Either the depletion of aHSCs or pharmacological inhibition of the PGE2-synthesizing enzyme Cyclooxygenase-2 (COX-2) with Celecoxib (CLX) restored NK cell function and suppressed LM. Notably, CLX treatment synergized with anti-NKG2A-based immunotherapy, significantly boosting its efficacy against LM in the fibrotic liver. Our findings unveil a critical "aHSC-PGE2-NK cell" axis in liver fibrosis-induced immunosuppression and provide a compelling therapeutic strategy for the clinical management of LM.
Micrographs of the ear's tissue clearly showed a decrease in thickness and infiltration of neutrophils, which correlates with the reduction of MPO and cytokines. Finally, molecular docking suggested that the series could inhibit cyclooxygenases and displayed a binding mode like that of celecoxib, though the enzymatic assay will be performed in future work.
Crucially, the addition of exogenous PGE2 restored VM formation in celecoxib-treated cells, confirming that celecoxib-mediated VM suppression is dependent on the reduction of PGE2 levels. These findings establish the COX-2/PGE2 signaling axis as a key regulator of VM in D17 canine osteosarcoma cells and that celecoxib warrants further preclinical evaluation as a strategy to target both tumor growth and alternative vascularization.
The combination also significantly downregulated IL-6, IL-17, and TNF-α levels, and showed potent COX-2 inhibition (0.10 ± 0.01 µg/mL), surpassing celecoxib (0.9 ± 0.05 µg/mL)...Notably, the combination reduced cell viability to 3.77 ± 0.4 % % at 400 µg/mL, consistent with apoptotic changes. Collectively, these findings highlight the synergistic potential of APs and eugenol as a multi-target therapeutic approach against MDR infections, inflammation, oxidative stress, and liver cancer.
P2, N=46, Active, not recruiting, Emory University | Trial completion date: Jan 2026 --> Jun 2026 | Trial primary completion date: Jan 2026 --> Jun 2026
1 month ago
Trial completion date • Trial primary completion date
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AFP (Alpha-fetoprotein)
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cyclophosphamide • etoposide IV • sirolimus • celecoxib oral
Intermediate-region APC mutations (e.g., codons 607 and 1062) predict an indolent course in mesenteric DTs. Comprehensive APC genotyping at diagnosis enables risk-adapted management, permitting safe use of conservative strategies (active surveillance/low-intensity therapy) and helps avoid unnecessary aggressive interventions. This underscores the critical role of molecular profiling in personalizing DT care.
Both probes integrate a celecoxib ligand for COX-2 targeting with a naphthalimide fluorophore...MM/PBSA calculations revealed favorable binding enthalpies for both S1 (-80.05 ± 7.19 kcal/mol) and S2 (-83.76 ± 3.88 kcal/mol) with COX-2, confirming stable and specific complex formation. This integrated experimental and computational strategy yields highly sensitive and selective probes, positioning S1 and S2 as promising tools for studying cancer-related biomarkers at the cellular level.