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INTRODUCTION: We assessed if obesity perturbs the esophageal epithelial barrier function independent of promotion of gastroesophageal reflux (GER). METHODS: Thirty-eight participants were divided into 4 groups: Obesity-/GER-, Obesity+/GER-, Obesity-/GER+, and Obesity+/GER+. Esophageal intercellular space and desmosome density (structural integrity) and fluorescein leak (functional integrity) were measured. RESULTS: The Obesity+/GER- group demonstrated increased intercellular space, reduced desmosome density, and increased fluorescein leak compared with control subjects. These changes were similar but not additive to findings seen in Obesity-/GER + and Obesity+/GER+ patients. DISCUSSION: Central obesity impairs structural and functional integrity of the esophageal barrier independent of GER, likely predisposing to esophageal injury.
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Mucosa Esofágica/metabolismo , Espacio Extracelular , Reflujo Gastroesofágico/metabolismo , Obesidad Abdominal/metabolismo , Permeabilidad , Adulto , Anciano , Desmosomas/ultraestructura , Mucosa Esofágica/patología , Mucosa Esofágica/ultraestructura , Femenino , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/patología , Humanos , Masculino , Persona de Mediana Edad , Obesidad Abdominal/complicaciones , Obesidad Abdominal/patologíaRESUMEN
INTRODUCTION: Esophageal epidermoid metaplasia (EEM) is a rare disease. METHODS: Patients with EEM diagnosed between 2014 and 2020 were reviewed. RESULTS: Forty EEM cases were identified. EEM occurred in 9 (23%) patients before, concordant, or after esophageal squamous cell carcinoma (ESCC). EEM was associated with previous esophageal lichen planus in 5 patients, Barrett's esophagus 7, and esophageal adenocarcinoma 1. EEM was focal in 28 (70%) or diffuse in 12 (30%) and not detected in 45% on recent previous endoscopy. DISCUSSION: EEM is a premalignant underrecognized condition associated with multiple conditions. Close follow-up or endoscopic treatment may be warranted because of its ESCC association.
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Enfermedades del Esófago/epidemiología , Neoplasias Esofágicas/epidemiología , Carcinoma de Células Escamosas de Esófago/epidemiología , Leucoplasia/epidemiología , Adenocarcinoma/epidemiología , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Esófago de Barrett/epidemiología , Trastornos de Deglución/fisiopatología , Progresión de la Enfermedad , Endoscopía del Sistema Digestivo , Enfermedades del Esófago/patología , Enfermedades del Esófago/fisiopatología , Femenino , Reflujo Gastroesofágico/epidemiología , Humanos , Leucoplasia/patología , Leucoplasia/fisiopatología , Liquen Plano/epidemiología , Masculino , Metaplasia , Persona de Mediana Edad , Uso de Tabaco/epidemiologíaRESUMEN
In insects, initiation of metamorphosis requires a surge in the production of the steroid hormone 20-hydroxyecdysone from the prothoracic gland, the primary endocrine organ of juvenile larvae. Here, we show that blocking TGFß/Activin signaling, specifically in the Drosophila prothoracic gland, results in developmental arrest prior to metamorphosis. The terminal, giant third instar larval phenotype results from a failure to induce the large rise in ecdysteroid titer that triggers metamorphosis. We further demonstrate that activin signaling regulates competence of the prothoracic gland to receive PTTH and insulin signals, and that these two pathways act at the mRNA and post-transcriptional levels, respectively, to control ecdysone biosynthetic enzyme expression. This dual regulatory circuitry may provide a cross-check mechanism to ensure that both developmental and nutritional inputs are synchronized before initiating the final genetic program leading to reproductive adult development. As steroid hormone production in C. elegans and mammals is also influenced by TGFß/Activin signaling, this family of secreted factors may play a general role in regulating developmental transitions across phyla.
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Activinas/metabolismo , Sistemas Neurosecretores/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Western Blotting , Drosophila , Ecdisteroides/metabolismo , Glándulas Endocrinas/metabolismo , Técnica del Anticuerpo Fluorescente , Hibridación in Situ , Hormonas de Insectos/metabolismo , Metamorfosis Biológica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
PURPOSE OF REVIEW: There is conflicting data on the effectiveness of the currently recommended endoscopic surveillance strategy in non-dysplastic BE patients. We reviewed the literature to evaluate the (cost) effectiveness of the current surveillance strategy. We also reviewed critical strategies and new technologies which could improve dysplasia detection. RECENT FINDINGS: Adherence to the current EGD surveillance guidelines is suboptimal with high rates of missed dysplasia/EAC. The influence of surveillance on EAC mortality appears modest. Careful cleansing, inspection and sampling of the BE mucosa using high resolution while light and (electronic) chromoendoscopy is critical. Newer sampling techniques coupled with computer aided diagnosis and emerging imaging technologies have shown promise in improving dysplasia detection. Personalized surveillance with risk stratification based on risk factors for progression may be on the horizon. SUMMARY: Current BE surveillance strategy will likely be further refined and optimized by emerging new technologies in tissue sampling, advanced imaging and risk stratification.
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Metabolism of oxidative stress is necessary for cellular survival. We have previously utilized the zebrafish as a model of the oxidative stress response. In this study, we found that gata1-expressing erythroid cells contributed to a significant proportion of total-body oxidative stress when animals were exposed to a strong pro-oxidant. RNA-seq of zebrafish under oxidative stress revealed the induction of tp53. Zebrafish carrying tp53 with a mutation in its DNA-binding domain were acutely sensitive to pro-oxidant exposure and displayed significant reactive oxygen species (ROS) and tp53-independent erythroid cell death resulting in an edematous phenotype. We found that a major contributing factor to ROS was increased basal mitochondrial respiratory rate without reserve. These data add to the concept that tp53, while classically a tumor suppressor and cell-cycle regulator, has additional roles in controlling cellular oxidative stress.
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Células Eritroides/metabolismo , Factor de Transcripción GATA1/genética , Estrés Oxidativo , Proteína p53 Supresora de Tumor/genética , Animales , Muerte Celular/genética , Células Eritroides/citología , Factor de Transcripción GATA1/metabolismo , Técnicas de Inactivación de Genes , Silenciador del Gen , Ratones , Mitocondrias/genética , Mitocondrias/metabolismo , Oxidación-Reducción , Estrés Oxidativo/genética , Especies Reactivas de Oxígeno/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Pez CebraRESUMEN
The Sno oncogene (Snoo or dSno in Drosophila) is a highly conserved protein and a well-established antagonist of Transforming Growth Factor-beta signaling in overexpression assays. However, analyses of Sno mutants in flies and mice have proven enigmatic in revealing developmental roles for Sno proteins. Thus, to identify developmental roles for dSno we first reconciled conflicting data on the lethality of dSno mutations. Then we conducted analyses of wing development in dSno loss of function genotypes. These studies revealed ectopic margin bristles and ectopic campaniform sensilla in the anterior compartment of the wing blade suggesting that dSno functions to antagonize Wingless (Wg) signaling. A subsequent series of gain of function analyses yielded the opposite phenotype (loss of bristles and sensilla) and further suggested that dSno antagonizes Wg signal transduction in target cells. To date Sno family proteins have not been reported to influence the Wg pathway during development in any species. Overall our data suggest that dSno functions as a tissue-specific component of the Wg signaling pathway with modest antagonistic activity under normal conditions but capable of blocking significant levels of extraneous Wg, a role that may be conserved in vertebrates.