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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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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Patients 65 years and older account for an increasing proportion of traumatic brain injury (TBI) patients. Aged TBI patients experience increased morbidity and mortality compared with young TBI patients. We previously demonstrated a marked accumulation of CD8 + T-cells within the brains of aged TBI mice compared with young TBI mice. ⋯ Contrastingly, no difference was detected in young mice after aCD49d Ab treatment. Collectively, aCD49 Ab treatment reduced T-cells in the injured brain, improved survival, and attenuated neurocognitive and gait deficits. Hence, aCD49d Ab may be a promising therapeutic intervention in aged TBI subjects-a population often excluded in TBI clinical trials.
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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.