Background: Endometriosis is still a difficult problem for women. The Nuclear Ubiquitous Casein and cyclin-dependent Kinase Substrate 1 (NUCKS1) gene is located on human chromosome 1q32.1. It encodes the NUCKS1 protein, a 27 kDa nuclear DNA binding protein that plays an important role in cell growth and proliferation. NUCKS1 plays an important role in the development of many diseases. However, its role in endometriosis is unclear. Methods: Ectopic endometrial tissues and normal tissue specimens were collected, and the expression of NUCKS1, NF-κB and PI3K was detected by RT-qPCR and immunohistochemistry. Inhibition of NUCKS1 in hEM15A cells, study the changes in cell viability, apoptosis, migration and protein expression by CCK8 assay, flow cytometry, wound-healing assay, western blot and ELISA techniques. The comparison of differences between the two groups was implemented using unpaired sample t test or Mann-whitney U test. One-way analysis of variance or Kruskal-wallis test was used for comparisons among the three groups. Results: (1) NUCKS1 is highly expressed in endometriosis tissues. (2) Inhibition of NUCKS1 decreases cell viability and capability of migration, and increases apoptosis in endometriosis cells. (3) Expressions of NF-κB and PI3K are increased in endometriosis tissues, and inhibition of NUCKS1 decreases the expression levels of PI3K and NF-κB in endometriosis cells. (4) Inhibition of NUCKS1 decreases the expression of VEGF. Conclusion: (1) NUCKS1 is overexpressed in endometriosis, and inhibition of NUCKS1 inhibits cell viability and capability of migration, and increases apoptosis. (2) NUCKS1 promotes the progress of endometriosis through activating PI3K and NF-κB pathways, and VEFG is also involved in this process.

Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) significantly impairs cancer therapy and patient quality of life, yet its pathogenic mechanisms remain unclear. Through integrated single-cell multi-omics analysis of paired peripheral blood, synovial fluid, and tumor samples from longitudinal ICI-IA cohorts and matched controls, we identified a unique regulatory T-cell (Treg) population co-expressing CD137 and IL-6R (AtpTreg). These cells exhibited reduced immunosuppressive capacity while aberrantly producing high level of IL-17 and promoting proinflammatory responses of synoviocytes. AtpTreg exhibits shared clonotypes and phenotypes across tissue compartments. Notably, AtpTreg frequency correlates with increased arthritis severity yet paradoxically associates with improved overall survival. Anti-IL6R therapy reduced AtpTreg levels, corresponding with improved arthritis outcomes and quality of life, without compromising anti-tumor immunity. Our findings define a pathogenic Treg subset in ICI-IA and validate IL-6R blockade as a mechanism-based therapeutic strategy, bridging mechanistic discovery to clinical translation. This study is registered at ClinicalTrials.gov (NCT07357636).

Paederia scandens (Lour.) Merr is a substance exhibiting medicine–food homology (MFH), commonly used in China. However, the antioxidant and anti-aging effects of paederoside (PSG) have not been thoroughly investigated; therefore, in this study, Caenorhabditis elegans (C. elegans) was treated with PSG to investigate these effects. We found that 50, 80, and 100 μg/mL of PSG could prolong the lifespan of C. elegans, and administration of 100 μg/mL PSG significantly reduced the accumulation of lipofuscin. Under conditions of oxidative stress, RT-qPCR analysis revealed that PSG treatment significantly up-regulated the expression of key antioxidant gene skn-1 and longevity-associated gene daf-16. In addition, PSG increased the activity of the antioxidant enzymes SOD and CAT and reduced the level of MDA. When DAF-2 activity is reduced or inhibited in C. elegans, DAF-16 and SKN-1 are activated and translocate to the nucleus to promote stress resistance and prolong lifespan. Finally, by utilizing HeLa cell models, we demonstrated that the core component of Paederia scandens, PSG, promotes targeted degradation of IGF1R through the ubiquitin–proteasome system. Our results suggest that feeding C. elegans PSG is effective in extending this organism’s lifespan by improving oxidative stress resistance; thus, PSG has significant potential for development as an anti-aging food product and drug.

Background: Metastasis and recurrence account for the failure of nasopharyngeal carcinoma (NPC) treatment. Growing evidence indicates the dominant roles of cancer stem cells (CSCs) in tumor progression and therapy resistance. However, the heterogeneity of CSCs and potential stemness-related markers in NPC patients are still largely unknown. Methods: Consensus clustering was first applied to identify robust stemness subtypes for NPC patients based on the activities of stem cell gene sets. The differences in clinical outcomes, tumor immune microenvironment (TIME), and drug response were compared between subtypes. The stemness-related markers were prioritized via weighted gene correlation network analysis (WGCNA) and Cox regression, and verified through in vitro experiments. Results: NPC patients were classified into C1 and C2 subtypes. The C2 subtype exhibited higher activities of stem cell gene sets, worse prognosis, and aggressive tumor progression thus defined as stem cell-like tumor phenotype. The exclusionary relationships between tumor stemness and TIME infiltration were observed. The efficacy of several drugs and immunotherapy varied between NPC stemness subtypes. Through the WGCNA and survival analysis, we found that PSMC3IP, NABP2, CDC45, and HJURP were stemness-relevant genes. Sphere formation assays and analysis of the protein expression of stem cell markers by Western blotting revealed the roles of PSMC3IP, NABP2, CDC45, and HJURP in promoting CSC properties. Moreover, these genes were found to be related to the therapeutic effect of telomerase inhibitor in CCK8 experiments. Conclusions: This study systematically characterized two NPC subtypes with distinct stemness features, clinical outcomes, and TIME features. Novel stemness-related markers will provide valuable targets against metastatic or recurrent NPC.