Epidermolysis bullosa with pyloric atresia associated with compound heterozygous ITGB4 pathogenic variants: Minimal skin involvement but severe mucocutaneous disease.

We report a case of junctional epidermolysis bullosa with pyloric atresia (JEB-PA) with minimal skin involvement but severe protein-losing enteropathy and airway involvement. Genetic analysis revealed heterozygous mutations in the ITGB4 gene encoding integrin ß4 protein. Parental testing confirmed inheritance of frameshift variant (c.794dupC) as maternal and splice site variant (c.1608C>T/p.Cys536Cys) as paternal. Immunofluorescence mapping of her skin revealed a subepidermal blister with decreased and frayed integrin ß4 at both the floor and the roof of the blister, while the intestinal mucosa showed complete absence of integrin ß4. We review the literature and discuss the differential expression of integrins in the skin and gastrointestinal tract, as well as the role of chronic inflammation in the pathogenesis of EB.

Morpho-histological characterisation of the alimentary canal of an important food fish, Asian seabass (Lates calcarifer).

Asian seabass (Lates calcarifer) is a food fish of increasing aquaculture importance. In order to improve our understanding on the digestive system and feeding of this species, morphological and histological features of the gut were studied. Morphologically, the Asian seabass gut is defined by a short and muscular esophagus, well-developed stomach and comparatively short intestine. Mucous secreting goblet cells reactive to PAS (Periodic Acid Schiff) and AB (Alcian Blue) stain were present throughout the esophagus. The stomach was sac-like and could be distinguished into the cardiac, fundic and pyloric regions. Gastric glands and mucus cells were predominately present in the cardiac and fundic regions. Five finger-like pyloric caeca were present between the stomach and intestine. The intestine was a short, tubular structure with no morphological differences between the various regions. Histologically, the intestinal regions were similar, the main difference being in the number of goblet cells that increased from anterior to posterior intestine, with 114 ± 9, 153 ± 7 and 317 ± 21 goblet cells in the anterior, mid and posterior regions, respectively. The intestinal epithelium stained positively for PAS, but the staining was stronger for acidic glycoproteins. The rectum was similar to intestine, except for increased goblet cell numbers (anterior rectum: 529 ± 26; posterior rectum: 745 ± 29). Gut morpho-histology did not respond to salinity changes, however, there was a significant reduction of mucosal height, goblet cell numbers and muscularis thickness upon food deprivation.

Tumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression.

The tumour-initiating cell (TIC) model accounts for phenotypic and functional heterogeneity among tumour cells. MicroRNAs (miRNAs) are regulatory molecules frequently aberrantly expressed in cancers, and may contribute towards tumour heterogeneity and TIC behaviour. More recent efforts have focused on miRNAs as diagnostic or therapeutic targets. Here, we identified the TIC-specific miRNAs, miR-1246 and miR-1290, as crucial drivers for tumour initiation and cancer progression in human non-small cell lung cancer. The loss of either miRNA impacted the tumour-initiating potential of TICs and their ability to metastasize. Longitudinal analyses of serum miR-1246 and miR-1290 levels across time correlate their circulating levels to the clinical response of lung cancer patients who were receiving ongoing anti-neoplastic therapies. Functionally, direct inhibition of either miRNA with locked nucleic acid administered systemically, can arrest the growth of established patient-derived xenograft tumours, thus indicating that these miRNAs are clinically useful as biomarkers for tracking disease progression and as therapeutic targets.

Immunohistochemical localization of cytokeratins in the junctional region of ectoderm and endoderm.

Although tridermic species have two junctional regions of ectoderm and endoderm between their epidermis and digestive tract, we actually know little about these particular boundaries. Cytokeratins are the major intermediate filaments of epithelial cells and show a high degree of tissue specificity. Therefore, to characterize the epithelial cells in the junctional region of ectoderm and endoderm, we immunohistochemically examined the localization of cytokeratins 5, 7/17, 14, 18, Sox17, and alpha-fetoprotein (AFP) in the oropharyngeal and anorectal regions during the mouse gastrulation process. At embryonic day (E) 9.5, cytokeratins 5, 7/17, 14, and 18 were detected in all epithelial cells of the oropharyngeal region. At E12.5, cytokeratin 5-positive cells were not observed in the middle area of the oral cavity; however, the immunoreactivity was strong in the anterior and posterior areas. The immunoreaction of cytokeratins 18 was seen only in the middle and posterior areas of the oral mucosa. Cytokeratins 7/17 and 14 were localized in all areas of the oropharyngeal region. Sox17 and AFP, which are endodermal markers, were detected in the middle and posterior areas of the oral mucosa, but not in the anterior area. Moreover, this same localization pattern of cytokeratins also existed in the anorectal region of the E12.5 embryo, suggesting that the localization of cytokeratins and endodermal markers might give an implication for the boundary between ectoderm and endoderm. These results also suggest that these cytokeratins are useful molecules for monitoring the epithelial cell differentiation in the junctional region of the germ layers.