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Intraoral appliances for in situ oral biofilm growth: a systematic review

Abdullah N, Al-Marzooq F, Mohamad S, Abd Rahman N, Chi Ngo H, Perera Samaranayake L

J Oral Microbiol, 2019;11(1):1647757.
PMID: 31489127 DOI: 10.1080/20002297.2019.1647757

Background: Oral biofilms are the root cause of major oral diseases. As in vitro biofilms are not representative of the intraoral milieu, various devices have been manufactured over the years to develop Appliance Grown Oral Biofilm (AGOB). Objective: To review various intraoral appliances used to develop AGOB for microbiological analysis, and to judge the optimal means for such analyses. Design: Four databases (PubMed, Science Direct, Scopus and Medline) were searched by two independent reviewers, and articles featuring the key words 'device' OR 'splint' OR 'appliance'; 'Oral biofilm' OR 'dental plaque'; 'in vivo' OR 'in situ'; 'Microbiology' OR 'Bacteria' OR 'microbiome'; were included. The standard Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) were adopted for data gathering. Results: Of the 517 articles which met the initial inclusion criteria, 24 were deemed eligible for review. The age of the AGOB, sampled at various intervals, ranged from 30 min to 28 days. The most commonly used microbiome analytical methods were fluorescence microscopy, total cell count using conventional, and molecular tools including Next Generation Sequencing (NGS) platforms. Conclusions: No uniformly superior method for collecting AGOB could be discerned. NGS platforms are preferable for AGOB analyses.
Myofibroblastoma of the breast

Shanmugasiva VV, Ramli Hamid MT, Fadzli F, Shaleen Kaur KS, Abd Rahman N, Rahmat K

Malays J Pathol, 2018 Dec;40(3):349-353.
PMID: 30580368

INTRODUCTION: Myofibroblastoma is a rare benign mesenchymal tumour arising from the stromal elements of the breast tissue. Histopathological variants such as classic, cellular, collagenous / fibrous, lipomatous, infiltrative, myxoid and epithelioid have been identified. Most myofibroblastomas are immunoreactive for CD34, actin, CD10 and desmin, usually express oestrogen receptor (ER), progesterone receptor (PR) and variably express androgen receptor (AR).
CASE REPORT: We report a case of myofibroblastoma in an octogenarian male presenting with painless solitary breast lump. Mammography (digital tomosynthesis) and ultrasound showed a well-circumscribed hyperdense mass and hypoechoic, solid, oval mass with peripheral vascularity respectively. Patient underwent wide local excision.
DISCUSSION: Diverse characteristics of myofibroblastoma on imaging necessitates histopathological analysis for an accurate diagnosis. Myofibroblastoma are often confused with fibroadenomas due to the benign imaging characteristics and with malignant neoplasia due to their wide morphological spectrum. Surgical excision is considered curative.
Early Detection of High-frequency Presbycusis Among Normal Hearing Individuals

Aziz A, Md Daud MK, Nik Othman NA, Abd Rahman N

Otol Neurotol, 2020 09;41(8):e989-e992.
PMID: 32472918 DOI: 10.1097/MAO.0000000000002725

BACKGROUND: Presbycusis is an age-related sensorineural hearing loss and it may reduce quality of life. We conducted a study to establish the prevalence of high-frequency presbycusis in normal hearing individuals and to validate the role of extended high-frequency distortion product otoacoustic emission (DPOAE) in the screening.
METHOD: A cross-sectional study was conducted among 205 normal hearing adult participants with an age range between 25 and 54 years old. Hearing analysis with extended high-frequency pure-tone audiometry (PTA) and high-frequency DPOAE was carried out for all eligible participants. High-frequency presbycusis was considered to be present when the impairment of more than 25 dB occurs at higher than 8 kHz frequencies on both ears.
RESULTS: Prevalence of high-frequency presbycusis using extended PTA was 31.7 (95% CI: 25.3, 38.1) and using high-frequency DPOAE was 57.4 (95% CI: 50.7, 64.4). The sensitivity and specificity of high-frequency DPOAE in detecting high-frequency presbycusis were 72.3 and 49.3% respectively with positive predictive value of 39.8% and negative predictive value of 79.3%. The association between age and high-frequency presbycusis was significant based on high-frequency DPOAE (p = 0.029).
CONCLUSIONS: The prevalence of high-frequency hearing loss is higher with increasing in age. High-frequency DPOAE may be used as a screening tool followed by confirmation using extended PTA. The early detection of presbycusis is important so that measures can be taken to prevent more severe problems developing.
Fulltext The antibacterial efficacy of silver diamine fluoride (SDF) is not modulated by potassium iodide (KI) supplements: A study on in-situ plaque biofilms using viability real-time PCR with propidium monoazide

Abdullah N, Al Marzooq F, Mohamad S, Abd Rahman N, Rani KGA, Chi Ngo H, et al.

PLoS One, 2020;15(11):e0241519.
PMID: 33141868 DOI: 10.1371/journal.pone.0241519

Silver diamine fluoride (SDF) is commonly used to arrest caries lesions, especially in early childhood caries. Recently, it was suggested that SDF can be combined with potassium iodide (KI) to minimize the discoloration of demineralized dentine associated with SDF application. However, the antibacterial efficacy of SDF alone or combined with KI on in-situ biofilm is unknown. Hence, we compared the anti-plaque biofilm efficacy of two different commercially available SDF solutions, with or without KI, using an in-situ biofilm, analysed using viability real-time PCR with propidium monoazide (PMA). Appliance-borne in-situ biofilm samples (n = 90) were grown for a period of 6 h in five healthy subjects who repeated the experiment on three separate occasions, using a validated, novel, intraoral device. The relative anti-biofilm efficacy of two SDF formulations; 38.0% Topamine (SDFT) and 31.3%, Riva Star (SDFR), KI alone, and KI in combination with SDFR (SDFR+KI) was compared. The experiments were performed by applying an optimized volume of the agents onto the biofilm for 1min, mimicking the standard clinical procedure. Afterwards the viability of the residual biofilm bacteria was quantified using viability real-time PCR with PMA, then the percentage of viable from total bacteria was calculated. Both SDF formulations (SDFT and SDFR) exhibited potent antibacterial activities against the in-situ biofilm; however, there was non-significant difference in their efficacy. KI alone did not demonstrate any antibacterial effect, and there was non-significant difference in the antibacterial efficacy of SDF alone compared to SDF with KI, (SDFT v SDFR/KI). Thus, we conclude that the antibacterial efficacy of SDF against plaque biofilms is not modulated by KI supplements. Viability real-time PCR with PMA was successfully used to analyze the viability of naturally grown oral biofilm; thus, the same method can be used to test the antimicrobial effect of other agents on oral biofilms in future research.
Effect of irradiance on the emission of short-lived halocarbons from three common tropical marine microalgae

Lim YK, Keng FS, Phang SM, Sturges WT, Malin G, Abd Rahman N

PeerJ, 2019;7:e6758.
PMID: 31041152 DOI: 10.7717/peerj.6758

Marine algae have been reported as important sources of biogenic volatile halocarbons that are emitted into the atmosphere. These compounds are linked to destruction of the ozone layer, thus contributing to climate change. There may be mutual interactions between the halocarbon emission and the environment. In this study, the effect of irradiance on the emission of halocarbons from selected microalgae was investigated. Using controlled laboratory experiments, three tropical marine microalgae cultures, Synechococcus sp. UMACC 371 (cyanophyte), Parachlorella sp. UMACC 245 (chlorophyte) and Amphora sp. UMACC 370 (diatom) were exposed to irradiance of 0, 40 and 120 µmol photons m-2s-1. Stress in the microalgal cultures was indicated by the photosynthetic performance (Fv/Fm, maximum quantum yield). An increase in halocarbon emissions was observed at 120 µmol photons m-2s-1, together with a decrease in Fv/Fm. This was most evident in the release of CH3I by Amphora sp. Synechococcus sp. was observed to be the most affected by irradiance as shown by the increase in emissions of most halocarbons except for CHBr3 and CHBr2Cl. High positive correlation between Fv/Fm and halocarbon emission rates was observed in Synechococcus sp. for CH2Br2. No clear trends in correlation could be observed for the other halocarbons in the other two microalgal species. This suggests that other mechanisms like mitochondria respiration may contribute to halocarbon production, in addition to photosynthetic performance.
Real-time loop-mediated isothermal amplification assay for rapid detection of human papillomavirus 16 in oral squamous cell carcinoma

Hamzan NI, Ab Rahman N, Suraiya S, Mohamad I, George Kalarakkal T, Mohamad S

Arch Oral Biol, 2021 Apr;124:105051.
PMID: 33581498 DOI: 10.1016/j.archoralbio.2021.105051

OBJECTIVE: The present study established a real-time loop-mediated isothermal amplification (qLAMP) for rapid detection of human papillomavirus subtype 16 (HPV-16) in oral squamous cell carcinoma (OSCC).
METHODS: The qLAMP assay was optimized targeting the HPV-16 E7 gene. The analytical sensitivity and specificity of the assay were determined using HPV-18 (ATCC® 45152D™), HPV-35 (ATCC® 40330™), HPV-43 (ATCC® 40338™) and HPV-56 (ATCC® 40549™) viral strains and oral bacteria. HPV-16 standard curve was constructed for determination of HPV-16 viral load. The diagnostic performance of the assay was evaluated from 63 OSCC patients comprising 63 tissue, 13 saliva and 49 blood samples, in comparison with p16 immunohistochemistry (IHC), in-house PCR and nested PCR assays.
RESULTS: The detection limit of developed LAMP and PCR assays was 4.68 × 101 and 4.68 × 103 copies/μl, respectively. qLAMP assay enabled detection of positive results as early as 23 min at 67 °C. This assay can detect HPV-16 positivity in 23 % (3/13) saliva and 4.8 % (3/63) tissue samples with the viral load ranging from 4.68 × 101 to 4.68 × 104 copies/μl. HPV-16 positivity was not detected in all the blood samples. The sensitivity and specificity of qLAMP were 100 % in comparison with that of p16 IHC and nested PCR.
CONCLUSION: This study reports for the first time on the use of qLAMP assay for detection of HPV-16 in OSCC in both tissue and saliva as the sample matrix which holds promise in improving the diagnostic application owing to its rapidity, simplicity, high sensitivity and specificity.
REPLY TO THE LETTER TO THE EDITOR: EARLY DETECTION OF HIGH-FREQUENCY PRESBYCUSIS AMONG NORMAL HEARING INDIVIDUALS

Aziz A, Md Daud MK, Nik Othman NA, Abd Rahman N

Otol Neurotol, 2021 02 01;42(2):345-346.
PMID: 33273310 DOI: 10.1097/MAO.0000000000002908
Computational-aided design: minimal peptide sequence to block dengue virus transmission into cells

Arumugam AC, Agharbaoui FE, Khazali AS, Yusof R, Abd Rahman N, Ahmad Fuaad AAH

J Biomol Struct Dyn, 2020 Dec 31.
PMID: 33382015 DOI: 10.1080/07391102.2020.1866074

Dengue virus (DV) infection is one of the main public health concerns, affecting approximately 390 million people worldwide, as reported by the World Health Organization. Yet, there is no antiviral treatment for DV infection. Therefore, the development of potent and nontoxic anti-DV, as a complement for the existing treatment strategies, is urgently needed. Herein, we investigate a series of small peptides inhibitors of DV antiviral activity targeting the entry process as the promising strategy to block DV infection. The peptides were designed based on our previously reported peptide sequence, DN58opt (TWWCFYFCRRHHPFWFFYRHN), to identify minimal effective inhibitory sequence through molecular docking and dynamics studies. The in silico designed peptides were synthesized using conventional Fmoc solid-phase peptide synthesis chemistry, purified by RP-HPLC and characterized using LCMS. Later, they were screened for their antiviral activity. One of the peptides, AC 001, was able to reduce about 40% of DV plaque formation. This observation correlates well with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) analysis - AC 001 showed the most favorable binding affinity through 60 ns simulations. Pairwise residue decomposition analysis has revealed four key residues that contributed to the binding of these peptides into the DV2 E protein pocket. This work identifies the minimal peptide sequence required to inhibit DV replication and explains the behavior observed on an atomic level using computational study.Communicated by Ramaswamy H. Sarma.
Fulltext Antibacterial Potential of Biosynthesized Zinc Oxide Nanoparticles against Poultry-Associated Foodborne Pathogens: An In Vitro Study

Mohd Yusof H, Abdul Rahman N, Mohamad R, Hasanah Zaidan U, Samsudin AA

Animals (Basel), 2021 Jul 14;11(7).
PMID: 34359225 DOI: 10.3390/ani11072093

Since the emergence of multidrug-resistant bacteria in the poultry industry is currently a serious threat, there is an urgent need to develop a more efficient and alternative antibacterial substance. Zinc oxide nanoparticles (ZnO NPs) have exhibited antibacterial efficacy against a wide range of microorganisms. Although the in vitro antibacterial activity of ZnO NPs has been studied, little is known about the antibacterial mechanisms of ZnO NPs against poultry-associated foodborne pathogens. In the present study, ZnO NPs were successfully synthesized using Lactobacillus plantarum TA4, characterized, and their antibacterial potential against common avian pathogens (Salmonella spp., Escherichia coli, and Staphylococcus aureus) was investigated. Confirmation of ZnO NPs by UV-Visual spectroscopy showed an absorption band center at 360 nm. Morphologically, the synthesized ZnO NPs were oval with an average particle size of 29.7 nm. Based on the dissolution study of Zn2+, ZnO NPs released more ions than their bulk counterparts. Results from the agar well diffusion assay indicated that ZnO NPs effectively inhibited the growth of the three poultry-associated foodborne pathogens. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were assessed using various concentrations of ZnO NPs, which resulted in excellent antibacterial activity as compared to their bulkier counterparts. S. aureus was more susceptible to ZnO NPs compared to the other tested bacteria. Furthermore, the ZnO NPs demonstrated substantial biofilm inhibition and eradication. The formation of reactive oxygen species (ROS) and cellular material leakage was quantified to determine the underlying antibacterial mechanisms, whereas a scanning electron microscope (SEM) was used to examine the morphological changes of tested bacteria treated with ZnO NPs. The findings suggested that ROS-induced oxidative stress caused membrane damage and bacterial cell death. Overall, the results demonstrated that ZnO NPs could be developed as an alternative antibiotic in poultry production and revealed new possibilities in combating pathogenic microorganisms.
Emergency department discharge instruction for mild traumatic brain injury: Evaluation on readability, understandability, actionability and content

Abdul Rahman N', Nurumal MS, Awang MS, Mohd Shah ANS

Australas Emerg Care, 2020 Dec;23(4):240-246.
PMID: 32713770 DOI: 10.1016/j.auec.2020.06.005

INTRODUCTION: Emergency departments (EDs) routinely provide discharge instructions due to a large number of patients with mild traumatic brain injury (mTBI) being discharged home directly from ED. This study aims to evaluate the quality of available mTBI discharge instructions provided by EDs of Malaysia government hospitals.
METHODS: All 132 EDs were requested for a copy of written discharge instruction given to the patients. The mTBI discharge instructions were evaluated using the Patient Education Materials Assessment-Printable Tool (PEMAT-P) for understandability and actionability. Readability was measured using an online readability tool of Malay text. The content was compared against the discharge instructions recommended by established guidelines.
RESULTS: 49 articles were eligible for the study. 26 of the articles met the criteria of understandability, and 3 met the criteria for actionability. The average readability level met the ability of average adult. Most of the discharge instructions focused on emergency symptoms, and none contained post-concussion features.
CONCLUSION: Majority of the discharge instructions provided were appropriate for average people to read but difficult to understand and act upon. Important information was neglected in most discharge instructions. Thus, revision and future development of mTBI discharge instruction should consider health literacy demand and cognitive ability to process such information.
Fulltext Screening of antiviral activities in medicinal plants extracts against dengue virus using dengue NS2B-NS3 protease assay

Rothan HA, Zulqarnain M, Ammar YA, Tan EC, Rahman NA, Yusof R

Trop Biomed, 2014 Jun;31(2):286-96.
PMID: 25134897 MyJurnal

Dengue virus infects millions of people worldwide and there is no vaccine or anti-dengue therapeutic available. Screening large numbers of medicinal plants for anti-dengue activities is an alternative strategy in order to find the potent therapeutic compounds. Therefore, this study was designed to identify anti-dengue activities in nineteen medicinal plant extracts that are used in traditional medicine. Local medicinal plants Vernonia cinerea, Hemigraphis reptans, Hedyotis auricularia, Laurentia longiflora, Tridax procumbers and Senna angustifolia were used in this study. The highest inhibitory activates against dengue NS2B-NS3pro was observed in ethanolic extract of S. angustifolia leaves, methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems. These findings were further verified by in vitro viral inhibition assay. Methanolic extract of V. cinerea leaves, ethanol extract of T. procumbens stems and at less extent ethanolic extract of S. angustifolia leaves were able to maintain the normal morphology of DENV2-infected Vero cells without causing much cytopathic effects (CPE). The percentage of viral inhibition of V. cinerea and T. procumbens extracts were significantly higher than S. angustifolia extract as measured by plaque formation assay and RT-qPCR. In conclusion, The outcome of this study showed that the methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems possessed high inhibitory activates against dengue virus that worth more investigation.
Impact of virtual reality games on psychological well-being and upper limb performance in adults with physical disabilities: A pilot study

Singh DKA, Rahman NNA, Seffiyah R, Chang SY, Zainura AK, Aida SR, et al.

Med J Malaysia, 2017 04;72(2):119-121.
PMID: 28473675 MyJurnal

INTRODUCTION: There is limited information regarding the effects of interactive virtual reality (VR) games on psychological and physical well-being among adults with physical disabilities. We aimed to examine the impact of VR games on psychological well-being, upper limb motor function and reaction time in adults with physical disabilities.
METHODS: Fifteen participants completed the intervention using Wii VR games in this pilot study. Depressive, Anxiety and Stress Scales (DASS) and Capabilities of Upper Extremity (CUE) questionnaires were used to measure psychological well-being and upper limb motor function respectively. Upper limb reaction time was measured using reaction time test.
RESULTS: Results showed that there was a significant difference (p<0.05) in DASS questionnaire and average reaction time score after intervention.
CONCLUSION: There is a potential for using interactive VR games as an exercise tool to improve psychological wellbeing and upper limb reaction time among adults with disabilities.
Fulltext Association between genetic polymorphisms and external apical root resorption: A systematic review and meta-analysis

Nowrin SA, Jaafar S, Ab Rahman N, Basri R, Alam MK, Shahid F

Korean J Orthod, 2018 Nov;48(6):395-404.
PMID: 30450332 DOI: 10.4041/kjod.2018.48.6.395

Objective: To date, only a few studies have investigated the relationships between genetic polymorphisms and external apical root resorption (EARR). Hence, the aim of this systematic review was to explore the relationship between different gene polymorphisms and their association with EARR.
Methods: A complete literature search was conducted by two independent reviewers. The PubMed, Science Direct, and Scopus databases were searched. In addition, the bibliographies of all textbooks and relevant articles were searched manually. A meta-analysis was performed using data entered into the electronic databases until February 28, 2017.
Results: On the basis of the search, we identified 17 and 7 publications for the systematic review and meta-analysis, respectively. Odds ratio (OR) was used to evaluate the association of the interleukin 1B (+3954) polymorphism and the risk of EARR. The overall OR from the studies was used to estimate the risk of EARR. However, no association was found and no publication bias was apparent for the risk of EARR in patients receiving orthodontic treatment.
Conclusions: More research on the relationship between gene polymorphism and EARR is necessary to determine better specificity of possible interactions.
Fulltext Extended high frequency hearing loss in tinnitus-positive chronic suppurative otitis media patient

Mohd Salehuddin NS, Md Daud MK, Nik Othman NA, Abd Rahman N

Laryngoscope Investig Otolaryngol, 2021 Oct;6(5):1137-1141.
PMID: 34667858 DOI: 10.1002/lio2.651

Objectives: To determine the association between extended high frequency hearing loss and tinnitus in normal cochlear function based on a conventional audiometry chronic suppurative otitis media (CSOM) patient.
Design and methods: A cross-sectional study was conducted on 220 ears diagnosed as having CSOM with an equal number of tinnitus and without tinnitus groups. Only those with normal cochlear function based on conventional pure tone audiometry (250 Hz to 8 kHz) were included. They were further tested for hearing at extended high frequencies of up to 16 kHz. The severity of tinnitus was tested using a tinnitus questionnaire.
Results: The prevalence of extended high frequency hearing loss in the normal cochlear function CSOM patients with tinnitus was 81.8% (95% CI 74.5%, 89.1%), whereas the prevalence in the tinnitus negative group was 30.0% (95% CI 21.3%, 38.7%). There was a significant association between extended high frequency hearing loss and tinnitus in CSOM patients (P
Effects of different light source and media on growth and production of phycobiliprotein from freshwater cyanobacteria

Khatoon H, Kok Leong L, Abdu Rahman N, Mian S, Begum H, Banerjee S, et al.

Bioresour Technol, 2018 Feb;249:652-658.
PMID: 29091850 DOI: 10.1016/j.biortech.2017.10.052

The aim of this study was to determine the effect of different light sources and media (wastewater and BBM) on the growth of Pseudanabaena mucicola and its phycobiliprotein production. Results showed that P. mucicola grown in white light using wastewater as medium attributed higher biomass (0.55 g L-1) and when extracted with water, also showed significantly higher (P 
Critical Parameters for Particle-Based Pulmonary Delivery of Chemotherapeutics

Dabbagh A, Abu Kasim NH, Yeong CH, Wong TW, Abdul Rahman N

J Aerosol Med Pulm Drug Deliv, 2018 06;31(3):139-154.
PMID: 29022837 DOI: 10.1089/jamp.2017.1382

Targeted delivery of chemotherapeutics through the respiratory system is a potential approach to improve drug accumulation in the lung tumor, while decreasing their negative side effects. However, elimination by the pulmonary clearance mechanisms, including the mucociliary transport system, and ingestion by the alveolar macrophages, rapid absorption into the blood, enzymatic degradation, and low control over the deposition rate and location remain the main complications for achieving an effective pulmonary drug delivery. Therefore, particle-based delivery systems have emerged to minimize pulmonary clearance mechanisms, enhance drug therapeutic efficacy, and control the release behavior. A successful implementation of a particle-based delivery system requires understanding the influential parameters in terms of drug carrier, inhalation technology, and health status of the patient's respiratory system. This review aims at investigating the parameters that significantly drive the clinical outcomes of various particle-based pulmonary delivery systems. This should aid clinicians in appropriate selection of a delivery system according to their clinical setting. It will also guide researchers in addressing the remaining challenges that need to be overcome to enhance the efficiency of current pulmonary delivery systems for aerosols.
Fulltext Synthesis and Characterization of Polyaniline/Graphene Composite Nanofiber and Its Application as an Electrochemical DNA Biosensor for the Detection of Mycobacterium tuberculosis

Mohamad FS, Mat Zaid MH, Abdullah J, Zawawi RM, Lim HN, Sulaiman Y, et al.

Sensors (Basel), 2017 Dec 02;17(12).
PMID: 29207463 DOI: 10.3390/s17122789

This article describes chemically modified polyaniline and graphene (PANI/GP) composite nanofibers prepared by self-assembly process using oxidative polymerization of aniline monomer and graphene in the presence of a solution containing poly(methyl vinyl ether-alt-maleic acid) (PMVEA). Characterization of the composite nanofibers was carried out by Fourier transform infrared (FTIR) and Raman spectroscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). SEM images revealed the size of the PANI nanofibers ranged from 90 to 360 nm in diameter and was greatly influenced by the proportion of PMVEA and graphene. The composite nanofibers with an immobilized DNA probe were used for the detection of Mycobacterium tuberculosis by using an electrochemical technique. A photochemical indicator, methylene blue (MB) was used to monitor the hybridization of target DNA by using differential pulse voltammetry (DPV) method. The detection range of DNA biosensor was obtained from of 10-6-10-9 M with the detection limit of 7.853 × 10-7 M under optimum conditions. The results show that the composite nanofibers have a great potential in a range of applications for DNA sensors.
Fulltext Synthesis, Biological Evaluation and Molecular Modelling of 2'-Hydroxychalcones as Acetylcholinesterase Inhibitors

Sukumaran SD, Chee CF, Viswanathan G, Buckle MJ, Othman R, Abd Rahman N, et al.

Molecules, 2016 Jul 22;21(7).
PMID: 27455222 DOI: 10.3390/molecules21070955

A series of 2'-hydroxy- and 2'-hydroxy-4',6'-dimethoxychalcones was synthesised and evaluated as inhibitors of human acetylcholinesterase (AChE). The majority of the compounds were found to show some activity, with the most active compounds having IC50 values of 40-85 µM. Higher activities were generally observed for compounds with methoxy substituents in the A ring and halogen substituents in the B ring. Kinetic studies on the most active compounds showed that they act as mixed-type inhibitors, in agreement with the results of molecular modelling studies, which suggested that they interact with residues in the peripheral anionic site and the gorge region of AChE.
Fulltext Comparative proteomics reveals that YK51, a 4-Hydroxypandurantin-A analogue, downregulates the expression of proteins associated with dengue virus infection

Tan WL, Lee YK, Ho YF, Yusof R, Abdul Rahman N, Karsani SA

PeerJ, 2018;5:e3939.
PMID: 29404200 DOI: 10.7717/peerj.3939

Dengue is endemic throughout tropical and subtropical regions of the world. Currently, there is no clinically approved therapeutic drug available for this acute viral infection. Although the first dengue vaccine Dengvaxia has been approved for use in certain countries, it is limited to those without a previous dengue infection while the safety and efficacy of the vaccine in those elderly and younger children still need to be identified. Therefore, it is becoming increasingly important to develop therapeutics/drugs to combat dengue virus (DENV) infection. YK51 is a synthetic analogue of 4-Hydroxypandurantin A (a compound found in the crude extract of the rhizomes of Boesenbergia rotunda) that has been extensively studied by our research group. It has been shown to possess outstanding antiviral activity due to its inhibitory activity against NS2B/NS3 DENV2 protease. However, it is not known how YK51 affects the proteome of DENV infected cells. Therefore, we performed a comparative proteomics analysis to identify changes in protein expression in DENV infected HepG2 cells treated with YK51. Classical two-dimensional gel electrophoresis followed by protein identification using tandem mass spectrometry was employed in this study. Thirty proteins were found to be down-regulated with YK51 treatment. In silico analysis predicted that the down-regulation of eight of these proteins may inhibit viral infection. Our results suggested that apart from inhibiting the NS2B/NS3 DENV2 protease, YK51 may also be causing the down-regulation of a number of proteins that may be responsible in, and/or essential to virus infection. However, functional characterization of these proteins will be necessary before we can conclusively determine their roles in DENV infection.
Fulltext Suppression of Staphylococcus aureus biofilm formation and virulence by a benzimidazole derivative, UM-C162

Kong C, Chee CF, Richter K, Thomas N, Abd Rahman N, Nathan S

Sci Rep, 2018 02 09;8(1):2758.
PMID: 29426873 DOI: 10.1038/s41598-018-21141-2

Staphylococcus aureus is a major cause of nosocomial infections and secretes a diverse spectrum of virulence determinants as well as forms biofilm. The emergence of antibiotic-resistant S. aureus highlights the need for alternative forms of therapeutics other than conventional antibiotics. One route to meet this need is screening small molecule derivatives for potential anti-infective activity. Using a previously optimized C. elegans - S. aureus small molecule screen, we identified a benzimidazole derivative, UM-C162, which rescued nematodes from a S. aureus infection. UM-C162 prevented the formation of biofilm in a dose-dependent manner without interfering with bacterial viability. To examine the effect of UM-C162 on the expression of S. aureus virulence genes, a genome-wide transcriptome analysis was performed on UM-C162-treated pathogen. Our data indicated that the genes associated with biofilm formation, particularly those involved in bacterial attachment, were suppressed in UM-C162-treated bacteria. Additionally, a set of genes encoding vital S. aureus virulence factors were also down-regulated in the presence of UM-C162. Further biochemical analysis validated that UM-C162-mediated disruption of S. aureus hemolysins, proteases and clumping factors production. Collectively, our findings propose that UM-C162 is a promising compound that can be further developed as an anti-virulence agent to control S. aureus infections.

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