The authors' results suggest that propofol preserves connexin 43 phosphorylation during acute myocardial ischemia, as compared with sevoflurane, and this might protect the heart from serious ventricular arrhythmias during acute coronary occlusion.

reports of original investigations 595 CAN J ANESTH 55: 9 www.cja-jca.org September, 2008 Purpose: Propofol exerts cardioprotective effects, but the involved mechanisms remain obscure. The present study examines the cardioprotective effects of propofol and its role in cardiac function, including its effect on K ATP channel opening and the inhibition of GSK-3β activity in ischemia-reperfused hearts.Methods: Ischemia-reperfusion (I/R) was produced in isolated guinea pig hearts by stopping coronary perfusion for 25 min, followed by reperfusion. The hearts were incubated for ten minutes, with or without propofol (25 or 50 µM), or for five minutes with 500 µM 5-hydroxydecanoate (a mitochondrial K ATP channel blocker) or 30 µM HMR1098 (sarcolemmal K ATP channel blocker), followed by five minutes with 50 µM propofol before ischemia. Action potentials on the anterior epicardial surface of the ventricle were monitored using a high-resolution charge-coupled device camera system, and at five minutes after reperfusion, GSK-3β phosphorylation at the serine residue, Ser9, was examined.Results: After 35 min of reperfusion, propofol (25 and 50 µM) blunted the adverse effects of I/R and reduced infarct size (P < 0.05). In addition, prior incubation with 5-hydroxydecanoate or HMR1098 had no effect on functional recovery improved by 50 µM propofol. At five minutes after reperfusion, propofol (25 and 50 µM) shortened the duration of the action potential and increased the levels of phospho-GSK-3β (P < 0.05). Conclusions:Propofol enhanced mechanical cardiac recovery and reduced infarct size. The data further suggest that GSK-3β play an important role in propofol cardioprotective actions during coronary reperfusion, but mitochondrial K ATP channels do not. Objectif : Le propofol exerce des effets cardioprotecteurs, mais les mécanismes sous-jacents demeurent obscurs. Cette étude examine les effets cardioprotecteurs du propofol et son rôle dans la fonction cardiaque, notamment son effet sur l'ouverture du canal K ATP et l'inhibition de l'activité du GSK-3β dans des coeurs ischémiques puis reperfusés. Méthode : L'ischémie reperfusion (I/R) a été provoquée dans des coeurs isolés de cobayes en interrompant la per fusion

Argifin, a 17-membered pentapeptide, inhibits chitinase. As argifin has properties that render it unsuitable as a drug development candidate, we devised a mechanism to create the structural component of argifin that bestows the chitinase inhibition and introduce it into a 14-membered macrolide scaffold. Here we describe (1) the designed macrolide, which exhibits ∼200-fold more potent chitinase inhibition than argifin, (2) the binding modes of the macrolide with Serratia marcescens chitinase B, and (3) the computed analysis explaining the reason for derivatives displaying increased inhibition compared to argifin, the macrolide aglycone displaying inhibition in a nanomolar range. This promises a class of chitinase inhibitors with novel skeletons, providing innovative insight for drug design and the use of macrolides as adaptable, flexible templates for use in drug discovery research and development.

SUMMARYLateral roots (LRs) are critical to root system architecture development in plants. Although the molecular mechanisms by which auxin regulates LR development have been extensively studied, several additional regulatory systems are hypothesized to be involved. Recently, the regulatory role of very long chain fatty acids (VLCFAs) has been shown in LR development. Our analysis showed that LTPG1 and LTPG2, transporters of VLCFAs, are specifically expressed in the developing LR primordium (LRP), while the number of LRs is reduced in the ltpg1/ltpg2 double mutant. Moreover, late LRP development was hindered when the VLCFA levels were reduced by the VLCFA synthesis enzyme mutant, kcs1‐5. However, the details of the regulatory mechanisms of LR development controlled by VLCFAs remain unknown. In this study, we propose a novel method to analyze the LRP development stages with high temporal resolution using a deep neural network and identify a VLCFA‐responsive transcription factor, MYB93, via transcriptome analysis of kcs1‐5. MYB93 showed a carbon chain length‐specific expression response following treatment of VLCFAs. Furthermore, myb93 transcriptome analysis suggested that MYB93 regulated the expression of cell wall organization genes. In addition, we also found that LTPG1 and LTPG2 are involved in LR development through the formation of root cap cuticle, which is different from transcriptional regulation by VLCFAs. Our results suggest that VLCFA is a regulator of LRP development through transcription factor‐mediated regulation of gene expression and the transportation of VLCFAs is also involved in LR development through root cap cuticle formation.