BBC3 (BCL2 Binding Component 3)

Immune cell metabolic dysfunction is present in patients with uncomplicated infection before the clinical onset of sepsis. Early mitochondrial dysfunction and oxidative stress may represent promising targets for further investigation as early biomarkers of immune dysfunction and sepsis risk.

Accordingly, various viruses have evolved strategies to modulate host cell viability to their advantage by targeting PUMA-either by suppressing transcription of the PUMA gene, binding and inactivating the PUMA protein, or, conversely, inducing its production. In this work, we describe the role of PUMA in infections caused by distinct viruses and in associated diseases, viral strategies for modulating PUMA-related signaling pathways, and potential therapeutic implications.

In summary, paclitaxel induces transcriptomic and proteomic signatures of the neuronal stress response, neuroinflammation, nociception, and disturbed metabolism. These may explain, in part, the clinical phenotype of sensory loss, hypersensitivity, and neuropathic pain frequently observed in patients suffering from CIPN, but constitute pharmacologically addressable targets.

High expression of PUMA combined with low expression of p53 and a high expression of Ki-67 were independent unfavorable prognostic indicators for both OS and CSS. Further studies are required to clarify the prognostic and therapeutic role of these markers in CRC.

The in vivo efficacy was further supported by Ki-67 expression in tumor tissues. Taken together, our findings demonstrated that although the combination of Act D and resveratrol showed better efficacy in vitro than any of the single agent, the in vivo efficacy was not improved.

Preferred treatment options for advanced or recurrent EC patients include a combination of carboplatin and paclitaxel, with modest clinical outcomes...This study identified the novel small-molecule inhibitor AC1Q3QWB (AQB) as a potent enhancer of carboplatin efficacy...In vivo studies using subcutaneous xenografts and a stage IV EC patient-derived xenograft (PDX) model demonstrated that AQB enhanced carboplatin's antitumor effects, reduced the required carboplatin dose, and alleviated associated toxicity. The combination of AQB with standard chemotherapy holds promise for improving outcomes in patients with advanced or recurrent EC.The schematic diagram illustrates the mechanism by which AQB enhances the sensitivity of EC cells to CBPt.

Furthermore, when challenged with identical intracellular oxaliplatin levels, AsPC‑1 cells exhibited delayed caspase 3/7 activity initiation, weaker induction of pro‑apoptotic genes BBC3 (1.7‑fold vs. 5‑fold) and PMAIP (2.5‑fold vs. 6‑fold), but stronger enhancement of anti‑apoptotic Jun expression (7‑fold vs. 3‑fold) than BxPC‑3 cells. Taken together, oxaliplatin resistance in PDAC models may be highly linked to a poor apoptotic response, whereas drug uptake seems to be of minor relevance.

Additionally, we discuss PUMA's role in cancer progression, its impact on the effectiveness of anti-cancer therapies, and its potential as a prognostic biomarker for therapeutic resistance. Finally, we propose critical questions to inspire future research, aiming to deepen the understanding of PUMA regulation and its significance in cancer therapy.

Integrating multi-omics and pharmacological evidence, we identify JUN as a master transcriptional regulator of the Nox4-inflammasome-PUMA apoptotic triad, thereby elucidating a previously unrecognized pathogenic pathway in obesity-exacerbated renal LLIRI. Targeting this axis with calcium channel blockers is a promising therapeutic strategy.

By inhibiting mitochondrial transcription, we show that XMH95 induces apoptosis by impairing both nuclear and mitochondrial transcription. In summary, XMH95 is a novel DNA binder that triggers apoptosis by upregulating multiple BH3-only genes.

Our findings position JC16 and JC36 as early-stage chemical leads with potential to restore mutant p53 function in a context-dependent manner. While their exact mechanism of action remains to be fully elucidated, these results provide a foundation for further development of indazole-based scaffolds as reactivators of the p53-Y220C mutant in cancer therapy.

Our validated composite model demonstrated strong predictive power. These findings establish an association between high-risk disease and specific tumor microenvironment alterations (M0 macrophages), epitranscriptomic dysregulation (m6A), and therapeutic vulnerabilities, providing valuable insights for refining prognosis and advancing targeted therapies for DLBCL.