Browse publications by year: 2016

  1. Brela MZ, Wójcik MJ, Witek ŁJ, Boczar M, Wrona E, Hashim R, et al.
    J Phys Chem B, 2016 04 28;120(16):3854-62.
    PMID: 27045959 DOI: 10.1021/acs.jpcb.6b01601
    In this study, the proton dynamics of hydrogen bonds for two forms of crystalline aspirin was investigated by the Born-Oppenheimer molecular dynamics (BOMD) method. Analysis of the geometrical parameters of hydrogen bonds using BOMD reveals significant differences in hydrogen bonding between the two crystalline forms of aspirin, Form I and Form II. Analysis of the trajectory for Form I shows spontaneous proton transfer in cyclic dimers, which is absent in Form II. Quantization of the O-H stretching modes allows a detailed discussion on the strength of hydrogen-bonding interactions. The focal point of our study is examination of the hydrogen bond characteristics in the crystal structure and clarification of the influence of hydrogen bonding on the presence of the two crystalline forms of aspirin. In the BOMD method, thermal motions were taken into account. Solving the Schrödinger equation for the snapshots of 2D proton potentials, extracted from MD, gives the best agreement with IR spectra. The character of medium-strong hydrogen bonds in Form I of aspirin was compared with that of weaker hydrogen bonds in aspirin Form II. Two proton minima are present in the potential function for the hydrogen bonds in Form I. The band contours, calculated by using one- and two-dimensional O-H quantization, reflect the differences in the hydrogen bond strengths between the two crystalline forms of aspirin, as well as the strong hydrogen bonding in the cyclic dimers of Form I and the medium-strong hydrogen bonding in Form II.
    MeSH terms: Aspirin/chemistry*; Hydrogen Bonding; Protons*; Crystallography, X-Ray; Molecular Dynamics Simulation*
  2. Murphy N, Cross AJ, Abubakar M, Jenab M, Aleksandrova K, Boutron-Ruault MC, et al.
    PLoS Med, 2016 Apr;13(4):e1001988.
    PMID: 27046222 DOI: 10.1371/journal.pmed.1001988
    BACKGROUND: Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.

    METHODS AND FINDINGS: The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01-1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of individuals as being hyperinsulinaemic-based on their C-peptide level-was arbitrary. However, when we used quartiles or the median of C-peptide, instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pattern of associations was observed.

    CONCLUSIONS: These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

    MeSH terms: Obesity, Metabolically Benign/blood; Obesity, Metabolically Benign/diagnosis; Obesity, Metabolically Benign/epidemiology*; C-Peptide/blood; Europe/epidemiology; Female; Health Status; Humans; Hyperinsulinism/blood; Hyperinsulinism/diagnosis; Hyperinsulinism/epidemiology*; Male; Middle Aged; Obesity/blood; Obesity/diagnosis; Obesity/epidemiology*; Phenotype; Prospective Studies; Risk Factors; Colorectal Neoplasms/diagnosis; Colorectal Neoplasms/epidemiology*; Biomarkers/blood; Body Mass Index; Incidence; Multivariate Analysis; Chi-Square Distribution; Logistic Models; Odds Ratio; Case-Control Studies; Risk Assessment; Body Size*; Adiposity; Waist Circumference; Protective Factors
  3. Castro-Aguirre E, Iñiguez-Franco F, Samsudin H, Fang X, Auras R
    Adv Drug Deliv Rev, 2016 12 15;107:333-366.
    PMID: 27046295 DOI: 10.1016/j.addr.2016.03.010
    Global awareness of material sustainability has increased the demand for bio-based polymers like poly(lactic acid) (PLA), which are seen as a desirable alternative to fossil-based polymers because they have less environmental impact. PLA is an aliphatic polyester, primarily produced by industrial polycondensation of lactic acid and/or ring-opening polymerization of lactide. Melt processing is the main technique used for mass production of PLA products for the medical, textile, plasticulture, and packaging industries. To fulfill additional desirable product properties and extend product use, PLA has been blended with other resins or compounded with different fillers such as fibers, and micro- and nanoparticles. This paper presents a review of the current status of PLA mass production, processing techniques and current applications, and also covers the methods to tailor PLA properties, the main PLA degradation reactions, PLA products' end-of-life scenarios and the environmental footprint of this unique polymer.
    MeSH terms: Humans; Polyesters/chemical synthesis*; Polyesters/chemistry*; Lactic Acid/chemistry; Nanoparticles/chemistry
  4. Mohd Nasir N, Lee BK, Yap SS, Thong KL, Yap SL
    Arch Biochem Biophys, 2016 09 01;605:76-85.
    PMID: 27046340 DOI: 10.1016/j.abb.2016.03.033
    Cold plasma is partly ionized non-thermal plasma generated at atmospheric pressure. It has been recognized as an alternative approach in medicine for sterilization of wounds, promotion of wound healing, topical treatment of skin diseases with microbial involvement and treatment of cancer. Cold plasma used in wound therapy inhibits microbes in chronic wound due to its antiseptic effects, while promoting healing by stimulation of cell proliferation and migration of wound relating skin cells. In this study, two types of plasma systems are employed to generate cold plasma: a parallel plate dielectric barrier discharge and a capillary-guided corona discharge. Parameters such as applied voltage, discharge frequency, treatment time and the flow of the carrier gas influence the cold plasma chemistry and therefore change the composition and concentration of plasma species that react with the target sample. Chronic wound that fails to heal often infected by multidrug resistant organisms makes them recalcitrant to healing. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (Pseudomonas aeruginosa) are two common bacteria in infected and clinically non-infected wounds. The efficacies of the cold plasma generated by the two designs on the inactivation of three different isolates of MRSA and four isolates of P. aeruginosa are reported here.
    MeSH terms: Atmospheric Pressure; Bacterial Infections/prevention & control; Cold Temperature; Humans; Methicillin/chemistry; Pseudomonas aeruginosa*; Staphylococcus aureus*; Wound Healing*; Wounds and Injuries/microbiology*; Wounds and Injuries/therapy; Drug Resistance, Bacterial; Cell Proliferation; Plasma Gases*
  5. Ahmad W, Jantan I, Bukhari SN
    Front Pharmacol, 2016;7:59.
    PMID: 27047378 DOI: 10.3389/fphar.2016.00059
    Tinospora crispa (L.) Hook. f. & Thomson (Menispermaceae), found in the rainforests or mixed deciduous forests in Asia and Africa, is used in traditional medicines to treat numerous health conditions. This review summarizes the up-to-date reports about the ethnobotany, phytochemistry, pharmacological activities, toxicology, and clinical trials of the plant. It also provides critical assessment about the present knowledge of the plant which could contribute toward improving its prospect as a source of lead molecules for drug discovery. The plant has been used traditionally in the treatment of jaundice, rheumatism, urinary disorders, fever, malaria, diabetes, internal inflammation, fracture, scabies, hypertension, reducing thirst, increasing appetite, cooling down the body temperature, and maintaining good health. Phytochemical analyses of T. crispa revealed the presence of alkaloids, flavonoids, and flavone glycosides, triterpenes, diterpenes and diterpene glycosides, cis clerodane-type furanoditerpenoids, lactones, sterols, lignans, and nucleosides. Studies showed that the crude extracts and isolated compounds of T. crispa possessed a broad range of pharmacological activities such as anti-inflammatory, antioxidant, immunomodulatory, cytotoxic, antimalarial, cardioprotective, and anti-diabetic activities. Most pharmacological studies were based on crude extracts of the plant and the bioactive compounds responsible for the bioactivities have not been well identified. Further investigations are required to transform the experience-based claims on the use of T. crispa in traditional medicine practices into evidence-based information. The plant extract used in pharmacological and biological studies should be qualitatively and quantitatively analyzed based on its biomarkers. There should be detail in vitro and in vivo studies on the mechanisms of action of the pure bioactive compounds and more elaborate toxicity study to ensure safety of the plant for human use. More clinical trials are encouraged to be carried out if there are sufficient preclinical and safety data.
    MeSH terms: Antimalarials; Antioxidants; Body Temperature; Flavonoids; Humans; Nucleosides; Scabies; Sterols; Triterpenes; Lignans; Ethnobotany; Menispermaceae; Tinospora; Diterpenes, Clerodane; Drug Discovery; Rainforest
  6. Movahed E, Tan GM, Munusamy K, Yeow TC, Tay ST, Wong WF, et al.
    Front Microbiol, 2016;7:360.
    PMID: 27047474 DOI: 10.3389/fmicb.2016.00360
    Cryptococcus neoformans is an opportunistic fungus that causes fatal meningoencephalitis especially in AIDS patients. There is an increasing need for discovery of new anti-cryptococcal drugs due to emergence of resistance cases in recent years. In this study, we aim to elucidate the antifungal effect of triclosan against C. neoformans.
    MeSH terms: Acquired Immunodeficiency Syndrome; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Humans; Meningoencephalitis; Triclosan
  7. Naqvi KF, Patin D, Wheatley MS, Savka MA, Dobson RC, Gan HM, et al.
    Front Microbiol, 2016;7:362.
    PMID: 27047475 DOI: 10.3389/fmicb.2016.00362
    The enzymes involved in synthesizing the bacterial cell wall are attractive targets for the design of antibacterial compounds, since this pathway is essential for bacteria and is absent in animals, particularly humans. A survey of the genome of a bacterium that belongs to the phylum Verrucomicrobia, the closest free-living relative to bacteria from the Chlamydiales phylum, shows genetic evidence that Verrucomicrobium spinosum possesses a novel fusion open reading frame (ORF) annotated by the locus tag (VspiD_010100018130). The ORF, which is predicted to encode the enzymes UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) and UDP-N-acetylmuramate:l-alanine ligase (MurC) that are involved in the cytoplasmic steps of peptidoglycan biosynthesis, was cloned. In vivo analyses using functional complementation showed that the fusion gene was able to complement Escherichia coli murB and murC temperature sensitive mutants. The purified recombinant fusion enzyme (MurB/C Vs ) was shown to be endowed with UDP-N-acetylmuramate:l-alanine ligase activity. In vitro analyses demonstrated that the latter enzyme had a pH optimum of 9.0, a magnesium optimum of 10 mM and a temperature optimum of 44-46°C. Its apparent K m values for ATP, UDP-MurNAc, and l-alanine were 470, 90, and 25 μM, respectively. However, all attempts to demonstrate an in vitro UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) activity were unsuccessful. Lastly, Hidden Markov Model-based similarity search and phylogenetic analysis revealed that this fusion enzyme could only be identified in specific lineages within the Verrucomicrobia phylum.
    MeSH terms: Alanine; Anti-Bacterial Agents; Carbohydrate Dehydrogenases; Cell Wall; Chlamydiales; Escherichia coli; Humans; Magnesium; Peptidoglycan; Phylogeny; Spores, Bacterial; Temperature; Open Reading Frames; Verrucomicrobia
  8. Ma ZF, Majid NA, Yamaoka Y, Lee YY
    Front Microbiol, 2016;7:368.
    PMID: 27047479 DOI: 10.3389/fmicb.2016.00368
    Based on the hygiene hypothesis, a low prevalence of Helicobacter pylori (H. pylori) infection may explain the recent high prevalence of allergic diseases including food allergy. However, there are very few studies that investigate the relationship between H. pylori and food allergy.
    MeSH terms: Food Hypersensitivity; Prevalence; Helicobacter pylori; Helicobacter Infections; Hygiene Hypothesis
  9. Ozyigit II, Filiz E, Vatansever R, Kurtoglu KY, Koc I, Öztürk MX, et al.
    Front Plant Sci, 2016;7:301.
    PMID: 27047498 DOI: 10.3389/fpls.2016.00301
    Among major reactive oxygen species (ROS), hydrogen peroxide (H2O2) exhibits dual roles in plant metabolism. Low levels of H2O2 modulate many biological/physiological processes in plants; whereas, its high level can cause damage to cell structures, having severe consequences. Thus, steady-state level of cellular H2O2 must be tightly regulated. Glutathione peroxidases (GPX) and ascorbate peroxidase (APX) are two major ROS-scavenging enzymes which catalyze the reduction of H2O2 in order to prevent potential H2O2-derived cellular damage. Employing bioinformatics approaches, this study presents a comparative evaluation of both GPX and APX in 18 different plant species, and provides valuable insights into the nature and complex regulation of these enzymes. Herein, (a) potential GPX and APX genes/proteins from 18 different plant species were identified, (b) their exon/intron organization were analyzed, (c) detailed information about their physicochemical properties were provided, (d) conserved motif signatures of GPX and APX were identified, (e) their phylogenetic trees and 3D models were constructed, (f) protein-protein interaction networks were generated, and finally (g) GPX and APX gene expression profiles were analyzed. Study outcomes enlightened GPX and APX as major H2O2-scavenging enzymes at their structural and functional levels, which could be used in future studies in the current direction.
  10. Chan WT, Espinosa M, Yeo CC
    Front Mol Biosci, 2016;3:9.
    PMID: 27047942 DOI: 10.3389/fmolb.2016.00009
    In their initial stages of discovery, prokaryotic toxin-antitoxin (TA) systems were confined to bacterial plasmids where they function to mediate the maintenance and stability of usually low- to medium-copy number plasmids through the post-segregational killing of any plasmid-free daughter cells that developed. Their eventual discovery as nearly ubiquitous and repetitive elements in bacterial chromosomes led to a wealth of knowledge and scientific debate as to their diversity and functionality in the prokaryotic lifestyle. Currently categorized into six different types designated types I-VI, type II TA systems are the best characterized. These generally comprised of two genes encoding a proteic toxin and its corresponding proteic antitoxin, respectively. Under normal growth conditions, the stable toxin is prevented from exerting its lethal effect through tight binding with the less stable antitoxin partner, forming a non-lethal TA protein complex. Besides binding with its cognate toxin, the antitoxin also plays a role in regulating the expression of the type II TA operon by binding to the operator site, thereby repressing transcription from the TA promoter. In most cases, full repression is observed in the presence of the TA complex as binding of the toxin enhances the DNA binding capability of the antitoxin. TA systems have been implicated in a gamut of prokaryotic cellular functions such as being mediators of programmed cell death as well as persistence or dormancy, biofilm formation, as defensive weapons against bacteriophage infections and as virulence factors in pathogenic bacteria. It is thus apparent that these antitoxins, as DNA-binding proteins, play an essential role in modulating the prokaryotic lifestyle whilst at the same time preventing the lethal action of the toxins under normal growth conditions, i.e., keeping the proverbial wolves at bay. In this review, we will cover the diversity and characteristics of various type II TA antitoxins. We shall also look into some interesting deviations from the canonical type II TA systems such as tripartite TA systems where the regulatory role is played by a third party protein and not the antitoxin, and a unique TA system encoding a single protein with both toxin as well as antitoxin domains.
    MeSH terms: Animals; Antitoxins; Bacteria; Bacteriophages; Chromosomes, Bacterial; DNA-Binding Proteins; Life Style; Operon; Plasmids; Toxins, Biological; Apoptosis; Wolves; Virulence Factors; DNA Copy Number Variations
  11. Hanefar SB, Sa'ari CZ, Siraj S
    J Relig Health, 2016 Dec;55(6):2069-85.
    PMID: 27048294 DOI: 10.1007/s10943-016-0226-7
    Spiritual intelligence is an emerging term that is widely discussed and accepted as one of the main components that addresses and solves many life problems. Nonetheless there is no specific study being done to synthesize the spiritual intelligence themes from Western and Islamic philosophical perspectives. This research aimed to identify common spiritual intelligence themes from these two perspectives and elucidated its contents by the view of two well-known Islamic scholars; al-Ghazali and Hasan Langgulung. Seven spiritual intelligence themes were identified through thematic analysis; meaning/purpose of life, consciousness, transcendence, spiritual resources, self-determination, reflection-soul purification and spiritual coping with obstacles. These findings will be the groundwork for centered theory of spiritual intelligence themes that synthesize the Islamic and Western philosophical perspectives. It is hoped that this study will contribute significantly to the development of valid and reliable spiritual intelligence themes beyond the social and cultural boundaries.
    MeSH terms: Humans; Intelligence*; Islam; Religion*; Spirituality
  12. Khairudin MN, Mohd Zahidin AZ, Bastion ML
    BMJ Case Rep, 2016 Apr 05;2016.
    PMID: 27048399 DOI: 10.1136/bcr-2016-214964
    We describe a case of extensive ocular injury secondary to an electronic cigarette (e-cigarette)-related explosion. The explosion was the result of modifications made to a heating element of the e-cigarette device by a non-professional. Extensive ocular injuries that result from an explosion of an e-cigarette device can potentially cause significant and permanent visual impairment.
    MeSH terms: Adolescent; Blast Injuries/pathology*; Eye Injuries/etiology*; Humans; Malaysia; Male; Electronic Cigarettes/adverse effects*; Vaping*
  13. Azmi F, Elliott AG, Marasini N, Ramu S, Ziora Z, Kavanagh AM, et al.
    Bioorg Med Chem, 2016 05 15;24(10):2235-41.
    PMID: 27048775 DOI: 10.1016/j.bmc.2016.03.053
    The spread of drug-resistant bacteria has imparted a sense of urgency in the search for new antibiotics. In an effort to develop a new generation of antibacterial agents, we have designed de novo charged lipopeptides inspired by natural antimicrobial peptides. These short lipopeptides are composed of cationic lysine and hydrophobic lipoamino acids that replicate the amphiphilic properties of natural antimicrobial peptides. The resultant lipopeptides were found to self-assemble into nanoparticles. Some were effective against a variety of Gram-positive bacteria, including strains resistant to methicillin, daptomycin and/or vancomycin. The lipopeptides were not toxic to human kidney and liver cell lines and were highly resistant to tryptic degradation. Transmission electron microscopy analysis of bacteria cells treated with lipopeptide showed membrane-damage and lysis with extrusion of cytosolic contents. With such properties in mind, these lipopeptides have the potential to be developed as new antibacterial agents against drug-resistant Gram-positive bacteria.
    MeSH terms: Anti-Bacterial Agents/pharmacology*; Anti-Bacterial Agents/chemistry*; Cell Line; Gram-Positive Bacteria/drug effects*; Humans; Microbial Sensitivity Tests; Drug Design; Gram-Positive Bacterial Infections/drug therapy; Lipopeptides/pharmacology*; Lipopeptides/chemistry*
  14. Jafarlou M, Baradaran B, Shanehbandi D, Saedi TA, Jafarlou V, Karimi P, et al.
    J Biol Regul Homeost Agents, 2016 Jan-Mar;30(1):55-65.
    PMID: 27049076
    A key issue in the treatment of acute myeloid leukemia (AML) is the development of drug resistance to chemotherapeutic agents. Overexpression of myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic protein, is associated with tumor progression and drug resistance in leukemia and several cancers. The purpose of this study was to investigate the effect of specific Mcl-1 small interference RNA (siRNA) on the proliferation and chemosensitivity of U-937 AML cell to etoposide. The siRNA transfection was conducted using Lipofectamine™ 2000. Quantitative real-time RT-PCR (qRT-PCR) and Western blot analysis were employed to measure the expression levels of mRNA and protein, respectively. To evaluate tumor cell growth after siRNA transfection, Trypan blue exclusion assay was conducted. The cytotoxic effects of siRNA and etoposide were determined using MTT assay on their own and in combination. DNA-histone ELISA and annexin-V/FITC assays were performed to study the apoptosis. Mcl-1 siRNA transfection significantly blocked the expression of Mcl-1 mRNA and protein in a time-dependent manner, leading to a strong growth inhibition and enhanced apoptosis (P less than 0.05). Furthermore, pretreatment with Mcl-1 siRNA, synergistically enhanced the cytotoxic and apoptotic effects of etoposide (P less than 0.05). Our results demonstrated that Mcl-1 plays a fundamental role in the survival and resistance of U-937 cells to etoposide. Therefore, Mcl-1 can be considered an attractive target in gene therapy of AML patients and siRNA-mediated silencing of this gene may be a novel strategy in AML treatment.
    MeSH terms: Antineoplastic Agents; Etoposide; Histones; Humans; Lipids; RNA, Messenger; Transfection; Trypan Blue; Leukemia, Myeloid, Acute; Fluorescein-5-isothiocyanate; Apoptosis; Annexin A5; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering
  15. Tan HK, Muhammad TST, Tan ML
    Toxicol Appl Pharmacol, 2016 06 01;300:55-69.
    PMID: 27049118 DOI: 10.1016/j.taap.2016.03.017
    14-Deoxy-11,12-didehydroandrographolide (14-DDA), a major diterpenoid isolated from Andrographis paniculata (Burm.f.) Nees, is known to be cytotoxic and elicits a non-apoptotic cell death in T-47D breast carcinoma cells. In this study, the mechanistic toxicology properties of 14-DDA in T-47D cells were further investigated. 14-DDA is found to induce the formation of endoplasmic reticulum (ER) vacuoles and autophagosomes, with concurrent upregulation of LC3-II in the breast carcinoma cells. It stimulated an increase in cytosolic calcium concentration and caused a collapse in mitochondrial membrane potential in these cells. In addition, both DDIT3 and GADD45A, molecules implicated in ER stress pathway, were significantly upregulated. DDIT3 knockdown suppressed the formation of both ER vacuoles and autophagosomes, indicating that 14-DDA-induced ER stress and autophagy is dependent on this transcription factor. Collectively, it is possible that GADD45A/p38 MAPK/DDIT3 pathway is involved in the 14-DDA-induced ER-stress-mediated autophagy in T-47D cells.
    MeSH terms: Autophagy; Breast Neoplasms/drug therapy*; Breast Neoplasms/pathology; Diterpenes/pharmacology*; Humans; Microtubule-Associated Proteins/drug effects; Microtubule-Associated Proteins/metabolism; Up-Regulation; MAP Kinase Signaling System/physiology; Cell Line, Tumor; Proto-Oncogene Proteins c-akt/metabolism; Mitochondrial Membranes/drug effects; Transcription Factor CHOP/biosynthesis*; Phosphatidylinositol 3-Kinase/metabolism; Endoplasmic Reticulum Stress/physiology*
  16. Chan SY, Toh SM, Khan NH, Chung YY, Cheah XZ
    Drug Dev Ind Pharm, 2016 Nov;42(11):1800-1812.
    PMID: 27049232
    Solution-mediated transformation has been cited as one of the main problems that deteriorate dissolution performances of solid dispersion (SD). This is mainly attributed by the recrystallization tendency of poorly soluble drug. Eventually, it will lead to extensive agglomeration which is a key process in reducing the dissolution performance of SD and offsets the true benefit of SD system. Here, a post-processing treatment is suggested in order to reduce the recrystallization tendency and hence bring forth the dissolution advantage of SD system.
    MeSH terms: Crystallization; Drug Carriers; Emollients; Solubility
  17. Yong YV, Shafie AA
    J Asthma, 2016 10;53(8):835-42.
    PMID: 27049693 DOI: 10.3109/02770903.2016.1156694
    OBJECTIVES: To develop and test the feasibility and validity of a computer-based utility assessment tool that used standard gamble (SG) method for measuring asthma-specific health utilities.

    METHODS: A computer-based SG (CBSG) tool was developed using Microsoft® PowerPoint 2007 to value asthma-specific health states in Malaysia. Eight hypothetical health states were considered, including two anchor states (healthy and dead), three chronic (C) states and three temporary (T) states (each numbered 1 through 3, with increasing severity) in addition to the subject's current health state. Twenty adult asthma patients completed the CBSG tool in addition to paper-based Asthma Control Test, three health status measures (EQ-5D, EQ-VAS, and Mini Asthma Quality of Life Questionnaire (MiniAQLQ)), and VAS utility assessment tool. Patients and interviewers rated the difficulty of the VAS and CBSG tools. Correlations between current health state values derived from the various measures were determined.

    RESULTS: The SG and the VAS received similar difficulty ratings. 17 patients completed the CBSG tool within 30 minutes. The mean utilities determined by the CBSG tool for the T1-T3 asthma health states met the expected logical order of 1>2>3, but those for the C1-C3 states did not. Correlation between current health state values derived from the CBSG tool and other measurement tools was poor.

    CONCLUSION: The CBSG tool developed for measuring utilities of asthma health states showed acceptable feasibility and overall validity.

    MeSH terms: Adult; Aged; Asthma*; Female; Health Status; Health Status Indicators*; Humans; Malaysia; Male; Middle Aged; Surveys and Questionnaires; Software; Reproducibility of Results; Young Adult; Visual Analog Scale
  18. Puah LN, Ong LD, Chong WY
    Int J Occup Saf Ergon, 2016 Sep;22(3):333-9.
    PMID: 27049935 DOI: 10.1080/10803548.2016.1159390
    Although knowledge is cumulating, very little is known about the effects of various sources of support on safety and health compliance. This study goes beyond previous research by investigating the relationships among perceived support from organizations, supervisors and co-workers, and employees' safety and health compliance behaviour at chemical and petroleum process plants. The results of this study show that the support from organizations, supervisors and co-workers was significantly related to employees' safety and health compliance. Also, the findings reveal that perceived supervisor support has the strongest influence in ensuring employees' safety and health compliance behaviour.
    MeSH terms: Oil and Gas Industry/organization & administration; Adult; Chemical Industry/organization & administration; Cooperative Behavior; Female; Humans; Malaysia; Male; Middle Aged; Surveys and Questionnaires; Social Perception*; Organizational Culture*; Occupational Health*; Safety Management/organization & administration*
  19. Fadlullah MZ, Chiang IK, Dionne KR, Yee PS, Gan CP, Sam KK, et al.
    Oncotarget, 2016 May 10;7(19):27802-18.
    PMID: 27050151 DOI: 10.18632/oncotarget.8533
    Emerging biological and translational insights from large sequencing efforts underscore the need for genetically-relevant cell lines to study the relationships between genomic alterations of tumors, and therapeutic dependencies. Here, we report a detailed characterization of a novel panel of clinically annotated oral squamous cell carcinoma (OSCC) cell lines, derived from patients with diverse ethnicity and risk habits. Molecular analysis by RNAseq and copy number alterations (CNA) identified that the cell lines harbour CNA that have been previously reported in OSCC, for example focal amplications in 3q, 7p, 8q, 11q, 20q and deletions in 3p, 5q, 8p, 18q. Similarly, our analysis identified the same cohort of frequently mutated genes previously reported in OSCC including TP53, CDKN2A, EPHA2, FAT1, NOTCH1, CASP8 and PIK3CA. Notably, we identified mutations (MLL4, USP9X, ARID2) in cell lines derived from betel quid users that may be associated with this specific risk factor. Gene expression profiles of the ORL lines also aligned with those reported for OSCC. By focusing on those gene expression signatures that are predictive of chemotherapeutic response, we observed that the ORL lines broadly clustered into three groups (cell cycle, xenobiotic metabolism, others). The ORL lines noted to be enriched in cell cycle genes responded preferentially to the CDK1 inhibitor RO3306, by MTT cell viability assay. Overall, our in-depth characterization of clinically annotated ORL lines provides new insight into the molecular alterations synonymous with OSCC, which can facilitate in the identification of biomarkers that can be used to guide diagnosis, prognosis, and treatment of OSCC.
    MeSH terms: Animals; Antineoplastic Agents/pharmacology; Antineoplastic Agents/therapeutic use*; Areca/adverse effects; Carcinoma, Squamous Cell/drug therapy*; Carcinoma, Squamous Cell/genetics*; Carcinoma, Squamous Cell/pathology; Female; Gene Amplification; Humans; Mouth Neoplasms/drug therapy*; Mouth Neoplasms/genetics*; Mouth Neoplasms/pathology; Mutation; Gene Expression Regulation, Neoplastic; Mice, SCID; Mice, Inbred NOD; Sequence Deletion; Sequence Analysis, RNA; Gene Expression Profiling; Xenograft Model Antitumor Assays; Cell Line, Tumor; Mice; Genes, Neoplasm/genetics; DNA Copy Number Variations; Molecular Targeted Therapy*; Transcriptome
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