Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids

Treatment of common bile duct disorders such as biliary atresia or ischaemic strictures is limited to liver transplantation or hepatojejunostomy due to the lack of suitable tissue for surgical reconstruction. Here, we report a novel method for the isolation and propagation of human cholangiocytes from the extrahepatic biliary tree and we explore the potential of bioengineered biliary tissue consisting of these extrahepatic cholangiocyte organoids (ECOs) and biodegradable scaffolds for transplantation and biliary reconstruction in vivo. ECOs closely correlate with primary cholangiocytes in terms of transcriptomic profile and functional properties (ALP, GGT). Following transplantation in immunocompromised mice ECOs self-organize into tubular structures expressing biliary markers (CK7). When seeded on biodegradable scaffolds, ECOs form tissue-like structures retaining biliary marker expression (CK7) and function (ALP, GGT). This bioengineered tissue can reconstruct the wall of the biliary tree (gallbladder) and rescue and extrahepatic biliary injury mouse model following transplantation. Furthermore, it can be fashioned into bioengineered ducts and replace the native common bile duct of immunocompromised mice, with no evidence of cholestasis or lumen occlusion up to one month after reconstruction. In conclusion, ECOs can successfully reconstruct the biliary tree following transplantation, providing proof-of-principle for organ regeneration using human primary cells expanded in vitro

Room-Temperature Organocatalytic Cycloaddition of Azides with β‑Keto Sulfones: Toward Sulfonyl-1,2,3-triazoles

Organocatalytic enamine–azide [3 + 2] cycloadditions between β-keto sulfones and aryl azides can be performed at room temperature in good to excellent yields of products in the presence of catalytic amounts of pyrrolidine (5 mol %). The proposed organocatalytic methodology was found to be applicable to β-keto arylsulfones containing a range of substituents. A wide variety of aryl azides also work. Basically, this constitutes a remarkably efficient protocol for the synthesis of novel 1,2,3-triazole compounds

National Institute for Health Research Health Informatics Collaborative: development of a pipeline to collate electronic clinical data for viral hepatitis research

Objective The National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) is a programme of infrastructure development across NIHR Biomedical Research Centres. The aim of the NIHR HIC is to improve the quality and availability of routinely collected data for collaborative, cross-centre research. This is demonstrated through research collaborations in selected therapeutic areas, one of which is viral hepatitis. Design The collaboration in viral hepatitis identified a rich set of datapoints, including information on clinical assessment, antiviral treatment, laboratory test results and health outcomes. Clinical data from different centres were standardised and combined to produce a research-ready dataset; this was used to generate insights regarding disease prevalence and treatment response. Results A comprehensive database has been developed for potential viral hepatitis research interests, with a corresponding data dictionary for researchers across the centres. An initial cohort of 960 patients with chronic hepatitis B infections and 1404 patients with chronic hepatitis C infections has been collected. Conclusion For the first time, large prospective cohorts are being formed within National Health Service (NHS) secondary care services that will allow research questions to be rapidly addressed using real-world data. Interactions with industry partners will help to shape future research and will inform patient-stratified clinical practice. An emphasis on NHS-wide systems interoperability, and the increased utilisation of structured data solutions for electronic patient records, is improving access to data for research, service improvement and the reduction of clinical data gaps

Pre-and post-puberty physiological plasma oxytocin concentrations in male domestic cats (Felis silvestris catus)

The hormone oxytocin is released by the neuropituitary gland through stimulation of the neurons of the supraoptic and paraventricular nuclei of the hypothalamus. In order to determine the physiological concentrations of this hormone in domestic cats, blood samples were collected from 15 male animals (Felis silvestris catus) during the pre- and post-puberty periods (at four and eight months of age, respectively). Oxytocin determination was accomplished by radioimmunoassay. The average oxytocin concentrations measured in the pre- and post-puberty periods were 2.54±0.24 (μg/dL) and 2.53±0.28 (μg/dL), respectively, and there were no statistical differences between these measurements. Because there are few literature on the analysis of this hormone, especially in the case of male Felis silvestris catus, more studies on the influence of oxytocin on the physiology and reproduction of this species should be conducted under maintenance and situations of stress (such as transportation), and other routine events