Displaying publications 61 - 80 of 405 in total

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  1. Liew SY, Looi CY, Paydar M, Cheah FK, Leong KH, Wong WF, et al.
    PLoS One, 2014;9(2):e87286.
    PMID: 24551054 DOI: 10.1371/journal.pone.0087286
    In this study, a new apoptotic monoterpenoid indole alkaloid, subditine (1), and four known compounds were isolated from the bark of Nauclea subdita. Complete (1)H- and (13)C- NMR data of the new compound were reported. The structures of isolated compounds were elucidated with various spectroscopic methods such as 1D- and 2D- NMR, IR, UV and LCMS. All five compounds were screened for cytotoxic activities on LNCaP and PC-3 human prostate cancer cell-lines. Among the five compounds, the new alkaloid, subditine (1), demonstrated the most potent cell growth inhibition activity and selective against LNCaP with an IC50 of 12.24±0.19 µM and PC-3 with an IC50 of 13.97±0.32 µM, compared to RWPE human normal epithelial cell line (IC50 = 30.48±0.08 µM). Subditine (1) treatment induced apoptosis in LNCaP and PC-3 as evidenced by increased cell permeability, disruption of cytoskeletal structures and increased nuclear fragmentation. In addition, subditine (1) enhanced intracellular reactive oxygen species (ROS) production, as reflected by increased expression of glutathione reductase (GR) to scavenge damaging free radicals in both prostate cancer cell-lines. Excessive ROS could lead to disruption of mitochondrial membrane potential (MMP), release of cytochrome c and subsequent caspase 9, 3/7 activation. Further Western blot analyses showed subditine (1) induced down-regulation of Bcl-2 and Bcl-xl expression, whereas p53 was up-regulated in LNCaP (p53-wild-type), but not in PC-3 (p53-null). Overall, our data demonstrated that the new compound subditine (1) exerts anti-proliferative effect on LNCaP and PC-3 human prostate cancer cells through induction of apoptosis.
    Matched MeSH terms: Models, Biological
  2. Brown D, Feeney M, Ahmadi M, Lonoce C, Sajari R, Di Cola A, et al.
    J Exp Bot, 2017 Nov 02;68(18):5045-5055.
    PMID: 29036360 DOI: 10.1093/jxb/erx331
    Natural rubber (polyisoprene) from the rubber tree Hevea brasiliensis is synthesized by specialized cells called laticifers. It is not clear how rubber particles arise, although one hypothesis is that they derive from the endoplasmic reticulum (ER) membrane. Here we cloned the genes encoding four key proteins found in association with rubber particles and studied their intracellular localization by transient expression in Nicotiana benthamiana leaves. We show that, while the cis-prenyltransferase (CPT), responsible for the synthesis of long polyisoprene chains, is a soluble, cytosolic protein, other rubber particle proteins such as rubber elongation factor (REF), small rubber particle protein (SRPP) and Hevea rubber transferase 1-REF bridging protein (HRBP) are associated with the endoplasmic reticulum (ER). We also show that SRPP can recruit CPT to the ER and that interaction of CPT with HRBP leads to both proteins relocating to the plasma membrane. We discuss these results in the context of the biogenesis of rubber particles.
    Matched MeSH terms: Models, Biological
  3. Madfa AA, Kadir MR, Kashani J, Saidin S, Sulaiman E, Marhazlinda J, et al.
    Med Eng Phys, 2014 Jul;36(7):962-7.
    PMID: 24834856 DOI: 10.1016/j.medengphy.2014.03.018
    Different dental post designs and materials affect the stability of restoration of a tooth. This study aimed to analyse and compare the stability of two shapes of dental posts (parallel-sided and tapered) made of five different materials (titanium, zirconia, carbon fibre and glass fibre) by investigating their stress transfer through the finite element (FE) method. Ten three-dimensional (3D) FE models of a maxillary central incisor restored with two different designs and five different materials were constructed. An oblique loading of 100 N was applied to each 3D model. Analyses along the centre of the post, the crown-cement/core and the post-cement/dentine interfaces were computed, and the means were calculated. One-way ANOVAs followed by post hoc tests were used to evaluate the effectiveness of the post materials and designs (p=0.05). For post designs, the tapered posts introduced significantly higher stress compared with the parallel-sided post (p<0.05), especially along the centre of the post. Of the materials, the highest level of stress was found for stainless steel, followed by zirconia, titanium, glass fibre and carbon fibre posts (p<0.05). The carbon and glass fibre posts reduced the stress distribution at the middle and apical part of the posts compared with the stainless steel, zirconia and titanium posts. The opposite results were observed at the crown-cement/core interface.
    Matched MeSH terms: Models, Biological*
  4. Abdullahi A, Shohaimi S, Kilicman A, Ibrahim MH
    J Biol Dyn, 2019 12;13(1):345-361.
    PMID: 31056007 DOI: 10.1080/17513758.2019.1605003
    Seed dispersals deal with complex systems through which the data collected using advanced seed tracking facilities pose challenges to conventional approaches, such as empirical and deterministic models. The use of stochastic models in current seed dispersal studies is encouraged. This review describes three existing stochastic models: the birth-death process (BDP), a 2 dimensional (
    2

    D

    ) symmetric random walks and a
    2

    D

    intermittent walks. The three models possess Markovian property, which make them flexible for studying natural phenomena. Only a few of applications in ecology are found in seed dispersals. The review illustrates how the models are to be used in seed dispersals context. Using the nonlinear BDP, we formulate the individual-based models for two competing plant species while the cover time model is formulated by the symmetric and intermittent random walks. We also show that these three stochastic models can be formulated using the Gillespie algorithm. The full cover time obtained by the symmetric random walks can approximate the Gumbel distribution pattern as the other searching strategies do. We suggest that the applications of these models in seed dispersals may lead to understanding of many complex systems, such as the seed removal experiments and behaviour of foraging agents, among others.
    Matched MeSH terms: Models, Biological*
  5. Yahya N, Ebert MA, Bulsara M, House MJ, Kennedy A, Joseph DJ, et al.
    Med Phys, 2016 May;43(5):2040.
    PMID: 27147316 DOI: 10.1118/1.4944738
    Given the paucity of available data concerning radiotherapy-induced urinary toxicity, it is important to ensure derivation of the most robust models with superior predictive performance. This work explores multiple statistical-learning strategies for prediction of urinary symptoms following external beam radiotherapy of the prostate.
    Matched MeSH terms: Models, Biological
  6. Chan YJ, Chong MF, Law CL
    Bioresour Technol, 2012 Dec;125:145-57.
    PMID: 23026327 DOI: 10.1016/j.biortech.2012.08.118
    Thermophilic treatment of palm oil mill effluent (POME) was studied in a novel integrated anaerobic-aerobic bioreactor (IAAB). The IAAB was subjected to a program of steady-state operation over a range of organic loading rate (OLR)s, up to 30 g COD/L day in order to evaluate its treatment capacity. The thermophilic IAAB achieved high chemical oxygen demand (COD), biochemical oxygen demand (BOD) and total suspended solids (TSS) removal efficiencies of more than 99% for OLR up to 18.5 g COD/L day. High methane yield of 0.32 LCH(4) (STP)/g COD(removed) with compliance of the final treated effluent to the discharge limit were achieved. This is higher than that of the mesophilic system due to the higher maximum specific growth rate (μ(max)) of the thermophilic microorganisms. Besides, coupling the model of Grau second order model (anaerobic system) with the model of Monod (aerobic system) will completely define the IAAB system.
    Matched MeSH terms: Models, Biological*
  7. Rene ER, Kar S, Krishnan J, Pakshirajan K, López ME, Murthy DV, et al.
    Bioresour Technol, 2015 Aug;190:529-35.
    PMID: 25827361 DOI: 10.1016/j.biortech.2015.03.049
    The performance of a compost biofilter inoculated with mixed microbial consortium was optimized for treating a gas-phase mixture of benzene and toluene. The biofilter was acclimated to these VOCs for a period of ∼18d. The effects of concentration and flow rate on the removal efficiency (RE) and elimination capacity (EC) were investigated by varying the inlet concentration of benzene (0.12-0.95g/m(3)), toluene (0.14-1.48g/m(3)) and gas-flow rate (0.024-0.072m(3)/h). At comparable loading rates, benzene removal in the mixture was reduced in the range of 6.6-41% in comparison with the individual benzene degradation. Toluene removal in mixture was even more affected as observed from the reductions in REs, ranging from 18.4% to 76%. The results were statistically interpreted by performing an analysis of variance (ANOVA) to elucidate the main and interaction effects.
    Matched MeSH terms: Models, Biological
  8. Lee CF, Abdullah MZ, Ahmad KA, Lutfi Shuaib I
    Comput Math Methods Med, 2013;2013:519071.
    PMID: 23840279 DOI: 10.1155/2013/519071
    This research focuses on creating a standardized nasal cavity model of adult Malaysian females. The methodology implemented in this research is a new approach compared to other methods used by previous researchers. This study involves 26 females who represent the test subjects for this preliminary study. Computational fluid dynamic (CFD) analysis was carried out to better understand the characteristics of the standardized model and to compare it to the available standardized Caucasian model. This comparison includes cross-sectional areas for both half-models as well as velocity contours along the nasal cavities. The Malaysian female standardized model is larger in cross-sectional area compared to the standardized Caucasian model thus leading to lower average velocity magnitudes. The standardized model was further evaluated with four more Malaysian female test subjects based on its cross-sectional areas and average velocity magnitudes along the nasal cavities. This evaluation shows that the generated model represents an averaged and standardized model of adult Malaysian females.
    Matched MeSH terms: Models, Biological*
  9. Tan MSF, Rahman S, Dykes GA
    Food Microbiol, 2017 Apr;62:62-67.
    PMID: 27889167 DOI: 10.1016/j.fm.2016.10.009
    This study investigated the removal of bacterial surface structures, particularly flagella, using sonication, and examined its effect on the attachment of Salmonella Typhimurium ATCC 14028 cells to plant cell walls. S. Typhimurium ATCC 14028 cells were subjected to sonication at 20 kHz to remove surface structures without affecting cell viability. Effective removal of flagella was determined by staining flagella of sonicated cells with Ryu's stain and enumerating the flagella remaining by direct microscopic counting. The attachment of sonicated S. Typhimurium cells to bacterial cellulose-based plant cell wall models and cut plant material (potato, apple, lettuce) was then evaluated. Varying concentrations of pectin and/or xyloglucan were used to produce a range of bacterial cellulose-based plant cell wall models. As compared to the non-sonicated controls, sonicated S. Typhimurium cells attached in significantly lower numbers (between 0.5 and 1.0 log CFU/cm2) to all surfaces except to the bacterial cellulose-only composite without pectin and xyloglucan. Since attachment of S. Typhimurium to the bacterial cellulose-only composite was not affected by sonication, this suggests that bacterial surface structures, particularly flagella, could have specific interactions with pectin and xyloglucan. This study indicates that sonication may have potential applications for reducing Salmonella attachment during the processing of fresh produce.
    Matched MeSH terms: Models, Biological
  10. Slik JW, Aiba S, Bastian M, Brearley FQ, Cannon CH, Eichhorn KA, et al.
    Proc Natl Acad Sci U S A, 2011 Jul 26;108(30):12343-7.
    PMID: 21746913 DOI: 10.1073/pnas.1103353108
    The marked biogeographic difference between western (Malay Peninsula and Sumatra) and eastern (Borneo) Sundaland is surprising given the long time that these areas have formed a single landmass. A dispersal barrier in the form of a dry savanna corridor during glacial maxima has been proposed to explain this disparity. However, the short duration of these dry savanna conditions make it an unlikely sole cause for the biogeographic pattern. An additional explanation might be related to the coarse sandy soils of central Sundaland. To test these two nonexclusive hypotheses, we performed a floristic cluster analysis based on 111 tree inventories from Peninsular Malaysia, Sumatra, and Borneo. We then identified the indicator genera for clusters that crossed the central Sundaland biogeographic boundary and those that did not cross and tested whether drought and coarse-soil tolerance of the indicator genera differed between them. We found 11 terminal floristic clusters, 10 occurring in Borneo, 5 in Sumatra, and 3 in Peninsular Malaysia. Indicator taxa of clusters that occurred across Sundaland had significantly higher coarse-soil tolerance than did those from clusters that occurred east or west of central Sundaland. For drought tolerance, no such pattern was detected. These results strongly suggest that exposed sandy sea-bed soils acted as a dispersal barrier in central Sundaland. However, we could not confirm the presence of a savanna corridor. This finding makes it clear that proposed biogeographic explanations for plant and animal distributions within Sundaland, including possible migration routes for early humans, need to be reevaluated.
    Matched MeSH terms: Models, Biological
  11. Hwang WH, Shen TJ
    Biometrics, 2010 Dec;66(4):1052-60.
    PMID: 20002401 DOI: 10.1111/j.1541-0420.2009.01371.x
    Many well-known methods are available for estimating the number of species in a forest community. However, most existing methods result in considerable negative bias in applications, where field surveys typically represent only a small fraction of sampled communities. This article develops a new method based on sampling with replacement to estimate species richness via the generalized jackknife procedure. The proposed estimator yields small bias and reasonably accurate interval estimation even with small samples. The performance of the proposed estimator is compared with several typical estimators via simulation study using two complete census datasets from Panama and Malaysia.
    Matched MeSH terms: Models, Biological
  12. Ibitoye AB, Hamouda AM, Wong SV, Umar RS
    Proc Inst Mech Eng H, 2009 Nov;223(8):1033-40.
    PMID: 20092099
    This study uses computer simulations to study the impact of a motorcycle with the conventional w-beam guardrail. A three-dimensional computer simulation of a scaled hybrid III 50th-percentile male dummy mounted on a motorcycle and colliding with a w-beam guardrail is carried out. A multi-body model of the motorcycle and finite element model of the guardrail are developed using commercially available software. The simulation model is validated with a physical crash test conducted with same initial impact configurations. Impacts at speeds of 32, 48, and 60 km/h at an impact angle at 45 degrees are considered. The predicted forces and accelerations are compared with the biomechanical limits for each body part and the risk of injury to the rider are evaluated. Speed was found to have a significant influence on the level of injury to the head, neck, chest, and femur. A significant reduction of the severity of injuries was found when the impact speed was reduced from 60 to 32km/h. The accelerations experienced by the head and chest are found to be higher than safe levels for impact speeds of 48 and 60 km/h. The biomechanical limit for the right femur is exceeded at all three considered impact speeds. Neck injuries are also a concern, with the predicted tension values and neck bending extent being higher than the biomechanical limit for the 60 km/h impact speed. In light of these results, it is suggested that the design of guardrails should be reviewed with a focus on the safety of motorcyclists.
    Matched MeSH terms: Models, Biological*
  13. Fuzi SF, Razali F, Jahim JM, Rahman RA, Illias RM
    Bioprocess Biosyst Eng, 2014 Sep;37(9):1887-98.
    PMID: 24633311 DOI: 10.1007/s00449-014-1163-z
    A xylanase gene (xyn2) from Trichoderma reesei ATCC 58350 was previously cloned and expressed in Kluyveromyces lactis GG799. The production of the recombinant xylanase was conducted in a developed medium with an optimised batch and with fed-batches that were processed with glucose. The glucose served as a carbon source for cell growth and as an inducer for xylanase production. In a 1-L batch system, a glucose concentration of 20 g L(-1) and 80 % dissolved oxygen were found to provide the best conditions for the tested ranges. A xylanase activity of 75.53 U mL(-1) was obtained. However, in the batch mode, glucose depletions reduced the synthesis of recombinant xylanase by K. lactis GG799. To maximise the production of xylanase, further optimisation was performed using exponential feeding. We investigated the effects of various nitrogen sources combined with the carbon to nitrogen (C/N) molar ratio on the production of xylanase. Of the various nitrogen sources, yeast extract was found to be the most useful for recombinant xylanase production. The highest xylanase production (110.13 U mL(-1)) was measured at a C/N ratio of 50.08. These conditions led to a 45.8 % increase in xylanase activity compared with the batch cultures. Interestingly, the further addition of 500 g L(-1) glucose led to a 6.2-fold increase (465.07 U mL(-1)) in recombinant xylanase activity. These findings, together with those of the exponential feeding strategy, indicate that the composition of the C/N molar ratio has a substantial impact on recombinant protein production in K. lactis.
    Matched MeSH terms: Models, Biological
  14. Gonzalez-Carter DA, Leo BF, Ruenraroengsak P, Chen S, Goode AE, Theodorou IG, et al.
    Sci Rep, 2017 03 02;7:42871.
    PMID: 28251989 DOI: 10.1038/srep42871
    Silver nanoparticles (AgNP) are known to penetrate into the brain and cause neuronal death. However, there is a paucity in studies examining the effect of AgNP on the resident immune cells of the brain, microglia. Given microglia are implicated in neurodegenerative disorders such as Parkinson's disease (PD), it is important to examine how AgNPs affect microglial inflammation to fully assess AgNP neurotoxicity. In addition, understanding AgNP processing by microglia will allow better prediction of their long term bioreactivity. In the present study, the in vitro uptake and intracellular transformation of citrate-capped AgNPs by microglia, as well as their effects on microglial inflammation and related neurotoxicity were examined. Analytical microscopy demonstrated internalization and dissolution of AgNPs within microglia and formation of non-reactive silver sulphide (Ag2S) on the surface of AgNPs. Furthermore, AgNP-treatment up-regulated microglial expression of the hydrogen sulphide (H2S)-synthesizing enzyme cystathionine-γ-lyase (CSE). In addition, AgNPs showed significant anti-inflammatory effects, reducing lipopolysaccharide (LPS)-stimulated ROS, nitric oxide and TNFα production, which translated into reduced microglial toxicity towards dopaminergic neurons. Hence, the present results indicate that intracellular Ag2S formation, resulting from CSE-mediated H2S production in microglia, sequesters Ag+ ions released from AgNPs, significantly limiting their toxicity, concomitantly reducing microglial inflammation and related neurotoxicity.
    Matched MeSH terms: Models, Biological
  15. Schilthuizen M
    BMC Evol. Biol., 2003 Jun 05;3:13.
    PMID: 12791170
    BACKGROUND: Many groups of land snails show great interspecific diversity in shell ornamentation, which may include spines on the shell and flanges on the aperture. Such structures have been explained as camouflage or defence, but the possibility that they might be under sexual selection has not previously been explored.

    PRESENTATION OF THE HYPOTHESIS: The hypothesis that is presented consists of two parts. First, that shell ornamentation is the result of sexual selection. Second, that such sexual selection has caused the divergence in shell shape in different species.

    TESTING THE HYPOTHESIS: The first part of the hypothesis may be tested by searching for sexual dimorphism in shell ornamentation in gonochoristic snails, by searching for increased variance in shell ornamentation relative to other shell traits, and by mate choice experiments using individuals with experimentally enhanced ornamentation. The second part of the hypothesis may be tested by comparing sister groups and correlating shell diversity with degree of polygamy.

    IMPLICATIONS OF THE HYPOTHESIS: If the hypothesis were true, it would provide an explanation for the many cases of allopatric evolutionary radiation in snails, where shell diversity cannot be related to any niche differentiation or environmental differences.

    Matched MeSH terms: Models, Biological
  16. Rahman NA, Sharudin A, Diah S, Muharram SH
    Microb Pathog, 2017 Sep;110:352-358.
    PMID: 28711510 DOI: 10.1016/j.micpath.2017.07.021
    INTRODUCTION: Pneumococcal infections have caused morbidity and mortality globally. Streptococcus pneumoniae (pneumococci) are commensal bacteria that colonize the nasopharynx, asymptomatically. From there, pneumococci can spread in the lungs causing pneumonia and disseminate in the bloodstream causing bacteremia (sepsis) and reach the brain leading to meningitis. Endothelial cells are one of the most important components of the blood-brain barrier that separates the blood from the brain and plays the first protective role against pneumococcal entry. Thus this study aimed to investigate on the ability of non-meningitis pneumococcal clinical strains to adhere and invade a brain endothelium model.

    METHODS: Two pneumococcal Brunei clinical strains were serotyped by multiplex PCR method using oligonucleotide sequences derived from Centers for Disease Control and Prevention. A validated immortalised mouse brain endothelial cell line (bEnd.3) was used as a brain endothelium model for the study of the pneumococcal breach of the blood-brain barrier using an adherence and invasion assay.

    RESULTS: Both of the pneumococcal clinical strains were found to be serotype 19F, a common circulating serotype in Southeast Asia and globally and possess the ability to adhere and invade the brain endothelial cells.

    CONCLUSION: In addition, this is the first report on the serotype identification of pneumococci in Brunei Darussalam and their application on a brain endothelium model. Further studies are required to understand the virulence capabilities of the clinical strains.

    Matched MeSH terms: Models, Biological
  17. Gaeid KS, Ping HW, Khalid M, Masaoud A
    Sensors (Basel), 2012;12(4):4031-50.
    PMID: 22666016 DOI: 10.3390/s120404031
    Fault Tolerant Control (FTC) systems are crucial in industry to ensure safe and reliable operation, especially of motor drives. This paper proposes the use of multiple controllers for a FTC system of an induction motor drive, selected based on a switching mechanism. The system switches between sensor vector control, sensorless vector control, closed-loop voltage by frequency (V/f) control and open loop V/f control. Vector control offers high performance, while V/f is a simple, low cost strategy with high speed and satisfactory performance. The faults dealt with are speed sensor failures, stator winding open circuits, shorts and minimum voltage faults. In the event of compound faults, a protection unit halts motor operation. The faults are detected using a wavelet index. For the sensorless vector control, a novel Boosted Model Reference Adaptive System (BMRAS) to estimate the motor speed is presented, which reduces tuning time. Both simulation results and experimental results with an induction motor drive show the scheme to be a fast and effective one for fault detection, while the control methods transition smoothly and ensure the effectiveness of the FTC system. The system is also shown to be flexible, reverting rapidly back to the dominant controller if the motor returns to a healthy state.
    Matched MeSH terms: Models, Biological
  18. Chan JY, Ooi EH
    Cryobiology, 2016 12;73(3):304-315.
    PMID: 27789380 DOI: 10.1016/j.cryobiol.2016.10.006
    Advancement in biomedical simulation and imaging modality have catalysed the development of in silico predictive models for cryoablation. However, one of the main challenges in ensuring the accuracy of the model prediction is the use of proper thermal and biophysical properties of the patient. These properties are difficult to measure clinically and thus, represent significant uncertainty that can affect the model prediction. Motivated by this, a sensitivity analysis is carried out to identify the model parameters that have the most significant impact on the lesion size during cryoablation. The study is initially carried out using the Morris method to screen for the most dominant parameters. Once determined, analysis of variance (ANOVA) is performed to quantitatively rank the order of importance of each parameter and their interactions. Results from the sensitivity analysis revealed that blood perfusion, water transport and ice nucleation parameters are critical in predicting the lesion size, suggesting that the acquisition of these parameters should be prioritised to ensure the accuracy of the model prediction.
    Matched MeSH terms: Models, Biological*
  19. Muhamad MAH, Che Hasan R, Md Said N, Ooi JL
    PLoS One, 2021;16(9):e0257761.
    PMID: 34555110 DOI: 10.1371/journal.pone.0257761
    Integrating Multibeam Echosounder (MBES) data (bathymetry and backscatter) and underwater video technology allows scientists to study marine habitats. However, use of such data in modeling suitable seagrass habitats in Malaysian coastal waters is still limited. This study tested multiple spatial resolutions (1 and 50 m) and analysis window sizes (3 × 3, 9 × 9, and 21 × 21 cells) probably suitable for seagrass-habitat relationships in Redang Marine Park, Terengganu, Malaysia. A maximum entropy algorithm was applied, using 12 bathymetric and backscatter predictors to develop a total of 6 seagrass habitat suitability models. The results indicated that both fine and coarse spatial resolution datasets could produce models with high accuracy (>90%). However, the models derived from the coarser resolution dataset displayed inconsistent habitat suitability maps for different analysis window sizes. In contrast, habitat models derived from the fine resolution dataset exhibited similar habitat distribution patterns for three different analysis window sizes. Bathymetry was found to be the most influential predictor in all the models. The backscatter predictors, such as angular range analysis inversion parameters (characterization and grain size), gray-level co-occurrence texture predictors, and backscatter intensity levels, were more important for coarse resolution models. Areas of highest habitat suitability for seagrass were predicted to be in shallower (<20 m) waters and scattered between fringing reefs (east to south). Some fragmented, highly suitable habitats were also identified in the shallower (<20 m) areas in the northwest of the prediction models and scattered between fringing reefs. This study highlighted the importance of investigating the suitable spatial resolution and analysis window size of predictors from MBES for modeling suitable seagrass habitats. The findings provide important insight on the use of remote acoustic sonar data to study and map seagrass distribution in Malaysia coastal water.
    Matched MeSH terms: Models, Biological
  20. Tabana YM, Hassan LE, Ahamed MB, Dahham SS, Iqbal MA, Saeed MA, et al.
    Microvasc Res, 2016 09;107:17-33.
    PMID: 27133199 DOI: 10.1016/j.mvr.2016.04.009
    We recently reported the antineovascularization effect of scopoletin on rat aorta and identified its potential anti-angiogenic activity. Scopoletin could be useful as a systemic chemotherapeutic agent against angiogenesis-dependent malignancies if its antitumorigenic activity is investigated and scientifically proven using a suitable human tumor xenograft model. In the present study, bioassay-guided (anti-angiogenesis) phytochemical investigation was conducted on Nicotiana glauca extract which led to the isolation of scopoletin. Further, anti-angiogenic activity of scopoletin was characterized using ex vivo, in vivo and in silico angiogenesis models. Finally, the antitumorigenic efficacy of scopoletin was studied in human colorectal tumor xenograft model using athymic nude mice. For the first time, an in vivo anticancer activity of scopoletin was reported and characterized using xenograft models. Scopoletin caused significant suppression of sprouting of microvessels in rat aortic explants with IC50 (median inhibitory concentration) 0.06μM. Scopoletin (100 and 200mg/kg) strongly inhibited (59.72 and 89.4%, respectively) vascularization in matrigel plugs implanted in nude mice. In the tumor xenograft model, scopoletin showed remarkable inhibition on tumor growth (34.2 and 94.7% at 100 and 200mg/kg, respectively). Tumor histology revealed drastic reduction of the extent of vascularization. Further, immunostaining of CD31 and NG2 receptors in the histological sections confirmed the antivascular effect of scopoletin in tumor vasculature. In computer modeling, scopoletin showed strong ligand affinity and binding energies toward the following angiogenic factors: protein kinase (ERK1), vascular endothelial growth factor A (VEGF-A), and fibroblast growth factor 2 (FGF-2). These results suggest that the antitumor activity of scopoletin may be due to its strong anti-angiogenic effect, which may be mediated by its effective inhibition of ERK1, VEGF-A, and FGF-2.
    Matched MeSH terms: Models, Biological*
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