Journal: Redox Biology

Article Title: Fenofibrate attenuates the adverse effects of radiation on endothelial cells through modulation of ROS-NO signalling and inflammation

doi: 10.1016/j.redox.2025.103994

Figure Lengend Snippet: Analysis of cytokines, interleukins and endothelial mesenchymal transition markers. qPCR analysis of inflammation markers 2d (A) and 7d (B), inflammatory regulators 2d (E) and 7d (F) and EndMT markers 2d (G) and 7d (H) were performed in irradiated HCAECs with and without fenofibrate (Feno). The release of different cytokines including GM-CSF, MCP-1 and IL-6 which were quantified using flow cytometry after 2d (C) and 7d (D). The error bars represent the standard deviation (±SD) (Two-way ANOVA, Tukey's multiple comparisons test; ∗ p ≤ 0.05; ∗∗ p ≤ 0.01; ∗∗∗p ≤ 0.001; ∗∗∗∗ p ≤ 0.0001; n = 3).

Article Snippet: Extracellular release of inflammatory cytokines (e.g., M-CSF, Granzyme B, IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17A, IL-21, MCP-1 (CCL2), Perforin and TNF-α) in cell culture supernatants were quantitatively measured based on a fluorescent bead-based system using MACSPlex Cytokine Kits (#130-125-800; Miltenyi Biotec, Germany) according to the manufacturer's protocol.

Techniques: Irradiation, Flow Cytometry, Standard Deviation

Journal: Redox Biology

Article Title: Fenofibrate attenuates the adverse effects of radiation on endothelial cells through modulation of ROS-NO signalling and inflammation

doi: 10.1016/j.redox.2025.103994

Figure Lengend Snippet: Proposed mechanism of action of fenofibrate in irradiated HCAECs in-vitro . Irradiation reduced NO signalling via inactivation of the PI3K–AKT–eNOS pathway, whereas fenofibrate reactivated this pathway and restored NO production (A). Consistent with this, irradiation increased ROS generation, NOX activity, MDA levels, and 3-NT levels, while fenofibrate mitigated this effect (B). Irradiation also triggered an inflammatory response, which was counteracted by fenofibrate (C). The released cytokines contribute to inflammation, changes in cytoskeleton organisation and initiation of EndMT, and fenofibrate effectively attenuated the processes (D). Alterations in the pathways described above play a crucial role in the remodelling of vascular endothelial cells involved in the initiation and progression of atherosclerosis. Fenofibrate acts to reduce or restore the effects of irradiation on these pathways (E–F). Solid lines indicate correlations validated in this study, while dashed lines indicate unvalidated correlations.

Article Snippet: Extracellular release of inflammatory cytokines (e.g., M-CSF, Granzyme B, IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17A, IL-21, MCP-1 (CCL2), Perforin and TNF-α) in cell culture supernatants were quantitatively measured based on a fluorescent bead-based system using MACSPlex Cytokine Kits (#130-125-800; Miltenyi Biotec, Germany) according to the manufacturer's protocol.

Techniques: Irradiation, In Vitro, Activity Assay

Journal: Scientific Reports

Article Title: IL-22 attenuates MAFLD progression by modulating oxidative stress and ferroptosis

doi: 10.1038/s41598-025-28718-8

Figure Lengend Snippet: Effect of IL-22 on liver appearance, body weight, and liver weight in CDAHFD-fed mice. (A) The scheme of the experimental study design. (B) Liver image. (C) Changes in mice body weight over the feeding period. (D) Measurement of liver weight. (E) The liver-to-body weight ratio. ( n = 8 for all). # p < 0.05, ## p < 0.005, and ### p < 0.001 vs. the Control group. * p < 0.05, ** p < 0.005, and *** p < 0.001 vs. the CDAHFD group.Abbreviation: CDAHFD, choline-deficient, L-amino acid-defined, high-fat diet.

Article Snippet: IL-22 and ML385 were purchased from Med Chem Express (USA).

Techniques: Control

Journal: Scientific Reports

Article Title: IL-22 attenuates MAFLD progression by modulating oxidative stress and ferroptosis

doi: 10.1038/s41598-025-28718-8

Figure Lengend Snippet: IL-22 reduced hepatic lipid accumulation in the CDAHFD mice. (A) Oil Red O staining of liver tissues. (Scale bar: 100 μm; original magnification: × 200) (B) HE staining of liver tissues. (Scale bar: 100 μm; original magnification: × 200) ( C ) TG levels; ( D ) TC levels; (E) LDL-C levels; (F) HDL-C levels; (G) Serum ALT content; (H) Serum AST content. ( n = 8 for panels C to H). (I) Measurement of Oil Red O-stained area; (J) Evaluation of MAFLD activity score. ( n = 3 for panels I and J). # p < 0.05, ## p < 0.005, and ### p < 0.001 vs. the Control group. * p < 0.05, ** p < 0.005, and *** p < 0.001 vs. the CDAHFD group. Abbreviation: ALT, alanine aminotransferase; AST, aspartate aminotransferase; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; MAFLD, Metabolic-associated fatty liver disease.

Article Snippet: IL-22 and ML385 were purchased from Med Chem Express (USA).

Techniques: Staining, Activity Assay, Control

Journal: Scientific Reports

Article Title: IL-22 attenuates MAFLD progression by modulating oxidative stress and ferroptosis

doi: 10.1038/s41598-025-28718-8

Figure Lengend Snippet: Mitigation of hepatic damage and fibrosis by IL-22 treatment in CDAHFD-induced mice. (A) MASSON staining of liver sections. (Scale bar: 100 μm; original magnification: × 200) (B) IHC staining of liver sections for α-SMA. (Scale bar: 100 μm; original magnification: × 100) (C) Area of liver fibrous expression; (D) Areas of α-SMA positive expression. ( E) α-SMA protein expression was determined by western blotting. (F) Relative mRNA level of α-SMA; (G) Relative protein expression of α-SMA. ( n = 3 for panels C, D, F and G). (H) The level of hyp; ( I ) Serum IL-6 level; ( J ) Serum IL-1β level; ( K ) Serum TNF-α level. ( n = 8 for panels H to K). # p < 0.05, ## p < 0.005, and ### p < 0.001 vs. the Control group. * p < 0.05, ** p < 0.005, and *** p < 0.001 vs. the CDAHFD group. Abbreviation: IHC, Immunohistochemistry; α-SMA, alpha Smooth Muscle Actin; hyp, hydroxyproline.

Article Snippet: IL-22 and ML385 were purchased from Med Chem Express (USA).

Techniques: Staining, Immunohistochemistry, Expressing, Western Blot, Control

Journal: Scientific Reports

Article Title: IL-22 attenuates MAFLD progression by modulating oxidative stress and ferroptosis

doi: 10.1038/s41598-025-28718-8

Figure Lengend Snippet: IL-22 intervention mitigated oxidative stress and ferroptosis in CDAHFD-fed mice liver. ( A ) Representative pictures of DHE staining. (Scale bar: 100 μm; original magnification: × 200). ( B ) Measurement of hepatic SOD content. ( C ) Measurement of hepatic MDA content. ( D ) Measurement of hepatic GSH content. ( E ) Measurement of hepatic Fe2 + content. ( n = 8 for panels B to E). ( F ) Mitochondria by transmission electron microscope. (The red arrows indicate the ruptured outer membrane. Scale bar = 1 μm.) # p < 0.05, ## p < 0.005, and ### p < 0.001 vs. the Control group. * p < 0.05, ** p < 0.005, and *** p < 0.001 vs. the CDAHFD group. Abbreviation: DHE, Dihydroethidium; SOD, superoxide dismutase; MDA, malondialdehyde; GSH, glutathion.

Article Snippet: IL-22 and ML385 were purchased from Med Chem Express (USA).

Techniques: Staining, Transmission Assay, Microscopy, Membrane, Control

Journal: Scientific Reports

Article Title: IL-22 attenuates MAFLD progression by modulating oxidative stress and ferroptosis

doi: 10.1038/s41598-025-28718-8

Figure Lengend Snippet: IL-22 activated the Nrf2/Gpx4/Slc7a11 signal pathway to improve oxidative stress and ferroptosis. (A-E) mRNA expression of Nrf2, Keap1, Hmox1, Gpx4, and Slc7a11 in liver tissues. ( n = 3). (F) Nrf2, Keap1, Hmox1, Gpx4, and Slc7a11 protein expressions were detected by western blotting. ( G ) Representative pictures of liver Nrf2 immunofluorescence staining. (Scale bar: 50 μm; original magnification: × 400). # p < 0.05, ## p < 0.005, and ### p < 0.001 vs. the Control group. * p < 0.05, ** p < 0.005, and *** p < 0.001 vs. the CDAHFD group. Abbreviation: Keap1, Kelch-like ECH-associated protein 1; Nrf2, Nuclear factor erythroid 2-related factor 2; Hmox1, Heme Oxygenase-1; Gpx4, glutathione peroxidase 4; Slc7a11, Solute Carrier Family 7 Member 11.

Article Snippet: IL-22 and ML385 were purchased from Med Chem Express (USA).

Techniques: Expressing, Western Blot, Immunofluorescence, Staining, Control

Journal: Scientific Reports

Article Title: IL-22 attenuates MAFLD progression by modulating oxidative stress and ferroptosis

doi: 10.1038/s41598-025-28718-8

Figure Lengend Snippet: IL-22 intervention mitigated lipid deposition in FFA-induced AML-12 cells. ( A ) Oil Red O staining (Scale bar: 50 μm; original magnification: × 400). ( B ) TG level. ( n = 3) ( C ) Quantification of Oil Red O-stained area. ( n = 3). # p < 0.05, ## p < 0.005, and ### p < 0.001 vs. the Control group. * p < 0.05, ** p < 0.005, and *** p < 0.001 vs. the Model group.

Article Snippet: IL-22 and ML385 were purchased from Med Chem Express (USA).

Techniques: Staining, Control

Journal: Scientific Reports

Article Title: IL-22 attenuates MAFLD progression by modulating oxidative stress and ferroptosis

doi: 10.1038/s41598-025-28718-8

Figure Lengend Snippet: IL-22 activated the Nrf2/Gpx4/Slc7a11 signal pathway in AML-12 cells. ( A ) Measurements of SOD content. ( B ) Measurements of MDA content. ( C ) Measurements of GSH content. (D) Keap1, Nrf2, and Hmox1 protein expressions were detected by western blotting. ( E ) mRNA expression of Keap1, Nrf2, and Hmox1. (F) Gpx4 and Slc7a11 protein expressions were detected by western blotting. (G) mRNA expression of Gpx4 and Slc7a1. ( n = 3 for panels A, B, C, E, G). # p < 0.05, ## p < 0.005, and ### p < 0.001 vs. the Control group. * p < 0.05, ** p < 0.005, and *** p < 0.001 vs. the Model group. Abbreviation: SOD, superoxide dismutase; MDA, malondialdehyde; GSH, glutathione; Keap1, Kelch-like ECH-associated protein 1; Nrf2, Nuclear factor erythroid 2-related factor 2; Hmox1, Heme Oxygenase-1 Gpx4, glutathione peroxidase 4; Slc7a11, Solute Carrier Family 7 Member 11.

Article Snippet: IL-22 and ML385 were purchased from Med Chem Express (USA).

Techniques: Western Blot, Expressing, Control

Journal: Scientific Reports

Article Title: IL-22 attenuates MAFLD progression by modulating oxidative stress and ferroptosis

doi: 10.1038/s41598-025-28718-8

Figure Lengend Snippet: ML385 weakened the antioxidant effects of IL-22 in AML-12 cells. ( A ) Oil Red O staining (Scale bar: 50 μm; original magnification: × 400). ( B ) Quantification of Oil Red O-stained area. ( C ) TG level. (D) Measurements of SOD content. ( E ) Measurements of MDA content. ( F ) Measurements of GSH content. (G) mRNA expression of Nrf2, Hmox1, Gpx4, Slc7a11. ( n = 3 for panels B to G) # p < 0.05, ## p < 0.005, and ### p < 0.001 vs. the Control group. * p < 0.05, ** p < 0.005, and *** p < 0.001 vs. the Model group. & p < 0.05, && p < 0.005, and &&& p < 0.001 vs. the IL-22-H group. Abbreviation: TG, triglyceride; SOD, superoxide dismutase; MDA, malondialdehyde; GSH, glutathione; Nrf2, Nuclear factor erythroid 2-related factor 2; Hmox1, Heme Oxygenase-1 Gpx4, glutathione peroxidase 4; Slc7a11, Solute Carrier Family 7 Member 11.

Article Snippet: IL-22 and ML385 were purchased from Med Chem Express (USA).

Techniques: Staining, Expressing, Control

Journal: Scientific Reports

Article Title: IL-22 attenuates MAFLD progression by modulating oxidative stress and ferroptosis

doi: 10.1038/s41598-025-28718-8

Figure Lengend Snippet: A schematic model illustrating that IL-22 alleviates MAFLD by activating the Nrf2/Gpx4/Slc7a11 axis to suppress oxidative stress and ferroptosis. Arrows denote activating effects; blunted lines denote inhibitory effects.

Article Snippet: IL-22 and ML385 were purchased from Med Chem Express (USA).

Techniques: