Alleviation of preeclampsia-like symptoms through PlGF and eNOS regulation by hypoxia- and NF-κB-responsive miR-214-3p deletion.

Preeclampsia is caused by placental hypoxia and systemic inflammation and is associated with reduced placental growth factor (PlGF) and endothelial nitric oxide synthase (eNOS) levels. The molecular signaling axes involved in this process may play a role in the pathogenesis of preeclampsia. Here, we found that hypoxic exposure increased hypoxia-inducible factor-1α (HIF-1α)/Twist1-mediated miR-214-3p biogenesis in trophoblasts, suppressing PlGF production and trophoblast invasion. TNF-α stimulation increased NF-κB-dependent miR-214-3p expression in endothelial cells, impairing eNOS expression and causing endothelial dysfunction. Synthetic miR-214-3p administration to pregnant mice decreased PlGF and eNOS expression, resulting in preeclampsia-like symptoms, including hypertension, proteinuria, and fetal growth restriction. Conversely, miR-214-3p deletion maintained the PlGF and eNOS levels in hypoxic pregnant mice, alleviating preeclampsia-like symptoms and signs. These findings provide new insights into the role of HIF-1/Twist1- and NF-κB-responsive miR-214-3p-dependent PlGF and eNOS downregulation in the pathogenesis of preeclampsia and establish miR-214-3p as a therapeutic or preventive target for preeclampsia and its complications.

Management of Neonatal Hepatic Hemangiomas: A Single-Center Experience Focused on Challenging Cases.

Background: Management of hepatic hemangioma (HH) in infancy ranges from close monitoring to surgical resection. We analyzed the clinical characteristics and outcomes of HH according to its treatment options, with particular focus on challenging cases. Methods: Data of patients diagnosed with HHs in their first year of life and followed up for at least 1 year were retrospectively reviewed and divided into treatment and observation groups. Serial imaging results, serum alpha-fetoprotein (AFP) levels, medications, and clinical outcomes were compared. The detailed clinical progress in the treatment group was reviewed separately. Results: A total of 87 patients (75 in the observation group and 12 in the treatment group) were included. The median HH size at the initial diagnosis and the maximum size were significantly larger in the treatment group than the observation group (2.2 [0.5-10.3] cm vs. 1.0 [0.4-4.0] cm and 2.1 [0.7-13.2] vs. 1.1 [0.4-4.0], respectively; all p < 0.05]. The median initial and last serum AFP levels were significantly higher in the treatment group than in the observation group (76,818.7 vs. 627.2 and 98.4 vs. 8.7, respectively; all p < 0.05). Serum AFP levels in both groups rapidly declined during the first 3 months of life and were almost undetectable after 6 months. Among the challenging cases, a large (14 × 10 × 6.5 cm sized) focal HH was successfully treated using stepwise medical-to-surgical treatment. Conclusions: Patients with large HH and mild symptoms can be treated using stepwise pharmacotherapy. More aggressive surgical treatment of tumors unresponsive to initial pharmacotherapy may help shorten the treatment period and improve outcomes.

Factors associated with the response to postnatal dexamethasone use in very low birthweight infants: a nationwide cohort study.

BACKGROUND: Dexamethasone is widely used as a systemic corticosteroid to treat and prevent bronchopulmonary dysplasia (BPD) in preterm infants. We evaluated the current epidemiology of dexamethasone use to prevent BPD and analyse the factors associated with the response to dexamethasone in very low birthweight infants using a nationwide database. METHODS: We included very low birthweight infants born between January 2013 and December 2020 with a gestational age of 23-31 weeks using data from the Korean Neonatal Network registry. Patients were grouped based on their dexamethasone use into 'Dex' or 'No Dex' groups. Clinical variables and data were collected, and the annual trends of dexamethasone use and the proportion of patients who received dexamethasone according to gestational age were analysed. Respiratory outcomes were compared between the groups. Univariate and multivariate analyses were performed to analyse factors associated with the response to dexamethasone in BPD. RESULTS: Of 11 261 eligible infants, 2313 (20.5%) received dexamethasone, and 1714 (74.1%) of them were diagnosed with moderate-to-severe BPD. The 8-year annual prevalence of dexamethasone use was 17.7-22.3%. The 'Dex' group had more moderate-to-severe BPD, more frequent invasive ventilation use at a postmenstrual age of 36 weeks and longer ventilator duration. Birth weight, 5-minute APGAR score, pulmonary hypertension within the first 28 days, surgical treatment of patent ductus arteriosus, medical treatment of patent ductus arteriosus, pathological chorioamnionitis, hydrocortisone or budesonide use, surgical management of necrotising enterocolitis and fungal sepsis were associated with BPD after dexamethasone use. CONCLUSIONS: Approximately 20.5% of preterm infants received dexamethasone, and the frequency increased as gestational age decreased. Poor response to dexamethasone was associated with antenatal and postnatal inflammation, low birth weight and early pulmonary hypertension.