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| http://dx.doi.org/10.3324/haematol.2020.247205 | DOI Listing |
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AOH1996 targets mitochondrial dynamics and metabolism in leukemic stem cells via mitochondrial PCNA inhibition.
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Department of Hematologic Malignancies Translational Science, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA.
Cytoplasmic proliferating cell nuclear antigen (PCNA) is highly expressed in acute myeloid leukemia (AML) cells, supporting oxidative metabolism and leukemia stem cell (LSC) growth. We report on AOH1996 (AOH), an oral compound targeting cancer-associated PCNA, which shows significant antileukemic activity. AOH inhibited growth in AML cell lines and primary CD34 + CD38 - blasts (LSC-enriched) in vitro while sparing normal hematopoietic stem cells (HSCs).
View Article and Find Full Text PDFADSCs-derived exosomes suppress macrophage ferroptosis via the SIRT1/NRF2 signaling axis to alleviate acute lung injury in sepsis.
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Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi 710032, China. Electronic address:
Acute lung injury being one of the earliest and most severe complications during sepsis and macrophages play a key role in this process. To investigate the regulatory effects and potential mechanisms of adipose mesenchymal stem cell derived-exosomes (ADSC-exo) on macrophages and septic mice, ADSCs-exo was administrated to both LPS-induced macrophage and cecal ligation and puncture (CLP) induced sepsis mice. ADSCs-exo was confirmed to inhibit M1 polarization of macrophages and to reduce excessive inflammation.
View Article and Find Full Text PDFAnlotinib enhances the pro-apoptotic effect of APG-115 on acute myeloid leukemia cell lines by inhibiting the P13K/AKT signaling pathway.
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Department of Hematopathy, Henan Institute of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China; The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China. Electronic address:
Background: APG-115 is a novel small-molecule selective inhibitor that destabilizes the p53-MDM2 complex and activates p53-mediated apoptosis in tumor cells. Anlotinib inhibits tumor angiogenesis and promotes apoptosis. In this study, we investigated the apoptotic effect and potential mechanism of APG-115 and anlotinib combination on AML cell lines with different p53 backgrounds.
View Article and Find Full Text PDFHMOX1-LDHB interaction promotes ferroptosis by inducing mitochondrial dysfunction in foamy macrophages during advanced atherosclerosis.
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Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; Heilongjiang Provincial Key Laboratory of Panvascular Disease, Harbin 150086, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin 150081, China; State Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin 150080, China. Electronic address:
Advanced atherosclerosis is the pathological basis for acute cardiovascular events, with significant residual risk of recurrent clinical events despite contemporary treatment. The death of foamy macrophages is a main contributor to plaque progression, but the underlying mechanisms remain unclear. Bulk and single-cell RNA sequencing demonstrated that massive iron accumulation in advanced atherosclerosis promoted foamy macrophage ferroptosis, particularly in low expression of triggering receptor expressed on myeloid cells 2 (TREM2) foamy macrophages.
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Department of Hematology, Affiliated Hangzhou First People's Hospital, Westlake University, School of Medicine, Hangzhou, China.
Background: The management of high-risk acute myeloid leukaemia (AML) remains challenging, highlighting the need for innovative conditioning strategies beyond current regimens.
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