted when the extract was administered at the highest dose (1000 mg/kg). Histopathological examination of the target tissues further confirmed that the extract was safe and had no observed toxicological features. Our study indicates that G. pedunculata fruit is nontoxic, has the potential to be effective against atherosclerosis, and may be used as a hepatoprotectant. The fruit extract is also beneficial to those with iron deficiency and hyperglycemia.
    MeSH terms: Alanine Transaminase; Methanol; Alkaline Phosphatase; Animals; Thoracica; Fruit; Hematologic Tests; Iron; Organ Size; Risk; Water; Odds Ratio; Anemia, Iron-Deficiency; Rats, Long-Evans; Garcinia; Atherosclerosis; Rats
  17. Khor SC, Wan Ngah WZ, Mohd Yusof YA, Abdul Karim N, Makpol S
    Oxid Med Cell Longev, 2017;2017:3868305.
    PMID: 28243354 DOI: 10.1155/2017/3868305
    During aging, oxidative stress affects the normal function of satellite cells, with consequent regeneration defects that lead to sarcopenia. This study aimed to evaluate tocotrienol-rich fraction (TRF) modulation in reestablishing the oxidative status of myoblasts during replicative senescence and to compare the effects of TRF with other antioxidants (α-tocopherol (ATF) and N-acetyl-cysteine (NAC)). Primary human myoblasts were cultured to young, presenescent, and senescent phases. The cells were treated with antioxidants for 24 h, followed by the assessment of free radical generation, lipid peroxidation, antioxidant enzyme mRNA expression and activities, and the ratio of reduced to oxidized glutathione. Our data showed that replicative senescence increased reactive oxygen species (ROS) generation and lipid peroxidation in myoblasts. Treatment with TRF significantly diminished ROS production and decreased lipid peroxidation in senescent myoblasts. Moreover, the gene expression of superoxide dismutase (SOD2), catalase (CAT), and glutathione peroxidase (GPX1) was modulated by TRF treatment, with increased activity of superoxide dismutase and catalase and reduced glutathione peroxidase in senescent myoblasts. In comparison to ATF and NAC, TRF was more efficient in heightening the antioxidant capacity and reducing free radical insults. These results suggested that TRF is able to ameliorate antioxidant defense mechanisms and improves replicative senescence-associated oxidative stress in myoblasts.
    MeSH terms: Antioxidants/pharmacology*; Cell Survival/drug effects*; Cells, Cultured; Free Radicals/metabolism; Glutathione/metabolism; Humans; Lipid Peroxidation/drug effects*; Cell Aging/drug effects*; Oxidative Stress/drug effects*; Tocotrienols/pharmacology*; Myoblasts/drug effects*; Myoblasts/metabolism; Myoblasts/pathology
  18. Norhayati MN, Masseni AA, Azlina I
    PeerJ, 2017;5:e2983.
    PMID: 28243527 DOI: 10.7717/peerj.2983
    BACKGROUND: The outcomes of the physician-patient discussion intervene in the satisfaction of cardiovascular disease risk patients. Adherence to treatment, provision of continuous care, clinical management of the illness and patients' adjustment are influenced by satisfaction with physician-patient interaction. This study aims to determine the patient satisfaction with doctor-patient interaction and over six months after following prevention counselling, its associations with modifiable cardiovascular risk factors amongst moderately-high risk patients in a primary healthcare clinic in Kelantan, Malaysia.
    METHODS: A prospective survey was conducted amongst patients with moderately-high cardiovascular risk. A total of 104 moderately-high risk patients were recruited and underwent structured prevention counselling based on the World Health Organization guideline, and their satisfaction with the doctor-patient interaction was assessed using 'Skala Kepuasan Interaksi Perubatan-11,' the Malay version of the Medical Interview Satisfaction Scale-21. Systolic blood pressure, total cholesterol and high-density lipoprotein cholesterol were measured at baseline and at a follow-up visit at six months. Descriptive analysis, paired t test and linear regression analyses were performed.
    RESULTS: A total of 102 patients responded, giving a response rate of 98.1%. At baseline, 76.5% of the respondents were satisfied with the relation with their doctor, with the favourable domain of distress relief (85.3%) and rapport/confidence (91.2%). The unfavourable domain was interaction outcome, with satisfaction in only 67.6% of the respondents. Between the two visits, changes had occurred in total cholesterol (P = 0.022) and in systolic blood pressure (P 
    MeSH terms: Ambulatory Care Facilities; Cardiovascular Diseases; Humans; Malaysia; Risk Factors*; Cohort Studies; Patient Satisfaction*
  19. Wong HT, Chee KH, Chong AW
    Eur Arch Otorhinolaryngol, 2017 Jun;274(6):2601-2606.
    PMID: 28243782 DOI: 10.1007/s00405-017-4491-1
    Obstructive sleep apnea (OSA) is a growing health hazard in the United States and worldwide. OSA is now recognized as a disorder with systemic manifestations and its association with obesity and adverse cardiovascular consequences. There is increasing evidence that OSA may be associated with systemic hypertension and an increased incidence of stroke, heart failure, myocardial infarction, and arrhythmias. Less information is available about the association between OSA and pulmonary hypertension (PH). We therefore conduct this study to look at the prevalence of the pulmonary hypertension in obstructive sleep apnea patient and to identify risk factors leading to pulmonary hypertension among OSA patient. We studied and analyzed all OSA patient confirmed by polysomnograph in the year 2015. Twenty-five patients with OSA were included in this study with prevalence of pulmonary hypertension of 16%. Univariate analysis of various factors revealed a statistically significant association between having the lowest SpO2 of <70% and pulmonary hypertension (p = 0.016). There were no statistically significant associations between age, gender, smoking status, hypertension, body mass index (BMI), or apnea-hypopnea index (AHI) with occurrence of pulmonary hypertension. AHI is not a good predictor for pulmonary hypertension. The real value of using AHI to predict the health risk of OSA is doubtful. We recommend routine echocardiogram among OSA patient. The objective information in the echocardiogram provides evidence for counseling of patient with disease of OSA and hence hopefully can improve compliance of patient to treatment especially usage of CPAP.
    MeSH terms: Arrhythmias, Cardiac; Counseling; Heart Failure; Humans; Hypertension; Hypertension, Pulmonary; Myocardial Infarction; Obesity; Risk Factors; Smoking; United States; Body Mass Index; Incidence; Prevalence; Polysomnography; Sleep Apnea, Obstructive; Stroke
  20. Juliana N, Shahar S, Sahar MA, Ghazali AR, Manaf ZA, Noah RM
    Asia Pac J Clin Nutr, 2017 Mar;26(2):278-286.
    PMID: 28244706 DOI: 10.6133/apjcn.122015.05
    BACKGROUND AND OBJECTIVES: Nutrition and physical activity interventions is beneficial in reversing obesity. However far too little attention has been paid to the effect of these interventions on breast tissues. Thus, the aim of this study was to explore the effect of a home-based dietary and physical activity intervention (the Her Shape Program) on metabolic parameters, blood biomarkers and adiposity at the breast.

    METHODS AND STUDY DESIGN: A randomized controlled study was conducted on obese women with high breast adiposity (<0.1 Sm-1), aged 40-60 years in Klang Valley, Malaysia. Subjects were assigned to intervention (n=16) and control group (n=15). Intervention group received a home based health education package with close monitoring weekly, personal diet consultation and physical training in group. Assessment was ascertained at three time points; baseline, weeks 8 and 16. Outcome measures were the energy intake, physical activity, body composition, blood tests, blood biomarkers and electrical impedance tomography (EIT) quantitative values. Analyses were done using 2-way repeated measures ANOVA.

    RESULTS AND CONCLUSIONS: All subjects completed the program without any drop-out. The HSI group had 100% compliance towards the intervention program; their energy intake was reduced for approximately 35% and their activity score was increased for approximately 11%. A significant interaction effect was found in body weight, body mass index (BMI), total cholesterol/HDL, vitamin C intake and matrix metallopeptidase 9 (MMP-9) (p<0.05). Interestingly, their EIT extremum values were also significantly increased indicating a reduction of breast adiposity. The intervention program was successful in improving body composition, physical activities, MMP9 and breast adipose tissue composition.

    MeSH terms: Adipose Tissue; Analysis of Variance; Ascorbic Acid; Attention; Body Composition; Body Weight; Energy Intake; Cholesterol; Female; Health Education; Hematologic Tests; Humans; Malaysia; Obesity; Referral and Consultation; Tomography; Biomarkers; Exercise; Body Mass Index; Outcome Assessment (Health Care); Electric Impedance; Control Groups; Metalloproteases; Adiposity
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