The tight junction protein claudin-2 is upregulated in inflammatory bowel disease, and yet its deficit worsens infectious and chemical colitis. In this issue of the JCI, Raju and Shashikanth et al. examined the contribution of claudin-2 to immune-mediated colitis. The authors used transgenic mouse models to show that claudin-2 deficiency attenuated colitis progression as well as a leak barrier defect, albeit at the risk of intestinal obstruction. Further, inhibition of claudin-2 by targeting casein kinase 2 (CK2) also ameliorated colitis. The findings reveal unsuspected links between the pore and leak pathways of intestinal permeability and immune responses leading to colitis. They additionally suggest potential targets for therapeutic intervention in inflammatory bowel disease.
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http://dx.doi.org/10.1172/JCI140528 | DOI Listing |
Nat Nanotechnol
January 2025
Department of Chemistry, University of Oxford, Oxford, UK.
Nanoscale photoswitchable proteins could facilitate precise spatiotemporal control of transmembrane communication and support studies in synthetic biology, neuroscience and bioelectronics. Here, through covalent modification of the α-haemolysin protein pore with arylazopyrazole photoswitches, we produced 'photopores' that transition between iontronic resistor and diode modes in response to irradiation at orthogonal wavelengths. In the diode mode, a low-leak OFF-state nanopore exhibits a reversible increase in unitary conductance of more than 20-fold upon irradiation at 365 nm.
View Article and Find Full Text PDFJ Biomed Mater Res B Appl Biomater
January 2025
Department of Polymer and Biomaterials Science, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology in Szczecin, Szczecin, Poland.
Fabricating complex hierarchical structures mimicking natural vessels and arteries is pivotal for addressing problems of cardiovascular diseases. Various fabrication strategies have been explored to achieve this goal, each contributing unique advantages and challenges to the development of functional vascular grafts. In this study, a three-layered tubular structure resembling vascular grafts was fabricated using biocompatible and biodegradable copolymers of poly(butylene succinate) (PBS) using advanced manufacturing techniques.
View Article and Find Full Text PDFIn the early stages of retinal development, a form of correlated activity known as retinal waves causes periodic depolarizations of immature retinal ganglion cells (RGCs). Retinal waves are crucial for refining visual maps in the brain's retinofugal targets and for the development of retinal circuits underlying feature detection, such as direction selectivity. Yet, how waves alter gene expression in immature RGCs is poorly understood, particularly at the level of the many distinct types of RGCs that underlie the retina's ability to encode diverse visual features.
View Article and Find Full Text PDFShock
December 2024
Department of Surgery and Emory Critical Care Center, Emory University, School of Medicine, Atlanta, Georgia, USA.
Curr Opin Gastroenterol
January 2025
Laboratory of Mucosal Barrier Pathobiology, Department of Pathology.
Purpose Of Review: The contributions of intestinal barrier loss, that is, increased permeability, to multiple disorders, including inflammatory bowel disease (IBD), have been a topic of speculation for many years, and the literature is replete with conclusions based on correlation and speculation. The goal of this article is to critically review recent advances in mechanistic understanding of barrier regulation and the evidence for and against contributions of intestinal barrier loss to disease pathogenesis.
Recent Findings: It is now recognized that intestinal permeability reflects the combined effects of two distinct routes across tight junctions, which form selectively permeable seals between adjacent epithelial cells, and mucosal damage that leads to nonselective barrier loss.
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