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The activated form of fibroblast, the myofibroblasts, increase the secretion of chemical signals, such as cytokines, chemokines, and growth factors, with a double effect: on the one hand, they stimulate the excessive accumulation of ECM components, including fibrillar collagens, fibronectin, proteoglycans, glycosaminoglycans, and hyaluronic acid, at the site of tissue injury, while on the other hand, they suppress the activity of the matrix-metalloproteinases (MMPs), a family of zinc-dependent metalloendopeptidases that can degrade or cleave many components of the ECM, as well as a wide range of other extracellular proteins [9,10]
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Gut microbiota severely hampers the efficacy of NAD-lowering therapy in leukemia