Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Environ Geochem Health ; 45(6): 3759-3775, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36513912

RESUMEN

The impact of the tailing dams and the economic feasibility of the remediation process is significant for future risk management for tailing dams. In this research, we develop a hypothetical failure scenario for a tailing dam in the Jinding mining area, Southwest China. We assess the exposure with the Geo-Environmental Risk Assessment System, tier-1 model, and health impact with Disability-Adjusted Life Years (DALY). Cost and benefit are also analyzed for the following clean-up process. The result shows that the exposure dose (mg/kg-BW/d) of As, Cd, and Pb right after the dam failure is 1.07 × 10-2 for As, 1.76 × 10-4 for Cd, and 5.68 × 10-3 for Pb, respectively. The DALY caused by heavy metal exposure is 2.63 × 10-2 DALY per year, which significantly exceeds the tolerable level. This indicates that the tailing dam failure will pose a high health risk to the residents, and remediation is necessary. After remediation, the DALY is 1.24 × 10-8 DALY per year, indicating the clean-up process effectively reduces the resident's health impact. From the financial point of view, the net present value of the clean-up is $- 1.02 × 107. This indicates that the clean-up process is not economically feasible. Sensitivity analysis shows that the amount of released tailing influences the output result. The time span for benefit estimation is also an important issue. This research shows that the impact of a tailing dam failure will be severe, and remediation may be effective but economically infeasible. Therefore, preventing tailing dam failure is the most crucial task for the local government.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Suelo , Análisis Costo-Beneficio , Cadmio/análisis , Plomo/análisis , Monitoreo del Ambiente , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Metales Pesados/análisis , Medición de Riesgo , China
2.
BMC Womens Health ; 17(1): 14, 2017 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-28264686

RESUMEN

BACKGROUND: Breast cancer (breast Ca) is recognised as a major public health problem in the world. Data on reproductive factors associated with breast Ca in the Central African Republic (CAR) is very limited. This study aimed to identify reproductive variables as risk factors for breast Ca in CAR women. METHODS: A case-control study was conducted among 174 cases of breast Ca confirmed at the Pathology Unit of the National Laboratory in Bangui between 2003 and 2015 and 348 age-matched controls. Data collection tools included a questionnaire, interviews and a review of medical records of patients. Data were analysed using SPSS software version 20. Odd ratios and 95% confidence intervals (CI) for the likelihood of developing breast Ca were obtained using unconditional logistic regression. RESULTS: In total, 522 women with a mean age of 45.8 (SD = 13.4) years were enrolled. Women with breast Ca were more likely to have attained little or no education (AOR = 11.23, CI: 4.65-27.14 and AOR = 2.40, CI: 1.15-4.99), to be married (AOR = 2.09, CI: 1.18-3.71), to have had an abortion (AOR = 5.41, CI: 3.47-8.44), and to be nulliparous (AOR = 1.98, CI: 1.12-3.49). Decreased odds of breast Ca were associated with being employed (AOR = 0.32, CI: 0.19-0.56), living in urban areas (AOR = 0.16, CI: 0.07-0.37), late menarche (AOR = 0.18, CI: 0.07-0.44), regular menstrual cycles (AOR = 0.44, CI: 0.23-0.81), term pregnancy (AOR = 0.26, CI: 0.13-0.50) and hormonal contraceptive use (AOR = 0.62, CI: 0.41-0.93). CONCLUSION: Breast Ca risk factors in CAR did not appear to be significantly different from that observed in other populations. This study highlighted the risk factors of breast Ca in women living in Bangui to inform appropriate control measures.


Asunto(s)
Neoplasias de la Mama/epidemiología , Reproducción , Medición de Riesgo , Aborto Inducido/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Neoplasias de la Mama/etiología , Estudios de Casos y Controles , República Centroafricana/epidemiología , Distribución de Chi-Cuadrado , Escolaridad , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Ocupaciones/estadística & datos numéricos , Oportunidad Relativa , Paridad , Embarazo , Sistema de Registros , Encuestas y Cuestionarios
3.
BMC Public Health ; 16(1): 1230, 2016 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-27923361

RESUMEN

BACKGROUND: Breast cancer is recognised as a major public health problem in developing countries; however, there is very limited evidence about its epidemiology in the Central African Republic. The aim of this study was to investigate the epidemiological and histopathological characteristics of breast cancer in Bangui. METHODS: This is a retrospective study based on the data collected from pathological anatomy records from 2003 to 2015 in Bangui. A questionnaire was designed to collect information and data was analysed using descriptive and inferential statistical methods. RESULTS: The mean age was 45.83 (SD = 13.5) years. The age group of 45-54 years represented the majority of the study population (29.3%). Over 69.5% of the women were housewives with a moderate economic status (56.9%). Less than 14% of the study population had a level of academic degree and 85.6% lived in cities. The breast cancer prevalence was 15.27%. The age-standardized incidence and death by world population (ASW) were 11.19/100,000 and 9.97/100,000 respectively. 50-54 years were most affected. Left breast cancer is mainly common and the time between first symptoms and consultation is more than 48 months. Most (69%) of the samples analysed were lumpectomy. The most common morphology of breast cancer was invasive ductal carcinoma (64.9%). Scarff Bloom Richardson III was the main grade in both common pathological types, but their proportion showed no significant increase along with time (χ2 = 7.06, p = 0.54). Invasion of regional lymph node differed significantly among the pathological type of breast cancer (χ2 = 24.6, p = 0.02). Surgery and chemotherapy were appropriate treatment yet 84.5% of the cases died. CONCLUSION: The findings of this study showed that breast cancer is common and mostly affected women. Epidemiological trends are more or less common to those of developing countries with a predominance of invasive ductal carcinoma. However, most of the women studied live in an urban area and developed the disease in advanced stage. The establishment of an appropriate framework will effectively contribute to promoting the early detection and reducing the incidence of this disease in the population.


Asunto(s)
Neoplasias de la Mama/epidemiología , Adulto , Neoplasias de la Mama/patología , República Centroafricana/epidemiología , Femenino , Humanos , Incidencia , Ganglios Linfáticos/patología , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Población Urbana/estadística & datos numéricos
4.
Chemistry ; 21(23): 8351-4, 2015 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-25907201

RESUMEN

Two attractive chirons, aldehyde 6 and chloride 7, exhibiting functionalized ent-spongiane-type tricyclic skeletons (ABC ring system), have been constructed and their absolute configurations have been studied by NMR spectroscopy and confirmed by single-crystal X-ray diffraction. Both of these chirons are derived from commercially available andrographolide in good yield. Aldehyde 6 is obtained through a novel K2 S2 O8 -catalyzed aquatic ring-closing reaction of allylic sodium sulfonate and intramolecular 1,7-hydrogen atom transfer process. Further mechanistic investigations demonstrate that the 1,7-hydrogen atom transfer is a free-radical process, whereby hydrogen migrates from C18 to C17, as evidenced by double-18- deuterium-labeled isotope experiments. Prospective applications of these two chiral sources are also discussed.

5.
Anal Biochem ; 441(2): 162-8, 2013 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-23811155

RESUMEN

Lipoxygenases (LOXs) are a family of non-heme iron-containing dioxygenases that catalyze the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. A rapid and reliable colorimetric assay for determination of the activity of three human functional lipoxygenase isoforms (5-lipoxygenase, platelet 12-lipoxygenase, and 15-lipoxygenase-1) is developed in this article. In the new assay, LOX-derived lipid hydroperoxides oxidize the ferrous ion (Fe²âº) to the ferric ion (Fe³âº), the latter of which binds with thiocyanate (SCN⁻) to generate a red ferrithiocyanate (FTC) complex. The absorbance of the FTC complex can be easily measured at 480 nm. Because 5-LOX can be stimulated by many cofactors, the effects of its cofactors (Ca²âº, ATP, dithiothreitol, glutathione, L-α-phosphatidylcholine, and ethylenediaminetetraacetic acid) on the color development of the FTC complex are also determined. The assay is adaptive for purified LOXs and cell lysates containing active LOXs. We use the new colorimetric assay in a 96-well format to evaluate several well-known LOX inhibitors, the IC50 values of which are in good agreement with previously reported data. The reliability and reproducibility of the assay make it useful for in vitro screening for inhibitors of LOXs and, therefore, should accelerate drug discovery for clinical application.


Asunto(s)
Colorimetría/métodos , Pruebas de Enzimas/métodos , Lipooxigenasa/metabolismo , Colorimetría/economía , Pruebas de Enzimas/economía , Células HEK293 , Humanos , Inhibidores de la Lipooxigenasa/farmacología , Isoformas de Proteínas/metabolismo
6.
Int J Pharm ; 638: 122914, 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37028571

RESUMEN

Cholesterol (CHOL) is essential for developing lipid nanoparticles (LNPs) for gene delivery because it enhances membrane fusion and improves the delivery efficiency of gene cargos. An attractive pDNA carrier, corosolic acid (CA)-modified lipid nanoparticles (CLNPs), was developed by replacing CHOL in LNPs to deliver pDNA at various ratios of nitrogen groups to phosphate groups (N/P). The resultant CLNPs with a higher CHOL/CA ratio exhibited similar mean particle size, zeta potential, and encapsulation efficiency to those of LNPs. In comparison with LNPs, CLNPs (CHOL:CA ratio = 2:1) achieved increased cellular uptake and enhanced transfection efficacy while maintaining low cytotoxicity. In vivo results from chicken experiments demonstrated that CLNPs encapsulating DNA vaccines against avian influenza at a N/P ratio of 3 could elicit similar-level humoral and cellular immune responses compared with those of LNPs at a higher N/P ratio, thereby suggesting the induction of desirable immune effects using less ionizable lipids. Our study provides a reference for further research on the application of CA in LNPs for gene delivery, and the development of novel delivery systems for DNA vaccines against avian influenza.


Asunto(s)
Gripe Aviar , Nanopartículas , Vacunas de ADN , Animales , Gripe Aviar/prevención & control , Lípidos
7.
Polymers (Basel) ; 14(6)2022 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-35335571

RESUMEN

Microparticles (MPs) and amorphous solid dispersions (SDs) are effective methods to improve the dissolution of insoluble drugs. However, stability is a concern for these two high-energy systems, resulting from high surface area and amorphous polymorph, respectively. As an amphiphilic polymer, Soluplus (SOL) is usually used as a carrier in SDs. In this study, erlotinib microparticles (ERL MPs) and erlotinib solid dispersions (ERL SDs) were prepared with SOL by bottom-up technology and solvent evaporation. The solid-state properties of ERL MPs and ERL SDs were characterized by Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Electron Microscopy (SEM). The ERL MPs existed in a metastable crystal form A while the ERL SDs existed in an amorphous state. Fourier transform infrared spectroscopy (FT-IR) showed that there was a hydrogen bond interaction between the N-H group of ERL and the carbonyl group of SOL in ERL MPs and SDs. The dissolution profiles of ERL SDs and ERL MPs were improved significantly. ERL MPs showed better stability than ERL SDs in accelerated stability test. The discrepant stabilizing effects of polymer SOL in two systems may provide effective ideas for solubilization of insoluble drugs and the stability of drugs after recrystallization.

8.
Ann Transl Med ; 8(7): 445, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32395489

RESUMEN

BACKGROUND: Secondhand smoke (SHS) may be related to worse outcomes in chronic obstructive pulmonary disease (COPD), but the reported SHS prevalence in different studies varied from 27% to 65% and the effects of SHS are still questionable among these patients. The study aims were to estimate the objective SHS prevalence and explore the SHS impact on outcomes among COPD patients without active smoking. METHODS: A cross-sectional design combined with longitudinal death outcome. We selected COPD patients over 40 years old based on the spirometry from National Health and Nutrition Examination Survey (2007-2012), and used the tobacco-specific biomarkers [cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanonol] to determine exposure statuses (active smoking, SHS exposure, or no smoke exposure). Then we estimated the short-term (past 2-4 days) and medium-term (past 6-12 weeks) SHS prevalence among 334 patients without active smoking. Weighted multiple regressions were performed to assess the associations between medium-term SHS exposure and outcomes (symptoms, health status, medical institution visits, and death). RESULTS: Among the patients without active smoking, the objective prevalence rates of short-term and medium-term SHS were 66.65% [95% confidence interval (CI), 59.63-73.67%] and 34.91% (95% CI, 28.86%-40.96%), respectively. Medium-term SHS exposure showed a significant effect (odds ratio, 3.57; 95% CI, 1.22-10.40) on more chronic coughing after adjusting for the covariates and indicated a trend of unadjusted increasing death risk (log-rank test, P=0.01). CONCLUSIONS: Among COPD patients without active smoking, both short-term and medium-term SHS exposure are prevalent. Chronic cough may be the most susceptible patient-centred outcome related to medium-term SHS exposure. The crude longitudinal trend of elevated death risk associated with medium-term SHS exposure deserves further study.

9.
J Pain Symptom Manage ; 57(4): 820-827, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30684634

RESUMEN

OBJECTIVES: To validate and use the Chinese Version of the M. D. Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI-C) to assess the symptom burden of Chinese-speaking patients with gastrointestinal cancer. METHODS: In total, 527 patients with postoperative or advanced digestive tract tumors were enrolled in the trial, who had definitive diagnoses and different treatments in our cancer center. MDASI-GI-C was administered to these patients between February and December 2017. The item-scale correlations and internal consistency were evaluated. Construct validity was established by factor analysis. Hierarchical cluster analysis was performed. RESULTS: Cronbach's alpha of the symptom severity and interference subscales was 0.842 and 0.859, respectively. Construct validity revealed a four-factor structure. Known-group validity was established by comparing the MDASI-GI-C scores between patients having different Karnofsky Performance Status scores (≤70 or >70), which were observed to have significant differences. The overall mean subscale scores for the core and interference subscales were 1.63 ± 2.02 and 2.17 ± 2.34, respectively. Fatigue, disturbed sleep, and lack of appetite had the highest scores for most serious symptoms. No significant differences in age, working status, and educational level were found. CONCLUSIONS: MDASI-GI-C is a reliable and valid tool for assessing cancer-related symptoms in Chinese-speaking patients with digestive tract tumors, facilitates the understanding of the common symptoms of patients with digestive tract tumors, and enables timely management of these symptoms. Cognitive debriefing demonstrated that the patients found MDASI-GI-C to be an easy-to-use and understandable instrument.


Asunto(s)
Neoplasias Gastrointestinales/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Evaluación de Síntomas , Traducciones
10.
Artículo en Inglés | MEDLINE | ID: mdl-28953262

RESUMEN

Cancer is a serious public health issue and the leading cause of death around the world. This article aimed to estimate the cancer incidence and the trend in standardized cancer incidence in Shenzhen, Guangdong province, South China during 2001-2015 by analyzing the cancer data of the population-based cancer registry in Shenzhen. Data were collected from the cancer registry in Shenzhen, which was conducted during 2001-2015. In this registry, the crude incidence rates, age-specific incidence rates, age-standardized incidence rates and cumulative incidence rates were calculated in every five years. Trends for standardized incidence rates of cancers were analyzed by using the joinpoint regression analysis. In total, 33,374.3 thousand person-years (17,593.9 thousand for males and 15,780.4 thousand for females) were monitored over this time period. The number of new cancer cases during 2001-2015 was 59,218 (30,144 and 29,074 for males and females, respectively). The crude incidence during 2001-2005 was 136.44 per 100,000 persons, while the age-standardized rates by Chinese standard population (ASR-China) and by world standard population (ASR-world) were 165.13 and 212.48 per 100,000 persons, respectively. The crude incidence during 2006-2010 was 179.01 per 100,000 persons, while the ASR-China and ASR-world were 168.08 and 214.44 per 100,000 persons, respectively. The crude incidence during 2011-2015 was 196.53 per 100,000 persons, while the ASR-China and ASR-world were 171.44 and 219.99 per 100,000 persons, respectively. During 2001 and 2015, the joinpoint regression analysis showed that the ASR-China of cancer had an overall increase of 0.96% per year and 0.84% per year for males and females respectively, although both of these values (males and females) were non-significant increases. The leading cancer types during 2011-2015 were lung, colorectal, thyroid gland, breast, liver, stomach, cervix, nasopharynx, leukemia and lymphoma. For males, the top five common cancers were lung, liver, colorectal, stomach and thyroid gland. For females, the top five common cancers were breast, thyroid gland, lung, colorectal and cervix. The results of this study showed a heavy cancer burden among the population of Shenzhen, China. Future researches of the etiology and prevention of cancers should be planned in order to reduce the incidence associated with cancers in the future.


Asunto(s)
Neoplasias/epidemiología , Anciano , Preescolar , China/epidemiología , Femenino , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Estándares de Referencia , Sistema de Registros , Proyectos de Investigación , Estudios Retrospectivos , Adulto Joven
11.
J Med Chem ; 60(5): 1817-1828, 2017 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-28218840

RESUMEN

Acute lung injury (ALI) and idiopathic pulmonary fibrosis (IPF) are both serious public health problems with high incidence and mortality rate in adults, and with few drugs available for the efficient treatment in clinic. In this study, we identified that two known histone deacetylase (HDAC) inhibitors, suberanilohydroxamic acid (SAHA, 1) and its analogue 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide (2), are effective inhibitors of Leukotriene A4 hydrolase (LTA4H), a key enzyme in the biosynthesis of leukotriene B4 (LTB4), across a panel of 18 HDAC inhibitors, using enzymatic assay, thermofluor assay, and X-ray crystallographic investigation. Importantly, both 1 and 2 markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose. Detailed mechanisms of down-regulation of proinflammatory cytokines by 1 or 2 were determined in vivo. Collectively, 1 and 2 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.


Asunto(s)
Lesión Pulmonar Aguda/prevención & control , Epóxido Hidrolasas/antagonistas & inhibidores , Inhibidores de Histona Desacetilasas/farmacología , Fibrosis Pulmonar Idiopática/prevención & control , Leucotrieno B4/antagonistas & inhibidores , Neutrófilos/efectos de los fármacos , Lesión Pulmonar Aguda/patología , Animales , Femenino , Fibrosis Pulmonar Idiopática/patología , Leucotrieno B4/biosíntesis , Ratones , Ratones Endogámicos C57BL
12.
PLoS One ; 12(2): e0171154, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28178283

RESUMEN

Breast cancer is recognized as a major public health problem in developing countries; however, there is very little evidence of behavioral factors associated with breast cancer risk. This study was conducted to identify lifestyles as risk factors for breast cancer among Central African women. A case-control study was conducted with 174 cases confirmed histologically by the pathology unit of the National Laboratory and 348 age-matched controls. Data collection tools included a questionnaire with interviews and medical records of patients. Data were analyzed using SPSS software version 20. Odd ratio (OR) and 95% confidence intervals (95% CI) were obtained by unconditional logistic regression. In total, 522 women were studied with a mean age of 45.8 (SD = 13.4) years. By unconditional logistic regression model, women with breast cancer were more likely to have attained illiterate and elementary education level [11.23 (95% CI, 4.65-27.14) and 2.40 (95% CI, 1.15-4.99)], married [2.09 (95% CI, 1.18-3.71)], positive family history [2.31 (95% CI, 1.36-3.91)], radiation exposure [8.21 (95% CI, 5.04-13.38)], consumption charcuterie [10.82 (95% CI, 2.39-48.90)], fresh fish consumption [4.26 (95% CI, 1.56-11.65)], groundnut consumption [6.46 (95% CI, 2.57-16.27)], soybean consumption [16.74 (95% CI, 8.03-39.84)], alcohol [2.53 (95% CI, 1.39-4.60)], habit of keeping money in bras[3.57 (95% CI, 2.24-5.69)], overweight [5.36 (95% CI, 4.46-24.57)] and obesity [3.11(95% CI, 2.39-20.42)]. However, decreased risk of breast cancer was associated with being employed [0.32 (95% CI, 0.19-0.56)], urban residence [0.16 (95% CI, 0.07-0.37)], groundnut oil consumption [0.05 (95% CI, 0.02-0.14)], wine consumption [0.16 (95% CI, 0.09-0.26)], non habit of keeping cell phone in bras [0.56 (95% CI, 0.35-0.89)] and physical activity [0.71(95% CI, 0.14-0.84)]. The study showed that little or no education, marriage, positive family history of cancer, radiation exposure, charcuterie, fresh fish, groundnut, soybean, alcohol, habit of keeping money in bras, overweight and obesity were associated with breast cancer risk among Central African women living in Bangui. Women living in Bangui should be more cautious on the behavioral risk associated with breast cancer.


Asunto(s)
Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Estilo de Vida , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pesos y Medidas Corporales , Estudios de Casos y Controles , República Centroafricana , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores Socioeconómicos , Adulto Joven
13.
Sci Rep ; 5: 8060, 2015 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-25622827

RESUMEN

Serotonin (5-HT) receptors are valuable molecular targets for antipsychotic drug discovery. Current reported methods for detecting 5-HT receptors, such as cAMP accumulation and calcium influx assay, are often demanding specialized instruments and inconvenient. The luciferase reporter gene assay, based on the responsible-element-regulated expression of luciferase, has been widely applied in the high-throughput functional assay for many targets because of its high sensitivity and reliability. However, 5-HT receptors couple to multiple G-proteins regulate respective downstream signalling pathways and are usually detected using different response elements. Hence, finding a suitable response element to fulfil the detection of different 5-HT receptors and make the results of luciferase reporter gene assays generalizable is very useful for active compounds screening. Here, we conducted three luciferase reporter assays using CRE, NFAT, and SRE response elements attached to 5-HT to detect the activation of different 5-HT receptors in CHO-K1 cells. The potencies and efficacies of the reported ligands (agonists and antagonists) were determined and compared. Our results indicate that CRE-luciferase reporter gene is sensitive and reliable to detect the activities of G protein-coupled 5-HT receptors.


Asunto(s)
Genes Reporteros , Luciferasas/metabolismo , Receptores de Serotonina/metabolismo , Animales , Células CHO , Cricetinae , Cricetulus , Humanos , Luciferasas/genética , Receptores de Serotonina/química , Receptores de Serotonina/genética , Elementos de Respuesta/genética , Transducción de Señal
14.
Sci Rep ; 5: 8114, 2015 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-25631039

RESUMEN

Non-steroidal anti-inflammatory drugs (NSAIDs) are worldwide used drugs for analgesic, antipyretic, and anti-inflammatory therapeutics. However, NSAIDs often cause several serious liver injuries, such as drug-induced liver injury (DILI), and the molecular mechanisms of DILI have not been clearly elucidated. In this study, we developed a systems pharmacology approach to explore the mechanism-of-action of NSAIDs. We found that the Farnesoid X Receptor (FXR) antagonism of NSAIDs is a potential molecular mechanism of DILI through systematic network analysis and in vitro assays. Specially, the quantitative real-time PCR assay reveals that indomethacin and ibuprofen regulate FXR downstream target gene expression in HepG2 cells. Furthermore, the western blot shows that FXR antagonism by indomethacin induces the phosphorylation of STAT3 (signal transducer and activator of transcription 3), promotes the activation of caspase9, and finally causes DILI. In summary, our systems pharmacology approach provided novel insights into molecular mechanisms of DILI for NSAIDs, which may propel the ways toward the design of novel anti-inflammatory pharmacotherapeutics.


Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidores , Biología de Sistemas , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Predisposición Genética a la Enfermedad , Células Hep G2 , Humanos , Ibuprofeno/efectos adversos , Indometacina/efectos adversos , Luciferasas/metabolismo , Fosforilación/efectos de los fármacos , Mapas de Interacción de Proteínas/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Factor de Transcripción STAT3/metabolismo , Transcripción Genética/efectos de los fármacos , Activación Transcripcional/genética , Técnicas del Sistema de Dos Híbridos
15.
Chem Biol Interact ; 213: 69-76, 2014 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-24412237

RESUMEN

The study of iron chelators as cancer chemotherapeutic agents is still in its infancy. Accordingly, there is a need to optimize new chelating molecules for iron chelation therapy and cancer treatment. Previous studies have demonstrated that the ligand tris(1-pyrazolyl) borohydride and its derivates were able to chelate ferrous iron, but very little research focused on their biological properties and applications in cancer treatment. So, in this study, several boron-pyrazole derivatives were chosen for the examination of their effects on the proliferation of human hepatocellular carcinoma (HCC) cell lines. The results suggested that potassium tris(4-methyl-1-pyrazolyl) borohydride (KTp(4-Me)) exhibited the most potent anti-tumor activities among the candidates. Hence, the antiproliferative activity and the iron chelating capacity of the iron chelator KTp(4-Me) in HCC cell lines HepG2 and Hep3B were characterized. KTp(4-Me) could disrupt cell iron uptake and affect signaling pathways of iron regulation in HCC cell lines and induced the expression of TfR1 and HIF-1α in a concentration-dependent manner, which was a typical cell response to iron deficiency. Moreover, KTp(4-Me) arrested cell cycle in S phase and induced cell apoptosis in both Hep3B and HepG2 cells. Overall, our results provide a promising starting point and the possibility of the future development and applications of KTp(4-Me) in HCC therapy.


Asunto(s)
Antineoplásicos/farmacología , Compuestos de Boro/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Pirazoles/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Compuestos de Boro/química , Compuestos de Boro/uso terapéutico , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Hep G2 , Humanos , Estructura Molecular , Pirazoles/química , Pirazoles/uso terapéutico , Transducción de Señal/efectos de los fármacos
16.
Fitoterapia ; 94: 55-61, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24468190

RESUMEN

Malaria is one of the most devastating infectious diseases in the developing world. Until now, only one candidate malaria vaccine RTS,S/AS01 has shown modest protection in phase 3 trial in African infants. Hence the treatment of malaria still depends on the current chemotherapeutic drugs. Considering the resistance of malaria parasites to almost all used antimalarial drugs, aiming at multi-targets rather than a single target will be a more promising strategy. Previous studies have shown that myricetin and fisetin exhibited in vitro antimalarial activity against Plasmodium falciparum, but very little research focused on the molecular mechanism for their parasiticidal activity. The cysteine protease falcipain-2 and aspartic protease plasmepsin II have long been considered as important antimalarial drug targets, especially combined inhibition of these two proteases. In this study, we determined that myricetin and fisetin are dual inhibitors of falcipain-2 and plasmepsin II, which might account for their antimalarial properties. Overall, the dual inhibition of falcipain-2 and plasmepsin II by myricetin and fisetin has shed light on a possible mechanism for their antimalarial activity and provided a rationale for further development as antimalarial drugs.


Asunto(s)
Antimaláricos/farmacología , Ácido Aspártico Endopeptidasas/antagonistas & inhibidores , Inhibidores de Cisteína Proteinasa/farmacología , Flavonoides/farmacología , Plasmodium falciparum/efectos de los fármacos , Proteínas Protozoarias/antagonistas & inhibidores , Antimaláricos/química , Ácido Aspártico Endopeptidasas/metabolismo , Cisteína Endopeptidasas/metabolismo , Inhibidores de Cisteína Proteinasa/química , Flavonoides/química , Flavonoles , Humanos , Cinética , Simulación del Acoplamiento Molecular , Estructura Molecular , Plasmodium falciparum/enzimología , Proteínas Protozoarias/metabolismo , Proteínas Recombinantes
17.
Yan Ke Xue Bao ; 23(4): 247-51, 2007 Dec.
Artículo en Zh | MEDLINE | ID: mdl-18303675

RESUMEN

PURPOSE: To compare with phacoemulsification, to evaluate the clinical outcomes and advantages of modified tunnel incision non-phacoemulsification and foldable intraocular lens (IOL) implantation. METHODS: One hundred and eighteen eyes of 118 cataract patients were randomly divided into two groups: phacoemulsification and foldable IOL implantation group (58 eyes) as well as modified tunnel incision non-phacoemulsification and foldable IOL implantation group (60 eyes). Intraoperative complications and postoperative visual acuity were evaluated. RESULTS: There was no significant difference in intraoperative complications and postoperative visual acuity between two groups. The cost of non-phacoemulsification was less than that of the phacoemulsification surgery. The Study curve is also short in non-phaco-emulsification surgery. CONCLUSION: Modified tunnel incision non-phacoemulsification and foldable intraocular lens (IOL) implantation surgery is suitable to be promoted in cataract treatment.


Asunto(s)
Extracción de Catarata/métodos , Catarata/terapia , Implantación de Lentes Intraoculares/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Facoemulsificación/métodos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA