Journal: Redox Biology

Article Title: GDF15 nanotherapy ameliorates NLRP3-associated redox imbalance and cardiac injury in sepsis

doi: 10.1016/j.redox.2025.103897

Figure Lengend Snippet: Multifaceted validation of GDF15 changes in serum from SICM patients and their clinical associations. (A) GDF15 levels were quantified using the Luminex platform. (B) A volcano plot illustrated the gene expression distribution of GDF15 among differentially expressed genes (DEGs) in whole blood. (C) A heatmap displayed the expression profiles of GDF15 and inflammatory cytokines. (D) Serum GDF15 levels in patients. (E) Pearson correlation analysis demonstrated the association between GDF15 and SOFA score, as well as EF. (F) ROC curves were plotted to assess the diagnostic accuracy of GDF15 and SOFA score in identifying SICM. (G) Multivariate logistic regression analysis was performed to identify independent risk factors for the development of SICM in septic patients. ∗p < 0.05 indicates significant differences; ns: no significant differences.

Article Snippet: Enzyme-linked immunosorbent assays (ELISA) were conducted using commercial kits to quantify serum levels of human GDF15 (Proteintech, Cat# KE00108), mouse GDF15 (Proteintech, Cat# KE10082), and mouse IL-6 (MULTI SCIENCES, Cat# EK206).

Techniques: Biomarker Discovery, Luminex, Gene Expression, Expressing, Diagnostic Assay

Journal: Redox Biology

Article Title: GDF15 nanotherapy ameliorates NLRP3-associated redox imbalance and cardiac injury in sepsis

doi: 10.1016/j.redox.2025.103897

Figure Lengend Snippet: Upregulation of GDF15 in the SICM model. (A) A schematic workflow for the establishment of the SICM model in C57BL/6J mice via intraperitoneal injection of LPS or saline. (B) Cardiac contractile function parameters, including EF and FS. (C) Serum levels of GDF15 and IL-6. (D) Histopathological analysis of heart tissue, H&E staining (left) and immunohistochemical staining for Ly6G and CD68 (right). Black arrows indicate inflammatory cell infiltration; scale bar: 50 μm. (E) Western blot analysis of GDF15 protein expression in heart tissue. n = 4. (F) qPCR analysis of Gdf15 , Bnp , Il-1β , Il-6 , Icam-1 and Vcam- 1 mRNA levels in heart tissue. (G) Identification of GDF15-positive cells in single-cell RNA-sequencing dataset ( GSE190856 ). (H) qPCR analysis of Gdf15 and Il-1β , Il-6, Nos2, Ptgs2 mRNA expression in BMDM after LPS stimulation. ∗p < 0.05 indicates significant differences; n = 6 per group.

Article Snippet: Enzyme-linked immunosorbent assays (ELISA) were conducted using commercial kits to quantify serum levels of human GDF15 (Proteintech, Cat# KE00108), mouse GDF15 (Proteintech, Cat# KE10082), and mouse IL-6 (MULTI SCIENCES, Cat# EK206).

Techniques: Injection, Saline, Staining, Immunohistochemical staining, Western Blot, Expressing, RNA Sequencing

Journal: Redox Biology

Article Title: GDF15 nanotherapy ameliorates NLRP3-associated redox imbalance and cardiac injury in sepsis

doi: 10.1016/j.redox.2025.103897

Figure Lengend Snippet: GDF15 deficiency exacerbates LPS-induced SICM in mice. (A) Schematic workflow for the establishment of the SICM model in Gdf15 −/− mice. Gdf15 −/− mice were intraperitoneally injected with LPS or saline to induce SICM, with tissue samples collected 24 h post-injection for further analysis. (B) Echocardiographic assessment of EF and FS. (C) H&E staining of heart tissue, black arrows indicate inflammatory cell infiltration. scale bar: 50 μm. (D) CD68 immunofluorescence staining of heart tissue. Blue staining highlights nuclei, red staining identifies CD68 + macrophages; scale bar: 20 μm. (E) qPCR analysis of mRNA expression levels of Bnp , Il-1β, Il-6, and Mcp-1 in heart tissue. n = 6 per group.

Article Snippet: Enzyme-linked immunosorbent assays (ELISA) were conducted using commercial kits to quantify serum levels of human GDF15 (Proteintech, Cat# KE00108), mouse GDF15 (Proteintech, Cat# KE10082), and mouse IL-6 (MULTI SCIENCES, Cat# EK206).

Techniques: Injection, Saline, Staining, Immunofluorescence, Expressing

Journal: Redox Biology

Article Title: GDF15 nanotherapy ameliorates NLRP3-associated redox imbalance and cardiac injury in sepsis

doi: 10.1016/j.redox.2025.103897

Figure Lengend Snippet: MGP exerts anti-inflammatory effects via the MYPT1/AKT/YBX-1 signaling pathway. (A) IP-MS of BMDM to identify the interaction with GDF15. MYPT1 is marked in red. (B) Z-DOCK predicted the interaction domain between GDF15 and MYPT1. Pink represents GDF15, green represents MYPT1, and the boxed region indicates the binding domain. (C) Co-IP combined with Western blot analysis of GDF-15 and MYPT1 binding in macrophages after LPS treatment. (n = 3). (D) Immunofluorescence detection of co-localization between GDF15 (green) and MYPT1 (red), with blue staining for nuclei. Scale bar: 20 μm. (E) Protein expression levels of p -YBX-1, YBX-1, and p -AKT, AKT in BMDM after LPS and/or MGP treatment, with gray-scale intensity analysis of relative expression differences. (F) Representative immunofluorescence images of YBX-1 staining in BMDM after LPS and/or MGP treatment. Blue staining highlights nuclei, and red staining identifies YBX-1. Scale bar: 20 μm ∗p < 0.05, significantly different from control group. #p < 0.05, significantly different from LPS group. n = 6 per group.

Article Snippet: Enzyme-linked immunosorbent assays (ELISA) were conducted using commercial kits to quantify serum levels of human GDF15 (Proteintech, Cat# KE00108), mouse GDF15 (Proteintech, Cat# KE10082), and mouse IL-6 (MULTI SCIENCES, Cat# EK206).

Techniques: Protein-Protein interactions, Binding Assay, Co-Immunoprecipitation Assay, Western Blot, Immunofluorescence, Staining, Expressing, Control

Journal: Redox Biology

Article Title: GDF15 nanotherapy ameliorates NLRP3-associated redox imbalance and cardiac injury in sepsis

doi: 10.1016/j.redox.2025.103897

Figure Lengend Snippet: YBX-1 mediates GDF15-mediated transcriptional regulation of the NLRP3 pathway. (A) qPCR analysis of mRNA expression levels of Nlrp3, Asc , and Il-1β in LPS-stimulated BMDM after Si- Ybx-1 . (B) Western blot analysis of protein expression levels of NLRP3 and IL-1β in LPS-stimulated BMDM after YBX-1 knockdown. (C) qPCR analysis of mRNA expression levels of Nlrp3 and Il-1β in LPS and MGP-treated BMDM after YBX-1 knockdown. (D) Schematic diagram of the luciferase reporter plasmid for the Nlrp3 promoter. (E) Luciferase activity of pcDNA3.1-YBX-1 or empty vector-transfected cells. (F) Luciferase activity after LPS and MGP treatment. n = 6 per group.

Article Snippet: Enzyme-linked immunosorbent assays (ELISA) were conducted using commercial kits to quantify serum levels of human GDF15 (Proteintech, Cat# KE00108), mouse GDF15 (Proteintech, Cat# KE10082), and mouse IL-6 (MULTI SCIENCES, Cat# EK206).

Techniques: Expressing, Western Blot, Knockdown, Luciferase, Plasmid Preparation, Activity Assay, Transfection

Journal: Redox Biology

Article Title: GDF15 nanotherapy ameliorates NLRP3-associated redox imbalance and cardiac injury in sepsis

doi: 10.1016/j.redox.2025.103897

Figure Lengend Snippet: Mechanism of action of macrophage-biomimetic nanocarriers delivering GDF15 to target the YBX-1-NLRP3 axis in SICM. Macrophage-biomimetic nanocarriers loaded with rhGDF15 are targeted to inflammatory sites in the heart, enhancing local drug accumulation, while GDF15 binds to MYPT1 to inhibit YBX-1 phosphorylation and block its nuclear translocation, leading to reduced nuclear YBX-1 expression and decreased transcriptional activity of the Nlrp3 promoter, which suppresses NLRP3 inflammasome assembly and pro-inflammatory cytokine release such as IL-1β, ultimately alleviating macrophage inflammatory responses, myocardial cell injury, and improving cardiac function in SICM.

Article Snippet: Enzyme-linked immunosorbent assays (ELISA) were conducted using commercial kits to quantify serum levels of human GDF15 (Proteintech, Cat# KE00108), mouse GDF15 (Proteintech, Cat# KE10082), and mouse IL-6 (MULTI SCIENCES, Cat# EK206).

Techniques: Phospho-proteomics, Blocking Assay, Translocation Assay, Expressing, Activity Assay