Targeting RSPO3-LGR4 Signaling for Leukemia Stem Cell Eradication in Acute Myeloid Leukemia

Scientists report that a positive modulator of canonical WNT signaling pathway, RSPO-LGR4, upregulates key self-renewal genes and is essential for leukemia stem cell self-renewal in a subset of acute myeloid leukemia.
[Cell Stem Cell]
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S100A6 Is a Critical Regulator of Hematopoietic Stem Cells

Researchers showed that S100A6 regulated intracellular and mitochondria calcium buffering of HSC upon cytokine stimulation and have demonstrated that Akt activator SC79 reverted the levels of intracellular and mitochondrial calcium in HSC.
[Leukemia]
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A Missense Mutation in the MLKL Brace Region Promotes Lethal Neonatal Inflammation and Hematopoietic Dysfunction

The authors isolated a mouse strain with a single missense mutation, MlklD139V, that altered the two-helix ‘brace’ that connects the killer four-helix bundle and regulatory pseudokinase domains.
[Nature Communications]
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YBX1 Mediates Autophagy by Targeting p110β and Decreasing the Sensitivity to Cisplatin in NSCLC

Scientists analyzed the expression and clinical significance of Y-box binding protein 1 and markers of autophagy in NSCLC and examined their roles in regulating sensitivity to cisplatin in NSCLC.
[Cell Death & Disease]
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Identification of a Periodontal Pathogen and Bihormonal Cells in Pancreatic Islets of Humans and a Mouse Model of Periodontitis

Investigators determined the specific localization of Porphyromonas gingivalis in relation to mouse and human pancreatic α- and β-cells using 3-D confocal and immunofluorescence microscopy and orthogonal analyses.
[Scientific Reports]
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Altered RNA Splicing by Mutant p53 Activates Oncogenic RAS Signaling in Pancreatic Cancer

Scientists uncovered sequence-specific changes in RNA splicing enforced by mutant p53 which enhanced KRAS activity. Mutant p53 increased expression of splicing regulator hnRNPK to promote inclusion of cytosine-rich exons within GTPase-activating proteins, negative regulators of RAS family members.
[Cancer Cell]
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The Influence of Hypoxia and Energy Depletion on the Response of Endothelial Cells to the Vascular Disrupting Agent Combretastatin A-4-Phosphate

Scientists found that active RhoA and ROCK effector phospho-myosin light chain (pMLC) were downregulated in endothelial cells by severe hypoxia. CA4P failed to activate RhoA/ROCK/pMLC but its activity was restored upon reoxygenation.
[Scientific Reports]
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Non-Canonical Chemical Feedback Self-Limits Nitric Oxide-Cyclic GMP Signaling in Health and Disease

Both endogenous nitric oxide (NO) from endothelial NO synthase and exogenous NO from NO donor compounds decreased soluble guanylate cyclase (sGC) protein and activity.
[Scientific Reports]
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Senolytic CAR T Cells Reverse Senescence-Associated Pathologies

Investigators tested the therapeutic concept that chimeric antigen receptor (CAR) T cells that target senescent cells could be effective senolytic agents. They identified the urokinase-type plasminogen activator receptor (uPAR)11 as a cell-surface protein that is broadly induced during senescence and showed that uPAR-specific CAR T cells efficiently ablated senescent cells in vitro and in vivo.
[Nature]
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Eosinophil Function in Adipose Tissue Is Regulated by Krüppel-Like Factor 3 (KLF3)

Investigators examined the transcriptomic profile of adipose-resident eosinophils and posit that KLF3 regulates adipose tissue function via transcriptional control of secreted molecules linked to beiging.
[Nature Communications]
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Macrophage Metabolic Reprogramming Presents a Therapeutic Target in Lupus Nephritis

Investigators found that human and mouse macrophages underwent a switch to glycolysis in response to IgG immune complex stimulation, mirroring macrophage metabolic changes in inflamed tissue in vivo. This metabolic reprogramming was required to generate a number of proinflammatory mediators, including IL-1β, and was dependent on mTOR and hypoxia-inducible factor-1α.
[Proceedings of the National Academy of Sciences of the United States of America]
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