88 results on '"Guo, Tong"'
Search Results
2. An in vitro cell model to study microglia activation in diabetic retinopathy
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Jingting Zhang, Dawei Luo, Qinghua Qiu, Guo-Tong Xu, Jingfa Zhang, Yihua Xu, Hai Xie, Chaoyang Zhang, and Kun Liu
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Male ,medicine.medical_specialty ,Phagocytosis ,Interleukin-1beta ,Cell ,Nitric Oxide Synthase Type II ,Inflammation ,Retina ,Cell Line ,Rats, Sprague-Dawley ,Mice ,Cell Movement ,Internal medicine ,medicine ,Animals ,Diabetic Retinopathy ,Microglia ,biology ,Chemistry ,Glyoxal ,Cell Biology ,General Medicine ,Diabetic retinopathy ,Hypoxia (medical) ,medicine.disease ,Cell Hypoxia ,In vitro ,Nitric oxide synthase ,Disease Models, Animal ,Glucose ,medicine.anatomical_structure ,Endocrinology ,nervous system ,Cyclooxygenase 2 ,biology.protein ,Inflammation Mediators ,medicine.symptom - Abstract
Microglial activation has been studied extensively in diabetic retinopathy. We have previously detected activation and migration of microglia in 8-week-old diabetic rat retinas. It is widely acknowledged that microglia-mediated inflammation contributes to the progression of diabetic retinopathy. However, existing cell models do not explore the role of activated microglia in vitro. In this study, microglia were subject to various conditions mimicking diabetic retinopathy, including high glucose, glyoxal, and hypoxia. Under high glucose or glyoxal treatment, microglia demonstrated only partially functional changes, while under hypoxia, microglia became fully activated showing enlarged cell bodies, enhanced migration and phagocytosis as well as increased production of pro-inflammatory factors such as cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS). The data indicate that hypoxia-treated microglia is an optimal in vitro model for exploration of microglia activation in diabetic retinopathy.
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- 2021
3. Identification of novel key molecular signatures in the pathogenesis of experimental diabetic retinopathy
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Caixia Jin, Furong Gao, Haibin Tian, Guo-Tong Xu, Qingjian Ou, Jingfa Zhang, Juan Wang, Jieping Zhang, Lixia Lu, Jing-Ying Xu, Tong Zhu, and Caiying Liu
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Male ,Databases, Factual ,Bioinformatics analysis ,Ependymoglial Cells ,Clinical Biochemistry ,Computational biology ,Biology ,Biochemistry ,Cell Line ,Diabetes Mellitus, Experimental ,Histones ,Rats, Sprague-Dawley ,Pathogenesis ,chemistry.chemical_compound ,Insulin resistance ,Gene expression ,Genetics ,medicine ,Animals ,Protein Interaction Maps ,Molecular Biology ,Diabetic Retinopathy ,Fatty acid metabolism ,Gene Expression Profiling ,Retinal ,Cell Biology ,Diabetic retinopathy ,medicine.disease ,Glucose ,Gene Expression Regulation ,chemistry ,Identification (biology) - Abstract
Aims Deep mining of the molecular mechanisms underlying diabetic retinopathy (DR) is critical for the development of novel therapeutic targets. This study aimed to identify key molecular signatures involved in experimental DR on the basis of integrated bioinformatics analysis. Materials and methods Four datasets consisting of 37 retinal samples were downloaded from the National Center of Biotechnology Information Gene Expression Omnibus (GEO). After batch-effect adjustment, bioinformatics tools such as Networkanalyst, Enrichr, STRING, and Metascape were used to evaluate the differentially expressed genes (DEGs), perform enrichment analysis, and construct protein-protein interaction (PPI) networks. The hub genes were identified using Cytoscape software. The DEGs of interest from the meta-analysis were confirmed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in diabetic rats and a high glucose-treated retinal cell model, respectively. Results A total of 743 DEGs related to lens differentiation, insulin resistance, and HDL cholesterol metabolism were obtained using the meta-analysis. Alterations of dynamic gene expression in the chloride ion channel, retinol metabolism, and fatty acid metabolism were involved in the course of DR in rats. Importantly, H3K27m3 modifications regulated the expression of most DEGs at the early stage of DR. This article is protected by copyright. All rights reserved. Conclusions Using an integrated bioinformatics approach, novel molecular signatures were obtained for different stages of DR progression, and the findings may represent distinct therapeutic strategies for DR patients.
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- 2021
4. Long noncoding RNA ERLR mediates epithelial-mesenchymal transition of retinal pigment epithelial cells and promotes experimental proliferative vitreoretinopathy
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Huiqian Bao, Zhi Zheng, Jingfa Zhang, Shuai Yang, Le Feng, Guo-Tong Xu, Conghui Zhang, Haipei Yao, Hui Li, Min Li, Yao Zhang, Fang Wang, and Liangjing Wu
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0301 basic medicine ,Proliferative vitreoretinopathy ,Epithelial-Mesenchymal Transition ,In situ hybridization ,Retinal Pigment Epithelium ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Downregulation and upregulation ,medicine ,Animals ,Humans ,Epithelial–mesenchymal transition ,Molecular Biology ,Transcription factor ,Chemistry ,Vitreoretinopathy, Proliferative ,Epithelial Cells ,Cell Biology ,TCF4 ,medicine.disease ,Cadherins ,eye diseases ,Cell biology ,030104 developmental biology ,030221 ophthalmology & optometry ,RNA, Long Noncoding ,sense organs ,Rabbits ,Chromatin immunoprecipitation ,Neurological disorders ,Transforming growth factor - Abstract
Proliferative vitreoretinopathy (PVR) is a disease that causes severe blindness and is characterized by the formation of contractile fibrotic subretinal or epiretinal membranes. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a hallmark of PVR. This work aims to examine the role of a long noncoding RNA (lncRNA) named EMT-related lncRNA in RPE (ERLR, LINC01705-201 (ENST00000438158.1)) in PVR and to explore the underlying mechanisms. In this study, we found that ERLR is upregulated in RPE cells stimulated with transforming growth factor (TGF)-β1 as detected by lncRNA microarray and RT-PCR. Further studies characterized full-length ERLR and confirmed that it is mainly expressed in the cytoplasm. In vitro, silencing ERLR in RPE cells attenuated TGF-β1-induced EMT, whereas overexpressing ERLR directly triggered EMT in RPE cells. In vivo, inhibiting ERLR in RPE cells reduced the ability of cells to induce experimental PVR. Mechanistically, chromatin immunoprecipitation (ChIP) assays indicated that the transcription factor TCF4 directly binds to the promoter region of ERLR and promotes its transcription. ERLR mediates EMT by directly binding to MYH9 protein and increasing its stability. TCF4 and MYH9 also mediate TGF-β1-induced EMT in RPE cells. Furthermore, ERLR is also significantly increased in RPE cells incubated with vitreous PVR samples. In clinical samples of PVR membranes, ERLR was detected through fluorescent in situ hybridization (FISH) and colocalized with the RPE marker pancytokeratin (pan-CK). These results indicated that lncRNA ERLR is involved in TGF-β1-induced EMT of human RPE cells and that it is involved in PVR. This finding provides new insights into the mechanism and treatment of PVR.
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- 2021
5. Activated microglia–induced neuroinflammatory cytokines lead to photoreceptor apoptosis in Aβ-injected mice
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Fanjun Shi, Haifeng Qin, Qian Yang, Jing Wu, Sichang Qu, Ge Gao, Hai Xie, Jingfa Zhang, Fang Liu, Guo-Tong Xu, Chaoyang Zhang, and Dandan Liu
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genetic structures ,MAP Kinase Signaling System ,medicine.medical_treatment ,p38 mitogen-activated protein kinases ,Interleukin-1beta ,Apoptosis ,p38 Mitogen-Activated Protein Kinases ,Retina ,Photoreceptor cell ,Cell Line ,Proinflammatory cytokine ,Macular Degeneration ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Drug Discovery ,medicine ,Animals ,Photoreceptor Cells ,Genetics (clinical) ,Neuroinflammation ,Amyloid beta-Peptides ,Microglia ,Chemistry ,Coculture Techniques ,Peptide Fragments ,eye diseases ,Cell biology ,Mice, Inbred C57BL ,Disease Models, Animal ,medicine.anatomical_structure ,Cytokine ,Cyclooxygenase 2 ,Neuroinflammatory Diseases ,Molecular Medicine ,Cytokine secretion ,sense organs ,Injections, Intraocular ,030215 immunology - Abstract
Age-related macular degeneration (AMD) is mainly characterized by the progressive accumulation of drusen deposits and loss of photoreceptors and retinal pigment epithelial (RPE) cells. Because amyloid β (Aβ) is the main component of drusen, Aβ-induced activated microglia most likely lead to neuroinflammation and play a critical role in the pathogenesis of AMD. However, the relationship between activated microglia-mediated neuroinflammatory cytokines and photoreceptor death has not been clarified. By subretinal injection of Aβ42 in mice, we mimicked an inflammatory milieu of AMD to better understand how activated microglia-induced neuroinflammatory cytokines lead to photoreceptor apoptosis in the AMD progression. We demonstrated that subretinal injection of Aβ42 induces microglial activation and increases inflammatory cytokine release, which gives rise to photoreceptor apoptosis in mice. Our results were verified in vitro by co-culture of Aβ42 activated primary microglia and the photoreceptor cell line 661W. We also demonstrated that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was involved in Aβ42-induced microglial activation and inflammatory cytokine release. Overall, our findings indicate that activated microglia-derived neuroinflammatory cytokines could contribute to photoreceptor apoptosis under the stimulation of Aβ42. Moreover, this study may provide a potential therapeutic approach for AMD. KEY MESSAGES: Further explore the association between activated microglia-derived neuroinflammatory cytokine secretion and photoreceptor apoptosis under the stimulation of Aβ42. Subretinal injection of Aβ42 induces the activation of microglia and increases proinflammatory cytokines IL-1β and COX-2 expression in the retina, which could give rise to the deterioration of visual function and aggravate photoreceptor apoptosis in mice. Primary microglial are activated and the levels of proinflammatory cytokines are increased by Aβ42 stimulation, which could increase the apoptosis of photoreceptor cell line 661W in vitro. The p38 MAPK signaling pathway is involved in microglial activation and photoreceptor apoptosis under Aβ42 treatment.
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- 2021
6. Melatonin maintains inner blood‐retinal barrier via inhibition of p38/TXNIP/NF‐κB pathway in diabetic retinopathy
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Guoxu Xu, Qian Yang, Lixia Lu, Guo-Tong Xu, Haibin Tian, Chaoyang Zhang, Kun Liu, Qinghua Qiu, Weiye Li, Dawei Luo, Jing-Ying Xu, Jingfa Zhang, Hai Xie, Lei Tang, and Dandan Liu
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Male ,0301 basic medicine ,medicine.medical_specialty ,Physiology ,Clinical Biochemistry ,Blood–retinal barrier ,Inflammation ,Vascular permeability ,Occludin ,medicine.disease_cause ,Antioxidants ,Retina ,Proinflammatory cytokine ,Capillary Permeability ,Rats, Sprague-Dawley ,Melatonin ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Blood-Retinal Barrier ,medicine ,Animals ,Diabetic Retinopathy ,Chemistry ,NF-kappa B ,Endothelial Cells ,Retinal Vessels ,Cell Biology ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,medicine.symptom ,Oxidative stress ,TXNIP ,medicine.drug - Abstract
The pathophysiology of diabetic retinopathy (DR) was complex. Under hyperglycemic conditions, the release of proinflammatory cytokines and the adhesion of leukocytes to retinal capillaries contribute to endothelial damage and the subsequent increase in vascular permeability resulting in macular edema. Melatonin, produced in the retina to regulate redox reactions and dopamine metabolism, plays protective roles against inflammation and oxidative stress. Considering its anti-inflammatory and antioxidative properties, melatonin was speculated to exert beneficial effects in DR. In this study, we characterized the protective effects of melatonin on the inner blood-retinal barrier (iBRB), as well as the possible mechanisms in experimental DR. Results showed that in diabetic rat retinas, the leakage of iBRB and the expression of inflammatory factors (VEGF, TNF-α, IL-1β, ICAM-1, and MMP9) increased dramatically, while the expression of tight junction proteins (ZO-1, occludin, JAM-A, and claudin-5) decreased significantly. The above changes were largely ameliorated by melatonin. The in vivo data were confirmed in vitro. In addition, the protein expressions of p38 MAPK, NF-κB, and TXNIP were upregulated significantly in diabetes and were downregulated following melatonin treatment. Melatonin could maintain the iBRB integrity by upregulating the expression of tight junction proteins via inhibiting p38/TXNIP/NF-κB pathway, thus decreasing the production of inflammatory factors. This study may shed light on the development of melatonin-based DR therapy.
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- 2021
7. Erythropoietin protects the inner blood–retinal barrier by inhibiting microglia phagocytosis via Src/Akt/cofilin signalling in experimental diabetic retinopathy
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Guoxu Xu, Qian Yang, Weiye Li, Jingfa Zhang, Jing-Ying Xu, Caixia Jin, Tianqin Wang, Chaoyang Zhang, Juan Wang, Hai Xie, Guo-Tong Xu, Dandan Liu, Lei Tang, Haibin Tian, Furong Gao, and Lixia Lu
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0301 basic medicine ,Microglia ,biology ,Chemistry ,Endocrinology, Diabetes and Metabolism ,Blood–retinal barrier ,030209 endocrinology & metabolism ,Cofilin ,Streptozotocin ,Cell biology ,Endothelial stem cell ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Integrin alpha M ,Erythropoietin ,Internal Medicine ,medicine ,biology.protein ,Protein kinase B ,medicine.drug - Abstract
Microglial activation in diabetic retinopathy and the protective effect of erythropoietin (EPO) have been extensively studied. However, the regulation of microglia in the retina and its relationship to inner blood–retinal barrier (iBRB) maintenance have not been fully characterised. In this study, we investigated the role of microglia in iBRB breakdown in diabetic retinopathy and the protective effects of EPO in this context. Male Sprague Dawley rats were injected intraperitoneally with streptozotocin (STZ) to establish the experimental model of diabetes. At 2 h after STZ injection, the right and left eyes were injected intravitreally with EPO (16 mU/eye, 2 μl) and an equivalent volume of normal saline (NaCl 154 mmol/l), respectively. The rats were killed at 2 or 8 weeks after diabetes onset. Microglia activation was detected by ionised calcium binding adaptor molecule (IBA)-1 immunolabelling. Leakage of the iBRB was evaluated by albumin staining and FITC-dextran permeability assay. BV2 cells and primary rat microglia under hypoxic conditions were used to model microglial activation in diabetic retinopathy. Phagocytosis was examined by confocal microscopy in flat-mounted retina preparations and in microglia and endothelial cell cocultures. Protein levels of IBA-1, CD11b, complement component 1r (C1r), and Src/Akt/cofilin signalling pathway components were assessed by western blotting. In diabetic rat retinas, phagocytosis of endothelial cells by activated microglia was observed at 8 weeks, resulting in an increased number of acellular capillaries (increased by 426.5%) and albumin leakage. Under hypoxic conditions, activated microglia transmigrated to the opposite membrane of the transwell, where they disrupted the endothelial cell monolayer by engulfing endothelial cells. The activation and phagocytic activity of microglia was blocked by intravitreal injection of EPO. In vitro, IBA-1, CD11b and C1r protein levels were increased by 50.9%, 170.0% and 135.5%, respectively, by hypoxia, whereas the phosphorylated proteins of Src/Akt/cofilin signalling pathway components were decreased by 74.2%, 47.8% and 39.7%, respectively, compared with the control; EPO treatment abrogated these changes. In experimental diabetic retinopathy, activated microglia penetrate the basement membrane of the iBRB and engulf endothelial cells, leading to iBRB breakdown. EPO exerts a protective effect that preserves iBRB integrity via activation of Src/Akt/cofilin signalling in microglia, as demonstrated in vitro. These data support a causal role for activated microglia in iBRB breakdown and highlight the therapeutic potential of EPO for the treatment of diabetic retinopathy.
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- 2020
8. Anti-VEGF therapy prevents Müller intracellular edema by decreasing VEGF-A in diabetic retinopathy
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Haibin Tian, Guo-Tong Xu, Chaoyang Zhang, Mengmeng Jiang, Hai Xie, Tianqin Wang, Jingfa Zhang, Lin Liu, and Lixia Lu
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medicine.medical_specialty ,Sodium ,medicine.medical_treatment ,Intraperitoneal injection ,chemistry.chemical_element ,03 medical and health sciences ,0302 clinical medicine ,Diabetic retinopathy ,Diabetic macular edema ,Edema ,Internal medicine ,medicine ,Intracellular edema ,Chemistry ,Research ,Müller cell ,Anti-VEGF ,RE1-994 ,Streptozotocin ,Ophthalmology ,Vascular endothelial growth factor A ,Aquaporin 4 ,Endocrinology ,030221 ophthalmology & optometry ,Ranibizumab ,medicine.symptom ,030217 neurology & neurosurgery ,Intracellular ,medicine.drug - Abstract
Background Although vascular endothelial growth factor A (VEGF-A) is known to play a key role in causing retinal edema, whether and how VEGF-A induces intracellular edema in the retina still remains unclear. Methods Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin. Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset. rMC-1 cells (rat Müller cell line) were treated with glyoxal for 24 h with or without ranibizumab. The expression levels of inwardly rectifying K+ channel 4.1 (Kir4.1), aquaporin 4 (AQP4), Dystrophin 71 (Dp71), VEGF-A, glutamine synthetase (GS) and sodium-potassium-ATPase (Na+-K+-ATPase) were examined using Western blot. VEGF-A in the supernatant of the cell culture was detected with ELISA. The intracellular potassium and sodium levels were detected with specific indicators. Results Compared with normal control, protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas, which were prevented by ranibizumab. The above changes were recapitulated in vitro. Similarly, the intracellular potassium level in glyoxal-treated rMC-1 cells was increased, while the intracellular sodium level and Na+-K+-ATPase protein level remained unchanged, compared with control. However, ranibizumab treatment decreased intracellular sodium, but not potassium. Conclusion Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A. It also caused a reduction in intracellular osmotic pressure.
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- 2021
9. Effectively Intervening Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells With a Combination of ROCK and TGF-β Signaling Inhibitors
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Junjie Luo, Jieping Zhang, Jingyao Chen, Jing-Ying Xu, Dandan Liu, Binxin Wu, Caixia Jin, Zi Wei Kang, Guo-Tong Xu, Chen Yi, Qingjian Ou, Jingfa Zhang, Haibin Tian, Xiaoxu Leng, Jian Feng He, Furong Gao, Kexin Fang, Lixia Lu, and Juan Wang
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0301 basic medicine ,TGF-β ,Proliferative vitreoretinopathy ,Epithelial-Mesenchymal Transition ,Pyridines ,PVR ,Signal transduction inhibitor ,Retinal Pigment Epithelium ,Rats, Sprague-Dawley ,Transforming Growth Factor beta1 ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Dispase ,ROCK ,medicine ,Animals ,Humans ,Epithelial–mesenchymal transition ,Enzyme Inhibitors ,Cells, Cultured ,Retina ,medicine.diagnostic_test ,Vitreoretinopathy, Proliferative ,EMT ,Retinal ,medicine.disease ,Embryonic stem cell ,Amides ,eye diseases ,Cell biology ,Rats ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Retinal Cell Biology ,030220 oncology & carcinogenesis ,embryonic structures ,Pyrazoles ,sense organs ,RPE ,Electroretinography - Abstract
Purpose Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a key pathological event in proliferative retinal diseases such as proliferative vitreoretinopathy (PVR). This study aimed to explore a new method to reverse EMT in RPE cells to develop an improved therapy for proliferative retinal diseases. Methods In vitro, human embryonic stem cell-derived RPE cells were passaged and cultured at low density for an extended period of time to establish an EMT model. At different stages of EMT after treatment with known molecules or combinations of molecules, the morphology was examined, transepithelial electrical resistance (TER) was measured, and expression of RPE- and EMT-related genes were examined with RT-PCR, Western blotting, and immunofluorescence. In vivo, a rat model of EMT in RPE cells was established via subretinal injection of dispase. Retinal function was examined by electroretinography (ERG), and retinal morphology was examined. Results EMT of RPE cells was effectively induced by prolonged low-density culture. After EMT occurred, only the combination of the Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor Y27632 and the TGF-β receptor inhibitor RepSox (RY treatment) effectively suppressed and reversed the EMT process, even in cells in an intermediate state of EMT. In dispase-treated Sprague-Dawley rats, RY treatment maintained the morphology of RPE cells and the retina and preserved retinal function. Conclusions RY treatment might promote mesenchymal-epithelial transition (MET), the inverse process of EMT, to maintain the epithelial-like morphology and function of RPE cells. This combined RY therapy could be a new strategy for treating proliferative retinal diseases, especially those involving EMT of RPE cells.
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- 2021
10. Establishment of Retinal Degeneration Model in Rat and Monkey by Intravitreal Injection of Sodium Iodate
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Chunpin Lian, Zongyi Li, Juan Wang, Peng Li, Li Wang, Lixia Lu, Jing-Ying Xu, Furong Gao, Hua Xu, Caixia Jin, Guo-Tong Xu, Tong Zhu, Haibin Tian, Qingjian Ou, Jieping Zhang, and Weiye Li
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Retinal degeneration ,Iodates ,Pharmacology ,Biochemistry ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Electroretinography ,Animals ,Humans ,Medicine ,Viability assay ,Fluorescein Angiography ,Fluorescein ,Molecular Biology ,Sodium iodate ,business.industry ,Retinal Degeneration ,Retinal ,General Medicine ,Glutathione ,medicine.disease ,Rats ,Disease Models, Animal ,Macaca fascicularis ,chemistry ,Intravitreal Injections ,Toxicity ,Molecular Medicine ,business ,Erg - Abstract
Background Animal models play critical roles in studies of the etiology and therapy of retinal degeneration (RD). Objective To establish an RD model without severe systemic side effects in monkeys. Methods Cynomolgus monkeys and Sprague-Dawley rats were treated with intravenous and intravitreal sodium iodate (SI). Electroretinographic (ERG) recording, fluorescein fundus angiography (FFA), optical coherence tomography (OCT) and a retinal morphology examination were conducted to evaluate retinal function and structure. ARPE-19 cells were treated with SI to assess cell viability and morphology. Glutathione (GSH) was administered to SI-treated cultured cells and rats for mechanistic studies. Results Intravenous SI failed to induce RD in monkeys due to its lethal toxicity and the spontaneous recovery of visual function. However, intravitreal SI injection induced very rapid and severe retinal damage in both monkeys and rats. Different doses of SI were tested in both rats and monkeys, and the SI dose appropriate for the model was calculated. GSH partially rescued oxidative damage to SI-treated retinas. A combination of the appropriate dose of intravitreal SI and intravenous GSH generated moderate subacute RD. Conclusions An RD model was established in cynomolgus monkeys by intravitreal SI injection. The key advantages of this model are that lethal SI side effects can be avoided and that the structural and functional changes are similar to those in patients with RD, although the development of RD in the model is too rapid and more severe. An appropriate dose of SI plus systemic GSH generates delayed and moderate RD; this prolonged therapeutic window allows the development of new therapies, such as gene or stem cell-based therapy, for RD.
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- 2019
11. SUMOylation of GMFB regulates the stability and function of GMFB in RPE cells under oxidative stress and inflammation
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Caixia Jin, Jing-Ying Xu, Jieping Zhang, Haibin Tian, Lixia Lu, Guo-Tong Xu, Wan Sun, Qingjian Ou, Jingfa Zhang, Furong Gao, Juan Wang, and Jian Huang
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Downregulation and upregulation ,Chemistry ,Transcription (biology) ,medicine ,SUMO protein ,Regulator ,Inflammation ,medicine.symptom ,Signal transduction ,Subcellular localization ,Intracellular ,Cell biology - Abstract
Glia maturation factor beta (GMFB) is a growth and differentiation factor that act as an intracellular regulator of signal transduction pathways. The SUMOylation is a post-translational modification (PTM) that plays a key role in protein subcellular localization, stability, transcription, and enzymatic activity. Recent studies have highlighted the importance of SUMOylation in the inflammation and progression of numerous diseases. But little is known about the relationship between GMFB and SUMOylation. Here we first report that GMFB can be mono-SUMOylated at multiple sites by the covalent addition of a single SUMO1 protein, and identified K20, K35, K58, and K97 as major SUMO acceptor sites. We also found that SUMOylation leading to increased stability and trans-localization of GMFB. Furthermore, RNA-seq data and Real-time quantitative polymerase chain reaction (rt-qPCR) also indicated that the SUMOylated GMFB upregulated multiple pathways, including the cytokine-cytokin receptor interaction, NOD-like receptor signaling pathway, TNF signaling pathway, RIG-I-like receptor signaling pathway, and NF-kappa B signaling pathway. Our studies intend to provide a novel direction for the study into the biofunction of GMFB, SUMOylated GMFB and the mechanism, clinical therapy, and prognosis of inflammation-related RPE disorders like age-related macular degeneration (AMD) and diabetic retinopathy (DR).
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- 2021
12. Ocular Stem Cell Research from Basic Science to Clinical Application: A Report from Zhongshan Ophthalmic Center Ocular Stem Cell Symposium
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Hong Ouyang, Jeffrey L. Goldberg, Shuyi Chen, Wei Li, Guo-Tong Xu, Kang Zhang, Robert B. Nussenblatt, Yizhi Liu, Ting Xie, Chi-Chao Chan, and Donald J. Zack
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stem cells ,eye diseases ,regenerative medicine ,limbal stem cell deficiency ,glaucoma ,age-related macular degeneration ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Stem cells hold promise for treating a wide variety of diseases, including degenerative disorders of the eye. The eye is an ideal organ for stem cell therapy because of its relative immunological privilege, surgical accessibility, and its being a self-contained system. The eye also has many potential target diseases amenable to stem cell-based treatment, such as corneal limbal stem cell deficiency, glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa (RP). Among them, AMD and glaucoma are the two most common diseases, affecting over 200 million people worldwide. Recent results on the clinical trial of retinal pigment epithelial (RPE) cells from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) in treating dry AMD and Stargardt’s disease in the US, Japan, England, and China have generated great excitement and hope. This marks the beginning of the ocular stem cell therapy era. The recent Zhongshan Ophthalmic Center Ocular Stem Cell Symposium discussed the potential applications of various stem cell types in stem cell-based therapies, drug discoveries and tissue engineering for treating ocular diseases.
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- 2016
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13. miR-194 suppresses epithelial-mesenchymal transition of retinal pigment epithelial cells by directly targeting ZEB1
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Juan Wang, Xiaoliang Jin, Zhongzhu Deng, Yali Lyu, Lixia Lu, Yueye Wang, Jieping Zhang, Nan Yang, Caixia Jin, Jing-Ying Xu, Furong Gao, Chao Wang, Guo-Tong Xu, Xiang Li, Yizheng Guo, Zixuan Zheng, Jingfa Zhang, Rui Mao, Lian Cui, and Haibin Tian
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0301 basic medicine ,Proliferative vitreoretinopathy ,Chemistry ,Cell adhesion molecule ,Cell ,General Medicine ,Transfection ,medicine.disease ,eye diseases ,Cell biology ,Focal adhesion ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Inner nuclear layer ,medicine ,sense organs ,Epithelial–mesenchymal transition ,Ganglion cell layer - Abstract
Background: Epithelial-mesenchymal transition (EMT) of the retinal pigment epithelial (RPE) cells is a critical step in the pathogenesis of proliferative vitreoretinopathy (PVR). Some microRNAs (miRNAs) participate in regulating RPE cell EMT as post-transcriptional regulators. However, the function of miR- 194 in RPE cell EMT remains elusive. Here, the role of miR-194 in PVR was investigated. Methods: Retinal layers were obtained using laser capture microdissection (LCM). Gene expression at the mRNA and protein level in the tissues and cells was examined using quantitative reverse transcription (RT)- polymerase chain reaction and Western blotting, respectively. The related protein expression was observed by immunostaining. The effect of miR-194 on RPE cell EMT was examined by gel contraction, wound healing, and cell migration assays. RNAseq was performed in ARPE-19 with transfection of pSuper-scramble and pSuper-miR-194. The target gene of miR-194 was identified and confirmed via bioinformatics analysis and dual-luciferase reporter assay. ARPE-19 (adult retinal pigment epithelium-19) cells were treated with transforming growth factor (TGF)-β1 in the same fashion as the in vitro RPE cell EMT model. A PVR rat model was prepared by intravitreous injection of ARPE-19 cells with plasma-rich platelets. Results: miR-194 was preferentially expressed in the RPE cell layer compared with the outer nuclear layer (ONL), inner nuclear layer (INL), and ganglion cell layer in rat retina. RNAseq analysis indicated that miR- 194 overexpression was involved in RPE cell processes, including phagocytosis, ECM-receptor interaction, cell adhesion molecules, and focal adhesion. miR-194 overexpression significantly inhibited the TGF-β1-induced EMT phenotype of RPE cells in vitro . Zinc finger E-box binding homeobox 1 (ZEB1), a key transcription factor in EMT, was confirmed as the direct functional target of miR-194. Knockdown of ZEB1 attenuated TGF-β1-induced α-smooth muscle actin expression in ARPE-19 cells, and overexpression of miR-194 could significantly reduce the expression of some genes which were up-regulated by ZEB1. Exogenous miR-194 administration in vivo effectively suppressed PVR in the rat model, both functionally and structurally. Conclusions: Our findings demonstrate for the first time that miR-194 suppresses RPE cell EMT by functionally targeting ZEB1. The clinical application of miR-194 in patients with PVR merits further investigation.
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- 2020
14. Protein Kinase A Inhibitor H89 Attenuates Experimental Proliferative Vitreoretinopathy
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Juan Wang, Qingyi Xiang, Furong Gao, Tianhao Tan, Haibin Tian, Qingjian Ou, Guo-Tong Xu, Jing-Ying Xu, Caixia Jin, Weiye Li, Lixia Lu, Wei Xu, Yao Li, Jingfa Zhang, Yali Lyu, Ao Rong, Li Mengwen, and Jieping Zhang
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0301 basic medicine ,Male ,Proliferative vitreoretinopathy ,MAP Kinase Signaling System ,H89 ,epithelial-mesenchymal transition ,Stimulation ,Smad Proteins ,Retinal Pigment Epithelium ,proliferative vitreoretinopathy ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Gene expression ,medicine ,Electroretinography ,Animals ,Humans ,Protein kinase A ,Cells, Cultured ,Aged ,transforming growth factor beta ,Cyclic AMP-Dependent Protein Kinase Catalytic Subunits ,Sulfonamides ,Smad6 ,Chemistry ,Vitreoretinopathy, Proliferative ,Epiretinal Membrane ,Epithelial Cells ,Middle Aged ,medicine.disease ,Isoquinolines ,In vitro ,eye diseases ,Cell biology ,030104 developmental biology ,Retinal Cell Biology ,030221 ophthalmology & optometry ,Phosphorylation ,Female ,protein kinase A ,sense organs ,Transforming growth factor - Abstract
Purpose This study aimed to explore the role of the protein kinase A (PKA) pathway in proliferative vitreoretinopathy (PVR) and the effect of the PKA inhibitor H89 on experimental PVR. Methods Epiretinal membranes (ERMs) were acquired from PVR patients and analyzed by frozen-section immunofluorescence. An in vivo model was developed by intravitreal injecting rat eyes with ARPE-19 cells and platelet-rich plasma, and changes in eye structures and vision function were observed. An in vitro epithelial-mesenchymal transition (EMT) cell model was established by stimulating ARPE-19 cells with transforming growth factor (TGF)-β. Alterations in EMT-related genes and cell function were detected. Mechanistically, PKA activation and activity were explored to assess the relationship between TGF-β1 stimulation and the PKA pathway. The effect of H89 on the TGF-β-Smad2/3 pathway was detected. RNA sequencing was used to analyze gene expression profile changes after H89 treatment. Results PKA was activated in human PVR membranes. In vivo, H89 treatment protected against structural changes in the retina and prevented decreases in electroretinogram b-wave amplitudes. In vitro, H89 treatment inhibited EMT-related gene alterations and partially reversed the functions of the cells. TGF-β-induced PKA activation was blocked by H89 pretreatment. H89 did not affect the phosphorylation or nuclear translocation of regulatory Smad2/3 but increased the expression of inhibitory Smad6. Conclusions PKA pathway activation is involved in PVR pathogenesis, and the PKA inhibitor H89 can effectively inhibit PVR, both in vivo and in vitro. Furthermore, the protective effect of H89 is related to an increase in inhibitory Smad6.
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- 2020
15. Transplantation Site Affects the Outcomes of Adipose-Derived Stem Cell-Based Therapy for Retinal Degeneration
- Author
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Juan Wang, Yue Zhou, Lixia Lu, Qingjian Ou, Huanzhi La, Jieping Zhang, Caixia Jin, Haibin Tian, Jingfa Zhang, Zhiyang Chen, Xuancheng Wei, Xiaoman Zhu, Jing-Ying Xu, Guo-Tong Xu, Furong Gao, and Chengyu Hu
- Subjects
0301 basic medicine ,Retinal degeneration ,Pathology ,medicine.medical_specialty ,Article Subject ,genetic structures ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Molecular Biology ,Internal medicine ,Retina ,Retinal ,Cell migration ,Cell Biology ,medicine.disease ,RC31-1245 ,eye diseases ,Transplantation ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Vitreous chamber ,030221 ophthalmology & optometry ,sense organs ,Epiretinal membrane ,Stem cell ,Research Article - Abstract
Adipose-derived stem cells (ASCs) have shown a strong protective effect on retinal degenerative diseases (RDD) after being transplanted into the subretinal space in an animal model. Recently, several clinical trials have been conducted to treat RDD with intravitreal transplantation of stem cells, including ASCs. However, the outcomes of the clinical trials were not satisfactory. To investigate if the transplantation site alters the outcome of stem cell-based therapy for RDD, we isolated rat ASCs (rASCs) and labeled them with green fluorescent protein. Autologous rASCs were grafted into the vitreous chamber or subretinal space in a rat RDD model induced by sodium iodate (SI). The electric response was recorded by ERG. The anatomic structure of the retina was observed in cryosections of rat eyes at posttransplantation weeks 1, 2, and 4. Neural retina apoptosis and epiretinal membrane- (ERM-) like structure formation were investigated by immunostaining. The intravitreal transplantation of rASCs resulted in an extinguished electric response, although the rosette formation and apoptosis of neural retina were reduced. However, the rASCs that grafted in the subretinal space protected the retina from the damage caused by SI, including a partial recovering of the electric response and a reduction in rosette formation. Intravitreally grafted rASCs formed a membrane, resulting in retina folding at the injection site. Müller cells, retinal pigment epithelial cells, and microglial cells migrated from the retina to the rASC-formed membrane and subsequently formed an ERM-like structure. Furthermore, vitreous fluid promoted rASC migration, and rASC-conditioned medium enhanced Müller cell migration as indicated by in vitro studies. These data suggested that the vitreous chamber is not a good transplantation site for ASC-based therapy for RDD and that a deliberate decision should be made before transplantation of stem cells into the vitreous chamber to treat RDD in clinical trials.
- Published
- 2020
16. Membrane proteome analysis of microdissected ovarian tumor tissues using capillary isoelectric focusing/reversed-phase liquid chromatography--tandem MS
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Wang, Weijie, Guo, Tong, Rudnick, Paul A., Song, Tao, Li, Jie, Zhuang, Zhengping, Zheng, Wenxin, DeVoe, Don L., Lee, Cheng S., and Balgley, Brian M.
- Subjects
Tissues -- Analysis ,Mass spectrometry -- Usage ,Ovarian cancer ,Chemistry - Abstract
This work expands our tissue proteome capabilities from the analysis of soluble proteins in previous studies to the examination of membrane proteins within the pellets of enriched and selectively isolated tumor cells procured from microdissected tissue specimens. The pellets of targeted ovarian tumor cells are treated by two different membrane protein extraction methods, including the use of detergent and organic solvent. The detergent-based membrane protein preparation protocol not only extracts proteins effectively from cell pellets but also is compatible with subsequent proteome analysis using combined capillary isoelctric focusing/nano reversed-phase liquid chromatography separations coupled with nano electrospray ionization mass spectrometry. Among proteins identified from an amount of pellet equivalent to 20 000 cells, 773 proteins are predicted to contain one or more transmembrane domains, corresponding to 22% membrane proteome coverage within the SwissProt Human protein sequence entries.
- Published
- 2007
17. miR-365 promotes diabetic retinopathy through inhibiting Timp3 and increasing oxidative stress
- Author
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Weiye Li, Debasish Sinha, Jing-Ying Xu, Lixia Lu, Haibin Tian, Yaping Sun, Min Wang, Caixia Jin, Zongyi Li, Jingfa Zhang, Jieping Zhang, Fang Wang, Guo-Tong Xu, Maihemuti Awuti, Chunpin Lian, Furong Gao, Xin Chen, Juan Wang, and Yiting Yang
- Subjects
0301 basic medicine ,Ependymoglial Cells ,Blotting, Far-Western ,medicine.disease_cause ,Retina ,Diabetes Mellitus, Experimental ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Recoverin ,Electroretinography ,medicine ,Animals ,Cells, Cultured ,Tissue Inhibitor of Metalloproteinase-3 ,Analysis of Variance ,Diabetic Retinopathy ,Glial fibrillary acidic protein ,biology ,medicine.diagnostic_test ,Chemistry ,Molecular biology ,Sensory Systems ,Rats ,MicroRNAs ,Oxidative Stress ,Ophthalmology ,Vascular endothelial growth factor A ,030104 developmental biology ,medicine.anatomical_structure ,Gliosis ,Inner nuclear layer ,030221 ophthalmology & optometry ,biology.protein ,sense organs ,medicine.symptom ,Reactive Oxygen Species ,Oxidative stress - Abstract
miRs play critical roles in oxidative stress-related retinopathy pathogenesis. miR-365 was identified in a previously constructed library from glyoxal-treated rat Müller cell. This report explores epigenetic alterations in Müller cells under oxidative stress to develop a novel therapeutic strategy. To examine the miR-365 expression pattern, in situ hybridization and quantitative RT-PCR were performed. Bioinformatical analysis and dual luciferase report assay were applied to identify and confirm target genes. Streptozotocin (STZ)-treated rats were used as the diabetic retinopathy (DR) model. Lentivirus-mediated anti-miR-365 was delivered subretinally and intravitreally into the rats' eyes. The functional and structural changes were evaluated by electroretinogram (ERG), histologically, and through examination of expression levels of metallopeptidase inhibitor 3 (Timp3), glial fibrillary acidic protein (Gfap), recoverin (Rcvrn) and vascular endothelia growth factor A (Vegfa). Oxidative stress factors and pro-inflammatory cytokines were analyzed. miR-365 expression was confirmed in the glyoxal-treated rat Müller cell line (glyoxal-treated rMC-1). In the retina, miR-365 mainly localized in the inner nuclear layer (INL). The increased miR-365 participated in Müller cell gliosis through oxidative stress aggravation, as observed in glyoxal-treated rMC-1 and DR rats before 6 weeks. Timp3 was a target and negatively regulated by miR-365. When miR-365 was inhibited, Timp3 expression was upregulated, Müller cell gliosis was alleviated, and retinal oxidative stress was attenuated. Visual function was also partially rescued as detected by ERG. miR-365 was found to be highly expressed in the retina and the abnormality of miR-365/Timp3 pathway is closely related to the pathology, like Müller gliosis, and the visual injury in DR. The mechanism might be through oxidative stress, and miR-365/Timp3 could be a potential therapeutic target for treating DR.
- Published
- 2018
18. Green and low-cost approach to modify the indium tin oxide anodes in organic light-emitting diodes by electrochemical treatment in NaCl aqueous solution
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Chuanhui Cheng, Wei Feng Liu, Yingmin Luo, Chao Sun, Guo Tong Du, Shulin Cong, Yuan Wang, Bi Long Zhang, and Ruo Xuan Li
- Subjects
Materials science ,General Physics and Astronomy ,chemistry.chemical_element ,02 engineering and technology ,Electrochemistry ,01 natural sciences ,0103 physical sciences ,OLED ,Work function ,Iridium ,010302 applied physics ,Aqueous solution ,business.industry ,Surfaces and Interfaces ,General Chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Surfaces, Coatings and Films ,Indium tin oxide ,chemistry ,Electrode ,Optoelectronics ,Quantum efficiency ,0210 nano-technology ,business ,Nuclear chemistry - Abstract
We demonstrate an environment-friendly, simple, and low energy cost approach as an alternative to conventional O 2 plasma treatment to modify the surface of indium tin oxide (ITO) anodes for use in organic light-emitting diodes (OLEDs). ITO is electrochemically treated in NaCl aqueous solution. A chlorinated ITO (Cl-ITO) electrode with a work function of 5.41 eV was obtained, which is 0.66 eV higher than that of pre-cleaned ITO. The increase of work function is due to the anodic oxidation reactions occurred on the surface of ITO. The power dissipation is only ∼3 mW in our approach, which is five orders of magnitude lower than that of O 2 plasma treatment (∼100 W). We fabricated the OLEDs with the configuration of Cl-ITO/NPB(35 nm)/CBP:Ir(ppy) 3 (15 nm, 8 wt%)/TPBi:Ir(ppy) 3 (10 nm, 8 wt%)/TPBi (10 nm)/Bphen (50 nm)/Cs 2 CO 3 (2 nm)/Al (100 nm), where NPB is N , Ń -di-1-naphthyl- N , Ń -diphenylbenzidine, CBP is 4′-bis(carbazol-9-yl)biphenyl, TPBi is 2,2′,2″-(1,3,5-benzinetriyl)-tris(1-phenyl-1-H-benzimidazole), Ir(ppy) 3 is bis(3-phenylpyridine) iridium(III) and Bphen is 4,7-diphenyl-1,10-phenanthroline. A maximum power efficiency of 95.0 lm W −1 and external quantum efficiency (EQE) of 24.2% were achieved, respectively, which was slightly higher than that of the OLED fabricated on O 2 -plasma-treated ITO (91.2 lm W −1 , EQE = 23.1%).
- Published
- 2017
19. Small molecule inhibitor regorafenib inhibits RET signaling in neuroblastoma cells and effectively suppresses tumor growth in vivo
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Jianhua Yang, Roma H. Patel, Yan Shi, Shan Guan, Huiyuan Zhang, Jonathan C. Pang, Jodi A. Muscal, Guo-Tong Xu, Zhenghu Chen, Sarah E. Woodfield, Shayahati Bieerkehazhi, Yanling Zhao, Joanna S. Yi, Sanjeev A. Vasudevan, Ling Tao, and Yang Yu
- Subjects
0301 basic medicine ,medicine.drug_class ,medicine.disease_cause ,chemotherapy ,Tyrosine-kinase inhibitor ,Receptor tyrosine kinase ,03 medical and health sciences ,chemistry.chemical_compound ,neuroblastoma ,0302 clinical medicine ,tyrosine kinase inhibitor ,In vivo ,Neuroblastoma ,Regorafenib ,medicine ,Glial cell line-derived neurotrophic factor ,neoplasms ,biology ,Chemistry ,Cell growth ,medicine.disease ,3. Good health ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,regorafenib ,Carcinogenesis ,RET ,Research Paper - Abstract
Neuroblastoma (NB), the most common extracranial pediatric solid tumor, continues to cause significant cancer-related morbidity and mortality in children. Dysregulation of oncogenic receptor tyrosine kinases (RTKs) has been shown to contribute to tumorigenesis in various human cancers and targeting these RTKs has had therapeutic benefit. RET is an RTK which is commonly expressed in NB, and high expression of RET correlates with poor outcomes in patients with NB. Herein we report that RET is required for NB cell proliferation and that the small molecule inhibitor regorafenib (BAY 73-4506) blocks glial cell derived neurotrophic factor (GDNF)-induced RET signaling in NB cells and inhibits NB growth both in vitro and in vivo. We found that regorafenib significantly inhibited cell proliferation and colony formation ability of NB cells. Moreover, regorafenib suppressed tumor growth in both an orthotopic xenograft NB mouse model and a TH-MYCN transgenic NB mouse model. Finally, regorafenib markedly improved the overall survival of TH-MYCN transgenic tumor-bearing mice. In summary, our study suggests that RET is a potential therapeutic target in NB, and that using a novel RET inhibitor, like regorafenib, should be investigated as a therapeutic treatment option for children with NB.
- Published
- 2017
20. The second-generation ALK inhibitor alectinib effectively induces apoptosis in human neuroblastoma cells and inhibits tumor growth in a TH-MYCN transgenic neuroblastoma mouse model
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Jodi A. Muscal, Huiyuan Zhang, Tianshu Yang, Jerry Gu, Shayahati Bieerkehazhi, Jianhua Yang, Shan Guan, Xiao-Nan Li, Guo-Tong Xu, Yanling Zhao, Jingling Jin, Jiaxiong Lu, Sarah E. Woodfield, Kristine L. Yang, Xin Xu, Yang Yu, and Lin Qi
- Subjects
0301 basic medicine ,Alectinib ,Cancer Research ,Time Factors ,Apoptosis ,Neuroblastoma ,0302 clinical medicine ,Piperidines ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Anaplastic lymphoma kinase ,Anaplastic Lymphoma Kinase ,N-Myc Proto-Oncogene Protein ,Chemistry ,TOR Serine-Threonine Kinases ,Tumor Burden ,Phenotype ,Oncology ,030220 oncology & carcinogenesis ,Female ,Signal Transduction ,medicine.drug_class ,Carbazoles ,Mice, Nude ,Antineoplastic Agents ,Mice, Transgenic ,Article ,Inhibitory Concentration 50 ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Kinase activity ,Protein Kinase Inhibitors ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Dose-Response Relationship, Drug ,Cell growth ,Receptor Protein-Tyrosine Kinases ,medicine.disease ,Xenograft Model Antitumor Assays ,Molecular biology ,ALK inhibitor ,030104 developmental biology ,Doxorubicin ,Mutation ,Phosphatidylinositol 3-Kinase ,Proto-Oncogene Proteins c-akt - Abstract
Activating germline mutations of anaplastic lymphoma kinase (ALK) occur in most cases of hereditary neuroblastoma (NB) and the constitutively active kinase activity of ALK promotes cell proliferation and survival in NB. Therefore, ALK kinase is a potential therapeutic target for NB. In this study, we show that the novel ALK inhibitor alectinib effectively suppressed cell proliferation and induces apoptosis in NB cell lines with either wild-type ALK or mutated ALK (F1174L and D1091N) by blocking ALK-mediated PI3K/Akt/mTOR signaling. In addition, alectinib enhanced doxorubicin-induced cytotoxicity and apoptosis in NB cells. Furthermore, alectinib induced apoptosis in an orthotopic xenograft NB mouse model. Also, in the TH-MYCN transgenic mouse model, alectinib resulted in decreased tumor growth and prolonged survival time. These results indicate that alectinib may be a promising therapeutic agent for the treatment of NB.
- Published
- 2017
21. The amino acid transporter SLC36A4 regulates the amino acid pool in retinal pigmented epithelial cells and mediates the mechanistic target of rapamycin, complex 1 signaling
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Lixia Lu, Guo-Tong Xu, Rhonda Grebe, Jiang Qian, James T. Handa, Sayan Ghosh, Debasish Sinha, Yuri V. Sergeev, Peng Shang, Jun Wan, J. Samuel Zigler, Stacey Hose, Imran Ahmed Bhutto, Rosa Puertollano, Mallika Valapala, and Gerard A. Lutty
- Subjects
visual cycle proteins ,0301 basic medicine ,Aging ,Amino Acid Transport Systems ,genetic structures ,Retinal Pigment Epithelium ,mTORC1 ,transcription factors EB (TFEB) and E3 (TFE3) ,Cytosol ,coordinated lysosomal expression and regulation (CLEAR) network ,Gene Regulatory Networks ,Amino Acids ,Phosphorylation ,Mice, Knockout ,chemistry.chemical_classification ,biology ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,TOR Serine-Threonine Kinases ,age‐related macular degeneration ,retinal pigmented epithelium (RPE) ,Cell biology ,Amino acid ,medicine.anatomical_structure ,Original Article ,signal transduction ,Protein Binding ,mouse model ,Mechanistic Target of Rapamycin Complex 1 ,beta-Crystallin A Chain ,03 medical and health sciences ,Lysosome ,medicine ,Animals ,Visual Pathways ,Amino acid transporter ,Mechanistic target of rapamycin ,photoreceptor degeneration ,amino acid transporter (PAT4/SLC36A4) ,Retinal pigment epithelium ,030102 biochemistry & molecular biology ,Epithelial Cells ,Original Articles ,lysosomes ,mechanistic target of rapamycin ,Cell Biology ,Retinal Photoreceptor Cell Outer Segment ,Crystallins ,eye diseases ,030104 developmental biology ,chemistry ,Multiprotein Complexes ,biology.protein ,TFEB ,sense organs ,Lecithin retinol acyltransferase ,Lysosomes ,complex 1 (mTORC1) - Abstract
Summary The dry (nonneovascular) form of age‐related macular degeneration (AMD), a leading cause of blindness in the elderly, has few, if any, treatment options at present. It is characterized by early accumulation of cellular waste products in the retinal pigmented epithelium (RPE); rejuvenating impaired lysosome function in RPE is a well‐justified target for treatment. It is now clear that amino acids and vacuolar‐type H+‐ATPase (V‐ATPase) regulate the mechanistic target of rapamycin, complex 1 (mTORC1) signaling in lysosomes. Here, we provide evidence for the first time that the amino acid transporter SLC36A4/proton‐dependent amino acid transporter (PAT4) regulates the amino acid pool in the lysosomes of RPE. In Cryba1 (gene encoding βA3/A1‐crystallin) KO (knockout) mice, where PAT4 and amino acid levels are increased in the RPE, the transcription factors EB (TFEB) and E3 (TFE3) are retained in the cytoplasm, even after 24 h of fasting. Consequently, genes in the coordinated lysosomal expression and regulation (CLEAR) network are not activated, and lysosomal function remains low. As these mice age, expression of RPE65 and lecithin retinol acyltransferase (LRAT), two vital visual cycle proteins, decreases in the RPE. A defective visual cycle would possibly slow down the regeneration of new photoreceptor outer segments (POS). Further, photoreceptor degeneration also becomes obvious during aging, reminiscent of human dry AMD disease. Electron microscopy shows basal laminar deposits in Bruch's membrane, a hallmark of development of AMD. For dry AMD patients, targeting PAT4/V‐ATPase in the lysosomes of RPE cells may be an effective means of preventing or delaying disease progression.
- Published
- 2017
22. MicroRNA-24 protects retina from degeneration in rats by down-regulating chitinase-3-like protein 1
- Author
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Weiye Li, Furong Gao, Chunpin Lian, Haibin Tian, Caixia Jin, Juan Wang, Lixia Lu, Guo-Tong Xu, Hui Lou, Qingjian Ou, Jieping Zhang, Jing-Ying Xu, Guoxu Xu, and Jingfa Zhang
- Subjects
0301 basic medicine ,Retinal degeneration ,MAPK/ERK pathway ,Male ,Blotting, Western ,Down-Regulation ,Retinal Pigment Epithelium ,Biology ,Rats, Mutant Strains ,Retina ,Cell Line ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Microscopy, Electron, Transmission ,medicine ,Autophagy ,Electroretinography ,In Situ Nick-End Labeling ,Animals ,Chitinase-3-Like Protein 1 ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Retinal Degeneration ,Retinal ,medicine.disease ,eye diseases ,Sensory Systems ,Cell biology ,Rats ,Ophthalmology ,Disease Models, Animal ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,030221 ophthalmology & optometry ,sense organs ,Signal transduction ,Signal Transduction - Abstract
MicroRNAs (miRNAs) have been shown to play critical roles in the pathogenesis and progression of degenerative retinal diseases like age-related macular degeneration (AMD). In this study, we first demonstrated that miR-24 plays an important role in maintaining retinal structure and visual function of rats by targeting chitinase-3-like protein 1 (CHI3L1). In the retinal pigment epithelial (RPE) cells of Royal College of Surgeons (RCS) rats, an animal model of genetic retinal degeneration (RD), miR-24 was found lower and CHI3L1 level was higher in comparison with those in Sprague-Dawley (SD) rats. Other changes in the eyes of RCS rats include activated AKT/mTOR and ERK pathways and abnormal autophagy in the RPE cells. Such roles of miR-24 and CHI3L1 were further confirmed in RCS rats by subretinal injection of agomiR-24, which decreased CHI3L1 level and preserved retinal structure and function. Upstream, NF-κB was identified as the regulator of miR-24 in the RPE cells of these rats. On the other hand, in SD rats, intraocular treatment of antagomiR-24 induced pathological changes similar to those in RCS rats. The results revealed the protective roles for miR-24 to RPE cells and a mechanism for RD in RCS rats was proposed: extracellular stress stimuli first activate the NF-κB signaling pathway, which lowers miR-24 expression so that CHI3L1 increased. CHI3L1 sequentially results in aberrant autophagy and RPE dysfunction by activating AKT/mTOR and ERK pathways. Taken together, although the possibility, that the therapeutic effects in RCS rats are caused by other transcriptional changes regulated by miR-24, cannot be excluded, these findings indicate that miR-24 protects rat retina by targeting CHI3L1. Thus, miR-24 and CHI3L1 might be the targets for developing more effective therapy for degenerative retinal diseases like AMD.
- Published
- 2019
23. Erythropoietin maintains VE-cadherin expression and barrier function in experimental diabetic retinopathy via inhibiting VEGF/VEGFR2/Src signaling pathway
- Author
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Weiye Li, Hua Xu, Jing-Ying Xu, Haibin Tian, Chaoyang Zhang, Lixia Lu, Qian Yang, Kun Liu, Xiaodong Sun, Guoxu Xu, Guo-Tong Xu, Jingfa Zhang, Hai Xie, and Dandan Liu
- Subjects
Male ,Vascular Endothelial Growth Factor A ,0301 basic medicine ,medicine.medical_specialty ,Blood–retinal barrier ,Down-Regulation ,030226 pharmacology & pharmacy ,General Biochemistry, Genetics and Molecular Biology ,Umbilical vein ,Diabetes Mellitus, Experimental ,Capillary Permeability ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Antigens, CD ,Internal medicine ,Blood-Retinal Barrier ,Human Umbilical Vein Endothelial Cells ,medicine ,Animals ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Fluorescein isothiocyanate ,Erythropoietin ,Barrier function ,Diabetic Retinopathy ,Chemistry ,Endothelial Cells ,Retinal Vessels ,General Medicine ,Cadherins ,Streptozotocin ,Vascular Endothelial Growth Factor Receptor-2 ,Recombinant Proteins ,Rats ,Vascular endothelial growth factor ,src-Family Kinases ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,VE-cadherin ,medicine.drug - Abstract
Aims To explore the mechanisms of erythropoietin (EPO)'s protection on inner blood-retinal barrier (iBRB) in experimental diabetic retinopathy. Material and methods Male SD rats were rendered diabetic with streptozotocin, followed by intravitreal injection of EPO. The permeability of iBRB was examined with fluorescein isothiocyanate (FITC)-dextran. Human retinal microvascular endothelial cells (HRMECs) and human umbilical vein endothelial cells (HUVECs) were treated with glyoxal and studied for cell viability and barrier function. The expressions of vascular endothelial (VE)-cadherin, Src kinase, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR2) were analyzed with Western blot, ELISA, qPCR, or immunofluorescence. Key findings VE-cadherin in rat retinas was down-regulated with diabetes progression. EPO treatment could increase VE-cadherin expression at week 8 and week 16. The expressions of p-Src and p-VE-cadherin were increased at week 2, while decreased at week 8 of diabetes; which were prevented by EPO. The leakage of FITC-dextran in 8-week diabetic rat retinas was ameliorated by EPO. In vitro results showed the expressions of VEGF, p-Src and p-VE-cadherin were increased significantly, accompanied with the decreased barrier function, which were prevented by EPO. Ranibizumab and CGP77675 also inhibited the glyoxal-induced phosphorylation of Src and VE-cadherin. Cellular fractionation showed EPO mitigated the VE-cadherin internalization in glyoxal-treated cells. Significance EPO maintained the expression of VE-cadherin in experimental diabetic retinopathy by inhibiting its phosphorylation and internalization through VEGF/VEGFR2/Src pathway, thus improved the integrity of iBRB.
- Published
- 2020
24. IL-37 Is a Novel Proangiogenic Factor of Developmental and Pathological Angiogenesis
- Author
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Gaoqin Liu, Qing Lin, Shangfeng Liu, Mengmeng Zhao, Tianshu Yang, Xuetao Zhang, Jianhua Yang, Shao Bo Su, Peirong Lu, Guo-Tong Xu, Jiayi Jin, Ying Yu, Xialin Liu, Rongbin Wei, Yongguang Hu, Xiaoping Yang, Hongyan Zhou, David B. Corry, and Xiao Hu
- Subjects
Time Factors ,Cell Survival ,Angiogenesis ,Basic fibroblast growth factor ,Neovascularization, Physiologic ,Retinal Neovascularization ,Biology ,Transfection ,chemistry.chemical_compound ,Cell Movement ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Retinopathy of Prematurity ,Extracellular Signal-Regulated MAP Kinases ,Cells, Cultured ,Cell Proliferation ,Dose-Response Relationship, Drug ,Hypoxia-Inducible Factor 1, alpha Subunit ,Cell Hypoxia ,Cell biology ,Mice, Inbred C57BL ,Endothelial stem cell ,Vascular endothelial growth factor ,Vascular endothelial growth factor B ,Disease Models, Animal ,Vascular endothelial growth factor A ,Animals, Newborn ,Vascular endothelial growth factor C ,chemistry ,Immunology ,Angiogenesis Inducing Agents ,RNA Interference ,Cardiology and Cardiovascular Medicine ,Proto-Oncogene Proteins c-akt ,Interleukin-1 - Abstract
Objective— Angiogenesis is tightly controlled by growth factors and cytokines in pathophysiological settings. Interleukin 37 (IL-37) is a newly identified cytokine of the IL-1 family, some members of which are important in inflammation and angiogenesis. However, the function of IL-37 in angiogenesis remains unknown. We aimed to explore the regulatory role of IL-37 in pathological and physiological angiogenesis. Approach and Results— We found that IL-37 was expressed and secreted in endothelial cells and upregulated under hypoxic conditions. IL-37 enhanced endothelial cell proliferation, capillary formation, migration, and vessel sprouting from aortic rings with potency comparable with that of vascular endothelial growth factor. IL-37 activates survival signals including extracellular signal-regulated kinase 1/2 and AKT in endothelial cells. IL-37 promoted vessel growth in implanted Matrigel plug in vivo in a dose-dependent manner with potency comparable with that of basic fibroblast growth factor. In the mouse model of retinal vascular development, neonatal mice administrated with IL-37 displayed increased neovascularization. We demonstrated further that IL-37 promoted pathological angiogenesis in the mouse model of oxygen-induced retinopathy. Conclusions— Our findings suggest that IL-37 is a novel and potent proangiogenic cytokine with essential role in pathophy siological settings.
- Published
- 2015
25. The Interplay Between E-Cadherin, Connexin 43, and Zona Occludens 1 in Retinal Pigment Epithelial Cells
- Author
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Shuai Yang, Haipei Yao, Jingfa Zhang, Hui Li, Yao Zhang, Fang Wang, Huiqian Bao, Haiying Jin, and Guo-Tong Xu
- Subjects
0301 basic medicine ,Connexin ,Retinal Pigment Epithelium ,Cell junction ,Tight Junctions ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Microscopy, Electron, Transmission ,medicine ,Animals ,Humans ,Cells, Cultured ,Retinal pigment epithelium ,Tight junction ,Chemistry ,Cadherin ,Vitreoretinopathy, Proliferative ,Gap junction ,Colocalization ,Retinal ,Cadherins ,Cell biology ,Intercellular Junctions ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Connexin 43 ,Zonula Occludens-1 Protein ,RNA ,sense organs ,030217 neurology & neurosurgery - Abstract
Purpose Cell-cell contact in retinal pigment epithelium (RPE) involves adherent junctions, gap junctions, and tight junctions, which are primarily composed by E-cadherin, zona occludens 1 (ZO-1), and connexin 43, respectively. Here, we aimed to explore the relationship and interplay between these junction-associated proteins. Methods E-cadherin, connexin 43, and ZO-1 expression in human primary RPE in the early phase after TGF-β1 stimulation was detected. The knockdown of E-cadherin, ZO-1, and connexin 43 was performed to characterize the regulatory network involving these three proteins. Dye transfer and FITC-dextran permeability assays were conducted to observe the epithelial functional alterations. Transmission electron microscopy (TEM) was used to observe the ultrastructure of the cell-cell junctions in mouse RPE. The immunofluorescence staining and coimmunoprecipitation were performed to observe the colocalization and the physical association of E-cadherin, ZO-1, and connexin 43. Results Among these three components, E-cadherin appeared to be the first protein that was downregulated after TGF-β1 treatment. The ultrastructures of adherent junctions, gap junctions, and tight junctions could be observed in mouse RPE by TEM. E-cadherin, ZO-1, and connexin 43 were colocalized and physically bound to each other. The knockdown of one of these three proteins led to downregulation of the other two proteins and compromised epithelial function. Conclusions E-cadherin, ZO-1, and connexin 43 were physically associated with each other and were mutually regulated. To enhance the understanding of cell-cell contacts, a holistic view is needed. Our results provide new insights in RPE disorders such as proliferative vitreoretinopathy.
- Published
- 2019
26. The combination of bFGF and CHIR99021 maintains stable self-renewal of mouse adult retinal progenitor cells
- Author
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Qingjian Ou, Lixia Lu, Guo-Tong Xu, Furong Gao, Zongyi Li, Haibin Tian, Caixia Jin, Jieping Zhang, Jing-Ying Xu, and Juan Wang
- Subjects
0301 basic medicine ,Pyridines ,Basic fibroblast growth factor ,Cellular therapy ,Cell- and Tissue-Based Therapy ,Wnt pathway ,Medicine (miscellaneous) ,Biology ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Progenitor cells ,Retina ,lcsh:Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,medicine ,Animals ,lcsh:QD415-436 ,Receptor, Fibroblast Growth Factor, Type 1 ,Progenitor cell ,Ganglion cell layer ,Cell Proliferation ,lcsh:R5-920 ,Transplantation ,Retinal pigment epithelium ,Stem Cells ,Research ,Retinal ,Cell Biology ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Pyrimidines ,chemistry ,Molecular Medicine ,sense organs ,Stem cell ,lcsh:Medicine (General) - Abstract
Background Millions of people are affected with retinal diseases that eventually cause blindness, and retinal progenitor cell (RPC) transplantation is a promising therapeutic avenue. However, RPC expansion and the underlying regulation mechanisms remain elusive. Methods Adult mouse neural RPCs (mNRPCs) were isolated and amplified with the combination of basic fibroblast growth factor (bFGF) and glycogen synthase kinase 3 (GSK3) inhibitor CHIR99021. The progenitor characteristics were evaluated with RT-PCR, immunocytochemistry (ICC), western blot, flow cytometry, and transcriptome analysis prior to transplantation. By treating cells with or without bFGF and CHIR99021 at different time points, the mechanism for mNRPCs’ self-renewal was investigated by transcriptome analysis and western blot assay. Results mNRPCs were self-renewing in the presence of bFGF and CHIR99021 and showed prominent RPC characteristics. bFGF was essential in promoting cell cycle by facilitating G1/S and G2/M transitions. bFGF combined with CHIR99021 activated the non-canonical Wnt5A/Ca2+ pathway and form a calcium homeostasis. In addition, the self-renewing mNRPCs could differentiate into rod photoreceptor-like cells and retinal pigment epithelium (RPE)-like cells by in vitro induction. When green fluorescent protein (GFP)-labeled cells were transplanted into the subretinal space (SRS) of Pde6b (rd1) mice (also known as RD1 mice, or rodless mice), the cells survived for more than 12 weeks and migrated into the retina. Parts of the recipient retina showed positive expression of photoreceptor marker rhodopsin. Transplanted cells can migrate into the retina, mainly into the inner cell layer (INL) and ganglion cell layer (GCL). Some cells can differentiate into astrocytes and amacrine cells. Cultured mNRPCs did not form tumors after transplanted into NOD/SCID mice for 6 months. Conclusions Present study developed an approach to maintain long-term self-renewal of RPCs from adult retinal tissues and revealed that activation of the non-canonical Wnt5A/Ca2+ pathway may participate in regulating RPC self-renewal in vitro. This study presents a very promising platform to expand RPCs for future therapeutic application. Electronic supplementary material The online version of this article (10.1186/s13287-018-1091-y) contains supplementary material, which is available to authorized users.
- Published
- 2018
27. A cell culture condition that induces the mesenchymal-epithelial transition of dedifferentiated porcine retinal pigment epithelial cells
- Author
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Qingjian Ou, Binxin Wu, Lixia Lu, Guo-Tong Xu, Jieping Zhang, Furong Gao, Weiye Li, Chunpin Lian, Haibin Tian, Yaqi Cao, Caixia Jin, Jingfa Zhang, Jing-Ying Xu, Juan Wang, and Yu Tian
- Subjects
0301 basic medicine ,Cell type ,RHOA ,Epithelial-Mesenchymal Transition ,Swine ,Blotting, Western ,Cell Culture Techniques ,Retinal Pigment Epithelium ,Cell morphology ,Polymerase Chain Reaction ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Mesenchymal–epithelial transition ,Animals ,Epithelial–mesenchymal transition ,Induced pluripotent stem cell ,Cells, Cultured ,biology ,Chemistry ,Intracellular Signaling Peptides and Proteins ,Epithelial Cells ,Cell Dedifferentiation ,Sensory Systems ,In vitro ,Cell biology ,Ophthalmology ,030104 developmental biology ,Cell culture ,030221 ophthalmology & optometry ,biology.protein ,sense organs ,Biomarkers - Abstract
The pathological change of retinal pigment epithelial (RPE) cells is one of the main reasons for the development of age-related macular degeneration (AMD). Thus, cultured RPE cells are a proper cell model for studying the etiology of AMD in vitro. However, such cultured RPE cells easily undergo epithelial-mesenchymal transition (EMT) that results in changes of cellular morphology and functions of the cells. To restore and maintain the mesenchymal-epithelial transition (MET) of the cultured RPE cells, we cultivated dedifferentiated porcine RPE (pRPE) cells and compared their behaviors in four conditions: 1) in cell culture dishes with DMEM/F12 containing FBS (CC dish-FBS), 2) in petri dishes with DMEM/F12 containing FBS (Petri dish-FBS), 3) in cell culture dishes with DMEM/F12 containing N2 and B27 supplements (CC dish-N2B27), and 4) in petri dishes with DMEM/F12 containing N2 and B27 (Petri dish-N2B27). In addition to observing the cell morphology and behavior, RPE specific markers, as well as EMT-related genes and proteins, were examined by immunostaining, quantitative real-time PCR and Western blotting. The results showed that dedifferentiated pRPE cells maintained EMT in CC dish-FBS, Petri dish-FBS and CC dish-N2B27 groups, whereas MET was induced when the dedifferentiated pRPE cells were cultured in Petri dish-N2B27. Such induced pRPE cells showed polygonal morphology with increased expression of RPE-specific markers and decreased EMT-associated markers. Similar results were observed in induced pluripotent stem cell-derived RPE cells. Furthermore, during the re-differentiation of those dedifferentiated pRPE cells, Petri dish-N2B27 reduced the activity of RhoA and induced F-actin rearrangement, which promoted the nuclear exclusion of transcriptional co-activator with PDZ-binding motif (TAZ) and TAZ target molecule zinc finger E-box binding protein (ZEB1), both of which are EMT inducing factors. This study provides a simple and reliable method to reverse dedifferentiated phenotype of pRPE cells into epithelialized phenotype, which is more appropriate for studying AMD in vitro, and suggests that MET of other cell types might be induced by a similar approach.
- Published
- 2018
28. Protective Effects of Fucoidan on Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells and Progression of Proliferative Vitreoretinopathy
- Author
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Min Li, Yao Zhang, Guo-Tong Xu, Fang Wang, Shuai Yang, Hui Li, Haipei Yao, Jingfa Zhang, Dongwan Zhao, and Chun Zhao
- Subjects
0301 basic medicine ,Proliferative vitreoretinopathy ,Physiology ,Retinal Pigment Epithelium ,Smad2 Protein ,Eye ,lcsh:Physiology ,chemistry.chemical_compound ,Cell Movement ,lcsh:QD415-436 ,Phosphorylation ,Cells, Cultured ,biology ,medicine.diagnostic_test ,lcsh:QP1-981 ,Fucoidan ,Cadherins ,Isoenzymes ,medicine.anatomical_structure ,Rabbits ,Tomography, Optical Coherence ,Epithelial-Mesenchymal Transition ,Down-Regulation ,Protective Agents ,Aldehyde Dehydrogenase 1 Family ,lcsh:Biochemistry ,Transforming Growth Factor beta1 ,03 medical and health sciences ,Western blot ,In vivo ,Polysaccharides ,medicine ,Animals ,Humans ,Epithelial–mesenchymal transition ,Smad3 Protein ,Neoplasm Staging ,Retinal pigment epithelium ,Vitreoretinopathy, Proliferative ,Retinal Dehydrogenase ,medicine.disease ,eye diseases ,Actins ,Fibronectins ,Fibronectin ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Cancer research ,biology.protein ,sense organs ,Transforming growth factor - Abstract
Background/Aims: Proliferative vitreoretinopathy (PVR) is a severe blinding complication of rhegmatogenous retinal detachment. Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is thought to play a pivotal role in the pathogenesis of PVR. Fucoidan, a marine extract, reportedly has many benefits effects in a variety of tissues and organs such as anti-inflammation, anti-oxidative stress, and anti-carcinogenesis. In this study, we investigated the potential role of fucoidan on EMT in RPE cells and its effect on the development of PVR. Methods: MTS, Transwell, and collagen gel contraction assays were employed to measure the viability, migration, and contraction of RPE cells, respectively. mRNA and protein expression were evaluated via real-time quantitative PCR and western blot analysis, respectively. In vivo, a pigmented rabbit model of PVR was established to examine the anti-PVR effect of fucoidan. Results: Fucoidan reversed the transforming growth factor (TGF)-β1-induced EMT of RPE cells, including the increased expression of α-smooth muscle actin (α-SMA) and fibronectin and down-regulation of E-cadherin in human primary RPE cells. Moreover, the upregulation of phosphorylated Smad2/3 induced by TGF-β1 was suppressed by fucoidan. Fucoidan also inhibited the migration and contraction of RPE cells induced by TGF-β1. In vivo, fucoidan inhibited the progression of experimental PVR in rabbit eyes. Histological findings showed that fucoidan suppressed the formation of α-SMA-positive epiretinal membranes. Conclusion: Our findings regarding the protective effects of fucoidan on the EMT of RPE cells and experimental PVR suggest the potential clinical application of fucoidan as an anti-PVR agent.
- Published
- 2017
29. Erythropoietin Protects Retina Against Ceramide 2-Induced Damage in Rat
- Author
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Guo-Tong Xu, Jieping Zhang, Zongyi Li, Haibin Tian, Lixia Lu, Hui Lou, Guoxu Xu, Chi Zhang, Christine G. Lian, Qian Yang, and Daohuan Kang
- Subjects
0301 basic medicine ,Male ,Ceramide ,Blood–retinal barrier ,Apoptosis ,Pharmacology ,Ceramides ,Protective Agents ,Biochemistry ,Neuroprotection ,Retina ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Retinal Diseases ,In vivo ,medicine ,Animals ,Viability assay ,Molecular Biology ,Erythropoietin ,Cell Proliferation ,business.industry ,Retinal ,General Medicine ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Intravitreal Injections ,Molecular Medicine ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background Ceramide plays critical roles in cell proliferation, senescence and apoptosis, and is implicated in neurodegenerative diseases, etc. To clarify if ceramide plays some roles in retinal diseases, we established in vivo and in vitro retinal injury models with ceramide 2 (C2) treatment. In addition, Erythropoietin (EPO), which showed protective effects on retinal cells and blood-retinal barrier (BRB), was also tested for its protection and possible mechanism(s) in these models. Methods Male Sprague-Dawley rats were divided into four groups, i.e., normal control, vehicle control, C2 treatment, and C2+EPO treatment. After intravitreal injection, the rats were examined for eye fundus, electroretinogram, histological study, and immunostaining, etc. In vitro, retinal neuronal cell line (R28) and the primary human retinal microvascular endothelial cells (HRMECs) were treated with C2, cell viability assay, transendothelial electrical resistance (TEER) and BRB-related molecules were studied to test the protective effect of EPO. Results Intravitreal C2-treatment caused significant vision loss in rats, as reflected by reduced b-wave amplitude, increased TUNEL positive cells and GFAP immunostaining in retina. Another major retinal injury observed was BRB breakdown following C2- treatment. Such C2-induced injuries were further confirmed by in vitro study. When HRMECs were treated with C2, the TEER was significantly reduced. The mechanisms for C2 to induce such injuries might be through evidently increased expressions of the related molecules like plasmalemma vesicle-associated protein (PLVAP or PV-1), ecto- 5'-nucleotidase (CD73) and intercellular adhesion molecule-1 (ICAM-1), as observed in C2-treated R28 cells. All these injuries induced by C2 were significantly prevented by EPO both in vivo and in vitro, and its protective mechanisms here might be, in addition to neuroprotective, closely related to its maintenance of BRB integrity, through reducing the expressions of PV-1, CD73 and ICAM-1. Conclusion C2 could induce severe retinal injury, and such injuries could be effectively prevented by EPO treatment.
- Published
- 2017
30. Loading cobalt phosphate on TaON surface as efficient noble-metal-free co-catalyst for enhanced photocatalytic water oxidation performance
- Author
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Huang Xi, Gang Chen, Wei Zeng, Guo Tong, Yue Liu, Wang Li, and Yansong Zhou
- Subjects
Materials science ,Mechanical Engineering ,Inorganic chemistry ,Oxygen evolution ,COPI ,Crystal structure ,engineering.material ,Condensed Matter Physics ,Catalysis ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,Mechanics of Materials ,Photocatalysis ,engineering ,General Materials Science ,Charge carrier ,Noble metal ,Cobalt phosphate - Abstract
Cobalt phosphate (CoPi) was loaded on the surface of TaON by a photochemical deposition method as an efficient oxygen evolution co-catalyst for the first time. Loading of CoPi showed little effect on the crystal structure and optical properties of TaON. While, the photogenerated charge carriers were efficiently separated in TaON after CoPi loading. Sample of CoPi/TaON (1 wt%) showed enhanced photocatalytic oxygen evolution performance of 1.75 mmol h −1 g −1 from water-splitting under visible light irradiation, which is about two times of that for pristine TaON.
- Published
- 2015
31. Erythropoietin Exerts a Neuroprotective Function Against Glutamate Neurotoxicity in Experimental Diabetic Retina
- Author
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Guo-Tong Xu, Jing Ying Xu, Debasish Sinha, Limin Gu, Jingfa Zhang, Lixia Lu, Juan Wang, Haibin Tian, Furong Gao, Hua Xu, Weiye Li, Fang Wang, and Guoxu Xu
- Subjects
Male ,Poly Adenosine Diphosphate Ribose ,medicine.medical_specialty ,Programmed cell death ,Amino Acid Transport System X-AG ,Glutamic Acid ,Biology ,Neuroprotection ,Retina ,Cell Line ,Diabetes Mellitus, Experimental ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Glutamate-Ammonia Ligase ,Internal medicine ,Receptors, Erythropoietin ,medicine ,Animals ,Viability assay ,Erythropoietin ,Diabetic Retinopathy ,Cell Death ,Glutamate receptor ,Neurotoxicity ,Apoptosis Inducing Factor ,Retinal ,Glutamic acid ,medicine.disease ,Sensory Systems ,Rats ,Disease Models, Animal ,Ophthalmology ,Endocrinology ,Receptors, Glutamate ,chemistry ,Intravitreal Injections ,Excitatory Amino Acid Antagonists ,medicine.drug - Abstract
Purpose Retinal neuronal cell dysfunction and even cell death are associated with increased excitotoxic glutamate (Glu) level in the retina. Our aim was to study a causative mechanism of Glu on retinal cell death and explore the neuroprotective role of erythropoietin (EPO) against Glu neurotoxicity in the diabetic retina. Methods Male Sprague-Dawley (SD) rats and R28 cell line were employed in this study. Diabetes was induced with intraperitoneal injection of streptozotocin (STZ) in SD rats. Two weeks after diabetes onset, the intravitreal injection was performed; 4 days later, the retinas were harvested for testing. R28 cells were treated with Glu, Glu+EPO, or Glu+EPO+soluble EPO receptor (sEPOR), respectively, for 24 hours, and then the cells were collected for the following studies. Glutamate level in the retina was measured with a glutamate assay kit. Cell death was determined with TUNEL staining. The changes in glutamine synthetase (GS), glutamate-aspartate transporter (GLAST), ionotropic glutamate receptors (iGluRs), apoptosis-inducing factor (AIF), and poly(ADP-ribose) (PAR) polymer were studied with RT-PCR, Western blot, and immunofluorescence. Results In 2-week diabetic rat retinas, Glu concentration was approximately 1.21-fold that in normal control. TUNEL staining demonstrated that retinal cell death was increased. Retinal GS and GLAST expressions were decreased, while the iGluRs, for example, KA1 and NR1, and PAR polymer expression was increased. In R28 cells, 24 hours after Glu (10 mM) treatment, the cell viability was decreased by 52.7%; KA1, NR1, PAR polymer, and nuclear AIF all increased in expression. The above conditions could be largely reversed by EPO both in vivo and in vitro. The protective effect of EPO was abolished by sEPOR. Conclusions Erythropoietin showed a neuroprotective function against Glu-mediated neurotoxicity both in diabetic rat retina and in Glu-treated R28 cells. The neuroprotective mechanisms were largely through maintaining the normal expression of glutamate-glutamine cycle-related proteins and inhibiting AIF translocation and PAR polymer formation.
- Published
- 2014
32. Development of Natural Bio-Plantation Waste as Pulp for Paper Making
- Author
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Chui Kim Ng and Guo Tong Ng
- Subjects
Absorption of water ,Materials science ,Waste management ,Pulp (paper) ,General Engineering ,engineering.material ,Pulp and paper industry ,Husk ,Environmentally friendly ,chemistry.chemical_compound ,chemistry ,Cellulosic ethanol ,Sodium hydroxide ,Soda pulping ,Ultimate tensile strength ,engineering - Abstract
This project investigated the use of facile pulping methods to produce pulp from mixed bio-plantation waste fibres using sodium hydroxide, ethanol and garbage enzyme. Papers were successfully made from mixture of corn husk fibres with other bio-based green fibres such as banana stems and pineapple leaves. Soda pulping was found to be efficient in converting the cellulosic bio-fibres to the pulps used for paper making. The papers produced have low tensile strength, high water absorption, high bio-decomposition and degradation rate, as compared to commercial papers. SEM observation revealed that paper made from mixed bio-fibres have lightly cross-linked structures compared to heavily cross-linked or compact network structures found in commercial papers. The paper can be used in applications that require high water absorbency. The paper making process is more environmental friendly as it reduces the usage of wood fibres and hence reduces the environmental problem caused by deforestation.
- Published
- 2014
33. Influence of Indium Interlayer on The Crystal and Optical Properties of InN Grown on Silicon Substrate
- Author
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景强 Jing Qiang, 李万程 Li Wan-cheng, 蔡旭浦 Cai Xu-pu, 吴国光 Wu Guo-guang, 杜国同 Du Guo-tong, 张宝林 Zhang Bao-lin, and 高福斌 Gao Fu-bin
- Subjects
Crystal ,Radiation ,Materials science ,Silicon ,chemistry ,business.industry ,chemistry.chemical_element ,Optoelectronics ,Substrate (electronics) ,Condensed Matter Physics ,business ,Indium ,Electronic, Optical and Magnetic Materials - Published
- 2014
34. Bst1 is required for Candida albicans infecting host via facilitating cell wall anchorage of Glycosylphosphatidyl inositol anchored proteins
- Author
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Mao Mao An, Lan Yan, Li Juan He, Shi Qun Zhang, Si Min Chen, Wei Liu, Guo-Tong Xu, Li Ping Li, Zheng Xu, Yuan Ying Jiang, Xin Huang, Zui Zou, Hui Shen, and Jun Dong Zhang
- Subjects
0301 basic medicine ,Glycosylphosphatidylinositols ,Acylation ,Mutant ,Virulence ,GPI-Linked Proteins ,Article ,Microbiology ,Cell wall ,Fungal Proteins ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Immune system ,Cell Wall ,Candida albicans ,medicine ,Animals ,Inositol ,Multidisciplinary ,biology ,Candidiasis ,medicine.disease ,biology.organism_classification ,Corpus albicans ,Phosphoric Monoester Hydrolases ,Cell biology ,030104 developmental biology ,chemistry ,Systemic candidiasis ,Gene Deletion - Abstract
Glycosylphosphatidyl inositol anchored proteins (GPI-APs) on fungal cell wall are essential for invasive infections. While the function of inositol deacylation of GPI-APs in mammalian cells has been previously characterized the impact of inositol deacylation in fungi and implications to host infection remains largely unexplored. Herein we describe our identification of BST1, an inositol deacylase of GPI-Aps in Candida albicans, was critical for GPI-APs cell wall attachment and host infection. BST1-deficient C. albicans (bst1Δ/Δ) was associated with severely impaired cell wall anchorage of GPI-APs and subsequen unmasked β-(1,3)-glucan. Consistent with the aberrant cell wall structures, bst1Δ/Δ strain did not display an invasive ability and could be recognized more efficiently by host immune systems. Moreover, BST1 null mutants or those expressing Bst1 variants did not display inositol deacylation activity and exhibited severely attenuated virulence and reduced organic colonization in a murine systemic candidiasis model. Thus, Bst1 can facilitate cell wall anchorage of GPI-APs in C. albicans by inositol deacylation, and is critical for host invasion and immune escape.
- Published
- 2016
35. Wettability of Sn-Zn Lead-Free Solder on Aluminum Substrate
- Author
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Yao Yao, Xu Chen, Xiao Yan Xu, Guo Tong Qian, and Jian Zhou
- Subjects
Diethanolamine ,Materials science ,Metallurgy ,General Engineering ,chemistry.chemical_element ,Zinc ,Solvent ,chemistry.chemical_compound ,chemistry ,Aluminum substrate ,Chemical engineering ,Aluminium ,Soldering ,Triethanolamine ,medicine ,Wetting ,medicine.drug - Abstract
The effects of flux components and compositions of solder alloys on the wettability of the Sn-Zn alloys on aluminum surface was investigated. The results show that the wettability of the Sn-9Zn solder on aluminum substrate improved with flux of double solvents composed of diethanolamine and triethanolamine, which is better than single solvent. When flux is composed of 3% zinc fluoborate as activator and 30% triethanolamine plus 67% diethanolamine as double solvents, the spreading area of the Sn-9Zn solder reaches to 75%. Trace addition (0.002%-0.005%) of Al results in significant improvement of the wettability of the Sn-9Zn based solder. However, additions of Bi or Sb are not beneficial to the wettability of the solder on aluminum substrate.
- Published
- 2013
36. Subretinal Transplantation of Rat MSCs and Erythropoietin Gene Modified Rat MSCs for Protecting and Rescuing Degenerative Retina in Rats
- Author
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Guo-Tong Xu, Jieping Zhang, Ying Jin, Haibin Tian, Feng Wang, Yuan Guan, Furong Gao, Zepeng Qu, L. Cui, Guoxu Xu, L. Xu, Weiye Li, Lixia Lu, and Y. Wu
- Subjects
Retinal degeneration ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Iodates ,Biology ,Mesenchymal Stem Cell Transplantation ,Biochemistry ,Retina ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,hemic and lymphatic diseases ,medicine ,Animals ,Erythropoietin ,Molecular Biology ,Retinal Degeneration ,Mesenchymal stem cell ,Gene Transfer Techniques ,Cell Differentiation ,Mesenchymal Stem Cells ,Retinal ,General Medicine ,Stem-cell therapy ,medicine.disease ,eye diseases ,Rats ,Surgery ,Transplantation ,medicine.anatomical_structure ,chemistry ,Molecular Medicine ,sense organs ,Stem cell ,medicine.drug - Abstract
For degenerative retinal diseases, like the acquired form exemplified by age-related macular degeneration (AMD), there is currently no cure. This study was to explore a stem cell therapy and a stem cell based gene therapy for sodium iodate (SI)-induced retinal degeneration in rats. Three cell types, i.e., rat mesenchymal stem cells (rMSCs) alone, erythropoietin (EPO) gene modified rMSCs (EPO-rMSCs) or doxycycline (DOX) inducible EPO expression rMSCs (Tet-on EPO-rMSCs), were transplanted into the subretinal spaces of SI-treated rats. The rMSCs were prepared for transplantation after 3 to 5 passages or modified with EPO gene. During the 8 weeks after the transplantation, the rats treated with rMSCs alone or with two types of EPO-rMSCs were all monitored with fundus examination, fundus fluorescein angiography (FFA) and electroretinogram. The transplantation efficiency of donor cells was examined for their survival, integration and differentiation. Following the transplantation, labeled donor cells were observed in subretinal space and adopted RPE morphology. EPO concentration in vitreous and retina of SI-treated rats which were transplanted with EPO-rMSCs or Tet-on EPO-rMSCs was markedly increased, in parallel with the improvement of retinal morphology and function. These findings suggest that rMSCs transplantation could be a new therapy for degenerative retinal diseases since it can protect and rescue RPE and retinal neurons, while EPO gene modification to rMSCs could be an even better option.
- Published
- 2013
37. Microstructure, Thermal and Wetting Properties of Sn-Bi-Zn Lead-Free Solder
- Author
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Jian Zhou, Xu Chen, Feng Xue, Sidong Liu, and Guo-tong Qian
- Subjects
Materials science ,Scanning electron microscope ,Metallurgy ,chemistry.chemical_element ,Condensed Matter Physics ,Microstructure ,Copper ,Electronic, Optical and Magnetic Materials ,Differential scanning calorimetry ,Chemical engineering ,chemistry ,Soldering ,Phase (matter) ,Materials Chemistry ,Eutectic bonding ,Electrical and Electronic Engineering ,Eutectic system - Abstract
The microstructures, phase transformations, and wettability of Sn-Bi-Zn solder alloys were investigated by scanning electron microscopy, x-ray diffraction, and differential scanning calorimetry (DSC). The results show that the alloys are composed of primary Sn-rich phase or Zn-rich phase, (Sn + Zn) eutectic structure, and (Sn + Bi + Zn) ternary eutectic structure. The microstructural characterization of Sn-xBi-Zn alloys indicates that, with increasing Bi content, more of the eutectic (Sn-Bi-Zn) structures is formed. DSC profiles reveal that the eutectic peak of the samples did not differ very much, but the reaction temperature of the alloys decreases with increased Bi content. The spreading rates of solders increased with the addition of Zn, which affects the interfacial reactions between the solders and copper.
- Published
- 2013
38. Int6/eIF3e silenced HIF2α stabilization enhances migration and tube formation of HUVECs via IL-6 and IL-8 signaling
- Author
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Alexander Endler, Kazuyo Uchida, Lixia Lu, Futoshi Shibasaki, Guo-Tong Xu, Takuya Hashimoto, Qin Li, and Li Chen
- Subjects
Transcription, Genetic ,Angiogenesis ,Eukaryotic Initiation Factor-3 ,Molecular Sequence Data ,Immunology ,Basic fibroblast growth factor ,Neovascularization, Physiologic ,Biology ,Response Elements ,Transfection ,Biochemistry ,Angiopoietin ,chemistry.chemical_compound ,Cell Movement ,Epidermal growth factor ,Basic Helix-Loop-Helix Transcription Factors ,Human Umbilical Vein Endothelial Cells ,medicine ,Humans ,Immunology and Allergy ,Gene Silencing ,RNA, Messenger ,RNA, Small Interfering ,Molecular Biology ,Base Sequence ,Interleukin-6 ,Protein Stability ,Interleukin-8 ,DNA ,Hematology ,Molecular biology ,Oxygen ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,Gene Expression Regulation ,Vascular endothelial growth factor C ,chemistry ,Hepatocyte growth factor ,Protein Binding ,Signal Transduction ,medicine.drug - Abstract
We previously identified the tumor suppressor INT6/eIF3e as a novel down regulator of HIF2α. Small interfering RNA targeting Int6 (siRNA-Int6) in HeLa cells led to normoxic stabilization of HIF2α, with concomitant transcription of angiogenic factors, including angiopoietin, basic fibroblast growth factor, and vascular endothelial growth factor. Here we used HIF2α normoxic up-regulation via Int6 silencing to investigate the role of HIF2α in endothelial cells. As a result Int6 silencing in human umbilical vein endothelial cells (HUVECs) and in human aortic endothelial cells (HAECs) led to robust enhanced cord formation and the medium supernatant of Int6 silenced HUVECs enhanced migration of untreated HUVECs, indicating a HIF2α triggered secretory signaling. Within the responsible genes were the cytokines interleukin-6 (IL-6) and IL-8 and not unlike in HeLa cells vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and epidermal growth factor (EGF). In addition application of IL-6 and IL-8 antibodies to the medium of Int6 silenced HUVECs could reverse the enhanced migration effect and also abrogated their tube formation. Finally, a CHIP assay analysis confirmed hypoxia-responsive elements (HREs) in the IL-6 and IL-8 promoters. Our results demonstrate that expression of both IL-6 and IL-8 is regulated by HIF2α and we suggest that IL-6 and IL-8 are HIF2α controlled cytokines for angiogenesis particularly in endothelial cells.
- Published
- 2013
39. Ga-doped and P-doped ZnO Films Grown by MOCVD
- Author
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杜国同 Du Guo-tong, 赵旺 Zhao Wang, 王辉 Wang Hui, 崔夕军 Cui Xi-jun, 殷伟 Yin Wei, 张金香 Zhang Jin-xiang, 董鑫 Dong Xin, 张宝林 Zhang Bao-lin, and 史志峰 Shi Zhi-feng
- Subjects
Radiation ,Photoluminescence ,Materials science ,business.industry ,Scanning electron microscope ,Doping ,Analytical chemistry ,chemistry.chemical_element ,Chemical vapor deposition ,Zinc ,Condensed Matter Physics ,Microstructure ,Electronic, Optical and Magnetic Materials ,chemistry ,Hall effect ,Optoelectronics ,Metalorganic vapour phase epitaxy ,business - Abstract
Gallium-doped zinc oxide(ZnO∶Ga) and phosphorus-doped zinc oxide(ZnO∶P) films were separately prepared on Al2O3 substrates by metal organic chemical vapor deposition(MOCVD) method.The microstructure,electrical and optical properties were studied by X-ray diffraction(XRD),scanning electron microscopy,Hall effect measurement,the room temperature photoluminescence(PL) spectrum,respectively.The n-type ZnO films with a carrier concentration of 1×1019 cm-3 and p-type films with carrier concentration of 1.66×1016 cm-3 were obtained.SEM images showed the films had highly oriented columnar structure.PL spectrum displayed p-type ZnO films showed good optical qualities.
- Published
- 2013
40. Preparation of Calcium Silicate Board by Fly-Ash Based Calcium Silicate Powder by Press Molding
- Author
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Wei Wei, Guo Tong Qin, and Shu Li Wang
- Subjects
Cement ,Materials science ,Silica fume ,Mechanical Engineering ,Pulp (paper) ,technology, industry, and agriculture ,engineering.material ,Condensed Matter Physics ,chemistry.chemical_compound ,chemistry ,Flexural strength ,Mechanics of Materials ,Fly ash ,Calcium silicate ,engineering ,General Materials Science ,Fiber ,Composite material ,Curing (chemistry) - Abstract
Calcium silicate board has been prepared by press molding from fly-ash based calcium silicate powder with the pulp fiber as the reinforcing fibre. The micro-morphology and crystal structure of the obtained calcium silicate board were analyzed by SEM and XRD. The effects of cement,silica fume and molding pressure on the flexural strength and thermal conductivity of calcium silicate board were investigated. When the molding pressure is 10MPa, samples flexural strength, bulk density and thermal conductivity are 5MPa, 0.7g/cm3and 0.12 W/m·K respectively. It was found that this kind of calcium silicate powder was complete hydrated and could not be further hydrated even in autoclave curing.
- Published
- 2013
41. Preparation of Corrosion-Resistant Ti/RuO2 Composite Powders
- Author
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Wei Wei, Pan Qiao Duan, and Guo Tong Qin
- Subjects
inorganic chemicals ,Materials science ,Annealing (metallurgy) ,Mechanical Engineering ,Metallurgy ,Composite number ,chemistry.chemical_element ,Sulfuric acid ,Condensed Matter Physics ,Ruthenium oxide ,Corrosion ,Ruthenium ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,Mechanics of Materials ,General Materials Science ,Mass fraction ,Titanium - Abstract
Ruthenium oxide coated titanium composite powders were prepared by precipitation of ruthenium salt to improve the resistance of titanium to corrosion. The composite powders were characterized by TEM and XPS. The results show that the ruthenium oxide is evenly deposited on the Ti powders. Corrosion test for the composite powders and Ti powders was conducted in 65% sulfuric acid (mass fraction). The composite powders exhibit good corrosion resistance. The corrosion rate decreased from 98.5% to 0.48% through modification. Ru/Ti molar ratio and annealing temperature have a major impact on the corrosion resistance.
- Published
- 2013
42. Preparation of Mesoporous Carbon Membranes for Ultrafiltration with Properties of Environmental Materials
- Author
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Wei Wei, Na Li, and Guo Tong Qin
- Subjects
Materials science ,Carbonization ,Supercritical drying ,Inorganic chemistry ,General Engineering ,Ultrafiltration ,chemistry.chemical_element ,Resorcinol ,Permeance ,chemistry.chemical_compound ,Membrane ,chemistry ,Mesoporous material ,Carbon - Abstract
Ultrafiltration carbon membrane is an important kind of environmental materials for removal of particular and macromolecular pollutants. The mesoporous carbon membranes were synthesized via sol-gel synthesis followed by supercritical drying and carbonization. The formaldehyde and resorcinol were used as original precursor. The membrane was analyzed using nitrogen adsorption. It was found that the carbon membrane was mesoporous material. The pure gases of H2, N2 and CO2 were used to characterize the selective and integrity of the carbon membrane. The gas permeance through the mesoporous carbon membrane is predominantly governed by the Knudsen mechanism. The pure water is 13.4 L•m-2•h-1 and the molecular weight cut-off is about 2000.
- Published
- 2012
43. Effects of Preparation Conditions on Characters of Hydrophobic Silica Granular Aerogel and its Applications
- Author
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Li Ping Wu, Wei Wei, Guo Tong Qin, and Jing Yi Zhang
- Subjects
Materials science ,Chromatography ,Scanning electron microscope ,General Engineering ,Aerogel ,chemistry.chemical_compound ,Adsorption ,Chemical engineering ,chemistry ,Phenol ,Particle size ,Mesoporous material ,Hydrophobic silica ,Ambient pressure - Abstract
The hydrophobic silica granular aerogels were synthesized via sol-gel synthesis followed by ambient pressure drying. The tetraethyloxylane (TEOS) was used as original precursor. The aerogels were analyzed using nitrogen adsorption, scanning electron microscopy (SEM) and laser particle size analyzer. It was found that the aerogel was mesoporous material with high surface area. The aerogels were prepared in grain form by dipping into disperse solution in order to adsorption application. The average particle size of the aerogel was controlled by pH and disperse solution volume. The pH also affected gel time. The aerogels were used to absorb phenol from water. The saturated adsorption amount could reach up to 145 mg•g-1.
- Published
- 2012
44. Inhibitory Effect of Bone Morphogenetic Protein 4 in Retinal Pigment Epithelial-Mesenchymal Transition
- Author
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Hui Li, Jingfa Zhang, Chun Zhao, Guo-Tong Xu, Min Li, Haipei Yao, Shuai Yang, and Fang Wang
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Proliferative vitreoretinopathy ,Epithelial-Mesenchymal Transition ,animal structures ,Down-Regulation ,Bone Morphogenetic Protein 4 ,Retinal Pigment Epithelium ,Biology ,Article ,Smad1 Protein ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Movement ,Transforming Growth Factor beta ,medicine ,Humans ,Bone morphogenetic protein receptor ,Epithelial–mesenchymal transition ,Phosphorylation ,Receptor ,Bone Morphogenetic Protein Receptors, Type I ,Multidisciplinary ,Retinal pigment epithelium ,Vitreoretinopathy, Proliferative ,Cell migration ,Retinal ,medicine.disease ,eye diseases ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Bone morphogenetic protein 4 ,chemistry ,Gene Knockdown Techniques ,embryonic structures ,030221 ophthalmology & optometry ,Collagen ,sense organs ,Activin Receptors, Type I - Abstract
Proliferative vitreoretinopathy (PVR), a serious vision-threatening complication of retinal detachment (RD), is characterized by the formation of contractile fibrotic membranes, in which epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is a major event. Recent studies suggest an important role of bone morphogenetic protein 4 (BMP4) in the suppression of fibrosis. In this study, we aimed to investigate the role of BMP4 in the pathological process of PVR, particularly in the EMT of RPE cells. We found that BMP4 and its receptors were co-labelled with cytokeratin and α-SMA positive cells within the PVR membrane. Moreover, the mRNA and protein expression levels of BMP4 were decreased whereas BMP4 receptors ALK2, ALK3 and ALK6 were increased during TGF-β-induced EMT in primary RPE cells. Exogenous BMP4 inhibited TGF-β-induced epithelial marker down-regulation, as well as mesenchymal marker up-regulation at both the mRNA and protein levels in RPE cells. In addition, BMP4 treatment attenuated the TGF-β-induced gel contraction, cell migration and Smad2/3 phosphorylation. However, knockdown of endogenous BMP4 stimulated changes in EMT markers. Our results confirm the hypothesis that BMP4 might inhibit TGF-β-mediated EMT in RPE cells via the Smad2/3 pathway and suppress contraction. This might represent a potential treatment for PVR.
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- 2016
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45. Involvement of IL-37 in the Pathogenesis of Proliferative Diabetic Retinopathy
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Jianhua Yang, Shao Bo Su, Tianshu Yang, Ying Yu, Qing Lin, Mengmeng Zhao, Guo-Tong Xu, and Yongguang Hu
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0301 basic medicine ,Male ,Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,medicine.medical_treatment ,Enzyme-Linked Immunosorbent Assay ,Pathogenesis ,Angiopoietin-2 ,03 medical and health sciences ,Cell Movement ,Internal medicine ,medicine ,Humans ,Cells, Cultured ,Aged ,Cell Proliferation ,Tube formation ,Diabetic Retinopathy ,Chemistry ,Cell growth ,Endothelial Cells ,Diabetic retinopathy ,Middle Aged ,medicine.disease ,Molecular biology ,In vitro ,Endothelial stem cell ,Vitreous Body ,Vascular endothelial growth factor A ,030104 developmental biology ,Cytokine ,Endocrinology ,Case-Control Studies ,Female ,Interleukin-1 - Abstract
Purpose Interleukin-37 is suggested as a novel proangiogenic factor in our previous study. In this study, the role of IL-37 was investigated in proliferative diabetic retinopathy (PDR). Methods Vitreous fluids from 10 patients with PDR and 8 controls were collected. The levels of IL-37 were determined by ELISA and the relationship between IL-37 and VEGF-A/Ang-2 was analyzed. The effects of IL-37 on chorioretinal endothelial cell (RF/6A) proliferation, migration, and tube formation were determined by BrdU incorporation assay, Boyden chamber assay, scratch-wound assay and tube formation assay. Results The concentration of IL-37 in the PDR group was 95.09 ± 5.22 pg/mL and 34.91 ± 5.61 pg/mL in control group (P = 0.001). The level of IL-37 was highly related to the level of Ang-2 (P = 0.009, r = 0.772) and VEGF-A (P = 0.003, r = 0.827) in the PDR group, and VEGF expression in RF/6A cell was upregulated by IL-37 at low concentration. Interleukin-37 remarkably promoted RF/6A cell proliferation and migration. Interleukin-37 (1 ng/mL) remarkably stimulated tube formation with an increase of 85.3% for total tubule length and 74.1% for branching points compared with PBS control. Conclusions The level of IL-37 is elevated in vitreous fluids of patients with PDR and correlates with the level of VEGF-A and Ang-2. Interleukin-37 stimulates proangiogenic response of retinal endothelial cells in vitro, suggesting the involvement of IL-37 in the pathogenesis of PDR.
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- 2016
46. Effects of Pyrolysis Conditions on the Permeance of Phenol-Formaldehyde Resin Based Carbon Membrane for CO2 Separation
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Pei Jing Tang, Li Ping Wu, Guo Tong Qin, and Wei Wei
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chemistry.chemical_classification ,Materials science ,Carbonization ,General Engineering ,chemistry.chemical_element ,Permeance ,engineering.material ,Membrane ,chemistry ,Chemical engineering ,Coating ,Phenol formaldehyde resin ,engineering ,Composite material ,Porosity ,Carbon ,Pyrolysis - Abstract
Carbon membranes were prepared by coating an ethanol solution of phenol-formaldehyde novolac resin with additive on the porous green support from the same material and further heat treatment. The heating process was divided into two steps, stabilization and carbonization. The influences of heat variables including heating rate, stabilization and carbonization temperature on membrane properties were investigated. Pure gas of N2, CH4, and CO2was used to test membrane permeance. These carbon membranes have good capabilities towards separation of CO2/N2and CO2/CH4.
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- 2011
47. EPO reduces reactive gliosis and stimulates neurotrophin expression in Muller cells
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Yaprak Banu Unver, Yalan Wu, Y. Luo, Jingfa Zhang, Jianfeng Shen, Liu Mei Hu, Weiye Li, Xia Lei, Guo-Tong Xu, Yong Zhong, and Mei Qin
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medicine.medical_specialty ,Neurite ,Blotting, Western ,Down-Regulation ,Enzyme-Linked Immunosorbent Assay ,Ciliary neurotrophic factor ,Polymerase Chain Reaction ,Retina ,General Biochemistry, Genetics and Molecular Biology ,Diabetes Mellitus, Experimental ,Rats, Sprague-Dawley ,Neurotrophic factors ,hemic and lymphatic diseases ,Internal medicine ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,Vimentin ,Gliosis ,Nerve Growth Factors ,Erythropoietin ,Cells, Cultured ,DNA Primers ,Base Sequence ,General Immunology and Microbiology ,biology ,Chemistry ,Rats ,Erythropoietin receptor ,medicine.anatomical_structure ,Endocrinology ,biology.protein ,sense organs ,medicine.symptom ,Neurotrophin ,medicine.drug - Abstract
To characterize Müller cell-mediated neuroprotective and neurotrophic functions of the erythropoietin (EPO)/EPO receptor (EpoR) system in diabetic rat retina. A single intravitreal injection of EPO (8 mU/eye) was administered in rats 4 or 24 weeks after diabetes onset. The results showed that intravitreal EPO ameliorated the up-regulation of GFAP and vimentin in the diabetic retina evaluated by immunofluorescence and Western blotting; but up-regulated BDNF and CNTF expressions, quantified by real-time PCR and ELISA, in the 24-week diabetic rat retinas. In vitro, BDNF and CNTF expressions were stimulated by EPO through both extracellular signal-regulated kinase1/2 (ERK1/2) and Akt pathways. The neuro-regenerative function of EPO, as indicated by promotion of neurite outgrowth, was corroborated in vitro. BDNF was involved in EPO-induced neurite outgrowth of primary rat retinal neurons. Exogenous EPO exerts neuroprotective and neurotrophic functions by attenuating reactive gliosis and promoting neurotrophic factors in Muller cells in diabetic retina. Signaling pathways that are responsible for these Muller cell-mediated EPO/EpoR functions may be therapeutic targets for diabetic retinopathy.
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- 2011
48. Photoluminescence and Electroluminescence of the Novel Soluble Zinc Phthalocyanine
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Zhang Chunhua, Bai Qinglong, LI Wan-Cheng, DU Guo-Tong, Shen Ren-Sheng, and Cheng Chuan-Hui
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Zinc phthalocyanine ,Spin coating ,Photoluminescence ,Materials science ,Analytical chemistry ,Electroluminescence ,Photochemistry ,Fluorescence ,Spectral line ,chemistry.chemical_compound ,chemistry ,Elemental analysis ,Phthalocyanine ,Physical and Theoretical Chemistry - Abstract
α(β)-tetra-(methoxy-phenoxy)-zinc phthalocyanine are synthesized by employing 3(4)- nitrobenzene-1,2-dicarbonitrile as precursors. They are characterized by spectrum methods and elemental analysis. The UV-Vis spectrum, photoluminescence spectra of spin-coated film and solid pellet are compared. The electroluminescent devices are fabricated by using spin coating. The results indicate that the fluorescence of solid phthalocyanine has a red-shift of more than 145 nm compared to that in solution. The fluorescences are broader in solid state than that in solution. The fluorescence of β-substituted phthalcyanines has a more red-shift than α-substituted phthalcyanines. The electroluminescent spectra around 856 and 862 nm are consisted with the photoluminescence spectra of spin-coated film. The shorter inter-molecule space leads to the large red-shift of the fluorescence.
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- 2011
49. 1.53μm electroluminescence from ErF3-doped organic light-emitting diodes
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Shao Hua Shi, Chuanhui Cheng, Jin Wang, Yingmin Luo, Zhao Qi Fan, Zhi Jie Du, Ren Sheng Shen, Guo Tong Du, and Dong Feng Geng
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Photoluminescence ,business.industry ,Doping ,Biophysics ,Analytical chemistry ,chemistry.chemical_element ,General Chemistry ,Electroluminescence ,Condensed Matter Physics ,Biochemistry ,Atomic and Molecular Physics, and Optics ,law.invention ,Erbium ,Full width at half maximum ,chemistry ,law ,OLED ,Optoelectronics ,business ,Luminescence ,Light-emitting diode - Abstract
Near-infrared (NIR) organic light-emitting devices (OLEDs) are demonstrated by employing erbium fluoride (ErF 3 )-doped tris-(8-hydroxyquinoline) aluminum (Alq 3 ) as the emitting layer. The device structure is ITO/N,N′-di-1-naphthyl-N,N′-diphenylbenzidine (NPB)/Alq 3 : ErF 3 /2,2′,2″-(1,3,5-phenylene)tris(1-phenyl-1H-benzimidazole) (TPBI)/Alq 3 /Al. Room-temperature electroluminescence around 1530 nm is observed due to the 4 I 13/2 – 4 I 15/2 transition of Er 3+ . Full width at half maximum (FWHM) of the electroluminescent (EL) spectrum is ∼50 nm. NIR EL intensity from the ErF 3 -based device is ∼4 times higher than that of Er(DBM) 3 Phen-based device at the same current. Alq 3 –ErF 3 composite films are investigated by the measurements of X-ray diffraction (XRD), absorption, photoluminescence (PL) and PL decay time. Electron-only devices are also fabricated. The results indicate that energy transfer mechanism and charge trapping mechanism coexist in the NIR EL process.
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- 2010
50. Influence of high-pressure hydrogen treatment on structural and electrical properties of ZnO thin films
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Yang Liu, Hongwei Liang, Guo Tong Du, Wangcheng Li, Guoguang Wu, Jianze Zhao, Chunye Li, Qiuju Feng, Jiming Bian, and Rensheng Shen
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Hydrogen ,Chemistry ,Scanning electron microscope ,General Physics and Astronomy ,chemistry.chemical_element ,Surfaces and Interfaces ,General Chemistry ,Chemical vapor deposition ,Condensed Matter Physics ,Electron spectroscopy ,Surfaces, Coatings and Films ,Surface coating ,Crystallography ,X-ray photoelectron spectroscopy ,X-ray crystallography ,Thin film - Abstract
ZnO thin films were treated by high-pressure hydrogen (H 2 ). Scanning electron microscope (SEM) images show that the surface morphology of ZnO films has been changed significantly by H 2 treatment. X-ray diffraction patterns show that the Zn(OH) 2 phases formed after H 2 treatment. The X-ray photoelectron spectroscopy results indicate that H atoms were doped into the surface of ZnO by forming H–O–Zn bond. The phenomenon shows that it is easy to form O–H bond in ZnO rather than H interstitial atom under high-pressure hydrogen circumstance.
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- 2010
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