RESUMEN
Missed lung cancers on chest radiograph (CXR) may delay the diagnosis and affect the prognosis. CXR is the primary imaging modality to evaluate the lungs and mediastinum in daily practice. The purpose of this article is to review chest radiographs for common blind spots and highlight the importance of various radiologic presentations in primary lung cancer to avoid significant diagnostic errors on CXR.
RESUMEN
Glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway, plays important roles in redox regulation and de novo lipogenesis. It was recently demonstrated that aberrant upregulation of G6PD in obese adipose tissue mediates insulin resistance as a result of imbalanced energy metabolism and oxidative stress. It remains elusive, however, whether inhibition of G6PD in vivo may relieve obesity-induced insulin resistance. In this study we showed that a hematopoietic G6PD defect alleviates insulin resistance in obesity, accompanied by reduced adipose tissue inflammation. Compared with wild-type littermates, G6PD-deficient mutant (G6PD(mut)) mice were glucose tolerant upon high-fat-diet (HFD) feeding. Intriguingly, the expression of NADPH oxidase genes to produce reactive oxygen species was alleviated, whereas that of antioxidant genes was enhanced in the adipose tissue of HFD-fed G6PD(mut) mice. In diet-induced obesity (DIO), the adipose tissue of G6PD(mut) mice decreased the expression of inflammatory cytokines, accompanied by downregulated proinflammatory macrophages. Accordingly, macrophages from G6PD(mut) mice greatly suppressed lipopolysaccharide-induced proinflammatory signaling cascades, leading to enhanced insulin sensitivity in adipocytes and hepatocytes. Furthermore, adoptive transfer of G6PD(mut) bone marrow to wild-type mice attenuated adipose tissue inflammation and improved glucose tolerance in DIO. Collectively, these data suggest that inhibition of macrophage G6PD would ameliorate insulin resistance in obesity through suppression of proinflammatory responses.
Asunto(s)
Tejido Adiposo/metabolismo , Deficiencia de Glucosafosfato Deshidrogenasa/metabolismo , Inflamación/inmunología , Inflamación/metabolismo , Resistencia a la Insulina/fisiología , Obesidad/inmunología , Obesidad/metabolismo , Células 3T3-L1 , Adipocitos/metabolismo , Tejido Adiposo/inmunología , Animales , Western Blotting , Medios de Cultivo Condicionados , Dieta Alta en Grasa/efectos adversos , Ayuno/sangre , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Inmunohistoquímica , Insulina/sangre , Resistencia a la Insulina/genética , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Mutantes , Obesidad/genética , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme that regulates cellular redox potential. In this study, we demonstrate that macrophage G6PD plays an important role in the modulation of proinflammatory responses and oxidative stress. The G6PD levels in macrophages in the adipose tissue of obese animals were elevated, and G6PD mRNA levels positively correlated with those of proinflammatory genes. Lipopolysaccharide (LPS) and free fatty acids, which initiate proinflammatory signals, stimulated macrophage G6PD. Overexpression of macrophage G6PD potentiated the expression of proinflammatory and pro-oxidative genes responsible for the aggravation of insulin sensitivity in adipocytes. In contrast, when macrophage G6PD was inhibited or suppressed via chemical inhibitors or small interfering RNA (siRNA), respectively, basal and LPS-induced proinflammatory gene expression was attenuated. Furthermore, macrophage G6PD increased activation of the p38 mitogen-activated protein kinase (MAPK) and NF-κB pathways, which may lead to a vicious cycle of oxidative stress and proinflammatory cascade. Together, these data suggest that an abnormal increase of G6PD in macrophages promotes oxidative stress and inflammatory responses in the adipose tissue of obese animals.
Asunto(s)
Glucosafosfato Deshidrogenasa/metabolismo , Macrófagos/metabolismo , Estrés Oxidativo , Adipocitos/metabolismo , Tejido Adiposo/enzimología , Tejido Adiposo/metabolismo , Animales , Línea Celular , Quimiocina CCL2/biosíntesis , Ácidos Grasos no Esterificados/metabolismo , Femenino , Glucosafosfato Deshidrogenasa/antagonistas & inhibidores , Glucosafosfato Deshidrogenasa/genética , Proteínas Fluorescentes Verdes/genética , Humanos , Inflamación/inmunología , Interleucina-1beta/biosíntesis , Interleucina-6/biosíntesis , Lipopolisacáridos/farmacología , Macrófagos/enzimología , Masculino , Ratones , Ratones Endogámicos C57BL , NADP/farmacología , FN-kappa B/metabolismo , Obesidad , Oxidación-Reducción , Interferencia de ARN , ARN Mensajero/análisis , ARN Interferente Pequeño , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Accumulating evidence suggests that the circadian clock is closely associated with metabolic regulation. However, whether an impaired circadian clock is a direct cause of metabolic dysregulation such as body weight gain is not clearly understood. In this study, we demonstrate that body weight gain in mice is not significantly changed by restricting feeding period to daytime or nighttime. The expression of peripheral circadian clock genes was altered by feeding period restriction, while the expression of light-regulated hypothalamic circadian clock genes was unaffected by either a normal chow diet (NCD) or a high-fat diet (HFD). In the liver, the expression pattern of circadian clock genes, including Bmal1, Clock, and Per2, was changed by different feeding period restrictions. Moreover, the expression of lipogenic genes, gluconeogenic genes, and fatty acid oxidation-related genes in the liver was also altered by feeding period restriction. Given that feeding period restriction does not affect body weight gain with a NCD or HFD, it is likely that the amount of food consumed might be a crucial factor in determining body weight. Collectively, these data suggest that feeding period restriction modulates the expression of peripheral circadian clock genes, which is uncoupled from light-sensitive hypothalamic circadian clock genes.