RESUMEN
Abstract The β-lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p<0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.
Resumo Os medicamentos combinados de β-lactâmicos / inibidores da lactamase (BLBLIs) são considerados uma alternativa eficaz aos carbapenêmicos. No entanto, existe uma preocupação crescente de que o aumento do uso de BLBLIs pode levar ao aumento da resistência. Este estudo determinou a associação temporal entre o consumo de BLBLI e a resistência antimicrobiana em bactérias gram-negativas. Neste estudo retrospectivo, os dados eletrônicos sobre as bactérias gram-negativas isoladas, incluindo A. baumannii, P. aeruginosa, E. coli e K. pneumoniae de pacientes internados e os resultados dos testes de suscetibilidade foram recuperados dos registros médicos do laboratório clínico. Uma regressão linear e análise de correlação cruzada foram realizadas nos dados adquiridos. Foram observadas tendências crescentes (p < 0,05) no consumo de BIBLI e carbapenem com uma mediana de uso de 27,68 e 34,46 DDD/1000 PD por trimestre, respectivamente. Foi observada uma tendência de diminuição (p = 0,023) no consumo de fluoroquinolonas com uma mediana de uso de 29,13 DDD/1000 PD por trimestre. A taxa de resistência de K. pneumoniae foi sincronizada com os consumos de BIBLI e carbapenem com coeficiente de correlação de 0,893 (p = 0,012) e 0,951 (p = 0,016), respectivamente. A análise de correlação cruzada contra o consumo de BIBLI e K. pneumoniae resistente ao meropenem atingiu o pico no intervalo de 0 quarto (r = 951, p = 0,016). Houve uma tendência de aumento no consumo de BLBLI e carbapenêmicos. A tendência crescente nas taxas de resistência a piperacilina/tazobactam, em linha com o consumo crescente de BLBLI, sugere que BLBLI deve ser usado com cautela e não pode ser considerado diretamente como alternativa de longo prazo aos carbapenêmicos.
Asunto(s)
Humanos , Infecciones por Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas/epidemiología , Antibacterianos/uso terapéutico , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos , Escherichia coli , Bacterias GramnegativasRESUMEN
Abstract The -lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p 0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.
Resumo Os medicamentos combinados de -lactâmicos / inibidores da lactamase (BLBLIs) são considerados uma alternativa eficaz aos carbapenêmicos. No entanto, existe uma preocupação crescente de que o aumento do uso de BLBLIs pode levar ao aumento da resistência. Este estudo determinou a associação temporal entre o consumo de BLBLI e a resistência antimicrobiana em bactérias gram-negativas. Neste estudo retrospectivo, os dados eletrônicos sobre as bactérias gram-negativas isoladas, incluindo A. baumannii, P. aeruginosa, E. coli e K. pneumoniae de pacientes internados e os resultados dos testes de suscetibilidade foram recuperados dos registros médicos do laboratório clínico. Uma regressão linear e análise de correlação cruzada foram realizadas nos dados adquiridos. Foram observadas tendências crescentes (p 0,05) no consumo de BIBLI e carbapenem com uma mediana de uso de 27,68 e 34,46 DDD/1000 PD por trimestre, respectivamente. Foi observada uma tendência de diminuição (p = 0,023) no consumo de fluoroquinolonas com uma mediana de uso de 29,13 DDD/1000 PD por trimestre. A taxa de resistência de K. pneumoniae foi sincronizada com os consumos de BIBLI e carbapenem com coeficiente de correlação de 0,893 (p = 0,012) e 0,951 (p = 0,016), respectivamente. A análise de correlação cruzada contra o consumo de BIBLI e K. pneumoniae resistente ao meropenem atingiu o pico no intervalo de 0 quarto (r = 951, p = 0,016). Houve uma tendência de aumento no consumo de BLBLI e carbapenêmicos. A tendência crescente nas taxas de resistência a piperacilina/tazobactam, em linha com o consumo crescente de BLBLI, sugere que BLBLI deve ser usado com cautela e não pode ser considerado diretamente como alternativa de longo prazo aos carbapenêmicos.
RESUMEN
Enzymes immobilized onto substrates with excellent selectivity and activity show a high stability and can withstand extreme experimental conditions, and their performance has been shown to be retained after repeated uses. Applications of immobilized enzymes in various fields benefit from their unique characteristics. Common methods, including adsorption, encapsulation, covalent attachment and crosslinking, and other emerging approaches (e.g., MOFs) of enzyme immobilization have been developed mostly in recent years. In accordance with these immobilization methods, the present review elaborates the application of magnetic separable nanoparticles and functionalized SBA-15 and MCM-41 mesoporous materials used in the immobilization of enzymes.(AU)
Enzimas imobilizadas em substratos com excelente seletividade e atividade apresentam alta estabilidade e podem suportar condições experimentais extremas, e seu desempenho foi mantido após repetidos usos. As aplicações de enzimas imobilizadas em vários campos se beneficiam de suas características únicas. Métodos comuns, incluindo adsorção, encapsulamento, ligação covalente e reticulação, e outras abordagens emergentes (por exemplo, MOFs) de imobilização de enzima, foram desenvolvidos principalmente nos últimos anos. De acordo com esses métodos de imobilização, a presente revisão elabora a aplicação de nanopartículas magnéticas separáveis e materiais mesoporosos funcionalizados SBA-15 e MCM-41 usados na imobilização de enzimas.(AU)
Asunto(s)
Agentes de Inmovilización de Enzimas , NanopartículasRESUMEN
Enzymes immobilized onto substrates with excellent selectivity and activity show a high stability and can withstand extreme experimental conditions, and their performance has been shown to be retained after repeated uses. Applications of immobilized enzymes in various fields benefit from their unique characteristics. Common methods, including adsorption, encapsulation, covalent attachment and crosslinking, and other emerging approaches (e.g., MOFs) of enzyme immobilization have been developed mostly in recent years. In accordance with these immobilization methods, the present review elaborates the application of magnetic separable nanoparticles and functionalized SBA-15 and MCM-41 mesoporous materials used in the immobilization of enzymes.
Enzimas imobilizadas em substratos com excelente seletividade e atividade apresentam alta estabilidade e podem suportar condições experimentais extremas, e seu desempenho foi mantido após repetidos usos. As aplicações de enzimas imobilizadas em vários campos se beneficiam de suas características únicas. Métodos comuns, incluindo adsorção, encapsulamento, ligação covalente e reticulação, e outras abordagens emergentes (por exemplo, MOFs) de imobilização de enzima, foram desenvolvidos principalmente nos últimos anos. De acordo com esses métodos de imobilização, a presente revisão elabora a aplicação de nanopartículas magnéticas separáveis e materiais mesoporosos funcionalizados SBA-15 e MCM-41 usados na imobilização de enzimas.
Asunto(s)
Enzimas Inmovilizadas/metabolismo , Nanopartículas de Magnetita , Estabilidad de Enzimas , Adsorción , Concentración de Iones de HidrógenoRESUMEN
Enzymes immobilized onto substrates with excellent selectivity and activity show a high stability and can withstand extreme experimental conditions, and their performance has been shown to be retained after repeated uses. Applications of immobilized enzymes in various fields benefit from their unique characteristics. Common methods, including adsorption, encapsulation, covalent attachment and crosslinking, and other emerging approaches (e.g., MOFs) of enzyme immobilization have been developed mostly in recent years. In accordance with these immobilization methods, the present review elaborates the application of magnetic separable nanoparticles and functionalized SBA-15 and MCM-41 mesoporous materials used in the immobilization of enzymes.
Enzimas imobilizadas em substratos com excelente seletividade e atividade apresentam alta estabilidade e podem suportar condições experimentais extremas, e seu desempenho foi mantido após repetidos usos. As aplicações de enzimas imobilizadas em vários campos se beneficiam de suas características únicas. Métodos comuns, incluindo adsorção, encapsulamento, ligação covalente e reticulação, e outras abordagens emergentes (por exemplo, MOFs) de imobilização de enzima, foram desenvolvidos principalmente nos últimos anos. De acordo com esses métodos de imobilização, a presente revisão elabora a aplicação de nanopartículas magnéticas separáveis e materiais mesoporosos funcionalizados SBA-15 e MCM-41 usados na imobilização de enzimas.
Asunto(s)
Agentes de Inmovilización de Enzimas , NanopartículasRESUMEN
Abstract Enzymes immobilized onto substrates with excellent selectivity and activity show a high stability and can withstand extreme experimental conditions, and their performance has been shown to be retained after repeated uses. Applications of immobilized enzymes in various fields benefit from their unique characteristics. Common methods, including adsorption, encapsulation, covalent attachment and crosslinking, and other emerging approaches (e.g., MOFs) of enzyme immobilization have been developed mostly in recent years. In accordance with these immobilization methods, the present review elaborates the application of magnetic separable nanoparticles and functionalized SBA-15 and MCM-41 mesoporous materials used in the immobilization of enzymes.
Resumo Enzimas imobilizadas em substratos com excelente seletividade e atividade apresentam alta estabilidade e podem suportar condições experimentais extremas, e seu desempenho foi mantido após repetidos usos. As aplicações de enzimas imobilizadas em vários campos se beneficiam de suas características únicas. Métodos comuns, incluindo adsorção, encapsulamento, ligação covalente e reticulação, e outras abordagens emergentes (por exemplo, MOFs) de imobilização de enzima, foram desenvolvidos principalmente nos últimos anos. De acordo com esses métodos de imobilização, a presente revisão elabora a aplicação de nanopartículas magnéticas separáveis e materiais mesoporosos funcionalizados SBA-15 e MCM-41 usados na imobilização de enzimas.
RESUMEN
The ß-lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p<0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.
Asunto(s)
Antibacterianos , Infecciones por Bacterias Gramnegativas , Antibacterianos/uso terapéutico , Escherichia coli , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , Estudios RetrospectivosRESUMEN
PURPOSE: The GEO database and KEGG database-based analyses identified the differential expression of cyclin-dependent kinase 1 (CDK1) in cervical cancer and its involvement in the cell cycle pathway. In the present study, we aim to clarify the role of CDK1 in cervical cancer and the function of upstream microRNA (miR)-143-3p/miR-495-3p. METHODS: The expression of miR-143-3p, miR-495-3p, and CDK1 in cervical cancer tissues and cells was determined using RT-qPCR. Cell bioactivities were examined by CCK-8 and flow cytometry. The binding affinity between CDK1 and miR-143-3p/miR-495-3p was investigated using dual luciferase gene reporter assay. A xenograft mouse model of cervical cancer was then established to explore their effect on the tumorigenicity of cervical cancer cells in vivo. RESULTS: CDK1 was found to be the common target gene of miR-143-3p and miR-495-3p. CDK1 overexpression occurred in cervical cancer tissues and cells, while expression of miR-495-3p and miR-143-3p was down-regulated. The viability was inhibited while the apoptosis was promoted in cervical cancer cells in response to miR-143-3p or miR-495-3p overexpression, or CDK1 silencing. Further, miR-143-3p or miR-495-3p overexpression was also substantiated to inhibit the tumorigenicity of cervical cancer cells in vivo, while CDK1 overexpression counteracted their effect. CONCLUSION: Taken together, miR-143-3p and miR-495-3p co-target CDK1, thereby inhibiting the occurrence and development of cervical cancer.
Asunto(s)
Proteína Quinasa CDC2/metabolismo , MicroARNs/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Animales , Apoptosis , Proteína Quinasa CDC2/genética , Ciclo Celular , Movimiento Celular , Proliferación Celular , Cuello del Útero/metabolismo , Bases de Datos Genéticas , Regulación hacia Abajo , Femenino , Silenciador del Gen , Genes Reporteros , Células HeLa , Xenoinjertos , Humanos , Luciferasas/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Trasplante de Neoplasias , Distribución Aleatoria , Regulación hacia Arriba , Neoplasias del Cuello Uterino/patologíaRESUMEN
Enzymes immobilized onto substrates with excellent selectivity and activity show a high stability and can withstand extreme experimental conditions, and their performance has been shown to be retained after repeated uses. Applications of immobilized enzymes in various fields benefit from their unique characteristics. Common methods, including adsorption, encapsulation, covalent attachment and crosslinking, and other emerging approaches (e.g., MOFs) of enzyme immobilization have been developed mostly in recent years. In accordance with these immobilization methods, the present review elaborates the application of magnetic separable nanoparticles and functionalized SBA-15 and MCM-41 mesoporous materials used in the immobilization of enzymes.
Asunto(s)
Enzimas Inmovilizadas , Nanopartículas de Magnetita , Adsorción , Estabilidad de Enzimas , Enzimas Inmovilizadas/metabolismo , Concentración de Iones de HidrógenoRESUMEN
PURPOSE: Laryngeal cancer has a poor prognosis when progressing to an advanced stage with limited treatment options. Therefore, understanding the underlying mechanisms is important to identify novel treatment targets. Long non-coding RNAs (lncRNAs) have been shown to play oncogenic roles in cancer, including in laryngeal cancer. We previously discovered that the lncRNA RP11-297P16.3 is overexpressed in laryngeal squamous cell carcinoma (LSCC) based on RNA-sequencing data. Therefore, the aim of the present study was to investigate the effects of knockdown of RP11-297P16.3 on the migration and invasion of LSCC cells, and the significance of these effects. METHODS: Six methods were employed to assess the function of RP11-297P16.3 including gene silencing, RT-PCR, the 5-Ethynyl-20-deoxyuridine (EdU) staining assay, Scratch wound-healing assay, transwell assay, and Western blot. RESULTS: The results show that the expression of RP11-297P16.3 in the si-lncRNA group was significantly decreased compared with those in the BC (blank control) and NC (negative control) groups. Moreover, knockdown of RP11-297P16.3 significantly inhibited the migration and invasion of LSCC cells but had no effect on cell proliferation. The protein expression of N-cadherin and vimentin was notably decreased after RP11-297P16.3 knockdown; whereas, the protein expression of cadherin was significantly increased CONCLUSION: These results suggested that RP11-297P16.3 may inhibit the migration and invasion of LSCC cells by regulating the epithelial-mesenchymal transition process, suggesting that RP11-297P16.3 is a potential new target for treating LSCC.
Asunto(s)
Movimiento Celular/genética , Proliferación Celular/genética , Silenciador del Gen , Neoplasias Laríngeas/genética , ARN Largo no Codificante/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Humanos , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patología , Invasividad Neoplásica/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Vimentina/metabolismoRESUMEN
PURPOSE: To explore the regulatory relationship between Chloride intracellular channel 1 (CLIC1) and Angiomotin (AMOT)-p130, and reveal the role of AMOT-p130 in gastric cancer (GC). METHODS: Immunohistochemistry was performed to analyze the expression of CLIC1 and AMOT-p130 in GC tissues and adjacent tissues. The expression of AMOT-p130 upon CLIC1 silencing was analyzed using RT-PCR, western blot, and immunofluorescence in GC cells. Transwell and wound-healing assays were performed to detect migration and invasion in GC cells. The changes in EMT-related proteins were detected using western blot. RESULTS: Our study found that high CLIC1 expression was significantly associated with low AMOT-p130 expression in GC tissues. Silencing CLIC1 expression in MGC-803 cells (MGC-803 CLIC1 KO) and AGS cells (AGS CLIC1 KO) decreased the invasive and migratory abilities of tumor cells, which were induced by the upregulation of AMOT-p130. Subsequently, we demonstrated that AMOT-p130 inhibits the invasive and migratory abilities of GC cells by inhibiting epithelial-mesenchymal transition. CONCLUSIONS: Our study suggests that AMOT-p130 could inhibit epithelial-mesenchymal transition in GC cells. CLIC1 may participate in the metastatic progression of GC by downregulating the expression of AMOT-p130.
Asunto(s)
Canales de Cloruro/metabolismo , Transición Epitelial-Mesenquimal , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas de Microfilamentos/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Angiomotinas , Línea Celular Tumoral , Movimiento Celular , Canales de Cloruro/genética , Femenino , Silenciador del Gen , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Estadificación de Neoplasias , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba , Cicatrización de HeridasRESUMEN
PURPOSE: To explore the diagnostic value of miR-21 combined with computed tomography (CT) in patients with liver cancer. METHODS: A total of 112 patients in our hospital were confirmed liver cancer by examination, and were collected as cancer group. Another 100 patients with hepatic focal nodular hyperplasia in the same period were collected as control group. The diagnostic value of miR-21 and CT on liver cancer was observed. RESULTS: The level of miR-21 in cancer group was significantly higher than that in control group, the difference was statistically significant (p < 0.05). The alpha-fetoprotein (AFP) level was tested. It was found that the AFP level in cancer group was significantly higher than that in control group (p < 0.001). The correlation between AFP and miR-21 levels in liver cancer patients was detected. It turned out that AFP and miR-21 had correlation. According to receiver operating curve (ROC) calculation results, the best cut-off value for miR-21 diagnosis was 4.142. The sensitivity, specificity and accuracy of diagnosis of miR-21 alone were 64.29%, 87.00% and 75.00%, respectively. The sensitivity, specificity and accuracy of diagnosis of CT alone were 91.07%, 62.00% and 77.36%, respectively. There were 108 cases of true positive and 80 cases of true negative after combined diagnosis in the two groups. The sensitivity, specificity and accuracy of combined diagnosis were 96.43%, 80.00% and 88.68%, respectively. Comparing the value of single diagnosis and combined diagnosis, we found that the accuracy, sensitivity and specificity of combined diagnosis were significantly higher than that of single diagnosis (p < 0.05). CONCLUSION: CT combined with miR-21 has great diagnostic value in liver cancer and may be a potential diagnostic indicator for liver cancer.
Asunto(s)
Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/diagnóstico por imagen , MicroARNs/sangre , Tomografía Computarizada por Rayos X , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To investigate the role of PRDX2 in esophageal carcinoma (ESCA). METHODS: The expression of PRDX2 was detected in ESCA tissues. And PRDX2 expression in two ESCA cell lines was knocked down. Cell proliferation, metastasis and invasion were detected in these cells. RESULTS: Here, we found that PRDX2 expression was significantly increased in ESCA tissues and was associated with a poor prognosis in ESCA patients. In addition, PRDX2 expression was significantly associated with pathological grading, infiltration degree and 5-year survival time in ESCA patients. Next, we knocked down PRDX2 expression by PRDX2-shRNA transfection in two ESCA cell lines, Eca-109 and TE-1. Proliferation analysis indicated that in vitro PRDX2 knockdown decreased growth and clone formation of ESCA cells. Scratch and transwell assays indicated that cell migration and invasion were significantly inhibited by PRDX2 knockdown. In addition, PRDX2 knockdown inhibited cell cycle of ESCA cells and down-regulated Cyclin D1-CDK4/6. Moreover, PRDX2 knockdown regulated proteins involved in mitochondrial-dependent apoptosis, including increased Bax and Caspase9/3 and decreased Bcl2. Mechanism investigation indicated that PRDX2 knockdown led to inactivation of Wnt/ß-catenin and AKT pathways. CONCLUSIONS: Our data suggest that PRDX2 may function as an oncogene in the development of ESCA via regulating Wnt/ß-catenin and AKT pathways. Our study fills a gap in the understanding of the role of PRDX2 in ESCA and provides a potential target for ESCA treatment.
Asunto(s)
Neoplasias Esofágicas/etiología , Carcinoma de Células Escamosas de Esófago/etiología , Peroxirredoxinas/fisiología , Proteínas Proto-Oncogénicas c-akt/fisiología , Vía de Señalización Wnt/fisiología , Apoptosis , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Humanos , Peroxirredoxinas/análisisRESUMEN
BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162â534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11â307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. (AU)
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Enfermedades Cardiovasculares , Neoplasias/mortalidadRESUMEN
OBJECTIVES: In recent years, docetaxel, cisplatin and fluorouracil (TPF)-based induction chemotherapy (IC) has been widely applied in the treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC). However, it remains unclear whether TPF is the ideal IC regimen. Thus, we carried out a meta-analysis to compare the efficacy and safety of TPF-based IC plus concurrent chemoradiotherapy (CCRT) versus CCRT alone or double-drug-based IC plus CCRT for LA-NPC. METHODS: We systematically searched PubMed, Embase and the Cochrane Library from inception until December 2018. After rigorous screening of all relevant studies that reported the use of TPF-based IC followed by CCRT for patients with LA-NPC, eight studies met the inclusion criteria and were assessed for design and quality. Among them, three articles were classified as having a high risk of bias and were excluded from the meta-analysis. The outcomes, including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), locoregional failure-free survival (LRFFS) and incidence of adverse events, were pooled with the use of hazard ratio (HR) or odds ratio (OR). Heterogeneity and sensitivity analyses were also carried out. RESULTS: Five trials involving 4223 patients were included in the meta-analysis. Compared to CCRT alone, TPF-based IC plus CCRT significantly improved OS (HR 0.54, 95% confidence interval [CI] 0.35-0.84, P = 0.006), PFS (HR 0.64, 95% CI 0.46-0.88, P = 0.006), LRFFS (HR 0.57, 95% CI 0.34-0.94, P = 0.03), and DMFS (HR 0.58, 95% CI 0.38-0.88, P = 0.01). Moreover, compared to double-drug-based IC plus CCRT, OS (HR 0.74, 95% CI 0.62-0.87, P = 0.0004), PFS (HR 0.76, 95% CI 0.66-0.88, P = 0.0001) and LRFFS (HR 0.75, 95% CI 0.61-0.92, P = 0.006) were also significantly improved by TPF-based IC plus CCRT. Notably, TPF-based IC plus CCRT mainly led to an increased risk of hematologic toxicities, such as leucopenia (OR = 3.20, 95% CI 2.13-4.81, P < 0.0001) and neutropenia (OR = 3.84, 95% CI 0.66-22.36, P = 0.13). However, these were uncomplicated and manageable with growth factor support. CONCLUSIONS: Compared to CCRT alone or double-drug-based IC plus CCRT, TPF-based IC plus CCRT results in better survival outcomes with manageable toxicities. Thus, it is reasonable to recommend the addition of TPF-based IC to CCRT as an excellent choice for patients with LA-NPC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Inducción , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Quimioradioterapia Adyuvante , Cisplatino/uso terapéutico , Docetaxel/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Fluorouracilo/uso terapéutico , Humanos , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Análisis de SupervivenciaRESUMEN
We report the electronic and magnetic properties of stoichiometric CeAuBi2 single crystals. At ambient pressure, CeAuBi2 orders antiferromagnetically below a Néel temperature (TN ) of 19 K. Neutron diffraction experiments revealed an antiferromagnetic propagation vector τ ^ = [ 0 , 0 , 1 ∕ 2 ] , which doubles the paramagnetic unit cell along the c axis. At low temperatures several metamagnetic transitions are induced by the application of fields parallel to the c axis, suggesting that the magnetic structure of CeAuBi2 changes as a function of field. At low temperatures, a linear positive magnetoresistance may indicate the presence of band crossings near the Fermi level. Finally, the application of external pressure favors the antiferromagnetic state, indicating that the 4f electrons become more localized.
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This study has the objective of investigating the effects of traditional Chinese medicine prescriptions (TCM) on serum lipid, abdominal and hepatic fat percentage, cholesterol content in eggs, and mRNA expression of genes apoA I and apoB100. One hundred and thirty five healthy (300-day-old) layers were randomly assigned to three treatments. The hens in control group were fed with the basal diet. The hens in the experimental groups (TCM 1 and TCM 2) were fed with the basal diet supplemented with 1% TCM 1 and 1% TCM 2 respectively over a period of 60 days. Laying performance and the serum parameters relevant to fat metabolism were measured. The results showed that no significant differences were found in average daily feed intake and egg weight among three treatments. Average daily laying rate in TCM treatments was increased, and the cholesterol content in eggs was decreased. The serum triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in experimental treatments were decreased (p<0.05), while the serum high-density lipoprotein cholesterol (HDL-C) level was increased (p<0.05) compared to the control group. Additionally, abdominal fat percentage decreased in TCM 1 treatment (p<0.05), and hepatic fat percentage decreased in both TCM treatments (p<0.05). The expression of apolipoproteinA I (apoA I) and apolipoproteinB100 (apoB100) mRNA in the liver increased in both TCM treatments (p<0.05). These results suggest that the diet supplemented with TCM could increase the expression of apoA I and apoB100 mRNA in the liver, and decrease lipid content in the serum, and reduce egg cholesterol in layers.
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Animales , Pollos/anomalías , Pollos/metabolismo , Medicina Tradicional China/efectos adversos , ColesterolRESUMEN
This study has the objective of investigating the effects of traditional Chinese medicine prescriptions (TCM) on serum lipid, abdominal and hepatic fat percentage, cholesterol content in eggs, and mRNA expression of genes apoA I and apoB100. One hundred and thirty five healthy (300-day-old) layers were randomly assigned to three treatments. The hens in control group were fed with the basal diet. The hens in the experimental groups (TCM 1 and TCM 2) were fed with the basal diet supplemented with 1% TCM 1 and 1% TCM 2 respectively over a period of 60 days. Laying performance and the serum parameters relevant to fat metabolism were measured. The results showed that no significant differences were found in average daily feed intake and egg weight among three treatments. Average daily laying rate in TCM treatments was increased, and the cholesterol content in eggs was decreased. The serum triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in experimental treatments were decreased (p<0.05), while the serum high-density lipoprotein cholesterol (HDL-C) level was increased (p<0.05) compared to the control group. Additionally, abdominal fat percentage decreased in TCM 1 treatment (p<0.05), and hepatic fat percentage decreased in both TCM treatments (p<0.05). The expression of apolipoproteinA I (apoA I) and apolipoproteinB100 (apoB100) mRNA in the liver increased in both TCM treatments (p<0.05). These results suggest that the diet supplemented with TCM could increase the expression of apoA I and apoB100 mRNA in the liver, and decrease lipid content in the serum, and reduce egg cholesterol in layers.(AU)
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Animales , Pollos/anomalías , Pollos/metabolismo , Medicina Tradicional China/efectos adversos , ColesterolRESUMEN
Glutathione synthetase deficiency (GSSD) is a rare inborn error of glutathione metabolism with autosomal recessive inheritance. The severe form of the disease is characterized by acute metabolic acidosis, usually present in the neonatal period with hemolytic anemia and progressive encephalopathy. A case of a male newborn infant who had severe metabolic acidosis with high anion gap, hemolytic anemia, and hyperbilirubinemia is reported. A high level of 5-oxoproline was detected in his urine and a diagnosis of generalized GSSD was made. DNA sequence analysis revealed the infant to be compound heterozygous with two mutations, c.738dupG in exon 8 of GSS gene resulting in p.S247fs and a repetitive sequence in exon 3 of GSS gene. Treatment after diagnosis of GSSD included supplementation with antioxidants and oral sodium hydrogen bicarbonate. However, he maintained a variable degree of metabolic acidosis and succumbed shortly after his parents requested discontinuation of therapy because of dismal prognosis and medical futility when he was 18 days old.