Browse publications by year: 2018

  1. Shahriman MS, Ramachandran MR, Zain NNM, Mohamad S, Manan NSA, Yaman SM
    Talanta, 2018 Feb 01;178:211-221.
    PMID: 29136814 DOI: 10.1016/j.talanta.2017.09.023
    In this present study, magnetic nanoparticles (MNPs) nanocomposites modified with polyaniline (PANI) coated newly synthesised dicationic ionic liquid (DICAT) forming MNP-PANI-DICAT were successfully synthesised as new generation material for magnetic solid phase extraction (MSPE). MNP-PANI-DICAT was characterised by FT-IR NMR, CHN, BET, SEM, TEM, and VSM techniques and the results were compared with MNP-PANI and native MNP. This new material was applied as a magnetic adsorbent for the pre-concentration and separation of polycyclic aromatic hydrocarbons (PAHs) due to the π-π interaction between polyaniline shell and dicationic ionic liquid (DICAT) with PAHs compounds. Under the optimal conditions, the proposed method was evaluated and applied for the analysis of PAHs in environmental samples using gas chromatography-mass spectrometry (GC-MS). The validation method showed good linearity (0.005-500µgL-1) with the coefficient of determination (R2) > 0.999. The limits of detection (LOD) and quantification (LOQ) of the developed method (MNP-PANI-DICAT-MSPE) were in the range of 0.0008-0.2086µgL-1and 0.0024-0.6320µgL-1, respectively. The enrichment factor (EF) of PAHs on MNP-PANI-DICAT-MSPE were in the range of 7.546-29.632. The extraction recoveries of natural water, sludge, and soil samples were ranged from 80.2% to 111.9% with relative standard deviation (RSD) less than 5.6%. The newly synthesised MNP-PANI-DICAT possess good sensitivity, reusability, and fast extraction of PAHs under the MSPE procedure in various environmental samples.
    MeSH terms: Aniline Compounds; Magnetics; Gas Chromatography-Mass Spectrometry; Sewage; Soil; Water; Spectroscopy, Fourier Transform Infrared; Ionic Liquids; Solid Phase Extraction; Nanocomposites; Limit of Detection; Magnetite Nanoparticles; Magnetic Phenomena
  2. Loow YL, Wu TY, Yang GH, Ang LY, New EK, Siow LF, et al.
    Bioresour Technol, 2018 Feb;249:818-825.
    PMID: 29136937 DOI: 10.1016/j.biortech.2017.07.165
    Deep eutectic solvents (DESs) have received considerable attention in recent years due to their low cost, low toxicity, and biodegradable properties. In this study, a sequential pretreatment comprising of a DES (choline chloride:urea in a ratio of 1:2) and divalent inorganic salt (CuCl2) was evaluated, with the aim of recovering xylose from oil palm fronds (OPF). At a solid-to-liquid ratio of 1:10 (w/v), DES alone was ineffective in promoting xylose extraction from OPF. However, a combination of DES (120°C, 4h) and 0.4mol/L of CuCl2 (120°C, 30min) resulted in a pretreatment hydrolysate containing 14.76g/L of xylose, remarkably yielding 25% more xylose than the CuCl2-only pretreatment (11.87g/L). Characterization studies such as FE-SEM, BET, XRD, and FTIR confirmed the delignification of OPF when DES was implemented. Thus, the use of this integrated pretreatment system enabled xylose recoveries which were comparable with other traditional pretreatments.
    MeSH terms: Lignin; Sodium Chloride; Solvents; Xylose*; Biomass
  3. Loo SK, Ab Hamid SS, Musa M, Wong KK
    Pathol Res Pract, 2018 Jan;214(1):134-143.
    PMID: 29137822 DOI: 10.1016/j.prp.2017.10.005
    Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shRNA targeting DNMT1(shDNMT1)-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells. Independent gene set enrichment analysis (GSEA) performed using GEPs of shRNA-treated HT cells and primary GCB-DLBCL cases derived from two publicly-available datasets (i.e. GSE10846 and GSE31312) produced three separate lists of enriched gene sets for each gene sets collection from Molecular Signatures Database (MSigDB). Subsequent Venn analysis identified 268, 145 and six consensus gene sets from analyzing gene sets in C2 collection (curated gene sets), C5 sub-collection [gene sets from gene ontology (GO) biological process ontology] and Hallmark collection, respectively to be enriched in positive correlation with DNMT1 expression profiles in shRNA-treated HT cells, GSE10846 and GSE31312 datasets [false discovery rate (FDR) <0.05]. Cell cycle progression and DNA replication were among the significantly enriched biological processes (FDR <0.05). Expression of genes involved in the activation of cell cycle and DNA replication (e.g. CDK1, CCNA2, E2F2, PCNA, RFC5 and POLD3) were highly correlated (r>0.8) with DNMT1 expression and significantly downregulated (log fold-change
    MeSH terms: B-Lymphocytes; Biological Phenomena; Cell Cycle; Cell Line; Cytosine; DNA; DNA Replication; Methyltransferases; Gene Expression; Lymphoma, Large B-Cell, Diffuse; Proliferating Cell Nuclear Antigen; Genes, cdc; Germinal Center; Consensus; RNA, Small Interfering; Gene Ontology
  4. Sheikh IA, Malik A, AlBasri SFM, Beg MA
    Life Sci, 2018 Jan 01;192:246-252.
    PMID: 29138116 DOI: 10.1016/j.lfs.2017.11.014
    AIMS: Chronic metabolic acidosis (CMA) refers to increased plasma acidity due to disturbed acid-base equilibrium in human body. CMA leads to many dysfunctions including disorders of intestinal metabolism and barrier functions. The human body responds to these intestinal dysfunctions by creating a compensatory mechanism at genomic level in intestinal epithelial cells. This study was to identify the molecular pathways involved in metabolic dysfunction and compensatory adaptations in intestinal epithelium during CMA.

    MAIN METHODS: In silico approaches were utilized to characterize a set of 88 differentially expressed genes (DEGs) from intestinal cells of rat CMA model. Interaction networks were constructed for DEGs by GeneMANIA and hub genes as well as enriched clusters in the network were screened using GLay. Gene Ontology (GO) was used for enriching functions in each cluster.

    KEY FINDINGS: Four gene hubs, i.e., trefoil factor 1, 5-hydroxytryptamine (serotonin) receptor 5a, solute carrier family 6 (neurotransmitter transporter), member 11, and glutamate receptor, ionotropic, n-methyl d-aspartate 2b, exhibiting the highest node degree were predicted. Six biologically related gene clusters were also predicted. Functional enrichment of GO terms predicted neurological processes such as neurological system process regulation and nerve impulse transmission which are related to negative and positive regulation of digestive system processes., intestinal motility and absorption and maintenance of gastrointestinal epithelium.

    SIGNIFICANCE: The study predicted several important genomic pathways that potentially play significant roles in metabolic disruptions or compensatory adaptations of intestinal epithelium induced by CMA. The results provide a further insight into underlying molecular mechanisms associated with CMA.

    MeSH terms: Acidosis/genetics*; Chronic Disease; Computer Simulation; Epithelial Cells/metabolism; Gastrointestinal Motility; Gene Expression Regulation; Humans; Intestines/cytology; Intestines/metabolism; Synaptic Transmission; Gene Expression Profiling; Gene Regulatory Networks
  5. Romli MH, Tan MP, Mackenzie L, Lovarini M, Kamaruzzaman SB, Clemson L
    Geriatr Gerontol Int, 2018 Mar;18(3):387-395.
    PMID: 29139186 DOI: 10.1111/ggi.13189
    AIM: Previous studies have investigated home hazards as a risk factor for falls without considering factors associated with the presence of home hazards. The present study aimed to determine patterns of home hazards among urban community-dwelling older Malaysians, and to identify factors contributing to home hazards.

    METHODS: Cross-sectional data from the initial wave of the Malaysian Elders Longitudinal Research study were used. Basic demographics were obtained from the Global Questionnaire. Basic and instrumental activities of daily living were measured using the Katz and Lawton-Brody scales, and home hazards were identified using the Home Falls and Accidents Screening Tool. Participants were also asked if they had fallen in the previous 12 months.

    RESULTS: Data were analyzed from 1489 participants. Hazards were frequently identified (>30%) in the toilet and bathroom areas (no grab rail, no non-slip mat, distant toilet), slippery floors, no bedside light access and inappropriate footwear. Lower educational attainment, traditional housing, Chinese ethnicity, greater number of home occupants, lower monthly expenditure, poor vision and younger age were the factors independently associated with home hazards.

    CONCLUSIONS: This study provides evidence that home hazards are a product of the interaction of the individual's function within their home environment. Hazards are also influenced by local sociocultural and environmental factors. The relationship between home hazards and falls appears complex and deserves further evaluation. Geriatr Gerontol Int 2018; 18: 387-395.

    MeSH terms: Accidental Falls*; Accidents, Home*; Activities of Daily Living; Aged; Cross-Sectional Studies; Humans; Longitudinal Studies; Malaysia; Risk Factors; Independent Living
  6. Connolly SJ, Eikelboom JW, Bosch J, Dagenais G, Dyal L, Lanas F, et al.
    Lancet, 2018 01 20;391(10117):205-218.
    PMID: 29132879 DOI: 10.1016/S0140-6736(17)32458-3
    BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.

    METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.

    FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012).

    INTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.

    FUNDING: Bayer AG.
    MeSH terms: Rivaroxaban/administration & dosage; Rivaroxaban/adverse effects; Rivaroxaban/therapeutic use*; Aged; Aspirin/administration & dosage; Aspirin/adverse effects; Aspirin/therapeutic use*; Cardiovascular Diseases/mortality; Cardiovascular Diseases/prevention & control; Coronary Artery Disease/drug therapy*; Coronary Artery Disease/epidemiology; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Hemorrhage/chemically induced; Hospitals; Hospitals, University; Humans; Malaysia; Male; Morbidity; Myocardial Infarction/epidemiology; Myocardial Infarction/prevention & control; Outpatient Clinics, Hospital; Platelet Aggregation Inhibitors/administration & dosage; Platelet Aggregation Inhibitors/adverse effects; Platelet Aggregation Inhibitors/therapeutic use*; Stroke/epidemiology; Stroke/prevention & control; Factor Xa Inhibitors/administration & dosage; Factor Xa Inhibitors/adverse effects; Factor Xa Inhibitors/therapeutic use*
  7. Karnad DR, Nor MBM, Richards GA, Baker T, Amin P, Council of the World Federation of Societies of Intensive and Critical Care Medicine
    J Crit Care, 2018 Feb;43:356-360.
    PMID: 29132978 DOI: 10.1016/j.jcrc.2017.11.007
    Severe malaria is common in tropical countries in Africa, Asia, Oceania and South and Central America. It may also occur in travelers returning from endemic areas. Plasmodium falciparum accounts for most cases, although P vivax is increasingly found to cause severe malaria in Asia. Cerebral malaria is common in children in Africa, manifests as coma and seizures, and has a high morbidity and mortality. In other regions, adults may also develop cerebral malaria but neurological sequelae in survivors are rare. Acute kidney injury, liver dysfunction, thrombocytopenia, disseminated intravascular coagulopathy (DIC) and acute respiratory distress syndrome (ARDS) are also common in severe malaria. Metabolic abnormalities include hypoglycemia, hyponatremia and lactic acidosis. Bacterial infection may coexist in patients presenting with shock or ARDS and this along with a high parasite load has a high mortality. Intravenous artesunate has replaced quinine as the antimalarial agent of choice. Critical care management as per severe sepsis is also applicable to severe malaria. Aggressive fluid boluses may not be appropriate in children. Blood transfusions may be required and treatment of seizures and raised intracranial pressure is important in cerebral malaria in children. Mortality in severe disease ranges from 8 to 30% despite treatment.
    MeSH terms: Adult; Antimalarials/therapeutic use; Child; Critical Care/methods*; Critical Care/standards; Female; Humans; Malaria/diagnosis; Malaria/therapy*; Male; Respiratory Distress Syndrome, Adult/parasitology; Respiratory Distress Syndrome, Adult/prevention & control*; Respiratory Distress Syndrome, Adult/therapy; Severity of Illness Index; Societies, Medical*; Tropical Medicine*; Advisory Committees*; Artemisinins/therapeutic use; Acute Kidney Injury/parasitology; Acute Kidney Injury/prevention & control*
  8. Taha M, Ullah H, Al Muqarrabun LMR, Khan MN, Rahim F, Ahmat N, et al.
    Eur J Med Chem, 2018 Jan 01;143:1757-1767.
    PMID: 29133042 DOI: 10.1016/j.ejmech.2017.10.071
    Thirty-two (32) bis-indolylmethane-hydrazone hybrids 1-32 were synthesized and characterized by 1HNMR, 13CNNMR and HREI-MS. All compounds were evaluated in vitro for β-glucuronidase inhibitory potential. All analogs showed varying degree of β-glucuronidase inhibitory potential ranging from 0.10 ± 0.01 to 48.50 ± 1.10 μM when compared with the standard drug d-saccharic acid-1,4-lactone (IC50 value 48.30 ± 1.20 μM). Derivatives 1-32 showed the highest β-glucuronidase inhibitory potentials which is many folds better than the standard drug d-saccharic acid-1,4-lactone. Further molecular docking study validated the experimental results. It was proposed that bis-indolylmethane may interact with some amino acid residues located within the active site of β-glucuronidase enzyme. This study has culminated in the identification of a new class of potent β-glucuronidase inhibitors.
    MeSH terms: Dose-Response Relationship, Drug; Glucuronidase/antagonists & inhibitors*; Glucuronidase/metabolism; Glycoproteins/chemical synthesis; Glycoproteins/pharmacology*; Glycoproteins/chemistry; Humans; Indoles/chemical synthesis; Indoles/pharmacology*; Indoles/chemistry; Structure-Activity Relationship; Molecular Structure; Molecular Docking Simulation*
  9. Abedinia A, Ariffin F, Huda N, Mohammadi Nafchi A
    Int J Biol Macromol, 2018 Apr 01;109:855-862.
    PMID: 29133087 DOI: 10.1016/j.ijbiomac.2017.11.051
    Edible duck feet gelatin (DFG)-based biocomposites with different glycerol (GLY) contents (15%, 25%, and 35% of dried DFG) were prepared. Physicochemical, mechanical, barrier, and heat seal properties of DFG films were characterized and compared as an alternative to bovine gelatin film. Increasing glycerol from 15 to 35% decreased the TS and YM and EB and HS increased, in value of 42.54-7.27 and 1240-157.10MPa and 22.82-50.33% and 42.06-347.15N/m respectively. The water vapor permeability (WVP) and oxygen permeability (OP) of films were increased from 4.78 to 5.6×10-11gm-1Pa-1s-1 and from 3.97 to 33.99cm3mμ/m2 d kPa respectively. GAB model estimations showed monolayer water content of films increased with the increase of plasticizer content. Moisture sorption isotherm modelling exhibited a type II BET classification. Fourier transform infrared (FTIR) spectra showed shifted peak at approximately 1024cm-1, which was related to glycerol. The results show that the properties of DFG film are suitable for use as an alternative material to bovine gelatin film.
    MeSH terms: Animals; Biocompatible Materials/isolation & purification; Biocompatible Materials/chemistry*; Cattle; Ducks; Gelatin/isolation & purification; Gelatin/chemistry*; Membranes, Artificial; Permeability; Spectroscopy, Fourier Transform Infrared; Mechanical Phenomena; Chemical Phenomena
  10. Theivasanthi T, Anne Christma FL, Toyin AJ, Gopinath SCB, Ravichandran R
    Int J Biol Macromol, 2018 Apr 01;109:832-836.
    PMID: 29133091 DOI: 10.1016/j.ijbiomac.2017.11.054
    Nanocellulose prepared from the natural material has a promising wide range of opportunities to obtain the superior material properties towards various end-products. In this research, commercially available natural cotton was treated with aqueous sodium hydroxide solution to eliminate the hemicellulose and lignin, then cellulose was collected. The collected cellulose was subjected to acid hydrolysis using sulfuric acid to obtain nanocellulose. The prepared nanocellulose was further characterized with the aid of Fourier transform infrared spectroscopy, X-ray diffraction and Scanning Electron Microscopy to elucidate the chemical structure, crystallinity and the morphology.
    MeSH terms: Cellulose/chemical synthesis; Cellulose/chemistry*; Hydrogen-Ion Concentration; Hydrolysis; Polymers/chemical synthesis; Polymers/chemistry; X-Ray Diffraction; Molecular Structure; Spectroscopy, Fourier Transform Infrared; Cotton Fiber*; Nanocomposites/ultrastructure; Nanocomposites/chemistry*; Chemistry Techniques, Synthetic
  11. Al-Alwani MAM, Ludin NA, Mohamad AB, Kadhum AAH, Mukhlus A
    Spectrochim Acta A Mol Biomol Spectrosc, 2018 Mar 05;192:487-498.
    PMID: 29133132 DOI: 10.1016/j.saa.2017.11.018
    The natural dyes anthocyanin and chlorophyll were extracted from Musa acuminata bracts and Alternanthera dentata leaves, respectively. The dyes were then applied as sensitizers in TiO2-based dye-sensitized solar cells (DSSCs). The ethanol extracts of the dyes had maximum absorbance. High dye yields were obtained under extraction temperatures of 70 to 80°C, and the optimal extraction temperature was approximately 80°C. Moreover, dye concentration sharply decreased under extraction temperatures that exceeded 80°C. High dye concentrations were obtained using acidic extraction solutions, particularly those with a pH value of 4. The DSSC fabricated with anthocyanin from M. acuminata bracts had a conversion efficiency of 0.31%, short-circuit current (Isc) of 0.9mA/cm2, open-circuit voltage (Voc) of 0.58V, and fill factor (FF) of 62.22%. The DSSC sensitized with chlorophyll from A. dentata leaves had a conversion efficiency of 0.13%, Isc of 0.4mA/cm-2,Voc of 0.54V, and FF of 67.5%. The DSSC sensitized with anthocyanin from M. acuminata bracts had a maximum incident photon-to-current conversion efficiency of 42%, which was higher than that of the DSSC sensitized with chlorophyll from A. dentata leaves (23%). Anthocyanin from M. acuminata bracts exhibited the best photosensitization effects.
    MeSH terms: Anthocyanins/chemistry; Calibration; Chlorophyll/chemistry; Coloring Agents/isolation & purification*; Electrochemistry; Hydrogen-Ion Concentration; Plant Extracts/chemistry; Solar Energy*; Solvents/chemistry; Spectrometry, X-Ray Emission; Surface Properties; Temperature; Titanium/chemistry; X-Ray Diffraction; Spectroscopy, Fourier Transform Infrared; Photons; Plant Leaves/chemistry*; Amaranthaceae/chemistry*; Musa/chemistry*
  12. SharifahNany RahayuKarmilla S, Aedrianee AR, Nur Haslindawaty AR, Nur Azeelah A, Panneerchelvam S, Norazmi MN, et al.
    Int J Legal Med, 2018 07;132(4):1091.
    PMID: 29134364 DOI: 10.1007/s00414-017-1729-9
    The original version of this article contains an error. The Author Abd Rashid Nur Haslindawaty has been added as to the above author group as third author. The original article was corrected.
    MeSH terms: Humans
  13. Zeeshan F, Tabbassum M, Jorgensen L, Medlicott NJ
    AAPS PharmSciTech, 2018 Feb;19(2):769-782.
    PMID: 29134579 DOI: 10.1208/s12249-017-0883-1
    Protein biologics are prone to conformational changes during formulation development. Limited methods are available for conformational analysis of proteins in solid state and in the presences of formulation excipients. The aim of this study was to investigate the secondary structures of proteins encased in solid lipid matrices as a novel indicator of their stability upon in vitro release. Model proteins namely catalase and lysozyme were incorporated into lipid namely Precirol® AT05 (glycerol palmitostearate, melting point 58°C) at 30% w/w loading using melting and mixing and wet granulation methods. Attenuated total reflectance (ATR-FTIR) spectroscopy, size-exclusion chromatography (SEC) and biological activity analyses were performed. The information about secondary structure was acquired using second derivative analysis of amide-I band (1600-1700 cm-1). ATR analysis demonstrated interference of lipid spectrum with protein amide-I band which was subsequently subtracted to allow the analysis of the secondary structure. ATR spectra amide-I bands showed shifts peak band positions compared to native protein for matrices prepared using wet granulation. SEC analysis gave evidence of protein aggregation for catalase which was increased using wet granulation. The biological activity of catalase was statistically different from that of control and was affected by the incorporation method and was found to be in alignment with ATR spectral changes and extent of aggregation. In conclusion, ATR spectroscopy could analyze protein secondary structure in lipid matrices provided lipid interference was minimized. The ATR spectral changes and formation of aggregates can indicate the loss in biological activity of protein released from solid lipid matrices.
    MeSH terms: Catalase/chemistry; Diglycerides/chemistry; Excipients/chemistry; Muramidase/chemistry; Protein Structure, Secondary*; Spectroscopy, Fourier Transform Infrared
  14. Eng CSY, Bhowruth D, Mayes M, Stronach L, Blaauw M, Barber A, et al.
    Nephrol Dial Transplant, 2018 05 01;33(5):847-855.
    PMID: 29136192 DOI: 10.1093/ndt/gfx287
    Background: Fluid balance is pivotal in the management of children with chronic kidney disease (CKD) and on dialysis. Although many techniques are available to assess fluid status, there are only a few studies for children, of which none have been comparable against cardiovascular outcome measures.

    Methods: We performed a longitudinal study in 30 children with CKD5-5D and 13 age-matched healthy controls (71 measurements) to determine a correlation between optimal weight by bioimpedance spectroscopy (Wt-BIS) and clinical assessment (Wt-CA). The accuracy of Wt-BIS [relative overhydration (Rel-OH)] was compared against indicators of fluid status and cardiovascular measures.

    Results: There was poor agreement between Wt-CA and Wt-BIS in children on dialysis (P = 0.01), but not in CKD5 or control subjects. We developed a modified chart to plot Rel-OH against systolic blood pressure (SBP) z-score for the appropriate representation of volume status and blood pressure (BP) in children. In total, 25% of measurements showed SBP >90th percentile but not with concurrent overhydration. Rel-OH correlated with peripheral pulse pressure (P = 0.03; R = 0.3), higher N-terminal pro-brain natriuretic peptide (P = 0.02; R = 0.33) and left ventricular end-diastolic diameter (P = 0.05; R = 0.38). Central aortic mean and pulse pressure significantly associated with the left ventricular end-diastolic diameter (P = 0.03; R = 0.47 and P = 0.01; R = 0.50, respectively), but not with Rel-OH. SBP was positively associated with pulse wave velocity z-score (P = 0.04). In total, 40% of children on haemodialysis and 30% on peritoneal dialysis had increased left ventricular mass index.

    Conclusions: BIS provides an objective method for the assessment of hydration status in children on dialysis. We noted a marked discrepancy between BP and hydration status in children on dialysis that warrants further investigation.

    MeSH terms: Adolescent; Blood Pressure*; Blood Pressure Determination; Child; Child, Preschool; Cross-Sectional Studies; Female; Renal Dialysis/methods*; Humans; Longitudinal Studies; Male; Prospective Studies; Water-Electrolyte Balance*; Case-Control Studies; Electric Impedance*; Renal Insufficiency, Chronic/therapy*; Pulse Wave Analysis/methods*
  15. Peyrot WJ, Van der Auwera S, Milaneschi Y, Dolan CV, Madden PAF, Sullivan PF, et al.
    Biol Psychiatry, 2018 Jul 15;84(2):138-147.
    PMID: 29129318 DOI: 10.1016/j.biopsych.2017.09.009
    BACKGROUND: The heterogeneity of genetic effects on major depressive disorder (MDD) may be partly attributable to moderation of genetic effects by environment, such as exposure to childhood trauma (CT). Indeed, previous findings in two independent cohorts showed evidence for interaction between polygenic risk scores (PRSs) and CT, albeit in opposing directions. This study aims to meta-analyze MDD-PRS × CT interaction results across these two and other cohorts, while applying more accurate PRSs based on a larger discovery sample.

    METHODS: Data were combined from 3024 MDD cases and 2741 control subjects from nine cohorts contributing to the MDD Working Group of the Psychiatric Genomics Consortium. MDD-PRS were based on a discovery sample of ∼110,000 independent individuals. CT was assessed as exposure to sexual or physical abuse during childhood. In a subset of 1957 cases and 2002 control subjects, a more detailed five-domain measure additionally included emotional abuse, physical neglect, and emotional neglect.

    RESULTS: MDD was associated with the MDD-PRS (odds ratio [OR] = 1.24, p = 3.6 × 10-5, R2 = 1.18%) and with CT (OR = 2.63, p = 3.5 × 10-18 and OR = 2.62, p = 1.4 ×10-5 for the two- and five-domain measures, respectively). No interaction was found between MDD-PRS and the two-domain and five-domain CT measure (OR = 1.00, p = .89 and OR = 1.05, p = .66).

    CONCLUSIONS: No meta-analytic evidence for interaction between MDD-PRS and CT was found. This suggests that the previously reported interaction effects, although both statistically significant, can best be interpreted as chance findings. Further research is required, but this study suggests that the genetic heterogeneity of MDD is not attributable to genome-wide moderation of genetic effects by CT.

    MeSH terms: Adult; Child; Child Abuse/psychology*; Depressive Disorder, Major/genetics*; Depressive Disorder, Major/epidemiology; Female; Humans; Male; Psychiatric Status Rating Scales; Risk Factors; Logistic Models; Case-Control Studies; Risk Assessment; Genetic Predisposition to Disease; Multifactorial Inheritance; Adult Survivors of Child Abuse/psychology; Gene-Environment Interaction
  16. Jain A, Jain A, Parajuli P, Mishra V, Ghoshal G, Singh B, et al.
    Drug Discov Today, 2018 05;23(5):960-973.
    PMID: 29129804 DOI: 10.1016/j.drudis.2017.11.003
    Galactosylated nanocarriers have recently emerged as viable and versatile tools to deliver drugs at an optimal rate specifically to their target tissues or cells, thus maximizing their therapeutic benefits while circumventing off-target effects. The abundance of lectin receptors on cell surfaces makes the galactosylated carriers suitable for the targeted delivery of bioactives. Additionally, tethering of galactose (GAL) to various carriers, including micelles, liposomes, and nanoparticles (NPs), might also be appropriate for drug delivery. Here, we review recent advances in the development of galactosylated nanocarriers for active tumor targeting. We also provide a brief overview of the targeting mechanisms and cell receptor theory involved in the ligand-receptor-mediated delivery of drug carriers.
    MeSH terms: Animals; Humans; Ligands; RNA, Small Interfering/administration & dosage*; Nanotechnology; Asialoglycoprotein Receptor/metabolism; Drug Discovery
  17. Yeo BPH, Foong LC, Tam SM, Lee V, Hwang SS
    Biochem Mol Biol Educ, 2018 01;46(1):47-53.
    PMID: 29131478 DOI: 10.1002/bmb.21089
    Structures and functions of protein motifs are widely included in many biology-based course syllabi. However, little emphasis is placed to link this knowledge to applications in biotechnology to enhance the learning experience. Here, the conserved motifs of nucleotide binding site-leucine rich repeats (NBS-LRR) proteins, successfully used for the isolation and characterization of many plant resistance gene analogues (RGAs), is featured in the development of a series of laboratory experiments using important molecular biology techniques. A set of previously isolated RGA sequences is used as the model for performing sequence alignment and visualising 3D protein structure using current bioinformatics programs (Clustal Omega and Argusdock software). A pair of established degenerate primer sequences is provided for the prediction of targeted amino acids sequences in the RGAs. Reverse transcription-polymerase chain reaction (RT-PCR) is used to amplify RGAs from total RNA samples extracted from the tropical wild relative of black pepper, Piper colubrinum (Piperaceae). This laboratory exercise enables students to correlate specific DNA sequences with respective amino acid codes and the interaction between conserved motifs of resistance genes with putatively targeted proteins. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(1):47-53, 2018.
    MeSH terms: Laboratories; Leucine/genetics; Proteins/genetics*; Proteins/chemistry; Software; Teaching*; Protein Structure, Secondary; DNA Primers/genetics*; DNA, Plant/genetics*; DNA, Plant/isolation & purification*; Computational Biology/education; Reverse Transcriptase Polymerase Chain Reaction; Amino Acid Motifs/genetics*; Piper/genetics*; Piper/chemistry
  18. Xiao B, Deng X, Ng EY, Allen JC, Lim SY, Ahmad-Annuar A, et al.
    JAMA Neurol, 2018 01 01;75(1):127-128.
    PMID: 29131875 DOI: 10.1001/jamaneurol.2017.3363
    MeSH terms: Aged; Female; Genotype; Great Britain/epidemiology; Humans; Male; Middle Aged; Mutation/genetics*; Parkinson Disease/genetics*; Age of Onset; Genetic Association Studies; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics*
  19. Bukvički D, Novaković M, Ab Ghani N, Marin PD, Asakawa Y
    Nat Prod Res, 2018 Aug;32(15):1849-1852.
    PMID: 29126369 DOI: 10.1080/14786419.2017.1402309
    This manuscript describes the first detailed chemical investigation of endemic species Iris adriatica, including isolation and structure elucidation. Chemical analyses of the rhizome CH2Cl2/MeOH (2:1) extract revealed fourteen secondary metabolites, mainly isoflavonoids. Among isoflavonoids, two groups have been found: nigricin-type and tectorigenin-type. Dominant group of the isolated compounds has been nigricin-type isoflavones: nigricin, nigricin-4'-(1-O-β-D-glucopyranoside) and nigricin-4'-(1-O-β-D-glucopyranosyl (1-6)-β-D-glucopyranoside) with 2.5, 10 and 1% of the total extract, respectively. Irisxanthone - xanthone C-glucoside, β-sitosterol, benzophenone and one of its derivatives have also been found. Nigricin-type isoflavonoids and irisxanthone can be considered as possible chemotaxonomic markers for I. adriatica. 5,3',5'-Trimethoxy-6,7-methylenedioxyisoflavone-4'-(1-O-β-D-glucopyranoside) and benzophenone have been isolated from Iris species for the first time.
    MeSH terms: Benzophenones/chemistry; Glucosides/chemistry; Isoflavones/chemistry; Magnetic Resonance Spectroscopy; Plant Extracts/analysis; Plant Extracts/chemistry; Molecular Structure; Rhizome/chemistry; Iris Plant/metabolism*; Iris Plant/chemistry*; Secondary Metabolism
  20. Saddique FA, Zaib S, Jalil S, Aslam S, Ahmad M, Sultan S, et al.
    Eur J Med Chem, 2018 Jan 01;143:1373-1386.
    PMID: 29126721 DOI: 10.1016/j.ejmech.2017.10.036
    Three series of 4-hydroxy-N'-[benzylidene/1-phenylethylidene]-2-H/methyl/benzyl-1,2-benzothiazine-3-carbohydrazide 1,1-dioxides (9-11)a-l were synthesized and unraveled to be highly potent dual inhibitors of monoamine oxidases (MAO-A and MAO-B). All the examined compounds demonstrated IC50 values in lower micro-molar range for both MAO-A as well as MAO-B. The most active MAO-A inhibitor was 4-hydroxy-N'-(1-phenylethylidene)-2H-benzo[e][1,2]thiazine-3-carbohydrazide 1,1-dioxide (9i) with an IC50 value of 0.11 ± 0.005 μM, whereas, methyl 4-hydroxy-2H-benzo[e][1,2]thiazine-3-carboxylate 1,1-dioxide (3) was the most active MAO-B inhibitor with an IC50 value of 0.21 ± 0.01 μM. Enzyme kinetics studies revealed that the most potent compounds inhibited both MAO enzymes (A & B) in a competitive fashion. Molecular docking studies were also performed to obtain an intuitive picture of inhibition potential for potent inhibitors. The high potency of these compounds is optimally combined with highly favorable ADME profile with predicted good oral bioavailability.
    MeSH terms: Animals; Benzylidene Compounds/chemistry*; Humans; Hydrazines/chemistry*; Monoamine Oxidase/metabolism*; Monoamine Oxidase/chemistry; Monoamine Oxidase Inhibitors/chemical synthesis; Monoamine Oxidase Inhibitors/metabolism; Monoamine Oxidase Inhibitors/pharmacology; Monoamine Oxidase Inhibitors/chemistry; Protein Conformation; Structure-Activity Relationship; Thiazines/chemical synthesis*; Thiazines/metabolism; Thiazines/pharmacology*; Thiazines/chemistry; Rats; Chemistry Techniques, Synthetic; Molecular Docking Simulation*
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