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EPO analogues are representative glycoprotein drugs composed of heterogeneous, multiple antennary N‐glycans. NESP® and Aranesp® are hyperglycosylated EPO, marketed under the same international nonproprietary name as darbepoetin alfa. The multiple antennary N‐glycans are a key factor that increases the half‐life of the drug in the body, which is closely related to efficacy. Thus, control of N‐glycosylation is important in providing patients with consistent efficacy. This paper reports on the comprehensive characterization of N‐glycosylation of darbepoetin alfa products. The results of N‐glycan analysis of NESP® and Aranesp® showed difference in the ratio of N‐glycans containing N‐acetyllactosamine and O‐acetylated sialic acid. Although there were some differences, the overall N‐glycan structures and profiles were comparable. In particular, darbepoetin alfa products accounted for the largest proportion of tetra‐sialo N‐glycans, greater than 75%. This study increases understanding of N‐glycan profiles and structural information of darbepoetin alfa. [ABSTRACT FROM AUTHOR]

This study examined the effects of the Durunuri programme in Korea, a Making Work Pay policy initiated in 2012 that subsidises social insurance contributions of low‐wage workers in workplaces with fewer than 10 employees. Using a nationally representative sample of Korean low‐wage workers between the years 2010 and 2015, the study employs a difference‐in‐differences method to isolate the effect of the Durunuri programme on workers' subscription rate to the national pension and employment insurance programmes. Results indicated that, compared with ineligible low‐wage workers in workplaces with 10 or more but fewer than 30 employees, eligible low‐wage workers in workplaces with fewer than 10 employees were found to experience an increase in the odds of being subscribed to both the national pension and employment insurance programmes during the first, second and third year following implementation of the Durunuri programme. Policy implications as well as future policy modifications are further discussed. [ABSTRACT FROM AUTHOR]

Abstract: In vitro anti-resorptive activity, mechanism of action, pharmacokinetic profile and in vivo anti-resorptive activity of N 1,N 1-diisopropyl-N 2-(diphenylphosphoryl)-2-(4-nitrophenyl)acetamidine (1) were evaluated. [Copyright &y& Elsevier]

The histone H3K27 demethylase, UTX, is a known component of the H3K4 methyltransferase MLL complex, but its functional association with H3K4 methylation in human cancers remains largely unknown. Here we demonstrate that UTX loss induces epithelial-mesenchymal transition (EMT)-mediated breast cancer stem cell (CSC) properties by increasing the expression of the SNAIL, ZEB1 and ZEB2 EMT transcription factors (EMT-TFs) and of the transcriptional repressor CDH1. UTX facilitates the epigenetic silencing of EMT-TFs by inducing competition between MLL4 and the H3K4 demethylase LSD1. EMT-TF promoters are occupied by c-Myc and MLL4, and UTX recognizes these proteins, interrupting their transcriptional activation function. UTX decreases H3K4me2 and H3 acetylation at these promoters by forming a transcriptional repressive complex with LSD1, HDAC1 and DNMT1. Taken together, our findings indicate that UTX is a prominent tumour suppressor that functions as a negative regulator of EMT-induced CSC-like properties by epigenetically repressing EMT-TFs., (© 2015 The Authors.)

Cellular response to a hypertonic environment is important for fluid clearance in the lung. Hypertonicity modulates prostaglandin synthesis by influencing cyclooxygenase-2 (COX-2) expression in tissues such as liver and kidney via a mitogen-activated protein kinase (MAPK)-dependent pathway. However, little is known about COX-2 expression in response to hypertonicity in the lung. COX-2 mRNA accumulation induced by hypertonic NaCl was detected after 1 h of treatment, and COX-2 mRNA continued to accumulate until 18 h, the longest time point examined, in human alveolar epithelial A549 cells. This induction was a transcriptional event that occurred in the absence of the protein synthesis inhibitor cycloheximide and was the result of enhanced promoter activity, as examined with the use of full-length COX-2 promoter-driven reporter plasmids. The induction of COX-2 expression by hypertonic NaCl did not require the activation of NF-kappaB. The p38 MAPK inhibitor, SB203580, or MEK1/2 inhibitor, U0126, inhibited hypertonic induction of COX-2 expression. We examined whether the hypertonic induction of COX-2 was under the influence of glucocorticoid; we found that COX-2 promoter activity and mRNA and protein levels were depressed by dexamethasone and antagonized by the glucocorticoid receptor (GR) antagonist RU486. Our data demonstrate that the induction of COX-2 expression by hypertonic NaCl occurs independently of NF-kappaB and is inhibited by the GR in A549 cells.