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      Novel Potential Biomarkers for Retinopathy of Prematurity

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          Abstract

          Retinopathy of prematurity (ROP) is the main risk factor for vision-threatening disease in premature infants with low birth weight. An accumulating number of independent studies have focused on ROP pathogenesis and have demonstrated that laser photocoagulation therapy and/or anti-VEGF treatment are effective. However, early diagnosis of ROP is still critical. At present, the main method of ROP screening is based on binocular indirect ophthalmoscopy. However, the judgment of whether ROP occurs and whether treatment is necessary depends largely on ophthalmologists with a great deal of experience. Therefore, it is essential to develop a simple, accurate and effective diagnostic method. This review describes recent findings on novel biomarkers for the prediction, diagnosis and prognosis of ROP patients. The novel biomarkers were separated into the following categories: metabolites, cytokines and growth factors, non-coding RNAs, iconography, gut microbiota, oxidative stress biomarkers, and others. Biomarkers with high sensitivity and specificity are urgently needed for the clinical applications of ROP. In addition, using non-invasive or minimally invasive methods to obtain samples is also important. Our review provides an overview of potential biomarkers of ROP.

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          Most cited references131

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          Circular RNAs are a large class of animal RNAs with regulatory potency.

          Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.
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            Epidemiology and causes of preterm birth

            Summary This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks' gestational age after: (1) spontaneous labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12–13% in the USA and 5–9% in many other developed countries; however, the rate of preterm birth has increased in many locations, predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple pregnancies. Common reasons for indicated preterm births include pre-eclampsia or eclampsia, and intrauterine growth restriction. Births that follow spontaneous preterm labour and PPROM—together called spontaneous preterm births—are regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race, periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.
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              Detecting and characterizing circular RNAs.

              Circular RNA transcripts were first identified in the early 1990s but knowledge of these species has remained limited, as their study through traditional methods of RNA analysis has been difficult. Now, novel bioinformatic approaches coupled with biochemical enrichment strategies and deep sequencing have allowed comprehensive studies of circular RNA species. Recent studies have revealed thousands of endogenous circular RNAs in mammalian cells, some of which are highly abundant and evolutionarily conserved. Evidence is emerging that some circRNAs might regulate microRNA (miRNA) function, and roles in transcriptional control have also been suggested. Therefore, study of this class of noncoding RNAs has potential implications for therapeutic and research applications. We believe the key future challenge for the field will be to understand the regulation and function of these unusual molecules.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                02 February 2022
                2022
                : 9
                : 840030
                Affiliations
                [1] 1Department of Ophthalmology, The Second Xiangya Hospital of Central South University , Changsha, China
                [2] 2Hunan Clinical Research Center of Ophthalmic Disease , Changsha, China
                [3] 3Department of Pediatrics, The Second Xiangya Hospital of Central South University , Changsha, China
                [4] 4Department of Ophthalmology, Kurume University School of Medicine , Kurume, Japan
                Author notes

                Edited by: Xiaoyan Ding, Sun Yat-sen University, China

                Reviewed by: Ye Liu, Zhejiang University, China; Wencui Wan, The First Affiliated Hospital of Zhengzhou University, China

                *Correspondence: Yedi Zhou zhouyedi@ 123456csu.edu.cn

                This article was submitted to Ophthalmology, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2022.840030
                8848752
                35187013
                6863a4cd-855b-471c-94c3-e51471f9786e
                Copyright © 2022 Tan, Li, Wang, Zou, Jia, Yoshida and Zhou.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 December 2021
                : 12 January 2022
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 133, Pages: 10, Words: 8492
                Funding
                Funded by: Changsha Science and Technology Project, doi 10.13039/501100019054;
                Funded by: Fundamental Research Funds for Central Universities of the Central South University, doi 10.13039/501100012476;
                Categories
                Medicine
                Review

                biomarker,retinopathy of prematurity,metabolites,cytokines and growth factors,non-coding rnas,gut microbiota,oxidative stress biomarkers,iconography

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