Hippo Pathway Activation in Aged Mesenchymal Stem Cells Contributes to the Dysregulation of Hepatic Inflammation in Aged Mice

Background Severe viral infections can precipitate acute lung injury, causing substantial morbidity and mortality. NETosis plays a crucial role in defending against pathogens and viruses, but its excessive or dysregulated formation can cause pulmonary damage, with research into its regulation offering potential insights and treatment strategies for viral lung injuries. Methods Elevated levels of NETosis were detected in the peripheral blood of patients with viral pneumonia. To explore the correlation between NETosis and virus-induced acute lung injury, we employed a murine model, administering poly(I:C) (polyinosinic-polycytidylic acid), an artificial substitute for double-stranded RNA, intratracheally to mimic viral pneumonia. Assessment of NETosis biomarkers in afflicted patients and poly(I:C)-stimulated mice was conducted, alongside mechanistic investigations into the involvement of the Hippo signaling pathway, inflammatory factors, and chemokines in the injury process. Cytokine assays, co-culture experiments, and downstream inflammatory mediator analyses were used to ascertain the role of the Hippo pathway in macrophage to mediate NETosis. Results Enhanced expression of NETosis biomarkers was found both in patients with viral pneumonia and in poly(I:C)-stimulated mice. Hippo pathway activation in conjunction with increased levels of inflammatory actors and chemokines was observed in lung tissues of the mouse model. Elevated IL-1β was detected in cells and macrophages isolated from infected mice; this was mitigated by Hippo pathway inhibitors. IL-1β was confirmed to induce NETosis in co-culture experiments, while NLRP3, functioning downstream of the Hippo pathway, mediated its secretion. Patients with viral pneumonia exhibited increased NLRP3 and IL-1β in monocyte-macrophages relative to healthy controls. Conclusions Activated Hippo pathway in macrophages during poly(I:C) exposure upregulates NLRP3 and IL-1β expression to promote the occurrence of NETosis, thereby aggravating virus-induced lung injury. This study identifies a potential target pathway for therapeutic intervention to mitigate lung injury stemming from viral infections.

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Advances in the Synthesis and Physiological Metabolic Regulation of Nicotinamide Mononucleotide

Zheng,

Li,

et al. 2024

Nutrients

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Nicotinamide mononucleotide (NMN), the direct precursor of nicotinamide adenine dinucleotide (NAD+), is involved in the regulation of many physiological and metabolic reactions in the body. NMN can indirectly affect cellular metabolic pathways, DNA repair, and senescence, while also being essential for maintaining tissues and dynamic metabolic equilibria, promoting healthy aging. Therefore, NMN has found many applications in the food, pharmaceutical, and cosmetics industries. At present, NMN synthesis strategies mainly include chemical synthesis and biosynthesis. Despite its potential benefits, the commercial production of NMN by organic chemistry approaches faces environmental and safety problems. With the rapid development of synthetic biology, it has become possible to construct microbial cell factories to produce NMN in a cost-effective way. In this review, we summarize the chemical and biosynthetic strategies of NMN, offering an overview of the recent research progress on host selection, chassis cell optimization, mining of key enzymes, metabolic engineering, and adaptive fermentation strategies. In addition, we also review the advances in the role of NMN in aging, metabolic diseases, and neural function. This review provides comprehensive technical guidance for the efficient biosynthesis of NMN as well as a theoretical basis for its application in the fields of food, medicine, and cosmetics.

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Hippo Pathway Activation in Aged Mesenchymal Stem Cells Contributes to the Dysregulation of Hepatic Inflammation in Aged Mice

Cited by 3 publications

References 93 publications

Yorkie negatively regulates the Crustin expression during molting in Chinese mitten crab, Eriocheir sinensis

Yorkie negatively regulates the Crustin expression during molting in Chinese mitten crab, Eriocheir sinensis

Hippo pathway and NLRP3-driven NETosis in macrophages: Mechanisms of viral pneumonia aggravation

Advances in the Synthesis and Physiological Metabolic Regulation of Nicotinamide Mononucleotide

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