Hepcidin as a Molecular Hub of Iron Homeostasis: From BMP-SMAD Signaling to Therapeutic Modulation

: Hepcidin, a 25-amino-acid peptide hormone produced primarily by hepatocytes, is the master regulator of systemic iron homeostasis. By binding the cellular iron exporter ferroportin and inducing its internalization and lysosomal degradation, hepcidin restricts iron entry into plasma from enterocytes, macrophages, and hepatocytes. Its transcription is governed by an intricate molecular network that integrates iron status, erythropoietic demand, oxygen tension, and inflammation, with the BMP-H...

Heme oxygenase-1/CO signaling suppresses NLRP3 inflammasome-mediated stromal fibrosis in primary myelofibrosis

Inflammation and oxidative stress are critical drivers of bone marrow (BM) fibrosis in primary myelofibrosis (MF). Here, we investigated the interplay between the heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway and NLRP3 inflammasome activation in MF microenvironment. Bioinformatic analysis of patient datasets (GSE53482 and GSE41812) revealed an approximately two-fold reduction of HO-1 expression in CD34+ peripheral blood cells compared with healthy controls (p < 0.01). Consistently, ...

Glutamate accumulation in myelofibrosis microenvironment rewires mesenchymal stromal cells metabolic and epigenetic profiles

Background: Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by bone marrow (BM) fibrosis, osteosclerosis, and a proinflammatory tumor microenvironment (TME). The interplay between malignant hematopoietic stem cells and mesenchymal stromal cells (MSCs) drives disease progression. Although glutamate has been implicated in various cancers, its contribution to MF pathogenesis remains unclear. Methods: High-performance liquid chromatography (HPLC) profiling was performed o...

Upgrading of a prototype biomass gasifier to produce H2 rich syngas, heat and power via SOFC