Development of ETB Selective Agonists: Solution Structure of a Linear Endothelin-1 Analogue,ET-1 [Cys(Acm)1,15, Ala3, Leu7, dAsp8, Aib11]

Abstract

The solution structure of a synthetic ET_B selective agonist, ET-l[Cys(Acm)^1,15, Ala³, Leu⁷, dAsp⁸, Aib¹¹] has been solved by ¹H NMR and molecular modelling studies. Such solution structures of linear modified peptides in aqueous methanol are being used in an ongoing program of research designed to assist in an understanding of the basic structural requirements for the biological activity of vasoconstrictors. The resulting structure of this peptide is characterised by an α-helical conformation between residues Leu⁶-His¹⁶ and by N- and C-termi- ni which assume no defined conformation. A knowledge of the solution structures of this and related peptides, which are ETB selective agonists, are proving to be important in the understanding of how they interact with the ETB receptor.     

Recent progresses in gene delivery-based bone tissue engineering

Gene therapy has converged with bone engineering over the past decade, by which a variety of therapeutic genes have been delivered to stimulate bone repair. These genes can be administered via in vivo or ex vivo approach using either viral or nonviral vectors. This article reviews the fundamental aspects and recent progresses in the gene therapy-based bone engineering, with emphasis on the new genes, viral vectors and gene delivery approaches.     

Histamine synergistically promotes bFGF‐induced angiogenesis by enhancing VEGF production via H1 receptor

Histamine, a major mediator present in mast cells that is released into the extracellular milieu upon degranulation, is well known to possess a wide range of biological activities in several classic physiological and pathological processes. However, whether and how it participates in angiogenesis remains obscure. In the present study, we observed its direct and synergistic action with basic fibroblast growth factor (bFGF), an important inducer of angiogenesis, on in vitro angiogenesis models of endothelial cells. Data showed that histamine (0.1, 1, 10 µM) itself was absent of direct effects on the processes of angiogenesis, including the proliferation, migration, and tube formation of endothelial cells. Nevertheless, it could concentration‐dependently enhance bFGF‐induced angiogenesis as well as production of vascular endothelial growth factor (VEGF) from endothelial cells. The synergistic effect of histamine on VEGF production could be reversed by pretreatments with diphenhydramine (H1‐receptor antagonist), SB203580 (selective p38 mitogen‐activated protein kinase (MAPK) inhibitor) and L ‐NAME (nitric oxide synthase (NOS) inhibitor), but not with cimetidine (H2‐receptor antagonist) and indomethacin (cyclooxygenase (COX) inhibitor). Moreover, histamine could augment bFGF‐incuced phosphorylation and degradation of IκBα, a key factor accounting for the activation and translocation of nuclear factor κB (NF‐κB) in endothelial cells. These findings indicated that histamine was able to synergistically augment bFGF‐induced angiogenesis, and this action was linked to VEGF production through H1‐receptor and the activation of endothelial nitric oxide synthase (eNOS), p38 MAPK, and IκBα in endothelial cells. J. Cell. Biochem. 114: 1009–1019, 2013. © 2012 Wiley Periodicals, Inc.     

Effects of 12‐Hour Rotating Shifts on Menstrual Cycles of Photoelectronic Workers in Taiwan

12 h rotating shifts are common in high‐tech industries in Taiwan. The aim of this longitudinal study was to evaluate the effect of the disruption of circadian rhythms by the shift schedule on menstrual cycle length (MCL) and regularity of female workers at an optoelectronic company in Taiwan. We recruited females who worked rotating shifts in a clean room environment as the shift‐work group and female office workers who worked normal business hours as the comparison group. Every participant recorded their MCL for each menstruation cycle up to eight consecutive months prospectively and provided demographic characteristics, reproductive history, and menstrual characteristics. We collected data on 1,135 and 117 menstruation cycles in the shift‐work (n=280) and comparison groups (n=49). Whereas the two groups had similar group means for MCL and number of menstrual bleeding days, the prevalence of menstrual cycle irregularity (cycles<25 or>35 days) was higher in the shift‐work group (p=0.04). Univariate and multivariate logistic regression analyses demonstrated that rotating shift work was an independent predictor of menstrual cycle irregularity (odds ratio=1.71, 95% confidence interval: 1.03–2.88) after adjusting for shift‐work history, employment duration, coffee consumption, and pre‐employment menstrual cycle irregularity. Although further study is required to confirm our findings plus to explore prevention and control measures, our data indicate rotating shift work can increase the risk of MCL irregularity.