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Knockdown of MYSM1 alleviates DOX-induced cardiotoxicity. A. Workflow depicting intraperitoneal injection of DOX at a dosage of 15 mg/kg/ week (three times per week for 2 weeks) in Mysm1 −/+ mice. Cardiac function evaluation was performed four weeks after the first DOX injection. B-D. Levels of serum lactic dehydrogenase (LDH, B), creatine kinase-MB (CK-MB, C), and cardiac troponin T (cTnT, D) following DOX treatment (n = 7). E. Representative left ventricular M-mode echocardiographic images. F-G. Relative levels of ejection fraction (EF%, F) and fractional shortening (FS%, G) in mice (n = 7). H. Representative whole heart images. I. Representative images of hematoxylin and eosin (H&E) of whole heart sections. J-K. Ratio of heart weight to tibia length (HW/TL, J) and heart weight to body weight (HW/BW, K) (n = 7). L-M. Cardiomyocyte cross-sectional area was assessed by wheat germ agglutinin (WGA, L) and statistical results (M, n = 7). N. Representative images of longitudinal H&E sections of cardiac tissues. O-P. Representative images of Sirius Red (O) and quantification analysis (P, n = 7). Q-R. Detection of apoptotic DNA fragmentation in cardiac tissues by TUNEL staining (Q) and corresponding statistical results (R, n = 7). (* P < 0.05, ** P < 0.01, *** P < 0.001)
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Anthracycline antitumor drug doxorubicin (DOX) induces severe cardiotoxicity. Deubiquitinating enzymes (DUBs) are crucial for protein stability and function and play a significant role in cardiac pathophysiology. By comparing RNA sequencing datasets and conducting functional screening, we determined that Myb-like, SWIRM, and MPN domains 1 (MYSM1) i...
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... investigate the role of MYSM1 in DOX-induced cardiotoxicity, we generated Mysm1-deficient mice (Fig. S2A). Whole-body MYSM1 knockout mice have been reported to exhibit partial embryonic lethality, complex hematopoietic immune phenotypes, growth retardation, reduced lifespan, and abnormalities in tail morphology [11,12]. We also observed these phenomena during the generation of Mysm1 −/− mice (Fig. S2B). However, heterozygous Mysm1 −/+ mice ...
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... we generated Mysm1-deficient mice (Fig. S2A). Whole-body MYSM1 knockout mice have been reported to exhibit partial embryonic lethality, complex hematopoietic immune phenotypes, growth retardation, reduced lifespan, and abnormalities in tail morphology [11,12]. We also observed these phenomena during the generation of Mysm1 −/− mice (Fig. S2B). However, heterozygous Mysm1 −/+ mice ( Fig. S2C) did not display phenotypic abnormalities, such as growth retardation, tail morphology ( Fig. S2B), or abnormal blood parameters ( Fig. S2D-G). Therefore, we selected Mysm1 −/+ mice to validate the function of MYSM1 in DOX-induced cardiotoxicity. The DOX dose for WT and Mysm1 −/+ mice ...
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... S2A). Whole-body MYSM1 knockout mice have been reported to exhibit partial embryonic lethality, complex hematopoietic immune phenotypes, growth retardation, reduced lifespan, and abnormalities in tail morphology [11,12]. We also observed these phenomena during the generation of Mysm1 −/− mice (Fig. S2B). However, heterozygous Mysm1 −/+ mice ( Fig. S2C) did not display phenotypic abnormalities, such as growth retardation, tail morphology ( Fig. S2B), or abnormal blood parameters ( Fig. S2D-G). Therefore, we selected Mysm1 −/+ mice to validate the function of MYSM1 in DOX-induced cardiotoxicity. The DOX dose for WT and Mysm1 −/+ mice was 15 mg/kg/week (three times per week for 2 ...
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... complex hematopoietic immune phenotypes, growth retardation, reduced lifespan, and abnormalities in tail morphology [11,12]. We also observed these phenomena during the generation of Mysm1 −/− mice (Fig. S2B). However, heterozygous Mysm1 −/+ mice ( Fig. S2C) did not display phenotypic abnormalities, such as growth retardation, tail morphology ( Fig. S2B), or abnormal blood parameters ( Fig. S2D-G). Therefore, we selected Mysm1 −/+ mice to validate the function of MYSM1 in DOX-induced cardiotoxicity. The DOX dose for WT and Mysm1 −/+ mice was 15 mg/kg/week (three times per week for 2 weeks) ( Fig. 2A). Four weeks after the first injection of DOX, the cardiac function was evaluated. As ...
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... growth retardation, reduced lifespan, and abnormalities in tail morphology [11,12]. We also observed these phenomena during the generation of Mysm1 −/− mice (Fig. S2B). However, heterozygous Mysm1 −/+ mice ( Fig. S2C) did not display phenotypic abnormalities, such as growth retardation, tail morphology ( Fig. S2B), or abnormal blood parameters ( Fig. S2D-G). Therefore, we selected Mysm1 −/+ mice to validate the function of MYSM1 in DOX-induced cardiotoxicity. The DOX dose for WT and Mysm1 −/+ mice was 15 mg/kg/week (three times per week for 2 weeks) ( Fig. 2A). Four weeks after the first injection of DOX, the cardiac function was evaluated. As shown in Fig. 2B-D, serum cardiac injury ...
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... S2C) did not display phenotypic abnormalities, such as growth retardation, tail morphology ( Fig. S2B), or abnormal blood parameters ( Fig. S2D-G). Therefore, we selected Mysm1 −/+ mice to validate the function of MYSM1 in DOX-induced cardiotoxicity. The DOX dose for WT and Mysm1 −/+ mice was 15 mg/kg/week (three times per week for 2 weeks) ( Fig. 2A). Four weeks after the first injection of DOX, the cardiac function was evaluated. As shown in Fig. 2B-D, serum cardiac injury markers LDH, CK-MB, and cTnT were significantly decreased in Mysm1 −/+ mice compared to WT mice after DOX treatment. Non-invasive transthoracic echocardiography revealed that Mysm1 −/+ mice significantly ...
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... or abnormal blood parameters ( Fig. S2D-G). Therefore, we selected Mysm1 −/+ mice to validate the function of MYSM1 in DOX-induced cardiotoxicity. The DOX dose for WT and Mysm1 −/+ mice was 15 mg/kg/week (three times per week for 2 weeks) ( Fig. 2A). Four weeks after the first injection of DOX, the cardiac function was evaluated. As shown in Fig. 2B-D, serum cardiac injury markers LDH, CK-MB, and cTnT were significantly decreased in Mysm1 −/+ mice compared to WT mice after DOX treatment. Non-invasive transthoracic echocardiography revealed that Mysm1 −/+ mice significantly alleviated DOX-induced cardiac dysfunction, indicated by ejection fraction (EF%) and fractional shortening ...
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... Fig. 2B-D, serum cardiac injury markers LDH, CK-MB, and cTnT were significantly decreased in Mysm1 −/+ mice compared to WT mice after DOX treatment. Non-invasive transthoracic echocardiography revealed that Mysm1 −/+ mice significantly alleviated DOX-induced cardiac dysfunction, indicated by ejection fraction (EF%) and fractional shortening (FS%) (Fig. 2E-G (Fig. 2N), myocardial fibrosis ( Fig. 2O-P) and cell death (Fig. 2Q-R). These results suggested that knockdown of MYSM1 alleviated DOX-induced ...
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... serum cardiac injury markers LDH, CK-MB, and cTnT were significantly decreased in Mysm1 −/+ mice compared to WT mice after DOX treatment. Non-invasive transthoracic echocardiography revealed that Mysm1 −/+ mice significantly alleviated DOX-induced cardiac dysfunction, indicated by ejection fraction (EF%) and fractional shortening (FS%) (Fig. 2E-G (Fig. 2N), myocardial fibrosis ( Fig. 2O-P) and cell death (Fig. 2Q-R). These results suggested that knockdown of MYSM1 alleviated DOX-induced ...
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... CK-MB, and cTnT were significantly decreased in Mysm1 −/+ mice compared to WT mice after DOX treatment. Non-invasive transthoracic echocardiography revealed that Mysm1 −/+ mice significantly alleviated DOX-induced cardiac dysfunction, indicated by ejection fraction (EF%) and fractional shortening (FS%) (Fig. 2E-G (Fig. 2N), myocardial fibrosis ( Fig. 2O-P) and cell death (Fig. 2Q-R). These results suggested that knockdown of MYSM1 alleviated DOX-induced ...
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... decreased in Mysm1 −/+ mice compared to WT mice after DOX treatment. Non-invasive transthoracic echocardiography revealed that Mysm1 −/+ mice significantly alleviated DOX-induced cardiac dysfunction, indicated by ejection fraction (EF%) and fractional shortening (FS%) (Fig. 2E-G (Fig. 2N), myocardial fibrosis ( Fig. 2O-P) and cell death (Fig. 2Q-R). These results suggested that knockdown of MYSM1 alleviated DOX-induced ...
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