Shotgun Proteomics and Quantitative Pathway Analysis of the Mechanisms of Action of Dehydroeffusol, a Bioactive Phytochemical with Anticancer Activity from Juncus effusus.

Dehydroeffusol (DHE) is a phenanthrene isolated from the Chinese medicinal plant Juncus effusus. Biological evaluation of DHE reveals in vitro and in vivo anticancer effects. We performed a shotgun proteomic analysis using liquid chromatography-tandem mass spectrometry to investigate the changes in the protein profiles in cancer cells upon DHE treatment. DHE affected cancer-associated signaling pathways, including NF-κB, ß-catenin, and endoplasmic reticulum stress. Through quantitative pathway and key node analysis of the proteomics data, activating transcription factor 2 (ATF-2) and c-Jun kinase (JNK) were found to be the key components in DHE's modulated biological pathways. Based on the pathway analysis as well as chemical similarity to estradiol, DHE is proposed to be a phytoestrogen. The proteomic, bioinformatic, and chemoinformatic analyses were further verified with individual cell-based experiments. Our study demonstrates a workflow for identifying the mechanisms of action of DHE through shotgun proteomic analysis.

Association of Adenotonsillectomy With Blood Pressure Among Hypertensive and Nonhypertensive Children With Obstructive Sleep Apnea.

Importance: Hypertension in childhood may continue into adulthood and lead to adverse cardiovascular outcomes. Evidence suggests that adenotonsillectomy for childhood obstructive sleep apnea (OSA) may be associated with blood pressure (BP) improvement. However, how adenotonsillectomy is associated with BP in hypertensive and nonhypertensive children with OSA remains unclear. Objective: To investigate disparities in BP changes after adenotonsillectomy in hypertensive and nonhypertensive children with OSA. Design, Setting, and Participants: From January 1, 2010, to April 30, 2016, children (aged <18 years) with symptoms of OSA treated at National Taiwan University Hospital were enrolled in this retrospective case series study. Interventions: Children underwent polysomnography for diagnosis of OSA (apnea-hypopnea index >1). All children with OSA underwent adenotonsillectomy. Main Outcomes and Measures: Preoperative and postoperative overnight polysomnographic data were obtained. Office BP was measured in a sleep center before (nocturnal BP) and after (morning) polysomnography. Results: A total of 240 nonobese children (mean [SD] age, 7.3 [3.0] years; 160 [66.7%] male and 80 [33.3%] female) with OSA were recruited. Postoperatively, the apnea-hypopnea index decreased significantly from 12.1 to 1.7 events per hour (95% CI of difference, -12.3 to -8.4 events per hour). The whole cohort had a significant decrease in nocturnal diastolic BP (66.9 to 64.5 mm Hg; 95% CI of difference, -4.1 to -0.7 mm Hg) and morning diastolic BP (66.9 to 64.4 mm Hg; 95% CI of difference, -4.2 to -0.8 mm Hg). The number (percentage) of patients with diastolic BP in the greater than 95th percentile decreased significantly nocturnally (48 [20.0%] to 33 [13.8%]; 95% CI of difference, -12.1% to -0.4%) and in the morning (52 [21.7%] to 34 [14.2%]; 95% CI of difference, -13.6% to -1.4%). Postoperatively, hypertensive children had a significant decrease in all BP measures, including mean (SD) nocturnal and morning systolic BP (nocturnal: 107.5 [8.6] mm Hg; morning: 106.0 [9.4] mm Hg), systolic BP index (nocturnal: -4.3 [8.6]; morning: -5.7 [8.5]), diastolic BP (nocturnal: 65.1 [11.5] mm Hg; morning: 64.4 [10.1] mm Hg), and diastolic BP index (nocturnal: -10.7 [17.3]; morning: -11.6 [15.7]), whereas the nonhypertensive group had a slight increase in nocturnal systolic BP (103.8 to 105.9 mm Hg; 95% CI of difference, 0.4-3.9 mm Hg). A generalized estimating equation model for subgroup comparisons revealed that children with hypertension, compared with those without, had greater improvement in all BP measures. Conclusions and Relevance: Hypertensive children with OSA had a significant improvement in BP after adenotonsillectomy. Hypertensive children with OSA should be screened and treated by adenotonsillectomy because proper treatment not only eases OSA symptoms but also potentially prevents future cardiovascular and end-organ disease.

Impacts of disease severity on postoperative complications in children with sleep-disordered breathing.

OBJECTIVES/HYPOTHESIS: To investigate the effects of diseases severity on postoperative complications following adenotonsillectomy (T&A) in children with sleep-disordered breathing (SDB). STUDY DESIGN: Retrospective study. METHODS: Children aged <18 years were enrolled and underwent T&A for treating SDB. Polysomnography was used to classify the disease severity: primary snoring (apnea-hypopnea index [AHI] <1), mild (AHI = 1-5), moderate (AHI = 5-10), and severe obstructive sleep apnea [OSA] (AHI ≥10). Postoperative bleeding was graded using a severity scale (level I, self-reported bleeding; level II, requiring inpatient admission; level III, requiring reoperation). Primary bleeding is defined as hemorrhage occurring within the initial 24 postoperative hours. Perioperative respiratory complications are defined as oxygen saturation of less than 90%, 92%, or 95% in the recovery room. Major respiratory complications include laryngospasm, pulmonary edema, pneumonia, and intubation at recovery stage. RESULTS: A total of 610 children were included, of whom 42 (6.9%), eight (1.3%), and six (1.0%) children showed levels I, II, and III postoperative bleeding, respectively. Only one child had primary bleeding. The incidence and timing of postoperative bleeding did not differ significantly for children with different OSA severities. The rate of perioperative respiratory complications ranged from 1.6% to 14.3% on the basis of their definitions. The Cochran-Armitage test supported the trend that perioperative respiratory complications increase with the AHI. Six children developed major respiratory complications, which were not significantly associated with OSA severity. CONCLUSIONS: Children with severe OSA have increased risks of perioperative respiratory complications. However, OSA severity does not influence major respiratory complications or postoperative bleeding in children. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2646-2652, 2017.