Journal: Blood Neoplasia

Article Title: The KDM-family inhibitor JIB-04 sensitizes AML cells to venetoclax by inducing a ferroptosis-like phenotype

doi: 10.1016/j.bneo.2026.100236

Figure Lengend Snippet: Induction of ferroptosis-like phenotype by JIB-04 drives synergism with VEN. (A-C) OCI-AML3 and MOLM-1 cells were treated with 40nM/50nM JIB-04, 8mM/4mM NAC (antioxidant), 25μM Z-VAD-FMK (caspase inhibitor), or the combination JIB-04+NAC and JIB-04+Z-VAD-FMK for up to 48 hours (mean ± SD; n = 3). Cells were stained for ferroptosis markers and analyzed by flow cytometry. JIB-04 treatment group was normalized to the DMSO group. Statistical significance was calculated by 2-way ANOVA with Tukey multiple-comparison test. (A) MitoSOX red for mitochondrial ROS at 24 hours. (B) MitoPerOx for mitochondrial lipid peroxidation at 24 hours. (C) BODIPY C11 for lipid peroxidation at 48 hours. (D) HMOX1 protein levels were visualized by immunoblotting in AML cell lines treated with DMSO, JIB-04, or JIB-04+NAC for 24 hours. (E-F) Quantification of apoptosis by annexin V/PI staining in OCI-AML3 and MOLM-13 cells after treatment with 40nM/50nM JIB-04, 1μM/1nM VEN, 8mM/4mM NAC, or the indicated drug combinations. Statistical significance was calculated by ordinary 1-way ANOVA with Tukey multiple-comparison test. ∗ P < .05; ∗∗ P < .01; ∗∗∗ P < .001; ∗∗∗∗ P < .0001. Z-VAD, Z-VAD-FMK.

Article Snippet: AML cells were treated with JIB-04, the antioxidant NAC, the pan caspase inhibitor Z-VAD-FMK (MedChemExpress), or indicated combinations for up to 48 hours.

Techniques: Staining, Flow Cytometry, Comparison, Western Blot

Journal: Journal of Advanced Research

Article Title: Andrographolide alleviates type 2 diabetic nephropathy through suppressing PI3K/AKT1/RRM2-triggered oxeiptosis

doi: 10.1016/j.jare.2025.10.070

Figure Lengend Snippet: PI3K/AKT1 mediates H 2 O 2 -induced oxeiptosis, while andrographolide (AND) reverses hyperglycemia-triggered upregulation of PI3K/AKT1 signaling, RRM2, and oxeiptosis. (A) Effect of miltefosine on hydrogen peroxide-induced alterations in the PI3K/AKT1 signaling pathway, RRM2 expression, and oxeiptosis-associated proteins. (B) Quantitative analysis of protein levels shown in (A). (C) Phosphorylation kinetics of the PI3K/AKT pathway in response to H 2 O 2 . (D) Molecular docking between H 2 O 2 and PI3K. (E) Expression profiles of PI3K/AKT1 pathway components, RRM2, and oxeiptosis markers under 50 mM glucose (GLU) stimulation. (F) Quantitative analysis of protein levels shown in (E). (G) Pan-caspase inhibitor Z-VAD-FMK (Z-VAD) and necroptosis inhibitor Necrostatin-1 (Nec-1) fail to completely reverse apoptosis induced by H 2 O 2 -triggered oxeiptosis. (H) Apoptosis detection using Annexin V-mCherry/SYTOX Green staining in cells exposed to 50 mM GLU. (I) Quantification of Annexin V-mCherry-positive expression from (H). (J) GLU-induced mitochondrial co-localization and expression of AIFM1 (pS116). (K) Quantitative analysis of AIFM1 (pS116) expression from (J). (L) AND-mediated restoration of PI3K/AKT1 signaling, RRM2 levels, and oxeiptosis regulation under GLU stimulation. (M) Quantitative analysis of protein levels shown in (L). (N) AND-dependent attenuation of GLU-induced apoptosis detected by Annexin V-mCherry/SYTOX Green. (O) Quantification of Annexin V-mCherry-positive expression from (N). (P) AND-mediated modulation of AIFM1 (pS116) expression and its co-localization with mitochondrial under GLU stress. (Q) Quantitative analysis of AIFM1 (pS116) expression from (P). (R) AND suppresses H 2 O 2 upregulation and modulates the high GLU-promoted PI3K/AKT1 pathway, RRM2 expression, and oxeiptosis. Scale bar: 10 µM. All data are presented as mean ± SD, n = 3. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Article Snippet: Moreover, Z-VAD-FMK (Z-VAD; HY-16658B, MCE, China) was used to inhibit pan-caspase activity, Necrostatin-1 (Nec-1; HY-15760, MCE, China) to inhibit necroptosis, and Hydroxyurea (HU; HY-B0313, MCE, China) to inhibit RRM2 enzymatic activity.

Techniques: Expressing, Phospho-proteomics, Staining

Journal: Cancers

Article Title: NSUN4 Suppresses Ferroptosis Through m 5 C-Dependent Stabilization of C-MYC and Activation of the PI3K/Akt Signaling Pathway in Cervical Cancer

doi: 10.3390/cancers18091392

Figure Lengend Snippet: NSUN4 is upregulated in cervical cancer and associated with poor patient prognosis. ( A ) Differential expression analysis of TCGA RNA-sequencing data showing that NSUN4 is significantly upregulated in cervical cancer tissues compared with normal tissues. ( B ) Kaplan–Meier survival curves demonstrating that patients with high NSUN4 expression exhibit significantly worse progression-free survival than those with low expression ( p < 0.05). ( C ) Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicating that NSUN4-associated genes are mainly involved in apoptosis, PI3K–Akt signaling, and oxidative phosphorylation pathways. ( D , E ) Validation of NSUN4 expression in paired cervical cancer and adjacent normal tissues by qRT-PCR and Western blot, confirming elevated NSUN4 levels at both mRNA and protein levels in tumor samples . The arrow indicates the specific NSUN4 band. ( F ) Representative NSUN4 IHC staining images of cervical cancer and matched adjacent normal tissues from a tissue microarray (TMA). ( G ) Analysis of IHC scores from a cohort of 30 cervical cancer patients, showing the comparison of NSUN4 expression between cervical cancer and matched adjacent normal tissues. Statistical analysis was performed using a paired Student’s t -test (*** p < 0.001).

Article Snippet: To assess the involvement of ferroptosis and the PI3K/AKT signaling pathway, cells were treated for 24 h with the apoptosis inhibitor Z-VAD-FMK (MedChemExpress, Monmouth Junction, NJ, USA), the necroptosis inhibitor Nec-1 (MedChemExpress, Monmouth Junction, NJ, USA), the ferroptosis inhibitors Ferrostatin-1 (MedChemExpress, Monmouth Junction, NJ, USA) and Liproxstatin-1 (MedChemExpress, Monmouth Junction, NJ, USA), or 3-Methyladenine (MedChemExpress, Monmouth Junction, NJ, USA), which was used in this study as an inhibitor of the PI3K pathway.

Techniques: Quantitative Proteomics, RNA Sequencing, Expressing, Phospho-proteomics, Biomarker Discovery, Quantitative RT-PCR, Western Blot, Immunohistochemistry, Microarray, Comparison

Journal: Cancers

Article Title: NSUN4 Suppresses Ferroptosis Through m 5 C-Dependent Stabilization of C-MYC and Activation of the PI3K/Akt Signaling Pathway in Cervical Cancer

doi: 10.3390/cancers18091392

Figure Lengend Snippet: NSUN4 promotes cervical cancer cell proliferation by suppressing ferroptosis. ( A ) KEGG pathway enrichment analysis of transcriptome sequencing data from NSUN4-overexpressing and control cells revealing a significant association with ferroptosis pathways. ( B ) Cell viability assays showing that ferroptosis inhibitors (Fer-1 and Lipro-1), but not apoptosis or necroptosis inhibitors (Z-VAD-FMK or Nec-1), rescue the proliferation defects induced by NSUN4 knockdown. ( C , D ) Western blot analysis demonstrating that NSUN4 depletion downregulates, whereas NSUN4 overexpression upregulates, ferroptosis-associated proteins SLC7A11, FTH1, and GPX4. ( E – G ) Quantification of intracellular GSH levels showing that NSUN4 overexpression increases, while NSUN4 knockdown decreases, GSH content; ferroptosis inhibition with Fer-1 or Lipro-1 restores GSH levels in NSUN4-deficient cells. Data are presented as mean ± SD. ns, not significant; * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: To assess the involvement of ferroptosis and the PI3K/AKT signaling pathway, cells were treated for 24 h with the apoptosis inhibitor Z-VAD-FMK (MedChemExpress, Monmouth Junction, NJ, USA), the necroptosis inhibitor Nec-1 (MedChemExpress, Monmouth Junction, NJ, USA), the ferroptosis inhibitors Ferrostatin-1 (MedChemExpress, Monmouth Junction, NJ, USA) and Liproxstatin-1 (MedChemExpress, Monmouth Junction, NJ, USA), or 3-Methyladenine (MedChemExpress, Monmouth Junction, NJ, USA), which was used in this study as an inhibitor of the PI3K pathway.

Techniques: Sequencing, Control, Knockdown, Western Blot, Over Expression, Inhibition