Browse publications by year: 2014

  1. Fun HK, Chantrapromma S, Ong LH
    Molecules, 2014 Jul 11;19(7):10137-49.
    PMID: 25019557 DOI: 10.3390/molecules190710137
    Crystals of 1,6-hexanedioic acid (I) undergo a temperature-dependent reversible phase transition from monoclinic P21/c at a temperature higher than the critical temperature (Tc) 130 K to another monoclinic P21/c at temperature lower than Tc. The phase transition is of first order, involving a discontinuity and a tripling of the b-axis at Tc whereas the other unit cell parameters vary continuously. The transition is described by the phenomenological Landau theory. The crystal structure analyses for data collected at 297(2) K and 120.0(1) K show that there is half of a molecule of (I) in the asymmetric unit at 297(2) K whereas there are one and a half molecules of (I) in the asymmetric unit at 120.0(1) K. At both temperatures, 297(2) and 120.0(1) K, intermolecular O-H···O hydrogen bonds link the molecules of I into infinite 1D chains along [101] direction. However there are significantly more O-H···O hydrogen bonds presented in the 120.0(1) K polymorph, thereby indicating this phase transition is negotiated via hydrogen bonds. The relationship of the conformational changes and hydrogen bonding for these two polymorphs are explained in detail.
    MeSH terms: Adipates/chemistry*; Hot Temperature*; Models, Theoretical*; Phase Transition*
  2. Cheng HJ, Ee R, Cheong YM, Tan WS, Yin WF, Chan KG
    Sensors (Basel), 2014;14(7):12511-22.
    PMID: 25019635 DOI: 10.3390/s140712511
    A multidrug-resistant clinical bacteria strain GB11 was isolated from a wound swab on the leg of a patient. Identity of stain GB11 as Pseudomonas aeruginosa was validated by using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Detection of the production of signaling molecules, N-acylhomoserine lactones (AHLs), was conducted using three different bacterial biosensors. A total of four different AHLs were found to be produced by strain GB11, namely N-butyryl homoserine lactone (C4-HSL), N-hexanoylhomoserine lactone (C6-HSL), N-octanoyl homoserine lactone (C8-HSL) and N-3-oxo-dodecanoylhomoserine lactone (3-oxo-C12-HSL) using high resolution liquid chromatography tandem mass spectrometry (LC-MS/MS). Of these detected AHLs, 3-oxo-C12-HSL was found to be the most abundant AHL produced by P. aeruginosa GB11.
    MeSH terms: Chromatography, Liquid/methods; Humans; Pseudomonas aeruginosa/physiology*; Biosensing Techniques/methods; Drug Resistance, Bacterial/physiology*; Quorum Sensing/physiology*; Tandem Mass Spectrometry/methods
  3. Tay ST, Lotfalikhani A, Sabet NS, Ponnampalavanar S, Sulaiman S, Na SL, et al.
    Mycopathologia, 2014 Oct;178(3-4):307-14.
    PMID: 25022264 DOI: 10.1007/s11046-014-9778-9
    BACKGROUND: Candida nivariensis and C. bracarensis have been recently identified as emerging yeast pathogens which are phenotypically indistinguishable from C. glabrata. However, there is little data on the prevalence and antifungal susceptibilities of these species.

    OBJECTIVE: This study investigated the occurrence of C. nivariensis and C. bracarensis in a culture collection of 185 C. glabrata isolates at a Malaysian teaching hospital.

    METHODS: C. nivariensis was discriminated from C. glabrata using a PCR assay as described by Enache-Angoulvant et al. (J Clin Microbiol 49:3375-9, 2011). The identity of the isolates was confirmed by sequence analysis of the D1D2 domain and internal transcribed spacer region of the yeasts. The isolates were cultured on Chromogenic CHROMagar Candida (®) agar (Difco, USA), and their biochemical and enzymic profiles were determined. Antifungal susceptibilities of the isolates against amphotericin B, fluconazole, voriconazole and caspofungin were determined using E tests. Clotrimazole MICs were determined using a microbroth dilution method.

    RESULTS: There was a low prevalence (1.1 %) of C. nivariensis in our culture collection of C. glabrata. C. nivariensis was isolated from a blood culture and vaginal swab of two patients. C. nivariensis grew as white colonies on Chromogenic agar and demonstrated few positive reactions using biochemical tests. Enzymatic profiles of the C. nivariensis isolates were similar to that of C. glabrata. The isolates were susceptible to amphotericin B, fluconazole, voriconazole and caspofungin. Clotrimazole resistance is suspected in one isolate.

    CONCLUSION: This study reports for the first time the emergence of C. nivariensis in our clinical setting.

    MeSH terms: Adult; Aged; Antifungal Agents/pharmacology; Candida/classification*; Candida/genetics; Candida/isolation & purification*; Candida/physiology; Candidiasis/microbiology*; Culture Media/chemistry; DNA, Fungal/genetics; DNA, Fungal/chemistry; Hospitals, Teaching; Humans; Malaysia; Microbial Sensitivity Tests; Microbiological Techniques/methods; Molecular Sequence Data; Phylogeny; Cluster Analysis; Polymerase Chain Reaction; Mycological Typing Techniques; Sequence Analysis, DNA; DNA, Ribosomal Spacer/genetics; DNA, Ribosomal Spacer/chemistry
  4. Zakaria Z, Zainordin NA, Sim BL, Zaid M, Haridan US, Aziz AT, et al.
    J Infect Dev Ctries, 2014 Jul;8(7):869-75.
    PMID: 25022297 DOI: 10.3855/jidc.4283
    INTRODUCTION: The latest revised version of the World Health Organization's dengue classification was released in 2009. A handful of studies have taken initiatives to evaluate the old and revised guidelines to determine early signs and symptoms of severe dengue. This retrospective study aimed to compare the classification of dengue using both the 1997 and 2009 guidelines in a selected cohort of dengue patients from Peninsular Malaysia between 2008 and 2012.
    METHODOLOGY: Adult dengue patients were recruited from tertiary hospitals in two different states, Selangor and Kelantan, in Peninsular Malaysia. Their clinical manifestations were assessed.
    RESULTS: A total of 281 confirmed dengue patients were enrolled; the mean duration of illness at admission was five days. Of these, 88.6%, 10.7%, and 0.7% were classified according to the 1997 guidelines as having dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), respectively. When the WHO 2009 guidelines were applied, 17.1%, 78.3%, and 4.6% were classified as dengue without warning signs, dengue with warning signs, and severe dengue, respectively.
    CONCLUSIONS: Our data suggests that the revised WHO 2009 guidelines stratify a much larger proportion of patients into a category that requires a higher level of medical and nursing care.
    MeSH terms: Adolescent; Adult; Aged; Aged, 80 and over; Dengue/classification*; Dengue/diagnosis*; Dengue/etiology*; Female; Hospitalization; Humans; Malaysia; Male; Middle Aged; Retrospective Studies; World Health Organization; Guidelines as Topic; Severe Dengue/classification; Severe Dengue/diagnosis; Severe Dengue/etiology; Young Adult
  5. Mukhametov A, Newhouse EI, Aziz NA, Saito JA, Alam M
    J Mol Graph Model, 2014 Jul;52:103-13.
    PMID: 25023665 DOI: 10.1016/j.jmgm.2014.06.008
    The allosteric pocket of the Dengue virus (DENV2) NS2B/NS3 protease, which is proximal to its catalytic triad, represents a promising drug target (Othman et al., 2008). We have explored this binding site through large-scale virtual screening and molecular dynamics simulations followed by calculations of binding free energy. We propose two mechanisms for enzyme inhibition. A ligand may either destabilize electronic density or create steric effects relating to the catalytic triad residues NS3-HIS51, NS3-ASP75, and NS3-SER135. A ligand may also disrupt movement of the C-terminal of NS2B required for inter-conversion between the "open" and "closed" conformations. We found that chalcone and adenosine derivatives had the top potential for drug discovery hits, acting through both inhibitory mechanisms. Studying the molecular mechanisms of these compounds might be helpful in further investigations of the allosteric pocket and its potential for drug discovery.
    MeSH terms: Allosteric Site*; Dengue Virus/drug effects; Dengue Virus/enzymology*; Drug Evaluation, Preclinical*; Hydrogen Bonding; Ligands; Protease Inhibitors/analysis*; Protease Inhibitors/pharmacology; Protease Inhibitors/chemistry; Serine Endopeptidases/metabolism*; Thermodynamics; Structural Homology, Protein; Molecular Dynamics Simulation*
  6. Kooy N, Mohamed K, Pin LT, Guan OS
    Nanoscale Res Lett, 2014;9(1):320.
    PMID: 25024682 DOI: 10.1186/1556-276X-9-320
    Since its introduction in 1995, nanoimprint lithography has been demonstrated in many researches as a simple, low-cost, and high-throughput process for replicating micro- and nanoscale patterns. Due to its advantages, the nanoimprint lithography method has been rapidly developed over the years as a promising alternative to conventional nanolithography processes to fulfill the demands generated from the recent developments in the semiconductor and flexible electronics industries, which results in variations of the process. Roll-to-roll (R2R) nanoimprint lithography (NIL) is the most demanded technique due to its high-throughput fulfilling industrial-scale application. In the present work, a general literature review on the various types of nanoimprint lithography processes especially R2R NIL and the methods commonly adapted to fabricate imprint molds are presented to provide a clear view and understanding on the nanoimprint lithography technique as well as its recent developments.
    MeSH terms: Fungi; Printing; Research Design; Semiconductors
  7. Aziz NS, Nishiyama T, Rusli NI, Mahmood MR, Yasui K, Hashim AM
    Nanoscale Res Lett, 2014;9(1):337.
    PMID: 25024694 DOI: 10.1186/1556-276X-9-337
    A seedless growth of zinc oxide (ZnO) structures on multilayer (ML) graphene by electrochemical deposition without any pre-deposited ZnO seed layer or metal catalyst was studied. A high density of a mixture of vertically aligned/non-aligned ZnO rods and flower-shaped structures was obtained. ML graphene seems to generate the formation of flower-shaped structures due to the stacking boundaries. The nucleation of ZnO seems to be promoted at the stacking edges of ML graphene with the increase of applied current density, resulting in the formation of flower-shaped structures. The diameters of the rods/flower-shaped structures also increase with the applied current density. ZnO rods/flower-shaped structures with high aspect ratio over 5.0 and good crystallinity were obtained at the applied current densities of -0.5 and -1.0 mA/cm(2). The growth mechanism was proposed. The growth involves the formation of ZnO nucleation below 80°C and the enhancement of the growth of vertically non-aligned rods and flower-shaped structures at 80°C. Such ZnO/graphene hybrid structure provides several potential applications in sensing devices.
  8. Lai PS, Wong YY, Low YC, Lau HL, Chin KF, Mahadeva S
    PeerJ, 2014;2:e451.
    PMID: 25024919 DOI: 10.7717/peerj.451
    Background. Proton pump inhibitors (PPIs) are currently the most effective agents for acid-related disorders. However, studies show that 25-75% of patients receiving intravenous PPIs had no appropriate justification, indicating high rates of inappropriate prescribing. Objective. To examine the appropriate use of intravenous PPIs in accordance with guidelines and the efficacy of a prescribing awareness intervention at an Asian teaching institution. Setting. Prospective audit in a tertiary hospital in Malaysia. Method. Every 4th intravenous PPI prescription received in the pharmacy was screened against hospital guidelines. Interventions for incorrect indication/dose/duration were performed. Patients' demographic data, medical history and the use of intravenous PPI were collected. Included were all adult inpatients prescribed intravenous PPI. Main Outcome Measure. Proportion of appropriate IV PPI prescriptions. Results. Data for 106 patients were collected. Most patients were male [65(61.3%)], Chinese [50(47.2%)], with mean age ± SD = 60.3 ± 18.0 years. Most intravenous PPI prescriptions were initiated by junior doctors from the surgical [47(44.3%)] and medical [42(39.6%)] departments. Only 50/106(47.2%) patients had upper gastrointestinal endoscopy/surgery performed to verify the source of bleeding. Unexplained abdominal pain [81(76.4%)] was the main driver for prescribing intravenous PPIs empirically, out of which 73(68.9%) were for suspected upper gastrointestinal bleed. Overall, intravenous PPI was found to be inappropriately prescribed in 56(52.8%) patients for indication, dose or duration. Interventions on the use of intravenous PPI were most effective when performed by senior doctors (100%), followed by clinical pharmacists (50%), and inpatient pharmacists (37.5%, p = 0.027). Conclusion. Inappropriate intravenous PPI usage is still prevalent despite the enforcement of hospital guidelines. The promotion of prescribing awareness and evidence-based prescribing through education of medical staff could result in more judicious use of intravenous PPI and dose-optimization.
    MeSH terms: Adult; Aged; Demography; Humans; Inpatients; Malaysia; Male; Medical Staff; Middle Aged; Pharmaceutical Services; Pharmacies; Pharmacists; Pharmacy; Abdominal Pain; Endoscopy, Gastrointestinal; Proton Pump Inhibitors; Prescriptions; Inappropriate Prescribing; Tertiary Care Centers
  9. Baharuddin MY, Salleh ShH, Zulkifly AH, Lee MH, Mohd Noor A
    Biomed Res Int, 2014;2014:692328.
    PMID: 25025068 DOI: 10.1155/2014/692328
    A morphology study was essential to the development of the cementless femoral stem because accurate dimensions for both the periosteal and endosteal canal ensure primary fixation stability for the stem, bone interface, and prevent stress shielding at the calcar region. This paper focused on a three-dimensional femoral model for Asian patients that applied preoperative planning and femoral stem design. We measured various femoral parameters such as the femoral head offset, collodiaphyseal angle, bowing angle, anteversion, and medullary canal diameters from the osteotomy level to 150 mm below the osteotomy level to determine the position of the isthmus. Other indices and ratios for the endosteal canal, metaphyseal, and flares were computed and examined. The results showed that Asian femurs are smaller than Western femurs, except in the metaphyseal region. The canal flare index (CFI) was poorly correlated (r < 0.50) to the metaphyseal canal flare index (MCFI), but correlated well (r = 0.66) with the corticomedullary index (CMI). The diversity of the femoral size, particularly in the metaphyseal region, allows for proper femoral stem design for Asian patients, improves osseointegration, and prolongs the life of the implant.
    MeSH terms: Adult; Ethnic Groups; Female; Femur/anatomy & histology*; Femur/pathology; Femur/radiography; Femur Head/anatomy & histology*; Femur Head/pathology; Femur Head/radiography; Hip Prosthesis; Humans; Male; Prosthesis Design/methods; Stress, Mechanical; Tomography, X-Ray Computed; Osseointegration*; Arthroplasty, Replacement, Hip*
  10. Rahman HS, Rasedee A, Yeap SK, Othman HH, Chartrand MS, Namvar F, et al.
    Biomed Res Int, 2014;2014:920742.
    PMID: 25025076 DOI: 10.1155/2014/920742
    Zerumbone (ZER) is a naturally occurring dietary compound, present in many natural foods consumed today. The compound derived from several plant species of the Zingiberaceae family that has been found to possess multiple biomedical properties, such as antiproliferative, antioxidant, anti-inflammatory, and anticancer activities. However, evidence of efficacy is sparse, pointing to the need for a more systematic review for assessing scientific evidence to support therapeutic claims made for ZER and to identify future research needs. This review provides an updated overview of in vitro and in vivo investigations of ZER, its cancer chemopreventive properties, and mechanisms of action. Therapeutic effects of ZER were found to be scientifically plausible and could be explained partially by in vivo and in vitro pharmacological activities. Much of the research outlined in this paper will serve as a foundation to explain ZER anticancer bioactivity, which will open the door for the development of strategies in the treatment of malignancies using ZER.
    MeSH terms: Antioxidants/administration & dosage; Antioxidants/therapeutic use; Diet; Humans; Neoplasms/drug therapy*; Neoplasms/pathology; Sesquiterpenes/therapeutic use*; Sesquiterpenes/chemistry; Apoptosis/drug effects; Chemoprevention*; Zingiberaceae/chemistry; Cell Proliferation/drug effects*
  11. Raj K, Kiliçman A
    ScientificWorldJournal, 2014;2014:398203.
    PMID: 25025085 DOI: 10.1155/2014/398203
    We construct some generalized difference Hahn sequence spaces by mean of sequence of modulus functions. The topological properties and some inclusion relations of spaces h p ((F, u, Δ(r)) are investigated. Also we compute the dual of these spaces, and some matrix transformations are characterized.
    MeSH terms: Mathematical Concepts*
  12. Wilson HB, Meijaard E, Venter O, Ancrenaz M, Possingham HP
    PLoS One, 2014;9(7):e102174.
    PMID: 25025134 DOI: 10.1371/journal.pone.0102174
    The Sumatran orangutan is currently listed by the IUCN as critically endangered and the Bornean species as endangered. Unless effective conservation measures are enacted quickly, most orangutan populations without adequate protection face a dire future. Two main strategies are being pursued to conserve orangutans: (i) rehabilitation and reintroduction of ex-captive or displaced individuals; and (ii) protection of their forest habitat to abate threats like deforestation and hunting. These strategies are often mirrored in similar programs to save other valued and endangered mega-fauna. Through GIS analysis, collating data from across the literature, and combining this information within a modelling and decision analysis framework, we analysed which strategy or combination of strategies is the most cost-effective at maintaining wild orangutan populations, and under what conditions. We discovered that neither strategy was optimal under all circumstances but was dependent on the relative cost per orangutan, the timescale of management concern, and the rate of deforestation. Reintroduction, which costs twelve times as much per animal as compared to protection of forest, was only a cost-effective strategy at very short timescales. For time scales longer than 10-20 years, forest protection is the more cost-efficient strategy for maintaining wild orangutan populations. Our analyses showed that a third, rarely utilised strategy is intermediate: introducing sustainable logging practices and protection from hunting in timber production forest. Maximum long-term cost-efficiency is achieved by working in conservation forest. However, habitat protection involves addressing complex conservation issues and conflicting needs at the landscape level. We find a potential resolution in that well-managed production forests could achieve intermediate conservation outcomes. This has broad implications for sustaining biodiversity more generally within an economically productive landscape. Insights from this analysis should provide a better framework to prioritize financial investments, and facilitate improved integration between the organizations that implement these strategies.
    MeSH terms: Animals; Asia, Southeastern; Conservation of Natural Resources*; Pongo pygmaeus*; Population Dynamics; Ecosystem; Endangered Species; Forests
  13. Ibitoye MO, Estigoni EH, Hamzaid NA, Wahab AK, Davis GM
    Sensors (Basel), 2014;14(7):12598-622.
    PMID: 25025551 DOI: 10.3390/s140712598
    The evoked electromyographic signal (eEMG) potential is the standard index used to monitor both electrical changes within the motor unit during muscular activity and the electrical patterns during evoked contraction. However, technical and physiological limitations often preclude the acquisition and analysis of the signal especially during functional electrical stimulation (FES)-evoked contractions. Hence, an accurate quantification of the relationship between the eEMG potential and FES-evoked muscle response remains elusive and continues to attract the attention of researchers due to its potential application in the fields of biomechanics, muscle physiology, and rehabilitation science. We conducted a systematic review to examine the effectiveness of eEMG potentials to assess muscle force and fatigue, particularly as a biofeedback descriptor of FES-evoked contractions in individuals with spinal cord injury. At the outset, 2867 citations were identified and, finally, fifty-nine trials met the inclusion criteria. Four hypotheses were proposed and evaluated to inform this review. The results showed that eEMG is effective at quantifying muscle force and fatigue during isometric contraction, but may not be effective during dynamic contractions including cycling and stepping. Positive correlation of up to r = 0.90 (p < 0.05) between the decline in the peak-to-peak amplitude of the eEMG and the decline in the force output during fatiguing isometric contractions has been reported. In the available prediction models, the performance index of the eEMG signal to estimate the generated muscle force ranged from 3.8% to 34% for 18 s to 70 s ahead of the actual muscle force generation. The strength and inherent limitations of the eEMG signal to assess muscle force and fatigue were evident from our findings with implications in clinical management of spinal cord injury (SCI) population.
    MeSH terms: Electromyography/methods*; Humans; Muscle Contraction*; Synaptic Transmission; Neuromuscular Junction; Spinal Cord Injuries/diagnosis; Spinal Cord Injuries/physiopathology*; Muscle, Skeletal/physiopathology*; Muscle Fatigue*; Evidence-Based Medicine; Muscle Strength*; Spinal Cord Stimulation/methods*
  14. Umar MI, Asmawi MZ, Sadikun A, Abdul Majid AM, Atangwho IJ, Khadeer Ahamed MB, et al.
    Pharm Biol, 2014 Nov;52(11):1411-22.
    PMID: 25026347 DOI: 10.3109/13880209.2014.895017
    Azadirachta indica A. Juss. (Meliaceaes) leaves have been used traditionally to treat swelling and rheumatism in Indian cultures.
    MeSH terms: Animals; Anti-Inflammatory Agents/isolation & purification; Anti-Inflammatory Agents/therapeutic use*; Dose-Response Relationship, Drug; Drug Synergism; Edema/blood; Edema/drug therapy*; Edema/pathology; Female; Humans; Male; Plant Extracts/isolation & purification; Plant Extracts/therapeutic use*; Sheep; Treatment Outcome; Rats, Sprague-Dawley; Plant Leaves*; Azadirachta*; Rats
  15. Kumar S, Neven LG, Yee WL
    J Econ Entomol, 2014 Jun;107(3):1032-44.
    PMID: 25026662
    Sweet cherries, Prunus avium (L.) L., grown in the western United States are exported to many countries around the world. Some of these countries have enforced strict quarantine rules and trade restrictions owing to concerns about the potential establishment and subsequent spread of western cherry fruit fly, Rhagoletis indifferens Curran (Diptera: Tephritidae), a major quarantine pest of sweet cherry. We used 1) niche models (CLIMEX and MaxEnt) to map the climatic suitability, 2) North Carolina State University-Animal and Plant Health Inspection Service Plant Pest Forecasting System to examine chilling requirement, and 3) host distribution and availability to assess the potential for establishment of R. indifferens in areas of western North America where it currently does not exist and eight current or potential fresh sweet cherry markets: Colombia, India, Indonesia, Malaysia, Taiwan, Thailand, Venezuela, and Vietnam. Results from niche models conformed well to the current distribution of R. indifferens in western North America. MaxEnt and CLIMEX models had high performance and predicted climatic suitability in some of the countries (e.g., Andean range in Colombia and Venezuela, northern and northeastern India, central Taiwan, and parts of Vietnam). However, our results showed no potential for establishment of R. indifferens in Colombia, Indonesia, Malaysia, Taiwan, Thailand, Venezuela, and Vietnam when the optimal chilling requirement to break diapause (minimum temperature < or = 3 degree C for at least 15 wk) was used as the criterion for whether establishment can occur. Furthermore, these countries have no host plant species available for R. indifferens. Our results can be used to make scientifically informed international trade decisions and negotiations by policy makers.
    MeSH terms: Animals; Asia; Fruit/growth & development; Models, Biological; North America; South America; Ecosystem*; Food Chain*; Prunus/growth & development; Tephritidae/physiology*; Geographic Mapping; Animal Distribution*
  16. Al Joudi FS
    Indian J Med Res, 2014 May;139(5):675-85.
    PMID: 25027076
    Human mammaglobin is a member of the uteroglobin proteins family that has recently been tested as a specific marker for breast cancer. While low levels may be seen in normal breast tissue, expression is increased dramatically in breast cancer and is correlated with higher grade. Detection in blood and body fluids is also correlated with cancer metastasis, and its levels with prognosis. This promises to be a useful screen for early detection of breast cancer, especially in high risk individuals. Mammoglobin has also been used for immunotherapeutic targeting of breast cancer cells. However, there are some controversies regarding its diagnostic efficacy and prognostic value, which warrant further study.
    MeSH terms: Breast Neoplasms/blood*; Breast Neoplasms/diagnosis; Breast Neoplasms/genetics; Female; Humans; Lymphatic Metastasis/genetics*; Prognosis; RNA, Messenger/biosynthesis; RNA, Messenger/blood; Biomarkers, Tumor/blood; Uteroglobin/blood*; Mammaglobin A/biosynthesis; Mammaglobin A/blood*
  17. Rullah K, Mohd Aluwi MF, Yamin BM, Abdul Bahari MN, Wei LS, Ahmad S, et al.
    Bioorg Med Chem Lett, 2014 Aug 15;24(16):3826-34.
    PMID: 25027933 DOI: 10.1016/j.bmcl.2014.06.061
    The discovery of potent inhibitors of prostaglandin E2 (PGE2) synthesis in recent years has been proven to be an important game changer in pharmaceutical industry. It is known that excessive production of PGE2 triggers a vast array of biological signals and physiological events that contributes to inflammatory diseases such as rheumatoid arthritis, atherosclerosis, cancer, and pain. In this Letter, we report the synthesis of a series of minor prenylated chalcones and flavonoids which was found to be significantly active in suppressing the PGE2 production secreted by lipopolysaccharide-induced mouse macrophage cells (RAW 264.7). Among the compounds tested, 14b showed a dose-response inhibition of PGE2 production with an IC50 value of 2.1 μM. The suppression upon PGE2 secretion was not due to cell death since 14b did not reduce the cell viability in close proximity to the PGE2 inhibition concentration. The obtained atomic coordinates for the single-crystal XRD of 14b was then applied in the docking simulation to determine the potential important binding interactions with murine COX-2 and mPGES-1 putative binding sites.
    MeSH terms: Animals; Binding Sites/drug effects; Cell Line; Cell Survival/drug effects; Dose-Response Relationship, Drug; Flavonoids/chemical synthesis; Flavonoids/pharmacology*; Flavonoids/chemistry; Humans; Lipopolysaccharides/antagonists & inhibitors; Lipopolysaccharides/pharmacology; Models, Molecular; Structure-Activity Relationship; Dinoprostone/antagonists & inhibitors*; Dinoprostone/biosynthesis; Molecular Structure; Intramolecular Oxidoreductases/metabolism; Chalcones/chemical synthesis; Chalcones/pharmacology*; Chalcones/chemistry; Mice; Cyclooxygenase 2/metabolism
  18. Monika, Sharma A, Suthar SK, Aggarwal V, Lee HB, Sharma M
    Bioorg Med Chem Lett, 2014 Aug 15;24(16):3814-8.
    PMID: 25027934 DOI: 10.1016/j.bmcl.2014.06.068
    The new series of pentacyclic triterpenoids reduced lantadene A (3), B (4), and 22β-hydroxy-3-oxo-olean-12-en-28-oic acid (5) analogs were synthesized and tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead analog (11) showed sub-micromolar activity against TNF-α induced activation of NF-κB and exhibited inhibition of IKKβ in a single-digit micromolar dose. At the same time, 11 showed promising cytotoxicity against A549 lung cancer cells with IC50 of 0.98 μM. The Western blot analysis further showed that the suppression of NF-κB activity by the lead analog 11 was due to the inhibition of IκBα degradation, a natural inhibitor of NF-κB. The physicochemical evaluation demonstrated that the lead analog 11 was stable in the simulated gastric fluid of pH 2, while hydrolyzed at a relatively higher rate in the human blood plasma to release the active parent moieties. Molecular docking analysis showed that 11 was hydrogen bonded with the Arg-31 and Gln-110 residues of the IKKβ.
    MeSH terms: Adenocarcinoma/drug therapy*; Adenocarcinoma/metabolism; Adenocarcinoma/pathology; Antineoplastic Agents/chemical synthesis*; Antineoplastic Agents/pharmacology*; Antineoplastic Agents/chemistry; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Lung Neoplasms/drug therapy*; Lung Neoplasms/metabolism; Lung Neoplasms/pathology; Oleanolic Acid/analogs & derivatives*; Oleanolic Acid/chemical synthesis; Oleanolic Acid/pharmacology; Oleanolic Acid/chemistry; Structure-Activity Relationship; Tumor Necrosis Factor-alpha/pharmacology*; Molecular Structure; NF-kappa B/metabolism*; Cell Line, Tumor; Cell Proliferation/drug effects; Molecular Docking Simulation
  19. Chiari L, Duque HV, Jones DB, Thorn PA, Pettifer Z, da Silva GB, et al.
    J Chem Phys, 2014 Jul 14;141(2):024301.
    PMID: 25028013 DOI: 10.1063/1.4885856
    We report on measurements of differential cross sections (DCSs) for electron impact excitation of a series of Rydberg electronic-states in α-tetrahydrofurfuryl alcohol (THFA). The energy range of these experiments was 20-50 eV, while the scattered electron was detected in the 10°-90° angular range. There are currently no other experimental data or theoretical computations against which we can directly compare the present measured results. Nonetheless, we are able to compare our THFA DCSs with earlier cross section measurements for Rydberg-state electronic excitation for tetrahydrofuran, a similar cyclic ether, from Do et al. [J. Chem. Phys. 134, 144302 (2011)]. In addition, "rotationally averaged" elastic DCSs, calculated using our independent atom model with screened additivity rule correction approach are also reported. Those latter results give integral cross sections consistent with the optical theorem, and supercede those from the only previous study of Milosavljević et al. [Eur. Phys. J. D 40, 107 (2006)].
    MeSH terms: Electronics*; Electrons; Energy Transfer; Furans/chemistry*; Models, Theoretical*
  20. Tey S, Ahmad-Annuar A, Drew AP, Shahrizaila N, Nicholson GA, Kennerson ML
    Neurogenetics, 2014 Oct;15(4):229-35.
    PMID: 25028179 DOI: 10.1007/s10048-014-0414-0
    The cytoplasmic dynein heavy chain (DYNC1H1) gene has been increasingly associated with neurodegenerative disorders including axonal Charcot-Marie-Tooth disease (CMT2), intellectual disability and malformations of cortical development. In addition, evidence from mouse models (Loa, catabolite repressor-activator (Cra) and Sprawling (Swl)) has shown that mutations in Dync1h1 cause a range of neurodegenerative phenotypes with motor and sensory neuron involvement. In this current study, we examined the possible contribution of other cytoplasmic dynein subunits that bind to DYNC1H1 as a cause of inherited peripheral neuropathy. We focused on screening the cytoplasmic dynein intermediate, light intermediate and light chain genes in a cohort of families with inherited peripheral neuropathies. Nine genes were screened and ten variants were detected, but none was identified as pathogenic, indicating that cytoplasmic dynein intermediate, light intermediate and light chains are not a cause of neuropathy in our cohort.
    MeSH terms: DNA-Binding Proteins; Female; Genetic Testing; Humans; Male; Mutation; Peripheral Nervous System Diseases/genetics*; Cytoplasmic Dyneins/genetics*
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