Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood. This condition compromises mucosal barrier integrity particularly in the gut and oral cavity. However, the mechanisms underlying this association remain unclear. This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions. Hypoxia upregulated methyltransferase-like protein 4 (METTL4) expression in platelets, resulting in N⁶-methyladenine modification of mitochondrial DNA (mtDNA). This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation, leading to cytosolic mtDNA accumulation. Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets. This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis. Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology. Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
DNA, Mitochondrial/metabolism* ; Mouth Mucosa/pathology* ; Hypoxia/immunology* ; Methyltransferases/metabolism* ; Blood Platelets/metabolism* ; Animals ; Periodontitis/immunology* ; Humans ; Platelet Activation ; Mice

Objective:To investigate the correlation between antiplatelet agents and the risk of ruptured intracranial aneurysm.Methods:Patients with intracranial aneurysm admitted to the Department of Neurology, East Hospital Area of Qingdao Municipal Hospital from June to December 2018 were selected retrospectively. The baseline data of patients and the characteristics of intracranial aneurysms were collected. The independent correlation between antiplatelet agents and the risk of ruptured intracranial aneurysm was identified by the univariable analysis and multivariate logistic regression analysis. Results:A total of 90 patients with intracranial aneurysm were included in the study. There were 31 males (34.44%) and 59 females (65.56%). The median diameter of the aneurysm was 4 mm. Forty-six patients taking antiplatelet agents before being diagnosed with intracranial aneurysm, of which 36 taking aspirin, 3 taking clopidogrel, and 7 taking aspirin+ clopidogrel. There were 31 patients (34.44%) with ruptured aneurysm and 59 (65.56%) with unruptured aneurysm. There were statistical differences in the proportion of patients with age <60 years ( P<0.05), diabetes ( P<0.1), ischemic heart disease ( P<0.05), history of previous stroke or transient ischemic attack ( P<0.01), internal carotid artery aneurysm ( P<0.01), anterior communicating artery aneurysm ( P<0.05), posterior communicating artery aneurysm ( P<0.01) and taking antiplatelet agents before diagnosis ( P<0.1) between the ruptured group and the unruptured group. Multivariate logistic regression analysis showed that age <60 years (odds ratio[ OR] 4.116, 95% confidence interval [ CI] 1.337-12.673; P=0.014), anterior communicating artery aneurysm ( OR 5.015, 95% CI 1.155-22.559; P=0.032) and posterior communicating artery aneurysm ( OR 68.796, 95% CI 6.762-699.951; P<0.001) were the independent risk factors for ruptured intracranial aneurysm, and taking antiplatelet agents was an independent protective factor for ruptured intracranial aneurysm ( OR 0.320, 95% CI 0.104-0.992; P=0.048). Conclusions:Taking antiplatelet agents, especially aspirin, does not increase the risk of ruptured intracranial aneurysm, but may be a protective factor of ruptured intracranial aneurysm. Unruptured aneurysms are not contraindications for antiplatelet therapy in patients with clear indications.