Browse publications by year: 2017

  1. Bamia C, Orfanos P, Juerges H, Schöttker B, Brenner H, Lorbeer R, et al.
    Maturitas, 2017 Sep;103:37-44.
    PMID: 28778331 DOI: 10.1016/j.maturitas.2017.06.023
    OBJECTIVES: To evaluate, among the elderly, the association of self-rated health (SRH) with mortality, and to identify determinants of self-rating health as "at-least-good".

    STUDY DESIGN: Individual data on SRH and important covariates were obtained for 424,791 European and United States residents, ≥60 years at recruitment (1982-2008), in eight prospective studies in the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES). In each study, adjusted mortality ratios (hazard ratios, HRs) in relation to SRH were calculated and subsequently combined with random-effect meta-analyses.

    MAIN OUTCOME MEASURES: All-cause, cardiovascular and cancer mortality.

    RESULTS: Within the median 12.5 years of follow-up, 93,014 (22%) deaths occurred. SRH "fair" or "poor" vs. "at-least-good" was associated with increased mortality: HRs 1.46 (95% CI 1·23-1.74) and 2.31 (1.79-2.99), respectively. These associations were evident: for cardiovascular and, to a lesser extent, cancer mortality, and within-study, within-subgroup analyses. Accounting for lifestyle, sociodemographic, somatometric factors and, subsequently, for medical history explained only a modest amount of the unadjusted associations. Factors favourably associated with SRH were: sex (males), age (younger-old), education (high), marital status (married/cohabiting), physical activity (active), body mass index (non-obese), alcohol consumption (low to moderate) and previous morbidity (absence).

    CONCLUSION: SRH provides a quick and simple tool for assessing health and identifying groups of elders at risk of early mortality that may be useful also in clinical settings. Modifying determinants of favourably rating health, e.g. by increasing physical activity and/or by eliminating obesity, may be important for older adults to "feel healthy" and "be healthy".

    MeSH terms: Cardiovascular Diseases/mortality*; Europe/epidemiology; Health Status*; Humans; Neoplasms/mortality*; Prospective Studies; United States/epidemiology; Proportional Hazards Models; Self Report*
  2. Thevarajoo S, Selvaratnam C, Chan KG, Goh KM, Chong CS
    Braz J Microbiol, 2017 07 19;49(1):10-12.
    PMID: 28778371 DOI: 10.1016/j.bjm.2017.03.013
    Vitellibacter aquimaris D-24T (=KCTC 42708T=DSM 101732T), a halophilic marine bacterium, was isolated from seawater collected from Desaru beach, Malaysia. Here, we present the draft genome sequence of D-24T with a genome size of approximately 3.1Mbp and G+C content of 39.93%. The genome of D-24T contains genes involved in reducing a potent greenhouse gas (N2O) in the environment and the degradation of proteinaceous compounds. Genome availability will provide insights into potential biotechnological and environmental applications of this bacterium.
    MeSH terms: Base Composition; Base Sequence; DNA, Bacterial/genetics; Malaysia; Molecular Sequence Data; Phylogeny; Seawater/microbiology*; Genome, Bacterial*; Flavobacteriaceae/classification; Flavobacteriaceae/genetics*; Flavobacteriaceae/isolation & purification
  3. Md Roduan MR, Hamid RA, Sulaiman H, Mohtarrudin N
    Biomed Pharmacother, 2017 Oct;94:481-488.
    PMID: 28779710 DOI: 10.1016/j.biopha.2017.07.133
    Annona muricata, locally known as soursop has been reported to exhibit antiproliferative activities against various cancer cell lines. In this current study, we have investigated the antitumor promotion of various fractions of Annona muricata leaves (AML); hexane (AMLH), dichloromethane (AMLD) and methanol (AMLM) fraction respectively on 7, 12-dimethylbenz[α]anthracene (DMBA) induced and 12-0-tetradecaboylphorbol-13-acetate (TPA) promoted skin tumorigenesis in mice via morphological assessment, biochemical analysis and histopathological evaluation. The results of the study revealed significant inhibition in tumor incidence, tumor burden and tumor volume in the groups received AMLH and AMLD, respectively, and suppressive effects in group received AMLM compared with carcinogen control group at week 21. Superoxide dismutase, catalase, and lipid peroxidation levels were returned to near normal by administration of AML to DMBA/TPA-induced mice. The above findings were supported by histopathological studies, in which the extensive epidermal hyperplasia in carcinogen control group was restored to normal in AML treated groups. Whilst, annonacin, a major annaonaceous acetogenin was found to be the highest in AMLH and AMLD. From the present study, it can be inferred that AML supressed DMBA/TPA-induced skin tumor and this antitumor-promoting activity may be linked to the antioxidant/free radical-scavenging constituents of the extract and annonacin contained in the extracts.
    MeSH terms: Administration, Topical; Animals; Antioxidants/metabolism*; Furans/analysis; Lactones/analysis; Male; Mice, Inbred ICR; Plant Extracts/pharmacology; Plant Extracts/therapeutic use*; Skin/drug effects; Skin/pathology; Skin Neoplasms/drug therapy*; Skin Neoplasms/enzymology; Skin Neoplasms/prevention & control*; Tetradecanoylphorbol Acetate; 9,10-Dimethyl-1,2-benzanthracene; Plant Leaves/chemistry*; Annona/chemistry*; Carcinogenesis/drug effects; Carcinogenesis/pathology*
  4. Saleem A, Khan A, Ahmad A, Khan MU, Babar ZU
    Res Social Adm Pharm, 2017 Nov;13(6):1218.
    PMID: 28768574 DOI: 10.1016/j.sapharm.2017.07.010
    MeSH terms: Antifungal Agents/economics; Antifungal Agents/supply & distribution*; Developing Countries; Fees, Pharmaceutical; Humans; Mycoses/drug therapy; Mycoses/economics; Pakistan
  5. Lin Y, Koh JKH, Koponen S, Li S
    Zookeys, 2017.
    PMID: 28769602 DOI: 10.3897/zookeys.661.10677
    Eight species of armored spiders belonging to two families, Pacullidae Simon, 1894 and Tetrablemmidae O. Pickard-Cambridge, 1873, are reported from Singapore. Five species are documented as new to science: Paculla bukittimahensis Lin & Li, sp. n. (male and female), Paculla globosa Lin & Li, sp. n. (male and female), Ablemma malacca Lin & Li, sp. n. (male and female), Singaporemma lenachanae Lin & Li, sp. n. (male and female), and Sulaimania brevis Lin & Li, sp. n. (male). The three known species are Brignoliella besutensis Lin, Li & Jäger, 2012, Brignoliella michaeli Lehtinen, 1981, and Singaporemma singulare Shear, 1978, of which the female of Brignoliella besutensis is described for the first time. For comparison, types of Singaporemma adjacens Lehtinen, 1981 from Vietnam, Singaporemma halongense Lehtinen, 1981 from Vietnam, Singaporemma singulare from Singapore and Sulaimania vigelandi Lehtinen, 1981 from Malaysia are studied and photographed.
    MeSH terms: Animals; Female; Malaysia; Male; Singapore; Spiders; Vietnam; Body Size; Animal Distribution
  6. Yang JH, Toda MJ, Suwito A, Hashim R, Gao JJ
    Zookeys, 2017.
    PMID: 28769630 DOI: 10.3897/zookeys.665.11609
    The genus Dichaetophora Duda comprises 61 described species classified into four species groups: agbo, tenuicauda, acutissima and sinensis. This genus is distributed exclusively in the Old World, and is rich in species in the tropical and subtropical areas of the Oriental, Australasian, and Afrotropical regions. In this paper, a new species group, the trilobita group, is established for six new species discovered from the Oriental region. The delimitation of these species is firstly performed in light of morphology and further with the aid of DNA sequences of the mitochondrial COI and COII (cytochrome c oxydase, subunits I and II, respectively) genes, considering also their respective geographical origins. Then, the new species (trilobita Yang & Gao, sp. n., heterochroma Yang & Gao, sp. n., flatosternata Yang & Gao, sp. n., borneoensis Yang & Gao, sp. n., javaensis Yang & Gao, sp. n., and sumatraensis Yang & Gao, sp. n.) are described, and a key, based on not only morphological but also molecular information, is provided.
    MeSH terms: Animals; DNA; Geography; Mitochondria; Drosophilidae; Cytochromes c
  7. Gabriš R, Trnka F, Wahab RA, Kundrata R
    Zookeys, 2017.
    PMID: 28769651 DOI: 10.3897/zookeys.669.12608
    The genera Anexodus Pascoe, 1866 and Pantilema Aurivillius, 1911 (Cerambycidae: Lamiinae: Morimopsini), both endemic to Borneo, are revised. Four species of Anexodus are recognized: A. aquilus Pascoe, 1886 (Malaysia: Sabah), A. sarawakensis Sudre, 1997 (Malaysia: Sarawak), A. syptakovaesp. n. (Malaysia: Sarawak), and A. tufisp. n. (Brunei). Pantilema is a monotypic genus containing P. angustum Aurivillius, 1911 (Malaysia: Sarawak) which is known only from the holotype. For the first time, genital structures are studied in these genera. An identification key for the species of Anexodus is provided and their intraspecific morphological variability and distributions are discussed.
    MeSH terms: Animals; Borneo; Brunei; Genitalia; Malaysia; Spiders
  8. Phung CC, Yu FTY, Liew TS
    Zookeys, 2017.
    PMID: 28769672 DOI: 10.3897/zookeys.673.12422
    Sabah, situated in one of the world's biodiversity hotspots, has the largest number of islands in Malaysia with more than 500 of various sizes and degrees of isolation. However, information on the islands' biodiversity is limited. This study provides an up-to-date checklist of land snail species found on 24 west coast islands in Sabah. A total of 67 species (nearly 20% of the total number of land snail species in the state) representing 37 genera and 19 families is enumerated based on systematic field surveys of 133 sampling plots, BORNEENSIS database records and species checklists published between 2000 and 2016. The number of species on the islands ranges from four to 29. Labuan Island has the highest number of species (29), followed by Tiga Island (25), Mantanani Besar Island (24) and Gaya Island (23). However, the populations of some land snail species may have declined as several previously recorded species on the islands were not found in a recent systematic field sampling. This checklist is provided as a baseline inventory for future island land snail studies and to better inform biodiversity conservation plans of marine parks and other islands on the Sabah west coast.
    MeSH terms: Animals; Malaysia; Surveys and Questionnaires; Snails; Biodiversity; Checklist; Islands
  9. Ng TH, Dulipat J, Foon JK, Lopes-Lima M, Alexandra Zieritz, Liew TS
    Zookeys, 2017.
    PMID: 28769673 DOI: 10.3897/zookeys.673.12544
    Sabah, a Malaysian state at the north-eastern tip of Borneo, is situated in one of the Earth's biodiversity hotspots yet its freshwater gastropod diversity remains poorly known. An annotated checklist of the freshwater gastropods is presented, based on specimens deposited in the BORNEENSIS collection of the Institute for Tropical Biology and Conservation at Universiti Malaysia Sabah, Malaysia. A KMZ file is also provided, which acts as a repository of digital images and complete collection data of all examined material, so that it can be shared and adapted to facilitate future research.
    MeSH terms: Animals; Borneo; Fresh Water; Malaysia; Biodiversity; Gastropoda; Checklist
  10. Foon JK, Clements GR, Liew TS
    Zookeys, 2017.
    PMID: 28769723 DOI: 10.3897/zookeys.682.12999
    Limestone hills are now gaining global conservation attention as hotspots for short-range endemic species. Levels of land snail endemism can be high at limestone hills, especially at hill clusters that are geographically isolated. In the State of Perak, Peninsular Malaysia, limestone hills have been opportunistically surveyed for land snails in the past, but the majority have yet to be surveyed. To address this knowledge gap, we systematically surveyed the terrestrial malacofauna of 12 limestone hills that, based on our opinion, are a representation of the limestone land snail assemblages within the State. Our inventory yielded high sampling completeness (>85%). We found 122 species of land snails, of which 34 species were unique to one of the surveyed hills. We identified 30 species that are potentially new to science. The number of land snail species recorded at each hill ranged between 39 and 63 species. Four of the sampled limestone hills namely, Prk 01 G. Tempurung, Prk 55 G. Pondok, Prk 47 Kanthan, and Prk 64 Bt Kepala Gajah, have high levels of species richness and unique species, representing 91% of the total species recorded in this study. We identified two clusters of limestone hills in central Perak with distinct differences in land snail species composition - a northern hill cluster on elevated granite bedrock and southern hill cluster in a low-lying valley surrounded by alluvial soils. As limestone hills continue to be quarried to meet the cement demand, the four identified limestone hills, along with other hills from the two clusters, warrant urgent conservation attention in order to maintain high species diversity within Perak's terrestrial malacofauna.
    MeSH terms: Animals; Attention; Calcium Carbonate; Conservation of Natural Resources; Malaysia; Surveys and Questionnaires; Silicon Dioxide; Snails; Soil
  11. Abdul SN, Ab Mutalib NS, Sean KS, Syafruddin SE, Ishak M, Sagap I, et al.
    Front Pharmacol, 2017;8:465.
    PMID: 28769798 DOI: 10.3389/fphar.2017.00465
    Despite global progress in research, improved screening and refined treatment strategies, colorectal cancer (CRC) remains as the third most common malignancy. As each type of cancer is different and exhibits unique alteration patterns, identifying and characterizing gene alterations in CRC that may serve as biomarkers might help to improve diagnosis, prognosis and predict potential response to therapy. With the emergence of next generation sequencing technologies (NGS), it is now possible to extensively and rapidly identify the gene profile of individual tumors. In this study, we aimed to identify actionable somatic alterations in Dukes' B and C in CRC via NGS. Targeted sequencing of 409 cancer-related genes using the Ion Ampliseq(TM) Comprehensive Cancer Panel was performed on genomic DNA obtained from paired fresh frozen tissues, cancer and normal, of Dukes' B (n = 10) and Dukes' C (n = 9) CRC. The sequencing results were analyzed using Torrent Suite, annotated using ANNOVAR and validated using Sanger sequencing. A total of 141 somatic non-synonymous sequence variations were identified in 86 genes. Among these, 64 variants (45%) were predicted to be deleterious, 38 variants (27%) possibly deleterious while the other 39 variants (28%) have low or neutral protein impact. Seventeen genes have alterations with frequencies of ≥10% in the patient cohort and with 14 overlapped genes in both Dukes' B and C. The adenomatous polyposis coli gene (APC) was the most frequently altered gene in both groups (n = 6 in Dukes' B and C). In addition, TP53 was more frequently altered in Dukes' C (n = 7) compared to Dukes' B (n = 4). Ten variants in APC, namely p.R283(∗), p.N778fs, p.R805(∗), p.Y935fs, p.E941fs, p.E1057(∗), p.I1401fs, p.Q1378(∗), p.E1379(∗), and p.A1485fs were predicted to be driver variants. APC remains as the most frequently altered gene in the intermediate stages of CRC. Wnt signaling pathway is the major affected pathway followed by P53, RAS, TGF-β, and PI3K signaling. We reported the alteration profiles in each of the patient which has the potential to affect the clinical decision. We believe that this study will add further to the understanding of CRC molecular landscape.
    MeSH terms: DNA; Humans; Oncogenes; Adenomatous Polyposis Coli; Prognosis; Colorectal Neoplasms; Cohort Studies; Biomarkers; Tumor Suppressor Protein p53; Transforming Growth Factor beta; Phosphatidylinositol 3-Kinases; Genomics; Early Detection of Cancer; High-Throughput Nucleotide Sequencing; Wnt Signaling Pathway
  12. Gillani SW, Sulaiman SAS, Abdul MIM, Saad SY
    PMID: 28770010 DOI: 10.1186/s13098-017-0257-6
    BACKGROUND: This study aimed to determine self-monitoring practices, awareness to dietary modifications and barriers to medication adherence among physically disabled type 2 diabetes mellitus patients.

    METHODS: Interview sessions were conducted at diabetes clinic-Penang general hospital. The invited participants represented three major ethnic groups of Malaysia (Malay, Chinese and Indians). An open-ended approach was used to elicit answers from participants. Interview questions were related to participant's perception towards self-monitoring blood glucose practices, Awareness towards diet management, behaviour to diabetes medication and cues of action.

    RESULTS: A total of twenty-one diabetes patients between the ages 35-67 years with physical disability (P1-P21) were interviewed. The cohort of participants was dominated by males (n = 12) and also distribution pattern showed majority of participants were Malay (n = 10), followed by Chinese (n = 7) and rest Indians (n = 4). When the participants were asked in their opinion what was the preferred method of recording blood glucose tests, several participants from low socioeconomic status and either divorced or widowed denied to adapt telemonitoring instead preferred to record manually. There were mixed responses about the barriers to control diet/calories. Even patients with high economic status, middle age 35-50 and diabetes history of 5-10 years were influenced towards alternative treatments.

    CONCLUSIONS: Study concluded that patients with physical disability required extensive care and effective strategies to control glucose metabolism.

    PRACTICE IMPLICATION: This study explores the patients' perspectives regarding treatment management with physical disability.

  13. Hassan R, Chong YC, Khairun Nisa M, Yew CG, Tan PG, Mazlin J
    J Neonatal Surg, 2017 Apr 15;6(2):49.
    PMID: 28770146 DOI: 10.21699/jns.v6i2.505
  14. Leong YY, Ng WH, Ellison-Hughes GM, Tan JJ
    PMID: 28770214 DOI: 10.3389/fcvm.2017.00047
    Heart failure is the number one killer worldwide with ~50% of patients dying within 5 years of prognosis. The discovery of stem cells, which are capable of repairing the damaged portion of the heart, has created a field of cardiac regenerative medicine, which explores various types of stem cells, either autologous or endogenous, in the hope of finding the "holy grail" stem cell candidate to slow down and reverse the disease progression. However, there are many challenges that need to be overcome in the search of such a cell candidate. The ideal cells have to survive the harsh infarcted environment, retain their phenotype upon administration, and engraft and be activated to initiate repair and regeneration in vivo. Early bench and bedside experiments mostly focused on bone marrow-derived cells; however, heart regeneration requires multiple coordinations and interactions between various cell types and the extracellular matrix to form new cardiomyocytes and vasculature. There is an observed trend that when more than one cell is coadministered and cotransplanted into infarcted animal models the degree of regeneration is enhanced, when compared to single-cell administration. This review focuses on stem cell candidates, which have also been tested in human trials, and summarizes findings that explore the interactions between various stem cells in heart regenerative therapy.
  15. Matsui M, Nishikawa K, Eto K, Hossman MYB
    Zoolog Sci, 2017 Aug;34(4):345-350.
    PMID: 28770684 DOI: 10.2108/zs170008
    A new small, semi-arboreal toad of the genus Pelophryne is described from western Sarawak, Malaysian Borneo, on the basis of molecular and morphological evidence. Of the two morphotypes recognized in the genus, the new species belongs to the one in which the tips of the fingers are expanded into truncate discs. Among the species in the morphotype, the new species is most similar to P. murudensis, but differs from it by body size, relative hindlimb length, and dorsal coloration. The new species is currently known only from a limited area on Gunung (= Mt.) Penrissen, and future measures of its habitat conservation are necessary.
    MeSH terms: Animals; Borneo; Bufonidae/classification*; Bufonidae/genetics; Species Specificity; Animal Distribution
  16. Loh YC, Ch'ng YS, Tan CS, Ahmad M, Asmawi MZ, Yam MF
    J Med Food, 2017 Sep;20(9):895-911.
    PMID: 28771084 DOI: 10.1089/jmf.2016.3804
    Uncaria rhynchophylla is one of the major components included in Traditional Chinese Medicine prescriptions for hypertensive treatment. Previous studies have suggested that U. rhynchophylla might contain vasodilation-mediating active compounds, especially indole alkaloids. Hence, this study was carried out to determine the vasodilatory effects of U. rhynchophylla, which was extracted by different solvents. The most effective extract was then further studied for its signaling mechanism pathways. The authenticity of U. rhynchophylla was assured by using modernized tri-step Fourier transform infrared (FTIR), including conventional 1D FTIR, second derivative scanning combined with 2D-correlated IR spectroscopy. Results obtained proved that the fingerprint of U. rhynchophylla used was identical to the atlas. Isolated aortic rings from male Sprague-Dawley rats were preconstricted with phenylephrine (PE) followed by cumulative addition of U. rhynchophylla extracts. The signaling mechanism pathways were studied by incubation with different receptor antagonists before the PE precontraction. In conclusion, the 95% ethanolic U. rhynchophylla extract (GT100) was found to be most effective with an EC50 value of 0.028 ± 0.002 mg/mL and an Rmax value of 101.30% ± 2.82%. The signaling mechanism pathways employed for exerting its vasodilatory effects included nitric oxide/soluble guanylyl cylcase/cyclic guanosine monophosphate (NO/sGC/cGMP) and PGI2 (endothelium-derived relaxing factors), G protein-coupled M3- and β2 receptors, regulation of membrane potential through voltage-operated calcium channel, intracellular Ca2+ released from inositol triphosphate receptor (IP3R), and all potassium channels except the Kca channel.
    MeSH terms: Animals; Humans; Hypertension/drug therapy*; Hypertension/metabolism; Hypertension/physiopathology; Male; Nitric Oxide/metabolism; Plant Extracts/administration & dosage*; Vasodilation/drug effects; Vasodilator Agents/administration & dosage*; Rats, Sprague-Dawley; Uncaria/chemistry*; Rats
  17. Yusuf NK, Lajis MA, Ahmad A
    Materials (Basel), 2017 Aug 03;10(8).
    PMID: 28771207 DOI: 10.3390/ma10080902
    Meltless recycling technique has been utilized to overcome the lack of primary resources, focusing on reducing the usage of energy and materials. Hot press was proposed as a novel direct recycling technique which results in astoundingly low energy usage in contrast with conventional recycling. The aim of this study is to prove the technical feasibility of this approach by characterizing the recycled samples. For this purpose, AA6061 aluminium chips were recycled by utilizing hot press process under various operating temperature (Ts = 430, 480, and 530 °C) and holding times (ts = 60, 90, and 120 min). The maximum mechanical properties of recycled chip are Ultimate tensile strength (UTS) = 266.78 MPa, Elongation to failure (ETF) = 16.129%, while, for surface integrity of the chips, the calculated microhardness is 81.744 HV, exhibited at Ts = 530 °C and ts = 120 min. It is comparable to theoretical AA6061 T4-temper where maximum UTS and microhardness is increased up to 9.27% and 20.48%, respectively. As the desired mechanical properties of forgings can only be obtained by means of a final heat treatment, T5-temper, aging after forging process was employed. Heat treated recycled billet AA6061 (T5-temper) are considered comparable with as-received AA6061 T6, where the value of microhardness (98.649 HV) at 175 °C and 120 min of aging condition was revealed to be greater than 3.18%. Although it is quite early to put a base mainly on the observations in experimental settings, the potential for significant improvement offered by the direct recycling methods for production aluminium scrap can be clearly demonstrated. This overtures perspectives for industrial development of solid state recycling processes as environmentally benign alternatives of current melting based practices.
    MeSH terms: Industrial Development; Aluminum; Employment; Feasibility Studies; Hot Temperature; Pressure; Temperature; Tensile Strength; Physical Phenomena; Recycling
  18. Jawad HM, Nordin R, Gharghan SK, Jawad AM, Ismail M
    Sensors (Basel), 2017 Aug 03;17(8).
    PMID: 28771214 DOI: 10.3390/s17081781
    Wireless sensor networks (WSNs) can be used in agriculture to provide farmers with a large amount of information. Precision agriculture (PA) is a management strategy that employs information technology to improve quality and production. Utilizing wireless sensor technologies and management tools can lead to a highly effective, green agriculture. Based on PA management, the same routine to a crop regardless of site environments can be avoided. From several perspectives, field management can improve PA, including the provision of adequate nutrients for crops and the wastage of pesticides for the effective control of weeds, pests, and diseases. This review outlines the recent applications of WSNs in agriculture research as well as classifies and compares various wireless communication protocols, the taxonomy of energy-efficient and energy harvesting techniques for WSNs that can be used in agricultural monitoring systems, and comparison between early research works on agriculture-based WSNs. The challenges and limitations of WSNs in the agricultural domain are explored, and several power reduction and agricultural management techniques for long-term monitoring are highlighted. These approaches may also increase the number of opportunities for processing Internet of Things (IoT) data.
    MeSH terms: Agriculture; Computer Communication Networks; Internet; Physical Phenomena*; Wireless Technology*
  19. Etti IC, Abdullah R, Kadir A, Hashim NM, Yeap SK, Imam MU, et al.
    PLoS One, 2017;12(8):e0182357.
    PMID: 28771532 DOI: 10.1371/journal.pone.0182357
    Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heterogenous aggressive triple negative breast cancer is still poor. This study was conducted to investigate the mechanism of inhibition of Artonin E, a prenylated flavonoid on MDA-MB 231 triple negative breast cancer cell, with a view of mitigating the hallmarks displayed by these tumors. The anti-proliferative effect, mode of cell death and the mechanism of apoptosis induction were investigated. Artonin E, was seen to effectively relinquish MDA-MB 231 breast cancer cells of their apoptosis evading capacity, causing a half-maximal growth inhibition at low concentrations (14.3, 13.9 and 9.8 μM) after the tested time points (24, 48 and 72 hours), respectively. The mode of cell death was observed to be apoptosis with defined characteristics. Artonin E was seen to induce the activation of both extrinsic and intrinsic caspases initiators of apoptosis. It also enhanced the release of total reactive oxygen species which polarized the mitochondrial membrane, compounding the release of cytochrome c. Gene expression studies revealed the upregulation of TNF-related apoptosis inducing ligand and proapoptotic genes with down regulation of anti-apoptotic genes and proteins. A G2/M cell cycle arrest was also observed and was attributed to the observed upregulation of p21 independent of the p53 status. Interestingly, livin, a new member of the inhibitors of apoptosis was confirmed to be significantly repressed. In all, Artonin E showed the potential as a promising candidate to combat the aggressive triple negative breast cancer.
    MeSH terms: Antineoplastic Agents, Phytogenic/toxicity*; Female; Flavonoids/toxicity*; Humans; Microscopy, Fluorescence; Up-Regulation/drug effects; Tumor Suppressor Protein p53/metabolism; Apoptosis/drug effects*; Reactive Oxygen Species/metabolism; Plant Roots/metabolism; Plant Roots/chemistry; Caspases/metabolism; Artocarpus/metabolism; Artocarpus/chemistry; Cell Line, Tumor; Cell Proliferation/drug effects; Cyclin-Dependent Kinase Inhibitor p21/metabolism; DNA Fragmentation/drug effects; G2 Phase Cell Cycle Checkpoints/drug effects; M Phase Cell Cycle Checkpoints/drug effects; Triple Negative Breast Neoplasms/metabolism; Triple Negative Breast Neoplasms/pathology
  20. Mandhane PJ, Paredes Zambrano de Silbernagel P, Aung YN, Williamson J, Lee BE, Spier S, et al.
    PLoS One, 2017;12(8):e0182411.
    PMID: 28771627 DOI: 10.1371/journal.pone.0182411
    BACKGROUND: Antibiotics are frequently used to treat wheezing children. Macrolides may be effective in treating bronchiolitis and asthma.

    METHOD: We completed a prospective, double-blinded, randomized placebo-control trial of azithromycin among pre-school children (12 to 60 months of age) presenting to the emergency department with wheeze. Patients were randomized to receive either five days of azithromycin or placebo. Primary outcome was time to resolution of respiratory symptoms after treatment initiation. Secondary outcomes included the number of days children used a Short-Acting Beta-Agonists during the 21 day follow-up and time to disease exacerbation during the following six months (unscheduled health care visit or treatment with an oral corticosteroid for acute respiratory symptoms).

    RESULTS: Of the 300 wheezing children recruited, 222 and 169 were analyzed for the primary and secondary outcomes, respectively. The treatment groups had similar demographics and clinical parameters at baseline. Median time to resolution of respiratory symptoms was four days for both treatment arms (interquartile range (IQR) 3,6; p = 0.28). Median number of days of Short-Acting Beta-Agonist use among those who received azithromycin was four and a half days (IQR 2, 7) and five days (IQR 2, 9; p = 0.22) among those who received placebo. Participants who received azithromycin had a 0.91 hazard ratio for time to six-month exacerbation compared to placebo (95% CI 0.61, 1.36, p = 0.65). A pre-determined subgroup analysis showed no differences in outcomes for children with their first or repeat episode of wheezing. There was no significant difference in the proportion of participants experiencing an adverse event.

    CONCLUSION: Azithromycin neither reduced duration of respiratory symptoms nor time to respiratory exacerbation in the following six months after treatment among wheezing preschool children presenting to an emergency department. There was no significant effect among children with either first-time or prior wheezing.

    MeSH terms: Anti-Bacterial Agents/therapeutic use*; Asthma/drug therapy*; Child, Preschool; Double-Blind Method; Emergency Service, Hospital; Female; Humans; Infant; Male; Prognosis; Prospective Studies; Respiratory Sounds/drug effects*; Survival Rate; Azithromycin/therapeutic use*; Disease Progression
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