Background: Inflammation in chronic active lesions occurs behind a closed blood-brain barrier and cannot be detected with MRI. Activated microglia are highly enriched for iron and can be visualized with quantitative susceptibility mapping (QSM), an MRI technique used to delineate iron.
Objective: To characterize the histopathological correlates of different QSM hyperintensity patterns in MS lesions.
Methods: MS brain slabs were imaged with MRI and QSM, and processed for histology. Immunolabeled cells were quantified in the lesion rim, center, and adjacent normal-appearing white matter (NAWM). Iron myeloid cell densities at the rims were correlated with susceptibilities. Human-induced pluripotent stem cell (iPSC)-derived microglia were used to determine the effect of iron on the production of reactive oxygen species (ROS) and pro-inflammatory cytokines.
Results: QSM hyperintensity at the lesion perimeter correlated with activated iron myeloid cells in the rim and NAWM. Lesions with high punctate or homogenous QSM signal contained no or minimally activated iron myeloid cells. In vitro, iron accumulation was highest in M1-polarized human iPSC-derived microglia, but it did not enhance ROS or cytokine production.
Conclusion: A high QSM signal outlining the lesion rim but not punctate signal in the center is a biomarker for chronic inflammation in white matter lesions.
Ferroptosis is a form of regulated cell death, which is dependent on iron metabolism imbalance and characterized by lipid peroxidation; it plays a crucial role in various pathological processes. Studies have shown that the occurrence of ferroptosis is closely associated with the progression of hepatocellular carcinoma (HCC). Ferroptosis is involved in regulating the lipid metabolism, iron homeostasis, mitochondrial metabolism, and redox processes in HCC.
Colorectal cancer (CRC) is one of the most frequent neoplasms and a major cause of cancer death worldwide. Despite recent advances in treatment approaches, the prognosis of advanced CRC remains poor, thus indicating the necessity of more effective treatments for CRC patients. CRC cells produce high levels of hepcidin, a peptide hormone that binds to the membrane-bound ferroportin and promotes its internalization and degradation, thus sequestering iron into the cancer cells with the downstream effect of enhancing tumor growth.
Introduction: Dysregulation of the hepcidin-ferroportin axis is a hallmark in the pathogenesis of iron overload, ultimately leading to end-organ injury. Hereditary hemochromatosis and iron-loading anemias are characterized by a hepcidin deficiency, making hepcidin a novel therapeutic target for preventing and managing iron overload.
Areas Covered: Modulators of hepcidin expression and molecules mimicking hepcidin are emerging as highly promising therapeutic strategies.
Thalassaemia, caused by over 250 mutations in the beta globin gene, changes the haematopoietic stem cell (HSC) differentiation, leading to ineffective erythropoiesis. This Wider Perspective article overlooks its underlying nature as a benign HSC disorder with a significant impact on the erythroid cell lineage. The simplicity of managing symptoms through transfusions and iron chelation therapy has shifted the focus away from the development of cell-based treatments.
Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing, China 400037. Electronic address:
Chemotherapy resistance is a significant clinical challenge in the treatment of leukemia. M2 macrophages have been identified as key contributors to the development of chemotherapy resistance in cancer, yet the precise mechanisms by which macrophages regulate this resistance remain elusive. Our study has identified CCL20 as a pivotal factor in the promotion of chemoresistance in AML cells by M2 macrophages.
