Inosine: A broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation

Wang, Ningning; Li, Entao; Deng, Hongxin; Yue, Lan-Xin; Zhou, Lian; Su, Rina; He, Baokun; Chen, Lai; Li, Gaofu; Gao, Yuwei; Zhou, Wei; Gao, Yue

doi:10.1016/j.jpha.2022.10.002

Cited by 5 publications

(3 citation statements)

References 45 publications

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“…Moreover, the upregulation of adenosine and inosine in the IL‐10+SPA eEV ‐treated mice could also be an indication of the therapeutic effect of these eEVs, as these metabolites have also been reported to play a role in anti‐inflammatory processes associated with acute lung disease. [ 109–112 ] Treatment with IL‐4+SPA eEVs also showed to cause a significant reduction of phenylalanine in BALF; the increased accumulation of this amino acid in blood plasma has been described as a potential biomarker and as a mortality predictor for ARDS patients. [ 113 ] Furthermore, the metabolomic changes caused by the treatment with sham eEVs also resulted in the upregulation of certain metabolites with antioxidant or anti‐inflammatory effects, including ubiquinone, citric acid, cortisone, uridine, and linoleic acid.…”

Section: Discussionmentioning

confidence: 99%

Engineered Extracellular Vesicles Derived from Dermal Fibroblasts Attenuate Inflammation in a Murine Model of Acute Lung Injury

et al. 2023

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Acute respiratory distress syndrome (ARDS) represents a significant burden to the healthcare system, with ≈200 000 cases diagnosed annually in the USA. ARDS patients suffer from severe refractory hypoxemia, alveolar‐capillary barrier dysfunction, impaired surfactant function, and abnormal upregulation of inflammatory pathways that lead to intensive care unit admission, prolonged hospitalization, and increased disability‐adjusted life years. Currently, there is no cure or FDA‐approved therapy for ARDS. This work describes the implementation of engineered extracellular vesicle (eEV)‐based nanocarriers for targeted nonviral delivery of anti‐inflammatory payloads to the inflamed/injured lung. The results show the ability of surfactant protein A (SPA)‐functionalized IL‐4‐ and IL‐10‐loaded eEVs to promote intrapulmonary retention and reduce inflammation, both in vitro and in vivo. Significant attenuation is observed in tissue damage, proinflammatory cytokine secretion, macrophage activation, influx of protein‐rich fluid, and neutrophil infiltration into the alveolar space as early as 6 h post‐eEVs treatment. Additionally, metabolomics analyses show that eEV treatment causes significant changes in the metabolic profile of inflamed lungs, driving the secretion of key anti‐inflammatory metabolites. Altogether, these results establish the potential of eEVs derived from dermal fibroblasts to reduce inflammation, tissue damage, and the prevalence/progression of injury during ARDS via nonviral delivery of anti‐inflammatory genes/transcripts.

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Section: Discussionmentioning

confidence: 99%

Engineered Extracellular Vesicles Derived from Dermal Fibroblasts Attenuate Inflammation in a Murine Model of Acute Lung Injury

et al. 2023

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“…In previous reports, overexpression of GSK3β was reported to enhance the activation of IRF3 and the transcription of IFN-β by Sendai virus (SeV), and this effect is produced by GSK3β by causing oligomerization and phosphorylation of TANK-binding kinase 1 (TBK1) ( 36 ). It was also reported that GSK3β can interact directly with TBK1 ( 37 ) to promote TBK1 phosphorylation ( 38 ) and that overexpression of TBK1 in DEF cells causes activation of GSK3β ( 39 ). In this study, whether the mechanism of chGSK3β affecting ALV-J replication is also related to TBK1 needs to be clarified by further studies.…”

Section: Discussionmentioning

confidence: 99%

Chicken Glycogen Synthase Kinase 3β Suppresses Innate Immune Responses and Enhances Avian Leukosis Virus Replication in DF-1 Cells

et al. 2023

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GSK3β regulates many life activities in mammals. Recent studies revealed that chGSK3β was involved in regulating antiviral innate immunity in DF-1 cells and also could positively regulate ALV-J replication. These results provide new insights into the biofunction of chGSK3β and the virus-host interactions of ALV-J. In addition, this study provides a basis for further research on the function of GSK3 in poultry.

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“…Studies have shown that inosine can exhibit excessive pro-inflammatory interleukins to improve acute inflammatory injury induced by various infectious factors, and improved the survival rate of mice significantly by inhibiting TANK-binding kinase phosphorylation. 52 Inosine can also reduce abnormal movement and weight loss induced by 3-nitropropionic acid, inhibit oxidative stress biomarkers, and pro-inflammatory cytokines, and reduce autosomal dominant neurodegenerative diseases in rats. 53 Inosine can also treat spinal cord injury, multiple sclerosis, traumatic brain injury, and diabetic peripheral neuropathy effectively.…”

Section: Changes Of Oligosaccharide Content In the Sbmmentioning

confidence: 99%

Quality improvement of soybean meal by yeast fermentation based on the degradation of anti‐nutritional factors and accumulation of beneficial metabolites

Cao,

Lu,

Cai

2023

J Sci Food Agric

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BackgroundSoybean meal (SBM) is the main protein source for animal diet, but its anti‐nutritional factors affect the animal growth and immunity. Yeast culture based on soybean meal (SBM‐YC) by simultaneous yeast fermentation and protease enzymolysis can effectively reduce anti‐nutritional factors and accumulate beneficial metabolites.ResultsThe crude protein and acid‐soluble protein content of SBM‐YC reached 542.5 g•kg‐1 and 117.2 g•kg‐1, respectively, and the essential amino acid content was increased by 17.9%. Raffinose and stachyose were decreased over 95.0%, and the contents of organic acid such as acetic acid, butyric acid, citric acid, lactic acid, succinic acid, and propionic acid produced by fermentation reached 6.1, 3.8, 3.6, 2.5, 1.2 and 0.4 g•kg‐1, respectively. As the biomarker of yeast culture, nucleosides and their precursors reached 1.7 g•kg‐1, especially inosine content increased from 0 to 0.3 g•kg‐1. In terms of antioxidant capacity evaluation, the total antioxidant capacity, ABTS free radical activity, metal chelating ability and DPPH scavenging ability were increased by 50.3%, 46.1%, 43.9%, and 20.6%, respectively.ConclusionThis study established a diversified evaluation index, which could lay a foundation for the production and quality control of SBM‐YC in the future.This article is protected by copyright. All rights reserved.

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Inosine: A broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation

Cited by 5 publications

References 45 publications

Engineered Extracellular Vesicles Derived from Dermal Fibroblasts Attenuate Inflammation in a Murine Model of Acute Lung Injury

Engineered Extracellular Vesicles Derived from Dermal Fibroblasts Attenuate Inflammation in a Murine Model of Acute Lung Injury

Chicken Glycogen Synthase Kinase 3β Suppresses Innate Immune Responses and Enhances Avian Leukosis Virus Replication in DF-1 Cells

Quality improvement of soybean meal by yeast fermentation based on the degradation of anti‐nutritional factors and accumulation of beneficial metabolites

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