Cirrhosis is a major cause of morbidity and mortality; however, there are no approved therapies except orthotopic liver transplantation. Preclinical studies showed that bone-marrow-derived macrophage injections reduce inflammation, resolve fibrosis and stimulate liver regeneration. In a multicenter, open-label, parallel-group, phase 2 randomized controlled trial ( ISRCTN10368050 ) in n = 51 adult patients with compensated cirrhosis and Model for End-Stage Liver Disease (MELD) score ≥10 and ≤17, we evaluated the efficacy of autologous monocyte-derived macrophage therapy (n = 27) compared to standard medical care (n = 24).
View Article and Find Full Text PDFHER2 and αβ integrin are independent predictors of breast cancer survival and metastasis. We identify an αβ/HER2 cross-talk mechanism driving invasion, which is dysregulated in drug-resistant HER2+ breast cancer cells. Proteomic analyses reveal ligand-bound αβ recruits HER2 and a trafficking subnetwork, comprising guanosine triphosphatases RAB5 and RAB7A and the Rab regulator guanine nucleotide dissociation inhibitor 2 (GDI2).
View Article and Find Full Text PDFThe study examines the reflections of various experts in risk management when asked about uncertainty generated by a health threat and the response to such a threat: what criteria should guide action when potential harm is anticipated, but not known with certainty? The objective of the research is to obtain a holistic perspective of ethical conflicts in risk management, based on experts' accounts within the Spanish territory. A qualitative study was conducted through semi-structured interviews with 27 experts from various fields related to health risk management and its ethical implications, following the grounded theory method. The method includes theory generation through an inductive approach, based on the identified categories.
View Article and Find Full Text PDFAptamers are oligonucleotides with antibody-like binding function, selected from large combinatorial libraries. In this study, we modified a DNA aptamer library with N-hydroxysuccinimide esters, enabling covalent conjugation with cognate proteins. We selected for the ability to bind to mouse monoclonal antibodies, resulting in the isolation of two distinct covalent binding motifs.
View Article and Find Full Text PDFBackground & Aims: In community pathways for detection of liver disease the most common reason for referral is fibrosis assessment. We investigated the impact of adding the Enhanced Liver Fibrosis (ELF) score as a second-line test (subsequent to an indeterminate or high Fibrosis-4 index [FIB-4] and/or non-alcoholic fatty liver disease fibrosis score) to guide referral and prognostication in our multi-aetiology pathway.
Methods: Patients with ELF results from the intelligent Liver Function Testing (iLFT) pathway were recruited.