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The Crumbs protein (CRB) family plays a crucial role in maintaining the apical-basal polarity and integrity of embryonic epithelia. The family comprises different isoforms in different animals and possesses diverse structural, localization, and functional characteristics. Mutations in the human CRB1 or CRB2 gene may lead to a broad spectrum of retinal dystrophies. Various CRB-associated experimental models have recently provided mechanistic insights into human CRB-associated retinopathies. The knowledge obtained from these models corroborates the importance of CRB in retinal development and maintenance. Therefore, complete elucidation of these models can provide excellent therapeutic prospects for human CRB-associated retinopathies. In this review, we summarize the current animal models and human-derived models of different CRB family members and describe the main characteristics of their retinal phenotypes.
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Proteínas de Membrana , Doenças Retinianas , Humanos , Animais , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Doenças Retinianas/genética , Doenças Retinianas/patologia , Doenças Retinianas/metabolismo , Retina/metabolismo , Retina/patologia , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Modelos Animais de Doenças , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , MutaçãoRESUMO
BACKGROUND: Presently, the global prevalence of myopia and high myopia reaches approximately 1.95 billion and 277 million individuals, respectively. Projections suggest that by 2050, the number of people with myopia may rise to 4.758 billion and those with high myopia to 938 million. In highly myopic eyes, the occurrence of MF is reported to be as high as 8-33%. SUMMARY: This review comprehensively addresses the classification, pathogenesis, natural progression, concomitant pathologies, and therapeutic strategies for macular foveoschisis in highly myopic patients. KEY MESSAGES: In recent years, macular foveoschisis has emerged as a prevalent complication in individuals with high myopia, primarily resulting from the combination of inward traction by vitreoretinal adhesions and outward traction exerted by posterior scleral staphyloma on the retina. While some maintain partial visual stability over an extended period, others may progress to macular holes or even retinal detachment. For highly myopic patients with macular foveoschisis, the mainstay procedures are vitrectomy, macular buckle, and posterior scleral reinforcement. However, there is controversy about whether to perform inner limiting membrane peeling and gas filling.
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Miopia Degenerativa , Retinosquise , Humanos , Retinosquise/diagnóstico , Retinosquise/etiologia , Miopia Degenerativa/complicações , Miopia Degenerativa/diagnóstico , Miopia Degenerativa/fisiopatologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Vitrectomia/métodos , Macula Lutea/patologiaRESUMO
BACKGROUND: Pars plana vitrectomy is the standard treatment for several vitreoretinal diseases. Continuous improvements in ophthalmic surgical techniques have led to excellent postoperative recovery of the anatomic structure of the fundus. However, postoperative visual outcomes are not always satisfactory. METHODS: A literature search of articles published before 31 December 2022 was conducted on PubMed using the following keywords: "diabetic retinopathy," "rhegmatogenous retinal detachment," "idiopathic epiretinal membrane," "idiopathic macular hole," "vitrectomy," "optical coherence tomography," "optical coherence tomography angiography," "microstructure," "microstructural," "hemodynamic," "hemodynamics," and "microcirculation." Additional studies were identified by hand-searching references for relevant studies. Articles were screened for language, repetition, and relevance to the direction of study. Studies with a sample size ≥ 7 and the final follow-up time ≥ 4 weeks after vitrectomy were included in this review. Only articles published in English were included. Articles not related to our topic were excluded. Reviews and single case reports were excluded. We structured this review by disease category. The thickness of the retina and choroid, the area of the foveal avascular zone, the vessel density of the retinal and choroidal capillary plexus, and the potential association of related parameters with postoperative visual outcomes are the main outcome measures of studies included in this review. RESULTS: A total of 48 studies were included in this review. There were contradictory results regarding the association between postoperative microcirculatory parameters and visual acuity in patients with diabetic macular edema, with some studies concluding that improvement in perimacular microcirculation may be an important factor that affects visual acuity, and others concluded that postoperative improvement in visual acuity was not related to changes in macular blood flow. The results of studies on the relationship between postoperative microstructural and microcirculatory parameters and visual acuity in rhegmatogenous retinal detachment, idiopathic epiretinal membrane, and idiopathic macular hole eyes have been inconsistent. In gas tamponade macula-off rhegmatogenous retinal detachment eyes, postoperative best-corrected visual acuity has been reported to correlate positively with vessel density of deep capillary plexus and negatively with foveal avascular zone area of superficial capillary plexus and deep capillary plexus. In silicone oil tamponade macula-off rhegmatogenous retinal detachment eyes, best-corrected visual acuity has been reported to be positively correlated with the retinal thickness of the parafoveal 3 mm temporal quadrant and positively correlated with the vessel density of the superficial capillary plexus in the foveal, parafoveal, and perifoveal area. In addition, best-corrected visual acuity was worse and associated with reduced thickness of the inner retina, ganglion cell layer, outer plexiform layer, and outer nuclear layer in silicone oil tamponade rhegmatogenous retinal detachment eyes compared to gas tamponade. Postoperative best-corrected visual acuity in idiopathic epiretinal membrane eyes was positively correlated with the foveal avascular zone area but negatively correlated with full retinal thickness and inner retinal thickness in the foveal and parafoveal areas. Improvement in postoperative best-corrected visual acuity in idiopathic macular hole eyes was associated with reduced inner retinal thickness and reduced foveal avascular zone area. CONCLUSIONS: Microstructural and hemodynamic changes are involved in the recovery process after PPV for different vitreoretinal diseases. The thickness of each retinal layer in different regions of the macula, foveal avascular zone area, and vessel density of different retinal capillary plexuses in different macular regions may be potential prognostic factors for postoperative visual recovery. However, the results of the existing literature are inconsistent and require further study.
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Sensitive detection of the SARS-CoV-2 protein remains a great research interest in clinical screening and diagnosis owing to the coronavirus epidemic. Here, an ultrasensitive chemiluminescence (CL) imaging strategy was developed through proximity hybridization to trigger the formation of a rolling circle-amplified G-quadruplex/hemin DNAzyme for the detection of the SARS-CoV-2 protein. The target protein was first recognized by a pair of DNA-antibody conjugates, Ab-1 and Ab-2, to form a proximity-ligated complex, Ab-1/SARS-CoV-2/Ab-2, which contained a DNA sequence complemental to block DNA and thus induced a strand displacement reaction to release the primer from a block/primer complex. The released primer then triggered a rolling circle amplification to form abundant DNAzyme units in the presence of hemin, which produced a strong chemiluminescent signal for the detection of the target protein by catalyzing the oxidation of luminol by hydrogen peroxide. The proposed assay showed a detectable concentration range over 5 orders of magnitude with the detection limit down to 6.46 fg/mL. The excellent selectivity, simple procedure, acceptable accuracy, and intrinsic high throughput of the imaging technique for analysis of serum samples demonstrated the potential applicability of the proposed detection method in clinical screening and diagnosis.
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Técnicas Biossensoriais , COVID-19 , DNA Catalítico , Quadruplex G , DNA Catalítico/metabolismo , Hemina , Humanos , Imunoensaio , Limite de Detecção , Luminescência , SARS-CoV-2RESUMO
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common prescription drugs for inflammation, and topical NSAIDs are often used in ophthalmology to reduce pain, photophobia, inflammation, and edema. In recent years, many published reports have found that NSAIDs play an important role in the treatment of retinal neurodegenerative diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, pathological myopia, and retinitis pigmentosa (RP). The aim of the current review is to provide an overview of the role of various NSAIDs in the treatment of retinal neurodegenerative diseases and the corresponding mechanisms of action. This review highlighted that the topical application of NSAIDs for the treatment of retinal degenerative diseases has been studied to a remarkable extent and that its beneficial effects in many diseases have been proven. In the future, prospective studies with large study populations are required to extend these effects to clinical settings.
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Doenças NeurodegenerativasRESUMO
Alcohol intake can cause a wide range of visual system abnormalities. In this study, we characterized how ethanol affects the growth, external morphology and locomotion of zebrafish, particularly with regard to retinal development. Zebrafish embryos were divided into 5 groups and put into hatching liquid for 6 hours. The embryos from 4 groups were treated with varying concentrations of ethanol (0.5%, 1.5%, 2.5% and 3% by volume) from 6 to 24 hours post-fertilization. The toxic effects of ethanol on embryonic development were assessed by mortality, hatching rate and morphologic deformity. The effects of ethanol on locomotive activity were assessed by autonomous motion detection and swimming behavior analysis. The effects of ethanol on retinal morphology were assessed by histologic, immunohistochemical and electron microscopy analyses. Ethanol treatment increased the mortality and induced growth retardation in zebrafish larvae. The locomotive activities of zebrafish embryos/larvae were impeded by exposure to higher (1.5% and 2.5%) concentrations of ethanol. Embryos exposed to higher levels of ethanol at the early developmental stage had a reduction in eye size. The ethanol treatment disrupts the architecture of the retina and reduces retinal size. Embryos exposed to 2.5% concentration of ethanol had morphologic abnormalities of the photoreceptors. Ethanol exposure also inhibited retinal cell differentiation and proliferation, but did not affect apical epithelial polarity. These findings suggest that ethanol affects the growth and external morphology of zebrafish, and higher levels of ethanol exposure can cause defects of locomotor activity and photoreceptor development.
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Etanol , Peixe-Zebra , Animais , Proliferação de Células , Embrião não Mamífero , Etanol/toxicidade , LocomoçãoRESUMO
Heart failure (HF) is a medical condition inability of the heart to pump sufficient blood to meet the metabolic demand of the body to take place. The number of hospitalized patients with cardiovascular diseases is estimated to be more than 1 million each year, of which 80% to 90% of patients ultimately progress to decompensated HF. Digitalis glycosides exert modest inotropic actions when administered to patients with decompensated HF. Although its efficacy in patients with HF and atrial fibrillation is clear, its value in patients with HF and sinus rhythm has often been questioned. A series of recent studies have cast serious doubt on the benefit of digoxin when added to contemporary HF treatment. We are hypothesizing the role and mechanism of exosome and its biological constituents responsible for worsening the disease state and mortality in decompensated HF patients on digitalis.
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Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Cardiotônicos/uso terapêutico , Digitalis/química , Digoxina/uso terapêutico , Exossomos/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Antiarrítmicos/farmacologia , Cardiotônicos/farmacologia , Digoxina/farmacologia , Humanos , Extratos Vegetais/farmacologia , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
Diabetic retinopathy (DR) is a devastating complication of diabetes. The aim of the present study is to investigate the exact role and mechanism of long noncoding RNA MALAT1 (MALAT1) in the progress of DR. An oxygen-induced retinopathy (OIR) mouse model and high glucose (HG) stimulated human retinal microvascular endothelial cells (HRMECs) were employed to mimic the pathological statues of DR. Quantitative real-time PCR (qRT-PCR) and Western blot results showed that MALAT1, VEGFA, and HIF-1α levels were increased in DR retinal tissues and HG-stimulated HRMECs, whereas the expression of miR-203a-3p was decreased. Knockdown of MALAT1 or upregulation of miR-203a-3p both suppressed HG-induced proliferation, migration, and tube formation of HRMECs. A dual-luciferase reporter assay showed that miR-203a-3p could bind to the predicted seed regions of MALAT1 as evidenced by the reduced luciferase activity. Furthermore, enforced downregulation of miR-203a-3p abolished the suppressive effect of MALAT1 silencing on HRMEC cell migration and tube formation. In conclusion, these data demonstrated that MALAT1 may affect angiogenesis by sponging miR-203a-3p in DR, suggesting that MALAT1 may act as a novel therapeutic target for the treatment of DR.
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Retinopatia Diabética/induzido quimicamente , Retinopatia Diabética/genética , MicroRNAs/genética , Neovascularização Patológica/genética , Oxigênio/farmacologia , RNA Longo não Codificante/genética , Animais , Linhagem Celular , Movimento Celular/genética , Proliferação de Células/genética , Diabetes Mellitus/genética , Retinopatia Diabética/patologia , Regulação para Baixo/genética , Células Endoteliais/patologia , Regulação Neoplásica da Expressão Gênica/genética , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/patologia , Retina/efeitos dos fármacos , Regulação para Cima/genéticaAssuntos
Fundo de Olho , Hemodinâmica , Doenças Retinianas , Vitrectomia , Humanos , Vitrectomia/métodos , Doenças Retinianas/cirurgia , Doenças Retinianas/fisiopatologia , Doenças Retinianas/diagnóstico , Hemodinâmica/fisiologia , Tomografia de Coerência Óptica/métodos , Vasos Retinianos/fisiopatologiaRESUMO
Dysregulation of microRNAs (miRNAs) has been implicated in cancer. Recently, miR-132 has been reported to be downregulated in the tissues of patients with breast cancer. In this study, we investigated the functional role of miR-132 and its direct target FOXA1 in breast cancer cells. In 30 human breast cancer tissues, FOXA1 was significantly overexpressed and negatively correlated with miR-132 expression. A bioinformatics analysis suggested that FOXA1 was a potential target of miR-132. Furthermore, dual luciferase reporter assays revealed that miR-132 dose-dependently inhibited the luciferase activity of the wt 3'UTR of FOXA1 rather than the mut 3'UTR of FOXA1 in human MDA-MB-468 and SK-BR3 breast cancer cells. Moreover, ectopic miR-132 expression significantly inhibited FOXA1 protein expression, whereas miR-132 knockdown promoted FOXA1 expression in the breast cancer cells. Ectopic miR-132 expression also suppressed proliferation of the breast cancer cells, whereas miR-132 knockdown promoted proliferation of the breast cancer cells, which was reversed by knockdown of FOXA1 expression. We conclude that MiR-132 suppresses proliferation of breast cancer cells at least partially though inhibition of FOXA1. These results suggest that miR-132 and FOXA1 may be potential biomarkers or therapeutic targets in breast cancer.
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Neoplasias da Mama/metabolismo , Fator 3-alfa Nuclear de Hepatócito/genética , MicroRNAs/genética , Adulto , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Fator 3-alfa Nuclear de Hepatócito/antagonistas & inibidores , Humanos , Pessoa de Meia-Idade , RNA Mensageiro/metabolismoRESUMO
Purpose: Daily modulation of gene expression is critical for the circadian rhythms of many organisms. One of the modulating mechanisms is based on nocturnin, a deadenylase that degrades mRNA in a circadian fashion. The nocturnin genes are expressed broadly, but their tissue expression patterns differ between mice and the frog Xenopus laevis; this difference suggests that the extent of the regulation of nocturin gene expression varies among species. In this study, we set out to characterize the expression patterns of two zebrafish nocturnin genes; in addition, we asked whether a frog nocturnin promoter has transcriptional activity in zebrafish. Methods: We used reverse transcription (RT)-PCR, quantitative real-time PCR (qRT-PCR), and rapid amplification of cDNA ends (RACE) analysis to determine whether the nocturnin-a and nocturnin-b genes are expressed in the eye, in situ hybridization to determine the cellular expression pattern of the nocturnin-b gene in the retina, and confocal microscopy to determine the protein expression pattern of the transgenic reporter green fluorescent protein (GFP) driven by the frog nocturnin promoter. Results: We found that the amino acid sequences of zebrafish nocturnin-a and nocturnin-b are highly similar to those of frog, mouse, and human nocturnin homologs. Only nocturnin-b is expressed in the eye. Within the retina, nocturnin-b mRNA was expressed at higher levels in the retinal photoreceptors layer than in other cellular layers. This expression pattern echoes the restricted photoreceptor expression of nocturnin in the frog. We also found that the frog nocturnin promoter can be specifically activated in zebrafish rod photoreceptors. Conclusions: The high level of similarities in amino acid sequences of human, mouse, frog, and zebrafish nocturnin homologs suggest these proteins maintain a conserved deadenylation function that is important for regulating retinal circadian rhythmicity. The rod-specific transcriptional activity of the frog nocturnin promoter makes it a useful tool to drive moderate and rod-specific transgenic expression in zebrafish. The results of this study lay the groundwork to study nocturnin-based circadian biology of the zebrafish retina.
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Regulação da Expressão Gênica/fisiologia , Proteínas Nucleares/genética , Regiões Promotoras Genéticas/genética , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Fatores de Transcrição/genética , Ativação Transcricional/fisiologia , Proteínas de Xenopus/genética , Proteínas de Peixe-Zebra/genética , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Ritmo Circadiano/fisiologia , Amplificação de Genes , Técnicas de Transferência de Genes , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hibridização In Situ , Microscopia Confocal , Dados de Sequência Molecular , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência , Xenopus laevis , Peixe-ZebraRESUMO
PURPOSE: To investigate the repeatability and agreement of corneal astigmatism measurements in eyes with irregular corneal astigmatism component (ICAC) using four devices: IOLMaster 700 biometer, Lenstar 900 biometer, iTrace, and Pentacam. DESIGN: Prospective cross-sectional reliability analysis. METHODS: Sixty-four eyes (52 patients) with ICAC were examined three times using the four devices. The eye with ICAC in this study is defined as the cornea has a certain degree of irregular astigmatism (asymmetric and/or skewed bowtie pattern of corneal topography according to corneal topography classification), accompanied with total corneal higher-order aberrations in the 4 mm zone of 0.3 µm or greater. Corneal astigmatism was evaluated using three categories: anterior corneal astigmatism (ACA), posterior corneal astigmatism, and total corneal astigmatism (TCA). The repeatability was determined using the ∆Ast (arithmetic mean of vector differences among three repeated corneal astigmatism measurements). Bland-Altman plots and astigmatism vector analyses were employed to assess agreement. RESULTS: The IOLMaster 700 (∆Ast = 0.27 ± 0.20 D) showcased higher repeatability in ACA measurements compared to iTrace (∆Ast = 0.37 ± 0.38 D, P = .040) and Pentacam (∆Ast = 0.50 ± 0.22 D, P < .001), and paralleled the performance of Lenstar 900 (∆Ast = 0.31 ± 0.26 D, P = .338). The Pentacam (∆Ast = 0.09 ± 0.07 D, P < .001) demonstrated superior repeatability in posterior corneal astigmatism, whereas the IOLMaster 700 (∆Ast = 0.33 ± 0.23 D, P < .001) excelled in TCA. The IOLMaster 700 exhibited good agreement with either Lenstar 900 or iTrace, characterized by narrow 95% limits of agreement and clinically acceptable vector differences. Conversely, vector differences between Pentacam and the other three devices in ACA and TCA measurements were clinically significant, exceeding 0.50 D (all P < .05). CONCLUSIONS: In terms of repeatability of corneal astigmatism measurements in eyes with ICAC, the IOLMaster 700 and Lenstar 900 outperformed iTrace and Pentacam. While the IOLMaster 700 can be used interchangeably with either Lenstar 900 or iTrace, the Pentacam is not interchangeable with the other three devices.
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Astigmatismo , Biometria , Córnea , Topografia da Córnea , Humanos , Astigmatismo/diagnóstico , Astigmatismo/fisiopatologia , Estudos Prospectivos , Reprodutibilidade dos Testes , Feminino , Masculino , Estudos Transversais , Topografia da Córnea/instrumentação , Pessoa de Meia-Idade , Adulto , Córnea/fisiopatologia , Biometria/instrumentação , Idoso , Adulto Jovem , Acuidade Visual/fisiologiaRESUMO
Retinal detachment caused by severe ocular trauma is a type of refractory vitreoretinal disease. Current treatment methods include vitrectomy combined with silicone oil tamponade. However, long-term use of silicone oil tamponade has various complications, including a risk of silicone oil dependence that eventually leads to eyeball atrophy and enucleation. Foldable capsular vitreous bodies (FCVBs) offer a good solution for these problems. However, FCVBs have not been used in large-scale clinical applications and few cases have been reported in the published literature. The main use of FCVBs, based on current evidence, is in the treatment of the relatively few (but important) patients whose eyes have no visual potential; the aim of treatment in these patients is globe preservation, rather than restoration of vision. Here, we describe two patients who underwent FCVB implantation. The findings in these patients indicated that FCVBs can effectively support the vitreous cavity and detached retina. FCVB implantation may thus offer a safe and effective method for treatment of severe retinal detachment, avoiding the inconvenience caused by silicone oil dependence and enucleation. To confirm its long-term usefulness in clinical applications, many additional case reports are needed.
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Traumatismos Oculares , Descolamento Retiniano , Humanos , Descolamento Retiniano/cirurgia , Óleos de Silicone , Vitrectomia , Corpo VítreoRESUMO
Diabetic retinopathy (DR) is a type of retinal microangiopathy caused by diabetes mellitus. It has become the leading cause of blindness among working individuals worldwide. DR is becoming increasingly common among younger diabetic patients and there is a need for lifelong treatment. The pathogenic mechanisms of DR are influenced by a number of factors, such as hyperglycemia, hyperlipidemia, inflammatory response and oxidative stress, among others. Currently, the treatment methods for DR mainly include retinal photocoagulation, vitrectomy, or antivascular endothelial growth factor (VEGF) therapy. However, these methods have some disadvantages and limitations. Therefore, it is a matter of great interest and urgency to discover drugs that can target the pathogenesis of DR. Since ancient times, traditional Chinese medicine practitioners have accumulated extensive experiences in the use of Chinese herbal medicine for the prevention and treatment of diseases. In the theory of traditional Chinese medicine, curcumin has the effects of promoting blood circulation and relieving pain. A number of studies have also demonstrated that curcumin has multiple biological activities, including exerting antiapoptotic, antiinflammatory, antioxidant and antitumor properties. In recent years, studies have also confirmed that curcumin can prevent a variety of diabetic complications, including diabetic nephropathy (DN). However, the preventive and curative effects of curcumin on DR and its mechanisms of action have not yet been fully elucidated. The present review aimed to explore the therapeutic potential of curcumin in diabetes mellitus and DR.
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Anti-Inflamatórios/uso terapêutico , Curcumina/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Animais , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Humanos , Medicina Tradicional ChinesaRESUMO
Purpose: Human Crb1 is implicated in some forms of retinal degeneration, suggesting a role in photoreceptor maintenance. Multiple Crumbs (Crb) polarity genes are expressed in vertebrate retina, although their functional roles are not well understood. To gain further insight into Crb and photoreceptor maintenance, we compared retinal cell densities between wild-type and Tg(RH2-2:Crb2b-sfEX/RH2-2:GFP)pt108b transgenic zebrafish, in which the extracellular domain of Crb2b-short form (Crb2b-sfEX) is expressed in the retina as a secreted protein, which disrupts the planar organization of RGB cones (red, green, and blue) by interfering with Crb2a/2b-based cone-cone adhesion. Methods: We used standard morphometric techniques to assess age-related changes in retinal cell densities in adult zebrafish (3 to 27 months old), and to assess effects of the Crb2b-sfEX transgene on retinal structure and photoreceptor densities. Linear cell densities were measured in all retinal layers in radial sections with JB4-Feulgen histology. Planar (surface) densities of cones were determined in retinal flat-mounts. Cell counts from wild-type and pt108b transgenic fish were compared with both a "photoreceptor maintenance index" and statistical analysis of cell counts. Results: Age-related changes in retinal cell linear densities and cone photoreceptor planar densities in wild-type adult zebrafish provided a baseline for analysis. Expression of Crb2b-sfEX caused progressive and selective degeneration of RGB cones, but had no effect on ultraviolet-sensitive (UV) cones, and increased numbers of rod photoreceptors. Conclusions: These differential responses of RGB cones, UV cones, and rods to sustained exposure to Crb2b-sfEX suggest that Crb-based photoreceptor maintenance mechanisms are highly selective.
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Modelos Animais de Doenças , Regulação da Expressão Gênica/fisiologia , Proteínas de Membrana/genética , Células Fotorreceptoras Retinianas Cones/patologia , Degeneração Retiniana/fisiopatologia , Proteínas de Peixe-Zebra/genética , Envelhecimento/fisiologia , Animais , Animais Geneticamente Modificados , Contagem de Células , Imuno-Histoquímica , Peixe-ZebraRESUMO
LncRNA H19 is involved in the development of multiple cancers. Here, we firstly provide new evidence that H19 can induce LIN28B, a conserved RNA binding protein, to accelerate lung cancer growth through sponging miR-196b. Abundance in LIN28B was observed in clinical lung cancer samples. A positive link was observed between H19 and LIN28B in clinical lung cancer samples. In lung cancer cells, H19 was capable of increasing LIN28B expression. Mechanistically, miR-196b directly targeted LIN28B to inhibit LIN28B expression. H19 was capable of promoting LIN28B expression through sequestering miR-196b. Functionally, H19-increased LIN28B conferred the cell proliferation of lung cancer. Our finding indicates that H19 depresses miR-196b to elevate LIN28B, resulting in accelerating cell proliferation in lung cancer.
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Progressão da Doença , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/metabolismo , Regiões 3' não Traduzidas/genética , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genéticaRESUMO
PURPOSE: Methanol exposure have been shown to produce retinal abnormalities and visual dysfunctions in rodents and other mammals developing in utero. In this study, we characterized how methanol affects the retinal development in an ex utero embryonic system, the zebrafish. METHODS: Zebrafish embryos were raised for 24 hours in fish water supplemented with various concentrations of methanol at 6 hours after fertilisation. The effects of methanol on retinal morphology were assessed by histologic and immunohistochemical analyses. RESULTS: Zebrafish embryos exposed to moderate (3%) and high (4%) levels of methanol during early embryonic development had a small eye phenotype. Embryos exposed to high (4%) level of methanol had morphological abnormalities of the retinal pigment epithelia and the photoreceptors. Methanol exposure also caused inhibition of cell differentiation and proliferation in the retina at the early developmental stage. CONCLUSIONS: Low concentrations of methanol affect photoreceptor function but do not disturb retinal morphology. Higher levels of methanol exposure cause retinal patterning defects and a small eye phenotype.
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OBJECTIVE: The purpose of this study was to elucidate the role of microRNA-130a (miR-130a) in obstructive sleep apnea hypopnea syndrome (OSAHS)-associated pulmonary hypertension (PHT) by targeting the growth arrest-specific homeobox (GAX) gene. METHODS: A total of 108 patients with OSAHS-associated PHT were recruited as the OSAHS-associated PHT group and 110 healthy individuals were randomly selected as the normal control group. Human umbilical vein endothelial cells (HUVECs) were selected and divided into the control, miR-130a mimic, mimic negative control (NC), miR-130a inhibitor, and inhibitor-NC groups. The dual luciferase reporter gene assay was used to identify the relationship between miR-130a and the GAX gene. The quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were applied for the relative expressions of miR-130a and the mRNA and protein expressions of GAX. Serum levels of endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), nitric oxide (NO), and super oxide dismutase (SOD) were detected. Cell apoptosis and angiogenic activity were analyzed by flow cytometry and cell tube formation assay. RESULTS: GAX was a target gene of miR-130a. Compared with the normal control group, the relative expression of miR-130a and the serum levels of ET-1 and VEGF were increased, whereas the mRNA expression of GAX and the serum levels of NO and SOD were decreased in the OSAHS-associated PHT group. Compared with the control, mimic-NC, and inhibitor-NC groups, the relative expressions of miR-130a in the miR-130a mimic group were enhanced, whereas the expression of miR-130a in the miR-130a inhibitor group was reduced. However, the mRNA and protein expressions of GAX showed an opposite trend in the miR-130a mimic and miR-130a inhibitor groups. In comparison to the control, mimic-NC, and inhibitor-NC groups, the miR-130a mimic group had an increase of ET-1 and VEGF expressions, whereas the expressions of NO and SOD were reduced. However, the miR-130a inhibitor group exhibited an opposite trend. The apoptosis rate and tube formation number in the miR-130a mimic group were obviously increased, whereas the miR-130a inhibitor group showed an obvious decrease. CONCLUSION: These data provided strong evidence that miR-130a may be involved in the progression of OSAHS-associated PHT by down-regulating GAX gene.
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Proteínas de Homeodomínio/metabolismo , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/metabolismo , MicroRNAs/metabolismo , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/metabolismo , Apoptose/fisiologia , Biomarcadores/metabolismo , Células Cultivadas , Regulação para Baixo , Endotelina-1/sangue , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Óxido Nítrico/sangue , RNA Mensageiro , Distribuição Aleatória , Superóxido Dismutase/sangue , Transfecção , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
OBJECTIVE: The aim of this study was to validate the G.LAB MD2680 digital automatic blood pressure (BP) monitor according to major international protocols. PARTICIPANTS AND METHODS: The device was evaluated against auscultatory sphygmomanometry according to the European Society of Hypertension International Protocol (ESH-IP) revision 2010, the British Hypertension Society (BHS), and the International Organization for Standardization (ISO) 81060-2:2013 protocols. Bland-Altman plots were completed for systolic (SBP) and diastolic blood pressures (DBP), and the mean differences and SDs between the test device and the reference device were computed for all BP values. RESULTS: The G.LAB MD2680 passed the ESH-IP revision 2010 on 33 participants with a mean device-observer difference of 0.89±4.97 mmHg for SBP and 0.72±4.91 mmHg for DBP, respectively. The device achieved A/A grading for the BHS protocol among 85 participants with a device-observer difference of 0.70±6.35 mmHg for SBP and 0.62±6.41 mmHg for DBP, respectively. Furthermore, it also fulfilled the two criteria of the ISO 81060-2:2013 protocol. CONCLUSION: The G.LAB MD2680 digital automatic BP monitor fulfilled the accuracy requirements of the ESH-IP revision 2010 and the ISO 81060-2:2013 protocols, and achieved A/A grade of the BHS protocol, and it can be recommended for self-measurement in adults.