Pre- and postoperative levels of serum pain mediators (SP, PGE2, β-EP, and Glu), inflammatory markers (IL-6, TNF-α, IL-10, and CD11b), coagulation function parameters (PT, APTT, TT, D-D, and TAT), platelet activation (GP IIb/IIIa, CD62P, GMP-140, and PAC-1) were detected...Buccal acupuncture combined with PCIA may exert analgesic effects through multiple mechanisms, including regulating the balance of pain mediators, relieving inflammation, enhancing vascular endothelial function, and correcting a hypercoagulable state. It can also improve clinical analgesic outcomes and reduce opioid consumption with good safety.

Our experiments revealed that AF exhibited antithrombotic activity comparable to that of rivaroxaban, a well-established direct FXa inhibitor, particularly in suppressing FXa activity and platelet aggregation induced by adenosine diphosphate (ADP) and U46619, a synthetic thromboxane A2 analog. AF also reduced the surface expression of P-selectin, inhibited phosphorylation of myristoylated alanine-rich C kinase substrate, and decreased PAC-1 activation following ADP or U46619 stimulation...In vivo experiments in mouse models of arterial and pulmonary thrombosis demonstrated that AF is a potent anticoagulant and antithrombotic agent. These findings indicate that AF could serve as a promising lead compound for developing innovative anti-FXa and antiplatelet therapeutics.

Density functional theory calculations confirmed their enhanced zinc-binding affinity, with adsorption energies (Eads) of -14.8332 eV (F17) and -14.8797 eV (F21), compared to -12.7474 eV for PAC-1, along with stronger electrostatic potential minima (-67.20 and -66.99 kcal/mol, respectively)...Importantly, in vivo neurotoxicity assessments revealed no significant neuronal damage at doses up to 50 mg/kg, underscoring their improved safety profile over earlier activators. These results establish F21 as a particularly promising preclinical candidate and provide a rational framework for developing target-specific, neurotoxicity-sparing procaspase-3 activators for TNBC therapy.

Consequently, PAC-1 induces progressive iron depletion and selective cytotoxicity in otherwise drug-resistant MDR1-expressing cancer cells. Together, these findings redefine PAC-1's mechanism-of-action and establish a framework for exploiting multidrug resistance as a therapeutic vulnerability through targeted iron starvation.

Combining tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-producing oncolytic viruses with procaspase-3 activator (PAC-1) presents a promising therapeutic strategy, as TRAIL initiates apoptosis while PAC-1 amplifies caspase activity...This integrative approach provides mechanistic insight into tumor behavior while improving predictive accuracy, supporting the development of personalized therapeutic strategies for GCTs. The framework also offers broader applicability to other cancers with limited treatment options and heterogeneous responses.

By hybridizing this natural product scaffold with optimized structural elements from PAC-1, a reference procaspase-3 activator, 28 target compounds (K-01 ∼ K-28) were successfully synthesized...These results demonstrate that the hybrid molecular design strategy effectively combines the pharmacophoric advantages of both natural products and synthetic activators. The developed procaspase-3 activators exhibit improved therapeutic potential and represent promising candidates for further development as targeted anticancer agents modulating the caspase-3 activation pathway.

ImmuProgML offers a promising avenue for understanding the intricate relationship between tumors and the immune system, providing a machine learning framework for personalized cancer immunotherapy selections.

Our data show that PAC-1 modulates sunitinib-induced autophagy and blocks lysosomal trapping, potentiating sunitinib activity and increasing death of cancer cells. As both drugs are well-tolerated in patients, the data suggest evaluation of the PAC-1/sunitinib combination in a clinical trial of patients with PNET.

In addition, relative expression levels of von Willebrand Factor, β-TG, and iNOS and serum concentrations of PAC-1, β-TG, and iNOS were inhibited. Sodium ferulate can treat AAV by inhibiting NET release and platelet activation and reducing endothelial cell damage.

Drug sensitivity analysis further demonstrated that tumors with elevated pyrimidine metabolism displayed increased responsiveness to several chemotherapeutic agents, including BI-2536, JW-7-24-1, and PAC-1, suggesting that targeting pyrimidine metabolism may enhance treatment efficacy. In conclusion, pyrimidine metabolism plays a critical role in prostate cancer progression, influencing immune infiltration and drug sensitivity. Targeting this metabolic pathway offers a promising strategy for the development of new therapeutic approaches, particularly for overcoming drug resistance and improving outcomes in patients with advanced prostate cancer.

The study suggests that the S. nabateorum stem extract holds promise as a potent antimicrobial, antioxidant, and anticancer agent. It provides valuable insights for considering the extract as a substitute for chemotherapy and/or protective agents.

FHOD3 was overexpressed and negatively associated with survival rate in lung cancer patients. FHOD3 regulates cell proliferation, invasion, and apoptosis through the caspase-3-mediated signaling pathway. This study indicates that FHOD3 is an important gene contributing to the progression of lung cancer and might be a new drug target for the therapy of lung cancer.