visualization-macrophage-lytic-cell-death-during-mycobacterial

Visualization of Macrophage Lytic Cell Death During Mycobacterial Infection in Zebrafish Embryos via Intravital Microscopy

Zebrafish is an excellent model organism for studying innate immune cell behavior due to its transparent nature and reliance solely on its innate immune ...

Fudan University

Quinacrine has been identified as a potent DR5-inducing agent that sensitizes cancer cells to TRAIL-induced apoptosis. In the current study, we found that quinacrine increased DR5 mRNA levels significantly in ovarian cancer cell lines regardless of p53 status. Further study showed the half-life of DR5 in quinacrine-treated cells was significantly prolonged, indicating that DR5 protein degradation was inhibited by quinacrine. We tested if the combination of TRAIL and quinacrine could be effective in ovarian cancer treatment  and in ovarian cancer xenograft mouse models. We found that quinacrine enhanced TRAIL sensitivity or reversed TRAIL resistance in all the ovarian cancer cell lines tested. Mice treated with quinacrine and TRAIL remained disease-free for up to 20 weeks, however, mice treated with TRAIL or quinacrine alone and in control group died within ~8 weeks after treatment. Intraperitoneal delivery of quinacrine and TRAIL is rational and practical with extraordinary synergistic anti-cancer effects in preclinical models of ovarian cancer. Clinical investigation of combining quinacrine with TRAIL for ovarian cancer treatment is warranted.

Repositioning Quinacrine Toward Treatment of Ovarian Cancer by Rational Combination With TRAIL.

The goal of this study was to investigate the status of FEN1 in colorectal cancer (CRC) and determine the potential correlation between FEN1 expression level and clinicopathological parameters in CRC patients.

FEN1 Status and Its Correlation with Clinicopathologic Characteristic in Colorectal Cancer.

Da-yuan-yin decoction (DYY) is a classical traditional Chinese medicine prescription for ulcerative colitis (UC).

Da-yuan-yin decoction alleviates ulcerative colitis by inhibiting complement activation, LPS-TLR4/NF-κB signaling pathway and NET formation.

 PANoptosis, a recently characterized inflammatory programmed cell death modality orchestrated by the PANoptosome complex, integrates molecular mechanisms of pyroptosis, apoptosis, and necroptosis. Although this pathway potentially mediates tumor progression, its role in lung adenocarcinoma (LUAD) remains largely unexplored.  Through comprehensive single-cell transcriptomic profiling, we systematically identified critical PANoptosis-associated gene signatures. Prognostic molecular determinants were subsequently delineated via univariate Cox proportional hazards regression analysis. We constructed a PANoptosis-related optimal model (PROM) through the integration of 10 machine learning algorithms. The model was initially developed using The Cancer Genome Atlas (TCGA)-LUAD cohort and subsequently validated across six independent LUAD cohorts. Model performance was evaluated using mean concordance index. Furthermore, we conducted extensive multiomics analyses to delineate differential pathway activation patterns and immune cell infiltration profiles between PROM-stratified risk subgroups.  Cellular populations exhibiting elevated PANoptosis signatures demonstrated enhanced intercellular signaling networks. PROM demonstrated superior prognostic capability across multiple validation cohorts. Receiver operating characteristic curve analyses revealed area under the curve values exceeding 0.7 across all seven cohorts, with several achieving values above 0.8, indicating robust discriminative performance. The model score exhibited significant correlation with immunological parameters. Notably, high PROM scores were associated with attenuated immune responses, suggesting an immunosuppressive tumor microenvironment. Multiomics investigations revealed significant alterations in critical oncogenic pathways and immune landscape between PROM-stratified subgroups.  This investigation establishes PROM as a clinically applicable prognostic tool for LUAD risk stratification. Beyond its predictive utility, PROM elucidates PANoptosis-associated immunological and biological mechanisms underlying LUAD progression. These findings provide novel mechanistic insights into LUAD pathogenesis and may inform the development of targeted therapeutic interventions and personalized treatment strategies to optimize patient outcomes.

Article	Year
Repositioning Quinacrine Toward Treatment of Ovarian Cancer by Rational Combination With TRAIL. Frontiers in oncology\| PubMed ID: 32766144	2020
FEN1 Status and Its Correlation with Clinicopathologic Characteristic in Colorectal Cancer. Combinatorial chemistry & high throughput screening\| PubMed ID: 33797361	2022
Da-yuan-yin decoction alleviates ulcerative colitis by inhibiting complement activation, LPS-TLR4/NF-κB signaling pathway and NET formation. Journal of ethnopharmacology\| PubMed ID: 38797378	2024
PANoptosis-Related Optimal Model (PROM): A Novel Prognostic Tool Unveiling Immune Dynamics in Lung Adenocarcinoma. International journal of genomics\| PubMed ID: 40008397	2025

Rui Liang

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