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Cardiac hypertrophy is a compensatory response to pathological stimuli, ultimately progresses to cardiomyopathy, heart failure, or sudden death. Although many signaling pathways have been reported to be involved in the hypertrophic process, it is still not fully clear about the underlying molecular mechanisms for cardiac hypertrophy. Hedgehog acyltransferase‐like (Hhatl), a sarcoplasmic reticulum‐resident protein, exhibits high expression in the heart and muscle. However, the biological role of Hhatl in the heart remains unknown. In this study, we first found that the expression level of Hhatl is markedly decreased in cardiac hypertrophy. We further studied the role of hhatla, homolog of Hhatl with the zebrafish model. The depletion of hhatla in zebrafish leads to cardiac defects, as well as an enhanced level of hypertrophic markers. Besides, we found that calcineurin signaling participates in hhatla depletion‐induced cardiac hypertrophy. Together, these results demonstrate a critical role for hhatla in cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

Cardiac hypertrophy is a common pathological change in patients with progressive cardiac function failure, which can be caused by hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) or arterial hypertension. Despite years of study, there is still limited knowledge about the underlying molecular mechanisms for cardiac hypertrophy. NDUFA7, a subunit of NADH:ubiquinone oxidoreductase (complex I), has been reported to be a novel HCM associated gene. However, the biological role of NDUFA7 in heart remains unknown. In this study, we found that NDUFA7 exhibited high expression in the heart, and its level was significantly decreased in mice model of cardiac hypertrophy. Moreover, we demonstrated that ndufa7 knockdown in developing zebrafish embryos resulted in cardiac development and functional defects, associated with increased expression of pathological hypertrophy biomarkers nppa (ANP) and nppb (BNP). Mechanistic study demonstrated that ndufa7 depletion promoted ROS production and calcineurin signalling activation. Moreover, NDUFA7 depletion contributed to cardiac cell hypertrophy. Together, these results report for the first time that ndufa7 is implicated in pathological cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

Background and Aim: Early life exposure to the famine may affect the susceptibility to the metabolic disorders. The objective of this study was to examine the associations of early life exposure to the Chinese Famine (1959-1961) with the risk of fatty liver disease, obesity, hypertension, and hyperglycemia in adulthood. Methods: We used the data of 10 935 adults born between 1956 and 1965 in Chongqing from check-up center at the 1st Affiliated Hospital of Chongqing Medical University in 2011. Logistic regression models were used to explore the effects of famine on the risk of fatty liver disease, obesity, hypertension, and hyperglycemia. Results In Chongqing, prevalences of fatty liver disease among adults in non-exposed (1956-1958 plus 1963-1965) group and born in 1959, 1960, 1961, and 1962 were 34.01%, 36.42%, 34.63%, 40.27%, and 36.09%, respectively. Prevalences of fatty liver disease, obesity, hypertension, and hyperglycemia were significantly higher in males versus females. The risk of fatty liver disease was about 1.375-fold (1.303 (95% confidence interval, 1.066-1.594) for male, 1.547(95% confidence interval, 1.195-2.002) for female) higher in subjects born in 1961, and 1.142-fold (1.117 (95% confidence interval, 0.957-1.305) for male, 1.242 (95% confidence interval, 1.003-1.537) for female) higher in subjects born in 1962 after adjustment of age and sex, compared with non-exposed subjects. Early life exposure to the Chinese famine was also associated with the increased risk of obesity and hyperglycemia. Conclusions: Exposure to the Chinese famine during fetal life and infancy was associated with an increased risk of fatty liver disease in adulthood. [ABSTRACT FROM AUTHOR]

Background: Vertebrate trunk induction requires inhibition of bone morphogenetic protein (BMP) signaling, whereas vertebrate head induction requires concerted inhibition of both Wnt and BMP signaling. RNA binding proteins play diverse roles in embryonic development and their roles in vertebrate head development remain to be elucidated. Results: We first characterized the human RBM47 as an RNA binding protein that specifically binds RNA but not single-stranded DNA. Next, we knocked down rbm47 gene function in zebrafish using morpholinos targeting the start codon and exon-1/intron-1 splice junction. Down-regulation of rbm47 resulted in headless and small head phenotypes, which can be rescued by a wnt8a blocking morpholino. To further reveal the mechanism of rbm47's role in head development, microarrays were performed to screen genes differentially expressed in normal and knockdown embryos. epcam and a2ml were identified as the most significantly up- and down-regulated genes, respectively. The microarrays also confirmed up-regulation of several genes involved in head development, including gsk3a, otx2, and chordin, which are important regulators of Wnt signaling. Conclusions: Altogether, our findings reveal that Rbm47 is a novel RNA-binding protein critical for head formation and embryonic patterning during zebrafish embryogenesis which may act through a Wnt8a signaling pathway. Developmental Dynamics 242:1395-1404, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Dysregulation of fibroblast growth factor receptor 3 (FGFR3) by the translocation t(4;14)(p16;q32) occurs in 15% of multiple myeloma (MM) patients and confers a growth and survival advantage to malignant plasma cells. As FGFR3 is a molecular target, we assessed the therapeutic potential of the FGFR-specific tyrosine kinase inhibitors SU5402 and SU10991 in MM. SU5402 inhibited FGFR3 phosphorylation in vitro and in murine MM tumour models. B cells dependent on FGFR3 for survival were specifically sensitive to SU5402. A panel of 11 human myeloma cell lines was studied, five bearing the t(4;14) translocation. The KMS11 human myeloma cell line, which expresses constitutively active mutant FGFR3, displayed an 85% decrease in S-phase cells, a 95% increase in G0/G1 cells, and 4.5-fold increase in apoptotic cells after 72 h treatment with 10 micromol/l SU5402. Activated extracellular signal-regulated kinases 1 and 2 and signal transducer and activator of transcription 3 were rapidly down-regulated after SU5402 treatment. In human myeloma cell lines expressing wild-type FGFR3 the stimulating effect of aFGF ligand was abrogated by SU5402 treatment. Myeloma cells lacking the t(4;14) or with the t(4;14) and a secondary RAS mutation did not respond to therapy. These findings support the development of clinical trials of early intervention with FGFR3 inhibitors in t(4;14) myeloma.