YouTube video by ZDFheute Nachrichten

Neuropathic pain involves spinal microglial activation and metabolic changes.Forsythoside B (FB) has anti-inflammatory effects, but its role in neuropathic pain and microglial glycolysis remains unclear. We investigated the effects and mechanisms of FB in mice with chronic constriction injury (CCI) and in LPS-stimulated BV2 microglia.FB reduced mechanical allodynia and thermal hyperalgesia in CCI mice. FB also reduced the spinal levels of HIF-1, HK2, PKM2, LDHA, and CD86. It decreased the proportion of IBA1+/CD86+ cells and the levels of IL-1{beta}, IL-6, and TNF-. In LPS20 stimulated BV2 microglia, FB reduced glycolysis-related proteins, proinflammatory markers, and cytokine release. FB also reduced glycolytic activity and partly restored basal mitochondrial respiration. FB did not change Hif1a mRNA levels. However, it Manuscript Click here to access/download;Manuscript;Manuscript.docx increased HIF-1 ubiquitination and promoted its proteasome-dependent degradation. HIF-1 overexpression partly reversed the effects of FB on glycolytic enzymes, CD86 expression, and proinflammatory cytokine production. Immunoprecipitation followed by mass spectrometry and UbiBrowser analysis identified USP7 as a candidate HIF27 1-associated deubiquitinase. Molecular docking and cellular thermal shift assays supported a possible interaction between FB and USP7. FB reduced the association between USP7 and HIF-1. USP7 knockdown produced effects similar to those of FB on HIF-1 ubiquitination and downstream glycolytic and inflammatory responses.Overall, FB alleviated neuropathic pain and reduced proinflammatory microglial responses. These effects may involve the promotion of HIF-1 degradation through modulation of the USP7-HIF-1 regulatory axis.

Read the full paper: Molecular mechanism of HUWE1-HAPSTR1-USP7-mediated ubiquitin chain amplification on nuclear proteins

Yatskevich et al. show that HUWE1 amplifies existing ubiquitin tags through chain elongation and branching. A cryo-EM structure reveals multivalent HUWE1-USP7 assembly and reciprocal regulation, while HAPSTR1 tunes substrate capture by engaging HUWE1 ubiquitin-binding motifs, defining a coordinated system for short-lived nuclear protein turnover.

Read the full paper: CCND1 Stability Regulated by USP7 Deubiquitination Controls Glioma Radioresistance via Ferroptosis

Background Postoperative peritoneal adhesions (PPAs) are a common and serious complication following abdominal surgery. The key pathological basis is the excessive accumulation of myofibroblasts durin...

YouTube video by ZDFheute Nachrichten

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and is often associated with dismal outcomes, underscoring the urgent need for new therapeutic strategies. RMS arises from emb...

Combining improved sample preparation, data-independent acquisition mass spectrometry and deep learning, the authors develop a workflow for more robust and precise quantitative ubiquitinome profiling....

Published in Journal of translational medicine

DUBs regulate key cellular processes, but selective tools are scarce. Here, the authors developed PROTACs for the DUB USP7, comparing degraders with inhibitors. The study provides a valuable toolbox f...

Ubiquitin-specific protease 7 (USP7) is implicated in many cancers including colorectal cancer in wh