Browse publications by year: 2014

  1. Wang X, Lamoureux E, Zheng Y, Ang M, Wong TY, Luo N
    Ophthalmology, 2014 Sep;121(9):1837-42.
    PMID: 24768238 DOI: 10.1016/j.ophtha.2014.03.017
    To assess the impact of visual impairment (VI) on health-related quality of life and to compare the health burden of VI and other health conditions in Singapore.
    MeSH terms: Adult; Aged; Aged, 80 and over; China/ethnology; Cross-Sectional Studies; Female; Health Status*; Humans; Hyperlipidemias/complications; Hypertension/complications; India/ethnology; Malaysia/ethnology; Male; Middle Aged; Obesity/complications; Quality of Life; Surveys and Questionnaires; Singapore/epidemiology; Vision Disorders/epidemiology*; Prevalence; Logistic Models; Cost of Illness*; Diabetes Complications
  2. Rajah T, Chow SC
    Toxicol Appl Pharmacol, 2014 Jul 15;278(2):100-6.
    PMID: 24768707 DOI: 10.1016/j.taap.2014.04.014
    The caspase inhibitor benzyloxycarbony (Cbz)-l-Val-Ala-Asp (OMe)-fluoromethylketone (z-VAD-FMK) has recently been shown to inhibit T cell proliferation without blocking caspase-8 and caspase-3 activation in primary T cells. We showed in this study that z-VAD-FMK treatment leads to a decrease in intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) levels in activated T cells. The inhibition of anti-CD3-mediated T cell proliferation induced by z-VAD-FMK was abolished by the presence of low molecular weight thiols such as GSH, N-acetylcysteine (NAC) and l-cysteine, whereas d-cysteine which cannot be metabolised to GSH has no effect. These results suggest that the depletion of intracellular GSH is the underlying cause of z-VAD-FMK-mediated inhibition of T cell activation and proliferation. The presence of exogenous GSH also attenuated the inhibition of anti-CD3-induced CD25 and CD69 expression mediated by z-VAD-FMK. However, none of the low molecular weight thiols were able to restore the caspase-inhibitory properties of z-VAD-FMK in activated T cells where caspase-8 and caspase-3 remain activated and processed into their respective subunits in the presence of the caspase inhibitor. This suggests that the inhibition of T cell proliferation can be uncoupled from the caspase-inhibitory properties of z-VAD-FMK. Taken together, the immunosuppressive effects in primary T cells mediated by z-VAD-FMK are due to oxidative stress via the depletion of GSH.
    MeSH terms: Amino Acid Chloromethyl Ketones/pharmacology*; Cells, Cultured; Dose-Response Relationship, Immunologic; Glutathione/metabolism; Growth Inhibitors/pharmacology*; Humans; Leukocytes, Mononuclear/drug effects; Leukocytes, Mononuclear/immunology; Leukocytes, Mononuclear/metabolism; Lymphocyte Activation/drug effects*; Lymphocyte Activation/immunology; Lymphocyte Activation/physiology; T-Lymphocyte Subsets/drug effects; T-Lymphocyte Subsets/immunology; T-Lymphocyte Subsets/metabolism*; Reactive Oxygen Species/metabolism; Oxidative Stress/drug effects*; Oxidative Stress/immunology; Caspase Inhibitors/pharmacology*
  3. Jamal J, Mustafa MR, Wong PF
    J Ethnopharmacol, 2014 Jun 11;154(2):428-36.
    PMID: 24768807 DOI: 10.1016/j.jep.2014.04.025
    Paeonol is a phenolic compound isolated mainly from Moutan cortex, root bark of Chinese Peony tree. Moutan cortex holds a significant value in traditional Chinese medicine for alleviating various oxidative stress-related diseases mainly atherosclerosis and myocardial infarction. The present study seeks to identify the protective mechanisms of paeonol in oxidative stress-induced premature senescence in endothelial cells.
    MeSH terms: Acetophenones/isolation & purification; Acetophenones/pharmacology*; Cell Survival/drug effects; Humans; Molecular Structure; Signal Transduction/drug effects*; Cell Aging/drug effects*; Reactive Oxygen Species/metabolism; Oxidative Stress/drug effects; Cell Culture Techniques; Ethnopharmacology; Endothelial Cells/drug effects*; Endothelial Cells/metabolism; Sirtuin 1/metabolism*; Human Umbilical Vein Endothelial Cells
  4. Nur Hanani ZA, Roos YH, Kerry JP
    Int J Biol Macromol, 2014 Nov;71:94-102.
    PMID: 24769086 DOI: 10.1016/j.ijbiomac.2014.04.027
    The manufacture and potential application of biodegradable films for food application has gained increased interest as alternatives to conventional food packaging polymers due to the sustainable nature associated with their availability, broad and abundant source range, compostability, environmentally-friendly image, compatibility with foodstuffs and food application, etc. Gelatin is one such material and is a unique and popularly used hydrocolloid by the food industry today due to its inherent characteristics, thereby potentially offering a wide range of further and unique industrial applications. Gelatin from different sources have different physical and chemical properties as they contain different amino acid contents which are responsible for the varying characteristics observed upon utilization in food systems and when being utilized more specifically, in the manufacture of films. Packaging films can be successfully produced from all gelatin sources and the behaviour and characteristics of gelatin-based films can be altered through the incorporation of other food ingredients to produce composite films possessing enhanced physical and mechanical properties. This review will present the current situation with respect to gelatin usage as a packaging source material and the challenges that remain in order to move the manufacture of gelatin-based films nearer to commercial reality.
    MeSH terms: Biodegradation, Environmental
  5. Rahman MM, Ali ME, Hamid SB, Mustafa S, Hashim U, Hanapi UK
    Meat Sci, 2014 Aug;97(4):404-9.
    PMID: 24769096 DOI: 10.1016/j.meatsci.2014.03.011
    A polymerase chain reaction (PCR) assay for the assessment of dog meat adulteration in meatballs was developed. The assay selectively amplified a 100-bp region of canine mitochondrial cytochrome b gene from pure, raw, processed and mixed backgrounds. The specificity of the assay was tested against 11 animals and 3 plants species, commonly available for meatball formulation. The stability of the assay was proven under extensively autoclaving conditions that breakdown target DNA. A blind test from ready to eat chicken and beef meatballs showed that the assay can repeatedly detect 0.2% canine meat tissues under complex matrices using 0.04 ng of dog DNA extracted from differentially treated meatballs. The simplicity, stability and sensitivity of the assay suggested that it could be used in halal food industry for the authentication of canine derivatives in processed foods.
    MeSH terms: Animals; Cattle; Chickens; Diet; DNA/analysis*; Dogs/genetics*; Food Contamination/analysis*; Gene Amplification; Humans; Meat/analysis; Meat Products/analysis*; Polymerase Chain Reaction/methods*; Cytochromes b/genetics*; Genes, Mitochondrial*
  6. Savadkoohi S, Hoogenkamp H, Shamsi K, Farahnaky A
    Meat Sci, 2014 Aug;97(4):410-8.
    PMID: 24769097 DOI: 10.1016/j.meatsci.2014.03.017
    The present investigation focuses on the textural properties, sensory attributes and color changes of beef frankfurter, beef ham and meat-free sausage produced by different levels of bleached tomato pomace. The texture and color profile were performed using an instrumental texture analyzer and colorimeter. The findings indicated that tomato pomace-added sausages had higher water holding capacity (WHC) compared to that of commercial samples. The frankfurters containing 5 and 7% (w/w) tomato pomace had the highest redness (a*), chroma (C*) and color differences (ΔE) values, while the meat-free sausages containing 7% (w/w) tomato pomace had significant (p<0.05) values for lightness (L*) and yellowness (b*). Furthermore, there were no significant (p>0.05) color differences between beef ham samples (with and without tomato pomace). A significant progression in the textural hardness and chewiness of systems containing tomato pomace was observed as well as higher sensory scores by panelists. According to sensorial evaluations, bleached tomato pomace improved the consumer acceptability and preference.
    MeSH terms: Animals; Cattle; Color*; Consumer Behavior; Diet; Fruit*; Hardness; Humans; Mastication; Meat Products/analysis*; Odors*; Taste*; Water*; Lycopersicon esculentum*
  7. Tan CW, Chan YF, Quah YW, Poh CL
    Antiviral Res, 2014 Jul;107:35-41.
    PMID: 24769243 DOI: 10.1016/j.antiviral.2014.04.004
    Enterovirus 71 (EV-71) infections are generally manifested as mild hand, foot and mouth disease, but have been reported to cause severe neurological complications with high mortality rates. Treatment options remain limited due to the lack of antivirals. Octaguanidinium-conjugated morpholino oligomers (vivo-MOs) are single-stranded DNA-like antisense agents that can readily penetrate cells and reduce gene expression by steric blocking of complementary RNA sequences. In this study, inhibitory effects of three vivo-MOs that are complementary to the EV-71 internal ribosome entry site (IRES) and the RNA-dependent RNA polymerase (RdRP) were tested in RD cells. Vivo-MO-1 and vivo-MO-2 targeting the EV-71 IRES showed significant viral plaque reductions of 2.5 and 3.5 log10PFU/ml, respectively. Both vivo-MOs reduced viral RNA copies and viral capsid expression in RD cells in a dose-dependent manner. In contrast, vivo-MO-3 targeting the EV-71 RdRP exhibited less antiviral activity. Both vivo-MO-1 and 2 remained active when administered either 4h before or within 6h after EV-71 infection. Vivo-MO-2 exhibited antiviral activities against poliovirus (PV) and coxsackievirus A16 but vivo-MO-1 showed no antiviral activities against PV. Both the IRES-targeting vivo-MO-1 and vivo-MO-2 inhibit EV-71 RNA translation. Resistant mutants arose after serial passages in the presence of vivo-MO-1, but none were isolated against vivo-MO-2. A single T to C substitution at nucleotide position 533 was sufficient to confer resistance to vivo-MO-1. Our findings suggest that IRES-targeting vivo-MOs are good antiviral candidates for treating early EV-71 infection, and vivo-MO-2 is a more favorable candidate with broader antiviral spectrum against enteroviruses and are refractory to antiviral resistance.
    MeSH terms: Antiviral Agents/pharmacology*; Cell Line; Enterovirus/drug effects; Humans; Microbial Sensitivity Tests; Viral Plaque Assay; Serial Passage; Virus Replication/drug effects*; Poliovirus/drug effects; Drug Resistance, Viral; Enterovirus A, Human/drug effects*; Enterovirus A, Human/physiology; Dendrimers/pharmacology*; Morpholinos/pharmacology*
  8. Chandirasekar R, Kumar BL, Sasikala K, Jayakumar R, Suresh K, Venkatesan R, et al.
    PMID: 24769293 DOI: 10.1016/j.mrgentox.2014.04.007
    Inexpensive forms of tobacco are widely used in developing countries such as India. We have evaluated genotoxicity endpoints (chromosome aberrations, micronucleus frequency, comet assay) and polymorphisms of the XRCC1 and p53 genes among smokers and smokeless tobacco (SLT) users in rural Tamilnadu, South India. Cytogenetic, DNA damage and SNP analyses were performed on peripheral blood samples; micronucleus frequency was measured in peripheral blood and buccal mucosa exfoliated cells. Both categories of tobacco users had elevated levels of genotoxic damage. SNP analysis of tobacco users revealed that 17% carry the XRCC1 gln399gln genotype and 19% carry the p53 pro72pro genotype. Both genotypes are associated with increased risk of cancer.
    MeSH terms: Adolescent; Adult; Aged; Blood Cells/metabolism; Blood Cells/pathology; DNA Damage*; Female; Genotype; Humans; India; Male; Middle Aged; Mouth Mucosa/metabolism; Mouth Mucosa/pathology; Risk Factors; Tobacco, Smokeless/adverse effects*; Polymorphism, Single Nucleotide
  9. Bonsu KO, Kadirvelu A, Reidpath DD
    Pharmacol Ther, 2014 Sep;143(3):350.
    PMID: 24769330 DOI: 10.1016/j.pharmthera.2014.04.003
    MeSH terms: Animals; Heart Failure/drug therapy*; Humans; Nitric Oxide Synthase/physiology*
  10. Hosseini S, Ibrahim F, Djordjevic I, Koole LH
    Analyst, 2014 Jun 21;139(12):2933-43.
    PMID: 24769607 DOI: 10.1039/c3an01789c
    Biosensor chips for immune-based assay systems have been investigated for their application in early diagnostics. The development of such systems strongly depends on the effective protein immobilization on polymer substrates. In order to achieve this complex heterogeneous interaction the polymer surface must be functionalized with chemical groups that are reactive towards proteins in a way that surface functional groups (such as carboxyl, -COOH; amine, -NH2; and hydroxyl, -OH) chemically or physically anchor the proteins to the polymer platform. Since the proteins are very sensitive towards their environment and can easily lose their activity when brought in close proximity to the solid surface, effective surface functionalization and high level of control over surface chemistry present the most important steps in the fabrication of biosensors. This paper reviews recent developments in surface functionalization and preparation of polymethacrylates for protein immobilization. Due to their versatility and cost effectiveness, this particular group of plastic polymers is widely used both in research and in industry.
    MeSH terms: Polymethacrylic Acids/chemistry*; Surface Properties; Biosensing Techniques*; Optics and Photonics*
  11. Ramli NM, Sidek S, Rahman FA, Peyman M, Zahari M, Rahmat K, et al.
    Graefes Arch Clin Exp Ophthalmol, 2014 Jun;252(6):995-1000.
    PMID: 24770532 DOI: 10.1007/s00417-014-2622-6
    PURPOSE: To measure optic nerve (ON) volume using 3 T magnetic resonance imaging (MRI), to correlate ON volume with retinal nerve fiber layer (RNFL) thickness, and to determine the viability of MRI as an objective tool in distinguishing glaucoma severity.

    METHODS: In this cross-sectional study, 30 severe glaucoma patients, 30 mild glaucoma patients and 30 age-matched controls were recruited. All subjects underwent standard automated perimetry, RNFL analysis and 3 T MRI examinations. Glaucoma patients were classified according to the Hodapp-Anderson-Parish classification. Pearson's correlation coefficient was used to correlate ON volume with RNFL, and receiver operating curve (ROC) analysis was performed to determine the sensitivity and specificity of ON volume in detecting glaucoma severity.

    RESULTS: Optic nerve volume was significantly lower in both the left and right eyes of the severe glaucoma group (168.70 ± 46.28 mm(3); 167.40 ± 45.36 mm(3)) than in the mild glaucoma group (264.03 ± 78.53 mm(3); 264.76 ± 78.88 mm(3)) and the control group (297.80 ± 71.45 mm(3); 296.56 ± 71.02 mm(3)). Moderate correlation was observed between: RNFL thickness and ON volume (r = 0.51, p <0.001), and in mean deviation of visual field and optic nerve volume (r = 0.60, p 

    MeSH terms: Aged; Aged, 80 and over; Cross-Sectional Studies; Glaucoma, Open-Angle/classification; Glaucoma, Open-Angle/diagnosis*; Humans; Intraocular Pressure/physiology; Magnetic Resonance Imaging*; Middle Aged; Nerve Fibers/pathology*; Optic Disk/pathology; Optic Nerve/pathology*; Optic Nerve Diseases/classification; Optic Nerve Diseases/diagnosis*; Organ Size; Retinal Ganglion Cells/pathology*; Sensitivity and Specificity; Visual Fields/physiology; Reproducibility of Results; Observer Variation; Glaucoma, Angle-Closure/classification; Glaucoma, Angle-Closure/diagnosis*
  12. Woi PM, Bakar MA, Rosli AN, Lee VS, Ahmad MR, Zain S, et al.
    J Mol Model, 2014 May;20(5):2219.
    PMID: 24770548 DOI: 10.1007/s00894-014-2219-3
    DFT and G4 results reveal that cations display the following trends in imparting its positive charge to acrylonitrile; H⁺ > Li⁺ > Na⁺ > K⁺ for group I and Be²⁺ > Mg²⁺ > Ca²⁺ for group II. Solvation by water molecules and interaction with cation make the cyano bond more polarized and exhibits ketene-imine character. Bond order in nitrile-cation complexes has been predicted based on the s character of the covalent bond orbitals. Mulliken, CHELPG, and NPA charges are in good agreement in predicting positive charge buildup and GIAO nuclear deshileding on C1. G4 enthalpies show that Mg²⁺ is more strongly bound to acrylonitrile than to acetonitrile by 3 kcal mol⁻¹, and the proton affinity of the former is higher by 0.8 kcal mol⁻¹. G4 enthalpies of reductions support prior experimental observation that metalated conjugated nitriles show enhanced reactivity toward weak nucleophiles to afford Michael addition products.
    MeSH terms: Acetonitriles/chemistry; Acrylonitrile/chemistry*; Cations/chemistry*; Computer Simulation; Energy Transfer; Gases; Hydrogen-Ion Concentration; Models, Chemical; Models, Molecular; Oxidation-Reduction; Protons; Solvents/chemistry; Structure-Activity Relationship; Vibration; Water/chemistry; Molecular Structure; Static Electricity; Carbon-13 Magnetic Resonance Spectroscopy
  13. Srikumar PS, Rohini K, Rajesh PK
    Protein J, 2014 Jun;33(3):289-95.
    PMID: 24770803 DOI: 10.1007/s10930-014-9561-2
    Mutations in human laforin lead to an autosomal neurodegenerative disorder Lafora disease. In N-terminal carbohydrate binding domain of laforin, two mutations W32G and K87A are reported as highly disease causing laforin mutants. Experimental studies reported that mutations are responsible for the abolishment of glycogen binding which is a critical function of laforin. Our current computational study focused on the role of conformational changes in human laforin structure due to existing single mutation W32G and prepared double mutation W32G/K87A related to loss of glycogen binding. We performed 10 ns molecular dynamics (MD) simulation studies in the Gromacs package for both mutations and analyzed the trajectories. From the results, the global properties like root mean square deviation, root mean square fluctuation, radius of gyration, solvent accessible surface area and hydrogen bonds showed structural changes in atomic level observed in W32G and W32G/K87A laforin mutants. The conformational change induced by mutants influenced the loss of the overall stability of the native laforin. Moreover, the change in overall motion of protein was analyzed by principal component analysis and results showed protein clusters expanded more than native and also change in direction in case of double mutant in conformational space. Overall, our report provides theoretical information on loss of structure-function relationship due to flexible nature of laforin mutants. In conclusion, comparative MD simulation studies support the experimental data on W32G and W32G/K87A related to the lafora disease mechanism on glycogen binding.
    MeSH terms: Glycogen; Humans; Mutation; Protein Binding; Principal Component Analysis; Protein Tyrosine Phosphatases, Non-Receptor/genetics*; Protein Tyrosine Phosphatases, Non-Receptor/metabolism; Protein Tyrosine Phosphatases, Non-Receptor/chemistry*; Molecular Dynamics Simulation
  14. Ho CC, Ngoo KS, Hamzaini AH, Rizal AM, Zulkifli MZ
    Clin Ter, 2014;165(2):75-81.
    PMID: 24770808 DOI: 10.7471/CT.2014.1680
    OBJECTIVE: To determine the clinical utility of urinary bladder and prostate characteristics measured by ultrasound scan in predicting acute urinary retention (AUR) for men with bladder outlet obstruction with an underlying benign prostate hyperplasia (BPH).
    MATERIALS AND METHODS: Consecutive men aged ≥50 years presenting with lower urinary tract symptoms (LUTS) or AUR were prospectively recruited in this cross-sectional study. International prostatic symptom score (IPSS) and serum prostate-specific antigen (PSA) were recorded. High-resolution ultrasound was used to measure bladder detrusor thickness (DT, mm), prostatic volume (PV, cm3), intravesical prostatic protrusion (IPP, mm), bladder wall thickness (BWT,mm), intravesical volume and bladder radius. The latter two parameters were used to estimate bladder weight (UEBW, g), assuming a spherical bladder.
    RESULTS: Among selected patients, thirty had AUR while 32 men presented with LUTS only. There were significant differences between those with and without AUR in their age (70.5 vs 66.0, p=0.017), IPSS (24.0 vs 18.5, p=0.009), serum PSA (6.18 vs 1.77, p=0.002), PV (56.7 vs 32.4, p=0.006), BWT (5.0 vs 4.4, p=0.034) and UEBW (39.1 vs 25.0, p=0.0003). Multivariate analysis revealed high IPSS and UEBW to be predictors for AUR. UEBW was the strongest predictor of AUR: area under ROC curve was 0.767, with sensitivity and specificity of 63.3% and 87.5%, respectively, at cut-off point of 35 g. The likelihood ratio for AUR was also best with UEBW≥35 g.
    CONCLUSIONS: Combined with IPSS, ultrasound determined bladder characteristic, particularly UEBW, is a useful tool in predicting AUR in men with BPH.
    MeSH terms: Acute Disease; Aged; Urinary Bladder/ultrasonography*; Cross-Sectional Studies; Humans; Male; Predictive Value of Tests; Prospective Studies; Prostatic Hyperplasia/complications*; Prostatic Hyperplasia/ultrasonography*; Urinary Retention/etiology*
  15. Masliza W, Daud W, Yazid Bajuri M, Shuhaila A, Hatta S, Rohaizat Hassan M, et al.
    Clin Ter, 2014;165(2):83-9.
    PMID: 24770809 DOI: 10.7471/CT.2014.1681
    Female sexual dysfunction (FSD) has a major impact on interpersonal relationships and quality of life. For many women it has been emotionally distressing, physically disconcerting, and socially disruptive. To determine the prevalence and factors that contribute to female sexual dysfunction (FSD) and to evaluate the different sexual domains that influence sexual function amongst post menopausal women.
    MeSH terms: Adult; Cross-Sectional Studies; Female; Humans; Middle Aged; Sexual Dysfunction, Physiological/etiology*; Sexual Dysfunction, Physiological/epidemiology*; Prevalence; Postmenopause*
  16. Ho CC, Rusdi AR
    Clin Ter, 2014;165(2):107-9.
    PMID: 24770814 DOI: 10.7471/CT.2014.1686
    Scrotal tuberculosis (TB) is rare. Lack of awareness may lead to a misdiagnosis and/or delayed diagnosis of scrotal TB. Clinicians should have a high suspicion index for scrotal TB when facing a patient with a chronic scrotal lump. Since scrotal TB can be medically cured, biopsy of the scrotal lump for pathology study and/or urine polymerase chain reaction (PCR) analysis for M. tuberculosis should be performed first for rapid diagnostic purposes, and therefore unnecessary surgery may thereby be circumvented.
    MeSH terms: Adolescent; Humans; Male; Scrotum*; Tuberculosis, Male Genital/diagnosis*
  17. Arora J, Mehta V, Abhishek K, Nisha S, Suri RK, Rath G, et al.
    Clin Ter, 2014;165(2):111-4.
    PMID: 24770815 DOI: 10.7471/CT.2014.1687
    During extensive osteological study of 150 dry skulls in the Department of Anatomy, Vardhman Mahavir Medical college, an unusual Paramedian Occipital (POC) condyle was detected in the occipital bone of a cadaveric skull. The anatomical details of this unusual occipital condyle were carefully studied and its morphometric measurements taken. A coronal multiplanner reformatted image and a volume rendered image were taken to study radiological details and establish significant clinical correlation. Precise understanding of anatomy of craniovertebral junction and its anomalies have become immensely important for the present day surgeon during orthopaedic and neurosurgical procedures of this region . Technical advancements in imaging modalities such as CT and MRI scans further signify the importance of these anatomical variations ,which are often missed in routine examination. Osteological study combined with radiological details of the paramedian occipital condyle in the present case aims to emphasize the importance of bony anomalies in the craniovertebral region and their role in diagnosis and appropriate treatment of neurovascular compression syndromes of craniovertebral junction. The present study highlights anatomical details, clinical relevance and embryological basis of such a rare unusual paramedian occipital condyle.
    MeSH terms: Cadaver; Humans; Occipital Bone/anatomy & histology*; Occipital Bone/radiography*; Tomography, X-Ray Computed; Anatomic Variation*
  18. Hussein SZ, Yusoff KM, Makpol S, Mohd Yusof YA
    Clin Ter, 2014;165(2):e125-33.
    PMID: 24770820 DOI: 10.7471/CT.2014.1695
    Honey is a supersaturated solution of sugars, enriched with proteins, minerals, vitamins, organic acids and polyphenols. Gamma irradiation is a physical technique of food preservation which protects the honey from insects' and microbial contamination during storage. We investigated the effect of gamma irradiation on physicochemical properties in two types of Malaysian honey, Gelam and Nenas.
    MeSH terms: Gamma Rays*; Honey/radiation effects*; Malaysia; Physicochemical Processes
  19. Kamarudin NH, Rahman RN, Ali MS, Leow TC, Basri M, Salleh AB
    Mol Biotechnol, 2014 Aug;56(8):747-57.
    PMID: 24771007 DOI: 10.1007/s12033-014-9753-1
    Terminal moieties of most proteins are long known to be disordered and flexible. To unravel the functional role of these regions on the structural stability and biochemical properties of AT2 lipase, four C-terminal end residues, (Ile-Thr-Arg-Lys) which formed a flexible, short tail-like random-coil segment were targeted for mutation. Swapping of the tail-like region had resulted in an improved crystallizability and anti-aggregation property along with a slight shift of the thermostability profile. The lipolytic activity of mutant (M386) retained by 43 % compared to its wild-type with 18 % of the remaining activity at 45 °C. In silico analysis conducted at 25 and 45 °C was found to be in accordance to the experimental findings in which the RMSD values of M386 were more stable throughout the total trajectory in comparison to its wild-type. Terminal moieties were also observed to exhibit large movement and flexibility as denoted by high RMSF values at both dynamics. Variation in organic solvent stability property was detected in M386 where the lipolytic activity was stimulated in the presence of 25 % (v/v) of DMSO, isopropanol, and diethyl ether. This may be worth due to changes in the surface charge residues at the mutation point which probably involve in protein-solvent interaction.
    MeSH terms: Bacterial Proteins/genetics*; Bacterial Proteins/metabolism*; Bacterial Proteins/chemistry; Biotechnology; Cold Temperature; Computer Simulation; Crystallization; Enzyme Stability/genetics; Genes, Bacterial; Lipase/genetics*; Lipase/metabolism*; Lipase/chemistry; Models, Molecular; Protein Conformation; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Recombinant Proteins/chemistry; Solubility; Solvents; Staphylococcus epidermidis/enzymology*; Staphylococcus epidermidis/genetics; Sequence Deletion; Molecular Dynamics Simulation
  20. Gupta G, Krishna G, Chellappan DK, Gubbiyappa KS, Candasamy M, Dua K
    Mol Cell Biochem, 2014 Aug;393(1-2):223-8.
    PMID: 24771068 DOI: 10.1007/s11010-014-2064-9
    Acetaminophen has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. Pioglitazone, PPARγ ligand, is clinically tested and used in treatment of diabetes. PPARγ is a key nuclear hormone receptor of lipid metabolisms and regulates several gene transcriptions associated with differentiation, growth arrest, and apoptosis. The aim of our study was to evaluate the hepatoprotective activity of pioglitazone on acetaminophen-induced hepatotoxicity and to understand the relationship between the PPARγ and acetaminophen-induced hepato injury. For the experiment, Sprague-Dawley rats (160-180 g) were used and divided into four groups. Groups I and II were normal and experimental controls, respectively. Groups III and IV received the pioglitazone 20 mg/kg for 10 days. Hepatotoxicity was induced in Groups II and III on the eighth day with acetaminophen (i.p. 350 mg/kg body weight). The hepatoprotective effect was evaluated by performing an assay of the total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and α-fetoprotein as well as glutathione peroxidase, lipid peroxidation, catalase, superoxide dismutase, and glutathione transferase and liver histopathology. The assay results were presented as mean and standard error of mean for each group. The study group was compared with the control group by one-way ANOVA test. A p value of <0.05 was considered significant. Pioglitazone significantly reduced the elevated level of above serum marker enzymes and also inhibits the free radical formation by scavenging hydroxyl ions. It also restored the level of LPO and significantly elevated the levels of endogenous antioxidant enzymes in acetaminophen-challenged hepatotoxicity. Liver histopathological examination showed that pioglitazone administration antagonized acetaminophen -induced liver pathological damage. Various biochemical estimations of different hepatic markers and antioxidant enzymes and histopathological studies of liver tissues glimpse a support to its significant hepatoprotective activity on acetaminophen -induced hepatotoxicity.
    MeSH terms: Acetaminophen/adverse effects*; Acetaminophen/therapeutic use; Animals; Lipid Peroxidation/drug effects; Thiazolidinediones/administration & dosage*; PPAR gamma/metabolism*; Rats; Drug-Induced Liver Injury/drug therapy*; Drug-Induced Liver Injury/metabolism; Drug-Induced Liver Injury/pathology
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