Int J Med Sci
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Background: Sepsis-induced liver injury (SILI) is an independent risk factor for organ dysfunction and mortality in critical care units. Methods: In this study, the roles of lipocalin 2 (LCN2) in SILI were investigated because LCN2 expression was increased in liver tissues of the septic mice induced by caecal ligation and puncture (CLP), as well as in hepatocytes treated with lipopolysaccharide (LPS). To evaluate liver injury in mice, the levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were measured in both serum and liver tissues. ⋯ Results: The results demonstrated that LCN2 depletion significantly exacerbated SILI, oxidative stress, and ferroptosis. Moreover, in in vitro sepsis model, LCN2 overexpression notably ameliorated LPS-induced cell injury, oxidative stress, and ferroptosis by inhibiting PTGS2 expression. Conclusion: In conclusion, our study provides evidence that LCN2 depletion aggravates SILI by regulating PTGS2-mediated ferroptosis.
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Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca3(PO4)2) in vivo, which was characterized with lower incidence of mouse AAA. ⋯ Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what's more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.
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Objective: Asthma is a chronic heterogeneous airway disease, and imbalanced T-helper type 1 (Th1) and Th2 cell-mediated inflammation contribute to its pathogenesis. Although it has been suggested that androgen and estrogen were involved in development of asthma, the underlying mechanisms remained largely unclear. Studies have demonstrated that Runx3 could promote naive CD4+ T cells to differentiate into Th1 cells. ⋯ In mice with experimental asthma, there were increased serum concentrations of estrogen and decreased serum concentrations of androgen, intervention with combination of androgen and estrogen alleviated airway inflammations, increased Runx3 expressions and elevated Th1 differentiation. In CD4+ T cells co-cultured with bronchial epithelial cells (BECs), treatment with androgen plus estrogen combination promoted Th1 differentiation, which was mitigated by Runx3 knockdown in BECs and enhanced by Runx3 overexpression. Conclusion: These findings suggest that androgen estrogen combination modulate the Th1/Th2 balance via regulating the expression of Runx3 in BECs, thereby providing experimental evidence supporting androgen and estrogen combination as a novel therapy for asthma.
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Background: Chronic Kidney Disease (CKD) is a systemic progressive disorder related to uremic toxins. Uremic toxins disturb intestinal epithelial destruction and barrier dysfunction leading to gut-renal axis disorders in CKD. We examine the protective role of Resveratrol (RSV) against uremic toxin indoxyl sulphate (IS) related intestinal barrier disturbances among CKD. ⋯ This study establishes RSV as a potential therapeutic agent that can ameliorate gut-renal axis disturbances in CKD. These findings provide valuable insights into mechanisms underlying RSV RSV-mediated gut-renal axis, highlighting its effectiveness as a potential treatment option for CKD-associated intestinal barrier dysfunction.
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This study unveils the pivotal roles of taurine metabolic reprogramming and its implications in the development and progression of Abdominal Aortic Aneurysm (AAA). Leveraging an integrated approach that combines single-cell RNA sequencing (scRNA-seq) and Weighted Gene Co-expression Network Analysis (WGCNA), our research investigates the intricate transcriptional and gene expression dynamics crucial to AAA. Our findings uniquely link metabolic shifts to the integrity of the extracellular matrix (ECM) and the functionality of smooth muscle cells (SMCs), key elements in the pathology of AAA. ⋯ This novel approach has pinpointed potential biomarkers and therapeutic targets, notably within taurine metabolism pathways, crucial for crafting non-surgical interventions. By merging state-of-the-art bioinformatics with thorough molecular analysis, our study not only enhances the understanding of AAA's complex pathophysiology but also catalyzes the development of targeted therapeutic strategies. This research represents a significant advancement in the molecular characterization of AAA, with substantial implications for its future diagnosis and treatment strategies.