The surface of the eye actively suppresses inflammation while maintaining a remarkable capacity for epithelial wound repair. Our understanding of mechanisms that balance inflammatory/reparative responses to provide effective host defense while preserving tissue function is limited, in particular, in the cornea. Lipoxin A 4 (LXA 4 ) and docosahexaenoic acid-derived neuroprotectin D1 (NPD1) are lipid autacoids formed by 12/15-lipoxygenase (LOX) pathways that exhibit anti-inflammatory and neuroprotective properties. Here, we demonstrate that mouse corneas generate endogenous LXA 4 and NPD1. 12/15-LOX (Alox15) and LXA 4 receptor mRNA expression as well as LXA 4 formation were abrogated by epithelial removal and restored during wound healing. Amplification of these pathways by topical treatment with LXA 4 or NPD1 (1 g) increased the rate of re-epithelialization (65-90%, n ؍ 6 -10, p < 0.03) and attenuated the sequelae of thermal injury. In contrast, the proinflammatory eicosanoids, LTB 4 and 12R-hydroxyeicosatrienoic acid, had no impact on corneal re-epithelialization. Epithelial removal induced a temporally defined influx of neutrophils into the stroma as well as formation of the proinflammatory chemokine KC. Topical treatment with LXA 4 and NPD1 significantly increased PMNs in the cornea while abrogating KC formation by 60%. More importantly, Alox15-deficient mice exhibited a defect in both corneal re-epithelialization and neutrophil recruitment that correlated with a 43% reduction in endogenous LXA 4 formation. Collectively, these results identify a novel action for the mouse 12/15-LOX (Alox15) and its products, LXA 4 and NPD1, in wound healing that is distinct from their well established anti-inflammatory properties.
We have developed a procedure for the synthesis of N-hydroxy-N(1)-phenyloctanediamide (suberoylanilide hydroxamic acid (SAHA)), providing the product in 79.8% yield. SAHA is a potent inhibitor of histone deacetylase, induces differentiation and/or apoptosis in certain transformed cells in culture, and suppressed the growth of human prostate cancer LNCaP and PC-3 cell lines. The combination of SAHA with other compounds inhibited cell proliferation of LNCaP cells in additive fashion and resulted in synergistic growth inhibition.
Purpose
Bioprinting is a promising technology, which has gained a recent attention, for application in all aspects of human life and has specific advantages in different areas of medicines, especially in ophthalmology. The three-dimensional (3D) printing tools have been widely used in different applications, from surgical planning procedures to 3D models for certain highly delicate organs (such as: eye and heart). The purpose of this paper is to review the dedicated research efforts that so far have been made to highlight applications of 3D printing in the field of ophthalmology.
Design/methodology/approach
In this paper, the state-of-the-art review has been summarized for bioprinters, biomaterials and methodologies adopted to cure eye diseases. This paper starts with fundamental discussions and gradually leads toward the summary and future trends by covering almost all the research insights. For better understanding of the readers, various tables and figures have also been incorporated.
Findings
The usages of bioprinted surgical models have shown to be helpful in shortening the time of operation and decreasing the risk of donor, and hence, it could boost certain surgical effects. This demonstrates the wide use of bioprinting to design more precise biological research models for research in broader range of applications such as in generating blood vessels and cardiac tissue. Although bioprinting has not created a significant impact in ophthalmology, in recent times, these technologies could be helpful in treating several ocular disorders in the near future.
Originality/value
This review work emphasizes the understanding of 3D printing technologies, in the light of which these can be applied in ophthalmology to achieve successful treatment of eye diseases.
A qualitative 3D pharmacophore model (a common feature based model or Catalyst HipHop algorithm) was developed for well-known natural product androgen receptor down-regulating agents (ARDAs). The four common chemical features identified included: one hydrophobic group, one ring aromatic group, and two hydrogen bond acceptors. This model served as a template in virtual screening of the Maybridge and NCI databases that resulted in identification of six new ARDAs (EC(50) values 17.5-212 microM). Five of these molecules strongly inhibited the growth of human prostate LNCaP cells. These novel compounds may be used as leads to develop other novel anti-prostate cancer agents.
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