Molecular Signatures Integral to Natural Reprogramming in the Pigment Epithelium Cells after Retinal Detachment in Pleurodeles waltl.

The reprogramming of retinal pigment epithelium (RPE) cells into retinal cells (transdifferentiation) lies in the bases of retinal regeneration in several Urodela. The identification of the key genes involved in this process helps with looking for approaches to the prevention and treatment of RPE-related degenerative diseases of the human retina. The purpose of our study was to examine the transcriptome changes at initial stages of RPE cell reprogramming in adult newt Pleurodeles waltl. RPE was isolated from the eye samples of day 0, 4, and 7 after experimental surgical detachment of the neural retina and was used for a de novo transcriptome assembly through the RNA-Seq method. A total of 1019 transcripts corresponding to the differently expressed genes have been revealed in silico: the 83 increased the expression at an early stage, and 168 increased the expression at a late stage of RPE reprogramming. We have identified up-regulation of classical early response genes, chaperones and co-chaperones, genes involved in the regulation of protein biosynthesis, suppressors of oncogenes, and EMT-related genes. We revealed the growth in the proportion of down-regulated ribosomal and translation-associated genes. Our findings contribute to revealing the molecular mechanism of RPE reprogramming in Urodela.

Improvement of clinical and radiological manifestations of coxitis in patients with ankylosing spondylitis treated with tumor necrosis factor-α inhibitor golimumab: Results of a 24-Month prospective observation study (GO-COX Study).

AIM: The hip joint is the most commonly affected non-axial joint in ankylosing spondylitis (AS). Data on the effects of tumor necrosis factor-α inhibitors (TNFi) in AS patients with coxitis are limited. The aim of this study was evaluation of coxitis treated with the TNFi golimumab in real-world settings. METHODS: This study was a prospective non-interventional cohort study. A total of 39 patients newly prescribed with golimumab were enrolled and followed for up to 24 months. The data collected included BASFI, BASMI, ASDAS-CRP, BASDAI indices. BASRI-hip X-ray score was assessed at baseline, and at 12 and 24 months. Magnetic resonance imaging (MRI) and ultrasound examination data were obtained at baseline, and at 6 and 12 months. RESULTS: Significant improvements in BASFI, BASMI, ASDAS-CRP, BASDAI scores were observed (P ≤ 0.0001), but the BASRI-hip score remained stable. After 6 months of treatment, MRI signs of joint effusion were found in a smaller percentage of patients compared with baseline (P = 0.005 for the right and P = 0.015 for the left hip joints). After 12 months, this percentage was significantly lower than at baseline for the right hip joint (P = 0.005) and numerically lower for the left hip joint (P = 0.098). Ultrasound showed a significant increase in the percentage of patients without inflammatory changes after 6 and 12 months compared with baseline (right hip joint: P = 0.026 and P = 0.045, respectively; left hip joint: P = 0.026 for both time points). CONCLUSION: Golimumab therapy in AS patients with coxitis was accompanied by improvement in clinical scores, and in MRI and ultrasound findings without obvious radiographic progress.