Displaying publications 1 - 20 of 76 in total

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  1. Pollutant source, ecological and human health risks assessment of heavy metals in soils from coal mining areas in Xinjiang, China
    Zhang H, Zhang F, Song J, Tan ML, Kung HT, Johnson VC
    Environ Res, 2021 11;202:111702.
    PMID: 34284019 DOI: 10.1016/j.envres.2021.111702
    This study aims to analyze the pollution characteristics and sources of heavy metal elements for the first time in the Zhundong mining area in Xinjiang using the linear regression model. Additionaly, the health risks with their probability and infleuencing factors on different groups of people's were also evaluated using Monte Carlo (MC) simulation approach. The results shows that 89.28% of Hg was from coal combustion, 40.28% of Pb was from transportation, and 19.54% of As was from atmospheric dust. The main source of Cu and Cr was coal dust, Hg has the greatest impact on potential ecological risks. which accounted for 60.2% and 81.46% of the Cu and Cr content in soil, respectively. The all samples taken from Pb have been Extremely polluted (100%). 93.3% samples taken from As have been Extremely polluted. The overall potential ecological risk was moderate. Adults experienced higher non-carcinogenic risks of heavy metals from their diets than children. Interestingly, body weight was the main factor affecting the adult's health risks. This research provides more comprehensive information for better soil management, soil remediation, and soil pollution control in the Xinjiang mining areas.
  2. No association between peroxisome proliferator-activated receptor and uncoupling protein gene polymorphisms and obesity in Malaysian university students
    Yiew SK, Khor LY, Tan ML, Pang CL, Chai VY, Kanachamy SS, et al.
    Obes Res Clin Pract, 2010 Oct-Dec;4(4):e247-342.
    PMID: 24345699 DOI: 10.1016/j.orcp.2010.03.002
    Peroxisome proliferator-activated receptors (PPARs) and uncoupling proteins (UCPs) are expressed in adipose tissue, where PPARs are nuclear receptors that function as transcription regulators of the expression of UCPs, mitochondria proteins which uncouple protons in exchange of heat released. The PPARα L162V; PPARγ2 C161T; UCP1 -3826A/G; UCP2 45 bp Ins/Del and -866G/A; and UCP3 -55C/T gene polymorphisms have been previously associated with obesity in different populations, but with inconclusive findings. This study was to investigate the prevalence of these gene polymorphisms and their possible association with obesity in a cohort of Malaysian university students in Kuala Lumpur. Random convenience sampling was performed with informed consents and anthropometric measurements were taken. Mouthwash samples were obtained for genomic DNA extraction and genotyping was performed using Polymerase Chain Reaction - Restriction Fragment Length Polymorphism. Out of the 256 subjects (140 males and 116 females), 170 were lean and 86 were overweight/obese. The mutated PPARα L162V; PPARγ2 C161T; UCP1 -3826A/G; UCP2 45 bp Ins/Del and -866G/A; and UCP3 -55C/T allele frequencies were 0.006, 0.36, 0.58, 0.12, 0.56 and 0.34, respectively. This study failed to find significant differences in the anthropometric indicators of obesity (Body Mass Index, Waist-Hip Ratio and Total Body Fat) between the genotypes of all the PPAR and UCP gene variants. Overall, the genotype and allele distributions were also not significantly different between genders and BMI status. In conclusion, overweight/obesity is not prevalent among the Malaysian university students and the PPAR and UCP gene polymorphisms are not associated with obesity.:
  3. Chronic obstructive pulmonary disease and emerging ER stress-related therapeutic targets
    Yeap JW, Ali IAH, Ibrahim B, Tan ML
    Pulm Pharmacol Ther, 2023 Aug;81:102218.
    PMID: 37201652 DOI: 10.1016/j.pupt.2023.102218
    COPD pathogenesis is frequently associated with endoplasmic reticulum stress (ER stress) progression. Targeting the major unfolded protein response (UPR) branches in the ER stress pathway may provide pharmacotherapeutic selection strategies for treating COPD and enable relief from its symptoms. In this study, we aimed to systematically review the potential role of the ER stress inhibitors of major UPR branches (IRE1, PERK, and ATF6) in COPD-related studies and determine the current stage of knowledge in this field. The systematic review was carried out adhering to the PRISMA checklist based on published studies obtained from specific keyword searches of three databases, namely PubMed, ScienceDirect and Springer Database. The search was limited to the year 2000-2022 which includes all in vitro studies, in vivo studies and clinical trials related to the application of ER stress inhibitors toward COPD-induced models and disease. The risk of bias was evaluated using the QUIN, SYRCLE, revised Cochrane risk of bias tool for randomized trials (RoB 2.0) and NIH tool respectively. A total of 7828 articles were screened from three databases and a final total of 37 studies were included in the review. The ER stress and UPR pathways are potentially useful to prevent COPD progression and attenuate the exacerbation of COPD and related symptoms. Interestingly, the off-target effects from inhibition of the UPR pathway may be desirable or undesirable depending on context and therapeutic applications. Targeting the UPR pathway could have complex consequences as the production of ER molecules involved in folding may be impaired which could continuously provoke misfolding of proteins. Although several emerging compounds were noted to be potentially useful for targeted therapy against COPD, clinical studies have yet to be thoroughly explored.
  4. Coupling SWAT and Bi-LSTM for improving daily-scale hydro-climatic simulation and climate change impact assessment in a tropical river basin
    Yang S, Tan ML, Song Q, He J, Yao N, Li X, et al.
    J Environ Manage, 2023 Mar 15;330:117244.
    PMID: 36621311 DOI: 10.1016/j.jenvman.2023.117244
    Global climate change has led to an increase in both the frequency and magnitude of extreme events around the world, the risk of which is especially imminent in tropical regions. Developing hydrological models with better capabilities to simulate streamflow, especially peak flow, is urgently needed to facilitate water resource planning and management as well as climate change mitigation efforts in the tropics. In view of the need, this paper explores the feasibility of improving streamflow simulation performance in the tropical Kelantan River Basin (KRB) of Peninsular Malaysia through coupling a conceptual process-based hydrological model - Soil and Water Assessment Tool (SWAT) with a deep learning model - Bidirectional Long Short-Term Memory (Bi-LSTM) in two ways. All SWAT parameters were set as their default values in one hybrid model (SWAT-D-LSTM), whereas three most sensitive SWAT parameters were calibrated in the other hybrid model (SWAT-T-LSTM). Comparison of daily streamflow simulation results have shown that SWAT-T-LSTM consistently performs better than SWAT-D-LSTM as well as the stand-alone SWAT and Bi-LSTM model throughout the simulation period. Particularly, SWAT-T-LSTM performs considerably better than the other three models in simulating daily peak flow. Based on the latest projection results of five GCMs from the Sixth Phase of the Coupled Model Intercomparison Project (CMIP6) under three emission scenarios (SSP1-2.6, SSP2-4.5, SSP5-8.5), the best-performed SWAT-T-LSTM was run to assess the potential impacts of climate change on streamflow in the KRB. Ensemble assessment results have concluded that both average and extreme streamflow is much likely to increase considerably in the already wet northeast monsoon season from November to January, which has surely raised the alarm for more frequent flood occurrence in the KRB.
  5. Fulltext Kratom use disorder and unfolded protein response: Evaluating their relationship in a case control study
    Yang B, Tan ML, Zhang R, Singh D, Leong Bin Abdullah MFI
    PLoS One, 2023;18(6):e0287466.
    PMID: 37352311 DOI: 10.1371/journal.pone.0287466
    BACKGROUND AND AIMS: Kratom (Mitragyna speciosa Korth.) is widely use worldwide despite its addictive potential. Although psychostimulant use has been linked to occurrence of endoplasmic reticulum (ER) stress, data is lacking on how regular kratom use affects ER stress. This case-control study first determined differences in ER stress sensor protein expression (BiP, sXBP1, ATF4, CHOP, JNK, and p-JNK) between regular kratom users and healthy controls. Second, it evaluated the association between kratom use characteristics, targeted ER stress sensor protein expression, and "kratom use disorder" diagnosed with Diagnostic and Statistical Manual for Mental Disorders 5th Edition (DSM-5) among regular kratom users.

    METHODS: In total, 60 regular kratom users and 50 healthy control-group participants were recruited and administered a sociodemographic and clinical characteristics questionnaire. While participants who used kratom were also administered a kratom use characteristics questionnaire. Blood samples were collected from all participants, and targeted ER stress sensor protein expression was determined via Western blot analysis.

    RESULTS: The study's findings revealed first that kratom users registered significantly higher protein expression in all targeted ER stress sensors compared to the control group. Second, higher protein expression of CHOP (B = 5.061, standard error [SE] = 2.547, Wald = 3.948, adjusted odds ratio [AOR] = 5.382, 95% confidence interval [CI] = 1.071 to 9.656, p = 0.047) and p-JNK (B = 5.795, SE = 2.635, Wald = 4.544, AOR = 17.025, 95% CI = 1.395 to 24.123, p = 0.017) increased the odds of kratom use disorder occurrence. Kratom use characteristics and other ER stress sensor protein expression were not associated with kratom use disorder.

    CONCLUSION: Regular kratom use may induce protracted ER stress, leading to the decompensation of the unfolded protein response to maintain ER homeostasis. This effect may be linked to kratom use disorder occurrence.

  6. Spatial-temporal pattern of change in production-living-ecological space of Nanchong City from 2000 to 2020 and underlying factors
    Xu H, Zhang F, Li W, Shi J, Johnson BA, Tan ML
    Environ Monit Assess, 2023 Dec 27;196(1):94.
    PMID: 38150164 DOI: 10.1007/s10661-023-12249-8
    This study analyzed the spatial-temporal change pattern and underlying factors in production-living-ecological space (PLES) of Nanchong City, China, over the past 20 years using historical land use data (2000, 2010, 2020). A land use transfer matrix was calculated from the historical land use maps, and spatial analysis was conducted to analyze changes in the land use dynamics degree, standard deviation ellipse, and center of gravity. The results showed that there was a rapid spatial evolution of the PLES in Nanchong from 2000 to 2010, followed by a stabilization in the second decade. The transfer of ecological-production space occurred mainly in the Jialing and Yilong River basins, while the reduction of production space and the increase of living space were most prominent in the intersection of three districts (Shunqing, Jialing, and Gaoping districts). The return of production-ecological space was observed in the south and northeast of Yingshan, and there was little notable transfer of other types. The distribution of production space in Nanchong evolved in a north-south to east-west trend, with the center of gravity moving from Yilong to Peng'an County. The living space and production space expanded in a north-south direction, and the center of gravity position was in Nanbu, indicating a more balanced growth or decrease in the last 20 years. The changes in the spatial-temporal pattern of PLES in Nanchong were attributed to the intertwined factors of national policies, economic development, population growth, and the natural environment. This study introduced a novel approach towards rational planning of land resources in Nanchong, which may facilitate more sustainable urban planning and development.
  7. Fulltext Vitamin D deficiency during pregnancy and its associated factors among third trimester Malaysian pregnant women
    Woon FC, Chin YS, Ismail IH, Batterham M, Abdul Latiff AH, Gan WY, et al.
    PLoS One, 2019;14(6):e0216439.
    PMID: 31233513 DOI: 10.1371/journal.pone.0216439
    BACKGROUND: Despite perennial sunshine, vitamin D deficiency is prevalent among Malaysians especially pregnant women. This study determines the vitamin D status and its associated factors among third trimester pregnant women attending government health clinics in Selangor and Kuala Lumpur, Malaysia.

    METHODS: Information on socio-demographic characteristics, obstetrical history, and sun exposure were obtained through face-to-face interviews. Vitamin D intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). Serum 25-hydroxyvitamin D concentration was measured and classified as deficient (< 30 nmol/L), insufficient (30-50 nmol/L), and sufficient (≥ 50 nmol/L).

    RESULTS: Of the 535 pregnant women recruited, 42.6% were vitamin D deficient. They consumed an average of 8.7 ± 6.7 μg of vitamin D daily. A total of 80.4% of the vitamin D were obtained from the food sources, while 19.6% were from dietary supplements. Fish and fish products showed the highest contribution to vitamin D intake (35.8%). The multivariable generalized linear mixed models, with clinic as a random effect, indicates that higher intake of vitamin D is associated with lower odds of vitamin D deficiency among pregnant women (OR = 0.96; 95% CI = 0.93-0.99). The odds of having vitamin D deficiency was reduced by 87% in non-Malays (OR = 0.14; 95% CI = 0.05-0.41) compared to Malays. No associations were found between age, educational level, monthly household income, work status, gravidity, parity, pre-pregnancy body mass index, total hours of sun exposure, total percentage of body surface area, and sun exposure index per day with vitamin D deficiency.

    CONCLUSION: Vitamin D deficiency is prevalent among Malaysian pregnant women. Considering the possible adverse obstetric and fetal outcomes of vitamin D deficiency during pregnancy, future nutrition education should emphasise on vitamin D-fortified foods consumption among pregnant women by taking into consideration ethnic differences.
  8. Determining the main contributing factors to nutrient concentration in rivers in arid northwest China using partial least squares structural equation modeling
    Wang W, Zhang F, Zhao Q, Liu C, Jim CY, Johnson VC, et al.
    J Environ Manage, 2023 Oct 01;343:118249.
    PMID: 37245314 DOI: 10.1016/j.jenvman.2023.118249
    Understanding the main driving factors of oasis river nutrients in arid areas is important to identify the sources of water pollution and protect water resources. Twenty-seven sub-watersheds were selected in the lower oasis irrigated agricultural reaches of the Kaidu River watershed in arid Northwest China, divided into the site, riparian, and catchment buffer zones. Data on four sets of explanatory variables (topographic, soil, meteorological elements, and land use types) were collected. The relationships between explanatory variables and response variables (total phosphorus, TP and total nitrogen, TN) were analyzed by redundancy analysis (RDA). Partial least squares structural equation modeling (PLS-SEM) was used to quantify the relationship between explanatory as well as response variables and fit the path relationship among factors. The results showed that there were significant differences in the TP and TN concentrations at each sampling point. The catchment buffer exhibited the best explanatory power of the relationship between explanatory and response variables based on PLS-SEM. The effects of various land use types, meteorological elements (ME), soil, and topography in the catchment buffer were responsible for 54.3% of TP changes and for 68.5% of TN changes. Land use types, ME and soil were the main factors driving TP and TN changes, accounting for 95.56% and 94.84% of the total effects, respectively. The study provides a reference for river nutrients management in arid oases with irrigated agriculture and a scientific and targeted basis to mitigate water pollution and eutrophication of rivers in arid lands.
  9. Functionalization of remote sensing and on-site data for simulating surface water dissolved oxygen: Development of hybrid tree-based artificial intelligence models
    Tiyasha T, Tung TM, Bhagat SK, Tan ML, Jawad AH, Mohtar WHMW, et al.
    Mar Pollut Bull, 2021 Sep;170:112639.
    PMID: 34273614 DOI: 10.1016/j.marpolbul.2021.112639
    Dissolved oxygen (DO) is an important indicator of river health for environmental engineers and ecological scientists to understand the state of river health. This study aims to evaluate the reliability of four feature selector algorithms i.e., Boruta, genetic algorithm (GA), multivariate adaptive regression splines (MARS), and extreme gradient boosting (XGBoost) to select the best suited predictor of the applied water quality (WQ) parameters; and compare four tree-based predictive models, namely, random forest (RF), conditional random forests (cForest), RANdom forest GEneRator (Ranger), and XGBoost to predict the changes of dissolved oxygen (DO) in the Klang River, Malaysia. The total features including 15 WQ parameters from monitoring site data and 7 hydrological components from remote sensing data. All predictive models performed well as per the features selected by the algorithms XGBoost and MARS in terms applied statistical evaluators. Besides, the best performance noted in case of XGBoost predictive model among all applied predictive models when the feature selected by MARS and XGBoost algorithms, with the coefficient of determination (R2) values of 0.84 and 0.85, respectively, nonetheless the marginal performance came up by Boruta-XGBoost model on in this scenario.
  10. The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr) and human ether-a-go-go-related gene (hERG) expression
    Teah YF, Abduraman MA, Amanah A, Adenan MI, Sulaiman SF, Tan ML
    Food Chem Toxicol, 2017 Sep;107(Pt A):293-301.
    PMID: 28689918 DOI: 10.1016/j.fct.2017.07.011
    Elephantopus scaber Linn and its major bioactive component, deoxyelephantopin are known for their medicinal properties and are often reported to have various cytotoxic and antitumor activities. This plant is widely used as folk medicine for a plethora of indications although its safety profile remains unknown. Human ether-a-go-go-related gene (hERG) encodes the cardiac IKr current which is a determinant of the duration of ventricular action potentials and QT interval. The hERG potassium channel is an important antitarget in cardiotoxicity evaluation. This study investigated the effects of deoxyelephantopin on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells. The hERG tail currents following depolarization pulses were insignificantly affected by deoxyelephantopin in the transfected cell line. Current reduction was less than 40% as compared with baseline at the highest concentration of 50 μM. The results were consistent with the molecular docking simulation and hERG surface protein expression. Interestingly, it does not affect the hERG expression at both transcriptional and translational level at most concentrations, although higher concentration at 10 μM caused protein accumulation. In conclusion, deoxyelephantopin is unlikely a clinically significant hERG channel and Ikr blocker.
  11. Fulltext Data on the construction of a recombinant HEK293 cell line overexpressing hERG potassium channel and examining the presence of hERG mRNA and protein expression
    Teah YF, Abduraman MA, Amanah A, Adenan MI, Fariza Sulaiman S, Tan ML
    Data Brief, 2017 Oct;14:584-591.
    PMID: 28879216 DOI: 10.1016/j.dib.2017.08.008
    The data presented in this article are related to the research article entitled "The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr) and human ether-a-go-go-related gene (hERG) expression" (Y.F. Teah, M.A. Abduraman, A. Amanah, M.I. Adenan, S.F. Sulaiman, M.L. Tan) [1], which the possible hERG blocking properties of deoxyelephantopin were investigated. This article describes the construction of human embryonic kidney 293 (HEK293) cells overexpressing HERG potassium channel and verification of the presence of hERG mRNA and protein expression in this recombinant cell line.
  12. Mitragynine and its potential blocking effects on specific cardiac potassium channels
    Tay YL, Teah YF, Chong YM, Jamil MFA, Kollert S, Adenan MI, et al.
    Toxicol Appl Pharmacol, 2016 08 15;305:22-39.
    PMID: 27260674 DOI: 10.1016/j.taap.2016.05.022
    Mitragyna speciosa Korth is known for its euphoric properties and is frequently used for recreational purposes. Several poisoning and fatal cases involving mitragynine have been reported but the underlying causes remain unclear. Human ether-a-go-go-related gene (hERG) encodes the cardiac IKr current which is a determinant of the duration of ventricular action potentials and QT interval. On the other hand, IK1, a Kir current mediated by Kir2.1 channel and IKACh, a receptor-activated Kir current mediated by GIRK channel are also known to be important in maintaining the cardiac function. This study investigated the effects of mitragynine on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells and Xenopus oocytes. The effects on Kir2.1 and GIRK channels currents were also determined in the oocytes. The hERG tail currents following depolarization pulses were inhibited by mitragynine with an IC50 value of 1.62μM and 1.15μM in the transfected cell line and Xenopus oocytes, respectively. The S6 point mutations of Y652A and F656A attenuated the inhibitor effects of mitragynine, indicating that mitragynine interacts with these high affinity drug-binding sites in the hERG channel pore cavity which was consistent with the molecular docking simulation. Interestingly, mitragynine does not affect the hERG expression at the transcriptional level but inhibits the protein expression. Mitragynine is also found to inhibit IKACh current with an IC50 value of 3.32μM but has no significant effects on IK1. Blocking of both hERG and GIRK channels may cause additive cardiotoxicity risks.
  13. Fulltext Mitragynine, an euphoric compound inhibits hERG1a/1b channel current and upregulates the complexation of hERG1a-Hsp90 in HEK293-hERG1a/1b cells
    Tay YL, Amanah A, Adenan MI, Wahab HA, Tan ML
    Sci Rep, 2019 12 24;9(1):19757.
    PMID: 31874991 DOI: 10.1038/s41598-019-56106-6
    Mitragyna speciosa Korth (M. speciosa) has been widely used as a recreational product, however, there are growing concerns on the abuse potentials and toxicity of the plant. Several poisoning and fatal cases involving kratom and mitragynine have been reported but the underlying causes remain unclear. The human ether-a-go-go-related gene 1 (hERG1) encodes the pore-forming subunit underlying cardiac rapidly delayed rectifier potassium current (IKr). Pharmacological blockade of the IKr can cause acquired long QT syndrome, leading to lethal cardiac arrhythmias. This study aims to elucidate the mechanisms of mitragynine-induced inhibition on hERG1a/1b current. Electrophysiology experiments were carried out using Port-a-Patch system. Quantitative RT-PCR, Western blot analysis, immunofluorescence and co-immunoprecipitation methods were used to determine the effects of mitragynine on hERG1a/1b expression and hERG1-cytosolic chaperones interaction. Mitragynine was found to inhibit the IKr current with an IC50 value of 332.70 nM. It causes a significant reduction of the fully-glycosylated (fg) hERG1a protein expression but upregulates both core-glycosylated (cg) expression and hERG1a-Hsp90 complexes, suggesting possible impaired hERG1a trafficking. In conclusion, mitragynine inhibits hERG1a/1b current through direct channel blockade at lower concentration, but at higher concentration, it upregulates the complexation of hERG1a-Hsp90 which may be inhibitory towards channel trafficking.
  14. Megacities' environmental assessment for Iraq region using satellite image and geo-spatial tools
    Tao H, Hashim BM, Heddam S, Goliatt L, Tan ML, Sa'adi Z, et al.
    Environ Sci Pollut Res Int, 2023 Mar;30(11):30984-31034.
    PMID: 36441299 DOI: 10.1007/s11356-022-24153-8
    Urban areas are quickly established, and the overwhelming population pressure is triggering heat stress in the metropolitan cities. Climate change impact is the key aspect for maintaining the urban areas and building proper urban planning because spreading of the urban area destroyed the vegetated land and increased heat variation. Remote sensing-based on Landsat images are used for investigating the vegetation circumstances, thermal variation, urban expansion, and surface urban heat island or SUHI in the three megacities of Iraq like Baghdad, Erbil, and Basrah. Four satellite imageries are used aimed at land use and land cover (LULC) study from 1990 to 2020, which indicate the land transformation of those three major cities in Iraq. The average annually temperature is increased during  30 years like Baghdad (0.16 °C), Basrah (0.44 °C), and Erbil (0.32 °C). The built-up area is increased 147.1 km2 (Erbil), 217.86 km2 (Baghdad), and 294.43 km2 (Erbil), which indicated the SUHI affects the entire area of the three cities. The bare land is increased in Baghdad city, which indicated the local climatic condition and affected the livelihood. Basrah City is affected by anthropogenic activities and most areas of Basrah were converted into built-up land in the last 30 years. In Erbil, agricultural land (295.81 km2) is increased. The SUHI study results indicated the climate change effect in those three cities in Iraq. This study's results are more useful for planning, management, and sustainable development of urban areas.
  15. The effects of Andrographis paniculata (Burm.f.) Nees extract and diterpenoids on the CYP450 isoforms' activities, a review of possible herb-drug interaction risks
    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.
  16. Device and circuit-level performance of carbon nanotube field-effect transistor with benchmarking against a nano-MOSFET
    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.
  17. Growth arrest and non-apoptotic programmed cell death associated with the up-regulation of c-myc mRNA expression in T-47D breast tumor cells following exposure to Epipremnum pinnatum (L.) Engl. hexane extract
    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.
  18. Methanolic extract of Pereskia bleo (Kunth) DC. (Cactaceae) induces apoptosis in breast carcinoma, T47-D cell line
    Tan ML, Sulaiman SF, Najimuddin N, Samian MR, Muhammad TS
    J Ethnopharmacol, 2005 Jan 4;96(1-2):287-94.
    PMID: 15588681
    Currently, breast cancer is the leading cause of cancer-related death in women. Therefore, there is an urgent need to develop alternative therapeutic measures against this deadly disease. Here, we report the cytotoxicity activity and the mechanism of cell death exhibited by the methanol extract prepared from Pereskia bleo (Kunth) DC. (Cactaceae) plant against human breast carcinoma cell line, T-47D. In vitro cytotoxicity screening of methanol extract of Pereskia bleo plant indicated the presence of cytotoxicity activity of the extract against T-47D cells with EC50 of 2.0 microg/ml. T-47D cell death elicited by the extract was found to be apoptotic in nature based a clear indication of DNA fragmentation which is a hallmark of apoptosis. In addition, ultrastructural analysis also revealed apoptotic characteristics (the presence of chromatin margination and apoptotic bodies) in the extract-treated cells. RT-PCR analysis showed the mRNA expression levels of c-myc, and caspase 3 were markedly increased in the cells treated with the plant extract. However, p53 expression was only slightly increased as compared to caspase 3 and c-myc. Thus, the results from this study strongly suggest that the methanol extract of Pereskia bleo may contain bioactive compound(s) that caused breast carcinoma, T-47D cell death by apoptosis mechanism via the activation of caspase-3 and c-myc pathways.
  19. Identification of genes involved in the regulation of 14-deoxy-11,12-didehydroandrographolide-induced toxicity in T-47D mammary cells
    Tan ML, Tan HK, Oon CE, Kuroyanagi M, Muhammad TS
    Food Chem Toxicol, 2012 Feb;50(2):431-44.
    PMID: 22101062 DOI: 10.1016/j.fct.2011.11.001
    14-Deoxy-11,12-didehydroandrographolide is one of the principle compounds of the medicinal plant, Andrographis paniculata Nees. This study explored the mechanisms of 14-deoxy-11,12-didehydroandrographolide-induced toxicity and non-apoptotic cell death in T-47D breast carcinoma cells. Gene expression analysis revealed that 14-deoxy-11,12-didehydroandrographolide exerted its cytotoxic effects by regulating genes that inhibit the cell cycle or promote cell cycle arrest. This compound regulated genes that are known to reduce/inhibit cell proliferation, induce growth arrest and suppress cell growth. The growth suppression activities of this compound were demonstrated by a downregulation of several genes normally found to be over-expressed in cancers. Microscopic analysis revealed positive monodansylcadaverine (MDC) staining at 8h, indicating possible autophagosomes. TEM analysis revealed that the treated cells were highly vacuolated, thereby suggesting that 14-deoxy-11,12-didehydroandrographolide may cause autophagic morphology in these cells. This morphology may be correlated with the concurrent expression of genes known to affect lysosomal activity, ion transport, protein degradation and vesicle transport. Interestingly, some apoptotic-like bodies were found, and these bodies contained multiple large vacuoles, suggesting that this compound is capable of eliciting a combination of apoptotic and autophagic-like morphological characteristics.
  20. Fulltext Beetroot as a Potential Functional Food for Cancer Chemoprevention, a Narrative Review
    Tan ML, Hamid SBS
    J Cancer Prev, 2021 Mar 30;26(1):1-17.
    PMID: 33842401 DOI: 10.15430/JCP.2021.26.1.1
    Patients with cancer are prone to several debilitating side effects including fatigue, insomnia, depression and cognitive disturbances. Beetroot (Beta vulgaris L.) as a health promoting functional food may be potentially beneficial in cancer. As a source of polyphenols, flavonoids, dietary nitrates and other useful nutrients, beetroot supplementation may provide a holistic means to prevent cancer and manage undesired effects associated with chemotherapy. The main aim of this narrative review is to discuss beetroot's nutrient composition, current studies on its potential utility in chemoprevention and cancer-related fatigue or treatment-related side effects such as cardiotoxicity. This review aims to provide the current status of knowledge and to identify the related research gaps in this area. The flavonoids and polyphenolic components present in abundance in beetroot support its significant antioxidant and anti-inflammatory capacities. Most in vitro and in vivo studies have shown promising results; however, the molecular mechanisms underlying chemopreventive and chemoprotective effects of beetroot have not been completely elucidated. Although recent clinical trials have shown that beetroot supplementation improves human performance, translational studies on beetroot and its functional benefits in managing fatigue or other symptoms in patients with cancer are still lacking.
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