Plasma-derived extracellular vesicles prime alveolar macrophages for autophagy and ferroptosis in sepsis-induced acute lung injury

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: Feb. 4, 2025

Abstract Sepsis-induced acute respiratory distress syndrome (ARDS) is a severe complication of sepsis and the leading cause mortality. Although role alveolar macrophages (AMs) in stabilizing pulmonary homeostasis well established, effects circulating extracellular vesicles (EVs) on AMs remain largely unknown. In this study, an investigation was conducted to map miRNA protein expression profiles EVs derived from septic plasma. Notably, EV-based panels (miR-122-5p, miR-125b-5p, miR-223-3p, OLFM4, LCN2) have been found be associated with severity or prognosis sepsis, promising AUC values. Moreover, levels LCN2, miR-122-5p, miR-223-3p were identified as independent predictors ARDS. The vitro coculture results revealed that LPS-EVs plasma sepsis-induced lung injury (ALI), which carry pro-inflammatory EVs, partly mediated by evidenced promotion inflammation, autophagy ferroptosis AMs. Mechanistically, upregulation triggers activating Hippo signaling via targeting MEF2C. vivo, inhibition effectively mitigated LPS-EV-induced inflammation AM death lungs, histological lesions. Overall, contributes ALI priming for through MEF2C/Hippo pathway. These findings suggest novel mechanism plasma-AM interaction ALI, offering plausible strategy assessing progression treating injury.

Language: Английский

---

A Bacteria-Targeting Supramolecular Nanophotosensitizer for Combating Multidrug Resistant Bacteria

ACS Biomaterials Science & Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

The increasing prevalence of multidrug-resistant bacteria is a significant global health threat. In contrast to conventional antibiotic treatments, photodynamic therapy (PDT) offers promising alternative by reducing the bacterial adaptability antibiotics and bactericides. However, traditional photosensitizers encounter poor antimicrobial efficacy due hydrophilicity photosensitizers, short lifespan, narrow diffusion radius reactive oxygen species (ROS), risk exacerbating inflammation. this study, we report bacterial-targeting supramolecular nanophotosensitizer for combating multidrug resistant bacteria. nanophotosensitizer, formed through host–guest interactions self-assembly tetra-cyclodextrin-modified silver porphyrin (AgTPP-CD4), adamantyl-modified phenylboronic acid (Ad-PBA), curcumin (Cur), can effectively target kill methicillin-resistant Staphylococcus aureus (MRSA). Moreover, it reduces inflammation promotes wound healing in MRSA-infected wounds without inducing drug resistance. combination chemistry targeted PDT strategy infections.

Language: Английский

---

Antimicrobial Potential of Scorpion-Venom-Derived Peptides

Molecules, Journal Year: 2024, Volume and Issue: 29(21), P. 5080 - 5080

Published: Oct. 27, 2024

The frequent and irrational use of antibiotics by humans has led to the escalating rise antimicrobial resistance (AMR) with a high rate morbidity-mortality worldwide, which poses challenge development effective treatments. A large number host defense peptides from different organisms have gained interest due their broad antibacterial spectrum, rapid action, low target resistance, implying that these natural sources might be new alternative drugs. As important effectors prey capture, against other animal attacks, competitor deterrence, scorpion venoms been developed as candidate for modern drug development. With progress bioanalytical throughput sequencing techniques, more scorpion-venom-derived peptides, including disulfide-bridged (DBPs) non-disulfide-bridged (NDBPs), recently identified having massive pharmacological activities in channelopathies, pathogen infections, cancer In this review, we summarize molecular diversity corresponding structural classification venom antibacterial, antifungal, and/or antiparasitic activity. We also aim improve understanding underlying mechanisms exert functions, finally highlight key aspects prospects therapeutic or pharmaceutical application.

Language: Английский

---

Protocol for isolating extracellular vesicles from alveolar macrophages phagocytosing MRSA in vitro cell culture models

STAR Protocols, Journal Year: 2024, Volume and Issue: 6(1), P. 103526 - 103526

Published: Dec. 20, 2024

Language: Английский

---