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Glaucine is an aporphine alkaloid with anti-inflammatory, bronchodilator and anti-cancer activities. However, the effects of glaucine in the regulation of age-related macular degeneration (AMD) remain unclear. Herein, we aimed to investigate the anti-angiogenetic and anti-inflammatory effects of glaucine in ARPE-19 cells. ARPE-19 cells were treated with N-(methoxyoxoacetyl)-glycine, methyl ester (DMOG) and cobalt chloride (CoCl 2 ) for induction of hypoxia, while lipopolysaccharide (LPS) treatment was used for elicitation of inflammatory response. Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by Western blot. The secretion of VEGF, interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1) was detected using enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were used for tube formation analysis. Expression of HIF-1α and secretion of VEGF were significantly increased under DMOG and CoCl 2 induction, whereas glaucine significantly attenuated both HIF-1α expression and VEGF secretion by DMOG- and CoCl 2 -induced ARPE-19 cells. In addition, glaucine suppressed the tube formation by DMOG- and CoCl 2 -induced HUVEC cells. Moreover, glaucine also attenuated the production of IL-6 and MCP-1 by LPS-induced ARPE-19 cells. This study indicated that glaucine exhibited anti-angiogenic and anti-inflammatory effects, suggesting that glaucine might have benefits for the treatment of AMD., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study aims to explore genetic variants that potentially lead to outer retinal tubulation (ORT), estimate the prevalence of ORT in these candidate genes, and investigate the clinical etiology of ORT in patients with inherited retinal diseases (IRDs), with respect to each gene., Design: Retrospective cohort study., Methods: A retrospective cross-sectional review was conducted on 565 patients with molecular diagnoses of IRD, confirming the presence of ORT as noted in each patient's respective spectral-domain optical coherence tomography (SD-OCT) imaging. Using SD-OCT imaging, the presence of ORT was analyzed in relation to specific genetic variants and phenotypic characteristics. Outcomes included the observed ORT frequencies across two gene-specific cohorts: non- retinal pigment epithelium (RPE)-specific genes, and RPE-specific genes; and to investigate the analogous characteristics caused by variants in these genes., Results: Among the 565 patients included in this study, 104 exhibited ORT on SD-OCT. We observed ORT frequencies among the following genes from our patient cohort: 100% (23/23) forCHM, 100%(2/2) forPNPLA6, 100% (4/4) forRCBTB1, 100% formtDNA[100% (4/4) forMT-TL1and 100% (1/1) formtDNAdeletion], 100% (1/1) forOAT, 95.2% (20/21) forCYP4V2, 72.7% (8/11) forCHMfemale carriers, 66.7% (2/3) forC1QTNF5, 57.1% (8/14) forPROM1, 53.8% (7/13) forPRPH2, 42.9% (3/7) forCERKL, 28.6% (2/7) forCDHR1, 20% (1/5) forRPE65, 4% (18/445) forABCA4.In contrast, ORT was not observed in any patients with photoreceptor-specific gene variants, such asRHO(n=13),USH2A(n=118),EYS(n=70),PDE6B(n=10),PDE6A(n=4),and others., Conclusion: These results illustrate a compelling association between the presence of ORT and IRDs caused by variants in RPE-specific genes, as well as non-RPE-specific genes. In contrast, IRDs caused by photoreceptor-specific genes are typically not associated with ORT occurrence. Further analysis revealed that ORT tends to manifest in IRDs with milder intraretinal pigment migration (IPM), a finding that is typically associated with RPE-specific genes. These findings regarding ORT, genetic factors, atrophic patterns in the fundus, and IPM provide valuable insight into the complex etiology of IRDs. Future prospective studies are needed to further explore the association and underlying mechanisms of ORT in these contexts., Competing Interests: Declaration of competing interest The authors report no conflicts of interest and are alone responsible for the content and writing of this article., (Copyright © 2024. Published by Elsevier Inc.)

Background: Mesenchymal stem cells (MSCs)-derived exosomes have been previously demonstrated to promote tissue regeneration in various animal disease models. This study investigated the protective effect of exosome treatment in carbon tetrachloride (CCl4)-induced acute liver injury and delineated possible underlying mechanism., Methods: Exosomes collected from conditioned media of previously characterized human umbilical cord-derived MSCs were intravenously administered into male CD-1 mice with CCl 4 -induced acute liver injury. Biochemical, histological and molecular parameters were used to evaluate the severity of liver injury. A rat hepatocyte cell line, Clone-9, was used to validate the molecular changes by exosome treatment., Results: Exosome treatment significantly suppressed plasma levels of AST, ALT, and pro-inflammatory cytokines, including IL-6 and TNF-α, in the mice with CCl 4 -induced acute liver injury. Histological morphometry revealed a significant reduction in the necropoptic area in the injured livers following exosome therapy. Consistently, western blot analysis indicated marked elevations in hepatic expression of PCNA, c-Met, Ets-1, and HO-1 proteins after exosome treatment. Besides, the phosphorylation level of signaling mediator JNK was significantly increased, and that of p38 was restored by exosome therapy. Immunohistochemistry double staining confirmed nuclear Ets-1 expression and cytoplasmic localization of c-Met and HO-1 proteins. In vitro studies demonstrated that exosome treatment increased the proliferation of Clone-9 hepatocytes and protected them from CCl4-induced cytotoxicity. Kinase inhibition experiment indicated that the exosome-driven hepatoprotection might be mediated through the JNK pathway., Conclusion: Exosome therapy activates the JNK signaling activation pathway as well as up-regulates Ets-1 and HO-1 expression, thereby protecting hepatocytes against hepatotoxin-induced cell death., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)