[D-Ala2, D-Leu5]-enkephalin (DADLE) provides protection against myocardial ischemia reperfusion injury by inhibiting Wnt/ß-Catenin pathway.

BACKGROUND: Acute myocardial infarction is one of the leading causes of death worldwide. Myocardial ischemia reperfusion (MI/R) injury occurs immediately after the coronary reperfusion and aggravates myocardial ischemia. Whether the Wnt/ß-Catenin pathway is involved in the protection against MI/R injury by DADLE has not been evaluated. Therefore, the present study aimed to investigate the protective effect of DADLE against MI/R injury in a mouse model and to further explore the association between DADLE and the Wnt/ß-Catenin pathway. METHODS: Forty-four mice were randomly allocated to four groups: Group Control (PBS Control), Group D 0.25 (DADLE 0.25 mg/kg), Group D 0.5 (DADLE 0.5 mg/kg), and Group Sham. In the control and DADLE groups, myocardial ischemia injury was induced by occluding the left anterior descending coronary artery (LAD) for 45 min. PBS and DADLE were administrated, respectively, 5 min before reperfusion. The sham group did not go through LAD occlusion. 24 h after reperfusion, functions of the left ventricle were assessed through echocardiography. Myocardial injury was evaluated using TTC double-staining and HE staining. Levels of myocardial enzymes, including CK-MB and LDH, in the serum were determined using ELISA kits. Expression of caspase-3, TCF4, Wnt3a, and ß-Catenin was evaluated using the Western blot assay. RESULTS: The infarct area was significantly smaller in the DADLE groups than in the control group (P < 0.01). The histopathology score and serum levels of myocardial enzymes were significantly lower in the DADLE groups than in the control group (P < 0.01). DADLE significantly improved functions of the left ventricle (P < 0.01), decreased expression of caspase-3 (P < 0.01), TCF4 (P < 0.01), Wnt3a (P < 0.05), and ß-Catenin (P < 0.01) compared with PBS. CONCLUSIONS: The present study showed that DADLE protected the myocardium from MI/R through suppressing the expression of caspase-3, TCF4, Wnt3a, and ß-Catenin and consequently improving functions of the left ventricle in I/R model mice. The TCF4/Wnt/ß-Catenin signaling pathway might become a therapeutic target for MI/R treatment.

Comparison of intravascular ultrasound-guided with angiography-guided double kissing crush stenting for patients with complex coronary bifurcation lesions: Rationale and design of a prospective, randomized, and multicenter DKCRUSH VIII trial.

BACKGROUND: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. TRIAL DESIGN: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. CONCLUSIONS: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.

Characterization of a novel multi-domain xylanase from Clostridium clariflavum with application in hydrolysis of corn cobs.

OBJECTIVES: To develop a novel multi-catalytic domain (CD) xylanase Xyn2083 from Clostridium clariflavum by expression of its truncated forms in Escherichia coli and cooperation of xylanase with cellulase in the hydrolysis of waste lignocellulosic resources. RESULTS: Xyn2083 has two glycoside hydrolase family (GH) domains GH11 and GH10. These two catalytic domains functioned synergistically in xylan hydrolysis. The recombinant protein with GH11 domain, Xyn2083GH11, had the highest xylanase activity among three constructed truncated forms. The deletion of N-terminal extra amino acid residues of Xyn2083GH11 decreased catalytic activity as well as the stability of the enzyme. The hydrolysis rates of cellulose and xylan in the pretreated corn cobs were 90.56% and 72.80% with the addition of Xyn2083GH11 and cellulase, whereas those were 67.95% and 34.45% using sole cellulase respectively. The structural analysis of substrates indicated that the addition of Xyn2083GH11 led to a looser structure and more exposure of crystal cellulose for cellulase to approach. CONCLUSIONS: Since the native multi-CDs' xylanases are rare, the thermostable Xyn2083 provides a good source for functional studies of two CDs coexisted in one xylanase and for potential applications after modification.