Synthesis, biological evaluation and docking studies of N-substituted resveratrol derivatives.

A total of 19 resveratrol derivatives, including 12 imines and 7 amines, were synthesized, among which compounds 1, 5, 6, 7', 11', and 13 are new compounds. The anti-inflammatory and antitumor activities of these compounds were evaluated in vitro. The results revealed that compounds 1, 6, 8', 12, and 12' exhibited significant inhibitory effects (> 50%) on NO production at the concentration of 10 µM and their NO production inhibitory activities have a significant concentration-dependent ability. Additionally, compounds 8' and 12' showed promising COX-2 inhibitory activity, and the molecular docking analysis indicated their stable binding to multiple amino acid residues within the active pocket of COX-2 through hydrogen bonding. Moreover, compound 12' exhibited inhibitory effects on various tumor cell lines and induced apoptosis in MCF-7 breast cancer cells, which was not observed with resveratrol alone. Therefore, the N-substituted structural modification of resveratrol would have possibly enhanced the bioactivity of resveratrol and facilitated its application.

Effect of intralipid on myocardial injury during valve replacement surgery with concomitant radiofrequency ablation: A randomized controlled trial.

BACKGROUND: This study aimed to evaluate the effect of intralipid postconditioning (ILPC) on myocardial damage in patients undergoing valve replacement surgery with concomitant radiofrequency ablation (RFA) for atrial fibrillation (AF). METHODS: Randomized patient and assessor-blind controlled trial conducted in adult patients undergoing valve replacement surgery with concomitant RFA. Sixty-nine patients were randomly assigned to ILPC group (n = 34) or control group (n = 35): ILPC group received an intravenous infusion of 20% intralipid (2 mL/kg) just 10 minutes before aortic cross-unclamping, and control group received an equivalent volume of normal saline. Serum cardiac troponin-T (cTnT) and creatine kinase-MB (CK-MB) was measured before surgery and at 4, 12, 24, 48, and 72 hours after surgery. The primary endpoints were the 72-hour area under the curve (AUC) for cTnT and CK-MB. RESULTS: The total 72-hour AUC of cTnT (P = .33) and CK-MB (P = .52) were comparable between 2 groups. The left ventricle ejection fraction at discharge (P = .011) was higher in the ILPC group than that in the control group, while the AF recurrence did not differ significantly between 2 groups. CONCLUSIONS: There was no observed beneficial effect of ILPC on myocardial injury documented by the cardiac biomarkers in patients undergoing valve replacement surgery with concomitant RFA, and the effect of intralipid against myocardial I/R injury is undetectable within the background of massive biomarker release following ablation owing to localized myocardial necrosis. Besides, there are no other published data about the cardioprotective role of intralipid in patients undergoing this procedure and benefits of this protection need further studies to validate.

Effect of intralipid postconditioning on myocardial injury in patients undergoing valve replacement surgery: a randomised controlled trial.

OBJECTIVE: This study was conducted to determine whether the administration of intralipid just before aortic cross-unclamping would reduce myocardial injury in patients undergoing valve replacement surgery. METHODS: Seventy-three adult patients, scheduled for elective aortic or mitral valve surgery without significant coronary stenosis (>70%), were randomly assigned to the intralipid postconditioning (ILPC) group (n=37) or control group (n=36): the ILPC group received an intravenous infusion of 20% intralipid (2 mL/kg) just 10 min before aortic cross-unclamping, and the control group received an equivalent volume of normal saline. Serum cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB) was measured before surgery and at 4, 12, 24, 48 and 72 hours after surgery. The primary end points were the 72-hour area under the curve (AUC) for cTnT and CK-MB. RESULTS: No significant difference between the ILPC and control arm was observed, including the age, sex or number of aortic versus mitral valves or left ventricular ejection fraction at baseline. The total 72-hour AUC of cTnT and CK-MB in patients assigned to ILPC were significantly reduced by 32.3% (p=0.004) and 26.4% (p=0.0185) compared with control, respectively. None of the treated patients had abnormal blood lipid metabolism, abnormal renal or hepatic function or significant related complications. CONCLUSION: The protective effect of postischaemic administration of intralipid prior to aortic cross-unclamping on reperfusion injury was found when determined by biomarkers of myocardial injury but not by cardiac function or other clinical outcomes in patients undergoing valve replacement surgery. Hence, clinical benefits of this protection need larger clinical trials to confirm. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: ChiCTR-IOR-14005318.

Mannitol-adenine-phosphate: a novel solution for intraoperative blood salvage.

BACKGROUND: Intraoperative blood salvage (IBS) procedures include washing with normal saline (NS), which may deplete red blood cell (RBC) nutrients. The mannitol-adenine-phosphate (MAP) solution, commonly used for RBC preservation, provides glycolytic substrates; therefore, MAP should be a better solution than NS in IBS. In this study, we determined whether using MAP could reduce washing-associated RBC damage and destruction. STUDY DESIGN AND METHODS: Adenine nucleotide contents, RBC morphology, and plasma free hemoglobin (PF-Hb) level of RBCs treated with NS or MAP solution were compared under three conditions: (1) 4-hour preservation of fresh blood from healthy volunteers, (2) collection from the shed blood of patients, and 3) incubation of the collected shed blood with plasma. RESULTS: Adenine nucleotide level and RBC elongation index were greater and PF-Hb level was lower in MAP groups than NS groups (p < 0.05) after preservation and incubation. In NS, RBCs lost their deformability and became stomatocytes, and even RBC "ghosts" 48 hours after incubation, while they remained normal in MAP solution. CONCLUSION: The MAP solution helps preserve RBC morphology and function, and reduces hemolysis, possibly due to improved energy production. Therefore, MAP should replace NS during IBS.