Displaying publications 21 - 40 of 51 in total

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  1. Fulltext Hepatoprotective action of various partitions of methanol extract of Bauhinia purpurea leaves against paracetamol-induced liver toxicity: involvement of the antioxidant mechanisms
    Zakaria ZA, Yahya F, Mamat SS, Mahmood ND, Mohtarrudin N, Taher M, et al.
    BMC Complement Altern Med, 2016;16(1):175.
    PMID: 27287196 DOI: 10.1186/s12906-016-1110-4
    Methanol extract of Bauhinia purpurea L. (family Fabaceae) (MEBP) possesses high antioxidant and anti-inflammatory activities and recently reported to exert hepatoprotection against paracetamol (PCM)-induced liver injury in rats. In an attempt to identify the hepatoprotective bioactive compounds in MEBP, the extract was prepared in different partitions and subjected to the PCM-induced liver injury model in rats.
  2. Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies
    Chigurupati S, Selvaraj M, Mani V, Selvarajan KK, Mohammad JI, Kaveti B, et al.
    Bioorg Chem, 2016 08;67:9-17.
    PMID: 27231830 DOI: 10.1016/j.bioorg.2016.05.002
    The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC50: 0.68±0.13μM) with strong DPPH and ABTS radical scavenging activity (IC50: 13.77±0.25μM and IC50: 12.59±0.21μM), respectively. While P3 exhibited as the second most potent compound with AChE inhibition (IC50: 0.74±0.09μM) and with DPPH and ABTS radical scavenging activity (IC50: 13.52±0.62μM and IC50: 13.13±0.85μM), respectively. Finally, molecular docking studies provided prospective evidence to identify key interactions between the active inhibitors and the AChE that furthermore led us to the identification of plausible binding mode of novel indolopyrazoline derivatives. Additionally, in-silico ADME prediction using QikProp shows that these derivatives fulfilled all the properties of CNS acting drugs. This study confirms the first time reporting of indolopyrazoline derivatives as potential anti-Alzheimer agents.
  3. Association of ABCC2 with levels and toxicity of methotrexate in Malaysian Childhood Acute Lymphoblastic Leukemia (ALL)
    Razali RH, Noorizhab MNF, Jamari H, James RJ, Teh KH, Ibrahim HM, et al.
    Pediatr Hematol Oncol, 2020 Apr;37(3):185-197.
    PMID: 31870219 DOI: 10.1080/08880018.2019.1705949
    Studies had shown that genetic polymorphism plays a significant role in the pharmacokinetics and pharmacodynamics variation of high dose methotrexate (MTX), 5000 mg/m2 regimen. The objective of this study was to investigate the genetic variations associated with the serum level and toxicity of MTX in Malaysian children with acute lymphoblastic leukemia (ALL). Thirty-eight patients were genotyped for rs717620 (ABCC2), rs4948496 (ARID5B), rs1801133 (MTHFR) and rs4149056 (SLCO1B1). Serum levels of MTX at 48 h post 24 h of intravenous infusion were analyzed by high-performance liquid chromatography-mass spectrometry. The ABCC2 genotype was significantly associated with the serum levels of MTX at 48 h after treatment (p = 0.017). Patients with CT and TT of rs717620 (ABCC2) and TC and CC of rs4948496 (ARID5B) were significantly associated with leukopenia grade I-IV (Fisher Exact Test; p = 0.03 and 0.02, respectively). The three most common MTX related toxicities were leukopenia (60.5%), increased alanine aminotransferase enzyme (47.4%), and thrombocytopenia (47.4%). Our results demonstrate that by prescreening of patients for ABCC2 and ARID5B associated with the serum levels and adverse effects of MTX would identify patients at risk and therefore help a pediatric oncologist to personalize chemotherapy drugs for precision health.
  4. Fulltext Adolescent kratom exposure affects cognitive behaviours and brain metabolite profiles in Sprague-Dawley rats
    Zul Aznal AN, Mohamad Nor Hazalin NA, Hassan Z, Mat NH, Chear NJ, Teh LK, et al.
    Front Pharmacol, 2022;13:1057423.
    PMID: 36518677 DOI: 10.3389/fphar.2022.1057423
    Adolescence is a critical developmental period during which exposure to psychoactive substances like kratom (Mitragyna speciosa) can cause long-lasting deleterious effects. Here, we evaluated the effects of mitragynine, the main alkaloid of kratom, and lyophilised kratom decoction (LKD) on cognitive behaviours and brain metabolite profiles in adolescent rats. Male Sprague-Dawley rats (Postnatal day, PND31) were given vehicle, morphine (5 mg/kg), mitragynine (3, 10, or 30 mg/kg), or LKD (equivalent dose of 30 mg/kg mitragynine) for 15 consecutive days. Later, a battery of behavioural testing was conducted, brain was extracted and metabolomic analysis was performed using LCMS-QTOF. The results showed that mitragynine did not affect the recognition memory in the novel object recognition task. In the social interaction task, morphine, mitragynine, and LKD caused a marked deficit in social behaviour, while in Morris water maze task, mitragynine and LKD only affected reference memory. Metabolomic analysis revealed distinct metabolite profiles of animals with different treatments. Several pathways that may be involved in the effects of kratom exposure include arachidonic acid, pantothenate and CoA, and tryptophan pathways, with several potential biomarkers identified. These findings suggest that adolescent kratom exposure can cause cognitive behavioural deficits that may be associated with changes in the brain metabolite profiles.
  5. Fulltext Mitochondrial DNA mutations in Malaysian female breast cancer patients
    Omasanggar R, Yu CY, Ang GY, Emran NA, Kitan N, Baghawi A, et al.
    PLoS One, 2020;15(5):e0233461.
    PMID: 32442190 DOI: 10.1371/journal.pone.0233461
    Cancer development has been ascribed with diverse genetic variations which are identified in both mitochondrial and nuclear genomes. Mitochondrial DNA (mtDNA) alterations have been detected in several tumours which include lung, colorectal, renal, pancreatic and breast cancer. Several studies have explored the breast tumour-specific mtDNA alteration mainly in Western population. This study aims to identify mtDNA alterations of 20 breast cancer patients in Malaysia by next generation sequencing analysis. Twenty matched tumours with corresponding normal breast tissues were obtained from female breast cancer patients who underwent mastectomy. Total DNA was extracted from all samples and the entire mtDNA (16.6kb) was amplified using long range PCR amplification. The amplified PCR products were sequenced using mtDNA next-generation sequencing (NGS) on an Illumina Miseq platform. Sequencing involves the entire mtDNA (16.6kb) from all pairs of samples with high-coverage (~ 9,544 reads per base). MtDNA variants were called and annotated using mtDNA-Server, a web server. A total of 18 of 20 patients had at least one somatic mtDNA mutation in their tumour samples. Overall, 65 somatic mutations were identified, with 30 novel mutations. The majority (59%) of the somatic mutations were in the coding region, whereas only 11% of the mutations occurred in the D-loop. Notably, somatic mutations in protein-coding regions were non-synonymous (49%) in which 15.4% of them are potentially deleterious. A total of 753 germline mutations were identified and four of which were novel mutations. Compared to somatic alterations, less than 1% of germline missense mutations are harmful. The findings of this study may enhance the current knowledge of mtDNA alterations in breast cancer. To date, the catalogue of mutations identified in this study is the first evidence of mtDNA alterations in Malaysian female breast cancer patients.
  6. Fulltext Antinociceptive Activity of Petroleum Ether Fraction of Clinacanthus nutans Leaves Methanolic Extract: Roles of Nonopioid Pain Modulatory Systems and Potassium Channels
    Zakaria ZA, Abdul Rahim MH, Roosli RAJ, Mohd Sani MH, Marmaya NH, Omar MH, et al.
    Biomed Res Int, 2019;2019:6593125.
    PMID: 31467905 DOI: 10.1155/2019/6593125
    Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been reported to exert antinociceptive activity. The present study aimed to elucidate the possible antinociceptive mechanisms of a lipid-soluble fraction of MECN, which was obtained after sequential extraction in petroleum ether. The petroleum ether fraction of C. nutans (PECN), administered orally to mice, was (i) subjected to capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged (intraperitoneal (i.p.)) with 0.15 mg/kg yohimbine, 1 mg/kg pindolol, 3 mg/kg caffeine, 0.2 mg/kg haloperidol, or 10 mg/kg atropine, which were the respective antagonist of α 2-adrenergic, β-adrenergic, adenosinergic, dopaminergic, or muscarinic receptors; and (iii) prechallenged (i.p.) with 10 mg/kg glibenclamide, 0.04 mg/kg apamin, 0.02 mg/kg charybdotoxin, or 4 mg/kg tetraethylammonium chloride, which were the respective inhibitor of ATP sensitive-, small conductance Ca2+-activated-, large conductance Ca2+-activated-, or nonselective voltage-activated-K+ channel. Results obtained demonstrated that PECN (100, 250, and 500 mg/kg) significantly (P<0.05) inhibited all models of nociception described earlier. The antinociceptive activity of 500 mg/kg PECN was significantly (P<0.05) attenuated when prechallenged with all antagonists or K+ channel blockers. However, only pretreatment with apamin and charybdotoxin caused full inhibition of PECN-induced antinociception. The rest of the K+ channel blockers and all antagonists caused only partial inhibition of PECN antinociception, respectively. Analyses on PECN's phytoconstituents revealed the presence of antinociceptive-bearing bioactive compounds of volatile (i.e., derivatives of γ-tocopherol, α-tocopherol, and lupeol) and nonvolatile (i.e., cinnamic acid) nature. In conclusion, PECN exerts a non-opioid-mediated antinociceptive activity involving mainly activation of adenosinergic and cholinergic receptors or small- and large-conductance Ca2+-activated-K+ channels.
  7. Fulltext Exposure of Helicobacter pylori to clarithromycin in vitro resulting in the development of resistance and triggers metabolic reprogramming associated with virulence and pathogenicity
    Rosli NA, Al-Maleki AR, Loke MF, Tay ST, Rofiee MS, Teh LK, et al.
    PLoS One, 2024;19(3):e0298434.
    PMID: 38446753 DOI: 10.1371/journal.pone.0298434
    In H. pylori infection, antibiotic-resistance is one of the most common causes of treatment failure. Bacterial metabolic activities, such as energy production, bacterial growth, cell wall construction, and cell-cell communication, all play important roles in antimicrobial resistance mechanisms. Identification of microbial metabolites may result in the discovery of novel antimicrobial therapeutic targets and treatments. The purpose of this work is to assess H. pylori metabolomic reprogramming in order to reveal the underlying mechanisms associated with the development of clarithromycin resistance. Previously, four H. pylori isolates were induced to become resistant to clarithromycin in vitro by incrementally increasing the concentrations of clarithromycin. Bacterial metabolites were extracted using the Bligh and Dyer technique and analyzed using metabolomic fingerprinting based on Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-Q-ToF-MS). The data was processed and analyzed using the MassHunter Qualitative Analysis and Mass Profiler Professional software. In parental sensitivity (S), breakpoint isolates (B), and induced resistance isolates (R) H. pylori isolates, 982 metabolites were found. Furthermore, based on accurate mass, isotope ratios, abundances, and spacing, 292 metabolites matched the metabolites in the Agilent METLIN precise Mass-Personal Metabolite Database and Library (AM-PCDL). Several metabolites associated with bacterial virulence, pathogenicity, survival, and proliferation (L-leucine, Pyridoxone [Vitamine B6], D-Mannitol, Sphingolipids, Indoleacrylic acid, Dulcitol, and D-Proline) were found to be elevated in generated resistant H. pylori isolates when compared to parental sensitive isolates. The elevated metabolites could be part of antibiotics resistance mechanisms. Understanding the fundamental metabolome changes in the course of progressing from clarithromycin-sensitive to breakpoint to resistant in H. pylori clinical isolates may be a promising strategy for discovering novel alternatives therapeutic targets.
  8. Fulltext Genome sequencing and annotation of multidrug resistant Mycobacterium tuberculosis (MDR-TB) PR10 strain
    Halim MZ, Jaafar MM, Teh LK, Ismail MI, Lee LS, Ngeow YF, et al.
    Genom Data, 2016 Mar;7:245-6.
    PMID: 26981419 DOI: 10.1016/j.gdata.2016.01.002
    Here, we report the draft genome sequence and annotation of a multidrug resistant Mycobacterium tuberculosis strain PR10 (MDR-TB PR10) isolated from a patient diagnosed with tuberculosis. The size of the draft genome MDR-TB PR10 is 4.34 Mbp with 65.6% of G + C content and consists of 4637 predicted genes. The determinants were categorized by RAST into 400 subsystems with 4286 coding sequences and 50 RNAs. The whole genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number CP010968.
  9. Fulltext Mechanism(s) of action underlying the gastroprotective effect of ethyl acetate fraction obtained from the crude methanolic leaves extract of Muntingia calabura
    Zakaria ZA, Balan T, Azemi AK, Omar MH, Mohtarrudin N, Ahmad Z, et al.
    BMC Complement Altern Med, 2016 Feb 24;16:78.
    PMID: 26912079 DOI: 10.1186/s12906-016-1041-0
    BACKGROUND: Muntingia calabura L. (family Muntingiaceae), commonly known as Jamaican cherry or kerukup siam in Malaysia, is used traditionally to treat various ailments. The aim of this study is to elucidate the possible underlying gastroprotective mechanisms of ethyl acetate fraction (EAF) of Muntingia calabura methanolic leaves extract (MEMC).

    METHODS: MEMC and its fractions were subjected to HPLC analysis to identify and quantify the presence of its phyto-constituents. The mechanism of gastroptotection of EAF was further investigated using pylorus ligation-induced gastric lesion rat model (100, 250, and 500 mg/kg). Macroscopic analysis of the stomach, evaluation of gastric content parameters such as volume, pH, free and total acidity, protein estimation, and quantification of mucus were carried out. The participation of nitric oxide (NO) and sulfhydryl (SH) compounds was evaluated and the superoxide dismutase (SOD), gluthathione (GSH), catalase (CAT), malondialdehyde (MDA), prostaglandin E2 (PGE2) and NO level in the ethanol induced stomach tissue homogenate was determined.

    RESULTS: HPLC analysis confirmed the presence of quercetin and gallic acid in EAF. In pylorus-ligation model, EAF significantly (p <0.001) prevent gastric lesion formation. Volume of gastric content and total protein content reduced significantly (p 

  10. Fulltext Metabolomics and partial least square discriminant analysis to predict history of myocardial infarction of self-claimed healthy subjects: validity and feasibility for clinical practice
    Mohamad N, Ismet RI, Rofiee M, Bannur Z, Hennessy T, Selvaraj M, et al.
    J Clin Bioinforma, 2015;5:3.
    PMID: 25806102 DOI: 10.1186/s13336-015-0018-4
    The dynamics of metabolomics in establishing a prediction model using partial least square discriminant analysis have enabled better disease diagnosis; with emphasis on early detection of diseases. We attempted to translate the metabolomics model to predict the health status of the Orang Asli community whom we have little information. The metabolite expressions of the healthy vs. diseased patients (cardiovascular) were compared. A metabotype model was developed and validated using partial least square discriminant analysis (PLSDA). Cardiovascular risks of the Orang Asli were predicted and confirmed by biochemistry profiles conducted concurrently.
  11. Determination toxic effects of Hystrix Brachyura Bezoar extracts using cancer cell lines and embryo zebrafish (Danio rerio) models and identification of active principles through GC-MS analysis
    Firus Khan AY, Ahmed QU, Nippun TS, Hilles A, Jalal TK, Teh LK, et al.
    J Ethnopharmacol, 2020 Nov 15;262:113138.
    PMID: 32726681 DOI: 10.1016/j.jep.2020.113138
    ETHNOPHARMACOLOGICAL RELEVANCE: Porcupine bezoar (PB) is used as folk medicine for various medical conditions including cancer treatment in Malaysia. However, its toxicity profile has never been thoroughly ascertained to confirm its safe nature as an efficacious traditional medicine in the treatment of cancer as well as other ailments.

    AIM OF THE STUDY: This study was aimed to reveal three different PBs' aqueous extracts(viz. PB-A, PB-B, PB-C) chemical constituent's profile using GC-MS analysis, anticancer property on A375, HeLa and MCF7 cancer cells, toxicity profile on zebrafish embryo morphology, EC50, LC50 and teratogenicity index.

    MATERIALS AND METHODS: PBs' extracts characterization was performed through GC-MS analysis, in vitro anticancer effect was carried out on A375, HeLa and MCF7 cancer cell lines and finally and toxicity properties on three different PBs aqueous extracts (viz. PB-A, PB-B, PB-C) were determined using zebrafish embryo model.

    RESULTS: The GC-MS analysis revealed 10 similar compounds in all PBs' extracts. Dilauryl thiodipropionate was found to be a major compound in all PBs' extracts followed by tetradecanoic acid. An in vitro anticancer study revealed PB extracts exerted median inhibition concentration (IC50) <50 μg/mL, on cancer cells viz. A375, HeLa and MCF7 with no significant toxicity on normal cells viz. NHDF cells. In vivo toxicity of PBs extracts found affecting tail detachment, hatching, craniofacial, brain morphology, soft tissues, edema, spinal, somites, notochord and cardiovascular system (brachycardia, disruption of blood circulation) deformities. The LC50 and EC50 demonstrated PB extracts effect as dose and time dependent with median concentration <150.0 μg/mL. Additionally, teratogenicity index (TI) viz. >1.0 revealed teratogenic property for PB extracts.

    CONCLUSIONS: The findings revealed that all three PBs aqueous extracts possessed anticancer activity and exhibited significant toxicological effects on zebrafish embryos with high teratogenicity index. Hence, its use as an anticancer agent requires further investigation and medical attentions to determine its safe dose.

  12. Fulltext Stress, Anxiety and Depression among a Cohort of Health Sciences Undergraduate Students: The Prevalence and Risk Factors
    Fauzi MF, Anuar TS, Teh LK, Lim WF, James RJ, Ahmad R, et al.
    Int J Environ Res Public Health, 2021 03 22;18(6).
    PMID: 33809939 DOI: 10.3390/ijerph18063269
    Stress, anxiety, and depression (SAD) have a negative impact on the learning and academic performance of university students. Hence, this study aimed to determine the prevalence, as well as the risk factors associated with SAD among a cohort of students pursuing undergraduate degree courses in health sciences. This is part of the strategy in building a healthy nation. A questionnaire containing socio-demographic factors and the short version of Depression, Anxiety, and Stress Scale-21 (DASS-21) was used to assess the likelihood of psychological distress. Logistic regression analysis was conducted to determine the risk factors of SAD. In total, 449 students completed the questionnaire (93.9% response rate). Of these, 65% had stress, 85.1% had anxiety and 51.4% had depression. Most cases of stress (74.6%) and depression (66.2%) were of normal-to-mild level, while 74.6% of them showed moderate-to-extremely severe anxiety. There was a statistically significant association between stress score and the year of study. In the regression analysis, poor sleep quality and fatigue were risk factors of anxiety and depression, whereas low-grade fever and frequent headaches were risk factors for stress and anxiety. Stress, anxiety, and depression scores were significantly higher among students studying medical imaging. A substantial proportion of health science students are suffering from SAD. This study recommends screening and close monitoring of the above-mentioned predictors and the formulation of comprehensive intervention strategies for students with SAD.
  13. Metabolomic-guided discovery of Alzheimer's disease biomarkers from body fluid
    Enche Ady CNA, Lim SM, Teh LK, Salleh MZ, Chin AV, Tan MP, et al.
    J Neurosci Res, 2017 Oct;95(10):2005-2024.
    PMID: 28301062 DOI: 10.1002/jnr.24048
    The rapid increase in the older population has made age-related diseases like Alzheimer's disease (AD) a global concern. Given that there is still no cure for this neurodegenerative disease, the drastic growth in the number of susceptible individuals represents a major emerging threat to public health. The poor understanding of the mechanisms underlying AD is deemed the greatest stumbling block against progress in definitive diagnosis and management of this disease. There is a dire need for biomarkers that can facilitate early diagnosis, classification, prognosis, and treatment response. Efforts have been directed toward discovery of reliable and distinctive AD biomarkers but with very little success. With the recent emergence of high-throughput technology that is able to collect and catalogue vast datasets of small metabolites, metabolomics offers hope for a better understanding of AD and subsequent identification of biomarkers. This review article highlights the potential of using multiple metabolomics platforms as useful means in uncovering AD biomarkers from body fluids. © 2017 Wiley Periodicals, Inc.
  14. Potential of dihydropyrimidine dehydrogenase genotypes in personalizing 5-fluorouracil therapy among colorectal cancer patients
    Teh LK, Hamzah S, Hashim H, Bannur Z, Zakaria ZA, Hasbullani Z, et al.
    Ther Drug Monit, 2013 Oct;35(5):624-30.
    PMID: 23942539 DOI: 10.1097/FTD.0b013e318290acd2
    Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine catabolic enzyme involved in the initial and rate-limiting step of the catabolic pathway of toxic metabolites of 5-fluorouracil (5-FU). Several studies have reported that deficiency of DPD and polymorphisms of its gene are related to 5-FU toxicities and death. Association between serum concentration of 5-FU and its related toxicity has also been previously demonstrated. Hence, this study aims to understand the role of DPYD variants in serum level of 5-FU and the risk of developing toxicity to prevent adverse reactions and maximize therapy outcome for personalized medicine.
  15. Discovery of polymethoxyflavones as potential cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and phosphodiesterase 4B (PDE4B) inhibitors
    Md Idris MH, Mohd Amin SN, Mohd Amin SN, Wibowo A, Zakaria ZA, Shaameri Z, et al.
    J Recept Signal Transduct Res, 2021 Jul 29.
    PMID: 34323638 DOI: 10.1080/10799893.2021.1951756
    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed to treat inflammatory-related diseases, pain and fever. However, the prolong use of traditional NSAIDs leads to undesirable side effects such as gastric, ulceration, and renal toxicity due to lack of selectivity toward respective targets for COX-2, 5-LOX, and PDE4B. Thus, targeting multiple sites can reduce these adverse effects of the drugs and increase its potency. A series of methoxyflavones (F1-F5) were synthesized and investigated for their anti-inflammatory properties through molecular docking and inhibition assays. Among these flavones, only F2 exhibited selectivity toward COX-2 (Selectivity Index, SI: 3.90, COX-2 inhibition: 98.96 ± 1.47%) in comparison with celecoxib (SI: 7.54, COX-2 inhibition: 98.20 ± 2.55%). For PDEs, F3 possessed better selectivity to PDE4B (SI: 4.67) than rolipram (SI: 0.78). F5 had the best 5-LOX inhibitory activity among the flavones (33.65 ± 4.74%) but less than zileuton (90.81 ± 0.19%). Docking analysis indicated that the position of methoxy group and the substitution of halogen play role in determining the bioactivities of flavones. Interestingly, F1-F5 displayed favorable pharmacokinetic profiles and acceptable range of toxicity (IC50>70 µM) in cell lines with the exception for F1 (IC50: 16.02 ± 1.165 µM). This study generated valuable insight in designing new anti-inflammatory drug based on flavone scaffold. The newly synthesized flavones can be further developed as future therapeutic agents against inflammation.
  16. Fulltext Draft Genome Sequences of Local Clinical Isolates of Drug-Resistant and Drug-Sensitive Mycobacterium tuberculosis
    Zainal Abidin N, Noorizhab MNF, Teh LK, Lim WF, Mohd Noordin N, Aziz ZA, et al.
    Microbiol Resour Announc, 2021 Jun 24;10(25):e0035221.
    PMID: 34165334 DOI: 10.1128/MRA.00352-21
    In the battle against tuberculosis (TB), plasticity of the Mycobacterium tuberculosis genome is believed to contribute to the pathogen's virulence and drug resistance. Here, we report 10 draft genome sequences of clinical M. tuberculosis isolated in Malaysia as the basis for understanding the genome plasticity of the M. tuberculosis isolates.
  17. A study on the genetic polymorphisms of CYP3A5 among the Orang Asli in Malaysia using a next generation sequencing platform
    Ang GY, Yu CY, Johari James R, Ahmad A, Abdul Rahman T, Mohd Nor F, et al.
    Ann Hum Biol, 2018 Mar;45(2):166-169.
    PMID: 29447003 DOI: 10.1080/03014460.2018.1440004
    BACKGROUND: CYP3A5 is the predominant sub-family of biotransformation enzymes in the liver and the genetic variations in CYP3A5 are an important determinant of inter-individual and inter-ethnic differences in CYP3A-mediated drug disposition and response.

    AIM: This study aims to investigate the genetic polymorphisms of CYP3A5 among the Orang Asli in Peninsular Malaysia using a next generation sequencing platform.

    METHODS: Genomic DNAs were extracted from blood samples of the three main Orang Asli tribes and whole-genome sequencing was performed.

    RESULTS: A total of 61 single nucleotide polymorphisms were identified and all the SNPs were located in introns except rs15524, which is in the 3'UTR, and 11 of these polymorphisms were novel. Two allelic variants and three genotypes were identified in the Orang Asli. The major allelic variant was the non-functional CYP3A5*3 (66.4%). The percentages of Orang Asli with CYP3A5*3/*3 (47.2%) and CYP3A5*1/*3 (38.1%) genotypes are more than twice the percentage of Orang Asli with CYP3A5*1/*1 (14.8%) genotype. Almost half of the Orang Asli harboured CYP3A5 non-expressor genotype (CYP3A5*3/*3).

    CONCLUSIONS: The predominance of the CYP3A5 non-expressor genotype among the Orang Asli was unravelled and the findings in this study may serve as a guide for the optimisation of pharmacotherapy for the Orang Asli community.

  18. Inference of the Genetic Polymorphisms of CYP2D6 in Six Subtribes of the Malaysian Orang Asli from Whole-Genome Sequencing Data
    Yu CY, Ang GY, Subramaniam V, Johari James R, Ahmad A, Abdul Rahman T, et al.
    Genet Test Mol Biomarkers, 2017 Jul;21(7):409-415.
    PMID: 28525288 DOI: 10.1089/gtmb.2016.0235
    AIMS: CYP2D6 is one of the major enzymes in the cytochrome P450 monooxygenase system. It metabolizes ∼25% of prescribed drugs and hence, the genetic diversity of a CYP2D6 gene has continued to be of great interest to the medical and pharmaceutical industries. This study was designed to perform a systematic analysis of the CYP2D6 gene in six subtribes of the Malaysian Orang Asli.

    METHODS: Genomic DNAs were extracted from the blood samples followed by whole-genome sequencing. The reads were aligned to the reference human genome hg19 and variants in the CYP2D6 gene were analyzed. CYP2D6*5 and duplication of CYP2D6 were analyzed using previously established methods.

    RESULTS: A total of 72 single nucleotide polymorphisms were identified. CYP2D6*1, *2, *4, *5, *10,*41, and duplication of the gene were found in the Orang Asli, whereby CYP2D6*2 and *41 alleles are reported for the first time in the Malaysian population.

    CONCLUSION: The findings in this study provide insights into the genetic polymorphisms of CYP2D6 in the Orang Asli of Peninsular Malaysia.

  19. Fulltext Semipurified Ethyl Acetate Partition of Methanolic Extract of Melastoma malabathricum Leaves Exerts Gastroprotective Activity Partly via Its Antioxidant-Antisecretory-Anti-Inflammatory Action and Synergistic Action of Several Flavonoid-Based Compounds
    Ismail Suhaimy NW, Noor Azmi AK, Mohtarrudin N, Omar MH, Tohid SF, Cheema MS, et al.
    Oxid Med Cell Longev, 2017;2017:6542631.
    PMID: 28168011 DOI: 10.1155/2017/6542631
    Recent study has demonstrated the gastroprotective activity of crude methanolic extract of M. malabathricum leaves. The present study evaluated the gastroprotective potential of semipurified extracts (partitions): petroleum ether, ethyl acetate (EAMM), and aqueous obtained from the methanolic extract followed by the elucidation of the gastroprotective mechanisms of the most effective partition. Using the ethanol-induced gastric ulcer assay, all partitions exerted significant gastroprotection, with EAMM being the most effective partition. EAMM significantly (i) reduced the volume and acidity (free and total) while increasing the pH of gastric juice and enhanced the gastric wall mucus secretion when assessed using the pylorus ligation assay, (ii) increased the enzymatic and nonenzymatic antioxidant activity of the stomach tissue, (iii) lost its gastroprotective activity following pretreatment with N-omega-nitro-L-arginine methyl ester (L-NAME; NO blocker) or carbenoxolone (CBXN; NP-SH blocker), (iv) exerted antioxidant activity against various in vitro oxidation assays, and (v) showed moderate in vitro anti-inflammatory activity via the LOX-modulated pathway. In conclusion, EAMM exerts a remarkable NO/NP-SH-dependent gastroprotective effect that is attributed to its antisecretory and antioxidant activities, ability to stimulate the gastric mucus production and endogenous antioxidant system, and synergistic action of several gastroprotective-induced flavonoids.
  20. Porous NiTi Dental Implant Fabricated by a Metal Injection Molding: An in Vivo Biocompatibility Evaluation in an Animal Model
    Mustafa NWNA, Ahmad R, Ahmad Khushaini MA, Kamar Affendi NH, Ab Ghani SM, Tan SK, et al.
    ACS Biomater Sci Eng, 2024 Jan 08;10(1):405-419.
    PMID: 38040671 DOI: 10.1021/acsbiomaterials.3c01551
    This study assessed the corrosion resistance, intracutaneous reactivity, acute systemic toxicity, and in situ tissue effect of the implantation of porous NiTi fabricated by metal injection molding in animal models. For the intracutaneous reactivity study, five intracutaneous injections were administered per site with and without the tested extract in polar and nonpolar solutions. The extract was also delivered via intravenous and intraperitoneal routes for acute systemic toxicity. TiAl6 V4 (control) and porous NiTi were implanted in rabbit femora for a period of 13 weeks to evaluate the in situ tissue response. Corrosion was evaluated through open and cyclic polarization in PBS, while biocompatibility was investigated by assessing the general conditions, skin irritation score (edema and erythema), and histopathology. No active dissolution or hysteresis loop was observed in the corrosion study. None of the animals exhibited death, moribundity, impending death, severe pain, self-mutilation, or overgrooming. No edema was observed at injection sites. Only the positive control showed an erythematous reaction at 24, 48, and 72 h observations (p < 0.001). Porous NiTi showed a low in situ biological response for inflammation, neovascularization, and fibrosis in comparison to the control implant (p = 0.247, 0.005, and 0.011, respectively). Porous NiTi also demonstrated high pitting corrosion resistance while causing no acute hypersensitivity or acute systemic toxicity. The study concludes that porous NiTi implants were unlikely to cause local sensitization, acute systemic toxicity, or chronic inflammatory reactions in an animal model. Porous NiTi also exhibited osseointegration equivalent to Ti6AI4 V of known biocompatibility.
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