Browse publications by year: 2016

  1. Chin ZW, Chong WS, Mani SA
    Oral Health Prev Dent, 2016;14(2):125-35.
    PMID: 26525124 DOI: 10.3290/j.ohpd.a34999
    PURPOSE: To assess the knowledge, attitude and utilisation regarding fissure sealants (FS) and preventive resin restorations (PRR) among Malaysian dentists.

    MATERIALS AND METHODS: A questionnaire consisting of 35 questions was distributed by mail or an online survey to 425 registered dentists selected according to place of work by stratified random sampling.

    RESULTS: One hundred fifty-three dentists responded to the survey. A positive attitude towards FS and PRR was noted among most Malaysian dentists. About half of the respondents used FS/PRR occasionally (48.4%), while few (13.7%) applied them routinely. The majority of the dentists agreed that minimally invasive dentistry is important and FS are effective in caries prevention, using them on high caries-risk individuals. Most of the dentists used pumice or paste to clean teeth before placing FS/PRR. A significant number of dentists used a bonding agent prior to placing FS. Although only 57.5% dentists were aware of guidelines for FS use, most dentists agreed that guidelines are important.

    CONCLUSION: Although there was a positive attitude towards FS/PRR, few dentists applied them routinely. Some of the steps undertaken for placement of FS and PRR were outdated. Updating local guidelines for dentists to ensure uniform practice of FS and PRR is justified.

    MeSH terms: Acid Etching, Dental/methods; Adult; Age Factors; Attitude of Health Personnel*; Composite Resins/chemistry*; Dental Caries/prevention & control*; Dental Caries Susceptibility; Dental Cements/chemistry; Dental Materials/chemistry*; Dental Prophylaxis/methods; Dentists/psychology*; Female; Humans; Malaysia; Male; Middle Aged; Pit and Fissure Sealants/therapeutic use*; Professional Practice; Practice Guidelines as Topic; Practice Patterns, Dentists'*; Tooth Preparation/methods; Young Adult; Dental Atraumatic Restorative Treatment/methods*
  2. Jothy SL, Saito T, Kanwar JR, Chen Y, Aziz A, Yin-Hui L, et al.
    Phys Med, 2016 Jan;32(1):150-61.
    PMID: 26526749 DOI: 10.1016/j.ejmp.2015.10.090
    The radioprotective effect of Polyalthia longifolia was studied in mice. P. longifolia treatment showed improvement in mice survival compared to 100% mortality in the irradiated mice. Significant increases in hemoglobin concentration, and red blood cell, white blood cell and platelet counts were observed in the animals pretreated with leaf extract. Pre-irradiation administration of P. longifolia leaf extract also increased the CFU counts of the spleen colony and increased the relative spleen size. A dose-dependent decrease in lipid peroxidation levels was observed in the animals pretreated with P. longifolia. However, although the animals pretreated with P. longifolia exhibited a significant increase in superoxide dismutase and catalase activity, the values remained below normal in both liver and the intestine. Pre-irradiation administration of P. longifolia also resulted in the regeneration of the mucosal crypts and villi of the intestine. Moreover, pretreatment with P. longifolia leaf extract also showed restoration of the normal liver cell structure and a significant reduction in the elevated levels of ALT, AST and bilirubin. These results suggested the radioprotective ability of P. longifolia leaf extract, which is significant for future investigation for human applications in developing efficient, economically viable, non-toxic natural and clinically acceptable novel radioprotectors.
    MeSH terms: Animals; Antioxidants/chemistry; Blood Platelets/radiation effects; Catalase/metabolism; Chromatography, Liquid; Erythrocytes/radiation effects; Leukocytes/radiation effects; Liver/radiation effects*; Male; Plant Extracts/chemistry*; Radiation Injuries/therapy*; Radiation-Protective Agents/chemistry*; Rutin/chemistry; Spleen/radiation effects*; Stem Cells; Superoxide Dismutase/metabolism; Temperature; Whole-Body Irradiation; X-Rays; Lipid Peroxidation; Plant Leaves/chemistry; Polyalthia/chemistry*; Mice; Tandem Mass Spectrometry
  3. Koay JB, Natasya NN, Nashithatul M, Ihsanuddin R, Salleh FM, Azil AH
    Biotech Histochem, 2016;91(1):63-70.
    PMID: 26528914 DOI: 10.3109/10520295.2015.1074286
    Permanent mounting of fourth instar mosquito larvae is essential for identifying Aedes spp. This procedure requires extensive exposure to xylene, a clearing agent in the mounting process. We investigated wintergreen oil as a substitute for xylene. Five hundred larvae were mounted on slides to evaluate shrinkage or expansion of specimens after clearing using xylene or wintergreen oil. We examined the ventral brush and siphonal hair tufts for species identification and for preservation of morphological characteristics after clearing specimens in xylene or wintergreen oil. Shrinkage of the length of whole larvae and width of the head, thorax and abdomen after mounting was significantly greater after clearing with xylene than with wintergreen oil. The length of the comb scale nearest the ventral brush was similar for both clearing agents. The clarity of the specimens after mounting was improved by clearing with wintergreen oil, but the integrity of the ventral brush and siphonal hair tufts were similar for both clearing agents.
  4. Riazalhosseini B, Mohamed Z, Apalasamy YD, Eng HS, Mohamed R
    Pharmacogenet Genomics, 2016 Feb;26(2):74-9.
    PMID: 26529280 DOI: 10.1097/FPC.0000000000000187
    MicroRNAs (miRNAs) are small noncoding RNAs that have been implicated in mechanisms underlying various types of cancers including hepatocellular carcinoma (HCC). Reports have indicated that single nucleotide polymorphisms in miRNA-196A2 and miRNA-146A genes may contribute to the risk of progression of hepatitis B virus (HBV) infection to cirrhosis and HCC. This study aimed to examine the effect of miRNA-196A2 and miRNA-146A polymorphisms on the progression of HBV infection to cirrhosis and/or HCC in HBV patients in the Malaysian population.
    MeSH terms: Hepatitis B; Hepatitis B virus; Carcinoma, Hepatocellular; Humans; Liver Cirrhosis; Liver Neoplasms; Disease Progression; Polymorphism, Single Nucleotide; MicroRNAs; RNA, Small Untranslated
  5. Yafouz B, Kadri NA, Rothan HA, Yusof R, Ibrahim F
    Electrophoresis, 2016 Feb;37(3):511-8.
    PMID: 26530354 DOI: 10.1002/elps.201500282
    Dielectrophoresis (DEP), the induced movement of dielectric particles placed in a nonuniform electric field, has been used as a potential technique for manipulation and separation of many biological samples without destructive consequences to the cell. Cells of the same genotype in different physiological and pathological states have unique morphological and structural features, therefore, it is possible to differentiate between them using their DEP responses. This paper reports the experimental discrimination of normal and dengue-infected human hepatic fetal epithelial cells (WRL-68 cells) based on their DEP crossover frequency, at which no resultant movement occurs in the cells in response to the DEP force. A microarray dot electrode was used to conduct the DEP experiments. The DEP forces applied to the cells were quantified by analyzing the light intensity shift within the electrode's dot region based on the Cumulative Modal Intensity Shift image analysis technique. The differences in dielectric properties between infected and uninfected cells were exploited by plotting a unique DEP spectrum for each set of cells. We observed that the crossover frequency decreased from 220 kHz for the normal WRL-68 cells to 140 kHz after infection with the dengue virus in a medium conductivity of 100 μS/cm. We conclude that the change in the DEP crossover frequency between dengue-infected cells and their healthy counterparts should allow direct characterization of these cell types by exploiting their electrophysiological properties.
  6. Baharuddin P, Satar N, Fakiruddin KS, Zakaria N, Lim MN, Yusoff NM, et al.
    Oncol Rep, 2016 Jan;35(1):13-25.
    PMID: 26531053 DOI: 10.3892/or.2015.4371
    Natural compounds such as curcumin have the ability to enhance the therapeutic effectiveness of common chemotherapy agents through cancer stem-like cell (CSC) sensitisation. In the present study, we showed that curcumin enhanced the sensitivity of the double-positive (CD166+/EpCAM+) CSC subpopulation in non-small cell lung cancer (NSCLC) cell lines (A549 and H2170) to cisplatin-induced apoptosis and inhibition of metastasis. Our results revealed that initial exposure of NSCLC cell lines to curcumin (10-40 µM) markedly reduced the percentage of viability to an average of ~51 and ~54% compared to treatment with low dose cisplatin (3 µM) with only 94 and 86% in both the A549 and H2170 cells. Moreover, sensitisation of NSCLC cell lines to curcumin through combined treatment enhanced the single effect induced by low dose cisplatin on the apoptosis of the double-positive CSC subpopulation by 18 and 20% in the A549 and H2170 cells, respectively. Furthermore, we found that curcumin enhanced the inhibitory effects of cisplatin on the highly migratory CD166+/EpCAM+ subpopulation, marked by a reduction in cell migration to 9 and 21% in the A549 and H2170 cells, respectively, indicating that curcumin may increase the sensitivity of CSCs to cisplatin-induced migratory inhibition. We also observed that the mRNA expression of cyclin D1 was downregulated, while a substantial increased in p21 expression was noted, followed by Apaf1 and caspase-9 activation in the double-positive (CD166+/EpCAM+) CSC subpopulation of A549 cells, suggested that the combined treatments induced cell cycle arrest, therefore triggering CSC growth inhibition via the intrinsic apoptotic pathway. In conclusion, we provided novel evidence of the previously unknown therapeutic effects of curcumin, either alone or in combination with cisplatin on the inhibition of the CD166+/EpCAM+ subpopulation of NSCLC cell lines. This finding demonstrated the potential therapeutic approach of using curcumin that may enhance the effects of cisplatin by targeting the CSC subpopulation in NSCLC.
    MeSH terms: Antineoplastic Agents/pharmacology*; Carcinoma, Non-Small-Cell Lung/genetics; Carcinoma, Non-Small-Cell Lung/metabolism*; Cell Cycle/drug effects; Cell Movement/drug effects; Cell Survival/drug effects; Cisplatin/pharmacology; Curcumin/pharmacology*; Drug Synergism; Humans; Lung Neoplasms/genetics; Lung Neoplasms/metabolism*; Neoplastic Stem Cells/drug effects*; Neoplastic Stem Cells/metabolism; Signal Transduction/drug effects; Gene Expression Regulation, Neoplastic/drug effects; Cyclin D1/genetics*; Cyclin D1/metabolism; Cell Line, Tumor; Cell Proliferation/drug effects; Cyclin-Dependent Kinase Inhibitor p21/genetics*; Cyclin-Dependent Kinase Inhibitor p21/metabolism
  7. Zia A, Kamaruzzaman S, Myint PK, Tan MP
    Maturitas, 2016 Feb;84:32-7.
    PMID: 26531071 DOI: 10.1016/j.maturitas.2015.10.009
    OBJECTIVE: While the anticholinergic activity of medications has been linked to cognitive decline, few studies have linked anticholinergic burden with falls in older people. We evaluated the relationship between anticholinergic burden and recurrent and injurious falls among community-dwelling older adults.
    STUDY DESIGN: This case-control study was performed on 428 participants aged ≥65 years, 263 cases with two or more falls or one injurious fall in the preceding 12 months, and 165 controls with no falls in the preceding 12 months. Anticholinergic burden was determined using the anticholinergic cognitive burden (ACB) scale. Upper and lower limb functional abilities were assessed with timed up and go (TUG), functional reach (FR) and grip strength (GS). Logistic regression analysis was employed to calculate the mediation effect of TUG, FR and GS on ACB associated falls.
    RESULTS: Univariate analysis revealed a significant association between an ACB score of ≥1 with falls (OR, 1.8; 95% CI; 1.1-3.0; p=0.01) and significantly poorer TUG and FR. The association between ACB≥1 and falls was no longer significant after adjustment for either TUG (OR for ACB associated falls, 1.4; 95% CI, 0.88-2.4; p=0.14) or FR (OR for ACB associated falls, 1.4; 95% CI, 0.89-2.4, p=0.12) but remained significant with GS.
    CONCLUSION: The association between recurrent and injurious falls and the use of any medications listed in the ACB scale was mediated through gait and balance impairment but not by muscular weakness, providing a novel insight into the potential mechanistic link between ACB and falls. Future studies should determine whether TUG and FR measurements could help inform risk to benefit decisions where ACB medications are being considered.
    KEYWORDS: Aged; Anticholinergic Cognitive Burden; Falls; Functional Reach; Scale; Timed up and go
    MeSH terms: Accidental Falls*
  8. Ali Z, Elamvazuthi I, Alsulaiman M, Muhammad G
    J Med Syst, 2016 Jan;40(1):20.
    PMID: 26531753 DOI: 10.1007/s10916-015-0392-2
    Voice disorders are associated with irregular vibrations of vocal folds. Based on the source filter theory of speech production, these irregular vibrations can be detected in a non-invasive way by analyzing the speech signal. In this paper we present a multiband approach for the detection of voice disorders given that the voice source generally interacts with the vocal tract in a non-linear way. In normal phonation, and assuming sustained phonation of a vowel, the lower frequencies of speech are heavily source dependent due to the low frequency glottal formant, while the higher frequencies are less dependent on the source signal. During abnormal phonation, this is still a valid, but turbulent noise of source, because of the irregular vibration, affects also higher frequencies. Motivated by such a model, we suggest a multiband approach based on a three-level discrete wavelet transformation (DWT) and in each band the fractal dimension (FD) of the estimated power spectrum is estimated. The experiments suggest that frequency band 1-1562 Hz, lower frequencies after level 3, exhibits a significant difference in the spectrum of a normal and pathological subject. With this band, a detection rate of 91.28 % is obtained with one feature, and the obtained result is higher than all other frequency bands. Moreover, an accuracy of 92.45 % and an area under receiver operating characteristic curve (AUC) of 95.06 % is acquired when the FD of all levels is fused. Likewise, when the FD of all levels is combined with 22 Multi-Dimensional Voice Program (MDVP) parameters, an improvement of 2.26 % in accuracy and 1.45 % in AUC is observed.
    MeSH terms: Algorithms; Humans; Voice/physiology; Voice Disorders/diagnosis*; Voice Disorders/physiopathology*; Fractals*; Wavelet Analysis*
  9. Tan CL, Hassali MA, Saleem F, Shafie AA, Aljadhay H, Gan VB
    Health Expect, 2016 Dec;19(6):1215-1225.
    PMID: 26426210 DOI: 10.1111/hex.12416
    OBJECTIVE: To improve pharmaceutical care delivery in Malaysia, the Ministry of Health (MOH) had introduced the concept of value added services (VAS). Despite its reported convenience and advantages, VAS utilization rate is low in the country. The study aims to explore patients' understanding, beliefs and expectations towards VAS in Malaysia using the theory of planned behaviour (TPB) as the theoretical model.

    METHODS: A qualitative methodology was used whereby face-to-face interviews were conducted with 12 patients who collected partial medicine supplies from government pharmacies. Participants were recruited using purposive and snowball sampling method in the state of Negeri Sembilan, Malaysia. Interviews were audio-recorded. Verbatim transcription and thematic content analysis were performed on the data.

    RESULTS: Thematic content analysis yielded five major themes: (i) attitudes towards using VAS, (ii) subjective norms, (iii) perceived behavioural control, (iv) lack of knowledge and understanding of VAS and (v) expectations towards VAS.

    CONCLUSION: The interviews explored and informed new information about salient beliefs towards pharmacy VAS. The findings suggest that VAS is still in its infancy and a more robust and effective advertising and marketing campaign is needed to boost the adoption rate. Behavioural attitudes, subjective norms and perceived control elements were discussed and serve as important variables of interest in future study. Expectations towards VAS serve as an important guideline to further improve patient-oriented services.

    MeSH terms: Adult; Aged; Attitude to Health; Female; Humans; Interviews as Topic; Health Knowledge, Attitudes, Practice*; Malaysia; Male; Middle Aged; Models, Theoretical; Patient Acceptance of Health Care*; Pharmaceutical Services/organization & administration*; Qualitative Research; Quality Improvement
  10. Ali-Seyed M, Jantan I, Vijayaraghavan K, Bukhari SN
    Chem Biol Drug Des, 2016 Apr;87(4):517-36.
    PMID: 26535952 DOI: 10.1111/cbdd.12682
    An important method of drug discovery is examination of diverse life forms, including medicinal plants and natural products or bioactive compounds isolated from these sources. In cancer research, lead structures of compounds from natural sources can be used to design novel chemotherapies with enhanced biological properties. Betulinic acid (3β-hydroxy-lup-20(29)-en-28-oic acid or BetA) is a naturally occurring pentacyclic triterpene with a wide variety of biological activities, including potent antitumor properties. Non-malignant cells and normal tissues are not affected by BetA. Because BetA exerts its effects directly on the mitochondrion and triggers death of cancerous cells, it is an important alternative when certain chemotherapy drugs fail. Mitochondrion-targeted agents such as BetA hold great promise to circumvent drug resistance in human cancers. BetA is being developed by a large network of clinical trial groups with the support of the U.S. National Cancer Institute. This article discusses recent advances in research into anticancer activity of BetA, relevant modes of delivery, and the agent's therapeutic efficacy, mechanism of action, and future perspective as a pipeline anticancer drug. BetA is a potentially important agent in cancer therapeutics.
  11. Younis KM, Usup G, Ahmad A
    Environ Sci Pollut Res Int, 2016 Mar;23(5):4756-67.
    PMID: 26538254 DOI: 10.1007/s11356-015-5687-9
    Quorum-sensing regulates bacterial biofilm formation and virulence factors, thereby making it an interesting target for attenuating pathogens. In this study, we investigated anti-biofilm and anti-quorum-sensing compounds from secondary metabolites of halophiles marine streptomyces against urinary catheter biofilm forming Proteus mirabilis without effect on growth viability. A total of 40 actinomycetes were isolated from samples collected from different places in Iraq including marine sediments and soil samples. Fifteen isolates identified as streptomyces and their supernatant screened as anti-quorum-sensing by inhibiting quorum-sensing regulated prodigiosin biosynthesis of Serratia marcescens strain Smj-11 as a reporter strain. Isolate Sediment Lake Iraq (sdLi) showed potential anti-quorum-sensing activity. Out of 35 clinical isolates obtained from Urinary catheter used by patient at the Universiti Kebangsaan Malaysia Medical Center, 22 isolates were characterized and identified as Proteus mirabilis. Isolate Urinary Catheter B4 (UCB4) showed the highest biofilm formation with highest resistance to used antibiotic and was chosen for further studies. Ethyl acetate secondary metabolites extract was produced from sdLi isolate. First, we determined the Minimum Inhibitory Concentration (MIC) of sdLi crude extract against UCB4 isolate, and all further experiments used concentrations below the MIC. Tests of subinhibitory concentrations of sdLi crude extract showed good inhibition against UCB4 isolate biofilm formation on urinary catheter and cover glass using Scanning electron microscopy and light microscopy respectively. The influence of sub-MIC of sdLi crude extract was also found to attenuate the quorum sensing (QS)-dependent factors such as hemolysin activity, urease activity, pH value, and motility of UCB4 isolate. Evidence is presented that these nontoxic secondary metabolites may act as antagonists of bacterial quorum sensing by competing with quorum-sensing signals for receptor binding.
    MeSH terms: Anti-Bacterial Agents/metabolism*; Anti-Bacterial Agents/pharmacology; Humans; Iraq; Malaysia; Prodigiosin/biosynthesis; Proteus mirabilis/drug effects*; Proteus mirabilis/metabolism; Serratia marcescens; Soil Microbiology; Streptomyces/metabolism*
  12. Yong SK, Skinner WM, Bolan NS, Lombi E, Kunhikrishnan A, Ok YS
    Environ Sci Pollut Res Int, 2016 Jan;23(2):1050-9.
    PMID: 26538256 DOI: 10.1007/s11356-015-5654-5
    Pristine chitosan beads were modified with sulfur (S)-containing functional groups to produce thiolated chitosan beads (ETB), thereby increasing S donor ligands and crosslinks. The effect of temperature, heating time, carbon disulfide (CS2)/chitosan ratio, and pH on total S content of ETB was examined using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The total S content of ETB increased with increasing CS2/chitosan ratio and decreased with decreasing pH and increasing temperature (>60 °C) and heating time (at 60 °C). Spectroscopic analyses revealed the presence of thiol (-SH)/thione, disulfide (-S-S-), and sulfonate groups in ETB. The thiolation mechanism involves decomposition of dithiocarbamate groups, thereby forming thiourea crosslinks and trithiocarbonate, resulting in -SH oxidation to produce -S-S- crosslinks. The partially formed ETB crosslinks contribute to its acid stability and are thermodynamically feasible in adsorbing Cd and Cu. The S-containing functional groups added to chitinous wastes act as sorbents for metal remediation from acidic environments.
    MeSH terms: Adsorption; Cadmium/chemistry*; Copper/chemistry*; Hydrogen-Ion Concentration; Sulfur/chemistry*; Thermodynamics; Water Pollutants, Chemical/chemistry*; Spectroscopy, Fourier Transform Infrared; Water Purification/instrumentation; Water Purification/methods*; Chitosan/chemistry*; Environmental Restoration and Remediation/instrumentation; Environmental Restoration and Remediation/methods*
  13. Tan L, Wang M, Li X, Li H, Zhao J, Qu Y, et al.
    Bioresour Technol, 2016 Jan;200:572-8.
    PMID: 26539970 DOI: 10.1016/j.biortech.2015.10.079
    In this work, fractionation of empty fruit bunch (EFB) by bisulfite pretreatment was studied for the production of bioethanol and high value products to achieve biorefinery of EFB. EFB was fractionated to solid and liquor components by bisulfite process. The solid components were used for bioethanol production by quasi-simultaneous saccharification and fermentation. The liquor components were then converted to furfural by hydrolysis with sulfuric acid. Preliminary results showed that the concentration of furfural was highest at 18.8g/L with 0.75% sulfuric acid and reaction time of 25min. The conversion of xylose to furfural was 82.5%. Furthermore, we attempted to fractionate the liquor into hemicellulose sugars and lignin by different methods for producing potential chemicals, such as xylose, xylooligosaccharide, and lignosulfonate. Our research showed that the combination of bisulfite pretreatment and resin separation could effectively fractionate EFB components to produce bioethanol and other high value chemicals.
    MeSH terms: Fermentation; Fruit; Furaldehyde; Hydrolysis; Lignin; Polysaccharides; Reaction Time; Sulfuric Acids; Xylose
  14. Garba NN, Ramli AT, Saleh MA, Sanusi SM, Gabdo HT
    Isotopes Environ Health Stud, 2016 Jun;52(3):214-8.
    PMID: 26540360 DOI: 10.1080/10256016.2016.1095189
    Measurements of the environmental terrestrial gamma radiation dose rate (TGRD) in each district of Kelantan state, Malaysia, were carried out using a portable hand-held radiation survey meter and global positioning system. The measurements were done based on geology and soil types of the area. The mean TGRD was found to be 209 nGy h(-1). Few areas of relatively enhanced activity were observed in Pasir Mas, Tanah Merah and Jeli districts, which have a mean TGRD between 300 and 500 nGy h(-1). An isodose map of the area was produced using ArcGIS software version 9.3.
    MeSH terms: Background Radiation*; Gamma Rays*; Malaysia; Radiation Dosage*; Radiation Monitoring/methods*; Soil Pollutants, Radioactive/analysis; Geologic Sediments/analysis; Geographic Information Systems; Geological Phenomena
  15. Mittal P, Klingler-Hoffmann M, Arentz G, Zhang C, Kaur G, Oehler MK, et al.
    Proteomics Clin Appl, 2016 Mar;10(3):217-29.
    PMID: 26541900 DOI: 10.1002/prca.201500055
    This review discusses the current status of proteomics technology in endometrial cancer diagnosis, treatment and prognosis. The first part of this review focuses on recently identified biomarkers for endometrial cancer, their importance in clinical use as well as the proteomic methods used in their discovery. The second part highlights some of the emerging mass spectrometry based proteomic technologies that promise to contribute to a better understanding of endometrial cancer by comparing the abundance of hundreds or thousands of proteins simultaneously.
  16. Hasmad HN, Lai KN, Wen WX, Park DJ, Nguyen-Dumont T, Kang PCE, et al.
    Gynecol Oncol, 2016 05;141(2):318-322.
    PMID: 26541979 DOI: 10.1016/j.ygyno.2015.11.001
    OBJECTIVE: Despite the discovery of breast and ovarian cancer predisposition genes BRCA1 and BRCA2 more than two decades ago, almost all the available data relate to women of European ancestry, with only a handful of studies in Asian populations. In this study, we determined the frequency of germline alterations in BRCA1 and BRCA2 in ovarian cancer patients from a multi-ethnic cross-sectional cohort of Asian ovarian cancer patients from Malaysia.

    METHODS: From October 2008 to February 2015, we established a hospital-based cohort of ovarian cancer patients and the germline status of all 218 women with invasive epithelial ovarian cancer was tested using targeted amplification and sequencing of the intron-exon junctions and exonic sequences of BRCA1, BRCA2, PALB2 and TP53.

    RESULTS: BRCA1 and BRCA2 mutations were found in 8% (17 cases) and 3% (7 cases) of the ovarian cancer patients, respectively. Mutation carriers were diagnosed at a similar age to non-carriers, but were more likely to be Indian, have serous ovarian cancer, and have more relatives with breast or ovarian cancer. Nonetheless, 42% (10/24) of mutation carriers did not have any family history of breast or ovarian cancer and offering genetic counselling and genetic testing only to women with family history would mean that 35% (6/17) of BRCA1 mutation carriers and 57% (4/7) of BRCA2 mutation carriers would not be offered genetic testing.

    CONCLUSIONS: Our data suggest that, similar to Caucasians, a significant proportion of Asian ovarian cancer was attributed to germline mutations in BRCA1 and to a lesser extent in BRCA2.

    MeSH terms: Cross-Sectional Studies; DNA Mutational Analysis; Female; Humans; Neoplasms, Glandular and Epithelial/genetics*; Ovarian Neoplasms/genetics*; Cohort Studies; Genes, p53; Tumor Suppressor Protein p53/genetics; Germ-Line Mutation*; BRCA1 Protein/genetics; Genes, BRCA1*; Genetic Predisposition to Disease; Genes, BRCA2*; BRCA2 Protein/genetics; Asian Continental Ancestry Group/genetics*
  17. Yeo FK, Wang Y, Vozabova T, Huneau C, Leroy P, Chalhoub B, et al.
    Theor Appl Genet, 2016 Feb;129(2):289-304.
    PMID: 26542283 DOI: 10.1007/s00122-015-2627-5
    Rphq2, a minor gene for partial resistance to Puccinia hordei , was physically mapped in a 188 kbp introgression with suppressed recombination between haplotypes of rphq2 and Rphq2 barley cultivars.
    MeSH terms: Hordeum/genetics*; Hordeum/microbiology; Basidiomycota; Chromosome Mapping; Haplotypes; Phenotype; Plant Diseases/genetics*; Plant Diseases/microbiology; Gene Library; Genes, Plant*; Sequence Analysis, DNA; DNA, Plant/genetics; Chromosomes, Artificial, Bacterial; Quantitative Trait Loci*; Molecular Sequence Annotation; Transcriptome; Disease Resistance/genetics*
  18. Magalingam KB, Radhakrishnan A, Haleagrahara N
    Int J Immunopathol Pharmacol, 2016 Mar;29(1):30-9.
    PMID: 26542606 DOI: 10.1177/0394632015613039
    There is increasing evidence that free radicals induced oxidative stress is a major causative agent in the pathogenesis of neurodegenerative diseases, particularly Parkinson's disease. Quercetin glycosides, namely rutin and isoquercitrin, are flavonoid polyphenol compounds found ubiquitously in fruits and vegetables and have been known to possess antioxidant effects. This study was designed to compare the neuroprotective effects of quercetin glycosides rutin and isoquercitrin in 6-OHDA-induced rat pheochromocytoma (PC-12) cells. The results showed that both rutin and isoquercitrin significantly increased antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, and glutathione level that were attenuated by 6-OHDA in PC-12 cells. There was no significant difference in the activation of glutathione and glutathione peroxidase enzymes between rutin and isoquercitrin. These two glycosides were equally effective in suppressing lipid peroxidation in 6-OHDA-induced PC-12 cells as both compounds suppressed the malondialdehyde generation and prevented cell damage. In conclusion, quercetin glycosides rutin and isoquercetrin are having a significant neuroprotective effect against 6-OHDA toxicity in PC-12 cells.
    MeSH terms: Animals; Quercetin/analogs & derivatives*; Quercetin/pharmacology; Rutin/pharmacology*; Oxidopamine/toxicity*; PC12 Cells; Neuroprotective Agents/pharmacology*; Rats
  19. Bei JX, Su WH, Ng CC, Yu K, Chin YM, Lou PJ, et al.
    Cancer Epidemiol Biomarkers Prev, 2016 Jan;25(1):188-192.
    PMID: 26545403 DOI: 10.1158/1055-9965.EPI-15-0144
    BACKGROUND: Genetic loci within the major histocompatibility complex (MHC) have been associated with nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer, in several GWAS. Results outside this region have varied.

    METHODS: We conducted a meta-analysis of four NPC GWAS among Chinese individuals (2,152 cases; 3,740 controls). Forty-three noteworthy findings outside the MHC region were identified and targeted for replication in a pooled analysis of four independent case-control studies across three regions in Asia (4,716 cases; 5,379 controls). A meta-analysis that combined results from the initial GWA and replication studies was performed.

    RESULTS: In the combined meta-analysis, rs31489, located within the CLPTM1L/TERT region on chromosome 5p15.33, was strongly associated with NPC (OR = 0.81; P value 6.3 × 10(-13)). Our results also provide support for associations reported from published NPC GWAS-rs6774494 (P = 1.5 × 10(-12); located in the MECOM gene region), rs9510787 (P = 5.0 × 10(-10); located in the TNFRSF19 gene region), and rs1412829/rs4977756/rs1063192 (P = 2.8 × 10(-8), P = 7.0 × 10(-7), and P = 8.4 × 10(-7), respectively; located in the CDKN2A/B gene region).

    CONCLUSIONS: We have identified a novel association between genetic variation in the CLPTM1L/TERT region and NPC. Supporting our finding, rs31489 and other SNPs in this region have been reported to be associated with multiple cancer sites, candidate-based studies have reported associations between polymorphisms in this region and NPC, the TERT gene has been shown to be important for telomere maintenance and has been reported to be overexpressed in NPC, and an EBV protein expressed in NPC (LMP1) has been reported to modulate TERT expression/telomerase activity.

    IMPACT: Our finding suggests that factors involved in telomere length maintenance are involved in NPC pathogenesis.

    MeSH terms: Carcinoma; Haplotypes; Humans; Membrane Proteins/genetics*; Nasopharyngeal Neoplasms/genetics*; Nasopharyngeal Neoplasms/pathology; Neoplasm Proteins/genetics*; Prognosis; Case-Control Studies; Telomerase/genetics*; Genetic Predisposition to Disease*; Polymorphism, Single Nucleotide/genetics*; Asian Continental Ancestry Group; Genome-Wide Association Study; Genetic Loci*
  20. Ning F, Luo L, Ahmad S, Valli H, Jeevaratnam K, Wang T, et al.
    Pflugers Arch, 2016 Apr;468(4):655-65.
    PMID: 26545784 DOI: 10.1007/s00424-015-1750-0
    Catecholaminergic polymorphic ventricular tachycardia (CPVT) predisposes to ventricular arrhythmia due to altered Ca(2+) homeostasis and can arise from ryanodine receptor (RyR2) mutations including RyR2-P2328S. Previous reports established that homozygotic murine RyR2-P2328S (RyR2 (S/S)) hearts show an atrial arrhythmic phenotype associated with reduced action potential (AP) conduction velocity and sodium channel (Nav1.5) expression. We now relate ventricular arrhythmogenicity and slowed AP conduction in RyR2 (S/S) hearts to connexin-43 (Cx43) and Nav1.5 expression and Na(+) current (I Na). Stimulation protocols applying extrasystolic S2 stimulation following 8 Hz S1 pacing at progressively decremented S1S2 intervals confirmed an arrhythmic tendency despite unchanged ventricular effective refractory periods (VERPs) in Langendorff-perfused RyR2 (S/S) hearts. Dynamic pacing imposing S1 stimuli then demonstrated that progressive reductions of basic cycle lengths (BCLs) produced greater reductions in conduction velocity at equivalent BCLs and diastolic intervals in RyR2 (S/S) than WT, but comparable changes in AP durations (APD90) and their alternans. Western blot analyses demonstrated that Cx43 protein expression in whole ventricles was similar, but Nav1.5 expression in both whole tissue and membrane fractions were significantly reduced in RyR2 (S/S) compared to wild-type (WT). Loose patch-clamp studies similarly demonstrated reduced I Na in RyR2 (S/S) ventricles. We thus attribute arrhythmogenesis in RyR2 (S/S) ventricles resulting from arrhythmic substrate produced by reduced conduction velocity to downregulated Nav1.5 reducing I Na, despite normal determinants of repolarization and passive conduction. The measured changes were quantitatively compatible with earlier predictions of linear relationships between conduction velocity and the peak I Na of the AP but nonlinear relationships between peak I Na and maximum Na(+) permeability.
    MeSH terms: Action Potentials*; Animals; Arrhythmias, Cardiac/metabolism*; Female; Heart Ventricles/metabolism*; Heart Ventricles/physiopathology; Male; Down-Regulation; Ventricular Function*; Connexin 43/genetics; Connexin 43/metabolism; Ryanodine Receptor Calcium Release Channel/genetics; Ryanodine Receptor Calcium Release Channel/metabolism*; Mutation, Missense*; Mice; NAV1.5 Voltage-Gated Sodium Channel/genetics; NAV1.5 Voltage-Gated Sodium Channel/metabolism*
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