Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells

BACKGROUND: Mast cells (MCs) have been found to play a critical role during development of inflammatory bowel disease (IBD) that characterized by dysregulation of inflammation and impaired intestinal barrier function. However, the function of MCs in IBD remains to be fully elucidated. RESULTS: In our study, we used exosomes isolated from human mast cells-1 (HMCs-1) to culture with NCM460, HT-29 or CaCO2 of intestinal epithelial cells (lECs) to investigate the communication between MCs and lECs. We found that MCs-derived exosomes significantly increased intestinal epithelial permeability and destroyed intestinal barrier function, which is attributed to exosome-mediated functional miRNAs were transferred from HMCs-1 into lECs, leading to inhibit tight junction-related proteins expression, including tight junction proteins 1 (TJP1, ZO-1), Occludin (OCLN), Claudin 8 (CLDN8). Microarray and bioinformatic analysis have further revealed that a panel of miRNAs target different tight junction-related proteins. Interestingly, miR-223 is enriched in mast cell-derived exosome, which inhibit CLDN8 expression in IECs, while treatment with miR-223 inhibitor in HT-29 cells significantly reversed the inhibitory effect of HMCs-1-derived exosomes on CLDN 8 expression. Most importantly, enrichment of MCs accumulation in intestinal mucosa of patients with IBD compared with those healthy control. CONCLUSIONS: These results indicated that enrichment of exosomal miR-223 from HMCs-1 inhibited CLDN8 expression, leading to destroy intestinal barrier function. These finding provided a novel insight of MCs as a new target for therapeutic treatment of IBD.

Caracterización de las causas de alopecia infantil / Aetiology of childhood alopecia

Introducción: La alopecia infantil es una afección poco frecuente en la consulta dermatológica pediátrica. Su etiología es variable según el grupo etario estudiado. El objetivo fue estudiar la causa de alopecia en niños en 2 hospitales pediátricos de referencia nacional en Chile. Pacientes y método: Análisis descriptivo de registros clínicos del total de pacientes atendidos entre enero de 2007 y junio de 2010 en los Servicios de Dermatología de los Hospitales Roberto del Río y Luis Calvo Mackenna. Se incluyeron pacientes con diagnóstico clínico de alopecia. Resultados: Se encontraron 345 registros clínicos, 179 varones (51,9%). La mediana de edad fue 72 meses. Los diagnósticos más prevalentes fueron alopecia areata (AA) (36,8%), tiña capitis (TC) (21%), nevo sebáceo (13,2%) y efluvio telógeno (8,7%). Según el grupo etario predominaron en recién nacidos: aplasia cutis y nevo sebáceo; en lactantes, preescolares y escolares: nevo sebáceo, AA y TC. En escolares se agregó tricotilomanía. En adolescentes nevo sebáceo, AA y efluvio telógeno. Se observó una correlación significativa entre AA con enfermedad autoinmune, enfermedad tiroidea, alteraciones ungueales, enfermedad psiquiátrica y síndrome de Down. En TC el agente etiológico más prevalente fue Microsporum Canis (86,6%). La tricotilomanía se correlacionó con enfermedad psiquiátrica significativamente. Conclusiones: Las principales causas de alopecia infantil fueron adquiridas y no cicatriciales. La etiología varía de acuerdo al grupo etario estudiado. Algunos tipos de alopecia infantil presentaron alta prevalencia de enfermedad psiquiátrica.

Introduction: Childhood alopecia is a relative rare event in general paediatric dermatology practice. Hair loss in children may have multiple causes, and there are different types of alopecia according to age groups. The aim of the study was to describe the clinical and epidemiological profile of alopecia in children from two Chilean paediatric hospitals. Patients and method: Descriptive analysis of clinical records of patients from the Dermatology Department of Roberto del Rio and Luis Calvo Mackenna Hospitals between January 2007 and June 2010. Patients with clinical diagnosis of alopecia were included. Results: A total of 345 clinical records were analysed, with 179 males (51.9%). The median age was 72 months. Overall, the most common diagnoses were: alopecia areata (AA), (36.8%), tinea capitis (TC), (21%), nevus sebaceous (13.2%), and tellogen effluvium (8.7%). According to age groups, in newborns, the most common causes were aplasia cutis and nevus sebaceous. In toddlers, pre-school and school children, the principal causes were nevus sebaceous, AA and TC. Trichotillomania was also significant in school children. In adolescents, nevus sebaceous, AA and tellogen effluvium were the most frequent diagnoses. AA was statistically associated with autoimmune disease, thyroid disease, nail disorder, psychiatric disease, and Down's syndrome. The most common aetiological agent in TC was M. canis (86.6%). Trichotillomania was also statistically associated to psychiatric disorders. Conclusions: In this study, the main causes of alopecia in children were acquired and non-scarring alopecia. In our results, the type of alopecia varies according to age group. Some types of childhood alopecia showed a close correlation to psychiatric disorders.

Adhesion molecules in breast carcinoma: a challenge to the pathologist / Moléculas de adesão no carcinoma mamário: um desafio ao patologista

The role of adhesion molecules is very important both in the activation of carcinogenesis and in the differentiation of subtypes of breast carcinoma, aiding in diagnosis, prognosis and therapeutic choice in these tumors. Therefore, understanding the functions and interrelationships among these molecules is crucial to the pathologist, who often uses these factors as a resource to differentiate tumors and further classify them according to a molecular point of view. Our goal is to describe the applicability and the difficulties encountered by the pathologist in the diagnosis of breast carcinoma, discussing the most commonly used markers of adhesion in routine analyses.

O papel das moléculas de adesão é de suma importância tanto na ativação da carcinogênese quanto na diferenciação dos subtipos de carcinomas mamários, auxiliando no diagnóstico, no prognóstico e na escolha terapêutica nessas neoplasias. Portanto, a compreensão das funções e das inter-relações entre essas moléculas é de suma importância para o patologista, que, muitas vezes, as utiliza como recurso na diferenciação dos tumores e, consequentemente, elas auxiliam em uma posterior classificação do ponto de vista molecular. O objetivo é descrever a aplicabilidade e as dificuldades encontradas pelo médico patologista no diagnóstico de carcinoma mamário, discutindo os marcadores de adesividade mais utilizados na rotina.

The Role of Barrier Dysfunction and Change of Claudin Expression in Inflammatory Bowel Disease

No abstract available.

Changes in the Expression and Distribution of Claudins, Increased Epithelial Apoptosis, and a Mannan-Binding Lectin-Associated Immune Response Lead to Barrier Dysfunction in Dextran Sodium Sulfate-Induced Rat Colitis

BACKGROUND/AIMS: This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. METHODS: Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. RESULTS: The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%+/-1.2% in controls and was significantly increased to 7.2%+/-1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. CONCLUSIONS: There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability.