Musashi RNA-binding protein 2 (MSI2) has important roles in human cancer. However, the regulatory mechanisms by which MSI2 alters breast cancer pathophysiology have not been clearly identified. Here we demonstrate that MSI2 directly regulates estrogen receptor 1 (ESR1), which is a well-known therapeutic target and has been shown to reflect clinical outcomes in breast cancer. Based on gene expression data analysis, we found that MSI2 expression was highly enriched in estrogen receptor (ER)-positive breast cancer and that MSI2 expression was significantly correlated with ESR1 expression, including expression of ESR1 downstream target genes. In addition, MSI2 levels were associated with clinical outcomes. MSI2 influenced breast cancer cell growth by altering ESR1 function. MSI2 alters ESR1 by binding specific sites in ESR1 RNA and by increasing ESR1 protein stability. Taken together, our findings identified a novel regulatory mechanism of MSI2 as an upstream regulator of ESR1 and revealed the clinical relevance of the RNA-binding protein MSI2 in breast cancer.
Purpose To assess the value of diabetic retinopathy (DR) severity as a possible predictive prognostic factor for the progression of chronic kidney disease (CKD). Patients and methods Retrospective cohort study. Patients (51) who were initially diagnosed with DR and CKD were enrolled and their medical records were evaluated. The following ophthalmic factors were assessed by fluorescein angiography at the initial visit: area of capillary nonperfusion, presence of neovascularization and vitreous hemorrhage, and DR grade. The effect of these factors on CKD progression over the 2-year period of the study, defined as doubling of serum creatinine or the development of end-stage renal disease requiring dialysis or renal transplant, was evaluated. Results The study included 51 patients with DR and CKD; of these, 11 patients (21.6%) were found to have proliferative DR (PDR) and seven patients (13.7%) had highrisk PDR at baseline. Patients with ischemic DR, who showed extensive capillary nonperfusion (Z10 optic disc areas) in the retina, had a greater risk for CKD progression (hazard ratio ¼ 6.64; P ¼ 0.002). Conclusion We found that extensive capillary nonperfusion in the retina greatly increased the risk of progression of CKD in patients with DR. This suggests that the retina and the kidney may have shared risk factors for microvascular disease secondary to diabetes mellitus, and emphasizes the need for a team approach to diabetes care.
Purpose: To evaluate the image quality of intraocular lenses (IOLs) using field-tracing optical simulation and then compare it with the image quality using conventional ray-tracing simulation. Methods: We simulated aspheric IOLs with a decenter, tilt, and no misalignment using an aspheric corneal eye model with a positive spherical aberration. The retinal image, Strehl ratio, and modulation transfer function (MTF) were compared between the ray-tracing and field-tracing optical simulation and confirmed by the results reported in an in vitro experiment using the same eye model. Results: The retinal image showed interference fringes from target due to diffraction from the object in a field-tracing simulation. When compared with the experimental results, the field tracing represented the experimental results more precisely than ray tracing after passing over 400 µm of the decentration and 4 degrees of the tilt of the IOLs. The MTF values showed similar results for the case of no IOL misalignment in both the field tracing and ray tracing. In the case of the 200-µm decentration or 8-degree tilt of IOL, the field-traced MTF shows lower values than the ray-traced one. Conclusions: The field-tracing optical bench simulation is a reliable method to evaluate IOL performance according to the IOL misalignment. It can provide retinal image quality close to real by taking into account the wave nature of light, interference and diffraction to explain to patients having the IOL misalignment.
Purpose To work out a way to measuring radius of scleral curvature using anterior segment optical coherence tomography (OCT). Methods Twenty four volunteers were enrolled. With OCT, horizontal and vertical images centered on the visual axis and four images centered on the upper, lower, nasal, and temporal limbus were obtained. To evaluate tangential radius of curvature, we used each nasal and temporal OCT image and calculated the radius of a circle, which passes by three points of scleral surface at 1, 2 and 3 mm from the limbus. To evaluate axial radius of curvature, central horizontal, nasal and temporal OCT images were composed to a new one and the radius of a circle, the center of which is on the visual axis and passes by the point of scleral surface at 2 mm from the limbus, was calculated. The differences in radius of curvature were analyzed by the student t‐test and correlation between two axial radii of curvature calculated by two different reviewers was measured by Pearson correlation coefficient. Results The mean axial radius of nasal curvature (13.33 ± 1.12 mm) was significantly longer than that of temporal curvature (12.32 ± 0.77 mm). The mean tangential radius of nasal curvature (15.14 ± 2.63 mm) was also longer than that of temporal curvature (14.18 ± 2.24 mm). The axial radii of nasal (13.33 ± 1.12 mm) and temporal (12.32 ± 0.77 mm) curvature from one reviewer were very close to those (13.01 ± 1.16 mm and 12.33 ± 0.78 mm) from the other reviewer (Pearson correlation coefficients 0.942 and 0.841, p < 0.001 in both). Conclusion Anterior segment OCT is a useful tool in measuring the radius of scleral curvature. Measurement of axial radius of curvature is more accurate than that of tangential radius of curvature, and has a good reproducibility.
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