Palmitic Acid, A Critical Metabolite, Aggravates Cellular Senescence Through Reactive Oxygen Species Generation in Kawasaki Disease

Zhu, Qiongjun; Dong, Qianqian; Wang, Xuliang; Xia, Tianhe; Fu, Yu; Wang, Qiaoyu; Wu, Rongzhou; Wu, Tingting

doi:10.3389/fphar.2022.809157

Cited by 7 publications

(5 citation statements)

References 34 publications

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“…Extensive evidence substantiates the significant involvement of excess ROS production in the development of cardiovascular lesions during KD in children [23,24] and murine models [11,25] of KD vasculitis. Despite the existing anti-inflammatory approaches employed in the treatment of coronary artery abnormalities in KD, their therapeutic efficacy is currently limited, leading to suboptimal treatment outcomes [26,27].…”

Section: Discussionmentioning

confidence: 67%

Hydrogen Gas Inhalation Treatment for Coronary Artery Lesions in a Kawasaki Disease Mouse Model

Shih,

Yeh,

Chen

et al. 2024

Life

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Background: Kawasaki disease (KD) is a syndrome primarily affecting young children, typically under the age of five, and is characterized by the development of acute vasculitis. Through extensive research conducted on both murine and human subjects, it has been demonstrated that heightened levels of reactive oxygen species (ROS) play a pivotal role in the development of KD, especial coronary artery lesions (CALs). Hydrogen gas exhibits potent antioxidant properties that effectively regulate ROS production and the inflammatory response. Methods: We used Lactobacillus casei cell wall extract (LCWE)-induced vasculitis in mice as an animal model of KD and treated the mice with hydrogen gas inhalation. Results: We observed significant dilatation and higher Z scores in the left coronary artery (LCA) in D21 and D28 in mice after LCWE treatment compared to the control group (p < 0.001) and a significant resolution of LCA diameters (p < 0.01) and Z scores (p < 0.01) after treatment with inhaled hydrogen gas. We further demonstrated that serum IL-6 expression was higher in mice after LCWE treatment (p < 0.01) and IL-6 significantly decreased after inhaled hydrogen gas therapy (p < 0.001). Conclusion: According to our literature review, this is the first report where hydrogen gas inhalation has been demonstrated to be effective for the treatment of coronary artery dilatation in a KD murine model.

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Section: Discussionmentioning

confidence: 67%

Hydrogen Gas Inhalation Treatment for Coronary Artery Lesions in a Kawasaki Disease Mouse Model

Shih,

Yeh,

Chen

et al. 2024

Life

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“…Besides the primary febrile symptoms, KD can lead to serious arterial lesions, and the prompt diagnosis of KD remains challenging 47 . Moreover, a recent study has indicated that KD can accelerate immune cell senescence through the generation of reactive oxygen species 48 . Therefore, we examined whether scRNA-seq data from KD, mapped to Panage_data, could capture KD-induced cellular senescence.…”

Section: Functional Shifting Of Inflammatory Myeloid Cells Is Associa...mentioning

confidence: 99%

Biologically informed machine learning modeling of immune cells to reveal physiological and pathological aging process

Zhang,

Ren,

Zhao

et al. 2024

Preprint

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The immune system undergoes progressive functional remodeling from neonatal stages to old age. Therefore, understanding how aging shapes immune cell function is vital for precise treatment of patients at different life stages. Here, we constructed the first transcriptomic atlas of immune cells encompassing human lifespan, ranging from newborns to supercentenarians, and comprehensively examined gene expression signatures involving cell signaling, metabolism, differentiation, and functions in all cell types to investigate immune aging changes. By comparing immune cell composition among different age groups, HLA highly expressing NK cells and CD83 positive B cells were identified with high percentages exclusively in the teenager (Tg) group, whereas CD4_CTL precursors were exclusively enriched in the supercentenarian (Sc) group. Notably, we found that the biological age (BA) of pediatric COVID-19 patients with multisystem inflammatory syndrome accelerated aging according to their chronological age (CA). Besides, we proved that inflammatory shift-myeloid abundance and signature correlate with the progression of complications in Kawasaki disease (KD). Finally, based on those age-related immune cell compositions, we developed a novel BA prediction model, PHARE (https://xiazlab.org/phare/), which applies to both scRNA-seq and bulk RNA-seq data. Overall, our study revealed changes in immune cell proportions and function associated with aging, both in health and disease, and provided a novel tool for successfully capturing features that accelerate or delay aging.

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“… 673 Furthermore, a study proven palmitic acid is a key metabolite as promising therapeutic target, which accelerates cellular senescence by producing living oxygen in kawasaki disease. 674 …”

Section: Functional Targetmentioning

confidence: 99%

Small molecule metabolites: discovery of biomarkers and therapeutic targets

Qiu

Cai

et al. 2023

Sig Transduct Target Ther

176

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Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks of diseases. Metabolite signatures that have close proximity to subject’s phenotypic informative dimension, are useful for predicting diagnosis and prognosis of diseases as well as monitoring treatments. The lack of early biomarkers could lead to poor diagnosis and serious outcomes. Therefore, noninvasive diagnosis and monitoring methods with high specificity and selectivity are desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool for metabolic biomarker and pathway analysis, for revealing possible mechanisms of human various diseases and deciphering therapeutic potentials. It could help identify functional biomarkers related to phenotypic variation and delineate biochemical pathways changes as early indicators of pathological dysfunction and damage prior to disease development. Recently, scientists have established a large number of metabolic profiles to reveal the underlying mechanisms and metabolic networks for therapeutic target exploration in biomedicine. This review summarized the metabolic analysis on the potential value of small-molecule candidate metabolites as biomarkers with clinical events, which may lead to better diagnosis, prognosis, drug screening and treatment. We also discuss challenges that need to be addressed to fuel the next wave of breakthroughs.

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Palmitic Acid, A Critical Metabolite, Aggravates Cellular Senescence Through Reactive Oxygen Species Generation in Kawasaki Disease

Cited by 7 publications

References 34 publications

Hydrogen Gas Inhalation Treatment for Coronary Artery Lesions in a Kawasaki Disease Mouse Model

Hydrogen Gas Inhalation Treatment for Coronary Artery Lesions in a Kawasaki Disease Mouse Model

Biologically informed machine learning modeling of immune cells to reveal physiological and pathological aging process

Small molecule metabolites: discovery of biomarkers and therapeutic targets

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