Journal: Non-coding RNA Research

Article Title: Exosomal miRNA-218–5p derived from low-passage dermal papilla cells modulates hair follicle growth and development

doi: 10.1016/j.ncrna.2026.01.004

Figure Lengend Snippet: Exosomes derived from low-passage DPCs regulated HFSC proliferation. (A) Indirect immunofluorescence showing ALPL and PCNA expression in low-passage (P1) and high-passage (P8) DPCs (scale bar = 50 μm). (B) RT-qPCR analysis of HF development-related gene expression in P1 and P8 DPCs (unpaired two-tailed t -test, n = 3). (C) TEM images of exosomes from P1 DPCs (DPC-Exos P1) and P8 DPCs (DPC-Exos P8). (D) NTA measurement of particle size of DPC-Exos P1 and DPC-Exos P8. (E) Western blot detection of exosome-specific proteins in DPC-Exos P1 and DPC-Exos P8. (F) CCK-8 assay evaluating HFSC proliferation after treatment with DPC-Exos from P1 and P8 (one-way ANOVA, n = 5). (G) Flow cytometry analysis of HFSC apoptosis after treatment with DPC-Exos from P1 and P8 (one-way ANOVA, n = 3). ∗ P < 0.05, ∗∗ P < 0.01.

Article Snippet: The Annexin V-FITC Apoptosis Detection Kit (Vazyme, China, Cat No. A214) was employed, and apoptosis rates were analyzed via flow cytometry using a FACSAria SORP instrument (Becton Dickinson, USA).

Techniques: Derivative Assay, Immunofluorescence, Expressing, Quantitative RT-PCR, Gene Expression, Two Tailed Test, Western Blot, CCK-8 Assay, Flow Cytometry

Journal: Molecular Therapy Oncology

Article Title: A comparative analysis of CD70-directed CAR-T cells for glioblastoma treatment demonstrates a superior efficacy of the ligand-based construct

doi: 10.1016/j.omton.2026.201134

Figure Lengend Snippet: In vitro assessment of the CD70-directed CAR-T cell anti-GB cytotoxicity (A) Measurement of secreted TNF-α and IFN-γ in the SN of GB/CAR-T cell co-cultures by ELISA. N = 3 biological replicates per group. For comparison between MCS and CD70 (upper bar plots), an unpaired two-tailed t test was used. For comparisons among constructs (bottom), a one-way ANOVA followed by a Holm-Šídák multiple comparisons test was used. (B) Measurement of tumor cell signal during co-culture with CAR-T cells on the Incucyte platform. N = 2 biological replicates per group. Every biological replicate is the mean of N = 5 technical replicates. Time point intervals = 45 min. A two-tailed Student’s t test was performed using the values of the last measured time point to determine statistical significance. For (A) and (B), data presented as mean (SD). ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001; n.s., not significant.

Article Snippet: The Incucyte Annexin-V Near Infrared Dye (#4768, Sartorius) was added at a final concentration of 1:200.

Techniques: In Vitro, Enzyme-linked Immunosorbent Assay, Comparison, Two Tailed Test, Construct, Co-Culture Assay

Journal: Molecular Therapy Oncology

Article Title: A comparative analysis of CD70-directed CAR-T cells for glioblastoma treatment demonstrates a superior efficacy of the ligand-based construct

doi: 10.1016/j.omton.2026.201134

Figure Lengend Snippet: Assessment of anti-CD70 CAR-T cell killing in naturally CD70 expressing cell lines (A) CD70 expression levels (blue histogram) on primary GB cell line MMKI by flow cytometry. Data gated on single live cells. An isotype control (red histogram) was used. (B) Quantification of activation marker CD137 after O/N co-culture of MMKI cells with CD70-targeting CAR-T cells by flow cytometry. N = 4 biological replicates per group. Data gated on single live CD3 + cells (NT) or single live CD3 + /tdTomato + cells (SFG, CD27z, LF28z, and LFBBz). Isotype control antibodies were used for gating. A one-way ANOVA followed by a Tukey’s multiple comparisons test was applied for significance. (C) Measurement of CD70 (blue histograms) on the surface of generated genetic knockout models by flow cytometry. An isotype control (red histogram) was used. Data gated on single live EGFP + cells. (D) Measurement of tumor cell signal during co-culture with CAR-T cells on the Incucyte platform. N = 2 biological replicates per group. Every biological replicate is the mean of N = 5 technical replicates. Time point intervals = 45 min. Statistical significance was assessed as in B). For (B) and (D), data are presented as mean (SD). ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001; n.s., not significant.

Article Snippet: The Incucyte Annexin-V Near Infrared Dye (#4768, Sartorius) was added at a final concentration of 1:200.

Techniques: Expressing, Flow Cytometry, Control, Activation Assay, Marker, Co-Culture Assay, Generated, Knock-Out

Journal: Redox Biology

Article Title: p300-mediated histone H3K18 lactylation promotes mitochondrial ROS accumulation via mitophagy inhibition to potentiate dopamine agonists efficacy in prolactinomas

doi: 10.1016/j.redox.2026.104077

Figure Lengend Snippet: Upregulation of p300 synergizes with DA to promote cell apoptosis by increasing mitochondrial ROS in pituitary tumor cells. (A-B) Cell Counting Kit-8 (CCK-8) assay was used to detect cell viability in MMQ and AtT-20 cells transfected with empty vector or p300 overexpression plasmid (OE-p300) treated with BRC (10 μM) for different durations (0, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48 h) (n = 3). (C-D) CCK-8 assay was used to detect cell viability in MMQ and AtT-20 cells (transfected with empty vector or OE-p300) treated with BRC (10 μM) or CAB (25 μM) for 48 h (n = 5). (E) AtT-20 cells (transfected with empty vector or OE-p300) were treated with BRC (10 μM) for 24 h, followed by bulk RNA sequencing and KEGG pathway enrichment analysis of differentially upregulated genes (n = 3). (F–I) Flow cytometry was used to detect mitochondrial ROS levels in MMQ and AtT-20 cells (transfected with empty vector or OE-p300) treated with BRC (10 μM) or CAB (25 μM) for 48 h. Flow cytometry was used to detect mitochondrial ROS levels in PA cells treated with BRC (10 μM), CAB (25 μM), N-(4-chloro-3-triffuoromethyl-phenyl)-2- ethoxy-benzamide (CTB, 50 μM), BRC (10 μM) + CTB (50 μM), or CAB (25 μM) + CTB (50 μM) for 48 h (n = 3). (J-L) Flow cytometry was used to detect cell apoptosis levels in MMQ and AtT-20 cells (transfected with empty vector or OE-p300) treated with BRC (10 μM) alone or combined with N-acetylcysteine (NAC, 5 mM) or glutathione (GSH, 2 mM) for 48 h (n = 3). (M) Schematic diagram of molecular structures of wild-type p300 and histone acetyltransferase (HAT) domain-mutated p300. (N–S) Flow cytometry was used to detect mitochondrial ROS levels and apoptosis levels in MMQ and AtT-20 cells (transfected with empty vector, wild-type p300 overexpression plasmid [OE-WT-p300], or HAT domain-mutated p300 overexpression plasmid [OE-Mut-p300]) treated with BRC (10 μM) for 48 h (n = 3). One-way ANOVA was used for comparison among multiple groups. Data are presented as the mean ± SD. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001.

Article Snippet: Cell apoptosis was investigated by using an Annexin V-FITC/PI apoptosis assay kit (Vazyme) according to the manufacturer's instructions.

Techniques: Cell Counting, CCK-8 Assay, Transfection, Plasmid Preparation, Over Expression, RNA Sequencing, Flow Cytometry, Comparison

Journal: Redox Biology

Article Title: p300-mediated histone H3K18 lactylation promotes mitochondrial ROS accumulation via mitophagy inhibition to potentiate dopamine agonists efficacy in prolactinomas

doi: 10.1016/j.redox.2026.104077

Figure Lengend Snippet: Upregulation of p300 synergizes with DA to elevate mitochondrial ROS levels via H3K18la-mediated transcription of Ndufs7 and Washc1 in pituitary tumor cells. (A-D) AtT-20 cells (transfected with empty vector or OE-p300) were treated with sodium lactate (5 mM) or BRC (10 μM) for 24 h, followed by bulk RNA sequencing. (A) Volcano plot showing the distribution of differentially expressed genes in the vector + sodium lactate group (Vec + L-Na) compared with the vector group (Vec). (B) Volcano plot showing the distribution of differentially expressed genes in the OE-p300+BRC group compared with the Vec + BRC group. (C) Venn diagram of the intersection of upregulated differentially expressed genes from groups A and B. (D) KEGG pathway enrichment of the 2273 genes obtained from the intersection in C (n = 3). (E) Peak plot showing H3K18la enrichment in genome-wide promoter regions of cells from the OE-p300+BRC group and Vec + BRC group in AtT-20 cells (transfected with empty vector or OE-p300) treated with BRC (10 μM) for 24 h. (F) Venn diagram of the intersection between the 2273 genes obtained from the intersection in C and the upregulated differentially expressed genes enriched by CUT&Tag using anti-H3K18la antibody in AtT-20 cells (transfected with OE-p300) treated with BRC (10 μM) for 24 h. (G) Venn diagram of the intersection between the 36 genes obtained from the intersection in F and the ROS-related gene set (KEGG: mmu05208). (H) Peak plot showing H3K18la enrichment in the NADH dehydrogenase [ubiquinone] Fe–S protein 7 (Ndufs7) promoter region in the Vec + BRC group and OE-p300+BRC group in AtT-20 cells. (I) Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) of H3K18la enrichment in the Ndufs7 promoter region in the Vec + BRC group, OE-p300+BRC group, and OE-p300+BRC + Gal group in AtT-20 cells (n = 3). AtT-20 cells in the vector group were treated with BRC (10 μM) or BRC (10 μM) + CTB (50 μM) for 48 h. AtT-20 cells in the OE-p300 group, OE-p300 with Ndufs7 knockdown group 1 (sh1+OE), and OE-p300 with Ndufs7 knockdown group 2 (sh2+OE) were treated with BRC (10 μM) for 48 h, followed by flow cytometry to detect mitochondrial ROS levels (J), hydrogen peroxide detection kit to measure intracellular hydrogen peroxide levels (K), and flow cytometry to detect cell apoptosis levels (L) (n = 3). (M) After AtT-20 cells in the vector group, OE-p300 group, OE-p300 with Ndufs7 knockdown group 1 (sh1+OE), and OE-p300 with Ndufs7 knockdown group 2 (sh2+OE) were treated with BRC (10 μM) for 36 h, electron leak was detected via high-resolution respirometry combined with fluorometry (n = 3). (N) AtT-20 cells (transfected with empty vector or OE-p300) were treated with BRC (10 μM) for 24 h, followed by bulk RNA sequencing and KEGG pathway enrichment analysis of differentially downregulated genes (n = 3). (O) TEM was used to observe mitochondrial morphological changes in AtT-20 cells (transfected with empty vector or OE-p300) treated with BRC (10 μM) for 24 h, the process indicated by the red arrows is mitophagy. (n = 3). (P) Venn diagram of the intersection between the 36 genes obtained from the intersection in F and the autophagy-related gene set (GO:0010506). (Q) Peak plot showing H3K18la enrichment in the WASH complex subunit 1 (Washc1) promoter region in the vector group and OE-p300+BRC group in AtT-20 cells. (R) ChIP-qPCR of H3K18la enrichment in the Washc1 promoter region in the Vec + BRC group, OE-p300+BRC group, and OE-p300+BRC + Gal group in AtT-20 cells (n = 3). AtT-20 cells in the vector group were treated with BRC (10 μM) or BRC (10 μM) + CTB (50 μM) for 48 h. AtT-20 cells in the OE-p300 group, OE-p300 with Washc1 knockdown group 1 (sh1+OE), and OE-p300 with Washc1 knockdown group 2 (sh2+OE) were treated with BRC (10 μM) for 48 h, followed by flow cytometry to detect mitochondrial ROS levels (S), hydrogen peroxide detection kit to measure intracellular hydrogen peroxide levels (T), and flow cytometry to detect cell apoptosis levels (U) (n = 3). (V) Schematic diagram showing that NDUFS7 increases mitochondrial ROS and WASH1 inhibits mitophagy, thereby inducing cell apoptosis. One-way ANOVA was used for comparison among multiple groups. Data are presented as the mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Article Snippet: Cell apoptosis was investigated by using an Annexin V-FITC/PI apoptosis assay kit (Vazyme) according to the manufacturer's instructions.

Techniques: Transfection, Plasmid Preparation, RNA Sequencing, Genome Wide, Chromatin Immunoprecipitation, Real-time Polymerase Chain Reaction, ChIP-qPCR, Knockdown, Flow Cytometry, Comparison

Journal: Redox Biology

Article Title: p300-mediated histone H3K18 lactylation promotes mitochondrial ROS accumulation via mitophagy inhibition to potentiate dopamine agonists efficacy in prolactinomas

doi: 10.1016/j.redox.2026.104077

Figure Lengend Snippet: WASH1 inhibits mitophagy by binding to the ubiquitin-associated (UBA) domain of p62 in pituitary tumor cells. (A) MMQ and AtT-20 cells in the vector group, OE-p300 group, OE-p300 with Washc1 knockdown group 1 (sh1+OE), and OE-p300 with Washc1 knockdown group 2 (sh2+OE) were treated with BRC (10 μM) for 48 h, followed by WB analysis to detect the expression of LC3BI/II, p62, translocase of outer mitochondrial membrane 20 (TOM20), translocase of inner mitochondrial membrane 23 (TIM23), and cytochrome c oxidase subunit IV (COX IV) (n = 3). (B) WASH1-Flag protein was overexpressed in AtT-20 cells with Washc1 knockout, and immunoprecipitation-mass spectrometry (IP-MS) was used to analyze potential interacting proteins of WASH1. (C) Mouse WASH1 protein and the UBA domain of p62 were subjected to molecular docking using the HDOCK server ( http://hdock.phys.hust.edu.cn/ ). Appropriate prediction models were selected, and docking results were analyzed using PyMOL (Version 3.1). (D) In MMQ and AtT-20 cells with p300 overexpression and Washc1 knockout, wild-type Washc1 (OE-WT-Flag) or mutant Washc1 (OE-Mut-Flag) was then overexpressed. Co-IP experiments were conducted using anti-Flag antibodies, and subsequent WB analysis was used to detect the expression of WASH1-Flag and p62 (n = 3). (E) MMQ and AtT-20 cells with p300 overexpression and Washc1 knockout in the vector group, OE-WT-Flag group, or OE-Mut-Flag group were treated with BRC (10 μM) for 48 h, followed by WB analysis to detect the expression of LC3BI/II, p62, TOM20, TIM23, and COX IV (n = 3). (F) MMQ and AtT-20 cells with p300 overexpression and Washc1 knockout in the vector group, OE-WT-Flag group, or OE-Mut-Flag group were treated with BRC (10 μM) for 24 h, followed by mt-Keima ratiometric analysis to quantify mitophagy levels (n = 4). (G) MMQ and AtT-20 cells in the vector group, OE-WT-Flag group, or OE-Mut-Flag group were treated with BRC (10 μM) for 24 h, and confocal fluorescence microscopy was used to observe the co-localization of mitochondria (TOM20) and lysosomes (lysosome-associated membrane protein 1, LAMP1) (n = 3). (H–I) MMQ and AtT-20 cells with p300 overexpression and Washc1 knockout in the vector group, OE-WT-Flag group, or OE-Mut-Flag group were treated with BRC (10 μM) for 48 h, followed by flow cytometry to detect mitochondrial ROS and cell apoptosis levels (n = 3). One-way ANOVA was used for comparison among multiple groups. Data are presented as the mean ± SD. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001.

Article Snippet: Cell apoptosis was investigated by using an Annexin V-FITC/PI apoptosis assay kit (Vazyme) according to the manufacturer's instructions.

Techniques: Binding Assay, Ubiquitin Proteomics, Plasmid Preparation, Knockdown, Expressing, Membrane, Knock-Out, Immunoprecipitation, Mass Spectrometry, Protein-Protein interactions, Over Expression, Mutagenesis, Co-Immunoprecipitation Assay, Fluorescence, Microscopy, Flow Cytometry, Comparison

Journal: Redox Biology

Article Title: p300-mediated histone H3K18 lactylation promotes mitochondrial ROS accumulation via mitophagy inhibition to potentiate dopamine agonists efficacy in prolactinomas

doi: 10.1016/j.redox.2026.104077

Figure Lengend Snippet: p300 activator YF-2 combined with DA exerts a synergistic anti-pituitary adenoma effect. (A) CCK-8 assay was used to detect cell viability in MMQ and AtT-20 cells treated with YF-2 at different concentrations (0, 1.25, 2.5, 5, 10, 20 μM) for 48 h, after which dose-response curves were fitted based on cell viability and half-maximal inhibitory concentration (IC50) was calculated (n = 4). (B–C) Synergy indices for MMQ cells treated with combinations of YF-2 (0, 2.5, 5, 10 μM) and either BRC (0, 5, 10, 20 μM) or CAB (0, 12.5, 25, 50 μM) for 48 h were calculated using the ZIP synergy scoring model via SynergyFinder Version 3.0 ( https://synergyfinder.fimm.fi ), with a synergy index >10 indicating synergy and a white dashed box denoting the concentration range with the highest potential for maximum synergy (n = 4). (D-G) MMQ and AtT-20 cells were treated with BRC (10 μM), CAB (25 μM), YF-2 (5 μM), BRC (10 μM) + YF-2 (5 μM), or CAB (25 μM) + YF-2 (5 μM) for 48 h. (D, F) CCK-8 assay was used to detect cell viability in MMQ and AtT-20 cells (n = 5). (E) PRL concentration in the supernatant of MMQ cells was detected using a PRL ELISA kit (n = 4). (G) ACTH concentration in the supernatant of AtT-20 cells was detected using an ACTH ELISA kit (n = 4). (H–I) Nude mice were subcutaneously implanted with MMQ and AtT-20 cells, followed by i.p. injection of PBS, BRC (10 mg/kg/d), YF-2 (20 mg/kg/d), or BRC (10 mg/kg/d) + YF-2 (20 mg/kg/d) for 2 weeks. Representative images of subcutaneous xenograft tumors (left), average volume of excised tumors (middle), and average weight of excised tumors (right) (n = 6). (J-K) Quantification of IF staining for Ki-67 expression in tumor tissue sections (n = 6). (L-O) MMQ and AtT-20 cells in the vector group were treated with BRC (10 μM), YF-2 (5 μM) or BRC (10 μM) + YF-2 (5 μM) for 48 h. MMQ and AtT-20 cells transfected with wild-type p300 overexpression plasmid (OE-WT), or HAT domain-mutated p300 overexpression plasmid (OE-Mut) treated with BRC (10 μM) + YF-2 (5 μM) for 48 h, followed by flow cytometry to detect mitochondrial ROS and cell apoptosis levels (n = 3). One-way ANOVA was used for comparison among multiple groups. Data are presented as the mean ± SD. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001.

Article Snippet: Cell apoptosis was investigated by using an Annexin V-FITC/PI apoptosis assay kit (Vazyme) according to the manufacturer's instructions.

Techniques: CCK-8 Assay, Concentration Assay, Enzyme-linked Immunosorbent Assay, Injection, Staining, Expressing, Plasmid Preparation, Transfection, Over Expression, Flow Cytometry, Comparison

Journal: Advances in Radiation Oncology

Article Title: Kupffer Cell-Derived Interleukin-6 Aggravates Radiation-Induced Liver Disease by Activating Hepatocyte STAT3 to Promote Ccng1 Transcription

doi: 10.1016/j.adro.2026.102003

Figure Lengend Snippet: Blockade of classical IL-6 signaling alleviates radiation-induced liver disease (RILD) in rats. (A) Quantitative enzyme-linked immunosorbent assay (ELISA) analysis of interleukin (IL)-6 protein concentrations in peripheral serum and liver homogenates from Ctrl and irradiation (IR) rats (n = 5). (B) Quantitative ELISA analysis of serum liver enzymes in Ctrl rats or IR rats treated with placebo, anti-IL-6, or sgp130Fc (n = 5). (C) Hematoxylin–eosin (H&E) staining of rat livers. (D) F4/80 staining (red) showing Kupffer cell infiltration in rat livers. (E) Myeloperoxidase (MPO) staining (red) revealed neutrophil infiltration in the rat liver. (F) Costaining of CD31 (red), HNF4α (blue), and TUNEL (green) in rat livers. Student’s t test or analysis of variance (ANOVA); ⁎⁎⁎ , P < .001; ns, nonsignificant.

Article Snippet: TUNEL staining was performed using a TUNEL BrightGreen Apoptosis Detection Kit (Vazyme, #A112-03) according to the manufacturer's instructions.

Techniques: Enzyme-linked Immunosorbent Assay, Irradiation, Staining, TUNEL Assay

Journal: Advances in Radiation Oncology

Article Title: Kupffer Cell-Derived Interleukin-6 Aggravates Radiation-Induced Liver Disease by Activating Hepatocyte STAT3 to Promote Ccng1 Transcription

doi: 10.1016/j.adro.2026.102003

Figure Lengend Snippet: Role of the JAK–STAT signaling pathway in hepatocytes during radiation-induced liver disease (RILD). (A) Volcano plot of differential gene expression analysis in hepatocytes after irradiation (IR). Red and blue indicate upregulated and downregulated genes, respectively. The dotted horizontal line represents a P value of 0.05. The dotted vertical lines represent a log2-fold change of 1.5 or −1.5. (Right) Bubble chart depicting the top 5 Kyoto Encyclopedia of Genes and Genomes (KEGG)-enriched pathways corresponding to down/upregulated genes in hepatocytes after IR (screening the pathways and sorting them from large to small according to the −log 10 P value). (B) Western blot analysis showing p-STAT3 and GAPDH expression in primary hepatocytes isolated from Ctrl rats or IR rats treated with placebo, anti-interleukin (IL)-6, or sgp130Fc (n = 5). (C) Western blot analysis showing p-STAT3 and GAPDH expression in primary hepatocytes isolated from IR rats treated with placebo, ruxolitinib (RUX), or tofacitinib (TOF) (n = 5). (D) Quantitative enzyme-linked immunosorbent assay (ELISA) analysis of serum liver enzymes in IR rats treated with placebo, RUX, or TOF (n = 5). (E) Hematoxylin–eosin (H&E) staining of the livers of IR rats treated with placebo, RUX, or TOF (n = 5). (F) Costaining of HNF4α (red) and TUNEL (green) in the livers of IR rats treated with placebo, RUX, or TOF (n = 5). (G) Overlap of p-STAT3-binding genes identified using ChIP-Seq with upregulated genes ( P < .05 and log2-fold change > 2) in hepatocytes identified using scRNA-seq. (H) Violin plots showing the expression levels of overlapping genes identified using scRNA-seq. (I) qRT‒PCR analysis of overlapping genes in isolated primary hepatocytes from IR rats treated with placebo, RUX, or TOF (n = 5). Analysis of variance (ANOVA); *, P < .05; ⁎⁎ , P < .01; ⁎⁎⁎ , P < .001; ns, nonsignificant.

Article Snippet: TUNEL staining was performed using a TUNEL BrightGreen Apoptosis Detection Kit (Vazyme, #A112-03) according to the manufacturer's instructions.

Techniques: Gene Expression, Irradiation, Western Blot, Expressing, Isolation, Enzyme-linked Immunosorbent Assay, Staining, TUNEL Assay, Binding Assay, ChIP-sequencing

Journal: Advances in Radiation Oncology

Article Title: Kupffer Cell-Derived Interleukin-6 Aggravates Radiation-Induced Liver Disease by Activating Hepatocyte STAT3 to Promote Ccng1 Transcription

doi: 10.1016/j.adro.2026.102003

Figure Lengend Snippet: Schematic of the Kuppfer cell (KC)-hepatocyte crosstalk mechanism in RILD. Irradiation (IR) stimulates KCs to secrete IL-6, which binds to the IL-6R/gp130 complex on hepatocytes to activate JAK; phosphorylated JAK induces STAT3 phosphorylation, and nuclear-translocated p-STAT3 binds to the Ccng1 promoter to promote its transcription; CCNG1 then regulates MDM2 to mediate ubiquitination-dependent TP53 proteolysis, ultimately enhancing hepatocyte apoptosis and driving radiation-induced liver disease (RILD) progression.

Article Snippet: TUNEL staining was performed using a TUNEL BrightGreen Apoptosis Detection Kit (Vazyme, #A112-03) according to the manufacturer's instructions.

Techniques: Irradiation, Phospho-proteomics, Ubiquitin Proteomics

Journal: Anti-Cancer Drugs

Article Title: EP4 influences bortezomib resistance in multiple myeloma by modulating endoplasmic reticulum stress via the phosphatidylinositol 3-kinase/protein kinase B pathway

doi: 10.1097/CAD.0000000000001792

Figure Lengend Snippet: EP4 overexpression suppresses proliferation and migration while enhancing apoptosis in multiple myeloma cells. (a) Validation of EP4 overexpression in NCI-H929 and RPMI 8226 cells by qRT-PCR and Western blot. (*** P < 0.001, NC: control group; EP4-OE: EP4 overexpression group). (b–d) Effects of EP4 overexpression on cell viability, proliferation, and apoptosis. (b) CCK-8 assay, (c) EdU staining, and (d) Annexin V-PI staining of apoptotic events. (e) GSEA analysis using the high and low- EP4 expression groups in GSE24080 dataset, showing correlation with endoplasmic reticulum membrane protein with high- EP4 expressing group. (f) Western blot analysis of GRP78 expression in control and EP4-overexpressing cells. (g, h) Transwell assays for cell migration and invasion in control and EP4-overexpressing cells. (** P < 0.01, *** P < 0.001). CCK-8, Cell Counting Kit-8; GSEA, gene set enrichment analysis; qRT-PCR, quantitative reverse transcription-PCR.

Article Snippet: The Annexin V-FITC/PI apoptosis kit was acquired from Hangzhou Lianke Biotechnology Co. (Hangzhou, Zhejiang, China).

Techniques: Over Expression, Migration, Biomarker Discovery, Quantitative RT-PCR, Western Blot, Control, CCK-8 Assay, Staining, Expressing, Membrane, Cell Counting, Reverse Transcription

Journal: Anti-Cancer Drugs

Article Title: EP4 influences bortezomib resistance in multiple myeloma by modulating endoplasmic reticulum stress via the phosphatidylinositol 3-kinase/protein kinase B pathway

doi: 10.1097/CAD.0000000000001792

Figure Lengend Snippet: EP4 overexpression enhances bortezomib sensitivity in resistant multiple myeloma cells. (a–c) Effects of EP4 overexpression combined with bortezomib treatment on (a) cell viability, (b) proliferation, and (c) apoptosis in OPM-2/BTZ and KMS-11/BTZ cells. (** P < 0.01, *** P < 0.001). (d, e) Western blot analysis of (d) GRP78 expression and (e) PI3K/AKT pathway activation in EP4-overexpressing resistant cells. All BTZ groups were treated with 10 nM bortezomib for 48 h. BTZ, bortezomib; PI3K/AKT, phosphatidylinositol 3-kinase/protein kinase B.

Article Snippet: The Annexin V-FITC/PI apoptosis kit was acquired from Hangzhou Lianke Biotechnology Co. (Hangzhou, Zhejiang, China).

Techniques: Over Expression, Western Blot, Expressing, Activation Assay

Journal: Anti-Cancer Drugs

Article Title: EP4 influences bortezomib resistance in multiple myeloma by modulating endoplasmic reticulum stress via the phosphatidylinositol 3-kinase/protein kinase B pathway

doi: 10.1097/CAD.0000000000001792

Figure Lengend Snippet: EP4 modulates bortezomib resistance through AKT-regulated endoplasmic reticulum stress. (a–c) Effects of EP4 overexpression, AKT agonist SC79, and ER stress inducer Thapsigargin on (a) cell viability, (b) apoptosis, and (c) GRP78 expression in OPM-2/BTZ and KMS-11/BTZ cells. All groups of cells were treated with 10 nM bortezomib for 48 h. (*** P < 0.001 vs. EP4-NC group, ### P < 0.001 vs. EP4-OE group, ^^^ P < 0.001 vs. EP4-OE+SC79 group). AKT, protein kinase B; ER, endoplasmic reticulum.

Article Snippet: The Annexin V-FITC/PI apoptosis kit was acquired from Hangzhou Lianke Biotechnology Co. (Hangzhou, Zhejiang, China).

Techniques: Over Expression, Expressing

Journal: Anti-Cancer Drugs

Article Title: EP4 influences bortezomib resistance in multiple myeloma by modulating endoplasmic reticulum stress via the phosphatidylinositol 3-kinase/protein kinase B pathway

doi: 10.1097/CAD.0000000000001792

Figure Lengend Snippet: Schematic illustration of EP4-mediated regulation of bortezomib resistance in multiple myeloma. EP4 expression decreases in bortezomib-resistant cells. EP4 overexpression restores sensitivity by inhibiting PI3K/AKT signaling, increasing ER stress, and promoting apoptosis. This mechanism suggests EP4 as a potential therapeutic target for overcoming bortezomib resistance. PI3K/AKT, phosphatidylinositol 3-kinase/protein kinase B.

Article Snippet: The Annexin V-FITC/PI apoptosis kit was acquired from Hangzhou Lianke Biotechnology Co. (Hangzhou, Zhejiang, China).

Techniques: Expressing, Over Expression