Project description:Doxorubicin (DOX) is a first-line chemotherapeutic agent widely used in the treatment of various cancers, but its clinical efficacy is limited by its early and late cardiotoxic effects. Prior to the visible morphological manifestation of lesions in cardiomyocytes after exposure to DOX, they can detect damage and initiate a complex cascade of responses, including the modulation of gene expression, including the regulation of microRNAs (miRNAs).In this study, we used small RNA sequencing to evaluate miRNA expression levels in cardiomyocytes exposed to DOX at a concentration of 10 μM for periods of 1 and 22 hours, compared to unexposed cells. By analyzing the normalized data and using DESeq2, we identified significant changes in the expression of certain miRNAs in DOX-treated cells. These miRNAs emerge as promising biomarker candidates that, if further investigated, could provide a valuable early detection tool for DOX sensitivity and guide the timely administration of cardioprotective agents.
Project description:We wanted to analyze the global gene expression to unravel molecular mechanisms underlying the combined action of DOX and IFNγ in mouse cardiomyocytes. We treated the cardiomyocytes respectively with PBS, DOX and DOX plus IFN-γ, and the differentially expressed genes and the gene expression patterns were supposed to be analyzed.
Project description:Doxorubicin (DOX) and other anthracyclines are effective chemotherapeutic agents, however, their use is influenced by the risk of cardiotoxicity. We still have an incomplete understanding of the cardiomyocyte protective pathways activated after anthracycline-induced cardiotoxicity (AIC).Danshen injection (DSI), astaxanthin (AXT) and diosmetin (DMT) are effective in the treatment of cardiovascular diseases, but the mechanism of protection against adriamycin-induced cardiotoxicity is unclear. Here, we performed RNA-seq screening in H9c2 cardiomyocytes to determine the potential protective mechanisms of Danshen injection, astaxanthin and diosmetin against AIC.
Project description:A Comprehensive Study To Decipher The Impact Of Simulated Microgravity On Human Induced Pluripotent Stem Cell-derived Cardiomyocytes
Project description:Phosphodiesterase 10A (PDE10A), by degrading cAMP/cGMP, play critical roles in cardiovascular biology/disease. Cardiotoxicity is a clinical complication of chemotherapy. We aim to determine the role of PDE10A in cancer growth and cardiotoxicity induced by doxorubicin (DOX), a chemotherapy drug. We found that PDE10A deficiency/inhibition alleviated DOX-induced cardiotoxicity in C57Bl/6J mice, including myocardial atrophy, apoptosis, and dysfunction. RNAseq study revealed several PDE10A-regulated signaling associated with DOX-induced cardiotoxicity. In cancer cells, PDE10A inhibition increased the death, decreased the proliferation, and potentiated the effect of DOX in various cancer-cell lines. Importantly, in nude mice with implanted ovarian cancer xenografts, PDE10A inhibition attenuated tumor growth while protected against DOX-induced cardiotoxicity. In isolated cardiomyocytes (CMs), PDE10A contributed to DOX-induced CM death via promoting mitochondrial dysfunction, and to CM atrophy via potentiating foxo3 signaling. Collectively, our study elucidates a novel role for PDE10A in cardiotoxicity and cancer growth in vitro and in vivo, and suggest that PDE10A inhibition may represent a novel strategy in cancer therapy.
Project description:SAGE identification of differentiation responsive genes in P19 embryonic cells induced to form cardiomyocytes in vitro. P19 embryonic carcinoma (EC) cells, induced to form cardiomyocytes in vitro - undifferentiated cells, day 3+0.5 and day 3+3.0 of differentiation protocol. Keywords = EC cells, P19, differentiation, cardiomyocytes Keywords: time-course