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1.
Bioorg Chem ; 148: 107434, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38744168

RESUMEN

Azaphilones represent a particular group of fascinating pigments from fungal source, with easier industrialization and lower cost than the traditional plant-derived pigments, and they also display a wide range of pharmacological activities. Herein, 28 azaphilone analogs, including 12 new ones, were obtained from the fermentation culture of a marine fungus Penicillium sclerotium UJNMF 0503. Their structures were elucidated by MS, NMR and ECD analyses, together with NMR and ECD calculations and biogenetic considerations. Among them, compounds 1 and 2 feature an unusual natural benzo[d][1,3]dioxepine ring embedded with an orthoformate unit, while 3 and 4 represent the first azaphilone examples incorporating a novel rearranged 5/6 bicyclic core and a tetrahydropyran ring on the side chain, respectively. Our bioassays revealed that half of the isolates exhibited neuroprotective potential against H2O2-induced injury on RSC96 cells, while compound 13 displayed the best rescuing capacity toward the cell viability by blocking cellular apoptosis, which was likely achieved by upregulating the PI3K/Akt signaling pathway.


Asunto(s)
Apoptosis , Benzopiranos , Relación Dosis-Respuesta a Droga , Peróxido de Hidrógeno , Fármacos Neuroprotectores , Penicillium , Fosfatidilinositol 3-Quinasas , Pigmentos Biológicos , Proteínas Proto-Oncogénicas c-akt , Apoptosis/efectos de los fármacos , Penicillium/química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasas/metabolismo , Pigmentos Biológicos/farmacología , Pigmentos Biológicos/química , Pigmentos Biológicos/aislamiento & purificación , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/antagonistas & inhibidores , Estructura Molecular , Benzopiranos/farmacología , Benzopiranos/química , Benzopiranos/aislamiento & purificación , Relación Estructura-Actividad , Animales , Supervivencia Celular/efectos de los fármacos , Ratas , Transducción de Señal/efectos de los fármacos
2.
Opt Express ; 31(26): 44703-44719, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38178534

RESUMEN

Bound states in the continuum (BICs) with infinite quality factor (Q-factor) and significant field enhancement pave the way for realizing highly sensitive optical sensors with enhanced light-matter interactions on the nanoscale. However, current optical sensing methods are difficult to discriminate between isotropic and anisotropic media from resonance spectral lines, resulting in optical sensing methods still being limited to isotropic media. In this work, we demonstrate that BICs can be realized by modulating the period of structural units to convert BICs to QBICs without changing their space group symmetry, and propose a polarization-independent metasurfaces-based realization of highly sensitive refractive index sensors for isotropic and anisotropic media as well as discrimination. We propose a metasurface of tetrameric silicon nanoboxes with C4 symmetry as structural units to achieve the conversion of BICs to QBICs by modulating the period of structural units without changing the geometry of the structure. Two QBICs modes dominated by electric toroidal dipole and magnetic toroidal dipole are identified by multipolar decomposition and electromagnetic distribution calculations. Meanwhile, we realize the refractive index detection and resolution of isotropic and anisotropic media based on polarization-independent metasurfaces combined with isotropic and anisotropic media layers. Our work provides what we believe to be a new method for realizing the fast resolution and refractive index optical sensing of isotropic and anisotropic media, and offers new ideas for the design and application of polarization-independent metasurfaces.

3.
Mar Drugs ; 21(11)2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37999417

RESUMEN

In our chemical investigation into Penicillium sp. UJNMF0740 derived from mangrove sediment, fourteen indole diterpene analogs, including four new ones, are purified by multiple chromatographic separation methods, with their structures being elucidated by the analyses of NMR, HR-ESIMS, and ECD data. The antibacterial and neuroprotective effects of these isolates were examined, and only compounds 6 and 9 exhibited weak antibacterial activity, while compounds 5, 8, and 10 showed protective effects against the injury of PC12 cells induced by 6-hydroxydopamine (6-OHDA). Additionally, compound 5 could suppress the apoptosis and production of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells as well as trigger the phosphorylation of PI3K and Akt. Taken together, our work enriches the structural diversity of indole diterpenes and hints that compounds of this skeleton can repress the 6-OHDA-induced apoptosis of PC12 cells via regulating the PI3K/Akt signaling pathway, which provides evidence for the future utilization of this fascinating class of molecules as potential neuroprotective agents.


Asunto(s)
Diterpenos , Fármacos Neuroprotectores , Penicillium , Ratas , Animales , Células PC12 , Proteínas Proto-Oncogénicas c-akt/metabolismo , Oxidopamina/toxicidad , Fosfatidilinositol 3-Quinasas/metabolismo , Penicillium/química , Especies Reactivas de Oxígeno/metabolismo , Apoptosis , Diterpenos/farmacología , Diterpenos/química , Indoles/farmacología , Indoles/química , Antibacterianos/farmacología , Fármacos Neuroprotectores/farmacología
4.
Appl Opt ; 61(10): 2675-2682, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35471338

RESUMEN

We propose, to the best of our knowledge, a novel kind of tunable liquid crystal core refractive index (RI) sensor based on photonic crystal fiber (PCF) covered with a nanoring gold film. The finite element method is used to discuss and analyze the sensing performance of the RI sensor. Gold is used as the excitation material for surface plasmon resonance, and a gold nanoring is embedded around the first cladding of the PCF. The liquid analytes penetrate the outermost layer of the cladding, and the central hole is filled with liquid crystal E7. Complete coupling and incomplete coupling are excited as the analyte RI increases, and the resonance strength of complete coupling is stronger than that of incomplete coupling. It can be proved by calculation that at different wavelengths, resonant coupling of fifth-order and sixth-order surface plasmon polaritons is obtained. The RI of liquid analytes ranges from 1.405 to 1.445. The diameters of the liquid crystal cores are 0.2, 0.4, 0.6, and 0.8 µm; their average sensitivities are 10700, 10566, 10167, and 9166 nm/RIU; and the linear fitting constants are 0.98025, 0.97387, 0.96597, and 0.95507, respectively. In short, the RI sensor has the advantages of tunability, wide range, and high sensitivity, and is expected to be applied in various fields.

5.
Appl Opt ; 61(24): 7225-7230, 2022 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-36256343

RESUMEN

Based on double U-groove photonic crystal fiber (PCF), a surface plasmon resonance sensor with dual parametric detection of temperature and refractive index is proposed. The birefringence of PCF is increased by using germanium ions doped in the core and introducing U-shaped notches on both sides of the D-shaped fiber. The polished surface of the PCF is coated with gold film and PDMS as a temperature sensing channel, and the U-shaped groove is coated with gold film as a refractive index sensing channel. Through the design of the sensor, it is finally possible to achieve independent measurement of the two parameters. The sensor has a maximum wavelength sensitivity of 4715 nm/RIU in the analyte refractive index range of 1.32-1.4, and maximum wavelength sensitivity of 18 nm/°C in the ambient temperature range of -30∘C-50∘C. The proposed sensor has broad application prospects in scenarios such as blood analysis, DNA hybridization analysis, and microenvironmental cell interactions.


Asunto(s)
Germanio , Refractometría , Resonancia por Plasmón de Superficie , Temperatura , Oro , ADN
6.
J Surg Oncol ; 123 Suppl 1: S81-S87, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33740257

RESUMEN

BACKGROUND AND OBJECTIVES: To investigate the effects of different suture reinforcement methods for anastomotic leakage and other postoperative complications after the use of a laparoscopic double stapling technique (DST). METHODS: We collected the data of 124 patients who underwent laparoscopic radical resection of colorectal cancer from July 2017 to September 2018 at our institution. Patients were divided into three groups according to the suture reinforcement methods: intermittent, continuous suture reinforcement, and non-reinforcement (n = 41, 41, and 42, respectively). One-way analysis of variance, χ2 , Fisher's exact, and nonparametric tests were used for statistical analysis. RESULTS: Among the 124 patients, there were no statistically significant differences in operation times, intraoperative blood loss, postoperative hospital stays and recovery of bowel movement. Nine patients were diagnosed with anastomotic leakage (AL). The incidences of serious AL in the intermittent and continuous suture reinforcement groups were lower than that in the control group, with lower reoperation rate, shorter average lengths of stay and lower treatment costs of two experimental groups. CONCLUSION: Intermittent and continuous sutures after laparoscopic DST is effective, safe, and feasible on anastomotic leakage prevention. These procedures could be popularized in rectal surgery on patients with high risk of AL.


Asunto(s)
Anastomosis Quirúrgica/métodos , Fuga Anastomótica/prevención & control , Neoplasias Colorrectales/cirugía , Anastomosis Quirúrgica/efectos adversos , Pérdida de Sangre Quirúrgica , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
7.
Appl Opt ; 57(26): 7591-7599, 2018 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-30461826

RESUMEN

In order to overcome the limitations in range of traditional prism structure surface plasmon resonance (SPR) single-point sensor measurement, a symmetric bimetallic film SPR multi-sensor structure is proposed. Based on this, the dual-channel sensing attenuation mechanism of SPR in gold and silver composite film and the improvement of sensing characteristics were studied. By optimizing the characteristics such as material and thickness, a wider range of dual-channel distributed sensing is realized. Using a He-Ne laser (632.8 nm) as the reference light source, prism-excited symmetric SPR sensing was studied theoretically for a symmetrical metal-clad dielectric waveguide using thin-film optics theory. The influence of the angle of incidence of the light source and the thickness of the dielectric layer on the performance of SPR dual formant sensing is explained. The finite-difference time-domain method was used for the simulation calculation for various thicknesses and compositions of the symmetric combined layer, resulting in the choice of silver (30 nm) and gold (10 nm). When the incident angle was 78 deg, the quality factor reached 5960, showing an excellent resonance sensing effect. The sensitivity reached a maximum of 5.25×10-5 RIU when testing the water content of an aqueous solution of honey, which proves the feasibility and practicality of the structure design. The structure improves the theoretical basis for designing an SPR multi-channel distributed sensing system, which can greatly reduce the cost of biochemical detection and significantly increase the detection efficiency.

8.
Mar Drugs ; 16(10)2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-30275406

RESUMEN

Four new meroterpenoids 1⁻4 and four new isocoumarinoids 5⁻8, along with five known isocoumarinoids (9⁻13), were isolated from the fungus Myrothecium sp. OUCMDZ-2784 associated with the salt-resistant medicinal plant, Apocynum venetum (Apocynaceae). Their structures were elucidated by means of spectroscopic analysis, X-ray crystallography, ECD spectra and quantum chemical calculations. Compounds 1⁻5, 7, 9 and 10 showed weak α-glucosidase inhibition with the IC50 values of 0.50, 0.66, 0.058, 0.20, 0.32, 0.036, 0.026 and 0.37 mM, respectively.


Asunto(s)
Apocynum/química , Hongos/química , Terpenos/química , Cristalografía por Rayos X/métodos , Inhibidores de Glicósido Hidrolasas/química
9.
J Asian Nat Prod Res ; 18(1): 92-115, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26880598

RESUMEN

Marine micro-organisms have been proven to be a major source of marine natural products (MNPs) in recent years, in which filamentous fungi are a vital source of bioactive natural products for their large metagenomes and more complex genetic backgrounds. This review highlights the 390 new MNPs from marine-derived Penicillium fungi during 1991 to 2014. These new MNPs are categorized based on the environment sources of the fungal hosts and their bioactivities are summarized.


Asunto(s)
Productos Biológicos/aislamiento & purificación , Penicillium/química , Productos Biológicos/química , Biología Marina , Estructura Molecular
10.
Wei Sheng Wu Xue Bao ; 56(3): 331-62, 2016 Mar 04.
Artículo en Zh | MEDLINE | ID: mdl-27382779

RESUMEN

Marine-derived fungi were the main source of marine microbial natural products (NPs) due to their complex genetic background, chemodiversity and high yield of NPs. According to our previous survey for marine microbial NPs from 2010 to 2013, Aspergillus fungi have received the most of attention among all the marine-derived fungi, which accounted for 31% NPs of the marine fungal origins. This paper reviewed the sources, chemical structures and bioactivites of all the 512 new marine NPs of Aspergillus fungal origins from 1992 to 2014. These marine NPs have diverse chemical structures including polyketides, fatty acids, sterols and terpenoids, alkaloids, peptides, and so on, 36% of which displayed bioactivities such as cytotoxicity, antimicrobial activity, antioxidant and insecticidal activity. Nitrogen compounds are the major secondary metabolites accounting for 52% NPs from the marine-derived Aspergillus fungi. Nitrogen compounds are also the class with the highest ratio of bioactive compounds, 40% of which are bioactive. Plinabulin, a dehydrodiketopiperazine derivative of halimide had been ended its phase II trial and has received its phase III study from the third quarter of 2015 for the treatment of advanced, metastatic non-small cell lung cancer.


Asunto(s)
Aspergillus/metabolismo , Productos Biológicos/metabolismo , Agua de Mar/microbiología , Animales , Antibacterianos/química , Antibacterianos/metabolismo , Aspergillus/genética , Aspergillus/aislamiento & purificación , Productos Biológicos/química , Humanos , Estructura Molecular
11.
PLoS One ; 19(9): e0310131, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39264965

RESUMEN

The article explains the economic dynamics of the sports industry with adoption of deep learning algorithms and data mining methodology. Despite outstanding improvements in research of sports industry, a significant gap prevails with regard to proper quantification of economic benefits of this industry. Therefore, the current research is an attempt to filling this gap by proposing a specific economic model for the sports sector. This paper examines the data of sports industry covering the time span of 2012 to 2022 by using data mining technology for quantitative analyses. Deep learning algorithms and data mining techniques transform the gained information from sports industry databases into sophisticated economic models. The developed model then makes the efficient analysis of diverse datasets for underlying patterns and insights, crucial in realizing the economic trajectory of the industry. The findings of the study reveal the importance of sports industry for economic growth of China. Moreover, the application of deep learning algorithm highlights the importance of continuous learning and training on the economic data from the sports industry. It is, therefore, an entirely novel approach to build up an economic simulation framework using deep learning and data mining, tailored to the intricate dynamics of the sports industry.


Asunto(s)
Minería de Datos , Modelos Económicos , Deportes , China , Humanos , Deportes/economía , Industrias/economía , Algoritmos , Aprendizaje Profundo
12.
Sci Rep ; 14(1): 15857, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982213

RESUMEN

According to the atmospheric scattering model (ASM), the object signal's attenuation diminishes exponentially as the imaging distance increases. This imposes limitations on ASM-based methods in situations where the scattering medium one wish to look through is inhomogeneous. Here, we extend ASM by taking into account the spatial variation of the medium density, and propose a two-step method for imaging through inhomogeneous scattering media. In the first step, the proposed method eliminates the direct current component of the scattered pattern by subscribing to the estimated global distribution (background). In the second step, it eliminates the randomized components of the scattered light by using threshold truncation, followed by the histogram equalization to further enhance the contrast. Outdoor experiments were carried out to demonstrate the proposed method.

13.
Light Sci Appl ; 13(1): 194, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39152120

RESUMEN

Imaging through dynamic scattering media is one of the most challenging yet fascinating problems in optics, with applications spanning from biological detection to remote sensing. In this study, we propose a comprehensive learning-based technique that facilitates real-time, non-invasive, incoherent imaging of real-world objects through dense and dynamic scattering media. We conduct extensive experiments, demonstrating the capability of our technique to see through turbid water and natural fog. The experimental results indicate that the proposed technique surpasses existing approaches in numerous aspects and holds significant potential for imaging applications across a broad spectrum of disciplines.

14.
Materials (Basel) ; 16(20)2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37895730

RESUMEN

High-quality milling of carbon fiber reinforced polymer (CFRP) composites is of great importance for the high-performance manufacturing of structures made of this hard-to-machine material. In this paper, a multiscale finite element (FE) model, considering the thermal-mechanical coupling effect, was developed to simulate the milling process and reveal its material removal mechanism. The corresponding milling experiments were conducted to validate the simulated cutting forces and temperature, which were in good agreement with the experiment results. In the macroscale model, the Hashin failure criteria were used to estimate the failure of the composites. In the microscale model, the fibers, matrix, and the fiber-matrix interface were modeled separately, to investigate the mechanisms of material removal behavior during milling, among fiber breakage, matrix cracking, and fiber-matrix debonding. Based on the macroscale numerical and experimental results, the higher cutting speed was demonstrated to improve the surface quality of CFRP milling. According to the results from the microscale model, the material removal mechanism varies depending on the orientation of the fibers and can be divided into four stages. The outcome of this work provides guidelines to further investigate optimal manufacturing parameters for the milling of CFRP composites and their cutting mechanisms.

15.
Neurocomputing (Amst) ; 92: 156-169, 2012 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-22844185

RESUMEN

In the present paper, we use data mining methods to address two challenges in the sharing and integration of data from electrophysiological (ERP) studies of human brain function. The first challenge, ERP metric matching, is to identify correspondences among distinct summary features ("metrics") in ERP datasets from different research labs. The second challenge, ERP pattern matching, is to align the ERP patterns or "components" in these datasets. We address both challenges within a unified framework. The utility of this framework is illustrated in a series of experiments using ERP datasets that are designed to simulate heterogeneities from three sources: (a) different groups of subjects with distinct simulated patterns of brain activity, (b) different measurement methods, i.e, alternative spatial and temporal metrics, and (c) different patterns, reflecting the use of alternative pattern analysis techniques. Unlike real ERP data, the simulated data are derived from known source patterns, providing a gold standard for evaluation of the proposed matching methods. Using this approach, we demonstrate that the proposed method outperforms well-known existing methods, because it utilizes cluster-based structure and thus achieves finer-grained representation of the multidimensional (spatial and temporal) attributes of ERP data.

16.
Micromachines (Basel) ; 13(6)2022 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-35744440

RESUMEN

In this work, a surface plasmon resonance (SPR) sensor based on a D-shaped germanium-doped photonic crystal fiber (PCF) is proposed. The finite element method (FEM) is introduced to analyze the structure parameters, such as germanium-doped concentration, lattice pitch, and air hole size. In addition, the coupling properties and birefringence properties of PCF are also studied. The computer simulation results indicate that two different surface plasmon polariton (SPP) coupling modes are produced on the polished surface, covered with metal film, when the analyte refractive index (RI) is 1.34. Then, with the increase of the RI, the incompleteness of one of the coupling modes will be transformed into the complete coupling. The effect of germanium concentration on the birefringence is also analyzed. It has an optimal wavelength sensitivity of 5600 nm/RIU when the RI is 1.37. This sensor exhibits a maximum birefringence of 1.06 × 10-2 and a resolution of 1.78 × 10-5 RIU with high linearity.

17.
Org Lett ; 24(37): 6750-6754, 2022 09 23.
Artículo en Inglés | MEDLINE | ID: mdl-36073973

RESUMEN

Pyridapeptide A (1), a cyclohexapeptide containing hexahydropyridazine-3-carboxylic acid (HPDA), 5-hydroxytetrahydropyridazine-3-carboxylic acid (γ-OH-TPDA), and (2S,3R,4E,6E)-2-amino-3-hydroxy-8-methylnona-4,6-dienoic acid residues, and its four glycopeptides, pyridapeptides B-E (2-5, respectively), were isolated from the fermentation broth of the marine sponge-derived Streptomyces sp. OUCMDZ-4539. Their structures were determined on the basis of spectroscopic analysis and chemical methods. Pyridapeptides B-E have one or more 2,3,6-trideoxyhexose sugar units glycosylated at the γ-OH-TPDA residue. The biosynthetic pathways were proposed on the basis of gene cluster analysis. Compounds 4 and 5, containing four sugar groups, displayed significant antiproliferative activity against five human cancer cell lines (PC9, MKN45, HepG2, HCT-116, and K562).


Asunto(s)
Poríferos , Streptomyces , Animales , Ácidos Carboxílicos , Glicopéptidos , Glicósidos/farmacología , Humanos , Estructura Molecular , Streptomyces/química , Azúcares
18.
Pharm Res ; 28(12): 3101-4, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21879385

RESUMEN

Identification and characterization of the important roles microRNAs (miRNAs) perform in human cancer is an increasingly active research area. Unfortunately, prediction of miRNA target genes remains a challenging task to cancer researchers. Current processes are time-consuming, error-prone, and subject to biologists' limited prior knowledge. Therefore, we propose a domain-specific knowledge base built upon Ontology for MicroRNA Targets (OMIT) to facilitate knowledge acquisition in miRNA target gene prediction. We describe the ontology design, semantic annotation and data integration, and user-friendly interface and conclude that the OMIT system can assist biologists in unraveling the important roles of miRNAs in human cancer. Thus, it will help clinicians make sound decisions when treating cancer patients.


Asunto(s)
Bases del Conocimiento , MicroARNs/genética , Neoplasias/genética , Humanos , Programas Informáticos , Interfaz Usuario-Computador
19.
Cancer Manag Res ; 13: 4567-4578, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34135633

RESUMEN

BACKGROUND: Circulating tumor cells (CTCs) are cells that have been shed into the vasculature from a primary tumor and circulate in the bloodstream. It has been suggested that detecting CTCs could help the clinician to detect early metastasis or recurrence more effectively. This trial sets out to assess the detection and clinical value of CTCs as an assisted prognostic marker in patients with colon cancer and rectal cancer. METHODS: A prospective cohort of patients with colorectal cancer (CRC) was enrolled from July 2015 to February 2018 in Shanghai Minimally Invasive Surgery Center, Shanghai, China. In this study, 149 patients with CRC were enrolled and underwent surgical treatment. There were 79 cases of colon cancer and 70 cases of rectal cancer, including 93 males and 56 females. To investigate the correlativity and clinical value of CTCs, the patients were statistically analyzed in different subgroups: colon cancer group vs rectal cancer group, and left hemicolon cancer group vs right hemicolon cancer group. RESULTS: The results of analysis comparing CTC counts and clinical pathological features in colon and rectal cancer indicated that with increased tumor stage, the number of CTCs also increased, with significant statistical differences. CTC counts in patients with colon and rectal cancer showed positive correlations with TNM staging (P=0.001, 0.013, respectively), T staging (P=0.021, 0.001), N staging (P=0.014, 0.035) and M staging (P=0.018, 0.203). Detection of serum biomarkers in CTC-positive and CTC-negative groups indicated a significantly increasing expression in the CTC-positive group. To confirm the correlations between CTCs and histoembryological differences, analysis was conducted with the patients in two subgroups: left hemicolon cancer group and right hemicolon cancer group. The results showed that the positive rate of CTCs increased in both groups with the increase in tumor stage. The survival analysis indicated that there was a steep gradient in survival in the follow-up period, particularly in the CTC-positive group (P=0.000). Risk assessment curves showed that the change escalated more rapidly in the CTC-positive group. Furthermore, with the increase in T stage, changes in the survival curve and risk curve escalated more rapidly in the CTC-positive group. CONCLUSION: It was confirmed that in the left hemicolon cancer group, a much higher coincidence rate could be found on CTC-positive rate and clinicopathological features, than in the right hemicolon cancer group. The sensitivity of CTCs may be related to the histoembryological location of the tumor, lymphatic metastasis and the depth of infiltration. Monitoring CTCs may have value in evaluating clinical staging and estimating clinical prognosis.

20.
Chem Biol Drug Des ; 97(1): 184-195, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32767850

RESUMEN

Ecdysteroids initiate the molting process in insects by binding to the ecdysone receptor (EcR), which is a promising target for identifying insect growth regulators. This paper presents an in silico/in vitro screening procedure for identifying new EcR ligands. The three-step virtual screening procedure uses a three-dimensional pharmacophore model, docking and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) rescoring routine. A novel hit (VS14) with good binding activity against Plutella xylostella EcR was identified from a library of over 200,000 chemicals. Subsequently, the 1-phenyl-4-cyano-5-aminopyrazole scaffold and twelve EcR ligands were synthesized. Their IC50 values against Plutella xylostella EcR ranged from 0.64 to 23.21 µm. Furthermore, a preliminary analysis of the structure-activity relationship for novel scaffolds provided a basis for designing new ligands with improved activity.


Asunto(s)
Simulación de Dinámica Molecular , Pirazoles/química , Receptores de Esteroides/química , Animales , Sitios de Unión , Insecticidas/química , Insecticidas/metabolismo , Insecticidas/farmacología , Larva/efectos de los fármacos , Ligandos , Mariposas Nocturnas/crecimiento & desarrollo , Mariposas Nocturnas/metabolismo , Unión Proteica , Pirazoles/metabolismo , Receptores de Esteroides/metabolismo , Relación Estructura-Actividad
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