Results 131 to 140 of about 277,018 (298)

PBRM1 Deficiency Reshapes an Immune Suppressive Microenvironment Through Epigenetic Tuning of PBRM1‐KDM5C‐IL6 Axis in ccRCC

open access: yesAdvanced Science, EarlyView.
PBRM1 ranks as the second most commonly mutated gene in ccRCC. This study reveals that PBRM1 loss promotes an immunosuppressive microenvironment by elevating M2 TAMs via the KDM5C–IL‐6 axis. These M2 TAMs, along with CAFs, form a barrier that excludes CD8+ T cells. Targeting IL‐6 synergizes with anti‐PD1 therapy, offering a promising strategy for PBRM1‐
Wenjiao Xia   +14 more
wiley   +1 more source

Menin inhibitor DS-1594b drives differentiation and induces synergistic lethality in combination with venetoclax in acute myeloid leukemia cells with rearranged mixed-lineage leukemia and mutated nucleophosmin-1

open access: yesHaematologica
Mixed-lineage leukemia (MLL) rearrangements and Nucleophosmin-1 (NPM1) mutations are associated with acute leukemias whose pathogenesis is critically influenced by protein-protein interactions between menin and MLL.
Valerio Ciaurro   +13 more
doaj   +1 more source

Unraveling the Morphological and Functional Maturation Mechanisms Underlying Human Neural Development Using iPSCs‐Derived Neuronal Model

open access: yesAdvanced Science, EarlyView.
Using human induced pluripotent stem cells (hiPSCs)‐derived neuronal model, Tian and colleagues reveal that voltage‐gated calcium channels Cav1.2 and Cav1.3, and their mediated calcium ion influx, are essential for early morphogenesis of human neuronal development, while ECEL1 underlies human neuronal functional developmental maturation through CALM3 ...
Yue Tian   +5 more
wiley   +1 more source

Iron oxide nanoparticles in leukemia: design, diagnostic applications, and therapeutic strategies

open access: yesJournal of the Egyptian National Cancer Institute
Leukemia, a heterogeneous group of hematologic malignancies, poses significant challenges in terms of early diagnosis and effective treatment. Recent advancements in nanotechnology have paved the way for innovative approaches in leukemia management, with
Henry Fenekansi Kiwumulo   +6 more
doaj   +1 more source

DualPG‐DTA: A Large Language Model‐Powered Graph Neural Network Framework for Enhanced Drug‐Target Affinity Prediction and Discovery of Novel CDK9 Inhibitors Exhibiting in Vivo Anti‐Leukemia Activity

open access: yesAdvanced Science, EarlyView.
This study introduces DualPG‐DTA, a framework integrating two pre‐trained models to generate molecular and protein representations. It constructs dual graphs processed by specialized neural networks with dynamic attention for feature fusion, achieving superior benchmark performance.
Yihao Chen   +7 more
wiley   +1 more source

Fibrates Inhibit PLTP‐induced M2 Macrophage Infiltration and Increase the Sensitivity of Hepatocellular Carcinoma to ICIs

open access: yesAdvanced Science, EarlyView.
Phospholipid transfer protein(PLTP) plays a critical role in forming a complex with kinase A (AURKA) and P65. This interaction facilitates phosphorylation of P65 at Ser536, leading to the activation of the NF‐κB signaling pathway. Ultimately, this leads to the upregulation of downstream cytokines, including IL‐6, IL‐8, and CSF‐1, which promotes M2 ...
Xinyue Liang   +14 more
wiley   +1 more source

WDR5‐H3K4me3 Epigenetic Axis Promotes TRMT6‐Dependent tRNA M1A Modification to Facilitate Triple‐Negative Breast Cancer Progression by Suppressing Ferroptosis

open access: yesAdvanced Science, EarlyView.
Upregulated TRMT6 forms aberrant hypermethylation of a specific tRNA pool and serves as a predictor of poor prognosis in TNBC. This m1A modification in tRNAs enhances translation of FTH1 and FTL, reducing the pool of bioavailable Fe2⁺. Reduced Fe2+ availability impairs RSL3‐induced lipid peroxidation and tumor progression.
Yuqing Lei   +12 more
wiley   +1 more source

Early Detection of Cell Death Using Transmembrane Water Exchange Magnetic Resonance Imaging

open access: yesAdvanced Science, EarlyView.
Cell death is important in both the development and treatment of cancer. In this study, it is demonstrated for the first time that a specific measurement of the transmembrane water exchange rate using magnetic resonance imaging can be used as an early marker of cell death in mammalian cells, in animals and in human patients. Abstract Cell death plays a
Athanasia Kaika   +22 more
wiley   +1 more source

Flipping the Switch: MeCP2‐Mediated Lactylation Rewires Microglial Metabolism and Inflammation via the HK2/mTOR Axis in Poststroke Neuroinflammation

open access: yesAdvanced Science, EarlyView.
Stroke‐induced lactate accumulation promotes p300‐mediated lactylation of methyl‐CpG binding protein 2 (MeCP2) at lysine 210, which reprograms microglial metabolism toward glycolysis and activates the hexokinase 2 (HK2)/mTOR axis. This cascade promotes proinflammatory responses and impairs neurofunctional outcomes.
Zengyu Zhang   +12 more
wiley   +1 more source

Loss of SOCS1 in Donor T Cells Exacerbates Intestinal GVHD by Driving a Chemokine‐Dependent Pro‐Inflammatory Immune Microenvironment

open access: yesAdvanced Science, EarlyView.
T cell‐specific Socs1 knockout leads to inflammatory differentiation of CD8+ T cells, prompting the STAT1/2 complex to drive the activation of Ccl5, Ccr5, and Cxcr3, and promoting the skewing of monocytes toward a pro‐inflammatory M1 macrophage lineage.
Zhigui Wu   +14 more
wiley   +1 more source

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