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      Aster koraiensis Extract and Chlorogenic Acid Inhibit Retinal Angiogenesis in a Mouse Model of Oxygen-Induced Retinopathy

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          Abstract

          Aster koraiensis extract (AKE) is a standard dietary herbal supplement. Chlorogenic acid (CA) is the major compound present in AKE. Retinal neovascularization is a common pathophysiology of retinopathy of prematurity, diabetic retinopathy, and wet form age-related macular degeneration. In this study, we aimed to evaluate the effects of AKE and CA on retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). Vascular endothelial growth factor- (VEGF-) induced tube formation was assayed in human vascular endothelial cells. Experimental retinal neovascularization was induced by exposing C57BL/6 mice to 75% oxygen on postnatal day 7 (P7) and then returning them to normal oxygen pressure on P12. AKE (25 and 50 mg/kg/day) and CA (25 and 50 mg/kg/day) were administered intraperitoneally for 5 days (P12–P16). Retinal flat mounts were prepared to measure the extent of retinal neovascularization at P17. The incubation of human vascular endothelial cells with AKE and CA (1–10  μg/mL) resulted in the inhibition of VEGF-mediated tube formation in a dose-dependent manner. The neovascular area was significantly smaller in AKE or CA-treated mice than in the vehicle-treated mice. These results suggest that AKE is a potent antiangiogenic agent and that its antiangiogenic activity may, in part, be attributable to the bioactive component CA.

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          Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature.

          Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is increasingly used for the treatment of a wide variety of retinal diseases, including age-related macular degeneration, diabetic retinopathy and retinal vascular occlusions, and retinopathy of prematurity. Despite encouraging results in halting the disease and improving the vision, intravitreal injection of anti-VEGF agents may be associated with systemic adverse events and devastating ocular complications. In this review, we provide an overview of safety data for intravitreal injection of common anti-VEGF agents.
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            The antitumor activities of flavonoids.

            The flavonoids are polyphenolic compounds found as integral components of the human diet. They are universally present as constituents of flowering plants, particularly of food plants. The flavonoids are phenyl substituted chromones (benzopyran derivatives) consisting of a 15-carbon basic skeleton (C6-C3-C6), composed of a chroman (C6-C3) nucleus (the benzo ring A and the heterocyclic ring C), also shared by the tocopherols, with a phenyl (the aromatic ring B) substitution usually at the 2-position. Different substitutions can typically occur in the rings, A and B. Several plants and spices containing flavonoid derivatives have found application as disease preventive and therapeutic agents in traditional medicine in Asia for thousands of years. The selection of a particular food plant, plant tissue or herb for its potential health benefits appears to mirror its flavonoid composition. The much lower risk of colon, prostate and breast cancers in Asians, who consume more vegetables, fruits and tea than populations in the Western hemisphere do, raises the question of whether flavonoid components mediate the protective effects of diets rich in these foodstuffs by acting as natural chemopreventive and anticancer agents. An impressive body of information exists on the antitumor action of plantflavonoids. In vitro work has concentrated on the direct and indirect actions of flavonoids on tumor cells, and has found a variety of anticancer effects such as cell growth and kinase activity inhibition, apoptosis induction, suppression of the secretion of matrix metalloproteinases and of tumor invasive behavior. Furthermore, some studies have reported the impairment of in vivo angiogenesis by dietary flavonoids. Experimental animal studies indicate that certain dietary flavonoids possess antitumor activity. The hydroxylation pattern of the B ring of the flavones and flavonols, such as luteolin and quercetin, seems to critically influence their activities, especially the inhibition of protein kinase activity and antiproliferation. The different mechanisms underlying the potential anticancer action of plant flavonoids await further elucidation. Certain dietary flavonols and flavones targeting cell surface signal transduction enzymes, such as protein tyrosine and focal adhesion kinases, and the processes of angiogenesis appear to be promising candidates as anticancer agents. Further in vivo studies of these bioactive constituents is deemed necessary in order to develop flavonoid-based anticancer strategies. In view of the increasing interest in the association between dietary flavonoids and cancer initiation and progression, this important field is likely to witness expanded effort and to attract and stimulate further vigorous investigations.
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              Incidence of endophthalmitis related to intravitreal injection of bevacizumab and ranibizumab.

              To report the overall incidence of endophthalmitis associated with office based intravitreal injections of bevacizumab and ranibizumab. This is a retrospective, consecutive, multicenter case series involving four large clinical sites. Included were all patients receiving at least one injection of intravitreal bevacizumab or intravitreal ranibizumab. Follow-up after each injection was at least 4 weeks. A total of 12,585 injections of intravitreal bevacizumab and 14,320 injections of intravitreal ranibizumab were given during the study period. Infectious endophthalmitis developed in three patients after administration of bevacizumab and in three patients after administration of ranibizumab. Four of these patients were culture positive. Rates of endophthalmitis were 0.02% and 0.02%, respectively, with an overall rate of 0.02%. The rate of endophthalmitis associated with intravitreal bevacizumab and ranibizumab is low, with an incidence of approximately 1 in 4,500 injections.
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                Author and article information

                Contributors
                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi
                1741-427X
                1741-4288
                2018
                22 April 2018
                : 2018
                : 6402650
                Affiliations
                1Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
                2Department of Oral Pathology, School of Dentistry, Chonbuk National University, Jeonju 54896, Republic of Korea
                Author notes

                Academic Editor: Gabino Garrido

                Author information
                http://orcid.org/0000-0002-9003-2158
                http://orcid.org/0000-0001-7610-9887
                http://orcid.org/0000-0002-8798-8220
                Article
                10.1155/2018/6402650
                5937502
                29849715
                38767d24-1566-458c-93f8-14f548aed77b
                Copyright © 2018 Junghyun Kim et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 July 2017
                : 4 February 2018
                Funding
                Funded by: Ministry of Agriculture, Food and Rural Affairs
                Award ID: 316023-05-2-CG000
                Funded by: Korea Institute of Oriental Medicine
                Award ID: K17270
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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