Results 201 to 210 of about 410,191 (299)

Dual Targeting of Mutant p53 and SNRPD2 via Engineered Exosomes Modulates Alternative Splicing to Suppress Ovarian Cancer

open access: yesAdvanced Science, EarlyView.
Mutant p53 drives oncogenic splicing to promote the progression of ovarian cancer by partnering with the spliceosome factor SNRPD2. Therefore, it is engineered iRGD‐exosomes to co‐deliver siRNAs against both targets. This approach restored tumor‐suppressive mRNA isoforms, effectively enhanced sensitivity to cisplatin, and ultimately blocked tumor ...
Wei Zhao   +14 more
wiley   +1 more source

Metabolic Reprogramming Driven by Trophoblasts and Decidual XCR1+PMN‐MDSC Crosstalk Controls Adverse Outcomes Associated With Advanced Maternal Age

open access: yesAdvanced Science, EarlyView.
The interaction between trophoblasts and decidual polymorphonuclear myeloid‐derived suppressor cells (dPMN‐MDSCs) via the XCL1–XCR1 axis is crucial for fetal development during the third trimester. Disruption of this axis impairs FOXO1 activity and causes metabolic imbalance in dPMN‐MDSCs, contributing to adverse outcomes associated with advanced ...
Meiqi Chen   +12 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

Discovery of a Novel DNMT1 Inhibitor with Improved Efficacy in Treating β‐Thalassemia

open access: yesAdvanced Science, EarlyView.
Context of Research: β‐thalassemia affects millions worldwide. DNMT inhibitors are effective HbF‐inducers that benefit patients with β‐thalassemia. Existing DNMT inhibitors are not approved for β‐thalassemia treatment due to dose‐limiting toxicity.What We Find: DMT207 traps DNMT1 into helix‐kinked inactive conformation and enhances its interaction with
Yijie Shen   +19 more
wiley   +1 more source

Endocytic Control of Cell‐Autonomous and Non‐Cell‐Autonomous Functions of p53

open access: yesAdvanced Science, EarlyView.
NUMB Ex3‐containing isoforms localize to the plasma membrane, where they recruit p53 through SNX9 and direct it to multivesicular bodies and exosomes. Exported p53 is taken up by neighboring cells and activates nuclear programs, revealing an intercellular, exosome‐based pathway that might help establish a tumor‐suppressive microenvironment.
Roberta Cacciatore   +20 more
wiley   +1 more source

APOE‐stratified Proteomic and Metabolomic Analysis Reveals Mitochondrial Dysfunction Inflammation and Lipid Dysregulation in Alzheimer's Disease

open access: yesAdvanced Science, EarlyView.
A large‐scale multiomic dataset (proteomic and metabolomic) comprising 3,060 plasma samples were analyzed to identify proteins, metabolites, pathways, and protein‐associated drugs linked to Alzheimer’s Disease (AD) independently of apolipoprotein E (APOE). AD was associated with a distinct molecular signature that captures.
Fuhai Li   +22 more
wiley   +1 more source

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