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1.
Hepatology ; 78(1): 103-119, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35713976

RESUMO

BACKGROUND AND AIMS: Succinate dehydrogenase enzyme (SDH) is frequently diminished in samples from patients with hepatocellular carcinoma (HCC), and SDH reduction is associated with elevated succinate level and poor prognosis in patients with HCC. However, the underlying mechanisms of how impaired SDH activity promotes HCC remain unclear. APPROACH AND RESULTS: In this study, we observed remarkable downregulations of SDH subunits A and B (SDHA/B) in chronic liver injury-induced murine HCC models and patient samples. Subsequent RNA sequencing, hematoxylin and eosin staining, and immunohistochemistry analyses of HCC samples revealed that Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) were significantly upregulated in HCC, with their levels inversely correlating with that of SDHA/B. YAP/TAZ stability was greatly enhanced in SDHA/B-depleted HCC cells along with accumulation of succinate. Further mechanistic analyses demonstrated that impaired activity of SDHA/B resulted in succinate accumulation, which facilitated the deNEDDylation of cullin1 and therefore disrupted the E3 ubiquitin ligase SCF ß-TrCP complex, consequently leading to YAP/TAZ stabilization and activation in HCC cells. The accelerated in vitro cell proliferation and in vivo tumor growth caused by SDHA/B reduction or succinate exposure were largely dependent on the aberrant activation of YAP/TAZ. CONCLUSIONS: Our study demonstrated that SDHA/B reduction promotes HCC proliferation by preventing the proteasomal degradation of YAP/TAZ through modulating cullin1 NEDDylation, thus binding SDH-deficient HCC cells to YAP/TAZ pathway and rendering these cells vulnerable to YAP/TAZ inhibition. Our findings warrant further investigation on the therapeutic effects of targeting YAP/TAZ in patients with HCC displaying reduced SDHA/B or elevated succinate levels.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Hepáticas/patologia , Transativadores/metabolismo , Proteínas de Sinalização YAP , Succinatos , Complexo II de Transporte de Elétrons/metabolismo
2.
Cytokine ; 179: 156640, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38735245

RESUMO

INTRODUCTION: To investigate the levels of angiogenesis and inflammatory cytokines in individuals with myopic choroidal neovascularization (mCNV) and the changes in these factors following intravitreal anti-VEGF injection. METHODS: Aqueous humor samples were gathered from eyes with mCNV, those with single macular bleeding (SMB) without mCNV in highly myopic eyes, and those with age-related cataracts. Using a multiplex bead immunoassay, we analyzed 28 angiogenesis and inflammatory factors in the aqueous humor. Furthermore, clinical data were documented for correlation analysis. RESULTS: In this study, the levels of vascular endothelial growth factor A (VEGF-A), interleukin 8 (IL-8), and fibroblast growth factors 1 (FGF-1) were significantly elevated in mCNV compared to SMB eyes (p < 0.05). Their odds ratios for mCNV occurrence were 1.05, 3.45, and 2.64, respectively. Hepatocyte growth factor (HGF) and VEGF-C were notably higher in mCNV than in cataract patients (p < 0.05), and VEGF-C correlated to the degree of myopic atrophic maculopathy (p = 0.024). Axial length exhibited a negative correlation with VEGF-A and positive correlations with VEGF-C, HGF, and MCP-1 (p < 0.01). Following anti-VEGF treatment, a reduction in VEGF-A, endothelin-1, and FGF-2 was noted in mCNV patients (p < 0.05), but MCP-1 levels increased. CONCLUSION: Our findings highlight the predominant role of angiogenesis and inflammation factors in mCNV pathogenesis. VEGF-C's correlation with axial length and atrophy suggests its involvement in the process of myopic atrophic maculopathy.


Assuntos
Neovascularização de Coroide , Miopia , Fator A de Crescimento do Endotélio Vascular , Humanos , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fator A de Crescimento do Endotélio Vascular/metabolismo , Miopia/tratamento farmacológico , Miopia/patologia , Miopia/metabolismo , Miopia/complicações , Injeções Intravítreas , Inflamação/metabolismo , Inflamação/patologia , Humor Aquoso/metabolismo , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Citocinas/metabolismo , Adulto , Angiogênese
3.
Prep Biochem Biotechnol ; 53(7): 880-890, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36563056

RESUMO

Trichoderma reesei was induced to produce cellulase by a combination of glucose and ß-disaccharide; however, lower levels of auxiliary proteins for degrading lignocellulosic biomass were detected by iTRAQ analysis compared with cellulose as an inducer, especially cellulose induced protein 1 (CIP1). In this study, A pdc1 promoter-driven overexpression of the endogenous Trcip1 gene was observed in T. reesei Rut C30, and the Trcip1 transcription levels of the two transformants, T. reesei OE-cip1-1 and OE-cip1-2, demonstrated 31.2- and 164.6-fold increases, respectively, but there was no significant change in cellobiohydrolase, endoglucanase and filter paper activity at 48 h. The crude enzyme was then used to hydrolyze corn stover. For T. reesei OE-cip1-1 and OE-cip1-2, the hydrolysis efficiency increased by 25.0 and 28.6% with a solid loading of 5% at 2 h, respectively. Simultaneously, 85.5 and 85.2 g/L glucose were released using a cellulase cocktail at high solid loading (20%), and these glucose release rates were significantly greater than that of T. reesei Rut C30 cellulase (77.4 g/L) at 120 h. Furthermore, scanning electron microscopy (SEM) and X-ray diffraction (XRD) showed that the enhanced hydrolysis efficiency was primarily triggered by the decrease in the crystallinity of lignocellulose, and the fiber structure had varying degrees of loosening and disintegration.


Assuntos
Celulase , Celulases , Trichoderma , Celulose/metabolismo , Zea mays/metabolismo , Glucose/metabolismo , Celulase/genética , Celulase/metabolismo
4.
Acta Pharmacol Sin ; 43(10): 2687-2695, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35296779

RESUMO

The small molecule chemical compound cinobufotalin (CB) is reported to be a potential antitumour drug that increases cisplatin (DDP) sensitivity in nasopharyngeal carcinoma. In this study, we first found that CB decreased DDP resistance, migration and invasion in lung adenocarcinoma (LUAD). Mechanistic studies showed that CB induced ENKUR expression by suppressing PI3K/AKT signalling to downregulate c-Jun, a negative transcription factor of ENKUR. Furthermore, ENKUR was shown to function as a tumour suppressor by binding to ß-catenin to decrease c-Jun expression, thus suppressing MYH9 transcription. Interestingly, MYH9 is a binding protein of ENKUR. The Enkurin domain of ENKUR binds to MYH9, and the Myosin_tail of MYH9 binds to ENKUR. Downregulation of MYH9 reduced the recruitment of the deubiquitinase USP7, leading to increased c-Myc ubiquitination and degradation, decreased c-Myc nuclear translocation, and inactivation of epithelial-mesenchymal transition (EMT) signalling, thus attenuating DDP resistance. Our data demonstrated that CB is a promising antitumour drug and may be a candidate chemotherapeutic drug for LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Antineoplásicos , Cisplatino , Neoplasias Nasofaríngeas , Proteínas Adaptadoras de Transdução de Sinal , Adenocarcinoma de Pulmão/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Bufanolídeos , Proteínas de Ligação a Calmodulina , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Cadeias Pesadas de Miosina , Miosinas/metabolismo , Neoplasias Nasofaríngeas/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição/metabolismo , Peptidase 7 Específica de Ubiquitina , beta Catenina/metabolismo
5.
Retina ; 42(3): 540-547, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35188492

RESUMO

PURPOSE: To explore the characteristics and underlying mechanisms of myopic traction maculopathy (MTM) with axial length less than 26.5 mm and to assess the effectiveness of macular buckling for the treatment of MTM. METHODS: Thirty-eight MTM eyes with axial length less than 26.5 mm were prospectively enrolled. Thirty-one eyes received surgery, and they were followed up for at least 6 months. Characteristics of MTM and surgical outcomes were evaluated. RESULTS: Of the MTM eyes, 92.11% (35/38) showed posterior staphyloma. Narrow macular staphyloma was the most common type (54.29%, 19/35), followed by peripapillary (37.14%, 13/35). Three cases (8.57%) had wide macular staphyloma, and 44.74% of cases (17/38) had vitreoretinal traction. Twenty-two MTM eyes of type T3 underwent macular buckling surgery, and all the cases achieved foveal reattachment after the surgery. The mean best-corrected visual acuity improved significantly at the 6-month follow-up (P < 0.001). Nine MTM eyes of type T4 or T5 received combined surgery, all macular holes recovered, and the best-corrected visual acuity also improved postoperatively (P = 0.008) as of the 6-month visit. CONCLUSION: Posterior staphyloma might serve as the initial force of the pathogenesis of MTM in eyes with axial length ˂26.5 mm. Macular buckling is a productive way to improve the MTM.


Assuntos
Comprimento Axial do Olho/patologia , Miopia Degenerativa/complicações , Doenças Retinianas/diagnóstico , Doenças Retinianas/cirurgia , Corpo Vítreo/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doenças Retinianas/fisiopatologia , Estudos Retrospectivos , Recurvamento da Esclera , Aderências Teciduais/diagnóstico , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Vitrectomia , Adulto Jovem
6.
Molecules ; 28(1)2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36615319

RESUMO

Molecular probes based on the excited-state intramolecular proton-transfer (ESIPT) mechanism have emerged to be attractive candidates for various applications. Although the steady-state fluorescence mechanisms of these ESIPT-based probes have been reported extensively, less information is available about the fluorescence lifetime characteristics of newly developed NIR-emitting dyes. In this study, four NIR-emitting ESIPT dyes with different cyanine terminal groups were investigated to evaluate their fluorescence lifetime characteristics in a polar aprotic solvent such as CH2Cl2. By using the time-correlated single-photon counting (TCSPC) method, these ESIPT-based dyes revealed a two-component exponential decay (τ1 and τ2) in about 2-4 nanoseconds (ns). These two components could be related to the excited keto tautomers. With the aid of model compounds (5 and 6) and low-temperature fluorescence spectroscopy (at -189 ℃), this study identified the intramolecular charge transfer (ICT) as one of the major factors that influenced the τ values. The results of this study also revealed that both fluorescence lifetimes and fractional contributions of each component were significantly affected by the probe structures.


Assuntos
Sondas Moleculares , Prótons , Espectrometria de Fluorescência , Corantes Fluorescentes/química , Solventes/química
7.
Graefes Arch Clin Exp Ophthalmol ; 259(9): 2513-2519, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33675393

RESUMO

PURPOSE: To compare the outcomes of macular buckling (MB) surgery between myopic foveal detachment (FD) eyes with and without ellipsoid zone (EZ) disruption. METHODS: A retrospective, case-control study. Forty-four consecutive eyes from 44 patients received MB surgery for myopic FD between November 2017 and January 2019 were included. The eyes were divided into two groups according to the integrity of EZ on spectral-domain optical coherence tomography (SD-OCT): 28 eyes with disrupted EZ band and 16 eyes with intact EZ band. Main outcome measures were visual acuity and the duration of subfoveal fluid (SFF) after MB. RESULTS: The mean follow-up time was 17.64 ± 6.61 and 16.06 ± 5.78 months in the disrupted EZ and intact EZ group, respectively (P = 0.430). The logMAR best-corrected visual acuity (BCVA) improved significantly, from 1.13 ± 0.46 and 1.12 ± 0.39 at baseline to 0.85 ± 0.65 (P = 0.002) and 0.53 ± 0.33 (P = 0.000) for the disrupted EZ group and intact EZ group, respectively. The mean visual improvement was 15.00 ± 14.14 Early Treatment Diabetic Retinopathy Study (ETDRS) letters for the disrupted EZ group and 26.88 ± 19.48 ETDRS letters for the intact EZ group. Significant difference was found on both final postoperative BCVA (P = 0.035) and visual improvement (P = 0.025). At 6 months, SFF remained in 53.57% (15/28) of the eyes in the disrupted EZ group and in only 12.50% (2/16) of the eyes in the intact EZ group (P = 0.018). CONCLUSION: The intact EZ group showed better functional and anatomical outcomes than the disrupted EZ group after MB surgery.


Assuntos
Fóvea Central , Tomografia de Coerência Óptica , Estudos de Casos e Controles , Humanos , Estudos Retrospectivos , Acuidade Visual
8.
Retina ; 41(7): 1496-1501, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33239543

RESUMO

PURPOSE: To analyze clinical characteristics in eyes with myopic traction maculopathy (MTM). METHODS: Nine hundred and ninety-one patients (1,334 eyes) with MTM, who visited Zhongshan Ophthalmic Center from January 2014 to December 2019, were involved. Myopic traction maculopathy was classified into six grades according to the new classification system: no macular schisis (T0), inner or outer foveoschisis (FS) (T1); inner and outer FS (T2), foveal detachment (T3), full-thickness macular hole (T4), and macular hole retinal detachment (T5). RESULTS: Seven hundred and seventy-eight (58.32%) eyes were in T0, 157 (11.77%) in T1, 177 (13.27%) in T2, 129 (9.67%) in T3, 45 (3.37%) in T4, and 48 (3.67%) in T5. With the severity of MTM, age increased and the best-corrected visual acuity became worse (P < 0.001). However, no significant differences were found on spherical equivalent refraction or axial length among different grades of MTM (P > 0.05). Moreover, significant differences on best-corrected visual acuity, spherical equivalent refraction, axial length, and staphyloma rate existed between eyes with inner FS and eyes with outer FS (P < 0.01), but not between eyes with outer FS and eyes with both inner FS and outer FS (P > 0.05). Besides, significant differences were found on spherical equivalent refraction, axial length, and staphyloma rate between full-thickness macular hole with and without macular schisis (P < 0.001). CONCLUSION: Spherical equivalent refraction and axial length were not correlated with the severity of MTM in this cohort. It might be preferable to categorize eyes with outer FS and eyes with both inner FS and outer FS as a same grade. Potential difference in the pathogenesis between full-thickness macular hole with and without macular schisis might exist.


Assuntos
Macula Lutea/diagnóstico por imagem , Degeneração Macular/classificação , Miopia Degenerativa/complicações , Refração Ocular/fisiologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Degeneração Macular/diagnóstico , Degeneração Macular/etiologia , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/fisiopatologia , Estudos Retrospectivos , Adulto Jovem
9.
Entropy (Basel) ; 23(12)2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34945923

RESUMO

With the rapid growth of the Internet, the curse of dimensionality caused by massive multi-label data has attracted extensive attention. Feature selection plays an indispensable role in dimensionality reduction processing. Many researchers have focused on this subject based on information theory. Here, to evaluate feature relevance, a novel feature relevance term (FR) that employs three incremental information terms to comprehensively consider three key aspects (candidate features, selected features, and label correlations) is designed. A thorough examination of the three key aspects of FR outlined above is more favorable to capturing the optimal features. Moreover, we employ label-related feature redundancy as the label-related feature redundancy term (LR) to reduce unnecessary redundancy. Therefore, a designed multi-label feature selection method that integrates FR with LR is proposed, namely, Feature Selection combining three types of Conditional Relevance (TCRFS). Numerous experiments indicate that TCRFS outperforms the other 6 state-of-the-art multi-label approaches on 13 multi-label benchmark data sets from 4 domains.

10.
J Cell Mol Med ; 24(1): 126-138, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31642192

RESUMO

Vascular endothelial growth factor receptors (VEGFRs) are major contributors to angiogenesis and lymphangiogenesis through the binding of VEGF ligands. We have previously shown that the bone marrow tyrosine kinase BMX is critical for inflammatory angiogenesis via its direct transactivation of VEGFR2. In the present study, we show that siRNA-mediated silencing of BMX led to a significant decrease in the total levels of VEGFR2 mRNA and protein, without affecting their stability, in human endothelial cells (ECs). Interestingly, BMX was detected in the nuclei of ECs, and the SH3 domain of BMX was necessary for its nuclear localization. Luciferase assays showed a significant decrease in the Vegfr2 (kdr) gene promoter activity in ECs after BMX silencing, indicating that BMX is necessary for Vegfr2 transcription. In addition, we found that wild-type BMX, but not a catalytic inactive mutant BMX-K445R, promoted Vegfr2 promoter activity and VEGF-induced EC migration and tube sprouting. Mechanistically, we show that the enhancement of Vegfr2 promoter activity by BMX was mediated by Sp1, a transcription factor critical for the Vegfr2 promoter. Loss of BMX significantly reduced Sp1 binding to the Vegfr2 promoter as assayed by chromatin immunoprecipitation assays. Wild-type BMX, but not a kinase-inactive form of BMX, associated with and potentially phosphorylated Sp1. Moreover, a nuclear-targeted BMX (NLS-BMX), but not cytoplasm-localized form (NES-BMX), bound to Sp1 and augmented VEGFR2 expression. In conclusion, we uncovered a novel function of nuclear-localized BMX in regulating VEGFR2 expression and angiogenesis, suggesting that BMX is a therapeutic target for angiogenesis-related diseases.


Assuntos
Núcleo Celular/metabolismo , Regulação da Expressão Gênica , Neovascularização Fisiológica , Regiões Promotoras Genéticas , Proteínas Tirosina Quinases/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Núcleo Celular/genética , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Humanos , Fosforilação , Transdução de Sinais , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
11.
Opt Express ; 28(6): 8132-8144, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32225444

RESUMO

Photon-limited imaging technique is desired in tasks of capturing and reconstructing images by detecting a small number of photons. However, it is still a challenge to achieve high photon-efficiency. Here, we propose a novel photon-limited imaging technique that explores the consistency of photon detection probability in a single pulse and light intensity distribution in a single-pixel correlated imaging system. We demonstrated theoretically and experimentally that our technique can reconstruct a high-quality 3D image by using only one pulse each frame, thereby achieving a high photon efficiency of 0.01 detected photons per pixel. Long-distance field experiments for 100 km cooperative target and 3 km practical target are conducted to verify its feasibility. Compared with the conventional single-pixel imaging, which requires hundreds or thousands of pulses per frame, our technique saves two orders of magnitude in the consumption of total light power and acquisition time.

12.
Entropy (Basel) ; 22(7)2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-33286568

RESUMO

Multi-label data often involve features with high dimensionality and complicated label correlations, resulting in a great challenge for multi-label learning. Feature selection plays an important role in multi-label learning to address multi-label data. Exploring label correlations is crucial for multi-label feature selection. Previous information-theoretical-based methods employ the strategy of cumulative summation approximation to evaluate candidate features, which merely considers low-order label correlations. In fact, there exist high-order label correlations in label set, labels naturally cluster into several groups, similar labels intend to cluster into the same group, different labels belong to different groups. However, the strategy of cumulative summation approximation tends to select the features related to the groups containing more labels while ignoring the classification information of groups containing less labels. Therefore, many features related to similar labels are selected, which leads to poor classification performance. To this end, Max-Correlation term considering high-order label correlations is proposed. Additionally, we combine the Max-Correlation term with feature redundancy term to ensure that selected features are relevant to different label groups. Finally, a new method named Multi-label Feature Selection considering Max-Correlation (MCMFS) is proposed. Experimental results demonstrate the classification superiority of MCMFS in comparison to eight state-of-the-art multi-label feature selection methods.

13.
Heredity (Edinb) ; 123(3): 395-406, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30911139

RESUMO

Genomic prediction benefits hybrid rice breeding by increasing selection intensity and accelerating breeding cycles. With the rapid advancement of technology, other omic data, such as metabolomic data and transcriptomic data, are readily available for predicting breeding values for agronomically important traits. In this study, the best prediction strategies were determined for yield, 1000 grain weight, number of grains per panicle, and number of tillers per plant of hybrid rice (derived from recombinant inbred lines) by comprehensively evaluating all possible combinations of omic datasets with different prediction methods. It was demonstrated that, in rice, the predictions using a combination of genomic and metabolomic data generally produce better results than single-omics predictions or predictions based on other combined omic data. Best linear unbiased prediction (BLUP) appears to be the most efficient prediction method compared to the other commonly used approaches, including least absolute shrinkage and selection operator (LASSO), stochastic search variable selection (SSVS), support vector machines with radial basis function and epsilon regression (SVM-R(EPS)), support vector machines with radial basis function and nu regression (SVM-R(NU)), support vector machines with polynomial kernel and epsilon regression (SVM-P(EPS)), support vector machines with polynomial kernel and nu regression (SVM-P(NU)) and partial least squares regression (PLS). This study has provided guidelines for selection of hybrid rice in terms of which types of omic datasets and which method should be used to achieve higher trait predictability. The answer to these questions will benefit academic research and will also greatly reduce the operative cost for the industry which specializes in breeding and selection.


Assuntos
Quimera/genética , Modelos Genéticos , Oryza/genética , Característica Quantitativa Herdável , Sementes/genética , Máquina de Vetores de Suporte , Produtos Agrícolas , Cruzamentos Genéticos , Genômica/métodos , Metabolômica/métodos , Melhoramento Vegetal/métodos , Locos de Características Quantitativas , Análise de Regressão , Sementes/anatomia & histologia
14.
BMC Dev Biol ; 18(1): 20, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30458702

RESUMO

BACKGROUND: Histone modifications are critical in regulating neuronal processes. However, the impacts of individual histone modifications on learning and memory are elusive. Here, we investigated the contributions of histone H3 lysine modifications to learning and memory in Drosophila by using histone lysine-to-alanine mutants. RESULTS: Behavioural analysis indicated that compared to the H3WT group, mutants overexpressing H3K23A displayed impaired courtship learning. Chromatin immunoprecipitation analysis of H3K23A mutants showed that H3K23 acetylation (H3K23ac) levels were decreased on learning-related genes. Knockdown of CREB-binding protein (CBP) decreased H3K23ac levels, attenuated the expression of learning-related genes, led to a courtship learning defect and altered development of the mushroom bodies. A decline in courtship learning ability was observed in both larvae and adult treatments with ICG-001. Furthermore, treatment of Drosophila overexpressing mutated H3K23A with a CBP inhibitor did not aggravate the learning defect. CONCLUSIONS: H3K23ac, catalysed by the acetyltransferases dCBP, contributes to Drosophila learning, likely by controlling the expression of specific genes. This is a novel epigenetic regulatory mechanism underlying neuronal behaviours.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Histonas/metabolismo , Lisina/metabolismo , Fatores de Transcrição de p300-CBP/metabolismo , Acetilação , Animais , Corte , Feminino , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Histonas/genética , Aprendizagem , Masculino , Mutação , Neurônios/metabolismo
15.
Exp Eye Res ; 176: 59-68, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30008389

RESUMO

Alkali burn (AB) is one of the most serious ocular traumas in the world, characterized by extreme ocular surface disorders, critical secondary dry eye and irreversible vision loss. The exact mechanisms involved are unknown. Innate immunity, including the involvement of Toll-like receptors (TLRs) and NOD-like receptors (NLRs), is believed to participate in the pathogenesis of the epithelia, but the exact mechanisms by which TLRs transduce signals to NLRs and downstream molecules to initiate innate immunity remain poorly defined. In this present study, we used murine models of AB and AB concomitant desiccating stress (DS) to investigate the potential functions and mechanisms of TLR4 in regulating NLRP3 and NLRP6 during AB injury and secondary dry eye. We demonstrated that AB injury induced activation of the TLR4-MyD88 pathway, leading to imbalanced NLRP3 and NLRP6 via the activation of caspase-8 signaling. DS worsened ocular surface disorders post-AB injury by magnifying this phenomenon. Caspase-8 signaling promoted NLRP3 upregulation via the nuclear factor (NF)-κB pathway, while NLRP6 suppressed NF-κB activation. Our findings also revealed that TLR4-MyD88 knockout can alleviate AB-induced or DS-worsened ocular surface disorders, shedding light on the potential therapeutic strategies in the future for AB injury. Taken together, our findings demonstrate that AB promotes the TLR4-MyD88-caspase-8 axis to cause imbalanced NLRP3/NLRP6, and DS exacerbates ocular surface damage via magnifying this imbalance.


Assuntos
Queimaduras Químicas/metabolismo , Caspase 8/metabolismo , Traumatismos Oculares/induzido quimicamente , Fator 88 de Diferenciação Mieloide/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptores de Superfície Celular/metabolismo , Receptor 4 Toll-Like/fisiologia , Animais , Western Blotting , Modelos Animais de Doenças , Traumatismos Oculares/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Glibureto/farmacologia , Humanos , Hipoglicemiantes/farmacologia , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Superfície Celular/genética , Transdução de Sinais/fisiologia , Hidróxido de Sódio
16.
BMC Ophthalmol ; 18(1): 9, 2018 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-29343222

RESUMO

BACKGROUND: Transscleral tunnel incisions are commonly made to avoid postoperative leakage in small gauge sutureless vitrectomy. We present an unreported intraoperative complication, tunnel incision related arterial hemorrhage from sclerotomy, in 23-gauge (23G) vitrectomy. CASE PRESENTATION: Two cases of intraocular arterial hemorrhage from superonasal sclerotomy were observed at the beginning of vitrectomy. The bleeding filled the vitreous cavity quickly and gushed out from the incision port after the involved supronasal cannula was removed. The active bleeding seemed not to stop spontaneously. We controlled the active bleeding by relocating the involved cannula, elevating the intraocular pressure and compressing the sclera wound. Post-operative intraocular hemorrhage from the sclerotomy was not found in any of the two cases. CONCLUSIONS: We suggest that the bleeding was from injured ciliary artery when the incision crossed 3 or 9 o'clock accidently. Surgeons might avoid this complication by locating the superior incisions away from the horizontal axis, and should be aware the proper management.


Assuntos
Perda Sanguínea Cirúrgica , Artérias Ciliares/lesões , Perfurações Retinianas/cirurgia , Esclera/cirurgia , Esclerostomia/efeitos adversos , Lesões do Sistema Vascular/complicações , Vitrectomia/efeitos adversos , Adulto , Hemostasia Cirúrgica/métodos , Humanos , Pressão Intraocular , Masculino , Microcirurgia/efeitos adversos , Pessoa de Meia-Idade , Perfurações Retinianas/diagnóstico , Técnicas de Sutura/instrumentação , Tomografia de Coerência Óptica , Lesões do Sistema Vascular/diagnóstico , Lesões do Sistema Vascular/cirurgia
17.
BMC Ophthalmol ; 18(1): 127, 2018 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-29843668

RESUMO

BACKGROUND: Subfoveal choroidal thickness (SFCT) in highly myopic eyes was found to be correlated with increasing age, refractive error (spherical equivalent), and axial length. Which factor is the most significant predictor of SFCT remains controversial. METHODS: A hospital-based cohort of highly myopic eyes (with spherical equivalent equal to or over 6.00 diopter) were retrospectively screened. Data from only right eye in those bilateral high myopia, and unilateral high myopia in any eye, were used for analysis. Correlations among the four biometric factors were analyzed. Linear correlation was performed to analyze the predictors of SFCT. RESULTS: A cohort of 312 eyes from 312 adults (98 men) was enrolled. Statistical analysis showed that axial length (R = - 0.592), spherical equivalent (R = - 0.471), and age (R = - 0.296) were significantly correlated with SFCT (P < 0.001). No significant correlation was found between age and axial length, or age and spherical equivalent. Partial correlation with controlled age confirmed that axial length (R = - 0.628) was a more significant predictor of SFCT than spherical equivalent (R = - 0.507). CONCLUSIONS: SFCT was inversely correlated with increasing age, spherical equivalent and axial length, with axial length as the most significant predictor of SFCT, in adult highly myopic eyes.


Assuntos
Comprimento Axial do Olho/fisiopatologia , Corioide/patologia , Miopia Degenerativa/fisiopatologia , Erros de Refração/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia de Coerência Óptica , Adulto Jovem
18.
Ophthalmology ; 123(1): 19-25, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26477846

RESUMO

PURPOSE: The purpose of this study was to classify combined persistent fetal vasculature (PFV) on the basis of the ultrasonographic and Doppler characteristics. The potential clinical significance for both surgery design and prognosis determination was discussed. DESIGN: A cross-sectional case series. PARTICIPANTS: The eyes of 54 children diagnosed with unilateral combined PFV were evaluated using B-mode ultrasound and color Doppler imaging (CDI). METHODS: Each participant's age at first presentation, diagnosis for referral, gender, family history, and systemic or other ocular anomalies were recorded. Retinal detachment, optic nerve abnormalities, and macular dislocation were also recorded in detail according to the RetCam (Clarity Medical Systems, Pleasanton, CA), ultrasound, and Doppler findings. The PFV eyes were divided into 4 groups on the basis of the ultrasound and CDI findings. Intergroup analysis was performed. MAIN OUTCOME MEASURES: Overall and intergroup analyses of the demographic features of the children with PFV were performed. The axial length, depth of the anterior chamber, and lens thickness were compared between the affected eyes and the fellow healthy eyes among the 4 groups. RESULTS: Some 22.2%, 18.5%, 33.3%, and 25.9% of the eyes were grouped into type I ("I" shape), II ("Y" shape), III (inverted "Y" shape), and IV ("X" shape) combined PFV, respectively. The age at first presentation for type I was older than that for the other groups (P = 0.014). The axial length was reduced (P = 0.012) and the anterior chamber more shallow (P = 0.011) than in fellow healthy eyes for type IV eyes, but not for the other 3 groups. CONCLUSIONS: Ultrasound and CDI are informative screening and diagnostic tools that show characteristic flow patterns in the 4 types of combined PFV. This novel classification system provides new and important information for the diagnosis of PFV and, if validated, may play a role in guiding treatment recommendations in the future.


Assuntos
Anormalidades do Olho/classificação , Síndrome da Persistência do Padrão de Circulação Fetal/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodos , Corpo Vítreo/anormalidades , Pré-Escolar , Estudos Transversais , Anormalidades do Olho/diagnóstico por imagem , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome da Persistência do Padrão de Circulação Fetal/patologia , Estudos Retrospectivos , Corpo Vítreo/irrigação sanguínea , Corpo Vítreo/diagnóstico por imagem
19.
Retina ; 36(10): 1919-26, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26991645

RESUMO

PURPOSE: To investigate the safety and efficacy of a novel macular buckling technique on foveoschisis in highly myopic eyes. METHODS: Highly myopic eyes with foveoschisis, posterior staphyloma, and axial length greater than 26.5 mm, but without a full-thickness macular hole, were included. Macular buckling was performed in the included eyes using a three-armed adjustable silicon capsule. RESULTS: Eight eyes from eight patients (five women) were enrolled in this study. The mean follow-up period was 11.6 (range 9-14) months. After surgery, the best-corrected visual acuity was improved in 7/8 (87.5%) eyes, optical coherence tomography imaging showed gradual anatomic improvement of macula over time. The final best-corrected visual acuity gained 21.5 early treatment diabetes retinopathy study letters from baseline on average (P = 0.014). Postoperatively, the most common complications were transiently elevated intraocular pressure (62.5%) and asymptomatic abduction limitation (100%), and the most serious complication was hemorrhagic choroidal detachment (25%). CONCLUSION: Macular buckling with a three-armed adjustable silicone capsule resulted in anatomic and visual improvement in eyes with myopic foveoschisis.


Assuntos
Miopia Degenerativa/cirurgia , Retinosquise/cirurgia , Recurvamento da Esclera/instrumentação , Elastômeros de Silicone , Adulto , Comprimento Axial do Olho/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/complicações , Miopia Degenerativa/fisiopatologia , Complicações Pós-Operatórias , Estudos Prospectivos , Retinosquise/etiologia , Retinosquise/fisiopatologia , Recurvamento da Esclera/métodos , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Vitrectomia
20.
Retina ; 36(6): 1209-15, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26655609

RESUMO

PURPOSE: To document a new clinical manifestation in familial exudative vitreoretinopathy (FEVR) eyes, especially in mild asymptomatic eyes with normal vision. METHODS: Twenty individuals with mild Stage I or II FEVR with a conventional "normal-appearing" posterior pole and 20 healthy control eyes were recruited. The crossing numbers of retinal vessels with peripapillary inner reference circle, peripapillary outer reference circle, peripapillary temporal inner arc, peripapillary temporal outer arc, and branching points between the peripapillary outer reference circle and peripapillary inner reference circle were counted. Vessel bifurcation was evaluated by B/CI (defined as the branching number divided by the crossing number on peripapillary inner reference circle) and CO/B (crossing number on peripapillary outer reference circle divided by the branching number) ratios. The inter- and intraobservers' agreements were analyzed. All these parameters were compared between FEVR and control groups. RESULTS: The coefficient of repeatability for the parameters ranged from 2.597 to 5.096, and the intraclass correlation coefficients were all above 0.85. All the parameters showed good interobserver agreement with a narrow range of 95% limit of agreement (from -3.16 to 3.37) and high Pearson correlation (P < 0.001). The mean crossing numbers on peripapillary inner reference circle, peripapillary outer reference circle, peripapillary temporal inner arc, peripapillary temporal outer arc, and the branching numbers were larger in the FEVR group. No significant differences were found in CO/B and B/CI ratios. CONCLUSION: Patients with FEVR have more vessels radiated from the optic disk in the posterior pole. Unlike the increased vessels in the peripheral retina, the increasing pattern of peripapillary vascularity in patients with FEVR does not appear to have a component of overbifurcation. This is a new documented clinical manifestation in patients with FEVR. Attention to an increased or arrangement pattern of retinal vessels may aid in the screening of FEVR.


Assuntos
Doenças Retinianas/diagnóstico , Vasos Retinianos/patologia , Oftalmopatias Hereditárias , Vitreorretinopatias Exsudativas Familiares , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Disco Óptico/irrigação sanguínea , Reprodutibilidade dos Testes , Doenças Retinianas/classificação , Acuidade Visual
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