A novel miRNA-762/NFIX pathway modulates LPS-induced acute lung injury.

Severe acute lung injury (ALI) cause significant morbidity and mortality worldwide. MicroRNAs (miRNAs) are possible biomarkers and therapeutic targets for ALI. We aimed to explore the role of miR-762, a known oncogenic factor, in the pathogenesis of ALI. Levels of miR-762 in lung tissues of LPS-treated ALI mice and blood cells of patients with lung injury were measured. Injury of human lung epithelial cell line A549 was induced by LPS stimulation. A downstream target of miR-762, NFIX, was predicted using online tools. Their interactions were validated by luciferase reporter assay. Effects of targeted regulation of the miR-762/NFIX axis on cell proliferation, apoptosis, and inflammatory responses were tested in vitro in A549 cells in vivo with an ALI mouse model. We found that upregulation of miR-762 expression and downregulation of NFIX expression were associated with lung injury. Either miR-762 inhibition or NFIX overexpression in A549 lung cells significantly attenuated LPS-mediated impairment of cell proliferation and viability. Notably, increasing expressions of miR-762 inhibitor or NFIX in vivo via airway lentivirus infection alleviated the LPS-induced ALI in mice. Further, targeted downregulation of miR-762 expression or upregulation of NFIX expression in A549 cells markedly down-regulates NF-κB/IRF3 activation, and substantially reduces the production of inflammatory factors, including TNF-α, IL-6, and IL-8. This study reveals a novel role for the miR-762/NFIX pathway in ALI pathogenesis and sheds new light on targeting this pathway for diagnosis, prevention, and therapy.

Survival after cardiac arrest secondary to high-risk pulmonary embolism without reperfusion therapies: A case report.

INTRODUCTION: High-risk pulmonary embolism (PE) needs reperfusion therapies. However, it is difficult to make medical decisions when thrombolysis is contraindicated, though pulmonary embolectomy and percutaneous catheter-directed treatment (CTD) are recommended for these patients. PATIENT CONCERNS: We reported here a case of high-risk PE patient with cardiac arrest (CA), vertebral compression fracture, as well as scalp and frontal hematoma. DIAGNOSIS: The diagnosis of PE was based on computed tomography pulmonary angiography (CTPA) which demonstrated filling defects in the right and left pulmonary arteries. INTERVENTIONS: Cardiopulmonary resuscitation was performed until the patient returned to idioventricular rhythm 3 minutes after admitted. She suffered another half-hour of hemodynamic disturbance after her shock improved 3 days later. The diagnosis of PE was confirmed by CTPA at that time. The patient did not receive any reperfusion therapies because hemoglobin decreased significantly. Moreover, anticoagulation was postponed for 2 weeks when bleeding appeared to be stopped. She received overlapping treatment with low molecular weight heparin and warfarin for 5 days then warfarin alone and discharged. OUTCOMES: She was discharged with normal vital signs and neurologically intact. She received anticoagulant therapy with warfarin and international normalized ratio regularly monitored after she was discharged, moreover, the pulmonary artery pressure turned normal, as determined by transthoracic echocardiography 1 month later. The warfarin treatment was discontinued after 12 months and no evidence of recurrence was seen until recently. CONCLUSIONS: This is the first case report of PE combined with CA that did not receive reperfusion therapy. We hypothesized that there was a spontaneous resolution in pulmonary emboli.