Browse publications by year: 2017

  1. Chong LS, Chin YS, Gan WY, Nasir MT
    Asia Pac J Clin Nutr, 2017 Mar;26(2):326-333.
    PMID: 28244713 DOI: 10.6133/apjcn.012016.10
    BACKGROUND AND OBJECTIVES: To determine the associations between socio-demographic characteristics and pubertal status with disordered eating among primary school children.

    METHODS AND STUDY DESIGN: Using a stratified multi-stage sampling, a total of 816 children (282 boys and 534 girls) aged 10 to 11 years from 12 selected primary schools in the state of Selangor, participated in this study. Data were collected on socio-demographic characteristics, pubertal status and disordered eating behaviors. The Pubertal Development Scale and the Children's Eating Attitudes Test (ChEAT) were used to assess pubertal status and disordered eating, respectively. Logistic regression analysis was conducted to determine the risk factors of disordered eating.

    RESULTS: The prevalence of disordered eating was 30.8% (32.8% in boys and 29.7% in girls). However, the sex difference in the prevalence was not statistically significant. Age, ethnicity and pubertal status were significantly associated with disordered eating in univariate logistic regression analysis. Multivariate logistic regression analysis showed that among boys, being either in an advanced or post-pubertal stage (adjusted OR=8.64) and older age group (adjusted OR=2.03) were risk factors of disordered eating. However, among girls, being a Malay (adjusted OR=3.79) or Indian (adjusted OR=5.04) in an advanced or post-pubertal stage (adjusted OR=2.34) and older age group (adjusted OR=1.53) were risk factors of disordered eating.

    CONCLUSION: This study found one in three children had disordered eating. Since ethnicity and pubertal status were identified as risk factors, ethnicity-specific intervention programs on the prevention of disordered eating among children should take into consideration their pubertal status.

    MeSH terms: Feeding and Eating Disorders; Attitude; Child; Eating; Ethnic Groups; Feeding Behavior; Female; Humans; Malaysia; Male; Risk Factors; Sex Characteristics; Sexual Maturation; Prevalence; Logistic Models
  2. Kardia E, Zakaria N, Sarmiza Abdul Halim NS, Widera D, Yahaya BH
    Regen Med, 2017 03;12(2):203-216.
    PMID: 28244823 DOI: 10.2217/rme-2016-0112
    The therapeutic use of mesenchymal stromal cells (MSCs) represents a promising alternative clinical strategy for treating acute and chronic lung disorders. Several preclinical reports demonstrated that MSCs can secrete multiple paracrine factors and that their immunomodulatory properties can support endothelial and epithelial regeneration, modulate the inflammatory cascade and protect lungs from damage. The effects of MSC transplantation into patients suffering from lung diseases should be fully evaluated through careful assessment of safety and associated risks, which is a prerequisite for translation of preclinical research into clinical practice. In this article, we summarize the current status of preclinical research and review initial MSC-based clinical trials for treating lung injuries and lung disorders.
    MeSH terms: Animals; Humans; Lung Diseases/therapy*; Regeneration/physiology*; Mesenchymal Stem Cell Transplantation*; Mesenchymal Stromal Cells/cytology*
  3. Lay KK, Cheong BM, Tong WL, Tan MK, Hung YM
    Nanotechnology, 2017 Apr 21;28(16):164003.
    PMID: 28244882 DOI: 10.1088/1361-6528/aa6385
    A graphene nanoplatelet (GNP) coating is utilized as a functionalized surface in enhancing the evaporation rate of micro-spray cooling for light-emitting diodes (LEDs). In micro-spray cooling, water is atomized into micro-sized droplets to reduce the surface energy and to increase the surface area for evaporation. The GNP coating facilitates the effective filmwise evaporation through the attribute of fast water permeation. The oxygenated functional groups of GNPs provide the driving force that initiates the intercalation of water molecules through the carbon nanostructure. The water molecules slip through the frictionless passages between the hydrophobic carbon walls, resulting an effective filmwise evaporation. The enhancement of evaporation leads to an enormous temperature reduction of 61.3 °C. The performance of the LED is greatly enhanced: a maximum increase in illuminance of 25% and an extension of power rating from 9 W to 12 W can be achieved. With the application of GNP coating, the high-temperature region is eliminated while maintaining the LED surface temperature for optimal operation. This study paves the way for employing the effective hybrid spray-evaporation-nanostructure technique in the development of a compact, low-power-consumption cooling system.
  4. Teoh CO, Middleton BW
    J Palliat Med, 2017 03;20(3):306-307.
    PMID: 27854547 DOI: 10.1089/jpm.2016.0453
  5. Price A, Liew SM, Kirkpatrick J, Price J, Lopreto T, Nelken Y
    J Eval Clin Pract, 2017 Feb;23(1):178-184.
    PMID: 27917564 DOI: 10.1111/jep.12678
    What are the strengths, gaps, expectations, and barriers to research engagement in clinical trials as communicated through social media? Clinical trials test treatments to provide reliable information for safety and effectiveness. Trials are building blocks in which what is learned in earlier research can be used to improve treatments, compare alternatives, and improve quality of life. For 20 years, the percentages of clinical trials volunteers have decreased whereas the costs of running clinical trials have multiplied. Participants enroll in trials to access latest treatments, to help others, and to advance science, but there is growing unrest. The priorities of those running the trials differ from those of the participants, and the roles for public research involvement lack clarity. Changes to bridge these gaps in the research culture are proposed through the use of participatory action research (PAR) in which stakeholders collaborate to improve research methodology, galvanize citizen participation, multiply health knowledge, problem-solve barriers to access, and explore the value of research volunteers as collaborators. PAR enabled the inclusion of citizens as full collaborators. Social media data were gathered for 120 days until saturation was reached. De-identified data were organized into a Strengths Weaknesses, Opportunities and Threats framework and coded into themes for analysis. After the analysis, the authors prioritized potential solutions for improving research engagement. Strengths and opportunities remained constant through trial phases, disease burdens, and interventions. Threats included alienation, litigation, disparity, and shaming. Poor management and barriers to inclusion were identified as weaknesses. Opportunities included improving resource management and information quality. Barriers were minimized when relationships between staff and participants were inclusive, respectful, tolerant, and open to change. Participants' communications ranged from fulfillment through trial involvement to disparities and rights violations. PAR provides a safe space without power imbalances in which researchers and citizen worked as equals rather than as researchers and objects of research.
    MeSH terms: Cooperative Behavior*; Humans; Health Knowledge, Attitudes, Practice; Research Design; Research Personnel; Research Subjects; Community-Based Participatory Research/organization & administration*; Social Media/utilization*
  6. Gong T, Heng BC, Xu J, Zhu S, Yuan C, Lo EC, et al.
    J Biomed Mater Res A, 2017 04;105(4):1083-1093.
    PMID: 28076902 DOI: 10.1002/jbm.a.36003
    Dental stem cells can serve as a potential source of functional endothelial cells for tissue engineering applications, but the endothelial-lineage differentiation efficiency is rather low even with growth factors and mechanical stimuli, which greatly limits their clinical applications. This is partly due to the deficiency of standard two-dimensional (2-D) culture systems, which is unable to recapitulate the three-dimensional (3-D) in vivo milieu that is rich in extracellular matrix. Hence, we extracted decellularized extracellular matrix from human umbilical vein endothelial cells (HUVECs-DECM) to provide a bioactive substratum conducive to the endothelial differentiation of dental stem cells. Compared to cells plated on tissue culture polystyrene (TCP), stem cells from exfoliated deciduous teeth (SHED) cultured on the HUVECs-DECM demonstrated more regular arrangement and elongated morphology. HUVECs-DECM significantly enhanced the rapid adhesion and proliferation rates of SHED, as demonstrated by WST-8 assay and immunocytochemistry indicating higher expression levels of vinculin by newly adherent SHED on HUVECs-DECM versus TCP. In addition, there was twofold to fivefold higher mRNA expression levels of endothelial-specific markers CD31 and VEGFR-2 in SHED after seven days of culture on DECM versus TCP. Functional testing with in vitro matrigel angiogenesis assay identified more capillary-like structure formation with significantly higher tubule length in SHED induced by DECM versus TCP. Hence, the results of this study provide a better understanding of the unique characteristics of cell-specific ECM and demonstrated the potential use of HUVECs-DECM as a culture substratum conducive for stimulating the endothelial differentiation of SHED for therapeutic angiogenic applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1083-1093, 2017.
    MeSH terms: Cell Differentiation*; Extracellular Matrix/chemistry*; Humans
  7. Harumain ZA, Parker HL, Muñoz García A, Austin MJ, McElroy CR, Hunt AJ, et al.
    Environ Sci Technol, 2017 03 07;51(5):2992-3000.
    PMID: 28191957 DOI: 10.1021/acs.est.6b04821
    Although a promising technique, phytoextraction has yet to see significant commercialization. Major limitations include metal uptake rates and subsequent processing costs. However, it has been shown that liquid-culture-grown Arabidopsis can take up and store palladium as nanoparticles. The processed plant biomass has catalytic activity comparable to that of commercially available catalysts, creating a product of higher value than extracted bulk metal. We demonstrate that the minimum level of palladium in Arabidopsis dried tissues for catalytic activity comparable to commercially available 3% palladium-on-carbon catalysts was achieved from dried plant biomass containing between 12 and 18 g·kg-1 Pd. To advance this technology, species suitable for in-the-field application: mustard, miscanthus, and 16 willow species and cultivars, were tested. These species were able to grow, and take up, palladium from both synthetic and mine-sourced tailings. Although levels of palladium accumulation in field-suitable species are below that required for commercially available 3% palladium-on-carbon catalysts, this study both sets the target, and is a step toward, the development of field-suitable species that concentrate catalytically active levels of palladium. Life cycle assessment on the phytomining approaches described here indicates that the use of plants to accumulate palladium for industrial applications has the potential to decrease the overall environmental impacts associated with extracting palladium using present-day mining processes.
    MeSH terms: Catalysis; Mining*; Mustard Plant; Palladium*; Soil Pollutants; Arabidopsis
  8. Williams HF, Vaiyapuri R, Gajjeraman P, Hutchinson G, Gibbins JM, Bicknell AB, et al.
    Toxicon, 2017 Feb 24;130:44-46.
    PMID: 28238804 DOI: 10.1016/j.toxicon.2017.02.025
    Snakebites cause death, disability and economic devastation to their victims, people who live almost exclusively in rural areas. Annually an estimated two million venomous bites cause as many as 100,000 deaths worldwide as well as hundreds of thousands of deformities and amputations. Recent studies suggest that India has the highest incidence of snakebite and associated deaths worldwide. In this study, we interviewed 25 hospital-based clinicians who regularly treat snakebites in Tamil Nadu, India, in order to gauge their opinions and views on the diagnostic tools and treatment methods available at that time, the difficulties encountered in treating snakebites and improvements to snakebite management protocols they deem necessary. Clinicians identified the improvement of community education, training of medical personnel, development of standard treatment protocols and improved medication as priorities for the immediate future.
    MeSH terms: Amputation; Antivenins; Attitude; Clinical Protocols; Health Education; Health Personnel; India; Snake Bites; Incidence
  9. Ali NM, Yeap SK, Abu N, Lim KL, Ky H, Pauzi AZM, et al.
    Cancer Cell Int, 2017;17:30.
    PMID: 28239299 DOI: 10.1186/s12935-017-0400-3
    AIMS: Curcumin is a lead compound of the rhizomes of Curcuma longa and possess a broad range of pharmacological activities. Chemically, curcumin is 1,3-dicarbonyl class of compound, which exhibits keto-enol tautomerism. Despite of its strong biological properties, curcumin has yet been recommended as a therapeutic agent because of its poor bioavailability.

    MAIN METHODS: A curcumin derivative (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1) was synthesized and its cytotoxicity was tested on breast cancer cell MCF-7 and normal cell MCF-10A using MTT assay. Meanwhile, cell cycle regulation and apoptosis on MCF-7 cell were evaluated using flow cytometry. Regulation of cell cycle and apoptosis related genes expression was investigated by quantitative real time polymerase chain reaction (qRT-PCR), western blot and caspases activity analyses. Activation of oxidative stress on MCF-7 were evaluated by measuring ROS and GSH levels.

    KEY FINDINGS: DK1 was found to possess selective cytotoxicity on breast cancer MCF-7 cell than normal MCF-10A cell. Flow cytometry cell cycle and AnnexinV/PI analyses reported that DK1 effectively arrested MCF-7 at G2/M phase and induced apoptosis after 72 h of incubation than curcumin. Upregulation of p53, p21 and downregulation of PLK-1 subsequently promote phosphorylation of CDC2 which were found contributed to the arrest of G2/M phase. Moreover, increased of reactive oxygen species and reduced of antioxidant glutathione level correlate with apoptosis observed with raised of cytochrome c and active caspase 9.

    SIGNIFICANCE: DK1 was found to be more effective in inducing cell cycle arrest and apoptosis against MCF-7 cell with much higher selectivity index of MCF-10A/MCF-7 than curcumin, which might be contributed by the overexpression of p53 protein.

  10. Rosli R, Dali AF, Aziz NA, Ming LC, Manan MM
    Front Pharmacol, 2017;8:30.
    PMID: 28239351 DOI: 10.3389/fphar.2017.00030
    Spontaneous adverse drug reactions (ADRs) reporting is a useful source of drug safety information in infants as only adult patients are routinely tested in clinical trials. This study was aimed to evaluate the spontaneously reported ADRs using WHO Adverse Reaction Terminology and to identify the common drugs associated with ADRs in children under 2 years of age. A retrospective analysis of ADR data for children below 2 years old from 2000 to 2013 was conducted using the data extracted from Malaysia's national pharmacovigilance database, QUEST2 System. From 2000 to 2013, Malaysia's National Pharmaceutical Control Bureau received a total of 11,932 reports for children from various healthcare facilities in Malaysia. 14.0% (n = 1667) of the ADRs reported for those children were related to children under 2 years old. The data retrieved was analyzed in terms of age, gender, source of reporting, type of reporters, suspected medicines and characteristics of ADRs (category, onset, severity, and outcomes). A total of 1312 ADRs reported in 907 ADR reports were analyzed. The most common ADRs reported were skin appendage disorders (60.1%), and the most frequently reported symptoms were rash (n = 215), maculopapular rash (n = 206), urticaria (n = 169), erythematous rash (n = 76), and pruritus (n = 58). In general, drugs from antibacterials for systemic use (58.8%) appeared to be the most common contributors to ADRs in children below 2 years old. Penicillins and other β-Lactam Antibacterials accounted for more than 40% of all drugs implicated in ADRs. The majority of ADRs were subacute reactions that occurred within 24 h of exposure to the drug. A high proportion of ADRs was classified as mild, and most victims had no sequela. Only one fatality was seen. There were 10 cases for each symptom, namely erythema multiforme and Stevens-Johnson Syndrome, observed in this study. A large proportion of ADRs in children under 2 years old were mainly caused by drugs from antibacterial for systemic use, with most of the ADRs manifesting in skin reactions. This study also reveals rare cutaneous ADRs experienced by Malaysian children under the age of 2, which constitutes a crucial cause of harm among children.
    MeSH terms: Adult; Anti-Bacterial Agents; Child; Child, Preschool; Erythema Multiforme; Exanthema; Humans; Infant; Malaysia; Penicillins; Pruritus; Retrospective Studies; Stevens-Johnson Syndrome; Urticaria; Pharmacovigilance
  11. Coccolini F, Montori G, Ceresoli M, Catena F, Ivatury R, Sugrue M, et al.
    World J Emerg Surg, 2017;12:10.
    PMID: 28239409 DOI: 10.1186/s13017-017-0123-8
    BACKGROUND: No definitive data about open abdomen (OA) epidemiology and outcomes exist. The World Society of Emergency Surgery (WSES) and the Panamerican Trauma Society (PTS) promoted the International Register of Open Abdomen (IROA).

    METHODS: A prospective observational cohort study including patients with an OA treatment. Data were recorded on a web platform (Clinical Registers®) through a dedicated website: www.clinicalregisters.org.

    RESULTS: Four hundred two patients enrolled. Adult patients: 369 patients; Mean age: 57.39±18.37; 56% male; Mean BMI: 36±5.6. OA indication: Peritonitis (48.7%), Trauma (20.5%), Vascular Emergencies/Hemorrhage (9.4%), Ischemia (9.1%), Pancreatitis (4.2%),Post-operative abdominal-compartment-syndrome (3.9%), Others (4.2%). The most adopted Temporary-abdominal-closure systems were the commercial negative pressure ones (44.2%). During OA 38% of patients had complications; among them 10.5% had fistula. Definitive closure: 82.8%; Mortality during treatment: 17.2%. Mean duration of OA: 5.39(±4.83) days; Mean number of dressing changes: 0.88(±0.88). After-closure complications: (49.5%) and Mortality: (9%). No significant associations among TACT, indications, mortality, complications and fistula. A linear correlationexists between days of OA and complications (Pearson linear correlation = 0.326 p<0.0001) and with the fistula development (Pearson = 0.146 p= 0.016). Pediatric patients: 33 patients. Mean age: 5.91±(3.68) years; 60% male. Mortality: 3.4%; Complications: 44.8%; Fistula: 3.4%. Mean duration of OA: 3.22(±3.09) days.

    CONCLUSION: Temporary abdominal closure is reliable and safe. The different techniques account for different results according to the different indications. In peritonitis commercial negative pressure temporary closure seems to improve results. In trauma skin-closure and Bogotà-bag seem to improve results.

    TRIAL REGISTRATION: ClinicalTrials.gov NCT02382770.

  12. Zahedi FD, Gendeh BS, Husain S, Kumar R, Kew TY
    Indian J Otolaryngol Head Neck Surg, 2017 Mar;69(1):125-129.
    PMID: 28239593 DOI: 10.1007/s12070-016-0978-0
    Esthesioneuroblastoma is a rare malignant neoplasm of oflactory neuroepithelium and usually located at the olfactory cleft at superior nasal cavity. Ectopic localization of esthesioneuroblastoma is even rarer and usually posed with a diagnostic dilemma and delay in the diagnosis and management, We report a rare case of ectopic esthesioneuroblastoma of the sphenoclivus with the presentation of intermittent unilateral epistaxis, intermittent intractable headache without anosmia. Nasal endoscopy findings showed a pulsatile mass at the anterior face of the sphenoid sinus with extension posteriorly towards the clivus region and occupying the floor of the sphenoid sinus. Endonasal transclival endoscopic excision of tumour was performed which involved otorhinolaryngology surgeon and neurosurgeon with intraoperative navigation imaging and frozen section. The histopathological findings was esthesioneuroblastoma. Due to its rarity and unusual presentation, the diagnosis of ectopic esthesioneuroblastoma is difficult and can be misdiagnosed with the other type of malignancy. Therefore, the histopathological result is important in confirming the type of tumour and can lead to the next step of management.
    MeSH terms: Neurosurgeons; Olfaction Disorders; Cranial Fossa, Posterior; Endoscopy; Epistaxis; Frozen Sections; Nasal Cavity; Nose Neoplasms; Otolaryngology; Smell; Sphenoid Sinus; Esthesioneuroblastoma, Olfactory; Headache Disorders; Surgeons
  13. Polgar G, Zaccara S, Babbucci M, Fonzi F, Antognazza CM, Ishak N, et al.
    J Fish Biol, 2017 May;90(5):1926-1943.
    PMID: 28239874 DOI: 10.1111/jfb.13276
    A study was conducted on the habitat distribution of four sympatric species of Periophthalmus (the silver-lined mudskipper Periophthalmus argentilineatus, the slender mudskipper Periophthalmus gracilis, the kalolo mudskipper Periophthalmus kalolo and the Malacca mudskipper Periophthalmus malaccensis) from northern Sulawesi. Molecular phylogenetic reconstructions based on one mtDNA marker (16S) were used to validate the morphological taxa, identifying five molecular clades. Periophthalmus argentilineatus includes two molecular species, which are named Periophthalmus argentilineatus clades F and K. Multivariate direct gradient analysis show that these species form three distinct ecological guilds, with the two molecular species occurring in different guilds. Periophthalmus clade F is ecologically eurytypic; Periophthalmus clade K and P. kalolo are prevalent in ecosystems isolated by strong oceanic currents and at shorter distances from the sea; P. gracilis plus P. malaccensis are prevalent in ecosystems connected by shallow coastal waters, in vegetated habitats at larger distances from the sea. This indicates for the first time that mudskipper species exhibit a range of adaptations to semiterrestrialism not only within genera, but even within morphospecies, delineating a much more complex adaptive scenario than previously assumed.
    MeSH terms: Acclimatization; Adaptation, Physiological*; Animals; DNA, Mitochondrial/genetics; Indonesia; Oceans and Seas; Perciformes/genetics; Perciformes/physiology*; Phylogeny; Species Specificity; Water Movements; Multivariate Analysis; Ecosystem*; Reproductive Isolation*
  14. Segura AM, Calliari D, Lan BL, Fort H, Widdicombe CE, Harmer R, et al.
    Ecol Lett, 2017 04;20(4):471-476.
    PMID: 28239940 DOI: 10.1111/ele.12749
    Determining statistical patterns irrespective of interacting agents (i.e. macroecology) is useful to explore the mechanisms driving population fluctuations and extinctions in natural food webs. Here, we tested four predictions of a neutral model on the distribution of community fluctuations (CF) and the distributions of persistence times (APT). Novel predictions for the food web were generated by combining (1) body size-density scaling, (2) Taylor's law and (3) low efficiency of trophic transference. Predictions were evaluated on an exceptional data set of plankton with 15 years of weekly samples encompassing c. 250 planktonic species from three trophic levels, sampled in the western English Channel. Highly symmetric non-Gaussian distributions of CF support zero-sum dynamics. Variability in CF decreased while a change from an exponential to a power law distribution of APT from basal to upper trophic positions was detected. Results suggest a predictable but profound effect of trophic position on fluctuations and extinction in natural communities.
    MeSH terms: England; Models, Biological; Oceans and Seas; Plankton/physiology*; Population Dynamics; Food Chain*; Extinction, Biological*
  15. Kirubakaran R, Chee Jia T, Mahamad Aris N
    Asian Pac J Cancer Prev, 2017 01 01;18(1):115-120.
    PMID: 28240018
    Background: Breast cancer is the commonest cancer among women worldwide. About one in nineteen women in
    Malaysia are at risk, compared to one in eight in Europe and the United States. The objectives of this study were: (1) to
    assess patients’ knowledge on risk factors, symptoms and methods of screening of breast cancer; and (2) to determine
    their perceptions towards the disease treatment outcomes. Methods: A cross-sectional survey using a validated selfadministered
    questionnaire was conducted among 119 consecutive surgical female patients admitted from 1st of
    September to 8th of October 2015 in Hospital Sultan Abdul Halim, Kedah. Data were analyzed using General linear
    regression and Spearman’s correlation with Statistical Package for Social Science (SPSS) version 20. Results: Mean (SD)
    age was 40.6 (15.1) years and majority of the patients were Malay (106, 89.1%). Mean scores for general knowledge,
    risk factors and symptoms of breast cancer were 50.2 (24.0%), 43.0 (22.9%) and 64.4 (28.4%) respectively. Mean
    total knowledge score was 52.1(19.7%). 80 (67.2%) and 55 (46.2%) patients were aware of breast self-examination
    and clinical breast examination recommendations, respectively. Generally, patients had positive perceptions towards
    breast cancer treatment outcomes. However, majority (59.7%) considered that it would be a long and painful process.
    Knowledge was significantly better among married women with spouses (p=0.046), those with personal history of
    breast cancer (p=0.022) and with monthly personal income (p=0.001) with the coefficient of determination, R2=0.16.
    Spearman’s correlation test showed a significant positive relationship between monthly personal income and breast
    cancer awareness (r = 0.343, p <0.001). Conclusion: Awareness on breast cancer among our patients was average. Thus,
    there is a need for more awareness programs to educate women about breast cancer and promote its early detection.
    MeSH terms: Cross-Sectional Studies; Europe; Female; Humans; Malaysia; Marriage; Mass Screening; Surveys and Questionnaires; Risk Factors; United States; Breast Self-Examination; Treatment Outcome; Spouses; Early Detection of Cancer
  16. Hussain Z, Katas H, Yan SL, Jamaludin D
    Curr Drug Deliv, 2017;14(7):1016-1027.
    PMID: 28240178 DOI: 10.2174/1567201814666170224142446
    BACKGROUND: Despite having excellent anticancer efficacy and ability to knockdown gene expression, the therapeutic feasibility of Dicer-substrate small interfering RNA (DsiRNA) is limited due to its poor cellular uptake, chemical instability and rapid degradation in biological environments.

    OBJECTIVE: The present study was aimed to circumvent the pharmaceutical issues related to DsiRNA delivery to colon for the treatment of colorectal cancer.

    METHOD: In this study, we have prepared water-soluble chitosan (WSC)-DsiRNA complex nanoparticles (NPs) by a simple complexation method and subsequently coated with pectin to protect DsiRNA from gastric milieu.

    RESULTS: The mean particle size and zeta potential of the prepared WSC-DsiRNA complexes were varied from 145 ± 4 nm to 867 ± 81 nm and +38 ± 4 to -6.2 ± 2.7 mV respectively, when the concentrations of WSC (0.1%, 0.2% and 0.3% w/v) and pectin (0.1%, 0.2% and 0.25% w/v) were varied. The electron microscopic analysis revealed that morphology of WSC-DsiRNA complexes was varied from smooth spherical to irregular spherical. Cytotoxicity analysis demonstrated that viability of colorectal adenocarcinoma cell was decreased when the dose of WSC-DsiRNA was increased over the incubation from 24 to 48 h. A significantly low cumulative release of DsiRNA in simulated gastric (<15%) and intestinal fluids (<30%) and a marked increase in its release (>90%) in simulated colonic fluid (SCF) evidenced the feasibility and suitability of WSC-DsiRNA complexes for the colonic delivery.

    CONCLUSION: These findings clearly indicated promising potential of WSC-DsiRNA complexes as a carrier to delivery DsiRNA to colon for the treatment of colorectal cancer.

    MeSH terms: Cell Survival/drug effects; Colon/metabolism*; Gastric Juice/chemistry; Humans; Intestinal Secretions/chemistry; Pectins/administration & dosage*; Pectins/chemistry; Stomach/metabolism; Caco-2 Cells; RNA, Small Interfering/administration & dosage*; RNA, Small Interfering/chemistry; Chitosan/administration & dosage*; Chitosan/chemistry; Nanoparticles/administration & dosage*; Nanoparticles/chemistry; Drug Liberation; Polyelectrolytes/administration & dosage*; Polyelectrolytes/chemistry
  17. Tan CH, Tan KY, Yap MK, Tan NH
    Sci Rep, 2017 02 27;7:43237.
    PMID: 28240232 DOI: 10.1038/srep43237
    Tropidolaemus wagleri (temple pit viper) is a medically important snake in Southeast Asia. It displays distinct sexual dimorphism and prey specificity, however its venomics and inter-sex venom variation have not been thoroughly investigated. Applying reverse-phase HPLC, we demonstrated that the venom profiles were not significantly affected by sex and geographical locality (Peninsular Malaya, insular Penang, insular Sumatra) of the snakes. Essentially, venoms of both sexes share comparable intravenous median lethal dose (LD50) (0.56-0.63 μg/g) and cause neurotoxic envenomation in mice. LCMS/MS identified six waglerin forms as the predominant lethal principles, comprising 38.2% of total venom proteins. Fourteen other toxin-protein families identified include phospholipase A2, serine proteinase, snaclec and metalloproteinase. In mice, HPLC fractions containing these proteins showed insignificant contribution to the overall venom lethality. Besides, the unique elution pattern of approximately 34.5% of non-lethal, low molecular mass proteins (3-5 kDa) on HPLC could be potential biomarker for this primitive crotalid species. Together, the study unveiled the venom proteome of T. wagleri that is atypical among many pit vipers as it comprises abundant neurotoxic peptides (waglerins) but little hemotoxic proteinases. The findings also revealed that the venom is relatively well conserved intraspecifically despite the drastic morphological differences between sexes.
    MeSH terms: Animals; Chromatography, High Pressure Liquid; Crotalid Venoms/genetics; Crotalid Venoms/isolation & purification; Crotalid Venoms/metabolism; Crotalid Venoms/toxicity*; Female; Lethal Dose 50; Malaysia; Male; Molecular Weight; Sex Factors; Snake Bites/mortality; Snake Bites/pathology; Gene Expression; Conserved Sequence; Proteome/genetics*; Proteome/metabolism; Metalloproteases/genetics; Metalloproteases/isolation & purification; Metalloproteases/metabolism; Metalloproteases/toxicity*; Phospholipases A2/genetics; Phospholipases A2/isolation & purification; Phospholipases A2/metabolism; Phospholipases A2/toxicity*; Chromatography, Reverse-Phase; Serine Proteases/genetics; Serine Proteases/isolation & purification; Serine Proteases/metabolism; Serine Proteases/toxicity*
  18. Lee HM, Lo KW, Wei W, Tsao SW, Chung GTY, Ibrahim MH, et al.
    J Pathol, 2017 05;242(1):62-72.
    PMID: 28240350 DOI: 10.1002/path.4879
    Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1, and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration. We also show that S1P receptor 3 (S1PR3) mRNA is overexpressed in EBV-positive NPC patient-derived xenografts and a subset of primary NPC tissues, and that knockdown of S1PR3 suppressed the activation of AKT and the S1P-induced migration of NPC cells. Taken together, our data point to a central role for EBV in mediating the oncogenic effects of S1P in NPC and identify S1P signalling as a potential therapeutic target in this disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    MeSH terms: Adult; Aged; Animals; Carcinoma; Cell Movement/drug effects; Cell Movement/physiology; Female; Humans; Lysophospholipids/pharmacology; Lysophospholipids/physiology*; Male; Middle Aged; Nasopharyngeal Neoplasms/genetics; Nasopharyngeal Neoplasms/metabolism; Nasopharyngeal Neoplasms/pathology; Nasopharyngeal Neoplasms/virology*; RNA, Messenger/genetics; Sphingosine/analogs & derivatives*; Sphingosine/pharmacology; Sphingosine/physiology; Signal Transduction/physiology; Up-Regulation; Gene Expression Regulation, Neoplastic/physiology; Epstein-Barr Virus Infections/complications*; Epstein-Barr Virus Infections/genetics; Epstein-Barr Virus Infections/metabolism; Epstein-Barr Virus Infections/pathology; Cell Line, Tumor; Receptors, Lysosphingolipid/genetics; Receptors, Lysosphingolipid/metabolism*; Receptors, Lysosphingolipid/physiology; Oncogene Protein v-akt/metabolism*; Gene Knockdown Techniques; Heterografts
  19. Hairol AO, Affirul CA, Azlanudin A, Zamri Z, Razman J, Choi SY
    Clin Ter, 2017 Jan-Feb;168(1):e5-e7.
    PMID: 28240755 DOI: 10.7417/CT.2017.1974
    Radiofrequency ablation (RFA) has evolved to become the treatment of choice for non-resectable recurrent colorectal liver metastasis. It is however, not without complications. Portal vein thrombosis following RFA is rare but can be fatal to the outcome of the patient. Here, we present a case of a 66-year-old man who developed portal vein thrombosis following RFA. CT scan revealed a left portal vein thrombosis. This case report highlights the challenges and multimodal treatment of portal vein thrombosis following Radiofrequency ablation (RFA) in a cirrhotic patient.
    MeSH terms: Aged; Humans; Male; Portal Vein; Tomography, X-Ray Computed; Catheter Ablation/adverse effects*; Venous Thrombosis/therapy*; Mechanical Thrombolysis/methods*
  20. Kwong HC, Chidan Kumar CS, Mah SH, Chia TS, Quah CK, Loh ZH, et al.
    PLoS One, 2017;12(2):e0170117.
    PMID: 28241010 DOI: 10.1371/journal.pone.0170117
    Biphenyl-based compounds are clinically important for the treatments of hypertension and inflammatory, while many more are under development for pharmaceutical uses. In the present study, a series of 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl benzoates, 2(a-q), and 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl pyridinecarboxylate, 2(r-s) were synthesized by reacting 1-([1,1'-biphenyl]-4-yl)-2-bromoethan-1-one with various carboxylic acids using potassium carbonate in dimethylformamide at ambient temperature. Single-crystal X-ray diffraction studies revealed a more closely packed crystal structure can be produced by introduction of biphenyl moiety. Five of the compounds among the reported series exhibited significant anti-tyrosinase activities, in which 2p, 2r and 2s displayed good inhibitions which are comparable to standard inhibitor kojic acid at concentrations of 100 and 250 μg/mL. The inhibitory effects of these active compounds were further confirmed by computational molecular docking studies and the results revealed the primary binding site is active-site entrance instead of inner copper binding site which acted as the secondary binding site.
    MeSH terms: Algorithms; Binding Sites; Biphenyl Compounds/chemical synthesis*; Copper/chemistry; Esters/chemical synthesis*; Pyrones/chemistry; Software; Solvents; Spectrophotometry, Infrared; Temperature; Monophenol Monooxygenase/antagonists & inhibitors*; Monophenol Monooxygenase/chemistry; X-Ray Diffraction; Least-Squares Analysis; Crystallography, X-Ray; Catalytic Domain; Molecular Docking Simulation
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