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Proliferative retinopathies, such as proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP) are major causes of visual impairment and blindness in industrialized countries. Prostaglandin E 2 (PGE 2) is implicated in cellular proliferation and migration via E-prostanoid receptor (EP 4 R). The aim of this study was to investigate the role of PGE 2 /EP 4 R signaling in the promotion of retinal neovascularisation. In a streptozotocin (STZ)-induced diabetic model and an oxygen-induced retinopathy (OIR) model, rats received an intravitreal injection of PGE 2 , cay10598 (an EP 4 R agonist) or AH23848 (an EP 4 R antagonist). Optical coherence tomography, retinal histology and biochemical markers were assessed. Treatment with PGE 2 or cay10598 accelerated pathological retinal angiogenesis in STZ and OIR-induced rat retina, which was ameliorated in rats pretreated with AH23848. Serum VEGF-A was upregulated in the PGE 2 -treated diabetic rats vs non-treated diabetic rats and significantly downregulated in AH23848-treated diabetic rats. PGE 2 or cay10598 treatment also significantly accelerated endothelial tip-cell formation in new-born rat retina. In addition, AH23848 treatment attenuated PGE 2 -or cay10598-induced proliferation and migration by repressing the EGF receptor (EGFR)/Growth factor receptor bound protein 2-associated binder protein 1 (Gab1)/Akt/NF-κB/VEGF-A signaling network in human retinal microvascular endothelial cells (hRMECs). PGE 2 /EP 4 R signaling network is thus a potential therapeutic target for pathological intraocular angiogenesis. [Display omitted] • Prostaglandin E 2 is a crucial growth-factor inducer and a potent proangiogenic mediator. • PGE 2 /EP 4 R cascade actually mediates retinal angiogenesis via transactivation of EGFR. • The PGE 2 /EP 4 R pathway could be a therapeutic target for pathological angiogenesis prevention and treatment in the retina. [ABSTRACT FROM AUTHOR]

• Bioinformatics data disclosed the central targets of calycosin for anti-fatty liver. • All top bio-functional process and pathway of calycosin for anti-fatty liver were highlighted. • The biochemical data of human samples were used to validate the predictive findings. • The biochemical experiments in vivo were used to validate the predictive findings. • The bioinformatic and biochemical findings disclosed the anti-fatty liver mechanism of calycosin. As revealed in previous reports, calycosin is a functional flavonoid characterized with identified pharmacological activities. Most of evidences are used to demonstrate the anti-cancer benefits of calycosin, however, the existing study of anti-fatty liver medicated by calycosin is limitedly reported. Recently, an emerging avenue based on network pharmacology may contribute to excavate the biological targets and molecular mechanisms of calycosin for anti-fatty liver. In confirmatory experiments, the human and animal studies were subjected to verify some of bioinformatic results. Accordingly, bioinformatic data based on network pharmacology suggested that discoverable biotargets of calycosin for anti-fatty liver were aldehyde dehydrogenase (ALDH2), Niemann pick C1 (NPC1), high mobility group protein 1 (HMGB1), bilirubin UDP glucuronosyltransferase 1 (UGT1A1), mitogen-activated protein kinase 3 (MAPK3), epidermal growth factor receptor (EGFR), hydroxytryptamine receptor 2 (HTR2), migration inhibitory factor (MIF), cytochrome P450, family 19A1 (CYP19A1). Furthermore, all significant biological characteristics and mechanisms of to treat fatty liver were revealed in several. In human findings, the blood tests showed changed glucose and lipid contents, elevated insulin resistance and inflammatory stress. And fatty liver sections from patients resulted in negative expressions of ALDH2, NPC1, and positive HMGB1 expression. In a study in vivo , calycosin-treated high fat diet (HFD)-fed mice exhibited reduced liver weights, decreased fasting serum glucose and insulin, liver functional transaminases, blood lipids, metabolic enzymes, and inflammatory cytokines. And the data in gene tests displayed up-regulations of ALDH2, NPC1 mRNAs, and down-regulation of HMGB1 mRNA in calycosin-treated liver samples. Together, the current bioinformatic data demonstrate biological targets, functions and mechanisms of calycosin for anti-fatty liver. Interestingly, these bioinformatic findings can be partially verified with clinical and animal samples. [ABSTRACT FROM AUTHOR]