ABSTRACT
BACKGROUND & AIMS: The intestinal barrier comprises a monolayer of specialized intestinal epithelial cells (IECs) that are critical in maintaining mucosal homeostasis. Dysfunction within various IEC fractions can alter intestinal permeability in a genetically susceptible host, resulting in a chronic and debilitating condition known as Crohn's disease (CD). Defining the molecular changes in each IEC type in CD will contribute to an improved understanding of the pathogenic processes and the identification of cell type-specific therapeutic targets. We performed, at single-cell resolution, a direct comparison of the colonic epithelial cellular and molecular landscape between treatment-naïve adult CD and non-inflammatory bowel disease control patients. METHODS: Colonic epithelial-enriched, single-cell sequencing from treatment-naïve adult CD and non-inflammatory bowel disease patients was investigated to identify disease-induced differences in IEC types. RESULTS: Our analysis showed that in CD patients there is a significant skew in the colonic epithelial cellular distribution away from canonical LGR5+ stem cells, located at the crypt bottom, and toward one specific subtype of mature colonocytes, located at the crypt top. Further analysis showed unique changes to gene expression programs in every major cell type, including a previously undescribed suppression in CD of most enteroendocrine driver genes as well as L-cell markers including GCG. We also dissect an incompletely understood SPIB+ cell cluster, revealing at least 4 subclusters that likely represent different stages of a maturational trajectory. One of these SPIB+ subclusters expresses crypt-top colonocyte markers and is up-regulated significantly in CD, whereas another subcluster strongly expresses and stains positive for lysozyme (albeit no other canonical Paneth cell marker), which surprisingly is greatly reduced in expression in CD. In addition, we also discovered transposable element markers of colonic epithelial cell types as well as transposable element families that are altered significantly in CD in a cell type-specific manner. Finally, through integration with data from genome-wide association studies, we show that genes implicated in CD risk show heretofore unknown cell type-specific patterns of aberrant expression in CD, providing unprecedented insight into the potential biological functions of these genes. CONCLUSIONS: Single-cell analysis shows a number of unexpected cellular and molecular features, including transposable element expression signatures, in the colonic epithelium of treatment-naïve adult CD.
Subject(s)
Crohn Disease , Adult , Crohn Disease/pathology , DNA Transposable Elements , Epithelium/pathology , Genome-Wide Association Study , Humans , Paneth Cells/metabolism , Single-Cell AnalysisABSTRACT
The host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn's disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course. We examined the expression of colonic ACE2 in 67 adult CD and 14 NIBD control patients using RNA-seq and quantitative (q) RT-PCR. We validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increased ACE2 expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients. Colonic ACE2 expression was significantly higher in a subset of adult CD patients which was defined as the ACE2-high CD subset. IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of CD diagnosis, and a Cox regression analysis found that high ACE2 levels is an independent risk factor for surgery (OR 2.17; 95% CI, 1.10-4.26; p = 0.025). Increased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that can impact CD disease-related outcomes.
Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Crohn Disease/pathology , Adolescent , Adult , Angiotensin-Converting Enzyme 2/genetics , Crohn Disease/metabolism , Crohn Disease/surgery , Female , Humans , Ileum/metabolism , Ileum/pathology , Immunohistochemistry , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Male , Prognosis , Proportional Hazards Models , RNA, Messenger/chemistry , RNA, Messenger/metabolism , Risk Factors , Sequence Analysis, RNA , Young AdultABSTRACT
Resumen Lagos-Hernández, R.I. et al. (2018). Perfil antropométrico e imagen corporal de escolares rugbistas de sexo femenino de la región de la Araucanía, Chile. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 16(2), 1-15. El objetivo de esta investigación fue determinar perfil antropométrico y su relación con el IMC e imagen corporal (IC) del total de escolares de sexo femenino de la Región de la Araucanía, Chile, que practican regular y competitivamente rugby 7. En relación a las participantes, se evaluaron 25 niñas que reunían los criterios de inclusión cuyas edades fluctuaron entre los 10 y 19 años (Media = 16.39 ± 2.81). Para efectos metodológicos se llevó a cabo una evaluación Antropométrica bajo los protocolos de la International Society for the Advancement of Kinanthropometry protocols (ISAK , 2017) y se hizo una apreciación de la percepción de la IC a través de la observación de una serie de imágenes corporales siguiendo el protocolo de Montero, Morales, & Carbajal (2004). Los resultados mostraron que las escolares evaluadas presentan una composición corporal (CC) alta en tejido adiposo con un 33.9% y un porcentaje muscular de 39%. En relación a la clasificación antropomética, se puede señalar que manifiestan características endo-mesomorficas, además se pudo constatar que las escolares presentaron una percepción de la IC según IMC percibido, diferente de los niveles reales de IMC presentados, no apreciándose relacion estadísticamente significativa entre la CC, el somatotipo y la imagen percibida.
Abstract Lagos-Hernández, R.I. et al. (2018). Anthropometric profile and body image of female junior Rugby players from the Region of Araucanía, Chile. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 16(2), 1-15. The objective of this paper was to determine the anthropometric profile of female students of the Region of Araucanía, Chile, and its relationship with BMI (IMCA) and body image (IC). Participants included 25 girls ages 10 to 19 (mean = 16.39 ± 2.81) that practice rugby sevens on a regular and competitive basis. For methodological purposes, an anthropometric assessment was conducted using the International Society for the Advancement of Kinanthropometry protocols (ISAK, 2017), and an appreciation of CI perception was made by observing a series of body images following the Montero, Morales, & Carbajal protocol (2004). Results showed that the students' body composition (CC) was high in adipose tissue (33.9%) and their muscle percentage was 39%. Regarding the anthropometric classification, it can be noted that participants show endo-mesomorph characteristics and that their perceived body image differed from the actual BMI levels, not showing a statistically significant relationship between the body composition, the somatotype and the perceived image.
Resumo Lagos-Hernández, R.I. et al. (2018). Perfil antropométrico e imagem corporal de escolares do sexo feminino jogadoras de rugby da região de Araucanía, Chile. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 16(2), 1-15. O objetivo desta pesquisa foi determinar o perfil antropométrico e sua relação com o IMC e a imagem corporal (IC) de todas as escolares da região de Araucania, Chile, que praticam regularmente o rugby 7 em carácter competitivo. Em relação aos participantes, foram avaliadas 25 meninas que atendiam aos critérios de inclusão cujas idades variaram entre 10 e 19 anos (média = 16,39 ± 2,81). Para fins metodológicos, foi levada a cabo uma avaliação antropométrica sob os protocolos da Society for Avancement in Kineanthropometric (ISAK, 2017) e feita uma apreciação da percepção do IC através da observação de uma série de imagens corporais seguindo o protocolo de Montero, Morales e Carbajal (2004). Os resultados mostraram que as estudantes avaliadas apresentam uma composição corporal (CC) elevada no tecido adiposo com 33,9% e um percentual muscular de 39%. Quanto à classificação antropométrica, pode-se destacar que se manifestam características endo-mesomórficas e, além disso, verificou-se que as escolares apresentaram uma percepção de IC de acordo com o IMC percebido, diferente dos níveis reais de IMC apresentados, não sendo apreciada uma relação estatisticamente significativa entre a CC, o somatótipo e a imagem percebida.
Subject(s)
Humans , Female , Child , Adolescent , Adult , Self Concept , Body Composition , Chile , Anthropometry , FootballABSTRACT
La condromatosis sinovial es una metaplasia cartilaginosa del tejido sinovial de las articulaciones. Es una enfermedad de etiología desconocida e infrecuente. Su localización en la articulación temporomandibular es más rara aún. Se describe el caso clínico de una paciente con diagnóstico de condromatosis sinovial de la articulación temporomandibular tratada con éxito mediante un abordaje quirúrgico combinado: externo y con endoscopios de 4 mm. Se realizó una revisión de la bibliografía sobre la información existente de la condromatosis sinovial.
Synovial chondromatosis is a cartilaginous metaplasia of the synovial tissue of joints. It is a disease of unknown etiology and infrequent. Its location in the temporomandibular joint is still more unusual. The case of a patient is described with a diagnosis of synovial chondromatosis of the temporomandibular joint successfully treated with a combined surgical approach: external and with 4 mm endoscopes. A review of the literature was conducted on the existing information on synovial chondromatosis.
A condromatose sinovial é uma metaplasia cartilaginosa do tecido sinovial das articulações. É uma doença de etiologia desconhecida e pouco frequente. A sua localização na articulação temporomandibular é ainda mais rara. Descreve-se o caso clínico de uma paciente com diagnóstico de condromatose sinovial da articulação temporomandibular tratada com sucesso mediante uma abordagem cirúrgica combinada: externa e com endoscópios de 4 mm. Realizou-se uma revisão da bibliografia sobre a informação existente da condromatose sinovial.
