Displaying publications 81 - 100 of 513 in total

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  1. Ahmad M
    Endod Dent Traumatol, 1990 Oct;6(5):230-1.
    PMID: 2133315
    The temperature rise of the irrigant in the root canal during free vibration of the ultrasonic file was studied in vitro in 10 human teeth. The mean temperature rise was found to be 0.6 degrees C. The minimal temperature increase may not significantly contribute to the effectiveness of ultrasonic root canal instrumentation.
  2. Adeel M, Lee JY, Zain M, Rizwan M, Nawab A, Ahmad MA, et al.
    Environ Int, 2019 06;127:785-800.
    PMID: 31039528 DOI: 10.1016/j.envint.2019.03.022
    BACKGROUND: Rare earth elements (REEs) are gaining attention due to rapid rise of modern industries and technological developments in their usage and residual fingerprinting. Cryptic entry of REEs in the natural resources and environment is significant; therefore, life on earth is prone to their nasty effects. Scientific sectors have expressed concerns over the entry of REEs into food chains, which ultimately influences their intake and metabolism in the living organisms.

    OBJECTIVES: Extensive scientific collections and intensive look in to the latest explorations agglomerated in this document aim to depict the distribution of REEs in soil, sediments, surface waters and groundwater possibly around the globe. Furthermore, it draws attention towards potential risks of intensive industrialization and modern agriculture to the exposure of REEs, and their effects on living organisms. It also draws links of REEs usage and their footprints in natural resources with the major food chains involving plants, animals and humans.

    METHODS: Scientific literature preferably spanning over the last five years was obtained online from the MEDLINE and other sources publishing the latest studies on REEs distribution, properties, usage, cycling and intrusion in the environment and food-chains. Distribution of REEs in agricultural soils, sediments, surface and ground water was drawn on the global map, together with transport pathways of REEs and their cycling in the natural resources.

    RESULTS: Fourteen REEs (Ce, Dy, Er, Eu, Gd, Ho, La, Lu, Nd, Pr, Sm, Tb, Th and Yb) were plighted in this study. Wide range of their concentrations has been detected in agricultural soils (<15.9-249.1 μg g-1) and in groundwater (<3.1-146.2 μg L-1) at various sites worldwide. They have strong tendency to accumulate in the human body, and thus associated with kidney stones. The REEs could also perturb the animal physiology, especially affecting the reproductive development in both terrestrial and aquatic animals. In plants, REEs might affect the germination, root and shoot development and flowering at concentration ranging from 0.4 to 150 mg kg-1.

    CONCLUSIONS: This review article precisely narrates the current status, sources, and potential effects of REEs on plants, animals, humans health. There are also a few examples where REEs have been used to benefit human health. However, still there is scarce information about threshold levels of REEs in the soil, aquatic, and terrestrial resources as well as living entities. Therefore, an aggressive effort is required for global action to generate more data on REEs. This implies we prescribe an urgent need for inter-disciplinary studies about REEs in order to identify their toxic effects on both ecosystems and organisms.

  3. Ashraf MA, Khan AM, Ahmad M, Akib S, Balkhair KS, Bakar NK
    Environ Geochem Health, 2014 12;36(6):1165-90.
    PMID: 24804829 DOI: 10.1007/s10653-014-9620-9
    Radionuclide contamination in terrestrial ecosystems has reached a dangerous level. The major artificial radionuclide present in the environment is (137)Cs, which is released as a result of weapon production related to atomic projects, accidental explosions of nuclear power plants and other sources, such as reactors, evaporation ponds, liquid storage tanks, and burial grounds. The release of potentially hazardous radionuclides (radiocesium) in recent years has provided the opportunity to conduct multidisciplinary studies on their fate and transport. Radiocesium's high fission yield and ease of detection made it a prime candidate for early radio-ecological investigations. The facility setting provides a diverse background for the improved understanding of various factors that contribute toward the fate and transfer of radionuclides in the terrestrial ecosystem. In this review, we summarize the significant environmental radiocesium transfer factors to determine the damaging effects of radiocesium on terrestrial ecosystem. It has been found that (137)Cs can trace the transport of other radionuclides that have a high affinity for binding to soil particles (silts and clays). Possible remedial methods are also discussed for contaminated terrestrial systems. This review will serve as a guideline for future studies of the fate and transport of (137)Cs in terrestrial environments in the wake of the Fukushima Nuclear Power Plant disaster in 2011.
  4. Munir M, Ahmad M, Rehan M, Saeed M, Lam SS, Nizami AS, et al.
    Environ Res, 2021 02;193:110398.
    PMID: 33127396 DOI: 10.1016/j.envres.2020.110398
    This study focused on producing high quality and yield of biodiesel from novel non-edible seed oil of abundantly available wild Raphnus raphanistrum L. using an efficient, recyclable and eco-friendly copper modified montmorillonite (MMT) clay catalyst. The maximum biodiesel yield of 83% was obtained by base catalyzed transesterification process under optimum operating conditions of methanol to oil ratio of 15:1, reaction temperature of 150 °C, reaction time of 5 h and catalyst loading of 3.5%. The synthesized catalyst and biodiesel were characterized for their structural features and chemical compositions using various state-of-the-art techniques, including x-ray diffraction, scanning electron microscopy, energy dispersive x-ray spectroscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance (1H, 13C) and gas chromatography-mass spectroscopy. The fuel properties of the biodiesel were estimated including kinematic viscosity (4.36 cSt), density (0.8312 kg/L), flash point (72 °C), acid value (0.172 mgKOH/g) and sulphur content (0.0002 wt.%). These properties were compared and found in good agreement with the International Biodiesel Standards of American (ASTM-951, 6751), European Committee (EN-14214) and China GB/T 20828 (2007). The catalyst was re-used in five consecutive transesterification reactions without losing much catalytic efficiency. Overall, non-edible Raphnus raphanistrum L.. seed oil and Cu doped MMT clay catalyst appeared to be highly active, stable, and cheap contenders for future biofuel industry. However, detailed life cycle assessment (LCA) studies of Raphnus raphanistrum L. seed oil biodiesel are highly recommended to assess the technical, ecological, social and economic challenges.
  5. Ahmad M, Muslija A, Satrovic E
    Environ Sci Pollut Res Int, 2021 May;28(18):22588-22601.
    PMID: 33420933 DOI: 10.1007/s11356-020-12276-9
    Since developing countries experience economic and environmental sustainability challenges, it is desirable digging into the linkages between economic and environmental parameters. The purpose of this work is to evaluate the existence of the environmental Kuznets curve (EKC) theory (i.e., the inverse U-shape connection between real GDP per capita and per capita carbon dioxide emissions) in the sample of 11 developing countries. By using balanced annual panel data in the period between 1992 and 2014 and two alternative estimation techniques, we explored the potential inverted U-shaped linkage between carbon dioxide emissions and real GDP per capita in the sample of interest. For analysis purposes, Pedroni and Westerlund co-integration techniques are employed. Then, fully modified ordinary least squares, pooled mean group methods are applied for long-run parameter estimations. And, the Dumitrescu-Hurlin causality approach is employed for causal directions. Firstly, this work's findings provide the supportive evidence to the inverse U-shaped linkage in the long-run, indicating that an increase in real GDP per capita and electricity consumption tends to mitigate long-run carbon dioxide emissions in the developing countries, for the whole sample. Secondly, the country-specific findings suggested the presence of EKC theory for Brazil, China, India, Malaysia, the Russian Federation, Thailand, and Turkey. It implicated that these countries are on the path of attaining environmental sustainability in the long-run. However, Mexico, Philippines, Indonesia, and South Africa failed to lend credence to the EKC theory. It manifested that these countries need to design strategies directed to reduce carbon dioxide emissions from economic activity and electricity generation through efficiency improvement or promotion of renewables. Finally, bidirectional causal links are observed among all the variables of interest. The findings suggest that country-specific targeted action plans should be implemented to ensure the environmental sustainability in the developing world.
  6. Ahmad M, Aziz ARA, Mazari SA, Baloch AG, Nizamuddin S
    Environ Sci Pollut Res Int, 2020 Jul;27(21):26239-26248.
    PMID: 32358758 DOI: 10.1007/s11356-020-08940-9
    Photo-Fenton oxidation is one of the most promising processes to remove recalcitrant contaminants from industrial wastewater. In this study, we developed a novel heterogeneous catalyst to enhance photo-Fenton oxidation. Multi-composition (Fe-Cu-Zn) on aluminosilicate zeolite (ZSM-5) was prepared using a chemical process. Subsequently, the synthesized catalyst was characterized by using X-ray diffraction (XRD), field emission scanning electron microscope (FESEM), high-resolution transmission electron microscopy (HRTEM), energy dispersive X-ray (spectroscopy) (EDX), and Brunauer-Emmett-Teller (BET). Activity of the synthesized catalyst is analysed to degrade an azo dye, methyl orange. Taguchi method is used to optimize color removal and total carbon content (TOC) removal. The dye completely degraded, and 76% of TOC removal was obtained at optimized process conditions. The amount of catalyst required for the desired degradation of dye significantly reduced up to 92% and 30% compared to conventional homogenous and heterogeneous Fenton oxidation processes, respectively.
  7. Ahmad F, Draz MU, Chandio AA, Su L, Ahmad M, Irfan M
    Environ Sci Pollut Res Int, 2021 Oct;28(39):55344-55361.
    PMID: 34137008 DOI: 10.1007/s11356-021-14641-8
    Since the development of the service sector and renewable energy reduce fossil-based energy consumption which mitigates CO2 emissions and this nexus provides a better understanding of the environmental sustainability. Considering the substantially increasing contribution of service sector and tremendous potential for renewable energy in ASEAN5 countries, leaning forward from ASEAN's energy and growth nexus, this study examines the impact of service sector contribution and renewable energy on the environmental quality of ASEAN5 using annual data from 1990 to 2018. The results of the fully modified ordinary least squared, dynamic ordinary least squared, and canonical co-integrating regressions depicted that the service sectors of Thailand, the Philippines, and Singapore augment CO2 emissions; however, the service sectors of Malaysia and Indonesia could reduce CO2 emissions. The increasing share of renewable energy can enhance environmental quality, but its magnitude varies in ASEAN5 economies; non-renewable energy, population, and economic development deteriorate the environment. Our results confirm the existence of environmental Kuznets curve in all the ASEAN5; the Gregory-Hansen test confirmed that results are robust. Finally, the Granger causality designated that economic development and non-renewable energy have a significant causal relationship with CO2 emission of ASEAN5 countries. These findings suggest that the ASEAN5 economies need to optimize their economic structure for promoting sustainable development in the long run.Graphical abstract.
  8. Bulut U, Ongan S, Dogru T, Işık C, Ahmad M, Alvarado R, et al.
    Environ Sci Pollut Res Int, 2023 Aug;30(36):86138-86154.
    PMID: 37400702 DOI: 10.1007/s11356-023-28319-w
    This study examines the impact of government spending, income, and tourism consumption on CO2 emissions in the 50 US states through a novel theoretical model derived from the Armey Curve model and the Environmental Kuznets Curve hypothesis. The findings of this research are essential for policymakers to develop effective strategies for mitigating environmental pollution. Utilizing panel cointegration analysis, the study provides valuable insights into whether continued increases in government spending contribute to higher pollution levels. By identifying the threshold point of spending as a percentage of GDP, policymakers can make informed decisions to avoid the trade-off between increased spending and environmental degradation. For instance, the analysis reveals that Hawaii's tipping point is 16.40%. The empirical results underscore the importance of adopting sustainable policies that foster economic growth while minimizing environmental harm. These findings will aid policymakers in formulating targeted and efficient approaches to tackle climate change and promote long-term environmental sustainability in the United States. Moreover, the impact of tourism development on CO2 emissions varies across states, with some US states experiencing a decrease while others see an increase.
  9. Ahmad MS, Abuzar MA, Razak IA, Rahman SA, Borromeo GL
    Eur J Dent Educ, 2017 Nov;21(4):e29-e38.
    PMID: 27273317 DOI: 10.1111/eje.12211
    Poor oral health has been associated with compromised general health and quality of life. To promote comprehensive patient management, the role of medical professionals in oral health maintenance is compelling, thus indicating the need for educational preparation in this area of practice. This study aimed to determine the extent of training in oral health in Malaysian and Australian medical schools. An audio-recorded semi-structured phone interview involving Academic Programme Directors in Malaysian (n = 9, response rate=81.8%) and Australian (n = 7, response rate = 35.0%) medical schools was conducted during the 2014/2015 and 2014 academic years, respectively. Qualitative data was analysed via thematic analysis, involving coding and grouping into emerging themes. Quantitative data were measured for frequencies. It was found that medical schools in Malaysia and Australia offered limited teaching of various oral health-related components that were mostly integrated throughout the curriculum, in the absence of structured learning objectives, teaching methodologies and assessment approaches. Barriers to providing oral health education included having insufficient expertise and overloaded curriculum. As medical educators demonstrated support for oral health education, collaboration amongst various stakeholders is integral to developing a well-structured curriculum and practice guidelines on oral health management involving medical professionals.
  10. Ahmad MS, Razak IA, Borromeo GL
    Eur J Dent Educ, 2015 Feb;19(1):44-52.
    PMID: 24779684 DOI: 10.1111/eje.12101
    A compromised oral health condition amongst patients with special health care needs (SHCN) has been associated with the reluctance and shortage of skills of dental professionals in managing such patients. Lack of training and experience at the undergraduate level are reported barriers to the provision of care for this patient cohort. Undergraduate education therefore, plays an important role in producing professionals with the knowledge, skills and positive attitude in treating patients with SHCN. This study aims to determine the level of knowledge, comfort and attitudes of Malaysian undergraduate dental students towards caring for patients with SHCN, as well as their perception on education in this field. A self-administered questionnaire was administered in the classroom style to final year undergraduate dental students in Malaysian public dental schools. Most students were aware of Special Needs Dentistry (SND) as a specialty after being informed by academic staff. The majority of the students demonstrated poor knowledge in defining SND and felt uncomfortable providing care for such patients. They perceived their undergraduate training in SND as inadequate with most students agreeing that they should receive didactic and clinical training at undergraduate level. A high percentage of students also expressed interest in pursuing postgraduate education in this area of dentistry despite the lack of educational exposure during undergraduate years. The study supports a need for educational reform to formulate a curriculum that is more patient-centred, with earlier clinical exposure in various clinical settings for students to treat patients with special health care needs, applying the concept of holistic care in a variable clinical condition.
  11. Borromeo GL, Ahmad MS, Buckley S, Bozanic M, Cao A, Al-Dabbagh M, et al.
    Eur J Dent Educ, 2018 Aug;22(3):e321-e326.
    PMID: 29024268 DOI: 10.1111/eje.12296
    INTRODUCTION: The role of dental auxiliaries in collaborative care of patients with special needs is compelling. This study was undertaken to investigate the perceptions of Special Needs Dentistry (SND) education and practice amongst students enrolled in Australian programmes in dental auxiliary, namely dental hygiene, dental therapy and oral health therapy (DH/DT/OHT).

    MATERIALS AND METHODS: All Australian institutions offering DH/DT/OHT programmes (n = 14) were invited to participate in a self-administered questionnaire survey, conducted online, involving students across all academic years. Twelve institutions agreed to participate, but only five institutions were included in the final analysis, with a student response rate of 31.1%. Answers to open-ended questions were coded and grouped for measurement of frequencies. Quantitative data were analysed via chi-squared and Fisher's exact tests (significance taken as P 

  12. Saddique FA, Zaib S, Jalil S, Aslam S, Ahmad M, Sultan S, et al.
    Eur J Med Chem, 2018 Jan 01;143:1373-1386.
    PMID: 29126721 DOI: 10.1016/j.ejmech.2017.10.036
    Three series of 4-hydroxy-N'-[benzylidene/1-phenylethylidene]-2-H/methyl/benzyl-1,2-benzothiazine-3-carbohydrazide 1,1-dioxides (9-11)a-l were synthesized and unraveled to be highly potent dual inhibitors of monoamine oxidases (MAO-A and MAO-B). All the examined compounds demonstrated IC50 values in lower micro-molar range for both MAO-A as well as MAO-B. The most active MAO-A inhibitor was 4-hydroxy-N'-(1-phenylethylidene)-2H-benzo[e][1,2]thiazine-3-carbohydrazide 1,1-dioxide (9i) with an IC50 value of 0.11 ± 0.005 μM, whereas, methyl 4-hydroxy-2H-benzo[e][1,2]thiazine-3-carboxylate 1,1-dioxide (3) was the most active MAO-B inhibitor with an IC50 value of 0.21 ± 0.01 μM. Enzyme kinetics studies revealed that the most potent compounds inhibited both MAO enzymes (A & B) in a competitive fashion. Molecular docking studies were also performed to obtain an intuitive picture of inhibition potential for potent inhibitors. The high potency of these compounds is optimally combined with highly favorable ADME profile with predicted good oral bioavailability.
  13. Ahmad S, Jalil S, Zaib S, Aslam S, Ahmad M, Rasul A, et al.
    Eur J Pharm Sci, 2019 Apr 01;131:9-22.
    PMID: 30735822 DOI: 10.1016/j.ejps.2019.02.007
    We report the synthesis and biological evaluation of two new series of 2-amino-6-benzyl-4-phenyl-4,6-dihydrobenzo[c]pyrano[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxides and 2-amino-6-methyl-4-phenyl-4,6-dihydrobenzo[c]pyrano[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxides. The synthetic methodology involves a multistep reaction starting with methyl anthranilate which was coupled with methane sulfonyl chloride. The product of the reaction was subjected to N-benzylation and N-methylation reactions followed by ring closure with sodium hydride resulting in the formation of respective 2,1-benzothiazine 2,2-dioxides. These 2,1-benzothiazine precursors were subjected to multicomponent reaction with malononitrile and substituted benzaldehydes for the synthesis of two new series of pyranobenzothiazines (6a-r and 7a-r). The synthesized compounds were screened as selective inhibitors of monoamine oxidase A and monoamine oxidase B. The in vitro results suggested that compound 6d and 7q are the selective inhibitors of monoamine oxidase A, however, the selective and potent inhibitors of monoamine oxidase B included compounds 6h and 7r. Moreover, some dual inhibitors were noticed like 7l having more inhibitory activity towards both the isozymes. Moreover, the binding modes of the selective and potent inhibitors of monoamine oxidase A and B were investigated by molecular docking analysis. The results suggested that the synthetic derivatives may be potential towards the monoamine oxidase isozymes.
  14. Yam MF, Tan CS, Ahmad M, Shibao R
    Eur J Pharmacol, 2016 Oct 15;789:27-36.
    PMID: 27370961 DOI: 10.1016/j.ejphar.2016.06.047
    Previous studies demonstrated that eupatorin content in Orthosiphon stamineus fractions correlated with their vasorelaxation activity. Even with previous studies, there is still very little information on the vasorelaxation effect of eupatorin, and not many scientific studies had been carried out. Therefore, the present study was designed to investigate the vasorelaxation activity and mechanism of action of eupatorin. The vasorelaxation activity and the underlying mechanisms of eupatorin was evaluated on thoracic aortic rings isolated from Sprague Dawley rats. Eupatorin caused the relaxation of aortic rings pre-contracted with phenylephrine with and without endothelium (pD2=6.66±0.13, EMAX=99.72±6.39%; pD2=6.10±0.22, EMAX=65.78±8.01%), and also the relaxation of endothelium-intact aortic rings pre-contracted with potassium chloride (pD2=6.20±0.30, EMAX=71.89±12.25%). In the presence of Nω-nitro-l-arginine methyl ester (pD2<4.60, EMAX=24.91±6.39%), methylene blue (pD2=6.05±0.38, EMAX=66.79±9.69%), ODQ (pD25.84±0.32, EMAX=60.47±9.6%), indomethacin (pD2=6.27±0.21, EMAX=76.03±9.45%), tetraethylammonium (pD2=6.09±0.35, EMAX=69.35±11.31%), 4-aminopyridine (pD2=6.34±0.12, EMAX=76±6.1%), barium chloride (pD2=6.47±0.14, EMAX=79.61±10.02%), atropine (pD2=6.36±0.29, EMAX=86.47±12.95%) and propranolol (pD2=6.49±0.26, EMAX=83.2±12.01%), relaxation stimulated by eupatorin was significantly reduced. Eupatorin was also found to be active in reducing Ca(2+) release from sarcoplasmic reticulum and in blocking calcium channels. The present study demonstrates the vasorelaxation effect of eupatorin involving NO/sGC/cGMP and indomethacin pathways, calcium and potassium channels, and muscarinic and beta-adrenergic receptors.
  15. Mohamed EA, Ahmad M, Ang LF, Asmawi MZ, Yam MF
    PMID: 26649063 DOI: 10.1155/2015/754931
    In the present study, a 50% ethanolic extract of Orthosiphon stamineus was tested for its α-glucosidase inhibitory activity. In vivo assays of the extract (containing 1.02%, 3.76%, and 3.03% of 3'hydroxy-5,6,7,4'-tetramethoxyflavone, sinensetin, and eupatorin, resp.) showed that it possessed an inhibitory activity against α-glucosidase in normal rats loaded with starch and sucrose. The results showed that 1000 mg/kg of the 50% ethanolic extract of O. stamineus significantly (P < 0.05) decreased the plasma glucose levels of the experimental animals in a manner resembling the effect of acarbose. In streptozotocin-induced diabetic rats, only the group treated with 1000 mg/kg of the extract showed significantly (P < 0.05) lower plasma glucose levels after starch loading. Hence, α-glucosidase inhibition might be one of the mechanisms by which O. stamineus extract exerts its antidiabetic effect. Furthermore, our findings indicated that the 50% ethanolic extract of O. stamineus can be considered as a potential agent for the management of diabetes mellitus.
  16. Daker M, Yeo JT, Bakar N, Abdul Rahman AS, Ahmad M, Yeo TC, et al.
    Exp Ther Med, 2016 Jun;11(6):2117-2126.
    PMID: 27284293
    Nasopharyngeal carcinoma (NPC) is a type of tumour that arises from the epithelial cells that line the surface of the nasopharynx. NPC is treated with radiotherapy and cytotoxic chemotherapeutic drugs such as cisplatin and 5-fluorouracil. However, current strategies are often associated with potential toxicities. This has prompted efforts to identify alternative methods of treatment. The present study aimed to investigate silvestrol and episilvestrol-mediated inhibition of cell proliferation in human NPC cells. The growth kinetics of NPC cells treated with silvestrol or episilvestrol were monitored dynamically using a real-time, impedance-based cell analyzer, and dose-response profiles were generated using a colorimetric cell viability assay. Furthermore, apoptosis was evaluated using flow cytometry and high content analysis. In addition, flow cytometry was performed to determine cell cycle distribution. Finally, the effects of combining silvestrol or episilvestrol with cisplatin on NPC cells was examined. Apoptosis was not observed in silvestrol and episilvestrol-treated NPC cells, although cell cycle perturbation was evident. Treatment with both compounds induced a significant increase in the percentage of cells in the G2/M phase, as compared with the control. In vitro cultures combining silvestrol or episilvestrol with cisplatin showed synergistic effects against NPC cells. The results of the present study suggested that silvestrol and episilvestrol had an anti-tumour activity in NPC cells. Silvestrol and episilvestrol, particularly in combination with cisplatin, merit further investigation, so as to determine the cellular mechanisms underlying their action(s) as anti-NPC agents.
  17. Daker M, Lin VY, Akowuah GA, Yam MF, Ahmad M
    Exp Ther Med, 2013 Jun;5(6):1701-1709.
    PMID: 23837058
    Nasopharyngeal carcinoma (NPC) is a malignancy that occurs in the epithelium of the nasopharynx. The standard treatment of NPC patients with locoregionally advanced stages is problematic and is often associated with toxicities. Therefore, it is essential to screen for naturally occurring compounds with strong apoptosis-inducing activity and minimal toxicity. This study investigated the effects of the standardized methanol extract of Cinnamomum burmannii Blume stem bark and its main constituent, trans-cinnamaldehyde (TCA), on human NPC cell lines. The content of TCA in C. burmannii methanol extract was standardized to be 13.61% w/w by means of gas chromatography-mass spectrometry (GC-MS). NPC cell proliferation was clearly inhibited within 24 h of treatment, with TCA exhibiting greater activity than the methanol extract. TCA was more active against NPC cells compared with cisplatin. There was a pronounced downregulation of the proliferation markers, Ki67 and proliferating cell nuclear antigen (PCNA) in the TCA-treated cells; while morphological observation indicated the induction of apoptosis. Caspase activation and prominent DNA damage, which are markers of apoptosis induction were detected. TCA demonstrated the ability to scavenge nitric oxide. The simultaneous combination of TCA and cisplatin produced synergistic anti-proliferative effects. Collectively, these data indicate the potential use of TCA for the treatment of NPC.
  18. Husaini R, Ahmad M, Zakaria Z
    Exp Ther Med, 2017 Jun;13(6):3209-3216.
    PMID: 28587395 DOI: 10.3892/etm.2017.4443
    Chronic myeloid leukaemia (CML) is a form of leukaemia derived from the myeloid cell lineage. Imatinib mesylate, the breakpoint cluster region-abelson murine leukeamia kinase inhibitor, is a specific reagent used in the clinical treatment of CML. The DNA topoisomerase II inhibitor, etoposide, is also employed as a therapeutic, though it is used to a lesser extent. The present study aims to evaluate the effects of CML-targeted therapy, utilising imatinib mesylate and etoposide in the in vitro treatment of parental sensitive and adriamycin-resistant CML in the K562 and K562/ADM cell lines, respectively. Preliminary work involved the screening of multidrug resistant (MDR) gene expression, including MDR1, MRP1 and B-cell lymphoma 2 (BCL-2) at the mRNA levels. The sensitive and resistant CML cell lines expressed the MRP1 gene, though the sensitive K562 cells expressed low, almost undetectable levels of MDR1 and BCL-2 genes relative to the K562/ADM cells. Following treatment with imatinib mesylate or etoposide, the IC50 for imatinib mesylate did not differ between the sensitive and resistant cell lines (0.492±0.024 and 0.378±0.029, respectively), indicating that imatinib mesylate is effective in the treatment of CML regardless of cell chemosensitivity. However, the IC50 for etoposide in sensitive K562 cells was markedly lower than that of K562/ADM cells (50.6±16.5 and 194±8.46 µM, respectively), suggesting that the higher expression levels of MDR1 and/or BCL-2 mRNA in resistant cells may be partially responsible for this effect. This is supported by terminal deoxynucleotidyl transferase dUTP nick-end labeling data, whereby a higher percentage of apoptotic cells were found in the sensitive and resistant K562 cells treated with imatinib mesylate (29.3±0.2 and 31.9±16.7%, respectively), whereas etoposide caused significant apoptosis of sensitive K562 cells (18.3±8.35%) relative to K562/ADM cells (5.17±3.3%). In addition, the MDR genes in K562/ADM cells were knocked down by short interfering RNAs. The percentage knockdowns were 15.4% for MRP1, 17.8% for MDR and 30.7% for BCL-2, which resulted in a non-significant difference in the half maximal inhibitory concentration value of K562/ADM cells relative to K562 cells upon treatment with etoposide.
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