Quinazoline-based alpha1-adrenoceptor antagonists, in particular doxazosin and terazosin, are suggested to display antineoplastic activity against prostate cancers. However, there are few studies elucidating the effect of prazosin. In this study, prazosin displayed antiproliferative activity superior to that of other alpha1-blockers, including doxazosin, terazosin, tamsulosin, and phentolamine. Prazosin induced G2 checkpoint arrest and subsequent apoptosis in prostate cancer PC-3, DU-145, and LNCaP cells. In p53-null PC-3 cells, prazosin induced an increase in DNA strand breaks and ATM/ATR checkpoint pathways, leading to the activation of downstream signaling cascades, including Cdc25c phosphorylation at Ser216, nuclear export of Cdc25c, and cyclin-dependent kinase (Cdk) 1 phosphorylation at Tyr15. The data, together with sustained elevated cyclin A levels (other than cyclin B1 levels), suggested that Cdk1 activity was inactivated by prazosin. Moreover, prazosin triggered mitochondria-mediated and caspase-executed apoptotic pathways in PC-3 cells. The oral administration of prazosin significantly reduced tumor mass in PC-3-derived cancer xenografts in nude mice. In summary, we suggest that prazosin is a potential antitumor agent that induces cell apoptosis through the induction of DNA damage stress, leading to Cdk1 inactivation and G2 checkpoint arrest. Subsequently, mitochondria-mediated caspase cascades are triggered to induce apoptosis in PC-3 cells.
Jeremy Lin and the resulting "Linsanity" has caused an unprecedented media and marketing frenzy worldwide. This essay examines its implication through reviewing media narratives in Taiwan, Lin's ancestral homeland. Japanese colonizers first brought modern sports to the Taiwanese as a symbol of "civilization" and "modernity." Although "athleticism" confronts Confucian tradition, sports began to play a subtle but crucial role in the Taiwan nationalismbuilding process. Although sports are marginally positioned in Taiwanese culture, various regimes have used sports and physical education to integrate national identity and national morale. Taiwanese nationalism lacks self-assurance and must be recognized by its significant others. "The glory of Taiwan" has become a common phrase in contemporary Taiwan media coverage. Regardless of how trivial the issue, the Taiwanese appear desperate for every chance to prove their existence and worth. Recently, Jeremy Lin became the famous "glory of Taiwan." However, "Is Jeremy Lin Taiwanese?" raises a tricky and ambiguous question reflecting the complexity and anxiety of Taiwanese national identity. Through the lens of Linsanity in Taiwan media discourses, we argue that the Linsanity situation significantly differs from that of most Western societies. Taiwanese sportsmen, such as Jeremy Lin, became national heroes without "beating any foreign enemies." Lin's identity has become the most important issue of Linsanity for Taiwan media discourses. In the process of exploiting Linsanity, a peculiar embodiment of sports nationalism has surfaced in Taiwan.
This article aims to build contextualised and cross-cultural understandings of gender discourses on sport and nationalism. With its multi-colonised history and its multi-ethnic groups, modern Taiwan has a very different 'national' story from most western societies. The way that sport is articulated with Taiwanese nationalism is also unique. With the Taiwanese being desperate for every chance to prove their existence and worth, sport becomes an important field for constructing national honour and identity. When sports women succeed on the international stage, especially when their male counterparts fail, the discourse on women, sport and nationalism becomes unusual. In sum, the unique character of Taiwanese sport nationalism creates empowerment opportunities for female athletes. But, we should bear in mind that men still take the dominant roles in Taiwan's sport field. Gendered disciplinary discourses, such as the beauty myth and compulsory heterosexuality, still dominate Taiwanese female athletes' media representation and further influence their practice and self-identity.
The physically-crosslinked collagen hydrogels can provide suitable microenvironments for cell-based functional vascular network formation due to their biodegradability, biocompatibility, and good diffusion properties. However, encapsulation of cells into collagen hydrogels results in extensive contraction and rapid degradation of hydrogels, an effect known from their utilization as a pre-vascularized graft in vivo. Various types of chemically-crosslinked collagen-based hydrogels have been successfully synthesized to decrease volume contraction, retard the degradation rate, and increase mechanical tunability. However, these hydrogels failed to form vascularized tissues with uniformly distributed microvessels in vivo. Here, the enzymatically chemically-crosslinked collagen-Phenolic hydrogel was used as a model to determine and overcome the difficulties in engineering vascular networks. Results showed that a longer duration of inflammation and excessive levels of hydrogen peroxide limited the capability for blood vessel forming cells-mediated vasculature formation in vivo. Lowering the unreacted amount of crosslinkers reduced the densities of infiltrating host myeloid cells by half on days 2–4 after implantation, but blood vessels remained at low density and were mainly located on the edge of the implanted constructs. Co-implantation of a designed spacer with cell-laden hydrogel maintained the structural integrity of the hydrogel and increased the degree of hypoxia in embedded cells. These effects resulted in a two-fold increase in the density of perfused blood vessels in the hydrogel. Results agreed with computer-based simulations. Collectively, our findings suggest that simultaneous reduction of the crosslinker-induced host immune response and increase in hypoxia in hydrogen peroxide-triggered chemically-crosslinked hydrogels can effectively improve the formation of cell-mediated functional vascular networks.
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