Browse publications by year: 2017

  1. Li Y, Qin T, Ingle T, Yan J, He W, Yin JJ, et al.
    Arch Toxicol, 2017 Jan;91(1):509-519.
    PMID: 27180073 DOI: 10.1007/s00204-016-1730-y
    In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. A key question is whether the observed toxicity comes from the silver ions (Ag(+)) released from the AgNPs or from the nanoparticles themselves. In this study, we explored the genotoxicity and the genotoxicity mechanisms of Ag(+) and AgNPs. Human TK6 cells were treated with 5 nM AgNPs or silver nitrate (AgNO3) to evaluate their genotoxicity and induction of oxidative stress. AgNPs and AgNO3 induced cytotoxicity and genotoxicity in a similar range of concentrations (1.00-1.75 µg/ml) when evaluated using the micronucleus assay, and both induced oxidative stress by measuring the gene expression and reactive oxygen species in the treated cells. Addition of N-acetylcysteine (NAC, an Ag(+) chelator) to the treatments significantly decreased genotoxicity of Ag(+), but not AgNPs, while addition of Trolox (a free radical scavenger) to the treatment efficiently decreased the genotoxicity of both agents. In addition, the Ag(+) released from the highest concentration of AgNPs used for the treatment was measured. Only 0.5 % of the AgNPs were ionized in the culture medium and the released silver ions were neither cytotoxic nor genotoxic at this concentration. Further analysis using electron spin resonance demonstrated that AgNPs produced hydroxyl radicals directly, while AgNO3 did not. These results indicated that although both AgNPs and Ag(+) can cause genotoxicity via oxidative stress, the mechanisms are different, and the nanoparticles, but not the released ions, mainly contribute to the genotoxicity of AgNPs.
    MeSH terms: Acetylcysteine/pharmacology; Cell Line; Cell Survival/drug effects; Chelating Agents/pharmacology; Chromans/pharmacology; Gene Expression Regulation/drug effects; Humans; Kinetics; Lymphocytes/drug effects*; Lymphocytes/enzymology; Lymphocytes/metabolism; Mutagens/analysis; Mutagens/toxicity*; Mutagens/chemistry; Particle Size; Silver/analysis; Silver/toxicity*; Silver/chemistry; Silver Nitrate/antagonists & inhibitors; Silver Nitrate/toxicity; Solubility; Surface Properties; Micronucleus Tests; Free Radical Scavengers/pharmacology; Reactive Oxygen Species/antagonists & inhibitors; Reactive Oxygen Species/metabolism; Reactive Oxygen Species/agonists; Oxidative Stress/drug effects*; Metal Nanoparticles/toxicity*
  2. Chiew MY, Boo NY, Voon K, Cheong SK, Leong PP
    Leuk Lymphoma, 2017 01;58(1):162-170.
    PMID: 27185517
    Acute monocytic leukemia (AML-M5), a subtype of acute myeloid leukemia (AML), affects mostly young children and has poor prognosis. The mechanisms of treatment failure of AML-M5 are still unclear. In this study, we generated iPSC from THP-1 cells from a patient with AML-M5, using retroviruses encoding the pluripotency-associated genes (OCT3/4, SOX2, KLF4 and c-MYC). These AML-M5-derived iPSC showed features similar with those of human embryonic stem cells in terms of the morphology, gene expression, protein/antigen expression and differentiation capability. Parental-specific markers were down-regulated in these AML-M5-derived iPSCs. Expression of MLL-AF9 fusion gene (previously identified to be associated with pathogenesis of AML-M5) was observed in all iPSC clones as well as parental cells. We conclude that AML-M5-specific iPSC clones have been successfully developed. This disease model may provide a novel approach for future study of pathogenesis and therapeutic intervention of AML-M5.
    MeSH terms: Animals; Cell Differentiation/genetics; Cell Line; Cell Transformation, Neoplastic/genetics*; Cell Transformation, Neoplastic/metabolism; Germ Layers/cytology; Germ Layers/metabolism; Humans; Leukemia, Monocytic, Acute/genetics*; Leukemia, Monocytic, Acute/metabolism; Leukemia, Monocytic, Acute/pathology; Organ Specificity/genetics; Stem Cells/metabolism*; Stem Cells/pathology; Biomarkers; Oncogene Proteins, Fusion/genetics*; Oncogene Proteins, Fusion/metabolism; Gene Expression; Gene Expression Profiling; Myeloid-Lymphoid Leukemia Protein/genetics*; Myeloid-Lymphoid Leukemia Protein/metabolism; Induced Pluripotent Stem Cells/metabolism; Cellular Reprogramming
  3. Liyanage T, Ninomiya T, Perkovic V, Woodward M, Stirnadel-Farrant H, Matsushita K, et al.
    Nephrology (Carlton), 2017 Jun;22(6):456-462.
    PMID: 27187157 DOI: 10.1111/nep.12821
    AIM: The burden of chronic kidney disease (CKD) is growing rapidly around the world. However, there is limited information on the overall regional prevalence of CKD, as well as the prognostic implications and treatment patterns in Asian region. We have established the Asian Renal Collaboration (ARC) with the goal of consolidating region-wide data regarding CKD.

    METHODS: This collaborative project will synthesize data and perform meta-analyses of observational studies conducted in Asia. Studies will be identified through a systematic literature search including abstracts, proceedings of meetings, electronic databases such as MEDLINE and EMBASE. Personal enquiry among collaborators and experts in the region will identify additional studies, or other data sources such as registries. Both cross-sectional and longitudinal studies that describe the prevalence of CKD and its complications will be included, as will longitudinal studies that describe important clinical outcomes for people with CKD. Individual participant data will be sought, where possible, from each of the studies included in the collaboration for baseline parameters and subsequent outcomes, in order to maximize flexibility and consistency of data analyses.

    CONCLUSIONS: This study is an initiative offering a unique opportunity to obtain information about the prevalence and manifestations of CKD in Asia, as well as its risk factors. The ARC will also provide insights into important outcomes including progression of CKD, CKD complications, cardiovascular disease and death. These findings will improve our understanding of kidney disease in Asia, and thus help inform service provision, preventive care and further research across the region.

    MeSH terms: Asia/epidemiology; Humans; Meta-Analysis as Topic; Prevalence; Renal Insufficiency, Chronic/epidemiology*
  4. Viecelli AK, Pascoe EM, Polkinghorne KR, Hawley CM, Paul-Brent PA, Badve SV, et al.
    Nephrology (Carlton), 2017 10;22(10):823-824.
    PMID: 27188542 DOI: 10.1111/nep.12823
    MeSH terms: Arteriovenous Shunt, Surgical; Aspirin; Fish Oils*; Humans; Kidney Diseases; Fatty Acids, Omega-3*
  5. Kho CM, Enche Ab Rahim SK, Ahmad ZA, Abdullah NS
    Mol Neurobiol, 2017 07;54(5):3506-3527.
    PMID: 27189617 DOI: 10.1007/s12035-016-9929-8
    Microdialysis is a sampling technique first introduced in the late 1950s. Although this technique was originally designed to study endogenous compounds in animal brain, it is later modified to be used in other organs. Additionally, microdialysis is not only able to collect unbound concentration of compounds from tissue sites; this technique can also be used to deliver exogenous compounds to a designated area. Due to its versatility, microdialysis technique is widely employed in a number of areas, including biomedical research. However, for most in vivo studies, the concentration of substance obtained directly from the microdialysis technique does not accurately describe the concentration of the substance on-site. In order to relate the results collected from microdialysis to the actual in vivo condition, a calibration method is required. To date, various microdialysis calibration methods have been reported, with each method being capable to provide valuable insights of the technique itself and its applications. This paper aims to provide a critical review on various calibration methods used in microdialysis applications, inclusive of a detailed description of the microdialysis technique itself to start with. It is expected that this article shall review in detail, the various calibration methods employed, present examples of work related to each calibration method including clinical efforts, plus the advantages and disadvantages of each of the methods.
    MeSH terms: Calibration; Reference Standards; Microdialysis/methods*
  6. Chew KS, Shaharudin AH
    Singapore Med J, 2017 Oct;58(10):601-605.
    PMID: 27193080 DOI: 10.11622/smedj.2016096
    INTRODUCTION: The use of intranasal fentanyl as an alternative type of analgesia has been shown to be effective in paediatric populations and prehospital settings. There are a limited number of studies on the use of intranasal fentanyl in adult patients in emergency settings.

    METHODS: An open-label study was conducted to evaluate the effectiveness of the addition of 1.5 mcg/kg intranasal fentanyl to 2 mg/kg intravenous tramadol (fentanyl + tramadol arm, n = 10) as compared to the administration of 2 mg/kg intravenous tramadol alone (tramadol-only arm, n = 10) in adult patients with moderate to severe pain due to acute musculoskeletal injuries.

    RESULTS: When analysed using the independent t-test, the difference between the mean visual analogue scale scores pre-intervention and ten minutes post-intervention was 29.8 ± 8.4 mm in the fentanyl + tramadol arm and 19.6 ± 9.7 mm in the tramadol-only arm (t[18] = 2.515, p = 0.022, 95% confidence interval 1.68-18.72 mm). A statistically significant, albeit transient, reduction in the ten-minute post-intervention mean arterial pressure was noted in the fentanyl + tramadol arm as compared to the tramadol-only arm (13.35 mmHg vs. 7.65 mmHg; using Mann-Whitney U test with U-value 21.5, p = 0.029, r = 0.48). There was a higher incidence of transient dizziness ten minutes after intervention among the patients in the fentanyl + tramadol arm.

    CONCLUSION: Although effective, intranasal fentanyl may not be appropriate for routine use in adult patients, as it could result in a significant reduction in blood pressure.

    MeSH terms: Administration, Intranasal; Adolescent; Adult; Aged; Analgesics, Opioid/therapeutic use; Bone and Bones/injuries*; Dizziness; Female; Fentanyl/administration & dosage*; Humans; Malaysia; Male; Middle Aged; Muscles/injuries*; Pain Measurement; Prospective Studies; Tramadol/administration & dosage*; Treatment Outcome; Young Adult; Musculoskeletal Pain/drug therapy*; Pain Management; Administration, Intravenous; Tertiary Care Centers
  7. Manap HH, Abdul Wahab AK
    J Artif Organs, 2017 Mar;20(1):8-17.
    PMID: 27193131 DOI: 10.1007/s10047-016-0905-x
    The implementation of extracorporeal carbon dioxide removal (ECCO2R) as one of the extracorporeal life support system is getting more attention today. Thus, the objectives of this paper are to study the clinical practice of commercial ECCO2R system, current trend of its development and also the perspective on future improvement that can be done to the existing ECCO2R system. The strength of this article lies in its review scope, which focuses on the commercial ECCO2R therapy in the market based on membrane lung and current investigation to improve the efficiency of the ECCO2R system, in terms of surface modification by carbonic anhydrase (CA) immobilization technique and respiratory electrodialysis (R-ED). Our methodology approach involves the identification of relevant published literature from PubMed and Web of Sciences search engine using the terms Extracorporeal Carbon Dioxide Removal (ECCO2R), Extracorporeal life support, by combining terms between ECCO2R and CA and also ECCO2R with R-ED. This identification only limits articles in English language. Overall, several commercial ECCO2R systems are known and proven safe to be used in patients in terms of efficiency, safety and risk of complication. In addition, CA-modified hollow fiber for membrane lung and R-ED are proven to have good potential to be applied in conventional ECCO2R design. The detailed technique and current progress on CA immobilization and R-ED development were also reviewed in this article.
    MeSH terms: Carbon Dioxide; Extracorporeal Circulation/methods*; Humans; Respiratory Insufficiency/therapy*; Extracorporeal Membrane Oxygenation/methods*
  8. Ho WY, Choo QC, Chew CH
    Microb Drug Resist, 2017 Mar;23(2):215-223.
    PMID: 27203527 DOI: 10.1089/mdr.2015.0250
    We investigated the epidemiology and clonality of 175 nonrepetitive methicillin-resistant Staphylococcus aureus (MRSA) isolates from clinical specimens collected between 2011 and 2012 in Kinta Valley in Malaysia. Molecular tools such as polymerase chain reaction, pulsed-field gel electrophoresis, and staphylococcal protein A (spa) typing were used. Our study revealed the predominance of three closely related ermA(+) SCCmec type III pulsotypes belonging to spa type t037 (Brazilian-Hungarian clone), which were deficient in the locus F, but positive for the ccrC gene in majority (65.7%) of the MRSA infections in this region. The first evidence of SCCmec type II MRSA in the country, belonging to spa type t2460, was also noted. Although the carriage of pvl gene was uncommon (8.6%) and mostly confined to either SCCmec type IV or SCCmec type V isolates, most of these isolates belonged to spa types t345 or t657, which are associated with the Bengal-Bay CA-MRSA clone. Interestingly, spa t304 and t690 SCCmec type IV pvl(+) were also detected among the MRSA isolates. Data from this study show the rise of uncommon clones among MRSA isolates in Malaysia.
    MeSH terms: Bacterial Proteins/genetics*; Brazil; Cross Infection/microbiology; Cross Infection/epidemiology; Genes, Bacterial/genetics*; Humans; Malaysia/epidemiology; Staphylococcal Infections/microbiology*; Staphylococcal Infections/epidemiology*; Staphylococcal Protein A/genetics*; Molecular Epidemiology/methods; Recombinases/genetics*; Methicillin-Resistant Staphylococcus aureus/genetics*; Methicillin-Resistant Staphylococcus aureus/isolation & purification*
  9. Parvizpour S, Razmara J, Shamsir MS, Illias RM, Abdul Murad AM
    J Biomol Struct Dyn, 2017 06;35(8):1685-1692.
    PMID: 27206405 DOI: 10.1080/07391102.2016.1191043
    MeSH terms: Adaptation, Physiological/genetics*; Amino Acid Sequence/genetics; Cold Temperature; Protein Conformation; Salts/chemistry; Cellulases/genetics; Cellulases/physiology; Cellulases/chemistry*
  10. Mohd Hasni DS, Lim SM, Chin AV, Tan MP, Poi PJH, Kamaruzzaman SB, et al.
    Geriatr Gerontol Int, 2017 May;17(5):839-846.
    PMID: 27215446 DOI: 10.1111/ggi.12783
    AIM: Cytokines released from chronically-activated microglia could result in neuroinflammation. An accurate profile of the relationship between cytokines and Alzheimer's disease (AD) pathogenesis, as well as the patterns of these inflammatory mediators in AD patients could lead to the identification of peripheral markers for the disease. The present study was undertaken to identify pro- and anti-inflammatory cytokines associated with AD in the Malaysian population.

    METHODS: Further to informed consent from 39 healthy subjects and 39 probable AD patients, 8.5 mL of peripheral blood was collected and serum was extracted. The differential levels of 12 serum cytokines extracted from peripheral blood samples were measured using Procarta Multiplex Cytokine and enzyme-linked immunoassay kits. Concentrations of cytokines were measured at 615 nm using a fluorometer.

    RESULTS: Except for tumor necrosis factor-α, all classical pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-12 and interferon-γ) were found to be significantly upregulated (P 53.65 ρg/mL and <9.315 ρg/mL, respectively).

    CONCLUSIONS: Both the non-classical pro-inflammatory CXCL-10 and anti-inflammatory IL-13 cytokines showed promising potential as blood-based cytokine biomarkers for AD. This is the first study of non-classical cytokine profiles of Malaysian AD patients. Geriatr Gerontol Int 2017; 17: 839-846.

    MeSH terms: Aged; Aged, 80 and over; Alzheimer Disease/blood*; Alzheimer Disease/diagnosis; Alzheimer Disease/epidemiology; Enzyme-Linked Immunosorbent Assay; Female; Fluorometry; Humans; Malaysia/epidemiology; Male; Tumor Necrosis Factor-alpha/blood; Biomarkers/blood; Prevalence; Cytokines/blood*; Interleukin-13/blood*
  11. Keshavarzifard M, Zakaria MP, Hwai TS
    Environ Geochem Health, 2017 Jun;39(3):591-610.
    PMID: 27216263 DOI: 10.1007/s10653-016-9835-z
    The bioaccumulation and bioavailability of polycyclic aromatic hydrocarbons (PAHs) were characterized in sediment and Paphia undulata (short-neck clam) from six mudflat areas in the west coasts of Peninsular Malaysia. The concentrations of total PAHs varied from 357.1 to 6257.1 and 179.9 ± 7.6 to 1657.5 ± 53.9 ng g -1 dry weight in sediment and short-neck clam samples, respectively. PAHs can be classified as moderate to very high level of pollution in sediments and moderate to high level of pollution in short-neck clams. The diagnostic ratios of individual PAHs and principal component analysis indicate both petrogenic and pyrogenic sources with significant dominance of pyrogenic source. The first PAHs biota-sediment accumulation factors and relative biota-sediment accumulation factors data for short-neck clam were obtained in this study, indicating a preferential accumulation of lower molecular weight PAHs. Evaluation of PAH levels in sediments and short-neck clams indicates that short-neck clam could be introduced as a good biomonitor in mudflats. The results also demonstrated that under environmental conditions, the sedimentary load of hydrocarbons appears to be one of the factors controlling their bioavailability to biota.
    MeSH terms: Animals; Biological Availability; Environmental Monitoring; Malaysia; Polycyclic Hydrocarbons, Aromatic/pharmacokinetics*; Water Pollutants, Chemical/pharmacokinetics*; Ecosystem; Bivalvia/metabolism*
  12. Bakhtiyari E, Ahmadian-Attari MM, Salehi P, Khallaghi B, Dargahi L, Mohamed Z, et al.
    Nutr Neurosci, 2017 Oct;20(8):469-477.
    PMID: 27219682 DOI: 10.1080/1028415X.2016.1183986
    OBJECTIVES: Although grape has been recently the topic of many investigations, Maviz (a kind of dried one) has remained neglected. The aim of this study was to assess anti-Alzheimer activity of Maviz.

    METHODS: To reach this goal, total phenolic content (TPC) of ethanolic (Eth) and aqueous (Aq) extracts were determined and radical scavenging activity was assayed by 2,2-diphenyl-1-picrylhydrazyl. Chemical compositions of each extract were also determined via GC-Mass. Behavioral changes were studied via passive avoidance and Morris water maze in Aβ-induced model of Alzheimer's disease. Catalase (CAT) and superoxide dismutase (SOD) determination were also done on rats' hippocampus.

    RESULTS: The results showed that seed Eth extract has a high level of TPC and radical scavenging activity. However, this extract had surprisingly no effect on memory and CAT and SOD activities. In contrast, fruit Aq and Eth extracts (containing furfurals as major compounds) inhibited memory impairment (P 

    MeSH terms: Alzheimer Disease/drug therapy; Animals; Antioxidants/administration & dosage; Antioxidants/analysis; Avoidance Learning; Disease Models, Animal; Fruit/chemistry*; Furaldehyde/analogs & derivatives; Furaldehyde/analysis; Furaldehyde/pharmacology; Hippocampus/enzymology; Iran; Male; Memory/drug effects; Phenols/administration & dosage; Phenols/analysis; Plant Extracts/administration & dosage*; Plant Extracts/adverse effects; Plant Extracts/chemistry; Seeds/chemistry; Free Radical Scavengers/analysis; Amyloid beta-Peptides/pharmacology*; Rats, Wistar; Maze Learning/drug effects; Vitis/chemistry*; Rats; Food, Preserved; Phytochemicals/analysis
  13. Asaithambi P, Aziz ARA, Sajjadi B, Daud WMABW
    Environ Sci Pollut Res Int, 2017 Feb;24(6):5168-5178.
    PMID: 27221586 DOI: 10.1007/s11356-016-6909-5
    In the present work, the efficiency of the sonication, electrocoagulation, and sono-electrocoagulation process for removal of pollutants from the industrial effluent of the pulp and paper industry was compared. The experimental results showed that the sono-electrocoagulation process yielded higher pollutant removal percentage compared to the sonication and electrocoagulation process alone. The effect of the operating parameters in the sono-electrocoagulation process such as electrolyte concentration (1-5 g/L), current density (1-5 A/dm(2)), effluent pH (3-11), COD concentration (1500-6000 mg/L), inter-electrode distance (1-3 cm), and electrode combination (Fe and Al) on the color removal, COD removal, and power consumption were studied. The maximum color and COD removal percentages of 100 and 95 %, respectively, were obtained at the current density of 4 A/dm(2), electrolyte concentration of 4 g/L, effluent pH of 7, COD concentration of 3000 mg/L, electrode combination of Fe/Fe, inter-electrode distance of 1 cm, and reaction time of 4 h, respectively. The color and COD removal percentages were analyzed by using an UV/Vis spectrophotometer and closed reflux method. The results showed that the sono-electrocoagulation process could be used as an efficient and environmental friendly technique for complete pollutant removal.
    MeSH terms: Color; Electrocoagulation/methods*; Electrodes; Electrolytes; Hydrogen-Ion Concentration; Industrial Waste*; Paper; Waste Disposal, Fluid/methods; Water Purification/methods*
  14. Chakraborty C, Teoh SL, Das S
    Curr Drug Targets, 2017;18(14):1653-1663.
    PMID: 27231109 DOI: 10.2174/1389450117666160527142321
    BACKGROUND: The present era is fast experiencing rapid innovation in the genome-editing technology. CRISPR Cas9-mediated targeted genetic manipulation is an easy, cost-effective and scalable method. As a result, it can be used for a broad range of targeted genome engineering.

    OBJECTIVE: The main objective of the present review is to highlight the structural signature, classification, its mechanism and application from basic science to medicine and future challenges for this genome editing tool kit.

    RESULTS: The present review provides a brief description of the recent development of CRISPR-Cas9 genome editing technology. We discuss the paradigms shift for this next generation genome editing technology, CRISPR. The CRISPR structural significance, classification and its different applications are also being discussed. We portray the future challenges for this extraordinary genome in vivo editing tool. We also highlight the role of CRISPR genome editing in curing many diseases.

    CONCLUSION: Scientists and researchers are constantly looking one genome editing tool that is competent, simple and low-cost assembly of nucleases. It can target any particular site without any off-target mutations in the genome. The CRISPR-Cas9 has all of the above characteristics. The genome engineering technology may be a strong and inspiring technology meant for the next generation of drug development.

    MeSH terms: Genetic Engineering/methods*; Humans; Clustered Regularly Interspaced Short Palindromic Repeats/genetics*; CRISPR-Cas Systems*; CRISPR-Associated Proteins/genetics*; Gene Editing*
  15. Won H, Abdul Manaf Z, Mat Ludin AF, Shahar S
    Geriatr Gerontol Int, 2017 Apr;17(4):554-560.
    PMID: 27231255 DOI: 10.1111/ggi.12753
    AIM: Studies of the association between body composition, both body fat and body muscle, and cognitive function are rarely reported. The aim of the present study was to determine the association between a wide range of body composition measures with cognitive function in older adults.

    METHODS: A total of 2322 Malaysian older adults aged 60 years and older were recruited using multistage random sampling in a population-based cross-sectional study. Out of 2322 older adults recruited, 2309 (48% men) completed assessments on cognitive function and body composition. Cognitive functions were assessed using the Malay version of the Mini-Mental State Examination, the Bahasa Malaysia version of Montreal Cognitive Assessment, Digit Span Test, Digit Symbol Test and Rey Auditory Verbal Learning Test. Body composition included body mass index, mid-upper arm circumference, waist circumference, calf circumference, waist-to-hip ratio, percentage body fat and skeletal muscle mass.

    RESULTS: The association between body composition and cognitive functions was analyzed using multiple linear regression. After adjustment for age, education years, hypertension, hypercholesterolemia, diabetes mellitus, depression, smoking status and alcohol consumption, we found that calf circumference appeared as a significant predictor for all cognitive tests among both men and women (P 

    MeSH terms: Age Factors; Aged; Body Composition*; Cognition*; Cross-Sectional Studies; Female; Humans; Malaysia; Male; Middle Aged; Sex Factors; Body Mass Index; Linear Models; Independent Living
  16. Chinigarzadeh A, Muniandy S, Salleh N
    Environ Toxicol, 2017 Mar;32(3):832-844.
    PMID: 27235753 DOI: 10.1002/tox.22283
    We hypothesized that genistein can interfere with the regulation of uterine fluid volume, secretion rate and expression of aquaporin in the uterus by female sex-steroids, i.e., estrogen and progesterone. Therefore, the aims of this study were to investigate changes in these parameters in the presence of genistein and female sex-steroids.

    METHODS: Female Sprague-Dawley rats were ovariectomized and received 3-days estradiol-17β benzoate (E2) plus genistein (25, 50, or 100 mg kg(-1)  day(-1) ) or 3-days E2 followed by 3-days E2 plus progesterone with genistein (25, 50, or 100 mg kg(-1)  day(-1) ). A day after last treatment, uterine fluid secretion rate was determined by in vivo uterine perfusion with rats under anesthesia. Animals were sacrificed and uteri were harvested and subjected for histological analyses. Luminal/outer uterine circumference was determined and distribution of AQP-1, 2, 5, and 7 in endometrium was visualized by immunofluorescence. Expression of AQP-1, 2, 5, and 7 proteins and mRNAs were determined by Western blotting and Real-time PCR respectively.

    RESULTS: Combined treatment of E2 with high dose genistein (50 and 100 mg kg(-1)  day(-1) ) resulted in significant decrease in uterine fluid volume, secretion rate and expression of AQP-1, 2, 5, and 7 proteins and mRNAs in uterus (p 

    MeSH terms: Animals; Endometrium/metabolism; Endometrium/pathology; Estradiol/pharmacology*; Female; Microscopy, Fluorescence; Progesterone/pharmacology*; RNA, Messenger/metabolism; Uterus/drug effects*; Uterus/metabolism; Uterus/pathology; Blotting, Western; Rats, Sprague-Dawley; Genistein/toxicity*; Aquaporins/genetics; Aquaporins/metabolism*; Rats; Aquaporin 1/genetics; Aquaporin 1/metabolism; Aquaporin 2/genetics; Aquaporin 2/metabolism; Aquaporin 5/genetics; Aquaporin 5/metabolism; Real-Time Polymerase Chain Reaction
  17. Deep A, Bhatia RK, Kaur R, Kumar S, Jain UK, Singh H, et al.
    Curr Top Med Chem, 2017;17(2):238-250.
    PMID: 27237332
    Imidazo[1,2-a]pyridine is one of the most potential bicyclic 5-6 heterocyclic rings that is recognized as a "drug prejudice" scaffold due to its broad range of applications in medicinal chemistry such as anticancer, antimycobacterial, antileishmanial, anticonvulsant, antimicrobial, antiviral, antidiabetic, proton pump inhibitor, insecticidal activities. This scaffold has also been represented in various marketed preparations such as zolimidine, zolpidem, alpidem. Therefore, several attempts were made to carry out the structural modifications of this scaffold to discover and develop novel therapeutic agents. This review provides a valuable insight into the research findings of wide range of derivatives of imidazo[1,2-a]pyridine scaffold leading to promising heterocyclic compounds which could be explored further for the synthesis of new derivatives as well as construction of potential drug-like chemical libraries for biological screening in search of new therapeutic agents.
    MeSH terms: Anti-Infective Agents/therapeutic use*; Anti-Infective Agents/chemistry; Microbial Sensitivity Tests; Pyridines/therapeutic use*; Pyridines/chemistry
  18. Prime SS, Cirillo N, Hassona Y, Lambert DW, Paterson IC, Mellone M, et al.
    J Oral Pathol Med, 2017 Feb;46(2):82-88.
    PMID: 27237745 DOI: 10.1111/jop.12456
    There is now compelling evidence that the tumour stroma plays an important role in the pathogenesis of cancers of epithelial origin. The pre-eminent cell type of the stroma is carcinoma-associated fibroblasts. These cells demonstrate remarkable heterogeneity with activation and senescence being common stress responses. In this review, we summarise the part that these cells play in cancer, particularly oral cancer, and present evidence to show that activation and senescence reflect a unified programme of fibroblast differentiation. We report advances concerning the senescent fibroblast metabolome, mechanisms of gene regulation in these cells and ways in which epithelial cell adhesion is dysregulated by the fibroblast secretome. We suggest that the identification of fibroblast stress responses may be a valuable diagnostic tool in the determination of tumour behaviour and patient outcome. Further, the fact that stromal fibroblasts are a genetically stable diploid cell population suggests that they may be ideal therapeutic targets and early work in this context is encouraging.
    MeSH terms: Fibroblasts/cytology; Fibroblasts/metabolism; Fibroblasts/physiology*; Humans; Mouth Neoplasms/metabolism; Mouth Neoplasms/pathology*; Mouth Neoplasms/physiopathology; Cell Aging; Metabolome
  19. Sivadas A, Salleh MZ, Teh LK, Scaria V
    Pharmacogenomics J, 2017 10;17(5):461-470.
    PMID: 27241059 DOI: 10.1038/tpj.2016.39
    Expanding the scope of pharmacogenomic research by including multiple global populations is integral to building robust evidence for its clinical translation. Deep whole-genome sequencing of diverse ethnic populations provides a unique opportunity to study rare and common pharmacogenomic markers that often vary in frequency across populations. In this study, we aim to build a diverse map of pharmacogenetic variants in South East Asian (SEA) Malay population using deep whole-genome sequences of 100 healthy SEA Malay individuals. We investigated the allelic diversity of potentially deleterious pharmacogenomic variants in SEA Malay population. Our analysis revealed 227 common and 466 rare potentially functional single nucleotide variants (SNVs) in 437 pharmacogenomic genes involved in drug metabolism, transport and target genes, including 74 novel variants. This study has created one of the most comprehensive maps of pharmacogenetic markers in any population from whole genomes and will hugely benefit pharmacogenomic investigations and drug dosage recommendations in SEA Malays.
    MeSH terms: Gene Frequency; Genetics, Population; Humans; Malaysia; Pharmacogenetics/methods*; Genome, Human; Molecular Epidemiology/methods*; Databases, Genetic; Asian Continental Ancestry Group/genetics*; Genome-Wide Association Study; Molecular Sequence Annotation; Pharmacogenomic Variants*
  20. Aksentijevic A, Elliott MA
    Q J Exp Psychol (Hove), 2017 Aug;70(8):1535-1548.
    PMID: 27244533 DOI: 10.1080/17470218.2016.1192657
    Dynamic distortion of the visual field has been shown to affect perceptual judgment of visual dimensions such as size, length, and distance. Here, we report four experiments demonstrating that the different aspects of a triangle differently influence judgments of distance. Specifically, when the base of the triangle faces the centre of the display, participants consistently underestimate and overestimate the distance of a small dot from the unmarked centre of the display relative to conditions in which the vertex of the triangle faces the centre. When the dot is close to the figure, the distance of the dot to the centre is underestimated. Conversely, when the dot is close to the figure, the distance to the centre is overestimated. The effect is replicated when the internal distances are equalized and when ellipses are used instead of triangles. These results support a ripple model of spatial distortion in which local curvature acts to attract or repel objects. In conclusion, we suggest some implications of our findings for theories of perceptual organization.
    MeSH terms: Adult; Analysis of Variance; Distance Perception/physiology*; Female; Humans; Judgment/physiology*; Male; Pattern Recognition, Visual/physiology*; Perceptual Distortion/physiology*; Photic Stimulation; Space Perception/physiology*; Visual Fields
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