191 results on '"Zhang, Fengyan"'
Search Results
152. Deposition and properties of spin on Pb5Ge3O11 ferroelectric thin film
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Zhang, Fengyan, primary, Maa, Jer-Shen, additional, Zhuang, Weiwei, additional, and Hsu, Sheng Teng, additional
- Published
- 2001
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153. Integration and characterization of MFISFET using Pb5Ge3O11
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Zhang, Fengyan, primary, Hsu, Sheng Teng, additional, Ono, Yoshi, additional, Zhuang, Weiwei, additional, Ulrich, Bruce, additional, Ying, Hong, additional, Stecker, Lisa, additional, Evans, Dave, additional, and Maa, Jer-Shen, additional
- Published
- 2001
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154. Studies of Ir–Ta–O as High Temperature Stable Electrode Material and Its Application for Ferroelectric SrBi2Ta2O9 Thin Film Deposition
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Zhang, Fengyan, primary, Maa, Jer-shen, additional, Hsu, Sheng Teng, additional, Ohnishi, Shigeo, additional, and Zhen, Wendong, additional
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- 1999
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155. Fatigue free ferroelectric Pb5Ge3O11 thin films prepared by metalorganic chemical vapor deposition
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Li, Tingkai, primary, Zhang, Fengyan, additional, Ono, Yoshi, additional, and Hsu, Sheng Teng, additional
- Published
- 1999
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156. The ferroelectric properties of c-axis oriented Pb5Ge3O11 thin films prepared by metalorganic chemical vapor deposition
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Li, Tingkai, primary, Zhang, Fengyan, additional, and Hsu, Sheng Teng, additional
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- 1999
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157. Phase and Microstructure Analysis of Lead Germanate Thin Film Deposited by Metalorganic Chemical Vapor Deposition
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Zhang, Fengyan, primary, Li, Tingkai, additional, Tweet, Douglas J., additional, and Hsu, Sheng Teng, additional
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- 1999
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158. Ferroelectric C-Axis Oriented Pb5Ge3O11 Thin Films for One Transistor Memory Application.
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Li, Tingkai, Zhang, Fengyan, and Hsu, Sheng Teng
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- 1998
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159. Deposition and properties of spin on Pb 5 Ge 3 O 11 ferroelectric thin film.
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Zhang, Fengyan, Maa, Jer-Shen, Zhuang, Weiwei, and Hsu, Sheng Teng
- Published
- 2001
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160. Fatigue free ferroelectric Pb 5 Ge 3 O 11 thin films prepared by metalorganic chemical vapor deposition.
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Li, Tingkai, Zhang, Fengyan, Ono, Yoshi, and Hsu, Sheng Teng
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- 1999
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161. Iridium Oxide Nanomonitors for Real-Time Health Monitoring Systems
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Venkatraman, Vinu L., Zhang, Fengyan, Evans, David, Ulrich, Bruce, and Prasad, Shalini
- Abstract
An innovative lab-on-a-chip device based on iridium oxide (IrOx) nanowires was designed, fabricated, and developed for real-time “point-of-care” diagnostics. The turnaround time in detection and the need for expensive equipment for analysis have considverably limited rapid and “point-of-care” diagnosis. This research demonstrates the potential of IrOx nanowires toward early disease diagnosis by detecting proteins that are disease markers. The device designed is based on electrical detection of protein biomarkers wherein a single capture immunoassay is built onto a vertically aligned IrOx nanowire platform. Detection of two inflammatory proteins, C-reactive protein (CRP) and myeloperoxidase (MPO) (Calbiochem, La Jolla, CA), that are biomarkers of cardiovascular diseases is demonstrated individually and concurrently. The performance metrics of the device in response to the two biomarkers in pure form and in serum samples were evaluated and compared with standard enzyme-linked immunosorbent assay (ELISA). The methodology that has been adopted is based on measuring real-time impedance changes because of the protein binding event through electrochemical impedance spectroscopy and calibrating its change in magnitude with concentration of proteins. We have demonstrated limit of detection up to 500 pg/mL for protein MPO and I ng/mL for CRP with cross-reactivity of less than 8% of selective binding of these two inflammatory biomarkers.
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- 2009
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162. Effect of temperature on etch rate of iridium and platinum in CF4/O2.
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Maa, Jer-shen, Ying, Hong, and Zhang, Fengyan
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- 2001
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163. Studies of Ir-Ta-O as High Temperature Stable Electrode Material and Its Application for Ferroelectric SrBi2Ta2O9Thin Film Deposition
- Author
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Zhang, Fengyan, Maa, Jer-shen, Hsu, Sheng Teng, Ohnishi, Shigeo, and Zhen, Wendong
- Abstract
An Ir-Ta-O/Ta/Si structure with Ir-Ta-O as electrode and Ta as diffusion barrier layer on silicon substrate has been fabricated. The Ir-Ta-O film was deposited by reactive sputtering using separate Ir and Ta targets in oxygen ambient. Annealing results performed from 500-1000°C in oxygen ambient showed that the Ir-Ta-O film exhibited extraordinary high temperature stability. This film showed good conductivity and integrity even after 5 min annealing at 1000°C. No destructive peeling and hillock formation were observed. By using this film as bottom electrode for depositing ferroelectric SrBi2Ta2O9thin film at 800°C, good ferroelectric properties were achieved.
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- 1999
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164. Effect of Implanted Capsular Tension Ring on Postoperative Refractive Shift: A Systematic Review and Meta-Analysis.
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Xu S, Zhang Y, Li X, Si W, Tian G, Yang Y, Hu Y, and Zhang F
- Abstract
Background: The capsular tension ring is a novel assistant tool for cataract surgery; however, controversy exists in its co-implantation. The potential for hyperopic or myopic shift resulting from the co-implantation of the capsular tension ring and intraocular lens remains unclear. This study aimed to determine the postoperative refractive prediction error and the direction of refractive shift in cataract patients who underwent capsular tension ring co-implantation., Methods: We conducted a systematic review and meta-analysis,searching electronic databases for studies of individuals diagnosed with cataracts receiving surgery with or without capsular tension ring implantation. Systematic searches were performed based on five databases: PubMed, Cochrane Library, Web of Science, Medline, and China National Knowledge Infrastructure. The primary outcome was the mean arithmetic refractive prediction error. Secondary outcomes were mean absolute refractive prediction error and the number of eyes within a certain refractive prediction error range. We applied a fixed-effectsmodel to pool effect sizes across trials using weighted mean differences (WMD) and risk ratios (RR) with their 95% confidence intervals (95% CI). Statistical heterogeneity scores were assessed with the I
2 statistic., Results: A total of 407 affected eyes were included in eight independent clinical studies. Meta-analysis suggested significant differences both in short-term (≤1 month) co-implantation (WMD = 0.16, p < .001, 95% CI: -0.13 ~ 0.19) and long-term (≥3 months) co-implantation between the capsular tension ring co-implantation group and the control group (WMD = 0.19, p < .001, 95% CI: 0.15 ~ 0.23). However, no significant difference was observed in the high myopia subgroup whether capsular tension ring co-implantation (WMD = 0.03, p = .083, 95% CI: -0.27 ~ 0.34). Heterogeneity was not found among the studies., Conclusion: Compared to simple intraocular lens implantation, capsular tension ring co-implantation is more susceptible to developing hyperopic shifts in non-myopic cataract patients, probably related to anterior chamber depth. It requires careful consideration by clinicians when determining the target diopter preoperatively. However, interpretation is limited, because there is a lack of studies available for analysis. There still needs to be additional studies to expand the evidence base.- Published
- 2024
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165. The generation and characterization of a transgenic zebrafish line with lens-specific Cre expression.
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Peng X, Jia X, Shang G, Xue M, Jiang M, Chen D, Zhang F, and Hu Y
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- Animals, Animals, Genetically Modified metabolism, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Integrases genetics, Plasmids, Promoter Regions, Genetic, Zebrafish metabolism, Zebrafish Proteins genetics, Zebrafish Proteins metabolism
- Abstract
Purpose: Danio rerio zebrafish constitute a popular model for studying lens development and congenital cataracts. However, the specific deletion of a gene with a Cre/LoxP system in the zebrafish lens is unavailable because of the lack of a lens-Cre-transgenic zebrafish. This study aimed to generate a transgenic zebrafish line in which Cre recombinase was specifically expressed in the lens., Methods: The pTol2 cryaa :Cre-polyA- cryaa :EGFP (enhanced green fluorescent protein) plasmid was constructed and co-injected with Tol2-transposase into one-to-two-cell-stage wild-type (WT) zebrafish embryos. Whole-mount in situ hybridization (ISH), tissue section, hematoxylin and eosin staining, a Western blot, a split-lamp observation, and a grid transmission assay were used to analyze the Cre expression, lens structure, and lens transparency of the transgenic zebrafish., Results: In this study, we generated a transgenic zebrafish line, zTg( cryaa :Cre- cryaa :EGFP), in which Cre recombinase and EGFP were driven by the lens-specific cryaa promoter. zTg( cryaa :Cre- cryaa :EGFP) began to express Cre and EGFP specifically in the lens at the 22 hpf stage, and this ectopic Cre could efficiently and specifically delete the red fluorescent protein (RFP) signal from the lens when zTg( cryaa :Cre- cryaa :EGFP) embryos were injected with the loxP -flanked RFP plasmid. The overexpression of Cre and EGFP did not impair zebrafish development or lens transparency. Accordingly, this zTg( cryaa :Cre- cryaa :EGFP) zebrafish line is a useful tool for gene editing, specifically with zebrafish lenses., Conclusions: We established a zTg( cryaa :Cre- cryaa :EGFP) zebrafish line that can specifically express an active Cre recombinase in lens tissues. This transgenic zebrafish line can be used as a tool to specifically manipulate a gene in zebrafish lenses., (Copyright © 2024 Molecular Vision.)
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- 2024
166. SARS-COV-2 spike protein promotes RPE cell senescence via the ROS/P53/P21 pathway.
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Zhang Y, Peng X, Xue M, Liu J, Shang G, Jiang M, Chen D, Liu B, Wang Y, Jia X, Xu J, Zhang F, and Hu Y
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- Animals, Humans, Reactive Oxygen Species metabolism, NF-kappa B metabolism, Tumor Suppressor Protein p53 metabolism, Zebrafish, SARS-CoV-2 metabolism, Cellular Senescence physiology, Spike Glycoprotein, Coronavirus metabolism, COVID-19
- Abstract
SARS-Cov-2 infection, which has caused the COVID-19 global pandemic, triggers cellular senescence. In this study, we investigate the role of the SARS-COV-2 spike protein (S-protein) in regulating the senescence of RPE cells. The results showed that administration or overexpression of S-protein in ARPE-19 decreased cell proliferation with cell cycle arrest at the G1 phase. S-protein increased SA-β-Gal positive ARPE-19 cells with high expression of P53 and P21, senescence-associated inflammatory factors (e.g., IL-1β, IL-6, IL-8, ICAM, and VEGF), and ROS. Elimination of ROS by N-acetyl cysteine (NAC) or knocking down p21 by siRNA diminished S-protein-induced ARPE cell senescence. Both administrated and overexpressed S-protein colocalize with the ER and upregulate ER-stress-associated BIP, CHOP, ATF3, and ATF6 expression. S-protein induced P65 protein nuclear translocation. Inhibition of NF-κB by bay-11-7082 reduced S-protein-mediated expression of senescence-associated factors. Moreover, the intravitreal injection of S-protein upregulates senescence-associated inflammatory factors in the zebrafish retina. In conclusions, the S-protein of SARS-Cov-2 induces cellular senescence of ARPE-19 cells in vitro and the expression of senescence-associated cytokines in zebrafish retina in vivo likely by activating ER stress, ROS, and NF-κb. These results may uncover a potential association between SARS-cov-2 infection and development of AMD., (© 2023. The Author(s).)
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- 2023
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167. Prevention of myopia shift and myopia onset using 0.01% atropine in premyopic children - a prospective, randomized, double-masked, and crossover trial.
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Wang W, Zhang F, Yu S, Ma N, Huang C, Wang M, Wei L, Zhang J, and Fu A
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- Humans, Child, Cross-Over Studies, Prospective Studies, Ophthalmic Solutions therapeutic use, Disease Progression, Atropine therapeutic use, Myopia diagnosis, Myopia etiology, Myopia prevention & control
- Abstract
This study aims to evaluate the efficacy of 0.01% atropine eye drops in preventing myopia shift and myopia onset in premyopic children. A prospective, randomized, double-masked, placebo-controlled, and crossover trial was conducted over 13 months. Sixty premyopic children aged 6-12 years with cycloplegic spherical equivalent refraction (SER) > - 0.75 D and ≤ + 0.50 D in both eyes were assigned in a 1:1 ratio to receive one drop of 0.01% atropine or placebo once nightly for 6 months (period 1), followed by a 1-month recovery period. Then, the 0.01% atropine group was crossed over to the placebo group, and the latter was crossed over to the 0.01% atropine group for another 6 months (period 2). The primary outcomes were changes in SER and axial length (AL), and the secondary outcomes were the proportion of myopia onset (SER ≤ - 0.75D) and fast myopic shift (change in SER ≤ - 0.25D) in the two periods. Generalized estimating equation (GEE) model performed a statistically significant treatment effect of 0.01% atropine compared with placebo (p
SER = 0.02, pAL < 0.001), with a mean SER and AL difference of 0.20D (- 0.15 ± 0.26D vs. - 0.34 ± 0.34D) and 0.11 mm (0.17 ± 0.11 mm vs. 0.28 ± 0.14 mm) in period 1, and 0.17D (- 0.18 ± 0.24D vs. - 0.34 ± 0.31D) and 0.10 mm (0.15 ± 0.15 mm vs. 0.24 ± 0.11 mm) in period 2. The GEE model showed that the proportion of myopia onset (p = 0.004) and fast myopic shift (p = 0.009) was significantly lower in the 0.01% atropine group than that in the placebo group. The period effect was not statistically significant (all p > 0.05). A total of 0.01% atropine significantly prevented myopic shift, axial elongation, and myopia onset in premyopic schoolchildren in central Mainland China., Conclusion: Within the limits of only two consecutive 6-month observation period, 0.01% atropine eye drops effectively prevented myopic shift, axial elongation, and myopia onset in premyopic children., Trial Registration: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000034760). Registered 18 July 2020., What Is Known: • Minimal studies on interventions for pre-myopia, despite the International Myopia Institute stating that preventing myopia is an "even more valuable target" for science and practice than reducing progression after onset., What Is New: • A total of 0.01% atropine eye drops may safely and effectively reduce the proportion of myopia onset and fast myopic shift in premyopic schoolchildren., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2023
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168. Improvement of transpiration estimation based on a two-leaf conductance-photosynthesis model with seasonal parameters for temperate deciduous forests.
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Jin J, Liu Y, Hou W, Cai Y, Zhang F, Wang Y, Fang X, Huang L, Yong B, and Ren L
- Abstract
Introduction: Conductance-photosynthesis (G
s -A) models, accompanying with light use efficiency (LUE) models for calculating carbon assimilation, are widely used for estimating canopy stomatal conductance (Gs ) and transpiration (Tc ) under the two-leaf (TL) scheme. However, the key parameters of photosynthetic rate sensitivity (gsu and gsh ) and maximum LUE (ϵmsu and ϵmsh ) are typically set to temporally constant values for sunlit and shaded leaves, respectively. This may result in Tc estimation errors, as it contradicts field observations., Methods: In this study, the measured flux data from three temperate deciduous broadleaved forests (DBF) FLUXNET sites were adopted, and the key parameters of LUE and Ball-Berry models for sunlit and shaded leaves were calibrated within the entire growing season and each season, respectively. Then, the estimations of gross primary production (GPP) and Tc were compared between the two schemes of parameterization: (1) entire growing season-based fixed parameters (EGS) and (2) season-specific dynamic parameters (SEA)., Results: Our results show a cyclical variability of ϵmsu across the sites, with the highest value during the summer and the lowest during the spring. A similar pattern was found for gsu and gsh , which showed a decrease in summer and a slight increase in both spring and autumn. Furthermore, the SEA model (i.e., the dynamic parameterization) better simulated GPP, with a reduction in root mean square error (RMSE) of about 8.0 ± 1.1% and an improvement in correlation coefficient (r) of 3.7 ± 1.5%, relative to the EGS model. Meanwhile, the SEA scheme reduced Tc simulation errors in terms of RMSE by 3.7 ± 4.4%., Discussion: These findings provide a greater understanding of the seasonality of plant functional traits, and help to improve simulations of seasonal carbon and water fluxes in temperate forests., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jin, Liu, Hou, Cai, Zhang, Wang, Fang, Huang, Yong and Ren.)- Published
- 2023
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169. The downregulation of HSP90-controlled CRALBP expression is associated with age-related vision attenuation.
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Chen DD, Liu B, Wang Y, Jiang M, Shang G, Xue M, Jia X, Lang Y, Zhou G, Zhang F, Peng X, and Hu Y
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- Mice, Animals, Swine, Down-Regulation, Retina metabolism, Dark Adaptation, HSP90 Heat-Shock Proteins metabolism, Zebrafish metabolism, Vision, Ocular
- Abstract
The dysfunction of CRALBP, a key regulator of the visual cycle, is associated with retinitis punctata albescens characterized by night vision loss and retinal degeneration. In this paper, we find that the expression of CRALBP is regulated by heat shock protein 90 (HSP90). Inhibition of HSP90α or HSP90β expression by using the CRISPR-Cas9 technology downregulates CRALBP's mRNA and protein expression in ARPE-19 cells by triggering the degradation of transcription factor SP1 in the ubiquitin-proteasome pathway. SP1 can bind to CRALBP's promoter, and inhibition of SP1 by its inhibitor plicamycin or siRNA downregulates CRALBP's mRNA expression. In the zebrafish, inhibition of HSP90 by the intraperitoneal injection of IPI504 reduces the thickness of the retinal outer nuclear layer and Rlbp1b mRNA expression. Interestingly, the expression of HSP90, SP1, and CRALBP is correlatedly downregulated in the senescent ARPE-19 and Pig primary RPE cells in vitro and in the aged zebrafish and mouse retinal tissues in vivo. The aged mice exhibit the low night adaption activity. Taken together, these data indicate that the HSP90-SP1 is a novel regulatory axis of CRALBP transcriptional expression in RPE cells. The age-mediated downregulation of the HSP90-SP1-CRALBP axis is a potential etiology for the night vision reduction in senior people., (© 2023 Federation of American Societies for Experimental Biology.)
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- 2023
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170. Extracellular HSP90 promotes differentiation of lens epithelial cells to fiber cells by activating LRP1-YAP-PROX1 axis.
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Li J, Yu J, Huang W, Sang F, Li J, Ren Y, Huang H, Wang M, Li K, Zhang J, Li H, Cui X, Zhang J, Hu M, Yuan F, Guo W, Zhang F, Mu H, and Hu Y
- Subjects
- Rats, Animals, Humans, Cell Differentiation, Transcription Factors genetics, Transcription Factors metabolism, Epithelial Cells metabolism, Low Density Lipoprotein Receptor-Related Protein-1 genetics, Proto-Oncogene Proteins c-akt metabolism, Lens, Crystalline metabolism
- Abstract
Capsular residual lens epithelial cells (CRLEC) undergo differentiation to fiber cells for lens regeneration or tansdifferentiation to myofibroblasts leading to posterior capsular opacification (PCO) after cataract surgery. The underlying regulatory mechanism remains unclear. Using human lens epithelial cell lines and the ex vivo cultured rat lens capsular bag model, we found that the lens epithelial cells secrete HSP90α extracellularly (eHSP90) through an autophagy-associated pathway. Administration of recombinant GST-HSP90α protein or its M-domain induces the elongation of rat CRLEC cells with concomitant upregulation of the crucial fiber cell transcriptional factor PROX1and its downstream targets, β- and γ-crystallins and structure proteins. This regulation is abolished by PROX1 siRNA. GST-HSP90α upregulates PROX1 by binding to LRP1 and activating LRP1-AKT mediated YAP degradation. The upregulation of GST-HSP90α on PROX1 expression and CRLEC cell elongation is inhibited by LRP1 and AKT inhibitors, but activated by YAP-1 inhibitor (VP). These data demonstrated that the capsular residue epithelial cells upregulate and secrete eHSP90α, which in turn drive the differentiation of lens epithelial cell to fiber cells. The recombinant HSP90α protein is a potential novel differentiation regulator during lens regeneration., (© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
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- 2023
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171. The toxicity mechanism of glabridin in prostate cancer cells is involved in reactive oxygen species-dependent PI3K/Akt pathway: Integrated utilization of bioinformatic analysis and in vitro test validation.
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Zhang F, Wang F, Li W, Liang L, and Sang X
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- Male, Humans, Reactive Oxygen Species metabolism, Proto-Oncogene Proteins c-akt metabolism, Caspase 3 metabolism, Computational Biology, Prospective Studies, Apoptosis, Cell Proliferation, Acetylcysteine pharmacology, In Vitro Techniques, Phosphatidylinositol 3-Kinases metabolism, Prostatic Neoplasms
- Abstract
Glabridin is a prenylated isoflavonoid with considerable anticancer property. Reactive oxygen species (ROS) have evolved as regulators of many cellular signaling pathways in prostate cancer (PC). However, the role of ROS signaling in the anticancer activity of glabridin has not been investigated. Here, we attempted to evaluate the effect of glabridin on PC and the involvement of ROS signaling. Intracellular ROS and mitochondrial ROS (mitoROS) production in PC cell lines, DU-145 and LNCaP, were measured by H2DCFDA and MitoSOX Red staining, respectively. MTT assay was used to analyze the cellular viability. EdU staining assay was conducted to analyze the cell proliferation. To analyze apoptotic rate, TUNEL assay was performed. Caspase-3 activity was detected to reflect cell apoptosis. Western blot was carried out to detect the expression levels of Akt and p-Akt. We found that intracellular ROS and mitoROS levels were dose-dependently upregulated after glabridin treatment in both DU-145 and LNCaP cells, which was reversed by the treatment of ROS inhibitor, N-acetyl-L-cysteine (NAC). Glabridin inhibited the cell viability and reduced the number of EdU-positive DU-145 and LNCaP cells, which were respectively proved by MTT assay and EdU staining assay. Glabridin promoted cell death with increased apoptotic rate and caspase-3 activity in DU-145 and LNCaP cells. The effects of glabridin on cell proliferation and apoptosis were reversed by NAC. Moreover, glabridin suppressed the ratio of p-Akt/Akt, while NAC mitigated the decreased p-Akt/Akt ratio. In addition, the effects of glabridin on cell proliferation and apoptosis were also attenuated by Akt activator, SC79. Collectively, our results demonstrated that glabridin suppressed proliferation and induced apoptosis in PC cells via regulating ROS-mediated PI3K/Akt pathway. These findings suggested that glabridin might hold a promising prospective as a therapeutic agent against PC., (© 2022 Wiley Periodicals LLC.)
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- 2022
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172. FOXO4 mediates resistance to oxidative stress in lens epithelial cells by modulating the TRIM25/Nrf2 signaling.
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Yang X, Zhang F, Liu X, Meng J, Du S, Shao J, Liu J, and Fang M
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- Antioxidants pharmacology, Apoptosis genetics, Cell Cycle Proteins metabolism, Epithelial Cells metabolism, Forkhead Transcription Factors metabolism, Humans, Hydrogen Peroxide metabolism, Hydrogen Peroxide pharmacology, Oxidative Stress, Reactive Oxygen Species metabolism, Superoxide Dismutase metabolism, Transcription Factors metabolism, Tripartite Motif Proteins metabolism, Ubiquitin-Protein Ligases, Cataract genetics, Cataract pathology, NF-E2-Related Factor 2 metabolism
- Abstract
Oxidative stress damage to the lens is a key factor in most cataracts. Forkhead box O 4 (FOXO4), a member of the forkhead box O family, plays a pivotal role in oxidative stress. FOXO4 is upregulated in lens of age-related cataract patients, but its role in cataract has not been elucidated. Herein, we investigated the role and mechanism of FOXO4 during oxidative stress damage in lens epithelial cells. H
2 O2 treatment enhanced FOXO4 expression in HLEpiC cells. Short hairpin RNAs mediated FOXO4 silence aggravated H2 O2 -induced cell apoptosis. In addition, upon H2 O2 exposure, silencing of FOXO4 reduced SOD and CAT activities, as well as increased intracellular MDA and ROS levels. FOXO4 silencing also inhibited Nrf2 nuclear translocation, followed by reducing the expressions of Nrf2-governed antioxidant genes HO-1 and NOQ-1. Exogenous overexpression of FOXO4 was also involved in this study and exhibited opposite effects of FOXO4-silencing. Mechanistically, FOXO4 directly bound the promoter of TRIM25 and regulated its transcription, thereby activating the Nrf2 signaling. Taken together, in the condition of oxidative stress, the expression of FOXO4 showed a compensatory upregulation and it exhibited an anti-oxidative effect by modulating the transcription of TRIM25, thus activating the Nrf2 signaling. The FOXO4/TRIM25/Nrf2 axis may be associated with the pathological mechanisms of cataract., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2022
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173. Ferrostatin-1 alleviates tissue and cell damage in diabetic retinopathy by improving the antioxidant capacity of the Xc - -GPX4 system.
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Shao J, Bai Z, Zhang L, and Zhang F
- Abstract
Diabetic retinopathy (DR) is a common microvascular complication leading to a high blindness rate among patients with diabetes. Ferroptosis is a type of cell death caused by the accumulation of iron-dependent lipid peroxides. Studies have shown that ferroptosis plays an important role in DR. The rat model of DR was constructed and treated with Ferrostatin-1 (Ferr-1). Haematoxylin and eosin (HE) were used to detect the degree of retinopathy. Oxidative stress levels were detected by ELISA. Perl's staining was used to detect iron deposition in retinal tissues. Ferritin levels were measured by ELISA. The expression of GPX4 was detected by immunohistochemistry (IHC). GSH/GSSG kit was used to detect the content and proportion of reduced/oxidized glutathione. Western blot was used to detect the expression of ferroptosis-related proteins. TUNEL assay was used to detect cell apoptosis. The expression of GSDMD was detected by fluorescence in situ hybridization (FISH). Western blot was used to detect the expression of apoptosis and pyroptosis-related proteins. Then, high glucose (HG)-induced retinal epithelial cell line ARPE-19 was treated by Erastin (ferroptosis activator) and Ferr-1. CCK-8, ELISA, western blot, flow cytometry, and immunofluorescence (IF) staining were used to detect oxidative stress levels, ferroptosis and cell damage. The mechanism was further explored by adding ferroptosis agonist Erastin. In vitro and in vivo results showed that oxidative stress was increased in DR model, resulting in ferroptosis and tissue or cell damage. After administration of Ferr-1, the antioxidant capacity was improved, ferroptosis levels were reduced and tissue or cell damage was alleviated. In vitro results showed that Ferr-1 reversed the impacts of Erastin on oxidative stress, ferroptosis, and cell damage in HG-induced ARPE-19 cells. Ferr-1 alleviated tissue and cell damage by improving the antioxidant capacity of the Xc
- -GPX4 system., (© 2022. The Author(s).)- Published
- 2022
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174. Diagnostic accuracy of ultrasound, CT and their combination in detecting cervical lymph node metastasis in patients with papillary thyroid cancer: a systematic review and meta-analysis.
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Yang J, Zhang F, and Qiao Y
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- Humans, Lymph Nodes diagnostic imaging, Lymph Nodes pathology, Lymphatic Metastasis diagnostic imaging, Lymphatic Metastasis pathology, Thyroid Cancer, Papillary diagnostic imaging, Thyroid Cancer, Papillary pathology, Tomography, X-Ray Computed, Thyroid Neoplasms diagnosis
- Abstract
Objectives: To determine the diagnostic accuracy of ultrasound (US), CT and their combination in detecting cervical lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC)., Methods: Medline (via PubMed), Web of Science, Embase were searched to identify studies published till 5 December 2021 that used US and CT to detect CLNM in patients with PTC. The primary outcomes were sensitivity, specificity and diagnostic ORs in neck-level-based (lymph nodes are analysed by neck level) or patient-based (lymph nodes are analysed by patient) analysis. Secondary outcomes were sensitivity, specificity and DORs in the central and lateral compartments., Results: Fourteen studies (6167 patients with 11 601 neck lymph nodes) met the inclusion criteria. Based on the neck-level-based analysis, the pooled sensitivity, specificity and DORs were 0.35 (95% CI 0.34 to 0.37), 0.95 (95% CI 0.94 to 0.95) and 13.94 (95% CI 9.34 to 20.82) for US, were 0.46 (95% CI 0.44 to 0.47), 0.88 (95% CI 0.87 to 0.89) and 7.24 (95% CI 5.46 to 9.62) for CT, were 0.51 (95% CI 0.49 to 0.52), 0.85 (95% CI 0.84 to 0.86), 6.01 (95% CI 3.84 to 9.40) for the combination of US and CT. In the patient-based analysis, the pooled estimates of sensitivity, specificity and DOR were 0.41 (95% CI 0.36 to 0.46), 0.92 (95% CI 0.89 to 0.94) and 7.56 (95% CI 4.08 to 14.01) for US, were 0.49 (0.44 to 0.54), 0.91 (0.89 to 0.94), 9.40 (5.79 to 15.27) for CT, and were 0.64 (95% CI 0.57 to 0.71), 0.83 (95% CI 0.77 to 0.88), 8.59 (95% CI 5.37 to 13.76) for the combination of US and CT., Discussion: These findings suggest US, with a DOR almost twice that of CT in the neck-level-based analysis, was superior to CT in detecting CLNM in patients with PTC, especially in the lateral compartment. The combination of US and CT increased the sensitivity from 41%-49% for the individual modalities to 64% for combined modalities in the patient-based analysis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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175. The effect of 3% diquafosol on the improvement of ocular surface post cataract surgery: A meta-analysis for time of intervention.
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Zhang Y, Qi Y, Xie X, and Zhang F
- Abstract
Purpose: The effect of interventional time for 3% Diquafosol reatment in post-cataract surgery has not been well established. A meta-analysis was performed to evaluate the improvement of ocular surface condition in post-cataract surgery patients who received 3% DQS for various treatment durations., Methods: Studies were performed based on 5 databases: PubMed, Cochrane Library, Web of Science, Embase, and China National Knowledge Infrastructure. Data on changes in Schirmer's test, tear breakup time (TBUT), corneal staining score, and OSDI score were collected for meta-analysis., Results: A total of 621 affected eyes from 9 independent clinical studies were included. 6 studies conducted Schirmer's test after the application of 3% DQS. Meta-analysis showed that the difference between 3% DQS and control groups was not statistically significant for short-term application (less than or equal to 1 month) (WMD = 0.14, P = 0.27, 95% CI:-0.11 to 0.39), but was statistically different for long-term application (longer than or equal to 3 months) (WMD = 0.76, P = 0.03, 95% CI:0.08 to 1.45). For the corneal fluorescence staining score, the data from 6 studies indicated that the improvement was statistically significant for short-term application (WMD = -0.40, P <0.00001, 95% CI:-0.72 to -0.08) and but not long-term application (WMD = -0.21, P = 0.26, 95% CI:-0.57 to 0.15). For TBUT, the data from 9 studies indicated that both short-term and long-term application showed significant improvement (WMD = 1.70, P <0.00001, 95% CI:1.38 to 2.03; WMD = 1.52, P <0.00001, 95% CI:1.09 to 1.95). Similar results were observed in data from 5 studies with OSDI scores, where both short-term and long-term application showed statistically significant improvements (WMD = -5.41, P <0.00001, 95% CI: -7.02 to -3.81; WMD = -6.10, P <0.00001, 95% CI:-8.52 to -3.67)., Conclusions: The application of 3% DQS in post-operative cataract patients has a positive effect on improving the ocular surface conditions. Short-term application resulted in lower corneal staining scores, prolonged TBUT, and improved OSDI scores. Long-term application improved Schirmer's test results, TBUT, and subjective symptoms., Key Messages: The updated article suggests that 3% Diquafosol is less effective in the short term after cataract surgery, and that application over three months can improve the patient's ocular surface condition., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc. on behalf of Zhejiang University Press.)
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- 2022
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176. Radiomics Profiling Identifies the Value of CT Features for the Preoperative Evaluation of Lymph Node Metastasis in Papillary Thyroid Carcinoma.
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Yang G, Yang F, Zhang F, Wang X, Tan Y, Qiao Y, and Zhang H
- Abstract
Background: The aim of this study was to identify the increased value of integrating computed tomography (CT) radiomics analysis with the radiologists' diagnosis and clinical factors to preoperatively diagnose cervical lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) patients., Methods: A total of 178 PTC patients were randomly divided into a training ( n = 125) and a test cohort ( n = 53) with a 7:3 ratio. A total of 2553 radiomic features were extracted from noncontrast, arterial contrast-enhanced and venous contrast-enhanced CT images of each patient. Principal component analysis (PCA) and Pearson's correlation coefficient (PCC) were used for feature selection. Logistic regression was employed to build clinical-radiological, radiomics and combined models. A nomogram was developed by combining the radiomics features, CT-reported lymph node status and clinical factors., Results: The radiomics model showed a predictive performance similar to that of the clinical-radiological model, with similar areas under the curve (AUC) and accuracy (ACC). The combined model showed an optimal predictive performance in both the training (AUC, 0.868; ACC, 86.83%) and test cohorts (AUC, 0.878; ACC, 83.02%). Decision curve analysis demonstrated that the combined model has good clinical application value., Conclusions: Embedding CT radiomics into the clinical diagnostic process improved the diagnostic accuracy. The developed nomogram provides a potential noninvasive tool for LNM evaluation in PTC patients.
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- 2022
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177. The Combination of 18 F-Fluorodeoxyglucose Positron Emission Tomography Metabolic and Clinical Parameters Can Effectively Distinguish Rheumatoid Arthritis and Polymyalgia Rheumatic.
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Wang G, Liu X, Chen J, Zhang F, Xu X, Wang Y, Wang R, Yao S, Zhu J, and Guan Z
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- Humans, Positron Emission Tomography Computed Tomography methods, Positron-Emission Tomography, Radiopharmaceuticals, Retrospective Studies, Arthritis, Rheumatoid diagnostic imaging, Fluorodeoxyglucose F18
- Abstract
Objective: To evaluate
18 F-fluorodeoxyglucose positron emission tomography (18 FDG PET) and clinical parameters to differentiate rheumatoid arthritis (RA) and polymyalgia rheumatic (PMR). Patients and Methods . This retrospective study evaluated 54 patients with suspected RA ( n = 23) and PMR ( n = 31) who underwent18 F-FDG PET/CT before treatment. The complete diagnosis was based on each classification criterion and at least followed up for 6 months. Demographic and clinical data were also collected. Semiquantitative analysis (maximum standardized uptake value, SUVmax) of abnormal18 F-FDG uptake was undertaken at 17 musculoskeletal sites, and two scoring systems (mean reference (liver/control) scores) were evaluated. The differential diagnostic efficacy of each independent parameter was evaluated using the receiver operating characteristic (ROC) curve. Integrated discriminatory improvement (IDI) and bootstrap tests were used to evaluate the improvement in diagnostic efficacy using a combination of multiple parameters., Results: The ROC curve analysis of SUVmax indicated that the interspinous ligament showed the highest discriminative diagnostic value (sensitivity, 64.5%; specificity, 78.3%; area under the curve (AUC), 0.764; positive predictive value, 0.800; negative predictive value, 0.621). The combined model with the rheumatoid factor (RF) and metabolic parameters of18 F-FDG PET resulted in the highest AUC of 0.892 and showed significant reclassification by IDI (IDI, 9.51%; 95% confidence interval: 0.021-0.175; P = 0.013). According to the bootstrap test, compared with RF alone, the combination of RF and metabolic parameters showed an improvement in ROC and was statistically significant ( P = 0.017)., Conclusions: The combination of18 F-FDG PET metabolic and clinical parameters can further improve the differential diagnosis of RA and PMR., Competing Interests: Yanmei Wang was employed by GE Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2022 Guanyun Wang et al.)- Published
- 2022
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178. Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation.
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Yan L, Li J, Hu J, Qu J, Li K, Wang M, An SS, Ke CC, Li H, Yuan F, Guo W, Hu M, Zhang J, Yang Z, Mu H, Zhang F, Zhang J, Cui X, and Hu Y
- Abstract
Genetic mutations in HSF4 cause congenital cataracts. HSF4 exhibits both positive and negative regulation on the transcription of heat shock and non-heat shock proteins during lens development, and its activity is regulated by posttranslational modifications. Biotin is an essential vitamin that regulates gene expression through protein biotinylation. In this paper, we report that HSF4b is negatively regulated by biotinylation. Administration of biotin or ectopic bacterial biotin ligase BirA increases HSF4b biotinylation at its C-terminal amino acids from 196 to 493. This attenuates the HSF4b-controlled expression of αB-crystallin in both lens epithelial cells and tested HEK293T cells. HSF4b interacts with holocarboxylase synthetase (HCS), a ubiquitous enzyme for catalyzing protein biotinylation in mammal. Ectopic HA-HCS expression downregulates HSF4b-controlled αB-crystallin expression. Lysine-mutation analyses indicate that HSF4b/K444 is a potential biotinylation site. Mutation K444R reduces the co-precipitation of HSF4b by streptavidin beads and biotin-induced reduction of αB-crystallin expression. Mutations of other lysine residues such as K207R/K209R, K225R, K288R, K294R and K355R in HSF4's C-terminal region do not affect HSF4's expression level and the interaction with streptavidin, but they exhibit distinct regulation on αB-crystallin expression through different mechanisms. HSF4/K294R leads to upregulation of αB-crystallin expression, while mutations K207R/K209R, K225R, K288R, K255R and K435R attenuate HSF4's regulation on αB-crystallin expression. K207R/K209R blocks HSF4 nuclear translocation, and K345R causes HSF4 destabilization. Taken together, the data reveal that biotin maybe a novel factor in modulating HSF4 activity through biotinylation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)
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- 2022
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179. The Therapeutic Roles of Recombinant Hsp90α on Cornea Epithelial Injury.
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Wang M, Hu J, Qu J, Huang H, Zhang J, Zhang J, Li H, Cui X, Zhang F, Hu MY, Li J, and Hu Y
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- Animals, Blotting, Western, Cell Line, Cell Movement physiology, Cell Proliferation physiology, Debridement, Enzyme-Linked Immunosorbent Assay, Epithelium, Corneal drug effects, Epithelium, Corneal metabolism, Eye Injuries metabolism, Gene Expression Regulation physiology, HSP90 Heat-Shock Proteins genetics, Heat Shock Transcription Factors metabolism, Humans, Immunohistochemistry, Low Density Lipoprotein Receptor-Related Protein-1 metabolism, Male, Mice, Mice, Inbred C57BL, Phosphorylation, Proto-Oncogene Proteins c-akt metabolism, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Recombinant Proteins genetics, Recombinant Proteins therapeutic use, Epithelium, Corneal injuries, Eye Injuries drug therapy, HSP90 Heat-Shock Proteins therapeutic use, Wound Healing drug effects
- Abstract
Purpose: The purpose of this study was to explore the therapeutic role of heat shock protein 90 (Hsp90) in wound healing of injury cornea epithelium., Methods: The right eye of C57BL/6N male mice were performed the debridement wounds in the center of the cornea using an algerbrush II blade. The injured area was determined by staining the cornea with fluorescein sodium and measured with image-J. Immunoblotting, ELISA and immunochemistry were used for determining protein expression. The quantitation PCR was performed to measure mRNA expression., Results: Hsp90α is upregulated at both the mRNA and protein levels, and is secreted extracellularly into the corneal stroma and tear film during the healing process after corneal injury in mice. This upregulation is associated with activation of HSF1. Administration of recombinant exogenous Hsp90α (eHsp90α) speeds up wound healing of injured corneal epithelium. The eHsp90α binds to low-density lipoprotein (LDL)-related protein-1 (LRP-1) on the corneal epithelial cells and increases phosphorylation of AKT at S473, which is associated with proliferation and migration corneal epithelial cells in vitro or vivo. Inhibition of AKT by its inhibitor LY294002 abolishes eHsp90α-induced migration and proliferation of corneal epithelial cells., Conclusion: Hsp90α is upregulated and secreted after corneal injury and acts to promote the healing process. Recombinant Hsp90α may be a promising therapeutic drug candidate for corneal injury.
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- 2022
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180. Establishment of myoblast cell line and identification of key genes regulating myoblast differentiation in a marine teleost, Sebastes schlegelii.
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Kong X, Wang X, Li M, Song W, Huang K, Zhang F, Zhang Q, Qi J, and He Y
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- Animals, Cryopreservation, Transcriptome, Cell Culture Techniques, Cell Line, Muscle Development genetics, Myoblasts, Skeletal physiology, Perciformes anatomy & histology
- Abstract
Skeletal myoblasts are activated satellite cells capable of proliferation and differentiation. Studies on mammalian myoblast differentiation and myogenesis could be carried out in vitro thanks to the availability of mouse myoblast cell line C2C12. Lacking of muscle cell line hinders the studies of teleost fish myogenesis. Here, we established a continuous skeletal muscle cell line from juvenile rockfish (Sebastes schlegelii) muscle using explant method and subcultured more than 50 passages for over 150 days. Stable expression of myoblast-specific marker, MyoD (myoblast determination protein) and the potential of differentiation into multi-nucleated skeletal myotubes upon induction suggested the cell line were predominately composed of myoblasts. Transcriptome analysis revealed a total of 4375 genes differentially expressed at four time points after the switch to differentiation medium, which were mainly involved in proliferation and differentiation of myoblasts. KIF22 (kinesin family member 22) and POLA1 (DNA polymerase alpha 1) were identified as the key genes involved in fish myoblast proliferation whereas MYL3 (myosin light chain 3) and TNNT2 (troponin T2) were determined as the crucial genes responsible for differentiation. In all, the continuous myoblasts cultured in this study provided a cell platform for future studies on marine fish myoblast differentiation and myogenesis. The molecular process of myoblast differentiation revealed in this study will open a window into the understanding of indeterminate muscle growth of large teleost., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2021
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181. Deficiency of heat shock factor 4 promotes lens epithelial cell senescence through upregulating p21 cip1 expression.
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Cui X, Du C, Wan S, Wu D, Yan L, Zhang J, Li J, Li H, Yang Z, Zhang H, Zhang J, Mu H, Zhang F, Peng X, Liu M, and Hu Y
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- Aging genetics, Animals, Animals, Genetically Modified, Cataract genetics, Cataract pathology, Cell Line, Cellular Senescence genetics, Cellular Senescence radiation effects, DNA Methylation, Disease Models, Animal, Enhancer of Zeste Homolog 2 Protein metabolism, Epithelial Cells pathology, Epithelial Cells radiation effects, Gene Expression Regulation, Developmental, Gene Knockout Techniques, Heat Shock Transcription Factors genetics, Histones genetics, Histones metabolism, Humans, Lens, Crystalline cytology, Lens, Crystalline growth & development, Lens, Crystalline radiation effects, Mice, Promoter Regions, Genetic, Ultraviolet Rays adverse effects, Zebrafish, Zebrafish Proteins metabolism, Cyclin-Dependent Kinase Inhibitor p21 genetics, Heat Shock Transcription Factors deficiency, Lens, Crystalline pathology, Zebrafish Proteins deficiency, Zebrafish Proteins genetics
- Abstract
Genetic mutations in heat shock factor 4 (Hsf4) is associated with both congenital and age-related cataracts. Hsf4 regulates lens development through its ability to both activate and inhibit transcription. Previous studies suggested Hsf4 is involved in modulating cellular senescence depending on p21
cip1 and p27kip1 expression in MEF cells. Here, we found that Hsf4 acts as a suppressor of p21cip1 expression and plays an anti-senescence role during lens development. Knocking out Hsf4 facilitated UVB-induced cellular senescence in mouse lens epithelial cells (mLECs). p21cip1 was upregulated at both the mRNA and protein levels in HSF4-/- mLECs under control and UVB-treated conditions, and knockdown of p21cip1 by siRNA alleviated UVB-induced cellular senescence. HSF4 directly bound to the p21cip1 promoter and increased H3K27m3 levels at the p21cip1 proximal promoter region by recruiting the methyltransferase EZH2. In animal models, p21cip1 was gradually upregulated in wild-type mouse lenses with increasing age, while Hsf4 levels decreased. We generated a Hsf4 mutant mice line (Hsf4del-42 ) which displayed obvious congenital cataract phenotype. The expression of p21cip1 and senescence-associated cytokines were induced in the cataractous lenses of Hsf4del-42 mice. H3K27m3 and EZH2 levels decreased in p21cip1 promoters in the lenses of Hsf4del-42 mice. The SA-β-Gal activities were positive in lens epithelia of aged Hsf4null zebrafish compared to wild-type lenses. p21cip1 and senescence-associated cytokines levels were also upregulated in lenses of Hsf4null zebrafish. Accordingly, we propose that HSF4 plays a protective role in lens epithelial cells against cellular senescence during lens development and aging, partly by fine-tuning p21cip1 expression., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
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182. Construction of Hyaluronic Acid-CeO₂ Conjugated Composite Nanoparticles and Their Activity Efficiency in Diabetic Retinopathy Alleviation.
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Shao J, Wan J, Zhang F, and Zhang L
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- Animals, Apoptosis, Hyaluronic Acid, Mice, Diabetes Mellitus, Diabetic Retinopathy drug therapy, Nanoparticles
- Abstract
We developed an effective nanoparticle-biomaterial in alleviating diabetic retinopathy (DR), hyaluronic acid (HA)-CeO₂, composed mainly of CeO₂ and HA. To demonstrate its anti-DR capacity, retinal cells from a B6/J mouse model were used to compare the efficiency of PEI-CeO₂ and HA-CeO₂. We investigated the transport performance, histolysis, immune cell infiltration, angiogenesis, and hyperemia induced by the transport system. The structural integrity, microvascular apoptosis, and superoxide and peroxide concentrations in the retina were measured to evaluate the clinical efficacy of CeO₂. The infiltration efficiency of HA-CeO₂ was higher than that of PEI-CeO₂. Lower levels of foreign body reaction were evident for HA-CeO₂ with less histolysis, immune cell infiltration, angiogenesis, and hyperemia. The clinical efficacy of HA-CeO₂ in terms of preservation of retinal structure and lowering of microvascular apoptosis and superoxide and peroxide concentrations was superior to those of PEI-CP. HA-CeO₂ was shown to have significant antioxidation and anti-vascular injury capacity in a mouse model, and may be a potential compound nanodrug for DR treatment in the future.
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- 2021
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183. Self-Attention-Guided Recurrent Neural Network and Motion Perception for Intelligent Prediction of Chronic Diseases.
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Ma B, Zhang F, and Ma B
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- Algorithms, Chronic Disease, Humans, Machine Learning, Neural Networks, Computer, Motion Perception
- Abstract
Parkinson's disease is a common chronic disease that affects a large number of people. In the real world, however, Parkinson's disease can result in a loss of physical performance, which is classified as a movement disorder by clinicians. Parkinson's disease is currently diagnosed primarily through clinical symptoms, which are highly dependent on clinician experience. As a result, there is a need for effective early detection methods. Traditional machine learning algorithms filter out many inherently relevant features in the process of dimensionality reduction and feature classification, lowering the classification model's performance. To solve this problem and ensure high correlation between features while reducing dimensionality to achieve the goal of improving classification performance, this paper proposes a recurrent neural network classification model based on self attention and motion perception. Using a combination of self-attention mechanism and recurrent neural network, as well as wearable inertial sensors, the model classifies and trains the five brain area features extracted from MRI and DTI images (cerebral gray matter, white matter, cerebrospinal fluid density, and so on). Clinical and exercise data can be combined to produce characteristic parameters that can be used to describe movement sluggishness. The experimental results show that the model proposed in this paper improves the recognition performance of Parkinson's disease, which is better than the compared methods by 2.45% to 12.07%., Competing Interests: All the authors do not have any possible conflicts of interest., (Copyright © 2021 Baojuan Ma et al.)
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- 2021
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184. HSP90 acts as a senomorphic target in senescent retinal pigmental epithelial cells.
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Chen DD, Peng X, Wang Y, Jiang M, Xue M, Shang G, Liu X, Jia X, Liu B, Lu Y, Mu H, Zhang F, and Hu Y
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- Animals, Cell Line, Cells, Cultured, Cytokinins metabolism, Epithelial Cells metabolism, Humans, Hydrogen Peroxide, Macaca mulatta, Macular Degeneration etiology, Macular Degeneration pathology, Retina pathology, Retinal Pigment Epithelium pathology, Senotherapeutics, Benzoquinones administration & dosage, Cellular Senescence, HSP90 Heat-Shock Proteins metabolism, Lactams, Macrocyclic administration & dosage, Retinal Pigment Epithelium metabolism
- Abstract
The senescence of retinal pigment epithelial (RPE) cells is associated with age-related macular degeneration (AMD), a leading cause of blindness in the world. HSP90 is a predominant chaperone that regulates cellular homeostasis under divergent physio-pathological conditions including senescence. However, the role of HSP90 in senescent RPE cells still remains unclear. Here, we reported that HSP90 acts as a senomorphic target of senescent RPE cells in vitro . Using H
2 O2 -induced senescent ARPE-19 cells and replicative senescent primary RPE cells from rhesus monkey, we found that HSP90 upregulates the expression of IKKα, and HIF1α in senescent ARPE-19 cells and subsequently controls the induction of distinct senescence-associated inflammatory factors. Senescent ARPE-19 cells are more resistant to the cytotoxic HSP90 inhibitor IPI504 (IC50 = 36.78 μM) when compared to normal ARPE-19 cells (IC50 = 6.16 μM). Administration of IPI504 at 0.5-5 μM can significantly inhibit the induction of IL-1β, IL-6, IL-8, MCP-1 and VEGFA in senescent ARPE-19 and the senescence-mediated migration of retinal capillary endothelial cells in vitro . In addition, we found that inhibition of HSP90 by IPI504 reduces SA-β-Gal's protein expression and enzyme activity in a dose-dependent manner. HSP90 interacts with and regulates SA-β-Gal protein stabilization in senescent ARPE-19 cells. Taken together, these results suggest that HSP90 regulates the SASP and SA-β-Gal activity in senescent RPE cells through associating with distinctive mechanism including NF-κB, HIF1α and lysosomal SA-β-Gal. HSP90 inhibitors (e.g. IPI504) could be a promising senomorphic drug candidate for AMD intervention.- Published
- 2021
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185. Decision making under ambiguity and risk in adolescent-onset schizophrenia.
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Li D, Zhang F, Wang L, Zhang Y, Yang T, Wang K, and Zhu C
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- Adolescent, Adult, Decision Making, Humans, Neuropsychological Tests, Risk-Taking, Gambling, Schizophrenia diagnosis
- Abstract
Objective: Numerous studies have identified impaired decision making (DM) under both ambiguity and risk in adult patients with schizophrenia. However, the assessment of DM in patients with adolescent-onset schizophrenia (AOS) has been challenging as a result of the instability and heterogeneity of manifestations. The Iowa Gambling Task (IGT) and Game of Dice Task (GDT), which are frequently used to evaluate DM respectively under ambiguity and risk, are sensitive to adolescents and neuropsychiatric patients. Our research intended to examine the performance of DM in a relatively large sample of patients with AOS using the above-mentioned two tasks. We also aimed to take a closer look at the relationship between DM and symptom severity of schizophrenia., Methods: We compared the performance of DM in 71 patients with AOS and 53 well-matched healthy controls using IGT for DM under ambiguity and GDT for DM under risk through net scores, total scores and feedback ration. Neuropsychological tests were conducted in all participants. Clinical symptoms were evaluated by using Positive and Negative Syndrome Scale (PANSS) in 71 patients with AOS. Pearson's correlation revealed the relationship among total score of DM and clinical and neuropsychological data., Results: Compared to healthy controls, patients with AOS failed to show learning effect and had a significant difference on the 5th block in IGT and conducted more disadvantageous choices as well as exhibited worse negative feedback rate in GDT. Apart from DM impairment under risk, diminished DM abilities under ambiguity were found related to poor executive function in AOS in the present study., Conclusions: Our findings unveiled the abnormal pattern of DM in AOS, mainly reflected under the risky condition, extending the knowledge on the performance of DM under ambiguity and risk in AOS. Inefficient DM under risk may account for the lagging impulse control and the combined effects of developmental disease. In addition, our study demonstrated that the performance on IGT was related to executive function in AOS.
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- 2021
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186. Matrine treatment reduces retinal ganglion cell apoptosis in experimental optic neuritis.
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Kang J, Liu S, Song Y, Chu Y, Wang M, Shi Y, Zhang F, and Zhu L
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- Animals, Axons drug effects, Axons metabolism, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes metabolism, Cell Death drug effects, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental drug therapy, Encephalomyelitis, Autoimmune, Experimental metabolism, Inflammation drug therapy, Inflammation metabolism, Multiple Sclerosis drug therapy, Multiple Sclerosis metabolism, Optic Nerve drug effects, Optic Nerve metabolism, Optic Neuritis metabolism, Plants, Medicinal chemistry, Rats, Rats, Wistar, Retinal Ganglion Cells metabolism, Signal Transduction drug effects, Matrines, Alkaloids pharmacology, Apoptosis drug effects, Optic Neuritis drug therapy, Quinolizines pharmacology, Retinal Ganglion Cells drug effects
- Abstract
Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of visual disturbance in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1
+ macrophages/microglia and CD4+ T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, reduced numbers of apoptosis in retinal ganglion cells (RGCs). Moreover, MAT treatment promoted Akt phosphorylation and shifted the Bcl-2/Bax ratio back towards an antiapoptotic one, which could be a mechanism for its therapeutic effect in the ON model. Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that may result in blindness.- Published
- 2021
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187. Physcion 8-O-β-glucopyranoside exerts protective roles in high glucose-induced diabetic retinopathy via regulating lncRNA NORAD/miR-125/STAT3 signalling.
- Author
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Wan W, Wan W, Long Y, Li Q, Jin X, Wan G, Zhang F, and Lv Y
- Abstract
Diabetic retinopathy (DR) is the leading cause of decreased vision and blindness globally. The aim of this study was to understand the role of physcion 8-O-β-glucopyranoside (PG) in high glucose (HG)-induced DR and to investigate whether lncRNA NORAD/miR-125/STAT3 signalling was the underlying mechanism involved in DR. To this end, the serum levels of NORAD, miR-125, and STAT3 were determined in patients with DR. The APRE-19 cells were subjected to HG treatment to construct the cell model of DR. HG-disposed APRE-19 cell injury was assessed by detecting cell viability, apoptosis, concentrations of pro-inflammatory cytokines including TNF-α and IL-1β, and ROS generation. Moreover, the effect of PG on HG-disposed APRE-19 cell injury was investigated. NORAD was then overexpressed to investigate the combined effects of NORAD overexpression and PG on HG-disposed APRE-19 cell injury. Furthermore, the regulatory relationship between NORAD and miR-125 as well as miR-125 and STAT3 was investigated. The expression levels of NORAD and STAT3 were significantly increased in the serum of DR patients, while the miR-125 expression was decreased. The HG treatment-induced injury to APRE-19 cells, which were alleviated by PG treatment. Moreover, PG alleviated HG-disposed injury to ARPE-19 cells by decreasing NORAD. NORAD negatively regulated miR-125 expression and the combined effects of NORAD and PG on HG-disposed ARPE-19 cell injury were reversed by miR-125 overexpression. Furthermore, STAT3 was confirmed as a target gene of miR-125. Our results show that PG exerts protective roles in HG-disposed DR via regulating lncRNA NORAD/miR-125/STAT3 signalling. NORAD/miR-125/STAT3 axis may provide a novel perspective for target therapy of DR.
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- 2020
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188. Therapeutic investigation of quercetin nanomedicine in a zebrafish model of diabetic retinopathy.
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Wang S, Du S, Wang W, and Zhang F
- Subjects
- Animals, Blood Glucose drug effects, Body Weight drug effects, Escape Reaction drug effects, Eye drug effects, Male, Nanomedicine, Organ Size drug effects, Reflex, Startle drug effects, Zebrafish, Diabetes Mellitus, Experimental drug therapy, Diabetic Retinopathy drug therapy, Hypoglycemic Agents therapeutic use, Quercetin therapeutic use
- Abstract
Diabetic retinopathy (DR) is progressive damage to the retina and it's caused by damage to the blood-retinal barrier. Quercetin has pleiotropic action like anti-oxidant, regulation cell cycle &vascular integrity, and preventive effect of neuroinflammation. The present study is designed to investigate the nano-formulation of quercetin (NQ) in a zebrafish model of DR. The DR was developed by a single intraperitoneal injection of streptozotocin (STZ; 350 mg/kg). The acceleration of retinopathy was made on 7 days of diabetic zebrafish by intravitreal injection of STZ (20 μL of 7 % w/v of STZ stock solution). The treatment of NQ (5 and 10 mg/kg; i.p.) was administered for 21 consecutive days. The reference control i.e., dexamethasone (DEX, 10 mg/kg; i.p.) was also administered for 21 consecutive days. The sign of DR was assessed by eyeball/body weight ratio, eyeball weight, optomotor response (OMR), startle response (SR), phototactic response (PTR), and escape response (ER). Furthermore, the biochemical changes like plasma glucose and homocysteine (HCY) levels; and eye retinal tissue lipid peroxidation, reduced glutathione (GSH), and arginase reductase (AR) activity levels were assessed. The NQ found to attenuate the effect of STZ induced DR along with the regulation of biochemical abnormalities. And, it also comparable with reference drug treatment i.e., DEX treated group. Hence, NQ can be used for the treatment of diabetic associated retinopathy and neurosensory disorder visits anti-hyperglycemic, regulation of homocysteine pathway, reduction of lipid peroxidation, and free radical scavenging actions., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2020
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189. Long non-coding RNA ANRIL alleviates H 2 O 2 -induced injury by up-regulating microRNA-21 in human lens epithelial cells.
- Author
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Du S, Shao J, Qi Y, Liu X, Liu J, and Zhang F
- Subjects
- AMP-Activated Protein Kinases physiology, Cataract etiology, Cataract genetics, Cells, Cultured, Epithelial Cells drug effects, Humans, Lens, Crystalline metabolism, Lens, Crystalline pathology, Oxidative Stress, Up-Regulation, beta Catenin physiology, Hydrogen Peroxide toxicity, Lens, Crystalline drug effects, MicroRNAs physiology, RNA, Long Noncoding physiology
- Abstract
The accurate role of ANRIL in cataract is poorly understood. We aimed to reveal the effects of ANRIL on H
2 O2 -treated HLECs, SRA01/04, as well as the regulatory mechanisms. Oxidative stress model of HLECs was induced by H2 O2 . Cell injury was evaluated according to cell proliferation, apoptosis and DNA damage using CCK-8 assay/flow cytometry and TUNEL assays/γH2AX staining. Expressions of ANRIL and miR-21 in HLECs were determined by RT-qPCR. The effects of miR-21, miR-34a and miR-122-5p inhibition as well as AMPK and β-catenin on HLECs with ANRIL overexpression and H2 O2 stimulation were analyzed. In vivo experiment was performed via RT-qPCR. H2 O2 repressed proliferation and induced apoptosis or DNA damage in HLECs. Those alterations induced by H2 O2 were attenuated by ANRIL overexpression. MiR-21 was positively regulated by ANRIL, and both of them were repressed in H2 O2 -induced HLECs and cataract patient tissues. Inhibition of miR-21 but not miR-34a or miR-122-5p reversed the effects of ANRIL on H2 O2 -treated HLECs. Phosphorylation of AMPK and expression of β-catenin were increased by ANRIL via regulating miR-21. AMPK and β-catenin affected beneficial function of ANRIL-miR-21 axis.Therefore, lncRNA ANRIL attenuated H2 O2 -induced cell injury in HELCs via up-regulating miR-21 via the activation of AMPK and β-catenin.- Published
- 2020
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190. MiR-25-3p promotes malignant phenotypes of retinoblastoma by regulating PTEN/Akt pathway.
- Author
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Wan W, Wan W, Long Y, Li Q, Jin X, Wan G, Zhang F, Lv Y, Zheng G, Li Z, and Zhu Y
- Subjects
- Animals, Cell Line, Tumor, Cell Survival genetics, HEK293 Cells, Humans, Mice, Nude, PTEN Phosphohydrolase genetics, Phosphorylation, Proto-Oncogene Proteins c-akt genetics, Retinal Neoplasms metabolism, Retinal Neoplasms pathology, Retinoblastoma metabolism, Retinoblastoma pathology, Signal Transduction, Up-Regulation, Xenograft Model Antitumor Assays, Epithelial-Mesenchymal Transition genetics, Gene Expression Regulation, Neoplastic, MicroRNAs genetics, PTEN Phosphohydrolase metabolism, Proto-Oncogene Proteins c-akt metabolism, Retinal Neoplasms genetics, Retinoblastoma genetics
- Abstract
Aberrant expression of microRNAs plays an important role in the pathogenesis and progression of retinoblastoma. MiR-25, a member of the miR-106b˜25 cluster, has been reported to be abnormally expressed in retinoblastoma, but the exact role of it remains unclear. In our study, we found that miR-25-3p was upregulated in retinoblastoma tissues and cell lines. Enforced expression of miR-25-3p in retinoblastoma cell line WERI-RB-1 increased cell growth, colony formation, anchorage-independent growth, cell migration and invasion in vitro and tumor xenograft growth in vivo. In contrast, inhibited miR-25-3p expression in retinoblastoma cell line Y79 suppressed cell growth, colony formation, anchorage-independent growth, cell migration and invasion. Through luciferase reporter assay, we found that phosphatase and tensin homolog (PTEN) was a direct target of miR-25-3p. This was verified by western blot that miR-25-3p overexpression suppressed PTEN and activated Akt signaling. In addition, miR-25-3p was found to promote epithelial-mesenchymal transition (EMT) of WERI-RB-1 cells through PTEN/Akt pathway. Western blot analysis revealed that miR-25-3p overexpression increased Vimentin and Snail expression, and suppressed E-cadherin expression, but this could be reversed by restoring PTEN. Moreover, LY294002 treatment or restoring PTEN expression abolished the effects of miR-25-3p on cell invasion, colony formation and anchorage-independent growth in vitro and tumor xenograft growth in vivo. Taken together, our results suggested that miR-25-3p promotes malignant transformation of retinoblastoma cells by suppressing PTEN., (Copyright © 2019. Published by Elsevier Masson SAS.)
- Published
- 2019
- Full Text
- View/download PDF
191. Glutathione-S-Transferase Deletions and Non-arteritic Anterior Ischemic Optic Neuropathy.
- Author
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Wan W, Peng T, Jin X, Li Q, Zhang F, Zheng G, Lv Y, Wan G, and Zhu Y
- Subjects
- Demography, Female, Humans, Male, Middle Aged, Gene Deletion, Genetic Predisposition to Disease, Glutathione Transferase genetics, Optic Neuropathy, Ischemic enzymology, Optic Neuropathy, Ischemic genetics
- Abstract
In this study, we aimed at investigating the association between glutathione-S-transferase (GSTM1 and GSTT1) deletion genotypes and susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION). We hope our findings may contribute to the understanding NAION pathogenesis and provide some clues for the prevention and treatment of optic diseases. The NAION group contains 113 subjects (33 males and 80 females, mean age 55.3 ± 9.8). And 98 subjects were enrolled in the control group (32 males and 66 females, mean age 56.7 ± 10.2). The individuals involved in the study were matched by gender and age to obtain two homogenous groups. GSTM1- and GSTT1- genotype and the combined genotype were investigated. The genotype distributions in NAION patients were compared with those in the controls. Significantly altered intraocular pressure (IOP) and cup-to-disc ratio (CDR) was detected between NAION patients and controls. An increased risk of NAION was observed among individuals with GSTM1- (P < 0.001). No significant difference was confirmed for GSTT1- (P = 0.290). Individuals with GSTM1-/GSTT1- have a higher susceptibility to NAION (P < 0.001); the GSTM1-/GSTT1+ genotype also had a significantly higher frequency in patients than in controls (P = 0.004). But the genotype of GSTM1+/GSTT1- seems to have no connection with NAION (P = 0.476). In conclusion, in this study, we confirmed the connection between NAION and GSTM1- genotype. But no significant association was observed between GSTT1- genotype and NAION susceptibility. In further analysis regarding combined genotype, a trend of protective effect was detected for GSTT1+ genotype. It is indicated by our result that oxidative compounds might play an important part in the pathogenesis of NAION.
- Published
- 2016
- Full Text
- View/download PDF
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