Results 111 to 120 of about 195,005 (265)
Ammonia Detoxification Inhibits Liver Metastasis by Reshaping Hepatic Microenvironment
Liver metastasis diverts aspartate into hyperactive pyrimidine synthesis, disrupting urea cycling and causing pathogenic ammonia accumulation. Ammonia dually reprograms the microenvironment by: (1) activating hepatic stellate cells (HSCs) into pro‐fibrotic metastasis‐associated fibroblasts (MAFs), and (2) suppressing anti‐tumor monocytes/macrophages ...
Sumin Sun +5 more
wiley +1 more source
THUMPD1 drives a tumor‐suppressive signaling cascade in lung adenocarcinoma by promoting IGF2R expression. IGF2R associates with PPP2R1A to suppress AKT and activate AMPK, leading to SLC31A1 upregulation and copper accumulation. Elevated copper disrupts mitochondrial metabolism and induces excessive mitophagy, thereby restraining tumor growth and ...
Kai Wu +10 more
wiley +1 more source
First Generation Proteolysis Targeting Chimeras (PROTACs) for the Treatment of Progeria
We report the first PROTACs designed to degrade progerin, introducing a novel therapeutic approach for progeria. The best compound, UCM‐18142, significantly reduces progerin levels and improves key disease phenotypes in patient‐derived cells and in the LmnaG609G/G609G mouse model, paving the way for new treatment strategies targeting the root cause of ...
Jon Macicior‐Michelena +5 more
wiley +1 more source
ABSTRACT The E3 ubiquitin ligase tripartite motif 27 (TRIM27) is a negative regulator of NF‐κB activation and the innate immune response, and TRIM27 deficiency significantly impairs dextran sulfate sodium (DSS)‐induced colitis. The function of TRIM27 in intestinal epithelial cells (IECs), the mechanism by which TRIM27 inhibits the NF‐κB pathway and its
Weimin Xu +10 more
wiley +1 more source
In this article, Shuai and colleagues demonstrate that metabolic remodeling drives self‐diploidization in murine haploid ESCs (haESCs). Mitochondrial dysfunction and imbalanced pyruvate metabolism underlie this process. Genome‐wide screening using haESCs identifies key mitochondrial quality‐control related genes, enabling a metabolism‐based medium that
Yi Fu +11 more
wiley +1 more source
Depletion of p75NTR in Schwann Cells Driven by Inflammation Mediates Cutaneous Pain in Psoriasis
Psoriasis‐like inflammation induces proliferation and molecular remodeling of cutaneous Schwann cells, marked by reduced p75NTR and increased NGF expression. IL‐17A promotes this process, whereas Schwann cell‐specific p75NTR overexpression alleviates cutaneous pain in vivo.
Yibo Wang +9 more
wiley +1 more source
ESCRT‐Mimetic Nanodegrader Targets STING for Anti‐Inflammatory Therapy
A nanoplatform‐enabled targeted protein degradation strategy is presented to regulate aberrant STING signaling. STING‐ATTEC induces selective autophagic degradation of STING via formation of a STING–ATTEC–LC3 ternary complex, while the cationic FA‐LNP+ system enhances LC3 generation and targeted delivery. Together, this synergistic approach efficiently
Fuyuan Zhou +9 more
wiley +1 more source
This research identifies DTX3L as a critical tumor suppressor that inhibits epithelial‐mesenchymal transition (EMT), invasion and metastasis in gastric cancer. By functioning as an E3 ubiquitin ligase, DTX3L targets the master EMT regulator SNAI1 for GSK‐3β‐dependent proteasomal degradation.
Yang Chen +7 more
wiley +1 more source
Structural dynamics of the midnolin-proteasome during ubiquitin-independent substrate turnover. [PDF]
Zhu C +7 more
europepmc +1 more source

