Browse publications by year: 2016

Fulltext Molecular characterization of Nipah virus from Pteropus hypomelanus in Southern Thailand

Wacharapluesadee S, Samseeneam P, Phermpool M, Kaewpom T, Rodpan A, Maneeorn P, et al.

Virol J, 2016;13(1):53.
PMID: 27016237 DOI: 10.1186/s12985-016-0510-x

Nipah virus (NiV) first emerged in Malaysia in 1998, with two bat species (Pteropus hypomelanus and P. vampyrus) as the putative natural reservoirs. In 2002, NiV IgG antibodies were detected in these species from Thailand, but viral RNA could not be detected for strain characterization. Two strains of NiV (Malaysia and Bangladesh) have been found in P. lylei in central Thailand, although Bangladesh strain, the causative strain for the outbreak in Bangladesh since 2001, was dominant. To understand the diversity of NiV in Thailand, this study identified NiV strain, using molecular characterizations, from P. hypomelanus in southern Thailand.

MeSH terms: Animals; Bangladesh; Chiroptera; Disease Outbreaks; Immunoglobulin G; Malaysia; RNA, Viral; Thailand; Nipah Virus; Henipavirus Infections
Pharmacological modulation of oncogenic Ras by natural products and their derivatives: Renewed hope in the discovery of novel anti-Ras drugs

Quah SY, Tan MS, Teh YH, Stanslas J

Pharmacol Ther, 2016 06;162:35-57.
PMID: 27016467 DOI: 10.1016/j.pharmthera.2016.03.010

Oncogenic rat sarcoma (Ras) is linked to the most fatal cancers such as those of the pancreas, colon, and lung. Decades of research to discover an efficacious drug that can block oncogenic Ras signaling have yielded disappointing results; thus, Ras was considered "undruggable" until recently. Inhibitors that directly target Ras by binding to previously undiscovered pockets have been recently identified. Some of these molecules are either isolated from natural products or derived from natural compounds. In this review, we described the potential of these compounds and other inhibitors of Ras signaling in drugging Ras. We highlighted the modes of action of these compounds in suppressing signaling pathways activated by oncogenic Ras, such as mitogen-activated protein kinase (MAPK) signaling and the phosphoinositide-3-kinase (PI3K) pathways. The anti-Ras strategy of these compounds can be categorized into four main types: inhibition of Ras-effector interaction, interference of Ras membrane association, prevention of Ras-guanosine triphosphate (GTP) formation, and downregulation of Ras proteins. Another promising strategy that must be validated experimentally is enhancement of the intrinsic Ras-guanosine triphosphatase (GTPase) activity by small chemical entities. Among the inhibitors of Ras signaling that were reported thus far, salirasib and TLN-4601 have been tested for their clinical efficacy. Although both compounds passed phase I trials, they failed in their respective phase II trials. Therefore, new compounds of natural origin with relevant clinical activity against Ras-driven malignancies are urgently needed. Apart from salirasib and TLN-4601, some other compounds with a proven inhibitory effect on Ras signaling include derivatives of salirasib, sulindac, polyamine, andrographolide, lipstatin, levoglucosenone, rasfonin, and quercetin.

MeSH terms: Antineoplastic Agents/pharmacology; Cell Membrane/metabolism; Guanosine Triphosphate/metabolism; Neoplasms/drug therapy; Neoplasms/metabolism; Down-Regulation; ras Proteins/antagonists & inhibitors*; ras Proteins/metabolism; Drug Discovery
Predicting points of departure for risk assessment based on in vitro cytotoxicity data and physiologically based kinetic (PBK) modeling: The case of kidney toxicity induced by aristolochic acid I

Abdullah R, Alhusainy W, Woutersen J, Rietjens IM, Punt A

Food Chem Toxicol, 2016 Jun;92:104-16.
PMID: 27016491 DOI: 10.1016/j.fct.2016.03.017

Aristolochic acids are naturally occurring nephrotoxins. This study aims to investigate whether physiologically based kinetic (PBK) model-based reverse dosimetry could convert in vitro concentration-response curves of aristolochic acid I (AAI) to in vivo dose response-curves for nephrotoxicity in rat, mouse and human. To achieve this extrapolation, PBK models were developed for AAI in these different species. Subsequently, concentration-response curves obtained from in vitro cytotoxicity models were translated to in vivo dose-response curves using PBK model-based reverse dosimetry. From the predicted in vivo dose-response curves, points of departure (PODs) for risk assessment could be derived. The PBK models elucidated species differences in the kinetics of AAI with the overall catalytic efficiency for metabolic conversion of AAI to aristolochic acid Ia (AAIa) being 2-fold higher for rat and 64-fold higher for mouse than human. Results show that the predicted PODs generally fall within the range of PODs derived from the available in vivo studies. This study provides proof of principle for a new method to predict a POD for in vivo nephrotoxicity by integrating in vitro toxicity testing with in silico PBK model-based reverse dosimetry.

MeSH terms: Animals; Carcinogens/toxicity*; Cell Survival/drug effects*; Computer Simulation; Humans; Kidney/drug effects*; Kidney/pathology; Kinetics; Models, Biological; Risk Assessment; Toxicity Tests/methods*; Aristolochic Acids/toxicity*; Mice; Rats
Adolescents as perpetrators of aggression within the family

Kuay HS, Lee S, Centifanti LC, Parnis AC, Mrozik JH, Tiffin PA

Int J Law Psychiatry, 2016 Jul-Aug;47:60-7.
PMID: 27016774 DOI: 10.1016/j.ijlp.2016.02.035

Although family violence perpetrated by juveniles has been acknowledged as a potentially serious form of violence for over 30years, scientific studies have been limited to examining the incidence and form of home violence. The present study examined the prevalence of family aggression as perpetrated by youths; we examined groups drawn from clinic-referred and forensic samples. Two audits of case files were conducted to systematically document aggression perpetrated by referred youths toward their family members. The purpose of the first audit was fourfold: i) to identify the incidence of the perpetration of family aggression among clinical and forensic samples; ii) to identify whether there were any reports of weapon use during aggressive episodes; iii) to identify the target of family aggression (parents or siblings); and iv) to identify the form of aggression perpetrated (verbal or physical). The second audit aimed to replicate the findings and to show that the results were not due to differences in multiple deprivation indices, clinical diagnosis of disruptive behavior disorders, and placement into alternative care. A sampling strategy was designed to audit the case notes of 25 recent forensic Child and Adolescent Mental Health Service (CAMHS) cases and 25 demographically similar clinic-referred CAMHS cases in the first audit; and 35 forensic cases and 35 demographically similar clinic-referred CAMHS cases in the second audit. Using ordinal chi-square, the forensic sample (audit 1=64%; audit 2=82.9%) had greater instances of family violence than the clinical sample (audit 1=32%; audit 2=28.6%). They were more likely to use a weapon (audit 1=69%; audit 2=65.5%) compared to the clinical sample (audit 1 and 2=0%). Examining only the aggressive groups, there was more perpetration of aggression toward parents (audit 1, forensic=92%, clinical=75%; audit 2, forensic=55.17%, clinical=40%) than toward siblings (audit 1, forensic=43%, clinical=50%; audit 2, forensic=27.58%, clinical=30%). Based on these findings, we would urge professionals who work within the child mental health, particularly the forensic area, to systematically collect reports of aggression perpetrated toward family members.

Study conducted in England

MeSH terms: Adolescent; Aggression/psychology*; Mental Disorders/diagnosis; Mental Disorders/epidemiology; Mental Disorders/psychology; Child; Commitment of Mentally Ill/legislation & jurisprudence; Female; Great Britain; Humans; Male; Parents*; Psychosocial Deprivation; Domestic Violence/legislation & jurisprudence*; Siblings*; Weapons/legislation & jurisprudence; Weapons/statistics & numerical data; Clinical Audit/legislation & jurisprudence
Comparison of Different Protein Extraction Methods for Gel-Based Proteomic Analysis of Ganoderma spp

Al-Obaidi JR, Saidi NB, Usuldin SR, Hussin SN, Yusoff NM, Idris AS

Protein J, 2016 Apr;35(2):100-6.
PMID: 27016942 DOI: 10.1007/s10930-016-9656-z

Ganoderma species are a group of fungi that have the ability to degrade lignin polymers and cause severe diseases such as stem and root rot and can infect economically important plants and perennial crops such as oil palm, especially in tropical countries such as Malaysia. Unfortunately, very little is known about the complex interplay between oil palm and Ganoderma in the pathogenesis of the diseases. Proteomic technologies are simple yet powerful tools in comparing protein profile and have been widely used to study plant-fungus interaction. A critical step to perform a good proteome research is to establish a method that gives the best quality and a wide coverage of total proteins. Despite the availability of various protein extraction protocols from pathogenic fungi in the literature, no single extraction method was found suitable for all types of pathogenic fungi. To develop an optimized protein extraction protocol for 2-DE gel analysis of Ganoderma spp., three previously reported protein extraction protocols were compared: trichloroacetic acid, sucrose and phenol/ammonium acetate in methanol. The third method was found to give the most reproducible gels and highest protein concentration. Using the later method, a total of 10 protein spots (5 from each species) were successfully identified. Hence, the results from this study propose phenol/ammonium acetate in methanol as the most effective protein extraction method for 2-DE proteomic studies of Ganoderma spp.

MeSH terms: Electrophoresis, Polyacrylamide Gel; Fungal Proteins/analysis*; Fungal Proteins/isolation & purification*; Electrophoresis, Gel, Two-Dimensional/methods*; Ganoderma/chemistry*; Proteomics/methods*
A review of polymer nanofibres by electrospinning and their application in oil-water separation for cleaning up marine oil spills

Sarbatly R, Krishnaiah D, Kamin Z

Mar Pollut Bull, 2016 May 15;106(1-2):8-16.
PMID: 27016959 DOI: 10.1016/j.marpolbul.2016.03.037

The growths of oil and gas exploration and production activities have increased environmental problems, such as oil spillage and the resulting pollution. The study of the methods for cleaning up oil spills is a critical issue to protect the environment. Various techniques are available to contain oil spills, but they are typically time consuming, energy inefficient and create secondary pollution. The use of a sorbent, such as a nanofibre sorbent, is a technique for controlling oil spills because of its good physical and oil sorption properties. This review discusses about the application of nanofibre sorbent for oil removal from water and its current developments. With their unique physical and mechanical properties coupled with their very high surface area and small pore sizes, nanofibre sorbents are alternative materials for cleaning up oil spills.

MeSH terms: Polymers; Water; Water Pollutants, Chemical; Nanofibers*; Petroleum Pollution*
Effects of changes in chemical and structural characteristic of ammonia fibre expansion (AFEX) pretreated oil palm empty fruit bunch fibre on enzymatic saccharification and fermentability for biohydrogen

Abdul PM, Jahim JM, Harun S, Markom M, Lutpi NA, Hassan O, et al.

Bioresour Technol, 2016 Jul;211:200-8.
PMID: 27017130 DOI: 10.1016/j.biortech.2016.02.135

Oil palm empty fruit bunch (OPEFB) fibre is widely available in Southeast Asian countries and found to have 60% (w/w) sugar components. OPEFB was pretreated using the ammonia fibre expansion (AFEX) method and characterised physically by the Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscopy. The results show that there were significant structural changes in OPEFB after the pretreatment step, and the sugar yield after enzymatic hydrolysis using a cocktail of Cellic Ctec2® and Cellic Htec2® increased from 0.15gg(-1) of OPEFB in the raw untreated OPEFB sample to 0.53gg(-1) of OPEFB in AFEX-pretreated OPEFB (i.e. almost a fourfold increase in sugar conversion), which enhances the economic value of OPEFB. A biohydrogen fermentability test of this hydrolysate was carried out using a locally isolated bacterium, Enterobacter sp. KBH6958. The biohydrogen yield after 72h of fermentation was 1.68mol H2 per mol sugar. Butyrate, ethanol, and acetate were the major metabolites.

MeSH terms: Ethanol; Ammonia; Butyrates; Carbohydrates; Dietary Fiber; Enterobacter; Fermentation; Fruit; Hydrolysis; Microscopy, Electron, Scanning; X-Ray Diffraction; Spectroscopy, Fourier Transform Infrared; Bioreactors
Fulltext NeisseriaBase: a specialised Neisseria genomic resource and analysis platform

Zheng W, Mutha NV, Heydari H, Dutta A, Siow CC, Jakubovics NS, et al.

PeerJ, 2016;4:e1698.
PMID: 27017950 DOI: 10.7717/peerj.1698

Background. The gram-negative Neisseria is associated with two of the most potent human epidemic diseases: meningococcal meningitis and gonorrhoea. In both cases, disease is caused by bacteria colonizing human mucosal membrane surfaces. Overall, the genus shows great diversity and genetic variation mainly due to its ability to acquire and incorporate genetic material from a diverse range of sources through horizontal gene transfer. Although a number of databases exist for the Neisseria genomes, they are mostly focused on the pathogenic species. In this present study we present the freely available NeisseriaBase, a database dedicated to the genus Neisseria encompassing the complete and draft genomes of 15 pathogenic and commensal Neisseria species. Methods. The genomic data were retrieved from National Center for Biotechnology Information (NCBI) and annotated using the RAST server which were then stored into the MySQL database. The protein-coding genes were further analyzed to obtain information such as calculation of GC content (%), predicted hydrophobicity and molecular weight (Da) using in-house Perl scripts. The web application was developed following the secure four-tier web application architecture: (1) client workstation, (2) web server, (3) application server, and (4) database server. The web interface was constructed using PHP, JavaScript, jQuery, AJAX and CSS, utilizing the model-view-controller (MVC) framework. The in-house developed bioinformatics tools implemented in NeisseraBase were developed using Python, Perl, BioPerl and R languages. Results. Currently, NeisseriaBase houses 603,500 Coding Sequences (CDSs), 16,071 RNAs and 13,119 tRNA genes from 227 Neisseria genomes. The database is equipped with interactive web interfaces. Incorporation of the JBrowse genome browser in the database enables fast and smooth browsing of Neisseria genomes. NeisseriaBase includes the standard BLAST program to facilitate homology searching, and for Virulence Factor Database (VFDB) specific homology searches, the VFDB BLAST is also incorporated into the database. In addition, NeisseriaBase is equipped with in-house designed tools such as the Pairwise Genome Comparison tool (PGC) for comparative genomic analysis and the Pathogenomics Profiling Tool (PathoProT) for the comparative pathogenomics analysis of Neisseria strains. Discussion. This user-friendly database not only provides access to a host of genomic resources on Neisseria but also enables high-quality comparative genome analysis, which is crucial for the expanding scientific community interested in Neisseria research. This database is freely available at http://neisseria.um.edu.my.

MeSH terms: Base Composition; Gonorrhea; Humans; Language; Meningitis, Meningococcal; Molecular Weight; Neisseria; RNA, Transfer; Software; Genetic Variation; Virulence; Genome; Computational Biology; Gene Transfer, Horizontal; Genomics; Hydrophobic and Hydrophilic Interactions
Neurobiology of Kratom and its main alkaloid mitragynine

Suhaimi FW, Yusoff NH, Hassan R, Mansor SM, Navaratnam V, Müller CP, et al.

Brain Res Bull, 2016 09;126(Pt 1):29-40.
PMID: 27018165 DOI: 10.1016/j.brainresbull.2016.03.015

Kratom or its main alkaloid, mitragynine is derived from the plant Mitragyna speciosa Korth which is indigenous to Southeast Asian countries. This substance has become widely available in other countries like Europe and United States due to its opium- and coca-like effects. In this article, we have reviewed available reports on mitragynine and other M. speciosa extracts. M. speciosa has been proven to have a rewarding effect and is effective in alleviating the morphine and ethanol withdrawal effects. However, studies in human revealed that prolonged consumption of this plant led to dependence and tolerance while cessation caused a series of aversive withdrawal symptoms. Findings also showed that M. speciosa extracts possess antinociceptive, anti-inflammatory, anti-depressant, and muscle relaxant properties. Available evidence further supports the adverse effects of M. speciosa preparations, mitragynine on cognition. Pharmacological activities are mainly mediated via opioid receptors as well as neuronal Ca2+ channels, expression of cAMP and CREB protein and via descending monoaminergic system. Physicochemical properties of mitragynine have been documented which may further explain the variation in pharmacological responses. In summary, current researchs on its main indole alkaloid, mitragynine suggest both therapeutic and addictive potential but further research on its molecular effects is needed.

MeSH terms: Animals; Cognition Disorders/chemically induced; Humans; Neurobiology*; Psychotropic Drugs/adverse effects*; Receptors, Opioid/metabolism; Mitragyna/chemistry*; Secologanin Tryptamine Alkaloids/adverse effects*; Phytochemicals
Electrodeposited Ge Nanostructures Prepared by Different Non-Aqueous Solutions and their Application in Lithium Ion Battery: A Review

Nadarajah K, Khan AF, Rahim NA

Recent Pat Nanotechnol, 2016;10(1):26-43.
PMID: 27018271

BACKGROUND: Germanium (Ge) nanostructures exhibit wide range of potential applications in the field of nanoscale devices due to their excellent optical and electrical properties and have gained significant interest due to the Bohr exciton radius. Bohr radius of Ge (24.3 nm) is larger than that of Si (4.9 nm), leading to quantum size effects and nanostructures with controllable bandgaps.
METHODS: This article provides a comprehensive review on various electrolytes for electrodeposition procedures developed to obtain the Ge nanostructures of desired structure, diameter, and density. We discuss the growth mechanisms and influence of different parameters such as type of solution, concentration, and value of applied potential or current density.
RESULTS: The ionic liquids can be used for the development of Ge nanostructures and provide extensive electrochemical windows for electrodeposition. The obtained SixGe1-x structures also exhibited strong color change (from red to blue) at room temperature during the electrodeposition, which is likely to be due to a quantum size effect.
CONCLUSION: The main advantages of the ionic liquids are 'it does not decompose', easy to purify and dry. Moreover, it exhibits fairly extensive electrochemical windows greater than 5 V for electrodeposition. Electrodeposition of SixGe1-x nanostructures from ionic liquids is quite a favorable process. The 3DOM Ge electrode is a promising material for nextgeneration lithium ion battery because of its high irreversible specific capacity. Few relevant patents to the topic have been reviewed and cited.

MeSH terms: Electrodes; Electrolytes; Electroplating; Germanium; Lithium; Electric Power Supplies; Radius; Temperature; Nanostructures; Ionic Liquids
Nanostructured SnO2-Ge Multi-layer thin Films with Quantum Confinement Effects for Solar Cell

Khan AF, Sajjad W, Rahim NA

Recent Pat Nanotechnol, 2016;10(1):77-82.
PMID: 27018275

BACKGROUND: It is well-known that multi-layer films with nanostructure can give novel properties by interfacial phenomenon and quantum confinement effects. Nanostructured multi-layer thin films are presently being analyzed for their vast applications in the area of optoelectronics technology particularly photovoltaics. Hereof, two dimensional thin films with nanostructure are of prime importance due to their structure dependent optical, electrical, and opto-electronic properties. It has been revealed that these films exhibit quantum confinement effects with band gap engineering. The main focus of the research is to evaluate the effect on structural and optical properties with number of layers.
METHODS: Nanostructured SnO2-Ge multi-layer thin films were fabricated using electron beam evaporation and resistive heating techniques. Alternate layers of SnO2 and Ge were deposited on glass substrate at a substrate temperature of 300 °C in order to obtain uniform and homogeneous deposition. The substrate temperature of 300 °C has been determined to be effective for the deposition of these multi-layer films from our previous studies. The films were characterized by investigating their structural and optical properties. The structural properties of the as-deposited films were characterized by Rutherford Backscattering Spectroscopy (RBS) and Raman spectroscopy and optical properties by Ultra-Violet-Near infrared (UV-VIS-NIR) spectroscopy.
RESULTS: RBS studies confirmed that the layer structure has been effectively formed. Raman spectroscopy results show that the peaks of both Ge and SnO2 shifts towards lower wavenumbers (in comparison with bulk Ge and SnO2, suggesting that the films consist of nanostructures and demonstrate quantum confinement effects. UV-VIS-NIR spectroscopy showed an increase in the band gap energy of Ge and SnO2 and shifting of transmittance curves toward higher wavelength by increasing the number of layers. The band gap lies in the range of 0.9 to 1.2 eV for Ge, while for SnO2, it lies between 1.7 to 2.1 eV.
CONCLUSION: Analysis of results suggests that the nanostructured SnO2-Ge multi-layer thin film can work as heterojunction materials with quantum confinement effects. Accordingly, the present SnO2-Ge multi-layer films may be employed for photovoltaic applications. Few relevant patents to the topic have been reviewed and cited.

MeSH terms: Electricity; Electrons; Glass; Heating; Spectrum Analysis, Raman; Temperature; Spectroscopy, Near-Infrared; Nanostructures
Recent Advances in Shape Memory Soft Materials for Biomedical Applications

Chan BQ, Low ZW, Heng SJ, Chan SY, Owh C, Loh XJ

ACS Appl Mater Interfaces, 2016 04 27;8(16):10070-87.
PMID: 27018814 DOI: 10.1021/acsami.6b01295

Shape memory polymers (SMPs) are smart and adaptive materials able to recover their shape through an external stimulus. This functionality, combined with the good biocompatibility of polymers, has garnered much interest for biomedical applications. In this review, we discuss the design considerations critical to the successful integration of SMPs for use in vivo. We also highlight recent work on three classes of SMPs: shape memory polymers and blends, shape memory polymer composites, and shape memory hydrogels. These developments open the possibility of incorporating SMPs into device design, which can lead to vast technological improvements in the biomedical field.

MeSH terms: Equipment Design*; Polymers*
Kinetic study on microwave-assisted esterification of free fatty acids derived from Ceiba pentandra Seed Oil

Lieu T, Yusup S, Moniruzzaman M

Bioresour Technol, 2016 Jul;211:248-56.
PMID: 27019128 DOI: 10.1016/j.biortech.2016.03.105

Recently, a great attention has been paid to advanced microwave technology that can be used to markedly enhance the biodiesel production process. Ceiba pentandra Seed Oil containing high free fatty acids (FFA) was utilized as a non-edible feedstock for biodiesel production. Microwave-assisted esterification pretreatment was conducted to reduce the FFA content for promoting a high-quality product in the next step. At optimum condition, the conversion was achieved 94.43% using 2wt% of sulfuric acid as catalyst where as 20.83% conversion was attained without catalyst. The kinetics of this esterification reaction was also studied to determine the influence of factors on the rate of reaction and reaction mechanisms. The results indicated that microwave-assisted esterification was of endothermic second-order reaction with the activation energy of 53.717kJ/mol.

MeSH terms: Attention; Catalysis; Esterification; Fatty Acids, Nonesterified; Kinetics; Microwaves; Plant Oils; Seeds; Sulfuric Acids; Ceiba; Biofuels
Malaysian nurses' evaluation of transnational higher education courses

Arunasalam N

Br J Nurs, 2016 Mar-Apr;25(6):337-40.
PMID: 27019174 DOI: 10.12968/bjon.2016.25.6.337

The internationalisation of higher education has led some UK and Australian universities to deliver transnational higher education (TNHE) post-registration top-up nursing degree courses in Malaysia. These are bridging courses that allow registered nurses to upgrade their diploma qualifications to degree level. What is not sufficiently explored in the literature is nurses' evaluation of these courses and the impact of TNHE qualifications. A hermeneutic phenomenology approach was used to explore the views of 18 Malaysian nurses from one Australian and two UK TNHE universities. Semi-structured interviews were conducted to enable the Malaysian nurses to evaluate the courses. Data were analysed by thematic analysis. Findings showed a gap between Malaysian and Western teaching and learning outlook, professional values and clinical practices. The data give important insights at a time when the aim of Malaysia's investment in TNHE courses is to attain a graduate workforce with changed mindsets and enhanced patient care.

MeSH terms: Attitude of Health Personnel*; Culture; Education, Nursing, Graduate*; Humans; Interviews as Topic; Malaysia; Nursing Theory
Fulltext Artonin E Induces Apoptosis via Mitochondrial Dysregulation in SKOV-3 Ovarian Cancer Cells

Rahman MA, Ramli F, Karimian H, Dehghan F, Nordin N, Ali HM, et al.

PLoS One, 2016;11(3):e0151466.
PMID: 27019365 DOI: 10.1371/journal.pone.0151466

Artonin E is a prenylated flavonoid isolated from the stem bark of Artocarpus elasticus Reinw.(Moraceae). This study aimed to investigate the apoptotic mechanisms induced by artonin E in a metastatic human ovarian cancer cell line SKOV-3 in vitro. MTT assay, clonogenic assay, acridine orange and propidium iodide double staining, cell cycle and annexin V analyses were performed to explore the mode of artonin E-induced cell death at different time points. DNA laddering, activation of caspases-3, -8, and -9, multi-parametric cytotoxicity-3 analysis by high-content screening, measurement of reactive oxygen species generation, and Western blot were employed to study the pathways involved in the apoptosis. MTT results showed that artonin E inhibited the growth of SKOV-3 cells, with IC50 values of 6.5±0.5 μg/mL after 72 h treatment, and showed less toxicity toward a normal human ovarian cell line T1074, with IC50 value of 32.5±0.5 μg/mL. Results showed that artonin E induced apoptosis and cell cycle arrest at the S phase. This compound also promoted the activation of caspases-3, -8, and -9. Further investigation into the depletion of mitochondrial membrane potential and release of cytochrome c revealed that artonin E treatment induced apoptosis via regulation of the expression of pro-survival and pro-apoptotic Bcl-2 family members. The expression levels of survivin and HSP70 proteins were also down regulated in SKOV-3 cells treated with artonin E. We propose that artonin E induced an antiproliferative effect that led to S phase cell cycle arrest and apoptosis through dysregulation of mitochondrial pathways, particularly the pro- and anti-apoptosis signaling pathways.

MeSH terms: Cell Survival/drug effects; Cell Survival/genetics; Enzyme Activation/drug effects; Female; Flavonoids/pharmacology*; Flavonoids/chemistry; Flow Cytometry; Humans; Mitochondria/drug effects*; Mitochondria/metabolism; Ovarian Neoplasms/genetics; Ovarian Neoplasms/metabolism; Ovarian Neoplasms/pathology; Blotting, Western; Molecular Structure; Apoptosis/drug effects*; Apoptosis/genetics; Reactive Oxygen Species/metabolism; Proto-Oncogene Proteins c-bcl-2/metabolism; Inhibitory Concentration 50; Artocarpus/chemistry; Cytochromes c/metabolism; Cell Line, Tumor; Cell Proliferation/drug effects*; Cell Proliferation/genetics; Caspase 3/metabolism; Caspase 8/metabolism; Caspase 9/metabolism; DNA Fragmentation/drug effects; S Phase Cell Cycle Checkpoints/drug effects; S Phase Cell Cycle Checkpoints/genetics
Pediatric cardiothoracic program in Malaysia: a study based on the outcome of the program

Piros Kulandasamy Pillai C, Yoshida Y, Justin Lawrence P, Yamamoto E, Reyer JA, Hamajima1 N

Nagoya J Med Sci, 2016 02;78(1):9-17.
PMID: 27019524

Vulnerable communities in Malaysia have been facing issues of accessibility and availability for pediatric cardiac services for years due to long waiting times, high costs and a lack of pediatric cardiothoracic surgeons. To ease this situation, the government has allocated a certain amount of funds, introduced through the Pediatric Cardiothoracic Program (PCP), in which the patients are transported to the Narayana Health Institute of Cardiac Science (NH) in India to receive a heart operation following an eligibility check at MediAssist4U Sdn Bhd in Selangor, Malaysia, a facility appointed by the NH. This study aimed to determine the demographic incidence of congenital heart diseases of patients in this program and to evaluate the outcome of the program in association with post-operative mortality rate and the beneficial factors of the program. In this study, 241 patients who participated in this program from August 2008 to September 2012 were reviewed. Fisher's exact tests were applied to calculate p-values of categorical data. Out of 241, 11 patients were rejected because of their poor health condition for flight transportation to India, leaving 230 patients for analysis. The majority of patients were 1 to 4 years of age (57.8%), Malays (61.7%), from families of monthly household income less than RM 1,500 (86.5%) and with primary school-educated parents (86.5%). Patients could apply from any government hospital in Malaysia, but 34.8% of the patients were from the state of Johor. The region (Peninsular Malaysia and East Malaysia) of patients seeking pediatric cardiac services was significantly associated with race (p<0.001), low household income (p<0.001) and low education background of parents (p=0.004). The associations between the age group and diagnosis group (p=0.010) and between duration of hospitalization and outcome of medical management (p=0.013) were significant. Post-operative mortality rate was 1.7% (95% confidence interval, 0.5-4.4). In conclusion, the patients and the government were considered to have benefited from the PCP.

MeSH terms: Child; Financial Management; Government; Heart Defects, Congenital; Cardiac Surgical Procedures; Hospitalization; Humans; India; Malaysia; Parents; Transportation; Incidence; Confidence Intervals; Surgeons
Fulltext MiRNA Transcriptome Profiling of Spheroid-Enriched Cells with Cancer Stem Cell Properties in Human Breast MCF-7 Cell Line

Boo L, Ho WY, Ali NM, Yeap SK, Ky H, Chan KG, et al.

Int J Biol Sci, 2016;12(4):427-45.
PMID: 27019627 DOI: 10.7150/ijbs.12777

Breast cancer is the second leading cause of cancer-related mortality worldwide as most patients often suffer cancer relapse. The reason is often attributed to the presence of cancer stem cells (CSCs). Recent studies revealed that dysregulation of microRNA (miRNA) are closely linked to breast cancer recurrence and metastasis. However, no specific study has comprehensively characterised the CSC characteristic and miRNA transcriptome in spheroid-enriched breast cells. This study described the generation of spheroid MCF-7 cell in serum-free condition and the comprehensive characterisation for their CSC properties. Subsequently, miRNA expression differences between the spheroid-enriched CSC cells and their parental cells were evaluated using next generation sequencing (NGS). Our results showed that the MCF-7 spheroid cells were enriched with CSCs properties, indicated by the ability to self-renew, increased expression of CSCs markers, and increased resistance to chemotherapeutic drugs. Additionally, spheroid-enriched CSCs possessed greater cell proliferation, migration, invasion, and wound healing ability. A total of 134 significantly (p<0.05) differentially expressed miRNAs were identified between spheroids and parental cells using miRNA-NGS. MiRNA-NGS analysis revealed 25 up-regulated and 109 down-regulated miRNAs which includes some miRNAs previously reported in the regulation of breast CSCs. A number of miRNAs (miR-4492, miR-4532, miR-381, miR-4508, miR-4448, miR-1296, and miR-365a) which have not been previously reported in breast cancer were found to show potential association with breast cancer chemoresistance and self-renewal capability. The gene ontology (GO) analysis showed that the predicted genes were enriched in the regulation of metabolic processes, gene expression, DNA binding, and hormone receptor binding. The corresponding pathway analyses inferred from the GO results were closely related to the function of signalling pathway, self-renewability, chemoresistance, tumorigenesis, cytoskeletal proteins, and metastasis in breast cancer. Based on these results, we proposed that certain miRNAs identified in this study could be used as new potential biomarkers for breast cancer stem cell diagnosis and targeted therapy.
Fulltext Saprophytic and Potentially Pathogenic Fusarium Species from Peat Soil in Perak and Pahang

Karim NF, Mohd M, Nor NM, Zakaria L

Trop Life Sci Res, 2016 Feb;27(1):1-20.
PMID: 27019679 MyJurnal

Isolates of Fusarium were discovered in peat soil samples collected from peat swamp forest, waterlogged peat soil, and peat soil from oil palm plantations. Morphological characteristics were used to tentatively identify the isolates, and species confirmation was based on the sequence of translation elongation factor-1α (TEF-1α) and phylogenetic analysis. Based on the closest match of Basic Local Alignment Search Tool (BLAST) searches against the GenBank and Fusarium-ID databases, five Fusarium species were identified, namely F. oxysporum (60%), F. solani (23%), F. proliferatum (14%), F. semitectum (1%), and F. verticillioides (1%). From a neighbour-joining tree of combined TEF-1α and β-tubulin sequences, isolates from the same species were clustered in the same clade, though intraspecies variations were observed from the phylogenetic analysis. The Fusarium species isolated in the present study are soil inhabitants and are widely distributed worldwide. These species can act as saprophytes and decomposers as well as plant pathogens. The presence of Fusarium species in peat soils suggested that peat soils could be a reservoir of plant pathogens, as well-known plant pathogenic species such F. oxysporum, F. solani, F. proliferatum, and F. verticillioides were identified. The results of the present study provide knowledge on the survival and distribution of Fusarium species.

MeSH terms: Malaysia
Fulltext Life History of Thalerosphyrus (Ephemeroptera: Heptageniidae) in Tropical Rivers with Reference to the Varying Altitude

Hamid SA, Rawi CS, Ahmad AH

Trop Life Sci Res, 2016 Feb;27(1):43-62.
PMID: 27019681 MyJurnal

The life history and the influence of environmental parameters on Thalerosphyrus were investigated in two first-order rivers-the Batu Hampar River and the Teroi River of Gunung Jerai, Kedah-in northern peninsular Malaysia. Based on nymphal body length, Thalerosphyrus was found to be trivoltine in both rivers, regardless of the altitudinal difference, but its population abundance was four times higher in the Teroi River, presumably related to its better survival in the lower water temperature. At least nine instars of Thalerosphyrus were detected in the field-collected nymphs. Its life cycle was completed within 2.5-3.0 months, with overlapping cohorts and continual emergence of up to 3 months. The main driving factors of the high abundance of Thalerosphyrus were the water temperature and habitat quality.

MeSH terms: Animals; Cold Temperature; Life Cycle Stages; Malaysia; Nymph; Temperature; Water; Ecosystem; Rivers
Fulltext Mechanism of action of novel piperazine containing a toxicant against human liver cancer cells

Samie N, Muniandy S, Kanthimathi MS, Haerian BS

PeerJ, 2016;4:e1588.
PMID: 27019772 DOI: 10.7717/peerj.1588

The purpose of this study was to assess the cytotoxic potential of a novel piperazine derivative (PCC) against human liver cancer cells. SNU-475 and 423 human liver cancer cell lines were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on liver cancer cells with an IC50 value of 6.98 ± 0.11 µM and 7.76 ± 0.45 µM against SNU-475 and SNU-423 respectively after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-κB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. Results of this study suggest that PCC is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines.

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