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Constructing redox semiconductor heterojunction photocatalysts is the most effective and important means to complete the artificial photosynthetic overall reaction (i.e., coupling CO2 photoreduction and water photo-oxidation reactions). However, multiphase hybridization essence and inhomogeneous junction distribution in these catalysts extremely limit the diverse design and regulation of the modes of photogenerated charge separation and transfer pathways, which are crucial factors to improve photocatalytic performance. Here, we develop molecular oxidation-reduction (OR) junctions assembled with oxidative cluster (PMo12, for water oxidation) and reductive cluster (Ni5, for CO2 reduction) in a direct (d-OR), alternant (a-OR), or symmetric (s-OR) manner, respectively, for artificial photosynthesis. Significantly, the transfer direction and path of photogenerated charges between traditional junctions are obviously reformed and enriched in these well-defined crystalline catalysts with monophase periodic distribution and thus improve the separation efficiency of the electrons and holes. In particular, the charge migration in s-OR shows a periodically and continuously opposite mode. It can inhibit the photogenerated charge recombination more effectively and enhance the photocatalytic performance largely when compared with the traditional heterojunction models. Structural analysis and density functional theory calculations disclose that, through adjusting the spatial arrangement of oxidation and reduction clusters, the energy level and population of the orbitals of these OR junctions can be regulated synchronously to further optimize photocatalytic performance. The establishment of molecular OR junctions is a pioneering important discovery for extremely improving the utilization efficiency of photogenerated charges in the artificial photosynthesis overall reaction.
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Dióxido de Carbono , Luz , Fotossíntese , Oxirredução , Água/químicaRESUMO
The multiple mortise-and-tenon joint parts are the core factors to provide the structural stability and diversity of Chinese Luban locks; however, constructing such structures is very challenging. Herein, single crystals of a covalent organic nanoribbon (named CityU-27) are prepared through the assembly of hexahydroxytriphenylene (HHTP), 4,4'-vinylenedipyridine (BYE), and phenylboronic acid (BA) together through dative boronânitrogen (BâN) bonds. The single-crystal X-ray diffraction analysis indicates that CityU-27 has a covalent organic nanoribbon structure, where each nanoribbon forms multiple and tight π-π interactions with four neighboring others to generate a Luban lock-like configuration. CityU-27 has been demonstrated to be an efficient photocatalyst in a one-pot tandem reaction of hydrogen evolution reaction (HER) and semi-hydrogenation reaction of alkynes in series to produce olefins without any additional photosensitizers and co-catalysts (metal-free).
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Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.
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Inibidores da Angiogênese , Vasculopatia Polipoidal da Coroide , Humanos , Inibidores da Angiogênese/uso terapêutico , Terapia Combinada , Fator A de Crescimento do Endotélio Vascular , Hemorragia Retiniana/tratamento farmacológico , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , Estudos RetrospectivosRESUMO
Cu(I)-based catalysts have proven to play an important role in the formation of specific hydrocarbon products from electrochemical carbon dioxide reduction reaction (CO2RR). However, it is difficult to understand the effect of intrinsic cuprophilic interactions inside the Cu(I) catalysts on the electrocatalytic mechanism and performance. Herein, two stable copper(I)-based coordination polymer (NNU-32 and NNU-33(S)) catalysts are synthesized and integrated into a CO2 flow cell electrolyzer, which exhibited very high selectivity for electrocatalytic CO2-to-CH4 conversion due to clearly inherent intramolecular cuprophilic interactions. Substitution of hydroxyl radicals for sulfate radicals during the electrocatalytic process results in an in situ dynamic crystal structure transition from NNU-33(S) to NNU-33(H), which further strengthens the cuprophilic interactions inside the catalyst structure. Consequently, NNU-33(H) with enhanced cuprophilic interactions shows an outstanding product (CH4) selectivity of 82% at -0.9 V (vs reversible hydrogen electrode, j = 391 mA cm-2), which represents the best crystalline catalyst for electrocatalytic CO2-to-CH4 conversion to date. Moreover, the detailed DFT calculations also prove that the cuprophilic interactions can effectively facilitate the electroreduction of CO2 to CH4 by decreasing the Gibbs free energy change of potential determining step (*H2COOH â *OCH2). Significantly, this work first explored the effect of intrinsic cuprophilic interactions of Cu(I)-based catalysts on the electrocatalytic performance of CO2RR and provides an important case study for designing more stable and efficient crystalline catalysts to reduce CO2 to high-value carbon products.
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PURPOSE: To evaluate the functional and structural outcomes of intravitreal conbercept monotherapy using a "3 + pro re nata (PRN)" regimen in treatment-naïve subjects with polypoidal choroidal vasculopathy (PCV) up to 12 months. METHODS: Thirty subjects (30 eyes) with PCV participated in this interventional, retrospective study. All subjects received intravitreal injections of 0.5 mg (0.05 ml) conbercept using a "3 + PRN" regimen for 12 months. The changes in best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, polyp lesion area, and regression rate were evaluated at baseline, month 3, and month 12. RESULTS: At the study end-point, BCVA improved significantly from 52.80 ± 17.17 ETDRS letters at baseline to 62.20 ± 18.96 letters (P < 0.001), with a mean gain of 9.40 ± 14.97 letters. The central retinal thickness (CRT) significantly reduced from 454.93 ± 147.31 µm at baseline to 308.73 ± 106.80 µm (P < 0.001) at end-point, and the total macular volume (TMV) decreased from 9.51 ± 1.04 mm3 at baseline to 8.32 ± 0.84 mm3 at end-point (P < 0.001). The mean volume of pigment epithelial detachment (PED) decreased from 0.73 ± 0.97 mm3 at baseline to 0.48 ± 0.71 mm3 (P < 0.05) at month 3. At month 12, the mean volume of PED was 0.57 ± 0.80 mm3 (P > 0.05 compared to baseline). After the 3-monthly loading injections, 6 eyes (20.0%) showed complete polyp regression, whereas a total of 19 eyes (63.5%) showed complete regression at month 12. The average injections given per subject were 7.70 ± 1.81. CONCLUSION: Intravitreal conbercept using the "3 + PRN" regimen was effective in the treatment of PCV.
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Inibidores da Angiogênese , Neovascularização de Coroide , Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade VisualRESUMO
Reticular chemistry has been an important guiding principle for the design of metal-organic frameworks (MOFs). This approach utilizes discrete building units (molecules and clusters) that are connected through strong bonds into extended networks assisted by topological considerations. Although the simple design principle of connecting points and lines has proved successful, new design strategies are still needed to further explore the structures and functions of MOFs. Herein, we report the design and synthesis of two mixed-ligand MOFs, [(CH3)2NH2]4[Zn4O]4[Zn(TCPP)]5[BTB]8/3 (PCN-137) and [Zr6(µ3-O)4(µ3-OH)4][TCPP][TBTB]8/3 (PCN-138) (BTB = 1,3,5-benzene(tris)benzoate, TBTB = 4,4',4â³-(2,4,6-trimethylbenzene-1,3,5-triyl)tribenzoate, and TCPP = tetrakis(4-carboxyphenyl)porphyrin) by the stacking of face-sharing Archimedean solids. In these two MOFs, high-symmetrical metal clusters serve as vertices, and tritopic or tetratopic carboxylate ligands function as triangular and square faces, leading to the formation of two kinds of Archimedean solids (rhombicuboctahedron and cuboctahedron). Furthermore, the ordered accumulation of Archimedean solids successfully gives rise to 3D structures through face-sharing, highlighting the polyhedron-based approach for the design and preparation of MOFs. In addition, PCN-138 was utilized as a heterogeneous catalyst toward CO2 photoreduction under visible-light irradiation. This structure shows high photocatalytic activity, which can be attributed to the coexistence of photosensitizing porphyrin fragments and Zr-oxo centers within the PCN-138 scaffold.
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Prostate cancer is one of the most frequent malignancies affecting men. Long non-coding RNAs (lncRNAs) are involved in the pathogenesis of prostate cancer. LncRNA LOXL1-AS1 participates in the pathogenesis of the exfoliation syndrome. However, the role of LOXL1-AS1 in cancer remains largely unknown. Here, we found that LOXL1-AS1 down-regulation inhibited prostate cancer cell proliferation and cell cycle progression. RNA sequencing analysis revealed that it regulates the expression of cell cycle-related genes. LOXL1-AS1 is predominantly distributed in the cytoplasm, where it interacts with miR-541-3p. In addition, miR-541-3p targets the cell cycle regulator CCND1 in prostate cancer cells. LOXL1-AS1 down-regulation inhibits the expression of CCND1 and cell cycle progression, whereas these effects are abolished upon miR-541-3p suppression. In summary, our study revealed that LOXL1-AS1 regulates prostate cancer cell proliferation and cell cycle progression through miR-541-3p and CCND1. Modulation of their levels may be used to treat prostate cancer.
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Ciclina D1/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , RNA Longo não Codificante/fisiologia , Regiões 3' não Traduzidas , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/metabolismo , Humanos , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , RNA Longo não Codificante/metabolismoRESUMO
Cardiomyocyte apoptosis correlates with the pathogenesis of heart disease. Long noncoding RNA (LncRNA) emerges as a class of noncoding RNAs that regulate gene expression and participate in various cellular processes. However, the role of lncRNAs in cardiomyocyte apoptosis remains to be elucidated. In our study, we found that lncRNA FTX is significantly down-regulated upon ischemia/reperfusion injury and hydrogen peroxide treatment. Enhanced expression of FTX inhibits cardiomyocyte apoptosis induced by hydrogen peroxide. miR-29b-1-5p was found to interact with FTX and regulate the expression of Bcl2l2. Inhibition of miR-29b-1-5p attenuated cardiomyocyte apoptosis upon hydrogen peroxide treatment. We then found that FTX functions as endogenous sponge for miR-29b-1-5p and regulates the activity of miR-29b-1-5p. The results demonstrate that FTX regulates cardiomyocyte apoptosis through modulating the expression of Bcl2l2 which is mediated by miR-29b-1-5p. Our findings reveal a novel regulatory model which is composed of FTX, miR-29b-1-5p and Bcl2l2. Manipulating of their levels may become a new approach to tackling cardiomyocyte apoptosis related heart diseases.
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Proteínas Reguladoras de Apoptose/genética , Apoptose/genética , Apoptose/fisiologia , MicroRNAs/genética , Miócitos Cardíacos/fisiologia , RNA Longo não Codificante/genética , Animais , Células Cultivadas , Regulação da Expressão Gênica/genética , Masculino , Camundongos , Miócitos Cardíacos/citologiaRESUMO
In this study, the baseline separations of xylene isomers and phthalate acid esters on a homemade DUT-67(Zr) packed column were achieved, respectively. The high selectivity for xylene isomers and phthalate acid esters was obtained with the increase in temperature and decrease in the retention time. The hydrophobicity of xylene isomers and phthalate acid esters resulted in the different separation time on the DUT-67(Zr) packed column. The relative standard deviation values of retention time, peak area, peak height, and half peak width for five repeat separation of the xylene isomers were 0.26-0.35, 2.11-2.26, 1.51-2.03, and 0.29-0.77%, and the values of the phthalate acid esters on DUT-67(Zr) column were 0.1-0.4, 4.4-5.2, 3.9-6.3, and 0.6-2.1%, respectively. The thermodynamic properties indicated that the separation of xylene isomers was controlled by ΔH and ΔS, but the separation of phthalate acid esters was mainly controlled by ΔS.
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In this study, a MIL-53(Al)-packed column was successfully prepared and firstly applied to separate phthalate acid esters (butyl benzyl phthalate, di-n-butyl phthalate, diethyl phthalate, bis(2-ethylhexyl) phthalate, and dimethyl phthalate). Their baseline separation could be achieved within 12 min with a mobile phase of methanol/H2 O ratio at 92:8, and the temperature and flow rate was 40°C and 0.6 mL/min, respectively. The stacking effect and electrostatic force were the key factors in the separation. Moreover, there was a substantial linear relation between the peak height, peak area, and the analyte mass, and the relative standard deviations of retention time, peak height, peak area, and half peak width for five replicate separations of the analytes were within the ranges 0.31-0.88%, 0.72-1.52%, 1.33-1.53%, and 0.46-0.95%, respectively. The results of the calculation of the thermodynamics parameters showed that the separation of phthalate acid esters was controlled by both enthalpy change (ΔH) and entropy change (ΔS).
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Background. Epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) is vital in proliferative vitreoretinopathy (PVR) development. Apoptosis-stimulating proteins of p53 (ASPP2) have recently been reported to participate in EMT. However, the role of ASPP2 in PVR pathogenesis has not been identified. Methods. Immunohistochemistry was used to investigate the expression of ASPP2 in epiretinal membranes of PVR patients. ARPE-19 cells were transfected with ASPP2-siRNA, followed with measurement of cell cytotoxicity, proliferation, and migration ability. EMT markers and related inflammatory and fibrosis cytokines were measured by western blot or flow cytometry. Additionally, PVR rat models were induced by intravitreal injection of ARPE-19 cells transfected with ASPP2-siRNA and evaluated accordingly. Results. Immunofluorescence analysis revealed less intense expression of ASPP2 in PVR membranes. ASPP2 knockdown facilitated the proliferation and migration of RPE cells and enhanced the expression of mesenchymal markers such as alpha smooth muscle actin, fibronectin, and ZEB1. Meanwhile, ASPP2-siRNA increased EMT-related and inflammatory cytokines, including TGF-ß, CTGF, VEGF, TNF-α, and interleukins. PVR severities were more pronounced in the rat models with ASPP2-siRNA treatment. Conclusions. ASPP2 knockdown promoted EMT of ARPE-19 cells in vitro and exacerbated the progression of experimental PVR in vivo, possibly via inflammatory and fibrosis cytokines.
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Proteínas Reguladoras de Apoptose/genética , RNA Interferente Pequeno/metabolismo , Vitreorretinopatia Proliferativa/genética , Vitreorretinopatia Proliferativa/metabolismo , Adulto , Idoso , Apoptose/genética , Apoptose/fisiologia , Western Blotting , Linhagem Celular , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Feminino , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno/genética , Retina/metabolismo , Retina/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Vitreorretinopatia Proliferativa/patologia , Adulto JovemRESUMO
Objective To evaluate the application of a mobile platform-based system in the management of fundus disease in outpatient settings. Methods In the outpatient departments of fundus disease,premature babies requiring eye examination under general anesthesia and adults requiring intraocular surgery were enrolled as the subjects. According to the existing clinical practices,we developed a system that met the requirements of clinical practices and optimized the clinical management. Based on the FileMaker database,the tablet computers were used as the mobile platform and the system could also be run in iPad and PC terminals.Results Since 2013,the system recorded 7500 cases of special examinations. Since July 2015,4100 cases of intravitreal drug injection were also recored in the system. Multiple-point and real-time reservation pattern increased the efficiency and opimize the clinical management. All the clinical data were digitalized. Conclusion The mobile platform-based system can increase the efficacy of examination and other clinical processes and standardize data collection;thus,it is feasible for the clinical practices in outpatient departments of ophthalmology.
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Computadores de Mão/estatística & dados numéricos , Doenças Retinianas/terapia , Adulto , Gerenciamento Clínico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Pacientes AmbulatoriaisRESUMO
C-reactive protein (CRP) is an established marker of inflammation and has been proposed to play a proinflammatory role in pathologies of several diseases. CRP is primarily produced by the liver and released into circulation as a pentameric molecule composed of five identical subunits. It has been suggested that the activation of the proinflammatory actions of CRP requires sequential conformational changes triggered by local inflammatory conditions. These include the dissociation into the subunit form (monomeric CRP, mCRP) and further reduction of the intra-subunit disulfide bond of mCRP. This model predicts that mCRP is the primary isoform present in inflamed but not healthy tissues, however the supporting evidence is lacking. Herein, we stained tissue samples across multiple anatomical locations from several types of human diseases with highly selective monoclonal antibodies that can differentiate CRP and mCRP. The results indicated that mCRP is the predominant form existing in the lesions. Further immunoblotting of the patient tissue samples revealed the potential presence of reduced mCRP. Together, we conclude that mCRP but not CRP is the major isoform present in local inflammatory lesions, supporting the so-called cascading model of CRP function and regulation.
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Proteína C-Reativa/análise , Imuno-Histoquímica , Mediadores da Inflamação/análise , Inflamação/imunologia , Anticorpos Monoclonais , Biomarcadores/análise , Western Blotting , Proteína C-Reativa/química , Estudos de Casos e Controles , Humanos , Mediadores da Inflamação/química , Valor Preditivo dos Testes , Conformação ProteicaRESUMO
In modern industries, the aerobic oxidation of C(sp3)-H bonds to achieve the value-added conversion of hydrocarbons requires high temperatures and pressures, which significantly increases energy consumption and capital investment. The development of a light-driven strategy, even under natural sunlight and ambient air, is therefore of great significance. Here we develop a series of hetero-motif molecular junction photocatalysts containing two bifunctional motifs. With these materials, the reduction of O2 and oxidation of C(sp3)-H bonds can be effectively accomplished, thus realizing efficient aerobic oxidation of C(sp3)-H bonds in e.g., toluene and ethylbenzene. Especially for ethylbenzene oxidation reactions, excellent catalytic capacity (861 mmol g cat-1) is observed. In addition to the direct oxidation of C(sp3)-H bonds, CeBTTD-A can also be applied to other types of aerobic oxidation reactions highlighting their potential for industrial applications.
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AIM: To introduce the macular hole (MH) hydromassage technique as a potentially beneficial approach for the treatment of large or persistent MH. METHODS: This retrospective observational case series comprised 16 consecutive patients (17 eyes) diagnosed with MH. Inclusion criteria involved a hole aperture diameter larger than 600 µm or the presence of an unclosed MH larger than 600 µm following the previous vitrectomy. Standard MH repair procedures were administered in all cases, involving the manipulation and aspiration of the hole margin through the application of water flow with a soft-tip flute needle. A comprehensive assessment was conducted for each case before and after surgery, and optical coherence tomography (OCT) images were captured at every follow-up point. RESULTS: The mean preoperative aperture diameter was 747±156 µm (range 611-1180 µm), with a mean base diameter of 1390±435 µm (range 578-2220 µm). Following surgery, all cases achieved complete anatomical closure of MH, with 13 cases (76.5%) exhibiting type 1 closure and 4 cases (23.5%) demonstrating type 2 closure. No significant differences were observed in the preoperative OCT variables between the two closure types. Eyes with type 1 closure showed a significantly improved visual acuity (0.70±0.10, range 0.50-0.80) compared to those with type 2 closure (0.90±0.12, range 0.80-1.00, P=0.014). CONCLUSION: The MH hydromassage technique demonstrates promising results, achieving acceptable closure rates in cases of large or persistent MH. This technique may serve as an effective adjunctive maneuver during challenging MH surgery.
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Branch retinal vein occlusion (BRVO) is the second most frequent retinal vascular disorder. Currently the first-line therapies for BRVO include anti-VEGF and dexamethasone implant treatment, however, with direct or indirect damage on retinal neurons, it has limited effect in improving patients visual acuity. Therefore, novel treatments with neuroprotective effect for BRVO retina were expected. Minocycline is a semisynthetic, broad spectrum tetracycline antibiotic with high penetration through the blood brain barrier. The neuroprotective effects of minocycline have been shown in various central nervous system (CNS) disease. Since both CNS and retina were composed of neurons and glials, it is reasonable to expect a neuroprotective effect by minocycline for BRVO retina. Therefore, the aim of the present study was to study whether minocycline has neuroprotective effect in branch retinal vein occlusion (BRVO) and the possible underlying molecular basis. We created BRVO in rats using laser photocoagulation. The animals were then randomly divided into 4 groups to evaluate the effect of minocycline: group A: minocycline 45 mg/kg intraperitoneal injection (i.p.), group B: minocycline 90 mg/kg i.p., group C: normal saline i.p., group D: sham injection. Fundus photography and fluorescein angiography (FA) were conducted. The changes in thickness of retinal layers were measured with optical coherence tomography (OCT) in vivo. We found that retinal edema occurred predominantly in the inner retinal layers. Intraperitoneal administration of minocycline significantly ameliorated retinal edema in the early stage of BRVO. We performed Full field Electroretinography (ffERG) to evaluate retinal function and found that the reduction of b wave amplitude decreased in the combined maximal response. The expressional levels of apoptosis related genes (Bax, Bcl-2) and inflammation related genes (IL-1 ß, TNF α, MCP-1 and CCR2) were measured by real-time PCR, the results showed that minocycline treatment upregulated Bcl-2 expression and inhibits TNF α expression since early stage of BRVO. We also performed Hematoxylin-Eosin (HE) and immunostaining for Iba 1 (a microgilal marker), active caspase-3, Bax, Bcl-2, IL-1 ß, TNF α and found that minocycline inhibits retinal microglial activation, prevents retinal ganglion cell loss, and inhibits retinal caspase-3 activation. Thus, our study indicates that systemic administration of minocycline ameliorates retinal edema and preserves retinal function in the early stage of BRVO possibly via inhibiting microglia activation and protecting RGC from apoptosis.
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Antibacterianos/uso terapêutico , Modelos Animais de Doenças , Microglia/efeitos dos fármacos , Minociclina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Papiledema/prevenção & controle , Oclusão da Veia Retiniana/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Citocinas/genética , Eletrorretinografia/efeitos dos fármacos , Feminino , Angiofluoresceinografia , Humanos , Injeções Intraperitoneais , Papiledema/fisiopatologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos , Ratos Endogâmicos BN , Reação em Cadeia da Polimerase em Tempo Real , Retina/fisiopatologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Oclusão da Veia Retiniana/genética , Oclusão da Veia Retiniana/fisiopatologia , Tomografia de Coerência Óptica , Acuidade Visual , Proteína X Associada a bcl-2/genéticaRESUMO
BACKGROUND: Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). Although much effort has been put into dealing with CMV retinitis secondary to acquired immunodeficiency syndrome (AIDS), the few reports which have been published have mainly focused on treatment of CMVR after HSCT. METHODS: This clinical interventional retrospective study included 14 patients (eight men; mean age 23.89 ± 12.09; 23 eyes) who suffered from CMV retinitis after stem-cell transplantation, in order to evaluate the efficacy and safety of multiple intravitreal injections of ganciclovir (IVG) for patients with CMV retinitis. All patients received 4 injections of IVG of 1 mg at 1 week intervals, and were followed up weekly for at least 2 months with measurement of best-corrected visual acuity (BCVA) and CMV levels in anterior aqueous humor with real-time polymerase chain reaction. Anterior aqueous humor was obtained before each injection. RESULTS: The levels of CMV in anterior aqueous humor showed significant decrease from (6.34 ± 15.78) × 10(5) copies/ml at baseline to (5.22 ± 12.15) × 10(3) copies/ml at 1 month (P < 0.001, Mann-Whitney U test). CMV couldn't be detected in 11 eyes (47.8 %) after two injections, and this rose to 18 eyes (78.3 %) at 1 month. The mean logMAR BCVA was 0.659 ± 0.572 at baseline and 0.680 ± 0.527 at 2 months, which suggested no significant improvement (P = 0.736, Mann-Whitney U test) during the procedure. All patients experienced improved vitreous opacity and diminished area of the lesion under funduscopy after 4 injections of IVG. No severe complications developed. CONCLUSIONS: Multiple IVG seemed to be beneficial for patients with CMV retinitis after stem-cell transplantation, in reducing CMV levels in aqueous humor. Further study to optimize the dose of ganciclovir is needed in order to achieve better treatment outcomes.
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Antivirais/uso terapêutico , Retinite por Citomegalovirus/tratamento farmacológico , Ganciclovir/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Humor Aquoso/virologia , Criança , Pré-Escolar , Citomegalovirus/isolamento & purificação , Retinite por Citomegalovirus/etiologia , Retinite por Citomegalovirus/fisiopatologia , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/genética , RNA Mensageiro/análise , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Retratamento , Estudos Retrospectivos , Proteínas da Matriz Viral/genética , Acuidade Visual/fisiologia , Adulto JovemRESUMO
AIMS: To investigate the expression of placental growth factor (PIGF) in alkali burn-induced murine corneal neovascularization (NV); to evaluate the effects of KH902, a vascular endothelial growth factor receptor decoy, on prevention and regression of new vessels growths in the cornea; and to determine the influence of KH902 on the levels of vascular endothelial growth factor (VEGF) and PIGF in alkali burn-induced corneal NV. METHODS: Mouse corneal NV was induced by alkali burn. The expression of PIGF was detected by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR). To evaluate the effects of KH902, corneal NV was observed and photographed every 3 days for a total of 28 days after the alkali burn. The percentage of NV area was measured and compared with that of the control group. The VEGF and PIGF levels in the cornea were evaluated by enzyme linked immunosorbent assay (ELISA). RESULTS: PIGF was expressed during the alkali burn-induced corneal neovascularization. On day 3 (D3), day 6 (D6) and day 9 (D9) after chemical cauterization, the length of the longest new vessel and the neovascularization areas in the KH902-treated groups were significantly smaller than those of the PBS-treated group (p < 0.05). The areas of established corneal NV of the KH902-treated groups regressed with time, but the control groups showed no natural regression. The VEGF and PIGF levels of the cornea in the treated groups were significantly decreased compared to those of the control group (p < 0.05). CONCLUSIONS: PIGF may be involved in alkali burn-induced corneal NV. KH902 significantly inhibited new vessel growth and promoted the regression of established vessels in a mouse model of corneal NV, and it also reduced the levels of VEGF and PIGF in the cornea.
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Queimaduras Químicas/complicações , Neovascularização da Córnea/tratamento farmacológico , Queimaduras Oculares/induzido quimicamente , Proteínas da Gravidez/metabolismo , Proteínas Recombinantes de Fusão/uso terapêutico , Animais , Queimaduras Químicas/metabolismo , Córnea/efeitos dos fármacos , Neovascularização da Córnea/induzido quimicamente , Neovascularização da Córnea/metabolismo , Modelos Animais de Doenças , Queimaduras Oculares/complicações , Queimaduras Oculares/metabolismo , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Crescimento Placentário , Proteínas Recombinantes de Fusão/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Recent studies on multi-contrast MRI reconstruction have demonstrated the potential of further accelerating MRI acquisition by exploiting correlation between contrasts. Most of the state-of-the-art approaches have achieved improvement through the development of network architectures for fixed under-sampling patterns, without considering inter-contrast correlation in the under-sampling pattern design. On the other hand, sampling pattern learning methods have shown better reconstruction performance than those with fixed under-sampling patterns. However, most under-sampling pattern learning algorithms are designed for single contrast MRI without exploiting complementary information between contrasts. To this end, we propose a framework to optimize the under-sampling pattern of a target MRI contrast which complements the acquired fully-sampled reference contrast. Specifically, a novel image synthesis network is introduced to extract the redundant information contained in the reference contrast, which is exploited in the subsequent joint pattern optimization and reconstruction network. We have demonstrated superior performance of our learned under-sampling patterns on both public and in-house datasets, compared to the commonly used under-sampling patterns and state-of-the-art methods that jointly optimize the reconstruction network and the under-sampling patterns, up to 8-fold under-sampling factor.
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Algoritmos , Processamento de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Extremidade SuperiorRESUMO
Pathological retinal neovascularization and choroidal neovascularization are major causes of vision loss in a variety of clinical conditions, such as retinopathy of prematurity, age-related macular degeneration, and diabetic retinopathy. Pigment epithelial-derived factor (PEDF) has been found to be the most potent natural, endogenous inhibitor of neovascularization, but its application is restricted because of its instability and short half-life. Polyethylene glycol (PEG) has been used as a drug carrier to slow clearance rate for decades. The present study investigated PEGylated-PEDF for the first time and evaluated its long-term effects on preventing angiogenesis in vitro and in vivo. PEG showed lower cytotoxicity to human umbilical vein endothelial cells (HUVECs). In vitro, PEGylated-PEDF inhibited HUVEC proliferation, migration, tube formation, and vascular endothelium growth factor secretion and induced HUVEC apoptosis in a dose-dependent manner, and it showed a statistically significant difference compared with the PEDF treatment group. In vivo, PEGylated-PEDF had a long-lasting effect in both plasma and retinal concentrations. In an oxygen-induced retinopathy model, one intravitreous injection of PEGylated-PEDF after mouse pups were moved into room air resulted in a significant difference in the inhibition of retinal neovascularization, which decreased the nonperfusion area, compared with the PEDF-treated group. Our present study demonstrated for the first time the long-term inhibitory effects of PEGylated-PEDF on the prevention of neovascularization in vitro and in vivo. These data suggest that PEGylated-PEDF could offer an innovative therapeutic strategy for preventing retinal neovascularization.