Nervilifordin F alleviates intestinal ischemia/reperfusion-induced acute lung injury via inhibiting inflammasome and mTOR pathway

Tan, Yanjun; Zuo, Wenpu; Huang, Lingling; Zhou, Bo; Liu, Hui; Zheng, Shu; Jia, Wenxian; Chen, Suixia; Liu, Jiayi; Yang, Xiaoli; Jiao, Yang

doi:10.1016/j.intimp.2020.107014

Cited by 8 publications

(7 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, it was suggested that activation of AMPK phosphorylation ameliorates the alleviation of caspase-1-associated pyroptosis in in vivo and in vitro models of diabetic cardiomyopathy [ 43 ]. Notably, caspase-1-associated pyroptosis and caspase-3-associated apoptosis can reportedly contribute to the process of ALI after intestinal ischemia–reperfusion injury [ 6 , 17 ]. We found a slight increase in AMPK phosphorylation, as indicated by the ratio of phosphorylated AMPK to total AMPK, in pulmonary tissue after intestinal ischemia–reperfusion injury; however, C-176 further increased phospho- AMPK .…”

Section: Discussionmentioning

confidence: 99%

“…A growing body of recent evidence indicates that distant lung organ injuries, including abdominal ischemia–reperfusion, infection, and surgery, can cause ALI [ 3 – 5 ]. Moreover, reports indicate that the inflammatory response after intestinal ischemia–reperfusion injury promotes ALI [ 6 ]. To date, potential treatments or drugs against intestinal ischemia–reperfusion injury-induced ALI are unavailable in clinical therapy.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibitors of IFN gene stimulators (STING) improve intestinal ischemia–reperfusion-induced acute lung injury by activating AMPK signaling

Yang

Zhi

et al. 2022

Eur J Med Res

View full text Add to dashboard Cite

Background Acute lung injury (ALI) caused by intestinal ischemia–reperfusion is a life-threatening disease. Interferon gene stimulator (STING) is a cytoplasmic DNA sensor that participates in the initiation of the inflammatory response. This study aims to establish whether C-176 (STING inhibitor) improves ALI under intestinal ischemia–reperfusion conditions. Methods To induce ALI, 72 male C57BL/6 mice were subjected to intestinal ischemia for 60 min and reperfusion for 3 h. Through intraperitoneal injection, C-176, a selective STING inhibitor, was injected 30 min before surgical treatment; meanwhile, compound C, an antagonist of adenosine monophosphate-activated protein kinase (AMPK), was administered 30 min after surgery. Based on immunofluorescence and Western blot assays, post-ALI assessments included lung water content (TLW), bronchoalveolar lavage fluid (BALF) protein, H&E staining, Masson staining, pulmonary pyroptosis [Gasdermin-D (GSDMD), cleaved caspase-1], and apoptosis (TUNEL, cleaved caspase-3). Results C-176 administration significantly attenuated intestinal ischemia–reperfusion-mediated ALI; this effect was reflected by exacerbated TLW and BALF protein, aggravated lung injury score, elevated degree of pulmonary fibrosis, increased TUNEL- and GSDMD-positive cells, and upregulated phospho-AMPK, cleaved caspase-1, cleaved caspase-3 and IFNβ mRNA expression. Moreover, C-176 increased phospho-AMPK under ALI conditions. Nonetheless, compound C partially reversed these beneficial effects. Conclusion C-176, a selective STING inhibitor, improves intestinal ischemia–reperfusion-mediated ALI, and its underlying mechanism may be associated with AMPK signal activation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibitors of IFN gene stimulators (STING) improve intestinal ischemia–reperfusion-induced acute lung injury by activating AMPK signaling

Yang

Zhi

et al. 2022

Eur J Med Res

View full text Add to dashboard Cite

show abstract

“…Furthermore, AMBR7 was used for energy optimization, and the active pockets were obtained in automatic mode. The parameters for SYBYL 2.1 were set as default, as recommended by previous studies ( Tan et al, 2020 ). The molecular docking scores reflected the binding effects between the small-molecule compounds and the co-DEPs, and the highest scoring small molecules were considered as potential drugs.…”

Section: Methodsmentioning

confidence: 99%

Deciphering the Protein, Modular Connections and Precision Medicine for Heart Failure With Preserved Ejection Fraction and Hypertension Based on TMT Quantitative Proteomics and Molecular Docking

Zhou

Chen

et al. 2021

Front. Physiol.

View full text Add to dashboard Cite

Background: Exploring the potential biological relationships between heart failure with preserved ejection fraction (HFpEF) and concomitant diseases has been the focus of many studies for the establishment of personalized therapies. Hypertension (HTN) is the most common concomitant disease in HFpEF patients, but the functional connections between HFpEF and HTN are still not fully understood and effective treatment strategies are still lacking.Methods: In this study, tandem mass tag (TMT) quantitative proteomics was used to identify disease-related proteins and construct disease-related networks. Furthermore, functional enrichment analysis of overlapping network modules was used to determine the functional similarities between HFpEF and HTN. Molecular docking and module analyses were combined to identify therapeutic targets for HFpEF and HTN.Results: Seven common differentially expressed proteins (co-DEPs) and eight overlapping modules were identified in HFpEF and HTN. The common biological processes between HFpEF and HTN were mainly related to energy metabolism. Myocardial contraction, energy metabolism, apoptosis, oxidative stress, immune response, and cardiac hypertrophy were all closely associated with HFpEF and HTN. Epinephrine, sulfadimethoxine, chloroform, and prednisolone acetate were best matched with the co-DEPs by molecular docking analyses.Conclusion: Myocardial contraction, energy metabolism, apoptosis, oxidative stress, immune response, and cardiac hypertrophy were the main functional connections between HFpEF and HTN. Epinephrine, sulfadimethoxine, chloroform, and prednisolone acetate could potentially be effective for the treatment of HTN and HFpEF.

show abstract

“…Intestinal I/R injury is a life-threatening condition, including mucosal barrier damage and bacterial translocation, which initially happens in the intestine and then leads to multiple organ dysfunction and a systemic inflammatory response [89,90]. The NLRP3 inflammasome has been reported to be involved in the inflammatory injury of intestines induced by I/R [91,92]. Zishuo Wang and colleagues found that the NLRP3 inflammasome was activated evidenced by the increased levels of NLRP3, ASC, cleaved caspase-1 and IL-1β in intestinal I/R in vivo.…”

Section: The Interplay Between Autophagy and Nlrp3 Inflammasome In Intestinal Ischemia/reperfusion Injurymentioning

confidence: 99%

The Interplay between Autophagy and NLRP3 Inflammasome in Ischemia/Reperfusion Injury

Liu

Wang

2021

IJMS

View full text Add to dashboard Cite

Ischemia/reperfusion (I/R) injury is characterized by a limited blood supply to organs, followed by the restoration of blood flow and reoxygenation. In addition to ischemia, blood flow recovery can also lead to very harmful injury, especially inflammatory injury. Autophagy refers to the transport of cellular materials to the lysosomes for degradation, leading to the conversion of cellular components and offering energy and macromolecular precursors. It can maintain the balance of synthesis, decomposition and reuse of the intracellular components, and participate in many physiological processes and diseases. Inflammasomes are a kind of protein complex. Under physiological and pathological conditions, as the cellular innate immune signal receptors, inflammasomes sense pathogens to trigger an inflammatory response. TheNLRP3 inflammasome is the most deeply studied inflammasome and is composed of NLRP3, the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Its activation triggers the cleavage of pro-interleukin (IL)-1β and pro-IL-18 mediated by caspase-1 and promotes a further inflammatory process. Studies have shown that autophagy and the NLRP3 inflammasome play an important role in the process of I/R injury, but the relevant mechanisms have not been fully explained, especially how the interaction between autophagy and the NLRP3 inflammasome participates in I/R injury, which remains to be further studied. Therefore, we reviewed the recent studies about the interplay between autophagy and the NLRP3 inflammasome in I/R injury and analyzed the mechanisms to provide the theoretical references for further research in the future.

show abstract

Nervilifordin F alleviates intestinal ischemia/reperfusion-induced acute lung injury via inhibiting inflammasome and mTOR pathway

Cited by 8 publications

References 36 publications

Inhibitors of IFN gene stimulators (STING) improve intestinal ischemia–reperfusion-induced acute lung injury by activating AMPK signaling

Inhibitors of IFN gene stimulators (STING) improve intestinal ischemia–reperfusion-induced acute lung injury by activating AMPK signaling

Deciphering the Protein, Modular Connections and Precision Medicine for Heart Failure With Preserved Ejection Fraction and Hypertension Based on TMT Quantitative Proteomics and Molecular Docking

The Interplay between Autophagy and NLRP3 Inflammasome in Ischemia/Reperfusion Injury

Contact Info

Product

Resources

About