Molecular docking confirmed that LT4 stably occupied the ATP‑binding pocket of PI3Kγ with a binding energy comparable to wortmannin and a conformation similar to antroquinonol. In conclusion, to the best of our knowledge, the present study is the first to comprehensively demonstrate the multi‑target anti‑CRC effects of LT4, highlighting its potential as a therapeutic agent, especially in KRAS‑mutant CRC.

SLC12A8 promotes immune evasion and metastasis in Luminal B breast cancer by inducing CD8+ T-cell exhaustion via activation of the TLR signaling pathway, suggesting its potential as a prognostic biomarker and therapeutic target.

P1, N=20, Not yet recruiting, University Health Network, Toronto

Integrated mechanistic studies, including network pharmacology, transcriptomics, and Western blot analysis, indicated that the anti-leukemic effects of oleandrin are associated with suppression of the PI3K/AKT signaling pathway, as evidenced by reduced levels of key proteins such as PIK3CA, phosphorylated AKT (p-AKT), phosphorylated GSK3β (p-GSK3β), c-Myc, Bcl-2, and Bcl-xL. These findings suggest oleandrin is a promising therapeutic candidate for T-ALL, likely through suppression of the PI3K/AKT pathway.

Pharmacological inhibition of the TNF signaling pathway with R-7050 completely abolished the synergistic efficacy of RT/TMZ/ACT001. Taken together, our results demonstrate that ACT001 combined with RT/TMZ can overcome the immunosuppressive barrier of GBM to achieve immune cure in GBM via TNF-CXCL10-CD8+ signaling, strongly suggesting the priority of combining ACT001 with RT/TMZ rather than with αPD-1 in clinical trials.

Emerging strategies to modulate NLRP3 include small-molecule inhibitors (e.g., MCC950, BAY-117082), plant-derived compounds (e.g., oridonin, Bacopa monnieri), and immunotherapy approaches, including intratumoral NLRP3 agonists combined with checkpoint blockade. This review synthesizes the multifaceted roles of NLRP3 in OSCC, highlighting its centrality in inflammation-driven tumor biology and its promise as a therapeutic target. Understanding the contextual duality of NLRP3 activation is critical for developing precision therapies that disrupt its tumor-supportive effects while preserving or enhancing its immunogenic functions.

We also discuss the repurposing of the oral adsorbent AST-120 and emerging bacteriophage therapies as strategies to disrupt this oncogenic axis. This review offers a comprehensive framework for stratified management of CKD-associated CRC.

P2/3, N=40, Active, not recruiting, Fundacio Institut D Investigacio Biomedica De Bellvitge IDIBELL | Recruiting --> Active, not recruiting

This study reveals that ETS1 transcriptionally suppresses NKIRAS1, activating NF-κB signaling and promoting pyroptosis and pancreatic injury in AP. Targeting ETS1 may represent a promising therapeutic strategy.

Our study indicated that MHSA could be considered a valuable option for cervical cancer screening in China.

Importantly, the pro-pyroptotic effect of GPNMB overexpression in Hcy-treated THP-1-derived macrophages was counteracted by either inhibition of NADPH oxidase 2 (NOX2) using the specific inhibitor gp91ds-tat or blockade of NF-κB activation with the inhibitor BAY11-7082. Moreover, serum GPNMB levels were correlated with serum Hcy levels and lipid profiles in both healthy individuals and HHcy patients. Collectively, these findings demonstrate that GPNMB facilitates Hcy-induced macrophage pyroptosis associated with the upregulation of the NOX2/NF-κB signaling pathway, highlighting the potential relevance of GPNMB as a candidate target for the clinical management of HHcy-related atherosclerotic cardiovascular disease.

Inhibition of NF-κB with BAY 11-7082 suppressed PLS3-AS1 expression and reversed its pro-tumorigenic effects. These findings identify PLS3-AS1 as a critical mediator of NF-κB-driven radioresistance in CRC and a potential therapeutic target to improve radiotherapy efficacy.