Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Background: Sepsis is a life-threatening systemic inflammatory disease that can cause many diseases, including acute kidney injury (AKI). Increasing evidence showed that a variety of circular RNAs were considered to be involved in the development of the disease. In this study, we aimed to elucidate the role and potential mechanism of circUSP42 in sepsis-induced AKI. ⋯ In addition, circUSP42 induced DUSP1 expression via sponging miR-182-5p to ameliorate LPS-induced HK2 cell damage. Conclusion : Our results showed that circUSP42 overexpression might attenuate LPS-induced HK2 cell injury by regulating miR-182-5p/DUSP1 axis. This might provide therapeutic strategy for the treatment of sepsis.
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Background: Intermediate-risk pulmonary embolism (PE) patients in the intensive care unit (ICU) are at a higher risk of hemodynamic deterioration than those in the general ward. This study aimed to construct a machine learning (ML) model to accurately identify the tendency for hemodynamic deterioration in the ICU patients with intermediate-risk PE. Method: A total of 704 intermediate-risk PE patients from the MIMIC-IV database were retrospectively collected. ⋯ Simplified XGBoost model demonstrated the best predictive performance with an area under the curve of 0.866 (95% confidence interval, 0.800-0.925), and after recalibrated by isotonic regression, the area under the curve improved to 0.885 (95% confidence interval, 0.822-0.935). Based on the simplified XGBoost model, a web app was developed to identify the tendency for hemodynamic deterioration in ICU patients with intermediate-risk PE. Conclusion: A simplified XGBoost model can accurately predict the occurrence of hemodynamic deterioration for intermediate-risk PE patients in the ICU, assisting clinical workers in providing more personalized management for PE patients in the ICU.
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The analysis of the single-cell transcriptome has emerged as a powerful tool to gain insights on the basic mechanisms of health and disease. It is widely used to reveal the cellular diversity and complexity of tissues at cellular resolution by RNA sequencing of the whole transcriptome from a single cell. Equally, it is applied to discover an unknown, rare population of cells in the tissue. ⋯ And with the development of numerous packages in R and Python, new directions in the computational analysis of single-cell transcriptomes can be taken to characterize healthy versus diseased tissues to obtain novel pathological insights. Downstream analysis such as differential gene expression analysis, gene ontology term analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, cell-cell interaction analysis, and trajectory analysis has become standard practice in the workflow of single-cell transcriptome analysis to further examine the biology of different cell types. Here, we provide a broad overview of single-cell transcriptome analysis in health and disease conditions currently applied in various studies.
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M1 macrophage-mediated inflammation is critical in sepsis. We previously found the protective role of astragaloside intravenous (AS-IV) in sepsis-associated gut impairment, whose specific mechanism remains unknown. Gut microbiota modulates gut homeostatic balance to avoid excessive inflammation. ⋯ In Caco-2 and THP-1 cocultured model, LPS and interferon γ caused THP-1 M1 polarization, Caco-2 barrier impairment, abnormal cytokines release, and high NLRP3 inflammasome expression in THP-1 cells, all of which were mitigated by butyrate administration. However, these protective effects of butyrate were abrogated by NLRP3 gene overexpression in THP-1. In conclusion, AS-IV can ameliorate sepsis-induced gut inflammation and barrier dysfunction by modulating M1/M2 polarization of gut macrophages, whose underlying mechanism may be restoring gut microbiome and SCFA to restrain NLRP3 inflammasome activation.
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The molecular mechanism for nobiletin's protective effect against heatstroke-induced acute lung injury (HS-ALI) remains largely unknown. Previous research has demonstrated that ferroptosis is an important pathogenic event in HS-ALI. Nobiletin is a natural polymethoxylated flavonoid. ⋯ Meanwhile, p53 knockdown significantly increased GPX4 and SLC7A11 expression levels compared with the HS group in HS-induced MLE-12 cells. Subsequently, nobiletin ameliorated HS-induced MLE-12 cells ferroptosis by activating the SLC7A11/GPX4 pathway, whereas p53 overexpression effectively abolished the protective effect of nobiletin. Taken together, our findings reveal that nobiletin attenuates HS-ALI by inhibiting ferroptosis through the p53/SLC7A11 pathway, indicating it to be a potential therapeutic agent for HS-ALI prevention and treatment.