Assessment of OCT-Based Macular Curvature and Its Relationship with Macular Microvasculature in Children with Anisomyopia.

INTRODUCTION: To evaluate the intraocular differences in optical coherence tomography (OCT)-based macular curvature index (MCI) among children with anisomyopia and to investigate the relationship between MCI and the macular microvasculature. METHODS: Fifty-two schoolchildren with anisometropia > 2.00 D were enrolled and underwent comprehensive examinations including cycloplegic refraction, axial length (AL), and swept source OCT/OCT angiography. OCT-based MCIs were determined from horizontal and vertical B-scans by a customized curve fitting model in MATLAB R2022 at 1-mm-, 3-mm-, and 6-mm-diameter circles at fovea. Characteristics and topographic variation of MCI was analyzed, and the relationships with microvascularity and its associated factors were investigated. RESULTS: MCI achieved high reliability and repeatability. There were overall larger MCIs in the more myopic eyes than the less myopic eyes in 1-mm-, 3-mm-, and 6-mm-diameter circles at fovea (all p < 0.001). For the topographic variation, horizontal MCI was significantly greater than vertical MCI (all p < 0.001), and was the largest in 6-mm circle, followed by 3-mm and 1-mm circles. Stronger correlation of horizontal MCI with myopic severity than vertical MCI was found. Partial Pearson's correlation found MCI was negatively associated with deep capillary plexus (DCP) vessel density (p = 0.016). Eyes with a higher MCI in a 6-mm circle were more likely to have longer AL (p < 0.001), lower DCP vessel density (p = 0.037), and thinner choroidal thickness (ChT) (p = 0.045). CONCLUSION: Larger MCI was found in the more myopic eyes of children with anisomyopia and was significantly associated with smaller DCP density, suggesting that MCI was an important indicator of myopia-related retinal microvascularity change, and it could be a valuable metric for myopia assessment in children.

A Fibrin Site-Specific Nanoprobe for Imaging Fibrin-Rich Thrombi and Preventing Thrombus Formation in Venous Vessels.

Venous thromboembolism (VTE) is a prevalent public health issue worldwide. Before treatment, spatiotemporally accurate thrombus detection is essential. However, with the currently available imaging technologies, this is challenging. Herein, the development of a novel fibrin-specific nanoprobe (NP) based on the conjugation of poly(lactic-co-glycolic acid) with the pentapeptide Cys-Arg-Glu-Lys-Ala (CREKA) for selective and semiquantitative imaging in vivo is presented. By integrating Fe3 O4 and NIR fluorochrome (IR780), the NP can function as a highly sensitive sensor for the direct analysis of thrombi in vivo. The fibrin-specific NP distinguishes fibrin-rich thrombi from collagen-rich or erythrocyte-rich thrombi, which can be beneficial for future individually tailored therapeutic strategy. Furthermore, loading NPs with the ketotifen fumarate results in mast cell degranulation inhibition, and hence, NPs can prevent thrombosis without the risk of excessive bleeding. Thus, the use of fibrin-specific NPs may serve as a safe alternative approach for the detection and prevention of VTEs in susceptible populations in the future.

Low-Intensity Focused Ultrasound-Responsive Ferrite-Encapsulated Nanoparticles for Atherosclerotic Plaque Neovascularization Theranostics.

Pathological angiogenesis is a crucial factor that causes atherosclerotic plaque rupture. Sinoporphyrin sodium-mediated sonodynamic therapy (DVDMS-SDT) induces regression of plaque neovascularization in humans without causing obvious side effects. However, a clinical noninvasive theranostic strategy for atherosclerotic plaque neovascularization is urgently needed. A nanoplatform designed for multimodality imaging-guided SDT in plaque angiogenesis theranostics, termed PFP-HMME@PLGA/MnFe2 O4 -ramucirumab nanoparticles (PHPMR NPs), is fabricated. It encapsulates manganese ferrite (MnFe2 O4 ), hematoporphyrin monomethyl ether (HMME), and perfluoropentane (PFP) stabilized by polylactic acid-glycolic acid (PLGA) shells and is conjugated to an anti-VEGFR-2 antibody. With excellent magnetic resonance imaging (MRI)/photoacoustic/ultrasound imaging ability, the distribution of PHPMR NPs in plaque can be observed in real time. Additionally, they actively accumulate in the mitochondria of rabbit aortic endothelial cells (RAECs), and the PHPMR NP-mediated SDT promotes mitochondrial-caspase apoptosis via the production of reactive oxygen species and inhibits the proliferation, migration, and tubulogenesis of RAECs. On day 3, PHPMR NP-mediated SDT induces apoptosis in neovessel endothelial cells and improves hypoxia in the rabbit advanced plaque. On day 28, PHPMR NP-mediated SDT reduces the density of neovessels, subsequently inhibiting intraplaque hemorrhage and inflammation and eventually stabilizing the plaque. Collectively, PHPMR NP-mediated SDT presents a safe and effective theranostic strategy for inhibiting plaque angiogenesis.

Combination Nanotherapeutics for Dry Eye Disease Treatment in a Rabbit Model.

PURPOSE: Anti-inflammation is essential for dry eye disease. Traditional anti-inflammation agent corticosteroids applied in dry eye disease (DED) treatment could result in high intraocular pressure, especially in long-term treatment. Thus, we have prepared a liposome loading 1-bromoheptadecafluorooctane and tetrandrine (PFOB@LIP-Tet) to treat DED via anti-inflammation that hardly affects intraocular pressure in this study, which provided another therapy strategy for dry eye disease. METHODS: We firstly detected the physicochemical properties of PFOB@LIP-Tet. Next, we tested the biosafety of synthesized liposomes for corneal epithelium. Then, we explored the accumulations and distribution of PFOB@LIP-Tet both in cellular and animal models. And then, we assessed the therapeutic effects of PFOB@LIP-Tet formulations by laboratory and clinical examinations. Last, we examined the changes in eye pressure before and after treatment. RESULTS: PFOB@LIP-Tet and Tet showed a characteristic absorption peak at 282 nm while PFOB@LIP did not. Large amounts of PFOB@LIP-Tet remained on the ocular surface and accumulated in the corneal epithelial cells in DED rabbits. Corneal staining scores of DED rabbits respectively treated by ATS, PFOB@LIP-ATS, Tet-ATS and PFOB@LIP-Tet-ATS for seven days were 3.7±0.5, 3.2±0.4, 1.5±0.5 and 0.5±0.5. The expressions of related cytokines were correspondingly downregulated significantly, indicating that the inflammation of DED was successfully suppressed. The intraocular pressure changes of DED rabbits before and after treatment by PFOB@LIP-Tet showed no statistical significance. CONCLUSION: We successfully synthesized PFOB@LIP-Tet, and it could effectively treat dry eye disease via anti-inflammation but hardly affected the intraocular pressure.

ROS attenuates the antitumor effect of Raddeanin on ovarian cancer cells Skov3.

Epithelial ovarian cancer is the fourth commonest cause of female cancer death, but no proper evidence had proved that surgery could prolong the survival time. Hence, new effective chemotherapy is necessary to improve the survival. Raddeanin A (RA), anoleanane-type triterpenoid sponin, is isolated from Anemone raddeana. Previous study had proved that RA exerted antitumor activity through inhibiting proliferation and promoting apoptosis of some kinds of cancer cell. ROS is a double-edged sword for tumors and might contribute to therapy resistant. In this study, we discuss at the first time whether ROS was involved in the antitumor effect of RA on Skov3 cells, and analysis the mechanism. The results showed that after be treated by RA, the proliferation of Skov3 was inhibited, and this effect can be enhanced by ROS inhibitor NAC. Pretreated with NAC can enhance the cell cycle block but not apoptosis induced by RA. Moreover, as a by-production of RA, ROS induced autophagy can attenuate RA's antitumor activity, and autophagy inhibitor 3-MA could recover RA's antitumor effect. These results demonstrated that ROS and autophagy could be considered as two pro-tumor factors in some conditions. The combination of RA and ROS inhibitor or autophagy inhibitor or both of them may be the novel strategies at least in ovarian cancer therapy.

Atrazine promotes RM1 prostate cancer cell proliferation by activating STAT3 signaling.

Atrazine, a widely used pesticide, is frequently detected in soil and surface water, which alarms epidemiologists and medical professionals because of its potential deleterious effects on health. Indeed, atrazine is a potent endocrine disruptor that increases aromatase expression in some human cancer cell lines. Both animal and human studies have suggested that atrazine is possibly carcinogenic, although discrepant results have been reported. In this study, RM1 cells were used to explore the atrazine effects on prostate cancer. Proliferation, migration and invasion of RM1 cells were assessed by colony formation, wound-healing and invasion assays, respectively, after in vitro exposure to atrazine. In addition, an RM1 cell xenograft model was generated to evaluate the effects of atrazine in vivo. To explore the molecular mechanisms, qRT­PCR, immunohistochemistry, and western blot analyses were employed to detect mRNA and protein levels of STAT3 signaling and cell cycle related proteins, including p53, p21, cyclin B1 and cyclin D1. Interestingly, RM1 cell proliferation was increased after treatment with atrazine, concomitantly with STAT3 signaling activation. These results suggest that atrazine promotes RM1 cell growth in vitro and in vivo by activating STAT3 signaling.