Novel 2-Amino-1,4-Naphthoquinone Derivatives Induce A549 Cell Death through Autophagy.

A series of 1,4-naphthoquinone derivatives containing were synthesized as anti-cancer agents and the crystal structure of compound 5a was confirmed by X-ray diffraction. In addition, the inhibitory activities against four cancer cell lines (HepG2, A549, K562, and PC-3) were tested, respectively, and compound 5i showed significant cytotoxicity on the A549 cell line with the IC50 of 6.15 µM. Surprisingly, in the following preliminary biological experiments, we found that compound 5i induced autophagy by promoting the recycling of EGFR and signal transduction in the A549 cell, resulting in the activation of the EGFR signal pathway. The potential binding pattern between compound 5i and EGFR tyrosine kinase (PDB ID: 1M17) was also identified by molecular docking. Our research paves the way for further studies and the development of novel and powerful anti-cancer drugs.

[The value of changes in end-tidal carbon dioxide pressure induced by passive leg raising test in predicting fluid responsiveness in mechanically ventilated patients with septic shock].

OBJECTIVE: To test whether the changes of partial end-tidal carbon dioxide pressure (PETCO2) during passive leg raising (PLR) predict fluid responsiveness in mechanically ventilated patients with septic shock. METHODS: Forty-two mechanically ventilated patients with septic shock admitted from January 2012 to November 2012 were prospectively recruited.Hemodynamic parameters monitored by a pulse indicator continuous cardiac output (PiCCO) device and PETCO2 monitored by an expiratory-CO2 device were studied at baseline, after PLR, and after volume expansion. Fluid responsiveness was defined as an increase in cardiac index (CI) of 15% or greater after volume expansion. The correlation between PLR-induced CI change (ΔCIPLR) and PETCO2 (ΔPETCO2-PLR) was analyzed. The value of ΔPETCO2-PLR to predict fluid responsiveness was evaluated by receiver operating characteristic (ROC) curves. RESULTS: A total of 42 patients were enrolled in this study, of whom, 24 had a CI increase of ≥ 15% after volume expansion (responders). After PLR, CI and PETCO2 were both significantly increased in the response group compared with baseline [(21.4 ± 12.9)% of CI and (9.6 ± 4.7)% of PETCO2, P < 0.05], while no significant changes were observed (P > 0.05) in the non-response group. Both ΔCIPLR and ΔPETCO2-PLR were significantly higher in responder group than in the non-responder group (both P < 0.05). ΔCI and ΔPETCO2 after PLR were strongly correlated (r = 0.64, P < 0.05). In responders after PLR, the area under ROC curve of ΔPETCO2-PLR was 0.900 ± 0.056 (95%CI 0.775-1.000, P < 0.05). An increase of ≥ 5% in ΔPETCO2-PLR predicted fluid responsiveness with a sensitivity of 88.0% and specificity of 88.2%. CONCLUSIONS: The change of PETCO2 induced by passive leg raising is a non-invasive and easy way to predict fluid responsiveness in mechanically ventilated patients with septic shock.

Is compromised intestinal barrier integrity responsible for the poor prognosis in critically ill patients with pre-existing hyperglycemia?

BACKGROUND: Compromised intestinal barrier integrity can be independently driven by hyperglycemia, and both hyperglycemia and intestinal barrier injury are associated with poor prognosis in critical illness. This study investigated the intestinal barrier biomarkers in critically ill patients, to explore the role of compromised intestinal barrier integrity on the prognosis of critically ill patients with pre-existing hyperglycemia. METHODS: This was a retrospective observational study. The relationships between intestinal barrier biomarkers and glycated hemoglobin A1c (HbA1c), fasting blood glucose (FBG), indicators of clinical characteristics, disease severity, and prognosis in critically ill patients were investigated. Then the metrics mentioned above were compared between survivors and non-survivors, the risk factors of 90-day mortality were investigated by logistic regression analysis. Further, patients were divided into HbA1c < 6.5% Group and HbA1c ≥ 6.5% Group, metrics mentioned above were compared between these two groups. RESULTS: A total of 109 patients with critical illness were included in the study. D-lactate and lipopolysaccharide (LPS) were associated with sequential organ failure assessment (SOFA) score and 90-day mortality. LPS was an independent risk factor of 90-day mortality. DAO, NEU (neutrophil) proportion, temperature, lactate were lower in HbA1c ≥ 6.5% Group while D-lactate, LPS, indicators of disease severity and prognosis showed no statistical difference between HbA1c < 6.5% Group and HbA1c ≥ 6.5% Group. CONCLUSIONS: Intestinal barrier integrity is associated with the disease severity and prognosis in critical illness. Compromised intestinal barrier integrity might be responsible for the poor prognosis in critically ill patients with pre-existing hyperglycemia.