Xinfuli improves cardiac function, histopathological changes and attenuate cardiomyocyte apoptosis in rats with doxorubicin-induced cardiotoxicity

Background Xinfuli Granule （XG）, a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with dox- orubicin-induced cardiotoxicity. Methods Sprague-Dawley rats were treated with intraperitoneal injection of Doxorubicin （DOX, 2.5 mg/kg per week） for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline （control group） or different dosage of XG （0.675 g/kg per day, 1.35 g/kg per day, and 2.7g/kg per day, respectively） for six weeks. Transtho- racic echocardiography was performed to evaluate the left ventricular fractional shortening （LVFS） and left ventricular ejection fraction （LVEF） before and after the XG treatment and histopathologic changes were also examined. Myocardial cell apoptosis was detected by TUNEL staining. The expression of related genes and proteins were analyzed using immunohistochemical staining. Results Compared to those in the control group, rats in XG treated groups showed significantly improved cardiac function and milder cardiac histopathological changes, lower cardiomyocyte apoptosis index, higher expression of Bcl-2 and lower expression of Bax. Conclusions Administration of XG improves cardiac function and histopathological changes in rats with doxorubicin-induced cardiotoxicity. These effects are associated with inhibition of cardiomyocyte apoptosis, perhaps via regulation of Bcl-2 and Bax protein expression.

A novel phenotype with splicing mutation identified in a Chinese family with desminopathy

Background:Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations.Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia.Combined with genotype, it helps us precisely diagnose and treat for desminopathy.Methods:Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing.Phenotypes were analyzed based on clinical characteristics associated with desminopathy.Results:A splicing mutation (c.735+1G>T) in DES was detected in the proband.A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons.Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium.There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified.Conclusions:We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy.Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.