Altered pulmonary angiogenesis contributes to disrupted alveolarization, which is the main characteristic of bronchopulmonary dysplasia (BPD). Transforming growth factor β (tGfβ) plays an important role during lung vascular development, and recent studies have demonstrated that endoglin is engaged in the modulation of tGfβ downstream signalling. Although there are two different isoforms of endoglin, L-and S-endoglin, little is known about the effect of S-endoglin in developing lungs. We analysed the expression of both L-and S-endoglin in the lung vasculature and its contribution to tGfβ-activin-like kinase (ALK)-Smad signalling with respect to BPD development. Hyperoxia impaired pulmonary angiogenesis accompanied by alveolar simplification in neonatal mouse lungs. S-endoglin, phosphorylated Smad2/3 and connective tissue growth factor levels were significantly increased in hyperoxia-exposed mice, while L-endoglin, phosphor-Smad1/5 and platelet-endothelial cell adhesion molecule-1 levels were significantly decreased. Hyperoxia suppressed the tubular growth of human pulmonary microvascular endothelial cells (ECs), and the selective inhibition of ALK5 signalling restored tubular growth. These results indicate that hyperoxia alters the balance in two isoforms of endoglin towards increased S-endoglin and that S-endoglin attenuates TGFβ-ALK1-Smad1/5 signalling but stimulates tGfβ-ALK5-Smad2/3 signalling in pulmonary ECs, which may lead to impaired pulmonary angiogenesis in developing lungs. open Scientific RepoRtS | (2020) 10:3043 | https://doi.org/10.1038/s41598-020-59928-x www.nature.com/scientificreports www.nature.com/scientificreports/ through enhancement of the TGFβ-ALK1-Smad1/5 pathway, while connective tissue growth factor (CTGF) expression increases through enhancement of the TGFβ-ALK5-Smad2/3 pathway [27][28][29][30][31] .Several independent findings have demonstrated that endoglin is engaged in TGFβ receptor complex formation and the modulation of downstream signalling [32][33][34][35] . The expression of two alternatively spliced isoforms, long (L-) endoglin and short (S-) endoglin, has been demonstrated in human and mouse lung tissues in vivo 33,34,36,37 . L-endoglin is the predominant isoform, and its pre-mRNA can be alternatively spliced by intron retention, producing the less abundant form, S-endoglin 36,37 . Evidence indicates that L-endoglin, the predominant isoform in ECs, promotes EC proliferation via TGFβ-ALK1 signalling, whereas S-endoglin acts as an antagonist of L-endoglin via activation of the TGFβ-ALK5 pathway 32,33,36,37 .To date, most studies published on endoglin have focused on L-endoglin. It has been found that L-endoglin enhances ALK1-Smad1/5 signalling in ECs, leading to proliferation and migration, which are the main characteristics of the activation phase of angiogenesis 15,18,20,22,[38][39][40][41][42][43] . However, a role of S-endoglin during endothelial senescence was recently described 36,37 . The S-endoglin:L-endoglin ratio increases during the senescence of ECs in vitro as well ...

Convulsions are a common problem in children. Benign convulsion with mild gastroenteritis (CwG) was first reported in Japan in 1982 [1], and is defined as an afebrile convulsion accompanied by symptoms of gastroenteritis in a child without a previous history of neurological disease or electrolyte abnormalities, moderate to severe dehydration, or metabolic acidosis. Longterm prognosis is favorable without serious sequelae. Most cases of CwG have been described in patients with rotavirus infection Purpose: This study investigated the relationship between serum uric acid levels and benign convulsions with mild gastroenteritis (CwG) caused by rotavirus and norovirus. Methods: This retrospective study identified 89 patients with CwG at Inha University Hospital from January 1999 to December 2019. We analyzed serum uric acid levels in patients with CwG and in patients with acute gastroenteritis without seizures according to the causative virus. Results: Among the 2,790 patients with rotavirus or norovirus gastroenteritis, 89 patients (3.2%) were diagnosed with CwG. The serum uric acid levels were significantly higher in CwG patients than in acute gastroenteritis patients (8.20±2.34 mg/dL vs. 5.44±2.69 mg/dL, P<0.001). When examined according to the virus type, serum uric acid levels were higher in the CwG group than in the acute gastroenteritis group in patients with rotavirus (8.05±2.48 mg/dL vs. 5.48±2.78 mg/ dL) and norovirus (8.43±2.13 mg/dL vs. 5.31±2.36 mg/dL) infections (P<0.001). However, there were no significant differences in uric acid levels between patients with CwG caused by rotavirus and those with CwG caused by norovirus. Conclusion: Patients with CwG, caused either by rotavirus or norovirus, showed significantly higher serum uric acid levels than those with acute gastroenteritis without seizures. Elevated serum uric acid levels could be a useful indicator for diagnosing CwG.