Ellagitannin-derived ellagic acid (EA) and colonic metabolite urolithins are functional dietary ingredients for cancer prevention, but the underlying mechanism need elucidation. Mucin-type O-glycosylation, initiated by polypeptide N-acetyl-α-galactosaminyltransferases (ppGalNAc-Ts), fine-tunes multiple biological processes and is closely associated with cancer progression. Herein, we aim to explore how specific tannin-based polyphenols affect tumor behavior of colorectal cancer cells (CRC) by modulating O-glycosylation. Utilizing HPLC-based enzyme assay, we find urolithin D (UroD), EA and gallic acid (GA) potently inhibit ppGalNAc-Ts. In particular, UroD inhibits ppGalNAc-T2 through a peptide/protein-competitive manner with nanomolar affinity. Computational simulations combined with site-directed mutagenesis further support the inhibitors’ mode of action. Moreover, lectin analysis and metabolic labelling reveal that UroD can reduce cell O-glycans but not N-glycans. Transwell experiments prove that UroD inhibits migration and invasion of CRC cells. Our work proves that specific tannin-based polyphenols can potently inhibit ppGalNAc-Ts activity to reduce cell O-glycosylation and lead to lowering the migration and invasion of CRC cells, suggesting that disturbance of mucin-type O-glycosylation is an important mechanism for the function of dietary polyphenols. 相似文献
Online water bioburden analyzers (OWBAs) can provide real-time feedback on viable bacteria in high-purity water (HPW) systems for pharmaceutical manufacturers. To calibrate and validate OWBAs, which detect bacteria using scattered light and bacterial autofluorescence, standards are needed that mimic the characteristics of bacteria in HPW. To guide selection of potential standards, e.g., fluorescent microspheres, a relevant bacterial contaminant, Ralstonia pickettii, was characterized for size, count, viability, and autofluorescence after exposure for 24 h to HPW or a nutrient environment. The cells exposed to HPW showed smaller sizes, with lower counts and autofluorescence intensities, but similar spectral features. The cell characteristics are discussed in comparison with a set of fluorescent microspheres, considering factors relevant to OWBAs. These studies suggest that fluorescent microspheres should be relatively small (< 1 µm diameter) and dim, while covering a broad emission range from ≈ (420 to 600) nm to best mimic the representative R. pickettii.
Objectives: The present study aims to evaluate the accuracy of the index of waist‐to‐height ratio (WHTR), and proposed the optimal thresholds of WHTR in the definition of childhood overweight and obesity in a bi‐ethnic Chinese school‐aged population. Research Methods and Procedures: Overweight and obese were identified by BMI for age and gender in a random sample including 2055 Han and 2132 Uygur ethnic school‐aged children (8 to 18 years old). WHTR was calculated by waist circumference divided by height on the basis of standard anthropometric measurements. Receiver operating characteristic (ROC) curve analyses were performed to assess the accuracy of WHTR as a diagnostic test for childhood overweight and obesity, compared with waist circumference. The optimal thresholds of WHTR for defining overweight and obesity were recommended respectively by gender. The correlation between WHTR and age was analyzed and compared with BMI. Results: A‐values (area under curve) of WHTR for diagnosing overweight and obesity were both over 0.90 in both genders and better than those of waist circumference. A threshold of 0.445 was identified for overweight in both genders, with the sensitivity and specificity >0.80. The thresholds for defining obesity was 0.485 in boys and 0.475 in girls, both having the sensitivity and specificity >0.90. WHTR showed less association with age than BMI. Conclusions: WHTR is a simple, easy, accurate, and non‐age‐dependent index with high applicability to screening overweight and obesity in children and adolescents. The use of WHTR in the general childhood population has been justified by this study. 相似文献
Here we report the NMR resonance assignments for the reduced form of human IgG1 CH3 domain, a 26 kDa dimer in solution (residues 341–447). The assignments have been deposited in the BioMagResBank with a BMRB
accession number of 15204. 相似文献