PDCD6IP (Programmed Cell Death 6 Interacting Protein)

Co-administration of CARM1 inhibitor with inosine significantly enhances tumor-infiltrating CD8+ T cell cytotoxicity, reduces PD-1+TIM-3+ exhausted CD8+ T cells, and suppresses tumor growth. These findings establish the CARM1-ALIX-hypoxanthine axis as an immunosuppressive mechanism and suggest that combining CARM1 inhibition with inosine supplementation represent a promising therapeutic strategy for breast cancer.

Critically, PARP1 inhibition rescues GBP6 loss by suppressing TP63 and prevents ESCC progression. Overall, this study provides a systematic proteomic atlas of ESCC progression, identifies MOD as a pivotal clinical decision point, and proposes PARP1-TP63-GBP6 axis targeting as a novel intervention strategy.

We demonstrate proof of principle of using hCEC-derived sEVs for delivery of potential therapeutic agents to the mouse CE in vivo via intracameral injection. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

We conclude that eliminating class I HDACs with specific PROTACs could be an effective and precise strategy for treating DLBCL that should be further tested for their potential clinical relevance. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

Collectively, our findings demonstrate that honokiol-induced oxidative stress in HCC Hep3B cells critically contributes to subsequent paraptotic events such as ER stress and mitochondrial damage, highlighting the potential of honokiol as a therapeutic agent for liver cancer treatment. The online version contains supplementary material available at 10.1007/s43188-025-00291-2.

Moreover, ALG-2 and ALIX overexpression attenuated TDCPP-induced lysosomal injury, enhancing cell survival. Our findings reveal a novel mechanism by which TDCPP disrupts lysosomal membrane repair through interference with ALG-2/ALIX-mediated ESCRT-III recruitment, providing the molecular mechanisms of TDCPP-induced neurotoxicity and highlighting potential therapeutic strategies for combating TDCPP toxicity.

NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

The critical role of ALIX in MSC-sEV biogenesis, in particular, underscores its potential as a target for modulating sEVs' yield in regenerative therapies. Through this comparative analysis, we identified shared molecular signatures, offering insights to guide therapeutic interventions and unlock the regenerative potential of stem cells.

Moreover, MCs may function as the recipients of EXOs that are released by other non-immune and immune cells, altering the secretome of MCs. In this review, we focus on how MC-EXOs modulate the biology of other cells and vice versa; and we highlight the role of MC-EXOs in the pathogenesis of allergic and non-allergic diseases.

Moreover, mutation of the CEP55-Alix interaction site strongly reduced the formation of CEP55 dots as well as CEP55 localization in extracellular vesicles. In summary, our data indicate that delivery of CEP55 into exosomes does not occur by the canonical early-to-late endosome pathway but by Alix-mediated recruitment to secretory late secretory CD63 endosomes.

Collectively, this study reveals how damaged lysosomes signal through calcium to trigger SG assembly, promoting cell survival. This establishes a novel link between membrane-bound and membraneless organelles, with implications for diseases involving lysosomal damage and SG dysfunction.

Finally, we validated a seven EV protein PDAC signature against a background of benign pancreatic diseases that yielded an 89% prediction accuracy for the diagnosis of PDAC. To our knowledge, our study represents the largest proteomics profiling of circulating EVs ever conducted in pancreatic cancer and provides a valuable open-source atlas to the scientific community with a comprehensive catalogue of novel cEVs that may assist in the development of biomarkers and improve the outcomes of patients with PDAC.