Mao-to Prolongs the Survival of and Reduces TNF-α Expression in Mice with Viral Myocarditis

Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC) virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n = 18), while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mg−1 kg−1 day−1) from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW) and organ weights including heart (HW), lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4%) was significantly improved compared with group A, B or D (0% of each, P < 0.05). HW and HW/BW ratio in group C was significantly (P < 0.05) lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-α (TNF-α) was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-α. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis

DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange

RAD51, an essential eukaryotic DNA recombinase, promotes homologous pairing and strand exchange during homologous recombination and the recombinational repair of double strand breaks. Mutations that up- or down-regulate RAD51 gene expression have been identified in several tumors, suggesting that inappropriate expression of the RAD51 activity may cause tumorigenesis. To identify chemical compounds that affect the RAD51 activity, in the present study, we performed the RAD51-mediated strand exchange assay in the presence of 185 chemical compounds. We found that 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) efficiently inhibited the RAD51-mediated strand exchange. DIDS also inhibited the RAD51-mediated homologous pairing in the absence of RPA. A surface plasmon resonance analysis revealed that DIDS directly binds to RAD51. A gel mobility shift assay showed that DIDS significantly inhibited the DNA-binding activity of RAD51. Therefore, DIDS may bind near the DNA binding site(s) of RAD51 and compete with DNA for RAD51 binding

Ultra-large single crystals by abnormal grain growth

金属分野の常識を打ち破る、単結晶成長メカニズムを解明 --形状記憶合金の量産プロセス開発で耐震分野の実用化に道筋 --. 京都大学プレスリリース. 2017-08-28.Producing a single crystal is expensive because of low mass productivity. Therefore, many metallic materials are being used in polycrystalline form, even though material properties are superior in a single crystal. Here we show that an extraordinarily large Cu-Al-Mn single crystal can be obtained by abnormal grain growth (AGG) induced by simple heat treatment with high mass productivity. In AGG, the sub-boundary energy introduced by cyclic heat treatment (CHT) is dominant in the driving pressure, and the grain boundary migration rate is accelerated by repeating the low-temperature CHT due to the increase of the sub-boundary energy. With such treatment, fabrication of single crystal bars 70 cm in length is achieved. This result ensures that the range of applications of shape memory alloys will spread beyond small-sized devices to large-scale components and may enable new applications of single crystals in other metallic and ceramics materials having similar microstructural features

Pulmonary hypertension predicts adverse cardiac events after restrictive mitral annuloplasty for severe functional mitral regurgitation

ObjectivesPulmonary hypertension (PH) is an indicator of a poor prognosis in patients with dilated cardiomyopathy. Few studies have investigated the prognostic role of PH in patients undergoing restrictive mitral annuloplasty (RMA) for severe functional mitral regurgitation secondary to advanced cardiomyopathy.MethodsA total of 46 patients undergoing RMA were classified into 3 groups on the basis of the Doppler-derived systolic pulmonary artery pressure (PAP) at baseline. Of the 46 patients, 19 had a systolic PAP less than 40 mm Hg (mild PH group), 17 had a systolic PAP of 40 to 60 mm Hg (moderate PH group), and 10 had a systolic PAP greater than 60 mm Hg (severe PH group).ResultsPostoperative cardiac catheterization showed that the RMA procedure resulted in a significant reduction of the left ventricular (LV) preload and improvements in LV systolic function in all 3 groups, along with the relief of symptoms. During the follow-up period (mean, 36 ± 19 months), cardiac death occurred in 6 patients, readmission because of heart failure in 3, and fatal arrhythmia in 1. The rate of freedom from these cardiac events at 3 years was 93% ± 7%, 88% ± 8%, and 56% ± 17% in the mild, moderate, and severe PH groups (P < .001). Serial echocardiography showed that significant LV reverse remodeling occurred in 89%, 71%, and 25% of the mild, moderate, and severe PH groups, respectively. Multivariate Cox regression analysis identified severe PH (systolic PAP > 60 mm Hg) as a significant predictor of adverse cardiac events, as well as LV remodeling after RMA.ConclusionsNoninvasive assessment of preoperative PH has a prognostic value in patients undergoing RMA for severe functional mitral regurgitation secondary to advanced cardiomyopathy