Journal: Journal of Nanobiotechnology

Article Title: CD8a antibody-functionalized biomimetic red blood cell membrane ectosomes delivering C646 reverse CD8⁺ T Cell exhaustion via H3K18la histone delactylation in gastric cardia adenocarcinoma

doi: 10.1186/s12951-025-03957-z

Figure Lengend Snippet: Bioinformatics Analysis Identifies Key Factors in Histone Lactylation Modification. Note: ( A ) Schematic workflow of bioinformatics analysis for identifying key factors; ( B ) Volcano plot of DEGs in tumor tissues and adjacent normal tissues from dataset GSE2685 (Normal = 8, Tumor = 22); ( C ) Heatmap showing the correlation of co-expression module genes with tumor and normal tissues, with each cell displaying the correlation coefficient and p -value; ( D ) Venn diagram illustrating the intersection of Blue module genes, DEGs, CD8 + T cell-related genes, and "Histone lactylation"-related genes; ( E ) Box plot of p300 differential expression; ( F ) The tSNE distribution map of EP300 in various cell types in the scRNA-seq data

Article Snippet: The p300 activator (cholera toxin B subunit, CTB; HY-134964) and p300 inhibitor (C646; HY-13823) were both purchased from MCE (USA); (3) PBS + vector group, CD8a-NVEs@C646 + vector group, and CD8a-NVEs@C646 + PDCD1 group, all treated with 20 mM sodium lactate for 24 h, with CD8a-NVEs@C646 treatment for 48 h. Cells from all groups were harvested for downstream analysis.

Techniques: Modification, Expressing, Quantitative Proteomics

Journal: Journal of Nanobiotechnology

Article Title: CD8a antibody-functionalized biomimetic red blood cell membrane ectosomes delivering C646 reverse CD8⁺ T Cell exhaustion via H3K18la histone delactylation in gastric cardia adenocarcinoma

doi: 10.1186/s12951-025-03957-z

Figure Lengend Snippet: p300 Regulates Histone Lactylation in CD8 + T Cells. Note: ( A ) Schematic representation of the experimental design, showing the workflow for detecting CD8 + T cells treated with lactate, p300 inhibitors, or activators. ( B–C ) WB analysis of PKla levels in CD8 + T cells over time (B) and under varying lactate concentrations ( C ). ( D–E ) WB analysis of the time-dependent ( D ) and dose-dependent ( E ) changes in H3K18la and H3K9la expression in CD8 + T cells following lactate treatment. *** p < 0.001, ** p < 0.01, and * p < 0.05 compared to the 0-h or untreated lactate group. ( F ) WB analysis of H3K18la and H3K9la expression in CD8 + T cells following p300 knockdown, activation, or inhibition. ( G ) ELISA detection of IFN-γ levels in the supernatant of CD8 + T cells across different treatment groups. (H) FCM analysis of GZMB expression in CD8 + T cells. ( I ) FCM analysis of CD8 + T cell proliferation. ( J ) LDH release assay showing the cytotoxic effects of CD8 + T cells on MKN-45 and SNU1 cells. In panels ( F–J ), * p < 0.05, ** p < 0.01, and *** p < 0.001 compared to the control group; # p < 0.05, ## p < 0.01, and ### p < 0.001 compared to the Lactate group; & p < 0.01 compared to the Lactate + sh-NC group. All cell-based experiments were performed in triplicate

Article Snippet: The p300 activator (cholera toxin B subunit, CTB; HY-134964) and p300 inhibitor (C646; HY-13823) were both purchased from MCE (USA); (3) PBS + vector group, CD8a-NVEs@C646 + vector group, and CD8a-NVEs@C646 + PDCD1 group, all treated with 20 mM sodium lactate for 24 h, with CD8a-NVEs@C646 treatment for 48 h. Cells from all groups were harvested for downstream analysis.

Techniques: Expressing, Knockdown, Activation Assay, Inhibition, Enzyme-linked Immunosorbent Assay, Lactate Dehydrogenase Assay, Control

Journal: Journal of Nanobiotechnology

Article Title: CD8a antibody-functionalized biomimetic red blood cell membrane ectosomes delivering C646 reverse CD8⁺ T Cell exhaustion via H3K18la histone delactylation in gastric cardia adenocarcinoma

doi: 10.1186/s12951-025-03957-z

Figure Lengend Snippet: CD8a-NVEs@C646 Facilitates Histone Delactylation Modification in CD8 + T Cells. Note: ( A ) Schematic workflow of RNA-seq and ChIP-seq experiments for CD8 + T cells treated with CD8a-NVEs@C646; ( B–C ) ChIP-seq analysis showing signals at TSS regions in PBS-treated (n = 3) and CD8a-NVEs@C646-treated groups (n = 3); ( D ) RNA-seq volcano plot illustrating significantly upregulated and downregulated genes in the CD8a-NVEs@C646-treated group compared to PBS (n = 3); ( E ) Venn diagram of overlapping genes from ChIP-seq and RNA-seq analyses related to CD8 + T cells; ( F ) ChIP analysis of p300 and H3K18la enrichment at the PDCD1 promoter region; ( G ) The protein interaction between p300 and H3K18la was detected by co-IP assay; ( H ) RT-qPCR analysis of PDCD1 mRNA expression in CD8 + T cells following CD8a-NVEs@C646 treatment; ( I ) WB analysis of PDCD1 and H3K18la protein expression levels in CD8 + T cells treated with CD8a-NVEs@C646. * p < 0.05, *** p < 0.001 compared to the PBS or sh-NC group; experiments were conducted in triplicate

Article Snippet: The p300 activator (cholera toxin B subunit, CTB; HY-134964) and p300 inhibitor (C646; HY-13823) were both purchased from MCE (USA); (3) PBS + vector group, CD8a-NVEs@C646 + vector group, and CD8a-NVEs@C646 + PDCD1 group, all treated with 20 mM sodium lactate for 24 h, with CD8a-NVEs@C646 treatment for 48 h. Cells from all groups were harvested for downstream analysis.

Techniques: Modification, RNA Sequencing, ChIP-sequencing, Co-Immunoprecipitation Assay, Quantitative RT-PCR, Expressing

Journal: Advanced Science

Article Title: MeCP2 Lactylation Protects against Ischemic Brain Injury by Transcriptionally Regulating Neuronal Apoptosis

doi: 10.1002/advs.202415309

Figure Lengend Snippet: HDAC3 and p300 play roles in regulating of MeCP2 lactylation in ischemic stroke. A) Western blot analysis of MeCP2 lactylation at K210 and K249 in cortical samples from MCAO mice treated with saline or RGFP966. B) Quantification of GVI PLA2 and PDCD4 expression levels in the saline or RGFP966‐treated MCAO mice ( n = 6 per group). C) Representative images of TTC staining showing RGFP966 reduced infarct volume of MCAO mice. D) Quantification of brain infarct volume in mice treated with saline and RGFP966 at 1 d and 3 d post‐MCAO ( n = 5–7 per group). E) Evaluation of grip strength, F) mNSS scores, and G) fault step ratio in stroke mice treated with saline and RGFP966 ( n = 6–7 per group). H) Western blot analysis showing the effect of CTB treatment on MeCP2 lactylation at K210 and K249 compared to saline. I) Quantification of GVI PLA2 and PDCD4 expression levels in mice treated with saline or CTB ( n = 3 per group). J) Representative images of brain sections stained for infarction from mice treated with saline or CTB. K) Quantification of brain infarct volume in mice treated with saline or CTB ( n = 5–7 per group). L) Grip strength test, M) mNSS scores, and N) fault step ratio for mice treated with saline or CTB ( n = 9–10 per group). Modified Neurological Severity Scores (F, M) are shown as median ± ranges, and other values are presented as mean ± SEM. * p < 0.05, ** p < 0.01, *** p < 0.001; ns, not significant.

Article Snippet: [ ] Additionally, 30 μmol kg −1 of the p300 activator CTB (Cat. E1107, Selleck, USA) or 10 mg kg −1 RGFP966 (Cat. S7229, Selleck, USA) was intraperitoneally injected 12 h post‐MCAO.

Techniques: Western Blot, Saline, Expressing, Staining, Modification