RESUMEN

Quorum sensing (QS) is a cell-to-cell communication mechanism mediated by small diffusible signaling molecules. Previous studies showed that RpfR controls Burkholderia cenocepacia virulence as a cis-2-dodecenoic acid (BDSF) QS signal receptor. Here, we report that the fatty acyl-CoA ligase DsfR (BCAM2136), which efficiently catalyzes in vitro synthesis of lauryl-CoA and oleoyl-CoA from lauric acid and oleic acid, respectively, acts as a global transcriptional regulator to control B. cenocepacia virulence by sensing BDSF. We show that BDSF binds to DsfR with high affinity and enhances the binding of DsfR to the promoter DNA regions of target genes. Furthermore, we demonstrate that the homolog of DsfR in B. lata, RS02960, binds to the target gene promoter, and perception of BDSF enhances the binding activity of RS02960. Together, these results provide insights into the evolved unusual functions of DsfR that control bacterial virulence as a response regulator of QS signal.

Asunto(s)

Proteínas Bacterianas , Burkholderia cenocepacia , Coenzima A Ligasas , Regulación Bacteriana de la Expresión Génica , Regiones Promotoras Genéticas , Percepción de Quorum , Percepción de Quorum/genética , Burkholderia cenocepacia/patogenicidad , Burkholderia cenocepacia/genética , Burkholderia cenocepacia/metabolismo , Virulencia , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Coenzima A Ligasas/metabolismo , Coenzima A Ligasas/genética , Animales , Transducción de Señal , Ácidos Grasos Monoinsaturados/metabolismo , Ratones , Unión Proteica , Ácidos Láuricos/metabolismo

RESUMEN

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.

RESUMEN

A growing body of evidence indicates that systemic lupus erythematosus (SLE) is associated with increased risk of cognitive impairment and dementia. However, to date, no studies have been conducted to quantitatively summarize and evaluate the consistency of data. OBJECTIVE: To quantitatively evaluate the relationship of SLE and antiphospholipid antibodies (aPL) with cognitive dysfunction and dementia. METHODS: All relevant literature was retrieved from Pubmed, Scopus, and PsycINFO databases. The meta-analysis was performed using effect estimates and 95% confidence intervals (CIs) to calculate pooled risk estimates. The heterogeneity among studies was also examined. RESULTS: The meta-analysis included 11 original studies involving a total of 81,668 patients with dementia and 407 patients with cognitive dysfunction. There were significant associations on fixed-effect models between SLE and dementia (3 studies; RR=1.50; 95% CI=1.37-1.64), SLE and cognitive dysfunction (4 studies; OR=2.97; 95% CI=1.72-5.15), and aPL and cognitive dysfunction (5 studies, OR=1.97; 95% CI=1.55-2.52). We also combined cognitive dysfunction and dementia outcomes as they both represented cognitive impairment. There were significant associations between aPL and cognitive impairment (6 studies; OR=2.03; 95% CI=1.62-2.55), and SLE and cognitive impairment (7 studies; OR=1.83; 95% CI=1.42-2.35). Moderate heterogeneity (I2=45.7%) was found in the association between SLE and cognitive impairment, low heterogeneity (I2=21.8%) in the association between SLE and dementia, and near zero heterogeneity for the other three main analyses. CONCLUSION: Both SLE and aPL are associated with cognitive impairment.

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Um volume crescente de evidências indica que o lúpus eritematoso sistêmico (LES) está associado ao aumento do risco de comprometimento cognitivo e demência. No entanto, até o presente momento nenhum estudo foi conduzido a fim de resumir e avaliar quantitativamente a consistência dos dados. OBJETIVO: Avaliar quantitativamente a relação entre o LES e anticorpos anticorpos antifosfolípides (aPL) com disfunção cognitiva e demência. MÉTODOS: Toda literatura relevante foi recuperada das bases de dados Pubmed, Scopus e PsycINFO. A meta-análise foi realizada utilizando as estimativas de efeito e os intervalos de confiança de 95% (ICs) para calcular as estimativas de risco combinadas. A heterogeneidade entre os estudos também foi examinada. RESULTADOS: A meta-análise incluiu 11 estudos originais com um total de 81.668 pacientes com demência e 407 pacientes com disfunção cognitiva. Houve associações significativas (modelos de efeitos fixos) entre LES e demência (3 estudos, RR=1,50; IC 95%=1,37-1,64), LES e disfunção cognitiva (4 estudos; OR=2,97; IC 95%=1,72-5,15), e aPL e disfunção cognitiva (5 estudos, OR=1,97; IC 95%=1,55-2,52). Além disso, combinamos os resultados da disfunção cognitiva e demência, uma vez que ambos representaram déficit cognitivo. Houve associações significativas entre aPL e comprometimento cognitivo (6 estudos, OR=2,03, IC 95%=1,62-2,55), e LES e comprometimento cognitivo (7 estudos, OR=1,83; IC 95%=1,42-2,35). Uma heterogeneidade moderada (I2=45,7%) foi encontrada na associação entre LES e comprometimento cognitivo, heterogeneidade baixa (I2=21,8%) na associação entre LES e demência e heterogeneidade quase zero para as outras três principais análises. CONCLUSÃO: Tanto o LES como aPL estão associados a déficit cognitivo.

RESUMEN

Abstract A growing body of evidence indicates that systemic lupus erythematosus (SLE) is associated with increased risk of cognitive impairment and dementia. However, to date, no studies have been conducted to quantitatively summarize and evaluate the consistency of data. Objective: To quantitatively evaluate the relationship of SLE and antiphospholipid antibodies (aPL) with cognitive dysfunction and dementia. Methods: All relevant literature was retrieved from Pubmed, Scopus, and PsycINFO databases. The meta-analysis was performed using effect estimates and 95% confidence intervals (CIs) to calculate pooled risk estimates. The heterogeneity among studies was also examined. Results: The meta-analysis included 11 original studies involving a total of 81,668 patients with dementia and 407 patients with cognitive dysfunction. There were significant associations on fixed-effect models between SLE and dementia (3 studies; RR=1.50; 95% CI=1.37-1.64), SLE and cognitive dysfunction (4 studies; OR=2.97; 95% CI=1.72-5.15), and aPL and cognitive dysfunction (5 studies, OR=1.97; 95% CI=1.55-2.52). We also combined cognitive dysfunction and dementia outcomes as they both represented cognitive impairment. There were significant associations between aPL and cognitive impairment (6 studies; OR=2.03; 95% CI=1.62-2.55), and SLE and cognitive impairment (7 studies; OR=1.83; 95% CI=1.42-2.35). Moderate heterogeneity (I2=45.7%) was found in the association between SLE and cognitive impairment, low heterogeneity (I2=21.8%) in the association between SLE and dementia, and near zero heterogeneity for the other three main analyses. Conclusion: Both SLE and aPL are associated with cognitive impairment.

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Resumo Um volume crescente de evidências indica que o lúpus eritematoso sistêmico (LES) está associado ao aumento do risco de comprometimento cognitivo e demência. No entanto, até o presente momento nenhum estudo foi conduzido a fim de resumir e avaliar quantitativamente a consistência dos dados. Objetivo: Avaliar quantitativamente a relação entre o LES e anticorpos anticorpos antifosfolípides (aPL) com disfunção cognitiva e demência. Métodos: Toda literatura relevante foi recuperada das bases de dados Pubmed, Scopus e PsycINFO. A meta-análise foi realizada utilizando as estimativas de efeito e os intervalos de confiança de 95% (ICs) para calcular as estimativas de risco combinadas. A heterogeneidade entre os estudos também foi examinada. Resultados: A meta-análise incluiu 11 estudos originais com um total de 81.668 pacientes com demência e 407 pacientes com disfunção cognitiva. Houve associações significativas (modelos de efeitos fixos) entre LES e demência (3 estudos, RR=1,50; IC 95%=1,37-1,64), LES e disfunção cognitiva (4 estudos; OR=2,97; IC 95%=1,72-5,15), e aPL e disfunção cognitiva (5 estudos, OR=1,97; IC 95%=1,55-2,52). Além disso, combinamos os resultados da disfunção cognitiva e demência, uma vez que ambos representaram déficit cognitivo. Houve associações significativas entre aPL e comprometimento cognitivo (6 estudos, OR=2,03, IC 95%=1,62-2,55), e LES e comprometimento cognitivo (7 estudos, OR=1,83; IC 95%=1,42-2,35). Uma heterogeneidade moderada (I2=45,7%) foi encontrada na associação entre LES e comprometimento cognitivo, heterogeneidade baixa (I2=21,8%) na associação entre LES e demência e heterogeneidade quase zero para as outras três principais análises. Conclusão: Tanto o LES como aPL estão associados a déficit cognitivo.

Asunto(s)

Humanos , Lupus Eritematoso Sistémico/complicaciones , Factores de Riesgo , Demencia , Disfunción Cognitiva

RESUMEN

BACKGROUND: Several epidemiological studies have found that the prevalence of bipolar disorder (BD) is significantly higher in obese population than non-obese population. However, no meta-analysis has been published to quantitatively summarize the related literature. METHODS: In this study, we conducted a meta-analysis to explore the association between obesity and BD by combining 9 cross-sectional studies with a total of 12,259 BD cases and 615,490 non-BD controls. The meta-analysis was performed using the effect estimates and 95% confidence intervals (CIs) to calculate the pooled odds ratio (OR), while the heterogeneity was assessed using I(2) and Q statistic. RESULTS: Our meta-analysis suggests that obesity is associated with increased prevalence of BD by a random-effect model (OR=1.77, 95% CI: 1.40-2.23; Q=44.62, P<0.001, I(2)=82.1%). LIMITATION: Without prospective studies, we cannot determine whether obesity increased the risk of developing BD or vice-versa. CONCLUSION: Obesity is positively associated with BD.

Asunto(s)

Trastorno Bipolar/complicaciones , Obesidad/complicaciones , Trastorno Bipolar/epidemiología , Humanos , Modelos Estadísticos , Obesidad/psicología , Oportunidad Relativa , Prevalencia , Factores de Riesgo

RESUMEN

This prospective cohort study aimed to analyze the association between serum ferritin levels and the risk of abnormal glucose metabolism (AGM) in Southwestern Chinese population. The 383 subjects who are aged ≥20 years and free of AGM at baseline between in 2007 and in 2008 were included in Southwestern China, and their baseline serum ferritin levels were measured. Among these subjects, 140 subjects were developed into AGM during the follow-up (2008-2012). In logistic regression models, the relative risk in the top versus that in the lowest quartile of serum ferritin levels was 2.86 (p = 0.013) in females and 3.50 (p = 0.029) in males after adjusting the age, gender, family history of diabetes, current smoking, and alcohol; however, serum ferritin levels were not significantly associated with incident of AGM after controlling for metabolic factors (waist circumference, systolic pressure (SBP), triglyceride (TG), and homeostasis model assessment formula insulin resistance (HOMA-IR)). Elevated serum ferritin levels are associated with AGM but not an independent risk factor.

Asunto(s)

Ferritinas/sangre , Trastornos del Metabolismo de la Glucosa/epidemiología , Glucosa/metabolismo , Adulto , Presión Sanguínea/fisiología , China/epidemiología , Estudios de Cohortes , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Resistencia a la Insulina , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Triglicéridos/sangre , Circunferencia de la Cintura

RESUMEN

BACKGROUND AND OBJECTIVE: Emerging evidence from biological and epidemiological studies has suggested that body iron stores and heme-iron intake may be related to the risk of type 2 diabetes (T2D). We aimed to examine the association of body iron stores and heme-iron intake with T2D risk by conducting a systematic review and meta-analysis of previously published studies. RESEARCH DESIGN AND METHODS: Systematic review and subsequent meta-analysis were conducted by searching MEDLINE database up to June 22, 2012 to identify studies that analyzed the association of body iron stores or dietary heme-iron intake with T2D risk. The meta-analysis was performed using the effect estimates and 95% confidence intervals (CIs) to calculate the pooled risk estimates, while the heterogeneity among studies was examined using the I(2) and Q statistic. RESULTS: The meta-analysis included 16 high-quality studies: 12 studies analyzed ferritin levels (4,366 T2D patients and 41,091 controls) and 4 measured heme-iron intake (9,246 T2D patients and 179,689 controls). The combined relative risk (RR) comparing the highest and lowest category of ferritin levels was 1.66 (95% CI: 1.15-2.39) for prospective studies, 2.29 (95% CI: 1.48-3.54) for cross-sectional studies with heterogeneity (Q = 14.84, p = 0.01, I(2) = 66.3%; Q = 44.16, p<0.001, I(2) = 88.7%). The combined RR comparing the highest and lowest category of heme-iron intake was 1.31 (95% CI: 1.21-1.43) with heterogeneity (Q = 1.39, p = 0.71, I(2) = 0%). No publication bias was found. Additional 15 studies that were of good quality, had significant results, and analyzed the association between body iron stores and T2D risk were qualitatively included in the systematic review. CONCLUSIONS: The meta-analysis and systematic review suggest that increased ferritin levels and heme-iron intake are both associated with higher risk of T2D.

Asunto(s)

Diabetes Mellitus Tipo 2/metabolismo , Hemo/metabolismo , Hierro/metabolismo , Animales , Transporte Biológico , Humanos , Riesgo

RESUMEN

Dopamine D1 receptor (DRD1) gene is associated with the pathogenesis of myocardial infarction (MI) in aspects of plaque rupture, platelet aggregation, and neutrophil-mediated injury of cardiac myocytes. Thus, the study was designed to explore whether the A-48G polymorphism of the DRD1 gene was associated with MI. The genotype of the DRD1A-48G polymorphism was determined by polymerase chain reaction in the 602 Han Chinese participants, 255 MI patients and 347 controls without MI. A significant association was found between the A-48G polymorphism of DRD1 and MI (genotype model: χ(2)=13.2, unadjusted p=0.001; χ(2)=13.9, adjusted p=0.0002; dominant model: adjusted OR 2.05, 95%CI 1.40-3.00, p=0.0002; recessive model: adjusted OR 2.34, 95%CI 1.01-5.39, p=0.047). The G allele was a risk-increased allele for MI (unadjusted OR 1.83, 95%CI 1.34-2.50, p=0.0001; adjusted OR 1.94, 95%CI 1.40-2.68, p=0.00007). Thus, the study demonstrated the significant association between A-48G polymorphism of the DRD1 gene and MI.

Asunto(s)

Infarto del Miocardio/genética , Polimorfismo Genético , Receptores de Dopamina D1/genética , Regiones no Traducidas 5'/genética , Anciano , Secuencia de Bases , Femenino , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

OBJECTIVES: To evaluate the association between the single nucleotide polymorphism rs189037 of the ataxia-telangiectasia mutated (ATM) gene and angiographically characterized coronary stenosis as well as the molecular basis of this association. RESULTS: In 562 patients treated at the Department of Cardiology, West China Hospital, a significant association was found between polymorphism rs189037 and angiographically characterized coronary stenosis. For the T versus C allele, the adjusted OR was 0.79 (95%CI 0.67-0.92, P=0.003), using the allele frequency model; for TT versus CT/CC, the adjusted OR was 0.36 (95%CI 0.21-0.59, P=0.00006), using the recessive model; and for TT/CT versus CC, the adjusted OR was 0.54 (95%CI 0.29-1.02, P=0.06), using the dominant model. An antagonism was found between polymorphism rs189037 and diabetes mellitus (P=0.003). In coronary artery disease (CAD) patients, the TT genotype of rs189037 was associated with higher ATM mRNA expression (F=4.23, P=0.02) in peripheral mononuclear cells than the CC or CT genotypes. CONCLUSION: Polymorphism rs189037 may influence the expression of ATM mRNA in CAD patients. It is also associated with the degree of coronary stenosis. Moderately low expression of the ATM gene may be associated with the development of coronary atherosclerosis.

Asunto(s)

Proteínas de Ciclo Celular/genética , Angiografía Coronaria , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/genética , Proteínas de Unión al ADN/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Proteínas Serina-Treonina Quinasas/genética , Proteínas Supresoras de Tumor/genética , Anciano , Análisis de Varianza , Proteínas de la Ataxia Telangiectasia Mutada , Distribución de Chi-Cuadrado , China , Estenosis Coronaria/enzimología , Femenino , Regulación Enzimológica de la Expresión Génica , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , ARN Mensajero/análisis , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad