Exendin-4, a GLP-1 receptor agonist, suppresses diabetic retinopathy in vivo and in vitro.

Diabetic retinopathy (DR) is a complication of diabetes and a leading cause of blindness in adults. Studies have shown that glucagon-like peptide-1 (GLP-1) exerts a protective effect on patients with DR. Here, we investigated the protective effects of Exendin-4, a GLP-1 analogue, on DR. We established a high-glucose-induced HREC cell model and an STZ-induced rat DR Model to study the effect of Exendin-4 in DR in vitro and in vivo. The qRT-PCR, CCK-8, TUNEL, western blotting, tube formation assays, and ELISA were performed. In addition, we overexpressed TGFB2 to observe whether the protective effect of Exendin-4 was reversed. Our results showed that Exendin-4 inhibited the progression of DR. Furthermore, the protective effect of Exendin-4 was suppressed in cells overexpressing TGFB2. Our findings suggest that Exendin-4 may be involved in the regulation of TGFB2 expression levels to inhibit DR. These results indicate that Exendin-4 could be an effective therapy for DR.

Evaluation of retinal vascular density and related factors using OCTA in children and adolescents with myopia without maculopathy.

BACKGROUND: Myopia is the most common ophthalmic condition worldwide with a rapidly increasing prevalence. This study aimed to compare the retinal microvasculature in the superficial capillary plexus (SCP) in children and adolescents with mild and moderate/high myopia using optical coherence tomography angiography, determine the relationship between retinal parameters and axial length (AL), and understand the occurrence and progression of myopia in microcirculation. METHODS: This prospective observational study included 39 participants with mild myopia and 33 participants with moderate/high myopia. Vessel density (VD) and perfusion density (PD) in the SCP, the foveal avascular zone (FAZ), and AL were compared between the groups and the relationship between these retinal parameters and AL was assessed. RESULTS: No difference in SCP VD or PD was observed between the two groups. The FAZ did not differ significantly between groups whereas significant differences in age, height, refractive status, and AL were observed. Significantly shorter AL was observed in participants with mild myopia compared with the moderate/high myopia group. Age was positively correlated with height (r = 0.852) and refractive status was negatively correlated with AL (r = -0.588). AL was positively correlated with VD (r = 0.317) and PD (r = 0.308) in the SCP and AL was negatively correlated with the FAZ (r = -0.434). CONCLUSIONS: This study revealed that superficial foveal microvessel density was unaffected in children and adolescents without pathological myopia. However, myopia progression was associated with a change in AL, and an AL increase altered macular blood flow.

Ferroptosis-related gene signature predicts prognosis in kidney renal papillary cell carcinoma.

Ferroptosis, an iron-dependent form of selective cell death, is involved in the development of many cancers. However, the role of ferroptosis-related genes (FRGs) in kidney renal papillary cell carcinoma (KIRP) is unclear. In this study, we examined the mRNA expression profiles and clinical data of patients with KIRP from the TCGA cohort. Consequently, 41 differentially-expressed FRGs were screened using the limma package, and 17 prognostic-related FRGs were identified by survival analysis and univariate Cox regression analyses. Thereafter, a ferroptosis-related gene prognostic index (FRGPI) was constructed based on five FRGs (AKR1C3, SAT1, FANCD2, HSBP1 and SQLE), using lasso Cox and multivariate Cox regression analyses. KIRP patients with high FRGPI scores displayed worse outcomes. Furthermore, the FRGPI was shown to be a reliable independent prognostic factor in both the training and testing cohorts. Comprehensive analysis also showed that the FRGPI can distinguish gene mutation, functional enrichment of immune cells and molecular function-related pathways. Interestingly, low FRGPI score could be more benefit from immune checkpoint inhibitors (ICIs) therapy. Then, the two hub prognostic genes (AKR1C3 and FANCD2) as a risk gene for KIRP were identified based on the FRGPI module, and the expression profiles of these two genes were validated using human KIRP cells, besides, we furthermore discovered that Fancd2 is significantly up-regulated in most cancers and is associated with prognosis. In conclusion, these findings showed that FRGPI can accurately predict the prognosis of patients with KIRP, suggesting that this risk model is a promising prognostic biomarker for these patients. Moreover, targeting ferroptosis (FANCD2) could be a potential therapeutic alternative for various cancers.

Compatibility of ticagrelor with pharmaceutical excipients studied with thermal and spectroscopic techniques.

The compatibility between ticagrelor and selected excipients (mannitol, calcium phosphate tribasic, sodium carboxymethyl starch, hydroxypropyl cellulose and magnesium stearate) was investigated by differential scanning calorimetry. The compatibility was further corroborated by Raman spectroscopy and isothermal stress testing experiments. These results revealed that ticagrelor has high compatibility with mannitol, calcium phosphate tribasic, sodium carboxymethyl starch, hydroxypropyl cellulose and magnesium stearate.