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1.
Biochem Biophys Res Commun ; 681: 249-270, 2023 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-37793311

RESUMEN

Chalcones have a long history of being used for many medical purposes. These are the most prestigious scaffolds in medicine. The potential of Millepachine and its derivatives to treat various malignancies has been demonstrated in this review. The anticancer effects of Millepachine and its derivatives on ovarian cancer, hepatocellular carcinoma, breast, liver, colon, cervical, prostate, stomach, and gliomas are highlighted in the current review. Several genes that are crucial in reducing the severity of the disease have been altered by these substances. They mainly work by preventing tubulin polymerizing. They also exhibit apoptosis and cell cycle arrest at the G2/M phase. Additionally, these compounds inhibit invasion and migration and have antiproliferative effects. Preclinical studies have shown that Millepachine and its derivatives offer exceptional potential for treating a number of cancers. These results need to be confirmed in clinical research in order to develop viable cancer therapies.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Chalconas , Neoplasias Hepáticas , Masculino , Humanos , Chalconas/farmacología , Chalconas/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Tubulina (Proteína)/metabolismo , Proliferación Celular , Línea Celular Tumoral , Relación Estructura-Actividad , Moduladores de Tubulina/farmacología , Ensayos de Selección de Medicamentos Antitumorales
2.
Front Cell Infect Microbiol ; 13: 1076251, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36844409

RESUMEN

Orthopoxvirus is one of the most notorious genus amongst the Poxviridae family. Monkeypox (MP) is a zoonotic disease that has been spreading throughout Africa. The spread is global, and incidence rates are increasing daily. The spread of the virus is rapid due to human-to-human and animals-to-human transmission. World Health Organization (WHO) has declared monkeypox virus (MPV) as a global health emergency. Since treatment options are limited, it is essential to know the modes of transmission and symptoms to stop disease spread. The information from host-virus interactions revealed significantly expressed genes that are important for the progression of the MP infection. In this review, we highlighted the MP virus structure, transmission modes, and available therapeutic options. Furthermore, this review provides insights for the scientific community to extend their research work in this field.


Asunto(s)
Monkeypox virus , Mpox , Animales , Humanos , Mpox/epidemiología , Zoonosis , África , Interacciones Microbiota-Huesped
3.
Molecules ; 27(4)2022 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-35209009

RESUMEN

Widely used in global households, fenugreek is well known for its culinary and medicinal uses. The various reported medicinal properties of fenugreek are by virtue of the different natural phytochemicals present in it. Regarded as a promising target, interleukin 2 receptor subunit alpha (IL2Rα) has been shown to influence immune responses. In the present research, using in silico techniques, we have demonstrated the potential IL2Rα binding properties of three polyphenol stilbenes (desoxyrhaponticin, rhaponticin, rhapontigenin) from fenugreek. As the first step, molecular docking was performed to assess the binding potential of the fenugreek phytochemicals with IL2Rα. All three phytochemicals demonstrated interactions with active site residues. To confirm the reliability of our molecular docking results, 100 ns molecular dynamics simulations studies were undertaken. As discerned by the RMSD and RMSF analyses, IL2Rα in complex with the desoxyrhaponticin, rhaponticin, and rhapontigenin indicated stability. The RMSD analysis of the phytochemicals alone also demonstrated no significant structural changes. Based on the stable molecular interactions and comparatively slightly better MM/PBSA binding free energy, rhaponticin seems promising. Additionally, ADMET analysis performed for the stilbenes indicated that all of them obey the ADMET rules. Our computational study thus supports further in vitro IL2Rα binding studies on these stilbenes, especially rhaponticin.


Asunto(s)
Subunidad alfa del Receptor de Interleucina-2/química , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Extractos Vegetales/química , Polifenoles/química , Estilbenos/química , Trigonella/química , Sitios de Unión , Fenómenos Químicos , Enlace de Hidrógeno , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Estructura Molecular , Fitoquímicos/química , Extractos Vegetales/farmacología , Polifenoles/farmacología , Unión Proteica , Estilbenos/farmacología
4.
Biomedicines ; 9(9)2021 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-34572383

RESUMEN

The cyclin-dependent kinase 7 (CDK7) plays a crucial role in regulating the cell cycle and RNA polymerase-based transcription. Overexpression of this kinase is linked with various cancers in humans due to its dual involvement in cell development. Furthermore, emerging evidence has revealed that inhibiting CDK7 has anti-cancer effects, driving the development of novel and more cost-effective inhibitors with enhanced selectivity for CDK7 over other CDKs. In the present investigation, a pharmacophore-based approach was utilized to identify potential hit compounds against CDK7. The generated pharmacophore models were validated and used as 3D queries to screen 55,578 natural drug-like compounds. The obtained compounds were then subjected to molecular docking and molecular dynamics simulations to predict their binding mode with CDK7. The molecular dynamics simulation trajectories were subsequently used to calculate binding affinity, revealing four hits-ZINC20392430, SN00112175, SN00004718, and SN00262261-having a better binding affinity towards CDK7 than the reference inhibitors (CT7001 and THZ1). The binding mode analysis displayed hydrogen bond interactions with the hinge region residues Met94 and Glu95, DFG motif residue Asp155, ATP-binding site residues Thr96, Asp97, and Gln141, and quintessential residue outside the kinase domain, Cys312 of CDK7. The in silico selectivity of the hits was further checked by docking with CDK2, the close homolog structure of CDK7. Additionally, the detailed pharmacokinetic properties were predicted, revealing that our hits have better properties than established CDK7 inhibitors CT7001 and THZ1. Hence, we argue that proposed hits may be crucial against CDK7-related malignancies.

5.
Ann Clin Microbiol Antimicrob ; 17(1): 16, 2018 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-29609660

RESUMEN

BACKGROUND: Antibiotic resistance is a defense mechanism, harbored by pathogens to survive under unfavorable conditions. Among several antibiotic resistant microbial consortium, Staphylococcus aureus is one of the most havoc microorganisms. Staphylococcus aureus encodes a unique enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (SaHPPK), against which, none of existing antibiotics have been reported. METHODS: Computational approaches have been instrumental in designing and discovering new drugs for several diseases. The present study highlights the impact of ginger phytochemicals on Staphylococcus aureus SaHPPK. Herein, we have retrieved eight ginger phytochemicals from published literature and investigated their inhibitory interactions with SaHPPK. To authenticate our work, the investigation proceeds considering the known antibiotics alongside the phytochemicals. Molecular docking was performed employing GOLD and CDOCKER. The compounds with the highest dock score from both the docking programmes were tested for their inhibitory capability in vitro. The binding conformations that were seated within the binding pocket showing strong interactions with the active sites residues rendered by highest dock score were forwarded towards the molecular dynamic (MD) simulation analysis. RESULTS: Based on molecular dock scores, molecular interaction with catalytic active residues and MD simulations studies, two ginger phytochemicals, gingerenone-A and shogaol have been proposed as candidate inhibitors against Staphylococcus aureus. They have demonstrated higher dock scores than the known antibiotics and have represented interactions with the key residues within the active site. Furthermore, these compounds have rendered considerable inhibitory activity when tested in vitro. Additionally, their superiority was corroborated by stable MD results conducted for 100 ns employing GROMACS package. CONCLUSIONS: Finally, we suggest that gingerenone-A and shogaol may either be potential SaHPPK inhibitors or can be used as fundamental platforms for novel SaHPPK inhibitor development.


Asunto(s)
Catecoles/antagonistas & inhibidores , Diarilheptanoides/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Fitoquímicos/antagonistas & inhibidores , Extractos Vegetales/antagonistas & inhibidores , Staphylococcus aureus/efectos de los fármacos , Zingiber officinale/química , Antibacterianos/farmacología , Sitios de Unión , Dominio Catalítico , Catecoles/química , Diarilheptanoides/química , Humanos , Enlace de Hidrógeno , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Fitoquímicos/química , Extractos Vegetales/química , Relación Estructura-Actividad
6.
Environ Sci Pollut Res Int ; 25(27): 26757-26765, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28871496

RESUMEN

Chemical stability of As(V) in amended mine-impacted soils was assessed according to functions of incubation period (0, 1, 2, 4, and 6 months), amendment dose (2.5 and 5%), and application timing (0 and 3rd month). Six soils contaminated with 26-209 mg kg-1 of As(V) were collected from two abandoned mine sites and were treated with two alkaline iron-rich materials (mine discharge sludge (MS) and steel-making slag (SS)). Seventeen to 23% of As(V) in soils was labile. After each designated time, As(V) stability was assessed by the labile fractions determined with sequential extraction procedures (F1-F5). Over 6 months, a reduction (26.9-70.4%) of the two labile fractions (F1 and F2) and a quantitative increase (7.4-29.9%) of As(V) in F3 were observed (r 2 = 0.956). Two recalcitrant fractions (F4 and F5) remained unchanged. Temporal change of As(V) stability in a sample was well described by the two-domain model (k fast, k slow, and Ffast). The stabilization (%) correlated well with the fast-stabilizing domain (Ffast), clay content (%), and Fe oxide content (mg kg-1), but correlated poorly with kinetic rate constants (k fast and k slow). Until the 3rd month, the 2.5%-MS amended sample resulted in lower As(V) stabilization (25-40%) compared to the 5% sample (50-60%). However, the second 2.5% MS addition on the 2.5% sample upon the lapse of the 3rd month led to a substantial reduction (up to 38%) of labile As(V) fraction in the following 4th and 6th months. As a result, an additional 15-25% of As(V) stability was obtained when splitting the amendment dose into 3-month intervals. In conclusion, the As(V) stabilization by Fe-rich amendment is time-dependent and its efficacy can be improved by optimizing the amendment dose and its timing.


Asunto(s)
Arsénico/química , Contaminantes del Suelo/química , Residuos Industriales , Hierro , Minería , Suelo/química , Acero
7.
J Diabetes Investig ; 8(3): 346-353, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27712034

RESUMEN

AIMS/INTRODUCTION: To assess the time to initiation of insulin therapy, and concurrently investigate both patient- and physician-related factors associated with delaying insulin therapy in Korean patients with type 2 diabetes uncontrolled by oral hypoglycemic agents (OHAs). MATERIALS AND METHODS: This prospective, observational disease registry study was carried out across 69 centers in Korea. Type 2 diabetes patients who had received two or more OHAs within the past 5 years, had a glycated hemoglobin ≥8% in the past 6 months and had not received insulin were included. Data recorded on data collection forms during a 12-month period were analyzed. RESULTS: Of 2168 patients enrolled, 1959 were evaluated and classified as the insulin-initiated or insulin-delayed group. Insulin was prescribed for just 20% of the patients during a 1-year follow-up period, and less than half (44.5%) of the patients who were taking two OHAs started insulin after 6 years. Patient-related factors for delay in insulin initiation included older age, shorter duration of diabetes and lower glycated hemoglobin. Physician-related factors included age (~50 to <60 years), sex (women) and number (<1000) of patients consulted per month. Patient refusal (33.6%) and physicians' concerns of patient non-compliance (26.5%) were the major physician-reported reasons for delaying insulin therapy. Inconvenience of insulin therapy (51.6%) and fear of injection (48.2%) were the major reasons for patient refusal. CONCLUSIONS: Insulin initiation is delayed in patients with type 2 diabetes uncontrolled by two or more OHAs in Korea. Patient- and physician-related factors associated with this delay need to be addressed for better diabetes management.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Relaciones Médico-Paciente , Administración Oral , Adulto , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Masculino , Persona de Mediana Edad , Participación del Paciente , Estudios Prospectivos , Sistema de Registros , República de Corea
8.
J Recept Signal Transduct Res ; 37(3): 224-238, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27485399

RESUMEN

High level of hematopoietic cell kinase (Hck) is associated with drug resistance in chronic myeloid leukemia. Additionally, Hck activity has also been connected with the pathogenesis of HIV-1 and chronic obstructive pulmonary disease. In this study, three-dimensional (3D) QSAR pharmacophore models were generated for Hck based on experimentally known inhibitors. A best pharmacophore model, Hypo1, was developed with high correlation coefficient (0.975), Low RMS deviation (0.60) and large cost difference (49.31), containing three ring aromatic and one hydrophobic aliphatic feature. It was further validated by the test set (r = 0.96) and Fisher's randomization method (95%). Hypo 1 was used as a 3D query for screening the chemical databases, and the hits were further screened by applying Lipinski's rule of five and ADMET properties. Selected hit compounds were subjected to molecular docking to identify binding conformations in the active site. Finally, the appropriate binding modes of final hit compounds were revealed by molecular dynamics (MD) simulations and free energy calculation studies. Hence, we propose the final three hit compounds as virtual candidates for Hck inhibitors.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/química , Proteínas Proto-Oncogénicas c-hck/química , Bases de Datos de Compuestos Químicos , Resistencia a Antineoplásicos/genética , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Simulación de Dinámica Molecular , Unión Proteica/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-hck/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-hck/genética , Relación Estructura-Actividad Cuantitativa , Interfaz Usuario-Computador
9.
Arch Pharm Res ; 39(10): 1356-1369, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27542119

RESUMEN

HDAC8 inhibitors have become an attractive treatment for cancer. This study aimed to facilitate the identification of potential chemical scaffolds for the selective inhibition of histone deacetylase 8 (HDAC8) using in silico approaches. Non-linear QSAR classification and regression models of HDAC8 inhibitors were developed with support vector machine. Mean impact value-based sequential forward feature selection and grid search strategy were used for molecular descriptor selection and parameter optimization, respectively. The generated QSAR models were validated by leave-one-out cross validation and an external test set. The best QSAR classification model yielded 84 % of accuracy on the external test prediction and Matthews correlation coefficient is 0.69. The best QSAR regression model showed low root-mean-square error (0.63) and high squared correlation coefficient (0.53) for the test set. The validated QSAR models together with various drug-like properties, molecular docking and molecular dynamics simulation were sequentially used as a multi-step query in chemical database virtual screening. Finally, two hit compounds were discovered as new structural scaffolds which can be used for further in vitro and in vivo activity analyses. The strategy used in this study could be a promising computational strategy which can be utilized for other target drug design.


Asunto(s)
Diseño de Fármacos , Inhibidores de Histona Desacetilasas/química , Simulación de Dinámica Molecular , Relación Estructura-Actividad Cuantitativa , Proteínas Represoras/antagonistas & inhibidores , Bases de Datos Factuales , Inhibidores de Histona Desacetilasas/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Humanos , Proteínas Represoras/metabolismo
10.
Environ Sci Pollut Res Int ; 23(20): 20739-20748, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27473623

RESUMEN

Variation of the chemical extractability and phytoavailability of two metallic elements (e.g., As and Pb) on amendment-treated soils was investigated. Four mine-impacted agricultural soils contaminated with both As (174-491 mg kg-1) and Pb (116-357 mg kg-1) were amended with an iron-rich sludge at the rate of 5 % (w/w). After a 4-, 8-, and 16-week incubation, the extractability of metallic elements was assessed by sequential extraction procedure (SEP; F1-F5). The control without amendment was also run. In amended soils, the labile element mass (i.e., F1 + F2) promptly decreased (15-48 % of As and 5-10 % of Pb) in 4 weeks, but the decrement was continued over 16 weeks up to 70 and 28 % for As and Pb, respectively. The labile mass decrement was quantitatively corresponded with the increment of F3 (bound to amorphous metal oxides). In plant test assessed by radish (Raphanus sativus) grown on the 16-week soils, up to 57 % of As and 28 % of Pb accumulation was suppressed and 10-43 % of growth (i.e., shoot/root elongation and fresh weight) was improved. For both the control and amended soils, element uptake by plant was well correlated with their labile soil concentrations (r 2 = 0.799 and 0.499 for As and Pb, respectively). The results confirmed that the iron-rich material can effectively suppress element uptake during R. sativus seedling growth, most likely due to the chemical stabilization of metallic elements in growth medium.


Asunto(s)
Arsénico/análisis , Hierro/química , Plomo/análisis , Minería , Raphanus/química , Contaminantes del Suelo/análisis , Suelo/química , Agricultura/métodos , Arsénico/metabolismo , Plomo/metabolismo , Raíces de Plantas/química , Raíces de Plantas/crecimiento & desarrollo , Raphanus/crecimiento & desarrollo , Aguas del Alcantarillado/química , Suelo/normas , Contaminantes del Suelo/metabolismo
11.
Acta Pharmacol Sin ; 36(8): 998-1012, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26051108

RESUMEN

AIM: Recent evidence suggests that aldo-keto reductase family 1 B10 (AKR1B10) may be a potential diagnostic or prognostic marker of human tumors, and that AKR1B10 inhibitors offer a promising choice for treatment of many types of human cancers. The aim of this study was to identify novel chemical scaffolds of AKR1B10 inhibitors using in silico approaches. METHODS: The 3D QSAR pharmacophore models were generated using HypoGen. A validated pharmacophore model was selected for virtual screening of 4 chemical databases. The best mapped compounds were assessed for their drug-like properties. The binding orientations of the resulting compounds were predicted by molecular docking. Density functional theory calculations were carried out using B3LYP. The stability of the protein-ligand complexes and the final binding modes of the hit compounds were analyzed using 10 ns molecular dynamics (MD) simulations. RESULTS: The best pharmacophore model (Hypo 1) showed the highest correlation coefficient (0.979), lowest total cost (102.89) and least RMSD value (0.59). Hypo 1 consisted of one hydrogen-bond acceptor, one hydrogen-bond donor, one ring aromatic and one hydrophobic feature. This model was validated by Fischer's randomization and 40 test set compounds. Virtual screening of chemical databases and the docking studies resulted in 30 representative compounds. Frontier orbital analysis confirmed that only 3 compounds had sufficiently low energy band gaps. MD simulations revealed the binding modes of the 3 hit compounds: all of them showed a large number of hydrogen bonds and hydrophobic interactions with the active site and specificity pocket residues of AKR1B10. CONCLUSION: Three compounds with new structural scaffolds have been identified, which have stronger binding affinities for AKR1B10 than known inhibitors.


Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Aldehído Reductasa/metabolismo , Diseño de Fármacos , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Aldo-Ceto Reductasas , Biomarcadores de Tumor/antagonistas & inhibidores , Biomarcadores de Tumor/metabolismo , Humanos , Modelos Moleculares , Relación Estructura-Actividad Cuantitativa , Termodinámica
12.
Int J Syst Evol Microbiol ; 64(Pt 4): 1317-1322, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24425747

RESUMEN

A Gram-staining-negative, strictly aerobic, white-colony-forming bacterium, designated strain 5-10(T), was isolated from forest soil of Bac Kan Province in Vietnam. Cells were non-motile rods or coccoids, showing oxidase- and catalase-positive reactions. Growth was observed at 10-37 °C (optimum, 30 °C), at pH 5.0-9.0 (optimum, pH 7.0) and in the presence of 0-1.0 % (w/v) NaCl (optimum, 0-0.5 %). The major cellular fatty acids were summed feature 3 (comprising C16 : 1ω6c and/or C16 : 1ω7c), C16 : 0, C10 : 0 3-OH and summed feature 8 (comprising C18 : 1ω6c and/or C18 : 1ω7c). The G+C content of the genomic DNA was 69.9 mol% and the only respiratory quinone detected was ubiquinone 8 (Q-8). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 5-10(T) formed a tight phyletic lineage with members of the genus Ramlibacter. Strain 5-10(T) was most closely related to Ramlibacter tataouinensis TTB310(T) (97.3 %), but the DNA-DNA relatedness level between the two strains was 38.2±1.8 %. Based on phenotypic, chemotaxonomic and molecular features, strain 5-10(T) was shown to represent a novel species of the genus Ramlibacter, for which the name Ramlibacter solisilvae sp. nov. is proposed. The type strain is 5-10(T) ( = KACC 17567(T) = JCM 19319(T)). An emended description of the genus Ramlibacter is also proposed.


Asunto(s)
Comamonadaceae/clasificación , Filogenia , Microbiología del Suelo , Árboles/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , Comamonadaceae/genética , Comamonadaceae/aislamiento & purificación , ADN Bacteriano/genética , Ácidos Grasos/química , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Ubiquinona/química , Vietnam
13.
Int J Nurs Pract ; 20(4): 382-9, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24118340

RESUMEN

Current advances in technology have enabled the development of a computer-based questionnaire that provides advantages over the paper-based mode of administration, such as automatic data entry, storage and calculations. However, before implementing a computer-based questionnaire, its equivalence with the original paper-based questionnaire must first be demonstrated. The purpose of this study was to evaluate the measurement equivalence of the computerized Diabetes-Specific Quality-of-Life questionnaire (cD-QOL) with its original paper-based counterpart. A two-period crossover design was used in this study. The measurement equivalence was evaluated using quadratic weighted kappa coefficients, intraclass correlations and Cronbach's alpha comparisons. The cD-QOL was equivalent to its original paper-based counterpart. Participants preferred the cD-QOL over the paper-based questionnaire and reported that it was easy to use.


Asunto(s)
Diabetes Mellitus , Calidad de Vida , Encuestas y Cuestionarios , Adulto , Anciano , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Interfaz Usuario-Computador
14.
J Mol Graph Model ; 46: 1-9, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24104184

RESUMEN

Activation of the peroxisome proliferator-activated receptor γ (PPARγ) is important for the treatment of type 2 diabetes and obesity through the regulation of glucose metabolism and fatty acid accumulation. Hence, the discovery of novel PPARγ agonists is necessary to overcome these diseases. In this study, a newly developed approach, multi-conformation dynamic pharmacophore modeling (MCDPM), was used for screening candidate compounds that can properly bind PPARγ. Highly populated structures obtained from molecular dynamics (MD) simulations were selected by clustering analysis. Based on these structures, pharmacophore models were generated from the ligand-binding pocket and then validated to check the rationality. Consequently, two hits were retrieved as final candidates by utilizing virtual screening and molecular docking simulations. These compounds can be used in the design of novel PPARγ agonists.


Asunto(s)
Simulación de Dinámica Molecular , PPAR gamma/química , Secuencias de Aminoácidos , Sitios de Unión , Análisis por Conglomerados , Descubrimiento de Drogas , Humanos , Enlace de Hidrógeno , Simulación del Acoplamiento Molecular , PPAR gamma/agonistas , Unión Proteica , Rosiglitazona , Bibliotecas de Moléculas Pequeñas , Tiazolidinedionas/química
15.
Bioresour Technol ; 138: 266-70, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23619139

RESUMEN

The objective of this study was to investigate the feasibility of biochar for removing Cd from aqueous solution. Biochars were produced from a Miscanthus sacchariflorus via slow pyrolysis at 300, 400, 500 and 600°C. Higher pyrolytic temperature resulted in biochar with a higher aromatic structure and fewer polar functional groups. In particular, pH and surface area of biochar increased greatly at pyrolytic temperatures ≥ 500°C, which increased Cd sorption capacity up to 13.24 mgg(-1). The diffuse-controlled Cd removal was likely due to a surface sorption or a precipitation reaction depending on pH. A simulation with the visual MINTEQ program indicated that the precipitate was Cd(OH)2. In addition, biochar treatment significantly removed the acute toxicity of Cd toward Daphnia magna, resulting in increase of EC50 (50% effective concentration) value from 0.16 to 0.76 mgL(-1).


Asunto(s)
Cadmio/aislamiento & purificación , Carbón Orgánico/química , Calor , Poaceae/química , Contaminantes Químicos del Agua/aislamiento & purificación , Adsorción/efectos de los fármacos , Animales , Biodegradación Ambiental/efectos de los fármacos , Cadmio/toxicidad , Daphnia/efectos de los fármacos , Cinética , Pruebas de Toxicidad Aguda
16.
Anal Chem ; 84(2): 901-7, 2012 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-22148852

RESUMEN

We propose a new method for performing in-channel electrochemical detection under a high electric field using a polyelectrolytic gel salt bridge (PGSB) integrated in the middle of the electrophoretic separation channel. The finely tuned placement of a gold working electrode and the PGSB on an equipotential surface in the microchannel provided highly sensitive electrochemical detection without any deterioration in the separation efficiency or interference of the applied electric field. To assess the working principle, the open circuit potentials between gold working electrodes and the reference electrode at varying distances were measured in the microchannel under electrophoretic fields using an electrically isolated potentiostat. In addition, "in-channel" cyclic voltammetry confirmed the feasibility of electrochemical detection under various strengths of electric fields (∼400 V/cm). Effective separation on a microchip equipped with a PGSB under high electric fields was demonstrated for the electrochemical detection of biological compounds such as dopamine and catechol. The proposed "in-channel" electrochemical detection under a high electric field enables wider electrochemical detection applications in microchip electrophoresis.


Asunto(s)
Electroquímica , Electroforesis por Microchip , Oro/química , Microelectrodos , Polímeros/química , Conductividad Eléctrica
17.
Environ Sci Technol ; 45(8): 3739-45, 2011 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-21417357

RESUMEN

For the rapid and reliable detection of oxidized contaminants (i.e., nitrite, nitrate, perchlorate, dichromate) in water, a novel toxicity detection methodology based on sulfur-oxidizing bacteria (SOB) has been developed. The methodology exploits the ability of SOB to oxidize elemental sulfur to sulfuric acid in the presence of oxygen. The reaction results in an increase in electrical conductivity (EC) and a decrease in pH. When oxidized contaminants were added to the system, the effluent EC decreased and the pH increased due to the inhibition of the SOB. We found that the system can detect these contaminants in the 5-50 ppb range (in the case of NO(3)(-), 10 ppm was detected), which is lower than many whole-cell biosensors to date. At low pH, the oxidized contaminants are mostly in their acid or nonpolar, protonated form which act as uncouplers and make the SOB biosensor more sensitive than other whole-cell biosensors which operate at higher pH values where the contaminants exist as dissociated anions. The SOB biosensor can detect toxicity on the order of minutes to hours which can serve as an early warning so as to not pollute the environment and affect public health.


Asunto(s)
Monitoreo del Ambiente/métodos , Bacterias Reductoras del Azufre/metabolismo , Contaminantes Químicos del Agua/metabolismo , Concentración de Iones de Hidrógeno , Dióxido de Nitrógeno/metabolismo , Oxidación-Reducción , Bacterias Reductoras del Azufre/efectos de los fármacos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad
18.
Artículo en Inglés | MEDLINE | ID: mdl-21206019

RESUMEN

Quinolinate phosphoribosyltransferase (QPRTase) is a key NAD-biosynthetic enzyme which catalyzes the transfer of quinolinic acid to 5-phosphoribosyl-1-pyrophosphate, yielding nicotinic acid mononucleotide. Homo sapiens QPRTase (Hs-QPRTase) appeared as a hexamer during purification and the protein was crystallized. Diffraction data were collected and processed at 2.8 Šresolution. Native Hs-QPRTase crystals belonged to space group P2(1), with unit-cell parameters a=76.2, b=137.1, c=92.7 Å, ß=103.8°. Assuming the presence of six molecules in the asymmetric unit, the calculated Matthews coefficient is 2.46 Å3 Da(-1), which corresponds to a solvent content of 49.9%.


Asunto(s)
Pentosiltransferasa/química , Estructura Cuaternaria de Proteína , Animales , Cristalización , Cristalografía por Rayos X , Humanos , Datos de Secuencia Molecular , NAD/biosíntesis , Pentosiltransferasa/metabolismo
19.
J Ginseng Res ; 35(2): 243-9, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23717067

RESUMEN

Korean red ginseng (KRG), the steamed root of Panax ginseng Meyer, has a variety of biological properties, including anti-inflammatory, antioxidant and anticancer effects. Aflatoxin B1 (AFB1) produced by the Aspergillus spp. causes acute hepatotoxicity by lipid peroxidation and oxidative DNA damage, and induces liver carcinoma in humans and laboratory animals. This study was performed to examine the protective effects of KRG against hepatotoxicity induced by AFB1 using liver-specific serum marker analysis, histopathology, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. In addition, to elucidate the possible mechanism of hepatoprotective effects, superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde were analyzed. Rats were treated with 250 mg/kg of KRG (KRG group) or saline (AFB1 group) for 4 weeks and then received 150 µg/kg of AFB1 intraperitoneally for 3 days. Rats were sacrificed at 12 h, 24 h, 48 h, 72 h, or 1 wk after AFB1 treatment. In the KRG pre-treatment group, serum alanine aminotransferase, aspartate aminotransferase, and malondialdehyde levels were low, but superoxide dismutase, catalase, and glutathione peroxidase activities were high as compared to the AFB1 alone group. Histopathologically, AFB1 treatment induced necrosis and apoptosis in hepatocytes, and led to inflammatory cells infiltration in the liver. KRG pre-treatment ameliorated these changes. These results indicate that KRG may have protective effects against hepatotoxicity induced by AFB1 that involve the antioxidant properties of KRG.

20.
Langmuir ; 23(3): 1209-14, 2007 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-17241034

RESUMEN

This report describes the reactivity of acid fluoride (AF)-terminated self-assembled monolayers (SAMs) on gold toward amine and alcohol compounds and the potentiality of AF as a reactive intermediate for surface functionalizations. The AF group was generated in situ on a gold surface by reacting the terminal carboxylic acid group in the SAM of 16-mercaptohexadecanoic acid with cyanuric fluoride and pyridine under the optimized conditions. AF was found to be highly reactive toward various amine groups, such as primary and secondary amines, but it did not react effectively with alcohol. In addition, the amide coupling reaction by microcontact printing (microCP) was compared with the solution-based reaction: when amine-derivatized ferrocene compound was used for 1-min microCP on the AF-activated surface, the surface coverage of the reaction product was about 83% of 3.45 x 1014 cm-2, the coverage obtained in the solution-based reaction. On the basis of the high reaction efficiency of microCP, the AF-activated surface was also used as a platform for patterning a biological ligand, biotin.


Asunto(s)
Ácidos Carboxílicos/química , Fluoruros/química , Oro/química , Alcoholes , Aminas , Biotina , Ácidos Palmíticos , Triazinas
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