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To develop a severe acute pancreatitis (SAP) model transited from mild symptoms, we investigated a "two-hit" strategy with L-arginine in mice. The mice were intraperitoneally injected with ice-cold L-arginine (4 g/kg) twice at an interval of 1 h on the first day and subjected to the repeated operation 72 h afterwards. The results showed the "two-hit" strategy resulted in the destructive damage and extensive necrosis of acinar cells in the pancreas compared with the "one-hit" model. Meanwhile, excessive levels of pro-inflammatory mediators, namely IL-6 and TNF-α, were released in the serum. Remarkably, additional deleterious effects on multiple organs were observed, including high intestinal permeability, kidney injury, and severe acute lung injury. Therefore, we confirmed that the SAP animal model triggered by a "two-hit" strategy with L-arginine was successfully established, providing a solid foundation for a deeper understanding of SAP initiation and therapy research to prevent worsening of the disease.
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http://dx.doi.org/10.3390/life12010126 | DOI Listing |
Theranostics
August 2025
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Mechanical ventilation (MV), a life-saving intervention for acute respiratory distress syndrome (ARDS), may exacerbate pulmonary fibrosis (PF) through unclear mechanisms. Although Phosphatase and Tensin homolog (PTEN) suppresses chronic PF, its role in MV-induced PF remains unknown. This study will determine whether PTEN mediates MV-PF via lung epithelial cell senescence.
View Article and Find Full Text PDFTransfusion-related acute lung injury (TRALI) is a leading cause of transfusion-related mortality. Though the precise mechanism is not fully understood, a two-hit model is widely accepted, involving both a predisposing patient condition and the transfusion itself. Mitochondrial damage-associated molecular patterns (mtDAMPs), such as mitochondrial DNA (mtDNA) and N-formylated peptides (NFPs), are elevated in trauma patients and stored blood products, and have been implicated in adverse transfusion outcomes, prompting us to investigated whether mtDAMPs could serve as a priming "first-hit" in TRALI.
View Article and Find Full Text PDFFront Oncol
July 2025
Department of Hematology, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
Background: VHL germline mutations are classically associated with von Hippel-Lindau syndrome, but their role in hematological malignancies remains underexplored.
Methods: We analyzed a pedigree with acute myeloid leukemia (AML) proband and two offspring: primary immune thrombocytopenia (ITP) and acute T-cell lymphoblastic leukemia (T-ALL) via targeted sequencing and familial validation.
Results: Genetic analysis revealed: (1) the proband carried concurrent VHL, ASXL3, and CCR7 germline mutations along with acquired BCOR/NF1 variants; (2) the ITP-affected offspring inherited ASXL3/CCR7 mutations only; and (3) the T-ALL case exhibited solely the VHL mutation.
FASEB J
August 2025
College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
Ferroptosis, an iron-dependent regulated cell death process driven by lipid peroxidation, has emerged as a pivotal mechanism in mycotoxin-induced redox pathology. This review synthesizes the molecular interplay between fungal secondary metabolites (e.g.
View Article and Find Full Text PDFFront Pharmacol
July 2025
Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, China.
Background: Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disorder characterized by progressive elevation of pulmonary vascular resistance, resulting to right ventricular dysfunction and premature mortality. Although genetic mutations are increasingly recognized in PAH pathogenesis, cases involving digenic mutations remain exceptionally rare.
Case Presentation: We report the case of a 47-year-old female presenting with a 5-year history of exertional dyspnea, which progressively worsened over the preceding 2 months.