ABSTRACT
Purpose: Diabetic retinopathy (DR) is a leading cause of irreversible blindness worldwide. Identifying risk factors associated with DR development and progression is crucial for improving treatment efficacy. Although proteomic changes in DR have been extensively studied, the results remain equivocal. Hence, this study aims to summarize and identify potential diagnostic or prognostic markers for DR. In addition, the upstream regulator responsible for protein deregulation of this disease was also validated. Methods: We systematically analyzed the current literature on proteomic profile changes in DR, followed by pathway analysis identification. To validate the protein level changes, ELISA was performed from serum samples collected from 27 patients with DR and 25 healthy controls. Results: Our analysis revealed that 1 candidate marker (afamin [AFM]) distinguished non-proliferative diabetic retinopathy (NPDR) from type 2 diabetic patients with no diabetic retinopathy/controls, 65 candidate markers distinguished proliferative diabetic retinopathy (PDR) from NPDR, 1 candidate marker (thyroid receptor-interacting protein 11 [TRIP11]) distinguished PDR from PDR-DME/DME, and 3 candidate markers for therapeutic evaluation of PDR. Our results pinpoint that inflammatory response, which IL-6 mainly modulated, is responsible for the changes of proteomic profiles identified in DR. This was also validated by ELISA analysis, indicating that IL-6 could be potentially useful for diagnosing DR. Conclusion: We report a comprehensive patient-based proteomic approach to identify potential biomarkers for DR diagnosis, prognosis, and treatment evaluation. Supplementary information: The online version contains supplementary material available at 10.1007/s40200-023-01204-6.
ABSTRACT
OBJECTIVE: Genetic variants in EFTUD2 were proven to influence variable phenotypic expressivity in mandibulofacial dysostosis Guion-Almeida type (MFDGA) or mandibulofacial dysostosis with microcephaly (MFDM). Yet, the association between the severity of clinical findings with variants within the EFTUD2 gene has not been established. Thus, we aim to elucidate a possible genotype-phenotype correlation in MFDM. METHODS: Forty articles comprising 156 patients were evaluated. The genotype-phenotype correlation was analyzed using a chi-square or Fisher's exact test. RESULTS: The proportion of patients with MFDM was higher in Caucasian relative to Asian populations. Although, in general, there was no apparent genotype-phenotype correlation in patients with MFDM, Asians tended to have more severe clinical manifestations than Caucasians. In addition, cardiac abnormality presented in patients with intronic variants located in canonical splice sites was a predisposing factor in affecting MFDM severity. CONCLUSION: Altogether, this article provides the pathogenic variants observed in EFTUD2 and possible genotype-phenotype relationships in this disease.
ABSTRACT
OBJECTIVE: To assess the performance of serum cytokine IL-6 and IL-6/IL-10 ratio as biomarkers for the diagnosis of primary open-angle glaucoma (POAG) and for determining its progression. METHODS: In this study, 20 POAG patients and 21 healthy individuals from the Indonesian population were enrolled. The serum concentration of IL-6 and IL-10 were quantified. Comparative analysis was performed in addition to assessment of the diagnostic performance of cytokines using receiver-operating-curve (ROC) analysis. RESULTS: POAG patients had a higher IL-6 (p < 0.0001) and IL-6/IL-10 ratio (p < 0.0001) than controls. Among the POAG subjects, advanced-stage patients exhibited a higher IL-6/IL-10 ratio than those in the early-moderate stage (p = 0.001; p = 0.006). The ROC curve analysis showed that both IL-6 level and IL-6/IL-10 ratio exhibited an excellent capability of diagnosing POAG (cut-off of 20.5 pg/mL (100% sensitivity and 94% specificity) and 4.4 (88% sensitivity and 94% specificity), respectively). Serum IL-6/IL-10 ratio displayed a better performance than IL-6 in discriminating POAG severity with cut-off of at least 6.6 (sensitivity of 86% and specificity of 90%) and 9.1 (sensitivity of 89% and specificity of 78%) classified according to C/D ratio and MD of VF, respectively. CONCLUSION: The balance between IL-6 and IL-10 serum levels is potentially useful in discriminating POAG severity.
