Browse publications by year: 2017

  1. Yen ST, Tan AKG, Mustapha FI
    J Diabetes, 2017 Sep;9(9):874-883.
    PMID: 27800662 DOI: 10.1111/1753-0407.12502
    BACKGROUND: Policy interventions for cardiovascular diseases require individual awareness of ailments. Such awareness is also key to individuals making changes to their lifestyle and dietary habits. The present study investigated the association of sociodemographic, health, and lifestyle factors with the awareness and prevalence of three ailments: diabetes, hypertension, and hypercholesterolemia.

    METHODS: Data were obtained from the Malaysia Non-Communicable Disease Surveillance-1. Logistic regressions were estimated and odds ratios of exposure variables calculated.

    RESULTS: Diabetes awareness was associated with work hours, age, family history of illnesses, and ethnicity. Individuals with diminished hypertension awareness included those who were younger, without family history of illnesses, not obese, working more hours, and not adhering to a healthy diet. Low awareness of hypercholesterolemia was associated with younger age, lower education level, living in rural areas, female gender, no family history of illnesses, non-obesity, and minority ethnic background. Prevalence generally had the same pattern of association with the exposure variables.

    CONCLUSIONS: Various sociodemographic and health and lifestyle characteristics were associated with diabetes, hypertension, and hypercholesterolemia awareness in Malaysia, albeit with varying outcomes. Therefore, programs focusing on lifestyle improvements should be targeted at high-risk subgroups, such as individuals working longer hours and young adults, who are less likely to be aware of their health risk factors.

  2. Adamu A, Shamsir MS, Wahab RA, Parvizpour S, Huyop F
    J Biomol Struct Dyn, 2017 Nov;35(15):3285-3296.
    PMID: 27800712 DOI: 10.1080/07391102.2016.1254115
    Dehalogenases are of high interest due to their potential applications in bioremediation and in synthesis of various industrial products. DehL is an L-2-haloacid dehalogenase (EC 3.8.1.2) that catalyses the cleavage of halide ion from L-2-halocarboxylic acid to produce D-2-hydroxycarboxylic acid. Although DehL utilises the same substrates as the other L-2-haloacid dehalogenases, its deduced amino acid sequence is substantially different (<25%) from those of the rest L-2-haloacid dehalogenases. To date, the 3D structure of DehL is not available. This limits the detailed understanding of the enzyme's reaction mechanism. The present work predicted the first homology-based model of DehL and defined its active site. The monomeric unit of the DehL constitutes α/β structure that is organised into two distinct structural domains: main and subdomains. Despite the sequence disparity between the DehL and other L-2-haloacid dehalogenases, its structural model share similar fold as the experimentally solved L-DEX and DehlB structures. The findings of the present work will play a crucial role in elucidating the molecular details of the DehL functional mechanism.
    MeSH terms: Amino Acid Sequence; Bacterial Proteins/chemistry*; Hydrolases/chemistry*; Protein Binding; Rhizobium/enzymology; Substrate Specificity; Conserved Sequence; Catalytic Domain; Structural Homology, Protein; Molecular Docking Simulation; Protein Conformation, alpha-Helical
  3. Lee YY, Tang TK, Phuah ET, Alitheen NB, Tan CP, Lai OM
    J Sci Food Agric, 2017 Mar;97(5):1379-1385.
    PMID: 27801514 DOI: 10.1002/jsfa.8124
    Non-enzymatic browning has been a wide and interesting research area in the food industry, ranging from the complexity of the reaction to its applications in the food industry as well as its ever-debatable health effects. This review provides a new perspective to the Maillard reaction apart from its ubiquitous function in enhancing food flavour, taste and appearance. It focuses on the recent application of Maillard reaction products as an inexpensive and excellent source of emulsifiers as well as superior encapsulating matrices for the entrapment of bioactive compounds. Additionally, it will also discuss the latest approaches employed to perform the Maillard reaction as well as several important reaction parameters that need to be taken into consideration when conducting the Maillard reaction. © 2016 Society of Chemical Industry.
    MeSH terms: Food-Processing Industry/methods; Maillard Reaction*; Emulsifying Agents/chemistry*
  4. Greuter T, Bertoldo F, Rechner R, Straumann A, Biedermann L, Zeitz J, et al.
    J Pediatr Gastroenterol Nutr, 2017 08;65(2):200-206.
    PMID: 27801751 DOI: 10.1097/MPG.0000000000001455
    BACKGROUND: There is a paucity of data on extraintestinal manifestations (EIM) and their treatment in pediatric patients with inflammatory bowel disease (IBD).

    METHODS: Since 2008, the Pediatric Swiss IBD Cohort Study has collected data on the pediatric IBD population in Switzerland. Data on 329 patients were analyzed retrospectively.

    RESULTS: A total of 55 patients (16.7%) experienced 1-4 EIM (39 Crohn disease, 12 ulcerative colitis, and 4 IBD-unclassified patients). At IBD onset, presence of EIM was more frequent than in the adult population (8.5% vs 5.0%, P = 0.014). EIM were more frequent in Crohn disease when compared to ulcerative colitis/IBD-unclassified (22.5% vs 10.3%, P = 0.003). The most prevalent EIM were peripheral arthritis (26/329, 7.9%) and aphthous stomatitis (24/329, 7.3%). Approximately 27.6% of all EIM appeared before IBD diagnosis. Median time between IBD diagnosis and occurrence of first EIM was 1 month (-37.5-149.0). Thirty-one of the 55 patients (56.4%) were treated with 1 or more anti-tumor necrosis factor (TNF) agents. IBD patients with EIM were more likely to be treated with anti-TNF compared to those without (56.4% vs 35.0%, P = 0.003). Response rates to anti-TNF depended on underlying EIM and were best for peripheral arthritis (61.5%) and uveitis (66.7%).

    CONCLUSIONS: In a cohort of pediatric patients with IBD, EIM were frequently encountered. In up to 30%, EIM appeared before IBD diagnosis. Knowledge of these findings may translate into an increased awareness of underlying IBD, thereby decreasing diagnostic delay. Anti-TNF for the treatment of certain EIM is effective, although a substantial proportion of new EIM may present despite ongoing anti-TNF therapy.

    MeSH terms: Adolescent; Anti-Inflammatory Agents/therapeutic use; Child; Child, Preschool; Colitis, Ulcerative/complications*; Colitis, Ulcerative/diagnosis; Colitis, Ulcerative/drug therapy; Crohn Disease/complications*; Crohn Disease/diagnosis; Crohn Disease/drug therapy; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Joint Diseases/diagnosis; Joint Diseases/drug therapy; Joint Diseases/etiology*; Joint Diseases/epidemiology; Male; Retrospective Studies; Skin Diseases/diagnosis; Skin Diseases/drug therapy; Skin Diseases/etiology*; Skin Diseases/epidemiology; Tumor Necrosis Factor-alpha/antagonists & inhibitors; Uveitis/diagnosis; Uveitis/drug therapy; Uveitis/etiology*; Uveitis/epidemiology; Cholangitis, Sclerosing/diagnosis; Cholangitis, Sclerosing/drug therapy; Cholangitis, Sclerosing/etiology*; Cholangitis, Sclerosing/epidemiology; Prevalence; Logistic Models
  5. Jee PF, Chen FS, Shu MH, Wong WF, Abdul Rahim R, AbuBakar S, et al.
    Biotechnol Prog, 2017 Jan;33(1):154-162.
    PMID: 27802566 DOI: 10.1002/btpr.2400
    Heterologous protein displayed on the surface of Lactococcus lactis using the binding domain of N-acetylmuramidase (AcmA) has a potential application in vaccine delivery. In this study, we developed a non-recombinant L. lactis surface displaying the influenza A (H1N1) 2009 hemagglutinin (HA1). Three recombinant proteins, HA1/L/AcmA, HA1/AcmA, and HA1 were overexpressed in Escherichia coli, and purified. In the binding study using flow cytometry, the HA1/L/AcmA, which contained the single-chain variable fragment (scFv) peptide linker showed significantly higher percentage of binding counts and mean fluorescence binding intensity (MFI) (51.7 ± 1.4% and 3,594.0 ± 675.9, respectively) in comparison to the HA1/AcmA without the scFv peptide linker (41.1 ± 1.5% and 1,652.0 ± 34.1, respectively). Higher amount of HA1/L/AcmA (∼2.9 × 10(4) molecules per cell) was displayed on L. lactis when compared to HA1/AcmA (∼1.1 × 10(4) molecules per cell) in the immunoblotting analysis. The HA1/L/AcmA completely agglutinated RBCs at comparable amount of protein to that of HA1/AcmA and HA1. Computational modeling of protein structures suggested that scFv peptide linker in HA1/L/AcmA kept the HA1 and the AcmA domain separated at a much longer distance in comparison to HA1/AcmA. These findings suggest that insertion of the scFv peptide linker between HA1 and AcmA improved binding of recombinant proteins to L. lactis. Hence, insertion of scFv peptide linker can be further investigated as a potential approach for improvement of heterologous proteins displayed on the surface of L. lactis using the AcmA binding domain. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:154-162, 2017.
    MeSH terms: Escherichia coli; Flow Cytometry; Fluorescence; Glycoside Hydrolases; Hemagglutinins; Influenza, Human; Recombinant Proteins; Lactococcus lactis; United States; Immunoblotting; Influenza A Virus, H1N1 Subtype; Single-Chain Antibodies
  6. Hamdi Y, Soucy P, Kuchenbaeker KB, Pastinen T, Droit A, Lemaçon A, et al.
    Breast Cancer Res Treat, 2017 01;161(1):117-134.
    PMID: 27796716 DOI: 10.1007/s10549-016-4018-2
    PURPOSE: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways.

    METHODS: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2.

    RESULTS: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10-6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance.

    CONCLUSION: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.

    MeSH terms: Alleles*; Breast Neoplasms/etiology*; Breast Neoplasms/epidemiology*; Chromosomes, Human, Pair 11; Female; Heterozygote*; Humans; Mutation*; Risk; Biomarkers, Tumor; Genetic Variation; Gene Expression; Genes, BRCA1*; Genetic Predisposition to Disease; Genes, BRCA2*; Quantitative Trait Loci
  7. Lim FT, Ogawa S, Smith AI, Parhar IS
    Zebrafish, 2017 Feb;14(1):10-22.
    PMID: 27797681 DOI: 10.1089/zeb.2016.1319
    The central nervous system (CNS) of the non-mammalian vertebrates has better neuroregenerative capability as compared with the mammalian CNS. Regeneration of habenula was observed 40 days after damage in zebrafish. During the early stage of regeneration, we found a significant increase of apoptotic cells on day-1 post-damage and of proliferative cells on day-3 post-damage. To identify the molecular factor(s) involved in the early stages of neuroregeneration, differentially expressed proteins during sham, 20- and 40-h post-habenula damage were investigated by proteomic approach by using two-dimensional differential gel electrophoresis (2D-DIGE) coupled with Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight (MALDI-ToF) and tandem mass spectrometry. Protein profiles revealed 17 differentially (>1.5-fold) expressed proteins: 10 upregulated, 4 downregulated, 2 proteins were found to be downregulated at the early stage but upregulated at a later stage, and 1 protein was found to be upregulated at 2 different time points. All proteins identified can be summarized under few molecular processes involved in the early stages of neuroregeneration in zebrafish CNS: apoptosis regulation (Wnt inhibitory factor 1 [WIF1]), neuroprotection (metallothionein), cell proliferation (Spred2, ependymin, Lhx1, and Wnts), differentiation (Spred2, Lhx9, and Wnts), and morphogenesis (cytoplasmic actins and draculin). These protein profiling results suggest that drastic molecular changes occur in the neuroregenerative process during this period, which includes cell proliferation, differentiation, and protection.
    MeSH terms: Animals; Brain/cytology; Brain/physiology*; Regeneration; Zebrafish/growth & development; Zebrafish/physiology*; Electrophoresis, Gel, Two-Dimensional; Biomarkers/metabolism; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Proteomics/methods*; Cell Proliferation/physiology*; Tandem Mass Spectrometry
  8. Agarwal R, Agarwal P
    Exp Biol Med (Maywood), 2017 Feb;242(4):374-383.
    PMID: 27798117 DOI: 10.1177/1535370216675065
    Disturbances of extracellular matrix homeostasis are associated with a number of pathological conditions. The ability of extracellular matrix to provide contextual information and hence control the individual or collective cellular behavior is increasingly being recognized. Hence, newer therapeutic approaches targeting extracellular matrix remodeling are widely investigated. We reviewed the current literature showing the effects of resveratrol on various aspects of extracellular matrix remodeling. This review presents a summary of the effects of resveratrol on extracellular matrix deposition and breakdown. Mechanisms of action of resveratrol in extracellular matrix deposition involving growth factors and their signaling pathways are discussed. Involvement of phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways and role of transcription factors and sirtuins on the effects of resveratrol on extracellular matrix homeostasis are summarized. It is evident from the literature presented in this review that resveratrol has significant effects on both the synthesis and breakdown of extracellular matrix. The major molecular targets of the action of resveratrol are growth factors and their signaling pathways, phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways, transcription factors, and SIRT-1. The effects of resveratrol on extracellular matrix and the molecular targets appear to be related to experimental models, experimental environment as well as the doses.
    MeSH terms: Extracellular Matrix/pathology*; Humans; Stilbenes/pharmacology*; Transcription Factors/metabolism; Signal Transduction/drug effects; Matrix Metalloproteinase 9/metabolism; Mitogen-Activated Protein Kinases/metabolism*; MAP Kinase Signaling System/drug effects*; Proto-Oncogene Proteins c-akt/metabolism*; Sirtuin 1/metabolism; Phosphatidylinositol 3-Kinase/metabolism*
  9. Lan YW, Theng SM, Huang TT, Choo KB, Chen CM, Kuo HP, et al.
    Stem Cells Transl Med, 2017 03;6(3):1006-1017.
    PMID: 28297588 DOI: 10.5966/sctm.2016-0054
    Mesenchymal stem cells (MSCs) are widely considered for treatment of pulmonary fibrosis based on the anti-inflammatory, antifibrotic, antiapoptotic, and regenerative properties of the cells. Recently, elevated levels of oncostatin M (OSM) have been reported in the bronchoalveolar lavage fluid of a pulmonary fibrosis animal model and in patients. In this work, we aimed to prolong engrafted MSC survival and to enhance the effectiveness of pulmonary fibrosis transplantation therapy by using OSM-preconditioned MSCs. OSM-preconditioned MSCs were shown to overexpress type 2 OSM receptor (gp130/OSMRβ) and exhibited high susceptibility to OSM, resulting in upregulation of the paracrine factor, hepatocyte growth factor (HGF). Moreover, OSM-preconditioned MSCs enhanced cell proliferation and migration, attenuated transforming growth factor-β1- or OSM-induced extracellular matrix production in MRC-5 fibroblasts through paracrine effects. In bleomycin-induced lung fibrotic mice, transplantation of OSM-preconditioned MSCs significantly improved pulmonary respiratory functions and downregulated expression of inflammatory factors and fibrotic factors in the lung tissues. Histopathologic examination indicated remarkable amelioration of the lung fibrosis. LacZ-tagged MSCs were detected in the lung tissues of the OSM-preconditioned MSC-treated mice 18 days after post-transplantation. Taken together, our data further demonstrated that HGF upregulation played an important role in mediating the therapeutic effects of transplanted OSM-preconditioned MSCs in alleviating lung fibrosis in the mice. Stem Cells Translational Medicine 2017;6:1006-1017.
    MeSH terms: Animals; Bleomycin; Bronchoalveolar Lavage Fluid; Diabetes Mellitus, Type 2; Extracellular Matrix; Fibroblasts; Humans; Pulmonary Fibrosis; Transforming Growth Factors; Up-Regulation; Hepatocyte Growth Factor; Models, Animal; Cell Proliferation; Mice; Receptors, Oncostatin M; Oncostatin M Receptor beta Subunit; Oncostatin M; Transforming Growth Factor beta1; Translational Medical Research; Mesenchymal Stromal Cells
  10. Ali HS, Abdul-Rahim AS, Ribadu MB
    Environ Sci Pollut Res Int, 2017 Jan;24(2):1967-1974.
    PMID: 27798805 DOI: 10.1007/s11356-016-7935-z
    The main aim of this article is to examine empirically the impact of urbanization on carbon dioxide emissions in Singapore from 1970 to 2015. The autoregressive distributed lags (ARDL) approach is applied within the analysis. The main finding reveals a negative and significant impact of urbanization on carbon emissions in Singapore, which means that urban development in Singapore is not a barrier to the improvement of environmental quality. Thus, urbanization enhances environmental quality by reducing carbon emissions in the sample country. The result also highlighted that economic growth has a positive and significant impact on carbon emissions, which suggests that economic growth reduces environmental quality through its direct effect of increasing carbon emissions in the country. Despite the high level of urbanization in Singapore, which shows that 100 % of the populace is living in the urban center, it does not lead to more environmental degradation. Hence, urbanization will not be considered an obstacle when initiating policies that will be used to reduce environmental degradation in the country. Policy makers should consider the country's level of economic growth instead of urbanization when formulating policies to reduce environmental degradation, due to its direct impact on increasing carbon dioxide emissions.
    MeSH terms: Air Pollutants/analysis*; Carbon Dioxide/analysis*; Conservation of Natural Resources; Regression Analysis; Singapore; Urbanization; Economic Development
  11. Khanday WA, Asif M, Hameed BH
    Int J Biol Macromol, 2017 Feb;95:895-902.
    PMID: 27789331 DOI: 10.1016/j.ijbiomac.2016.10.075
    Cross-linked beads of activated oil palm ash zeolite/chitosan (Z-AC/C) composite were prepared through the hydrothermal treatment of NaOH activated oil palm ash followed by beading with chitosan. The effects of initial dye concentration (50-400mg/L), temperature (30°C-50°C) and pH (3-13) on batch adsorption of methylene blue (MB) and acid blue 29 (AB29) were studied. Adsorption of both dyes was better described by Pseudo-second-order kinetics and Freundlich isotherm model. The maximum adsorption capacities of Z-AC/C were 151.51, 169.49, and 199.20mg/g for MB and 212.76, 238.09, and 270.27mg/g for AB29 at 30°C, 40°C, and 50°C, respectively.
    MeSH terms: Adsorption; Azo Compounds/isolation & purification*; Azo Compounds/chemistry*; Hydrogen-Ion Concentration; Industrial Waste; Kinetics; Methylene Blue/isolation & purification*; Methylene Blue/chemistry*; Naphthalenes/isolation & purification*; Naphthalenes/chemistry*; Plant Oils/chemistry*; Temperature; Water Pollutants, Chemical/isolation & purification; Water Pollutants, Chemical/chemistry; Zeolites/chemistry*; Water Purification; Chitosan/chemistry*
  12. Ramli AN, Aznan TN, Illias RM
    J Sci Food Agric, 2017 Mar;97(5):1386-1395.
    PMID: 27790704 DOI: 10.1002/jsfa.8122
    Bromelain is a mixture of proteolytic enzymes found in pineapple (Ananas comosus) plants. It can be found in several parts of the pineapple plant, including the stem, fruit, leaves and peel. High demand for bromelain has resulted in gradual increases in bromelain production. These increases have led to the need for a bromelain production strategy that yields more purified bromelain at a lower cost and with fewer production steps. Previously, bromelain was purified by conventional centrifugation, ultrafiltration and lyophilisation. Recently, the development of more modern purification techniques such as gel filtration, ion exchange chromatography, affinity chromatography, aqueous two-phase extraction and reverse micelle chromatography has resulted in increased industrial bromelain production worldwide. In addition, recombinant DNA technology has emerged as an alternative strategy for producing large amounts of ultrapure bromelain. An up-to-date compilation of data regarding the commercialisation of bromelain in the clinical, pharmaceutical and industrial fields is provided in this review. © 2016 Society of Chemical Industry.
    MeSH terms: Biotechnology/methods; Bromelains/isolation & purification*; Bromelains/chemistry; DNA, Recombinant; Food Technology/methods*; Ananas/enzymology; Ananas/chemistry
  13. Liew YT, Soo SS, Nathan AM, Manuel AM
    Auris Nasus Larynx, 2017 Oct;44(5):635-638.
    PMID: 27793496 DOI: 10.1016/j.anl.2016.10.001
    Congenital bony nasal stenosis (CBNS) is a very rare but life-threatening cause of airway obstruction in neonates and infants. This review aims to assess the presentation and early airway management of 4 new cases of craniosynostosis with bilateral nasal cavity stenosis. Patients were treated with endoscopic endonasal widening of the nasal cavity and stenting. All patients were extubated well post-operatively with resolution of symptoms. They remained asymptomatic with stents in situ for at least 6 months with no complications reported. Minimally invasive endoscopic endonasal widening of the nasal cavity with stenting is an effective and safe way of addressing nasal cavity stenosis.
    MeSH terms: Craniosynostoses*; Cyanosis/etiology; Dilatation; Endoscopy; Female; Humans; Infant; Infant, Newborn; Male; Nasal Cavity/abnormalities*; Nasal Cavity/surgery; Respiratory Distress Syndrome, Newborn/etiology; Sleep Apnea Syndromes/etiology; Nasal Obstruction/congenital*; Nasal Obstruction/surgery; Stents
  14. Farooq AV, Gibbons AG, Council MD, Harocopos GJ, Holland S, Judelson J, et al.
    Am J Ophthalmol, 2017 Feb;174:119-125.
    PMID: 27793603 DOI: 10.1016/j.ajo.2016.10.007
    PURPOSE: To report a series of patients who developed corneal toxicity after exposure to aquarium coral palytoxin.

    DESIGN: Multicenter retrospective case series.

    METHODS: Retrospective review.

    RESULTS: Seven patients presented with corneal findings ranging from superficial punctate epitheliopathy to bilateral corneal melt with subsequent perforation. Among those with mild corneal findings, resolution was achieved with topical steroids and lubrication, whereas some patients who developed progressive corneal melt required therapeutic penetrating keratoplasty. The history in all patients revealed exposure to aquarium zoanthid corals shortly before disease onset. A review of the literature revealed that there are few prior reports of coral-associated corneal toxicity and that some species of coral secrete a substance known as palytoxin, a potent vasoconstrictor that inhibits the membranous sodium-potassium ATPase pump across cell types and can cause rapid death if inhaled or ingested.

    CONCLUSIONS: This is the largest case series to date demonstrating patients with aquarium coral palytoxin-associated corneal toxicity, and is the first to provide details of related histopathologic findings. Similar to other forms of toxic keratoconjunctivitis, a detailed history and careful clinical assessment are required, as well as timely removal of the offending agent from the patients' ocular milieu and environment. Mild ocular surface and corneal disease may be treated effectively with aggressive topical steroid therapy and lubrication. Given the potential severity of ocular as well as systemic adverse effects, there should be increased awareness of this entity among eye care professionals, aquarium enthusiasts, and the general public.

    MeSH terms: Acrylamides/adverse effects*; Adult; Aged; Animals; Cnidarian Venoms; Female; Humans; Keratitis/chemically induced*; Keratitis/diagnosis; Keratitis/surgery; Male; Middle Aged; Retrospective Studies; Keratoplasty, Penetrating; Anthozoa/chemistry*
  15. Ariffin SH, Manogaran T, Abidin IZ, Wahab RM, Senafi S
    Curr Stem Cell Res Ther, 2017;12(3):247-259.
    PMID: 27784228 DOI: 10.2174/1574888X11666161026145149
    Stem cells (SCs) are capable of self-renewal and multilineage differentiation. Human mesenchymal stem cells (MSCs) and haematopoietic stem cells (HSCs) which can be obtained from multiple sources, are suitable for application in regenerative medicine and transplant therapy. The aim of this review is to evaluate the potential of genomic and proteomic profiling analysis to identify the differentiation of MSCs and HSCs towards osteoblast and odontoblast lineages. In vitro differentiation towards both of these lineages can be induced using similar differentiation factors. Gene profiling cannot be utilised to confirm the lineages of these two types of differentiated cells. Differentiated cells of both lineages express most of the same markers. Most researchers have detected the expression of genes such as ALP, OCN, OPN, BMP2 and RUNX2 in osteoblasts and the expression of the DSPP gene in odontoblasts. Based on their cell-type specific protein profiles, various proteins are differentially expressed by osteoblasts and odontoblasts, except for vimentin and heterogeneous nuclear ribonucleoprotein C, which are expressed in both cell types, and LOXL2 protein, which is expressed only in odontoblasts.
    MeSH terms: Amino Acid Oxidoreductases/genetics; Amino Acid Oxidoreductases/metabolism; Cell Differentiation/genetics; Humans; Odontoblasts/cytology; Odontoblasts/metabolism*; Osteoblasts/cytology; Osteoblasts/metabolism*; Osteogenesis/genetics*; Phosphoproteins/genetics; Phosphoproteins/metabolism; Sialoglycoproteins/genetics; Sialoglycoproteins/metabolism; Biomarkers/metabolism; Extracellular Matrix Proteins/genetics*; Extracellular Matrix Proteins/metabolism; Cell Lineage/genetics; Gene Expression Profiling; Proteomics; Mesenchymal Stem Cell Transplantation*; Core Binding Factor Alpha 1 Subunit/genetics; Core Binding Factor Alpha 1 Subunit/metabolism; Bone Morphogenetic Protein 2/genetics; Bone Morphogenetic Protein 2/metabolism; Mesenchymal Stromal Cells/cytology; Mesenchymal Stromal Cells/metabolism*
  16. Mittal P, Klingler-Hoffmann M, Arentz G, Winderbaum L, Kaur G, Anderson L, et al.
    Biochim Biophys Acta Proteins Proteom, 2017 Jul;1865(7):846-857.
    PMID: 27784647 DOI: 10.1016/j.bbapap.2016.10.010
    The prediction of lymph node metastasis using clinic-pathological data and molecular information from endometrial cancers lacks accuracy and is therefore currently not routinely used in patient management. Consequently, although only a small percentage of patients with endometrial cancers suffer from metastasis, the majority undergo radical surgery including removal of pelvic lymph nodes. Upon analysis of publically available data and published research, we compiled a list of 60 proteins having the potential to display differential abundance between primary endometrial cancers with versus those without lymph node metastasis. Using data dependent acquisition LC-ESI-MS/MS we were able to detect 23 of these proteins in endometrial cancers, and using data independent LC-ESI-MS/MS the differential abundance of five of those proteins was observed. The localization of the differentially expressed proteins, was visualized using peptide MALDI MSI in whole tissue sections as well as tissue microarrays of 43 patients. The proteins identified were further validated by immunohistochemistry. Our data indicate that annexin A2 protein level is upregulated, whereas annexin A1 and α actinin 4 expression are downregulated in tumours with lymph node metastasis compared to those without lymphatic spread. Moreover, our analysis confirmed the potential of these markers, to be included in a statistical model for prediction of lymph node metastasis. The predictive model using highly ranked m/z values identified by MALDI MSI showed significantly higher predictive accuracy than the model using immunohistochemistry data. In summary, using publicly available data and complementary proteomics approaches, we were able to improve the prediction model for lymph node metastasis in EC.
    MeSH terms: Actinin/metabolism*; Chromatography, Liquid/methods; Female; Humans; Immunohistochemistry/methods; Lymph Nodes/metabolism; Lymph Nodes/pathology; Lymphatic Metastasis/pathology; Down-Regulation/physiology; Up-Regulation/physiology; Endometrial Neoplasms/metabolism*; Endometrial Neoplasms/pathology*; Annexin A2/metabolism*; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods; Tandem Mass Spectrometry/methods
  17. AlMatar M, Eldeeb M, Makky EA, Köksal F, Var I, Kayar B
    Curr Microbiol, 2017 Jan;74(1):132-144.
    PMID: 27785553 DOI: 10.1007/s00284-016-1152-3
    Microbial-derived natural products have functional and structural diversity and complexity. For several decades, they have provided the basic foundation for most drugs available to modern medicine. Microbial-derived natural products have wide-ranging applications, especially as chemotherapeutics for various diseases and disorders. By exploring distinct microorganisms in different environments, small novel bioactive molecules with unique functionalities and biological or biomedical significance can be identified. Aquatic environments, such as oceans or seas, are considered to be sources of abundant novel bioactive compounds. Studies on marine microorganisms have revealed that several bioactive compounds extracted from marine algae and invertebrates are eventually generated by their associated bacteria. These findings have prompted intense research interest in discovering novel compounds from marine microorganisms. Natural products derived from Dermacoccus exhibit antibacterial, antitumor, antifungal, antioxidant, antiviral, antiparasitic, and eventually immunosuppressive bioactivities. In this review, we discussed the diversity of secondary metabolites generated by genus Dermacoccus with respect to their chemical structure, biological activity, and origin. This brief review highlights and showcases the pivotal importance of Dermacoccus-derived natural products and sheds light on the potential venues of discovery of new bioactive compounds from marine microorganisms.
    MeSH terms: Animals; Anti-Infective Agents/metabolism; Anti-Infective Agents/pharmacology; Anti-Infective Agents/chemistry; Antineoplastic Agents/metabolism; Antineoplastic Agents/pharmacology; Antineoplastic Agents/chemistry; Biological Products/metabolism; Biological Products/pharmacology*; Biological Products/chemistry; Invertebrates/microbiology; Actinobacteria/isolation & purification; Actinobacteria/metabolism; Actinobacteria/chemistry*
  18. Toh LS, Lai PSM, Othman S, Wong KT, Low BY, Anderson C
    Res Social Adm Pharm, 2017 11;13(6):1142-1150.
    PMID: 27780658 DOI: 10.1016/j.sapharm.2016.10.004
    OBJECTIVES: This study describes the perspective of patients, nurses, pharmacists, doctors and policy makers to identify the level of collaboration and the areas for improvement to achieve inter-professional collaboration between doctors, nurses, pharmacists and policy makers in a primary care clinic.

    METHODS: Patients (n = 20), Nurses (n = 10), pharmacists (n = 11), doctors (n = 10) and policy makers (n = 5) from a primary care were individually interviewed using a semi-structured topic guide. Purposive sampling was used. Interviews were transcribed verbatim and analysed using thematic analysis informed by constant comparison.

    RESULTS: Patients, doctors, nurses, pharmacists and policy makers were eager for pharmacists to be more proactive in creating health awareness and conducting osteoporosis screening at the primary care clinic via inter-professional collaboration. These findings were further examined using the D'Amour's structural model of collaboration which encompasses four main themes: shared goals and visions, internalization, formalization and governance. This model supports our data which highlights a lack of understanding of the pharmacists' role among the doctors, nurses, policy makers and pharmacists themselves. There is also a lack of governance and formalization, that fosters consensus, leadership, protocol and information exchange. Nonetheless, the stakeholders trust that pharmacists have sufficient knowledge to contribute to the screening of osteoporosis. Our primary care clinic can be described as developing towards an inter-professional collaboration in managing osteoporosis but is still in its early stages.

    CONCLUSIONS: Inter-professional collaboration in osteoporosis management at the primary care level is beginning to be practised. Efforts extending to awareness and acceptance towards the pharmacists' role will be crucial for a successful change.
    MeSH terms: Administrative Personnel; Aged; Ambulatory Care Facilities; Female; Humans; Interprofessional Relations*; Malaysia; Middle Aged; Nurses; Osteoporosis/diagnosis*; Pharmacists; Physicians; Primary Health Care; Models, Organizational*; Professional Role; Qualitative Research
  19. Cheng AL, Cornelio G, Shen L, Price T, Yang TS, Chung IJ, et al.
    Clin Colorectal Cancer, 2017 06;16(2):e73-e88.
    PMID: 27780749 DOI: 10.1016/j.clcc.2016.08.005
    BACKGROUND: In patients with KRAS wild-type (wt) metastatic colorectal cancer (mCRC), outcomes with first-line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first-line once-every-2-weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed.

    PATIENTS AND METHODS: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region. Patients (n = 289) received once-every-2-weeks cetuximab with investigator's choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression-free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated.

    RESULTS: In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations.

    CONCLUSION: The observed activity and safety profile is similar to that reported in prior first-line pivotal studies involving weekly cetuximab, suggesting once-every-2-weeks cetuximab is effective and tolerable as first-line therapy and may represent an alternative to weekly administration.

    MeSH terms: Cetuximab/administration & dosage; Aged; Antineoplastic Combined Chemotherapy Protocols/administration & dosage*; Antineoplastic Combined Chemotherapy Protocols/adverse effects; Camptothecin/administration & dosage; Camptothecin/adverse effects; Camptothecin/analogs & derivatives; Leucovorin/administration & dosage; Leucovorin/adverse effects; Drug Administration Schedule; Female; Fluorouracil/administration & dosage; Fluorouracil/adverse effects; Humans; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds/administration & dosage; Organoplatinum Compounds/adverse effects; Biomarkers, Tumor/metabolism; Colorectal Neoplasms/drug therapy*; Colorectal Neoplasms/genetics; Colorectal Neoplasms/pathology; Survival Rate; Proto-Oncogene Proteins p21(ras)/genetics*; Disease-Free Survival; ras Proteins/genetics
  20. Sharma AK, Gothwal A, Kesharwani P, Alsaab H, Iyer AK, Gupta U
    Drug Discov Today, 2017 02;22(2):314-326.
    PMID: 27671487 DOI: 10.1016/j.drudis.2016.09.013
    Dendrimers are novel nanoarchitectures with unique properties including a globular 3D shape, a monodispersed unimicellar nature and a nanometric size range. The availability of multiple peripheral functional groups and tunable surface engineering enable the facile modification of the dendrimer surface with different therapeutic drugs, diagnostic agents and targeting ligands. Drug encapsulation, and solubilizing and passive targeting also equally contribute to the therapeutic use of dendrimers. In this review, we highlight recent advances in the delivery of anticancer drugs using dendrimers, as well as other biomedical and diagnostic applications. Taken together, the immense potential and utility of dendrimers are envisaged to have a significant positive impact on the growing arena of drug delivery and targeting.
    MeSH terms: Animals; Antineoplastic Agents/administration & dosage*; Antineoplastic Agents/therapeutic use; Humans; Neoplasms/diagnosis*; Neoplasms/drug therapy*; Drug Delivery Systems*; Nanostructures/administration & dosage*; Nanostructures/therapeutic use; Nanostructures/toxicity; Nanostructures/chemistry; Dendrimers/administration & dosage*; Dendrimers/therapeutic use; Dendrimers/toxicity; Dendrimers/chemistry
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