Journal: Journal of Advanced Research

Article Title: Inflammation-driven biomimetic nano-polyphenol drug delivery system alleviates severe acute pancreatitis by inhibiting macrophage PANoptosis and pancreatic enzymes oversecretion

doi: 10.1016/j.jare.2025.04.006

Figure Lengend Snippet: Schematic illustration of FePTX@CM NPs against SAP. (A) The preparation of FePTX@CM NPs. (B) Mechanisms of FePTX@CM NPs in SAP treatment. After intravenous injection, FePTX@CM NPs targeted the damaged pancreas. On the one hand, drugs released from NPs could suppress the pro-inflammatory mediators release and the recruitment of macrophages and neutrophils to limit systemic inflammation. On the other hand, SAP-associated macrophages and acinar cells internalized NPs and then drugs were released in the cytoplasm. PTX prevented macrophage PANoptosis by inhibiting the Zbp1 signal pathway. And PYD inhibited mtROS/Golgi stress to limit amylase and lipase release.

Article Snippet: Antibodies included anti-cleaved casp1 (cat. 89332S, CST, USA), cleaved-caspase 3 (cat. 9661, CST, USA), caspase 9 (cat. A0281, Abclonal, China), cleaved caspase 9 (9505S, CST, China), β-actin (cat. AC038, Abclonal, China), p-MLKL (cat. AF7420, Affinity, China, China), MLKL (cat. A17312, Abclonal, China), p-RIPK3 (cat. 91702S, CST, USA), RIPK3 (10188S, CST), cleaved casp9 (cat. 9509, CST, USA), ZBP1 (sc-271483, Santa, USA), Amylase (sc-46657, Santa, USA), Lipase (cat. 11209-1-AP, Proteintech, USA) and casp6 (cat. ab185645, Abcam, USA) were incubated overnight on a shaker at 4 °C.

Techniques: Injection

Journal: Journal of Advanced Research

Article Title: Inflammation-driven biomimetic nano-polyphenol drug delivery system alleviates severe acute pancreatitis by inhibiting macrophage PANoptosis and pancreatic enzymes oversecretion

doi: 10.1016/j.jare.2025.04.006

Figure Lengend Snippet: PTX and its formulations could effectively inhibit Zbp1-mediated PANoptosis of BMDMs. (A) Heatmap of PANoptosis associated genes among each group. (B) qPCR analysis of Zbp1 in each group after various interventions (n = 4). (C) Fluorescent images of Zbp1 in BMDMs and its statistic graph. Scale bar = 100 μm. (D) Co-IP images of PANoptosis biomarkers after various treatments involving Zbp1-overexpressed macrophages. (E) Fluorescent co-localization images of Zbp1 and RIPK3 in BMDMs of each group. Scale bar = 15 μm. (F) Fluorescence images of NF-κB expression and localization in BMDMs in each group. Scale bar = 50 μm. (G) Results of qPCR and ELISA assay of IL-1β in Zbp1-overexpressed BMDMs after various interventions (n = 4). *P < 0.05, **P < 0.01, ***P < 0.001, N.s. = no significance. Data = mean ± SD.

Article Snippet: Antibodies included anti-cleaved casp1 (cat. 89332S, CST, USA), cleaved-caspase 3 (cat. 9661, CST, USA), caspase 9 (cat. A0281, Abclonal, China), cleaved caspase 9 (9505S, CST, China), β-actin (cat. AC038, Abclonal, China), p-MLKL (cat. AF7420, Affinity, China, China), MLKL (cat. A17312, Abclonal, China), p-RIPK3 (cat. 91702S, CST, USA), RIPK3 (10188S, CST), cleaved casp9 (cat. 9509, CST, USA), ZBP1 (sc-271483, Santa, USA), Amylase (sc-46657, Santa, USA), Lipase (cat. 11209-1-AP, Proteintech, USA) and casp6 (cat. ab185645, Abcam, USA) were incubated overnight on a shaker at 4 °C.

Techniques: Co-Immunoprecipitation Assay, Fluorescence, Expressing, Enzyme-linked Immunosorbent Assay

Journal: Journal of Advanced Research

Article Title: Inflammation-driven biomimetic nano-polyphenol drug delivery system alleviates severe acute pancreatitis by inhibiting macrophage PANoptosis and pancreatic enzymes oversecretion

doi: 10.1016/j.jare.2025.04.006

Figure Lengend Snippet: Mechanisms study of FePTX@CM NPs against SAP in vivo (n = 8). (A-B) Fluorescent images of mtROS and Golgi stress biomarkers in primary pancreas after different treatments and statistical analysis. Scale bar of A = 25 μm, B = 10 μm. (C) Results of western blot for detection of amylase and lipase in pancreas of C57BL/6J after FePTX@CM NPs treatments. (D) IF images of Zbp1 in pancreas in vivo and statistical analysis. Scale bar = 25 μm. (E) IF images of cleaved caspase3 in pancreas in vivo and statistical analysis. Scale bar = 25 μm. (F) IF images of p-MLKL in pancreas in vivo and statistical analysis. Scale bar = 25 μm. (G) IF images of cleaved caspase1 in pancreas in vivo and statistical analysis. Scale bar = 25 μm. (H) IF images of NF-κB in pancreas in vivo and statistical analysis. Scale bar = 25 μm. *P < 0.05, **P < 0.01, ***P < 0.001. N.s. = no significance. Data = mean ± SD.

Article Snippet: Antibodies included anti-cleaved casp1 (cat. 89332S, CST, USA), cleaved-caspase 3 (cat. 9661, CST, USA), caspase 9 (cat. A0281, Abclonal, China), cleaved caspase 9 (9505S, CST, China), β-actin (cat. AC038, Abclonal, China), p-MLKL (cat. AF7420, Affinity, China, China), MLKL (cat. A17312, Abclonal, China), p-RIPK3 (cat. 91702S, CST, USA), RIPK3 (10188S, CST), cleaved casp9 (cat. 9509, CST, USA), ZBP1 (sc-271483, Santa, USA), Amylase (sc-46657, Santa, USA), Lipase (cat. 11209-1-AP, Proteintech, USA) and casp6 (cat. ab185645, Abcam, USA) were incubated overnight on a shaker at 4 °C.

Techniques: In Vivo, Western Blot