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1.
Opt Express ; 32(4): 5362-5379, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38439265

RESUMEN

The light field (LF) imaging systems face a trade-off between the spatial and angular resolution in a limited sensor resolution. Various networks have been proposed to enhance the spatial resolution of the sub-aperture image (SAI). However, the spatial shift-variant characteristics of the LF are not considered, and few efforts have been made to recover a full-resolution (FR) image. In this paper, we propose an FR image restoration method by embedding LF degradation kernels into the network. An explicit convolution model based on the scalar diffraction theory is first derived to calculate the system response and imaging matrix. Based on the analysis of LF image formation, we establish the mapping from an FR image to the SAI through the SAI kernel, which is a spatial shift-variant degradation (SSVD) kernel. Then, the SSVD kernels are embedded into the proposed network as prior knowledge. An SSVD convolution layer is specially designed to handle the view-wise degradation feature and speed up the training process. A refinement block is designed to preserve the entire image details. Moreover, our network is evaluated on extensive simulated and real-world LF images to demonstrate its superior performance compared with other methods. Experiments on a multi-focus scene further prove that our network is suitable for any in-focus or defocused conditions.

2.
Appl Opt ; 61(17): 5260-5268, 2022 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-36256210

RESUMEN

An image mapping spectrometer (IMS) is a kind of snapshot imaging spectrometer characterized by containing several array components including the image mapper, prism array, and reimaging lens array. We propose a hybrid non-sequential modeling method of IMS and present the complete optical model of the system built in Zemax. This method utilizes the spatial periodicity of the array components and requires only a small number of input parameters. Moreover, we design a collimating lens of a large relative aperture, sufficient working distance, and low aberration to meet the requirements of an IMS with good optical performance and compact volume. The designed lens is quantitatively evaluated in the entire IMS model, and the results demonstrate that the lens has excellent optical performance. The evaluation on the collimating lens also demonstrates the capability of the proposed modeling method in the design and optimization of systems such as the IMS that contain multiple array components. The designed collimating lens is manufactured and assembled in the experimental setup of the IMS. The proposed modeling method is verified by experimental results.

3.
Opt Express ; 29(5): 7247-7260, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33726230

RESUMEN

As the key component of the image mapping spectrometer, the image mapper introduces complex image degradation in the reconstructed images, including low spatial resolution and intensity artifacts. In this paper, we propose a novel image processing method based on the convolutional neural network to perform artifact correction and super-resolution (SR) simultaneously. The proposed joint network contains two branches to handle the artifact correction task and SR task in parallel. The artifact correction module is designed to remove the artifacts in the image and the SR module is used to improve the spatial resolution. An attention fusion module is constructed to combine the features extracted by the artifact correction and SR modules. The fused features are used to reconstruct an artifact-free high-resolution image. We present extensive simulation results to demonstrate that the proposed joint method outperforms state-of-the-art methods and can be generalized to other image mapper designs. We also provide experimental results to prove the efficiency of the joint network.

4.
Sensors (Basel) ; 21(24)2021 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-34960428

RESUMEN

Microstrip transmission lines loaded with dumbbell defect-ground-structure (DB-DGS) resonators transversally oriented have been exhaustively used in microwave circuits and sensors. Typically, these structures have been modelled by means of a parallel LC resonant tank series connected to the host line. However, the inductance and capacitance of such model do not have a physical meaning, since this model is inferred by transformation of a more realistic model, where the DB-DGS resonator, described by means of a resonant tank with inductance and capacitance related to the geometry of the DB-DGS, is magnetically coupled to the host line. From parameter extraction, the circuit parameters of both models are obtained by considering the DB-DGS covered with semi-infinite materials with different dielectric constant. The extracted parameters are coherent and reveal that the general assumption of considering the simple LC resonant tank series-connected to the line to describe the DB-DGS-loaded line is reasonable with some caution. The implications on the sensitivity, when the structure is devoted to operating as a permittivity sensor, are discussed.

5.
Sensors (Basel) ; 21(4)2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33672180

RESUMEN

Planar phase-variation microwave sensors have attracted increasing interest in recent years since they combine the advantages of planar technology (including low cost, low profile, and sensor integration with the associated circuitry for post-processing and communication purposes, among others) and the possibility of operation at a single frequency (thereby reducing the costs of the associated electronics). This paper reviews and compares three different strategies for sensitivity improvement in such phase-variation sensors (devoted to material characterization). The considered approaches include line elongation (through meandering), dispersion engineering (by considering slow-wave artificial transmission lines), and reflective-mode sensors based on step-impedance open-ended lines. It is shown that unprecedented sensitivities compatible with small sensing regions are achievable with the latter approach.

6.
Opt Express ; 28(2): 2251-2262, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-32121919

RESUMEN

The image mapper plays a key role in the imaging process of the image mapping spectrometer (IMS), which is a snapshot imaging spectrometer with superiority in light throughput, temporal resolution, and compactness. In this paper, an accurate ray tracing model of the imaging units of the IMS, especially the image mapper, is presented in the form of vector operation. Based on the proposed model, the behavior of light reflection on the image mapper is analyzed thoroughly, including the precise position of the reflection point and interaction between adjacent facets. Rigorous spatial correspondence between object points and pixels on the detector is determined by tracing the chief ray of an arbitrary point in the field. The shadowing effect, which is shadowing between adjacent facets and blocking caused by the facets' side walls, is analyzed based on our model. The experimental results verify the fidelity of the model and the existence of the shadowing effect. The research is meaningful for comprehending the imaging mechanism of the IMS and facilitates the design and analysis process in the future.

7.
Sensors (Basel) ; 20(4)2020 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-32098251

RESUMEN

Temporally-spatially modulated Fourier transform imaging spectrometers (TSMFTISs) provide high-throughout-type push-broom spectrometry with both temporal and spatial modulation features. The system requires strict registration between the detector and the interferogram. However, registration errors are unavoidable and directly change the corresponding optical path difference values of the interferogram. As a result, the interferogram should be corrected before restoring the spectrum. In order to obtain the correct optical path difference (OPD) values, an online registration error correction method based on robust least-square linear fitting is presented. The model of the registration error was constructed to analyze its effect on the reconstructed spectra. Fitting methods were used to obtain correct optical path difference information. Simulations based on the proposed method were performed to determine the influence of the registration error on the restored spectra and the effectiveness of the proposed correction method. The simulation results prove that the accuracy of the recovered spectrum can be improved after correcting the interferogram deviation caused by the registration error. The experimental data were also corrected using the proposed methods.

8.
Sensors (Basel) ; 20(5)2020 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-32182916

RESUMEN

Mixed pixels commonly exist in low-resolution remote sensing images, and they are the key factors hindering the classification of land covers and high-precision mapping. To obtain the spatial information at the subpixel level, subpixel mapping (SPM) technologies, including the pixel-swapping algorithm (PSA), that use the unmixed proportions of various land covers and allocate subpixel land covers have been proposed. However, the PSA often falls into a local optimum solution. In this paper, we propose a SPM method, the PSA_MSA algorithm, that combines the PSA and the modified simulated annealing algorithm to find the global optimum solution. The modified simulated annealing algorithm swaps subpixels within a certain range to escape the local optimum solution. The method also optimizes all the mixed pixels in a randomized sequence to further improve the mapping accuracy. The experimental results demonstrate that the proposed PSA_MSA algorithm outperforms the existing PSA-based algorithms for SPM. The images with different spatial dependences are tested and the results show that the proposed algorithm is more suitable for images with high spatial autocorrelation. In addition, the effect of proportion error is analyzed by adding it in the experiments. The result shows that a higher proportion error rate leads to larger degradation of the subpixel mapping accuracy. Finally, the performance of PSA_MSA algorithm with different ranges of selection on subpixel-swapping is analyzed.

9.
Sensors (Basel) ; 20(21)2020 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-33142909

RESUMEN

In this paper, reflective-mode phase-variation sensors based on open-ended stepped-impedance transmission lines with optimized sensitivity for their use as defect detectors and dielectric constant sensors are reported. The sensitive part of the sensors consists of either a 90° high-impedance or a 180° low-impedance open-ended sensing line. To optimize the sensitivity, such a sensing line is cascaded to a 90° transmission line section with either low or high characteristic impedance, resulting in a stepped-impedance transmission line configuration. For validation purposes, two different sensors are designed and fabricated. One of the sensors is implemented by means of a 90° high impedance (85 Ω) open-ended sensing line cascaded to a 90° low impedance (15 Ω) transmission line section. The other sensor consists of a 180° 15-Ω open-ended sensing line cascaded to a 90° 85-Ω line. Sensitivity optimization for the measurement of dielectric constants in the vicinity of that corresponding to the Rogers RO4003C substrate (i.e., with dielectric constant 3.55) is carried out. The functionality as a defect detector is demonstrated by measuring the phase-variation in samples consisting of the uncoated Rogers RO4003C substrate (the reference sample) with arrays of holes of different densities.

10.
Opt Express ; 27(15): 21116-21129, 2019 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-31510194

RESUMEN

In this study, a spectral acquisition method is proposed in which axial chromatic and spherical aberrations are introduced as an error function. These aberrations lead to changes in the focal lengths as the wavelengths of the incident light changes. A coefficient matrix representing the variation in the intensity distribution of each image, formed at the focal point (the detection position) corresponding to a wavelength, is obtained by calibration. The least square method is used to reconstruct the spectrum. The numerical simulation results show that the spectral correlation coefficient and the spectral mean square error between the reconstructed spectrum and the original spectrum are 0.9997 and 0.0025, and 0.9683 and 0.0204, respectively, for the polychromatic light spectrum obtained from the mercury lamp using our experimental set-up. These results confirm the feasibility and efficiency of the proposed spectral imaging method.

11.
J Cell Mol Med ; 22(1): 123-130, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28799211

RESUMEN

The most common forms of oesophageal cancers are adenocarcinomas and squamous cell carcinoma (SCC). Although the incidence of SCC in the United States tends to be declining, the adenocarcinoma incidence caused by Barrett's oesophagus has been increasing. Oesophageal cancer is regarded as one of the most fatal malignancies with a short prognosis. Systemic manifestations of patients with PCNSL keep backward in spite of recent development of chemoradiotherapy. MicroRNAs are small non-coding RNAs that can post-transcriptionally down-regulate the expression of genes by targeting mRNAs, causing their translational repression as well as degradation. MicroRNAs exert critical functions in many malignancy-related biological processes, including cell apoptosis, metabolism, proliferation and differentiation. Many deregulated miRNAs have been identified in oesophageal adenocarcinomas, but their biological importance has not yet been fully elucidated. In this study, we review present evidence regarding the potential applications of oesophageal adenocarcinomas associated microRNAs for prognosis and diagnosis of this lethal disease.


Asunto(s)
Adenocarcinoma/genética , Neoplasias Esofágicas/genética , Perfilación de la Expresión Génica , MicroARNs/genética , Adenocarcinoma/diagnóstico , Esófago de Barrett/patología , Progresión de la Enfermedad , Neoplasias Esofágicas/diagnóstico , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/metabolismo
12.
Sensors (Basel) ; 18(4)2018 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-29587460

RESUMEN

In this paper, an analytical method to estimate the complex dielectric constant of liquids is presented. The method is based on the measurement of the transmission coefficient in an embedded microstrip line loaded with a complementary split ring resonator (CSRR), which is etched in the ground plane. From this response, the dielectric constant and loss tangent of the liquid under test (LUT) can be extracted, provided that the CSRR is surrounded by such LUT, and the liquid level extends beyond the region where the electromagnetic fields generated by the CSRR are present. For that purpose, a liquid container acting as a pool is added to the structure. The main advantage of this method, which is validated from the measurement of the complex dielectric constant of olive and castor oil, is that reference samples for calibration are not required.

13.
Appl Opt ; 56(22): 6138-6145, 2017 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-29047807

RESUMEN

The multimode light-field camera can capture spatial location and spectral and polarization characteristics of a target simultaneously. There is an aliasing effect, which causes the directly extracted image of a certain filter to include information from other filters. The reconstruction method proposed by Li (Jingzhen Li, thesis of Beihang University, 2015) can improve the accuracy of the polarization images, but the gray values still have gradient variations. In this paper, a method for reconstructing polarization images from the light-field image is proposed along with an aliasing model. Compared with the conventional direct-extraction and Li's methods, the proposed method can greatly reduce energy loss, and the accuracy of the reconstructed image increases more than fivefold.

14.
J Surg Res ; 206(2): 298-306, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27884323

RESUMEN

BACKGROUND: Acute pancreatitis (AP) is a commonly occurring and potentially life-threatening disease. Recently, toll-like receptor 4 (TLR4) has been considered as a new clue for studying the pathogenesis of AP due to its important role in inflammatory response cascade. MATERIALS AND METHODS: The aim of this study was to investigate the potential protective effect of transforming growth factor-ß-activated kinase (TAK)-242, a novel TLR4 antagonist, in taurocholate-treated mice pancreatic acinar cells. The protective effects were measured by cell viability, lactate dehydrogenase release and apoptosis, and oxidative stress was assayed by lipid peroxidation and oxidative enzyme activities. To determine the potential underlying mechanisms, mitochondrial cytochrome c release, swelling, and calcium buffering capacity were measured in isolated mitochondria, and mitochondrial biogenesis and expression of mitochondrial dynamic proteins were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: Treatment with 6-mM taurocholate significantly increased the expression of TLR4 at both mRNA and protein levels. TAK-242 markedly increased cell viability, decreased lactate dehydrogenase release, and inhibited apoptotic cell death as measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining in pancreatic acinar cells. These protective effects were accompanied by the suppressed lipid peroxidation and enhanced endogenous antioxidative enzyme activity. Using isolated and purified mitochondria from pancreatic acinar cells, we found that TAK-242 treatment also inhibited cytochrome c release into the cytoplasm, mitochondrial swelling, and decrease in mitochondrial Ca2+ buffering capacity after taurocholate exposure. In addition, TAK-242 significantly promoted mitochondrial biogenesis, as evidenced by increased mtDNA and upregulated mitochondrial transcription factors. The results of Western blot analysis showed that TAK-242 also differently regulated the expression of mitochondrial fusion and fission proteins. CONCLUSIONS: All these data strongly indicated that blocking TLR4 activity via TAK-242 exerts protective effects in an in vitro AP model, and it could be a possible strategy to improve clinical outcome in AP patients.


Asunto(s)
Células Acinares/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Pancreatitis/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Sulfonamidas/uso terapéutico , Receptor Toll-Like 4/antagonistas & inhibidores , Células Acinares/metabolismo , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/metabolismo , Western Blotting , Supervivencia Celular/efectos de los fármacos , Etiquetado Corte-Fin in Situ , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Pancreatitis/inducido químicamente , Pancreatitis/metabolismo , Sustancias Protectoras/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sulfonamidas/farmacología , Ácido Taurocólico
15.
J Insect Sci ; 16(1)2016.
Artículo en Inglés | MEDLINE | ID: mdl-27638955

RESUMEN

Aiming at learning the association between the gut microbiota and termites with different diet habits and phylogenetic positions, the gut bacteria of three populations for each of the two higher termites (wood-feeding Mironasutitermes shangchengensis and fungus-feeding Odontotermes formosanus) and two wood-feeding lower termites (Tsaitermes ampliceps and Reticulitermes flaviceps) were analyzed by high-throughput 454 pyrosequencing of 16S V1-V3 amplicons. As results, 132 bacterial genera and some unidentified operational taxonomic units within 29 phyla in the gut bacteria were detected, with Spirochaetes (11-55%), Firmicutes (7-18%), Bacteroidetes (7-31%), and Proteobacteria (8-14%) as the main phyla, and Treponema, TG5, Dysgonomonas, Tannerella, za29, Lactococcus, Pseudomonas, and SJA-88 as the common genera in all the four termites. The diversity of gut bacterial communities in the higher termite guts was significantly greater than that in the lower termites; while the gut microbiota in M. shangchengensis (wood-feeding higher termite) was more similar to those of the wood-feeding lower termites rather than that of O. formosanus (fungus-feeding higher termite), and phylum Spirochaetes and nitrogen-fixing bacteria were super-dominant in the wood-feeding termites, despite of their phylogenetic relations. This study reported for the first time the gut bacterial communities for the termites of M. shangchengensis and T. ampliceps and the comparative analyses showed that the gut microbial communities varied according to the phylogeny and the diet habits of termites.


Asunto(s)
Bacterias/genética , Microbioma Gastrointestinal/fisiología , Isópteros/microbiología , Animales , Bacterias/citología , Microbioma Gastrointestinal/genética , Filogenia , Análisis de Secuencia de ADN
16.
Sensors (Basel) ; 16(12)2016 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-27999399

RESUMEN

In this paper, several configurations of splitter/combiner microstrip sections loaded with stepped impedance resonators (SIRs) are analyzed. Such structures are useful as sensors and comparators, and the main aim of the paper is to show that the proposed configurations are useful for the optimization of sensitivity and discrimination. Specifically, for comparison purposes, i.e., to determine anomalies, abnormalities or defects of a sample under test (SUT) in comparison to a reference sample, it is shown that up to three samples can be simultaneously tested. Simple models of the proposed structures are presented, and these models are validated through electromagnetic simulation and experiment. Finally, the principle of operation is validated through a proof-of-concept demonstrator.

17.
J Food Sci Technol ; 53(10): 3685-3694, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28017983

RESUMEN

In the study, osmotically dehydrated cherry tomatoes were partially dried to water activity between 0.746 and 0.868, vacuum-packed and stored at 4-30 °C for 60 days. Adaptive neuro-fuzzy inference system (ANFIS) was utilized to predict the physicochemical and microbiological parameters of these partially dried cherry tomatoes during storage. Satisfactory accuracies were obtained when ANFIS was used to predict the lycopene and total phenolic contents, color and microbial contamination. The coefficients of determination for all the ANFIS models were higher than 0.86 and showed better performance for prediction compared with models developed by response surface methodology. Through ANFIS modeling, the effects of storage conditions on the properties of partially dried cherry tomatoes were visualized. Generally, contents of lycopene and total phenolics decreased with the increase in water activity, temperature and storage time, while aerobic plate count and number of yeasts and molds increased at high water activities and temperatures. Overall, ANFIS approach can be used as an effective tool to study the quality decrease and microbial pollution of partially dried cherry tomatoes during storage, as well as identify the suitable preservation conditions.

18.
Biochim Biophys Acta ; 1840(7): 2244-52, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24594223

RESUMEN

BACKGROUND: Cellular nucleic acid binding protein (CNBP) has been implicated in vertebrate craniofacial development and in myotonic dystrophy type 2 (DM2) and sporadic inclusion body myositis (sIBM) human diseases by controlling cell proliferation and survival to mediate neural crest expansion. CNBP has been found to bind single-stranded nucleic acid and promote rearrangements of nucleic acid secondary structure in an ATP-independent manner, acting as a nucleic acid chaperone. METHODS: A variety of methods were used, including cell viability assays, wound-scratch assays, chemotaxis assays, invasion assays, circular dichroic (CD) spectroscopy, NMR spectroscopy, chromatin immunoprecipitation, expression and purification of recombinant human CNBP, electrophoretic mobility shift assay (EMSA), surface plasmon resonance (SPR), fluorescence resonance energy transfer (FRET) analyses, luciferase reporter assay, Western blotting, and isothermal titration calorimetry (ITC). RESULTS: Up-regulation of CNBP induced human fibrosarcoma cell death and suppressed fibrosarcoma cell motility and invasiveness. It was found that CNBP transcriptionally down-regulated the expression of heterogeneous ribonucleoprotein K (hnRNP K) through its conversion of a G-rich sequence into G-quadruplex in the promoter of hnRNP K. G-quadruplex stabilizing ligand tetra-(N-methyl-4-pyridyl) porphyrin (TMPyP4) could interact with and stabilize the G-quadruplex, resulting in downregulation of hnRNP K transcription. CONCLUSIONS: CNBP overexpression caused increase of cell death and suppression of cell metastasis through its induction of G-quadruplex formation in the promoter of hnRNP K resulting in hnRNP K down-regulation. GENERAL SIGNIFICANCE: The present result provided a new solution for controlling hnRNP K expression, which should shed light on new anticancer drug design and development.


Asunto(s)
Fibrosarcoma/genética , G-Cuádruplex , Ribonucleoproteína Heterogénea-Nuclear Grupo K/genética , Proteínas de Unión al ARN/genética , Muerte Celular/genética , Línea Celular Tumoral , Supervivencia Celular/genética , Inmunoprecipitación de Cromatina , Fibrosarcoma/patología , Transferencia Resonante de Energía de Fluorescencia , Regulación Neoplásica de la Expresión Génica/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo K/biosíntesis , Humanos , Metástasis de la Neoplasia , Ácidos Nucleicos/genética , Regiones Promotoras Genéticas , Proteínas de Unión al ARN/metabolismo
19.
Biochim Biophys Acta ; 1840(3): 1051-62, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24246954

RESUMEN

BACKGROUND: Farnesyl pyrophosphate synthase (FPPS) is a key regulatory enzyme in the biosynthesis of cholesterol and in the post-translational modification of signaling proteins. It has been reported that non-bisphosphonate FPPS inhibitors targeting its allosteric binding pocket are potentially important for the development of promising anti-cancer drugs. METHODS: The following methods were used: organic syntheses of non-bisphosphonate quinoline derivatives, enzyme inhibition studies, fluorescence titration assays, synergistic effect studies of quinoline derivatives with zoledronate, ITC studies for the binding of FPPS with quinoline derivatives, NMR-based HAP binding assays, molecular modeling studies, fluorescence imaging assay and MTT assays. RESULTS: We report our syntheses of a series of quinoline derivatives as new FPPS inhibitors possibly targeting the allosteric site of the enzyme. Compound 6b showed potent inhibition to FPPS without significant hydroxyapatite binding affinity. The compound showed synergistic inhibitory effect with active-site inhibitor zoledronate. ITC experiment confirmed the good binding effect of compound 6b to FPPS, and further indicated the binding ratio of 1:1. Molecular modeling studies showed that 6b could possibly bind to the allosteric binding pocket of the enzyme. The fluorescence microscopy indicated that these compounds could get into cancer cells. CONCLUSIONS: Our results showed that quinoline derivative 6b could become a new lead compound for further optimization for cancer treatment. GENERAL SIGNIFICANCE: The traditional FPPS active-site inhibitors bisphosphonates show poor membrane permeability to tumor cells, due to their strong polarity. The development of new non-bisphosphonate FPPS inhibitors with good cell membrane permeability is potentially important.


Asunto(s)
Inhibidores Enzimáticos/síntesis química , Geraniltranstransferasa/antagonistas & inhibidores , Quinolinas/síntesis química , Secuencia de Aminoácidos , Difosfonatos/farmacología , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Imidazoles/farmacología , Microscopía Fluorescente , Modelos Moleculares , Datos de Secuencia Molecular , Neoplasias/tratamiento farmacológico , Quinolinas/farmacología , Quinolinas/uso terapéutico , Ácido Zoledrónico
20.
Biochim Biophys Acta ; 1840(10): 3123-30, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25018006

RESUMEN

BACKGROUND: Accelerated proliferation of solid tumor and hematologic cancer cells is related to accelerated transcription of ribosomal DNA by the RNA polymerase I to produce elevated level of ribosomal RNA. Therefore, down-regulation of RNA polymerase I transcription in cancer cells is an important anticancer therapeutic strategy. METHODS: A variety of methods were used, including cloning, expression and purification of protein, electrophoretic mobility shift assay (EMSA), circular dichroic (CD) spectroscopy, CD-melting, isothermal titration calorimetry (ITC), chromatin immunoprecipitation (Ch-IP), RNA interference, RT-PCR, Western blot, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell assay. RESULTS: Our results showed that 2,4-disubstituted quinazoline derivative Sysu12d could down-regulate c-myc through stabilization of c-myc promoter G-quadruplex, resulting in down-regulation of nucleolin expression. Sysu12d could also disrupt nucleolin/G-quadruplex complex. Both of the above contributed to the down-regulation of ribosomal RNA synthesis, followed by activation of p53 and then cancer cell apoptosis. CONCLUSIONS: These mechanistic studies set up the basis for further development of Sysu12d as a new type of lead compound for cancer treatment. GENERAL SIGNIFICANCE: 2,4-Disubstituted quinazoline derivatives may have multi-functional effect for cancer treatment.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Quinazolinas/farmacología , Antineoplásicos/química , Regulación hacia Abajo/efectos de los fármacos , Células HEK293 , Células HL-60 , Células HeLa , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Quinazolinas/química , ARN Neoplásico/biosíntesis , ARN Ribosómico/biosíntesis , Proteína p53 Supresora de Tumor/metabolismo
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