Acute medicine & surgery · 2025
mRNA-miRNA integration analysis of T-cell exhaustion in sepsis from community-acquired pneumonia.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Oda Sayaka, Matsumoto Hisatake, Togami Yuki, Yoshimura Jumpei, Ito Hiroshi, Onishi Shinya, Muratsu Arisa, Mitsuyama Yumi, Okuzaki Daisuke, Ogura Hiroshi, Tanaka Susumu, Oda Jun
Аннотация
AIM: Community-acquired pneumonia is an acute lung infection in patients without recent healthcare exposure that can progress to severe sepsis. Despite the well-established influence of miRNAs on inflammation, their specific roles in pneumonia-associated sepsis remain underexplored. In this pilot study, we aimed to provide insights into the pathogenesis of community-acquired pneumonia-associated sepsis by performing an integrative mRNA-miRNA analysis to identify key cellular signaling pathways and potential molecular targets for future research and treatment development.
METHODS: We conducted a prospective, observational, single-center study including 14 critically ill patients with community-acquired pneumonia-associated sepsis and 15 healthy controls (median age: 78 [interquartile range 67.3-83.5] and 55 [interquartile range 40.5-59.0] years, respectively).
RESULTS: Eleven patients required ventilatory support, and six met the diagnostic criteria for septic shock. All patients survived. RNA sequencing revealed 1209 upregulated and 1461 downregulated differentially expressed genes for mRNAs (false discovery rate < 0.05, |log2 fold change| >1.2), 51 upregulated and 21 downregulated genes for miRNAs, and 646 upregulated and 1274 downregulated for mRNA related to miRNAs. Canonical pathway analysis revealed activation of the programmed death-1/programmed death-ligand-1 cancer immunotherapy pathway and suppression of the Th1 pathway, indicating T-cell exhaustion in the acute phase of community-acquired pneumonia-associated sepsis.
CONCLUSION: This study provides valuable insights into the molecular mechanisms underlying CAP-associated sepsis, confirming the occurrence of immune dysregulation, particularly T-cell exhaustion. Our findings suggest that specific miRNAs and signaling pathways identified here may serve as potential therapeutic targets or biomarkers.
METHODS: We conducted a prospective, observational, single-center study including 14 critically ill patients with community-acquired pneumonia-associated sepsis and 15 healthy controls (median age: 78 [interquartile range 67.3-83.5] and 55 [interquartile range 40.5-59.0] years, respectively).
RESULTS: Eleven patients required ventilatory support, and six met the diagnostic criteria for septic shock. All patients survived. RNA sequencing revealed 1209 upregulated and 1461 downregulated differentially expressed genes for mRNAs (false discovery rate < 0.05, |log2 fold change| >1.2), 51 upregulated and 21 downregulated genes for miRNAs, and 646 upregulated and 1274 downregulated for mRNA related to miRNAs. Canonical pathway analysis revealed activation of the programmed death-1/programmed death-ligand-1 cancer immunotherapy pathway and suppression of the Th1 pathway, indicating T-cell exhaustion in the acute phase of community-acquired pneumonia-associated sepsis.
CONCLUSION: This study provides valuable insights into the molecular mechanisms underlying CAP-associated sepsis, confirming the occurrence of immune dysregulation, particularly T-cell exhaustion. Our findings suggest that specific miRNAs and signaling pathways identified here may serve as potential therapeutic targets or biomarkers.