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21.
Ethan L. Sanford Kwong W. Choy Patricia K. Donahoe Adam A. Tracy Regis Hila Maria Loscertales Mauro Longoni 《PloS one》2016,11(2)
Congenital diaphragmatic hernia is associated with pulmonary hypoplasia and respiratory distress, which result in high mortality and morbidity. Although several transgenic mouse models of lung hypoplasia exist, the role of miRNAs in this phenotype is incompletely characterized. In this study, we assessed microRNA expression levels during the pseudoglandular to canalicular phase transition of normal human fetal lung development. At this critical time, when the distal respiratory portion of the airways begins to form, microarray analysis showed that the most significantly differentially expressed miRNA was miR-449a. Prediction algorithms determined that N-myc is a target of miR-449a and identified the likely miR-449a:N-myc binding sites, confirmed by luciferase assays and targeted mutagenesis. Functional ex vivo knock-down in organ cultures of murine embryonic lungs, as well as in ovo overexpression in avian embryonic lungs, suggested a role for miR-449a in distal epithelial proliferation. Finally, miR-449a expression was found to be abnormal in rare pulmonary specimens of human fetuses with Congenital Diaphragmatic Hernia in the pseudoglandular or canalicular phase. This study confirms the conserved role of miR-449a for proper pulmonary organogenesis, supporting the delicate balance between expansion of progenitor cells and their terminal differentiation, and proposes the potential involvement of this miRNA in human pulmonary hypoplasia. 相似文献
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Ting Zhu Shu An Man‐Ting Choy Junhao Zhou Shanshan Wu Shihua Liu Bangdong Liu Zhicheng Yao Xun Zhu Jueheng Wu Zhenjian He 《Journal of cellular and molecular medicine》2019,23(3):1852-1864
Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumours, including non‐small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of their specific association with NSCLC have not been fully elucidated. Here, we report that a cytoplasmic lncRNA, DUXAP9‐206 is overexpressed in NSCLC cells and closely related to NSCLC clinical features and poor patient survival. We reveal that DUXAP9‐206 induced NSCLC cell proliferation and metastasis by directly interacting with Cbl‐b, an E3 ubiquitin ligase, and reducing the degradation of epidermal growth factor receptor (EGFR) and thereby augmenting EGFR signaling in NSCLC. Notably, correlations between DUXAP9‐206 and activated EGFR signaling were also validated in NSCLC patient specimens. Collectively, our findings reveal the novel molecular mechanisms of DUXAP9‐206 in mediating the progression of NSCLC and DUXAP9‐206 may serve as a potential target for NSCLC therapy. 相似文献
24.
Peirlinck M. Sahli Costabal F. Sack K. L. Choy J. S. Kassab G. S. Guccione J. M. De Beule M. Segers P. Kuhl E. 《Biomechanics and modeling in mechanobiology》2019,18(6):1987-2001
Biomechanics and Modeling in Mechanobiology - Heart failure is a progressive chronic condition in which the heart undergoes detrimental changes in structure and function across multiple scales in... 相似文献
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Daiwen Yang Ronald A. Venters Geoffrey A. Mueller W.Y. Choy Lewis E. Kay 《Journal of biomolecular NMR》1999,14(4):333-343
HNCO-based 3D pulse schemes are presented for measuring 1HN-15N,15N-13CO, 1HN-13CO,13CO-13C and 1HN-13C dipolar couplings in 15N,13C,2-labeled proteins. The experiments are based on recently developed TROSY methodology for improving spectral resolution and sensitivity. Data sets recorded on a complex of Val, Leu, Ile (1 only) methyl protonated 15N,13C,2H-labeled maltose binding protein and -cyclodextrin as well as 15N,13C,2H-labeled human carbonic anhydrase II demonstrate that precise dipolar couplings can be obtained on proteins in the 30–40 kDa molecular weight range. These couplings will serve as powerful restraints for obtaining global folds of highly deuterated proteins. 相似文献
27.
Inhibition of glucose uptake and suppression of glucose transporter 1 mRNA expression in L929 cells by tumour necrosis factor-alpha 总被引:1,自引:0,他引:1
Liong E Kong SK Au KK Li JY Xu GY Lee YL Kwok TT Choy YM Lee CY Fung KP 《Life sciences》1999,65(15):PL215-PL220
Recombinant human tumour necrosis factor-alpha (rhTNF-alpha) arrested the growth and suppressed glucose uptake of mouse fibrosarcoma L929 cells in vitro. When the cells were treated with rhTNF-alpha for 24 hours, the mRNA level of glucose transporter 1 (GLUT 1), which is the only GLUT found to be present in L929 cells in our study, was suppressed in a dose-dependent manner. Since the growth of tumour cells depends mainly on glucose catabolism, our findings may indicate that rhTNF-alpha inhibits L929 cells growth by lowering the glucose transport through suppression of GLUT 1 mRNA expression in the cells. 相似文献
28.
Association of active caspase 8 with the mitochondrial membrane during apoptosis: potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion-endoplasmic reticulum cross talk in etoposide-induced cell death
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Chandra D Choy G Deng X Bhatia B Daniel P Tang DG 《Molecular and cellular biology》2004,24(15):6592-6607
It was recently demonstrated that during apoptosis, active caspase 9 and caspase 3 rapidly accumulate in the mitochondrion-enriched membrane fraction (D. Chandra and D. G. Tang, J. Biol. Chem.278:17408-17420, 2003). We now show that active caspase 8 also becomes associated with the membranes in apoptosis caused by multiple stimuli. In MDA-MB231 breast cancer cells treated with etoposide (VP16), active caspase 8 is detected only in the membrane fraction, which contains both mitochondria and endoplasmic reticulum (ER), as revealed by fractionation studies. Immunofluorescence microscopy, however, shows that procaspase 8 and active caspase 8 predominantly colocalize with the mitochondria. Biochemical analysis demonstrates that both procaspase 8 and active caspase 8 are localized mainly on the outer mitochondrial membrane (OMM) as integral proteins. Functional analyses with dominant-negative mutants, small interfering RNAs, peptide inhibitors, and Fas-associated death domain (FADD)- and caspase 8-deficient Jurkat T cells establish that the mitochondrion-localized active caspase 8 results mainly from the FADD-dependent and tumor necrosis factor receptor-associated death domain-dependent mechanisms and that caspase 8 activation plays a causal role in VP16-induced caspase 3 activation and cell death. Finally, we present evidence that the OMM-localized active caspase 8 can activate cytosolic caspase 3 and ER-localized BAP31. Cleavage of BAP31 leads to the generation of ER- localized, proapoptotic BAP20, which may mediate mitochondrion-ER cross talk through a Ca(2+)-dependent mechanism. 相似文献
29.
A quantitative analysis of 2D 1H-15N spectra is often complicated by resonance overlap. Here a simple method is presented for resolving overlapped correlations by recording 2D projection planes from HNCO data sets. Applications are presented involving the measurement of 15N T1 relaxation rates in a high molecular weight protein, malate synthase G, and in a system that exchanges between folded and unfolded states, the drkN SH3 domain. By supplementing relaxation data recorded in the conventional way as a series of 2D 1H-15N data sets with a series of a pair of projection planes the number of dynamics probes is increased significantly for both systems studied. 相似文献
30.
The potential role of green tea polyphenol (GtPP) in preserving the human saphenous vein was investigated under physiological conditions. The vein segments were incubated for 1, 3, 5, 7 and 14 days, either after 4h of treatment with 1.0mg/ml GtPP or in the presence of GtPP at the same concentration. After incubation, the endothelial cell viability, endothelial nitric oxide synthase (eNOS) expression and the vein histology were evaluated. When the veins were not treated with GtPP, the viability of the endothelial cells was significantly reduced with the progress in the culture time, and none of the cells expressed eNOS after 5 days. Furthermore, severe histological changes and structural damage were observed in the non-treated veins. In contrast, incubating the veins after 4h of GtPP treatment significantly prevented these phenomena. The cellular viability of the GtPP-treated vein was approximately 64% after 7 days, and eNOS expression was maintained up to 40%, compared to that of the fresh vein. The histological observations showed that the vasculature was quite similar to that of the fresh vein. When incubated with GtPP, the vein could also be preserved for 1 week under physiological conditions retaining both its cellular viability (61%) and eNOS expression level (45%) and maintaining its venous structure without any morphological changes. These results demonstrate that GtPP treatment may be a useful method for preserving the HSV. 相似文献