Transcatheter mitral valve implantation using a novel system: preclinical results.

BACKGROUND: This preclinical study in sheep sought to demonstrate the initial safety and feasibility of a novel transcatheter mitral valve system (Mi-thos valve) composed of a self-expanding frame and a bovine pericardial tissue bioprosthesis. METHODS: The valve was implanted in 26 sheep using a transapical approach for short- and long-term evaluation. The technical feasibility, safety, durability, and valve function were evaluated during and 6 months after the procedure using intracardiac and transthoracic echocardiography, multisliced computed tomography, histological analysis, and electron microscopy. RESULTS: The success rate of valve implantation was 100%, and the immediate survival rate after surgery was 84%. Five animals died within 90 min after the development of the prosthetic valve due to an acute left ventricular outflow tract obstruction (n = 2) and sudden intraoperative ventricular fibrillation (n = 3). Twelve animals died within 1 month due to acute left heart dysfunction. Mild (n = 5) and moderate (n = 2) paravalvular leakage occurred in seven animals, and two moderate PVL animals died of chronic heart failure within three months. Multimodality imaging studies of the remaining seven animals showed excellent function and alignment of the valves, with no coronary artery obstruction, no left ventricular outflow tract obstruction, no severe transvalvular gradients and no paravalvular leakage. Macroscopic evaluation demonstrated stable, secure positioning of the valve, with full endothelialization of the valve leaflets without injury to the ventricular or atrial walls. Histological and electron microscopic examinations at six months showed no obvious macro- or microcalcification in the leaflets. CONCLUSIONS: Preclinical studies indicate that transcatheter implantation of the Mi-thos valve is technically safe and feasible. The durability, functionality, and lack of leaflet calcification were all verified in animal experiments. The information from these preclinical studies will be applied to patient selection criteria and the first-in-human studies.

Spatiotemporal distribution of Streptococcus agalactiae attenuated vaccine strain YM001 in the intestinal tract of tilapia and its effect on mucosal associated immune cells.

In this study, the tilapia was orally vaccinated by the attenuated Streptococcus agalactiae(S. agalactiae) strain YM001, and the distribution and the pathological effect of strain YM001 in different intestinal segments of tilapia were evaluated by real-time PCR(qPCR), immunohistochemistry(IHC) and histomorphology. The qPCR results showed that the number of bacteria was the highest in the intestinal tracts at 12 h post oral gavage in the YM001 group, then began to decrease sharply and eliminated at 7 d. And the number of bacteria was highest in the foregut, hindgut, and rectum at 12 h, 24 h, and 3 d, respectively. IHC indicated that bacteria mainly distributed in the margin epithelium and the goblet cells at 12 h - 24 h, and in the submucosa and muscle layer in the YM001 group in 3 d post gavage, then almost disappeared at 7 d. Histological examination of intestines post gavage displayed that an inflammation was observed at 7 d in the YM001 group and the intestinal structure was fully recovered at 15 d. and the intestinal structure was fully recovered at 15 d. Conclusion: The attenuated S. agalactiae vaccine strain YM001 could enter the intestinal tissue after oral gavage and had a strong spatial and temporal selectivity in the intestinal tract, which could cause obvious mucosal immune response and mild pathological reaction, but the pathological change could be gradually repaired with the extinction of bacteria in the body.

Naringenin ameliorates hypoxia/reoxygenation-induced endoplasmic reticulum stress-mediated apoptosis in H9c2 myocardial cells: involvement in ATF6, IRE1α and PERK signaling activation.

Naringenin, a flavanone mainly derived from grapes and citrus fruits, has been reported to exhibit cardioprotective effects. Accumulating evidence has confirmed that endoplasmic reticulum (ER) stress-mediated apoptosis participates in the process of myocardial ischemia/reperfusion injury and inhibiting ER stress is a potential therapeutic target/strategy in preventing cardiovascular diseases. Herein, the current study was designed to investigate whether naringenin protects H9c2 myocardial cells against hypoxia/reoxygenation (H/R) injury via attenuating ER stress or ER stress-mediated apoptosis. Our results showed that naringenin treatment resulted in obvious increases in the viability of H9c2 cells and the expression of Bcl-2 (anti-apoptotic protein), and decreases in the morphological changes of apoptotic cells, the activity of caspase-3 and the expression of Bax (pro-apoptotic protein) in H/R-treated H9c2 cells, implying the protective effects of naringenin against H/R-induced injury. In addition, naringenin also significantly reversed H/R-induced ER stress as evidenced by the up-regulation of Glucose-regulated protein 78, C/EBP homologous protein and Cleaved caspase-12 proteins. Meanwhile, naringenin remarkably reversed H/R-induced the increases in the expression of cleaved activating transcription factor 6 (ATF6) and phosphorylation levels of phospho-extracellular regulated protein kinases (PERK) and inositol-requiring enzyme-1α (IRE1α) in H9c2 cells. Finally, we found that ATF6 siRNA, PERK siRNA or IRE1α siRNA abolished H/R-induced cytotoxicity and apoptosis in H9c2 cells. In conclusion, these results confirmed that ER stress-mediated apoptosis contributes to the protection effects of naringenin against H/R injury, which is potentially involved in ATF6, IRE1α and PERK signaling activation.