LncRNA XIST promotes neovascularization in diabetic retinopathy by regulating miR-101-3p/VEGFA.

Objective: This study sought to investigate the regulation of long noncoding RNA (lncRNA) XIST on the microRNA (miR)-101-3p/vascular endothelial growth factor A (VEGFA) axis in neovascularization in diabetic retinopathy (DR). Materials and methods: Serum of patients with DR was extracted for the analysis of XIST, miR-101-3p, and VEGFA expression levels. High glucose (HG)-insulted HRMECs and DR model rats were treated with lentiviral vectors. MTT, transwell, and tube formation assays were performed to evaluate cell viability, migration, and angiogenesis, and ELISA was conducted to detect the levels of inflammatory cytokines. Dual-luciferase reporter, RIP, and RNA pull-down experiments were used to validate the relationships among XIST, miR-101-3p, and VEGFA. Results: XIST and VEGFA were upregulated and miR-101-3p was downregulated in serum from patients with DR. XIST knockdown inhibited proliferation, migration, vessel tube formation, and inflammatory responsein HG-treated HRMECs, whereas the above effects were nullified by miR-101-3p inhibition or VEGFA overexpression. miR-101-3p could bind to XIST and VEGFA. XIST promoted DR development in rats by regulating the miR-101-3p/VEGFA axis. Conclusion: LncRNA XIST promotes VEGFA expression by downregulating miR-101-3p, thereby stimulating angiogenesis and inflammatory response in DR.

Application of optical coherence tomography angiography in the assessment of diabetic macular edema staging and laser photocoagulation efficacy.

OBJECTIVE: This study aimed to analyze the effect of optical coherence tomography angiography (OCTA) on diabetic macular edema (DME) staging and assess the efficacy of laser photocoagulation. METHODS: Eighty-six patients (141 eyes) with suspected DME who visited our hospital from August 2019 to March 2022 were selected and underwent fundus angiography and OCTA. The two examination methods were compared in terms of their efficacy in macular edema staging. Subsequently, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of OCTA in diagnosing DME were assessed using fundus angiography as the gold standard. In patients with clinically significant macular edema (CSME) treated with laser photocoagulation, the central concave non-perfused zone (FAZ), vascular density (VD), central macular retinal thickness (CRT), whole retinal blood flow density (FD-300), superficial capillary plexus (SCP), and deep capillary plexus (DCP) were measured using the OCTA 3 mm × 3 mm mode before treatment, at 3 months after treatment, and at 6 months after treatment. SCP, deep capillary plexus (DCP), blood flow density (VD), best corrected visual acuity (BCVA), and central retinal thickness (CRT) were recorded before treatment, 3 months after treatment, and 6 months after treatment. The correlation between BCVA and pre-treatment OCTA parameters at 6 months after treatment was analyzed using Pearson's correlation. RESULTS: Fundus angiography was performed in 86 patients (141 eyes) with suspected DME. Of the 141 eyes, 44 had no leakage, 52 had diffuse edema, 40 had focal macular edema, and 5 had eyes ischemia. A total of 97 eyes showed CSME on fundus angiography. Using fundus angiography as the gold standard, OCTA exhibited a sensitivity of 97.94 %, a specificity of 63.64 %, and an accuracy of 87.23 % in diagnosing CSME. The Kappa value between OCTA and fundus angiography was 0.674. The receiver operating characteristic curve revealed that the area under the curve (AUC) of OCTA in diagnosing CSME was 0.808 (95 % confidence interval: 0.717-0.899). The BCVA was higher, while the CRT was lower in CSME patients at 3 and 6 months after treatment (P<0.05). No significant difference was observed in the OCTA parameters in CSME patients at 3 months after treatment compared with that before treatment (P>0.05). Similarly, no significant difference was found in the FD300 of CSME patients at 6 months after treatment compared with that before treatment (P>0.05). However, the FAZ area, DCP-VD (overall, central concave, and paracentral concave), and SCP-VD (overall, central concave, and paracentral concave) were higher in CSME patients at 6 months after treatment compared with that before treatment (P<0.05). Pearson's correlation showed that BCVA was positively correlated with pre-treatment FAZ area, DCP-VD, and SCP-VD (r>0, P<0.05), and negatively associated with CRT (r<0, P<0.05). CONCLUSION: OCTA exhibited high sensitivity and specificity in diagnosis and staging DME. It adeptly captures the microvascular and visual changes in the central macular recess before and after laser photocoagulation therapy, which can quantitatively guide the follow-up treatment of DME.

Novel insights into the pathogenesis of thyroid eye disease through ferroptosis-related gene signature and immune infiltration analysis.

Thyroid eye disease (TED) has brought great physical and mental trauma to patients worldwide. Although a few potential signaling pathways have been reported, knowledge of TED remains limited. Our objective is to explore the fundamental mechanism of TED and identify potential therapeutic targets using diverse approaches. To perform a range of bioinformatic analyses, such as identifying differentially expressed genes (DEGs), conducting enrichment analysis, establishing nomograms, analyzing weighted gene correlation network analysis (WGCNA), and studying immune infiltration, the datasets GSE58331, GSE105149, and GSE9340 were integrated. Further validation was conducted using qPCR, western blot, and immunohistochemistry techniques. Eleven ferroptosis-related DEGs derived from the lacrimal gland were originally screened. Their high diagnostic value was proven, and diagnostic prediction nomogram models with high accuracy and robustness were established by using machine learning. A total of 15 hub gene-related DEGs were identified by WGCNA. Through CIBERSORTx, we uncovered five immune cells highly correlated with TED and found several special associations between these immune cells and the above DEGs. Furthermore, EGR2 from the thyroid sample was revealed to be closely negatively correlated with most DEGs from the lacrimal gland. High expression of APOD, COPB2, MYH11, and MYCN, as well as CD4/CD8 T cells and B cells, was verified in the periorbital adipose tissues of TED patients. To summarize, we discovered a new gene signature associated with ferroptosis that has a critical impact on the development of TED and provides valuable insights into immune infiltration. These findings might highlight the new direction and therapeutic strategies of TED.

Association between red blood cell distribution width/albumin ratio and all-cause mortality or cardiovascular diseases mortality in patients with diabetic retinopathy: A cohort study.

BACKGROUND: Red blood cell distribution width/albumin ratio (RAR) has been reported as an independent risk factor for diabetic retinopathy (DR), while its association and predictive value in the prognosis of DR patients has not been reported. This study aims to explore the association and predictive value of RAR in the prognosis of DR patients. METHODS: This was a retrospective cohort study based on the National Health and Nutrition Examination Survey (NHANES). The independent variable was RAR, and dependent variables were all-cause mortality and cardiovascular diseases (CVD) mortality. The association between RAR and the risk of all-cause mortality and CVD mortality was assessed using univariate and multivariate cox regression models. The results were shown as HR (hazard ratio) with 95% confidence intervals (CIs). Subgroup analysis based on age or hyperlipidemia was performed. The discrimination of the prediction model was assessed using concordance index (C-index). RESULTS: A total of 725 eligible patients were finally included in this study. The increase of RAR was associated with increased risk of all-cause mortality (HR: 1.15, 95%CI: 1.01-1.31) and CVD mortality (HR: 1.35, 95%CI: 1.12-1.63) after adjusting the covariates. We also found the significant association between higher RAR and higher risk of CVD mortality in DR patients with age < 65 years (HR: 1.35, 95%CI: 1.09-1.67) and with hyperlipidemia (HR: 1.34, 95%CI: 1.10-1.64). C-index of RAR for all-cause mortality and CVD mortality was 0.63 (95%CI: 0.59-0.67) and 0.65 (95%CI: 0.59-0.71), respectively. CONCLUSIONS: Higher RAR was associated with the higher risk of all-cause mortality and CVD mortality in DR patients, and RAR may be a useful predictor for the prognosis of DR patients.

LncRNA XIST promotes neovascularization in diabetic retinopathy by regulating miR-101-3p/VEGFA

ABSTRACT Objective: This study sought to investigate the regulation of long noncoding RNA (lncRNA) XIST on the microRNA (miR)-101-3p/vascular endothelial growth factor A (VEGFA) axis in neovascularization in diabetic retinopathy (DR). Materials and methods: Serum of patients with DR was extracted for the analysis of XIST, miR-101-3p, and VEGFA expression levels. High glucose (HG)-insulted HRMECs and DR model rats were treated with lentiviral vectors. MTT, transwell, and tube formation assays were performed to evaluate cell viability, migration, and angiogenesis, and ELISA was conducted to detect the levels of inflammatory cytokines. Dual-luciferase reporter, RIP, and RNA pull-down experiments were used to validate the relationships among XIST, miR-101-3p, and VEGFA. Results: XIST and VEGFA were upregulated and miR-101-3p was downregulated in serum from patients with DR. XIST knockdown inhibited proliferation, migration, vessel tube formation, and inflammatory response in HG-treated HRMECs, whereas the above effects were nullified by miR-101-3p inhibition or VEGFA overexpression. miR-101-3p could bind to XIST and VEGFA. XIST promoted DR development in rats by regulating the miR-101-3p/VEGFA axis. Conclusions: LncRNA XIST promotes VEGFA expression by downregulating miR-101-3p, thereby stimulating angiogenesis and inflammatory response in DR.