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Beta thalassemia major (βT) is a hereditary anemia characterized by transfusion-dependency, lifelong requirement of chelation, and organ dysfunction. MicroRNA (miRNA) can be packed into extracellular vesicles (EVs) that carry them to target cells. We explored EV-miRNA in βT and their pathophysiologic role. Circulating EVs were isolated from 35 βT-patients and 15 controls. EV miRNA was evaluated by nano-string technology and real-time quantitative polymerase chain reaction (RT-qPCR). We explored effects of EVs on cell culture proliferation, apoptosis, and signal transduction. Higher amounts of small EV (exosomes) were found in patients than in controls. The expression of 21 miRNA was > two-fold higher, and of 17 miRNA < three-fold lower in βT-EVs than control-EVs. RT-qPCR confirmed differential expression of six miRNAs in βT, particularly miR-144-3p, a regulator of erythropoiesis. Exposure of endothelial, liver Huh7, and pancreatic 1.1B4 cells to βT-EVs significantly reduced cell viability and increased cell apoptosis. βT-EV-induced endothelial cell apoptosis involved the MAPK/JNK signal-transduction pathway. In contrast, splenectomized βT-EVs induced proliferation of bone marrow mesenchymal stem cells (BM-MSC). In summary, the miR-144-3p was strongly increased; βT-EVs induced apoptosis and decreased endothelial, pancreatic, and liver cell survival while supporting BM-MSC proliferation. These mechanisms may contribute to βT organ dysfunction and complications.

Purpose - The purpose of this paper is to address the subject of knowledge citizenship from the perspective of citizen participation in their city's decision-making processes. It focuses on a case study of the city of Holon, Israel.Design methodology approach - This paper presents three distinct methods for citizen participation processes which were used by Holon: citizen-based consensus conference, neighborhood conversations, and knowledge café sessions, all of which allow the municipality to implement citizen participation as part of its routine, fluent operations.Findings - The story of Holon presents the methods and processes for the creation of citizen dialog aimed to allow a city to develop itself into a knowledge city.Originality value - The case study shows how the theory of knowledge cities can be transferred into actual practicality. It describes three different ways to combine knowledge sharing in a city as part of the town's development into a knowledge city. Holon's experience can serve other cities to learn what processes are more suitable and applicable for them.