EphrinA1/EphA2 Promotes Epithelial Hyperpermeability Involving in Lipopolysaccharide-induced Intestinal Barrier Dysfunction.

Background/Aims: Lipopolysaccharide (LPS) is the key factor inducing mucosal and systemic inflammation in various intestinal and parenteral diseases, which could initially disrupt the epithelial barrier function. EphrinA1/ephA2 is speculated to increase the epithelial permeability for its "repulsive interaction" between adjacent cells. This study aim to investigate the role of ephrinA1/ephA2 in LPS-induced epithelial hyperpermeability. Methods: In vivo model challenged with oral LPS in C57BL/6 mice and in vitro model exposed to LPS in Caco2 monolayer were established. The barrier function was assessed including expression of tight junction proteins (occludin and claudin-1), transepithelial electrical resistance, and permeability to macromolecules (fluorescein isothiocyanate-labeled fluorescent dextran 4 kDa [FD4]). Moreover, the expression and phosphorylation of ephrinA1/ephA2 were quantified, and its roles in the process of epithelial barrier disruption were confirmed via stimulating ephA2 with ephrinA1-Fc chimera (ephrinA1-Fc) and inactivating ephA2 with ephA2-Fc chimera (ephA2-Fc), or ephA2 monoclonal antibody (ephA2-mab), as well as inhibiting extracellular signal-regulated kinase 1/2 (ERK1/2) with PD98059. Results: LPS induced significant barrier dysfunction with dismissed occludin and claudin-1 expression, reduced transepithelial electrical resistance and increased FD4 permeability, accompanied by upregulated ephrinA1/ephA2 pathway and phosphorylation of ephA2 receptor. Furthermore, ephA2-Fc, and ephA2-mab ameliorated LPS-induced epithelial hyperpermeability, which was also inhibited by PD98059. Additionally, ephrinA1-Fc led to apparent epithelial leakage in Caco2 monolayer by promoting the phosphorylation of ERK1/2, which could be obviously blocked by ephA2-mab and PD98059. Conclusion: EphrinA1/ephA2 promotes epithelial hyperpermeability with an ERK1/2-dependent pathway, which involves in LPS-induced intestinal barrier dysfunction.

Outcomes and implications of diarrhea in patients with SARS-CoV-2 infection.

BACKGROUND AND AIMS: Diarrhea was not uncommon in patients with coronavirus disease 2019 (COVID-19), but the significance remains undetermined. METHODS: This retrospective study included 157 diarrhea cases form 564 hospitalized COVID-19 patients who were admitted to Wuhan Union Hospital from January 20 to February 29, 2020. Clinical characteristics, the course and the outcome of patients with diarrhea were analyzed. The correlation between diarrhea and fecal presence of coronavirus was also determined. RESULTS: The overall morbidity of diarrhea was 27.8% (157/564) in COVID-19 patients. Among them, 38 cases presented only with diarrhea, and 119 cases in both diarrhea and respiratory symptoms. Patients with diarrhea and respiratory symptoms had higher levels of inflammatory activity, longer hospital stay (27.5 vs. 23.0 vs. 22.0 days, p = .029) and higher odds ratio of mortality (3.2 times and 2.2 times, respectively) than those with diarrhea only or respiratory symptoms only. However, patients with diarrhea had longer time from onset to admission (14.5 days vs. 11.0 days, p = .04), higher positive viral RNA in stool (80.0% vs. 52.4%, p = .016) than those with both diarrhea and respiratory symptoms. CONCLUSIONS: Diarrhea caused by high enteric viral burden may lead to long course and poor outcome in COVID-19 patients. The patients with diarrhea and respiratory symptoms were prone to serious condition, and had worse outcomes. However, the patients with diarrhea alone showed mild illness but delayed health-seeking.

Perinatal depressive and anxiety symptoms of pregnant women during the coronavirus disease 2019 outbreak in China

BACKGROUND: On January 20, 2020, a new coronavirus epidemic with human-to-human transmission was officially declared by the Chinese government, which caused significant public panic in China. In light of the coronavirus disease 2019 outbreak, pregnant women may be particularly vulnerable and in special need for preventive mental health strategies. Thus far, no reports exist to investigate the mental health response of pregnant women to the coronavirus disease 2019 outbreak. OBJECTIVE: This study aimed to examine the impact of coronavirus disease 2019 outbreak on the prevalence of depressive and anxiety symptoms and the corresponding risk factors among pregnant women across China. STUDY DESIGN: A multicenter, cross-sectional study was initiated in early December 2019 to identify mental health concerns in pregnancy using the Edinburgh Postnatal Depression Scale. This study provided a unique opportunity to compare the mental status of pregnant women before and after the declaration of the coronavirus disease 2019 epidemic. A total of 4124 pregnant women during their third trimester from 25 hospitals in 10 provinces across China were examined in this cross-sectional study from January 1, 2020, to February 9, 2020. Of these women, 1285 were assessed after January 20, 2020, when the coronavirus epidemic was publicly declared and 2839 were assessed before this pivotal time point. The internationally recommended Edinburgh Postnatal Depression Scale was used to assess maternal depression and anxiety symptoms. Prevalence rates and risk factors were compared between the pre- and poststudy groups. RESULTS: Pregnant women assessed after the declaration of coronavirus disease 2019 epidemic had significantly higher rates of depressive symptoms (26.0% vs 29.6%, P=.02) than women assessed before the epidemic declaration. These women were also more likely to have thoughts of self-harm (P=.005). The depressive rates were positively associated with the number of newly confirmed cases of coronavirus disease 2019 (P=.003), suspected infections (P=.004), and deaths per day (P=.001). Pregnant women who were underweight before pregnancy, primiparous, younger than 35 years, employed full time, in middle income category, and had appropriate living space were at increased risk for developing depressive and anxiety symptoms during the outbreak. CONCLUSION: Major life-threatening public health events such as the coronavirus disease 2019 outbreak may increase the risk for mental illness among pregnant women, including thoughts of self-harm. Strategies targeting maternal stress and isolation such as effective risk communication and the provision of psychological first aid may be particularly useful to prevent negative outcomes for women and their fetuses.