Background: Hypoxia-induced M1 polarization of microglia and resultant inflammation take part in the damage caused by hypoxic-ischemic encephalopathy (HIE). Histone lactylation, a novel epigenetic modification where lactate is added to lysine residues, may play a role in HIE pathogenesis. This study investigates the role of histone lactylation in hypoxia-induced M1 microglial polarization and inflammation, aiming to provide insights for HIE treatment. Methods: In this study, we assessed the effects of hypoxia on microglial polarization using both an HIE animal model and an oxygen–glucose deprivation cell model. Histone lactylation at various lysine residues was detected by Western blotting. Microglial polarization and inflammatory cytokines were analyzed by immunofluorescence, qPCR, and Western blotting. RNA sequencing, ChIP-qPCR, and siRNA were used to elucidate mechanisms of H3K9 lactylation. Results: H3K9 lactylation increased due to cytoplasmic lactate during M1 polarization. Inhibiting P300 or reducing lactate dehydrogenase A expression decreased H3K9 lactylation, suppressing M1 polarization. Transcriptomic analysis indicated that H3K9 lactylation regulated M1 polarization via the TNF signaling pathway. ChIP-qPCR confirmed H3K9 lactylation enrichment at the TNFα locus, promoting OGD-induced M1 polarization and inflammation. Conclusions: H3K9 lactylation promotes M1 polarization and inflammation via the TNF pathway, identifying it as a potential therapeutic target for neonatal HIE.
Background: COVID-19 has spread rapidly over the world. Little is known about the outcomes of infections in pregnant women. The management and characteristics of preterm infants born to COVID-19 mothers need to be clarified. Methods: In this retrospective, single-center cohort study, we describe the clinical courses of 6 preterm infants born to COVID-19 mothers, the management protocol, and related outcomes. Results: Six preterm infants were admitted to Tongji Hospital between January 23 and March 19, 2020. Gestational age ranged from 28+5 to 36+3 weeks. One late preterm infant was delivered early due to maternal dyspnea from COVID-19. Five infants were delivered by Caesarean section. None had perinatal asphyxia. Two infants required respiratory support due to respiratory distress syndrome and apnea of prematurity. All infants did not develop severe complications of prematurity and are negative for severe acute respiratory syndrome (SARS)-CoV-2 nucleic acid testing. Conclusion: With an expedited and adequate delivery protocol, less invasive treatment principle, and active infection precautious, we found a limited impact of COVID-19 mothers on preterm delivery and neonatal short-term outcomes. The risk of vertical transmission of SARS-CoV-2 is low in preterm infants born to COVID-19 mothers if appropriate management is implemented.
Case Report Novel TTC37 mutations in a patient with Trichohepatoenteric syndrome: a case report and literature review Jinzhi Gao, Xiaolin Hu, Wei Hu, Xuan Sun, Ling Chen