Mechanism of TLR4 mediated immune effect in transfusion-induced acute lung injury based on Slit2/Robo4 signaling pathway

Xiao, Kun; Zhao, Fei; Xie, Wenjie; Ding, Jun; Gong, XiaoAn; Ouyang, Chensi; Le, Aiping

doi:10.1016/j.transci.2022.103500

Cited by 3 publications

(1 citation statement)

References 25 publications

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“…Transfusion-related acute lung injury (TRALI) is a highly severe complication of blood transfusion that can cause noncardiogenic pulmonary edema and hypoxemia during or within 6 h of the transfusion ( 1 ). It can affect individuals of any sex and age and has a mortality rate of 6% to 10% ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

The Alarmin Effect of Hmgb1/Rip3 on Transfusion-Related Acute Lung Injury via Tlr4/Nf-Κb or Mapk Pathway

Liu

Lin

Zhang

et al. 2023

Shock

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Non-antibody-mediated transfusion-related acute lung injury (TRALI) may account for up to 25% of TRALI cases. This indicates the need for further research to understand the pathophysiological mechanisms involved beyond antibody mediation fully. During this research, a TRALI rat model was developed using the trauma-blood loss-massive transfusion method. The severity of pulmonary edema was checked via measurement of lung histopathological changes and the amount of Evans blue dye fluid and bronchoalveolar lavage fluid protein leakage. In addition, potential mechanisms of pathophysiological pathways and inflammation cascades were investigated in TRALI rats in vivo. The findings indicated that TRALI increased inflammatory cytokines and triggered elevated levels of high-mobility group box 1(HMGB1)/ receptor-interacting protein kinase 3 (RIP3), apoptosis protein, and mRNAs in the TM (TRALI Model) group as opposed to the normal control.Furthermore, TRALI activated the Toll-like receptor 4 (TLR4) / Nuclear Factor-Kappa B (NF-κB) and mitogen-activated protein kinase (MAPK)signaling pathways, which partially regulated the inflammatory response in the TRALI rats. A significant increase was observed in the inflammatory mediators HMGB1 and RIP3 during the early stages of TRALI, suggesting that these mediators could be used as diagnostic markers for TRALI. In addition, HMGB1 and RIP3 promoted the inflammatory response by stimulating the TLR4/NF-κB and MAPK signaling pathways in the lung tissue of rats. Identifying efficient agents from inflammatory mediators such as alarmin can be an innovative scheme for diagnosing and preventing TRALI. These findings give HMGB1 and RIP3 a strong theoretical and experimental foundation for clinical use.

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Section: Introductionmentioning

confidence: 99%

The Alarmin Effect of Hmgb1/Rip3 on Transfusion-Related Acute Lung Injury via Tlr4/Nf-Κb or Mapk Pathway

Liu

Lin

Zhang

et al. 2023

Shock

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Evaluating Molecular Mechanism of Viral Inhibition of Aerosolized Smart Nano-Enabled Antiviral Therapeutic (Snat) on Sars-Cov-2 Infected Hamsters

Bauer,

Williams,

Pokhrel

et al. 2023

Preprint

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Evaluating Molecular Mechanism of Viral Inhibition of Aerosolized Smart Nano-Enabled Antiviral Therapeutic (SNAT) on SARS-CoV-2-Infected Hamsters

Bauer,

Williams,

Pokhrel

et al. 2024

Toxics

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Smart Nano-enabled Antiviral Therapeutic (SNAT) is a promising nanodrug that previously demonstrated efficacy in preclinical studies to alleviate SARS-CoV-2 pathology in hamsters. SNAT comprises taxoid (Tx)-decorated amino (NH2)-functionalized near-atomic size positively charged silver nanoparticles (Tx–[NH2-AgNPs]). Herein, we aimed to elucidate the molecular mechanism of the viral inhibition and safety of aerosolized SNAT treatment in SARS-CoV-2-infected golden Syrian hamsters. High-resolution transmission electron microscopy (HR-TEM) coupled with energy dispersive spectroscopy (EDS) and ELISAs showed SNAT binds directly to the SARS-CoV-2 virus by interacting with intact spike (S) protein, specifically to S2 subunit. SNAT (≥1 µg/mL) treatment significantly lowered SARS-CoV-2 infections of Calu-3 cells. Extraction-free whole transcriptome assay was used to detect changes in circulatory micronome in hamsters treated intranasally with SNAT (two doses of 10 µg/mL of 2 mL each administered 24 h apart). Uninfected hamsters treated with SNAT had altered circulatory concentrations of 18 microRNAs (8 miRNAs upregulated, 10 downregulated) on day 3 post-treatment compared to uninfected controls. SNAT-induced downregulation of miR-141-3p and miR-200b-3p may reduce viral replication and inflammation by targeting Ythdf2 and Slit2, respectively. Further, SNAT treatment significantly lowered IL-6 expression in infected hamster lungs compared to untreated infected hamsters. Taken together, we demonstrate that SNAT binds directly to SARS-CoV-2 via the S protein to prevent viral entry and propose a model by which SNAT alters the cellular miRNA-directed milieu to promote antiviral cellular processes and neutralize infection. Our results provide insights into the use of low-dose intranasally delivered SNAT in treating SARS-CoV-2 infections in a hamster model.

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Mechanism of TLR4 mediated immune effect in transfusion-induced acute lung injury based on Slit2/Robo4 signaling pathway

Cited by 3 publications

References 25 publications

The Alarmin Effect of Hmgb1/Rip3 on Transfusion-Related Acute Lung Injury via Tlr4/Nf-Κb or Mapk Pathway

The Alarmin Effect of Hmgb1/Rip3 on Transfusion-Related Acute Lung Injury via Tlr4/Nf-Κb or Mapk Pathway

Evaluating Molecular Mechanism of Viral Inhibition of Aerosolized Smart Nano-Enabled Antiviral Therapeutic (Snat) on Sars-Cov-2 Infected Hamsters

Evaluating Molecular Mechanism of Viral Inhibition of Aerosolized Smart Nano-Enabled Antiviral Therapeutic (SNAT) on SARS-CoV-2-Infected Hamsters

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