Results 111 to 120 of about 69,864 (260)

Targeting E3 Ubiquitin Ligases in Post-Traumatic Osteoarthritis: Therapeutic Opportunities and Pharmacological Perspectives

open access: yesPharmaceutics
Post-traumatic osteoarthritis (PTOA) is a rapidly progressing joint disorder initiated by acute injury, characterized by persistent inflammation, chondrocyte dysfunction, and extracellular matrix (ECM) degradation.
Yinqiu Wu   +6 more
doaj   +1 more source

UCHL3 Regulates Subgenomic Flaviviral RNA Condensates to Promote Virus Propagation

open access: yesAdvanced Science, EarlyView.
ABSTRACT Flavivirus subgenomic RNAs (sfRNAs) antagonise antiviral defences, yet how sfRNAs are organized and maintained in cells remains poorly understood. Here we identify ubiquitin C‐terminal hydrolase L3 (UCHL3) as a post‐translational regulator of flavivirus sfRNA stability and function.
Oscar Trejo‐Cerro   +7 more
wiley   +1 more source

Epithelial TRIM27 Inhibits Intestinal Inflammation in Ulcerative Colitis by the USP7/TRIM27‐IKK Double Negative‐Feedback

open access: yesAdvanced Science, EarlyView.
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

Targeting Supramolecular Active Complexes of Nav1.7/Nav1.8 to Relieve Chronic Neuropathic Pain

open access: yesAdvanced Science, EarlyView.
In mice and patients with severe chronic neuropathic pain (NP), Nav1.7, Nav1.8, TrkB, and five cytoskeletal proteins form supramolecular active complexes (SMACs) with polygonal lattice structures as noxious signal amplifiers in dorsal root ganglion (DRG) neurons.
Liting Sun   +27 more
wiley   +1 more source

Combining Fret and Super‐Resolution Microscopy Reveals Kinase Activation and Mitochondrial Activity at the Nanoscale

open access: yesAdvanced Science, EarlyView.
BioSenSRRF is an open‐source workflow that combines conventional FRET biosensors with SRRF reconstruction to generate sub‐diffraction FRET index maps on standard microscopes. The pipeline integrates automated image registration, SRRF reconstruction, quantitative FRET index calculation, and random line‐based hotspot analysis to uncover AURKA‐dependent ...
Nicolas Y. Jolivet   +5 more
wiley   +1 more source

Targeting METTL3 Attenuates Thyroid Inflammatory Injury by Restoring Th17/Treg Balance through a YTHDC2‐m6A‐Dependent KDR/VEGFA Loop

open access: yesAdvanced Science, EarlyView.
METTL3‐mediated m6A modification stabilizes KDR/Kdr mRNA through YTHDC2, amplifying the VEGFA‐KDR feedback loop and disturbing Th17/Treg balance. This pathway promotes persistent inflammation and tissue damage in patients with AIT, and inhibiting the METTL3‐KDR axis effectively disrupts this circuit, alleviating thyroid tissue injury and disease ...
Qingyi Hu   +7 more
wiley   +1 more source

Metabolic Imbalance Triggers Adaptive Remodeling to Accelerate Diploidization in Murine Haploid Embryonic Stem Cells

open access: yesAdvanced Science, EarlyView.
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

MG53 Coordinates Macrophage Polarization and Neuroimmune Coupling to Promote Corneal Nerve Regeneration via the MPEG1–MVP–STAT6 Axis

open access: yesAdvanced Science, EarlyView.
Corneal nerve regeneration is critical to corneal wound healing processes. The current study reveals a novel role of MG53 in promoting corneal nerve regeneration after alkali induced injury. Mechanistically, MG53 enters macrophages via its receptor, MPEG1, promotes MVP K63 ubiquitination, and triggers STAT6 induced repair‐related genes expression ...
Peng Chen   +14 more
wiley   +1 more source

Harnessing MDM2‐Mediated Targeted Degradation of Transcriptional and Epigenetic Machinery to Disrupt Oncogenic Addictions in Pediatric Sarcoma

open access: yesAdvanced Science, EarlyView.
MDM2 dependency in pediatric sarcomas is driven by a novel p53‐independent oncogenic cistrome alongside canonical p53 pathway suppression. This study introduces MDM2‐recruiting transcriptional and epigenetic machinery degraders (MDM2‐TEMADs) as a novel precision oncology modality.
Jiawei Zhou   +21 more
wiley   +1 more source

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