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1.
ACS Nano ; 16(9): 15141-15154, 2022 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-35977379

RESUMEN

Nanomedicine-based and unmodified drug interventions to address COVID-19 have evolved over the course of the pandemic as more information is gleaned and virus variants continue to emerge. For example, some early therapies (e.g., antibodies) have experienced markedly decreased efficacy. Due to a growing concern of future drug resistant variants, current drug development strategies are seeking to find effective drug combinations. In this study, we used IDentif.AI, an artificial intelligence-derived platform, to investigate the drug-drug and drug-dose interaction space of six promising experimental or currently deployed therapies at various concentrations: EIDD-1931, YH-53, nirmatrelvir, AT-511, favipiravir, and auranofin. The drugs were tested in vitro against a live B.1.1.529 (Omicron) virus first in monotherapy and then in 50 strategic combinations designed to interrogate the interaction space of 729 possible combinations. Key findings and interactions were then further explored and validated in an additional experimental round using an expanded concentration range. Overall, we found that few of the tested drugs showed moderate efficacy as monotherapies in the actionable concentration range, but combinatorial drug testing revealed significant dose-dependent drug-drug interactions, specifically between EIDD-1931 and YH-53, as well as nirmatrelvir and YH-53. Checkerboard validation analysis confirmed these synergistic interactions and also identified an interaction between EIDD-1931 and favipiravir in an expanded range. Based on the platform nature of IDentif.AI, these findings may support further explorations of the dose-dependent drug interactions between different drug classes in further pre-clinical and clinical trials as possible combinatorial therapies consisting of unmodified and nanomedicine-enabled drugs, to combat current and future COVID-19 strains and other emerging pathogens.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Amidas , Inteligencia Artificial , Auranofina , Guanosina Monofosfato/análogos & derivados , Humanos , Fosforamidas , Pirazinas
2.
J Intellect Disabil Res ; 62(3): 187-198, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29114946

RESUMEN

BACKGROUND: Several risk factors for cardiovascular disease (CVD) have been identified among adults with intellectual disabilities (ID). Periodontitis has been reported to increase the risk of developing a CVD in the general population. Given that individuals with ID have been reported to have a higher prevalence of poor oral health than the general population, the purpose of this study was to determine whether adults with ID with informant reported gum disease present greater reported CVD than those who do not have reported gum disease and whether gum disease can be considered a risk factor for CVD. METHODS: Using baseline data from the Longitudinal Health and Intellectual Disability Study from which informant survey data were collected, 128 participants with reported gum disease and 1252 subjects without reported gum disease were identified. A series of univariate logistic regressions was conducted to identify potential confounding factors for a multiple logistic regression. RESULTS: The series of univariate logistic regressions identified age, Down syndrome, hypercholesterolemia, hypertension, reported gum disease, daily consumption of fruits and vegetables and the addition of table salt as significant risk factors for reported CVD. When the significant factors from the univariate logistic regression were included in the multiple logistic analysis, reported gum disease remained as an independent risk factor for reported CVD after adjusting for the remaining risk factors. Compared with the adults with ID without reported gum disease, adults in the gum disease group demonstrated a significantly higher prevalence of reported CVD (19.5% vs. 9.7%; P = .001). CONCLUSION: After controlling for other risk factors, reported gum disease among adults with ID may be associated with a higher risk of CVD. However, further research that also includes clinical indices of periodontal disease and CVD for this population is needed to determine if there is a causal relationship between gum disease and CVD.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Enfermedades de las Encías/epidemiología , Discapacidad Intelectual/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/etiología , Comorbilidad , Femenino , Enfermedades de las Encías/complicaciones , Encuestas Epidemiológicas , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Medio Oeste de Estados Unidos/epidemiología , Factores de Riesgo , Adulto Joven
3.
Curr Top Med Chem ; 15(2): 136-62, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25496270

RESUMEN

This review discusses the state of the art, challenges and perspectives in recent applications of electrochemistry in the life sciences. It deals mainly with the elucidation of molecular mechanisms of drug action, drug design and development, involving electron transfer, pharmaco-electrochemistry (the combination of electrochemical and pharmacological assays), and electrochemical studies of membrane models and drug delivery. It aims to shed light on the question: does electrochemistry really contribute to this area? It includes a general introduction for the use of electrochemistry in the life sciences, with a focus on how electrochemistry can uniquely provide both kinetic and thermodynamic information. A number of studies are reported in the literature and from the authors' laboratories, including the investigation of biooxidative/bioreductive activation of pro-drugs, DNA alkylation, electrochemically- based release of reactive oxygen and nitrogen species, with a particular emphasis on quinones, ferrocifens and compounds with mixed-functionality. Within the context of drug delivery and bioavailability, the electrochemical investigation of supramolecular interactions of the chosen classes of compounds with cyclodextrins and lipid bilayers, in relation to their solubilization and vectorization was also carried out. The updated examples herein illustrate how relevant and challenging the integration of electrochemistry, supramolecular and materials chemistry, biochemistry and medical knowledge for the design and development of redox-selective molecular approaches is. Many questions related to these fields are still unclear and the search for selectivity toward redox therapeutic agents remains of expanding interest. This review hopes to stimulate researchers to become more involved in this fruitful interface between electrochemistry and the life sciences.


Asunto(s)
Técnicas Electroquímicas , Compuestos Ferrosos/química , Quinonas/química , Animales , Compuestos Ferrosos/metabolismo , Humanos , Oxidación-Reducción , Quinonas/metabolismo
4.
Curr Top Med Chem ; 2014 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-25547099

RESUMEN

This review discusses the state of the art, challenges and perspectives in recent applications of electrochemistry in the life sciences. It deals mainly with the elucidation of molecular mechanisms of drug action, drug design and development, involving electron transfer, pharmaco-electrochemistry (the combination of electrochemical and pharmacological assays), and electrochemical studies of membrane models and drug delivery. It aims to shed light on the question: does electrochemistry really contribute to this area? It includes a general introduction for the use of electrochemistry in the life sciences, with a focus on how electrochemistry can uniquely provide both kinetic and thermodynamic information. A number of studies are reported in the literature and from the authors' laboratories, including the investigation of biooxidative/bioreductive activation of pro-drugs, DNA alkylation, electrochemically-based release of reactive oxygen and nitrogen species, with a particular emphasis on quinones, ferrocifens and compounds with mixed-functionality. Within the context of drug delivery and bioavailability, the electrochemical investigation of supramolecular interactions of the chosen classes of compounds with cyclodextrins and lipid bilayers, in relation to their solubilization and vectorization was also carried out. The updated examples herein illustrate how relevant and challenging the integration of electrochemistry, supramolecular and materials chemistry, biochemistry and medical knowledge for the design and development of redox-selective molecular approaches is. Many questions related to these fields are still unclear and the search for selectivity toward redox therapeutic agents remains of expanding interest. This review hopes to stimulate researchers to become more involved in this fruitful interface between electrochemistry and the life sciences.

5.
Bioorg Med Chem ; 22(5): 1608-19, 2014 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-24530030

RESUMEN

1,2,3-Triazole-, arylamino- and thio-substituted naphthoquinones (24, 8, and 2 representatives, respectively) were synthesized in moderate yields and evaluated against several human cancer cell lines (blood, ovarian, breast, central nervous system, colon, and prostate cancers and melanoma), showing, for some of them, IC50 values below 2 µM. The cytotoxic potential of the tested naphthoquinones was also assayed on non-tumor cells such as human peripheral blood mononucluear cells (PBMC) and two murine fibroblast lines (L929 and V79 cells). α-Lapachone- and nor-α-lapachone-based 1,2,3-triazoles and arylamino-substituted naphthoquinones showed potent cytotoxicity against different cancer cell lines. The compounds may represent promising new lead derivatives for anticancer drug development. The electrochemical properties of selected compounds were evaluated in an attempt to correlate them with antitumor activity.


Asunto(s)
Naftoquinonas/química , Triazoles/química , Proliferación Celular , Química Clic , Humanos , Modelos Moleculares , Estructura Molecular , Relación Estructura-Actividad
6.
Eye (Lond) ; 23(5): 1187-91, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-18535586

RESUMEN

PURPOSE: To directly compare the per-operative safety and efficacy of the 20- and 23-gauge vitrectomy systems as well as day 1 intraocular pressure (IOP). METHODS: Data were collected on 50 consecutive vitrectomy cases performed using the 20-gauge system and 23-gauge sutureless vitrectomy. All surgeries were carried out by one surgeon (RLB) at a single centre. Data collected prospectively included indication for surgery, iatrogenic retinal tears, and operating times. RESULTS: Most common indications for surgery were macular hole, rhegmatogenous retinal detachment, diabetic vitreous haemorrhage (no tractional retinal detachment), and macular pucker. Intraocular tamponade with air, sulphur hexafluoride (SF6), hexafluoroethane (C2F6) or octafluoropropane (C3F8), or silicone oil was used in 25 patients in the 20-gauge group and 46 patients in the 23-gauge group. One scleral port required suture in patients who underwent 23-gauge vitrectomy (0.67%). Every 20-gauge patient had all the three ports sutured. The mean first day IOP was 22.88 mm Hg in the 20-gauge vs 17.58 mm Hg in the 23-gauge (P<0.001). Four patients in the 20-gauge group had an IOP >40 mm Hg compared to none in the 23-gauge group. In contrast, four patients had postoperative hypotony in the 23-gauge group compared to none in the 20-gauge group. The mean operating time for all the 50 cases in each group was 39.4 (20 gauge) vs 29 min (23 gauge) P<0.001. CONCLUSION: Our study indicates less risk of considerably raised IOPs and reduced surgical operating time with the 23-gauge system. Additional advantages observed included faster wound healing, diminished conjunctival scarring, improved patient comfort, and decreased postoperative inflammation.


Asunto(s)
Enfermedades de la Retina/cirugía , Vitrectomía/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Complicaciones Posoperatorias , Estudios Prospectivos , Enfermedades de la Retina/fisiopatología , Vitrectomía/efectos adversos , Cicatrización de Heridas , Adulto Joven
7.
IEEE Trans Neural Netw ; 19(2): 245-59, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18269956

RESUMEN

The self-organizing map (SOM) is an efficient tool for visualizing high-dimensional data. In this paper, the clustering and visualization capabilities of the SOM, especially in the analysis of textual data, i.e., document collections, are reviewed and further developed. A novel clustering and visualization approach based on the SOM is proposed for the task of text mining. The proposed approach first transforms the document space into a multidimensional vector space by means of document encoding. Afterwards, a growing hierarchical SOM (GHSOM) is trained and used as a baseline structure to automatically produce maps with various levels of detail. Following the GHSOM training, the new projection method, namely the ranked centroid projection (RCP), is applied to project the input vectors to a hierarchy of 2-D output maps. The RCP is used as a data analysis tool as well as a direct interface to the data. In a set of simulations, the proposed approach is applied to an illustrative data set and two real-world scientific document collections to demonstrate its applicability.


Asunto(s)
Inteligencia Artificial , Simulación por Computador , Redes Neurales de la Computación , Reconocimiento de Normas Patrones Automatizadas , Análisis por Conglomerados , Gráficos por Computador , Dinámicas no Lineales
8.
IEEE Trans Inf Technol Biomed ; 12(1): 118-30, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18270044

RESUMEN

Diabetic retinopathy is a leading cause of blindness in developed countries. Diabetic patients can prevent severe visual loss by attending regular eye examinations and receiving timely treatments. In the United States, standard protocols have been developed and refined for years to provide better screening and evaluation procedures of the fundus images. Due to the emerging number of diabetic retinopathy cases, accurate and efficient evaluations of the fundus images have become a serious burden for the ophthalmologists or care providers. While diabetic retinopathy remains too complicated to call for an automatic diagnosis system, an efficient tool to facilitate the grading process with a limited number of personnel is in great demand. The current study is to develop a sorting system with a user-friendly interface, based upon the standardized early treatment diabetic retinopathy study (ETDRS) protocol, to assist the professional graders. The raw fundus images will be screened and assigned to different graders according to their skill levels and experiences. The developed hierarchical sorting process will greatly support the graders and enhance their efficiency and throughput. The proposed hybrid intelligent system with multilevel knowledge representation is used to construct this sorting system. A preliminary case study is conducted using only the features of the spot lesion group coupled with the ETDRS standard to demonstrate its feasibility and performance. The results obtained from the case study show a promising future.


Asunto(s)
Retinopatía Diabética/patología , Fondo de Ojo , Humanos , Interfaz Usuario-Computador
10.
Brain Res Mol Brain Res ; 96(1-2): 59-67, 2001 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-11731009

RESUMEN

The rat Zfhep gene encodes a member of the Zfh family of transcription factors having a homeodomain-like sequence and multiple zinc fingers. We examined expression of Zfhep in the rat forebrain during embryonic and postnatal development. Zfhep mRNA was strongly expressed in the progenitor cells of the ventricular zone around the lateral ventricles on E14 and E16, but showed little expression in cells that had migrated to form the developing cortex. Dual labeling with PCNA demonstrated expression of Zfhep mRNA in proliferating cells. Expression of Zfhep in the ventricular zone decreases during late development as the population of progenitor cells decreases. This pattern is distinctly different from other members of the Zfh family. We also examined the expression of Zfhep protein during retinoic acid-induced neurogenesis of P19 embryonal carcinoma cells. Zfhep is highly expressed in P19 neuroblasts, and expression decreases by the time of morphological neurogenesis. Hence, both P19 cells and embryonic brain demonstrate a loss of Zfhep expression during the transition from proliferating precursor to differentiated neural cells. We investigated a possible link between Zfhep and proliferation by treating human glial cell lines with Zfhep antisense phosphorothioate oligodeoxynucleotides. Two Zfhep antisense oligonucleotides repressed proliferation of either U-138 or U-343 glioblastoma cells more than control oligonucleotides. Based on the expression patterns of Zfhep in vivo and in the P19 cell model of neurogenesis, we suggest that Zfhep may play a role in proliferation or differentiation of neural cells.


Asunto(s)
Corteza Cerebral/citología , Corteza Cerebral/embriología , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Neuronas/fisiología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Animales , Diferenciación Celular/fisiología , División Celular/fisiología , Femenino , Regulación del Desarrollo de la Expresión Génica/fisiología , Glioblastoma , Hibridación in Situ , Masculino , Neuronas/citología , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Oligodesoxirribonucleótidos Antisentido/farmacología , Embarazo , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Células Tumorales Cultivadas , Homeobox 1 de Unión a la E-Box con Dedos de Zinc
11.
Int J Neural Syst ; 11(5): 427-43, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11709810

RESUMEN

In this paper, a method for automatic construction of a fuzzy rule-based system from numerical data using the Incremental Learning Fuzzy Neural (ILFN) network and the Genetic Algorithm is presented. The ILFN network was developed for pattern classification applications. The ILFN network, which employed fuzzy sets and neural network theory, equips with a fast, one-pass, on-line, and incremental learning algorithm. After trained, the ILFN network stored numerical knowledge in hidden units, which can then be directly interpreted into if then rule bases. However, the rules extracted from the ILFN network are not in an optimized fuzzy linguistic form. In this paper, a knowledge base for fuzzy expert system is extracted from the hidden units of the ILFN classifier. A genetic algorithm is then invoked, in an iterative manner, to reduce number of rules and select only discriminate features from input patterns needed to provide a fuzzy rule-based system. Three computer simulations using a simulated 2-D 3-class data, the well-known Fisher's Iris data set, and the Wisconsin breast cancer data set were performed. The fuzzy rule-based system derived from the proposed method achieved 100% and 97.33% correct classification on the 75 patterns for training set and 75 patterns for test set, respectively. For the Wisconsin breast cancer data set, using 400 patterns for training and 299 patterns for testing, the derived fuzzy rule-based system achieved 99.5% and 98.33% correct classification on the training set and the test set, respectively.


Asunto(s)
Algoritmos , Inteligencia Artificial , Lógica Difusa , Aprendizaje/fisiología , Modelos Genéticos , Redes Neurales de la Computación , Neoplasias de la Mama , Simulación por Computador , Interpretación Estadística de Datos , Procesamiento Automatizado de Datos , Humanos , Modelos Teóricos
12.
J Agric Food Chem ; 49(10): 5000-4, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11600058

RESUMEN

Our aim was to determine the antimutagenic activity of various solvent extracts from an herb Mesona procumbens Hemsl, normally called Hsian-tsao in China. We also investigated the relationships between the special components in the water extract of Hsian-tsao (WEHT) and the antimutagenic activity. It was found that the extracts at 0-0.6 mg/plate from three solvents (water, methanol, and ethyl acetate) exhibited a dose-dependent antimutagenic effect against benzo[a]pyrene [B(a)P] and 2-amino-3-methylimidazo(4,5-f)quinoline (IQ), both are indirect mutagens in Salmonella tester strains TA98 and TA100. The WEHT from three different plantations revealed a similar inhibitory effect on the mutagenicity of IQ in TA 98 at 2.5-5.0 mg/plate. The inhibitory effect of WEHT on the mutagenicity of IQ correlates with their polyphenol and ascorbic acid contents but not with their chlorophyll contents. These findings suggest that the antimutagenicity activity of WEHT may be attributed mainly to their polyphenolic compounds and ascorbic acid.


Asunto(s)
Antimutagênicos/química , Flavonoides , Extractos Vegetales/química , Plantas Medicinales/química , Acetatos , Antimutagênicos/farmacología , Ácido Ascórbico/análisis , Benzo(a)pireno/farmacología , Clorofila/análisis , Medicina Tradicional China , Metanol , Pruebas de Mutagenicidad , Mutágenos/farmacología , Fenoles/análisis , Extractos Vegetales/farmacología , Polímeros/análisis , Polifenoles , Quinolinas/farmacología , Solventes , Agua
13.
Genome Res ; 11(9): 1584-93, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11544203

RESUMEN

We have constructed NheI and XhoI optical maps of Escherichia coli O157:H7 solely from genomic DNA molecules to provide a uniquely valuable scaffold for contig closure and sequence validation. E. coli O157:H7 is a common pathogen found in contaminated food and water. Our approach obviated the need for the analysis of clones, PCR products, and hybridizations, because maps were constructed from ensembles of single DNA molecules. Shotgun sequencing of bacterial genomes remains labor-intensive, despite advances in sequencing technology. This is partly due to manual intervention required during the last stages of finishing. The applicability of optical mapping to this problem was enhanced by advances in machine vision techniques that improved mapping throughput and created a path to full automation of mapping. Comparisons were made between maps and sequence data that characterized sequence gaps and guided nascent assemblies.


Asunto(s)
Mapeo Contig/métodos , Escherichia coli O157/genética , Genoma Bacteriano , Mapeo Restrictivo/métodos , Análisis de Secuencia de ADN/métodos , Programas Informáticos
14.
Food Chem Toxicol ; 39(11): 1045-53, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11527563

RESUMEN

This study evaluates the toxic, mutagenic and antimutagenic effects of emerging edible plants that are consumed as new leafy vegetables in Taiwan. Among eight plant extracts, only the extracts of Sol (Solanum nigrum L.) showed cytotoxicity to Salmonella typhimurium TA100 in the absence of S9 mix. The toxicity of extracts from different parts of the Sol plant, such as leaf and stem, immature fruit and mature fruit, towards S. typhimurium TA100 and human lymphocytes was also assayed. The immature fruit extracts of Sol exhibited strong cytotoxicity with dose dependence and induced significant DNA damage in human lymphocytes based on the comet assay. However, no mutagenicity was found in eight plant extracts to TA98 or TA100 either with or without the S9 mixture. Sol and Sec [Sechium edule (Jacq.) Swartz] extracts showed the strongest inhibitory effect towards the mutagenicity of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) in S. typhimurium TA98 and TA100; the ID(50) was less then 1 mg/plate. Cra [Crassocephalum creidioides (Benth.) S. Moore] extracts also expressed moderate antimutagenic activities towards IQ and benzo[a]pyrene (B[a]P) either in TA98 or in TA100; the ID(50) was 1.63-2.41 mg/plate. The extracts from Bas (Basella alba L.), Bou (Boussingaultia gracilis Miers var. pseudobaselloides Bailey), Cen (Centella asiatica L. Urban), Cor (Corchorus olitorius L.) and Por (Portulaca oleracea L.) showed weak to moderate inhibition of mutagenicity of IQ. However, the potential antimutagenicity of these plant extracts towards B[a]P was weaker than that towards IQ. For a direct mutagen, 4-nitroquinoline-N-oxide (NQNO), only the Sol extracts showed strong inhibitory effects in the TA100 system. The antimutagenic activity of water extracts of Sec was partly reduced by heating at 100 degrees C for 20 min. The heat-stable antimutagens in Sec extracts could be produced in the plant extract preparation process. Fractions with molecular weights above 30,000 showed the strongest antimutagenicity and peroxidase activity in all the fractions of the Sec extracts.


Asunto(s)
Antimutagênicos/farmacología , Antineoplásicos Fitogénicos/farmacología , Mutágenos/farmacología , Mutágenos/toxicidad , Plantas/toxicidad , Animales , Ensayo Cometa , Frutas/química , Frutas/toxicidad , Humanos , Técnicas In Vitro , Linfocitos/efectos de los fármacos , Pruebas de Mutagenicidad , Fenoles/aislamiento & purificación , Fenoles/farmacología , Fenoles/toxicidad , Extractos Vegetales/química , Plantas/química , Ratas , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Taiwán , Verduras/química , Verduras/toxicidad
15.
ISA Trans ; 40(2): 99-110, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11368088

RESUMEN

The validation of sensor measurements has become an integral part of the operation and control of modern industrial equipment. The sensor under harsh environment must be shown to consistently provide the correct measurements. Analysis of the validation hardware or software should trigger an alarm when the sensor signals deviate appreciably from the correct values. Neural network based models can be used to on-line estimate critical sensor values when neighboring sensor measurements are used as inputs. The underlying assumption is that the neighboring sensors share an analytical relationship. The discrepancy between the measured and predicted sensor values may then be used as an indicator for sensor health. The proposed Winner Take All Experts (WTAE) network based on a 'divide and conquer' strategy significantly reduces the computational time required to train the neural network. It employs a growing fuzzy clustering algorithm to divide a complicated problem into a series of simpler sub-problems and assigns an expert to each of them locally. After the sensor approximation, the outputs from the estimator and the real sensor readings are compared both in the time domain and the frequency domain. Three fault indicators are used to provide analytical redundancy to detect the sensor failure. In the decision stage, the intersection of three fuzzy sets accomplishes a decision level fusion, which indicates the confidence level of the sensor health. Two data sets, the Spectra Quest Machinery Fault Simulator data set and the Westland vibration data set, were used in simulations to demonstrate the performance of the proposed WTAE network. The simulation results show the proposed WTAE is competitive with or even superior to the existing approaches.

16.
J Agric Food Chem ; 49(5): 2579-86, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11368639

RESUMEN

The effects of water extracts from Cassia tora L. (WECT) treated with different degrees of roasting on benzo[a]pyrene (B[a]P)-induced DNA damage in human hepatoma cell line HepG2 were investigated via the comet assay without exogenous activation mixtures, such as S9 mix. WECT alone, at concentrations of 0.1-2 mg/mL, showed neither cytotoxic nor genotoxic effect toward HepG2 cells. B[a]P-induced DNA damage in HepG2 cells could be reduced by WECT in a dose-dependent manner (P < 0.05). At a concentration of 1 mg/mL, the inhibitory effects of WECT on DNA damage were in the order unroasted (72%) > roasted at 150 degrees C (60%) > roasted at 250 degrees C (23%). Ethoxyresorufin-O-dealkylase activity of HepG2 cells was effectively inhibited by WECT, and a similar trend of inhibition was observed in the order unroasted (64%) > roasted at 150 degrees C (42%) > roasted at 250 degrees C (18%). The activity of NADPH cytochrome P-450 reductase was also decreased by unroasted and 150 degrees C-roasted samples (50% and 38%, respectively). Furthermore, glutathione S-transferase activity was increased by treatment with unroasted (1.26-fold) and 150 degrees C-roasted (1.35-fold) samples at 1 mg/mL. In addition, the contents of anthraquinones (AQs) in WECT, including chrysophanol, emodin, and rhein, were decreased with increasing roasting temperature. Each of these AQs also demonstrated significant antigenotoxic activity in the comet assay. The inhibitory effects of chrysophanol, emodin, and rhein on B[a]P-mediated DNA damage in HepG2 cells were 78, 86, and 71%, respectively, at 100 microM. These findings suggested that the decreased antigenotoxicity of the roasted samples might be due to a reduction in their AQs content.


Asunto(s)
Benzo(a)pireno/antagonistas & inhibidores , Cassia , ADN/química , Plantas Medicinales , Línea Celular , Ensayo Cometa , Culinaria , Daño del ADN , Relación Dosis-Respuesta a Droga , Humanos
17.
J Agric Food Chem ; 49(3): 1426-31, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11312875

RESUMEN

The objectives of this study were to isolate the antioxidative components in the broth filtrate of Aspergillus candidus (CCRC 31543), to characterize their antioxidative properties, and to evaluate their safety. Three major compounds were isolated and identified as 3,3' '-dihydroxyterphenyllin, 3-hydroxyterphenyllin, and candidusin B. In the linoleic acid peroxidation system, the inhibition of peroxidation in these three compounds was greater than 95% and was significantly higher than that of alpha-tocopherol but equal to that of BHA at 12.5-200 microg/mL. As measured using the Rancimat method in lard, 3,3' '-di-OH-terphenyllin exhibited a protection factor value of 7.82, which was substantially higher than those of BHA (5.58) and alpha-tocopherol (4.29) at 200 microg/mL. 3,3' '-di-OH-terphenyllin and 3-OH-terphenyllin also exhibited marked scavenging effects on the alpha,alpha-diphenyl-beta-picrylhydrazyl radicals (94.7 and 96.0%, respectively), which were similar to those of BHA and alpha-tocopherol. Safety studies showed that these three compounds were neither cyto- nor geno-toxic toward human intestine 407 (INT 407) cells, nor mutagenic toward Salmonella typhimurium TA98 and TA100.


Asunto(s)
Antioxidantes/análisis , Aspergillus/crecimiento & desarrollo , Compuestos de Terfenilo/análisis , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Hidroxitolueno Butilado/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Medios de Cultivo/análisis , Depuradores de Radicales Libres/farmacología , Humanos , Ácido Linoleico/química , Peroxidación de Lípido/efectos de los fármacos , Pruebas de Mutagenicidad , Mutágenos/farmacología , Seguridad , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Compuestos de Terfenilo/aislamiento & purificación , Compuestos de Terfenilo/farmacología
18.
J Agric Food Chem ; 49(3): 1455-63, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11312880

RESUMEN

The antioxidant effects of water extracts of roasted barley (WERB) were investigated under different roasting temperatures and compared with those of the water extracts of unroasted barley (WEUB). It was found that the Maillard reaction products increased upon increasing the roasting temperatures. Both WERB and WEUB exhibited significant antioxidant activities in linoleic acid and liposome model systems. Although WERB and WEUB afforded considerable protection against the damage of deoxyribose and proteins, the antioxidant efficiency of roasted samples was weaker than that of unroasted samples because of the reduction of antioxidant components (catechin, tocopherol, and lutein) with increasing roasting temperature. Unroasted samples were more effective in reducing power, quenching free radical, hydroxyl radical, and chelating iron than the roasted samples. The different antioxidant activity among roasted and unroasted barley samples may be partly attributed to the changes in catechin, tocopherol, and lutein contents.


Asunto(s)
Hordeum/química , Extractos Vegetales/química , Aminoácidos/análisis , Quelantes/química , Culinaria , Desoxirribosa/química , Disacáridos/análisis , Calor , Radical Hidroxilo/química , Ácido Linoleico/química , Peroxidación de Lípido , Liposomas , Monosacáridos/análisis , Oxidación-Reducción , Proteínas/química , Albúmina Sérica Bovina/química , Agua
19.
J Agric Food Chem ; 49(4): 1767-72, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11308324

RESUMEN

Genistein, daidzein, and glycitein, as primary isoflavones in soybeans, are reported to have beneficial effects on atherosclerosis, chronic inflammatory diseases, and cancers that are conducted by nitric oxide (NO) injury. The objectives of this study were to investigate the effects and mechanisms of these soy isoflavones on the inducible nitric oxide synthase (iNOS) system in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Genistein, daidzein, and glycitein dose-dependently suppress NO production (IC(50) = 50 microM) in supernatants of LPS-activated macrophages as measured on the basis of nitrite accumulation. In addition, direct inhibition of iNOS activity, determined by means of the conversion of L-[(3)H]arginine to L-[(3)H]citrulline, and markedly reduced iNOS protein and mRNA levels, evaluated by means of Western blot and RT-PCR, respectively, were found in homogenates of LPS-activated cells treated with each isoflavone. Moreover, genistein was found to have a greater inhibitory effect on NO production but no significant effect on iNOS activity or protein and gene expression to daidzein and glycitein. These observations reveal that the suppression of NO production by genistein, daidzein, and glycitein might be due to the inhibition of both the activity and expression of iNOS in LPS-activated macrophages. The result suggests that soy isoflavones might attenuate excessive NO generation at inflammatory sites.


Asunto(s)
Glycine max/química , Isoflavonas/farmacología , Macrófagos/efectos de los fármacos , Óxido Nítrico/metabolismo , Western Blotting , Células Cultivadas , Lipopolisacáridos , Macrófagos/enzimología , Óxido Nítrico Sintasa/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
20.
J Food Prot ; 64(2): 240-5, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11271774

RESUMEN

Since the fume of cooking oil has been reported to increase the risk of lung cancer, the objectives of this study were to evaluate the mutagenicity and to find the mutagens in the fumes of peanut oil heated to the smoke point. Peanut oil prepared from roasted peanut kernel showed a lower smoke point, less unsaturated fatty acids, more fume formation, and stronger mutagenicity than that from unroasted kernel. Further investigation of mutagenic compounds was performed by the Ames test and gas chromatography/mass spectrometry analysis. Among the 12 compounds identified from the neutral fraction of methanol extract, four compounds at a dose of 10 microg per plate were mutagenic to Salmonella Typhimurium TA98 and TA100 in the order of trans-trans-2,4-decadienal > trans-trans-2,4-nonadienal > trans-2-decenal > trans-2-undecenal. Results report the enal compounds formed as the mutagens in the fumes of peanut oil and indicate that inhaling cooking fumes might cause carcinogenic risk.


Asunto(s)
Mutágenos/toxicidad , Aceites de Plantas/química , Salmonella typhimurium/efectos de los fármacos , Humo/efectos adversos , Cromatografía de Gases y Espectrometría de Masas , Pruebas de Mutagenicidad , Mutágenos/análisis , Aceite de Cacahuete , Aceites de Plantas/efectos adversos
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