Displaying publications 1 - 20 of 42 in total

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  1. Tan ML, Lim LE
    Drug Chem Toxicol, 2015;38(3):241-53.
    PMID: 25156015 DOI: 10.3109/01480545.2014.947504
    Andrographis paniculata (Burm.f.) Nees is a popular medicinal plant and its components are used in various traditional product preparations. However, its herb-drug interactions risks remain unclear. This review specifically discusses the various published studies carried out to evaluate the effects of Andrographis paniculata (Burm.f.) Nees plant extracts and diterpenoids on the CYP450 metabolic enzyme and if the plant components pose a possible herb-drug interaction risk. Unfortunately, the current data are insufficient to indicate if the extracts or diterpenoids can be labeled as in vitro CYP1A2, CYP2C9 or CYP3A4 inhibitors. A complete CYP inhibition assay utilizing human liver microsomes and the derivation of relevant parameters to predict herb-drug interaction risks may be necessary for these isoforms. However, based on the current studies, none of the extracts and diterpenoids exhibited CYP450 induction activity in human hepatocytes or human-derived cell lines. It is crucial that a well-defined experimental design is needed to make a meaningful herb-drug interaction prediction.
  2. Tan HK, Muhammad TST, Tan ML
    Toxicol. Appl. Pharmacol., 2016 06 01;300:55-69.
    PMID: 27049118 DOI: 10.1016/j.taap.2016.03.017
    14-Deoxy-11,12-didehydroandrographolide (14-DDA), a major diterpenoid isolated from Andrographis paniculata (Burm.f.) Nees, is known to be cytotoxic and elicits a non-apoptotic cell death in T-47D breast carcinoma cells. In this study, the mechanistic toxicology properties of 14-DDA in T-47D cells were further investigated. 14-DDA is found to induce the formation of endoplasmic reticulum (ER) vacuoles and autophagosomes, with concurrent upregulation of LC3-II in the breast carcinoma cells. It stimulated an increase in cytosolic calcium concentration and caused a collapse in mitochondrial membrane potential in these cells. In addition, both DDIT3 and GADD45A, molecules implicated in ER stress pathway, were significantly upregulated. DDIT3 knockdown suppressed the formation of both ER vacuoles and autophagosomes, indicating that 14-DDA-induced ER stress and autophagy is dependent on this transcription factor. Collectively, it is possible that GADD45A/p38 MAPK/DDIT3 pathway is involved in the 14-DDA-induced ER-stress-mediated autophagy in T-47D cells.
  3. Tan HK, Moad AI, Tan ML
    Asian Pac. J. Cancer Prev., 2014;15(16):6463-75.
    PMID: 25169472
    The mammalian target of rapamycin (mTOR) kinase plays an important role in regulating cell growth and cell cycle progression in response to cellular signals. It is a key regulator of cell proliferation and many upstream activators and downstream effectors of mTOR are known to be deregulated in various types of cancers. Since the mTOR signalling pathway is commonly activated in human cancers, many researchers are actively developing inhibitors that target key components in the pathway and some of these drugs are already on the market. Numerous preclinical investigations have also suggested that some herbs and natural phytochemicals, such as curcumin, resveratrol, timosaponin III, gallic acid, diosgenin, pomegranate, epigallocatechin gallate (EGCC), genistein and 3,3'-diindolylmethane inhibit the mTOR pathway either directly or indirectly. Some of these natural compounds are also in the clinical trial stage. In this review, the potential anti-cancer and chemopreventive activities and the current status of clinical trials of these phytochemicals are discussed.
  4. Mundada P, Tan ML, Soh AW
    Med J Malaysia, 2015 Aug;70(4):256-8.
    PMID: 26358025
    Although it is common to have extra-hepatic metastasis of hepatocellular carcinoma (HCC) at the time of presentation, it is extremely rare to have extra-hepatic metastatic HCC without a detectable primary in the liver. We report a unique case in which a patient presented with bilateral large adrenal masses which were subsequently proven to be metastases from HCC. However, there was no tumour seen in the liver on imaging.
  5. Tan ML, Lentaris G, Amaratunga Aj G
    Nanoscale Res Lett, 2012;7(1):467.
    PMID: 22901374
    The performance of a semiconducting carbon nanotube (CNT) is assessed and tabulated for parameters against those of a metal-oxide-semiconductor field-effect transistor (MOSFET). Both CNT and MOSFET models considered agree well with the trends in the available experimental data. The results obtained show that nanotubes can significantly reduce the drain-induced barrier lowering effect and subthreshold swing in silicon channel replacement while sustaining smaller channel area at higher current density. Performance metrics of both devices such as current drive strength, current on-off ratio (Ion/Ioff), energy-delay product, and power-delay product for logic gates, namely NAND and NOR, are presented. Design rules used for carbon nanotube field-effect transistors (CNTFETs) are compatible with the 45-nm MOSFET technology. The parasitics associated with interconnects are also incorporated in the model. Interconnects can affect the propagation delay in a CNTFET. Smaller length interconnects result in higher cutoff frequency.
  6. Tan ML, Ho JJ, Teh KH
    Cochrane Database Syst Rev, 2016 Sep 28;9:CD009398.
    PMID: 27678554 DOI: 10.1002/14651858.CD009398.pub3
    BACKGROUND: About 5% of school children have a specific learning disorder, defined as unexpected failure to acquire adequate abilities in reading, writing or mathematics that is not a result of reduced intellectual ability, inadequate teaching or social deprivation. Of these events, 80% are reading disorders. Polyunsaturated fatty acids (PUFAs), in particular, omega-3 and omega-6 fatty acids, which normally are abundant in the brain and in the retina, are important for learning. Some children with specific learning disorders have been found to be deficient in these PUFAs, and it is argued that supplementation of PUFAs may help these children improve their learning abilities.

    OBJECTIVES: 1. To assess effects on learning outcomes of supplementation of polyunsaturated fatty acids (PUFAs) for children with specific learning disorders.2. To determine whether adverse effects of supplementation of PUFAs are reported in these children.

    SEARCH METHODS: In November 2015, we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, 10 other databases and two trials registers. We also searched the reference lists of relevant articles.

    SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing PUFAs with placebo or no treatment in children younger than 18 years with specific learning disabilities, as diagnosed in accordance with the fifth (or earlier) edition of theDiagnostic and Statistical Manual of Mental Disorders (DSM-5), or the 10th (or earlier) revision of the International Classification of Diseases (ICD-10) or equivalent criteria. We included children with coexisting developmental disorders such as attention deficit hyperactivity disorder (ADHD) or autism.

    DATA COLLECTION AND ANALYSIS: Two review authors (MLT and KHT) independently screened the titles and abstracts of articles identified by the search and eliminated all studies that did not meet the inclusion criteria. We contacted study authors to ask for missing information and clarification, when needed. We used the GRADE approach to assess the quality of evidence.

    MAIN RESULTS: Two small studies involving 116 children, mainly boys between 10 and 18 years of age, met the inclusion criteria. One study was conducted in a school setting, the other at a specialised clinic. Both studies used three months of a combination of omega-3 and omega-6 supplements as the intervention compared with placebo. Although both studies had generally low risk of bias, we judged the risk of reporting bias as unclear in one study, and as high in the other study. In addition, one of the studies was funded by industry and reported active company involvement in the study.None of the studies reported data on the primary outcomes of reading, writing, spelling and mathematics scores, as assessed by standardised tests.Evidence of low quality indicates that supplementation of PUFAs did not increase the risk of gastrointestinal disturbances (risk ratio 1.43, 95% confidence interval 0.25 to 8.15; two studies, 116 children). Investigators reported no other adverse effects.Both studies reported attention deficit hyperactivity disorder (ADHD)-related behaviour outcomes. We were unable to combine the results in a meta-analysis because one study reported findings as a continuous outcome, and the other as a dichotomous outcome. No other secondary outcomes were reported.We excluded one study because it used a cointervention (carnosine), and five other studies because they did not provide a robust diagnosis of a specific learning disorder. We identified one ongoing study and found three studies awaiting classification.

    AUTHORS' CONCLUSIONS: Evidence is insufficient to permit any conclusions about the effect of PUFAs on the learning abilities of children with specific learning disorders. Well-designed RCTs with clearly defined populations of children with specific learning disorders who have been diagnosed by standardised diagnostic criteria are needed.

  7. Chong YM, Kaur G, Tan ML
    J Asian Nat Prod Res, 2019 Aug;21(8):754-771.
    PMID: 30606060 DOI: 10.1080/10286020.2018.1520704
    Andrographolide, a major bioactive compound isolated from Andrographis paniculata (Burm. F.) Nees, was evaluated for its effects on the hOAT1 membrane transporter. Substrate determination and inhibition of hOAT1-mediated uptake transport assay was carried out using recombinant CHO-hOAT1 cells. The results showed that the uptake ratio of andrographolide was less than 2.0 at all concentrations tested, indicating that andrographolide is not a hOAT1 substrate. Andrographolide has no significant effects on the p-aminohippuric acid uptake and on the mRNA and protein expression of hOAT1. In conclusion, andrographolide may not pose a drug-herb interaction risk related to hOAT1.
  8. Moad AI, Muhammad TS, Oon CE, Tan ML
    Cell Biochem. Biophys., 2013 Jul;66(3):567-87.
    PMID: 23300026 DOI: 10.1007/s12013-012-9504-5
    Autophagy is an evolutionarily conserved lysosomal degradation pathway and plays a critical role in the homeostatic process of recycling proteins and organelles. Functional relationships have been described between apoptosis and autophagy. Perturbations in the apoptotic machinery have been reported to induce autophagic cell deaths. Inhibition of autophagy in cancer cells has resulted in cell deaths that manifested hallmarks of apoptosis. However, the molecular relationships and the circumstances of which molecular pathways dictate the choice between apoptosis and autophagy are currently unknown. This study aims to identify specific gene expression of rapamycin-induced autophagy and the effects of rapamycin when the autophagy process is inhibited. In this study, we have demonstrated that rapamycin is capable of inducing autophagy in T-47D breast carcinoma cells. However, when the autophagy process was inhibited by 3-MA, the effects of rapamycin became apoptotic. The Phlda1 gene was found to be up-regulated in both autophagy and apoptosis and silencing this gene was found to reduce both activities, strongly suggests that Phlda1 mediates and positively regulates both autophagy and apoptosis pathways.
  9. Moad AI, Tan ML, Kaur G, Mabruk M
    Asian Pac. J. Cancer Prev., 2012;13(12):6239-44.
    PMID: 23464438
    BACKGROUND: The basal cell carcinoma (BCC) is the most common non-melanoma skin cancer (NMSK). BCC might develop because of the faulty cell cycle arrest. P15INK4b is a tumor suppressor gene, involved in cell cycle arrest and inactivated in most human cancers. The role of p15INK4b protein expression in the genesis of BCC is as yet unknown. In a previous study we showed the absence of p15INK4b expression in the majority of tissue microarray cores of cutaneous squamous cell carcinoma (SCCs), another type of non-melanoma skin cancer, indicating that p15INK4b could possibly be involved in the pathogenesis of cutaneous SCC. The aim of this study was to investigate p15INK4b protein expression in BCCs.

    MATERIALS AND METHOD: Protein expression of p15INK4b in 35 cases of BCC tissue arrays and 19 cases of normal human skin tissue was studied using an immunohistochemical approach.

    RESULTS: The expression of p15INK4b was not significantly different in the BCC cases as compared with normal human skin (p=0.356; p>0.05). In addition, there were no significant relationship between clinicopathologic variables of patients (age and sex) and p15INK4b protein expression.

    CONCLUSIONS: Our finding may indicate that p15INK4b protein expression does not play a role in the genesis of BCC.

  10. Tan ML, Muhammad TS, Najimudin N, Sulaiman SF
    J Ethnopharmacol, 2005 Jan 15;96(3):375-83.
    PMID: 15619555
    Epipremnum pinnatum (L.) Engl. hexane extract produced a significant growth inhibition against T-47D breast carcinoma cells and analysis of cell death mechanisms indicated that the extract elicited a non-apoptotic programmed cell death. T-47D cells exposed to the extract at EC(50) concentration (72 h) for 24 h failed to demonstrate typical DNA fragmentation associated with apoptosis, as carried out using a modified TUNEL assay. In addition, acute exposure to the extract produced an insignificant regulation of caspase-3 and p53 mRNA expression but increased in the c-myc mRNA expression. Ultrastructural analysis using transmission electron microscope demonstrated distinct vacuolated cells, which strongly indicated a Type II non-apoptotic cell death although the changes in chromatin were also detected. The presence of non-apoptotic programmed cell death was then reconfirmed with annexin-V and propidium iodide staining. These findings suggested that up-regulation of c-myc mRNA expression may have contributed to the growth arrest and Type II non-apoptotic programmed cell death in the Epipremnum pinnatum (L.) Engl. hexane extract-treated T-47D cells.
  11. Ooi KL, Muhammad TS, Tan ML, Sulaiman SF
    J Ethnopharmacol, 2011 Jun 1;135(3):685-95.
    PMID: 21497647 DOI: 10.1016/j.jep.2011.04.001
    The decoction of the whole plant of Elephantopus mollis Kunth. is traditionally consumed to treat various free radical-mediated diseases including cancer and diabetes.
  12. Brindha K, Paul R, Walter J, Tan ML, Singh MK
    PMID: 32601907 DOI: 10.1007/s10653-020-00637-9
    Monitoring the groundwater chemical composition and identifying the presence of pollutants is an integral part of any comprehensive groundwater management strategy. The present study was conducted in a part of West Tripura, northeast India, to investigate the presence and sources of trace metals in groundwater and the risk to human health due to direct ingestion of groundwater. Samples were collected from 68 locations twice a year from 2016 to 2018. Mixed Ca-Mg-HCO3, Ca-Cl and Ca-Mg-Cl were the main groundwater types. Hydrogeochemical methods showed groundwater mineralization due to (1) carbonate dissolution, (2) silicate weathering, (3) cation exchange processes and (4) anthropogenic sources. Occurrence of faecal coliforms increased in groundwater after monsoons. Nitrate and microbial contamination from wastewater infiltration were apparent. Iron, manganese, lead, cadmium and arsenic were above the drinking water limits prescribed by the Bureau of Indian Standards. Water quality index indicated 1.5% had poor, 8.7% had marginal, 16.2% had fair, 66.2% had good and 7.4% had excellent water quality. Correlation and principal component analysis reiterated the sources of major ions and trace metals identified from hydrogeochemical methods. Human exposure assessment suggests health risk due to high iron in groundwater. The presence of unsafe levels of trace metals in groundwater requires proper treatment measures before domestic use.
  13. Tan HK, Tengku Muhammad TS, Tan ML
    Data Brief, 2016 Jun;7:1506-10.
    PMID: 27182548 DOI: 10.1016/j.dib.2016.04.046
    The data presented in this article are related to the research article entitled "14-deoxy-11,12-didehydroandrographolide induces DDIT3-dependent endoplasmic reticulum stress-mediated autophagy in T-47D breast carcinoma cells", which the mechanistic toxicology properties of 14-deoxy-11,12-didehydroandrographolide (14-DDA) were investigated (Tan et al., 2016 [1]). This article describes the derivation of cytotoxic parameters of 14-DDA, cell viability data after double transfection and DDIT3 silencing in T-47D cells.
  14. Ooi KL, Loh SI, Tan ML, Muhammad TS, Sulaiman SF
    J Ethnopharmacol, 2015 Mar 13;162:55-60.
    PMID: 25554642 DOI: 10.1016/j.jep.2014.12.030
    The juice of the entire fresh herb and infusion of dried sample of Murdannia bracteata are consumed to treat liver cancer and diabetes in Malaysia. However, no scientific evidence of these bioactivities has been reported.
  15. Say YH, Ban ZL, Arumugam Y, Kaur T, Tan ML, Chia PP, et al.
    J. Biosci., 2014 Dec;39(5):867-75.
    PMID: 25431415
    This study investigated the association of Uncoupling Protein 2 gene (UCP2) 45-bp I/D polymorphism with obesity and adiposity in 926 Malaysian subjects (416 males;265 obese; 102/672/152 Malays/Chinese/Indians). The overall minor allele frequency (MAF) was 0.14, while MAFs according to Malay/Chinese/Indian were 0.17/0.12/0.21. The polymorphism was associated with ethnicity, obesity and overall adiposity (total body fat percentage, TBF), but not gender and central adiposity (waist-hip ratio, WHR). Gender- and ethnicity-stratified analysis revealed that within males, the polymorphism was not associated with ethnicity and anthropometric classes. However, within females, significantly more Indians, obese and those with high TBF carried I allele. Logistic regression analysis among females further showed the polymorphism was associated with obesity and overall adiposity; however, when adjusted for age and ethnicity, this association was abolished for obesity but remained significant for overall adiposity [Odds Ratio (OR) for ID genotype = 2.02 (CI=1.18, 3.45; p=0.01); I allele =1.81 (CI=1.15, 2.84; p=0.01)]. Indeed, covariate analysis controlling for age and ethnicity also showed that those carrying ID genotype or I allele had significantly higher TBF than the rest. In conclusion, UCP2 45-bp I/D polymorphism is associated with overall adiposity among Malaysian women.
  16. Lu J, Wei H, Wu J, Jamil MF, Tan ML, Adenan MI, et al.
    PLoS One, 2014;9(12):e115648.
    PMID: 25535742 DOI: 10.1371/journal.pone.0115648
    INTRODUCTION: Mitragynine is a major bioactive compound of Kratom, which is derived from the leave extracts of Mitragyna speciosa Korth or Mitragyna speciosa (M. speciosa), a medicinal plant from South East Asia used legally in many countries as stimulant with opioid-like effects for the treatment of chronic pain and opioid-withdrawal symptoms. Fatal incidents with Mitragynine have been associated with cardiac arrest. In this study, we determined the cardiotoxicity of Mitragynine and other chemical constituents isolated using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).

    METHODS AND RESULTS: The rapid delayed rectifier potassium current (IKr), L-type Ca2+ current (ICa,L) and action potential duration (APD) were measured by whole cell patch-clamp. The expression of KCNH2 and cytotoxicity was determined by real-time PCR and Caspase activity measurements. After significant IKr suppression by Mitragynine (10 µM) was confirmed in hERG-HEK cells, we systematically examined the effects of Mitragynine and other chemical constituents in hiPSC-CMs. Mitragynine, Paynantheine, Speciogynine and Speciociliatine, dosage-dependently (0.1∼100 µM) suppressed IKr in hiPSC-CMs by 67%∼84% with IC50 ranged from 0.91 to 2.47 µM. Moreover, Mitragynine (10 µM) significantly prolonged APD at 50 and 90% repolarization (APD50 and APD90) (439.0±11.6 vs. 585.2±45.5 ms and 536.0±22.6 vs. 705.9±46.1 ms, respectively) and induced arrhythmia, without altering the L-type Ca2+ current. Neither the expression, and intracellular distribution of KCNH2/Kv11.1, nor the Caspase 3 activity were significantly affected by Mitragynine.

    CONCLUSIONS: Our study indicates that Mitragynine and its analogues may potentiate Torsade de Pointes through inhibition of IKr in human cardiomyocytes.

  17. Koe XF, Tengku Muhammad TS, Chong AS, Wahab HA, Tan ML
    Food science & nutrition, 2014 Sep;2(5):500-20.
    PMID: 25473508 DOI: 10.1002/fsn3.122
    A multiplex RT-qPCR was developed to examine CYP1A2, CYP2D6, and CYP3A4 induction properties of compounds from food and herbal sources. The induction of drug metabolizing enzymes is an important pharmacokinetic interaction with unique features in comparison with inhibition of metabolizing enzymes. Cytochrome induction can lead to serious drug-drug or drug-food interactions, especially if the coadministered drug plasma level is critical as it can reduce therapeutic effects and cause complications. Using this optimized multiplex RT-qPCR, cytochrome induction properties of andrographolide, curcumin, lycopene, bergamottin, and resveratrol were determined. Andrographolide, curcumin, and lycopene produced no significant induction effects on CYP1A2, CYP2D6, and CYP3A4. However, bergamottin appeared to be a significant in vitro CYP1A2 inducer starting from 5 to 50 μmol/L with induction ranging from 60 to 100-fold changes. On the other hand, resveratrol is a weak in vitro CYP1A2 inducer. Examining the cytochrome induction properties of food and herbal compounds help complement CYP inhibition studies and provide labeling and safety caution for such products.
  18. Pourasl AH, Ahmadi MT, Rahmani M, Chin HC, Lim CS, Ismail R, et al.
    Nanoscale Res Lett, 2014 Jan 15;9(1):33.
    PMID: 24428818 DOI: 10.1186/1556-276X-9-33
    In recent years, carbon nanotubes have received widespread attention as promising carbon-based nanoelectronic devices. Due to their exceptional physical, chemical, and electrical properties, namely a high surface-to-volume ratio, their enhanced electron transfer properties, and their high thermal conductivity, carbon nanotubes can be used effectively as electrochemical sensors. The integration of carbon nanotubes with a functional group provides a good and solid support for the immobilization of enzymes. The determination of glucose levels using biosensors, particularly in the medical diagnostics and food industries, is gaining mass appeal. Glucose biosensors detect the glucose molecule by catalyzing glucose to gluconic acid and hydrogen peroxide in the presence of oxygen. This action provides high accuracy and a quick detection rate. In this paper, a single-wall carbon nanotube field-effect transistor biosensor for glucose detection is analytically modeled. In the proposed model, the glucose concentration is presented as a function of gate voltage. Subsequently, the proposed model is compared with existing experimental data. A good consensus between the model and the experimental data is reported. The simulated data demonstrate that the analytical model can be employed with an electrochemical glucose sensor to predict the behavior of the sensing mechanism in biosensors.
  19. Hariono M, Wahab HA, Tan ML, Rosli MM, Razak IA
    PMID: 24764997 DOI: 10.1107/S1600536814001986
    In the title compound, C19H17N5S, the dihedral angles between the purine ring system (r.m.s. deviation = 0.009 Å) and the S-bound and methyl-ene-bound phenyl rings are 74.67 (8) and 71.28 (7)°, respectively. In the crystal, inversion dimers linked by pairs of N-H⋯N hydrogen bonds generate R 2 (2)(8) loops. C-H⋯N inter-actions link the dimers into (100) sheets.
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